Demographic variables in Auckland medical students.
To review the important background details of students admitted to the Auckland School of Medicine over its 25 years. Data collected at the time of application on 2448 students who successfully gained entry to the course has been analysed and compared with similar demographic variables in the New Zealand population as a whole, and with some of the findings from a survey performed on the total student population enrolling at Auckland University during 1990. Successful applicants had a mean age of 18.6 years, 39.7% were females and 77% were born in New Zealand. Eighty-three percent were European, 3.6% Maori, 2.4% Pacific Islanders and 10.8% Chinese, Indian or other Asian. Sixty-three percent came from cities over 100,000, 16% being from towns less than 20,000 people. State schools were attended by 77% of entrants and 55% went to single sex schools. University students enrolling in 1990 came from affluent backgrounds with 70% of medical students that year being from socioeconomic levels one and two. Parental occupation was found to clearly influence the career choice of students. Auckland medical students are predominantly from large cities and affluent backgrounds with only those of European origin being admitted in the same proportion as they occupy in the New Zealand population. The high ratio of Asian students reflects their commitment to senior secondary school studies while the lower admission rate for Maori and Polynesian students is due in part to the large number who leave school without completing their secondary education. The possible impact of these demographic variables on recruitment and loss from the course and on the choice and location of practice is discussed.


The inhomogeneous distribution of liver function: possible impact on the prediction of post-operative remnant liver function.
Previous studies have shown that liver function is inhomogeneously distributed in diseased livers, and this uneven distribution cannot be compensated for if a global liver function test is used for the prediction of post-operative remnant liver function. Dynamic Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) can assess segmental liver function, thus offering the possibility to overcome this problem. In 10 patients with liver cirrhosis and 10 normal volunteers, the contribution of individual liver segments to total liver function and volume was calculated using dynamic Gd-EOB-DTPA-enhanced MRI. Remnant liver function predictions using a segmental method and global assessment were compared for a simulated left hemihepatectomy. For the prediction based on segmental functional MRI assessment, the estimated function of the remnant liver segments was added. Global liver function assessment overestimated the remnant liver function in 9 out of 10 patients by as much as 9.3% [median -3.5% (-9.3-3.5%)]. In the normal volunteers there was a slight underestimation of remnant function in 9 out of 10 cases [median 1.07% (-0.7-2.5%)]. The present study underlines the necessity of a segmental liver function test able to compensate for the non-homogeneous nature of liver function, if the prediction of post-operative remnant liver function is to be improved.


Effects of lifelong ethanol consumption on the ultrastructure and lipopigmentation of rat heart.
The myocardial interactions of ageing and lifelong ethanol ingestion were studied in the ethanol-preferring AA (Alko Alcohol) line of rats. Samples of the left ventricle from young control rats (3-month), old control rats (30-month) and rats exposed to ethanol from 3 to 30 months of age, were studied in terms of myocardial ultrastructure and lipopigmentation. Electron microscopic morphometry showed an age-related increase in the volumetric densities of lipofuscin and unspecified sarcoplasm, while the proportions of mitochondria, myofibrils and tubular structures remained unaltered in the left ventricular myocardium. Lifelong ethanol exposure increased the proportion of sarcoplasmic reticulum and transverse tubules, apparently due to dilation of the tubular structures. Mitochondria were significantly larger in the ethanol-exposed rats compared to the control rats of the same age, while the volumetric proportion of mitochondria tended to decrease in the ethanol-exposed group. Fluorescence microscopic image analysis showed that myocardial lipopigmentation (proportion of myocardial area covered by autofluorescent lipopigments) was about two-fold in the old ethanol-exposed rats compared to the old control rats, and 13-fold compared to the young controls. It is concluded that ageing and chronic ethanol ingestion produce rather different patterns of alteration in myocardial ultrastructure, which does not support the concept of ethanol-induced accelerated ageing. The enhancement of myocardial lipofuscin accumulation is thought to reflect chronic oxidative stress in the hearts exposed to ethanol.


Evaluation of a novel method based on PCR Restriction Fragment Length Polymorphism Analysis of the tuf gene for the identification of Staphylococcus species.
A novel method, based on PCR Restriction Fragment Length Polymorphism Analysis (PRA) of a part of the tuf gene (370 bp), was designed for the identification of 11 staphylococcal species, including the most common staphylococcal pathogens. A total of 258 clinical isolates were validated by this assay, and the results were in concordance with those obtained by the reference method of Kloos and Schleifer.


Trends in short-term and 1-year mortality in very elderly intensive care patients in the Netherlands: a retrospective study from 2008 to 2014.
To describe the trends in short-term and long-term mortality in very elderly intensive care unit (ICU) patients between 2008 and 2014. A retrospective cohort study was conducted using data from the National Intensive Care Evaluation Foundation from 31 Dutch ICUs. Generalized linear mixed-effects models were used to determine the change in adjusted short-term mortality (ICU/hospital deaths) and long-term mortality (3, 6, and 12 months after ICU admission) over the period 2008-2014 in very elderly patients and in patients less than 80 years old admitted to the ICU. A total of 216,196 patients admitted to 31 ICUs in the period from 2008 to 2014 were included in the study, including 28,284 (13.1%) very elderly patients (80 years or older). Follow-up data for determination of 3-, 6-, and 12-month mortality were available for, respectively, 210,005 (97.1%), 202,551 (93.7%), and 176,847 (81.8%) ICU admissions. The crude ICU and in-hospital mortality decreased, respectively, from 17.6% to 13.0% and from 30.7% to 21.0%. The annual risk-adjusted ICU and in-hospital mortality of very elderly patients (adjusted for APACHE III score, comorbidities, and admission type) decreased significantly during the study period [adjusted odds ratio 0.97 (0.95-0.99) and 0.92 (0.91-0.93), respectively]. Additionally, the annual risk-adjusted 3-, 6-, and 12-month mortality decreased significantly from 2008 to 2014 [adjusted odds ratio 0.96 (0.95-0.97), 0.96 (0.94-0.97), and 0.97 (0.95-0.98), respectively]. A similar significant annual decrease in risk-adjusted short-term and long-term mortality was observed in patients aged less than 80 years. Both short-term and long-term risk-adjusted mortality decreased significantly during the study period in both very elderly ICU patients and patients aged less than 80 years in the Netherlands. This study clearly shows that in our setting very elderly patients benefit almost as much as their younger counterparts from improvement in quality of care over time.


Degradation of endogenous proteins and generation of a null-like phenotype in zebrafish using Trim-Away technology.
Trim-Away is a recent technique to rapidly deplete a protein from any cell type. Guided by antibodies, TRIM21 selects proteins for destruction. However, the applicability of this method in model organisms has not been investigated. Here, we show that Trim-Away can degrade proteins in zebrafish embryos. Trim-Away depletes proteins faster than morpholinos, which enables analysis of protein function during early embryogenesis. Furthermore, Trim-Away can be applied to evaluate the role of maternally contributed proteins in zebrafish embryos. Our findings indicate that Trim-Away is a powerful tool to perform functional analysis of proteins during zebrafish development.


Synthesis and P-P cleavage reactions of [P(X)X']2; X-ray structures of [Co[P(X)X'](CO)3] and P4[P(X)X']2[X = N(SiMe3)2, X'= NPri2].
Treatment of P(X)(X')Cl with KC8 gave the crystalline diphosphine [P(X)X']2 (1) which dissociated reversibly into the phosphinyl radical *P(X)X' (2), a plausible intermediate in the reaction of with [Cr(CO)6], [Co(NO)(CO)3] or P4, yielding [Cr[P(X)X']2(CO)3] (3), [Co[P(X)X'](CO)3] (4), or 1,4-P4[P(X)X']2 (5); the P(X)X' substituent is pyramidal at P in but planar in [X = N(SiMe3)2, X'= NPri2].


The acylampicillins: mezlocillin, piperacillin, and azlocillin.
The new acylampicillin derivatives azlocillin, mezlocillin, and piperacillin have an increased activity against many gram-negative bacilli, especially Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa, when compared with the carboxypenicillins carbenicillin and ticarcillin. The new penicillins show synergistic activity in combination with aminoglycosides but, when combined with other beta-lactams, may be synergistic (piperacillin and moxalactam; mezlocillin and cefoperazone), indifferent, or antagonistic (azlocillin, mezlocillin, or piperacillin and cefoxitin or cefamandole). The in vitro activity of these agents, either alone or in combination, appears to correlate with in vivo efficacy in animal models. The new penicillins are clinically effective for a very broad range of infections, including life-threatening nosocomial infections. Adverse effects with these, as with other semisynthetic penicillins, are minimal. Attention must be paid to the potential for infection by naturally resistant, gram-negative bacilli such as beta-lactamase-producing Escherichia coli and for the emergence of resistance during therapy. The granulocytopenic patient should receive these agents only in conjunction with another agent, such as an aminoglycoside; this combination will often result in a synergistic effect when tested in vitro. The carboxypenicillins and the newer penicillins have substantial similarities, and prospective, comparative studies have so far failed to demonstrate significant clinical superiority. However, the increased activity of the acylampicillins may be advantageous for the treatment of infections due to K. pneumoniae and P. aeruginosa.


Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death.
Although the authors of several studies report elevated numbers of immunosuppressive regulatory T cells (Tregs) in hematologic and solid malignancies, the underlying mechanism is not fully clarified. Cancer is associated with oxidative stress mediated through reactive oxygen species produced by malignant cells, granulocytes, tumor-associated macrophages, and myeloid-derived suppressor cells. Oxidative stress is known to have detrimental effects on natural killer (NK) and T cells during chronic inflammatory conditions and cancer. Paradoxically, greater numbers of Tregs can be detected at tumor sites, indicating that Tregs can persist in this environment of increased oxidative stress. We demonstrate that Tregs, especially naive CD45RA(+), exhibit reduced sensitivity to oxidative stress-induced cell death and maintain their suppressive function, a phenomenon that may be attributed to their observed high antioxidative capacity. This newly described characteristic could explain their enrichment in malignancies associated with increased levels of oxidative stress.


CD137 expression is induced by Epstein-Barr virus infection through LMP1 in T or NK cells and mediates survival promoting signals.
To clarify the mechanism for development of Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms, we focused on the costimulatory receptor CD137. We detected high expression of CD137 gene and its protein on EBV-positive T- or NK-cell lines as compared with EBV-negative cell lines. EBV-positive cells from EBV-positive T- or NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) patients also had significantly higher CD137 gene expression than control cells from healthy donors. In the presence of IL-2, whose concentration in the serum of EBV-T/NK-LPDs was higher than that of healthy donors, CD137 protein expression was upregulated in the patients' cells whereas not in control cells from healthy donors. In vitro EBV infection of MOLT4 cells resulted in induction of endogenous CD137 expression. Transient expression of LMP1, which was enhanced by IL-2 in EBV-T/NK-LPDs cells, induced endogenous CD137 gene expression in T and NK-cell lines. In order to examine in vivo CD137 expression, we used EBV-T/NK-LPDs xenograft models generated by intravenous injection of patients' cells. We identified EBV-positive and CD8-positive T cells, as well as CD137 ligand-positive cells, in their tissue lesions. In addition, we detected CD137 expression on the EBV infected cells from the lesions of the models by immune-fluorescent staining. Finally, CD137 stimulation suppressed etoposide-induced cell death not only in the EBV-positive T- or NK-cell lines, but also in the patients' cells. These results indicate that upregulation of CD137 expression through LMP1 by EBV promotes cell survival in T or NK cells leading to development of EBV-positive T/NK-cell neoplasms.


Polyaspartic acid, 2-acrylamido-2-Methyl propane sulfonic acid and sodium alginate based biocompatible stimuli responsive polymer gel for controlled release of GHK-Cu peptide for wound healing.
Stimuli responsive polymer based on Polyaspartic acid, 2-Acrylamido-2-methylpropane sulfonic acid and sodium alginate (NaAlg) were synthesized using two cross-linkers Ethylene glycol dimethacrylate (EGDMA) and TMPTA (Trimethylolpropane triacrylate). The polymers were standardized and optimized to obtain a polymer with maximum swelling in distilled water, saline, glucose and solutions of varying pH. The synthesized polymer swelled well in distilled water, glucose solution and acidic- alkaline medium. The biocompatibility of the polymer was evaluated for blood compatibility and protein adsorption. The polymer with maximum swelling property was used for peptide release studies. The polymer was further used to study the peptide encapsulation and release efficiency of the polymeric material which was confirmed by FTIR, Scanning Emission Microscope and EDX. The encapsulation efficiency of the polymer for encapsulating (glycyl-l-histidyl-l-lysine-copper) GHK-Cu was observed to be 55.26% and peptide release of 51.84% was observed for Ethylene glycol dimethacrylate based polymer after 24 h whereas for Trimethylolpropane triacrylate based polymer the encapsulation efficiency was observed to be 49.6% and release was 39.01%. The EGDMA based polymer was further examined under in vivo studies in order to evaluate the efficiency of the synthesized polymer. The in vivo studies include wound closure, histopathological analysis, biochemical and toxicity assay. The material has shown promising results for both in vivo and in vitro studies.


Influence of previous host plants on the reproductive success of a polyphagous mite pest, Halotydeus destructor (Trombidiformes: Penthaleidae).
In the evolution of phytophagous arthropods, adaptation to a single type of host plant is generally assumed to lead to a reduction in fitness on other host plant types, resulting in increasing host specialization. While this process is normally considered to be genetically based, short-term effects acting within one generation (plasticity) or across two generations (cross-generation variation) could also play a role. Here, we test these effects in the redlegged earth mite, Halotydeus destructor (Tucker) (Prostigmata: Penthaleidae), a major agricultural pest of multiple crop plants. Field populations of mites were collected from grasses, legumes, and broad-leaf weeds and placed into enclosures with different plant types. The survival, net reproductive output (Ro), and feeding damage of each mite population were assessed across two generations. The interaction between the origin of mites and plant type had a significant effect on parental survival, Ro, offspring development, and feeding damage. Mites collected from legumes showed higher parental survival on all host types; however, Ro, offspring development and feeding damage were all higher when mites were placed onto the same plant type from which they were collected. These patterns point to the ability of H. destructor to perform well on host plants even in the absence of genetically differentiated host races, but also the likelihood of performance trade-offs when populations are forced to rapidly change hosts within and across sequential generations.


Multiple signaling functions of song in a polymorphic species with alternative reproductive strategies.
Vocal traits can be sexually selected to reflect male quality, but may also evolve to serve additional signaling functions. We used a long-term dataset to examine the signaling potential of song in dimorphic white-throated sparrows (Zonotrichia albicollis). We investigated whether song conveys multifaceted information about the vocalizing individual, including fitness, species identity, individual identity, and morph. We also evaluated whether song traits correlate differently with fitness in the two morphs, as the more promiscuous strategy of white, relative to tan, morph males might impose stronger sexual selection. Males with high song rates achieved higher lifetime reproductive success, and this pattern was driven by white morph males. In addition, males that sang songs with many notes survived longer, but this pattern was less robust. Thus, song traits reflect differences in fitness and may more strongly affect fitness in the white morph. Song frequency was unrelated to fitness, body size, or morph, but was individual specific and could signal individual identity. Songs of the two morphs displayed similar frequency ratios and bandwidths. However, tan morph males sang songs with longer first notes, fewer notes, and higher variability. Thus, song could be used in morph discrimination. Variation in frequency ratios between notes was low and could function in conspecific recognition, but pitch change dynamics did differ between four different song types observed. Our results support a multiple messages model for white-throated sparrow song, in which different song traits communicate discrete information about the vocalizing individual.


Ligand-induced conformational changes with cation ejection upon binding to human telomeric DNA G-quadruplexes.
The rational design of ligands targeting human telomeric DNA G-quadruplexes is a complex problem due to the structural polymorphism that these sequences can adopt in physiological conditions. Moreover, the ability of ligands to switch conformational equilibria between different G-quadruplex structures is often overlooked in docking approaches. Here, we demonstrate that three of the most potent G-quadruplex ligands (360A, Phen-DC3, and pyridostatin) induce conformational changes of telomeric DNA G-quadruplexes to an antiparallel structure (as determined by circular dichroism) containing only one specifically coordinated K(+) (as determined by electrospray mass spectrometry) and, hence, presumably only two consecutive G-quartets. Control ligands TrisQ, known to bind preferentially to hybrid than to antiparallel structures, and L2H2-6M(2)OTD, known not to disrupt the hybrid-1 structure, did not show such K(+) removal. Instead, binding of the cyclic oxazole L2H2-6M(2)OTD was accompanied by the uptake of one additional K(+). Also contrasting with telomeric G-quadruplexes, the parallel-stranded Pu24-myc G-quadruplex, to which Phen-DC3 is known to bind by end-stacking, did not undergo cation removal upon ligand binding. Our study therefore evidences that very affine ligands can induce conformational switching of the human telomeric G-quadruplexes to an antiparallel structure and that this conformational change is accompanied by removal of one interquartet cation.


Membrane association and release of wild-type and pathological tau from organotypic brain slice cultures.
The spatiotemporal transmission of pathological tau in the brain is characteristic of Alzheimer's disease. Release of both soluble and abnormal tau species from healthy neurons is increased upon stimulation of neuronal activity. It is not yet understood whether the mechanisms controlling soluble tau release from healthy neurons is the same as those involved in the spread of pathological tau species. To begin to understand these events, we have studied tau distribution and release using organotypic brain slice cultures. The slices were cultured from postnatal wild-type and 3xTg-AD mice for up to 1 month. Tau distribution in subcellular compartments was examined by western blotting, and tau release into culture medium was determined using a sensitive sandwich ELISA. We show here that 3xTg-AD cultures have an accelerated development of pathological tau abnormalities including the redistribution of tau to synaptic and membrane compartments. The 3xTg-AD slice cultures show elevated basal tau release relative to total tau when compared with wild-type cultures. However, tau release from 3xTg-AD slices cannot be further stimulated when neuronal activity is increased with potassium chloride. Moreover, we report that there is an increased pool of dephosphorylated membrane-associated tau in conditions where tau release is increased. These data suggest that there may be differential patterns of tau release when using integrated slice culture models of wild-type and transgenic mouse brain, although it will be important to determine the effect of tau overexpression for these findings. These results further increase our knowledge of the molecular mechanisms underlying tau release and propagation in neurodegenerative tauopathies.


Adenocarcinoma of the Appendix Presenting as a Palpable Right Thigh Mass.
Intra-abdominal and intra-pelvic pathologies initially presenting in extra-abdominal/pelvic locations is unusual. This spread predominantly occurs with infectious processes to sites including the buttock, thigh, and calf. The routes of extension into adjacent anatomically weak compartments include the pelvic outlet, greater sciatic foramen, obturator foramen, inguinal or femoral canal, weak bones, or along nerves and blood vessels. Malignant neoplasms of the appendix, while extremely rare and accounting for only 0.4% of all gastrointestinal cancers, is one of the intra-abdominal pathologies that can spread via these routes. Adenocarcinoma of the appendix accounts for 10-20% of primary appendiceal tumors. They usually present as acute appendicitis or as a right lower quadrant abdominal mass when associated with a mucocele. We report the unique case of mucinous appendiceal adenocarcinoma in a 57-year-old male who initially presented with a right thigh mass secondary to extension of the neoplasm from the right lower quadrant through the femoral canal. A similar presentation of a mucinous appendiceal cystadenoma has been previously reported, however, to our knowledge, this is the first case of a malignant appendiceal tumor extending into the thigh. We review the literature and discuss imaging findings and treatment of this tumor.


Combined ecotoxicity of binary zinc oxide and copper oxide nanoparticles to Scenedesmus obliquus.
A combined ecotoxicity study was carried out with nano-zinc oxide (nZnO) and nano-copper oxide (nCuO) to freshwater algae Scenedesmus obliquus. Concentration-response analysis indicated that the dissolved metal fraction was not the major source of individual and combined toxicity of the metal-oxide nanoparticles (MONPs). Moreover, the contribution of the nCuO (based on metallic mass) to the combined toxicity was greater than that of the nZnO. The observed combined toxicity can be predicted by the pharmacological concepts of concentration addition (CA) and independent action (IA). Combined toxicity prediction (in terms of median effect concentration) based on both concepts tends to overestimate the overall observed toxicity of the MONP mixtures. CA was more accurate for predicting the combined toxicity than IA. It may be concluded that CA gives a valid estimation of the overall ecotoxicity for mixtures comprising of similar acting MONPs.


Dynamic structure of T4 gene 32 protein filaments facilitates rapid noncooperative protein dissociation.
Bacteriophage T4 gene 32 protein (gp32) is a model single-stranded DNA (ssDNA) binding protein, essential for DNA replication. gp32 forms cooperative filaments on ssDNA through interprotein interactions between its core and N-terminus. However, detailed understanding of gp32 filament structure and organization remains incomplete, particularly for longer, biologically-relevant DNA lengths. Moreover, it is unclear how these tightly-bound filaments dissociate from ssDNA during complementary strand synthesis. We use optical tweezers and atomic force microscopy to probe the structure and binding dynamics of gp32 on long (∼8 knt) ssDNA substrates. We find that cooperative binding of gp32 rigidifies ssDNA while also reducing its contour length, consistent with the ssDNA helically winding around the gp32 filament. While measured rates of gp32 binding and dissociation indicate nM binding affinity, at ∼1000-fold higher protein concentrations gp32 continues to bind into and restructure the gp32-ssDNA filament, leading to an increase in its helical pitch and elongation of the substrate. Furthermore, the oversaturated gp32-ssDNA filament becomes progressively unwound and unstable as observed by the appearance of a rapid, noncooperative protein dissociation phase not seen at lower complex saturation, suggesting a possible mechanism for prompt removal of gp32 from the overcrowded ssDNA in front of the polymerase during replication.


Severe Fever with Thrombocytopenia Syndrome Virus in Humans, Domesticated Animals, Ticks, and Mosquitoes, Shaanxi Province, China.
AbstractThe first human infection with severe fever with thrombocytopenia syndrome virus (SFTSV) was detected in Shaanxi Province, China, in 2013, although the virus had been reported in 13 other provinces of China since 2010. We collected and analyzed a total of 4,011 samples, including 936 human serum samples, 155 animal serum samples, 895 ticks, 1,950 mosquitoes, 30 midges, and 20 sandflies. SFTSV antibodies were found in 44 human samples (4.7%) with no significant differences between males and females or across counties. The incidence rate of severe fever with thrombocytopenia syndrome was significantly higher among individuals 20-60 years of age. Moreover, SFTSV-specific antibodies were detected in goats (66.7%), cattle (13.2%), and dogs (15.0%), but not in pigs (0%). We detected the virus in Haemaphysalis concinna ticks with a prevalence rate of 21.3% (17/80 pools). All mosquito, midge, and sandfly samples were negative for SFTSV. These results support wide circulation of the virus in western China. Haemaphysalis concinna ticks may serve as a novel SFTSV vector, and the role of these ticks requires further investigation.


Dynamic graph convolutional networks with attention mechanism for rumor detection on social media.
Social media has become an ideal platform for the propagation of rumors, fake news, and misinformation. Rumors on social media not only mislead online users but also affect the real world immensely. Thus, detecting the rumors and preventing their spread became an essential task. Some of the recent deep learning-based rumor detection methods, such as Bi-Directional Graph Convolutional Networks (Bi-GCN), represent rumor using the completed stage of the rumor diffusion and try to learn the structural information from it. However, these methods are limited to represent rumor propagation as a static graph, which isn't optimal for capturing the dynamic information of the rumors. In this study, we propose novel graph convolutional networks with attention mechanisms, named Dynamic GCN, for rumor detection. We first represent rumor posts with their responsive posts as dynamic graphs. The temporal information is used to generate a sequence of graph snapshots. The representation learning on graph snapshots with attention mechanism captures both structural and temporal information of rumor spreads. The conducted experiments on three real-world datasets demonstrate the superiority of Dynamic GCN over the state-of-the-art methods in the rumor detection task.


Determination of inorganic ions and carbohydrates in cardioplegia and nephroplegia solutions by ion chromatography.
In this study, methods for analyzing inorganic ions and carbohydrates in cardioplegia and nephroplegia solutions were developed and validated using ion chromatography with both conductivity and pulsed amperometric detection. The inorganic ions such as sodium, potassium, and calcium were separated by a cation-exchange column with 27 mM methanesulfonic acid as mobile phase at 0.5 mL/min. The anion (chloride) and carbohydrates (mannitol and glucose) were analyzed by an anion-exchange column using a mobile phase of 20 mM sodium hydroxide at 1.0 mL/min. The methods showed a high sensitivity for all analytes, with quantification limits from 0.0002 to 0.06 mg/L. Good linearities between the peak areas and concentrations were found for all analytes within the selected concentration range (R2 > 0.999). Relative standard deviation values for repeatability and interday precision were 0.1%-1.0% and 0.7%-1.6%, respectively. The accuracy was validated by determining the percentage recovery, which was between 98.0% and 101.3% for all analytes, indicating good accuracy of the methods. The robustness was verified by using an experimental design. Finally, real samples were analyzed to determine the content of the analytes. All assay values were between 96.8% and 102.5%.


Causality relationships between coagulation factors in type 2 diabetes mellitus: path analysis approach.
Type 2 diabetic mellitus patients are amongst the most susceptible groups to vascular abnormalities, which predominantly lead to myocardial disease. The hypercoagulable state has been widely studied by researchers as being the major suspicious mechanism facilitating the consecutive chain of molecular events leading to these complications. However, there is no consensus on the definition of the hypercoagulable state with respect to coagulation quantities, their interrelations and basic factor(s) initiating this pathogenic event, by which the prognosis of myocardial complications could be determined. Path analysis was used to study the interactions between coagulation factors as well as other factors beyond coagulation factors in relation with pathogenic events in both diabetics and healthy subjects. In the present work, coagulation factors of 40 healthy and 40 type 2 diabetics were determined experimentally. The data were then analyzed using SPSS and AMOS software. Multivariate regression analysis was done to draw path diagrams. Our results show that FII, as the main cause for hypercoagulable state, is directly induced by FX and FVIII in normal individuals and by FX, FXI, FV and VWF cofactors in diabetic patients. In general, our findings showed complicated relationship between coagulation factors and their effects either separately or combined.


Aminopeptidases in Caenorhabditis elegans and Panagrellus redivivus: detection using peptide and non-peptide substrates.
Aminopeptidase activities were detected in extracts of the free-living nematodes Caenorhabditis elegans and Panagrellus redivivus using the aminoacyl substrate L-alanine-4-nitroanilide. The activities exhibited similarities in Km (C. elegans = 2.22 mM; P. redivivus = 2.09 mM) and specific activity (C. elegans = 1.38 +/- 0.43 mAU min(-1) x g(-1); P. redivivus, 1.23 +/- 0.18m AU min(-1) microg(-1). Each is inhibited competitively by amastatin (C. elegans IC50 = 0.46 microM; P. redivivus IC50 = 15.90 microM) and non-competitively by leuhistin (C. elegans IC50 = 3.00 microM; P. redivivus IC50 = 37.35 microM). The bioactive peptides adipokinetic hormone and substance P decrease the apparent aminopeptidase activities of each extract suggesting that the peptides compete with the Ala-pNA as substrates. With each extract, adipokinetic hormone appeared to be the more effective substrate. Digestion of adipokinetic hormone by C. elegans and P. redivivus extracts in the presence and absence of 1 mM amastatin produced distinct chromatographic profiles that suggest different digestion patterns for the two species. However, amastatin had clear effects on chromatographic profiles from each species indicating that an aminopeptidase is involved in the digestion of the peptide substrates. The data presented indicate that extracts of free-living nematodes are capable of metabolizing peptide hormones, and that this metabolism involves substrate-selective aminopeptidases.


Preparation and characterization of lectin-conjugated chitosan fluorescent nanoparticles.
The purpose of this study was to design and evaluate a novel target nanoparticle for disease detection and drug delivery using the biotin-avidin binding system. The formed lectin-conjugated chitosan fluorescent nanoparticles were of spherical shape(100-200 nm in diameter), which were more stable under light than pure fluorescein isothiocyanate (FITC).


Genetic markers in human bone: I. Deoxyribonucleic acid (DNA) analysis.
Deoxyribonucleic acid (DNA) was isolated from a number of spongy and compact human bone tissue specimens, and the yield was estimated on a "per milligram of starting tissue" basis. DNA was, in addition, isolated from a number of corresponding blood and bone tissue specimens. Spectrophotofluorometry and ethidium bromide visualization on minigels were used to estimate the quantity and degree of degradation of DNA. The DNA from several blood-bone pairs is shown to give concordant restriction fragment length polymorphism (RFLP) typing results by two different typing protocols with five different single-locus probes. DNA from several additional blood-bone pairs is shown to give concordant results for human leucocyte antigen (HLA)-DQ alpha phenotypes following polymerase chain reaction (PCR) amplification and hybridization to specific allele-specific oligonucleotide (ASO) probes, and for the variable numbers of tandem repeats (VNTR) length polymorphisms 3' to the human apolipoprotein B (APOB) gene following PCR amplification with specific primers and analysis of the products by electrophoresis and ethidium bromide visualization.


Baseline fetal heart rate analysis: eleven automatic methods versus expert consensus.
Visual analysis of fetal heart rate (FHR) during labor is subject to inter- and intra-observer variability that is particularly troublesome for anomalous recordings. Automatic FHR analysis has been proposed as a promising way to reduce this variability. The major difficulty with automatic analysis is to determine the baseline from which accelerations and decelerations will be detected. Eleven methods for automatic FHR analysis were reprogrammed using description from the literature and applied to 66 FHR recordings collected during the first stage of delivery. The FHR baselines produced by the automatic methods were compared with the baseline defined by agreement among a panel of three experts. The better performance of the automatic methods described by Mongelli, Lu, Wrobel and Pardey was noted despite their different approaches on signal processing. Nevertheless, for several recordings, none of the automatic studied methods produced a baseline similar to that defined by the experts.


Scrutinizing low-spin Cr(II) complexes.
The oxidation state of the chromium center in the following compounds has been probed using a combination of chromium K-edge X-ray absorption spectroscopy and density functional theory: [Cr(phen)(3)][PF(6)](2) (1), [Cr(phen)(3)][PF(6)](3) (2), [CrCl(2)((t)bpy)(2)] (3), [CrCl(2)(bpy)(2)]Cl(0.38)[PF(6)](0.62) (4), [Cr(TPP)(py)(2)] (5), [Cr((t)BuNC)(6)][PF(6)](2) (6), [CrCl(2)(dmpe)(2)] (7), and [Cr(Cp)(2)] (8), where phen is 1,10-phenanthroline, (t)bpy is 4,4'-di-tert-butyl-2,2'-bipyridine, and TPP(2-) is doubly deprotonated 5,10,15,20-tetraphenylporphyrin. The X-ray crystal structures of complexes 1, [Cr(phen)(3)][OTf](2) (1'), and 3 are reported. The X-ray absorption and computational data reveal that complexes 1-5 all contain a central Cr(III) ion (S(Cr) = (3)/(2)), whereas complexes 6-8 contain a central low-spin (S = 1) Cr(II) ion. Therefore, the electronic structures of 1-8 are best described as [Cr(III)(phen(•))(phen(0))(2)][PF(6)](2), [Cr(III)(phen(0))(3)][PF(6)](3), [Cr(III)Cl(2)((t)bpy(•))((t)bpy(0))], [Cr(III)Cl(2)(bpy(0))(2)]Cl(0.38)[PF(6)](0.62), [Cr(III)(TPP(3•-))(py)(2)], [Cr(II)((t)BuNC)(6)][PF(6)](2), [Cr(II)Cl(2)(dmpe)(2)], and [Cr(II)(Cp)(2)], respectively, where (L(0)) and (L(•))(-) (L = phen, (t)bpy, or bpy) are the diamagnetic neutral and one-electron-reduced radical monoanionic forms of L, and TPP(3•-) is the one-electron-reduced doublet form of diamagnetic TPP(2-). Following our previous results that have shown [Cr((t)bpy)(3)](2+) and [Cr(tpy)(2)](2+) (tpy = 2,2':6',2"-terpyridine) to contain a central Cr(III) ion, the current results further refine the scope of compounds that may be described as low-spin Cr(II) and reveal that this is a very rare oxidation state accessible only with ligands in the strong-field extreme of the spectrochemical series.


Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53.
The transcriptional regulator c-MYC is abnormally overexpressed in many human cancers. Evasion from apoptosis is critical for cancer development, particularly c-MYC-driven cancers. We explored which anti-apoptotic BCL-2 family member (expressed under endogenous regulation) is essential to sustain c-MYC-driven lymphoma growth to reveal which should be targeted for cancer therapy. Remarkably, inducible Cre-mediated deletion of even a single Mcl-1 allele substantially impaired the growth of c-MYC-driven mouse lymphomas. Mutations in p53 could diminish but not obviate the dependency of c-MYC-driven mouse lymphomas on MCL-1. Importantly, targeting of MCL-1 killed c-MYC-driven human Burkitt lymphoma cells, even those bearing mutations in p53. Given that loss of one allele of Mcl-1 is well tolerated in healthy tissues, our results suggest that therapeutic targeting of MCL-1 would be an attractive therapeutic strategy for MYC-driven cancers.


Evaluation of the TALON Cooperative Acquisitions Program for monographs.
The TALON Cooperative Acquisitions Program for monographs (TALON/CAP) was implemented in 1979 by eleven resource libraries in the South Central Regional Medical Library Program. Each participating library acquired books from selected publishers within a profile covering subject and format. The program was evaluated by comparing interlibrary loan requests, surveying participants, and analyzing cataloging records. The results were that ten of the eleven libraries significantly increased their coverage of assigned publishers, and that academic medical libraries are not all buying the same books, even from major medical publishers. The fifty-six publishers in the program accounted for 60% to 83% of the titles with 1977-80 imprints held by participating libraries. The computer-generated collection analysis reports provide a baseline for future collection management studies.


[Diagnosis and monitoring of patients with type IIa multiple endocrine neoplasms].
Syndrome of multiple endocrine neoplasia, type IIa, is a rare disturbance made by medullar carcinoma of the thyroid gland, pheochromacytoma and hyperparathyroidism. The article deals with three patients with multiple endocrine neoplasia, type IIa, with special emphasis to detection of the disease in time and treatment of the patients in the early phase of the illness. This is a hereditary autosomal dominant disturbance. Tests performed among members of family with high risk factors of the disease are of great importance. In this way early diagnosis is possible, and consequently, prevention of fatal issue due to pheochromocytoma and medullar carcinoma.


A Lipid Micellar System Loaded with Dexamethasone Palmitate Alleviates Rheumatoid Arthritis.
Glucocorticoids have been confirmed to be effective in the treatment of a variety of inflammatory diseases. However, their application encounters limitations in terms of tissue distribution and bioavailability in vivo. To address these key issues, we designed and developed a nanopreparation by using egg yolk lecithin/sodium glycocholate (EYL/SGC) and utilize such mixed micelles (MMs) to encapsulate dexamethasone palmitate (DMP) for the treatment of rheumatoid arthritis (RA). The prepared DMP-MMs had an average particle size of 49.18 ± 0.43 nm and were compared with an emulsion-based dexamethasone palmitate. Pharmacokinetic and in vivo fluorescence imaging showed that mixed micelles had higher bioavailability and targeting efficiency in inflammatory sites. An arthritis rat model was established via induction by Complete Freund's Adjuvant (CFA), followed by the efficacy studies by the observations of paw volume, histology, spleen index, pro-inflammatory cytokines, and CT images. It was confirmed that intravenous injection of DMP-MMs exhibited advantages in alleviating joint inflammation compared with the emulsion system. Composed of pharmaceutical adjuvants only, the nanoscale mixed micelles seem a promising carrier system for the RA treatment with lipophilic drugs.


Ovarian function of the trout preovulatory ovary: new insights from recent gene expression studies.
During the preovulatory period the follicle-enclosed oocyte progressively acquires maturational and developmental competence. In addition, the follicle is also preparing for the release of the oocyte from the follicle at ovulation. Using real-time PCR and cDNA microarrays we have investigated the molecular mechanisms of oocyte competence acquisition and ovulation in rainbow trout (Oncorhynchus mykiss) by monitoring gene expression in the preovulatory ovary. These studies have demonstrated that many molecular events related to maturational competence and developmental competence acquisition, and ovulation occur concomitantly in the preovulatory ovarian follicle. Oocyte maturational competence acquisition is associated with a decrease of estrogen synthesis and signaling capacities. We also observed a differential expression of genes encoding for igfs and related binding protein, members of the TGF beta superfamily, proteins involved in ion and water transport, bone morphogenetic proteins, and cathepsins. In addition, our observation of a strong up-regulation, prior to ovulation, of genes encoding for proteins putatively involved in proteolysis, inflammation, coagulation, vasodilatation, and angiogenesis further supports the hypothesis comparing ovulation with an inflammatory-like reaction. Together, our results suggest that a finely tuned cross-talk exists between oocyte and follicular layers and between the ovulatory process and the oocyte maturational and developmental competence acquisition processes.


Free-space propagation of diffuse light: theory and experiments.
In this Letter we present a simple and novel theoretical approach for modeling the intensity distribution from an arbitrarily shaped turbid volume in a noncontact geometry by considering diffuse light propagation in free space. This theory is validated with experiments for a diffusive volume of known geometry in a noncontact situation, both with and without the presence of an embedded absorber. The implications of this new formulation in the context of optical tomography in turbid media are discussed.


Corneal thickness measurements and frequency doubling technology perimetry abnormalities in ocular hypertensive eyes.
It has been suggested that some patients currently diagnosed with ocular hypertension (OHT) may have thicker than average corneas that result in an overestimation of their true intraocular pressure. Consequently, patients with OHT with greater corneal thickness may be at a lower risk for functional glaucomatous damage, including visual field loss measured with frequency doubling technology (FDT) perimetry. The purpose of this study was to evaluate the frequency of FDT perimetry deficits in patients with OHT and to correlate these findings with central corneal thickness (CCT) measurements. Observational case control study. Sixty-five patients with OHT with normal optic discs and normal standard achromatic automated perimetry (SAP) visual fields and 52 normal control subjects. All participants underwent SAP, FDT perimetry, and CCT measurements using ultrasound pachymetry. CCT measurements in patients with OHT with abnormal repeatable FDT test results were compared with CCT measurements in patients with OHT with normal FDT results. In addition, CCT measurements in patients with OHT were compared with CCT measurements in normal control subjects. Fourteen of 65 patients with OHT (21.5%) demonstrated repeatable FDT abnormalities. The mean CCT of patients with OHT with abnormal FDT results was significantly lower than the mean CCT of patients with OHT with normal FDT results (542+/-35 microm versus 575+/-35 microm; P = 0.003). The mean CCT in the normal control group was 556+/-36 microm. The mean CCT in patients with OHT with normal FDT results was significantly higher than in normal subjects (P = 0.008). No statistically significant difference was found between mean CCT in normal subjects and in patients with OHT with abnormal FDT results (P = 0.18). Patients currently diagnosed with OHT, but with visual field loss detected by FDT perimetry, had significantly lower CCT measurements than patients with OHT with normal FDT results. These findings suggest that patients with OHT with thinner corneas are more likely to develop early glaucomatous functional damage and that CCT measurements should be taken into account when assessing risk for the development of glaucoma among OHT subjects.


On the use of double haploids for detecting QTL in outbred populations.
The power to detect quantitative trait loci (QTL) using the double haploid (DH), full-sib (FS) and hierarchical (HI) designs implemented in outbred fish populations was assessed for interval mapping using deterministic methods. The predictions were tested using simulation. The DH design was most efficient for the range of designs and parameters considered and was most beneficial when the FS design was not very powerful. The difference between the design was largest for a low amount of residual genetic variation. Accounting for an increase of the environmental variance due to the genetic constitution of the double haploid progeny changed the magnitude of the power, but the ranking of the designs remained the same. As large full sib family sizes can be obtained in fish, the practical value of HI designs as a strategy for increasing the power of QTL mapping experiments is limited when compared with the FS design. Overall, the results suggested that the DH design could be a very useful tool for QTL mapping in fish, and of particular importance when the effect of the QTL is low and the residual genetic variation from other chromosomes can be controlled by using multiple markers.


Ovarian thecoma with massive pleural effusion in postmenopausal women: A case report.
Previous clinical reports of benign ovarian thecoma, associated with hydrothorax, are rare. The present study presents the case of a 58-year-old women exhibiting right massive pleural effusions and elevated cancer antigen (CA)125, and a pelvic ultrasound revealed a hypoechoic mass. An exploratory laparotomy was subsequently performed. During the surgery, the left ovary measured 20×15×15 cm and had a smooth surface with no excrescences or papillary projections. The patient underwent right salpingo-oophorectomy. Pathological diagnosis was determined as benign ovarian thecoma. The chest radiograph revealed no pleural effusion 6 days following the surgery. The present case demonstrated a benign ovarian thecoma, associated with massive hydrothorax and elevated CA125, which mimicked an ovarian malignancy.


Mechanism for Remodeling of the Acyl Chain Composition of Cardiolipin Catalyzed by Saccharomyces cerevisiae Tafazzin.
Remodeling of the acyl chains of cardiolipin (CL) is responsible for final molecular composition of mature CL after de novo CL synthesis in mitochondria. Yeast Saccharomyces cerevisiae undergoes tafazzin-mediated CL remodeling, in which tafazzin serves as a transacylase from phospholipids to monolyso-CL (MLCL). In light of the diversity of the acyl compositions of mature CL between different organisms, the mechanism underlying tafazzin-mediated transacylation remains to be elucidated. We investigated the mechanism responsible for transacylation using purified S. cerevisiae tafazzin with liposomes composed of various sets of acyl donors and acceptors. The results revealed that tafazzin efficiently catalyzes transacylation in liposomal membranes with highly ordered lipid bilayer structure. Tafazzin elicited unique acyl chain specificity against phosphatidylcholine (PC) as follows: linoleoyl (18:2) > oleoyl (18:1) = palmitoleoyl (16:1) ≫ palmitoyl (16:0). In these reactions, tafazzin selectively removed the sn-2 acyl chain of PC and transferred it into the sn-1 and sn-2 positions of MLCL isomers at equivalent rates. We demonstrated for the first time that MLCL and dilyso-CL have inherent abilities to function as an acyl donor to monolyso-PC and acyl acceptor from PC, respectively. Furthermore, a Barth syndrome-associated tafazzin mutant (H77Q) was shown to completely lack the catalytic activity in our assay. It is difficult to reconcile the present results with the so-called thermodynamic remodeling hypothesis, which premises that tafazzin reacylates MLCL by unsaturated acyl chains only in disordered non-bilayer lipid domain. The acyl specificity of tafazzin may be one of the factors that determine the acyl composition of mature CL in S. cerevisiae mitochondria.


Dopaminergic alterations in populations at increased risk for psychosis: A systematic review of imaging findings.
Alterations of the dopaminergic system may be important neurobiological correlates of vulnerability and transition to psychosis. We systematically reviewed the evidence for dopaminergic alterations demonstrated by in-vivo imaging studies in humans at increased risk of developing psychosis, covering clinical, genetic, and environmental high-risk groups. All 63 included studies utilized Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), or neuromelanin-sensitive Magnetic Resonance Imaging (NM-MRI) methods to collect data concerning the dopaminergic system during rest and/or following pharmacological, behavioural, or cognitive challenges. The current evidence highlights that 1) striatal dopamine D2/3 receptor availability is unaltered in all three high-risk groups compared with healthy individuals; 2) striatal dopamine synthesis capacity (sDSC) is increased in some clinical and genetic high-risk individuals relative to controls (e.g. people that meet clinical criteria for being at ultra-high risk of developing psychosis and individuals with 22q11.2 deletion syndrome), while sDSC is decreased in cannabis-using environmental high-risk individuals. It seems likely that all three high-risk groups can be stratified into multiple subgroups, with varying risks to develop psychosis, transition rates, and underlying neurobiology. The present results support the hypothesis that dopaminergic abnormalities occur before high-risk individuals develop psychosis.


The SELF-PRUNING gene of tomato regulates vegetative to reproductive switching of sympodial meristems and is the ortholog of CEN and TFL1.
Vegetative and reproductive phases alternate regularly during sympodial growth in tomato. In wild-type 'indeterminate' plants, inflorescences are separated by three vegetative nodes. In 'determinate' plants homozygous for the recessive allele of the SELF-PRUNING (SP) gene, sympodial segments develop progressively fewer nodes until the shoot is terminated by two consecutive inflorescences. We show here that the SP gene is the tomato ortholog of CENTRORADIALIS and TERMINAL FLOWER1, genes which maintain the indeterminate state of inflorescence meristems in Antirrhinum and Arabidopsis respectively. The sp mutation results in a single amino acid change (P76L), and the mutant phenotype is mimicked by overexpressing the SP antisense RNA. Ectopic and overexpression of the SP and CEN transgenes in tomato rescues the 'indeterminate' phenotype, conditions the replacement of flowers by leaves in the inflorescence and suppresses the transition of the vegetative apex to a reproductive shoot. The SELF-PRUNING gene is expressed in shoot apices and leaves from very early stages, and later in inflorescence and floral primordia as well. This expression pattern is similar to that displayed by the tomato ortholog LEAFY and FLORICAULA. Comparison of the sympodial, day-neutral shoot system of tomato and the monopodial, photoperiod-sensitive systems of Arabidopsis and Antirrhinum suggests that flowering genes that are required for the processing of floral induction signals in Arabidopsis and Antirrhinum are required in tomato to regulate the alternation between vegetative and reproductive cycles in sympodial meristems.


(Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity.
Pathogenesis of AKI is complex and involves both local events in the kidney as well as systemic effects in the body that are interconnected and interdependent. Despite intensive investigations there is still no pharmacological agent that could provide complete protection against cisplatin nephrotoxicity. In the last decade mesenchymal stem cells (MSCs) have been proposed as a potentially useful therapeutic strategy in various diseases, including acute kidney injury. Although MSCs have potent immunosuppressive properties, animal studies also suggest that transplanted MSCs may elicit immune response. Interestingly, tumorigenicity of transplanted MSCs in animal studies has been rarely studied. Since the risk of tumorigenicity of particular therapy as well as the immune response to solid or cell grafts is a major issue in clinical trials, the aim of the present paper is to critically summarize the results of MSC transplantation on animal models of AKI, particularly cisplatin-induced animal models, and to expose results and main concerns about immunogenicity and tumorigenicity of transplanted MSCs, two important issues that need to be addressed in future studies.


[Excitable actions of counterirritants on cutaneous sensation].
Studies were conducted on the actions of counterirritants on sensory receptors in the skin and spinal monosynaptic reflex. Nerve discharges in the cat's saphenous nerve were promoted by the external application of menthol and nonylic vanillyl amide ( NVA ) dissolved in ethanol on the receptive field. When plasters containing counterirritants were externally applied on the receptive field, marked activation was recognized in touch-pressure-pin prick fibers immediately after the application as seen with plaster without drugs, but significantly high activity was maintained thereafter, and the increased firing rate in touch-pressure-pin prick-cold fibers lasted for 60 min. The activity of pressure-pin prick fibers was increased with the lapse of time and warm fibers was not influenced. Effects on activities of spinal dorsal horn cells were almost similar to the changes in activities of primary afferent from the skin. Monosynaptic reflex elicited by stimulation on the medial gastrocnemius nerve was weekly inhibited (significantly different from control at P less than 0.05), by the external application of plasters, and motoneuron receiving IPSP from the skin lightly touched on was observed. These findings suggest that the receptors activated with counterirritants were thought to be as follows: A delta and C polymodal nociceptors, A delta and C cold nociceptors, and slow adapting cutaneous mechanoreceptors. The cutaneous mechanoreceptors were also activated by the application of plasters. The volley from sensory nerve excited with counterirritants was thought to cause a suppression on the spinal monosynaptic reflex resulting from an inhibition on the motoneuron.


Nodular lymphocyte predominant Hodgkin lymphoma: a Lymphoma Study Association retrospective study.
Nodular lymphocyte predominant Hodgkin lymphoma represents a distinct entity from classical Hodgkin lymphoma. We conducted a retrospective study to investigate the management of patients with nodular lymphocyte predominant Hodgkin lymphoma. Clinical characteristics, treatment and outcome of adult patients with nodular lymphocyte predominant Hodgkin lymphoma were collected in Lymphoma Study Association centers. Progression-free survival (PFS) and overall survival (OS) were analyzed, and the competing risks formulation of a Cox regression model was used to control the effect of risk factors on relapse or death as competing events. Among 314 evaluable patients, 82.5% had early stage nodular lymphocyte predominant Hodgkin lymphoma. Initial management consisted in watchful waiting (36.3%), radiotherapy (20.1%), rituximab (8.9%), chemotherapy or immuno-chemotherapy (21.7%), combined modality treatment (12.7%), or radiotherapy plus rituximab (0.3%). With a median follow-up of 55.8 months, the 10-year PFS and OS estimates were 44.2% and 94.9%, respectively. The 4-year PFS estimates were 79.6% after radiotherapy, 77.0% after rituximab alone, 78.8% after chemotherapy or immuno-chemotherapy, and 93.9% after combined modality treatment. For the whole population, early treatment with chemotherapy or radiotherapy, but not rituximab alone (Hazard ratio 0.695 [0.320-1.512], P=0.3593) significantly reduced the risk of progression compared to watchful waiting (HR 0.388 [0.234-0.643], P=0.0002). Early treatment appears more beneficial compared to watchful waiting in terms of progression-free survival, but has no impact on overall survival. Radiotherapy in selected early stage nodular lymphocyte predominant Hodgkin lymphoma, and combined modality treatment, chemotherapy or immuno-chemotherapy for other patients, are the main options to treat adult patients with a curative intent.


Nitric Oxide in Salmonella and Escherichia coli Infections.
This review discusses the role that nitric oxide (NO) and its congeners play on various stages in the pathophysiology of Escherichia coli and Salmonella infections, with special emphasis on the regulatory pathways that lead to high NO synthesis, the role of reactive nitrogen species (RNS) in host resistance, and the bacterial molecular targets and defense mechanisms that protect enteric bacteria against the nitrosative stress encountered in diverse host anatomical sites. In general, NO can react directly with prosthetic groups containing transition metal centers, with other radicals, or with sulfhydryl groups in the presence of an electron acceptor. Binding to iron complexes is probably the best characterized direct reaction of NO in biological systems. The targets of RNS are numerous. RNS can facilitate oxidative modifications including lipid peroxidation, hydroxylation, and DNA base and protein oxidation. In addition, RNS can inflict nitrosative stress through the nitrosation of amines and sulfhydryls. Numerous vital bacterial molecules can be targeted by NO. It is therefore not surprising that enteropathogenic bacteria are armed with a number of sensors to coordinate the protective response to nitrosative stress, along with an assortment of antinitrosative defenses that detoxify, repair, or avoid the deleterious effects of RNS encountered within the host. NO and NO-derived RNS play important roles in innate immunity to Salmonella and E. coli. Enzymatic NO production by NO synthases can be enhanced by microbial and other inflammatory stimuli and it exerts direct antimicrobial actions as well as immunomodulatory and vasoregulatory effects.


Impact of 10% SF6 Gas Compared to 100% Air Tamponade in Descemet's Membrane Endothelial Keratoplasty.
To compare the clinical outcomes following Descemet's membrane endothelial keratoplasty (DMEK) with 100% air tamponade versus 10% sulfur hexafluoride (SF6) tamponade. Retrospective analysis of 108 consecutive DMEK cases subdivided by anterior chamber tamponade with 54 eyes receiving 10% SF6 and 54 eyes receiving 100% air injection. A post-hoc matched analysis revealed no statistically significant differences between the groups. The main outcome measurements were the complication rate, including intra- and postoperative complications and graft detachment rate requiring re-bubbling. Clinical outcome included best-corrected visual acuity (BCVA), endothelial cell count (ECC), and central corneal thickness (CCT) measured 1, 3, and 6 months after DMEK surgery. The graft detachment rate with consecutive re-bubbling was 18.5% in the air group and 22.2% in the SF6 group (p = 0.2). Remaining small peripheral graft detachments with a clear cornea occurred more often in the 100% air group (air: 22.2%; 12/54, 6/12 inferior compared to SF6: 7.4%; 4/54, 2/4 inferior; p = 0.06). The primary graft failure rate was comparable between the two groups. No complete graft detachment occurred. Outcome results for BCVA, ECC, and CCT at all follow-up time points were comparable between the two groups. The clinical outcomes (including re-bubbling rate, primary graft failure rate, and endothelial cell loss) were comparable with 100% air versus 10% SF6 tamponade, whereas other studies suggest that a higher SF6 concentration (20%) may result in a lower re-bubbling rate.


Use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs and risk of glioma: a case-control study.
Few studies have examined the association between use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) and risk of glioma and the results have been equivocal. We therefore investigated the influence of NSAID use on glioma risk in a nationwide setting. We used national registries in Denmark to identify all patients aged 20-85 years with a first diagnosis of histologically verified glioma during 2000-2009. Each case was matched on birth year and sex to eight population controls using risk-set sampling. We used prescription data to assess NSAID use and classified exposure to low-dose aspirin or non-aspirin (NA) NSAIDs into ever use or long-term use, defined as continuous use for 5 years. Conditional logistic regression was used to compute odds ratios (ORs), with 95% confidence intervals (CIs), for glioma associated with NSAID use, adjusted for potential confounders. A total of 2688 glioma cases and 18,848 population controls were included in the study. Ever use of low-dose aspirin (OR=0.90; 95% CI: 0.77-1.04) or NA-NSAIDs (OR=1.05; 95% CI: 0.96-1.14) was not associated with glioma risk. Compared with never use, long-term use of low-dose aspirin or of NA-NSAIDs was associated with ORs of 0.80 (95% CI: 0.53-1.21) and 1.11 (0.57-2.17), respectively. We observed no clear patterns of risk in stratified analysis according to estimated doses of low-dose aspirin (≤ 100 mg, 150 mg). We did not find any apparent association between aspirin or NA-NSAID use and risk of glioma, although our results may be consistent with a slight reduction in glioma risk with long-term use of low-dose aspirin.


Acute conjunctivitis caused by an atypical chlamydial strain: Chlamydia IOL 207.
A case of acute conjunctivitis in man caused by Chlamydia IOL 207 is described. Chlamydiae were isolated from the eye, and rising titres of type-specific antibodies to C. IOL 207, in serum and tears demonstrated an aetiological role for this agent. C. IOL 207 is an atypical chlamydial strain which serological studies suggest is widespread in some communities.


Molecular characterization of serotype III group B-streptococcus isolates causing neonatal meningitis.
We studied a collection of 110 serotype III group B streptococcus (GBS) isolates causing neonatal meningitis, by means of both pulsed-field gel electrophoresis (PFGE) with SmaI and Southern hybridization with probes for genes potentially associated with virulence (neuA, cpsA, scpB, and hylB and, for mobile genetic elements [MGEs], GBSi1 and IS1548), in comparison with 44 serotype III GBS isolates colonizing healthy neonates. Using polymerase chain reaction, we assessed both the insertion of MGEs downstream of the scpB gene and the insertion of IS1548 within the hylB gene. PFGE clustered the isolates into 3 main groups. One PFGE group accounted for 80% of typeable cerebrospinal fluid (CSF) isolates, versus 24% of colonization isolates (P=1.8 x 10-9). GBSi1 was found in 67% of CSF isolates and in only 23% of colonization isolates (P=5.3 x 10-7). A 15-kbp SmaI restriction-DNA fragment bearing the neuA gene was significantly associated with CSF isolates (P=1.1 x 10-11).


Numerical simulation of cardiovascular dynamics with left heart failure and in-series pulsatile ventricular assist device.
This article presents a numerical model for investigations of the human cardiovascular circulation system response, where the function of the impaired left ventricle is augmented by the pumping action of a pulsatile ventricular assist device (VAD) connected in series to the native heart. The numerical model includes a module for detailed heart valve dynamics, which helps to improve the accuracy of simulation in studying the pulsatile type VAD designs. Simulation results show that, for the case with left ventricular (LV) failure, the VAD support successfully compensates the impaired cardiovascular response, and greatly reduces the after-load of the diseased ventricle, thus assisting possible recovery of the ventricle from the diseased condition. The effects of these conditions on pulmonary circulation are also shown. To investigate the effect of different pumping-activation functions (VAD motion profiles) on the cardiovascular response, three different VAD motion profiles are investigated. The numerical results suggest that Hermitian type motion profiles (smooth curves skewed toward early systole) have the advantage of requiring minimum power to the VAD, and producing the minimum after-load to the left ventricle, minimum ventricular wall stress, and minimum ventricular work to the diseased ventricle; while sawtooth type motions need slightly more power input, and induce slightly increased aortic pressure in diastole, thus improving coronary perfusion.


An Inverse Optimization Method for the Parameter Determination of the High-Temperature Damage Model and High-Temperature Damage Graph of Ti6Al4V Alloy.
Ti6AL4V alloy is widely used in the biomedical and energy vehicle industries, among others. Ti6Al4V alloy cannot be fabricated at ambient temperatures; hence, it requires hot forming. However, this method is susceptible to crack defects. The crack defect problem of Ti6AL4V alloy in the hot-forming process cannot be ignored, so we must develop a precise hot-forming damage prediction model. In this study, three high-temperature damage models of Ti6Al4V alloy were developed, considering the temperature and strain rate. These models were derived from the normalized Cockcroft and Latham (NCL), Oyane, and Rice and Tracey (RT) damage models. The damage parameters of the models were identified using a genetic algorithm combined with finite element simulation. The force accumulation error of the Ti6AL4V alloy specimen, which was obtained from a simulated thermal tensile test and an actual test, was used as an optimization target function. Then, the damage parameters were optimized using the genetic algorithm until the target function reached the minimum value. Finally, the optimal damage model parameter was obtained. Through program development, the three high-temperature damage models established in this paper were embedded into Forge® NxT 2.1 finite element software. The simulated thermal tensile test of Ti6AL4V alloy was performed at a temperature of 800-1000 °C and a strain rate of 0.01-5 s-1. The simulated and actual fracture displacements of the tensile specimens were compared. The correlation coefficients (R) were calculated, which were 0.997, 0.951, and 0.912. Of the high-temperature damage models, the normalized Cockcroft and Latham high-temperature damage model had higher accuracy in predicting crack defects of Ti6Al4V alloy during the hot-forming process. Finally, a fracture strain graph and a high-temperature damage graph of Ti6Al4V alloy were constructed. The Ti6Al4V alloy damage evolution and thermal formability were analyzed in relation to the temperature and strain rate.


The African swine fever epidemic in West Africa, 1996-2002.
African swine fever (ASF) is a contagious, highly fatal, haemorrhagic viral disease that only affects members of the Suidae family. Currently, no vaccine or treatment exists, so the disease has potentially devastating consequences for the pig industries, availability of affordable protein livelihoods and trade. This study aimed to consolidate historical information generated by working towards the control and eradication of ASF in previously unaffected countries in West Africa during 1996-2002. This descriptive analysis entailed the evaluation and review of archived records and reports of outbreaks, data from veterinary services, veterinary consultants and peer-reviewed publications. Specifically, the analysis focused on establishing the sequence of events in the spread of the disease throughout the region, as well as the possible sources and pathways (mostly human-driven, i.e., movement of pigs and swill feeding). The socio-economic aspects of the epidemic were also assessed. Finally, the prevention and control measures applied were described and evaluated. Major challenges for control that were identified involved lack of capacity to respond to an outbreak of animal disease and the nature of the pig sector in the affected countries. Most of the pigs were produced in low biosecurity subsistence husbandry systems. Actions taken by producers to limit economic losses due to the epidemic (e.g., illegal selling of pigs and infected pork, hiding of outbreaks) increased the risk of spread and frustrated control efforts. The disease has persisted in an endemic state ever since and has negatively affected pig production and marketing in most of these countries. The analysis of this information will allow a better understanding of the disease dynamics in a region infected for the first time, and learning how the prevention and control interventions that were implemented worked or failed. This will help the development of better tailored, sustainable and locally sound interventions. The authors provide a set of recommendations for ASF prevention and control.


Predominant Bacterial and Viral Otopathogens Identified Within the Respiratory Tract and Middle Ear of Urban Australian Children Experiencing Otitis Media Are Diversely Distributed.
Otitis media (OM) is one of the most common infections in young children, arising from bacterial and/or viral infection of the middle ear. Globally, Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the predominant bacterial otopathogens. Importantly, common upper respiratory viruses are increasingly recognized contributors to the polymicrobial pathogenesis of OM. This study aimed to identify predominant bacteria and viruses in the nasopharynx, adenoids and middle ears of peri-urban/urban South-East Queensland Australian children, with and without clinical history of chronic otitis media with effusion (COME) and/or recurrent acute otitis media (RAOM). Sixty children, 43 diagnosed with OM and 17 controls with no clinical history of OM from peri-urban/urban South-East Queensland community were recruited to the study. Respiratory tract bacterial and viral presence were examined within nasopharyngeal swabs (NPS), middle ear effusions (MEE) and adenoids, using real-time polymerase chain reaction (RT-PCR) and bacterial culture. At least one otopathogen present was observed in all adenoid samples, 86.1% and 82.4% of NPS for children with and without OM, respectively, and 47.1% of the MEE from the children with OM. NTHi was the most commonly detected bacteria in both the OM and control cohorts within the adenoids (90.0% vs 93.8%), nasopharynx (67.4% vs 58.8%) respectively, and in the MEE (OM cohort 25.9%). Viruses were detected in all adenoid samples, 67.4% vs 47.1% of the NPS from the OM and control cohorts, respectively, and 37% of the MEE. Rhinovirus was the predominant virus identified in the adenoids (85.0% vs 68.8%) and nasopharynx (37.2% vs 41.2%) from the OM and control cohorts, respectively, and the MEE (19.8%). NTHi and rhinovirus are predominant otopathogens within the upper respiratory tract of children with and without OM from peri-urban and urban South-East Queensland, Australia. The presence of bacterial otopathogens within the middle ear is more predictive of concurrent URT infection than was observed for viruses, and the high otopathogen carriage within adenoid tissues confirms the complex polymicrobial environment in children, regardless of OM history.


[Risk of premature rupture of the fetal membranes in cases of fetal maturity].
In this study data of labour, delivery and neonatal outcome were compared in term pregnancies in 100 patients with premature rupture of the membranes (PROM) amniotomy. According to the data in cases of PROM there are more unfavourable cervix findings at the beginning of labour (54%), more pathologic cardiotocograms in the first stage (14% vs. 12%), more prolonged first stages (21.5 vs 14.5 hours) more caesarean section (9% vs 7%) and more newborns were born with a 5 minute Apgar score below 8 than in the control group. Intrauterine infection was detected in 1% of all cases. The authors conclude, that careful monitoring of the fetal state and with no signs of intrauterine infection expectant management of delivery is advisable to improve to improve perinatal mortality and morbidity.


Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.
There are over 50 lysosomal hydrolase deficiencies, many of which cause neurodegeneration, cognitive decline and death. In recent years, a number of broad innovative therapies have been proposed and investigated for lysosomal storage diseases (LSDs), such as enzyme replacement, substrate reduction, pharmacologic chaperones, stem cell transplantation, and various forms of gene therapy. Murine models that accurately reflect the phenotypes observed in human LSDs are critical for the development, assessment and implementation of novel translational therapies. The goal of this review is to summarize the neurodegenerative murine LSD models available that recapitulate human disease, and the pre-clinical studies previously conducted. We also describe some limitations and difficulties in working with mouse models of neurodegenerative LSDs.


Creatine phosphate kinase elevations signaling muscle damage following exposures to anticholinesterases: 2 sentinel patients.
In this study, the authors describe 2 patients who experienced confirmed exposures to anticholinesterases that commenced in the 1970s. Subsequently, elevations in creatine phosphate kinase (CPK) were initially detected more than a decade following the first acute exposure. Beginning in the early 1980s, the patients suffered from progressive generalized muscle weakness, chronic fatigue, myopathy, neuropathy, and severe neurobehavioral impairments. Previous occupational exposures included pyridostigmine, as well as isopropyl methylphosphonofluoridate (percutaneous lethal dose [LD50] < 28 mg/kg body weight), and 1 patient had exposure to agricultural organophosphates. The authors hypothesize that the workers' CPK elevations, first detected more than a decade following acute exposures to anticholinesterases, were sentinel events for impending muscle damage and necrosis. Many Gulf War veterans with Gulf War disease who reported exposures to anticholinesterases 1 decade earlier currently suffer from vague neuromuscular and cognitive impairments. Therefore, medical programs for Gulf War veterans with Gulf War Syndrome should include surveillance for elevated CPK, abnormalities of neuromuscular conduction, and genetic susceptibility, and they should promote therapeutic trials for palliation.


AUD-DSS: a decision support system for early detection of patients with alcohol use disorder.
Alcohol use disorder (AUD) causes significant morbidity, mortality, and injuries. According to reports, approximately 5% of all registered deaths in Denmark could be due to AUD. The problem is compounded by the late identification of patients with AUD, a situation that can cause enormous problems, from psychological to physical to economic problems. Many individuals suffering from AUD never undergo specialist treatment during their addiction due to obstacles such as taboo and the poor performance of current screening tools. Therefore, there is a lack of rapid intervention. This can be mitigated by the early detection of patients with AUD. A clinical decision support system (DSS) powered by machine learning (ML) methods can be used to diagnose patients' AUD status earlier. This study proposes an effective AUD prediction model (AUDPM), which can be used in a DSS. The proposed model consists of four distinct components: (1) imputation to address missing values using the k-nearest neighbours approach, (2) recursive feature elimination with cross validation to select the most relevant subset of features, (3) a hybrid synthetic minority oversampling technique-edited nearest neighbour approach to remove noise and balance the distribution of the training data, and (4) an ML model for the early detection of patients with AUD. Two data sources, including a questionnaire and electronic health records of 2571 patients, were collected from Odense University Hospital in the Region of Southern Denmark for the AUD-Dataset. Then, the AUD-Dataset was used to build ML models. The results of different ML models, such as support vector machine, K-nearest neighbour, decision tree, random forest, and extreme gradient boosting, were compared. Finally, a combination of all these models in an ensemble learning approach was selected for the AUDPM. The results revealed that the proposed ensemble AUDPM outperformed other single models and our previous study results, achieving 0.96, 0.94, 0.95, and 0.97 precision, recall, F1-score, and accuracy, respectively. In addition, we designed and developed an AUD-DSS prototype. It was shown that our proposed AUDPM achieved high classification performance. In addition, we identified clinical factors related to the early detection of patients with AUD. The designed AUD-DSS is intended to be integrated into the existing Danish health care system to provide novel information to clinical staff if a patient shows signs of harmful alcohol use; in other words, it gives staff a good reason for having a conversation with patients for whom a conversation is relevant.


Chondrogenesis in mouse limb buds in vitro: effects of dibutyryl cyclic AMP treatment.
We studied the effects of dibutyryl cyclic AMP (dbcAMP) on mouse limb-bud chondrogenesis at three stages of embryonic development. After 24 h of culture, limb buds with or without a covering of ectoderm were treated with 1 mM dbcAMP for 48 h and were then compared with untreated cultured limb buds. Treatment with dbcAMP enhanced cartilaginous differentiation in organ cultures of stage-17 and -19 (according to Theiler's) limb buds, although the presence of ectoderm reduced the level of dbcAMP stimulation. By stage 20, treatment with dbcAMP irreversibly inhibited cartilaginous differentiation. These results suggest that the responsiveness of mesenchymal limb-bud cells to dbcAMP is stage related. The results of histological studies as well as of analyses of DNA content and sulphated glycosaminoglycan accumulation supported the hypothesis that dbcAMP treatment induces recruitment of initially non-chondrogenic cells whose commitment explains the enhancement of cartilaginous differentiation. Limb-bud competence for chondrogenesis throughout the three developmental stages studied is also discussed.


Detection of HPV16 and 18 by in situ hybridization in precancerous and cancerous lesions of cervix.
Fifty cervical biopsies from women with preinvasive and invasive malignancies of uterine cervix and ten normal cervical biopsies were examined for the presence of human papilloma virus (HPV) 16 and 18 DNA sequences by in situ hybridization (ISH) method with biotinylated DNA probes. The overall positivity of HPV DNA was 48% (24/50). The positivity of HPV 16 DNA for low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) were 33.33%, 45.45%, 42.30% respectively. The positivity for HPV 18 DNA for LSIL, HSIL and SCC were 0%, 18.18%, 30.76% respectively. Two cases of cervical adenocarcinomas showed positivity for HPV 18 DNA only.


Activation of alpha 2-adrenergic receptors decreases Ca2+ influx to inhibit insulin secretion in a hamster beta-cell line: an action mediated by a guanosine triphosphate-binding protein.
Activation of the sympathetic nervous system inhibits insulin secretion. We tested the hypothesis that activation of alpha 2-adrenergic receptors on the beta-cell by epinephrine or clonidine attenuates insulin release by an effect on the voltage-dependent Ca2+ channel (VDCC) and examined the role of G-proteins in this signal transduction pathway. Using a cultured SV40-transformed hamster beta-cell line (HIT cells) as a model system, we determined the effect of alpha 2-adrenergic agonists on insulin secretion, 86Rb+ efflux (a marker for K+ channel flux), and the free cytosolic Ca2+ level [( Ca2+]i) monitored in fura-2-loaded cells. In a dose-dependent manner, epinephrine and clonidine (10(-8)-10(-5)M) attenuated the increase in [Ca2+]i and insulin secretion induced by either K+ depolarization or stimulation of the VDCC with the agonist Bay K 8644. Epinephrine failed to affect the rise in [Ca2+]i induced by carbamylcholine, an agent that mobilizes intracellular Ca2+. Epinephrine also did not changes 86Rb+ efflux from HIT cells. The inhibitory effects of epinephrine were prevented by the alpha 2-adrenergic antagonist idazoxan, but were unaffected by the alpha 1-adrenergic antagonist phenoxybenzamine. Pretreatment of HIT cells with pertussis toxin (0.1 micrograms/ml) overnight abolished the inhibitory effects of epinephrine and clonidine on both [Ca2+]i and insulin secretion. These data suggest that one mechanism by which alpha 2-adrenergic agonists inhibit insulin secretion is by inhibiting Ca2+ influx through VDCC, an action that is mediated through a pertussis toxin-sensitive G-protein.


Polymorphisms in the promoter regions of FAS and FASL genes as candidate genetic factors conferring susceptibility to endometriosis.
Although the pathophysiological mechanisms leading to endometriosis remain unknown, several hypothesis have been proposed, including a dysregulation of the normal apoptotic process which takes place in the endometrium. One of the apoptotic pathways playing a crucial role in the programmed cell death within the endometrium is the Fas-FasL system. In this study we have performed a case-control analysis in order to evaluate three polymorphisms located within FAS (-1377G>A and -670A>G) and FASL (-843C>T) genes, as susceptibility factors for endometriosis. We have analysed a series of women with endometriosis compared respectively to a group of women without symptoms of the disease, and to a group of confirmed unaffected women. The genotyping of the three variants was carried out by Fluorescence Resonance Energy Transfer (FRET) technology, and statistical analysis was performed using chi2 test with Yates correction. Our results show that the differences in the distribution of the polymorphic variants were not statistically significant when the group of patients was compared to the other groups. Thus, it seems to indicate that the variants here analysed are not involved in the pathogenesis of the disease in our population. However this does not let us to completely exclude such genes as potential candidates for the disease. A complete genetic analysis of the genes involved in the intricate regulatory system of the apoptosis may lead to the identification of susceptibility factors for the disease and a better understanding of its etiology.


Computational Analysis of Vibrational Sum Frequency Generation Spectroscopy.
Vibrational sum frequency generation (VSFG) spectroscopy is a widely used probe of interfaces and, having ideal surface sensitivity and selectivity, is particularly powerful when applied to wet and soft interfaces. Although VSFG spectroscopy can sensitively detect molecular details of interfaces, interpretation of observed spectra has, until recently, been challenging and often ambiguous. The situation has been greatly improved by remarkable advances in computational VSFG analysis on the basis of molecular modeling and molecular dynamics simulation. This article reviews the basic idea of computational VSFG analysis and recent applications to both aqueous and organic interfaces.


A proposed biparticle fluidized-bed for lactic acid fermentation and simultaneous adsorption.
A bioreactor configuration is proposed for simultaneous fermentation and separation of the desired product. The bioreactor consists of a columnar fluidized bed of immobilized microorganisms. Denser adsorbent particles are added to this column. These adsorbent particles fall through the bed, absorb the product, and are removed from the base of the columnar reactor. The system hydrodynamics and the separability of the two types of particles were confirmed for low-density gel beads. The addition of the adsorbent, activated carbon, to a fermentation of Lactobacillus delbreuckii absorbed lactic acid. The addition of adsorbent enhanced the fermentation and controlled the pH.


Assessment of Density Functional Approximations for Highly Correlated Oxides: The Case of CeO2 and Ce2O3.
CeO2 based materials are very attractive as catalytic components for industrial processes and environmentally friendly technologies; therefore, a reliable and computationally affordable theoretical description of the main properties of ceria is needed. In particular, the description of the interconversion between the Ce(IV) and Ce(III) oxidation states, on which lies the main chemical features of the cerium oxide, results in quite a challenge at the Density Functional Theory level. Here, we tested several density functional approximations, spanning from GGA to hybrid (Global, Meta-Global, and Range Separated Corrected) functionals, on the structural, vibrational, electronic, and thermochemical properties of bulk CeO2 and Ce2O3. GGA and Meta-GGA xc best predict the thermochemical data, while the discrepancies increase with the introduction of the exact exchange in hybrid functionals. Overall, the Short Range Corrected and Global Hybrid functionals with a percentage of Exact Exchange between 16 and 25 give the best description of the crystal properties. Then, a group of the best performing functionals has been tested on the formation energy of an oxygen vacancy at the (111) CeO2 surface. In general, increasing the amount of exact exchange in the hybrid functionals leads to a better description of the localized Ce 4 f states, while the energy of formation of the O vacancy decreases, worsening compared to the experiment.


Teleconsultation at a tertiary care government medical university during COVID-19 Lockdown in India - A pilot study.
COVID-19 related pan- India lockdown brought teleophthalmology to the forefront. The study ventures to understand the relevance of this modality in a government setup. The objective is to understand the feasibility, clinical profile and addressability of patients using teleconsultation in ophthalmology at a tertiary care government medical university during the COVID-19 Lockdown in India. An online survey targeting faculty members and resident doctors in a tertiary eye center in a government medical university in north India was conducted. Various aspects of teleconsultation were analyzed including the number and preferential mode of consultations, commonest complaints and diagnoses made. Frequency and factors mandating physical examination of patients was also analyzed. The questionnaire was sent to 40 ophthalmologists of whom 38 responded. A total of 4880 teleconsultations were given. The commonest mode of communication was by WhatsApp messages (65.6%) and E-mail was the least preferred medium. More than 80% consultations were from previously seen patients. Red eye was the commonest presenting complaint (22.8%), followed by watering (18.7%) and foreign body sensation (14.5%). Computer vision syndrome was the commonest diagnosis (25.9%) followed by conjunctivitis (17.7%) and refractive error (17.7%). About 40% required physical examination, mostly due to uncertain diagnosis (22%) or inadequate response to prescribed treatment (19%). Teleconsultation was feasible in a government medical university for providing ophthalmic services during lockdown. WhatsApp was the preferred communication modality, computer vision syndrome was the most frequent tentative diagnosis and approximately 60% did not require in-person physical examination.


Effect of original water content in acrylic resin on processing shrinkage.
The aim of this study was to determine the original water content of a supplied acrylic resin powder and a monomer and of dry heat-processed acrylic bars. The effect of the original water content of acrylic resin on processing shrinkage was also investigated. Ten bar specimens were fabricated using dried and as-supplied (control) acrylic resins. The resins were polymerized and cooled, then weighed and measured to determine the amount of shrinkage. The initial water content of the specimens was determined by thorough drying, and results were compared with the Student ttest. The initial water content and processing shrinkage of the dried acrylic resin bars were both significantly lower (P < .0001) than those of the as-supplied acrylic resin bars. The processing shrinkage of acrylic resin made from dried constituents was significantly less than that of resin made from products as supplied by the manufacturer. However, it is not known if this change is of clinical significance.


Neuroleptic malignant syndrome in pregnancy: case report and literature review.
Neuroleptic malignant syndrome (NMS) is a serious complication associated with the use of drugs that affect dopaminergic system neurotransmission. The occurrence of NMS during pregnancy or gestation is considered a life-threatening obstetric emergency. We are reporting the first case in Latin America of NMS in one pregnant women with acute psychotic episode. One day after starting with antipsychotic therapy, she developed a fever higher than 39.0 °C with tachycardia, tachypnea, generalized muscle rigidity and somnolence, with creatine kinase (CPK) levels evidencing a result of 2800 U/L. She was treated successfully with levetiracetam, biperiden and quetiapine. A search in PubMed, Embase and Ovid from 1988 to 2016 resulted in seven cases reported in either pregnant or puerperal women. In general, NMS resolves within 3-14 days; most NMS cases reported during pregnancy have involved the use of haloperidol (5 case reports) which is concordant with this report. The obstetric results were good in cases reported, only two women showed signs, among them: hyperemesis gravidarum and preterm delivery. Most of the pregnant women who had NMS presented other associated comorbidities, being mostly of infectious origin. In other investigations, it has been affirmed that NMS can become lethal in adults; however, in our search for pregnant women with this disease, no associated mortality was found. NMS is seen infrequently during pregnancy. The clinical diagnosis requires high suspicion by the examiner. It is important that obstetricians timely recognize the condition.


Filter-based ultralow-frequency Raman measurement down to 2 cm-1 for fast Brillouin spectroscopy measurement.
Simultaneous Stokes and anti-Stokes ultralow-frequency (ULF) Raman measurement down to ∼2 cm-1 or 60 GHz is realized by a single-stage spectrometer in combination with volume-Bragg-grating-based notch filters. This system reveals its excellent performance by probing Brillouin signal of acoustic phonons in silicon, germanium, gallium arsenide, and gallium nitride. The deduced sound velocity and elastic constants are in good accordance with previous results determined by various methods. This system can shorten the integration time of the Brillouin signal with a good signal-to-noise ratio by more than 2000-fold compared to a Fabry-Perot interferometer (FPI). This study shows how a filter-based ULF Raman system can be used to reliably achieve Brillouin spectroscopy for condensed materials with high sensitivity and high signal-to-noise ratio, stimulating fast Brillouin spectrum measurements to probe acoustic phonons in semiconductors.


Presenting signs of retinoblastoma.
A retrospective chart review was performed on the charts of 1265 patients with retinoblastoma who were on file at New York Hospital and whose conditions had been diagnosed between the years 1960 and 1990. The mean follow-up was 90 months, ranging from 0 to 409 months. Thirty-two distinct presenting signs of retinoblastoma were identified, the most common of which were leukocoria (56.2%), strabismus (23.6%), poor vision (7.7%), and family history (6.8%). No correlation was found between any of the presenting signs and laterality, sex, race, or survival. Leukocoria correlated to Reese-Ellsworth Group Va or Vb, whereas strabismus was invariably associated with either macular tumors or macular retinal detachments. Eighty-three (96.5%) patients presenting with a family history did so before the age of 24 months. The presenting sign leading to a diagnosis of retinoblastoma was correlated with degree of advancement and tumor location. Leukocoria and strabismus are the most common presenting signs, with leukocoria correlated to more advanced disease and strabismus always associated with macular involvement. Vitreous hemorrhage (1 case, 0.1%), microphthalmos (4 cases, 0.3%), and orbital cellulitis (3 cases, 0.2%) are extremely rare presenting findings in retinoblastoma.


Motion analysis study of a scapular orientation exercise and subjects' ability to learn the exercise.
Exercises to retrain the orientation of the scapula are often used by physiotherapists to optimise shoulder girdle function. The movements and muscle activity required to assume this position have not yet been quantified. Further, patients often find this a difficult exercise to learn accurately, with no data being available on the accuracy of repeated performance. The primary objective of this study was to quantify the movements occurring during a commonly used scapular orientation exercise. The secondary objective was to describe the ability of subjects to learn this position after a brief period of instruction. A group of normal subjects (13 subjects; mean age 32, SD=9) were taught the scapular orientation exercise. Measurement of the position and muscle actions were made with a motion analysis system and surface electromyography. Further comparison was made of the accuracy of repeated trials. The most consistent movements were upward (mean=4 degrees, SEM=0.9 degrees) and posterior rotation (mean=4 degrees, SEM=1.6 degrees). All parts of the trapezius muscle demonstrated significant activity in maintaining the position while latissimus dorsi did not. Repeated trials showed that subjects were able to accurately repeat the movement without guidance. The key movements of, and immediate efficacy of a teaching approach for, scapular orientation have been established.


Mechanisms counteracting swelling in brain cells during hyponatremia.
Water gain in the brain consequent to hyponatremia is counteracted by mechanisms that initially include a compensatory displacement of liquid from the interstitial space to cerebrospinal fluid and systemic circulation and subsequently an active reduction in cell water accomplished by extrusion of intracellular osmolytes to reach osmotic equilibrium. Potassium (K+), chloride (Cl-), amino acids, polyalcohols, and methylamines all contribute to volume regulation, with a major contribution of ions at the early phase and of organic osmolytes at the late phase of the regulatory process. Experimental models in vitro show that osmolyte fluxes occur via leak pathways for organic osmolytes and separate channels for Cl- and K+. Osmotransduction signaling cascades for Cl- and taurine efflux pathways involve tyrosine kinases and phosphoinositide kinases, while Ca2+ and serine-threonine kinases modulate K+ pathways. In-depth knowledge of the cellular and molecular adaptive mechanisms of brain cells during hyponatremia contributes to a better understanding of the associated complications, including the risks of inappropriate correction of the hyponatremic condition.