Ethical issues in haemophilia.
Ethical issues surrounding both the lack of global access to care as well as the implementation of advancing technologies, continue to challenge the international haemophilia community. Haemophilia is not given the priority it deserves in most developing countries. Given the heavy burdens of sickness and disease and severe resource constraints, it may not be possible to provide effective treatment to all who suffer from the various 'orphan' diseases. Nevertheless, through joint efforts, some package of effective interventions can be deployed for a significant number of those who are afflicted with 'orphan' diseases. With cost-effective utilization of limited resources, a national standard of care is possible and affordable. Gene-based diagnosis carries attendant ethical concerns whether for clinical testing or for research purposes, even as the list of its potential benefits to the haemophilia community grows rapidly. As large-scale genetic sequencing becomes quicker and cheaper, moving from the research to the clinic, we will face decisions about the implementation of prenatal, neonatal and other screening programs. Such debates will require input from not just the health care professionals but from all stakeholders in the haemophilia community. Finally, long-term therapeutic success gene transfer in small and large animal models raises the question of when and in which patient population the novel therapeutic approach should first be studied in humans with haemophilia. Although gene therapy represents a worthy goal, the central question for the haemophilia community should be whether it wishes to volunteer itself as a model for a much broader set of innovations.


Linking functional connectome gradient to individual creativity.
Human brain network is organized as a hierarchical organization, exhibiting various connectome gradients. The principal gradient is anchored by the modality-specific primary areas and the transmodal regions. Previous studies have suggested that the unimodal-transmodal gradient in the functional connectome may offer an overarching framework for high-order cognitions of human brain. However, there is still a lacking of direct evidence to associate these two. Therefore, we aim to explore the association between creativity, a typical human high-order cognitive function, and unimodal-transmodal gradient, using two independent datasets of young adults. For each individual, we identified the unimodal-transmodal gradient in functional connectome and calculated its global measures. Then we correlated the individual creativity score with measures of unimodal-transmodal gradient at global-brain, subsystem, and regional level. The results suggested that better creative performance was associated with greater distance between primary areas and transmodal regions in gradient axes, and less distance between ventral attention network and default mode network. Individual creativity was also found positively correlated with regional gradients in ventral attention network, and negatively correlated with gradients of regions in visual cortex. Together, these findings directly link the unimodal-transmodal gradient to individual creativity, providing empirical evidence for the cognitive implications of functional connectome gradient.


Expression and differential glycosylation of human sex hormone-binding globulin by mammalian cell lines.
The human sex hormone-binding globulin (SHBG) gene is responsible for the production of plasma SHBG by the liver and androgen-binding protein in the testis. Cell-specific glycosylation events during synthesis may account for minor differences in the biochemical properties of SHBG and androgen-binding protein, and we have, therefore, expressed a human SHBG cDNA in chinese hamster ovary (CHO) cells and a mouse hepatoma cell line (BW-1), and compared the products to SHBG in serum. The SHBG produced in this way is a homodimer of subunits that exhibit size microheterogeneity similar to SHBG in human serum, and its affinity for 5 alpha-dihydrotestosterone (Kd = 0.6 nM) and other steroids is essentially identical to that of natural SHBG. When medium from transfected CHO and BW-1 cells was subjected to Concanavalin-A (Con-A) chromatography, the relative amounts of SHBG retained by Con-A were 74% and 86%, respectively. In addition, when SHBG produced by CHO cells was separated into two fractions by Con-A chromatography and analyzed by polyacrylamide gel electrophoresis, SHBG that did not interact with Con-A migrated with a slightly larger apparent mol wt than that of SHBG that binds Con-A; this can be explained by the presence of triantennary, rather than biantennary, N-linked oligosaccharide chains. These data also demonstrate that the subunit microheterogeneity associated with plasma SHBG reflects differences in glycosylation during synthesis, which appear to be cell type specific.


Silicon promotes adventitious shoot regeneration and enhances salinity tolerance of Ajuga multiflora bunge by altering activity of antioxidant enzyme.
We investigated the effect of Si concentration on shoot regeneration and salinity tolerance of Ajuga multiflora. Addition of Si to the shoot induction medium significantly increased the frequency of shoot induction. The average number of shoots regenerated per explant decreased on the medium containing NaCl alone, while there was less decrease when the shoot induction medium was supplemented with both NaCl and Si. The shoot induction percentage increased linearly with increasing concentration of Si in the NaCl containing medium. Addition of Si to the shoot induction medium significantly increased SOD, POD, APX, and CAT activity in regenerated shoot buds as compared with the control. The inclusion of Si to the NaCl containing medium significantly increased the SOD activity in leaves and roots, while it decreased POD, APX, and CAT activity in both organs. Scanning electron microscopic analysis showed that there are no distinct differences in the structure of stomata between the control and Si-treated plants. However, NaCl treatment significantly affected the structure and number of stomata as compared to the control. Wavelength dispersive X-ray analysis confirmed the high Si deposition in trichomes of plants grown in the Si containing medium but not in plants grown in the medium without Si.


Attention Deficit Hyperactivity Disorder Symptoms and Low Educational Achievement: Evidence Supporting A Causal Hypothesis.
Attention Deficit Hyperactivity Disorder (ADHD) and educational achievement are negatively associated in children. Here we test the hypothesis that there is a direct causal effect of ADHD on educational achievement. The causal effect is tested in a genetically sensitive design to exclude the possibility of confounding by a third factor (e.g. genetic pleiotropy) and by comparing educational achievement and secondary school career in children with ADHD who take or do not take methylphenidate. Data on ADHD symptoms, educational achievement and methylphenidate usage were available in a primary school sample of ~10,000 12-year-old twins from the Netherlands Twin Register. A substantial group also had longitudinal data at ages 7-12 years. ADHD symptoms were cross-sectionally and longitudinally, associated with lower educational achievement at age 12. More ADHD symptoms predicted a lower-level future secondary school career at age 14-16. In both the cross-sectional and longitudinal analyses, testing the direct causal effect of ADHD on educational achievement, while controlling for genetic and environmental factors, revealed an association between ADHD symptoms and educational achievement independent of genetic and environmental pleiotropy. These findings were confirmed in MZ twin intra-pair differences models, twins with more ADHD symptoms scored lower on educational achievement than their co-twins. Furthermore, children with ADHD medication, scored significantly higher on the educational achievement test than children with ADHD who did not use medication. Taken together, the results are consistent with a direct causal effect of ADHD on educational achievement.


General anesthesia for treating scoliosis with congenital myasthenia syndrome: a case report.
Congenital myasthenia syndrome is a heterogeneous disease with impaired neuromuscular transmission. This report describes a 13-year-old child with congenital myasthenia syndrome who underwent surgery for scoliosis under general anesthesia. We used a small dose of rocuronium, neuromuscular transmission monitoring, and non-invasive positive pressure ventilation for postoperative respiratory management. There were no respiratory complications during the perioperative period. As there are only a few reports on the anesthetic management of patients with congenital myasthenia syndrome, we applied the principles of managing autoimmune myasthenia gravis. The postoperative management described herein can prevent respiratory complications in patients with congenital myasthenia syndrome.


[A case report of huge abdominal recurrent tumor of small intestinal GIST after 15 years from the operation with primary lesion].
A man in his 60s was given an emergency operation 15 years ago for abdominal bleeding. His tumor of small intestine was resected and diagnosed as small intestinal leiomyosarcoma. He came to our hospital because of his abdominal masses 15 years after the initial operation. CT scan showed a 15 cm-sized solid and cystic tumor in the pelvic cavity. The tumor was diagnosed as GIST by PET-CT and MRI. The tumor was resected, and pathological findings led to the diagnosis of GIST with this tumor. Previous tumor cells were slightly-positive for kit immunohistological examination, but did not resemble this tumor cells morphologically. So genetic tests were performed and revealed two tumors had same mutations of c- kit. Finally, we could diagnose the tumor was recurrent metastases of small intestinal GIST 15 years after the initial surgery. kit mutation analysis was useful for a diagnosis of recurrences and predictions of the clinical response to imatinib in GISTs.


Isolation of separate mRNAs for alpha- and beta-tubulin and characterization of the corresponding in vitro translation products.
The messenger RNAs coding for alpha- and beta-tubulin have been isolated from embryonic chick brain. Although the mRNAs for the two tubulin subunits have been resolved on native gels, they are very similar in molecular weight (650,000 daltons) as judged by mobility on denaturing gels containing methy mercury. The mRNAs for beta- and gamma-actin have also been resolved on native gels, but migrate as an unresolved peak (molecular weight 6500,000-700,000 daltons) under denaturing conditions. Since the nonmuscle actins are substantially smaller proteins than alpha- and beta-tubulin, the large size of chick nonmuscle actin mRNAs suggests an unusually long untranslated region. Since tubulin and actin polypeptides are internal structural proteins, one would expect them to be synthesized only on free polysomes. Translation of mRNA derived directly from a purified membrane fraction or by puromycin release from that fraction, however, showed the synthesis of a small proportion of these proteins on polysomes that are membrane-associated. Peptide mapping has in all cases confirmed the identity of the products of cell-free synthesis with authentic alpha-tubulin, beta-tubulin and actin. Approximately 67% of the alpha- and 13% of the beta-tubulin chains produced by in vitro translation are competent for co-assembly into microtubules with added carrier microtubule protein.


Aerobic Plate Counts of 100-ml Samples in Plastic Bags 1.
Counts from samples that contained low numbers of bacteria were determined by mixing the samples with double-strength agar media in 42-oz (1.2-L) Whirl-Pak bags. The bag-plate method was compared with other direct-plating methods and the most-probable-number and membrane-filtration procedures. Results obtained by using the bag method were as reliable as methods commonly used for analysis of samples that contain low numbers of viable bacteria.


[Geographical differences in the mortality of the elderly in Finland since the 1850s].
Mortality data for the elderly in Finland are compared for geographical differences between the east and the west. The author utilizes simulated data from 1853 to 1878 to evaluate mortality in the past and compare it to the present, which indicates high levels of male mortality from heart disease in eastern Finland. "The historical evidence is compatible with the view that the causes of the high premature mortality in Finland are to be found in diet and smoking and perhaps also in genetics." (SUMMARY IN ENG)


Perceived exposure to substance use and risk-taking behavior in early adolescence: cross-sectional study.
To examine the relation between perceived exposure to parents, siblings, and peers' substance use and self-reported substance consumption among early adolescents in Primorsko-goranska county, Croatia, and between perceived exposure to substance use and risk-taking behaviors such as going out late at night, gathering at secluded places, skipping school, and gambling. A self-reported cross-sectional survey was conducted in 2007 among 2219 eight-grade (14-year old) pupils in elementary schools in Primorsko-goranska county. Exposure to substance use in their immediate social environment, self-reported consumption of cigarettes, alcohol, inhalants, and marihuana, ways of spending free time, and family and peer relationships were assessed. There was a significant association between perceived exposure to substance use and self-reported consumption of cigarettes, alcohol, inhalants, and marihuana in both sexes (P < 0.001). Pupils whose parents, siblings, and peers used substances significantly more often developed the same behavioral patterns. Level of exposure to substance use in the immediate social environment had the strongest effect on experimenting with smoking among girls (from 26.6% in low exposure to 76.2% in high exposure group) and among boys (from 15.8% in low exposure to 69.4% in high exposure); on regular everyday smoking among girls (from 4.4% in low exposure to 45% in high exposure group) and among boys (from 2.7% in low exposure to 36.7% in high exposure group); on hard liquor consumption among girls (from 25.1% in low exposure to 79.5% in high exposure group) and among boys (from 28.1% in low exposure to 78.4% in high exposure group), as well as on binge drinking among girls (from 10.9% in low exposure to 56.6% in high exposure group) and among boys (from 15.5% in low exposure to 62.4% in high exposure group). Girls and boys exposed to substance use engaged more often in risk-taking and potentially delinquent behaviors (F(2, 1180) = 166 502; P < 0.001, two-way ANOVA). High exposure to substance use in immediate social environment and its great impact on substance use among early adolescents indicate that there is a need for the introduction of preventive programs that would reduce inappropriate behavior among adolescents' social models.


Glucocorticoid signaling in the arcuate nucleus modulates hepatic insulin sensitivity.
Glucocorticoid receptors are highly expressed in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC). As glucocorticoids have pronounced effects on neuropeptide Y (NPY) expression and as NPY neurons projecting from the ARC to the PVN are pivotal for balancing feeding behavior and glucose metabolism, we investigated the effect of glucocorticoid signaling in these areas on endogenous glucose production (EGP) and insulin sensitivity by local retrodialysis of the glucocorticoid receptor agonist dexamethasone into the ARC or the PVN, in combination with isotope dilution and hyperinsulinemic-euglycemic clamp techniques. Retrodialysis of dexamethasone for 90 min into the ARC or the PVN did not have significant effects on basal plasma glucose concentration. During the hyperinsulinemic-euglycemic clamp, retrodialysis of dexamethasone into the ARC largely prevented the suppressive effect of hyperinsulinemia on EGP. Antagonizing the NPY1 receptors by intracerebroventricular infusion of its antagonist largely blocked the hepatic insulin resistance induced by dexamethasone in the ARC. The dexamethasone-ARC-induced inhibition of hepatic insulin sensitivity was also prevented by hepatic sympathetic denervation. These data suggest that glucocorticoid signaling specifically in the ARC neurons modulates hepatic insulin responsiveness via NPY and the sympathetic system, which may add to our understanding of the metabolic impact of clinical conditions associated with hypercortisolism.


Effect of the insect phenoloxidase on the metabolism of l-DOPA.
Insect prophenoloxidase (PPO) induces melanization around pathogens. Before melanization, PPO is cleaved into phenoloxidase (PO) by serine proteases. Insect PPO can also be activated by exogenous proteases secreted by pathogens as well as by other compounds, such as ethanol and cetylpyridinium chloride (CPC). However, the effect of these activators on the activity of PO is unclear. In this study, the insect endogenous serine protease AMM1, α-chymotrypsin, and ethanol were used to activate recombinant Drosophila PPO1 (rPPO1), and the PO activity differed depending on the activator applied. The PO-induced intermediates during melanization also varied markedly in their numbers and abundances. Therefore, this study indicates that the mechanism of PPO activation influences PO activity. It also suggests that PO-induced different intermediates may affect the antibacterial activity during melanization due to their toxicity.


The PI3K/AKT/mTOR signaling pathway is overactivated in primary aldosteronism.
To date, the available non-invasive remedies for primary aldosteronism are not satisfactory in clinical practice. The phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway is essential for tumorigenesis and metastasis in many types of human tumors, including renal cancer, adrenal carcinoma and pheochromocytoma. The possibility that this pathway is also necessary for the pathogenesis of primary aldosteronism has not yet been explored. To answer this question, we investigated the activity of the PI3K/AKT/mTOR signaling pathway in normal adrenal glands (NAGs), primary aldosteronism (PA) patients and NCI-H295R cells. Between January 2005 and December 2011, we retrospectively reviewed the records of 45 patients with PA. We compared clinical characteristics (age, gender and biochemical data) and the expression of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), phospho-S6 (p-S6) and vascular endothelial growth factor (VEGF) by immunohistochemical staining and western blotting, analyzing 30 aldosterone-producing adenomas (APAs), 15 idiopathic hyperaldosteronism (IHA) tissues and 12 NAGs following nephrectomy for renal tumors (control group). Compared with the control group, most of the PA patients presented with polydipsia, polyuria, resistant hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. Compared with normal zona glomerulosa, the levels of p-AKT, p-mTOR, p-S6 and VEGF were significantly upregulated in APA and IHA. No significant differences were found between APA and IHA in the expression of these proteins. Additionally, positive correlations existed between the plasma aldosterone levels and the expression of p-AKT and p-mTOR. In vitro studies showed that mTOR inhibitor rapamycin could inhibit cell proliferation in NCI-H295R cells in a dose- and time-dependent manner. Furthermore, this inhibitor also decreased aldosterone secretion. Our data suggest that the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA.


Evaluation of Strip Meniscometry and Association with Clinical and Demographic Variables in a Community Eye Study (in Bangladesh).
Strip meniscometry (SM) is a relatively new technique for evaluating inferior tear meniscus. We described SM in an epidemiology study and its potential associations with clinical and tear parameters. This cross-sectional study involved 1050 factory garment workers in Gazipur, Bangladesh. The Ocular Surface Disease Index (OSDI) questionnaire and a standard examination for dry eye and meibomian gland dysfunction (MGD), including the five-second SM, were performed by a single ophthalmologist. The participants' ages were 35.56 ± 12.12 years (range 18-59), with 53.8% women. The overall SM was 7.7 ± 3.6 mm, with skewness of 0.126 and kurtosis of 1.84 in frequency distribution. SM values were significantly lower in men than women, and significantly correlated with schirmers (r = 0.71) and tear break up time (TBUT) (r = 0.89). A lower SM value was associated with higher OSDI, lower Schirmer test, increased MG severity and lower TBUT. In multivariable analysis, when adjusted by age, SM values remained associated with schirmers and TBUT, and inversely associated with OSDI. In a separate regression model, higher SM was associated with increasing age, reduced severity of MGD grading, and increased TBUT. To conclude, SM is a rapid clinical test associated with dry eye symptoms and signs, with findings affected by both tear secretion and tear stability.


[Role of antiarrhythmics in the treatment of paroxysmal atrial fibrillation].
Atrial fibrillation is not a homogenous entity. Numerous parameters affect its cause, its continuation, and the arrest of an attack. The presence or absence of cardiopathy and left ventricular dysfunction play a major role via the electrophysiological and haemodynamic consequences and the repercussions on the state of the autonomic nervous system, and finally on the effect of anti-arrhythmics themselves. This shows the importance of taking into account all of these parameters together in order to adapt the therapeutic approach. Equally, this underlines the difficulty in interpreting clinical studies comparing pharmacological treatments when the populations treated are poorly defined or very heterogenous. Most often, one drug is not more or less effective than another, it is more or less suited to the patients treated. The frequency of recurrences of AF despite anti-arrhythmic treatment (on average 50% to 60% at one year) means that in paroxysmal AF the goal of anti-arrhythmic treatment is relatively modest: essentially reducing the frequency, duration and severity of AF attacks, allowing an improvement in the quality of life. The consequences in daily practice are clear: one must ensure good patient compliance and minimise the risks of treatment: side effects of and pro-arrhythmic effects of anti-arrhythmics.


Enhanced Transrectal Ultrasound, Real-Time Sonoelastography, and Contrast-Enhanced Transrectal Ultrasound in Heavily Prescreened Chinese Men With Naive and Repetitive Biopsy: A Comparison of Detection Rate of Prostate Cancer Per Man and Per Lesion.
Multiparametric magnetic resonance imaging and targeted biopsy have been widely accepted as the most accurate technique to detect localize prostate cancer. It is a time-consuming and expensive option and may not be widely available in China, making ultrasound the first choice for the detection of prostate cancer. In this current retrospective study, the diagnostic values of enhanced transrectal ultrasound, contrast-enhanced transrectal ultrasound, and real-time sonoelastography were evaluated. Symptomatic 315 men older than 40 years with prostate-specific antigen level greater than 4.0 ng/mL, with abnormal digital rectal examinations, and with suspicious lesions for prostate cancer under enhanced transrectal ultrasound included in the study. Enhanced transrectal ultrasound was suspicious in all 315 men, with 189 of 315 men with prostate cancer according to the prostate biopsy report. Sonoelastography was suspicious in 294 of 315 men, with 166 of 315 men with prostate cancer according to the prostate biopsy report. Contrast-enhanced transrectal ultrasound was suspicious in 221 of 315 men, with 159 of 315 men with prostate cancer according to the prostate biopsy report. Real-time sonoelastography alone and contrast-enhanced transrectal ultrasound alone were missed in 27 (11%) and 39 (15%) lesions to report cancer through biopsies. Working area for enhanced transrectal ultrasound, real-time sonoelastography, and contrast-enhanced transrectal ultrasound for detection of prostate cancer were 0 to 1 diagnostic confidence, 0.11 to 0.895 diagnostic confidence, and 0.39 to 0.63 diagnostic confidence respectively. Real-time sonoelastography and contrast-enhanced transrectal ultrasound may improve the detection of prostate cancer in men with suspicious prostate lesions under enhanced transrectal ultrasound (Level of Evidence: III; Technical Efficacy Stage: 2).


Robin sequence with facial and digital anomalies in two half-brothers by the same mother.
Two half-brothers by the same mother presented with the Robin sequence and facial and digital anomalies. The mother has a normal face and mild hyperopia without abnormality on radiographs of the hands, feet, and pelvis. The older son is 4 years and the younger is 6 months old. Both have normal psychomotor development. To the best of our knowledge this familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome. The occurrence of the syndrome in 2 half-brothers by the same unaffected mother suggests X-linked recessive inheritance.


Depression and post-traumatic stress disorder among Haitian immigrant students: implications for access to mental health services and educational programming.
Previous studies of Haitian immigrant and refugee youth have emphasized "externalizing" behaviors, such as substance use, high risk sexual behavior, and delinquency, with very little information available on "internalizing" symptoms, such as depression and anxiety. Analyzing stressors and "internalizing" symptoms offers a more balanced picture of the type of social and mental health services that may be needed for this population. The present study aims to: 1) estimate the prevalence of depression and post-traumatic stress disorder (PTSD) among Haitian immigrant students; and 2) examine factors associated with depression and PTSD to identify potential areas of intervention that may enhance psychosocial health outcomes among immigrant youth from Haiti in the U.S. A stratified random sample of Haitian immigrant students enrolled in Boston public high schools was selected for participation; 84% agreed to be interviewed with a standardized questionnaire. Diagnosis of depression and PTSD was ascertained using the best estimate diagnosis method. The prevalence estimates of depression and PTSD were 14.0% and 11.6%; 7.9% suffered from comorbid PTSD and depression. Multivariate logistic regression demonstrated factors most strongly associated with depression (history of father's death, self-report of schoolwork not going well, not spending time with friends) and PTSD (concern for physical safety, having many arguments with parents, history of physical abuse, and lack of safety of neighborhood). A significant level of depression and PTSD was observed. Stressors subsequent to immigration, such as living in an unsafe neighborhood and concern for physical safety, were associated with an increased risk of PTSD and should be considered when developing programs to assist this population. Reducing exposure to these stressors and enhancing access to social support and appropriate school-based and mental health services may improve educational attainment and psychosocial health outcomes among Haitian immigrant youth.


Structural studies of the cell wall polysaccharide from Lactococcus lactis UC509.9.
Lactococcus lactis is the most widely utilised starter bacterial species in dairy fermentations. The L. lactis cell envelope contains polysaccharides, which, among other known functions, serve as bacteriophage receptors. Our previous studies have highlighted the structural diversity of these so-called cell wall polysaccharides (CWPSs) among L. lactis strains that could account for the narrow host range of most lactococcal bacteriophages. In the present work, we studied the CWPS of L. lactis strain UC509.9, an Irish dairy starter strain that is host to the temperate and well-characterized P335-type phage Tuc2009. The UC509.9 CWPS structure was analyzed by methylation, deacetylation/deamination, Smith degradation and 2D NMR spectroscopy. The CWPS consists of a linear backbone composed of a tetrasaccharide repeat unit, partially substituted with a branched phosphorylated oligosaccharide having a common trisaccharide and three non-stoichiometric substitutions.


Acute Acquired Concomitant Esotropia From Excessive Application of Near Vision During the COVID-19 Lockdown.
The public health measures imposed in many countries to slow the spread of the novel coronavirus (COVID-19) outbreak could have negative effects on children's physical and mental health. The authors describe four cases of acquired concomitant acute esotropia likely caused from excessive application of near vision during the COVID-19 lockdown. [J Pediatr Ophthalmol Strabismus. 2020;57:e88-e91.].


Position measurement/tracking comparison of the instrumentation in a droplet-actuated-robotic platform.
This paper reports our work on developing a surface tension actuated micro-robotic platform supported by three bubbles (liquid environment) or droplets (gaseous environment). The actuation principle relies on the force developed by surface tension below a millimeter, which benefits from scaling laws, and is used to actuate this new type of compliant robot. By separately controlling the pressure inside each bubble, three degrees of freedom can be actuated. We investigated three sensing solutions to measure the platform attitude in real-time (z-position of each droplet, leading to the knowledge of the z position and Θx and Θy tilts of the platform). The comparison between optical, resistive, and capacitive measurement principles is hereafter reported. The optical technique uses SFH-9201 components. The resistive technique involves measuring the electrical resistance of a path flowing through two droplets and the platform. This innovative technique for sensing table position combines three pairs of resistances, from which the resistance in each drop can be deduced, thus determining the platform position. The third solution is a more usual high frequency (~200 MHz) capacitive measurement. The resistive method has been proven reliable and is simple to implement. This work opens perspectives toward an interesting sensing solution for micro-robotic platforms.


Do clouds save the great barrier reef? satellite imagery elucidates the cloud-SST relationship at the local scale.
Evidence of global climate change and rising sea surface temperatures (SSTs) is now well documented in the scientific literature. With corals already living close to their thermal maxima, increases in SSTs are of great concern for the survival of coral reefs. Cloud feedback processes may have the potential to constrain SSTs, serving to enforce an "ocean thermostat" and promoting the survival of coral reefs. In this study, it was hypothesized that cloud cover can affect summer SSTs in the tropics. Detailed direct and lagged relationships between cloud cover and SST across the central Great Barrier Reef (GBR) shelf were investigated using data from satellite imagery and in situ temperature and light loggers during two relatively hot summers (2005 and 2006) and two relatively cool summers (2007 and 2008). Across all study summers and shelf positions, SSTs exhibited distinct drops during periods of high cloud cover, and conversely, SST increases during periods of low cloud cover, with a three-day temporal lag between a change in cloud cover and a subsequent change in SST. Cloud cover alone was responsible for up to 32.1% of the variation in SSTs three days later. The relationship was strongest in both El Niño (2005) and La Niña (2008) study summers and at the inner-shelf position in those summers. SST effects on subsequent cloud cover were weaker and more variable among study summers, with rising SSTs explaining up to 21.6% of the increase in cloud cover three days later. This work quantifies the often observed cloud cooling effect on coral reefs. It highlights the importance of incorporating local-scale processes into bleaching forecasting models, and encourages the use of remote sensing imagery to value-add to coral bleaching field studies and to more accurately predict risks to coral reefs.


On gifts, payments and disputes: divorce and changing family structures in contemporary Britain.
"This article considers ethnographic data collected among divorcing men and women in Britain and adopts a Maussian view of exchange in order to understand the cultural dimensions of divorce in more depth. I argue that divorcing men and women express discontinuities and continuities in their relationships by means of particular kinds of exchanges. What is of particular interest is the way that former husbands and wives place discrepant and conflicting constructions on the transfer of money and material goods between them and between themselves and their children. The article illustrates these points by examining the conflicts between fathers, mothers and their children over the emotional and economic significance of particular transactions."


Variation in management of small invasive breast cancers detected on screening in the former south east Thames region: observational study.
To examine the variation in surgical and adjuvant treatment of breast cancer of known histology and detected on screening in a large cohort of patients treated by the surgeons of a health region. Part prospective, part retrospective observational study using the databases of a region's breast screening programme and of the cancer registry. The former South East Thames region. 600 women aged 49-79 who presented during 1991-2 with invasive breast cancer up to 20 mm in diameter that had been detected on screening. These patients were treated by 35 surgeons. Mastectomy rate by surgeon and the use of adjuvant treatment (radiotherapy, tamoxifen, and chemotherapy) were compared with risk factors, tumour grade, resection margins, and axillary node status. The mastectomy rate varied between nil and 80%, although the numbers at these extremes were small (0/13 v 8/10). Surgeons operating on more than 20 such cases had a lower mastectomy rate (15%) than surgeons treating fewer cases (23%), but this difference was confounded by variation in casemix. There were also wide variations in mastectomy rates and in axillary sampling rates that were independent of casemix or caseload. There was broad agreement on the use of adjuvant tamoxifen (94%), but few patients received chemotherapy (2.5%). 78 patients (19%) did not receive radiotherapy, including 51 out of 317 patients with unfavourable tumours, and 26 patients did not receive tamoxifen. Whether the patient received adjuvant treatment was more dependent on referral by the surgeon than the risk factors for local recurrence and was independent of caseload. Mastectomy rates for similar tumours vary widely by surgeon independently of casemix or caseload, but surgeons with a higher caseload tend to have a lower mastectomy rate. Omission of postoperative radiotherapy or tamoxifen after conservative treatment is not related to risk factors for local recurrence or caseload. Confidential feedback of treatment profiles to individual surgeons has been used, but when benefit has been established treatment should be guided by evidence based protocol.


Takayasu's Arteritis with Systemic Lupus Erythematosus: A Rare Association.
We report the case of a 24-year-old nondiabetic, nonhypertensive lady with history of fatigue, dyspnoea and limb claudication. She has been diagnosed with Takayasu's arteritis. Subsequently she developed rash, alopecia, joint pain, and various other laboratory abnormalities which led to a diagnosis of SLE. Takayasu's arteritis (TA) rarely coexists with systemic lupus erythematosus (SLE). The absence of specific SLE markers in patients with TA who subsequently develop SLE suggests that the coexistence of these conditions may be coincidental. The antiphospholipid syndrome in patients with SLE may mimic the occlusive vasculitis of TA.


Explicit Analytical Solution for Random Close Packing in d=2 and d=3.
We present an analytical derivation of the volume fractions for random close packing (RCP) in both d=3 and d=2, based on the same methodology. Using suitably modified nearest neighbor statistics for hard spheres, we obtain ϕ_{RCP}=0.658 96 in d=3 and ϕ_{RCP}=0.886 48 in d=2. These values are well within the interval of values reported in the literature using different methods (experiments and numerical simulations) and protocols. This statistical derivation suggests some considerations related to the nature of RCP: (i) RCP corresponds to the onset of mechanical rigidity where the finite shear modulus emerges, (ii) the onset of mechanical rigidity marks the maximally random jammed state and dictates ϕ_{RCP} via the coordination number z, (iii) disordered packings with ϕ>ϕ_{RCP} are possible at the expense of creating some order, and z=12 at the fcc limit acts as a boundary condition.


Reducing environmental emissions in tanneries.
Tanning, in particular chrome leather production, is still characterised by an inefficient use of raw material and the production of highly polluted wastewater and solid wastes. A part of the emissions can be prevented by introducing clean tanning technologies, the remaining emissions can be treated. Clean production technologies and waste (water) treatment technologies should have a designed complimentarity. Anaerobic wastewater treatment with recovery of sulfides, sulfur and energy (biogas) is a cornerstone in such integral clean chrome leather technology.


Prognostic value and non-neuroendocrine role of INSM1 in small cell lung cancer.
Small cell lung cancer (SCLC) is a malignant lung neuroendocrine tumor with early metastasis, rapid progression, and poor outcomes. Insulinoma-associated protein 1 (INSM1) has been an excellent marker for neuroendocrine (NE) differentiation and widely used in the diagnosis of NE neoplasms, including SCLC. However, its role beyond NE diagnostic marker remained little reported. We examined immunohistochemical expression of INSM1 in 73 surgically resected SCLC, analyzed its prognostic value by Kaplan-Meier method, and investigated clinical-pathological features of INSM1 high SCLC. In vitro, We assessed INSM1 function on glucose intake, tumor migration, and Cisplatin resistance by 2-NBDG glucose uptake fluorescent assay, transwell assay, and ANNEXIN V/PI assay, respectively. In vivo, we evaluated the therapeutic value of metformin on reversing INSM1 induced chemoresistance by BALB/c nude mice xenograft tumor model. High INSM1 expression was correlated with lymph node metastasis (LNM) (p = 0.0005), later TNM stages (p = 0.0003), and predicted poor survival (Log-rank p = 0.038). Multivariate Cox analysis confirmed INSM1 as an independent prognostic factor in SCLC (p = 0.012, HR:3.195, 95%CI:1.288-7.927). Interestingly, LNM was correlated with worse prognosis only in patients received chemotherapy (Log-rank p = 0.027) rather than the others (Log-rank p = 0.40). In patients having LNM and treated with chemotherapy, high INSM1 was correlated with worse clinic outcome (Log-rank p = 0.009). In vitro, overexpression of INSM1 decreased AMPK-α expression as well as glucose intake, promoted tumor cell migration, and limited the apoptosis induced by Cisplatin, which all could be reversed by Metformin. In vivo, INSM1 overexpression also contributed to tumor growth beyond inducing Cisplatin resistance. Our finding suggested INSM1 played more role than a NE marker, partly through down-regulating AMPK signal. INSM1 may serve as a novel prognostic marker and therapeutic target in SCLC.


Is the pressure difference between the oval and round windows the effective acoustic stimulus for the cochlea?
The assumption that the pressure difference between the cochlear windows is the stimulus that produces cochlear responses is tested experimentally in the ears of anesthetized cats. Cochlear potential is used as a measure of cochlear response. The sound pressures at the oval and round windows are individually controlled with both pressures at the same frequency and amplitude. When the angle difference between the two pressures is varied over one cycle, cochlear-potential magnitude varies by about 40 dB, with a sharp minimum occurring with the angle difference near zero. A linear model of the response to the two input pressures estimates a complex common-mode gain C and a complex difference-mode gain D; magnitude of D is about 35 dB greater than magnitude of C over the frequency range that was tested (75 to 1000 Hz). Thus, except for conditions that make the common-mode input much larger than the difference-mode input, the pressure difference between the oval and round windows is, to a good approximation, the effective acoustic stimulus for the cochlea.


Pathological tremor prediction using surface electromyogram and acceleration: potential use in 'ON-OFF' demand driven deep brain stimulator design.
We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson's disease (PD) and essential tremor (ET). The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson's chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.


Redundant and specific roles of individual MIR172 genes in plant development.
Evolutionarily conserved microRNAs (miRNAs) usually have high copy numbers in the genome. The redundant and specific roles of each member of a multimember miRNA gene family are poorly understood. Previous studies have shown that the miR156-SPL-miR172 axis constitutes a signaling cascade in regulating plant developmental transitions. Here, we report the feasibility and utility of CRISPR-Cas9 technology to investigate the functions of all 5 MIR172 family members in Arabidopsis. We show that an Arabidopsis plant devoid of miR172 is viable, although it displays pleiotropic morphological defects. MIR172 family members exhibit distinct expression pattern and exert functional specificity in regulating meristem size, trichome initiation, stem elongation, shoot branching, and floral competence. In particular, we find that the miR156-SPL-miR172 cascade is bifurcated into specific flowering responses by matching pairs of coexpressed SPL and MIR172 genes in different tissues. Our results thus highlight the spatiotemporal changes in gene expression that underlie evolutionary novelties of a miRNA gene family in nature. The expansion of MIR172 genes in the Arabidopsis genome provides molecular substrates for the integration of diverse floral inductive cues, which ensures that plants flower at the optimal time to maximize seed yields.


Benefits of music training in mandarin-speaking pediatric cochlear implant users.
The aims of this study were to assess young (5- to 10-year-old) Mandarin-speaking cochlear implant (CI) users' musical pitch perception and to assess the benefits of computer-based home training on performance. Melodic contour identification (MCI) was used to assess musical pitch perception in 14 Mandarin-speaking pediatric CI users; the instrument timbre and the contour length were varied as experimental parameters. Six subjects received subsequent MCI training on their home computer in which auditory and visual feedback were provided. MCI performance was generally poor (grand mean=33.3% correct) and highly variable, with scores ranging from 9.3% to 98.1% correct; there was no significant effect of instrument timbre or contour length on performance (p>.05). After 4 weeks of training, performance sharply improved. Follow-up measures that were conducted 8 weeks after training was stopped showed no significant decline in MCI performance. For the 6 trained subjects, there was a significant effect of contour length for the training and follow-up measures. These preliminary data suggest that although baseline MCI performance initially may be poor, training may greatly improve Mandarin-speaking pediatric CI users' melodic pitch perception.


Image Analysis of Geo-Induced Inhibition, Compression, and Promotion of Growth in an Inverted Helianthus annuus L. Seedling.
The growth responses of a sunflower seedling (Helianthus annuus L.), subjected to repeated inversion, were characterized by time-lapse recording in conjunction with video image analysis. The investigation revealed a characteristic response pattern and established that the directional movement of the seedling is achieved by both inhibition and stimulation of growth in the normal growing regions. The complex growth changes in contiguous regions of the hypocotyl are such as seem to be inexplicable in terms of an environmentally imposed gradient of a single growth substance.


Cytokeratin and vimentin expression in breast cancer.
The transition from epithelial keratin to mesenchymal vimentin expression marks an important step in the malignant progression of breast cancer. This study analyzed the clinical significance of cytokeratin and vimentin in patients with breast cancer. Expression of cytokeratin and vimentin was evaluated by immunohistochemistry on paraffin-embedded tissue sections of patients with breast cancer. Loss of cytokeratin was seen in 11% of the patients. A clearer trend towards loss of cytokeratin was observed in patients with stage IV disease and PR negativity. Weak cytokeratin expression was present in patients who developed recurrence or metastatic disease. Loss of cytokeratin was associated with reduced overall survival in univariate and multivariate analysis, gain of vimentin expression was seen in 57% of breast carcinoma patients. It was higher in patients with lymph node positivity, advanced stage, HER2 positivity, and disease recurrence or metastasis. Multivariate survival analysis indicated that gain of vimentin expression was associated with reduced relapse-free survival. Loss of cytokeratin and gain of vimentin expression are indicators of biologically aggressive breast carcinoma.


Modulation of the gut microbiota by the mixture of fish oil and krill oil in high-fat diet-induced obesity mice.
Previous studies confirmed that dietary supplements of fish oil and krill oil can alleviate obesity in mice, but the underlying mechanism remains unclear. This study aims to discern whether oil treatment change the structure of the gut microbiota during the obesity alleviation. The ICR mice received high-fat diet (HFD) continuously for 12 weeks after two weeks of acclimatization with a standard chow diet, and the mice fed with a standard chow diet were used as the control. In the groups that received HFD with oil supplementation, the weight gains were attenuated and the liver index, total cholesterol, triglyceride and low-density lipoprotein cholesterol were reduced stepwise compared with the HFD group, and the overall structure of the gut microbiota, which was modulated in the HFD group, was shifted toward the structure found in the control group. Moreover, eighty-two altered operational taxonomic units responsive to oil treatment were identified and nineteen of them differing in one or more parameters associated with obesity. In conclusion, this study confirmed the effect of oil treatment on obesity alleviation, as well as on the microbiota structure alterations. We proposed that further researches are needed to elucidate the causal relationship between obesity alleviation and gut microbiota modulation.


Exploring why young Australians participate in the sport of fencing: Future avenues for sports-based health promotion.
Australian sport policy calls for a diverse sector to get more individuals more active. This study contributes to an evidence base of alternative sport options that may increase physical activity levels in adolescents, as we sought to understand why Australians decide to participate in fencing when aged <18 years. A retrospective, mixed-methods survey design was employed to measure why a participant started fencing and what participants like about fencing compared to other sports. Free-text qualitative data were analysed thematically. Quantitative data were collected to answer secondary objectives, using nonparametric tests to determine significance between the median scores prefencing and postfencing for enjoyment and frequency of participation. One hundred and one fencers across Australia who started fencing aged <18 years completed the survey. Respondents primarily started fencing for fun/enjoyment, followed by the desire to try something different/alternative/nonmainstream. Four themes were identified relating to why a participant decided to start fencing: (i) external motivators, (ii) influence of interest and imagination, (iii) developing the self and (iv) the supportive culture. Fencing may encourage adolescent participation in physical activity due to unique characteristics which attracts individuals for reasons beyond the need to be active alone, and instead affords a space for self-exploration, learning, and belonging. Further research is required to identify how fencing can engage different cohorts of adolescents, and any barriers to participation. SO WHAT?: Fencing could be utilised to promote engagement in physical activity among Australian adolescents by emphasising the creative, mental, and inclusive aspects of the sport.


Effects of ivabradine and atenolol on heart rate and heart rate variability in healthy cats over a 24 h period: A pilot study.
Ivabradine is used to treat tachycardia; unlike atenolol, it does not affect blood pressure or myocardial contractility. This study compared the impact of ivabradine and atenolol on heart rate (HR) and HR variability (HRV) during a 24 h period, feeding and sleeping times, via a Holter electrocardiogram in healthy cats. We hypothesised that ivabradine and atenolol would lower the HRs equally well, even at times of excitement and rest, such as during feeding and sleep; that ivabradine, unlike atenolol, would have an effect on HRV. Five clinically healthy cats were used in the prospective blinded crossover study receiving 3 days of ivabradine (0.30 mg/kg per os twice daily) followed by atenolol (6.25 mg/cat per os twice daily, range 1.3-2.0 mg/kg) or receiving atenolol followed by ivabradine. A placebo period was initiated before the start of the crossover test, data obtained during that period were used as a baseline (BL). Evaluation parameters included HR and HRV, for the whole 24 h period and for feeding and sleeping times, comparing the effect of ivabradine and atenolol with BL. The HR for the whole 24 h, feeding and sleeping times, were significantly lower with ivabradine and atenolol, compared to BL (p < 0.05). The HRV for the whole 24 h and sleeping time were significantly higher after ivabradine compared with BL and after atenolol. In healthy cats, ivabradine and atenolol significantly reduced the HR regardless of excitement and rest; their effects were comparable. Ivabradine significantly increased HRV in comparison to BL whereas atenolol did not.


Noscapine Inhibiting the Growth and Angiogenesis of Human Eutopic Endometrium of Endometriosis Patients through Expression of Apoptotic Genes and Nitric Oxide Reduction in Three-Dimensional Culture Model.
Noscapine is a natural alkaloid with anti-angiogenesis activities. The aim of the present study was to examine the effect of noscapine on eutopic endometrium of endometriosis patients (EEE) and normal endometrium (NE) in a three-dimensional (3D) culture model. In this experimental in-vitro study, EEE (n = 8) and NE (n = 8) biopsies were taken from 16 reproductive aged women. The biopsies were cleared from blood and mucus. Each biopsy was cut into small fragments (1 × 1 mm) in a sterile condition. For 3D culture, the endometrial fragments were put between two layers of fibrin jell made of fibrinogen solution [3 mg/mL in Medium199 (M199) + thrombin]. Twenty-four wells of culture dish was divided into 5 groups for each biopsy: the control wells were treated with M199 containing 5% fetal bovine serum (FBS) while, the test wells were exposed to the same media containing one of the noscapine doses (10, 50, 100, and 200 μM). The expression of apoptotic genes, growth score, angiogenesis, and nitric oxide (NO) secretion were evaluated. The mean of growth score of groups exposed to 0, 10, 50, 100, and 200 μM were 2.2 ± 0.55, 1.7 ± 0.45, 1.44 ± 0.27, 0.29 ± 0.1, and 0.1 ± 0.08 in EEE, and also, 2.11 ± 0.6, 1.65 ± 0.5, 0.79 ± 0.41, 0.18 ± 0.1, and 0.1 ± 0.1 in NE, respectively, and the difference between the groups was significant (P < 0.05). The expression of apoptotic genes significantly increased while, the levels of Bcl-2 and Sirt1 reduced (P = 0.004). NO secretion reduced significantly (P < 0.05) in both EEE and NE groups. In conclusion, higher doses of noscapine showed inhibitory effect on growth and angiogenesis of EEE and NE.


Assessment of the allosteric mechanism of aspartate transcarbamoylase based on the crystalline structure of the unregulated catalytic subunit.
The lack of knowledge of the three-dimensional structure of the trimeric, catalytic (C) subunit of aspartate transcarbamoylase (ATCase) has impeded understanding of the allosteric regulation of this enzyme and left unresolved the mechanism by which the active, unregulated C trimers are inactivated on incorporation into the unliganded (taut or T state) holoenzyme. Surprisingly, the isolated C trimer, based on the 1.9-A crystal structure reported here, resembles more closely the trimers in the T state enzyme than in the holoenzyme:bisubstrate-analog complex, which has been considered as the active, relaxed (R) state enzyme. Unlike the C trimer in either the T state or bisubstrate-analog-bound holoenzyme, the isolated C trimer lacks 3-fold symmetry, and the active sites are partially disordered. The flexibility of the C trimer, contrasted to the highly constrained T state ATCase, suggests that regulation of the holoenzyme involves modulating the potential for conformational changes essential for catalysis. Large differences in structure between the active C trimer and the holoenzyme:bisubstrate-analog complex call into question the view that this complex represents the activated R state of ATCase.


Validity and reliability of the Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale in patients undergoing bariatric surgery in Sweden: a prospective psychometric evaluation study.
The aim was to psychometrically test and evaluate the Swedish functional health literacy scale and the Swedish communicative and critical health literacy scale in patients undergoing bariatric surgery. A prospective cross-sectional psychometric study. Patients from three bariatric centres in Sweden were consecutively included in this study. A total of 704 patients undergoing bariatric surgery filled in the questionnaires preoperatively. Inclusion criteria were scheduled for primary bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) and greater than 17 years, proficiency in Swedish. Psychometric outcomes of the Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale. There was a higher proportion of females (74.4%, n=523) to males (25.6%, n=180). The mean age was 42 years (SD 11.5). Limited functional health literacy and limited communicative and critical health literacy (including both inadequate and problematic health literacy) was reported in 55% (n=390) and 40% (n=285), respectively. Cronbach alpha for the Swedish Functional Health Literacy scale was α=0.86 and for the Swedish Communicative and Critical Health Literacy scale, α=0.87. Construct validity showed weak to negative correlations between the Swedish Functional Health Literacy scale and income, education and SF-36/RAND36 summary scores. Confirmatory factor analysis showed a one-factor solution for the Swedish Functional Health Literacy scale and a two-factor solution for the Swedish Communicative and Critical Health Literacy scale. The Swedish Functional Health Literacy scale and the Swedish Communicative and Critical Health Literacy scale are valid and reliable to use for patients undergoing bariatric surgery in a Swedish context. Measuring dimensions of health literacy can be used as a guide for the development of health literacy friendly patient information in patients undergoing bariatric surgery.


Salivary immunoglobulins in recipients of bone marrow grafts. III. A longitudinal follow-up of CMV specific antibodies.
Cytomegalovirus (CMV) infection is a major complication of BMT. The oral cavity is a common route for CMV infection, whose protection is provided by salivary anti-CMV antibodies. We developed an ELISA assay for the detection of CMV-specific antibodies in parotid saliva. Saliva of patients receiving BMT from CMV-positive donors was transiently reconstituted with IgG and IgA anti-CMV antibodies shortly after transplantation. The concentration of these antibodies gradually decreased during the 2 months after transplantation and increased again around day 80. A remarkable rise in the salivary concentrations of IgG and IgM anti-CMV was observed shortly after i.v. administration of Sandoglobulin. These results demonstrate, for the first time accurate monitoring of CMV-specific antibodies in saliva using a quantitative ELISA assay. The study suggests that secretion of CMV-specific antibodies in saliva of immunocompromised patients can be reconstituted by donor-derived B and plasma cells transferred with the BM or by i.v. administration of pooled Ig.


Role of ripples in altering the electronic and chemical properties of graphene.
Ripples of graphene are known to manipulate electronic and hydrogenation properties of graphitic materials. More detailed work is needed to elucidate the structure-property relationship of these systems. In this work, the density functional theory is used to compute the energy and electronic structure of the graphene models with respect to variable curvatures and hydrogen adsorption sites. The magnitude of finite bandgap opening depends on the orientation of ripples, and the hydrogen adsorption energy depends on the local curvature of graphene. An adsorbed hydrogen alters the local curvature, resulting in relatively weakened adsorption on the neighboring three sites, which gives a rationale to experimentally observed dynamic equilibrium stoichiometry (H:C = 1:4) of hydrogenated graphene. The surface diffusion transition state energy of adsorbed hydrogen is computed, which suggests that the Eley-Rideal surface recombination mechanism may be important to establish the dynamic equilibrium, instead of the commonly assumed Langmuir-Hinshelwood mechanism.


Contrast-enhanced imaging in hepatic epithelioid hemangioendothelioma: retrospective study of 10 patients.
The purpose of this study was to analyze imaging findings in hepatic epithelioid hemangioendothelioma (HEHE) with a particular focus on contrast-enhanced ultrasound (CEUS). This retrospective multicenter study included 10 patients with histologically proven HEHE from 5 European centers. All existing ultrasound images/videos were independently analyzed by 2 experienced examiners (DEGUM level III, internal medicine) using a standardized evaluation form. Patterns of contrast enhancement were correlated with computed tomography (CT), magnetic resonance imaging (MRI), and pathological findings. B-mode ultrasound, CEUS, CT, and MRI were performed in 90 %, 70 %, 100 %, and 90 % of patients, respectively. Multifocal HEHE could be observed in 80 % with affection of both liver lobes in 70 %. Analysis of CEUS revealed 3 characteristic patterns that correlated well with contrast patterns on CT and MRI: (a) peripheral nodular enhancement with centripetal fill-in and wash-out in the portal venous and late venous phase (PVLP), (b) rim-like arterial enhancement with wash-out in the PVLP, and (c) inversed target sign with/without wash-out in the PVLP. Wash-out in the PVLP as a sign suspicious of malignancy was observed in 6/7 patients (85.7 %). Knowledge of the different characteristic CEUS patterns is of importance to avoid misdiagnosis due to resemblance of patterns A and B to the much more common focal liver lesions hemangioma and intrahepatic cholangiocarcinoma. Of importance, sonographers should be aware that wash-out in the PVLP might be absent in some patients.


The Anatomy of Inference: Generative Models and Brain Structure.
To infer the causes of its sensations, the brain must call on a generative (predictive) model. This necessitates passing local messages between populations of neurons to update beliefs about hidden variables in the world beyond its sensory samples. It also entails inferences about how we will act. Active inference is a principled framework that frames perception and action as approximate Bayesian inference. This has been successful in accounting for a wide range of physiological and behavioral phenomena. Recently, a process theory has emerged that attempts to relate inferences to their neurobiological substrates. In this paper, we review and develop the anatomical aspects of this process theory. We argue that the form of the generative models required for inference constrains the way in which brain regions connect to one another. Specifically, neuronal populations representing beliefs about a variable must receive input from populations representing the Markov blanket of that variable. We illustrate this idea in four different domains: perception, planning, attention, and movement. In doing so, we attempt to show how appealing to generative models enables us to account for anatomical brain architectures. Ultimately, committing to an anatomical theory of inference ensures we can form empirical hypotheses that can be tested using neuroimaging, neuropsychological, and electrophysiological experiments.


Importance of positron emission tomography-computed tomography (PET-CT) examination in rectal cancer staging--initial clinical experience.
Accurate preoperative staging is essential in determining optimal therapeutic procedures and planning for individual patients. Advances in imaging technology have raised interest in the potential role of positron emission tomography-computed tomography (PET-CT) examination for staging of rectal cancer. The primary end point of the study was the correct classification of the tumor node-metastases (TNM) tumor stage using whole-body PET-CT examination. This prospective study was performed from October 2011 to October 2012. Patients with histopathological diagnosis of rectal cancer after biopsy underwent PET-CT before surgical treatment and TNM staging. Twenty patients who fulfilled inclusion criteria were included in the study. All of the patients were operated and histopathology served as the standard of reference. There was no statistical significance in T staging comparing PET-CT and histopathological staging, according to the Monte Carlo simulation (p=.066). Also, there was no statistical significance between two methods in mesorectal fascia involvement analysis (p=1). There was statistical difference between PET-CT and histopathological staging. Sensitivity of the PET-CT for N staging was 86.7% and it was higher than for the histopathology. Two patients showed liver metastases. Positron emission tomography-computed tomography examination could play an important role in the initial staging for the rectal cancer. Good patient selection for preoperative chemoradiotherapy ensures survival benefit. Avoidance of unnecessary therapeutic procedures allows an acceptable quality of patient's life.


Characteristics and localization of a determinant conferring partial macrolide resistance in Staphylococcus aureus carrying plasmid.
Staphylococcus aureus TPR-27, a clinically isolated strain, showed constitutive resistance to some macrolide antibiotics (erythromycin, oleandomycin, spiramycin, and josamycin), but susceptibility to the other macrolide (tylosin, rokitamycin, and mycinamicin), lincosamide, and streptogramin type B antibiotics (PM-resistance). The PM-resistant strain TPR-27 has carried for visible plasmids. Attempts to eliminate the resistant determinant in terms of ethidium bromide (about 3 micrograms/ml) did not succeed, and every trial to transduce the PM-resistant determinant into rec- mutant ISP105 using phage 80L2 propagated on strain TPR-27 also failed at the frequency of less than 1.1 x 10(-10) transductants per plaque-forming unit. These results suggest that the PM-resistance determinant is localized in chromosomal DNA.


A Game Show-Based Curriculum for Teaching Principles of Reproductive Infectious Disease (GBS PRIDE Trial).
The purpose of this study was to evaluate whether a game show-based curriculum improves obstetrics and gynecology (OBGYN) residents' confidence in and understanding of the principles of reproductive infectious disease (RID), clinical manifestations and sequelae of sexually transmitted infection (STI), and management of serious long-term consequences of STIs. A game show-based curriculum was developed from the basic principles of RID, which include the following: (1) distinguishing between clinical manifestations of STIs and management of long-term sequelae of STIs; (2) evaluation and management of common gynecologic infectious diseases, including chronic vaginitis, pelvic inflammatory disease, and other pelvic infections; (3) diagnosis and management of perinatal infectious diseases, such as parvovirus, varicella-zoster virus, cytomegalovirus, human immunodeficiency virus, toxoplasmosis, and infection-mediated prematurity; (4) evaluation and management of obstetric and gynecologic postoperative infections; and (5) diagnosis and management of acute and chronic human immunodeficiency virus and hepatitis C virus infections in pregnancy. OBGYN residents at a large urban academic training program were randomized to either a Jeopardy-style educational game show intervention plus a traditional didactic-based curriculum or traditional didactic-based curriculum alone. The study team recruited participants by sending out an e-mail to all of the residents, detailing the study and consent process. Participants from both the intervention and control groups completed confidence and knowledge-based pretests. Posttests were administered 4 weeks after completion of the pretests. Statistical methods were applied to analyze the data. Thirty-eight residents were randomized to a Jeopardy-style game show-based educational intervention (n = 19) or to a traditional didactic-based curriculum (n = 19). All of the participants (100%) completed the pre- and posttests. Pretest median scores were similar between both groups, in which the Jeopardy group had a median score of 48.5 and the traditional group had a median score of 51.4 (P = 0.091). The Jeopardy group median test scores improved between the pretest and posttest (48.5 vs 62.8, P ≤ 0.001). The traditional didactic-based curriculum had a minimal increase in its median posttest scores (51.4 compared with 54.2, P = 0.773). The Jeopardy group had significantly higher posttest median scores and confidence scores than the traditional didactic-based curriculum (Jeopardy = 62.8, traditional = 54.2, P = 0.002). A game show-based curriculum improves OBGYN residents' confidence and retention of knowledge regarding RIDs, clinical manifestations and sequelae of STIs, and management of serious long-term consequences of STIs. Additional studies that include longer posttest time intervals are needed to assess the longer-term impact of game show-based curriculum on knowledge retention among OBGYN residents.


Characterization of a pigeon paramyxovirus (PPMV-1) isolated from chickens in South Africa.
A paramyxovirus with a thermostability of 60 min (typical of velogenic viruses) and a mean death time of > 90 h (typical of lentogenic viruses) was isolated from layers near Mooi River, South Africa. Our results, based on comparative nucleotide sequence data indicated that the virus is pigeon paramyxovirus 1 (PPMV-1), a variant of Newcastle disease virus. The F0 cleavage site contains a 112RRKKRF117 motif, and the virus had 98% sequence identity with PPMV-1 strains from the Far East. PPMV-1 was last reported in South Africa during the 1980s, with this being the first report of PPMV-1 isolated from chickens in South Africa.


Left axis deviation in electrocardiogram with normal QRS duration in ambulatory adults without cardiac symptoms: a possible marker of glucose intolerance.
We are increasingly noticing isolated left axis deviation (LAD) in electrocardiogram in younger people with diabetes without obvious heart disease and association of LAD with glucose intolerance has not been explicitly raised before. We planned a study of ambulatory adults with borderline (0° to -30°) and moderate-to-marked (<-30° to -90°) LAD looking into their possible association with glucose intolerance with fasting plasma glucose (FPG)≥100 mg/dL. We consecutively enrolled adults aged 30 or more, with electrocardiogram normal duration QRS axis between 0° to -90°, without cardiac symptoms, not on any medication, attending outdoor-clinics for health checkup. Out of 100 participants enrolled, about 90% were aged between 30 and 60 and 47% had borderline and 53% moderate-to-marked LAD. Moderate-to-marked LAD group had higher frequencies of abnormal blood pressure (BP), FPG, and lipids than borderline LAD group even after conditioning effects of age and sex (p≤0.03) and of FPG after conditioning effects of BP (p=0.02). The frequencies of glucose intolerance were 48.9% even in borderline LAD with 84.9% in moderate-to-marked LAD group. In moderate-to-marked LAD group mean values of BP, FPG, and lipid profiles were higher (p<0.001) and abnormal. In borderline LAD group though mean BP and lipid values were normal, FPG was impaired. Impaired mean FPG values and high frequencies of glucose intolerance in both borderline LAD group with normal BP and moderate-to-marked LAD group with conditioning of effects of BP in relatively younger ambulatory adults without cardiac symptoms indicate possible association between LAD and glucose intolerance.


Severe truncal valve stenosis: diagnosis and management.
Severe truncal valve stenosis, due to dysplastic valve, may be found in a small number of patients with truncus arteriosus. Its presence complicates the surgical management of this anomaly due to lack of optimal therapeutic options and associated ventricular dysfunction. We report a case of truncal root replacement using a homograft for the management of such condition, and review the literature related to its management and outcome.


[Current recommendations for aftercare in patients following hernia repair].
Abdominal wall hernias, in particular inguinal hernias are the most frequently encountered entity in general surgery. Consequently, the socio-economic burden results from the in-hospital phase itself and to a considerable extent from the convalescence period. In addition to the surgical procedure and the occupation of the patient there are two factors of particular significance influencing the aftercare: the post-operative pain and the given recommendations for postoperative strain. Next to patient-factor adapted operative procedures it is therefore essential, to offer a standardized pain management and recommendations for postoperative strain. Currently there is no conclusion, whether the minimally invasive techniques will be established as the "Gold-standard", particularly from an economic point of view and the introduction of the DRG in Switzerland.


Environmental constraints on oviposition limit egg supply of a stream insect at multiple scales.
Species with complex life cycles pose challenges for understanding what processes regulate population densities, especially if some life stages disperse. Most studies of such animals that are thought to be recruitment limited focus on the idea that juvenile mortality limits the density of recruits (and hence population density), fewer consider the possibility that egg supply may be important. For species that oviposit on specific substrata, environmental constraints on oviposition sites may limit egg supply. Female mayflies in the genus Baetis lay egg masses on the underside of stream rocks that emerge above the water's surface. We tested the hypothesis that egg mass densities are constrained by emergent rock densities within and between streams, by counting egg masses on emergent rocks. All emergent rocks were counted along 1-km lengths of four streams, revealing significant variation in emergent rock density within streams and a more than three-fold difference between streams. In each stream, egg mass density increased with the density of emergent rocks in 30-m stretches. We used regression equations describing these small-scale relationships, coupled with the large-scale spatial variation of emergent rocks, to estimate egg mass densities for each 1-km stream length, a scale relevant to population processes. Scaled estimates were positively associated with emergent rock density and provided better estimates than methods that ignored environmental variation. Egg mass crowding was inversely related to emergent rock density at the stream scale, a pattern consistent with the idea that oviposition substrata were in short supply in streams with few emergent rocks, but crowding did not compensate entirely for differences in emergent rock densities. The notion that egg supply, not larval mortality, may limit population density is an unusual perspective for stream insects. Environmental constraints on egg supply may be widespread among other species with specialised oviposition behaviours.


Endoscopic diagnosis of unilateral ectopic ureter in a yearling filly.
Unilateral ectopic ureter was diagnosed by endoscopic examination in an 18-month-old filly examined because of chronic urine dribbling. Intramuscular administration of azosulfamide discolored the urine and enhanced visualization of the ectopic ureter. Endoscopy proved valuable in determining that only one ureter entered the urinary bladder and in locating the ectopic ureter in the ventral portion of the vagina.


Time Series UAV Image-Based Point Clouds for Landslide Progression Evaluation Applications.
Landslides are major and constantly changing threats to urban landscapes and infrastructure. It is essential to detect and capture landslide changes regularly. Traditional methods for monitoring landslides are time-consuming, costly, dangerous, and the quality and quantity of the data is sometimes unable to meet the necessary requirements of geotechnical projects. This motivates the development of more automatic and efficient remote sensing approaches for landslide progression evaluation. Automatic change detection involving low-altitude unmanned aerial vehicle image-based point clouds, although proven, is relatively unexplored, and little research has been done in terms of accounting for volumetric changes. In this study, a methodology for automatically deriving change displacement rates, in a horizontal direction based on comparisons between extracted landslide scarps from multiple time periods, has been developed. Compared with the iterative closest projected point (ICPP) registration method, the developed method takes full advantage of automated geometric measuring, leading to fast processing. The proposed approach easily processes a large number of images from different epochs and enables the creation of registered image-based point clouds without the use of extensive ground control point information or further processing such as interpretation and image correlation. The produced results are promising for use in the field of landslide research.


Global meta-analysis reveals no net change in local-scale plant biodiversity over time.
Global biodiversity is in decline. This is of concern for aesthetic and ethical reasons, but possibly also for practical reasons, as suggested by experimental studies, mostly with plants, showing that biodiversity reductions in small study plots can lead to compromised ecosystem function. However, inferring that ecosystem functions will decline due to biodiversity loss in the real world rests on the untested assumption that such loss is actually occurring at these small scales in nature. Using a global database of 168 published studies and >16,000 nonexperimental, local-scale vegetation plots, we show that mean temporal change in species diversity over periods of 5-261 y is not different from zero, with increases at least as likely as declines over time. Sites influenced primarily by plant species' invasions showed a tendency for declines in species richness, whereas sites undergoing postdisturbance succession showed increases in richness over time. Other distinctions among studies had little influence on temporal richness trends. Although maximizing diversity is likely important for maintaining ecosystem function in intensely managed systems such as restored grasslands or tree plantations, the clear lack of any general tendency for plant biodiversity to decline at small scales in nature directly contradicts the key assumption linking experimental results to ecosystem function as a motivation for biodiversity conservation in nature. How often real world changes in the diversity and composition of plant communities at the local scale cause ecosystem function to deteriorate, or actually to improve, remains unknown and is in critical need of further study.


Inhibition of the synthesis of glycoproteins and induction of the differentiation of HL-60 promyelocytic leukemia cells by 6-methylmercaptopurine ribonucleoside.
HL-60 promyelocytic leukemia cells were induced to differentiate along the granulocytic pathway by exposure to 6-methylmercaptopurine ribonucleoside (6-MMPR). The interference with cellular replication and the induction of terminal maturation by 6-MMPR appeared to be a consequence of the inhibition of purine nucleotide biosynthesis de novo, since the simultaneous exposure of HL-60 cells to 6-MMPR and adenine completely prevented cellular differentiation, as measured by both nitro-blue tetrazolium reduction and the phagocytosis of latex beads, and partially prevented growth inhibition. The induction of HL-60 leukemia cell maturation by 6-MMPR was preceded by a marked reduction in the incorporation of [3H]mannose into glycoproteins and into the dolichol-oligosaccharide precursors of N-linked glycoprotein biosynthesis. Simultaneous exposure of HL-60 cells to 6-MMPR and adenine completely prevented the reduction in [3H]mannose incorporation into glycoproteins produced by the purine nucleoside antimetabolite. These findings suggest that the utilization of mannose for glycoprotein biosynthesis may be a component of the mechanism by which 6-MMPR causes the induction of the terminal differentiation of HL-60 leukemia cells.


[Antibacterial effect of food additives and detergents against histamine-producing bacteria on food contact material surfaces].
We investigated the antibacterial activity of food additives and detergents against histamine-producing bacteria on food contact material surfaces. Based on minimum inhibitory concentration (MIC) testing with Morganella morganii NBRC3848, Raoultella planticola NBRC3317 and Enterobacter aerogenes NCTC10006, we screened nine food additives and four detergents with relatively high inhibitory potency. We prepared food contact material surfaces contaminated with histamine-producing bacteria, and dipped them into fourteen agents (100 µg/mL). Sodium hypochlorite, benzalkonium chloride, benzethonium chloride, n-hexadecyltrimethylammonium chloride and 1-n-hexadecylpyridinium chloride showed antibacterial activity against histamine-producing bacteria. We prepared low concentrations of the five agents (10 and 50 µg/mL) and tested them in the same way. Sodium hypochlorite showed high antibacterial activity at 10 µg/mL, and the other four showed activity at 50 µg/mL. So, washing the material surface with these reagents might be effective to prevent histamine food poisoning owing to bacterial contamination of food contact surfaces.


Fast vector quantization algorithms based on nearest partition set search.
A fast search method for vector quantization is proposed in this paper. It makes use of the fact that in the generalized Lloyd algorithm (GLA) a vector in a training sequence is either placed in the same minimum distance partition (MDP) as in the previous iteration or in a partition within a very small subset of partitions. The proposed method searches for the MDP for a training vector only in this subset of partitions plus the single previous MDP. As the size of this subset is much smaller than the total number of codevectors, the search process is speeded up significantly. The creation of the subset is essential, as it has a direct effect on the improvement in computation time of the proposed method. The schemes that create the subset efficiently have been proposed. The proposed method generates a codebook identical to that generated using the GLA. It is simple and requires only minor modification of the GLA and a modest amount of additional memory. The experimental results show that the computation time of codebook training was improved by factors from 6.6 to 50.7 and from 5.8 to 70.4 for two test data sets when codebooks of sizes from N = 16 to 2048 were trained. The proposed method was also combined with an earlier published method to further improve the computation time.


Transport of intensity equation method and its applications.
A phase retrieval technique based on a transport of intensity equation (TIE) is one of the defocus series reconstruction techniques in microscopy. Since it does not require any dedicated devices like a biprism, and only three defocus images are enough to retrieve phase information, it has been applied to observe magnetic fields, magnetic domains, electrostatic potentials and strains. It is also used to improve image resolution by correcting spherical aberration. This technique is simple and easy to use, but some artifacts often appear in the retrieved phase map. One should pay careful attention to the experimental conditions and the algorithms and boundary conditions used to solve the TIE. This paper reviews the principle of the TIE method, the algorithms used to solve it and application results in materials science.


Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.
Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis. 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up. Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups. In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea. EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.


Altered gastric emptying in the head-injured patient: relationship to feeding intolerance.
Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.


[Difficulties in multi-organ harvesting].
Planning in transplantation is always a difficult process mainly due to the difficulty presented in attaining the required estimated, as well as the problems inherent in transplant units. According to data from European Countries and USA, the ideal number of donors is 50/1 million inhabitants per year, 90% of whom will be multiorgan donors. In 1999 Portugal climbed to 19.2 donors/1 million inhabitants per year, 80 of whom were kidney and liver donors. A data comparison with European Countries, particularly France shows that Portugal is well placed in terms of the number of transplants units per million of population (p.m.p.). In fact, the problem lies in the area of heart and lung transplantation where the annual figures are well below requirements. Estimates for the year 2000 forecast 18 heart transplantation, % the 1999 figure.


[Pregnancy, tuberculosis and inappropriate antidiuretic hormone secretion].
We report a pregnant woman presenting with seizure secondary to hyponatremia by inappropriate antidiuretic hormone secretion. Aetiology was unknown urinary and lung tuberculosis. This case report presents diagnosis strategy of inappropriate antidiuretic hormone secretion and the arguments for its aetiology.


Induction of Medicarpin Biosynthesis in Ladino Clover Callus by p-Chloromercuribenzoic Acid Is Reversed by Dithiothreitol.
Treatment of Ladino clover (Trifolium repens L.) callus with 1 millimolar p-chloromercuribenzoic acid (PCMBA) stimulated the biosynthesis of the phytoalexin medicarpin. Increased medicarpin concentration was detected at 6 hours, and maximum level was achieved by 36 hours. Dithiothreitol (DTT), added to callus at 2, 6, 10, and 18 hours following addition of PCMBA, partially counteracted the effect of PCMBA in the cells. The greatest effect on reversal of medicarpin accumulation was found at the earlier times for DTT addition. Compared to a 24-hour PCMBA control, final medicarpin concentrations were 9 to 19%, 37 to 45%, and 92 to 105% of the control value when DTT was added at 0.5, 1 or 2 hours, 3 or 4 hours, and 6, 8, 10, or 12 hours, respectively, after PCMBA addition. The results indicate that stimulation of medicarpin biosynthesis is reversible, but once activated, the pathway is not shut down by removal of elicitor.


Genetics in Idiopathic Pulmonary Fibrosis Pathogenesis, Prognosis, and Treatment.
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia (IIP), is characterized by irreversible scarring of the lung parenchyma and progressive decline in lung function leading to eventual respiratory failure. The prognosis of IPF is poor with a median survival of 3-5 years after diagnosis and no curative medical therapies. Although the pathogenesis of IPF is not well understood, there is a growing body of evidence that genetic factors contribute to disease risk. Recent studies have identified common and rare genetic variants associated with both sporadic and familial forms of pulmonary fibrosis, with at least one-third of the risk for developing fibrotic IIP explained by common genetic variants. The IPF-associated genetic loci discovered to date are implicated in diverse biological processes, including alveolar stability, host defense, cell-cell barrier function, and cell senescence. In addition, some common variants have also been associated with distinct clinical phenotypes. Better understanding of how genetic variation plays a role in disease risk and phenotype could identify potential therapeutic targets and inform clinical decision-making. In addition, clinical studies should be designed controlling for the genetic backgrounds of subjects, since clinical outcomes and therapeutic responses may differ by genotype. Further understanding of these differences will allow the development of personalized approaches to the IPF management.


Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia.
Biotin is a water-soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism. Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects. Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days. Plasma samples obtained at baseline and after treatment were analyzed for total triglyceride, cholesterol, very low density lipoprotein (VLDL), glucose and insulin. We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group. Biotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects. We conclude that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia.


Manipulating solute nucleophilicity with room temperature ionic liquids.
In this work we report the effect of ionic liquids on a class of charge-neutral nucleophiles. We have studied the reactions of (n)butylamine, di-(n)butylamine, and tri-(n)butylamine with methyl p-nitrobenzenesulfonate in [bmpy][N(Tf)(2)], [bmpy][OTf], and [bmim][OTf] (bmpy = 1-butyl-1-methylpyrrolidinium; bmim = 1-butyl-3-methylimidazolium) and compared their reactivities, k(2), to those for the same reactions in the molecular solvents dichloromethane and acetonitrile. It was shown that all of the amines are more nucleophilic in the ionic liquids than in the molecular solvents studied in this work. Comparison is also made with the effect of ionic liquids on the reactivity of chloride ions, which are deactivated in ionic liquids. The Eyring activation parameters revealed that changes in the activation entropies are largely responsible for the effects seen. This can be explained in part by the differing hydrogen-bonding properties, as shown by the Kamlet-Taft solvent parameters, of each of these solvents and the formation of hydrogen bonds between the solvents and the nucleophiles.


Are we providing adequate postnatal services?
Over the past 10 years, there have been significant changes to postnatal services. There is insufficient research that evaluates the effect these changes have on the physical and psychological outcomes of women and families or the level of support women and children actually require in the first postnatal year. We argue that there is an urgent need for research which tests the outcomes and cost effectiveness of different models of postnatal care currently being offered. The most rigorous research methods possible are necessary to provide robust evidence to prevent the degradation of postnatal maternity services. This research should evaluate the relative advantages and disadvantages of different models of postnatal care as well as describe the content and quality of postnatal services. Knowledge gained from such research would and should assist the development of recommendations and policies for postnatal midwifery and early childhood practice in Australia.


Further characterization of the target of a potential aptamer biomarker for pancreatic cancer: cyclophilin B and its posttranslational modifications.
Posttranslational modifications on proteins can serve as useful biomarkers for disease. However, their discovery and detection in biological fluids is challenging. Aptamers are oligonucleotide ligands that demonstrate high affinity toward their target proteins and can discriminate closely related proteins with superb specificity. Previously, we generated a cyclophilin B aptamer (M9-5) that could discriminate sera from pancreatic cancer patients and healthy volunteers with high specificity and sensitivity. In our present work we further characterize the aptamer and the target protein, cyclophilin B, and demonstrate that the aptamer could discriminate between cyclophilin B expressed in human cells versus bacteria. Using mass-spectrometric analysis, we discovered post-translational modifications on cyclophilin B that might be responsible for the M9-5 selectivity. The ability to distinguish between forms of the same protein with differing post-translational modifications is an important advantage of aptamers as tools for identification and detection of biomarkers.


New proposal for skin grafts on tendon-exposed wounds.
Performing a skin graft is not feasible for tendon-exposed defect reconstruction because tendons are fibrous connective tissues with relatively poor blood supply. This study proposes a method to effectively perform skin graft surgery in tendon-exposed wounds. A 48-year-old male patient with diabetes mellitus had a very large left dorsal foot defect (8×8 cm). The wound bed had healthy granular tissue, with tendon exposure. The tendons were turned over so that the posterior side would behave as the anterior side. The edge of the paratenon was then fixed together to the surrounding granulation tissue or dense remnant fascia using absorbable sutures, and the close granulation tissue was approximated and buried. A split-thickness skin graft was performed after 1 week. The graft site was stably taken on postoperative day 3. A small disruption was then observed at the graft site within 1 week postoperatively, but conservative treatment was continued for 1 month, after which the defect site was completely restored. This technique can increase the success rate of skin grafts for defects with tendon exposure.