Age-related changes in the composition of the cornified envelope in human skin.
The main function of the epidermis is to protect us against a multitude of hostile attacks from the environment. Its main cell type, the keratinocytes have a sophisticated system of different proteins and lipids available to form the cornified envelope, which is responsible for the barrier function of the skin. During ageing, dramatic changes are taking place. Some proteins of the SPRR-, S100- and LCE3-family are massively up-regulated, whereas others like loricrin, filaggrin and the LCE1&2 protein families are significantly down-regulated. The latter ones are known to be under control of calcium and/or 'calcium response elements'. We were able to show that the calcium peak specific for the stratum granulosum, which is the site where loricrin and the LCE1&2 families are synthesized, is reduced during ageing. The resulting cornified envelope in old skin has an extensively changed composition on the molecular level compared to young skin. This knowledge is of critical importance to understand chronic wound formation and ulcers in old age.


Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries.
The effects of three Ca2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl2-, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca2+ entry blockers and the extracellular Ca2+ dependence of the contractions was also examined. In 'nominally' Ca2(+)-free medium, addition of CaCl2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca2(+)-free medium almost abolished the noradrenaline-response but did not increase the inhibition of the KCl-induced contractions. The Ca2+ entry blockers induced concentration-dependent relaxation of the precontracted arteries (100 mM KC1) with the following order of potency: nimodipine greater than nicardipine greater than verapamil. The CaCl2-, KCl- and noradrenaline-induced contractions were depressed in a concentration-related manner by nicardipine, nimodipine and verapamil. Dihydropyridines showed a greater inhibitory effect than verapamil. These results show that Ca2+ entry blockers are able to inhibit the contractile responses of goat cerebral arteries to KCl and noradrenaline, an effect which may be explained by the strong dependence of both responses on extracellular Ca2+.


Prelimbic cortex glucocorticoid receptors regulate the stress-mediated inhibition of pain contagion in male mice.
Experiencing pain with a familiar individual can enhance one's own pain sensitivity, a process known as pain contagion. When experiencing pain with an unfamiliar individual, pain contagion is suppressed in males by activating the endocrine stress response. Here, we coupled a histological investigation with pharmacological and behavioral experiments to identify enhanced glucocorticoid receptor activity in the prelimbic subdivision of the medial prefrontal cortex as a candidate mechanism for suppressing pain contagion in stranger mice. Acute inhibition of glucocorticoid receptors in the prelimbic cortex was sufficient to elicit pain contagion in strangers, while their activation prevented pain contagion in cagemate dyads. Slice physiology recordings revealed enhanced excitatory transmission in stranger mice, an effect that was reversed by pre-treating mice with the corticosterone synthesis inhibitor metyrapone. Following removal from dyadic testing, stranger mice displayed enhanced affective-motivational pain behaviors when placed on an inescapable thermal stimulus, which were reversed by metyrapone. Together, our data suggest that the prelimbic cortex may play an integral role in modulating pain behavior within a social context and provide novel evidence towards the neural mechanism underlying the prevention of pain contagion.


Use of etomidate in patients with heart failure undergoing noncardiac surgery.
Patients with symptomatic and asymptomatic heart failure undergoing noncardiac surgery may benefit from the haemodynamic profile of etomidate. However, the safety of etomidate in this population is unknown. We examined anaesthesiologist variation in etomidate use and assessed its safety using an instrumental variable approach to account for differences in treatment selection. A retrospective cohort study of 19 714 patients with heart failure undergoing noncardiac surgery at two tertiary care institutions from January 2006 to December 2017 was performed. The proportion of etomidate use among 294 anaesthesiologists was examined and adjusted risk differences (aRD) for in-hospital and 30-day mortality were calculated using physician preference for etomidate as an instrumental variable. Etomidate was used in 14.3% (2821/19 714) of patients. Preference for etomidate varied substantially among individual anaesthesiologists with the lowest and highest quartile users using etomidate in 0-4.7% and 20.4-66.7% of their own heart failure patients, respectively. The adjusted instrumental variable analysis showed no significant differences in the risk of in-hospital (aRD -0.2%; 95% confidence interval, -2.4%-1.9%; P=0.83) or 30 day mortality (aRD 0.2%; 95% confidence interval, -2.5%-2.9%; P=0.90). Anaesthesiologists with higher preferences for etomidate were more experienced (greater heart failure and total case volume) than anaesthesiologists with lower preferences for etomidate. We found substantial variability in anaesthesiologists' preference for etomidate for use in patients with heart failure undergoing noncardiac surgery. There was no association between etomidate use and in-hospital or 30-day mortality. Etomidate is not inferior to other currently used options for induction of general anaesthesia in patients with heart failure.


Adipose tissue lipoprotein lipase activity in type III hyperlipoproteinemia.
An impairment in the catabolism of chylomicron and very low density lipoprotein remnants appears to cause the lipid abnormalities in type III hyperlipoproteinemia. A reduction in the activity of lipoprotein lipase (LPL) has been suggested as the catabolic defect. Results in this study indicate that the activity of adipose tissue LPL measured in the fasted and fed states are in the normal range in type III hyperlipoproteinemia (fasted: type III = 2.7 +/- 1.8 mU/10(6) cells, N = 8; normals = 3.4 +/- 2.5, N = 23, p, not significant; fed: type III = 3.6 +/- 2.1, N = 7; normals = 4.8 +/- 1.8, N = 12, p, not significant). This suggests that perhaps another mechanism, such as the interaction between LPL and its lipid substrate, is abnormal, or that the activity of LPL derived from another tissue source is deficient.


Ultrasound- and microwave-assisted extractions followed by hydride generation inductively coupled plasma optical emission spectrometry for lead determination in geological samples.
Followed the current idea of simplified sample pretratmet before analysis we evaluated the procedure for the determination of Pb in calcium-rich materials such as dolomites after ultrasound- or microwave- assisted extraction with diluted acids using hydride generation inductively coupled plasma optical emission spectrometry (HG-ICP-OES). Corresponding Pb hydride was generated in the reaction of an acidified sample solution with NaBH4 after pre-oxidation of Pb(II) to Pb(IV) by K3[Fe(CN)6]. Several chemical (acidic media: HCl, HNO3 or CH3COOH, concentration of the reductant as well as type and concentration of oxidazing agents) and physical (reagents flow rates, reaction coil length) parameters affecting the efficiency of plumbane formation were optimized in order to improve the detectability of Pb using HG-ICP-OES. Limitation of the method derived from the matrix effects was pointed out. Employing Pb separation by HG technique allows the significant reduction of interferences caused by sample matrix constituents (mainly Ca and Mg), nevertheless they could not be overcame at all, hence calibration based on the standard addition method was recommended for Pb quantification in dolomites. Under the selected conditions, i.e. 0.3 mol L(-1) HCl, HNO3 or CH3COOH, 1.5% NaBH4 and 3.0% K3[Fe(CN)6] the limits of detection (LODs) between 2.3-5.6 μg L(-1) (3.4-6.8 μg L(-1) considering matrix effects) and the precision below 5% were achieved. The accuracy of the procedure was verified by analysis of certified reference materials (NCS DC70308 (Carbonate Rock) and NIST 14000 (Bone Ash)) and recovery test with satisfactory results of Pb recoveries ranging between 94-108% (CRMs analysis) and 92-114% (standard addition method). The applicability of the proposed method was demonstrated by the determination of Pb in dolomites used by different fertiliser factories.


Changes in late-latency auditory evoked potentials after tinnitus suppression using auditory stimulation.
Tinnitus can result from auditory system reorganization due to neural activity dysfunctions. Auditory stimulation can cause temporary or persistent tinnitus alleviation by altering the neural generators. The present study investigated the changes in Late-Latency Auditory Evoked Potentials (LLAEPs) after tinnitus suppression using auditory stimulation with short-term Residual Inhibition (RI) and long-term Tinnitus Masker (TM). The study included 40 participates with equal numbers in the Tinnitus Group (TG), including the chronic tinnitus subjects, and the Control Group (CG), including matched volunteers. The participants had normal hearing in conventional audiometry. All the participants underwent LLAEP recording pre-intervention and after a one-minute auditory stimulation (RI), as well as a pre-intervention Dichotic Digit Test (DDT) as a behavioral assessment of the selective attention. Moreover, TG underwent a 3-month course of TM, a third LLAEP recording post-TM, a second DDT post-TM, and the Tinnitus Handicap Inventory (THI) before and after the TM. In the baseline LLAEP recording, the TG had significantly later N1, P3a, and P3b latencies, as well as significantly lower P3a and P3b amplitudes. The second LLAEP recording showed a significant intragroup increase in P3a amplitude and a significant decrease in P3a latency in the TG, while no significant intragroup difference was observed in the CG. In the third LLAEP recording performed on TG, the P3a amplitude and latency had significant changes compared to the second recording, while the N1 latency was significantly decreased. Moreover, the DDT and THI scores had significant improvement after the TM in TG. The present study showed the neurophysiological changes after short-term (RI) and long-term (TM) auditory stimulations in tinnitus subjects. The LLAEP changes suggest that these interventions lead to tinnitus suppression through common mechanisms. The electrophysiological observation was also confirmed using behavioral assessments. This study type is a "comparative study" with the level of evidence "3".


Characterization of trace amounts of aluminium in biological reference materials by electrothermal atomic absorption spectrometry.
The homogeneity of aluminium at the ppm level in a set of reference materials provided by Agriculture Canada was determined by electrothermal atomic absorption spectrometry. The materials included bran, wheat flour, gluten, whole egg powder, whole milk powder, meat powder, starch, cellulose, corn kernel and corn stalk. Reproducible values were obtained, which indicated that all of the materials studied can be considered to have a homogeneous distribution of aluminium between samples at test portion sizes of 250 mg. All of the materials, except milk, egg and meat, required HF in addition to HNO3 to effect complete dissolution, indicating the presence of mineral matter.


Metabolic syndrome and all-cause and cardiovascular mortality in an Italian elderly population: the Progetto Veneto Anziani (Pro.V.A.) Study.
The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population. Metabolic syndrome, diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria, all-cause mortality, and cardiovascular mortality, was evaluated in 2,910 subjects aged > or =65 years of the Progetto Veneto Anziani (Pro.V.A.) Study during a mean follow-up time of 4.4 years. After multivariable adjustment, metabolic syndrome was associated with increased all-cause mortality in all subjects (hazard ratio 1.41 [95% CI 1.16-1.72], P = 0.001), among men (1.42 [1.06-1.89], P = 0.017), and among women (1.47 [1.13-1.91], P = 0.004). High glucose in all subjects (1.27 [1.02-1.59], P = 0.037) and in women (1.61 [1.16-2.24], P = 0.005) and low HDL cholesterol in women (1.48 [1.08-2.02], P = 0.014) were predictors of all-cause mortality, even independently of the interactions of different metabolic syndrome components. After multivariable adjustment, metabolic syndrome was also associated with increased cardiovascular mortality in all subjects (1.60 [1.17-2.19], P = 0.003), among men (1.66 [1.00-2.76], P = 0.051), and among women (1.60 [1.06-2.33], P = 0.025). High glucose (2.17 [1.28-3.68], P = 0.004) and low HDL cholesterol (1.78 [1.07-2.95], P = 0.026) among women predicted higher cardiovascular mortality. In this general Italian elderly population, among metabolic syndrome components, all-cause mortality is better predicted by high glucose in all subjects and in women and by low HDL cholesterol in women, whereas cardiovascular mortality is better predicted by high glucose and low HDL cholesterol in women.


Evaluation of knowledge of priapism in sickle cell patients in Senegal.
Erectile dysfunction is a dreadful complication of priapism especially with delay in diagnosis and management. The lack of awareness of priapism as a vaso-occlusive complication of sickle cell disease (SCD) is more concerning. The objective of this study was to evaluate the burden of priapism in adult Senegalese males adults with sickle cell disease. A cross-sectional study was carried out amongst consecutive consenting males aged 18 years and older with SCD presenting to the in Haematology Department of the National Blood Transfusion Centre (Dakar, Senegal). All participants completed a questionnaire detailing knowledge on the definition of priapism, its association with SCD, consequences of untreated priapism and treatment options. A total of 219 participants completed the questionnaire. The mean age of the respondents was 27.1 years with a range of (18-54). Of the respondents, 78.5% (n = 172) did not have any knowledge of the term "priapism". After the term was explained, 38.4% (n = 84) thought that there may be a risk of developing priapism given the diagnosis of sickle cell disease. Among the participants, 41.5% (n = 91) reported having a history of priapism. Among all patients who experienced priapism, 36.3% (n = 33) did not seek medical attention with episodes of priapism. It was found that 48.4% (n = 106) of the participants thought there may be a risk of irreversible complications associated with priapism and a corresponding proportion, 42% (n = 92) thought this risk was time dependent. 36.5% (n = 80) of patients believed priapism could lead to erectile dysfunction. Priapism is a common complication of sickle cell disease in Senegalese adults which is not well known by sickle cell patients. The health authorities must undertake efforts to raise awareness of priapism as a complication amongst sickle cell patients.


Tissue characterization using optical coherence tomography and cone beam computed tomography: a comparative pilot study.
To evaluate the ability of optical coherence tomography (OCT) in differentiating human oral tissues in comparison with cone beam computed tomography. In this study, we imaged four types of tissues ex vivo: human enamel, human cortical bone, human trabecular bone, and fatty tissue plus water and air by using OCT (Axsun Inc., Billerica, MA). We then developed a method for qualitative and quantitative analyses of the human specimens. The same types of tissues were also imaged using cone beam computed tomography, and gray-scale values were measured. The qualitative indices (intensity profile, contour plot, and histogram) for OCT images were able to provide information regarding surface characteristics as well as changes in tissue properties at different interfaces. The quantitative index (pixel intensity values) was also able to render information regarding the distribution and density of the pixels in different samples. A similar pattern was observed in the pixel intensity values and gray-scale values in both imaging modalities. Within the limitations of this ex vivo pilot study, OCT can reliably differentiate between a range of hard and soft tissues.


Psychogenic nonepileptic seizures and health-related quality of life: the relationship with psychological distress and other physical symptoms.
This study explores the relationship between the frequency of psychogenic nonepileptic seizures (PNES) and health-related quality of life (HRQoL), as well as the effect of psychological distress and other physical symptoms on this relationship. Data were collected on 96 patients with PNES. Correlations of seizure frequency with HRQoL, psychological distress, and physical symptoms were computed. Partial correlations of seizure frequency with HRQoL while controlling for psychological distress and physical symptoms were also computed. Seizure frequency was found to be significantly related to subjective HRQoL, although the relationship with HRQoL was rendered nonsignificant when the effects of psychological distress and the number of other physical symptoms were taken into account. The results of this study suggest that summary scores of HRQoL are not independently related to frequency of PNES and that there is a close association between PNES frequency, levels of psychological distress, and number of other physical symptoms experienced.


Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease.
We hypothesized that ABCC2 gene variants may contribute to susceptibility to nonalcoholic fatty liver disease (NAFLD). Additionally, we tested the hypothesis of a relation between gene variants and disease severity. The study involved 167 individuals: 109 consecutively presenting unrelated patients with features of NAFLD and different stages of disease severity, and a group of 58 healthy individuals. Four tag single-nucleotide polymorphisms (SNPs; rs717620 A/G, rs2756105 C/T, rs2002042 C/T and rs3740066 A/G) representing 46 polymorphic sites (r(2)>.8) were genotyped. Furthermore, two additional SNPs (rs17222723 A/T and rs8187710 G/A) were included. On univariate analysis, after multiple comparison correction by permutation tests, there were significant differences observed in the allele frequencies of rs17222723 and rs8187710 between healthy individuals and NAFLD patients (empirical P=.037 and .035, respectively). Allelic odds ratios [95% confidence interval] for rs17222723 and rs8187710 were 2.80 [1.11-7.04] and 2.80 [1.11-7.04], respectively. When we tested the hypothesis of a relation between gene variants and the clinical and histological spectra of NAFLD by multinomial regression analysis, a significant association was observed with the same markers: rs17222723 (P=.0029) and rs8187710 (P=.015). Our study suggests a potential role of ABCC2 in susceptibility to NAFLD and disease severity.


Arsenate removal from water by a weak-base anion exchange fibrous adsorbent.
A weak-base anion exchange fiber named FVA with primary amino groups for selective and rapid removal of arsenate species was prepared by means of electron irradiation induced liquid phase graft polymerization of N-vinylformamide onto polyethylene coated polypropylene fibers and by the subsequent alkaline hydrolysis of amide group on the grafted polymer chains. Two types of FVA were prepared. One was a non-woven cloth type named FVA-c for the batch-mode study, which clarified that uptake of arsenate species decreases with an increase in pH, and chloride and sulfate do not strongly interfere with uptake of arsenate species different from conventional anion exchange resins based on crosslinked polystyrene matrices. The other was a filamentary type one named FVA-f used in the column-mode study, which clarified that arsenate species were successfully removed from neutral pH arsenate solutions containing 1.0-99 mg of As/L at feed flow rates of 100-1050 h(-1) in space velocity (SV). The most important findings are that the 1% breakthrough point in uptake from the arsenate solution containing 1.0mg of As/L at the high feed flow rate of 1050h(-1) in SV was as large as 4670 bed volumes, giving the 1% breakthrough capacity of 0.298 mmol/g of FVA-f. Adsorbed arsenate was able to be quantitatively eluted with 1M hydrochloric acid and FVA-f was simultaneously regenerated. Then, the repeated use of FVA-f was possible.


HE4 and CA125 as preoperative risk stratifiers for lymph node metastasis in endometrioid carcinoma of the endometrium: A retrospective study in a cohort with histological proof of lymph node status.
To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy. Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios. 9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p < 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p < 0.001. Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.


[Tomodensitometric visualization of the pituitary gland in a case of empty sella tucica (author's transl)].
The authors describe a method of using tomodensitometry, after intravenous injection, to demonstrate pituitary remnants in a case of empty sella turcica.


Synthesis and Characterization of a New Copolymer Consisting of Polyamide 1210 and Reactive Phosphorus-Nitrogen Flame-Retardant.
The thermal stability and reactivity of organophosphorus flame-retardants play a critical role in synthesizing copolymerized flame-retardant polyamides. Herein, this work successfully synthesizes a flame-retardant CEPPA-DDA salt (CDS) with both good thermal stability and high reactivity by reacting 2-carboxyethyl phenyl phosphonic acid (CEPPA) with 1,12-dodecanediamine (DDA). Flame-retardant polyamide 1210 (FRPA) is further prepared by copolymerizing the CDS, DDA, and sebacic acid (SEA). The test results show that the introduction of CDS can significantly improve the flame-retardant properties of FRPA. Specifically, the flame-retardant polyamide 1210 (FRPA-7) with 7 wt% CDS addition can reach V-0 grade according to UL-94 standard, accompanying limiting oxygen index value of 30.2% and tensile strength of 38.62 MPa. Compared with pure polyamide 1210, the peak heat release rate and total heat release rate of FRPA-7 reduce by 24.11% and 9.40%, respectively. This study provides a simple strategy to prepare flame-retardant polyamides with high flame retardancy and good mechanical properties, which are expected to show great potentials in future industrial applications.


Association between nasal polyposis, Dubowitz syndrome and hyper-IgE syndrome.
Dubowitz syndrome is a rare, autosomal recessive disorder characterized by intrauterine growth retardation, short stature, microcephaly, distinct facial dysmorphism, and psychomotoric retardation. The hyper-immunoglobulin E (hyper-IgE or Job syndrome) is a primary immunodeficiency characterized by recurrent staphylococcal abscesses, recurrent cyst-forming pneumonia, and an elevated serum IgE level of >2000 IU/ml. We present the first case to our knowledge of an association between Dubowitz syndrome, hyper-IgE syndrome, and nasal polyposis (due to allergic fungal sinusitis) in a 14-year-old girl. Eosinophilic inflammatory reaction is the feature present in all three conditions. Unlike most cases of allergic fungal sinusitis, this case was not treated with an initial booster of oral steroids due to the risk of disseminated invasive fungal infection, reported in other cases of hyper-IgE syndrome. The case and its management is presented and discussed.


Expression Level of IL-17 in Peripheral Blood of Patients with Late Pregnancy and Diagnosis of Maternal-Fetal Tolerance Based on Brain MRI Image Segmentation Algorithm.
To study the expression of IL-17 in peripheral blood and its effect on maternal-fetal tolerance in patients with eclampsia in late pregnancy using MRI image segmentation algorithm. Thirty-nine patients with severe preeclampsia and eclampsia with brain symptoms were examined by cranial MRI. Pregnant women with 32 weeks of pregnancy were selected to detect the percentage of Th17 and Treg cells in CD4 + T lymphocytes and the expression of cytokines IL-17 and IL-10 in peripheral blood. MRI examination was normal in 26 cases, 9 cases showed reversible posterior encephalopathy syndrome, three cases were cerebral hemorrhage, and one case was intracranial cavernous sinus thrombosis. two. Compared with the mild preeclampsia group, the relative number of Thl7 cells increased and that of Treg cells decreased in the severe preeclampsia group (P>0.05). The major types of cerebrovascular diseases (CVD) in severe preeclampsia and eclampsia were reversible posterior encephalopathy syndrome and cerebral hemorrhage. It was speculated that the damage to the blood-brain barrier may play an important role in the pathogenesis. The balance of the number of Th17 cells/the number of Treg cells was more inclined to the Th17 cell-mediated pro-inflammatory state, Treg cell-mediated immune tolerance decreases, and it becomes more obvious with the worsening of the disease.


Klinefelter's syndrome and lupus erythematosus: report of a case.
We report a case of SLE related polyarthritis in a 28 year-old man with Klinefelter's syndrome treated with testosterone for 13 years. Clinical outcome was favorable with low doses of corticosteroids. The pathogenesis of that strange association is discussed.


Oxygen requirements of the isolated rat heart during hypothermic cardioplegia. Effect of oxygenation on metabolic and functional recovery after five hours of arrest.
Previous studies from this laboratory demonstrated that the use of an oxygenated cardioplegic solution in the hypothermic arrested rat heart resulted in improved preservation of high-energy phosphate stores (adenosine triphosphate and creatine phosphate), mechanical recovery during reperfusion, and preservation of myocardial ultrastructure. In the current study the effect of cardioplegic solutions oxygenated with 30%, 60%, and 95% oxygen was evaluated in the isolated rat heart with reference to the maintenance of adenosine triphosphate, creatine phosphate, oxygen consumption, functional recovery, and mitochondrial oxidative phosphorylation in vitro. Results indicate that the hearts receiving cardioplegic solutions supplemented with 95% oxygen and 5% carbon dioxide maintained adenosine triphosphate and creatine phosphate at control values for at least 5 hours. The oxygen consumption during elective cardiac arrest, mechanical performance during reperfusion, and in vitro mitochondrial oxygen uptake and phosphorylation rate were highest in the hearts receiving cardioplegic solutions supplemented with 95% oxygen when compared to solutions with 30% and 60% oxygen. Addition of glucose and insulin to the cardioplegic solution (95% oxygen) increased the adenosine triphosphate levels but failed to improve function after reperfusion. Although myocardial adenosine triphosphate and creatine phosphate were well preserved by the oxygenated cardioplegic solution, there was a discrepancy between the adenosine triphosphate levels at the end of the arrest period, which represents the potential for mechanical function, and the actual function of the hearts after 5 hours.


Context Dependency of Epithelial-to-Mesenchymal Transition for Metastasis.
Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis. The incidence of metastasis was much higher in SCCs presenting EMT compared to SCCs without EMT, supporting the notion that a certain degree of EMT is required to initiate the metastatic cascade in primary skin SCCs. Most circulating tumor cells presented EMT, whereas most lung metastasis did not present EMT, showing that mesenchymal-to-epithelial transition is important for metastatic colonization. In contrast, immunodeficient mice transplanted with SCCs, whether displaying EMT or not, presented metastasis. Altogether, our data demonstrate that the association of EMT and metastasis is model dependent, and metastasis of primary skin SCCs is associated with EMT.


Increased physical activity reduces prevalence of periodontitis.
Physical activity has been shown to have a protective relationship with several chronic diseases. Recently, physical activity was also found to reduce the risk of periodontitis in a study in male health professionals. However, the relationship between physical activity and periodontitis in a diverse group of individuals is not thoroughly examined. The purpose of this study was to examine if there is an association between sustained physical activity and periodontitis in a subset of the third national health and nutrition examination survey (NHANES III). NHANES III participants 18 years of age or older who had had a periodontal examination and reported to have a similar physical activity (or inactivity) level for 10 years or longer were selected (n=2521). Multivariable logistic regression analysis was used to estimate the association between physical activity and periodontitis. The analysis was adjusted for: age, gender, race, education, smoking, body mass index, poverty index, vitamin use, healthy eating index, time since last dental visit, gingival bleeding, and dental calculus. Engaging in the recommended level of physical activity was significantly associated with lower periodontitis prevalence (OR=0.58, 95% CI, 0.35-0.96). Smoking, however, was found to modify this relationship. The association was strong and significant among never (OR=0.46, 95% CI, 0.23-0.93) and former smokers (OR=0.26, 95% CI: 0.09-0.72), but not among current smokers (OR=1.10, 95% CI: 0.48-2.53). These results suggest that engaging in the recommended level of exercise is associated with lower periodontitis prevalence, especially among never and former smokers.


In vivo quantification of the cat patellofemoral joint contact stresses and areas.
A new method for in vivo measurement of patellofemoral joint contact areas, stresses, and patellar displacements, with joint loading approximating physiologic conditions was developed. Joint contact measurements were obtained using pressure sensitive film inserted directly between articular joint surfaces. Two-dimensional joint kinematics were measured using a high-speed video based motion analysis system. Joint loading, provided by quadriceps muscle stimulation, was measured with an implantable force transducer (IFT). Variations in joint mechanics as a function of joint flexion angle, joint loading and joint stability (anterior cruciate ligament intact or transected) were determined for four adult male cats. The contact measurements obtained with the pressure sensitive film displayed high repeatability with a standard error of +/- 6.8% of the mean value of the median pressure and +/- 4.4% of the mean contact area value. Substantial differences in joint mechanics were reliably detected with the new technique. The influence of experimental procedures, such as incisions in the joint capsule and insertion of pressure sensitive film between the articular surfaces, produced minimal changes in the joint kinematics during muscular contraction.


Temperature influence on the NAPL-water interfacial area between 10 °C and 60 °C for trichloroethylene.
Underground thermal energy storage (UTES) can contribute to renewable energy usability, especially in urban areas with the most demand and available infrastructure. But UTES may interact in those areas with non-aqueous phase liquids (NAPL) by increasing the temperature in storage formations. To determine temperature effects on NAPL dissolution rates into groundwater, the effective specific interfacial area (anw) between trichloroethylene (TCE) and water, as a function of temperature and TCE pore saturations, was calculated. The interfacial tension between the flushing solution and the NAPL, the adsorption coefficient and the retardation of a reactive tracer were determined by the drop weight method and interfacial tracer tests at 10 °C, 30 °C and 60 °C. From 10 to 60 °C anw increased by a factor of six to eight. Based on the results, a function to describe the anw between TCE and water was developed, which could improve numerical models on NAPL dissolution rates. The main mechanisms for the increase in anw are suggested to be NAPL blob migration on pore scale, and thermal-induced changes in wettability and in blob shape correlating with a temperature-induced decline in effective porosity of up to 32%. These results contribute to the understanding and predictability of UTES in contaminated aquifers, the general response of NAPL behavior on artificial increasing aquifer temperatures and the improvement of thermal and other groundwater remediation techniques.


Development of an integrated sensor to measure odors.
Odorous air samples collected from several sources were presented to an olfactometer, an electronic nose, a hydrogen sulfide (H(2)S) detector and an ammonia (NH(3)) detector. The olfactometry measurements were used as the expected values while measurements from the other instrumentation values became input variables. Five hypotheses were established to relate the input variables and the expected values. Both linear regression and artificial neural network analyses were used to test the hypotheses. Principal component analysis was utilized to reduce the dimensionality of the electronic nose measurements from 33 to 3 without significant loss of information. The electronic nose or the H(2)S detector can individually predict odor concentration measurements with similar accuracy (R(2) = 0.46 and 0.50, respectively). Although the NH(3) detector alone has a very poor relationship with odor concentration measurements, combining the H(2)S and NH(3) detectors can predict odor concentrations more accurately (R(2) = 0.58) than either individual instrument. Data from the integration of the electronic nose, H(2)S, and NH(3) detectors produce the best prediction of odor concentrations (R(2) = 0.75). With this accuracy, odor concentration measurements can be confidently represented by integrating an electronic nose, and H(2)S and NH(3) detectors.


A {0001} faceted single crystal NiS nanosheet electrocatalyst for dye-sensitised solar cells: sulfur-vacancy induced electrocatalytic activity.
Hydrothermally synthesised single crystal NiS nanosheets with an exposed (0001) surface exhibited a light conversion efficiency of 8.62% as an electrocatalyst for dye-sensitised solar cells (DSSCs), significantly higher than that of Pt-based DSSCs (7.36%). The theoretical calculations revealed the exposed (0001) surface with superior catalytic activity owing to the existence of sulfur vacancies.


Evidence of linkage disequilibrium between polymorphisms at the IRF6 locus and isolate tooth agenesis, in a Turkish population.
Recently, the IRF6 contribution that was reported for Van der Woude syndrome and non-syndromic oral clefts was extended to isolated tooth agenesis. Here we report the first study that tries to replicate this finding and we provide further evidence that IRF6 contributes to isolated tooth agenesis. Fifty-two sporadic tooth agenesis cases and their parents were studied. DNA samples were obtained from whole blood or saliva samples. Genotyping was performed by TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. A haplotype involving the most 5'IRF6 markers was associated with sporadic tooth agenesis (p=0.006). An association could still be seen when only cases with at least one missing incisor (p=0.01) and cases with at least one missing premolar (p=0.004) were included in the analysis.


Movement speed effects on beta-band oscillations in sensorimotor cortex during voluntary activity.
Beta-band oscillations are a dominant feature in the sensorimotor system, which includes movement-related beta desynchronization (MRBD) during the preparation and execution phases of movement and postmovement beta synchronization (PMBS) on movement cessation. Many studies have linked this rhythm to motor functions. However, its associations to the movement speed are still unclear. We make a hypothesis that PMBS will be modulated with increasing of movement speeds. We assessed the MRBD and PMBS during isotonic slower self-paced and ballistic movements with 15 healthy subjects. Furthermore, we conduct an additional control experiment with the isometric contraction with two levels of forces to match those in the isotonic slower self-paced and ballistic movements separately. We found that the amplitude of PMBS but not MRBD in motor cortex is modulated by the speed during voluntary movement. PMBS was positively correlated with movement speed and acceleration through the partial correlation analysis. However, there were no changes in the PMBS and MRBD during the isometric contraction with two levels of forces. These results demonstrate a different function of PMBS and MRBD to the movement speed during voluntary activity and suggest that the movement speed would affect the amplitude of PMBS.NEW & NOTEWORTHY Beta-band oscillations are a dominant feature in the sensorimotor system that associate to the motor function. We found that the movement-related postmovement beta synchronization (PMBS) over the contralateral sensorimotor cortex was positively correlated with the speed of a voluntary movement, but the movement-related beta desynchronization (MRBD) was not. Our results show a differential response of the PMBS and MRBD to the movement speed during voluntary movement.


Transient Formation of Hemiketals from Pentafluoro-gem-diols in the Presence of Alcohols.
Pentafluoro-gem-diols have emerged as a source of reactive intermediates for synthesizing fluorinated molecules. When pentafluoro-gem-diols were exposed to alcohols as solvents, the formation of transient hemiketals was detected by 19F NMR. The conversion rates to hemiketals were found to be higher with primary alcohols than with secondary or fluorinated alcohols. These findings provide valuable insight for developing novel techniques to construct intricate fluorinated structures using pentafluoro-gem-diols.


Insulin secretion and sensitivity before and after surgical treatment for aldosterone-producing adenoma.
Primary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed. To assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic-euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27-559 (194±132) days, and 14-142 (51±38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic-euglycaemic clamp analyses were evaluated. Surgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic-euglycaemic clamp was reduced after surgery. Primary aldosteronism impairs insulin secretion.


[Shared decision making in involuntary treatment: four case studies from court ordered psychiatric treatment].
Shared decision making (SDM) can result in better treatment outcomes. Little is known about the practice of SDM in forensic psychiatry; a context in which not only psychiatric problems are present, but also freedom restrictions and involuntary hospitalisation. To explore the current degree of SDM in a forensic psychiatric setting and to identify factors that influence SDM. Semi-structured interviews (n = 4 triads: treatment coordinator, sociotherapeutic mentor and patient) combined with scores on questionnaires (SDM-Q-Doc and SDM-Q-9). The SDM-Q showed a relatively high degree of SDM. Themes like cognitive and executive functions of the patient, subcultural differences, insight into the disease and reciprocal cooperation appeared to influence the SDM. In addition, SDM in forensic psychiatry appeared to be more of a means of improving communication about the decisions of the treatment team than truly 'shared' decision making. This first exploration shows that SDM is applied in forensic psychiatry, however operationalised differently than the theory behind SDM prescribes.


Should Organizational Investment in Robotic Surgical Technology Ever Influence Surgeons' Decisions About Surgical Approach to Patients' Surgical Care?
This commentary on a case considers balancing prospective benefits and harms of robotic technology use and argues that health care organizations should invest in centralizing robotic expertise in departments rather than having a mere collection of surgeons trained in robotics. This commentary also examines costs that should be considered in organizational determinations of robotics investments.


Public health, epidemiology and war.
The delivery of humanitarian aid in wartime is difficult. However, it is essential that aid is provided in the most effective manner possible, targeted on those most in need whilst minimizing waste. Furthermore the delivery of aid should be sensitive to the future needs of the communities in conflict. This requires information on the needs of the vulnerable population. There is little experience of collecting data on the impact of war on a civilian population. The war in Bosnia disrupted surveillance of communicable disease. The local authorities were assisted by the World Health Organization in re-establishing surveillance. The data generated was valuable in planning interventions to minimise the possibility of major outbreaks of infection, reduce the impact of infectious disease and in guiding the humanitarian aid effort. The experience described suggests that public health surveillance of the civilian population in wartime is possible and useful. Besides the need for planning, the public health doctor in wartime has a role as an advocate for those suffering; this function can be carried out much more effectively if it is based on objective data collection rather than hearsay.


Critical illness is associated with decreased plasma levels of coenzyme Q10: a cross-sectional study.
Plasma coenzyme Q10 (CoQ10) levels are lower in patients with septic shock (SS) than in healthy controls (HCs). However, CoQ10 status in critically ill patients without SS is unknown. Here, we investigated CoQ10 concentrations in patients with SS and without SS as compared with HCs. We enrolled 36 critically ill patients and 18 HCs. Plasma CoQ10 concentrations were measured, and patients' clinical and demographical data were collected. Plasma CoQ10 concentrations were lower in critically ill patients (0.50±0.36 μg/mL, P<.001), both in patients with SS (0.37±0.25 μg/mL, P=.002) and patients without SS (0.56±0.39, P=.04), as compared with HCs (0.79±0.19). Coenzyme Q10 levels did not differ between patients with SS and patients without SS (P=.13). In critically ill patients, CoQ10 levels inversely correlated with age (r=-0.40, P=.015) and did not correlate with partial pressure of oxygen in the arterial blood/fraction of inspired oxygen, Simplified Acute Physiology Score II, Systemic Organ Failure Assessment score, or mortality. Lower CoQ10 levels were associated with lower activities of daily living score after discharge (P=.005), independent of age. Decreased plasma CoQ10 levels are not specific to patients with SS, but rather observed in a broad range of critically ill patients. In critically ill patients, CoQ10 insufficiency may be associated with various conditions; age may be a risk factor.


The impact on health and risk factors of the diarrhoea epidemics in the 1998 Bangladesh floods.
The 1998 flood in Bangladesh ravaged approximately 60% of the land and affected over 30 million people. The aim of this study is to examine the impact of the flood on the health of the communities affected and to explore factors associated with episodes of diarrhoea. We conducted structured interviews with 517 people in two districts that had been affected in October 1998, when the flood water level was at its peak. Of the 517 respondents, 98.3% developed health problems or found that existing health problems were exacerbated. Many perceived that their general health condition was 'much worse' (16.9%) or 'worse' (64.3%). The most prevalent condition was fever (63.6%), followed by respiratory problems (46.8%), diarrhoea (44.3%), and skin problems (41.0%). Only 1.0% and 6.7% of the respondents treated water before drinking, by boiling and chlorination, respectively, although water collected from tube-wells (93.2%) and rivers (6.0%) was perceived by 75.0% of the respondents to be contaminated. Factors associated with developing or worsening diarrhoea were as follows; the number of family members, poor economic status, a lack of distribution of water purification tablets, the type of water storage vessels, not putting a lid on the vessel, no use of latrines, perceived change of drinking water, food scarcity, and worries about the future. In logistic regression analysis, men, poor economic status, lack of distribution of water purification tablets, and the type of water storage vessels had a significant association with diarrhoea. The 1998 Bangladesh flood had a substantial impact on the health of communities. Diarrhoea was associated with socioeconomic status, water handling and household sanitation. There ought to be more emphasis on health education in the pre-disaster period in order to empower communities against floods.


Familial coaggregation of major psychiatric disorders in first-degree relatives of individuals with autism spectrum disorder: a nationwide population-based study.
Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive. This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID). FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50-19.67), ADHD 3.94 (CI 3.72-4.17), schizophrenia 3.05 (CI 2.74-3.40), BD 2.22 (CI 1.98-2.48) and MDD 1.88 (CI 1.76-2.00). Higher RRs of schizophrenia (4.47, CI 3.95-5.06) and ASD (18.54, CI 16.18-21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only. The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.


Process intensification in continuous flow biocatalysis by up and downstream processing strategies.
In this review, we focus on the holistic continuous enzymatic production and put special emphasis on process intensification by up- and downstream processing in continuous flow biocatalysis. After a brief introduction, we provide an overview of current examples of enzyme immobilization as an upstream process for flow biocatalysis. Thereafter, we provide an overview of unit operations as downstream processing strategies, namely continuous (i) liquid-liquid extraction, (ii) adsorptive downstream processing, and (iii) crystallization and precipitation. Eventually, we present our perspectives on future trends in this research field.


Increased contrast enhancing lesion activity in relapsing-remitting multiple sclerosis migraine patients.
While the literature supports the idea that multiple sclerosis (MS) and migraine are related, the exact mechanism(s) of this association is not well understood. Observations of increased contrast enhancing (CE) lesion activity in individual MS patients suffering from migraine prompted us to determine a relationship between migraine and MRI outcomes in a large cohort of MS patients. We included 509 MS and 64 clinically isolated syndrome (CIS) patients and 251 age- and sex-matched healthy individuals (HIs) who obtained 3 T MRI and were assessed for history of migraine. Number and volume of T2, T1 and CE lesions and brain volume measures were determined. The MRI findings were analyzed adjusting for key covariates and correcting for multiple comparisons. More MS (22.2%) and CIS (17.2%) patients had migraine, compared to HIs (14.6%, p = 0.067). More MS patients with migraine presented with CE lesions compared to those without (35.4% vs. 23.7%, p = 0.013). MS migraine patients had significantly increased number (p = 0.019) and volume (p = 0.022) of CE lesions compared to those without. In the regression analysis, MS migraine patients had an increased number of CE lesions (B = 1.242, p = 0.001), specifically those with relapsing-remitting disease course (B = 1.377, p = 0.001). No significant association of other MRI measures and migraine was found in MS and CIS patients or in HIs. Our findings suggest an increased inflammatory pathobiology in MS patients with migraine headaches requiring possibly more frequent MRIs and also more efficient anti-inflammatory treatment.


Elimination of acetate production to improve ethanol yield during continuous synthesis gas fermentation by engineered biocatalyst Clostridium sp. MTEtOH550.
Acetogen strain Clostridum sp. MT653 produced acetate 273 mM (p < 0.005) and ethanol 250 mM (p < 0.005) from synthesis gas blend mixture of 64% CO and 36% H(2). Clostridum sp. MT653 was metabolically engineered to the biocatalyst strain Clostridium sp. MTEtOH550. The biocatalyst increased ethanol yield to 590 mM with no acetate production during single-stage continuous syngas fermentation due to expression of synthetic adh cloned in a multi-copy number expression vector. The acetate production was eliminated by inactivation of the pta gene in Clostridium sp. MTEtOH550. Gene introduction and gene elimination were achieved only using Syngas Biofuels Energy, Inc. electroporation generator. The electrotransformation efficiencies were 8.0 ± 0.2 × 10(6) per microgram of transforming DNA of the expression vector at cell viability ~15%. The frequency of suicidal vector integration to inactivate pta was ~10(-5) per the number of recipient cells. This is the first report on elimination of acetate production and overexpression of synthetic adh gene to engineer acetogen biocatalyst for selective biofuel ethanol production during continuous syngas fermentation.


ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis.
Epithelial-mesenchymal transition (EMT) has fundamental roles in various biological processes. However, there are still questions pending in this fast-moving field. Here we report that in TGFβ-induced EMT, ERK-mediated Smurf1 phosphorylation is a prerequisite step for RhoA degradation and the consequent mesenchymal state achievement. Upon TGFβ treatment, activated ERK phosphorylates Thr223 of Smurf1, a member of HECT family E3 ligase, to promote Smurf1-mediated polyubiquitination and degradation of RhoA, thereby leading to cell skeleton rearrangement and EMT. Blockade of phosphorylation of Smurf1 inhibits TGFβ-induced EMT, and accordingly, dramatically blocks lung metastasis of murine breast cancer in mice. Hence, our study reveals an unknown role of ERK in TGFβ-induced EMT and points out a potential strategy in therapeutic intervention.


Prospective associations between intervention components and website engagement in a publicly available physical activity website: the case of 10,000 Steps Australia.
Effectiveness of and engagement with website-delivered physical activity interventions is moderate at best. Increased exposure to Internet interventions is reported to increase their effectiveness; however, there is a lack of knowledge about which specific intervention elements are able to maintain website engagement. To prospectively study the associations of website engagement and exposure to intervention components for a publicly available physical activity website (10,000 Steps Australia). Between June and July 2006 a total of 348 members of 10,000 Steps completed a Web-based survey to collect demographic characteristics. Website engagement was subsequently assessed over a 2-year period and included engagement data on website components; individual challenges, team challenges, and virtual walking buddies; and indicators of website engagement (average steps logged, days logging steps, and active users). On average participants logged steps on 169 (SD 228.25) days. Over a 2-year period this equated to an average of 1.6 logons per week. Binary logistic regression showed that individuals who participated in individual challenges were more likely to achieve an average of 10,000 steps per day (odds ratio [OR] = 2.80, 95% confidence interval [CI] 1.45-5.40), log steps on a higher than average number of days (OR = 6.81, 95% CI 2.87-13.31), and remain an active user (OR = 4.36, 95% CI 2.17-8.71). Additionally, those using virtual walking buddies (OR = 5.83, 95% CI 1.27-26.80) and of older age logged steps on a higher than average number of days. No significant associations were found for team challenges. Overall engagement with the 10,000 Steps website was high, and the results demonstrate the relative effectiveness of interactive components to enhance website engagement. However, only exposure to the interactive individual challenge feature was positively associated with all website engagement indicators. More research is needed to examine the influence of intervention components on website engagement, as well as the relationship between website engagement and physical activity change.


Effects of soil pH and organic carbon content on in vitro Cr bioaccessibility in Ultisol, Alfisol, and Inceptisol.
Hexavalent chromium (Cr(VI)) is a toxic heavy metal and its mobility and bioaccessibility in soils are influenced by soil properties. In this study, the soil pH and organic carbon contents of Ultisol, Alfisol, and Inceptisol were adjusted before they were polluted with 230 mg kg-1 Cr(VI). Alkaline digestion, sequential extraction, and an in vitro experiment were conducted to study the valence state, species, and bioaccessibility of Cr in the soils. The results showed that a high soil pH was not favorable for reduction of Cr(VI); therefore the Cr(VI) and exchangeable Cr contents were positively related to soil pH. Soil organic carbon promoted the reduction of Cr(VI). Almost all Cr(VI) was reduced to Cr(III) when the soil organic carbon content reached 10 g kg-1. Chromium bioaccessibility in simulated gastric and intestinal phase solutions was influenced by Cr(VI) and Cr(III) adsorption/desorption, dissolution/precipitation, and redox reactions. Chromium bioaccessibility differences between the gastric and intestinal phases were associated with the Cr(VI)/Cr(III) ratio. Acidic conditions and a high organic carbon content promoted the conversion of Cr(VI) to Cr(III). When soil pH was increased from 4.01 to 5.85, Cr(VI) in Alfisol without the addition of humic acid increased from 96.38 to 174.78 mg kg-1, the exchangeable Cr proportion increased from 9.7% to 22.6%, and Cr bioaccessibility increased from 41.29% to 49.14% in the gastric phase and from 41.32% to 48.24% in the intestinal phase. When the organic carbon content increased from 3.95 to 9.28 g kg-1 in Alfisol, Cr(VI) content decreased from 167.66 to 20.52 mg kg-1, which led to a decrease in Cr bioaccessibility from 49.15% to 13.8% in the gastric phase and from 45.85% to 7.67% in the intestinal phase. Therefore, acidic conditions and increasing soil organic carbon levels can reduce the health risk posed by Cr in soils.


A study of the human hair structure with a Zernike phase contrast X-ray microscope.
We have observed the internal structure of human hair shafts with a transmission Zernike phase contrast hard X-ray microscope. Due to the high spatial resolution and the high contrast of the microscope, we could image scales, macrofibrils, medulla and melanin without staining. The structure of a black hair shaft is compared with that of a white one.


Categories and causality: the neglected direction.
The standard approach guiding research on the relationship between categories and causality views categories as reflecting causal relations in the world. We provide evidence that the opposite direction also holds: categories that have been acquired in previous learning contexts may influence subsequent causal learning. In three experiments we show that identical causal learning input yields different attributions of causal capacity depending on the pre-existing categories to which the learning exemplars are assigned. There is a strong tendency to continue to use old conceptual schemes rather than switch to new ones even when the old categories are not optimal for predicting the new effect, and when they were motivated by goals that differed from the present context of causal discovery. However, we also found that the use of prior categories is dependent on the match between categories and causal effect. Whenever the category labels suggest natural kinds which can be plausibly related to the causal effects, transfer was observed. When the categories were arbitrary, or could not be plausibly related to the causal effect learners abandoned the categories, and used different categories to predict the causal effect.


Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice.
The classical motor symptoms of Parkinson's disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuroprotection. We investigated the neuroprotective and disease-modifying potential of physical exercise in a preclinical animal model of PD. C57BL/6 mice (adult males) ran on a horizontal treadmill for 6 weeks (moderate intensity, 5 times/week) and were treated intranasally with 65 mg/kg of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exercise did not protect against MPTP-induced nigrostriatal neurodegeneration or frontostriatal dopamine depletion but decreased striatal dopamine turnover. Exercise also attenuated procedural and working memory impairment and D2 receptor hypersensitivity in MPTP-treated mice. In summary, exercise improved dopaminergic neurotransmission and enhanced cognition in a preclinical animal model of PD.


Conjoined twins and opocephaly in guinea-pigs: 4 cases of congenital malformation.
A case of opocephaly in inbred guinea-pig strain 2/N and another in strain 13/N, a conjoined twin and an opocephaly concurrent with conjoined twins in the Dunkin-Hartley/FD strain are described. The incidence of congenital malformations in the inbred strain 2/N and strain 13/N was 0-0013 and 0-0073% respectively. The incidence in the random-bred Dunkin-Hartley/FD strain was 0-0007%.


MYB4 transcription factor, a member of R2R3-subfamily of MYB domain protein, regulates cadmium tolerance via enhanced protection against oxidative damage and increases expression of PCS1 and MT1C in Arabidopsis.
Here, we describe functional characterization of Arabidopsis thaliana MYB4 transcription factor, a member of R2R3-subfamily of MYB domain protein, in the regulation of Cd-stress tolerance in Arabidopsis. Transgenic Arabidopsis plants overexpressing MYB4 showed appreciable Cd tolerance than wild-type plants, while MYB4 loss of function mutant lines (atmyb4) showed increased sensitivity to Cd-stress. MYB4 overexpression lines showed strong activation of anti-oxidant defense components and increased Cd accumulation than wild-type and atmyb4 mutant lines under Cd-stress. MYB4 overexpression resulted in the coordinated activation of the expression of phytochelatin (PC) synthesis related genes and specifically enhanced the transcript abundance of phytochelatin synthase 1 (PCS1) and metallothionein 1C (MT1C) genes under Cd-stress. In contrast, atmyb4 mutant lines showed reduced Cd accumulation and compromised expression of PC-synthesis related genes. Electrophoretic gel mobility shift assays have demonstrated specific binding activity of recombinant AtMYB4 to the putative MYB4-binding motifs ACCAACCAA and GGTAGGT identified in the promoters of PCS1 and MT1C genes, respectively. Further analyses have revealed that MYB4 binds directly to PCS1 and MT1C promoters in vivo and positively regulates their transcriptional expression, suggesting that PCS1 and MT1C are the key targets of MYB4. Overall, our results have provided evidence that MYB4 regulates Cd-tolerance via the coordinated activity of improved anti-oxidant defense system and through the enhanced expression of PCS1 and MT1C under Cd-stress in Arabidopsis.


Assessment of behavioural effects of three water-soluble polymers in zebrafish embryos.
The water-soluble polymers (WSPs) are widely used in many industrial applications and are present in several commonly used products due to their physical-chemical characteristics: as their name indicates, despite being synthetic polymers, they are able to solubilize in water. Because of this peculiar property, both the qualitative-quantitative evaluation in aquatic ecosystems and their potential (eco)toxicological effects have been neglected until now. The aim of this study was to evaluate the possible effects of three of the most widely used WSPs as polyacrylic acid (PAA), polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) on the swimming behaviour of zebrafish (Danio rerio) embryos after the exposure to different concentrations (0.001, 0.5, 1 mg/L). The exposure lasted from the eggs' collection up to 120 h post fertilization (hpf) also using three different light intensity (300 lx, 2200 lx, 4400 lx) to better evaluate any effects related to different gradients of light/dark transitions. In order to analyze individual behavioural changes in embryos, their swimming movements were tracked and a number of parameters for locomotion and directionality were quantified. The main results showed that all three WSPs resulted in significant (p ≤ 0.05) variations in different movement parameters, suggesting a possible toxicity scale: PVP > PEG ≫ PAA.


Assessment of early anthracycline-induced cardiotoxicity and liver injury with T2 and T2* mapping in rabbit models.
To evaluate the early prevalence of anthracycline-induced cardiotoxicity (AIC) and anthracycline-induced liver injury (AILI) using T2 and T2* mapping and to explore their correlations. The study included 17 cardiotoxic rabbits that received weekly injections of doxorubicin and magnetic resonance imaging (MRI) every 2 weeks for 10 weeks. Cardiac function and T2 and T2* values were measured on each period. Histopathological examinations for two to five rabbits were performed after each MRI scan. The earliest sensitive time and the threshold of MRI parameters for detecting AIC and AILI based on these MRI parameters were obtained. Moreover, the relationship between myocardial and liver damage was assessed. Early AIC could be detected by T2 mapping as early as the second week and focused on the 7th, 11th, and 12th segments of left ventricle. The cutoff value of 46.64 for the 7th segment had the best diagnostic value, with an area under the curve (of 0.767, sensitivity of 100%, and specificity of 52%. T2* mapping could detect the change in iron content for early AIC at the middle interventricular septum and AILI as early as the sixth week (p = 0.014, p = 0.027). The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver (r = 0.39, p = 0.002). T2 and T2* mapping showed value one-stop assessment of AIC and AILI and could obtain the earliest MRI diagnosis point and optimal parameter thresholds for these conditions. Anthracycline-induced cardiotoxicity could be detected by T2 mapping as earlier as the second week, mainly focusing on the 7th, 11th, and 12th segments of left ventricle. Combined with T2* mapping, hepatoxicity and supplementary cardiotoxicity were assessed by one-stop scan. • MRI screening time of cardiotoxicity was as early as the second week with focusing on T2 values of the 7th, 11th, and 12th segments of left ventricle. • T2* mapping could be used as a complement to T2 mapping to evaluate cardiotoxicity and as an effective index to detect iron change in the early stages of chemotherapy. • The T2* values of the middle interventricular septum showed a significant positive association with the T2* values of the liver, indicating that iron content in the liver and heart increased with an increase in the chemotherapeutic drugs.


Lipid kinase PIP5Kα contributes to Hippo pathway activation via interaction with Merlin and by mediating plasma membrane targeting of LATS1.
The Hippo pathway plays a critical role in controlled cell proliferation. The tumor suppressor Merlin and large tumor suppressor kinase 1 (LATS1) mediate activation of Hippo pathway, consequently inhibiting the primary effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid present in the plasma membrane (PM), binds to and activates Merlin. Phosphatidylinositol 4-phosphate 5-kinase α (PIP5Kα) is an enzyme responsible for PIP2 production. However, the functional role of PIP5Kα in regulation of Merlin and LATS1 under Hippo signaling conditions remains unclear. PIP5Kα, Merlin, or LATS1 knockout or knockdown cells and transfected cells with them were used. LATS1, YAP, and TAZ activities were measured using biochemical methods and PIP2 levels were evaluated using cell imaging. Low/high cell density and serum starvation/stimulation conditions were tested. Colocalization of PIP5Kα and PIP2 with Merlin and LATS1, and their protein interactions were examined using transfection, confocal imaging, immunoprecipitation, western blotting, and/or pull-down experiments. Colony formation and adipocyte differentiation assays were performed. We found that PIP5Kα induced LATS1 activation and YAP/TAZ inhibition in a kinase activity-dependent manner. Consistent with these findings, PIP5Kα suppressed cell proliferation and enhanced adipocyte differentiation of mesenchymal stem cells. Moreover, PIP5Kα protein stability and PIP2 levels were elevated at high cell density compared with those at low cell density, and both PIP2 and YAP phosphorylation levels initially declined, then recovered upon serum stimulation. Under these conditions, YAP/TAZ activity was aberrantly regulated by PIP5Kα deficiency. Mechanistically, either Merlin deficiency or LATS1 deficiency abrogated PIP5Kα-mediated YAP/TAZ inactivation. Additionally, the catalytic domain of PIP5Kα directly interacted with the band 4.1/ezrin/radixin/moesin domain of Merlin, and this interaction reinforced interaction of Merlin with LATS1. In accordance with these findings, PIP5Kα and PIP2 colocalized with Merlin and LATS1 in the PM. In PIP5Kα-deficient cells, Merlin colocalization with PIP2 was reduced, and LATS1 solubility increased. Collectively, our results support that PIP5Kα serves as an activator of the Hippo pathway through interaction and colocalization with Merlin, which promotes PIP2-dependent Merlin activation and induces local recruitment of LATS1 to the PIP2-rich PM and its activation, thereby negatively regulating YAP/TAZ activity. Video Abstract.


Effects of Hemolysis on Routine Coagulation Tests when Tested on an Optical Coagulation Analyzer.
The Clinical and Laboratory Standards Institute recommends rejecting hemolyzed samples for coagulation tests. Sysmex CS5100 analyzer using an optical method is commonly used in laboratories. The influence of hemolysis on coagulation test has rarely been studied when tested on Sysmex CS5100. Determining this influence is necessary. Freshly collected samples were artificially hemolyzed to simulate the hemolysis processes. Coagulation tests were conducted on a Sysmex CS5100 coagulation analyzer. Detection values before and after hemolysis were compared. The results showed that after hemolysis detection, the prothrombin time (PT) statistically decreased, while the partial thromboplastin time (APTT) statistically increased. There were no significant differences in fibrinogen (Fg), thrombin time (TT), D-dimer (DD) or fibrinogen degradation products (FDPs). Antithrombin activity was elevated in hemolyzed samples. Although differences in PT and APTT were statistically significant, there was no need for rejection of hemolyzed samples due to insufficient clinical effects when tested on Sysmex CS5100 analyzer. Falsely elevated AT result may lead to misdiagnosis in patients with severe diseases, which should be carefully considered.


Dot or pointillistic method for improvement in results of hypertrophic scarring in the argon laser treatment of portwine hemangiomas.
In an attempt to limit scarring, 51 patients have been treated over a period of 2 years with the argon laser in a dot or pointillistic fashion. One- to 2-mm dots are blanched at intervals of 1-2 mm with minimal power, and the interspaces are filled in at 12 weeks. Scar-prone areas of the face such as the upper lip, nasolabial fold, nose, and lower lip have been successfully treated with minimal scarring and good fading. Lesions of the trunk and extremity have also been successfully treated.


Superficial siderosis of the central nervous system.
Two patients with superficial siderosis of the central nervous system are reported. Both developed progressive deafness over many years; one with associated anosmia and partial seizures; the other with progressive ataxia and diplopia. The cerebrospinal fluid was xanthochromic in one and the protein was raised in both. Magnetic resonance imaging revealed a hypodense rim around the eighth cranial nerve, cerebellum, brain stem and spinal cord. Despite extensive investigations the cause of the superficial siderosis in both patients remains undetermined.


A hybrid approach to full-scale reconstruction of renal arterial network.
The renal vasculature, acting as a resource distribution network, plays an important role in both the physiology and pathophysiology of the kidney. However, no imaging techniques allow an assessment of the structure and function of the renal vasculature due to limited spatial and temporal resolution. To develop realistic computer simulations of renal function, and to develop new image-based diagnostic methods based on artificial intelligence, it is necessary to have a realistic full-scale model of the renal vasculature. We propose a hybrid framework to build subject-specific models of the renal vascular network by using semi-automated segmentation of large arteries and estimation of cortex area from a micro-CT scan as a starting point, and by adopting the Global Constructive Optimization algorithm for generating smaller vessels. Our results show a close agreement between the reconstructed vasculature and existing anatomical data obtained from a rat kidney with respect to morphometric and hemodynamic parameters.


Surgical management of ovarian tumors without the support of intraoperative pathology readings in Bhaktapur Cancer Hospital.
Intraoperative frozen section plays an important role in surgical management of ovarian masses. Many hospitals in low- and middle-income countries lack this intraoperative pathologic guidance. In this retrospective analysis, we assessed the management of 62 patients who underwent surgical treatment for ovarian masses at Bhaktapur Cancer Hospital in Nepal in light of the final histopathology results. Final histopathology found that 64.5% of the ovarian masses were malignant, 1.0% were borderline, and 30.6% were benign. 55 of the 62 total cases were considered "clinically suspicious" and 52 of the 62 cases underwent hysterectomy and staging procedures in addition to oophorectomy. There was no significant difference in the surgical management or in the postoperative complications when comparing benign, borderline, and malignant masses. Without the support of intraoperative frozen section, benign and malignant masses were treated the same way. The majority of benign cases were overtreated and were exposed to additional risks of postoperative complications. Several malignant cases were undertreated and required additional surgery to appropriately treat and stage malignant ovarian masses. Improved pathology support in Bhaktapur Cancer Hospital would result in better patient outcomes, fewer complications, and avoidance of additional staging surgeries.


TRH-extended peptides in the olfactory lobe are formed by incomplete cleavage at pairs of arginine residues in the TRH prohormone.
High concentrations of thyrotrophin-releasing hormone (TRH) are known to be present in the olfactory lobe, and the processing of the TRH prohormone in this region of the brain has been examined in this study. TRH-extended peptides have been detected in the rat olfactory lobe: these peptides accounted for approximately 11% of the total TRH immunoreactivity present in the tissue and contained the sequence pGlu-His-Pro-Gly-Arg exclusively at their N-termini. Extended peptides containing pGlu-His-Pro-Gly-Lys at their N-termini were not detected suggesting that incomplete cleavage occurs only at Arg-Arg residues in the TRH-prohormone. In view of the highly specific processing of the prohormone, it is likely that the TRH-extended peptides play important physiological roles.


Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10-Color flow cytometry diagnosis and HyperCVAD therapy.
Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four-tube 10-color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA-DR, CD71. Seven patients received front-line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo-HCT). For a median follow up of 13.3 months, the 1-year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10-color FCM using a four-tube AL panel demonstrating a characteristic pattern of antigen expression. Front-line induction chemotherapy with HyperCVAD can yield high remission rates, but allo-HCT is required for long-term durable remissions.


Influence of the preplacement holding time and feeding hydration supplementation before placement on yolk sac utilization, the crop filling rate, feeding behavior and first-week broiler performance.
This study investigated the effects of the broiler chick preplacement holding time and feeding hydration supplementation before placement on yolk sac utilization, the crop filling rate, feeding-drinking behavior and first-wk broiler performance. Broiler hatching eggs were obtained from a commercial broiler breeder flock of Ross 308 at 37 wk of age and incubated in a commercial hatchery. At 510 h of incubation, all chicks were removed from the hatcher and separated into cardboard chick boxes containing 80 chicks each. The chick boxes were randomly separated into two groups with either added commercial hydration supplementation (gel: Hydrogel-95) or the control (no gel). Then, the chicks were randomly distributed into 5 groups with different holding times across each hydration supplementation treatment (gel and control). The preplacement holding times were 6, 24, 48, 60, and 72 h from the pull time from the hatchers in the hatchery to placement in the broiler house on the farm, at which point the chicks were able to access feed and water. There were 10 subtreatment groups comprising 5 chick preplacement holding time groups × 2 hydration supplementation groups. There were 12 replicates (160 chicks per pen) per holding period × gel treatment, with a total of 19,200 chicks placed. The feed and water access time did not influence yolk sac utilization, but the absolute or relative residual yolk sac (g, %) decreased linearly with the duration after the pull time (P < 0.001). Longer preplacement holding times were associated with a higher percentage of chicks with full crops at 3 h after placement (P < 0.001). Chicks with the shortest (6 h) preplacement holding time had a lower percentage of feed-seeking activity compared to the 24, 48, and 72 h holding time groups at 3 h after placement (P < 0.001). The highest chick eating and drinking activity was observed in the 72 h group at both 3 and 8 h after placement. Chick weight at placement was significantly reduced linearly with the duration after the pull time (0.106 g/h; R2 = 0.775), and as expected, the highest and lowest BW were found in the 6 (41.51 g) and 72 h (34.50 g) preplacement holding time groups, respectively. However, BW and BW gain were higher in the 24 h group than in the other preplacement holding time groups (P < 0.001) at 7 d after placement. Mortality within the first 3 d after placement increased only when the preplacement holding time was extended to 72 h (P = 0.002). Mortality during 4 to 7 d postplacement was not affected by the holding time at all, but the 72-h holding time group still had statistically significantly higher mortality cumulatively from 0 to 7 d (P = 0.024). Neither BW nor mortality was affected by feeding the hydration supplement at placement, and the lack of effect persisted through 7 d after placement (P > 0.05). It can be concluded that the BW at 7 d after placement was greater in the 24 h holding time group than in shorter (6 h) or longer (48, 60, and 72 h) preplacement holding time groups. In the present study, a greater number of chicks were raised, and it was clearly demonstrated that mortality, as a direct indicator of flock health and welfare, was not affected by preplacement holding times up to and including a 60 h after take-off under thermal comfort conditions, but holding for a further 12 h to 72 h, mortality at 7 d of age after placement was increased. On the other hand, holding chicks in a short period (6 h) did not improve mortality and the BW at 7 d, suggesting that some delay to placement can be beneficial. In addition, feeding hydrogel during the preplacement holding period had no positive effect on BW gain and cumulative mortality during the first week of the growing period.


Uveitis Registries - A Digital Tool for Patient Care, Education, Research, and Collaboration.
Clinical registries are increasingly important in research and clinical advancement. This review explores and compares current uveitis registries and recommends future directions on how uveitis registries can complement one another for synergistic effect and benefit. From a systematic search, 861 citations were screened for longitudinal, non-interventional, and multicenter uveitis-specific registries. Additional registries were identified via consultations with uveitis experts. Characteristics of all registries were analyzed and compared. Four registries were identified: Treatment Exit Options for Non-infectious Uveitis, AutoInflammatory Disease Alliance International Registry, Ocular Autoimmune Systemic Inflammatory Infectious Study, and Fight Uveitis Blindness!. Despite certain differences, these registries have the overarching goal of collecting large quantities of real-world, high-quality patient data to improve the understanding of uveitis. The four uveitis registries share similar goals and collect clinical data from overlapping geographical regions. There is vast potential for collaboration, including data sharing to further augment datasets for analysis.


Hot topics from the Assemblies.
Mannitol improves mucus clearance in non-cystic fibrosis (CF) bronchiectasis and improves mucus clearance and pulmonary function test results in patients with CF. It is not clear to what extent inhaled mannitol has an impact on exacerbation rates and quality of life in patients with non-CF bronchiectasis.


Development of albumin-based nanoparticles for the delivery of abacavir.
The study was designed to prepare and evaluate albumin nanoparticles containing antiviral drug abacavir sulphate. Various batches of albumin nanoparticles containing abacavir sulphate were prepared by desolvation method. The abacavir loaded particles were characterized for their yield, percentage of drug loading, surface morphology, particle size, surface charge, pattern of in vitro drug release and release mechanism studies. Drug loading ranged from 1.2 to 5.9%w/w. The mean particle size and the surface charge were 418.2nm and -40.8mV respectively. The in vitro drug release varied between 38.73 and 51.36%w/w for 24h. The n value for Korsmeyer-Peppas was 0.425 indicating Fickian type drug release. The preliminary findings indicated that albumin nanoparticles of abacavir can be prepared by desolvation method with good yield, high drug loading and sustained release.


Efficacy of antimicrobial interventions in reducing Salmonella enterica, Shiga toxin-producing Escherichia coli, Campylobacter, and Escherichia coli biotype I surrogates on non-chilled and chilled, skin-on and skinless pork.
Effect of various antimicrobial interventions on pork carcass cuts - skin-on and skinless, non-chilled and chilled - was studied. Carcass pieces were inoculated with Salmonella enterica, Shiga toxin-producing Escherichia coli (STEC), Escherichia coli pathogen surrogates or Campylobacter spp. Inoculated pieces were assigned to one of the following antimicrobial treatments: 2.5% and 5.0% room temperature lactic acid, 2.5% and 5.0% warm (55 °C) lactic acid, 400 ppm (0.4 mg/mL) room temperature peroxyacetic acid (PAA) or warm (55 °C) water. Treated pieces were sampled before antimicrobial treatment of non-chilled pork tissue, then at 30 m and 24 h post-treatment. For chilled pork, samples were collected after 24 h chilling and 30 m post-treatment. Lactic acid and PAA treatments reduced (P < 0.05) pathogenic and surrogate bacteria; warm water did not produce similar results. Objective and sensory color evaluations on treated pork indicated minimal negative impacts on pork color. Various antimicrobial interventions were effective in reducing surrogates on pork without diminishing quality.


The Unexpected Detection of a Novel Mutation in a Patient with Hb G-Taipei During Glycated Hemoglobin Test.
There are occasional unexpected detections in HbA1c tests. Here, we described a novel β-globin gene mutation and its hematological phenotype. The proband is a 60-year-old woman who was admitted to the hospital for two weeks due to chest pain. Complete blood count, fasting blood glucose, and glycated hemoglobin tests were performed before admission. High-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) were used to detect HbA1c. The hemoglobin variant was verified by Sanger sequencing. An abnormal peak was observed on HPLC and CE, but the value of HbA1c was normal. Sanger sequencing revealed a GAA>GGA mutation at codon 22 (corresponding to Hb G-Taipei) and a deletion (-GCAATA) at position 659_664 of the second intron of the β-globin gene. The proband and her son, who inherited this new mutation, have no hematological phenotype changes. This is the first report of this mutation, named IVS II-659_664 (-GCAATA). It has a normal phenotype and does not cause thalassemia. IVS II-659_664 (-GCAATA) compounded Hb G-Taipei did not affect the detection of HbA1c.


Biochemical studies of the excitable membrane of Paramecium tetraurelia. II. Phospholipids of ciliary and other membranes.
The phospholipids of cilia and deciliated bodies of Paramecium tetraurelia were isolated and characterized. 1-alkyl-2-acyl-sn-glycero-3-(2'-aminoethyl) phosphonate (GAEPL), phosphatidylethanolamine, and 1-alkyl-2-acyl-sn-glycero-3-phosphorylcholine (GPC) were the major lipids of Paramecium, and the minor lipids included phosphatidylinositol, cardiolipin, ceramide-(2-aminoethyl) phosphonate (CAEP), ceramide phosphorylethanolamine (COPE) and four sphingolipids whose identity was not established. The deciliated bodies contained 4% cardiolipin, 15% GAEPL, 41% phosphatidylethanolamine, 30% GPC and 3% each of CAEP and phosphatidylinositol; the cilia contained no cardiolipin, 24% GAEPL, 37% phosphatidylethanolamine, 15% GPC, 15% CAEP, 3% phosphatidylinositol, 2% COPE and small amounts (approx. 1%) of the four uncharacterized sphingolipids. No alteration in phospholipid composition was found among cells harvested in the various stages of growth. The phospholipids of six Paramecium mutants of three distinct phenotypes (pawn, paranoiac and fast) were also examined. Only one significant difference was found on comparison of the whole cell, deciliated body and cilia fraction of the mutants with the analogous fractions from wild type cells: the fast mutant, fA 97, had two extra, minor phospholipids (approx. 2%) in the deciliated body fraction that were tentatively identified as 1,2-diacyl-sn-glycero-3-(2'-aminoethyl) phosphonate (AEPL) and 1-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine (GPE).


Effect of flavoring oils on preservative concentrations in oral liquid dosage forms.
The partitioning of methyl-, ethyl-, propyl-, and butylparabens into flavoring oils from aqueous systems was studied. The partitioning is dependent on the concentration of the flavoring oil, the pH of the aqueous medium, and the nature and concentration of additives to the aqueous medium.


Development of machine learning-based clinical decision support system for hepatocellular carcinoma.
There is a significant discrepancy between the actual choice for initial treatment option for hepatocellular carcinoma (HCC) and recommendations from the currently used BCLC staging system. We develop a machine learning-based clinical decision support system (CDSS) for recommending initial treatment option in HCC and predicting overall survival (OS). From hospital records of 1,021 consecutive patients with HCC treated at a single centre in Korea between January 2010 and October 2010, we collected information on 61 pretreatment variables, initial treatment, and survival status. Twenty pretreatment key variables were finally selected. We developed the CDSS from the derivation set (N = 813) using random forest method and validated it in the validation set (N = 208). Among the 1,021 patients (mean age: 56.9 years), 81.8% were male and 77.0% had positive hepatitis B BCLC stages 0, A, B, C, and D were observed in 13.4%, 26.0%, 18.0%, 36.6%, and 6.3% of patients, respectively. The six multi-step classifier model was developed for treatment decision in a hierarchical manner, and showed good performance with 81.0% of accuracy for radiofrequency ablation (RFA) or resection versus not, 88.4% for RFA versus resection, and 76.8% for TACE or not. We also developed seven survival prediction models for each treatment option. Our newly developed HCC-CDSS model showed good performance in terms of treatment recommendation and OS prediction and may be used as a guidance in deciding the initial treatment option for HCC.


Vibrant SoundBridge combined with auricle reconstruction for bilateral congenital aural atresia.
To report an integrating surgical method of Vibrant SoundBridge (VSB) implant and auricle reconstruction. 4 cases of congenital bilateral external/middle ear malformation were enrolled. All of them were diagnosed as bilateral bony atresia and grade III microtia. Stapes vibroplasty was performed for all subjects in one operation with auricle reconstruction stage 3. The clinical information and hearing outcomes were analyzed. Satisfied aesthetic outcomes were confirmed by sculptured outline and symmetric shape on both sides. Mean improvement in hearing threshold with VSB activation was 25.9 dB HL, while mean scores of speech recognition test were 21.8-46.3%. Combined surgical method of VSB implant and aesthetic reconstruction is safe and efficient for congenital external/middle ear malformation case.


Aquatic Insect Herbivore Functional Community Traits Respond to a Different Niche Between a Riparian and Sugar Cane Leaf Litter Processing.
The niche of aquatic insect herbivores can be determined by the resource quality of leaf litter species. We compared the niche functional trait of aquatic insect herbivores between Magnolia ovata (riparian tree) and Saccharum officinarum (sugar cane) leaf litter processing. We hypothesized M. ovata and sugar cane leaf litter species would influence different functional traits niche of aquatic insect herbivores due to different quality resource leaves. We performed colonization experiments using dry leaves in five streams during 30-34 days. We utilized five replicates per leaf litter (n = 25) containing 12 g of dry leaves. We compared the niche specialization of herbivore functional traits using the Community Weight Mean (CWM) index and throughout herbivore abundance and the similarity composition of taxa. Additionally, we analysed the influence of organic matter in the CMW index of herbivore functional trait niche. We observed a higher abundance of shredders than scrapers in both leaf litter species. The M. ovata leaf litter selected a more specialized niche of respiration trait composed mainly chironomid shredder larvae, with the osmotic mechanism. The community structure differs weakly with a stronger and positive relationship between organic matter and respiration CWM index in riparian than sugar cane leaf litter. Concerning different composition communities between leaf plants, we consider that aquatic insect herbivore demonstrates a preference to leaf litter species with a specific resource. Additionally, most taxa adapt their feeding habit dependent on the availability of resource food.


Infections onboard ship--analysis of 1290 advice calls to the Radio Medical (RM) doctor in Sweden. Results from 1997, 2002, 2007, and 2009.
Results from a descriptive study on Swedish Telemedical Advice Services (TMAS) from 1997, 2002, 2007, and the first six months of 2009 on infectious conditions are presented. These findings concern symptoms, actions taken, number of evacuations, means of communication, and use of digital photos. They show that infectious conditions are a significant contributor to calls to the service and that they can be more frequently treated on board than can other conditions.


Randomized trial investigating zirconia electroplated telescopic retainers: quality of life outcomes.
The study aims to evaluate the effect of electroplated telescopic removable dental prostheses (E-RDPs) with zirconia primary crowns on oral-health-related quality of life (OHRQoL). For E-RDPs, electroplating is used to produce precisely fitting gold copings on telescopic primary crowns. These copings are bonded intra-orally to the denture framework. Fifty-six participants in need of 60 removable restorations were randomly allocated one of two materials for the primary crowns: cobalt-chromium alloy or zirconia. OHRQoL was assessed by use of the 49-item Oral Health Impact Profile (OHIP-49) and by additional patient self-rating at baseline before treatment, and after 6 and 12 months. Statistical analysis was performed by use of one- and two-sample t-tests and analysis of covariance. Mean OHIP sum score at baseline was 53.4 (SD 37.4, 95 % CI 41.3-62). At follow-ups, it decreased significantly (after 6 months: mean 20, SD 26, 95 % CI 13-27.1; after 12 months: mean 16.4, SD 17.9, 95 % CI 11.6-21.2). The mean reduction in OHIP sum score after 12 months was 25 (SD 31.2, 95 % CI 13.1-36.9) for cobalt-chromium alloy and 44.4 (SD 32.3, 95 % CI 31.1-57.8) for zirconia. However, no statistically significant difference of the two materials on OHIP change or patient self-rating was detected. Although OHRQoL was improved by using both cobalt-chromium alloy and zirconia primary crowns for E-RDPs, post-treatment differences between the groups were not statistically significant. Zirconia E-RDPs enhance OHRQoL. However, zirconia primary crowns do not outperform cobalt-chromium alloy crowns regarding patient satisfaction-despite their tooth-like color.


Male Gender Is Associated with a High Risk for Chronic Antibiotic-Refractory Pouchitis and Ileal Pouch Anastomotic Sinus.
The impact of gender on the development of chronic ileal pouch disorders following ileal pouch-anal anastomosis (IPAA) has not been evaluated. This study was aimed to assess the association between gender and pouch outcomes. Comparisons of long-term pouch outcomes between male and female patients were performed using both univariate and multivariate analyses. Of all patients enrolled (n = 1564), 881(56.3 %) were males. Male patients were older at the time of inflammatory bowel disease (IBD) diagnosis and pouch construction. The frequencies of neoplasia as the indication for colectomy and significant comorbidity were higher in males, while fewer male patients had IBD-related extra-intestinal manifestations or concurrent autoimmune disorders. There was no significant difference between the genders in other clinicopathological characteristics. More male patients (n = 144, 16.3 %) developed chronic antibiotic-refractory pouchitis (CARP) than females (n = 73, 10.7 %) (P = 0.001). Seventy-four males (8.4 %) had ileal pouch anastomotic sinus versus 22 female patients (3.2 %) (P < 0.001). Multivariate logistic regression analyses confirmed the association between male gender and CARP (odds ratio (OR) 1.64, 95 % confidence interval (CI) 1.21-2.24, P = 0.002) and male gender and ileal pouch anastomotic sinus (OR 2.85, 95 % CI 1.48-5.47, P = 0.002). After a median follow-up of 9.0 (interquartile range 4.0-14.0) years, pouch failed in a total of 126 patients (8.1 %). No significant difference was identified between male and female patients in pouch failure (P = 0.61). Among the pouch patients referred to our subspecialty Pouch Center, male patients were found to have an increased risk for the CARP and ileal pouch sinus. The pathogenic mechanisms of the association warrant further study.