Private space, shared space and private housing prices in Hong Kong: An exploratory study.
This exploratory study examines the relationship between internal space, shared space and private housing prices. Housing floor area is an ambiguous concept in Hong Kong because it covers a possible exaggeration of the amount of 'private space' exclusively enjoyed by the owner and an unidentifiable portion of 'public space' shared with other owners within the development. Using hedonic pricing models, this study has found that different distributions between private and shared space command different values from the housing buyers. Shared communal space generally exerts a downward pressure on housing prices. The buyers are willing to pay more for the private space and some desirable forms of communal space. A higher willingness-to-pay for the desirable attributes such as clubhouse indicates that the Hong Kong people are increasingly concerned about the quality of living space in the built environment. This study suggests a need of further research into the exact measurement and the different forms of housing space rather than simply taking the stated floor space figures for granted.


Perspectives in physiological monitoring.
Clinical monitoring systems that have been developed in response to the need to acquire patient physiological data have only recently been accepted as standard equipment in the operating room, and burgeoned into the variety of sophisticated patient-monitoring equipment available today. This article traces the history of the recognition of the importance of physiological data in diagnosing and treating disease, the inclusion of the four vital signs on patient charts, and the first instrumental recording of these signs, all of which occurred before 1900. The earliest operating room monitoring system, which was not developed until the mid 1940s, is described.


Assays using digital fluorescence: 1985-1998
Luminescence continues to provide comprehensive literature surveys which will be published in most issues. These are a continuation of the literature surveys begun in 1986 in the Journal of Bioluminescence and Chemiluminescence which, up until 1998, encompassed more than 6000 references cited by year or specialized topic. With this newly named journal these searches are expanding to reflect the journal's wider scope. In future we will cover all fundamental and applied aspects of biological and chemical luminescence and include not only bioluminescence and chemiluminescence but also fluorescence, time resolved fluorescence, electrochemiluminescence, phosphorescence, sonoluminescence, lyoluminescence and triboluminescence. The compilers would be pleased to receive any comments from the readership. Contact by e-mail: L.J. Kricka: firstname.lastname@example.com or P.E. Stanley: email@example.com Copyright 1999 John Wiley & Sons, Ltd.


Hip arthroscopy: analysis of a single surgeon's learning experience.
The aim of this study was to objectively quantify a surgeon's learning experience for hip arthroscopy. We prospectively reviewed the first 100 hip arthroscopic procedures performed between 1999 and 2004 by a single experienced consultant orthopaedic surgeon. In the second part of the study, three groups of patients were sequentially analyzed: Group 1 included the first thirty patients treated by the surgeon; group 2, the sixty-first through ninetieth patients; and group 3, the 121st through 150th patients. The groups were compared with regard to the diagnosis, the duration of the central and peripheral compartment procedure, patient satisfaction, conversion to arthroplasty, and the nonarthritic hip score. There was a decrease in complications from the first thirty cases to the remaining seventy operations. There was an overall decrease in operative time over the 100 cases, representing a gradual learning process. A marked decrease in the operative time for central compartment arthroscopy was noted when we compared group 1 (mean, seventy minutes; range, forty-five to ninety-eight minutes), group 2 (mean, forty-eight minutes; range, twenty-six to fifty-nine minutes), and group 3 (mean, thirty-seven minutes; range, eighteen to sixty-one minutes). The operative time for peripheral compartment arthroscopy also decreased from group 2 (mean, ninety-one minutes; range, sixty to 126 minutes) to group 3 (mean, forty-five minutes; range, thirty-six to sixty-two minutes). There was an overall decrease in operative time over the first 100 cases. No difference among groups was noted in the number of cases requiring a reoperation or conversion to arthroplasty. There was a higher complication rate in the first thirty cases. An increase in the nonarthritic hip scores was noted postoperatively in the two groups in which the preoperative score had been measured. The postoperative score improved from group 1 (mean, 69; range, 39 to 84) to group 2 (mean, 79; range, 58 to 92) to group 3 (mean, 86; range, 51 to 98). Patient satisfaction was highest in group 3. Hip arthroscopy is associated with high patient satisfaction and good short-term outcomes, but there is a learning curve that we estimate to be approximately thirty cases.


[Study of the aluminum-zinc alloy as an alternative method of filtration in dental X-ray devices].
The aim of this study was to evaluate the effects of alternative filtration with the aluminum-zinc alloy in dental X-ray devices, regarding the energy spectrum, dose, contrast and image quality. This study was carried out comparing the conventional aluminum filter with aluminum-zinc alloy filters of various thicknesses and with different percentages of zinc in the alloy (2, 3, 4 and 5%). A conventional X-ray device operating with 60 and 70 kVp as well as D- and E-speed films were utilized in order to obtain images of a phantom and an aluminum step wedge. The utilization of Al-Zn filters resulted in a spectrum without hardening of beams. The rate of kerma in the air decreased 18.53%, without any alteration in contrast and image quality. The results revealed that the 2% Al-Zn alloy filter with 1.99 mm of thickness, utilized with the tension of 60 kVp and D-speed film, had the best performance. It reduced the rate of kerma without varying the indices of contrast and maintained image quality at acceptable levels, without increasing the time of exposure.


Immobilization of nisin producer Lactococcus lactis strains to chitin with surface-displayed chitin-binding domain.
In this study, nisin producer Lactococcus lactis strains displaying cell surface chitin-binding domain (ChBD) and capable of immobilizing to chitin flakes were constructed. To obtain ChBD-based cell immobilization, Usp45 signal sequence with ChBD of chitinase A1 enzyme from Bacillus circulans was fused with different lengths of PrtP (153, 344, and 800 aa) or AcmA (242 aa) anchors derived from L. lactis. According to the whole cell ELISA analysis, ChBD was successfully expressed on the surface of L. lactis cells. Scanning electron microscope observations supported the conclusion of the binding analysis that L. lactis cells expressing the ChBD with long PrtP anchor (800 aa) did bind to chitin surfaces more efficiently than cells with the other ChBD anchors. The attained binding affinity of nisin producers for chitin flakes retained them in the fermentation during medium changes and enabled storage for sequential productions. Initial nisin production was stably maintained with many cycles. These results demonstrate that an efficient immobilization of L. lactis cells to chitin is possible for industrial scale repeated cycle or continuous nisin fermentation.


Pregnancy & neonatal outcomes in spondyloarthritis.
Limited research has been conducted on the impact of spondylitis (SpA) on fertility, but some studies suggest a higher risk of subfertility in women with SpA compared to the general population. Factors associated with impaired fertility in SpA include pain, fatigue, stiffness, functional disorders, depression, anxiety, negative body image, and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) preconceptionally, while TNF alpha inhibitors may play a role in improving fertility in certain cases. There has been a recent increase in clinical research focused on pregnancy outcomes in SpA. However, clear trends in terms of risk of pregnancy and fetal complications have been slow to emerge and many questions remain for women with SpA planning a pregnancy. This article discusses the current evidence for risk of specific pregnancy and fetal complications in women with axial and psoriatic SpA.


The role of toll-like and protease-activated receptors and associated intracellular signaling in Porphyromonas gingivalis-infected gingival fibroblasts.
Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P. gingivalis exposure and how silencing of one receptor affects the expression of the other receptors. The importance of protein kinase C (PKC) and p38 in the regulation of CXCL8 and IL-6 was also examined. Receptors were knockdown with small-interfering RNA. PKC or p38 was blocked prior to stimulation with P. gingivalis. Fibroblasts were able to compensate for PAR1 knockdown with increased expression of PAR2. PKC and p38 were involved in the regulation of P. gingivalis-induced CXCL8 and IL-6. Our results indicate that PAR1 and PAR2 could be implicated in periodontitis and that PKC and P38 play a role in the inflammatory response in P. gingivalis-infected gingival fibroblasts.


British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 2: decompensated cirrhosis.
There are two distinct phases in the natural history of cirrhosis: compensated disease (corresponding to Child Pugh A and early Child Pugh B disease), where the patient may be largely asymptomatic, progressing with increasing portal hypertension and liver dysfunction to decompensated disease (corresponding to Child Pugh late B-C), characterised by the development of overt clinical signs, including jaundice, hepatic encephalopathy (HE), ascites, renal dysfunction and variceal bleeding. The transition from compensated cirrhosis to decompensated cirrhosis (DC) heralds a watershed in the nature and prognosis of the disease. DC is a systemic disease, characterised by multiorgan/system dysfunction, including haemodynamic and immune dysfunction. In this second part of our three-part series on the outpatient management of cirrhosis, we address outpatient management of DC, including management of varices, ascites, HE, nutrition, liver transplantation and palliative care. We also introduce an outpatient DC care bundle. For recommendations on screening for osteoporosis, hepatocellular carcinoma surveillance and vaccination see part one of the guidance. Part 3 of the guidance focusses on special circumstances encountered in patients with cirrhosis, including surgery, pregnancy, travel, management of bleeding risk for invasive procedures and portal vein thrombosis.


Toward optimal outcome following pivotal response treatment: a case series.
There is a growing literature on children with autism spectrum disorder (ASD) who respond favorably to behavioral treatment, which is often termed "optimal outcome." Rates and definitions of optimal outcome vary widely. The current case series describes an empirically validated behavioral treatment approach called Pivotal Response Treatment (PRT). We present two preschool-aged children who received an intensive course of PRT and seem to be on a trajectory toward potential optimal outcome. Understanding response to treatment and predictors of response is crucial, not necessarily to predict who may succeed, but to individualize medicine and match children with customized treatment programs that will be best tailored to their unique and varied needs.


Decreased lipoprotein lipase in obstructive sleep apnea syndrome.
Lipoprotein lipase (LPL) might play a major role in lipid metabolism by hydrolyzing triglyceride-rich lipoproteins. Decreased LPL activity can trigger early inflammatory responses central to atherosclerosis. However, whether repeated apnea-related hypoxemia influences lipid metabolism in patients with obstructive sleep apnea syndrome (OSAS) remain undefined. This investigation determined whether circulating LPL was influenced by repeated apnea-related hypoxemia, and the effect of nasal continuous positive airway pressure (CPAP) therapy on LPL concentrations in OSAS patients. The participants of the study were 155 men with OSAS and 39 men without OSAS. Circulating LPL concentrations decreased with the severity of OSAS. They correlated negatively with serum triglyceride, and the linear regression lines between LPL concentrations and triglyceride in OSAS patients were shifted downward compared with those in non-OSAS patients, suggesting that any pathophysiological factor might decrease LPL activity in OSAS patients. Some OSAS patients were subjected to CPAP therapy for 3 months. CPAP therapy increased LPL concentrations and decreased C-reactive protein (CRP) concentrations. The present study suggests that repeated apnea-related hypoxemia might affect lipid metabolism and augment inflammatory responses, and CPAP therapy could be effective to decrease inflammatory responses and ameliorate lipid metabolism in patients with OSAS.


Extending the Mann-Whitney-Wilcoxon rank sum test to survey data for comparing mean ranks.
Statistical methods for analysis of survey data have been developed to facilitate research. More recently, Lumley and Scott (2013) developed an approach to extend the Mann-Whitney-Wilcoxon (MWW) rank sum test to survey data. Their approach focuses on the null of equal distribution. In many studies, the MWW test is called for when two-sample t-tests (with or without equal variance assumed) fail to provide meaningful results, as they are highly sensitive to outliers. In such situations, the null of equal distribution is too restrictive, as interest lies in comparing centers of groups. In this article, we develop an approach to extend the MWW test to survey data to test the null of equal mean rank. Although not as popular as the mean and median, the mean rank is also a meaningful measure of the center of a distribution and is the same as the median for a symmetric distribution. We illustrate the proposed approach and show major differences with Lumley and Scott's alternative using both real and simulated data.


Pharmacoproteomics-based reconstruction of in vivo P-glycoprotein function at blood-brain barrier and brain distribution of substrate verapamil in pentylenetetrazole-kindled epilepsy, spontaneous epilepsy, and phenytoin treatment models.
The purpose of this study was to demonstrate experimentally that alterations of in vivo transporter function at the blood-brain barrier (BBB) in disease and during pharmacotherapy can be reconstructed from in vitro data based on our established pharmacoproteomic concept of reconstructing in vivo function by integrating intrinsic transport activity per transporter molecule and absolute protein expression level at the BBB. Pentylenetetrazole (PTZ)-kindled and spontaneous model of epilepsy (EL) mice were used as models of chemically induced and spontaneous epilepsy, respectively. A mouse model of antiepileptic drug treatment was prepared by consecutive 5-week administration of phenytoin (PHT). Quantitative targeted absolute proteomic analysis of 31 membrane proteins showed that P-glycoprotein (P-gp/mdr1a) protein expression levels were significantly increased in brain capillaries of PTZ (129%), EL (143%), and PHT mice (192%) compared with controls. The brain-to-plasma concentration ratios (Kp brain) of P-gp/mdr1a substrate verapamil were 0.563, 0.394, 0.432, and 0.234 in control, PTZ, EL, and PHT mice, respectively. In vivo P-gp/mdr1a function at the BBB was reconstructed from the measured P-gp/mdr1a protein expression levels and intrinsic transport activity for verapamil per P-gp/mdr1a previously reported by our group. Then, the reconstructed P-gp/mdr1a functional activities were integrated with unbound fractions of verapamil in plasma and brain to reconstruct Kp brain of verapamil. In all mice, reconstructed Kp brain values agreed well with the observed values within a 1.21-fold range. These results demonstrate that altered P-gp functions at the BBB in epilepsy and during pharmacotherapy can be reconstructed from in vitro data by means of our pharmacoproteomic approach.


Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach.
Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders.


Work hard, play hard?: A comparison of male and female lawyers' time in paid and unpaid work and participation in leisure activities.
There has been a considerable amount of research that documents how women and men spend their time in different work and home tasks. We examine how much time professional women and men spend in paid and unpaid work and how this relates to their participation in different leisure activities. We also explore whether time in paid and unpaid work has gender-specific effects on leisure participation. In examining these issues, we rely on data from lawyers working in different legal settings. Our results show that, as hypothesized, men report more time in paid work and leisure whereas women devote more time to housework and childcare. An unexpected finding is that the time men spend in housework or childcare is either unrelated or positively related to their leisure participation. These results suggest that men's greater overall opportunities for leisure compared with women's appear to stem from the unanticipated relationships between men's involvement in housework and childcare and their leisure activities. We raise several possible explanations for these findings.


New methodology to measure the dynamics of ocular wave front aberrations during small amplitude changes of accommodation.
We present a methodology to measure the systematic changes of aberrations induced by small changes in amplitude of accommodation. We use a method similar the one used in electrophysiology, where a periodic stimulus is presented to the eye and many periods (epochs) of the stimulus are averaged. Using this technique we have measured changes in higher order aberrations from 0.006 mum to 0.02 mum and correlated them with amplitude changes of accommodation as small as 0.14D. These small changes would have been undetectable without epoch averaging. The correlation coefficients of Zernike terms with defocus were calculated, demonstrating higher values of correlation for epoch averaging. The accurate monitoring of defocus at the start of the accommodation response has shown some interesting trends that may be related with the mechanisms behind accommodation.


Pro-neoangiogenic cytokines (VEGF and bFGF) and anemia in solid tumor patients.
Using a commercial ELISA assay, we evaluated circulating VEGF and bFGF levels in 203 consecutive patients with solid tumors, and sought a correlation between them and with the grade of anemia. Serum VEGF values were within the normal range in 128 patients (63.05%), with a mean value of 675.04 pg/ml (median, 571.00; range, 0-2796.54). The analysis of VEGF values per tumor group did not provide any statistically significant difference. Regarding bFGF, 143 patients (70.44%) had measurable, and thus abnormal, bFGF values. Overall, mean bFGF serum value was 57.14 pg/ml (median, 8.30; range, 0-4334.71), with the highest bFGF levels found in breast carcinoma patients. As expected, a large number of our patients was fairly anemic, mean hemoglobin level being 11.47 g/dl (median, 11.30; range, 7.1-19.20), the lowest titers being observed in prostate carcinoma patients. No statistically significant correlation was found between serum VEGF and hemoglobin values (r=0.004) but a significant negative correlation was seen between serum bFGF and hemoglobin (r=-0.22, p<0.05). Considering the different tumor groups, a statistically significant negative correlation between bFGF and hemoglobin becomes even more apparent in the subgroup of renal carcinoma patients (r=-0.55, p<0.05). In conclusion, our results demonstrate that there is a statistically significant correlation between systemic hypoxia (evaluated in terms of hemoglobin levels) and circulating bFGF values, but not VEGF; this correlation may lead to therapeutic interventions.


Chicken muscle antibody array reveals the regulations of LDHA on myoblast differentiation through energy metabolism.
Myoblast proliferation and differentiation are highly dynamic and regulated processes in skeletal muscle development. Given that proteins serve as the executors for the majority of biological processes, exploring key regulatory factors and mechanisms at the protein level offers substantial opportunities for understanding the skeletal muscle development. In this study, a total of 607 differentially expressed proteins between proliferation and differentiation in myoblasts were screened out using our chicken muscle antibody array. Biological function analysis revealed the importance of energy production processes and compound metabolic processes in myogenesis. Our antibody array specifically identified an upregulation of LDHA during differentiation, which was associated with the energy metabolism. Subsequent investigation demonstrated that LDHA promoted the glycolysis and TCA cycle, thereby enhancing myoblasts differentiation. Mechanistically, LDHA promotes the glycolysis and TCA cycle but inhibits the ETC oxidative phosphorylation through enhancing the NADH cycle, providing the intermediate metabolites that improve the myoblasts differentiation. Additionally, increased glycolytic ATP by LDHA induces Akt phosphorylation and activate the PI3K-Akt pathway, which might also contribute to the promotion of myoblasts differentiation. Our studies not only present a powerful tool for exploring myogenic regulatory factors in chicken muscle, but also identify a novel role for LDHA in modulating myoblast differentiation through its regulation of cellular NAD+ levels and subsequent downstream effects on mitochondrial function.


Vesicular phospholipid gels as drug delivery systems for small molecular weight drugs, peptides and proteins: State of the art review.
Lipid-based drug delivery has been investigated for a long time when it comes to liposomes and solid-lipid implants or solid-lipid nanoparticles. The promising, characteristic properties of these systems have led to the development of newer lipid-based drug delivery systems for the sustained release of drugs like liposomes for sustained delivery of substances, DepoFoam™ technology, phospholipid-based phase separation gels and vesicular phospholipid gels. Vesicular phospholipid gels (VPGs) are highly concentrated, viscous dispersions of high amounts of phospholipids in aqueous drug solution. The easy, solvent-free manufacturing process, high biocompatibility and various applications, as depot formulation for the sustained delivery of drugs and as a storage form of small unilamellar vesicles make VPGs highly attractive as drug carriers. Over the last years, the solvent free preparation process has advanced from high pressure homogenization to dual centrifugation (DC). Thereby a very simple one step process has been established for the preparation of VPGs. The semisolid VPG was first described in 1997 by Brandl et al. Since then, many formulations have been developed, encapsulating small molecular weight drugs like 5-FU (2003), cetrorelix (2005), cytarabine (2012) and exenatide (2015). In 2010, the first pharmaceutical protein, erythropoietin, was encapsulated in VPGs and sustained release of the substance was shown in vitro. In 2015, G-CSF was encapsulated in VPGs and tested in vivo for rotator cuff repair in a rat model and for PEGylated IFN-β-1b sustained release from vesicular phospholipid gels was demonstrated in vitro. Further, a very elegant administration technique for VPGs via needle-free injection was established. However this promising drug delivery system does still leave space for improvement and optimization. This review summarizes information about lipid-based depot systems in general and focuses on the historical development of VPGs. It emphasizes the advantages and drawbacks of VPGs as drug delivery device. Additionally, novel preparation methods and applications of VPGs will be discussed. A focus will be set on delivery of pharmaceutical proteins and peptides.


The readiness to change questionnaire in subjects with hazardous alcohol consumption, alcohol misuse and dependence in a general population survey.
To investigate properties and aspects of validity of the Readiness to Change Questionnaire (RCQ) when applied to hazardous drinking, alcohol-abusing or alcohol-dependent subjects sampled from the general population. In a representative survey conducted in the general population of a region in northern Germany, participants were randomly selected from resident registration office files, contacted and interviewed personally (n = 4.075). A total of 302 subjects who showed hazardous drinking behaviour (n = 202) or met diagnostic criteria of alcohol misuse (n = 46) or alcohol dependence (n = 54) were assessed and diagnosed using the Munich Composite International Diagnostic Interview (M-CIDI) according to DSM-IV diagnostic criteria. The battery of self-report questionnaires comprised, among others, the RCQ, and two methods of allocation were used, the quick method and the refined method of allocation. According to the method of allocation used, the stages are: precontemplation (PC), contemplation (C), preparation (P) and action (A); P may only be assigned using the refined method. The RCQ, a brief instrument to assess stages of change in individuals sampled from the general population, gave internal consistencies of: PC = 0.68, C = 0.79, A = 0.83. Allocation to stages of change according to the quick method resulted in 67% of subjects being allocated to PC, 24% to C and 8% to A and according to the refined method in 58% to PC, 15% to C, 4% to P, 4% to A, with 19% not being classified because of non-theory-consistent scale profiles. Classification did not differ substantially according to the method of allocation. A three-factor solution, as reported in the literature, could not be replicated. Allocation to stages of change with the RCQ reflected predictions made from the Transtheoretical Model of behaviour change.


PI3K inhibitors reverse the suppressive actions of insulin on CYP2E1 expression by activating stress-response pathways in primary rat hepatocytes.
Insulin-associated signaling pathways are critical in the regulation of hepatic physiology. Recent inhibitor-based studies have implicated a mechanistic role for phosphatidylinositol 3' kinase (PI3K) in the insulin-mediated suppression of CYP2E1 mRNA levels in hepatocytes. We investigated the dose dependence for this response and for the effects of insulin and extracellular matrix on PI3K signaling and CYP2E1 mRNA expression levels using a highly defined rat primary hepatocyte culture system. The PI3K inhibitors wortmannin and LY294002 stimulated stress-activated protein kinase/c-Jun NH(2)-terminal kinase (SAPK/JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation in a rapid and concentration-dependent manner that paralleled the inhibition of protein kinase B (PKB) phosphorylation. Although PI3K inhibitors reversed the suppressive effects of insulin on CYP2E1 expression, these effects only occurred at concentrations well in excess of those required to achieve complete inhibition of PKB phosphorylation. These same concentrations produced cytotoxic responses as evidenced by perturbed cellular morphology and elevated release of lactate dehydrogenase. Wortmannin-mediated activation of the SAPK/JNK and p38 MAPK pathways also resulted in the mobilization of activator protein-1 complex to the nuclear compartment. We conclude that the suppression of CYP2E1 mRNA expression by insulin is not directly associated with PI3K-dependent pathway activation, but rather is linked to a cytotoxic response stemming from acute challenge with PI3K inhibitors.


Comparison of number of Streptococcus uberis calculated on a volume or weight basis in sand and sawdust bedding.
To determine a method for comparing counts of Streptococcus uberis in sand and sawdust and account for the influence of weight or volume of the bedding material. 2 sources of kiln-dried sawdust and 2 sources of washed sand. Sterilized bedding material (100 ml) was weighed and uniformly distributed in an aluminum pan. Each sterilized bedding material was inoculated with a mean of 3.6 X 10(6) (experiment 1) or 2.4 X 10(7) (experiment 2) colony-forming units (CFU) of S uberis/ml of bedding material. Without allowing time for replication of S uberis, inoculated bedding materials were washed with sterile saline (0.9% NaCl) solution. A 200-ml aliquot of wash solution was serially diluted up to 2,500 times with additional saline solution and inoculated on plates containing tryptose agar with 5% sheep blood. After incubation for 48 hours, number of CFU of S uberis was counted. This procedure was replicated 19 and 16 times for each bedding material in experiments 1 and 2, respectively. Evaluation of Bonferroni 95% confidence intervals revealed significant differences for counts of S uberis calculated on a weight basis between sand and sawdust. Comparison of counts of S uberis determined on a volume basis for sand and sawdust accentuates to a lesser degree the weight difference of the bedding materials and ensures a more appropriate comparison of number of S uberis.


The effect of online visual games on visual perception, oculomotor, and balance skills of children with developmental dyslexia during the COVID-19 pandemic.
To evaluate the effect of online visual games on the balance, visual perception, and oculomotor skills of children with developmental dyslexia during the COVID-19 pandemic. In this single-blind randomized clinical trial, 50 children with developmental dyslexia, aged 7 to 11 years, were recruited from rehabilitation centers in Tehran, Iran, using a convenience sampling strategy. Participants were randomly divided into two groups: intervention (25) and control (25), with close matching based on sex, age, IQ, and type of disease. The interventions consisted of web-based online computer games focusing on visual perception and oculomotor skills. Outcome measures included the Test of Visual Perception Skills-Revised, the Pediatric Balance Scale, and videonystagmography. The Wechsler Intelligence Scale for Children-IV and the Reading and Dyslexia Test were used to evaluate IQ and reading skills, respectively. The intervention group exhibited significant post-intervention improvements in the Test of Visual Perception Skills-Revised, tracking gain, saccade latency, and saccade velocity scores (all P < 0.001). In contrast, the control group showed no significant differences in these tests in pre- and post-intervention (all P > 0.05). Notably, post-intervention comparisons between the groups revealed significant differences in smooth pursuit eye movements (P < 0.001), saccade latency (P = 0.027), and saccade velocity (P < 0.001). The Pediatric Balance Scale scores remained unchanged in both groups post-intervention (intervention: P = 0.317; control: P = 0.999). Game face validity was affirmed with impact scores above 1.5 for all items, suggesting that the games were straightforward, clear, and relevant. Online visual games enhanced oculomotor and visual perception skills in children with dyslexia but did not influence balance skills.


[Analysis of reproduction by schizophrenics and chronic alcoholics].
With the aid of a specially elaborated chart certain indices of fertility and sexual behaviour were determined in 1113 females with schizophrenia and in 275 patients with chronic alcoholism of fertile age. A correlation of these indices with similar indices in normal females demonstrated that the level of reproductivity in schizophrenic females is lower than in normals and in chronic alcoholic females. The feasibility of applying measures of hygiene in marital and sexual relations of patients with schizophrenia and chronic alcoholism is discussed.


Influence of N₂ on Formation Conditions and Guest Distribution of Mixed CO₂ + CH₄ Gas Hydrates.
In this contribution, a method based on a solid solution theory of clathrate hydrate for multiple cage occupancy, host lattice relaxation, and guest-guest interactions is presented to estimate hydrate formation conditions of binary and ternary gas mixtures. We performed molecular modeling of the structure, guest distribution, and hydrate formation conditions for the CO₂ + CH₄ and CO₂ + CH₄ + N₂ gas hydrates. In all considered systems with and without N₂, at high and medium content of CO₂ in the gas phase, we found that CO₂ was more favorable in occupying clathrate hydrate cavities than CH₄ or N₂. The addition of N₂ to the gas phase increased the ratio concentration of CO₂ in comparison with the concentration of CH₄ in clathrate hydrates and made gas replacement more effective. The mole fraction of CO₂ in the CO₂ + CH₄ + N₂ gas hydrate rapidly increased with the growth of its content in the gas phase, and the formation pressure of the CO₂ + CH₄ + N₂ gas hydrate rose in comparison to the formation pressure of the CO₂ + CH₄ gas hydrate. The obtained results agreed with the known experimental data for simple CH₄ and CO₂ gas hydrates and the mixed CO₂ + CH₄ gas hydrate.


Histone H3 lysine 79 methyltransferase Dot1 is required for immortalization by MLL oncogenes.
Chimeric oncoproteins resulting from fusion of MLL to a wide variety of partnering proteins cause biologically distinctive and clinically aggressive acute leukemias. However, the mechanism of MLL-mediated leukemic transformation is not fully understood. Dot1, the only known histone H3 lysine 79 (H3K79) methyltransferase, has been shown to interact with multiple MLL fusion partners including AF9, ENL, AF10, and AF17. In this study, we utilize a conditional Dot1l deletion model to investigate the role of Dot1 in hematopoietic progenitor cell immortalization by MLL fusion proteins. Western blot and mass spectrometry show that Dot1-deficient cells are depleted of the global H3K79 methylation mark. We find that loss of Dot1 activity attenuates cell viability and colony formation potential of cells immortalized by MLL oncoproteins but not by the leukemic oncoprotein E2a-Pbx1. Although this effect is most pronounced for MLL-AF9, we find that Dot1 contributes to the viability of cells immortalized by other MLL oncoproteins that are not known to directly recruit Dot1. Cells immortalized by MLL fusions also show increased apoptosis, suggesting the involvement of Dot1 in survival pathways. In summary, our data point to a pivotal requirement for Dot1 in MLL fusion protein-mediated leukemogenesis and implicate Dot1 as a potential therapeutic target.


Epidemiology of elderly patients' burns in the South West of France.
A retrospective study of 716 patients aged 60 years and above (324 men, 392 women) was undertaken in order to determine quality control in burns management in the South West of France. The following epidemiological data was obtained: high hospitalization rate (7 per cent of the general admissions); monthly and seasonal periodicity; predominance of indoor accidents (86 per cent) with domestic accidents being more frequent in women (63 vs. 37 per cent). Outdoor accidents were mainly recreational and were five times more frequent in men than in women. The overall mortality was 39 per cent and was influenced by the burns extent, depth, predisposing factors and early management. More burns occurred in urban areas (53 per cent) but mortality was higher in patients from rural areas (62 vs. 38 per cent). It was observed that delay in management, especially fluid resuscitation of patients from the rural areas, was partly responsible for this outcome. Propositions were made to diffuse more information on the importance of early management of burns in rural areas.


Objectively Measured Sedentary Behavior and Physical Activity Across 3 Trimesters of Pregnancy: The Monitoring Movement and Health Study.
Though moderate- to vigorous-intensity physical activity is recommended, limited research exists on sedentary behavior (SED) during pregnancy. The authors conducted a prospective cohort study to describe objectively measured patterns of SED and activity during each trimester of pregnancy. Women wore thigh- (activPAL3) and waist-mounted (ActiGraph GT3X) activity monitors. SED and activity were compared across trimesters using likelihood ratio tests and described using group-based trajectories. Exploratory analyses associated SED and activity trajectories with adverse pregnancy outcomes and excessive gestational weight gain. Pregnant women (n = 105; mean [SD] age = 31 [5] y; prepregnancy body mass index = 26.2 [6.6] kg/m2) had mean SED of 9.7, 9.5, and 9.5 hours per day (P = .062) across trimesters, respectively. Some activities differed across trimesters: standing (increased, P = .01), stepping (highest in second trimester, P = .04), steps per day (highest in second trimester, P = .008), and moderate- to vigorous-intensity physical activity (decreased, P < .001). Prolonged SED (bouts ≥ 30 min) and bouted moderate- to vigorous-intensity physical activity (≥10 min) were stable (P > .05). In exploratory analyses, higher SED and lower standing, stepping, and steps per day trajectories were associated with increased odds of adverse pregnancy outcomes (P < .05). No trajectories were associated with excessive gestational weight gain. Pregnant women exhibited stable SED of nearly 10 hours per day across pregnancy. Future research evaluating SED across pregnancy and adverse pregnancy outcome risk is warranted.


Natural history predicts patterns of thermal vulnerability in amphibians from the Atlantic Rainforest of Brazil.
In the Brazilian Atlantic Rainforest (AF), amphibians (625 species) face habitat degradation leading to stressful thermal conditions that constrain animal activity (e.g., foraging and reproduction). Data on thermal ecology for these species are still scarce. We tested the hypothesis that environmental occupation affects the thermal tolerance of amphibian species more than their phylogenetic relationships. We evaluated patterns of thermal tolerance of 47 amphibian species by assessing critical thermal maxima and warming tolerances, relating these variables with ecological covariates (e.g., adult macro- and microhabitat and site of larval development). We used mean and maximum environmental temperature, ecological covariates, and morphological measurements in the phylogenetic generalized least squares model selection to evaluate which traits better predict thermal tolerance. We did not recover phylogenetic signal under a Brownian model; our results point to a strong association between critical thermal maxima and habitat and development site. Forest species were less tolerant to warm temperatures than open area or generalist species. Species with larvae that develop in lentic environment were more tolerant than those in lotic ones. Thus, species inhabiting forest microclimates are more vulnerable to the synergistic effect of habitat loss and climate change. We use radar charts as a quick evaluation tool for thermal risk diagnoses using aspects of natural history as axes.


Phenotypic masquerade: Polymorphism in the life cycle of the centrohelid heliozoan Raphidiophrys heterophryoidea (Haptista: Centroplasthelida).
The life cycle of the centrohelid heliozoan Raphidiophrys heterophryoidea Zlatogursky, 2012 was studied with light and electron microscopy in clonal cultures from the type locality. The alternation of two types of trophozoites, having contrastingly different morphology, was observed. Type 1 trophozoites morphology matched the original description. Type 2 trophozoites tended to form colonies usually of 6-8 individuals, connected with cytoplasmic bridges and their cell size was noticeably bigger, namely 43-45 μm compared to 24.5 μm on average in type 1 trophozoites. Some colonies were forming stalks composed of three or four axopodia covered with scales. Spicules were lacking completely, while plate-scales differed from those of type 1 trophozoites: they had oblong-elliptical shape, larger (5.9-14.1 × 2.4-5.8 μm) size, non-branching septa always reaching scale centre, solid upper plate. The conspecificity of the two trophozoite types was confirmed with the comparison of SSU rDNA gene sequence data. Both types of trophozoites were capable of encystment and excysted individuals always were type 1 trophozoites. A new type of cyst-scales (cup-scales) was described. Transitions between cysts and the two trophozoites types were documented. The diagnosis of R. heterophryoidea was improved accordingly. The possible functions, driving forces, and taxonomic consequences of the polymorphism were discussed.


The initial pharmaceutical development of an artesunate/amodiaquine oral formulation for the treatment of malaria: a public-private partnership.
Artemisinin-based combination therapy is currently recommended worldwide for the treatment of uncomplicated malaria. Fixed-dose combinations are preferred as they favour compliance. This paper reports on the initial phases of the pharmaceutical development of an artesunate-amodiaquine (ASAQ) bilayer co-formulation tablet, undertaken following pre-formulation studies by a network of scientists and industrials from institutions of both industrialized and low income countries. Pharmaceutical development was performed by a research laboratory at the University Bordeaux Segalen, School of Pharmacy, for feasibility and early stability studies of various drug formulations, further transferred to a company specialized in pharmaceutical development, and then provided to another company for clinical batch manufacturing. The work was conducted by a regional public-private not-for-profit network (TropiVal) within a larger Public Private partnership (the FACT project), set up by WHO/TDR, Médecins Sans Frontières and the Drugs for Neglected Disease initiative (DNDi). The main pharmaceutical goal was to combine in a solid oral form two incompatible active principles while preventing artesunate degradation under tropical conditions. Several options were attempted and failed to provide satisfactory stability results: incorporating artesunate in the external phase of the tablets, adding a pH regulator, alcoholic wet granulation, dry granulation, addition of an hydrophobic agent, tablet manufacturing in controlled conditions. However, long-term stability could be achieved, in experimental batches under GMP conditions, by physical separation of artesunate and amodiaquine in a bilayer co-formulation tablet in alu-alu blisters. Conduction of the workplan was monitored by DNDi. Collaborations between research and industrial groups greatly accelerated the process of development of the bi-layered ASAQ tablet. Lack of public funding was the main obstacle hampering the development process, and no intellectual property right was claimed. This approach resulted in a rapid technology transfer to the drug company Sanofi-Aventis, finalizing the process of development, registration and WHO pre-qualification of the fixed-dose co-formulation together with DNDi. The bi-layered tablet is made available under the names of Coarsucam® and Artesunate amodiaquine Winthrop®, Sanofi-Aventis. The issue related to the difficulty of public institutions to valorise their participation in such initiative by lack of priority and funding of applied research is discussed.


Oocyte freezing: here to stay?
Oocyte freezing is an established technology but, in contrast to embryo freezing, it has very limited application in clinical IVF programmes. Is there a chance that oocyte freezing will become an integrated routine in assisted reproductive technology? The delicate cytological architecture of the oocyte with a cold-sensitive spindle and a hardening zona have made the frozen oocyte 'unwanted' in assisted reproductive technology. Nevertheless, empirical improvements in freezing protocols and the use of ICSI for fertilization have led to an increasing number of live births. This mitigates against a simple ban on oocyte freezing. While efficiency of oocyte freezing can certainly be further improved by basic research, it is clear that there are humanitarian reasons for considering oocyte freezing as a future fully utilized assisted reproductive technology. The storage of the female genome as a particulate entity can provide an alternative in case of moral, ethical, legal or religious concerns about embryo freezing. Oocyte freezing can also offer hope for oocyte donation and preservation of fertility for women facing ovarian loss. The message is one of cautious optimism when looking for a place for oocyte freezing in routine assisted reproductive technology.


Effects of vitamin E on the distribution and metabolism of nitrofurantoin in rats.
Previous studies have shown a significant increase in the pulmonary toxicity of nitrofurantoin (NF) in animals fed a diet lacking vitamin E. The authors have therefore examined the pharmacokinetics of NF in control and vitamin E-deficient male Sprague-Dawley rats. NF was rapidly absorbed following subcutaneous injection and was cleared from all tissues examined (blood, lung, liver and kidney) in a biphasic manner. Substantial metabolism of the drug was observed, and the disposition of NF metabolites was qualitatively similar to that of the parent compound. The most apparent difference between control and vitamin E-deficient animals was a significant increase in tissue metabolite levels 4-16 hr after treatment. Unchanged NF was also elevated in all tissues examined 16 hr after treatment in the vitamin E-deficient animals. Urinary excretion of NF and metabolites accounted for 68% of the total dose in control rats and 35% in vitamin E-deficient rats. This study illustrates a marked alteration in NF disposition in animals fed a diet lacking vitamin E when compared with controls. The observed alterations appear to be related to a decreased renal clearance of both NF and metabolites.


Triclosan stimulates human vascular endothelial cell injury via repression of the PI3K/Akt/mTOR axis.
Triclosan (TCS) has potentially toxic effects on humans and animals. However, the possible roles and mechanisms of TCS in endothelial cells (ECs) are still unknown. Abnormal damage to ECs and vascular function is a critical process in various cardiovascular diseases, including coronary artery disease (CAD), atherosclerosis, stroke, and hypertension. Hence, we explored the potential toxicological roles of TCS in EC functions. Cell Counting Kit-8, apoptosis, transwell, wound healing, and tube-formation experiments were performed to evaluate the effects of TCS on human umbilical vein endothelial cell (HUVEC) function. Additionally, the levels of PI3K, Akt, and mTOR phosphorylation were measured by Western blot. The results indicated that TCS treatment suppressed HUVECs viability, migration and angiogenesis. TCS treatment increased the expression of inflammatory markers and ROS in cultured HUVECs. Moreover, TCS treatment inhibited PI3K/Akt/mTOR expression. All of these results reveal that TCS induces notable vascular injury and affects the viability, migration and angiogenic capacity of HUVECs, at least in part via the PI3K/Akt/mTOR signaling pathway.


Aldrin and dieldrin: loss under sterile conditions.
After their application to sterile nutrient agar, both aldrin and dieldrin disappeared rather rapidly from the agar in glass-covered petri dishes. In most instances this disappearance was considerably retarded from agar inoculated with either fungi or bacteria. In the presence of microorganisms, aldrin was also epoxidized into dieldrin. Half of the applied aldrin volatilized from the agar during the first day of incubation; dieldrin volatilized more slowly and at a constant rate.


Annotated expressed sequence tags and cDNA microarrays for studies of brain and behavior in the honey bee.
To accelerate the molecular analysis of behavior in the honey bee (Apis mellifera), we created expressed sequence tag (EST) and cDNA microarray resources for the bee brain. Over 20,000 cDNA clones were partially sequenced from a normalized (and subsequently subtracted) library generated from adult A. mellifera brains. These sequences were processed to identify 15,311 high-quality ESTs representing 8912 putative transcripts. Putative transcripts were functionally annotated (using the Gene Ontology classification system) based on matching gene sequences in Drosophila melanogaster. The brain ESTs represent a broad range of molecular functions and biological processes, with neurobiological classifications particularly well represented. Roughly half of Drosophila genes currently implicated in synaptic transmission and/or behavior are represented in the Apis EST set. Of Apis sequences with open reading frames of at least 450 bp, 24% are highly diverged with no matches to known protein sequences. Additionally, over 100 Apis transcript sequences conserved with other organisms appear to have been lost from the Drosophila genome. DNA microarrays were fabricated with over 7000 EST cDNA clones putatively representing different transcripts. Using probe derived from single bee brain mRNA, microarrays detected gene expression for 90% of Apis cDNAs two standard deviations greater than exogenous control cDNAs. [The sequence data described in this paper have been submitted to Genbank data library under accession nos. BI502708-BI517278. The sequences are also available at http://titan.biotec.uiuc.edu/bee/honeybee_project.htm.]


Herpes Simplex Encephalitis (HSE) and its outcome in the Patients who were Admitted to a Tertiary Care Hospital in Mashhad, Iran, over a 10-year Period.
The effective cure rate of acyclovir emphasizes the importance of an early diagnosis and treatment in reducing the considerable mortality and the morbidity in patients with Herpes Simplex Encephalitis (HSE). The demographic as well as clinical features, the lab data and the neuroimaging findings of the patients with HSE, which were confirmed by Cerebrospinal Fluid (CSF) PCR and/or brain MRI, were reviewed and analyzed statistically over a 10-year period. Over a 10-year period, the characteristics of 45 patients with HSE were reviewed. 34 (76%) out of the 45 patients showed positive CSF HSV-1 PCR results. 8 (18%) had a normal CSF analysis and a CSF/blood glucose ratio of less than 0.5 was observed in 13 (29%) patients, while 14% had PMN-dominant pleocytosis. 68% of the patients for whom brain MRI was performed, had temporal lobe involvement. While 37 (83%) patients recovered completely, 6 (13%) survived with sequelae, and 2 (4%) died. Because of the increasing number of atypical forms of HSE and the great impact of an early diagnosis and treatment on a favourable outcome, the acyclovir therapy should be administrated for any type of febrile encephalopathy of unknown aetiology, until HSE can be excluded.


Occupational asthma due to chrome and nickel electroplating.
Exposure to chromium during electroplating is a recognised though poorly characterised cause of occupational asthma. The first series of such patients referred to a specialist occupational lung disease clinic is reported. The diagnosis of occupational asthma was made from a history of asthma with rest day improvement and confirmed by specific bronchial provocation testing with potassium dichromate and nickel chloride. Seven workers had been exposed to chrome and nickel fumes from electroplating for eight months to six years before asthma developed. One subject, although exposed for 11 years without symptoms, developed asthma after a single severe exposure during a ventilation failure. This was the only subject who had never smoked. The diagnosis was confirmed by specific bronchial challenges. Two workers had isolated immediate reactions, one a late asthmatic reaction, and four a dual response following exposure to nebulised potassium dichromate at 1-10 mg/ml. Two of the four subjects were also challenged with nebulised nickel chloride at 0.1-10 mg/ml. Two showed isolated late asthmatic reactions, in one at 0.1 mg/ml, where nickel was probably the primary sensitising agent. Four workers carried out two hourly measurements of peak expiratory flow over days at and away from work. All were scored as having occupational asthma using OASYS-2. Breathing zone air monitoring was carried out in 60 workers from four decorative and two hard chrome plating shops from workers with similar jobs to those sensitised. No measurement exceeded the current occupational exposure standard for chromate or nickel, the mean levels of chromate exposure for jobs similar to those of the affected workers were 9-15 micrograms/m3. Chrome used in electroplating is a potential cause of occupational asthma. Sensitivity to chrome in electroplaters may occur in situations where exposure levels are likely to be within the current exposure standards. There may be cross reactivity with nickel. Inhalation challenge with nebulised potassium dichromate solution is helpful in making the specific diagnosis where doubt exists.


Bilateral Versus Unilateral Cochlear Implantation in Adult Listeners: Speech-On-Speech Masking and Multitalker Localization.
Binaural hearing helps normal-hearing listeners localize sound sources and understand speech in noise. However, it is not fully understood how far this is the case for bilateral cochlear implant (CI) users. To determine the potential benefits of bilateral over unilateral CIs, speech comprehension thresholds (SCTs) were measured in seven Japanese bilateral CI recipients using Helen test sentences (translated into Japanese) in a two-talker speech interferer presented from the front (co-located with the target speech), ipsilateral to the first-implanted ear (at +90° or -90°), and spatially symmetric at ±90°. Spatial release from masking was calculated as the difference between co-located and spatially separated SCTs. Localization was assessed in the horizontal plane by presenting either male or female speech or both simultaneously. All measurements were performed bilaterally and unilaterally (with the first implanted ear) inside a loudspeaker array. Both SCTs and spatial release from masking were improved with bilateral CIs, demonstrating mean bilateral benefits of 7.5 dB in spatially asymmetric and 3 dB in spatially symmetric speech mixture. Localization performance varied strongly between subjects but was clearly improved with bilateral over unilateral CIs with the mean localization error reduced by 27°. Surprisingly, adding a second talker had only a negligible effect on localization.


Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus.
Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection. To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice. Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus. The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infection-associated changes in IFN-gamma, IL-1beta, IL-6, tumor necrosis factor-alpha, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1alpha, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis. These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.


Chemotherapy for salivary gland cancer.
Because of the scarcity of such lesions, little is known about the efficacy of chemotherapy for advanced salivary gland cancers. Although surgery and irradiation are the mainstays of treatment, patients with recurrent tumors and those with unresectable or metastatic cancer are not candidates for this usual approach. Ten patients with recurrent, metastatic, or unresectable salivary gland tumors were treated with combination chemotherapy, primarily with cisplatin, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide, or cisplatin with 5-fluorouracil. In patients whose tumors exhibited no response, second-line drugs were used. The overall response rate was 50%--with one complete response--but the duration of response was short. This report contributes to the growing data base that demonstrates definite chemosensitivity of these tumors. To date, 116 patients have been reviewed. Adenocarcinoma-like cancers respond best to cisplatin, doxorubicin hydrochloride, and 5-fluorouracil. High-grade mucoepidermoid carcinoma may show a sensitivity similar to that of squamous cell carcinoma. Multi-institutional protocols need to be developed to assess the roles of adjuvant and palliative chemotherapy in the treatment of salivary gland cancer.


Trajectories of diurnal cortisol in mothers of children with autism and other developmental disabilities: relations to health and mental health.
This study used a stress biomarker, diurnal cortisol, to identify how elevated stress in mothers of children and adults with autism and other disabilities relates to their health and mental health. Based on semi-parametric, group-based trajectory analysis of 91 mothers, two distinctive cortisol trajectories emerged: blunted (63 %) or steep (37 %). Mothers in the blunted (vs. steep) trajectory had higher stress levels, lower health ratings, and 89 % of mothers of children with autism, and 53 % with other disabilities, belonged to this trajectory. Atypical cortisol awakening responses and evening rises were differentially associated with anxiety, depression, health problems and employment status. Stress-reducing interventions are needed for parents of children with autism and other disabilities that include biomarkers as indices of risk or treatment outcome.


[A new class of phenomena identified during the analysis of neural network of multidimensional data from patients with inflammatory lung diseases].
To apply the neural network analysis method of multi-data of patients with community-acquired pneumonia (CAP) to recognize the variability of their diagnoses and discovery of new analytical capabilities of NSA based on new methodological approaches of the meeting. In this paper, we applied a new approach of neural network analysis of multivariate data, obtained based on clinical, laboratory and instrumental tests in 60 patients older than 65 years at various stages of the treatment of community-acquired pneumonia. Anthropometric data were used together with the results of immunological and immunochemical studies of blood serum of patients with community-acquired pneumonia who were in the acute phase of the disease. A new approach analysis of these data revealed the presence of characteristic groups of the biomarkers, which consist from a combination of a small number of the signs that are necessary and sufficient in the aggregate for accurate classification of diagnoses for patients. The presence of these symptoms characteristic series shows that we have discovered a new class of phenomena. These phenomena manifest themselves in the hidden relationships between the signs which included in these groups and are reflect features of the flow processes in the pathogenesis of inflammatory diseases of the lungs in different diagnostic areas. Their study can be an important and interesting in terms of understanding the many aspects of this disease.


The immunomodulatory functions of chromogranin A-derived peptide pancreastatin.
Chromogranin A (CgA) is a 439 amino acid protein secreted by neuroendocrine cells. Proteolytic processing of CgA results in the production of different bioactive peptides. These peptides have been associated with inflammatory bowel disease, diabetes, and cancer. One of the chromogranin A-derived peptides is ∼52 amino acid long Pancreastatin (PST: human (h)CgA250-301, murine (m)CgA263-314). PST is a glycogenolytic peptide that inhibits glucose-induced insulin secretion from pancreatic islet β-cells. In addition to this metabolic role, evidence is emerging that PST also has inflammatory properties. This review will discuss the immunomodulatory properties of PST and its possible mechanisms of action and regulation. Moreover, this review will discuss the potential translation to humans and how PST may be an interesting therapeutic target for treating inflammatory diseases.


Polypyrroles formed from porphobilinogen and amines by uroporphyrinogen synthetase of Rhodopseudomonas spheroides.
1. Uroporphyrinogen I synthetase of Rhodopseudomonas spheroides was purified more than 200-fold from the soluble protein of broken bacterial cells. The enzyme had molecular weight 36000, an isoelectric point of 4.46 and migrated as a single active protein band on disc-gel electrophoresis at pH7.5 and 8.9. 2. The enzyme consumed porphobilinogen and formed uroporphyrinogen at pH8.2 without the accumulation of intermediates. In the presence of hydroxylamine, ammonia or methoxyamine the production of porphyrinogen was inhibited and the enzyme formed open-chain polypyrroles instead. 3. These polypyrroles behaved like uroporphyrinogen on Sephadex G-25; they were colourless and had unsubstituted alpha-pyrrolic positions. The inhibitory amines were incorporated into the molecules. 4. The polypyrroles formed porphyrins non-enzymically and the cyclization reaction was accompanied by the release of the inhibitory amine. Exchange of the amino function of the original porphobilinogen in the polypyrrole was complete with hydroxylamine and almost complete with methoxyamine, both ammonia and methoxyamine being present in the polypyrrolic material. 5. The behaviour, properties and composition of the radioactive hydroxylamine derivative were consistent with a tetrapyrrolic structure, probably a pyrrylmethane, that was not cyclized, rather than with di-, tri- or penta-pyrrolic structures. No monopyrrolic or dipyrrolic Ehrlich-positive material was released on cyclization. The ammonia and methoxyamine derivatives had properties similar to the hydroxylamine derivative. 6. Another modified pyrrole was detected only in experiments with hydroxylamine. It differed from both porphobilinogen and known dipyrroles and appeared to be a monopyrrole. 7. The participation of positively charged reaction centres in the enzymic mechanism, particularly in the cyclization step, is discussed.


Monoclonal antibodies to rat androgen-binding protein recognize both of its subunits and cross-react with rabbit and human testosterone-binding globulin.
A series of four monoclonal antibodies to rat androgen-binding protein (ABP) has been developed. These antibodies recognize both the heavy (48,400-dalton) and light (43,000-dalton) subunits of the native ABP molecule. In addition, they recognize the subunits from which Asn-linked oligosaccharides have been removed by treatment with N-glycanase, indicating that these moieties do not form the immunological determinants recognized by the antibodies. Two of these antibodies are capable of recognizing both nondenatured ABP, as assessed by dot blot analysis, and denatured ABP, as determined by Western blot analysis of ABP after electrophoresis under denaturing conditions. The immunoreactivity of denatured ABP is decreased with two of the antibodies, suggesting that they more readily recognize the antigenic epitopes when the protein is in its native configuration. The antibodies were capable of immunoprecipitating covalently labeled ABP from solution. All four monoclonal antibodies produced were determined to be immunoglobulins M by both enzyme-linked immunosorbent assay and Ouchterlony immunodiffusion even though the initial serum response of the immunized animals indicated the presence of immunoglobulins G. All of the monoclonal antibodies raised against rat ABP cross-reacted with rabbit and human testosterone-binding globulin (TeBG). They were able to detect two subunits when Western blots of intact rabbit [mol wt (Mr, 43,000 and 40,500] or human (Mr, 47,600 and 44,500) TeBG were probed, but only a single subunit (Mr, 39,300) when deglycosylated samples of rabbit TeBG were analyzed.


Women's positions during the second stage of labour: views of primary care midwives.
This paper is a report of a study to explore the views of midwives on women's positions during the second stage of labour. Many authors recommend encouraging women to use positions that are most comfortable to them. Others advocate encouragement of non-supine positions, because offering 'choice' is not enough to reverse the strong cultural norm of giving birth in the supine position. Midwives' views on women's positions have rarely been explored. Six focus groups were conducted in 2006-2007 with a purposive sample of 31 midwives. The data were interpreted using Thachuk's models of informed consent and informed choice. The models were useful in distinguishing between two different approaches of midwives to women's positions during labour. When giving informed consent, midwives implicitly or explicitly ask a woman's consent for what they themselves prefer. When offering informed choice, a woman's preference is the starting point, but midwives will suggest other options if this is in the woman's interest. Obstetric factors and working conditions are reasons to deviate from women's preferences. To give women an informed choice about birthing positions, midwives need to give them information during pregnancy and discuss their position preferences. Women should be prepared for the unpredictability of their feelings in labour and for obstetric factors that may interfere with their choice of position. Equipment for non-supine births should be more midwife-friendly. In addition, midwives and students need to be able to gain experience in assisting births in non-supine positions.


Use of a radioimmunoassay to quantify thrombospondin.
Results of radioimmunoassay procedures applied to samples containing thrombospondin indicated that reliable values are obtained either in saline or in plasma. Plasma levels in apparently normal individuals ranged from approximately 20 to 300 ng/ml. The mean for 20 individuals was 175 ng/ml. Plasma specimens stored either refrigerated at 4 degrees C or frozen at -80 degrees C showed significantly diminished thrombospondin levels over a period of 90 days. Serum levels of thrombospondin were found to range from 10,000 to 30,000 ng/ml.


Grassland intensification effects cascade to alter multifunctionality of wetlands within metaecosystems.
Sustainable agricultural intensification could improve ecosystem service multifunctionality, yet empirical evidence remains tenuous, especially regarding consequences for spatially coupled ecosystems connected by flows across ecosystem boundaries (i.e., metaecosystems). Here we aim to understand the effects of land-use intensification on multiple ecosystem services of spatially connected grasslands and wetlands, where management practices were applied to grasslands but not directly imposed to wetlands. We synthesize long-term datasets encompassing 53 physical, chemical, and biological indicators, comprising >11,000 field measurements. Our results reveal that intensification promotes high-quality forage and livestock production in both grasslands and wetlands, but at the expense of water quality regulation, methane mitigation, non-native species invasion resistance, and biodiversity. Land-use intensification weakens relationships among ecosystem services. The effects on grasslands cascade to alter multifunctionality of embedded natural wetlands within the metaecosystems to a similar extent. These results highlight the importance of considering spatial flows of resources and organisms when studying land-use intensification effects on metaecosystems as well as when designing grassland and wetland management practices to improve landscape multifunctionality.


Autism and the transition to university from the student perspective.
University provides individuals with the opportunity to develop greater independence in living skills and social networks, while also gaining valuable qualifications. Despite a high proportion of autistic individuals aspiring to attend university, many either do not seek or gain entry or drop out prematurely. Although some steps have been taken to develop effective support, a recent review highlighted the scarcity of research into programmes designed to support autistic students transitioning to university. In addition, few studies have examined the views of autistic students themselves. This study investigated the perspectives of autistic students transitioning to university. Three focus groups were conducted with 25 autistic students preparing to start university. Participants were asked about their hopes for starting university, as well as their worries and concerns. Data were analysed using thematic analysis, from which five main themes were identified: The Social World, Academic Demands, Practicalities of University Living, Leaving the Scaffolding of Home and Transition to Adulthood. The results provide an important account of the challenges autistic students face when transitioning to university, as well as their aspirations. These findings have a number of practical implications.


Effects on musculoskeletal pain from "Take a Stand!" - a cluster-randomized controlled trial reducing sitting time among office workers.
Objectives Prolonged sitting at work has been found to increase risk for musculoskeletal pain. The office-based intervention "Take a Stand!" was effective in reducing sitting time at work. We aimed to study the effect of the intervention on a secondary outcome: musculoskeletal pain. Methods Take a Stand! included 19 offices (317 workers) at four workplaces cluster randomized to intervention or control. The multicomponent intervention lasted three months and included management support, environmental changes, and local adaptation. Control participants behaved as usual. Musculoskeletal pain was measured by self-report questionnaire assessing pain in neck-shoulders, back and extremities in three categories at baseline, and one and three months follow-up. Results At one month, there was no difference in odds ratio (OR) for pain in neck-shoulders between the two groups. However, after three months, the OR was 0.52 [95% confidence interval (95% CI) 0.30-0.92] for pain in neck-shoulders in the intervention compared to the control group. No differences were found between the intervention and control group for pain in back and extremities over the three months. For total pain score a slight reduction was found in the intervention compared to the control group at one and three months [-0.13 (95% CI -0.23- -0.03) and -0.17 (95% CI -0.32- -0.01)]. Conclusions The secondary analyses showed that the office-based intervention Take a Stand! reduced neck-shoulder pain after three months and total pain score after one and three months among office workers, but not neck-shoulder pain after one month or pain in the back and extremities.


Immigrant girls perceive less stress.
To develop a new stress scale and use it for investigating impact of ethnicity on perception of stress. One thousand one hundred and twenty-four students (grades 6-9) from 14 schools filled in a questionnaire at school with questions about age, sex, use of language at home (proxy for cultural background), stress and stressors. Factor analysis and analysis of variance were used to analyze the data. Two-stress dimensions were identified, 'pressure'(7 items, Cronbach's alpha 0.862) and 'activation'(4 items, Cronbach's alpha 0.767). Scores on the two scales and a separate 'stress' item were higher in girls and increased with grade. Use of another language than Swedish at home showed a significant effect only for activation, with lower scores in girls. The interaction effect between sex and language was significant for all variables and was due mainly to lower stress in girls using another language than Swedish at home. This new stress scale has some promising qualities like a condensed format, basis in a specific stress concept and formulated to be as age and culture independent as possible. Immigrant girls seem to perceive less stress than Swedish born girls, which opens up for questions about protective mechanisms.


Coadministration of polyinosinic:polycytidylic acid and immunostimulatory complexes modifies antigen processing in dendritic cell subsets and enhances HIV gag-specific T cell immunity.
Currently approved adjuvants induce protective Ab responses but are more limited for generating cellular immunity. In this study, we assessed the effect of combining two adjuvants with distinct mechanisms of action on their ability to prime T cells: the TLR3 ligand, polyinosinic:polycytidylic acid (poly I:C), and immunostimulatory complexes (ISCOMs). Each adjuvant was administered alone or together with HIV Gag protein (Gag), and the magnitude, quality, and phenotype of Gag-specific T cell responses were assessed. For CD8 T cells, all adjuvants induced a comparable response magnitude, but combining poly I:C with ISCOMs induced a high frequency of CD127(+), IL-2-producing cells with decreased expression of Tbet compared with either adjuvant alone. For CD4 T cells, combining poly I:C and ISCOMs increased the frequency of multifunctional cells, producing IFN-γ, IL-2, and TNF, and the total magnitude of the response compared with either adjuvant alone. CD8 or CD4 T cell responses induced by both adjuvants mediated protection against Gag-expressing Listeria monocytogenes or vaccinia viral infections. Poly I:C and ISCOMs can alter Ag uptake and/or processing, and we therefore used fluorescently labeled HIV Gag and DQ-OVA to assess these mechanisms, respectively, in multiple dendritic cell subsets. Poly I:C promoted uptake and retention of Ag, whereas ISCOMs enhanced Ag degradation. Combining poly I:C and ISCOMs caused substantial death of dendritic cells but persistence of degraded Ag. These data illustrate how combining adjuvants, such as poly I:C and ISCOMs, that modulate Ag processing and have potent innate activity, can enhance the magnitude, quality, and phenotype of T cell immunity.


Specific carbonate-microbe interactions in the modern microbialites of Lake Alchichica (Mexico).
The role of microorganisms in microbialite formation remains unresolved: do they induce mineral precipitation (microbes first) or do they colonize and/or entrap abiotic mineral precipitates (minerals first)? Does this role vary from one species to another? And what is the impact of mineral precipitation on microbial ecology? To explore potential biogenic carbonate precipitation, we studied cyanobacteria-carbonate assemblages in modern hydromagnesite-dominated microbialites from the alkaline Lake Alchichica (Mexico), by coupling three-dimensional imaging of molecular fluorescence emitted by microorganisms, using confocal laser scanning microscopy, and Raman scattering/spectrometry from the associated minerals at a microscale level. Both hydromagnesite and aragonite precipitate within a complex biofilm composed of photosynthetic and other microorganisms. Morphology and pigment-content analysis of dominant photosynthetic microorganisms revealed up to six different cyanobacterial morphotypes belonging to Oscillatoriales, Chroococcales, Nostocales and Pleurocapsales, as well as several diatoms and other eukaryotic microalgae. Interestingly, one of these morphotypes, Pleurocapsa-like, appeared specifically associated with aragonite minerals, the oldest parts of actively growing Pleurocapsa-like colonies being always aragonite-encrusted. We hypothesize that actively growing cells of Pleurocapsales modify local environmental conditions favoring aragonite precipitation at the expense of hydromagnesite, which precipitates at seemingly random locations within the biofilm. Therefore, at least part of the mineral precipitation in Alchichica microbialites is most likely biogenic and the type of biominerals formed depends on the nature of the phylogenetic lineage involved. This observation may provide clues to identify lineage-specific biosignatures in fossil stromatolites from modern to Precambrian times.


Knit Architecture for Water-Actuating Woolen Knitwear and Its Personalized Thermal Management.
Personalized thermal management using water-actuated woolen knitwear has great potential for smart textile production. However, woolen knitwear exists in a wide range of forms with different derivatives. Manufacturing of smart woolen structures with excellent cooling properties is linked to certain parameters such as changes in loop formation, loop shape, and yarn arrangement upon stimulation of body fluids. To address this issue, textile knit structures with different physical and mechanical properties have been prepared using water-responsive descaled wool fibers and their smart heat and moisture regulation behavior have been investigated and compared to detect the fabric architectural effect on water actuation and cooling performance of woolen garments. The evidence suggests that the technical structure of the fabrics plays a crucial role in pore actuation and fabric cooling performance. The water actuation and thermal management abilities of single jersey were greatly enhanced because of unbalanced structures with lower mechanical stress among the loops and yarns. The experimental data is also in line with the theoretical analysis. Hence, the unbalanced structures control fast heat and mass transfer from the human body, which may offer a promising year-round clothing material to the wearer. This material can have a similar response upon contact with body sweat and humid environments and hence can act as a skinlike fabric. Their possible applications can lie in different fields, such as thermoregulation, functional clothing, sportswear, and medical care.


Use of a Portable Assistive Glove to Facilitate Rehabilitation in Stroke Survivors With Severe Hand Impairment.
Treatment options for stroke survivors with severe hand impairment are limited. Active task practice can be restricted by difficulty in voluntarily activating finger muscles and interference from involuntary muscle excitation. We developed a portable, actuated glove-orthosis, which could be employed to address both issues. We hypothesized that combining passive cyclical stretching (reducing motoneuronal hyperexcitability) imposed by the device with active-assisted, task-oriented training (rehabilitating muscle activation) would improve upper extremity motor control and task performance post-stroke. Thirteen participants who experienced a stroke 2-6 months prior to enrollment completed 15 treatment sessions over five weeks. Each session involved cyclically stretching the long finger flexors (30 min) followed by active-assisted task-oriented movement practice (60 min). Outcome measures were completed at six intervals: three before and three after treatment initiation. Overall improvement in post-training scores was observed across all outcome measures, including the Graded Wolf Motor Function Test, Action Research Arm Test, and grip and pinch strength (p ≤ 0.02), except finger extension force. No significant change in spasticity was observed. Improvement in upper extremity capabilities is achievable for stroke survivors even with severe hand impairment through a novel intervention combining passive cyclical stretching and active-assisted task practice, a paradigm which could be readily incorporated into the clinic.


Structural basis for near unity quantum yield core/shell nanostructures.
Aberration-corrected Z-contrast scanning transmission electron microscopy of core/shell nanocrystals shows clear correlations between structure and quantum efficiency. Uniform shell coverage is obtained only for a graded CdS/ZnS shell material and is found to be critical to achieving near 100% quantum yield. The sublattice sensitivity of the images confirms that preferential growth takes place on the anion-terminated surfaces. This explains the three-dimensional "nanobullet" shape observed in the case of core/shell nanorods.


Cdc50p, a protein required for polarized growth, associates with the Drs2p P-type ATPase implicated in phospholipid translocation in Saccharomyces cerevisiae.
Cdc50p, a transmembrane protein localized to the late endosome, is required for polarized cell growth in yeast. Genetic studies suggest that CDC50 performs a function similar to DRS2, which encodes a P-type ATPase of the aminophospholipid translocase (APT) subfamily. At low temperatures, drs2Delta mutant cells exhibited depolarization of cortical actin patches and mislocalization of polarity regulators, such as Bni1p and Gic1p, in a manner similar to the cdc50Delta mutant. Both Cdc50p and Drs2p were localized to the trans-Golgi network and late endosome. Cdc50p was coimmunoprecipitated with Drs2p from membrane protein extracts. In cdc50Delta mutant cells, Drs2p resided on the endoplasmic reticulum (ER), whereas Cdc50p was found on the ER membrane in drs2Delta cells, suggesting that the association on the ER membrane is required for transport of the Cdc50p-Drs2p complex to the trans-Golgi network. Lem3/Ros3p, a homolog of Cdc50p, was coimmunoprecipitated with another APT, Dnf1p; Lem3p was required for exit of Dnf1p out of the ER. Both Cdc50p-Drs2p and Lem3p-Dnf1p were confined to the plasma membrane upon blockade of endocytosis, suggesting that these proteins cycle between the exocytic and endocytic pathways, likely performing redundant functions. Thus, phospholipid asymmetry plays an important role in the establishment of cell polarity; the Cdc50p/Lem3p family likely constitute potential subunits specific to unique P-type ATPases of the APT subfamily.


Preformation and neoformation in shoots of Nothofagus antarctica (G. Forster) Oerst. (Nothofagaceae) shrubs from northern Patagonia.
The size (length and diameter) and number of leaf primordia of winter buds of Nothofagus antarctica (G. Forster) Oerst. shrubs were compared with the size and number of leaves of shoots derived from buds in equivalent positions. Buds developed in two successive years were compared in terms of size and number of leaf primordia. Bud size and the number of leaf primordia per bud were greater for distal than for proximally positioned buds. Shoots that developed in the five positions closest to the distal end of their parent shoots had significantly more leaves than more proximally positioned shoots of the same parent shoots. The positive relationship between the size of a shoot and that of its parent shoot was stronger for proximal than for distal positions on the parent shoots. For each bud position on the parent shoots there were differences in the number of leaf primordia per bud between consecutive years. The correlations between the number of leaf primordia per bud and bud size, bud position and parent shoot size varied between years. Only shoots produced close to the distal end of a parent shoot developed neoformed leaves; more proximal sibling shoots consisted entirely of preformed leaves. Leaf neoformation, a process usually linked with high shoot vigour in woody plants, seems to be widespread among the relatively small shoots developed in N. antarctica shrubs, which may relate to the species' opportunistic response to disturbance.


Separate and unequal: clinics where minority and nonminority patients receive primary care.
Few studies have examined the influence of physician workplace conditions on health care disparities. We compared 96 primary care clinics in New York, New York, and in the upper Midwest serving various proportions of minority patients to determine differences in workplace organizational characteristics. Cross-sectional data are from surveys of 96 clinic managers, 388 primary care physicians, and 1701 of their adult patients with hypertension, diabetes mellitus, or congestive heart failure participating in the Minimizing Error, Maximizing Outcome (MEMO) study. Data from 27 clinics with at least 30% minority patients were contrasted with data from 69 clinics with less than 30% minority patients. Compared with clinics serving less than 30% minority patients, clinics serving at least 30% minority patients have less access to medical supplies (2.7 vs 3.4, P < .001), referral specialists (3.0 vs 3.5, P < .005) on a scale of 1 (none) to 4 (great), and examination rooms per physician (2.2 vs 2.7, P =.002) . Their patients are more frequently depressed (22.8% vs 12.1%), are more often covered by Medicaid (30.2% vs 11.4%), and report lower health literacy (3.7 vs 4.4) on a scale of 1 (low) to 5 (high) (P < .001 for all). Physicians from clinics serving higher proportions of minority populations perceive their patients as frequently speaking little or no English (27.1% vs 3.4%, P =.004), having more chronic pain (24.1% vs 12.9%, P < .001) and substance abuse problems (15.1% vs 10.1%, P =.005), and being more medically complex (53.1% vs 39.9%) and psychosocially complex (44.9% vs 28.2%) (P < .001 for both). In regression analyses, clinics with at least 30% minority patients are more likely to have chaotic work environments (odds ratio, 4.0; P =.003) and to have fewer physicians reporting high work control (0.2; P =.003) or high job satisfaction (0.4; P =.01). Clinics serving higher proportions of minority patients have more challenging workplace and organizational characteristics.


Overexpression of the medium‑conductance calcium‑activated potassium channel (SK4) and the HCN2 channel to generate a biological pacemaker.
Ion channels serve important roles in the excitation‑contraction coupling of cardiac myocytes. Previous studies have shown that the overexpression or activation of intermediate‑conductance calcium‑activated potassium channel (SK4, encoded by KCNN4) in embryonic stem cell‑derived cardiomyocytes can significantly increase their automaticity. The mechanism underlying this effect is hypothesized to be associated with the activation of hyperpolarization‑activated cyclic nucleotide‑gated channel 2 (HCN2). The aim of the present study was to explore whether a biological pacemaker could be constructed by overexpressing SK4 alone or in combination with HCN2 in a rat model. Ad‑green fluorescent protein (GFP), Ad‑KCNN4 and Ad‑HCN2 recombinant adenoviruses were injected into the left ventricle of Sprague‑Dawley rat hearts. The rats were divided into a GFP group (n=10), an SK4 group (n=10), a HCN2 group (n=10) and an SK4 + HCN2 (SK4/HCN2) group (n=10). The isolated hearts were perfused at 5‑7 days following injection, and a complete heart block model was established. Compared with the GFP group, overexpressing SK4 alone did not significantly increase the heart rate after establishment of a complete heart block model [98.1±8.9 vs. 96.7±7.6 beats per min (BPM)], The heart rates in the SK4/HCN2 (139.9±21.9 BPM) and HCN2 groups (111.7±5.5 BPM) were significantly increased compared with the GFP and SK4 groups, and the heart rates in the SK4/HCN2 group were significantly increased compared with the SK4 or HCN2 groups. In the HCN2 (n=8) and the SK4/HCN2 (n=7) groups, the shape of the spontaneous ventricular rhythm was the same as the pacing‑induced ectopic rhythm in the transgenically altered site. By contrast, these rhythms were different in the SK4 (n=10) and GFP (n=10) groups. There were no significant differences in action potential duration alternans or ventricular arrhythmia inducibility between the four groups (all P>0.05). Western blotting, reverse transcription‑quantitative PCR and immunohistochemistry analyses showed that the expression levels of SK4 and HCN2 were significantly increased at the transgene site. Biological pacemaker activity could be successfully generated by co‑overexpression of SK4 and HCN2 without increasing the risk of ventricular arrhythmias. The overexpression of SK4 alone is insufficient to generate biological pacemaker activity. The present study provided evidence that SK4 and HCN2 combined could construct an ectopic pacemaker, laying the groundwork for the development of improved biological pacing mechanisms in the future.


Interfacial surface roughness determination by coherence scanning interferometry using noise compensation.
The capability of coherence scanning interferometry has been extended recently to include the determination of the interfacial surface roughness between a thin film and a substrate when the surface perturbations are less than ∼10 nm in magnitude. The technique relies on introducing a first-order approximation to the helical complex field (HCF) function. This approximation of the HCF function enables a least-squares optimization to be carried out in every pixel of the scanned area to determine the heights of the substrate and/or the film layers in a multilayer stack. The method is fast but its implementation assumes that the noise variance in the frequency domain is statistically the same over the scanned area of the sample. This results in reconstructed surfaces that contain statistical fluctuations. In this paper we present an alternative least-squares optimization method, which takes into account the distribution of the noise variance-covariance in the frequency domain. The method is tested using results from a simulator and these show a significant improvement in the quality of the reconstructed surfaces.


[Biological markers of interenvironmental distribution of trace elements in the environmental objects].
Priority trace elements were identified in the environmental objects, such as drinking water, atmosphere of residential areas (by their levels in the snow cover), soil, and foodstuffs. The identification of trace elements in the environmental objects revealed various total loads and distribution of trace elements in the study environments of urban and rural areas, which might be largely determined by the degree of interenvironmental transition and the routes of their migration. By identifying of priority trace elements, the authors constructed models describing the correlation of elements in the study conjugate environments and the specific features of their interenvironmental transition in the environment-man system in the urban and rural areas. Paired correlation and multiple regression analyses on the basis of systemic modeling were used to determine a relationship of trace elements in the study environments to the specific features of their interenvironmental transition. Examination of the trace element status of children's hairs and its comparison with the content of trace elements in the environmental objects allowed an association to be determined between the qualitative and quantitative trace element composition of portable water, soil, snow cover, foodstuffs, and the body's biological media. Summing up the findings leads to a conclusion about the origin of trace element pollutions and the possible routes of their entry into the body and allows consideration of the trace elements Zn, Mn, and Ni as markers of biological exposure of the environment while making a sociohygienic monitoring and assessing the risk to human health.


Genome-wide association analysis unveils novel QTLs for seminal root system architecture traits in Ethiopian durum wheat.
Genetic improvement of root system architecture is essential to improve water and nutrient use efficiency of crops or to boost their productivity under stress or non-optimal soil conditions. One hundred ninety-two Ethiopian durum wheat accessions comprising 167 historical landraces and 25 modern cultivars were assembled for GWAS analysis to identify QTLs for root system architecture (RSA) traits and genotyped with a high-density 90 K wheat SNP array by Illumina. Using a non-roll, paper-based root phenotyping platform, a total of 2880 seedlings and 14,947 seminal roots were measured at the three-leaf stage to collect data for total root length (TRL), total root number (TRN), root growth angle (RGA), average root length (ARL), bulk root dry weight (RDW), individual root dry weight (IRW), bulk shoot dry weight (SDW), presence of six seminal roots per seedling (RT6) and root shoot ratio (RSR). Analysis of variance revealed highly significant differences between accessions for all RSA traits. Four major (- log10P ≥ 4) and 34 nominal (- log10P ≥ 3) QTLs were identified and grouped in 16 RSA QTL clusters across chromosomes. A higher number of significant RSA QTL were identified on chromosome 4B particularly for root vigor traits (root length, number and/or weight). After projecting the identified QTLs on to a high-density tetraploid consensus map along with previously reported RSA QTL in both durum and bread wheat, fourteen nominal QTLs were found to be novel and could potentially be used to tailor RSA in elite lines. The major RGA QTLs on chromosome 6AL detected in the current study and reported in previous studies is a good candidate for cloning the causative underlining sequence and identifying the beneficial haplotypes able to positively affect yield under water- or nutrient-limited conditions.


The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts.
IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants harbor an amino acid replacement of His435 to Arg that reverts the half-life of the resulting IgG3 to the same level as the other IgG subclasses. Because of its functional impact, we hypothesized that the p.Arg435His variation could be associated with susceptibility to autoantibody-mediated diseases like pemphigus vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German, Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate a genetic association of the p.Arg435His variation with PV risk, but not with BP risk. Our results suggest a hitherto unknown role for the function of IgG3 in the pathogenesis of PV.