Blast-induced brain injury and posttraumatic hypotension and hypoxemia.
Explosive munitions account for more than 50% of all wounds sustained in military combat, and the proportion of civilian casualties due to explosives is increasing as well. But there has been only limited research on the pathophysiology of blast-induced brain injury, and the contributions of alterations in cerebral blood flow (CBF) or cerebral vascular reactivity to blast-induced brain injury have not been investigated. Although secondary hypotension and hypoxemia are associated with increased mortality and morbidity after closed head injury, the effects of secondary insults on outcome after blast injury are unknown. Hemorrhage accounted for approximately 50% of combat deaths, and the lungs are one of the primary organs damaged by blast overpressure. Thus, it is likely that blast-induced lung injury and/or hemorrhage leads to hypotensive and hypoxemic secondary injury in a significant number of combatants exposed to blast overpressure injury. Although the effects of blast injury on CBF and cerebral vascular reactivity are unknown, blast injury may be associated with impaired cerebral vascular function. Reactive oxygen species (ROS) such as the superoxide anion radical and other ROS, likely major contributors to traumatic cerebral vascular injury, are produced by traumatic brain injury (TBI). Superoxide radicals combine with nitric oxide (NO), another ROS produced by blast injury as well as other types of TBI, to form peroxynitrite, a powerful oxidant that impairs cerebral vascular responses to reduced intravascular pressure and other cerebral vascular responses. While current research suggests that blast injury impairs cerebral vascular compensatory responses, thereby leaving the brain vulnerable to secondary insults, the effects of blast injury on the cerebral vascular reactivity have not been investigated. It is clear that further research is necessary to address these critical concerns.


Theranostics in nuclear medicine practice.
The importance of personalized medicine has been growing, mainly due to a more urgent need to avoid unnecessary and expensive treatments. In nuclear medicine, the theranostic approach is an established tool for specific molecular targeting, both for diagnostics and therapy. The visualization of potential targets can help predict if a patient will benefit from a particular treatment. Thanks to the quick development of radiopharmaceuticals and diagnostic techniques, the use of theranostic agents has been continually increasing. In this article, important milestones of nuclear therapies and diagnostics in the context of theranostics are highlighted. It begins with a well-known radioiodine therapy in patients with thyroid cancer and then progresses through various approaches for the treatment of advanced cancer with targeted therapies. The aim of this review was to provide a summary of background knowledge and current applications, and to identify the advantages of targeted therapies and imaging in nuclear medicine practices.


Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists.
Narrow-band imaging (NBI) is a novel, noninvasive optical technique that uses reflected light to visualize the organ surface. However, few prospective studies that examine the efficacy of NBI screening for esophageal cancer have been reported. To compare the diagnostic yield of NBI endoscopy for screening of squamous mucosal high-grade neoplasia of the esophagus between experienced and less experienced endoscopists. Patients with a history of esophageal neoplasia or head and neck cancer received NBI endoscopic screening for esophageal neoplasia followed by chromoendoscopy using iodine staining. Biopsy specimens were taken from iodine-unstained lesions and the histological results of mucosal high-grade neoplasias served as the reference standard. The primary outcome was the sensitivity of NBI for detecting new lesions. The secondary outcome was the positive predictive value of NBI and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of NBI in a per lesion basis. A total of 350 patients (170 by experienced endoscopists and 180 by less experienced endoscopists) underwent endoscopic examination. A total of 42 new mucosal high-grade neoplastic lesions (25 in the experienced endoscopist group and 17 in the less experienced endoscopist group) were detected. In the per-lesion-based analysis, the sensitivity was significantly higher in the experienced endoscopist group (100%; 25/25) compared with the less experienced endoscopist group (53%; 9/17) (P < 0.001). The positive predictive value of NBI was higher in the experienced endoscopist group than in the less experienced endoscopist group (45%, 25/55 vs. 35%, 9/26), although the difference was not significant (P = 0.50). The sensitivity of NBI in the less experienced endoscopist group was 43% in the former half of patients, and increased to 60% in the latter half of patients. In the per-patient-based analysis, the sensitivity of NBI was significantly higher in the experienced endoscopist group (100%) than in the less experienced endoscopist group (100 vs. 69%, respectively; P = 0.04). The positive predictive values of the experienced endoscopist group and the less experienced endoscopist group were similar, and were 48 and 47%, respectively. In conclusion, compared with the gold standard of chromoendoscopy with iodine staining, the sensitivity of NBI for screening of mucosal high-grade neoplasia was 100% with the experienced endoscopists but was low with the less experienced endoscopists. Electronic chromoendoscopy with NBI is a promising screening tool in these high-risk patients with esophageal mucosal high-grade neoplasia, particularly when performed by endoscopists with experience of using NBI.


A framework to benchmark the quality of clinical assessment in a South African undergraduate medical programme.
The outcome of the undergraduate medical programme is to produce clinically competent health care providers relevant for the South African context. Educational institutions find it hard to ensure the quality of assessments where competency must be assessed. This study aimed to compile an assessment framework that can be used to benchmark current assessment practices in the clinical phase of the undergraduate medical programme where competency must be certified. In this observational, descriptive study, qualitative data were gathered using the steps described by the World Health Organization for rapid reviews. Literature was searched, screened and selected before data were analysed and a framework was constructed. Twenty-five official documents were included in the study. The framework addressed the three components of quality assessment, namely, accreditation, assessment and quality assurance. Assessors should attend to the principles of assessment, namely, validity, reliability, fairness, feasibility, educational effect and acceptability, but realise that no assessment meets all these criteria. The first step to ensure quality assessment is to identify a clear outcome. Assessment should be planned and aligned with this outcome. It is clear that clinical assessment is multidimensional and that no assessment is perfect. Programme accreditation, assessment practices and psychometrics can assist to improve the quality of assessment but cannot judge clinical competence. Using experienced assessors with a variety of assessment methods on a continuous basis is the proposed way to assess clinical competence. An assessment framework can assist to improve assessment, but it cannot guarantee quality assessment.


"Feasible and effective administration of Bortezomib with Rituximab in children with relapsed/resistant B-cell precursor acute lymphoblastic leukemia (BCP-ALL): A step toward the first line".
Despite a high cure rate in childhood BCP-ALL, 20% of children still presents with relapse, mostly due to a persistent leukemic clone during the first-line treatment. In this context, obtaining a molecular remission is crucial for reaching a successful allogeneic hematopoietic stem cell transplantation. Bortezomib was effectively administered to children with resistant/relapsed (r/r) BCP-ALL. Moreover, high risk ALL is characterized by the increasing expression of CD20. For the first time we reported two children with r/r BCP-ALL who received a treatment schema including Bortezomib and Rituximab, achieving morphological and molecular remission. Children with high risk features, such as persistent minimal residual disease during induction, will benefit from this combination. Is it time to move toward the first line?


Interaction of nicotine and other amines with the endocytic and exocytic functions of macrophages.
Nicotine inhibits endocytosis and stimulates exocytosis in macrophages. At the same concentrations (5-15 mM) that the alkaloid exerts these effects, it is also vacuologenic. Consideration was given to one hypothesis that the membrane internalization was a result of surfactant activity. Nicotine was found to have surfactant properties. Studies involving measurements of the contact angles of a sessile drop of saline on cell monolayers suggested that nicotine increased the hydrophilicity of the membrane. The possibility has been considered that this may be indicative of membrane expansion and that this expansion leads to collapse and vesicle formation. This would be analogous to the effects of surface-active amines (e.g., local anesthetics, tranquilizers, antihistamines) on lipid monolayers and erythrocytic membranes. It is suggested that if such a mechanism does occur, then the possibility exists for a variety of amines to nonspecifically alter membrane and receptor availability of the macrophage.


The electromyographic behavior of the thyroarytenoid muscle during swallowing.
The electromyographic (EMG) behavior of the laryngeal adductors (e.g., the thyroarytenoid [TA] muscle) during swallowing has been scarcely studied. However, the detailed analysis of TA muscle is important to understand the physiology of swallowing. We investigated 14 healthy adult subjects. Activation of the TA laryngeal adductor muscle was compared with the mechanically measured laryngeal up-down movement and with the onset of excitation of laryngeal elevators, such as submental (SM) muscles, during swallowing. The laryngeal adductor of TA and laryngeal elevators of SM muscles were electromyographically (integrated/rectified) recorded. The vertical laryngeal movements during swallowing were recorded using a piezoelectric sensor. The EMG behavior of the TA muscle revealed three different activities during swallowing. The basic activity was stable; it almost started with the upward movement of larynx and after the SM-EMG onset. A fore-burst was recorded just before the upward movement of the larynx and a late-burst appeared just after the downward movement. The fore-burst was proposed to be related with oral-laryngeal reflexes, and the late-burst could be a rebound activity after a short expiration of swallowing, while the basic activity is accepted to be a part of activity of central-pattern generator of swallowing program.


Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.
Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome-wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing-1-like (DOT1L). We have been studying thyroid hormone (T3)-dependent amphibian metamorphosis in two highly related species, the pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study. We previously showed that H3K79 methylation levels are induced at T3 target genes during natural and T3-induced metamorphosis and that Dot1L is itself a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in turn functions as a T3 receptor (TR) coactivator to promote vertebrate development. We show here that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3. Furthermore, making use of the ability to carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we demonstrate that endogenous Dot1L is critical for T3-induced activation of endogenous TR target genes while transgenic Dot1L enhances endogenous TR function in premetamorphic tadpoles in the presence of T3. Our studies thus for the first time provide complementary gain- and loss-of functional evidence in vivo for a cofactor, Dot1L, in gene activation by TR during vertebrate development.-Wen, L., Fu, L., Shi, Y.-B. Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.


Chronopotentiometric carbonate detection with all-solid-state ionophore-based electrodes.
We present here for the first time an all-solid-state chronopotentiometric ion sensing system based on selective ionophores, specifically for the carbonate anion. A chronopotentiometric readout is attractive because it may allow one to obtain complementary information on the sample speciation compared to zero-current potentiometry and detect the sum of labile carbonate species instead of only ion activity. Ferrocene covalently attached to the PVC polymeric chain acts as an ion-to-electron transducer and provides the driving force to initiate the sensing process at the membrane-sample interface. The incorporation of a selective ionophore for carbonate allows one to determine this anion in a background electrolyte. Various inner electrolyte and all-solid-state-membrane configurations are explored, and localized carbonate depletion is only observed for systems that do not contain ion-exchanger additives. The square root of the transition times extracted from the inflection point of the chronopotentiograms as a function of carbonate specie concentration follows a linear relationship. The observed linear range is 0.03-0.35 mM in a pH range of 9.50-10.05. By applying the Sand equation, the diffusion coefficient of carbonate is calculated as (9.03 ± 0.91) 10(-6) cm(2) s(-1), which corresponds to the established value. The reproducibility of assessed carbonate is better than 1%. Additionally, carbonate is monitored during titrimetric analysis as a precursor to an in situ environmental determination. Based on these results, Fc-PVC membranes doped with ionophores may form the basis of a new family of passive/active all-solid-state ion selective electrodes interrogated by a current pulse.


Genetic mapping of natural variation in schooling tendency in the threespine stickleback.
Although there is a heritable basis for many animal behaviors, the genetic architecture of behavioral variation in natural populations remains mostly unknown, particularly in vertebrates. We sought to identify the genetic basis for social affiliation in two populations of threespine sticklebacks (Gasterosteus aculeatus) that differ in their propensity to school. Marine sticklebacks from Japan school strongly whereas benthic sticklebacks from a lake in Canada are more solitary. Here, we expanded on our previous efforts to identify quantitative trait loci (QTL) for differences in schooling tendency. We tested fish multiple times in two assays that test different aspects of schooling tendency: 1) the model school assay, which presents fish with a school of eight model sticklebacks; and 2) the choice assay, in which fish are given a choice between the model school and a stationary artificial plant. We found low-to-moderate levels of repeatability, ranging from 0.1 to 0.5, in schooling phenotypes. To identify the genomic regions that contribute to differences in schooling tendency, we used QTL mapping in two types of crosses: benthic × marine backcrosses and an F2 intercross. We found two QTL for time spent with the school in the model school assay, and one QTL for number of approaches to the school in the choice assay. These QTL were on three different linkage groups, not previously linked to behavioral differences in sticklebacks. Our results highlight the importance of using multiple crosses and robust behavioral assays to uncover the genetic basis of behavioral variation in natural populations.


Seasonal Dynamics of Mosquito-Borne Viruses in the Southwestern Florida Everglades, 2016, 2017.
Mosquitoes were collected for 12 consecutive months beginning June 2016, from 11 locations in the Florida Everglades, Collier County, and tested for viruses by isolation in Vero cells and subsequent identification. One species complex and 31 species of mosquitoes were identified from 668,809 specimens. Ochlerotatus taeniorhynchus comprised 72.2% of the collection. Other notable species were Anopheles crucians complex, Culex nigripalpus, Cx. erraticus, and Cx. cedecei. Seven species of virus were identified from 110 isolations: Everglades, Gumbo Limbo, Mahogany Hammock, Pahayokee, Shark River, Tensaw, and West Nile viruses. Everglades, West Nile, Tensaw, and Mahogany Hammock viruses were most frequently isolated. Largest numbers of viruses were identified from Cx. cedecei, Cx. nigripalpus, and An. crucians complex. Five species of virus were isolated from Cx. cedecei. Viruses were isolated from mangrove, cypress swamp, hardwood hammock, and sawgrass habitats. West Nile virus was isolated August through October when Cx. nigripalpus was most abundant. Everglades virus was the most frequently isolated virus from nine species of mosquitoes collected from June through August. Tensaw virus was isolated primarily from Anopheles species. Isolations were made in July, August, January, February, and April, suggesting that this virus may be present in host-seeking mosquitoes throughout the year. Mahogany Hammock, Shark River, Gumbo Limbo, and Pahayokee viruses were isolated primarily from Cx. cedecei from June through December. Shotgun metagenomic sequencing was used to document that seven pools of Cx. cedecei were infected with two arboviruses. As communities expand into the Everglades, more humans will become exposed to arboviruses.


The role of nonspecific hydrophobic interactions in the biological activity of N epsilon-acyl derivatives of glucagon. Studies of conformation, receptor binding, and adenylate cyclase activation.
Glucagon was acylated at position 12 using conditions favoring reaction with the epsilon-amino group of lysine. The N epsilon-acetyl, N epsilon-hexanoyl, and N epsilon-decanoyl derivatives were prepared and purified. Secondary structure as measured by circular dichroism was lower in all derivatives than in glucagon, both in 95% methanol and in 25 mM sodium dodecyl sulfate at pH 2 and pH 12. N epsilon-Acetyl glucagon was less active than the native hormone in a radioreceptor assay and higher concentrations of this derivative were required to stimulate the adenylate cyclase activity of rat liver plasma membranes. The maximal extent of cyclase activation by this derivative was less than that found with the native hormone. N epsilon-Hexanoyl glucagon and N epsilon-decanoyl glucagon had greater activity than N epsilon-acetyl glucagon in receptor binding as well as in adenylate cyclase activation, although these two derivatives were not as active as the native hormone. N epsilon-hexanoyl glucagon and N epsilon-decanoyl glucagon were more potent in receptor binding than in adenylate cyclase activation. From these results it appears that the positive charge of the epsilon-amino groups may have a specific role in obtaining maximal biological activity, while the acyl groups contribute to the nonspecific hydrophobic interactions between the hormone and its receptor. In addition, a possible relationship between stabilization of the amphipathic helix in solution and the activity of these and other N epsilon-derivatives of glucagon is discussed.


Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study.
Low skeletal muscle mass is associated with insulin resistance and metabolic syndrome. Serum creatinine may serve as a surrogate marker of muscle mass, and a possible relationship between low serum creatinine and type 2 diabetes has recently been demonstrated. We aimed to validate this finding in a population of Caucasian morbidly obese subjects. Cross-sectional study of 1,017 consecutive morbidly obese patients with an estimated glomerular filtration rate >60 ml/min/1.73 m2. Logistic regression (univariate and multiple) was used to assess the association between serum creatinine and prevalent type 2 diabetes, including statistically testing for the possibility of non-linearity in the relationship by implementation of Generalized Additive Models (GAM) and piecewise linear regression. Possible confounding variables such as age, family history of diabetes, waist-to-hip ratio, hypertension, current smoking, serum magnesium, albuminuria and insulin resistance (log HOMA-IR) were adjusted for in three separate multiple logistic regression models. The unadjusted GAM analysis suggested a piecewise linear relationship between serum creatinine and diabetes. Each 1 mumol/l increase in serum creatinine was associated with 6% (95% CI; 3%-8%) and 7% (95% CI; 2%-13%) lower odds of diabetes below serum creatinine levels of 69 and 72 mumol/l in women and men, respectively. Above these breakpoints the serum creatinine concentrations did not reduce the odds further. Adjustments for non-modifiable and modifiable risk factors left the piecewise effect for both women and men largely unchanged. In the fully adjusted model, which includes serum magnesium, albuminuria and log HOMA-IR, the piecewise effect for men was statistically non-significant, but it remained present for women. Patients with creatinine levels below median had approximately 50% (women) and 75% (men) increased odds of diabetes. Low serum creatinine is a predictor of type 2 diabetes in Caucasian morbidly obese patients, independent of age, gender, family history of diabetes, anthropometric measures, hypertension, and current smoking. Longitudinal studies of both obese and non-obese populations are needed to investigate whether serum creatinine may be causally linked with type 2 diabetes, and if so, precisely how they are linked.


[Evaluation of left ventricular function in patients with mammary carcinoma after treatment with epidoxorubicin using a high-dose, short-term protocol].
Anthracyclines are effective chemotherapeutic agents against various malignancies but their therapeutic value is limited by well-known dose-related cardiotoxicity, mainly induced by oxygen free radicals. Left ventricular diastolic and systolic functional abnormalities precede the clinical evidence of cardiotoxicity. The aim of this study was to evaluate the possible cardiotoxicity of epidoxorubicin administered as "high-dose short-term" protocol. Twenty patients (mean age 50.4 +/- 7.9 years) without cardiac disease, affected by advanced breast cancer were studied. All patients were treated with epidoxorubicin as neoadjuvant chemotherapy according to the new protocol "high-dose short-term" (cumulative dose 475.8 +/- 35.6 mg/m2, range 450-600 mg/m2, in 4-6 weeks). The effectiveness of cancer chemotherapy was monitored by clinical evaluation and mammography performed before and after treatment. All patients underwent color Doppler echocardiography and resting radionuclide angiocardiography in baseline condition and 30 +/- 10 days after the last cycle of chemotherapy. All patients showed a significant reduction of tumor lesion after chemotherapy. Left ventricular systolic and diastolic function parameters obtained by echocardiography (fractional shortening 33.1 +/- 4.5% vs 32.4 +/- 4.8%; ejection fraction 63.6 +/- 6.2% vs 62.9 +/- 5.7%; E/A ratio 1.73 +/- 0.64 vs 1.82 +/- 0.67; E wave deceleration time 204 +/- 24.6 ms vs 208.5 +/- 31.7 ms;isovolumetric relaxation time 79 +/- 15.7 ms vs 80 +/- 17.8 ms) and radionuclide angiocardiography (ejection fraction 62.4 +/- 7% vs 61.8 +/- 5.9; peak ejection rate 2.87 +/- 0.44 VTD/s vs 2.74 +/- 0.46 VTD/s; peak filling rate 2.72 +/- 0.54 VTD/s vs 2.6 +/- 0.58 VTD/s) did not show significant changes after treatment. In conclusion, our results suggest that epidoxorubicin administration using the "high-dose short-term" protocol in patients with breast cancer does not induce early significant abnormalities of left ventricular systolic and diastolic function.


Isolation of Arthrobacter spp. from clinical specimens and description of Arthrobacter cumminsii sp. nov. and Arthrobacter woluwensis sp. nov.
Arthrobacter spp. are very widely distributed in the environment (e.g., soil) but have not been described as causing disease in humans. Over a 6-year period, two reference laboratories isolated or received 11 strains which were eventually identified as belonging to the genus Arthrobacter. These strains had been initially identified as Centers for Disease Control and Prevention coryneform group B-1 and B-3 bacteria (whitishgrayish colonies of 2 mm or greater in diameter after 24 h of incubation, respiratory metabolism, absent or weak acid production from sugars, and hydrolysis of gelatin). However, chemotaxonomic investigations revealed lysine as the diamino acid of the cell wall and the presence of branched cellular fatty acids (with anteiso-pentadecanoic acid predominating) which was compatible with an assignment of the 11 isolates to the genus Arthrobacter only. Peptidoglycan and 16S rRNA gene sequence analyses demonstrated that three of the strains studied were representatives of a new Arthrobacter species for which the name Arthrobacter cumminsii sp. nov. is proposed and that one other strain represented a second new Arthrobacter species for which the name Arthrobacter woluwensis sp. nov. is proposed. This report is the first on the isolation of Arthrobacter spp. from clinical specimens.


Gambling behaviors and perceived health among incarcerated older adults.
The proliferation of lotteries and casinos has led to increased participation in gambling. Older adults who have opportunities to gamble may be vulnerable to gambling problems, and incarcerated older adults may be the most vulnerable. Furthermore, research has linked decreased health to gambling problems. This study compared perceived health and gambling problems among 43 incarcerated older adults from two county jails in the midwestern United States. Results from the South Oaks Gambling Screen indicated 48.83% of the sample scored in the problem or pathological range. Short Form-36 results were compared with U.S. norms for ages 55 to 64 and showed significantly lower perceived health scores on Role-Physical, Bodily Pain, Mental Health, Social Functioning, and Role-Emotional subscales. The problem and pathological gamblers showed significantly lower social functioning than the recreational gamblers. Assessment of health conditions and gambling behaviors is important for quantifying current and anticipated burdens of these conditions on correctional health care systems and the community.


[Selenium deficiency in patients with cardiovascular diseases and its correction with the drug "selena"].
Blood selenium concentrations, erythrocytic glutathione peroxidase (GPO) activity, and plasma lipid peroxides were investigated in patients with ischemic heart disease (IHD) and dilated cardiomyopathy (DCMP). Patients with IHD and DCMP displayed depressed activity of GPO with activation of lipid peroxides associated with lower blood selenium. The daily intake of 300 micrograms of selenium from Selena during a month treatment augmented selenium concentrations by 71% in IHD and DCMP patients. This augmentation showed an inverse correlation with primary plasma selenium concentrations. Plasma malonic dialdehyde levels decreased by 17%. The findings suggest that selenium is involved in the pathogenesis of DCMP and IHD, which may be a ground for selecting patients with selenium deficiency for its correction with Selena.


Biodistribution of gadolinium-based contrast agents, including gadolinium deposition.
The biodistribution of approved gadolinium (Gd)-based contrast agents (GBCAs) is reviewed. After intravenous injection GBCAs distribute in the blood and the extracellular space and transiently through the excretory organs. Preclinical animal studies and the available clinical literature indicate that all these compounds are excreted intact. Elimination tends to be rapid and, for the most part, complete. In renally insufficient patients the plasma elimination half-life increases substantially from hours to days depending on renal function. In patients with impaired renal function and nephrogenic systemic fibrosis (NSF), the agents gadodiamide, gadoversetamide, and gadopentetate dimeglumine have been shown to result in Gd deposition in the skin and internal organs. In these cases, it is likely that the Gd is no longer present as the GBCA, but this has still not been definitively shown. In preclinical models very small amounts of Gd are retained in the bone and liver, and the amount retained correlates with the kinetic and thermodynamic stability of the GBCA with respect to Gd release in vitro. The pattern of residual Gd deposition in NSF subjects may be different than that observed in preclinical rodent models. GBCAs are designed to be used via intravenous administration. Altering the route of administration and/or the formulation of the GBCA can dramatically alter the biodistribution of the GBCA and can increase the likelihood of Gd deposition. J. Magn. Reson. Imaging 2009;30:1259-1267. (c) 2009 Wiley-Liss, Inc.


The preparation and properties of a group of proteins from the high-sulphur fraction of wool.
A method is reported for the preparation of a group of three proteins from the S-carboxymethylated high-sulphur fraction of wool. These proteins have been partially characterized by their tryptic peptides. All have similar structural features and show an interesting homology within the group and some similarities of sequence with a different group of wool high-sulphur proteins. The evidence for the sequence of some of the peptides is given in a supplementary paper that has been deposited as Supplementary Publication 50008 at the National Lending Library for Science and Technology, Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1972) 126, 5.


Is there a role for TNFα antagonists in the treatment of SSc? EUSTAR expert consensus development using the Delphi technique.
To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc. Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-α inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNF-α antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-α antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-α antagonists for arthritis associated with SSc. Most of the experts do not recommend the routine use of TNF-α antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given.


Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).
Autoimmunity is prevented by the function of the autoimmune regulator [AIRE (Aire in mice)], which promotes the expression of a wide variety of tissue-restricted antigens (TRAs) from medullary thymic epithelial cells (mTECs) and from a subset of peripheral antigen-presenting cells (APCs). We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of immunological tolerance. Our results also highlight the importance of coordinated action between central tolerance and peripheral tolerance under the common control of Aire.


Cancer Risk Awareness and Concern among Women with a Family History of Breast or Ovarian Cancer.
Women with a documented deleterious mutation in BRCA1 or BRCA2 are at substantially elevated risk for ovarian cancer. To understand what percentage of women with high-risk family histories know their risk is elevated we surveyed 1,885 women with a high- or moderate-risk family history and no personal history of breast or ovarian cancer, and asked about their perceived risk of breast and ovarian cancer. Among high-risk women, fewer than 20% reported use of genetic counseling, and knowledge of elevated risk of ovarian cancer was low. Prior genetic counseling was associated with greater perceived risk for ovarian cancer. Results suggest that most high-risk women (>75%) do not know their risk for ovarian cancer. Identification of potentially high-risk women for referral to genetic counseling may improve informed ovarian cancer risk management.


Zipcode RNA-Binding Proteins and Membrane Trafficking Proteins Cooperate to Transport Glutelin mRNAs in Rice Endosperm.
In rice (Oryza sativa) endosperm cells, mRNAs encoding glutelin and prolamine are translated on distinct cortical-endoplasmic reticulum (ER) subdomains (the cisternal-ER and protein body-ER), a process that facilitates targeting of their proteins to different endomembrane compartments. Although the cis- and trans-factors responsible for mRNA localization have been defined over the years, how these mRNAs are transported to the cortical ER has yet to be resolved. Here, we show that the two interacting glutelin zipcode RNA binding proteins (RBPs), RBP-P and RBP-L, form a quaternary complex with the membrane fusion factors n-ethylmaleimide-sensitive factor (NSF) and the small GTPase Rab5a, enabling mRNA transport on endosomes. Direct interaction of RBP-L with Rab5a, between NSF and RBP-P, and between NSF and Rab5a, were established. Biochemical and microscopic analyses confirmed the co-localization of these RBPs with NSF on Rab5a-positive endosomes that carry glutelin mRNAs. Analysis of a loss-of-function rab5a mutant showed that glutelin mRNA and the quaternary complex were mis-targeted to the extracellular paramural body structure formed by aborted endosomal trafficking, further confirming the involvement of endosomal trafficking in glutelin mRNA transport. Overall, these findings demonstrate that mRNA localization in plants co-opts membrane trafficking via the acquisition of new functional binding properties between RBPs and two essential membrane trafficking factors, thus defining an endosomal anchoring mechanism in mRNA localization.


Simultaneous automatic insufflation and smoke-evacuation system in flexible gastrointestinal endoscopy.
Automatic smoke evacuation has not been feasible inside the gastrointestinal tract as evacuation collapses pneumoviscera. As previously reported, steady pressure automatically controlled endoscopy (SPACE) may resolve this problem. The aims of this study were to clarify the potential dangers of surgical smoke, and to evaluate the feasibility and potential usefulness of automatic smoke evacuation in flexible gastrointestinal endoscopy. Seven pigs were enrolled. SPACE was established by using a flexible endoscope, an overtube, and a surgical CO2 insufflator. Smoke was generated by gastric mucosal ablation for component analysis and was evacuated by a commercially available surgical-use smoke evacuator connected to an additional line attached to the endoscope. Endoscopic images with evacuation were evaluated subjectively in comparison to those from cases without evacuation. After each session, the residual intraluminal smoke was collected by a smoke testing device for objective evaluation. Ten chemical compounds were detected. Smoke evacuation was achieved without collapse of the pneumostomach. Smoke was significantly reduced with the use of evacuation. Surgical smoke generated inside the gut lumen was potentially hazardous. Automatic evacuation was feasible and potentially useful in conjunction with SPACE technology.


Tetrazolium microplate assay as a rapid and inexpensive colorimetric method for determination of antibiotic susceptibility of Mycobacterium tuberculosis.
The emergence of multidrug-resistant tuberculosis underscores the need for low-cost, rapid methods to determine the susceptibility of Mycobacterium tuberculosis to antibiotics. A new, rapid, easily read, and inexpensive colorimetric method with a tetrazolium indicator performs this determination as quickly and accurately as the more expensive Alamar Blue technique.


Mapping of retinal function in diabetic retinopathy using the multifocal electroretinogram.
To investigate focal abnormalities in the electroretinogram (ERG) signal in diabetic patients, with and without retinopathy, using a multifocal ERG. Sixteen patients with diabetes mellitus, 8 of whom had diabetic retinopathy (mean duration of diabetes: 18.5 years) and 19 approximately age-matched healthy volunteers underwent multifocal ERG testing. One hundred three retinal locations within the central 50 degrees were stimulated concurrently, according to a pseudorandom m-sequence. Response components were extracted for each stimulated retinal location. In diabetic patients with retinopathy, the overall amplitudes were reduced (P < 0.01), and peak implicit times were increased (P < 0.01) in the first-order component (mean flash response) and in the first slice of the second-order component (local two flash interaction). In addition, local reductions of amplitude could be seen in the first- and second-order components. In patients without retinopathy, only amplitudes of the second-order component were reduced (P < 0.01). Another salient difference was observed in a special feature of the second-order component that was reduced in diabetic patients, with and without retinopathy (P < 0.05). Second-order components depend on nonlinear dynamics. Thus our findings indicate changes in the nonlinear dynamics of a fast-gain control in diabetic patients, presumably located in the inner retina. This suggests that early functional changes of the inner retina are evident in diabetic patients before impairment of the outer retina is observed. Multifocal nonlinear analysis permits the detection of subclinical diabetic retinopathy and offers the advantage of topographic mapping of retinal dysfunction.


Performance of Empirical Mode Decomposition for Frequency Identification in SSVEP Based BCI.
Empirical mode decomposition based conventional correlation (EMDCC) method is proposed to identify the frequency components in steady state visual evoked potentials (SSVEP) in electroencephalogram(EEG).The main aim of the proposed EMDCC method is to recognise narrow band frequency components that are present in SSVEP. The study is evaluated on two datasets. The first one is a 40 target benchmark dataset obtained from 35 subjects and the second is a 4 class Inhouse dataset collected from 10 healthy participants. The mean detection accuracy of the conventional correlation method is 85.64 % for the benchmark dataset and it is improved to 93.79 % in the proposed method. The mean detection accuracy of the conventional correlation method is 67.5 % for the Inhouse dataset and it is increased to 82.5 % in the proposed method. The mean detection accuracy of the proposed EMDCC method is also compared to time-weighting canonical correlation analysis (TWCCA) for the benchmark dataset. The mean detection accuracy of TWCCA is 91.04 %. Hence the results show better detection accuracies in the proposed EMDCC method than the simple conventional correlation method and also the existing TWCCA method.


X-Ray spectroscopy of the photosynthetic oxygen-evolving complex.
Water oxidation to dioxygen in photosynthesis is catalyzed by a Mn(4)Ca cluster with O bridging in Photosystem II (PS II) of plants, algae and cyanobacteria. A variety of spectroscopic methods have been applied to analyzing the participation of the complex. X-ray spectroscopy is particularly useful because it is element-specific, and because it can reveal important structural features of the complex with high accuracy and identify the participation of Mn in the redox chemistry. Following a brief history of the application of X-ray spectroscopy to PS II, an overview of newer results will be presented and a description of the present state of our knowledge based on this approach.


Factors related to starting and continuing smoking among senior high school boys in Fukuoka, Japan.
The purpose of this study was to identify factors that influence starting and quitting smoking among Japanese male adolescents aged 15-18. Two thousand and twelve senior high school boys in Fukuoka City, Japan, answered unsigned self-administrated anonymous questionnaires in July 2001. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were computed to assess the strength of associations between students' smoking status and alcohol consumption habits. Additionally, the link between a students' smoking status and parental influence (parental smoking) was also assessed. Approximately 90% of the students, both current and ex-smokers, had ever smoked prior to senior high school while 77% of the students (smokers and non-smokers) had the experience of drinking alcohol prior to admission to senior high school. After adjustment for school year (i.e., freshman, sophomore, junior, senior), academic education level, after-school club activities, time of first drinking experience and the frequency of drinking, there was a significant increased risk to become a smoker when one parent was a smoker (OR = 1.67, 95% CI = 1.18-2.37) or when both parents were smokers (OR = 2.94, 95% CI = 1.66-5.18) compared to both parents being non-smokers. The consumption of alcohol prior to entering senior high school was significantly associated with more than 2.5-fold greater risk for the onset of smoking when compared to the risk of becoming a smoker when alcohol consumption started after entering senior high school. An increased frequency of drinking was also associated with starting smoking (OR =14.00, 95% CI = 8.08-24.26; 2-3 times/week vs. never). Similarly, an increase in drinking frequency resulted in less likelihood of smoking cessation. For instance, the data showed that, the subjects were 1/3 less likely to quit smoking. Paternal smoking had a significant impact on whether or not a child would quit smoking (OR = 0.55, 95% CI = 0.38-0.81) as compared to a child that had paternal and maternal non-smokers. This study suggested that drinking habits started earlier than smoking habits among adolescents. Many students had already experienced drinking before admission to senior high school, while the experience of smoking mostly typically started after admission to high school. These data show the urgency of developing anti-smoking educational programs that could be developed and introduced prior to admission to high school.


Simulating Ising and n-State Planar Potts Models and External Fields with Nonequilibrium Condensates.
Classical spin models with discrete or continuous degrees of freedom arise in many studies of complex physical systems. A wide class of hard real-life optimization problems can be formulated as a minimization of a spin Hamiltonian. Here we show how to simulate the discrete Ising and n-state planar Potts models with or without external fields using the physical gain-dissipative platforms with continuous phases, such as lasers and various nonequilibrium Bose-Einstein condensates. The underlying operational principle originates from a combination of resonant and nonresonant pumping. Our results lay grounds for the physical simulations of a broad range of Hamiltonians with complex interactions that can vary in time and space and with combined symmetries.


Is the technically limited echocardiographic study an endangered species? endocardial border definition with native tissue harmonic imaging and Optison contrast: a review of 200 cases.
Our goal was to determine whether contrast adds diagnostic value to both fundamental and native tissue harmonic imaging (NTHI) for endocardial border definition. Two hundred consecutive patients who underwent stress echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders. Two- and 4-chamber views were analyzed before and after administration of contrast at peak stress for grading of 5 endocardial border segments. Scores from 0 to 5 were assigned to each study for all the images both before and after contrast (0 = 0 segments completely visualized; 5 = 5 segments completely visualized). The use of Optison contrast significantly enhanced border definition when imaging was performed in either fundamental or NTHI mode. Addition of contrast resulted in better endocardial border definition in fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in NTHI mode, the presence of contrast resulted in enhanced definition of endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or - 1.1, P <.001). The combination of NTHI and contrast resulted in more visualization of endocardium when compared with the combination of fundamental imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In addition, interobserver agreement for border detection increased from 83% in fundamental mode without contrast to 95% with the use of NTHI with Optison (P <.001). As defined in 200 cases, the combination of NTHI with Optison contrast results in nearly complete and consistent endocardial border definition.


[Abortive influenza virus infection in Ehrlich ascitic cancer cells. Further studies of the properties of ascitic virus].
Non-infectious virus particles produced by influenza virus (classical fowl plague)-infected Ehrlich ascitic carcinoma cells have the same morphology, size and sedimentation rate as the standard virions. Their main difference from the allantoic virus is their extreme fragility. They remain intact upon a short-term centrifugation in sucrose solutions but desintegrate upon prolonged centrifugation. In isopicnic fractionation they are detected in two forms, with a density of 1.23 g/ml retaining the hemagglutinating but not the neuraminidase activity and with a density of 1.27 g/ml deprived of both hemagglutinating and neuraminidase activity. In the electron microscopic examination the 1.23 g/ml structure appears as virus particles with defective areas in the surface spikes layer whereas the 1.27 g/ml structure has no spike layer at all. The protein analysis by polyacryl amide gel electrophoresis revealed a sharply reduced amount of the membrane protein in the ascitic virus. A hypothesis is suggested according to which the reduced amount of the membrane protein is the cause of the unusual fragility of ascitic virus particle membranes as a result of which they readily lose glycoproteins which, in its turn, leads to their reduced infectious activity.


Bioavailability evaluation, uptake of heavy metals and potential health risks via dietary exposure in urban-industrial areas.
A verity of human activities i.e. urbanization and industrialization have been resulted serious environmental contaminations by heavy metals in all over the world. The settlement of populations in urban and nearby industrial areas for economic development has significant share in their exposure to these metallic contaminants. Depending on the nature and type of the pollutants, targeted urban-industrial environments can have harmful and chronic health risk impacts on exposed local inhabitants and may require detoxification, healing and remedial therapy. Consequently, environmental monitoring as well as human health risk assessments of urban environments under industrial influence are key dominant features. We believe this work will provide new insights into the studies of metals exposure and associated health risks in emerging industrials cities of developing countries. Present study aimed to study the bioavailability of metals, quantify the changeability in soil and vegetable metal concentrations and estimation of human health risks via dietary exposure, focusing on urban-industrial environment. Soil and vegetable samples were collected in six random sites within the urban, periurban and industrial areas and analyzed for metal concentrations. In addition, risk assessment model proposed by US-EPA was employed to estimate the potential health risk of heavy metals via dietary intake. Results indicated that the heavy metal concentrations were noteworthy in periurban and urban-industrial areas. However, contamination levels varied with the type of vegetable, and the point source pollution such as traffic, urban wastes and industrial effluent. According to the estimated THQ and HI values for non-carcinogenic risk, little or no negative impact of heavy metals was observed on local inhabitants. However, the concentrations of Cr, Cd, Pb and Ni were nearly closed to the permissible limits described by US-EPA in urban-industrial areas. Conclusively, some efficient remedial strategies should be focus to overcome the increasing levels of Cr, Cd, Pb and Ni in this study area to protect the health of local inhabitants.


Highly lipophilic phorbol esters as inhibitors of specific [3H]phorbol 12,13-dibutyrate binding.
We examined the ability of a series of highly lipophilic phorbol esters to inhibit [20-3H]phorbol 12,13-dibutyrate binding to the cytosolic aporeceptor from mouse brain. If added in the usual fashion directly into the aqueous phase of the assay mixture, phorbol 12,13-distearate, phorbol 12,13-dioleate, and phorbol 12,13-dimyristate showed very weak inhibitory activities, with apparent inhibitor equilibrium dissociation constant values above 4 microM. In contrast, if incorporated directly into the liposomes used to reconstitute the aporeceptor, all three derivatives inhibited binding with high apparent affinities, 7.4 to 34 nM. The less lipophilic derivative phorbol 12,13-didecanoate showed a similar high affinity, 2.4 to 3.2 nM, by either route of addition. Consistent with the activity of the lipophilic derivatives being masked by an inability to transfer from the aqueous to the lipid phase, phorbol 12,13-distearate added to the aqueous phase inhibited efficiently (apparent inhibitor equilibrium dissociation constant, 14 nM) in the presence of 0.03% Triton X-100. The results suggest that the phorbol ester receptor recognizes phorbol esters which are inserted into the lipid bilayer. They indicate, moreover, that the apparent low activity of the more lipophilic phorbol esters is strongly influenced by factors other than equilibrium binding affinities.


Quantitative transcriptional analysis of fusing and nonfusing cranial suture complexes in mice.
Previous studies have documented the differences in expression of various genes associated with the process of osteogenesis in fusing and nonfusing cranial sutures, including growth factors, growth factor receptors, and extracellular matrix molecules. Most of these studies were performed in rats, and although the biology regulating cranial suture fusion in mice and rats is presumed to be similar, studies are needed to verify these expression patterns as mice become increasingly utilized for scientific inquiry into the molecular biology of suture fusion and patency. The purpose of this study was to determine the differences in expression of several genes known to be critical to osteoblast biology. Posterior frontal and sagittal suture complexes (including the associated dura mater, suture mesenchyme, and osteogenic fronts) were isolated from 5-, 15-, 25-, 35-, and 45-day-old male CD-1 mice (n = 8 per age; n = 40 total). Total cellular RNA was extracted and converted to cDNA. Quantitative real-time reverse transcriptase polymerase chain reaction was then performed for the following genes: transforming growth factor beta1 and beta3, fibroblast growth factor receptor 1, Runx2,Osteopontin, and Osteocalcin. Expression of all genes examined was increased significantly in the posterior frontal suture as compared with the sagittal suture. Peak expression for all genes was observed on day 25. These data demonstrate that the expression of osteogenic growth factors, growth factor receptors, transcription factors, and extracellular matrix molecules is increased in the fusing posterior frontal suture in mice.


[Risk assessment for emergency events of infectious disease in outlying areas of large-scale activities].
To identify and assess the potential public health risks of emergency events of infectious disease in the surrounding areas of Hangzhou during the 11th G20 summit, and to assess their impacts on the G20 summit. The surrounding cities of Hangzhou included Ningbo, Wenzhou, Jiaxing, Huzhou, Shaoxing, Jinhua, Quzhou, Zhoushan, Taizhou and Lishui. Background information on infectious diseases in Zhejiang province was collected, and the brainstorming and expert consultation methods were used to identify the risks. The local risks and the impact of local risks on the G20 summit were assessed. The criteria for public health risk was first established. Through the assessments,a total of 27 kinds of infectious diseases in 4 types of public health risks were identified. The impact of these risks on Hangzhou G20 summit was divided into 1 item of high-risk, 12 items of medium risk and 14 items of low risk.According to the results of risk assessment, the recommendations for risk management of respiratory infectious diseases, intestinal infectious diseases, imported infectious diseases like Middle East respiratory syndrome and other infectious diseases were made. With risk management, Middle East respiratory syndrome was not occurred during the G20 summit, and the epidemic situation of other infectious diseases with middle or low risks was almost the same with that of past years. sThe public health risks of Hangzhou G20 summit from sudden infectious diseases in outlying areas are mainly medium and low risks. The recommendations on risk management provide a basis for reducing the adverse consequences of public health risks in the event of an outbreak of infectious diseases, avoiding the impact of various risk factors in the outlying areas on G20 summit.


Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.
T cells can be genetically modified to express an anti-CD19 chimeric antigen receptor (CAR). We assessed the safety and efficacy of administering autologous anti-CD19 CAR T cells to patients with advanced CD19(+) B-cell malignancies. We treated 15 patients with advanced B-cell malignancies. Nine patients had diffuse large B-cell lymphoma (DLBCL), two had indolent lymphomas, and four had chronic lymphocytic leukemia. Patients received a conditioning chemotherapy regimen of cyclophosphamide and fludarabine followed by a single infusion of anti-CD19 CAR T cells. Of 15 patients, eight achieved complete remissions (CRs), four achieved partial remissions, one had stable lymphoma, and two were not evaluable for response. CRs were obtained by four of seven evaluable patients with chemotherapy-refractory DLBCL; three of these four CRs are ongoing, with durations ranging from 9 to 22 months. Acute toxicities including fever, hypotension, delirium, and other neurologic toxicities occurred in some patients after infusion of anti-CD19 CAR T cells; these toxicities resolved within 3 weeks after cell infusion. One patient died suddenly as a result of an unknown cause 16 days after cell infusion. CAR T cells were detected in the blood of patients at peak levels, ranging from nine to 777 CAR-positive T cells/μL. This is the first report to our knowledge of successful treatment of DLBCL with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach.


Oseltamivir exposure in pregnancy and the risk of specific birth defects.
Influenza during pregnancy contributes to maternal morbidity and mortality. Neuraminidase inhibitors, including oseltamivir, are recommended for treating women with influenza during pregnancy. Data from the Slone Birth Defects Study from 2009 to 2015 were used to investigate associations between oseltamivir and specific birth defects. We classified exposures according to timing in pregnancy and examined 52 and 16 defects with early and potential late pregnancy etiology, respectively; we calculated crude odds ratios (ORs) and 95% confidence intervals (CIs) for defects with three or more exposures. Among 8,379 cases and 4,190 nonmalformed controls, we identified 79 and 42 oseltamivir exposures, respectively. The majority of defects had no exposures. ORs were elevated for several defects, but the CI excluded the null only for intestinal malrotation (OR: 10.7 [1.8, 45.2]; three exposures). Largely null findings for specific defects are reassuring. The association with intestinal malrotation, while unstable, warrants further investigation.


Computer/gaming station use in youth: Correlations among use, addiction and functional impairment.
Computer/gaming station use is ubiquitous in the lives of youth today. Overuse is a concern, but it remains unclear whether problems arise from addictive patterns of use or simply excessive time spent on use. The goal of the present study was to evaluate computer/gaming station use in youth and to examine the relationship between amounts of use, addictive features of use and functional impairment. A total of 110 subjects (11 to 17 years of age) from local schools participated. Time spent on television, video gaming and non-gaming recreational computer activities was measured. Addictive features of computer/gaming station use were ascertained, along with emotional/behavioural functioning. Multiple linear regressions were used to understand how youth functioning varied with time of use and addictive features of use. Mean (± SD) total screen time was 4.5±2.4 h/day. Addictive features of use were consistently correlated with functional impairment across multiple measures and informants, whereas time of use, after controlling for addiction, was not. Youth are spending many hours each day in front of screens. In the absence of addictive features of computer/gaming station use, time spent is not correlated with problems; however, youth with addictive features of use show evidence of poor emotional/ behavioural functioning.


Energy transfer from two luteins to chlorophylls in light-harvesting complex II study by using exciton models with phase correction.
In light-harvesting complex II of plants, the two lutein pigments (LUT1 and LUT2) are always paired and an energy transfer pathway between them is believed to exist. However, it remains unclear whether this pathway is essential for the energy transfer between carotenoids and chlorophylls. In this work, we performed hybrid quantum mechanics/molecular mechanics simulations with Frenkel exciton models to investigate this energy transfer. The results show that the energy transfer pathways between the S2 state of LUT1 and CLAs are not affected by LUT2 S2. The energy transfer between LUT and chlorophyll-a (CLA) also follows a resonance mechanism. The two LUTs have different energy transfer pathways according to their energy gaps and coupling strengths with each CLA. The present work sheds light on the energy transfer pathways involved in the two LUTs.


Utility of the advanced chronic kidney disease patient management tools: case studies.
Appropriate management of advanced chronic kidney disease (CKD) delays or limits its progression. The Advanced CKD Patient Management Toolkit was developed using a process-improvement technique to assist patient management and address CKD-specific management issues. We pilot tested the toolkit in 2 community nephrology practices, assessed the utility of individual tools, and evaluated the impact on conformance to an advanced CKD guideline through patient chart abstraction. Tool use was distinct in the 2 sites and depended on the site champion's involvement, the extent of process reconfiguration demanded by a tool, and its perceived value. Baseline conformance varied across guideline recommendations (averaged 54%). Posttrial conformance increased in all clinical areas (averaged 59%). Valuable features of the toolkit in real-world settings were its ability to: facilitate tool selection, direct implementation efforts in response to a baseline performance audit, and allow selection of tool versions and customizing them. Our results suggest that systematically created, multifaceted, and customizable tools can promote guideline conformance.


Coordinated Regulation of Axonal Microtubule Organization and Transport by Drosophila Neurexin and BMP Pathway.
Neurexins are well known trans-synaptic cell adhesion molecules that are required for proper synaptic development and function across species. Beyond synapse organization and function, little is known about other roles Neurexins might have in the nervous system. Here we report novel phenotypic consequences of mutations in Drosophila neurexin (dnrx), which alters axonal microtubule organization and transport. We show that dnrx mutants display phenotypic similarities with the BMP receptor wishful thinking (wit) and one of the downstream effectors, futsch, which is a known regulator of microtubule organization and stability. dnrx has genetic interactions with wit and futsch. Loss of Dnrx also results in reduced levels of other downstream effectors of BMP signaling, phosphorylated-Mad and Trio. Interestingly, postsynaptic overexpression of the BMP ligand, Glass bottom boat, in dnrx mutants partially rescues the axonal transport defects but not the synapse undergrowth at the neuromuscular junctions. These data suggest that Dnrx and BMP signaling are involved in many diverse functions and that regulation of axonal MT organization and transport might be distinct from regulation of synaptic growth in dnrx mutants. Together, our work uncovers a novel function of Drosophila Neurexin and may provide insights into functions of Neurexins in vertebrates.


Mathematical arterialization of venous blood in emergency medicine patients.
Arterial punctures represent a painful and unpleasant experience. Acid-base and oxygenation status can be assessed from peripheral venous blood, but agreement with arterial values is not always clinically acceptable. This study evaluates a method for mathematically transforming peripheral venous values into arterial values in emergency medicine patients. Paired arterial and peripheral venous samples were analysed in groups A (47 patients) and B (101 patients), corresponding to the clinical need for arterial blood sampling (A) and without (B). Venous values were input into the mathematical arterialization method and the values of arterial pH, PCO2 and PO2 were calculated and compared with the measured values. The calculated and measured arterial pH and PCO2 values correlated well with the correlation coefficients (r ) of group A, pH 0.94, PCO2 0.97; group B, pH 0.87, PCO2 0.83; and Bland-Altman limits of agreement well within the limits of acceptable laboratory and clinical performance. The calculated values of arterial PO2 followed a set of predefined rules relating calculated and measured PO2 levels in all cases. The method represents an improvement on the use of venous blood alone where the correlation coefficients were as follows: group A, pH 0.85, PCO2 0.88; group B, pH 0.79, PCO2 0.59; and limits of agreement for PCO2 at the border of (group A) or beyond (group B) acceptable clinical limits. Application of the mathematical arterialization method may reduce the pain associated with assessment of acid-base and oxygenation status, maximize the information obtained from peripheral venous blood and allow venous measurements to be presented as more commonly interpreted arterial values.


Gastric polypectomy. Long-term results (survey of 23 centres in Germany).
In a survey of 23 endoscopy centres in the Federal Republic of Germany 6,182 cases are reported in which gastric polypectomies were performed. 1,177 patients were observed over a period of up to 7 years. Primary benign gastric polyps recurred in 6.1% most of them within 1 year after polypectomy, and genuinely recurrent polyps usually had a histological pattern identical to that of the ectomized polyps. In 32.5% new polyps occurred at different locations in the stomach, and most of them exhibited the same histological structure as the primary polyp. In 1.7% of primary benign solitary or multiple gastric polyps gastric carcinoma must be expected to develop. Follow-up examinations revealed only one carcinoma in 68 polyposis patients (= 1.5%), but in these cases, consideration must be given to a simultaneous carcinoma, which was observed in 8.5% at the first examination. In high-risk patients, endoscopic removal of protruded-type early gastric cancer and borderline lesion represents very satisfactory therapy. The recurrence rate of early gastric cancer was only 13.6% and of borderline lesion 9.7%. However, in cases of borderline lesions a cancer can be expected to develop in a further 8.6%. The consequences of this study are discussed.


Blurred star image processing for star sensors under dynamic conditions.
The precision of star point location is significant to identify the star map and to acquire the aircraft attitude for star sensors. Under dynamic conditions, star images are not only corrupted by various noises, but also blurred due to the angular rate of the star sensor. According to different angular rates under dynamic conditions, a novel method is proposed in this article, which includes a denoising method based on adaptive wavelet threshold and a restoration method based on the large angular rate. The adaptive threshold is adopted for denoising the star image when the angular rate is in the dynamic range. Then, the mathematical model of motion blur is deduced so as to restore the blurred star map due to large angular rate. Simulation results validate the effectiveness of the proposed method, which is suitable for blurred star image processing and practical for attitude determination of satellites under dynamic conditions.


Genotype diversity and distribution of Orientia tsutsugamushi causing scrub typhus in Thailand.
Scrub typhus, caused by antigenically disparate isolates of Orientia tsutsugamushi, is a widely distributed mite-borne human disease in the Asia Pacific region. Information regarding the heterogeneity of the immunodominant 56-kDa type-specific antigen (TSA) gene is crucial for the design and evaluation of scrub typhus-specific diagnostic assays and vaccines. Using indirect immunofluorescence assays (IFA) and PCR assays, O. tsutsugamushi was detected samples from rodents and patients with fever of unknown origin obtained from six provinces of Thailand during 2004 to 2007. Sequences were determined for a fragment of the 56-kDa TSA gene, and the relationship between these sequences and those previously determined were assessed. The phylogenetic analyses of partial 56-kDa TSA gene sequences demonstrated wide diversity and distribution of O. tsutsugamushi genotypes in Thailand. Furthermore, the genetic diversity grouped the scrub typhus agents into two commonly and five infrequently found genotypes within six provinces of Thailand. The two most commonly found genotypes of O. tsutsugamushi described in this study do not associate with the prototype strains that are widely used for the design and evaluation of diagnostic assays and vaccine candidates. Thus, these new genotypes should be considered for future scrub typhus assay and vaccine development.


Impact of temperature dependent sampling procedures in proteomics and peptidomics--a characterization of the liver and pancreas post mortem degradome.
Little is known about the nature of post mortem degradation of proteins and peptides on a global level, the so-called degradome. This is especially true for nonneural tissues. Degradome properties in relation to sampling procedures on different tissues are of great importance for the studies of, for instance, post translational modifications and/or the establishment of clinical biobanks. Here, snap freezing of fresh (<2 min post mortem time) mouse liver and pancreas tissue is compared with rapid heat stabilization with regard to effects on the proteome (using two-dimensional differential in-gel electrophoresis) and peptidome (using label free liquid chromatography). We report several proteins and peptides that exhibit heightened degradation sensitivity, for instance superoxide dismutase in liver, and peptidyl-prolyl cis-trans isomerase and insulin C-peptides in pancreas. Tissue sampling based on snap freezing produces a greater amount of degradation products and lower levels of endogenous peptides than rapid heat stabilization. We also demonstrate that solely snap freezing related degradation can be attenuated by subsequent heat stabilization. We conclude that tissue sampling involving a rapid heat stabilization step is preferable to freezing with regard to proteomic and peptidomic sample quality.


Standardization of Shirishavaleha with reference to physico-chemical characteristics.
Ten batches of Shirishavaleha were prepared by using Twak (Bark) and Sara (Heartwood) of Shirisha [Albizzia lebbeck Benth]. The adopted formulation was based on Shirisharishta of Bhaishajya Ratnavali. Though Shirisharishta has significant therapeutic effect in cases of Tamaka swasa, etc.; it has few difficulties during the pharmaceutical procedure like consuming long time, climatic influences etc. Considering these inconveniencies, the formulation composition has been converted in to Shirishavaleha. Avaleha has been prepared by using Twak and Sara of Shirisha. No significant differences were found in pharmaceutical aspects of both the samples of Shirishavaleha and the current method of preparation can be considered as standard. Attempts were also made to develop analytical profile of avaleha, which were almost similar in both the samples, except showing more Rf values in High Performance Thin Layer Chromatography profile of Sara group.


Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma.
Myofibroblasts are differentiated contractile cells that can secrete extracellular matrix components, cytokines, proteases, and proangiogenic factors. In neoplastic processes such as oral squamous cell carcinoma (OSCC), myofibroblasts are recognized as cancer-associated fibroblasts (CAFs) and actively participate in tumor progression. As the presence of myofibroblasts in the stroma may be an important parameter of invasion and proliferation, the aim of this study was to evaluate the presence of CAFs in OSCC by immunophenotyping and their association with histologic classification and clinicopathologic parameters. A total of 34 formalin-fixed, paraffin-embedded samples of OSCC were analyzed for CAF histology and immunophenotype established on the basis of the simultaneous immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin. According to the histologic classification of CAFs, 16 (47%) cases were classified as the mature subtype and 18 (53%) as the immature subtype. CAF immunophenotype was detected in 19 (56%) cases, and the immunophenotype was variable in 15 (44%) cases. The CAFs immunophenotype was significantly associated with the immature histologic subtype. Immunohistochemical expression of α-SMA, fibronectin, FSP1, HHF35, and vimentin represents a suitable CAF immunophenotype in OSCC. The CAF immunophenotype is associated with the immature histologic subtype. The characterization of CAFs may identify tumors with a distinct biological profile in OSCC. Studies extending the investigation of CAFs to OSCC are needed to determine the actual role of this cell population as a possible prognostic marker.


Effects of exercise on sRAGE levels and cardiometabolic risk factors in patients with type 2 diabetes: a randomized controlled trial.
Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM). We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM. Seventy-five patients with T2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk). We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flow-mediated dilatation. Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2=0.244). After 12 wk of exercise training, the exercise group showed significantly decreased body weight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulse-wave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r=-0.27; P=0.019). Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.


Differential Rates of Change in Measures of Ovarian Reserve in Young Cancer Survivors Across the Reproductive Lifespan.
Recent studies have examined level and rate of change of anti-Müllerian hormone (AMH) for predicting time to menopause. Limited prospective, longitudinal data exists evaluating measures of ovarian reserve (MOR) in cancer survivors. Determine the rate of change of MOR in survivors (15 to 39 years) compared with similar-aged controls and compared with late reproductive-aged controls (40 to 50 years). Prospective cohort. Quaternary university hospital. Survivors at least 1 year from therapy completion, similar-aged controls, and late reproductive-aged controls. Annual visits with early follicular-phase hormone analysis and ultrasound. Changes in AMH and antral follicle count (AFC) were modeled using random effects linear regression. Cancer survivors (170) and 135 similar-aged controls had annual visits for an average of 38 months; 71 late reproductive-aged controls were followed for an average of 24 months. In models adjusted for body mass index, time since cancer therapy (for survivors), and exogenous hormone use, the geometric mean AMH and AFC levels were lower in the survivors than similar-aged controls at all ages. After age 24.5 AMH and AFC declined in both groups at rates that were similar (P = 0.78 for AMH, P = 0.37 for AFC). Late reproductive-aged controls declined at a much more precipitous rate of 30% per year for AMH and 16% per year for AFC (P < 0.01 compared with survivors). Although survivors had lower levels of AMH and AFC at the time of enrollment, the rate of change of AMH and AFC is not significantly different than similar-aged controls.


A simple, inexpensive technique for clearing obstructed closed suction drainage catheters.
Closed suction drains are frequently used after a variety of surgical procedures. Occlusion of these drains by thrombus or debris is a common postoperative event. A simple, inexpensive technique for clearing occluded drains with the readily available polyvinylpropylene catheter used for central venous cannulation is described herein. This method represents an inexpensive alternative to a Fogarty balloon tipped thrombectomy catheter for the same purpose. Prompt recognition and clearance of an obstructed drain is essential to minimize postoperative wound complications.


Effect of metabolic inhibition on the excitability of isolated hippocampal CA1 neurons: developmental aspects.
1. The effects of brief exposures to hypoxia on the membrane currents of isolated hippocampal CA1 neurons were studied with the use of the whole-cell variation of the patch-clamp technique. Neurons were acutely dissociated from immature (day 2-7) and mature (day 21-43) rats. 2. In the current-clamp mode, Na-cyanide (CN) hyperpolarized both mature and immature neurons. In the voltage-clamp mode, CN decreased the magnitude of the hyperpolarizing holding current in both age groups. 3. CN did not have a consistent effect on the voltage-dependent calcium and potassium currents of immature and mature CA1 neurons but decreased the voltage-dependent inward current of neurons at both ages. This effect was age dependent: the inward current of immature neurons decreased by only 10%, but that of mature neurons decreased by approximately 40%. 4. The decrease in the magnitude of the hyperpolarizing holding current and the depression of the voltage-dependent inward current of mature neurons were observed during brief exposure to N2 (PO2 = 0), indicating that the electroresponses observed with CN were the result of blocking oxidative respiration. 5. The hypoxia-sensitive inward current was blocked by tetrodotoxin (TTX) but was not blocked by cadmium or cesium + tetraethylammonium (TEA). Therefore this current was identified as the voltage-dependent, fast-inactivating sodium current (INa). 6. The isolated sodium current was studied with the use of cadmium to block calcium and TEA + cesium to block potassium currents. In mature neurons, CN left-shifted the steady-state inactivation curve for INa and slowed the deactivation kinetics of INa. CN caused little or no change in INa activation, fast inactivation, recovery from inactivation, or current-voltage (I-V) relationship. 7. We conclude that brief exposures to CN and hypoxia alter the intrinsic excitability of CA1 neurons by at least two mechanisms: 1) alterations in leakage currents and 2) alterations in the fast Na+ conductance that are maturationally dependent. We propose that the alterations in the Na+ conductance may play an adaptive role by reducing O2 demands and thus possibly delaying neuronal injury.


A new pericentric inversion of chromosome 6 in an abnormal infant.
An apparently de novo case of a previously unreported pericentric inversion of a No. 6 chromosome present in an abnormal infant is described. The possibility of an association between the abnormal karyotype and phenotype is discussed. The authors express the desirability for precise documentation of balanced chromosomal rearrangements.


Experiences with the use of caspofungin in paediatric patients.
Invasive fungal infections are important causes for treatment-related morbidity and mortality in severely immunocompromised paediatric patients with haematological malignancies or in children undergoing haematopoietic stem cell transplantation. In addition, neonates, in particular preterm infants, are at risk for invasive mycoses. The past decade witnessed a major expansion of antifungal drug research, which has resulted in the development of new antifungal agents. Caspofungin is the first licensed compound of the novel class of echinocandin lipopeptides. Although the compound is not yet licensed in the paediatric population, caspofungin is increasingly prescribed in children. This article reviews the clinical pharmacology of caspofungin and the published experience with the drug in neonates and immunocompromised children.


flex, an X-linked female-lethal mutation in Drosophila melanogaster controls the expression of Sex-lethal.
The Sex-lethal (Sxl) gene is required in Drosophila females for sexual differentiation of the soma, for gem cell differentiation and dosage compensation. We have isolated three new alleles of female-lethal-on-X (flex), an X-linked female-lethal mutation and have characterized its function in sex determination. SXL protein is missing in flex/flex embryos, however transcription from both Sxl(Pe), the early Sxl promoter and Sxl(Pm), the late maintenance promoter, is normal in flex homozygotes. In flex/flex embryos, Sxl mRNA is spliced in the male mode. Analysis of flex germline clones shows that it also functions in oogenesis, but in contrast to Sxl mutants that show an early arrest tumorous phenotype, flex mutant egg chambers develop to stage 10. In flex ovarian clones, Sxl RNA is also spliced in the male form. Hence, flex is a sex-specific regulator of Sxl functioning in both the soma and the germline. Genetic interaction studies show that flex does not enhance female lethality of Sxl loss-of-function alleles but it rescues the male-specific lethality of both of the gain-of-function Sxl mutations, Sxl(M1 )and Sxl(M4.) In contrast to mutations in splicing regulators of Sxl, the female lethality of flex is not rescued by either Sxl(M1 )or Sxl(M4). Based on these observations, we propose that flex regulates Sxl at a post-splicing stage and regulates either its translation or the stability of the SXL protein.


Parapelvic cysts, a distinguishing feature of renal Fabry disease.
Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P < 0.001). The presence of other renal abnormalities did not differ between the groups, nor differences exist in the main demographic and laboratory parameters between the groups. In Study 2, the greater accuracy of ultrasound increased PC prevalence from 29.8% to 43.3% in the same subjects (P < 0.05). In both studies, no correlation was detected between PC and the main demographic, clinical and biochemical parameters, including use of enzyme replacement therapy (P < 0.1, minimum value). Finally, no difference existed between FD patients with and without PC. The present study suggests that the presence of PC in renal patients should alert physicians to consider the diagnosis of FD, primarily in subjects with an unclear family history of renal disease and in the presence of other stigmata of the disease.


Discovery, validation and characterization of 1039 cattle single nucleotide polymorphisms.
We identified approximately 13 000 putative single nucleotide polymorphisms (SNPs) by comparison of repeat-masked BAC-end sequences from the cattle RPCI-42 BAC library with whole-genome shotgun contigs of cattle genome assembly Btau 1.0. Genotyping of a subset of these SNPs was performed on a panel containing 186 DNA samples from 18 cattle breeds including 43 trios. Of 1039 SNPs confirmed as polymorphic in the panel, 998 had minor allele frequency > or =0.25 among unrelated individuals of at least one breed. When Btau 4.0 became available, 974 of these validated SNPs were assigned in silico to known cattle chromosomes, while 41 SNPs were mapped to unassigned sequence scaffolds, yielding one SNP every approximately 3 Mbp on average. Twenty-four SNPs identified in Btau 1.0 were not mapped to Btau 4.0. Of the 1015 SNPs mapped to Btau 4.0, 959 SNPs had nucleotide bases identical in Btau 4.0 and Btau 1.0 contigs, whereas 56 bases were changed, resulting in the loss of the in silico SNP in Btau 4.0. Because these 1039 SNPs were all directly confirmed by genotyping on the multi-breed panel, it is likely that the original polymorphisms were correctly identified. The 1039 validated SNPs identified in this study represent a new and useful resource for genome-wide association studies and applications in animal breeding.


Giant Cell Ependymoma of Lateral Ventricle: Case Report, Literature Review, and Analysis of Prognostic Factors and Genetic Profile.
Giant cell ependymoma (GCE) is a rare primary central nervous system neoplasm. We report a case of GCE arising in the lateral ventricle. A 22-year-old female presented with generalized seizures. Magnetic resonance imaging demonstrated a diffuse, nonenhancing, multicystic mass centered in the atrium of the right lateral ventricle with extension throughout the frontal and temporal horns. An initial subtotal resection yielded the signature biphasic pattern of GCE. The dominant component contained pleomorphic, bizarre-appearing giant cells with low mitotic index, and a minor component comprised monomorphic, highly cellular, mitotically active cells that formed perivascular pseudorosettes. Array-comparative genomic hybridization showed copy number abnormalities consistent with chromosomal instability without evidence of RELA- or YAP1-fusion-features most often seen in posterior fossa ependymoma group B. Given expectedly poor radiation sensitivity, a second-look surgery was undertaken to minimize residual before proton beam radiotherapy. Review of the literature identified 28 reported cases, with a median age of 34 and bimodal peaks at approximately 20 and 50 years of age, including 9 supratentorial, 5 infratentorial, and 15 spinal ependymomas. Two infratentorial cases involved the fourth ventricle; no cases arose from the third or lateral ventricles. Supratentorial tumors predominated in younger patients, whereas other locations were observed among older patients (21.6 vs. 46.3 years of age; P = 0.01). Cases with Ki-67 index ≥10% showed worse progression-free survival than those of <10% (P = 0.049). Although rare, GCE should be considered in the differential of young patients with atypical intraventricular lesions, particularly given that extent of resection is associated with increased survival and GCE is thought to be radiation resistant.


Tuning of spinal networks to frequency components of spike trains in individual afferents.
Cord dorsum potentials (CDPs) evoked by primary afferent fiber stimulation reflect the response of postsynaptic dorsal horn neurons. The properties of these CDPs have been shown to vary in accordance with the type of primary afferent fiber stimulated. The purpose of the present study was to determine the relationships between frequency modulation of the afferent input trains, the amplitude modulation of the evoked CDPs, and the type of primary afferent stimulated. The somata of individual primary afferent fibers were impaled in the L7 dorsal root ganglion of alpha-chloralose-anesthetized cats. Action potentials (APs) were evoked in single identified afferents via the intracellular microelectrode while simultaneously recording the response of dorsal horn neurons as CDPs, or activity of individual target interneurons recorded extracellularly or intracellularly. APs were evoked in afferents using temporal patterns identical to the responses of selected afferents to natural stimulation of their receptive fields. Two such physiologically realistic trains, one recorded from a hair follicle and the other from a slowly adapting type 1 receptor, were chosen as standard test trains. Modulation of CDP amplitude in response to this frequency-modulated afferent activity varied according to the type of peripheral mechanoreceptor innervated. Dorsal horn networks driven by A beta afferents innervating hair follicles, rapidly adapting pad (Krause end bulb), and field receptors seemed "tuned" to amplify the onset of activity in single afferents. Networks driven by afferents innervating down hair follicles and pacinian corpuscles required more high-frequency activity to elicit their peak response. Dorsal horn networks driven by afferents innervating slowly adapting receptors including high-threshold mechanoreceptors exhibited some sensitivity to the instantaneous frequency, but in general they reproduced the activity in the afferent fiber much more faithfully. Responses of synaptically coupled dorsal horn neurons belonging to either hair follicle or SA1 fiber-driven networks to frequency-modulated input were in agreement with the CDP results, confirming that CDP amplitude modulation is a true reflection of EPSP amplitude modulation in at least a subset of dorsal horn neurons comprising the network.


Affine-invariant geometric shape priors for region-based active contours.
We present a new way of constraining the evolution of a region-based active contour with respect to a reference shape. Minimizing a shape prior, defined as a distance between shape descriptors based on the Legendre moments of the characteristic function, leads to a geometric flow that can be used with benefits in a two-class segmentation application. The shape model includes intrinsic invariance with regard to pose and affine deformations.


Cerebral scintigraphy--the phoenix rises again.
This paper reviews the development of cerebral scintigraphy from its early days of planar imaging with simple technetium-99m labelled compounds to the recent revival of the technique in the form of positron-emission and single-photon emission tomography. A short explanation of instrumentation and radiopharmaceuticals is given as a prelude to a description of both techniques in normal and pathological situations. Particular emphasis is placed on the more readily-available single-photon emission-tomographic techniques using labelled amines in the functional investigation of disorders not readily diagnosed by computed tomography.


Integration of soil magnetometry and geochemistry for assessment of human health risk from metallurgical slag dumps.
The main objective of the study was an assessment of the pollution level of agricultural land located close to dumps of industrial waste remaining after former Zn and Pb ore processing in Poland. The integrated geophysical-geochemical methods were applied for assessment of soil quality with respect to trace element pollution. Additionally, human health risk induced by the contaminated arable soil and dusting slag heap was estimated. The investigations pointed out that soils in the vicinity of the metallurgical slag dump in Piekary were heavily polluted. Spatial distribution of magnetic susceptibility corresponding well with distribution of the content of potentially toxic elements indicated the local "pollution hotspots." Proper geophysical and geochemical data interpretation supported by statistical factor analysis enabled identification of three different sources of pollution including metallurgical slug dump as a main source, but also traffic pollution influencing the area located along the busy road and relatively strong influence of the geochemical background. Computed health hazard index revealed no adverse health effect to the farmers cultivating arable soil, but in the direct vicinity of dusting, slag dump health risk occurred, caused mostly by very toxic elements as As and Tl. In the future, investigation should be focused on contribution of different sources to the heavy metal pollution in soil-crop system in this area. It should be highlighted that a site-specific approach should be taken in order to redevelop this kind of area in order to reduce ecological and human health threat. The study proved the integrated two-stage geophysical-geochemical method to be a feasible, reliable, and cost-effective tool for identification of the extent of soil pollution and areas at risk.


AtATG18a is required for the formation of autophagosomes during nutrient stress and senescence in Arabidopsis thaliana.
Vacuolar autophagy is a major pathway by which eukaryotic cells degrade macromolecules, either to remove damaged or unnecessary proteins, or to produce respiratory substrates and raw materials to survive periods of nutrient deficiency. During autophagy, a double membrane forms around cytoplasmic components to generate an autophagosome, which is transported to the vacuole. The outer membrane fuses with the vacuole or lysosome, and the inner membrane and its contents are degraded by vacuolar or lysosomal hydrolases. We have identified a small gene family in Arabidopsis thaliana, members of which show sequence similarity to the yeast autophagy gene ATG18. Members of the AtATG18 gene family are differentially expressed in response to different growth conditions, and one member of this family, AtATG18a, is induced both during sucrose and nitrogen starvation and during senescence. RNA interference was used to generate transgenic lines with reduced AtATG18a expression. These lines show hypersensitivity to sucrose and nitrogen starvation and premature senescence, both during natural senescence of leaves and in a detached leaf assay. Staining with the autophagosome-specific fluorescent dye monodansylcadaverine revealed that, unlike wild-type plants, AtATG18a RNA interference plants are unable to produce autophagosomes in response to starvation or senescence conditions. We conclude that the AtATG18a protein is likely to be required for autophagosome formation in Arabidopsis.


Tissue Culture Models of AKI: From Tubule Cells to Human Kidney Organoids.
AKI affects approximately 13.3 million people around the world each year, causing CKD and/or mortality. The mammalian kidney cannot generate new nephrons after postnatal renal damage and regenerative therapies for AKI are not available. Human kidney tissue culture systems can complement animal models of AKI and/or address some of their limitations. Donor-derived somatic cells, such as renal tubule epithelial cells or cell lines (RPTEC/hTERT, ciPTEC, HK-2, Nki-2, and CIHP-1), have been used for decades to permit drug toxicity screening and studies into potential AKI mechanisms. However, tubule cell lines do not fully recapitulate tubular epithelial cell properties in situ when grown under classic tissue culture conditions. Improving tissue culture models of AKI would increase our understanding of the mechanisms, leading to new therapeutics. Human pluripotent stem cells (hPSCs) can be differentiated into kidney organoids and various renal cell types. Injury to human kidney organoids results in renal cell-type crosstalk and upregulation of kidney injury biomarkers that are difficult to induce in primary tubule cell cultures. However, current protocols produce kidney organoids that are not mature and contain off-target cell types. Promising bioengineering techniques, such as bioprinting and "kidney-on-a-chip" methods, as applied to kidney nephrotoxicity modeling advantages and limitations are discussed. This review explores the mechanisms and detection of AKI in tissue culture, with an emphasis on bioengineered approaches such as human kidney organoid models.


GldI is a lipoprotein that is required for Flavobacterium johnsoniae gliding motility and chitin utilization.
Cells of Flavobacterium johnsoniae glide rapidly over surfaces by an unknown mechanism. Seven genes (gldA, gldB, gldD, gldF, gldG, gldH, and ftsX) that are required for gliding motility have been described. Complementation of the nonmotile mutants UW102-41, UW102-85, and UW102-92 identified another gene, gldI, that is required for gliding motility. gldI mutants formed nonspreading colonies, and individual cells were completely nonmotile. They were also resistant to bacteriophages that infect wild-type cells, and they failed to digest chitin. Introduction of wild-type gldI on a plasmid restored colony spreading, cell motility, phage sensitivity, and the ability to digest chitin to the gldI mutants. gldI encodes a predicted 199-amino-acid protein that localized to the membrane fraction. Labeling studies with [(3)H]palmitate indicated that GldI is a lipoprotein. GldI is similar to peptidyl-prolyl cis/trans-isomerases of the FK506-binding protein family and may be involved in folding cell envelope protein components of the motility machinery.