Interpersonal coordination and ball dynamics in futsal (indoor football).
Here, we report an investigation of the patterned movement behavior of players for a specific sub-phase of the game of futsal, namely when the goalkeeper for the attacking team is substituted with an extra outfield player. The movement trajectories of the ball and players were recorded in both lateral and longitudinal directions and investigated using relative phase analysis. Some differences in phase relations between different playing dyads were noted, indicating specificity of phase attractions, or otherwise, for certain players. In general terms, the defenders demonstrated strong in-phase attractions with the ball and with each other, whereas weaker phase attractions, indicated by increased relative phase variability, were observed for the attackers and ball, as well as between attackers themselves. These results demonstrate different coordination dynamics for the defending and attacking dyads, from which we interpret evidence for different playing sub-systems consistent with different team objectives linked together in an overarching game structure. In keeping with dynamical systems theory for complex systems, we view this sub-phase of futsal as being characterized by coordinated behavior patterns that emerge as a result of self-organizing processes. These dynamic patterns are generated within functional constraints, with players and teams exerting mutual influence on each other.


[DEX and executive dysfunction in activities of daily living in Alzheimer's disease and frontotemporal dementia].
The questionnaire DEX was designed by Wilson et al. in 1996 to explore the disturbances of executive functions (EF) in activities of daily living (ADL). This study was performed to explore the specificity of the DEX to evaluate executive dysfunction in ADL, and its contribution to the distinction between Alzheimer's disease (AD) and frontotemporal dementia (FTD). 13 patients with the frontal variant of FTD, 19 patients with FTD associated with amyotrophic lateral sclerosis, FTD/SLA, 18 patients with Alzheimer's disease, AD, and 24 controlled subjects. The scores on the DEX completed by a proxy as well as those on two scales assessing ADL (the Cognitive Difficulties Scale by McNair & Kahn, and a composite scale (NADL) including the evaluation of basic (BADL) and instrumental (IADL) by the Lawton & Brody scales, and of social activities (SADL) from Katz & Lyerly) were compared to neuropsychological tests assessing EF (Behavioural Assessment of Dysexecutive Syndrome (BADS), Wisconsin Card Sorting Test, Stroop test, Trail Making Test B, lexical and categorical verbal fluencies, WAIS-III similarities). No correlation was found between the scores on the DEX or the other ADL scales, and the BADS scores. Scores on DEX showed some weak correlations with some executive tasks, but no stronger than those found with the other ADL scales. Analysis of the most frequently perturbed DEX items failed to show a characteristic profile for EF dysfunction. No significant difference was found between patients with AD and DFT on the scores on the DEX as well as on other ADL scales, when adjusted for dementia severity (assessed by the Mattis Dementia Rating Scale (MDRS)). No difference was found between MA and DFT patients neither in the profile of the most frequently perturbed DEX items, nor in decreased awareness of the disorders assessed by comparison of the scores on the DEX completed by patients and familiars. In this study, DEX does not appear as a specific tool for assessing EF dysfunction in ADL compared to other ADL scales. It was more related to global cognitive difficulties as assessed by the CDS and the MDRS. Scores on the DEX as well as on other ADL scales do not contribute to the distinction between AD and FTD.


Stability and reproducibility of radiometric properties of light curing units (LCUs). Part I: QTH LCUs.
The present study, divided into two parts, analyses the stability and reproducibility of the spectral and energy emission of the present light-curing units (LCUs), quartz tungsten halogen (QTH) and light-emitting diodes (LEDs). In part I, QTH LCUs were studied. The results showed that the QTH LCUs studied presented high stability and reproducibility in terms of their spectral emission with VAF (variance accounting for) values from the Cauchy-Schwarz inequality, all close to 100%. With respect to the energy stability, the QTH LCUs studied can be considered stable under practical clinical conditions, although for some devices the initial irradiance value is critical. This result should be taken into account in those works which is researched in polymerization kinetics of dental materials as well as in clinical practice.


Germ layer specification and axial patterning in the embryonic development of the freshwater planarian Schmidtea polychroa.
Although patterning during regeneration in adult planarians has been studied extensively, very little is known about how the initial planarian body plan arises during embryogenesis. Herein, we analyze the process of embryo patterning in the species Schmidtea polychroa by comparing the expression of genes involved in the establishment of the metazoan body plan. Planarians present a derived ectolecithic spiralian development characterized by dispersed cleavage within a yolk syncytium and an early transient embryo capable of feeding on the maternally supplied yolk cells. During this stage of development, we only found evidence of canonical Wnt pathway, mostly associated with the development of its transient pharynx. At these stages, genes involved in gastrulation (snail) and germ layer determination (foxA and twist) are specifically expressed in migrating blastomeres and those giving rise to the temporary gut and pharyngeal muscle. After yolk ingestion, the embryo expresses core components of the canonical Wnt pathway and the BMP pathway, suggesting that the definitive axial identities are established late. These data support the division of planarian development into two separate morphogenetic stages: a highly divergent gastrulation stage, which segregates the three germ layers and establishes the primary organization of the feeding embryo; and subsequent metamorphosis, based on totipotent blastomeres, which establishes the definitive adult body plan using mechanisms that are similar to those used during regeneration and homeostasis in the adult.


Rapid method for construction of yeast artificial chromosome human DNA libraries involving the trapping of cells in agarose films.
A simple method for the molecular cloning of fragments of more than one hundred kilobase pairs of exogenous DNA, by the encapsulation of cells in agarose beads, was reported previously for the construction of a human genomic DNA library in a yeast artificial chromosome (YAC) vector (in situ YAC construction) [1]. The efficiency of this procedure is impaired by the step in which agarose beads that contain human DNA fragments are melted before transformation. The incomplete solubility of the ligated human DNA fragment-YAC vector often results in lower than desirable frequencies of transformation. To overcome this problem we have developed a new improved method that involves use of an agarose film. The technical manipulations involved in the construction of clones of very large segments of human DNA are discussed.


A scoping review of patterns, motives, and risk and protective factors for adolescent firearm carriage.
Firearm carriage is a key risk factor for interpersonal firearm violence, a leading cause of adolescent (age < 18) mortality. However, the epidemiology of adolescent firearm carriage has not been well characterized. This scoping review examined four databases (PubMed; Scopus; EMBASE; Criminal Justice Abstracts) to summarize research on patterns, motives, and underlying risk/protective factors for adolescent firearm carriage. Of 6156 unique titles, 53 peer-reviewed articles met inclusion criteria and were reviewed. These studies mostly examined urban Black youth, finding that adolescents typically carry firearms intermittently throughout adolescence and primarily for self-defense/protection. Seven future research priorities were identified, including: (1) examining adolescent carriage across age, gender, and racial/ethnic subgroups; (2) improving on methodological limitations of prior research, including disaggregating firearm from other weapon carriage and using more rigorous methodology (e.g., random/systematic sampling; broader population samples); (3) conducting longitudinal analyses that establish temporal causality for patterns, motives, and risk/protective factors; (4) capitalizing on m-health to develop more nuanced characterizations of underlying motives; (5) increasing the study of precursors for first-time carriage; (6) examining risk and protective factors beyond the individual-level; and, (7) enhancing the theoretical foundation for firearm carriage within future investigations.


Renal tumors in solid organ recipients: clinical and pathologic features.
Solid organ recipients are several times more likely to develop renal cell carcinoma (RCC) compared with the general population, but little is known about the features of these tumors. The aim of this study is to report on the characteristics of renal tumors in solid organ recipients compared with the general population. Patients undergoing surgery for a localized renal mass between 2000 and 2008 were studied. Demographic, clinical, radiographic, and pathologic characteristics were compared between patients with and without a history of organ transplant. A subanalysis focused on the features of a kidney compared with another non-renal organ transplant. Of 950 patients identified, 19 were organ recipients. Transplant recipients were younger and had lower body mass indices. Most organ recipients (94.7%) were asymptomatic at presentation. Transplant recipients had higher incidence of malignant pathology (88.2% vs. 78.7%), but had smaller masses, of lower stage and grade, and a higher proportion of papillary histology (35.3% vs. 19.8%). Papillary subtype accounted for almost one-half of the RCCs in kidney recipients compared with 20% in other organ recipients. Over a median follow-up of 4 years, 1 (5.9%) local recurrence, no metastatic progressions, and no RCC-related deaths occurred in the transplant cohort. Organ recipients typically present with incidental renal masses of smaller size. However, these are twice more likely to be malignant compared with the general population. RCC arising in transplant recipients tend to be of lower stage and grade, contributing to the apparently excellent oncologic outcomes of surgical treatment.


Preventative laparoscopic repair of Petersen's space following gastric bypass surgery reduces the incidence of Petersen's hernia: a comparative study.
Internal hernias (IH) are late complications of bariatric surgery, specifically gastric bypass and manifest with diffuse abdominal pain and/or intestinal obstruction. They have a low incidence, however, are increasingly common in patients undergoing laparoscopic gastric bypass (LGBP). Petersen's internal hernia is one of the most frequent internal hernias following Bariatric surgery. We describe our experience at a third-level surgical center using a prophylactic Petersen's space herniorrhaphy immediately following LGBP as a preventative strategy for post-bariatric internal hernias. In addition, we perform a retrospective descriptive study with 667 patients undergoing LGBP under which we divided into two groups. In the first group, the Petersen's space was not closed, and in the second group, the Petersen´s space closure was performed using non-absorbable polypropylene non-interrupted sutures. 667 patients were taken to LGBP, and of which 5 presented internal hernias. From the 346 patients who had Petersen´s herniorrhaphy performed, one developed signs of an internal hernia at 22 months follow-up and was subsequently confirmed later with laparoscopy (0.02%). Of the 321 patients not having had Petersen's space closure, 4 developed Petersen's internal hernia at an average of 22-month post-op, incidence of 0.1%. We analyzed and compared our results with those reported in the literature. Petersen's space closure immediately after a LGBP with an alimentary loop in the anterior colic position (prophylactic herniorrhaphy) with non-interrupted non-absorbable suture is a useful, safe, and effective technique to prevent the development of Petersen's IH during the post-operative period following LGBP.


Childhood and adolescent anorexia nervosa.
Eating disorders are common during childhood and adolescence. Early intervention is associated with the best prognosis. Treatment interventions that focus on achieving ideal body weight and use various family therapy approaches are most likely to be effective. Much remains to be learned about the origin of AN, but there are promising recent advances.


Evaluation of Models for Temperature-Dependent Viscosity Changes in Dairy Protein Beverage Formulations During Thermal Processing.
Rheological modeling as a function of temperature is a useful tool for describing products undergoing thermal processing. The rheological behavior of a range of dairy-based (4%, w/w) protein beverages was investigated for applicability to semi-empirical temperature-dependent viscosity equations. The viscosity at 16.8 rad/s of the beverages was measured during heating, holding, and cooling over a temperature range of 25 to 90 o C using a rheometer with starch pasting cell geometry. Five established fitting methods were applied based on the Arrhenius and Williams-Landel-Ferry (WLF) equations using nonlinear regression analysis. A two-parameter WLF (WLF2 ) model, using viscosity at a reference temperature of 25 o C resulted in high R2 values (0.974 to 0.988) and a statistically superior fit compared to the Arrhenius, Generalized Arrhenius, and exponential equations (P < 0.001). Deviation from the WLF2 modeled equation was used to describe and investigate the effect formulation had on the changes in viscosity during thermal heating. This study successfully applied the WLF equation to a liquid protein system, proving that a consistent and close fit can be achieved across a range of formulations. A rapid, quantitative method for viscosity-temperature profile evaluation is presented, which can ease product development and optimization of product processing stability. This study validated the use of the Williams-Landel-Ferry equation to describe the behavior of dairy beverages during thermal processing, providing a better fit to rheological data than the widely used Arrhenius-based equations. In conjunction with the WLF equation, a method was presented which reduced the complex rheological data to a single value, which can aid in the comparison of formulations for product development and optimization in both research and industry.


ECG in patients with acute heart failure can predict in-hospital and long-term mortality.
Initial risk stratification in patients with acute heart failure (AHF) is poorly validated. Previous studies tended to evaluate the prognostic significance of only one or two selected ECG parameters. The aim of this study was to evaluate the impact of multiple ECG parameters on mortality in AHF. The Acute Heart Failure Database (AHEAD) registry collected data from 4,153 patients admitted for AHF to seven hospitals with Catheter Laboratory facilities. Clinical variables, heart rate, duration of QRS, QT and QTC intervals, type of rhythm and ST-T segment changes on admission were collected in a web-based database. 12.7 % patients died during hospitalisation, the remainder were discharged and followed for a median of 16.2 months. The most important parameters were a prolonged QRS and a junctional rhythm, which independently predict both in-hospital mortality [QRS > 100 ms, odds ratio (OR) 1.329, 95 % CI 1.052-1.680; junctional rhythm, OR 3.715, 95 % CI 1.748-7.896] and long-term mortality (QRS > 120 ms, OR 1.428, 95 % CI 1.160-1.757; junctional rhythm, OR 2.629, 95 % CI 1.538-4.496). Increased hospitalisation mortality is predicted by ST segment elevation (OR 1.771, 95 % CI 1.383-2.269) and prolonged QTC interval >475 ms (OR 1.483, 95 % CI 1.016-2.164). Presence of atrial fibrillation and bundle branch block is associated with increased unadjusted long-term mortality, but mostly reflects more advanced heart disease, and their predictive significance is attenuated in the multivariate analysis. ECG in patients admitted for acute heart failure carries significant short- and long-term prognostic information, and should be carefully evaluated.


Results of the surgical treatment of carcinoma of the esophagus.
Between 1972 and 1980, 360 patients were operated upon for the treatment of carcinoma of the esophagus at this university hospital. By adopting a policy of routine endoscopy in all patients with minor esophageal symptoms, early diagnosis was possible. Nutritional and respiratory support preoperatively and postoperatively diminished anastomotic leakages and pulmonary complications. We were able to lower our mortality from 17.6 to 2.6 per cent and to increase our resectablity rate from 60.2 to 85.0 per cent. It is still too early to determine if the Akiyama technique, while permitting an improvement of the results, will increase the five year survival rate.


Additive prognostic value of gamma-glutamyltransferase in coronary artery disease.
Serum gamma-glutamyltransferase activity (GGT) has been documented as an independent cardiovascular risk factor. However, to-date its value has not been compared with C-reactive protein (CRP) and other indexes in a multimarker prognostic strategy in patients with coronary artery disease. We prospectively evaluated 474 subjects with angiographically documented CAD. GGT and traditional humoral and clinical parameters were measured at hospital admission. A multivariate model was used to predict all-cause and cardiac mortality. GGT showed an independent prognostic value after adjustment for possible confounders, including alcohol consumption, and beyond established risk factors, such as extent of coronary atherosclerotic disease, left ventricular ejection fraction, age, serum glucose, cholesterol subfractions, and C-reactive protein (CRP). At a 3-year follow-up, cardiac mortality was 9% in patients with serum GGT activity >25 U/L vs. 3.5% in those with serum GGT<25 U/L (p=0.028). The association of three independent biomarkers (higher GGT, CRP, fasting glucose) identified a subgroup of 45 patients with the highest risk of cardiac death at 3 years (26.6%, vs. no event or 2.7% in the subsets of 87 and 198 patients with, respectively, no/one risk factor above cut-off value, p<0.0001). GGT is confirmed as independent risk factor in patients with established coronary artery disease. GGT, CRP, fasting glucose show an additive prognostic value, whereas low values of these biomarkers identify a subset of patients with the lowest risk of cardiac death.


Site-specific discrimination of Cytosine and 5-methylcytosine in duplex DNA by Peptide nucleic acids.
For site-specific discrimination of cytosine (C) and 5-methylcytosine (mC) in duplex DNA, we developed a new method using peptide nucleic acids (PNAs). The combination of a PNA-assisted DNA displacement complex and a fluorescein-labeled probe oligomer allowed the detection of mC at the defined sites in target DNA using a restriction enzyme. After treatment of the complex with a restriction enzyme, strong fluorescence emission was observed for the complex containing C at the target site, whereas the fluorescence intensity for the complex containing mC was extremely weak.


[Protective effect of Xingnaojing injection on traumatic brain injury].
To investigate the protective effect and mechanism of Xingnaojing(Traditional Chinese Medicine) injection on brain injury in rats. Sixty-three healthy adult male SD rats were randomly divided into 3 groups (n = 21): sham operation group, model group, xingnaojing group. The model of traumatic brain injury model group and Xingnaojing group used the free fall impact injury method, the sham operation group underwent craniotomy, did not cause brain damage. Xingnaojing group in rats after 10 min by tail vein injection Xingnaojing injection 10 ml/(kg x d), model group and sham operation group were intravenously injected with 0.9% sodium chloride solution, three groups were administered continuously for 7 days. At administration of the seventh days compared the S-100B protein in the serum and neuro specific enolase (NSE) level, the water content of brain tissue, serum superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) content, and neurological function of rats among groups. Compared with the sham operation group, the nerve defect, brain water content, MDA, S100B protein and NSE levels were obvigusly increased in Xingnaojing group and model group; SOD, GSH-Px content decreased significantly; In Xingnaojing group nerve impairment and brain moisture were significantly lower than those of model group, the serum MDA, S-100B protein and NSE levels were significantly lower than those in the model group, the SOD, GSH-Px activity was significantly higher than that in the model group. Xingnaojing injection has protective effects on rat brain injury, and its mechanism may be related to reduce brain edema after traumatic brain injury and inhibit the reaction of oxygen free radical, protect nerve cells.


The immunology of pregnancy.
Pregnancy is an immunological balancing act in which the mother's immune system has to remain tolerant of paternal major histocompatibility (MHC) antigens and yet maintain normal immune competence for defense against microorganisms. The placenta separates fetal and maternal blood and lymphatic systems and it is fetal trophoblast that plays the major role in evading recognition by the maternal immune system. Trophoblast cells fail to express MHC class I or class II molecules and the extravillous cytotrophoblast cells strongly express the nonclassic MHC gene encoding HLA-G, which may downregulate natural killer (NK) cell function. In addition, the trophoblast expresses Fas ligand, thereby conferring immune privilege: maternal immune cells expressing Fas will undergo apoptosis at the placenta/decidua interface. A third protective mechanism exploited by the trophoblast is the expression of the complement regulatory proteins CD46, CD55, and CD59. Uterine decidual and placental cells produce a huge array of cytokines which, in part, contribute to the deviation of the immune response from Th1 to Th2. This may leave the mother more open to infection whose control is Th1-dependent, but increased production of Th1 cytokines has been linked to spontaneous abortion and small-for-dates babies. This bias in cytokines and hormonally mediated effects on the thymus and on B cells may also contribute to the suppression of autoimmune responses and changes in circulating and local T-cell subsets in pregnancy.


Pseudotumour cerebri in children: etiological, clinical features and treatment modalities.
To investigate the etiological and clinical features of pseudotumour cerebri (PTC) in children, features of 12 children with PTC were documented. The etiology could be clarified in 6 patients. The other 6 patients were accepted as idiopathic intracranial hypertension (primary PTC). Acetazolamide was used as the first drug and was effective in only 4 patients who had no underlying cause. Repeated lumbar punctures (LP) were performed in 6 patients and 5 of them were unresponsive. Prednisone was used in 3 patients and was effective in only one patient. The CSF pressure continued to be high in five patients and could be normalized only by withdrawing of the precipitating drug in three patients and by ventricular-peritoneal shunting in two patients with cerebral venous thrombosis. Although, medical treatment and repeated LP are usually effective in children with PTC, clarifying and solving the underlying cause can be crucial.


Alcohol increases commission error rates for a continuous performance test.
Studying the effects of alcohol on Continuous Performance Test (CPT) performance was of interest for two reasons, i.e., (1) perhaps because of the ease of the task used in previous experiments, alcohol has not been found to impair performance, and (2) CPT commission errors (described below) have been related to impulsive behavior. In this study, the CPT featured both an Immediate Memory Task (IMT) and a more difficult Delayed Memory Task (DMT). We compared the performance of 18 subjects under both alcohol and placebo conditions, using a within-subject design. Both the IMT (0.5-sec delay) and the DMT (3.5-sec delay, with distracter stimuli at 0.5-sec intervals) required the subject to respond if a briefly displayed number was identical to the one presented before it. Stimuli included target (identical match), catch (4 of 5 digits matched), and novel (random number) stimuli. On 2 separate days, subjects performed between administrations of three hourly placebo drinks or three hourly drinks containing 0.20 g/kg of alcohol (producing peak breath alcohol concentrations of approximately 0.035%). The main finding was that alcohol consumption increased responses to catch stimuli (i.e., commission errors) in the DMT. In contrast, performance in the IMT (the easier task) was unaffected by alcohol. Commission errors measured during peak breath alcohol concentrations were significantly correlated with scores on the Barratt Impulsivity Scale for both the IMT and DMT. Discriminability (A') between target and catch stimuli was reduced by alcohol for the DMT only. These data indicate that even small amounts of alcohol can produce measurable changes in CPT performance parameters if the task is of sufficient difficulty and that commission errors can be increased by alcohol consumption.


Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus.
Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. In a prospective study, we assessed long-term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38) or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion. After a mean post-conversion follow-up of 27+/-1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at D180 (P = 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n = 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n = 14), those with a decrease in creatinine clearance at 6 months post-conversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P < 0.0009), which was >2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30. Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.


[Socioeconomic status and health insurance expenditures for children and adolescents with conduct disorder : An analysis of statutory health insurance data].
For various psychiatric and somatic disorders, there is evidence of an association between patients' socioeconomic status (SES), healthcare utilisation, and the resulting costs. In the field of child and adolescent psychiatric disorders, studies on this topic are lacking. To exploratively analyse the association of healthcare expenditures for children and adolescents with conduct disorder (including oppositional-defiant disorder) - one of the most prevalent child and adolescent psychiatric disorders - and SES. The analysis is based on routine data from the German statutory health insurance company AOK Nordost for the calendar year 2011, covering 6461 children and adolescents (age 5-18 years) with an ICD-10 diagnosis of conduct disorder. The insureds' SES was estimated indirectly, based on the social structure of the postcode area, using the German Index of Multiple Deprivation (Mecklenburg-Vorpommern, Brandenburg), and the Berliner Sozialindex I (Berlin), respectively. From the two indices, quintiles were derived. Based on these quintiles, average costs per case for the following cost types were analysed: inpatient healthcare, outpatient healthcare (general practitioners, paediatricians, child and adolescent psychiatrists, child and adolescent psychotherapists), and prescribed medication. There was no significant functional association between SES and healthcare costs for any of the analysed cost types. In contrast to findings in adults, this study on children and adolescents with conduct disorders did not reveal an association between SES and healthcare costs. Within this group of patients, social inequality does not seem to have a significant influence on healthcare utilisation in Germany.


Preliminary study on assessment of lead exposure in Thai children aged between 3-7 years old who live in Umphang district, Tak Province.
Centers of Disease Control of the United States of America (CDC) informs Ministry of Public Health, Thailand that up to 13% of Burmese refugee children who are transferred to the United States of America during 2007-2009 have elevated blood lead levels (EBLL, Blood Lead Level > or = 10 microg/dl). These are children from a number of refugee camps in Tak Province; two camps are near Umphang but other camps are not. In June 2008, CDC, the result of investigation of Centers for Disease Control/Thailand Ministry of Public Health Collaboration (CDC/TUC) and International Organization for Migration, Thailand indicates that 33 of 64 children aged 6 months to 15 years (5.1%) who live in Mae La, Umpiem and Nupo camps have elevated blood lead level. However, no study on how Thai children who live nearby those camps are exposed to lead. Subsequently, Queen Sirikit National Institute of Child Health, Bangkok, Thailand contacts relevant organizations in Tak Province in order to investigate lead exposure and evaluate health status of Thai children who live close to Burmese refugee camps. 1) Evaluation of lead exposure of Thai children who live nearby Burmese refugee camps; 2) Assessment of risk factors on lead exposure of the children as mentioned above. The present study adopts a retrospective study based on information gathered from health assessment on 213 Thai children aged between 3-7 years old who live nearby Burmese refugee camps. The health assessment was conducted from April 30th, 2010 to May 5th, 2010. The information is from 3 sources. The first source is from blood sampling in order to assess lead level and ferritin level. The next source is from interview of persons who provide primary care in order to identify risk factors on lead exposure of target children. The last source is from physical examination and developmental assessment conducted by pediatricians and special nurses for child development in order to identify health and developmental problems. The population of the present study was 213 of Thai children are 3-7 years old, average age is 54.54 +/- 12.41 months-old. The average blood lead level is 7.71 +/- 4.62 microg/dl (range = 3-25 microg/dl). Elevated blood lead levels of all populations show that 57 children (26%) have blood lead level at 10 microg/dl or more. Analysis of odds by controlling all risk factors (adjusted OR) that effect on blood lead level (> or =10 microg/dl) indicates that only gender and source of drinking water are risk factors. To clarify, male children would have 2.8 times higher risk than female children. Children who drink water from tap and canal have 15 times and 72 times, respectively, higher risk than children drinking from bottle water. The result of the present study shows that 1 of 4 of Thai children at Umphang district, Tak Province who lived near Burmese refugee camps aged between 3-7 years old have blood lead level higher than concerning level. Thus, it is necessary to identify risk factors on lead exposure and policy of blood lead screening in some areas in Thailand.


Biotinylated Cyclophane: Synthesis, Cyclophane-Avidin Conjugates, and Their Enhanced Guest-Binding Affinity.
Cationic and anionic cyclophanes bearing a biotin moiety were synthesized as a water-soluble host (1a and 1b, respectively). Both hosts 1a and 1b were found to strongly bind avidin with binding constants of 1.3 × 10(8) M(-1), as confirmed by surface plasmon resonance measurements. The present conjugate of 1a with avidin (1a-avidin) showed an enhanced guest binding affinity toward fluorescence guests such as TNS and 2,6-ANS. The K values of 1a-avidin conjugate with TNS and 2,6-ANS were ~19-fold larger than those of monocyclic cyclophane 1a with the identical guests. Favorable hydrophobic and electrostatic interactions between 1a-avidin and TNS were suggested by computer-aided molecular modeling calculations. Moreover, addition of excess biotin to the complexes of 1a-avidin with the guests resulted in dissociation of 1a-avidin to avidin and 1a having less guest-binding affinity. Conversely, such enhancements in the guest-binding affinity were not obviously observed for the conjugate of anionic 1b with avidin (1b-avidin) due to electrostatic repulsion between anionic 1b and anionic guests.


Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis.
Aminoglycoside antibiotics have been shown to induce adaptive resistance in Pseudomonas aeruginosa in vitro and in a mouse model of infection, but adaptive resistance has not been described in human infections. Seven patients with cystic fibrosis were treated with inhaled tobramycin to determine whether adaptive resistance occurred in P. aeruginosa in their sputum. In three patients who had not recently taken antibiotics, 80 mg tobramycin was administered by nebuliser and resulting peak sputum tobramycin concentrations were 90-240 mg/L (elimination half-life 1.9-2.1 h). Adaptive resistance was detected in P. aeruginosa 1-4 h after the dose of tobramycin. Moderate resistance was present at 24 h and full susceptibility returned between 24 and 48 h. In four other patients on long-term twice-daily inhaled aminoglycoside treatment, adaptive resistance was present before, and 4 h after, 80 mg of tobramycin administered by nebuliser. The presence and time course of adaptive resistance in humans may have implications for improving aminoglycoside dosing regimens.


Oxo-rhenium catalyzed reductive coupling and deoxygenation of alcohols.
Representative benzylic, allylic and α-keto alcohols are deoxygenated to alkanes and/or reductively coupled to alkane dimers by reaction with PPh3 catalyzed by (PPh3)2ReIO2 (1). The newly discovered catalytic reductive coupling reaction is a rare C-C bond-forming transformation of alcohols.


A gene encoding a DUF523 domain protein is involved in the conversion of 2-thiouracil into uracil.
Modified nucleotides are present in many RNA species in all Domains of Life. While the biosynthetic pathways of such nucleotides are well studied, much less is known about the degradation of RNAs and the return to the metabolism of modified nucleotides, their respective nucleosides or heterocyclic bases. Using an E. coli uracil auxotroph, we screened the metagenomic libraries for genes, which would allow the conversion of 2-thiouracil to uracil and thereby lead to the growth on a defined synthetic medium. We show that a gene encoding a protein consisting of previously uncharacterized Domain of Unknown Function 523 (DUF523) is responsible for such phenotype. We have purified this recombinant protein and demonstrated that it contains a FeS cluster. The substitution of cysteines, which have been predicted to form such clusters, with alanines abolished the growth phenotype. We conclude that DUF523 is involved in the conversion of 2-thiouracil into uracil in vivo.


Neurohypophysial hormones and steroidogenesis in the interrenals of Xenopus laevis.
The influence of arginine vasotocin (AVT) on the interrenal secretion of the clawed toad (Xenopus laevis) was studied combining in vivo and in vitro experiments. In vivo: A single injection of 3 nmol AVT per 100 g body weight was given, and the concentrations of corticosterone and aldosterone in the serum were measured after 1, 3, 6, 12, and 24 hr. The serum levels of both steroids remained elevated over 6 hr and declined to normal levels within 12 hr. The increase of the aldosterone concentration was relatively stronger than that of corticosterone. In vitro: A perifusion system was used to study the influence of AVT concentrations ranging from 0.1 to 50 nM on the secretion rates of corticosterone and aldosterone. The response of the interrenals was dose dependent; corresponding to the in vivo results, the elevation rate was higher for aldosterone than for corticosterone. The effects of several nonapeptides were compared. AVT was most effective, followed by mesotocin and arginine vasopressin (AVP). Isotocin and oxytocin had less effect. The selective agonist of the mammalian V2 receptor (1-deamino-8-D-arginine)-vasopressin (DDAVP) did not stimulate the interrenals, while the V1 receptor-selective antagonist ((1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)-2-(O-methyl)-tyrosine)-AVP could not diminish the stimulation by AVT. Thus, the AVT receptor of the amphibian interrenal must be a special one and is different from the V1 and V2 types of mammals. In a comparison of the effects of AVT with other stimulators such as ACTH(1-28) or urotensin II, it was found that the sensitivity of the interrenals to AVT was similar to that of these peptides. The results indicate that AVT plays an important role in the osmomineral regulation of Xenopus laevis by acting on the corticosteroid secretion of the interrenals.


Held to account. tt.
Representatives of two nursing organisations offer a summary of nurses' legal position in relation to unsafe staffing levels.


Primary cutaneous Langerhans cell sarcoma without Birbeck granules: indeterminate cell sarcoma?
An 88-year-old white male presented with a rapidly growing skin nodule on the scalp. Clinically, the nodule did not appear unusual for an ordinary cutaneous neoplasm on sun-exposed skin of an elderly white male. Histopathological examination showed sheet-like epithelioid tumor cell growth with a vaguely nested pattern and frank malignant features, resembling malignant melanoma. However, the tumor cells possessed irregularly convoluted nuclei with nuclear groves, frequent multinucleation and fine vesicular cytoplasm, features highly suggestive of histiocytes. Immunohistochemistry studies showed that the tumor cells were diffusely positive for S-100 protein and CD1a and negative for HMB-45, Melan-A, cytokeratin and CD30. The provisional diagnosis of Langerhans cell sarcoma was thus favored. To confirm this diagnosis, electron microscopic examination was performed. Although classic features of histiocytes were readily identifiable, no Birbeck granules could be found upon a thorough search on repeated sections. These results are indicative of the indeterminate cell nature of the tumor. We propose a diagnosis of primary cutaneous indeterminate cell sarcoma for this unusual histiocytic neoplasm. Current classification of histiocytic neoplasms and differential diagnosis are reviewed.


Back pain in the elderly.
Back pain in the elderly is a complex chief complaint, because numerous life-threatening or disabling conditions may present with signs and symptoms similar to those of more benign disease processes. An understanding of the limitations of physical examination and history distinguishing dangerous from benign causes is essential to avoid misdiagnosis and patient morbidity or mortality. This article describes the presentation and evaluation of dangerous causes of back pain, including vascular catastrophes, spinal cord compression syndromes, and infectious diseases. Less emergent musculoskeletal injuries are discussed briefly.


Scintigraphic characteristics of non-ossifying fibroma in military recruits undergoing bone scintigraphy for suspected stress fractures and lower limb pains.
Non-ossifying fibroma (NOF) is the most common fibrous bone lesion in children and young adults. This benign lesion is not a true neoplasm but is considered a developmental defect. Clinically, the lesion is asymptomatic and has a predilection for the long bones, particularly the femur and the tibia. NOF that ossify can show increased uptake on bone scintigraphy. Although the radiographic and histopathological findings of NOF have been well described, the scintigraphic findings of the abnormality have only been incidentally mentioned in the literature. To document the scintigraphic features of NOF in a group of military recruits undergoing bone scintigraphy for suspected stress fractures. Features to differentiate co-existent NOF and stress fractures lesions are discussed. Eighty-three military recruits, 67 male and 16 female, aged 18 to 22 years (mean, 19.4 years), who underwent Tc-methylene diphosphonate bone scans for suspected stress fractures or because of pain of the lower limbs had 91 focal lesions on bone scan which on further evaluation demonstrated characteristic radiographic findings of NOF. We evaluated the anatomical site of the lesions, documented the intensity of uptake on bone scan and compared the findings with the radiographic description of the lesions. Comparison with the characteristic scintigraphic pattern of co-existent stress fracture lesions and with previously reported data was performed. A total of 91 NOF lesions were detected. Overall, 89% of NOF were located about the knee. Anatomic distribution of NOF lesions was as follows: 43 (47.3%, R=25, L=18) were located in the postero-medial aspect of the distal femur, 18 (19.8%, R=12, L=6) in the postero-medial aspect of the proximal tibia, 11 (12%, R=5, L=6) in the postero-lateral aspect of the distal femur, 10 (11%, R=4, L=6) in the postero-lateral aspect of the distal tibia, 4 (4.4%, R=2, L=2) in the postero-lateral aspect of the proximal tibia, 3 (3.3%, L=3) in the antero-central aspect of proximal tibia, 1 (1.1%, L=1) in the antero-lateral aspect of distal femur, 1 (1.1%, L=1) in the medial-central aspect of the proximal tibia. In this series NOF lesions were not found in the fibula. Eighty five of 91 (93.4%) of all NOF were located at the metaphysis of the long bones, 2/91 (2.2%) were located at the meta-diaphyseal region of the long bones and only 4/91 (4.4%) of the lesions were located at the diaphysis. All the NOF showed variable degrees of focal increased tracer uptake on bone scan. The bone scan appearance of the focal lesions was: faint uptake in 29 (31.9%), mild uptake in 27 (29.7%), moderate uptake in 28 (30.7%) and intensely increased uptake in seven (7.7%). The radiographic description of the NOF was: lucent NOF three (3.3%), mixed sclerotic and lucent 68 (74.7%) and sclerotic in 20 (22%). Most of the NOF which demonstrated moderate or intensely increased tracer uptake had mixed lucent and sclerotic radiographic appearance (healing). Most of the sclerotic lesions (healed) showed faint uptake. Co-existent stress fractures were predominantly located in the diaphysis of the long bones, characteristically in the postero-medial aspect of the mid-third of the tibia or femur. Military recruits undergoing bone scan for suspected stress fracture might have incidental findings which require further evaluation. Focal lesions on bone scan located about the knee in the lateral aspect of the distal femur or lateral aspect of the proximal tibia in the metaphyseal region of these bones are not compatible with the characteristic scintigraphic features of stress fracture. Such a finding should raise the suspicion for other bony lesions such as NOF, which is commonly located in this region. During the healing phase of the NOF which commonly occur in the age range of this group, the lesion shows mild-to-moderate increased tracer uptake on bone scan. Plain film radiography is usually diagnostic and patients are followed up conservatively. Some NOF lesions are still indistinguishable from stress fracture or splints on bone scan.


Developmental competence and post-thaw survivability of buffalo embryos produced in vitro: effect of growth factors in oocyte maturation medium and of embryo culture system.
The present study was conducted to examine the effects of supplementation to IVM medium of epidermal growth factor (EGF), fibroblast growth factor (FGF) and vasoactive intestinal peptide (VIP) along with pregnant mare serum gonadotrophin (PMSG) on oocyte maturation and cleavage of buffalo embryos (experiment 1). The developmental competence of cleaved embryos cultured in either a complex co-culture system (TCM-199+10% serum+oviduct cell monolayer) or defined media (a) modified form of synthetic oviductal fluid (mSOF) was evaluated (experiment 2). The post-thaw morphology and survivability of frozen blastocysts developed from embryos cultured either in complex or defined medium was compared (experiment 3). Aspirated oocytes were cultured in maturation medium (TCM-199+PMSG (40 IU/ml-control)) supplemented with EGF (20 ng/ml), FGF (20 ng/ml) and VIP (20 ng/ml), either alone or in combination, in a CO(2) incubator at 38.5 degrees C for 24h. Maturation rate was assessed and oocytes were inseminated in vitro with frozen-thawed sperm processed in Brackett and Oliphant (BO) medium. The cleaved embryos were cultured either in complex co-culture system or mSOF. Results suggested that EGF had more beneficial effect on buffalo oocyte maturation, and embryo cleavage than FGF. Addition of VIP to the oocyte maturation medium did not improve the results. Blastocyst yields from buffalo oocytes were significantly higher in a complex co-culture system than in defined media (mSOF) when oocytes were matured in presence of EGF either alone or in combination with FGF and VIP. The mean percent of morphologically normal blastocysts after thawing and their survivability were significantly higher in blastocysts obtained from embryos cultured in mSOF than those cultured in complex co-culture system.


Superoleophobic Slippery Lubricant-Infused Surfaces: Combining Two Extremes in the Same Surface.
The ability to create superoleophobic surfaces repellent toward low-surface-tension liquids is important for various applications, and has been recently demonstrated using re-entrant or doubly re-entrant microtopography. Liquid droplets on such surfaces feature composite liquid-solid-air interfaces, whereas composite liquid-lubricant-air interfaces would have potential for additional repellency. Here, the development of a novel slippery superoleophobic surface with low adhesion is demonstrated via combining doubly re-entrant microtopography with slippery lubricant-infused porous surfaces. This is realized by using 3D direct laser writing to fabricate doubly re-entrant micropillars with dedicated nanostructures on top of each pillar. The top nanostructures stabilize the impregnated slippery lubricant, while the re-entrant geometry of the micropillars prevents lubricant from spreading. The slippery layer reduces the adhesion of liquid to the pillars, as proved using scanning droplet adhesion microscopy (SDAM), while the doubly re-entrant micropillars make the surface superoleophobic. This novel interface combining two extremes, superoleophobicity and slippery lubricant-infused surface, is of importance for designing superoleophobic and superhydrophobic surfaces with advanced liquid repellent, anti-icing, or anti-fouling properties.


Apoptosis induction of Persicae Semen extract in human promyelocytic leukemia (HL-60) cells.
The major ingredient of Persicae Semen is a cynogenic compound, amygdalin (D-mandelonitrile-beta-gentiobioside). Controversial results on the anticancer activity of amygdalin were reported due to its conversion to its inactive isomer, neoamygdalin. In order to inhibit the epimerization of amygdalin, we used newly developed simple acid boiling method in preparation of Persicae Semen extract. HPLC analysis revealed most of amygdalin in Persicae Semen extract was active D-form. Persicae Semen extract was used to analyze its effect on cell proliferation and induction of apoptosis in human promyelocytic leukemia (HL-60) cells. Persicae Semen extract was cytotoxic to HL-60 cells with IC50 of 6.4 mg/mL in the presence of 250 nM of beta-glucosidase. The antiproliferative effects of Persicae Semen extract appear to be attributable to its induction of apoptotic cell death, as Persicae Semen extract induced nuclear morphology changes and internucleosomal DNA fragmentation.


Formation of adenovirus DNA replication compartments.
Adenoviruses induce an extensive reorganization of the host cell nucleus during replication. Such a process results in the assembly of viral and cellular macromolecules into nuclear structures called adenovirus replication compartments (AdRCs), which function as platforms for viral DNA replication and gene expression. AdRCs co-opt host proteins and cellular pathways that restrict viral replication, suggesting that the mechanisms that control AdRC formation and function are essential for viral replication and lay at the basis of virus-host interactions. Here, we review the hallmarks of AdRCs and recent progress in our understanding of the formation, composition, and function of AdRCs. Furthermore, we discuss how AdRCs facilitate the interplay between viral and cellular machineries and hijack cellular functions to promote viral genome replication and expression.


Regulation of naturally occurring autoantibody secretion by a radiosensitive lymphocyte: initial characterization and ontogeny.
Low level irradiation (400-500 R) of normal mice or of murine spleen cells resulted in the detection of an enhanced number of plaque-forming cells against bromelain-treated autologous red cells (Br MRBC) 1 day later. The mechanism responsible for the increased numbers of plaques is apparently the elimination of a suppressor T cell since the addition of thymocytes or of Lyt 1+2+ splenic cells to cultures of irradiated cells reversed the radiation-induced increase. Studies on the ontogeny of the phenomenon indicate that anti-Br MRBC plaques can be formed by spleen cells taken from mice shortly after birth although adult levels are not reached until after 3 weeks of age. Radiation-induced increases in the number of plaques were not seen until 3 weeks of age, thus, suggesting a temporal developmental sequence of the ability to produce autoantibodies and to regulate such production.


Surface-enhanced Raman spectroscopy of microorganisms: limitations and applicability on the single-cell level.
Detection and characterization of microorganisms is essential for both clinical diagnostics and environmental studies. An emerging technique to analyse microbes at single-cell resolution is surface-enhanced Raman spectroscopy (surface-enhanced Raman scattering: SERS). Optimised SERS procedures enable fast analytical read-outs with specific molecular information, providing insight into the chemical composition of microbiological samples. Knowledge about the origin of microbial SERS signals and parameter(s) affecting their occurrence, intensity and/or reproducibility is crucial for reliable SERS-based analyses. In this work, we explore the feasibility and limitations of the SERS approach for characterizing microbial cells and investigate the applicability of SERS for single-cell sorting as well as for three-dimensional visualization of microbial communities. Analyses of six different microbial species (an archaeon, two Gram-positive bacteria, three Gram-negative bacteria) showed that for several of these organisms distinct features in their SERS spectra were lacking. As additional confounding factor, the physiological conditions of the cells (as influenced by e.g., storage conditions or deuterium-labelling) were systematically addressed, for which we conclude that the respective SERS signal at the single-cell level is strongly influenced by the metabolic activity of the analysed cells. While this finding complicates the interpretation of SERS data, it may on the other hand enable probing of the metabolic state of individual cells within microbial populations of interest.


Macrophagic myofasciitis in childhood: a controversial entity.
Macrophagic myofasciitis is an unusual inflammatory myopathy, which has been almost exclusively reported in French adults with diffuse arthromyalgias and asthenia. It is characterized by an infiltrate of densely packed macrophages, with granular periodic-acid-Schiff positive content, on muscle biopsies at the site of vaccination. The presence of aluminum inclusions in these macrophages points to an inappropriate reaction to aluminum used as an adjuvant in some vaccines. Although in adults this entity is well defined, less than 15 cases have been reported in children. This study describes seven children, younger than 3 years of age, with typical lesions of macrophagic myofasciitis on quadriceps muscle biopsy. In five cases, biopsies were performed to exclude mitochondrial pathology. All the children developed hypotonia and motor or psychomotor delay, associated with others symptoms. Abnormal neuroimaging was evident in six cases. Spectrometry studies detected elevated levels of aluminum in muscle in three of four cases tested. Despite the wide use of vaccines in childhood, macrophagic myofasciitis was rarely observed in children and its characteristic histologic pattern could not be correlated with a distinctive clinical syndrome.


Simple, selective, and rapid quantification of 1-deoxynojirimycin in mulberry leaf products by high-performance anion-exchange chromatography with pulsed amperometric detection.
1-Deoxynojirimycin (DNJ) occurs in mulberry and other plants and is a highly potent glycosidase inhibitor reported to suppress blood glucose levels, thus preventing diabetes. Derivatization is required for quantification of DNJ upon use of spectral detection methods. Because of this difficulty, the DNJ contents of mulberry-based food products are rarely stated, even if DNJ is their active component. A simple, selective, and rapid method of high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) to quantify DNJ in mulberry-based food products was developed. Stability testing of DNJ under heat treatment was also performed. A water extract of mulberry tea sample was subjected to HPAEC-PAD in a CarboPac MA1 column with a sodium hydroxide gradient. DNJ was clearly separated at a retention time of 7.26 min without interference and was selectively detected in the water extract. The detection limit was 5 ng. Heat stability studies suggested that DNJ was heat stable. HPAEC-PAD was not subject to interference, was highly selective for DNJ, and was superior to other high-performance liquid chromatography (HPLC) techniques in terms of sample preparation, resolution, and sensitivity. The method allowed simple, selective, and rapid analysis of DNJ in food matrices and might be useful for development of mulberry-based food products. Heat treatment could be an option for sterilizing mulberry-based products.


Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism.
In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.


Kinetic and metabolic studies of 7-(1,3-dithiolan-2-ylmethyl)-1,3-dimethylxanthine in the rat.
The kinetics (absorption, tissue distribution and excretion) of 7-(1,3-dithiolan-2-ylmethyl)-1, 3-dimethylxanthine(ABC 99) were studied in the rat. ABC 99 was administered orally at doses of 10, 30 and 100 mg/kg for the serum kinetic studies. Only the 30 mg/kg dose was used for the tissue distribution and excretion kinetic studies. ABC 99 is rapidly absorbed, metabolized in the liver and partially excreted in the urine. It is equally distributed in the tissues, including the brain, although in much lower amounts than those absorbed. Three metabolites were identified: theophylline, which forms in very small quantities, and two isomers (cis and trans) of the sulfoxide. The latter two compounds form in larger amounts with respect to theophylline, and the trans-isomer predominates. The metabolites are distributed to the tissues, but do not accumulate. Elimination is virtually complete at 24 h. The pharmacological activity of ABC 99 (antibronchospastic, mucoregulatory and anti-inflammatory) can be attributed the compound, which is absorbed in its original form. Similar activity of the two sulfoxides (met 1 and 2) cannot be excluded at present as they have a structure analogous to ABC 99.


Spontaneous Resorption of a Penetrating Orbital Bone Fracture Fragment.
The authors describe a 20-year-old man who sustained multiple facial fractures in a high-speed motor vehicle crash, including a bone fragment from a skull base fracture that penetrated the orbital soft tissues superomedially. Serial CT scans documented spontaneous resorption over a 6-month period. While it is known that autologous bone grafts used in craniofacial reconstruction exhibit variable amounts of bone resorption, the complete resorption of an intraorbital fracture fragment has not been documented in the literature. His clinical care and the report of his case were undertaken in a fashion in accordance with the principles of the Health Insurance Portability and Accountability Act regulations.


Attentional Bias in Children with Asthma with and without Anxiety Disorders.
Children with asthma have a high prevalence of anxiety disorders, however, very little is known about the mechanisms that confer vulnerability for anxiety in this population. This study investigated whether children with asthma and anxiety disorders display attentional biases towards threatening stimuli, similar to what has been seen in children with anxiety disorders more generally. We also examined the relationships between attentional biases and anxiety symptomatology and asthma control for children with asthma. Ninety-three children, aged 8-13, took part in the study and were recruited into one of four conditions (asthma/anxiety, asthma, anxiety, control). Asthma was medically confirmed and anxiety was assessed through clinical interview. We used self- and parent-report questionnaires to measure child asthma (ATAQ) and anxiety (SCAS, CASI) variables. Participants completed a visual dot-probe task designed to measure attentional bias towards two types of stimuli: asthma related words and general threat words, as well as tasks to assess reading ability and attentional control. Results showed that attentional biases did not differ between the groups, although children with anxiety disorders displayed poorer attentional control. A significant correlation was found between poor asthma control and an attentional bias of asthma stimuli. While we found no evidence that anxiety disorders in children with asthma were associated with threat- or asthma-related attentional biases, preliminary evidence suggested that children with poor asthma control displayed biases towards asthma-specific stimuli. Future research is needed to explore whether these attentional biases are adaptive.


Growth and division of Streptococcus pneumoniae: localization of the high molecular weight penicillin-binding proteins during the cell cycle.
The bacterial peptidoglycan, the main component of the cell wall, is synthesized by the penicillin-binding proteins (PBPs). We used immunofluorescence microscopy to determine the cellular localization of all the high molecular weight PBPs of the human pathogen Streptococcus pneumoniae, for a wild type and for several PBP-deficient strains. Progression through the cell cycle was investigated by the simultaneous labelling of DNA and the FtsZ protein. Our main findings are: (i) the temporal dissociation of cell wall synthesis, inferred by the localization of PBP2x and PBP1a, from the constriction of the FtsZ-ring; (ii) the localization of PBP2b and PBP2a at duplicated equatorial sites indicating the existence of peripheral peptidoglycan synthesis, which implies a similarity between the mechanism of cell division in bacilli and streptococci; (iii) the abnormal localization of some class A PBPs in PBP-defective mutants which may explain the apparent redundancy of these proteins in S. pneumoniae.


The tensor hypercontracted parametric reduced density matrix algorithm: coupled-cluster accuracy with O(r(4)) scaling.
Tensor hypercontraction is a method that allows the representation of a high-rank tensor as a product of lower-rank tensors. In this paper, we show how tensor hypercontraction can be applied to both the electron repulsion integral tensor and the two-particle excitation amplitudes used in the parametric 2-electron reduced density matrix (p2RDM) algorithm. Because only O(r) auxiliary functions are needed in both of these approximations, our overall algorithm can be shown to scale as O(r(4)), where r is the number of single-particle basis functions. We apply our algorithm to several small molecules, hydrogen chains, and alkanes to demonstrate its low formal scaling and practical utility. Provided we use enough auxiliary functions, we obtain accuracy similar to that of the standard p2RDM algorithm, somewhere between that of CCSD and CCSD(T).


Treatment of anorexia and malnutrition in peritoneal dialysis patients with megestrol acetate.
Anorexia and malnutrition are common complications and powerful predictors of morbidity and mortality in peritoneal dialysis (PD) patients. Megestrol acetate (MA) is a progestogen that has been demonstrated to increase appetite and weight in patients with cancer or acquired immunodeficiency syndrome. To determine whether MA might benefit PD patients, we treated 32 patients with 160 mg MA daily. Treatment lasted a mean of 5.93 +/- 5.12 months (range: 1 - 23 months). In 68.8% of the patients, appetite improved. Weight gain was statistically significant starting in the third month (initial weight: 66.5 +/- 11.4 kg; weight at third month: 68 +/- 10.4 kg; p < 0.05). We observed a nonsignificant increase in serum albumin at the third treatment month (initial serum albumin: 3.44 +/- 0.27 g/L; serum albumin at third month: 3.54 +/- 0.27 g/L; p = 0.45). No side effects were observed. Our experience suggests that treatment with 160 mg MA daily in PD patients leads to an increase in appetite, serum albumin, and weight gain in most patients, with no negative side effects.


The Use of Microdosing in the Development of Small Organic and Protein Therapeutics.
Microdosing as a regulatory concept was introduced to facilitate exploratory studies in humans. The concept involves the use of very low doses of a radionuclide-labeled compound for imaging studies or for assessing plasma pharmacokinetics using equipment that has a highly sensitive readout. The supporting principle is that use of these low doses for a limited time in well-controlled, small populations will limit exposure and have a low risk of adverse effects. Microdosing regulations specify a reduced preclinical toxicology-assessment package in order to shorten the route to human studies and reduce its cost. However, for extrapolation to therapeutically relevant doses and plasma concentrations, there are specific aspects of the use of these low doses and low plasma concentrations that require special attention. These specific aspects are reviewed in this article, with separate attention being paid to small organic molecules and protein therapeutics. The indications for microdosing in drug development are discussed in terms of the 3 pillars of survival in drug development, the first of which is characterization of tissue distribution and access to the site of action; the second, engagement of the target; and the third, induction of tissue responses relevant to a therapeutic response.


[Preparation of molecularly imprinted chiral monolithic column and its applications for separation of diastereomers].
A cinchonine imprinted chiral monolithic column was prepared for the separation of the diastereomers of cinchonine and cinchonidine by in-situ molecular imprinting technique. This type of molecularly imprinted column can be prepared only by a single-step procedure. In order to improve the selectivity and efficiency, a new in-situ molecular imprinting polymerization system was introduced by adopting porogenic solvents of toluene and 1-dodecanol with relatively low polarity and appropriate ratios of polymerization mixture. Diastereomers of cinchonine and cinchonidine were fully separated both under isocratic and gradient elutions on the chiral monolithic column. The broad peak shown in isocratic elution could be improved in gradient elution. Effects of mobile phase composition, flow rate and temperature on retention and separation factor were investigated. Due to the large throughput pores in the chiral monolithic column, low backpressure was observed during the separation process and a separation factor of 3.18 was obtained at 1.0 mL/min. The increase of temperature could improve the separation factor and a maximum separation factor of 5.40 was obtained at 60 degrees C.


Pneumococcal serology in children's respiratory infections.
The role of Streptococcus pneumoniae in the etiology of respiratory tract infections has been studied serologically using microbe-specific antibody and immune complex assays. Serological methods are sensitive in the bacteremic pneumococcal pneumonia of adults. In children, however, pneumococcal pneumonia is seldom bacteremic, and, thus, in the absence of a gold standard for the detection of pneumococcal infection, serological methods are still insufficiently validated. We report here indirect evidence for the sensitivity and specificity of pneumococcal serology in children. Serological evidence of pneumococcal infection has been found in 27% to 38% of children with radiologically confirmed pneumonia, in 7% to 8% of children with viral wheezy bronchitis, and in <1% to 5% of children and young adults with viral upper respiratory infection. Serological findings for pneumococcal infection have been dependent on the study venue, whether in hospital or ambulatory subjects, and on the test panel used. Where both antibody and immune complex assays have been available, the proportion of children with pneumococcal infection has been 32% to 37% in inpatients and 27% to 28% in outpatients. The respective rates have been 10% to 18% by antibody assays alone. Pneumococcal acute otitis media, when present with pneumonia, may confound findings in pneumococcal serology, but pure nasopharyngeal carriage of S. pneumoniae has little effect. In contrast, carriage acquisition of a new serotype may induce significant antibody production. Thus, understandably, significant rises between paired sera in antibodies to pneumococcal capsular polysaccharides and pneumococcal pneumolysin have been found in <1% to 3% of non-symptomatic children and young adults. Findings from the last 20 years indirectly suggest that pneumococcal antibody and immune complex assays are sensitive and specific enough for the detection of pneumococcal infection in children. However, the methods are too complex for routine clinical practice, and, so far, serological methods for S. pneumoniae infections have only been used for research purposes.


Magnetic fields from electric toothbrushes promote corrosion in orthodontic stainless steel appliances but not in titanium appliances.
Electric toothbrushes are widely used, and their electric motors have been reported to produce low-frequency electromagnetic fields that induced electric currents in metallic objects worn by the users. In this study, we showed that electric toothbrushes generated low-frequency magnetic fields (MFs) and induced electric currents in orthodontic appliances in artificial saliva (AS), which accelerated corrosion in stainless steel (SUS) appliances, but not in titanium (Ti) appliances; the corrosion was evaluated by using an inductively coupled plasma-optical emission spectrometer and a three-dimensional laser confocal microscope. The pH of AS used for appliance immersion did not change during or after MF exposure. These results suggested that MF-induced currents from electric toothbrushes could erode SUS appliances, but not Ti appliances, because of their high corrosion potentials. Further studies are required to clarify the mechanisms of metallic corrosion by induced currents in dental fields, which may trigger metal allergies in patients.


[Comparative efficacy and tolerability of drotaverine 80 mg and ibuprofen 400 mg in patients with primary dysmenorrhoea--protocol DOROTA].
To compare efficacy and tolerability of drotaverine 80 mg and ibuprofen 400 mg in patients with primary dysmenorrhoea. Nine-month, multicenter (11 study centers in Poland), randomised, double-blind, phase III study, conducted in two parallel group, included 345 women between the ages of 18 and 35, suffering from primary dysmenorrhoea with presence of moderate to severe pain in each of the last 3 cycles. Patients had regular menstrual cycles and used an adequate barrier contraception method with a negative pregnancy test before randomization. Patients were given 80 mg drotaverine or 400 mg ibuprofen and asked to assess the pain intensity rated on a 4 point categorical scale (0--none, 1--mild, 2--moderate, 3--severe) at baseline and 0.5, 1, 2, 3, 4, 5 and 6 hours after the first intake and evaluate the efficacy (excellent, good, fair, poor) at the end of the treatment period. They were also asked to asses the tolerance of the medication (excellent, good, fair, poor). The weighted sum of pain intensity differences over the 6-hour observation period (SPID-6) was calculated. The pain intensity before the first intake was comparable in the two groups. At the time-points, the decrease of pain was always greater in the ibuprofen 400 mg group, than in the drotaverine 80 mg group and was maximum at the 4th hour in the drotaverine 80 mg group (-1.2+/-1.18) and at the 3rd hour in the ibuprofen 400 mg group (-1.7+/-0.99). 41.8% patients treated with drotaverine and 68.6% patients treated with ibuprofen assessed drug efficacy as excellent or good. Although the patients' global assessment of tolerability was significantly better (p=0.02) with ibuprofen 400 mg (excellent or good: 86.8%), than with drotaverine 80 mg (excellent or good: 78.4%), no relevant difference between the both groups was observed for frequency, nature intensity and causality of the reported adverse events. After analizing the data statistically and clinically, significant differences in favour of ibuprofen 400 mg were evidenced for efficacy criteria. Ibuprofen was more efficient and the effect was faster, than drotaverine in relieving pain in dysmenorrhoea. Both drugs were well tolerated. The reported adverse events were typical drug reactions or expected events in patients suffering from dysmenorrhoea.


True associations between resting fMRI time series based on innovations.
We calculated voxel-by-voxel pairwise crosscorrelations between prewhitened resting-state BOLD fMRI time series recorded from 60 cortical areas (30 per hemisphere) in 18 human subjects (nine women and nine men). Altogether, more than a billion-and-a-quarter pairs of BOLD time series were analyzed. For each pair, a crosscorrelogram was computed by calculating 21 crosscorrelations, namely at zero lag ± 10 lags of 2 s duration each. For each crosscorrelogram, in turn, the crosscorrelation with the highest absolute value was found and its sign, value, and lag were retained for further analysis. In addition, the crosscorrelations at zero lag (irrespective of the location of the peak) were also analyzed as a special case. Based on known varying density of anatomical connectivity, we distinguished four general brain groups for which we derived summary statistics of crosscorrelations between voxels within an area (group I), between voxels of paired homotopic areas across the two hemispheres (group II), between voxels of an area and all other voxels in the same (ipsilateral) hemisphere (group III), and voxels of an area and all voxels in the opposite (contralateral) hemisphere (except those in the homotopic area) (group IV). We found the following. (a) Most of the crosscorrelogram peaks occurred at zero lag, followed by ± 1 lag; (b) over all groups, positive crosscorrelations were much more frequent than negative ones; (c) average crosscorrelation was highest for group I, and decreased progressively for groups II-IV; (d) the ratio of positive over negative crosscorrelations was highest for group I and progressively smaller for groups II-IV; (e) the highest proportion of positive crosscorrelations (with respect to all positive ones) was observed at zero lag; and (f) the highest proportion of negative crosscorrelations (with respect to all negative ones) was observed at lag = 2. These findings reveal a systematic pattern of crosscorrelations with respect to their sign, magnitude, lag and brain group, as defined above. Given that these groups were defined along a qualitative gradient of known overall anatomical connectivity, our results suggest that functional interactions between two voxels may simply reflect the density of such anatomical connectivity between the areas to which the voxels belong.


Crystallization and preliminary X-ray analysis of (1,3)- and (1,3;1,4)-beta-D-glucanases from germinating barley.
(1,3)-beta-D-Glucanase isoenzyme GII and (1,3;1,4)-beta-D-glucanase isoenzyme EII from barley have been crystallized by the hanging drop method in the presence of ammonium sulphate. The crystals of the (1,3)-beta-D-glucanase, which diffract to about 1.8 A resolution, belong to the trigonal space group P3(1)2(1)2 (or P3(2)2(1)2) with cell constants a = b = 86.9 A, c = 156.0 A and contain two molecules in the asymmetric unit. The crystals of the (1,3;1,4)-beta-D-glucanase which diffract to better than 1.8 A resolution, belong to the tetragonal space group P4(3)2(1)2 (or P4(1)2(1)2) with cell constants a = b = 87.4 A, c = 109.5 A and contain one molecule in the asymmetric unit.


Cytokine-induced expression of transforming growth factor-alpha and the epidermal growth factor receptor in neonatal skin explants.
Hyperproliferative diseases of the epidermal keratinocytes, such as psoriasis vulgaris, are characterized by overexpression and altered distribution of the epidermal growth factor/transforming growth factor (EGF/TGF)-alpha receptor, and of TGF-alpha itself. It is believed that overexpression of this lignad/receptor system contributes to the hyperproliferative state of keratinocytes in an autocrine fashion. However, little is known about the factors that regulate expression of the EGF/TGF-alpha receptor, as well as expression of TGF-alpha in stratified epithelium. We examined modulation of the immunoreactive EGF/TGF-alpha receptor and TGF-alpha expression in normal neonatal foreskin explants by a variety of cytokines present in psoriatic lesions. Human (hu) recombinant (r) tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma induced EGF/TGF-alpha receptor and TGF-alpha expression by keratinocytes as determined by immunohistochemistry. Neutralizing antibodies to TNF-alpha and IFN-gamma inhibited upregulation of EGF/TGF-alpha receptors and TGF-alpha by the respective cytokines. Interleukin (IL)-8 induced expression of TGF-alpha, but not of its receptor. Other cytokines (TNF-beta, IFN-beta, IL-1 alpha, IL-2, IL-3, IL-5, IL-6, granulocyte/macrophage colony-stimulating factor, and macrophage colony-stimulating factor) did not alter the expression patterns of EGF/TGF-alpha receptors or TGF-alpha in normal neonatal skin explants. These experiments demonstrate that specific cytokines known to be present in psoriatic lesions can induce normal epidermis to express TGF-alpha and its receptor in a pattern similar to that observed in psoriatic skin.


[Effect of sowing dates on cotton yield, fiber quality, and uptake and utilization of nutrients in Inner Mongolia west desert area, China].
Field experiments were conducted in 2014 and 2015 at the "Inner Mongolia cotton comprehensive test station" (39°27' N, 105°39' E) in Alxa Left Banner of Alxa League in Inner Mongolia. By using cotton cultivar CCRI-50 as material and the "6 cotton rows with 3 dripping pipes under a plastic film mulching" plantation pattern, different sowing dates (20-Apr, 30-Apr and 10-May) were set to study the effect of sowing dates on cotton yield, fiber quality and nutrient uptake and utilization. The results showed that as the sowing date delayed, the development of cotton plant was delayed, the yield forming stage shortened, and the mean daily temperature of boll deve-lopment reduced, but the harvesting density increased. Sowing date influenced the biomass accumulation, fiber yield and fiber quality, it also influenced the absorption and distribution of N, P and K. Among the three sowing dates, the biomass distribution proportion to reproductive organ, nutrition (N, P and K) accumulation, lint production efficiency of nutrient and yield were higher in the cotton plant that was sowing at 30-Apr, the seed cotton and lint yield were the highest which could reach up to 6505.9 kg·hm-2 and 2660.9 kg·hm-2, respectively, and the fiber quality was better than that of 10-Mar. For the plant which was sowed at 20-Apr, harvesting density, biomass and nutrient accumulation were the lowest, although economic coefficients of biomass and nutrient were the highest, and the seed cotton and lint yield were respectively 10.9%-14.0% and 11.1%-14.2% lower than that of 30-Apr. When sowing at 10-May, cotton could avoid the low temperature during seed germination, but mean daily temperature during boll development were the lowest, although biomass and nutrient accumulation were the highest. The economic index, lint production efficiency of nutrient were the lowest, which leading to the poorest fiber quality, lowest seed cotton and lowest lint yield which were respectively 32.5%-34.7% and 35.9%-36.2% lower than that of 30-Apr. These results suggested that the optimum sowing date for cotton planting was about 30-Apr in Inner Mongolia west desert area.


A₁ adenosine receptor modulation of chemically and electrically evoked lumbar locomotor network activity in isolated newborn rat spinal cords.
It is not well-studied how the ubiquitous neuromodulator adenosine (ADO) affects mammalian locomotor network activities. We analyzed this here with focus on roles of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)-sensitive A(1)-type ADO receptors. For this, we recorded field potentials from ventral lumbar nerve roots and electrically stimulated dorsal roots in isolated newborn rat spinal cords. At ≥ 25μM, bath-applied ADO slowed synchronous bursting upon blockade of anion-channel-mediated synaptic inhibition by bicuculline (20 μM) plus strychnine (1 μM) and this depression was countered by DPCPX (1 μM) as tested at 100 μM ADO. ADO abolished this disinhibited rhythm at ≥ 500 μM. Contrary, the single electrical pulse-evoked dorsal root reflex, which was enhanced in bicuculline/strychnine-containing solution, persisted at all ADO doses (5 μM-2 mM). In control solution, ≥ 500 μM ADO depressed this reflex and pulse train-evoked bouts of alternating fictive locomotion; this inhibition was reversed by 1 μM DPCPX. ADO (5 μM-2 mM) did not depress, but stabilize alternating fictive locomotion evoked by serotonin (10 μM) plus N-methyl-d-aspartate (4-5 μM). Addition of DPCPX (1μM) to control solution did not change either the dorsal root reflex or rhythmic activities indicating lack of endogenous A(1) receptor activity. Our findings show A(1) receptor involvement in ADO depression of the dorsal root reflex, electrically evoked fictive locomotion and spontaneous disinhibited lumbar motor bursting. Contrary, chemically evoked fictive locomotion and the enhanced dorsal root reflex in disinhibited lumbar locomotor networks are resistant to ADO. Because ADO effects in standard solution occurred at doses that are notably higher than those occurring in vivo, we hypothesize that newborn rat locomotor networks are rather insensitive to this neuromodulator.


Comparison of different solar reactors for household disinfection of drinking water in developing countries: evaluation of their efficacy in relation to the waterborne enteropathogen Cryptosporidium parvum.
Solar water disinfection (SODIS) is a type of treatment that can significantly improve the microbiological quality of drinking water at household level and therefore prevent waterborne diseases in developing countries. Cryptosporidium parvum is an obligate protozoan parasite responsible for the diarrhoeal disease cryptosporidiosis in humans and animals. Recently, this parasite has been selected by the WHO as a reference pathogen for protozoan parasites in the evaluation of household water treatment options. In this study, the field efficacy of different static solar reactors [1.5 l transparent plastic polyethylene terephthalate (PET) bottles as well as 2.5 l borosilicate glass and 25 l methacrylate reactors fitted with compound parabolic concentrators (CPC)] for solar disinfection of turbid waters experimentally contaminated with C. parvum oocysts was compared. Potential oocyst viability was determined by inclusion/exclusion of the fluorogenic vital dye propidium iodide. The results demonstrate that static solar reactors fitted with CPCs are an excellent alternative to the conventional SODIS method with PET bottles. These reactors improved the efficacy of the SODIS method by enabling larger volumes of water to be treated and, in some cases, the C. parvum oocysts were rendered totally unviable, minimising the negative effects of turbidity.


Molecular detection of Chlamydia abortus in a stranded Mediterranean striped dolphin Stenella coeruleoalba.
This study reports gross, histopathological, and molecular features of a Chlamydia abortus infection in a stranded female striped dolphin Stenella coeruleoalba from the Tyrrhenian coast of southern Italy. Post-mortem examination revealed liver congestion, splenic lymphoid depletion with capsular petechiae, and pneumonia. Histology revealed disseminated intravascular coagulation with vasculitis and congestion. Hepatocellular and acute myocardial degeneration were also observed. Basophilic, coccobacillary inclusions consistent with Chlamydia spp. were observed histologically in the type II pneumocytes, myocardial fibers, and hepatocytes, and in macrophages and plasma cells of liver, spleen, and prescapular lymph nodes. Chlamydial antigen was detected by immunofluorescence assay using genus-specific anti-Chlamydia antibodies. PCR assay revealed C. abortus in spleen, liver, heart, and lungs. C. abortus was the only pathogen detected. The main pathological changes suggest that Chlamydia infection may have been the cause of stranding and death of the striped dolphin. This case represents the first molecular detection of a member of the Chlamydiaceae in a marine mammal.


Effect of hyperbaric oxygen on the growth factor profile of fibroblasts.
Hyperbaric oxygen (HBO) has been used in the clinical setting to heal problem wounds, yet its direct effects on fibroblasts are not clear. The present study evaluates the effects of HBO on the growth and autocrine production of growth factors by fibroblasts grown in an in vitro, serum-free environment. Human dermal fibroblasts were propagated in serum-free media and subjected to daily 90-minute HBO treatments at 1.0, 1.5, 2.0, 2.5, and 3.0 atm of pressure for 7 consecutive days. Cell proliferation and growth-factor assays for basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta1 (TGF-beta1) were performed on days 1, 3, 5, and 7. On day 1, HBO inhibited growth of fibroblasts at all atmospheric pressures compared with control. By day 7, cell proliferation was significantly enhanced only in cells treated with 2.0-atm HBO compared with controls. Secretion of bFGF was significantly increased by HBO-treated fibroblasts on day 1; VEGF levels slightly increased with HBO treatment on day 1, but this effect was not statistically significant; TGF-beta1 levels were detectable on day 1 only for control and HBO-treated cells at 1.0 atm, and not detectable for any cell groups after day 1. These results suggest that daily HBO treatment enhances the growth of fibroblasts when administered to a critical degree. Also, HBO appears to directly effect fibroblast production of autocrine growth factors on initial exposure. We postulate that fibroblasts possess the ability to respond to hyperoxia directly, which causes changes in cell signaling pathways involved in cellular proliferation and growth factor production.


Insulin control of placental gene expression shifts from mother to foetus over the course of pregnancy.
The human placenta is a complex organ situated at the interface between mother and foetus that separates maternal from foetal blood. The placental surfaces exposed to the two bloodstreams are different, i.e. trophoblasts and endothelial cells are in contact with the maternal and foetal circulation, respectively. Both cell types produce high insulin receptor levels. The aim of the present study was to test the hypothesis that spatio-temporal changes in insulin receptor expression in trophoblasts from first trimester to the endothelium at term shift the control of insulin-dependent processes from mother to foetus. Global microarray analysis of primary trophoblasts from first trimester and term human placentas and endothelial cells from term human placentas cultured under hyperinsulinaemic and control conditions identified different sets of regulated genes in trophoblasts and endothelial cells. Insulin effects on placental gene expression underwent developmental changes from trophoblasts in the first trimester to endothelial cells at term that were paralleled by changes in levels of activated insulin receptors. The changes in gene regulation were both quantitative (i.e. magnitude of effect) and qualitative (i.e. specific genes affected and direction of regulation). This spatio-temporal shift in insulin sensitivity throughout pregnancy allows maternal and foetal insulin to regulate different processes within the placenta at different gestational stages, facilitated by compartmentalisation of the insulin response. Thus, by altering the levels and function of insulin receptors in space and time, control of insulin-dependent processes in the human placenta will change from mother to foetus throughout gestation. This will be of particular interest in conditions associated with altered maternal or foetal insulin levels, i.e. diabetes mellitus or intrauterine growth restriction.


Biotransformation of 8:2 fluorotelomer alcohol by recombinant human cytochrome P450s, human liver microsomes and human liver cytosol.
Biotransformation of 8:2 fluorotelomer alcohol (8:2 FTOH) can form potentially more toxic metabolites. However, the responsible cytochrome P450 (CYP) isoform(s) and phase II metabolism have not been studied in humans. Here, we characterized the in vitro metabolism of 8:2 FTOH by recombinant human CYPs, human liver microsomes, and human liver cytosol. The results showed that among the 11 isoforms investigated, CYP2C19 was the only enzyme capable of catalyzing 8:2 FTOH with Km and Vmax values of 18.8 μM and 8.52 pmol min(-1) pmol(-1) P450, respectively. The phase I metabolite was identified as 8:2 fluorotelomer aldehyde (8:2 FTAL). HLMs also catalyzed 8:2 FTOH transformation, with the Vmax and intrinsic clearance (CLint) values similar to those of CYP2C19 after the protein content is taken into account. Molecular docking showed that the hydroxyl group of 8:2 FTOH accesses the heme iron-oxo of CYP2C19 in an energetically favored orientation. 8:2 FTOH was also transformed by phase II enzymes to form O-glucuronide and O-sulfate conjugates. The CLint values follow the order of sulfation > oxidation > glucuronidation, suggesting that conjugation is the major metabolic pathway, which explains the low yield of perfluoroalkyl acids (PFCAs). These results provide new insight into fluorotelomer alcohol biotransformation and indirect human exposure to PFCAs.


Metabolic syndrome and risks of colon and rectal cancer: the European prospective investigation into cancer and nutrition study.
Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case-control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16-1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57-2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45-2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47-2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02-2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions.


Transthoracic Doppler echocardiographic assessment of left anterior descending coronary artery and intramyocardial artery predicts left ventricular remodeling and wall-motion recovery after acute myocardial infarction.
Previous studies reported that a coronary flow velocity (FV) pattern with a rapid diastolic deceleration time (DDT) immediately after percutaneous coronary intervention implies advanced microvascular damage in patients who have experienced an acute myocardial infarction (AMI). Using transthoracic echocardiography, we recorded the coronary FV in the left anterior descending coronary artery (LAD) and the FV in the intramyocardial artery 2 days after successful percutaneous coronary intervention in 24 patients who had experienced an anterior AMI. We measured the DDT of the LAD and the intramyocardial artery. DDT of the LAD and the intramyocardial artery was detected in the anteroseptal lesion, the wall motion of which revealed severe hypokinesis or akinesis. We performed echocardiography during both the acute phase and 6 months after the AMI. Patients were divided into two groups (group A: DDT of the LAD < or = 600 milliseconds [n = 10], group B: DDT of the LAD > or = 600 milliseconds [n = 14]). DDT of the LAD and the intramyocardial artery was significantly shorter for group A than group B (373 +/- 223 vs 786 +/- 105 milliseconds, P < .0001). In the acute phase, there were no significant differences in left ventricular (LV) wall-motion score index (WMSI), LV end-diastolic volume (EDV), or ejection fraction (WMSI: 2.38 +/- 0.24 vs 2.08 +/- 0.58, P = .20; LV EDV: 160 +/- 41 vs 154 +/- 34 mL; ejection fraction: 45 +/- 11 vs 46 +/- 5%). However, WMSI and LV EDV in group A were significantly greater than in group B (WMSI: 2.47 +/- 0.16 vs 1.84 +/- 0.57, P = .01; LV EDV: 198 +/- 28 vs 132 +/- 37 mL, P = .0004) and the ejection fraction in group A was significantly lower than in group B (38 +/- 9 vs 55 +/- 10%, P = .001) during the chronic phase. In patients who had experienced an anterior AMI, we could predict wall-motion recovery of the infarcted area by using the coronary FV of the LAD and FV of the intramyocardial artery.


[Mechanodependent cell movements in the axial rudiments of Xenopus gastrulae].
Sandwich explants of the suprablastoporal area of Xenopus early-mid gastrula and same stages of entire embryos were stretched with two needles perpendicular to the direction of natural elongation of the axial rudiments. The changes in the embryonic shape and histological structure were monitored as well as the arrangement of descendants of one of dorsal blastomers labeled with fluorescein-dextran at the 16-cell stage. A substantial fraction of stretched explants reoriented along the applied stretch direction. The arrangement dynamics of fluorescein-dextran-labeled cells and explant shape demonstrate that this is an active response based on convergent intercalation of cells induced by stretching. Stretched gastrulae demonstrated arrested gastrulation, dorsoventral extension of the blastopore, and ventral flow of labeled cells towards the lateral lips of the blastopore, which was also mediated by convergent intercalation and tensotaxis. The obtained data are discussed in terms of the hypothesis of mechanical stress hyper-restoration.


Primary angiosarcoma of the bladder.
Primary bladder angiosarcomas are extremely rare, and their clinical and pathologic features are not well described. To further refine the clinical features of primary bladder angiosarcomas and define their pathologic spectra. Relevant sources were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews. We also searched the M. D. Anderson pathology archives. After excluding 4 cases that likely secondarily involved the bladder, we identified 9 true primary bladder angiosarcomas. Data were extracted on the following: demographics, clinical presentation, predisposing factors, gross pathology, microscopic pathology, immunophenotype, therapy, and outcomes. Primary bladder angiosarcomas were found at a mean age of 64.2 years, with a male-female ratio of 8:1. Two cases arose in a postirradiation setting. Primary bladder angiosarcomas typically presented with hematuria and were grossly hemorrhagic, raised masses (mean size, 6.7 cm) of the trigone and/or dome. Histologically, most showed classic anastomosing channels lined by plump hyperchromatic cells, though many showed variant histology such as solid growth and epithelioid cytology. Three (43%) of 7 patients died within a year, but only 1 patient died with evidence of disease. The remaining patients were alive at the time of publication of their respective cases (mean, 22 months). Primary angiosarcomas of the bladder are typically rare tumors of middle-aged and elderly men that present with locally advanced disease and show a wide histologic spectrum. However, their prognosis may be better than previously thought.


Ultra-performance supercritical fluid chromatography: A powerful tool for the enantioseparation of thermotropic fluorinated liquid crystals.
A fast and simple supercritical fluid chromatography method for the enantioseparation of twenty newly synthesized orthoconic antiferroelectric liquid crystals is reported for the first time. The effects of alkoxy spacer length and fluorine atom presence and position in the phenyl ring on chromatographic behavior were investigated. Baseline enantioseparation of all compounds was achieved using simple mobile phases consisting of carbon dioxide and alcohol as cosolvent on (3,5-dimethylphenylcarbamate) derivative of amylose as chiral stationary phase. The analysis times ranged from 2 to 4 and from 4 to 7 min for most samples when using methanol and propane-2-ol, respectively. The significant effect of cosolvent type on the enantioseparation of these compounds was assessed and partial complementarity of methanol and propane-2-ol was observed.