Neuropsychological and behavioral functioning in children with and without obstructive sleep apnea referred for tonsillectomy.
Adenotonsillectomy (AT) is among the most common pediatric surgical procedures and is performed as often for obstructive sleep apnea (OSA) as for recurrent tonsillitis. This study compared behavioral, cognitive, and sleep measures in 27 healthy control children recruited from a university hospital-based pediatric general surgery clinic with 40 children who had OSA (AT/OSA+) and 27 children who did not have OSA (AT/OSA-) scheduled for AT. Parental ratings of behavior, sleep problems, and snoring, along with specific cognitive measures (i.e., short-term attention, visuospatial problem solving, memory, arithmetic) reflected greater difficulties for AT children compared with controls. Differences between the AT/OSA- and control groups were larger and more consistent across test measures than were those between the AT/OSA+ and control groups. The fact that worse outcomes were not clearly demonstrated for the AT/OSA+ group compared with the other groups was not expected based on existing literature. This counterintuitive finding may reflect a combination of factors, including age, daytime sleepiness, features of sleep-disordered breathing too subtle to show on standard polysomnography, and academic or environmental factors not collected in this study. These results underscore the importance of applying more sophisticated methodologies to better understand the salient pathophysiology of childhood sleep-disordered breathing.


Defining the 3'Epigenetic Boundary of the FMR1 Promoter and Its Loss in Individuals with Fragile X Syndrome.
This study characterizes the DNA methylation patterns specific to fragile X syndrome (FXS) with a full mutation (FM > 200 CGGs), premutation (PM 55-199 CGGs), and X inactivation in blood and brain tissues at the 3' boundary of the FMR1 promoter. Blood was analyzed from 95 controls and 462 individuals (32% males) with FM and PM alleles. Brain tissues (62% males) were analyzed from 12 controls and 4 with FXS. There was a significant increase in intron 1 methylation, extending to a newly defined 3' epigenetic boundary in the FM compared with that in the control and PM groups (p < 0.0001), and this was consistent between the blood and brain tissues. A distinct intron 2 site showed a significant decrease in methylation for the FXS groups compared with the controls in both sexes (p < 0.01). In all female groups, most intron 1 (but not intron 2 sites) were sensitive to X inactivation. In all PM groups, methylation at the 3' epigenetic boundary and the proximal sites was significantly decreased compared with that in the control and FM groups (p < 0.0001). In conclusion, abnormal FMR1 intron 1 and 2 methylation that was sensitive to X inactivation in the blood and brain tissues provided a novel avenue for the detection of PM and FM alleles through DNA methylation analysis.


PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit.
Daily sleep cycles in humans are driven by a complex circuit within which GABAergic sleep-promoting neurons oppose arousal. Drosophila sleep has recently been shown to be controlled by GABA, which acts on unknown cells expressing the Rdl GABAA receptor. We identify here the relevant Rdl-containing cells as PDF-expressing small and large ventral lateral neurons (LNvs) of the circadian clock. LNv activity regulates total sleep as well as the rate of sleep onset; both large and small LNvs are part of the sleep circuit. Flies mutant for pdf or its receptor are hypersomnolent, and PDF acts on the LNvs themselves to control sleep. These features of the Drosophila sleep circuit, GABAergic control of onset and maintenance as well as peptidergic control of arousal, support the idea that features of sleep-circuit architecture as well as the mechanisms governing the behavioral transitions between sleep and wake are conserved between mammals and insects.


Physiologically based pharmacokinetic modelling of acetaminophen in preterm neonates-The impact of metabolising enzyme ontogeny and reduced cardiac output.
In preterm neonates, physiologically based pharmacokinetic (PBPK) models are suited for studying the effects of maturational and non-maturational factors on the pharmacokinetics of drugs with complex age-dependent metabolic pathways like acetaminophen (APAP). The aim of this study was to determine the impact of drug metabolising enzymes ontogeny on the pharmacokinetics of APAP in preterm neonates and to study the effect of reduced cardiac output (CO) on its PK using PBPK modelling. A PBPK model for APAP was first developed and validated in adults and then scaled to paediatric age groups to account for the effect of enzyme ontogeny. In preterm neonates, CO was reduced by 10%, 20%, and 30% to determine how this might affect APAP PK in preterm neonates. In all age groups, the predicted concentration-time profiles of APAP were within 5th and 95th percentile of the clinically observed concentration-time profiles and the predicted Cmax and AUC were within 2-folds of the reported parameters in clinical studies. Sulfation accounted for most of APAP metabolism in children, with the highest contribution of 68% in preterm neonates. A reduction in CO by up to 30% did not significantly alter the clearance of APAP in preterm neonates. The model successfully incorporated the ontogeny of drug metabolising enzymes involved in APAP metabolism and adequately predicted the PK of APAP in preterm neonates. A reduction in hepatic perfusion as a result of up to 30% reduction in CO has no effect on the PK of APAP in preterm neonates.


L-dopa-induced dyskinesia improvement after STN-DBS depends upon medication reduction.
The authors studied the long-term evolution of levodopa-induced dyskinesia (LID) after levodopa challenge in two groups of six STN-deep brain stimulation-treated Parkinson disease (PD) patients, one requiring medication after surgery and the other not. A dramatic (96%) reduction of LID severity was obtained in the six postoperatively untreated patients compared to a moderate improvement (47%) in the treated group (p < 0.03). These data support dopaminergic stimulation and striatal desensitization as major determinants of LID in PD.


Recent advances in the use of microcarriers for cell cultures and their ex vivo and in vivo applications.
Microcarriers are 100- to 300-micron support matrices that permit the growth of adherent cells in bioreactor systems. They have a larger surface area to volume ratio in comparison to single cell monolayers, enabling cost-effective cell production and expansion. Microcarriers are composed of a solid matrix that must be separated from expanded cells during downstream processing stages. The detachment method is chosen on the basis of several factors like cell type, microcarrier surface chemistry, cell confluency and degree of aggregation. The development of microcarriers with a range of physiochemical properties permit controlled cell and protein associations that hold utility for novel therapeutics. In this review, we provide an overview of the recent advances in microcarrier cell culture technology. We also discuss its significance as an ex vivo research tool and the therapeutic potential of newly designed microcarrier systems in vivo.


A novel hybrid classification model of genetic algorithms, modified k-Nearest Neighbor and developed backpropagation neural network.
Among numerous artificial intelligence approaches, k-Nearest Neighbor algorithms, genetic algorithms, and artificial neural networks are considered as the most common and effective methods in classification problems in numerous studies. In the present study, the results of the implementation of a novel hybrid feature selection-classification model using the above mentioned methods are presented. The purpose is benefitting from the synergies obtained from combining these technologies for the development of classification models. Such a combination creates an opportunity to invest in the strength of each algorithm, and is an approach to make up for their deficiencies. To develop proposed model, with the aim of obtaining the best array of features, first, feature ranking techniques such as the Fisher's discriminant ratio and class separability criteria were used to prioritize features. Second, the obtained results that included arrays of the top-ranked features were used as the initial population of a genetic algorithm to produce optimum arrays of features. Third, using a modified k-Nearest Neighbor method as well as an improved method of backpropagation neural networks, the classification process was advanced based on optimum arrays of the features selected by genetic algorithms. The performance of the proposed model was compared with thirteen well-known classification models based on seven datasets. Furthermore, the statistical analysis was performed using the Friedman test followed by post-hoc tests. The experimental findings indicated that the novel proposed hybrid model resulted in significantly better classification performance compared with all 13 classification methods. Finally, the performance results of the proposed model was benchmarked against the best ones reported as the state-of-the-art classifiers in terms of classification accuracy for the same data sets. The substantial findings of the comprehensive comparative study revealed that performance of the proposed model in terms of classification accuracy is desirable, promising, and competitive to the existing state-of-the-art classification models.


A knowledge based approach for representing and reasoning about signaling networks.
In this paper we propose to use recent developments in knowledge representation languages and reasoning methodologies for representing and reasoning about signaling networks. Our approach is different from most other qualitative systems biology approaches in that it is based on reasoning (or inferencing) rather than simulation. Some of the advantages of our approach are, we can use recent advances in reasoning with incomplete and partial information to deal with gaps in signal network knowledge; and can perform various kinds of reasoning such as planning, hypothetical reasoning and explaining observations. Using our approach we have developed the system BioSigNet-RR for representation and reasoning about signaling networks. We use a NFkappaB related signaling pathway to illustrate the kinds of reasoning and representation that our system can currently do. The system is available on the Web at http://www.public.asu.edu/~cbaral/biosignet


Distinct subsets of accessory cells activate Thy-1+ triple negative (CD3-, CD4-, CD8-) cells and Th-1 delayed-type hypersensitivity effector T cells.
The SJL strain of mice possess a unique developmental delay in the ability to exhibit delayed-type hypersensitivity (DTH) responses after immunization with a wide variety of Ag. Similar to other models of DTH, the adoptive transfer of syngeneic Ag-pulsed macrophages from DTH-responsive mice into these DTH-unresponsive mice results in the activation of Ag-specific, CD4+ DTH effector Th1 T cells. The absence of other defects in APC-dependent immune responses indicate that the macrophages is the sole APC required for the induction of DTH effector T cells in SJL mice. The defect occurs during the sensitization phase of the DTH response; however, it has not been determined whether a Th cell, which is required for the induction of CD4+ DTH effector T cells, was present in the DTH unresponsive SJL mice. In this study, we have determined that the Thy-1+ helper cell is induced upon Ag stimulation of nonresponder mice and present evidence for the existence of an accessory cell distinct from the macrophage that induces CD4+ DTH effector T cells. Our data indicate that CD4+ DTH effector T cells are induced in an Ag-specific and MHC-restricted manner by an adherent macrophage that expresses the Mac-1+, Mac-2-, Mac-3+, I-A+ phenotype. Adoptive transfer of as few as 100 of the Mac-1+, Mac-2-, or Mac-3+ subsets from DTH responsive donors to DTH unresponsive recipients is able to overcome the DTH deficit. The activation of CD4+ DTH effector T cells in the SJL mouse cells also requires a Thy-1+, Lyt-1+, CD3-, CD4-, CD8-, helper cell. In contrast to the Mac-1+, Mac-3+, I-A+ accessory cell, this helper cell requires an adherent, irradiation resistant, accessory cell that expresses the Mac-1+, Mac-2-, Mac-3-, I-A- surface phenotype for activation. Further, the interaction between this accessory cell and the Thy-1+ helper cell is neither Ag-specific nor MHC restricted. This is the first demonstration of an accessory cell requirement for the Thy-1+, Lyt-1+, B220-, CD4-, CD8-, CD3- DTH Th cell. These data indicate that the activation of the triple negative helper cells and subsequent activation of the CD4+ effector T cells are regulated by two distinct macrophage subpopulations.


Dopamine systems adaptation during acquisition and consolidation of a skill.
The striatum plays a key role in motor learning. Striatal function depends strongly on dopaminergic neurotransmission, but little is known about neuroadaptions of the dopamine system during striatal learning. Using an established task that allows differentiation between acquisition and consolidation of motor learning, we here investigate D1 and D2-like receptor binding and transcriptional levels after initial and long-term training of mice. We found profound reduction in D1 binding within the dorsomedial striatum (DMS) after the first training session on the accelerated rotarod and a progressive reduction in D2-like binding within the dorsolateral striatum (DLS) after extended training. Given that similar phase- and region-specific striatal neuroadaptations have been found also during learning of complex procedural tasks including habit formation and automatic responding, the here observed neurochemical alterations are important for our understanding of neuropsychiatric disorders that show a dysbalance in the function of striatal circuits, such as in addictive behaviors.


Association of Serum Triglycerides and Renal Outcomes among 1.6 Million US Veterans.
Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied. We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components. The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification. Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-lowering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials.


Calm1 signaling pathway is essential for the migration of mouse precerebellar neurons.
The calcium ion regulates many aspects of neuronal migration, which is an indispensable process in the development of the nervous system. Calmodulin (CaM) is a multifunctional calcium ion sensor that transduces much of the signal. To better understand the role of Ca(2+)-CaM in neuronal migration, we investigated mouse precerebellar neurons (PCNs), which undergo stereotyped, long-distance migration to reach their final position in the developing hindbrain. In mammals, CaM is encoded by three non-allelic CaM (Calm) genes (Calm1, Calm2 and Calm3), which produce an identical protein with no amino acid substitutions. We found that these CaM genes are expressed in migrating PCNs. When the expression of CaM from this multigene family was inhibited by RNAi-mediated acute knockdown, inhibition of Calm1 but not the other two genes caused defective PCN migration. Many PCNs treated with Calm1 shRNA failed to complete their circumferential tangential migration and thus failed to reach their prospective target position. Those that did reach the target position failed to invade the depth of the hindbrain through the required radial migration. Overall, our results suggest the participation of CaM in both the tangential and radial migration of PCNs.


Gastric conduit obstruction due to gastroduodenal compression: a new complication post-Ivor-Lewis oesophagectomy.
Oesophagectomy for oesophageal carcinoma carries a high risk of significant morbidity and mortality. Delayed gastric emptying is a relatively common complication following this procedure. A variety of medical, surgical and endoscopic strategies have been described to manage it. The vast majority of cases are related to post-operative pyloric dysfunction and are amenable to conventional management strategies. We present a new case of a patient with a duodenal hiatus hernia resulting in extrinsic gastroduodenal compression by the massively distended gastric conduit as a cause of gastric outlet obstruction following laparoscopic-assisted Ivor-Lewis oesophagectomy 2 years previously. Surgical repair of the hiatus hernia restored the post-oesophagectomy anatomy and resolved this patient's symptoms where conventional management of post-oesophagectomy gastric outlet obstruction had failed on multiple occasions. Most cases of delayed gastric emptying post-oesophagectomy occur as a result of pyloric dysfunction and can be managed using a combination of prokinetics, surgical intervention or more commonly, endoscopic dilatation. Other potential causes and therefore investigative and management strategies should be considered in patients who repeatedly fail conventional management. We offer an alternative diagnosis that may be considered in these patients and present a novel approach to their investigation and management.


Trio-Drug Combination of Sodium Valproate, Baclofen and Thymoquinone Exhibits Synergistic Anticonvulsant Effects in Rats and Neuro-Protective Effects in HEK-293 Cells.
Epilepsy is a chronic brain disorder, with anti-epileptic drugs (AEDs) providing relief from hyper-excitability of neurons, but largely failing to restrain neurodegeneration. We investigated a progressive preclinical trial in rats, whereby the test drugs; sodium valproate (SVP; 150 and 300 mg/kg), baclofen (BFN; 5 and 10 mg/kg), and thymoquinone (THQ; 40 and 80 mg/kg) were administered (i.p, once/day for 15 days) alone, and as low dose combinations, and subsequently tested for antiseizure and neuroprotective potential using electrical stimulation of neurons by Maximal electroshock (MES). The seizure stages were monitored, and hippocampal levels of m-TOR, IL-1β, IL-6 were measured. Hippocampal histopathology was also performed. Invitro and Insilco studies were run to counter-confirm the results from rodent studies. We report the synergistic effect of trio-drug combination; SVP (150 mg/kg), BFN (5 mg/kg) and THQ (40 mg/kg) against generalized seizures. The Insilco results revealed that trio-drug combination binds the Akt active site as a supramolecular complex, which could have served as a delivery system that affects the penetration and the binding to the new target. The potential energy of the ternary complex in the Akt active site after dynamics simulation was found to be -370.426 Kcal/mol, while the supramolecular ternary complex alone was -38.732 Kcal/mol, with a potential energy difference of -331.694 Kcal/mol, which favors the supramolecular ternary complex at Akt active site binding. In addition, the said combination increased cell viability by 267% and reduced morphological changes induced by Pentylenetetrazol (PTZ) in HEK-293 cells, which indicates the neuroprotective property of said combination. To conclude, we are the first to report the anti-convulsant and neuroprotective potential of the trio-drug combination.


The Competition of Termination and Shielding to Evaluate the Success of Surface-Initiated Reversible Deactivation Radical Polymerization.
One of the challenges for brush synthesis for advanced bioinspired applications using surface-initiated reversible deactivation radical polymerization (SI-RDRP) is the understanding of the relevance of confinement on the reaction probabilities and specifically the role of termination reactions. The present work puts forward a new matrix-based kinetic Monte Carlo platform with an implicit reaction scheme capable of evaluating the growth pattern of individual free and tethered chains in three-dimensional format during SI-RDRP. For illustration purposes, emphasis is on normal SI-atom transfer radical polymerization, introducing concepts such as the apparent livingness and the molecular height distribution (MHD). The former is determined based on the combination of the disturbing impact of termination (related to conventional livingness) and shielding of deactivated species (additional correction due to hindrance), and the latter allows structure-property relationships to be identified, starting at the molecular level in view of future brush characterization. It is shown that under well-defined SI-RDRP conditions the contribution of (shorter) hindered dormant chains is relevant and more pronounced for higher average initiator coverages, despite the fraction of dead chains being less. A dominance of surface-solution termination is also put forward, considering two extreme diffusion modes, i.e., translational and segmental. With the translational mode termination is largely suppressed and the living limit is mimicked, whereas with the segmental mode termination occurs more and the termination front moves upward alongside the polymer layer growth. In any case, bimodalities are established for the tethered chains both on the level of the chain length distribution and the MHD.


[Value of procalcitonin and critical illness score in etiological diagnosis and prognosis of sepsis caused by intra-abdominal infections].
To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis. The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation II (APACHE II) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI. A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G+) bacterial infection of patients was significantly higher than that caused by Gram-negative (G-) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G+ bacterial infection, the PCT value of patients with G- bacterial infection was higher [μg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHE II score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHE II score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (μg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: (1) the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95%CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 μg/L, the sensitivity of diagnosis of G- bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 μg/L, the specificity of diagnosis of G- bacterial infection could reach 81.8%. (2) In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHE II score achieved the highest AUC [28 days: 0.791 (95%CI was 0.680-0.902), 60 days: 0.748 (95%CI was 0.645-0.851)]. APACHE II score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95%CI was 0.495-0.725), 60-day AUC: 0.558 (95%CI was 0.450-0.667)]. PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHE II score may perform better in predicting early and late mortality.


Size discrepancies in molars and first key to optimal occlusion.
The aim of this research project was to determine whether the sizes of the first molars allow clinicians to achieve the first goal of an ideal clinical outcome. Seventy-eight sets of dental casts that have been presented to the American Board of Orthodontics were evaluated. A Boley gauge was used to measure the length from the mesiobuccal cusp to the distobuccal cusp of the maxillary first molar and the length from the mesiobuccal groove of the mandibular first molar to the occlusal embrasure between the mandibular first and second molars. These two measurements were taken on both sides of each set of dental casts for a total of four measurements per set. The maxillary measurements ranged from 3.6 to 6.9 mm with an average of 5.2 mm. The mandibular measurements ranged from 5.0 to 8.0 mm with an average of 6.5 mm. The data were tested for normality and found to be equally distributed. A t-test revealed significant differences in tooth sizes between maxillary and mandibular first molars on both sides. On average, the mesiodistal length measured on maxillary first molars was about 80% of that of their mandibular counterparts. Only 5 of the 78 sets of dental casts evaluated had equal maxillary and mandibular measurements on one side (either left or right), and none of them had equal measurements on both sides. Clinicians have to understand that tooth size discrepancies do exist in patients and that these discrepancies make the completion of a perfect case challenging.


Histology of Pericardial Tissue Substitutes Used in Congenital Heart Surgery.
Pericardium is used as a tissue substitute during pediatric heart surgery. However, little is known about the histological characteristics of pericardial tissue substitutes. We searched our clinical and Pathology databases to identify cases in which glutaraldehyde-preserved autologous pericardium, PhotoFix bovine pericardium, or Peri-Guard Repair Patch glutaraldehyde-preserved bovine pericardium was used as patch material during cardiac surgery and in which explanted tissue substitute was available for histologic examination. Tissue sections were stained with hematoxylin and eosin, Masson trichrome, and Movat pentachrome, and were graded for inflammation, tissue substitute degeneration, neointima formation, and calcification. Nonparametric statistical methods were used to test differences between groups because of small sample size. The eight patients who received PhotoFix pericardium were older (median 10 months vs 10 days, P < 0.05) and the material was in situ longer (median 14 vs 2.5 months, P < 0.05) compared to the eight who received autologous pericardium. Only three patients received glutaraldehyde-preserved bovine pericardium precluding statistical comparison. Inflammation and tissue degeneration were greater in PhotoFix pericardium compared to autologous pericardium but were no more than moderate. Neointima formation and calcification did not differ significantly between the two groups. PhotoFix bovine pericardium is associated with more inflammation and material degeneration but calcification, and neointima formation are similar to autologous pericardium. Although the short-term outcomes are acceptable, calcification and degeneration seen in some cases suggest that long-term outcomes and performance at certain anatomic locations need further study.


Lateral flow immunoassay integrated with competitive and sandwich models for the detection of aflatoxin M1 and Escherichia coli O157:H7 in milk.
Pathogens, mycotoxins, or antibiotics may exist in a food sample. Micro- and macromolecular substances must be detected quickly. A rapid and convenient lateral flow immunoassay (LFI) integrated with competitive and sandwich models was developed to detect micro- and macromolecular substances. In this study, aflatoxin M1 (AFM1) and Escherichia coli O157:H7 were selected as the micro- and macromolecular substances, respectively. Two test lines in the LFI test strip were evaluated to detect AFM1 and E. coli O157:H7 by competitive and sandwich models. Results showed that the limits of detection for detecting AFM1 and E. coli O157:H7 were 50 pg·mL-1 and 1.58 × 104 cfu·mL-1, respectively. The whole assay time was 30 min. The recoveries of gold nanoparticle-LFI ranged from 78.0 to 111.6% with coefficients of variation in the range of 3.9 to 8.5% for the detection of AFM1. For the detection of E. coli O157:H7, the range of recoveries was from 70.1 to 89.6% with coefficients of variation ranging from 4.9 to 13.0%. This study not only tested sensitivity and specificity, but also was a systematic study of location of 2 test lines of the LFI test strip integrated with competitive and sandwich models.


Individual differences in behavioral activation and cardiac vagal control influence affective startle modification.
The startle response (SR) has a close relationship with stress responses. Startle modification (SRM) has been widely used to study stress disorders (e.g., posttraumatic stress disorder). The framework of the behavioral inhibition and activation systems (BIS/BAS) has been thought to correspond with withdrawal and approach motivational processes underlying affective SRM and can influence stress reactivity. Vagally-mediated cardiac activity as indexed by heart rate variability (HRV) has been associated with SRM and regulatory processes during stress. In the present study, the influence of individual differences in the BIS/BAS and resting HRV on affective SRM were examined. Eighty-six subjects viewed affective pictures while acoustic SR stimuli were delivered. Individual differences in motivation were measured by the BIS/BAS scales. The magnitude of SR was assessed as electromyographic activity of the SR eyeblink during pictures of different valences. Resting HRV was derived from electrocardiography. In contrast to previous studies, the present results showed that startle inhibition and potentiation were related to BAS and HRV, but not to BIS. There was also an interaction of BAS and HRV, indicating that the relationship between HRV and SRM strengthened as BAS scores decreased. The present findings suggest that BAS may relate to both withdrawal and approach, and trait stress reactivity is influenced by BAS and cardiac vagal activity. In addition, BAS moderates the relationship between cardiac vagal activity and SRM. These findings have both theoretical and practical implications for the study of SRM, stress disorders, and health.


Eosinophilic Esophagitis.
Eosinophilic esophagitis (EoE) is a relatively new disease that has reached an incidence similar to that of Crohn disease and ulcerative colitis. With this increased presence, greater recognition is essential. This applies both to children with nonspecific but potentially debilitating symptoms and to adults who have spent years behaviorally compensating for narrow esophageal strictures. The pathogenesis of EoE is rapidly being unraveled and is based on initiation of a type II allergic response to specific food antigens, leading to dense esophageal eosinophilia, chronic inflammation, and esophageal fibrosis. With greater familiarity and understanding of EoE, treatments are evolving, including identification and avoidance of food antigens; broad applications of topical steroids; and, eventually, pathway-specific biologic therapy.


Lactobacilli-fermented Hwangryunhaedoktang has enhanced anti-inflammatory effects mediated by the suppression of MAPK signaling pathway in LPS-stimulated RAW 264.7 cells.
Hwangryunhaedoktang (HR) has been traditionally used in oriental medicine as a drug for the treatment of melena, hemoptysis, and apoplexy. We investigated whether HR and lactobacilli-fermented HRs have an inhibitory effect on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The investigation was focused on whether HR and fermented HRs could inhibit the production of prostaglandin (PG)E2, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. We found that HR weakly inhibited various inflammatory mediators induced by LPS. However, fermentation with lactobacilli significantly increased the inhibitory effect of HR on most of the inflammatory mediator expression. Furthermore, fermented HRs exerted a stronger inhibitory effect on MAPKs phosphorylation than that by non-fermented HR. These results suggest that lactobacilli-fermented HRs contains elevated potent anti-inflammatory activity that is mediated by inhibiting MAPKs pathway in macrophages.


A comparison of temperature-mediated immunomodulation between two species of flounder.
The kinetics of the temperature-mediated immunomodulation of the humoral antibody response to an erythrocyte antigen was remarkably different in two species of a marine teleost, the winter flounder (Pseudopleuronectes americanus) and the summer flounder (Paralichthys dentatus). These two species were caught in the same area, maintained under the same conditions and injected with the same antigen (horse red blood cells). Experiments were performed at 8, 12 and 17 degrees C during the same time of the year. Summer flounder showed only a delay in the appearance of circulating antibody at lower temperatures while winter flounder showed both a delay and a marked suppression at lower temperatures. Antibody titers remained high for over three months in summer flounder while in winter flounder antibody levels began decreasing after one month.


Synaptotagmin 5 regulates Ca2+-dependent Weibel-Palade body exocytosis in human endothelial cells.
Elevations of intracellular free Ca2+ concentration ([Ca2+]i) are a potent trigger for Weibel-Palade body (WPB) exocytosis and secretion of von Willebrand factor (VWF) from endothelial cells; however, the identity of WPB-associated Ca2+-sensors involved in transducing acute increases in [Ca2+]i into granule exocytosis remains unknown. Here, we show that synaptotagmin 5 (SYT5) is expressed in human umbilical vein endothelial cells (HUVECs) and is recruited to WPBs to regulate Ca2+-driven WPB exocytosis. Western blot analysis of HUVECs identified SYT5 protein, and exogenously expressed SYT5-mEGFP localised almost exclusively to WPBs. shRNA-mediated knockdown of endogenous SYT5 (shSYT5) reduced the rate and extent of histamine-evoked WPB exocytosis and reduced secretion of the WPB cargo VWF-propeptide (VWFpp). The shSYT5-mediated reduction in histamine-evoked WPB exocytosis was prevented by expression of shRNA-resistant SYT5-mCherry. Overexpression of SYT5-EGFP increased the rate and extent of histamine-evoked WPB exocytosis, and increased secretion of VWFpp. Expression of a Ca2+-binding defective SYT5 mutant (SYT5-Asp197Ser-EGFP) mimicked depletion of endogenous SYT5. We identify SYT5 as a WPB-associated Ca2+ sensor regulating Ca2+-dependent secretion of stored mediators from vascular endothelial cells.


Effects of chronic nicotine exposure on Δ9-tetrahydrocannabinol-induced locomotor activity and neural activation in male and female adolescent and adult rats.
High rates of comorbid tobacco and cannabis use in adolescents and young adults may be related to functional interactions between the nicotinic cholinergic and cannabinoid systems in the brain during development. This study examined the effects of chronic exposure to nicotine (the psychoactive component in tobacco) on acute exposure to delta-9-tetrahydrocannabinol (THC) (the psychoactive component of cannabis). Male and female adolescent and adult Sprague-Dawley rats (N = 112) were injected daily with nicotine (1 mg/kg, i.p.) or vehicle for 14 days, followed by a 14-day drug-free period. On test day, rats were injected with THC (5 mg/kg, i.p.) or vehicle, locomotor activity was recorded for 2 h, and brains harvested for c-Fos immunoreactivity (IR). Locomotor activity and c-Fos IR changes induced by THC challenge were altered by nicotine pre-exposure and modified by age and sex. THC-induced suppression of locomotor activity was attenuated by nicotine pre-exposure in adult but not adolescent males. THC-induced suppression of locomotor activity was potentiated by nicotine pre-exposure in female adolescents, with no effects of THC or nicotine observed in female adults. THC increased c-Fos IR in the caudate, nucleus accumbens, stria terminalis, septum, amygdala, hypothalamus, and thalamus. Nicotine pre-exposure potentiated this effect in all regions. Several brain regions showed age and sex differences in c-Fos IR such that expression was greater in adults than adolescents and in females than males. Chronic nicotine pre-exposure produces lasting effects on cannabinoid-mediated signalling in the brain and on behaviour that are mediated by age and sex. NSERC.


Effect of interferon treatment on glucose metabolism in children with chronic hepatitis B infection.
Interferon is known to have some effects on glucose metabolism, but this issue has not been investigated in children with chronic hepatitis B infection. The aim of this study was to investigate the impact of interferon on glucose metabolism and to investigate whether autoimmunity has a role in the pathogenesis. Fourteen patients (9 male, 6.3+/-2.7 years) with children with chronic hepatitis B infection were prospectively evaluated. They received interferon 10 MU/m2 for six months. Vral glucose tolerance test, fasting insulin and C-peptide, postprandial insulin and C-peptide, anti-GAD antibody, HOMA-IR and glucose/insulin ratio were measured before and after treatment. Before interferon, oral glucose tolerance test showed glucose intolerance in two patients (14.5%) and hypoglycemia in one patient (7.1%). One patient had hyperinsulinemia and insulin resistance (7.1%), and four patients had hypoinsulinemia and insulin hypersensitivity (28.5%). After interferon, oral glucose tolerance test was normal in 13 patients (92.8%). Abnormal oral glucose tolerance test persisted in the same patient, but no difference was found in insulin resistance. Hypoinsulinemia and insulin hypersensitivity were present in five patients (35.7%). DM related autoantibodies were negative in all patients before interferon; however, one patient, whose glucose metabolism was within normal limits, developed anti-GAD antibody after interferon. Children with children with chronic hepatitis B infection were shown to have hypoinsulinemia and insulin hypersensitivity. These children may have risk of progresssing to insuline dependent drabetes mellitus. We demonstrated that interferon did not seem to worsen glucose metabolism, but it had minimal positive impact on it. These results should be supported with other studies and interferon should be used carefully, especially in children with decreased beta cell reserve.


The development of a speech sound screening test for European French-speaking monolingual and bilingual children.
This study presents normative data on a screening test, referred to as the Dépistage Rapide Articulation et Phonologie (DRAP), designed to detect European French-speaking children who are at risk for having speech sound disorders. The test consists of 20 words which contain late-acquired phonological features such as medial and final /r/, consonant clusters, /s/C sequences, and alveolar and post-alveolar fricatives. The test was given to 196 children, monolingual and bilingual, living in Geneva and San Francisco, and ranging in age from 2.11 through to 6.11. Our analyses examined the influence of bilingualism, context (Geneva or San Francisco), gender and age on the test scores and also looked at the influence of these factors on phonological features in the test. There were no strong effects of bilingualism, context, and gender on the test results but strong effects of age. Validity and internal consistency of the test were in the acceptable range. A focus on phonological features indicated that children had difficulty with final clusters and post-alveolar fricatives. The study provides encouraging results for the use of this test as a screening measure with French-speaking children.


A long non-coding RNA Leat1 mediates the hormone responsiveness of EfnB2 during male urogenital development.
The novel long non-coding RNA (lncRNA) Leat1 is extraordinarily conserved in both its location (syntenic with EfnB2, an essential gene in anogenital patterning) and sequence. Here we show that Leat1 is upregulated following the testosterone surge from the developing testis and directly interacts with EfnB2, positively regulating its expression. Leat1 expression is suppressed by estrogen, which in turn suppresses the expression of EfnB2. Moreover, the loss of Leat1 leads to reduced EfnB2, resulting in a severe hypospadias phenotype. The human LEAT1 gene is also co-expressed with EFNB2 in the developing human penis suggesting a conserved function for this gene in urethral closure. Together our data identify Leat1 as a novel molecular regulator of urethral closure and implicate it as a target of endocrine disruption in the etiology of hypospadias.


Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.
Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.


A large anastomotic leakage after esophageal surgery treated with endoluminal vacuum-assisted closure: a case report.
The treatment of anastomotic post-esophagectomy leaks and fistula is challenging. Endoluminal vacuum-assisted closure (EVAC) is an emerging technique that employs negative pressure wound therapy to treat anastomotic leaks endoscopically. Esosponge is specifically designed for esophageal EVAC therapy. We report on a 49-year-old woman who underwent a totally mini-invasive Ivor-Lewis esophagectomy and developed a giant postoperative leak with a complex pleural collection, but she was not fit for surgical re-intervention. The patient healed almost completely after 14 exchange sessions of Esosponge over 35 days.


Sirolimus-Versus Zotarolimus-Eluting Stents in Acute Coronary Syndromes With C Type Left Anterior Descending Artery Lesions: A Three-Year Clinical Follow-Up.
Drug-eluting stents have improved the efficacy of percutaneous coronary intervention and made it the preferred therapy in the treatment of ischemic heart diseases including acute coronary syndromes. The objective of the study was to compare the clinical efficacy and safety of sirolimus-eluting stent with that of zotarolimus-eluting stent following percutaneous coronary intervention for acute coronary syndrome patients with C-type left anterior descending stenosis. A total of 154 acute coronary syndrome patients with C-type lesions in the left anterior descending artery, requiring a stent > 28 mm in length, were randomized into two groups to receive either sirolimus- (n = 74) or zotarolimus-eluting stent (n = 80). The follow-up period after stent implantation was approximately 36 months. The primary endpoint was a major cardiac event (a composite of cardiac death, myocardial infarction, or ischemia-related target vessel revascularization), and the secondary endpoint included these individual end points plus stent thrombosis. After 3 years follow-up, the rate of the primary end point (major cardiac event: cardiac death, myocardial infarction, ischemia-related target vessel revascularization) was 16% in the sirolimus group (n = 12) versus 11.2% in the zotarolimus group (n = 9) (P = 0.2). Although there were four cases of stent thrombosis with sirolimus-eluting stent and one with zotarolimus-eluting stent (4.0% sirolimus vs. 1.25% zotarolimus; P = 0.2), neither non-Q myocardial infarction (4.0%sirolimus vs. 1.25% zotarolimus; P = 0.2) nor stent thrombosis, differed significantly. Although zotarolimus-eluting stent implantation showed more favorable results with respect to stent thrombosis and major adverse cardiac event rates compared to sirolimus-eluting stent implantation, statistically, both stent groups have nearly similar clinical safety and efficacy in the treatment of acute coronary syndromes with C-type lesions in the left anterior descending artery disease.


Longitudinal electroencephalographic (EEG) findings in pediatric anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis: the Padua experience.
To contribute to characterize electroencephalographic (EEG) activity in pediatric anti-N-methyl-d-aspartate (anti-NMDA) receptor encephalitis, we reviewed electroclinical data of 5 children with anti-NMDA receptor encephalitis diagnosed in our department. We identified 4 longitudinal electroencephalographic phases: in the early phase, background activity was normal, with intermixed nonreactive slow waves; in the florid phase, background activity deteriorated with appearance of sequences of peculiar rhythmic theta and/or delta activity unrelated to clinical changes, unresponsive to stimuli and antiepileptic medications; in the recovery phase, these sequences decreased and reactive posterior rhythm re-emerged; electroencephalogram normalized 2 to 5 months after onset. In conclusion, in the presence of evocative clinical history, recognizing a characteristic longitudinal electroencephalographic activity could provide ancillary aspects addressing the diagnosis and the overall management of children with anti-N-methyl-d-aspartate receptor encephalitis; in particular, knowing that peculiar and recurrent paroxysmal nonepileptic rhythmic theta-delta patterns can occur in these patients could help distinguish paroxysmal epileptic and nonepileptic electroencephalographic activity.


Revealing enterovirus infection in chronic human disorders: An integrated diagnostic approach.
Enteroviruses (EVs) causing persisting infection are characterized by minimal replication and genetic changes. Typing of these agents may complement disease assessment and shed light on pathogenesis. Here we report an integrated approach for EV detection in human samples that is based on pre-enrichment of virus in cell culture before search for the viral genome and viral antigens. Cases of post-polio syndrome, type 1 diabetes, and chronic cardiomyopathy were investigated. As tissue-based approaches require invasive procedures, information was mainly gleaned from virus in blood. Molecular assays targeting conserved genome regions of all EV types (5'UTR, 2 C, 3Dpol) were employed. As compared to direct assays of plasma or leukocytes, the EV detection rate was significantly enhanced by co-culture of leukocytes with cell lines prior to molecular and immunologic tests. Results of RT-PCR and sequencing were confirmed by staining cell cultures with a panel of EV-specific antibodies. Sequence and phylogenetic analysis showed that EVs of the C species (polioviruses) were associated with the post-polio syndrome, while members of the B species were found in type 1 diabetes and cardiomyopathy. The procedure may be used for investigating the possible association of different EVs with a variety of chronic neurologic, endocrine, and cardiac disorders.


[14C]-urea breath test to confirm eradication of Helicobacter pylori.
Treatment for Helicobacter pylori reduces ulcer recurrence. Eradication rates of the organism vary with different drug regimens from 30% to 90%. There is a need to identify patients who have failed treatment. [14C]-Urea breath test (UBT) is non-invasive, sensitive, safe and highly reliable test for diagnosis of H. pylori infection. As there is a paucity of reports on the utility of [14C]-UBT in confirming H. pylori eradication, this study was undertaken. Thirty-eight patients (age 34 +/- 17 years, range 16-84 years, 27 men) with upper gastrointestinal symptoms underwent upper gastrointestinal endoscopy. Baseline H. pylori infection was diagnosed by identification of the organism on antral biopsies and positive rapid urease test (RUT). After 1 month of completion of treatment, repeat RUT and histological examination of antral endoscopic biopsies were performed. Eradication of H. pylori was defined as absence of the organism on histology, and negative RUT. The [14C]-UBT was performed using 185 kBq [14C]-urea dissolved in 300 mL water. Breath samples were collected once before ingestion of [14C]-urea, and subsequently at 5 and 15 min. Results were expressed as 14CO2/mmol CO2 exhaled as per cent of administered urea. Endoscopy revealed antral gastritis (n = 14), duodenal ulcer (n = 8), duodenitis (n = 2), oesophagitis (n = 1), antral gastritis and duodenal ulcer (n = 3), antral gastritis and duodenitis (n = 7) and normal upper gastrointestinal endoscopy (n = 3). All the 20 patients who were negative for H. pylori on RUT and histology, tested negative for H. pylori on [14C]-UBT. However, of 18 patients shown to have H. pylori infection on RUT and histology, 16 were positive for H. pylori on [14C]-UBT. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of [14C]-UBT were 100, 89, 91, 100 and 95% respectively. The [14C]-UBT is a reliable indicator of H. pylori eradication after treatment. It can obviate the need for antral biopsies to confirm eradication of H. pylori after completion of treatment.


Tissue Engineering in Neuroscience: Applications and Perspectives.
Neurological disorders have always been a threat to human physical and mental health nowadays, which are closely related to the nonregeneration of neurons in the nervous system (NS). The damage to the NS is currently difficult to repair using conventional therapies, such as surgery and medication. Therefore, repairing the damaged NS has always been a vast challenge in the area of neurology. Tissue engineering (TE), which integrates the cell biology and materials science to reconstruct or repair organs and tissues, has widespread applications in bone, periodontal tissue defects, skin repairs, and corneal transplantation. Recently, tremendous advances have been made in TE regarding neuroscience. In this review, we summarize TE's recent progress in neuroscience, including pathological mechanisms of various neurological disorders, the concepts and classification of TE, and the most recent development of TE in neuroscience. Lastly, we prospect the future directions and unresolved problems of TE in neuroscience.


Circadian function of suprachiasmatic nuclei: molecular and cellular biology.
Suprachiasmatic nuclei (SCN) contain a circadian oscillator that is normally synchronized by the light/dark cycle. Embryonic SCN grafted into the brain of an SCN-lesioned arrhythmic host define the period of the restored circadian locomotor rhythm. Gene expression of immediate-early genes, such as c-fos and jun-B, in the ventrolateral SCN is associated with circadian synchronization by light pulses and subjected to circadian control. Vasopressin and somatostatin gene expression in dorsomedial SCN show distinct circadian rhythms with higher peptide levels occurring during the day. It is currently unknown whether the circadian oscillator in SCN resides in a single cell or is a property of cellular network. Briefly presented are some model views about the circadian oscillator in SCN and the molecular and cellular approaches to the circadian function of the nucleus.


Blending Mechanism of PS- b-PEO and PS Homopolymer at the Air/Water Interface and Their Morphological Control.
We report a blending mechanism of polystyrene- b-poly(ethylene oxide) (PS- b-PEO) and PS homopolymer (homoPS) at the air/water interface. Our blending mechanism is completely different from the well-known "wet-dry brush theory" for bulk blends; regardless of the size of homoPS, the domain size increased and the morphology changed without macrophase separation, whereas the homoPS of small molecular weight (MW) leads to a transition after blending into the block copolymer domains, and the large MW homoPS is phase-separated in bulk. The difference in blending mechanism at the interface is attributed to adsorption kinetics at a water/spreading solvent interface. Upon spreading, PS- b-PEO is rapidly adsorbed to the water/spreading solvent interface and forms domain first, and then homoPS accumulates on them as the solvent completely evaporates. On the basis of our proposed mechanism, we demonstrate that rapid PS- b-PEO adsorption is crucial to determine the final morphology of the blends. We additionally found that spreading preformed self-assemblies of the blends slowed down the adsorption, causing them to behave similar to bulk blends, following the "wet-dry brush theory". This new mechanism provides useful information for various block copolymer-homopolymer blending systems with large fluid/fluid interfaces such as emulsions and foams.


The role of serum leptin levels in chronic hepatitis C with steatosis.
Leptin has recently been suggested to play a role in the pathogenesis of hepatic steatosis and steatohepatitis in the absence of viral infection. The aim of this study was to evaluate whether leptin levels are associated with hepatic steatosis in chronic hepatitis C. Thirty-one patients (22 female, 9 male, mean age: 51 +/- 9) with histologically proven chronic hepatitis C were included in this prospective, controlled, observational, clinical study with blind outcome assessment. Patients with and without steatosis in liver biopsy served as each others' controls. Chronic hepatitis C patients with (n=23) and without steatosis (n=8) were similar with respect to their serum glucose, lipid and leptin levels (p>0.05). Serum leptin levels were correlated with both patient factors, such as obesity and with liver enzymes, such as ALT, AST only in patients with steatosis. Chronic hepatitis C patients with or without steatosis had similar leptin levels of 6.3 +/- 2.5 and 4.9 +/- 2.5, respectively. Leptin levels were well correlated with antropometrical parameters in chronic hepatitis C patients. Leptin levels were associated with evidence of impaired hepatic function in patients with chronic HCV related steatosis. Serum leptin may be a prognostic marker for patients with chronic HCV infection with steatosis.


[Microbiologic state of the vagina in labor and puerperal fever].
Vaginal smears have been collected from 520 delivering women for bacteriological evaluation and analysis of the relationship between present organisms with puerperal fever. A relationship between the composition of vaginal flora before labour and pathological organisms isolated during puerperal fever has been shown. Presence of the exogenous source of infections has also been confirmed.


Effect of gamma interferon on the expression of class I MHC antigens on fresh leukemic cells and their susceptibility to lysis by lymphokine activated killer cells.
Relationship between MHC class I antigen expression on PBLs from leukemia patients and their susceptibility to lysis by LAK cells was investigated. LAK cells induced small yet significant lysis of leukemic cells. In nine out of 14 cases studied, treatment with Interferon gamma (200 U/ml for 48 hours) resulted in a decrease in the LAK susceptibility of leukemic cells. In six of these cases, there was a concomitant increase in the expression of class I MHC antigen expression. In three samples, the increase in MHC class I antigen expression was not accompanied by a decrease in LAK susceptibility. IFN treatment had no effect on the binding of leukemic cells to LAK effector cells.


Early reversal of acidosis and metabolic recovery following ischemia.
Tissue acidosis is believed to be a key element in ischemic injury of neural tissue. The goal of this study was to determine whether persisting postischemic acidosis or the extent of acidosis would affect metabolic recovery following an ischemic event. Intracellular pH (pHi), adenosine triphosphate, phosphocreatine, and lactate levels were measured in the cerebral cortex during the early stages of reperfusion, following either 5 or 10 minutes of global ischemia in both normo- and hyperglycemic gerbils. A total of 130 gerbils were injected with a solution containing 1.5 ml Neutral Red (1%) (+/- 2.5 gm/kg glucose); 30 minutes later, the gerbils were placed under halothane anesthesia, and the carotid arteries were occluded for either 5 or 10 minutes. The brains were frozen in liquid nitrogen at 0, 15, 30, 60, and 120 seconds after reperfusion; they were sectioned and the block face was photographed to determine the pHi by using Neutral Red histophotometry. At the conclusion of the ischemia, the pHi in all groups had decreased significantly from a control value of 7.05 +/- 0.03) (mean +/- standard error of the mean). In normoglycemic brains, the pHi values fell to 6.71 +/- 0.04 and 6.68 +/- 0.11 after 5 and 10 minutes of ischemia, respectively. Hyperglycemic brains were more acidotic; values fell to 6.57 +/- 0.10 and 6.52 +/- 0.24 after 5 and 10 minutes of ischemia, respectively. Lactate levels were approximately fivefold greater than those of control tissue in normoglycemic brains, while lactate levels in hyperglycemic brains were increased eightfold. The adenosine triphosphate and phosphocreatine levels were depleted at the end of ischemia in all groups. After 2 minutes of reflow activity, the pHi levels in both normo- and hyperglycemic brains were restored to those of control values in the '5-minute ischemic group, while the pHi levels remained significantly depressed in the 10-minute ischemic group. Restoration of high-energy phosphates was similar in normoglycemic brains regardless of ischemic duration, recovering to only 20% of the restoration obtained in control tissue at 2 minutes. In hyperglycemic brains, however, there was complete recovery of high-energy phosphates by 2 minutes of reflow activity following 5 minutes of ischemia. Extending the ischemic period to 10 minutes in hyperglycemic brains slowed the rate of metabolic recovery to that observed in normoglycemic brains. The results indicate that the reflow period permits the rapid restoration of pHi levels substantially before the normalization of primary energetic compounds.(ABSTRACT TRUNCATED AT 400 WORDS)


Miro1 Enhances Mitochondria Transfer from Multipotent Mesenchymal Stem Cells (MMSC) to Neural Cells and Improves the Efficacy of Cell Recovery.
A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain.


Availability of psychotropic drugs and suicidal self-poisoning mortality in Belgium from 1971-1984.
Trends in completed suicide by solid or liquid substances in Belgium were investigated for the period 1971-1984 in relation with data about sales of psychotropic drugs. Mortality rose sharply between 1973 and 1980 (from 21.1 per million population of 15 years and older to 52.2 in males and from 26.7 to 61.7 in females) and decreased slightly thereafter. No apparent coincidence with the availability of psychotropic drugs was found, and the increasing risk of suicidal persons dying at home suggested an increase in the severity of the attempts until 1980. However, incidence changes could also have affected these trends. The evolution in accidental and in suicidal hospital rates suggested that emergency care had improved. Although barbiturate sales decreased continuously (from 46.7 packages per year per 100 population in 1974 to 28.5 in 1984), these drugs still account for a high proportion of fatal self-poisonings (23%) in Belgium. Possible shortcomings that could affect the validity of our findings are discussed.


A coarse-grained approach to protein design: learning from design to understand folding.
Computational studies have given a great contribution in building our current understanding of the complex behavior of protein molecules; nevertheless, a complete characterization of their free energy landscape still represents a major challenge. Here, we introduce a new coarse-grained approach that allows for an extensive sampling of the conformational space of a large number of sequences. We explicitly discuss its application in protein design, and by studying four representative proteins, we show that the method generates sequences with a relatively smooth free energy surface directed towards the target structures.


A preliminary investigation on single nucleotide polymorphism rs2287622 of bile salt export pump gene in patients with chronic hepatitis C virus infection in Hunan, China.
European researchers have underscored associations between single nucleotide polymorphism (SNP) rs2287622 of the hepatobiliary bile salt export pump (BSEP) gene and the risk of hepatitis C virus (HCV) infection. The distributions of SNP rs2287622 are racially specific. This study was aimed to preliminarily investigate the distribution of BSEP gene SNP rs2287622 in the Han patients with chronic HCV-infection (CHC) in Hunan, China. BSEP gene SNP rs2287622 of 165 CHC patients, 99 patients with chronic hepatitis B virus infection (CHB) and 99 healthy individuals were analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis and nucleotide sequencing. The overall frequencies of the C allele of BESP gene SNP rs2287622 in the CHC patients, CHB patients and healthy individuals were 74.2, 72.7 and 74.2%, respectively (P > 0.05). The overall odds ratios (ORs) aiming at predicting CHC risk by comparing the ratios of the frequency distribution of alleles or genotypes in the CHC group with those in the non-CHC group had no statistical significance (P > 0.05). However, the CHC ORs of CC vs TT, TC vs TT and CC + CT vs TT among the individuals aged over 40 years were 2.680, 3.122 and 2.824 respectively (P < 0.05), and the higher risk did not relate to gender, HCV genotypes and presence of HCV-related liver cirrhosis. Among the Han individuals aged over 40 years in Hunan, China, genotype CC or CT of BSEP gene SNP rs2287622 may correlate with higher risk of CHC in comparison with genotype TT. Further study with a larger cohort is essential.


Quartz crystal microbalance immunosensor for highly sensitive 2,3,7,8-tetrachlorodibenzo-p-dioxin detection in fly ash from municipal solid waste incinerators.
A quartz crystal microbalance (QCM) immunosensor was developed for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxins (TCDD) in environmental pollutants. An anti-TCDD antibody was immobilized on the gold surface of the QCM via chemical coupling, and its immunologic activity was then maintained by treatment with an artificial stabilizing reagent such as poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate). A competitive immunoreaction with TCDD conjugated ovalbumin (TCDD-ovalbumin) was used to detect TCDD. A calibration curve was obtained through the competitive immunoreaction, and linearity was shown from 100 ng mL(-1) to 0.1 ng mL(-1). Also, the cross-reactivities of the anti-TCDD monoclonal antibody were thoroughly evaluated with several TCDD derivatives. The relationships between GC-MS, ELISA, and QCM were compared using fly ash samples from a municipal solid waste, which were prepared using an accelerated solvent extractor. For 23 samples, the experimental relationship between the TCDD concentration by QCM vs. the TCDD concentration by ELISA was y= 1.07x + 2.70, r= 0.99, and the TCDD concentration by QCM vs. the toxic equivalent quantity (TEQ) value by GC-MS was y= 2.46x - 14.98, r= 0.89.


Universal behavior of the coefficients of the continuous equation in competitive growth models.
The competitive growth models (CGM) involving only one kind of particles, are a mixture of two processes, one with probability p and the other with probability 1-p. The p dependence produce crossovers between two different regimes. We demonstrate that the coefficients of the continuous equation, describing their universality classes, are quadratic in p (or 1-p ). We show that the origin of such dependence is the existence of two different average time rates. Thus, the quadratic p dependence is a universal behavior of all the (CGM). We derive analytically the continuous equations for two CGM, in 1+1 dimensions, from the microscopic rules using a regularization procedure. We propose generalized scalings that reproduce the scaling behavior in each regime. In order to verify the analytic results and the scalings, we perform numerical integrations of the derived analytical equations. The results are in excellent agreement with those of the microscopic CGM presented here and with the proposed scalings.


Comparing prenatal providers' approaches to four different risks: alcohol, tobacco, drugs, and domestic violence.
We explored prenatal care providers' methods for addressing four behavioral risks in their pregnant patients: alcohol use, smoking, drug use, and domestic violence. We used qualitative, purposively sampled, focus group data. Groups met in professional focus group settings. We conducted six focus groups (five with OB/Gyn physicians, one with nurse practitioners and certified nurse midwives), with a total of N = 49. The moderator used a focus group guide with open-ended questions, with probes where appropriate. Providers' discussions reflected differences in how they approach each risk, including: (1) ambivalence about abstinence messages for alcohol; (2) relative comfort and confidence about assessing smoking and counseling to reduce smoking; (3) disparities across practice settings for toxicology screening for drugs; and (4) discomfort and pessimism with domestic violence. Investigators also analyzed providers' statements for each risk within the framework of the "Five A's" construct (Assess, Advise, Agree, Assist, and Arrange) for evaluating risk behavior interventions. A comparison of each risk across the Five A's illuminates the gaps between recommended and actual prevention methods and suggests directions for development of interventions and educational efforts.


Chondrosarcoma of the nasal cavity in a patient with Maffucci syndrome: case report and review of the literature.
Maffucci syndrome is a rare, congenital, non-hereditary mesodermal dysplasia, manifested by multiple enchondromas and hemangiomas. Malignant transformation of these lesions is seen in up to 40% of the cases. We present a case of a patient with Maffucci syndrome and an associated chondrosarcoma of the nose. Treatment consisted of surgical resection. Because of the low grade of the tumor, additional treatment, such as radiotherapy, was not necessary. Maffucci syndrome is an exceedingly rare mesodermal dysplasia. Its manifestation in the head and neck region is even less common. Malignant transformation of the associated enchondromas is common, and should be considered whenever a change of the clinical course occurs. Random, periodically performed X-ray examinations give little additional information on malignant transformation and are considered useless.


Osteoporosis in Rett syndrome: A study on normal values.
Osteoporosis is the reduction of calcium density in bones, usually evident in postmenopausal females, yet the tendency for osteoporosis can also be identified at a young age, especially in patients with chronic diseases, disabilities, and on chronic anticonvalsant treatment. Individuals with Rett syndrome (RS) have been found to show signs of osteoporosis at a young age. This condition may cause pathological fractures, inflict pain, and seriously damage mobility. In such cases, the quality of life of the individual and her primary caretakers will be severely hampered. This article reviews the current knowledge of the phenomenon and suggests some clinical directions for the individual with RS who shows signs of osteoporosis. The article also presents novel findings from a screening test of bone strength in 35 individuals with RS at different ages using the Sunlight Omnisense 7000P ultrasound apparatus. The primary results from this investigation showed a strong and significant positive correlation between calcium intake and bone strength (p < 0.0001) as well as bone density Z values (p < 0.005). The occurrence and frequency of fractures were found connected with reduced bone strength in measurements of both the radius (p < 0.0001) and the tibia (p < 0.004) as well as with negative bone strength Z values (p = 0.03). Other findings specified within the content of the article support the implementation of a comprehensive antiosteoporotic preventive management for this population.


Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.
Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.


Cytogenetic and morphometric analysis in the species Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae) from the Iguatemi River Basin, Brazil.
The genus Astyanax is relatively common and encompasses various similar taxa forming a highly complex group that is difficult to precisely delimit. The present study aims to analyze cytogenetically and morphologically specimens of A. altiparanae belonging to distinct populations of the Iguatemi River Basin, Mato Grosso do Sul State, Brazil, for a better understanding of the evolutionary processes in this fish group. This study analysed 32 specimens of Astyanax altiparanae from Iguatemi River basin, MS, Brazil: 24 from the Agua Boa stream and 8 from the Santa Maria stream. All specimens showed a diploid number equal to 50 chromosomes with differences in the karyotypic formula and types of chromosomes bearing the NOR between the two localities. The constitutive heterochromatin showed interstitial markings evident in the region of some chromosomes in both populations. In the morphometric analysis, the first three axes were retained for interpretation which together explained 81% of variance, showing morphometric distinction between populations. Chromosomal and morphometric data obtained may be useful for taxonomic and phylogenetic studies in this group of fish.


Coupled Effect of Ferrous Ion and Oxygen on the Electron Selectivity of Zerovalent Iron for Selenate Sequestration.
Although the electron selectivity (ES) of zerovalent iron (ZVI) for target contaminant and its utilization ratio (UR) decide the removal capacity of ZVI, little effort has been made to improve them. Taking selenate [Se(VI)] as a target contaminant, this study investigated the coupled influence of aeration gas and Fe(II) on the ES and UR of ZVI. Oxygen was necessary for effective removal of Se(VI) by ZVI without Fe(II) addition. Due to the application of 1.0 mM Fe(II), the ES of ZVI was increased from 3.2-3.6% to 6.2-6.8% and the UR of ZVI was improved by 5.0-19.4% under aerobic conditions, which resulted in a 100-180% increase in the Se(VI) removal capacity by ZVI. Se(VI) reduction by Fe0 was a heterogeneous redox reaction, and the enrichment of Se(VI) on ZVI surface was the first step of electron transfer from Fe0 core to Se(VI). Oxygen promoted the generation of iron (hydr)oxides, which facilitated the enrichment of Se(VI) on the ZVI particle surface. Therefore, the high oxygen fraction (25-50%) in the purging gas resulted in only a slight decrease in the ES of ZVI. Fe(II) addition resulted in a pH drop and promoted the generation of lepidocrocite and magnetite, which benefited Se(VI) adsorption and the following electron transfer from underlying Fe0 to surface-located Se(VI).


Downregulation of Cytokines and Chemokines by GB Virus C After Transmission Via Blood Transfusion in HIV-Positive Blood Recipients.
An association between GB virus C (GBV-C) and improved outcomes of human immunodeficiency virus (HIV) infection has been reported in HIV-positive individuals with active GBV-C coinfection. This study provides insights into the immune mechanisms underlying the protective role of GBV-C in HIV-infected patients. The concentrations of 64 cytokines and chemokines were measured in plasma samples obtained from the Viral Activation Transfusion Study cohort before transfusion and longitudinally from 30 patients positive for both HIV and GBV-C (hereafter, "cases") and 30 patients positive for HIV and negative for GBV-C (hereafter, "controls"). Cases had lower HIV viral loads and higher CD4 T-cell counts than controls after acquisition of GBV-C infection. Most of the modulated cytokines and chemokines were reduced after GBV-C detection, including many proinflammatory cytokines, suggesting an overall antiinflammatory effect of GBV-C in HIV-positive subjects. Most pathways and functions of the measured cytokines were downregulated in cases, except cell death pathways, which were upregulated in various cell subsets in the 3 months after GBV-C detection. GBV-C has a protective effect, in part through a competition mechanism leading to decreased inflammation and improved HIV disease outcome in cases. Further studies are necessary to establish whether GBV-C may have deleterious effects on the host at the cellular level, including depleting the cells that are the targets of HIV.


Snapping Knee Syndrome of the Medial Hamstrings.
Snapping of the medial hamstrings is a rare condition, with few cases reported throughout the literature. The snapping sensation reportedly occurs when a hamstring tendon passes over the medial tibial condyle, a muscle belly, or another tendon. The semitendinosus tendon is frequently involved, but concomitant involvement of the semitendinosus and gracilis tendons has also been described. Although the exact etiology remains unclear, authors have theorized that the condition results from a congenital malformation or degradation of the accessory tendinous expansions of the semitendinosus. Whereas most cases resolve with conservative treatments, select cases require surgical intervention. Both the distal surgical release and tendon harvest have proved viable surgical procedures, achieving symptom alleviation with minimal patient morbidity. In this article, a case of medial snapping hamstring tendons involving both the semitendinosus and gracilis tendons is reviewed. A 17-year-old African American girl presented with extreme pain and snapping on the posteromedial aspect of her knee was appreciated. Radiographs were ordered and showed no acute fracture, no acute dislocation, normal medial joint space, normal lateral joint space, and normal patellofemoral space. Conservative and surgical options were reviewed, and the patient elected to undergo harvest of the tendons. Four weeks postoperatively, the patient reported complete resolution of symptoms. To date, there has been no recurrence of symptoms. The authors hope to increase awareness of this condition and add to the existing body of literature.


Fluorination Effects on Indacenodithienothiophene Acceptor Packing and Electronic Structure, End-Group Redistribution, and Solar Cell Photovoltaic Response.
Indacenodithienothiophene (IDTT)-based postfullerene electron acceptors, such as ITIC (2,2'-[[6,6,12,12-tetrakis(4-hexylphenyl)-6,12-dihydrodithieno[2,3- d:2',3'- d']-s-indaceno[1,2- b:5,6- b']dithiophene-2,8-diyl]-bis[methylidyne(3-oxo-1 H-indene-2,1(3 H)-diylidene)]]bis[propanedinitrile]), have become synonymous with high power conversion efficiencies (PCEs) in bulk heterojunction (BHJ) polymer solar cells (PSCs). Here we systematically investigate the influence of end-group fluorination density and positioning on the physicochemical properties, single-crystal packing, end-group redistribution propensity, and BHJ photovoltaic performance of a series of ITIC variants, ITIC- nF ( n = 0, 2, 3, 4, and 6). Increasing n from 0 → 6 contracts the optical bandgap, but only marginally lowers the LUMO for n > 4. This yields enhanced photovoltaic short-circuit current density and good open-circuit voltage, so that ITIC-6F achieves the highest PCE of the series, approaching 12% in blends with the PBDB-TF donor polymer. Single-crystal diffraction reveals that the ITIC- nF molecules cofacially interleave with ITIC-6F having the shortest π-π distance of 3.28 Å. This feature together with ZINDO-level computed intermolecular electronic coupling integrals as high as 57 meV, and B3LYP/DZP-level reorganization energies as low as 147 meV, rival or surpass the corresponding values for fullerenes, ITIC-0F, and ITIC-4F, and track a positive correlation between the ITIC- nF space-charge limited electron mobility and n. Finally, a heretofore unrecognized solution-phase redistribution process between the 2-(3-oxo-indan-1-ylidene)-malononitrile-derived end-groups (EGs) of IDTT-based NFAs, i.e., EG1-IDTT-EG1 + EG2-IDTT-EG2 ⇌ 2 EG1-IDTT-EG2, with implications for the entire ITIC PSC field, is identified and mechanistically characterized, and the effects on PSC performance are assessed.


Design, Intervention Fidelity, and Behavioral Outcomes of a School-Based Water, Sanitation, and Hygiene Cluster-Randomized Trial in Laos.
Evidence of the impact of water, sanitation, and hygiene (WASH) in schools (WinS) interventions on pupil absence and health is mixed. Few WinS evaluations rigorously report on output and outcome measures that allow for comparisons of effectiveness between interventions to be made, or for an understanding of why programs succeed. The Water, Sanitation, and Hygiene for Health and Education in Laotian Primary Schools (WASH HELPS) study was a randomized controlled trial designed to measure the impact of the United Nations Children's Fund (UNICEF) Laos WinS project on child health and education. We also measured the sustainability of intervention outputs and outcomes, and analyzed the effectiveness of group hygiene activities on behavior change and habit formation. Here, we present the design and intermediate results from this study. We found the WinS project improved the WASH environment in intervention schools; 87.8% of schools received the intervention per design. School-level adherence to outputs was lower; on average, schools met 61.4% of adherence-related criteria. The WinS project produced positive changes in pupils' school WASH behaviors, specifically increasing toilet use and daily group handwashing. Daily group hygiene activities are effective strategies to improve school WASH behaviors, but a complementary strategy needs to be concurrently promoted for effective and sustained individual handwashing practice at critical times.


Motor cortical regulation of sparse synergies provides a framework for the flexible control of precision walking.
We have previously described a modular organization of the locomotor step cycle in the cat in which a number of sparse synergies are activated sequentially during the swing phase of the step cycle (Krouchev et al., 2006). Here, we address how these synergies are modified during voluntary gait modifications. Data were analysed from 27 bursts of muscle activity (recorded from 18 muscles) recorded in the forelimb of the cat during locomotion. These were grouped into 10 clusters, or synergies, during unobstructed locomotion. Each synergy was comprised of only a small number of muscles bursts (sparse synergies), some of which included both proximal and distal muscles. Eight (8/10) of these synergies were active during the swing phase of locomotion. Synergies observed during the gait modifications were very similar to those observed during unobstructed locomotion. Constraining these synergies to be identical in both the lead (first forelimb to pass over the obstacle) and the trail (second limb) conditions allowed us to compare the changes in phase and magnitude of the synergies required to modify gait. In the lead condition, changes were observed particularly in those synergies responsible for transport of the limb and preparation for landing. During the trail condition, changes were particularly evident in those synergies responsible for lifting the limb from the ground at the onset of the swing phase. These changes in phase and magnitude were adapted to the size and shape of the obstacle over which the cat stepped. These results demonstrate that by modifying the phase and magnitude of a finite number of muscle synergies, each comprised of a small number of simultaneously active muscles, descending control signals could produce very specific modifications in limb trajectory during locomotion. We discuss the possibility that these changes in phase and magnitude could be produced by changes in the activity of neurones in the motor cortex.


A maternal high-fat, high-sucrose diet has sex-specific effects on fetal glucocorticoids with little consequence for offspring metabolism and voluntary locomotor activity in mice.
Maternal overnutrition and obesity during pregnancy can have long-term effects on offspring physiology and behaviour. These developmental programming effects may be mediated by fetal exposure to glucocorticoids, which is regulated in part by placental 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and 2. We tested whether a maternal high-fat, high-sucrose diet would alter expression of placental 11β-HSD1 and 2, thereby increasing fetal exposure to maternal glucocorticoids, with downstream effects on offspring physiology and behaviour. C57BL/6J mice were fed a high-fat, high-sucrose (HFHS) diet or a nutrient-matched low-fat, no-sucrose control diet prior to and during pregnancy and lactation. At day 17 of gestation, HFHS dams had ~20% lower circulating corticosterone levels than controls. Furthermore, there was a significant interaction between maternal diet and fetal sex for circulating corticosterone levels in the fetuses, whereby HFHS males tended to have higher corticosterone than control males, with no effect in female fetuses. However, placental 11β-HSD1 or 11β-HSD2 expression did not differ between diets or show an interaction between diet and sex. To assess potential long-term consequences of this sex-specific effect on fetal corticosterone, we studied locomotor activity and metabolic traits in adult offspring. Despite a sex-specific effect of maternal diet on fetal glucocorticoids, there was little evidence of sex-specific effects on offspring physiology or behaviour, although HFHS offspring of both sexes had higher circulating corticosterone at 9 weeks of age. Our results suggest the existence of as yet unknown mechanisms that mitigate the effects of altered glucocorticoid exposure early in development, making offspring resilient to the potentially negative effects of a HFHS maternal diet.


Perceived Autonomy Support and Behavioral Engagement in Physical Education: Comment on Yoo (2015).
The role of emotion as moderator of the relationships between perceived autonomy supportive behavior and autonomous motivation and between motivation and behavioral engagement in physical education are discussed.


[Antiestrogen treatment in postmenopausal patients with metastatic breast cancer].
This review discusses the evidence for endocrine treatment in postmenopausal patients with metastatic breast cancer. First line treatment with non-steroid aromatase inhibitors (AI) yields response rates of 30% and improves progression free survival, but not overall survival, compared to tamoxifen. With second line treatment using steroid AI, estrogen antagonists or selective estrogen receptor modulators prolonged disease stabilisation is achieved in 40% of patients. With third line treatment using steroid AI and estrogen antagonists disease stabilisation is achieved in up to 30% of patients.


Assessment of 105 Patients with Angiotensin Converting Enzyme-Inhibitor Induced Angioedema.
Objective. To asses a cohort of 105 consecutive patients with angiotensin converting enzyme-inhibitor induced angioedema with regard to demographics, risk factors, family history of angioedema, hospitalization, airway management, outcome, and use of diagnostic codes used for the condition. Study Design. Cohort study. Methods. This was a retrospective cohort study of 105 patients with angiotensin converting enzyme-inhibitor induced angioedema in the period 1995-2014. Results. The cohort consisted of 67 females and 38 males (F : M ratio 1.8), with a mean age of 63 [range 26-86] years. Female gender was associated with a significantly higher risk of angiotensin converting enzyme-inhibitor induced angioedema. 6.7% had a positive family history of angioedema. Diabetes seemed to be a protective factor with regard to angioedema. 95% experienced angioedema of the head and neck. 4.7% needed intubation or tracheostomy. 74 admissions took place during the study period with a total of 143 days spent in the hospital. The diagnosis codes most often used for this condition were "DT783 Quincke's oedema" and "DT78.4 Allergy unspecified". Complement C1 inhibitor was normal in all tested patients. Conclusion. Female gender predisposes to angiotensin converting enzyme-inhibitor induced angioedema, whereas diabetes seems to be a protective factor.


Telehealth rehabilitation for adults with cochlear implants in response to the Covid-19 pandemic: platform selection and case studies.
Effective information giving and goal setting before cochlear implantation and individualised rehabilitation following implantation are both crucial for shaping patients' expectations and optimising outcomes. The Covid-19 pandemic led to temporary cessation of face to face clinic appointments. This created a need for telehealth rehabilitation for adults whose hearing loss presents unique communication challenges. We describe the piloting and implementation of telehealth rehabilitation within an adult cochlear implant service. Video conferencing and telehealth tools were assessed in terms of security, accessibility and functionality. Written support materials were developed. Telehealth sessions were piloted with lay volunteers. During service implementation, feedback was collected from patients and staff. A video call platform was identified that was supported by the host Trust and also met the rehabilitation service's needs. A telehealth service was successfully implemented, ensuring continuity of care during lockdown. We share the platform selection framework used, practical lessons learned and patient support materials. .Telehealth rehabilitation facilitated a well-received, effective service for adult cochlear implant patients. It is predicted that the benefits of telehealth rehabilitation will last beyond the lockdown restrictions posed by Covid-19.


Optic flow stabilizes flight in ruby-throated hummingbirds.
Flying birds rely on visual cues for retinal image stabilization by negating rotation-induced optic flow, the motion of the visual panorama across the retina, through corrective eye and head movements. In combination with vestibular and proprioceptive feedback, birds may also use visual cues to stabilize their body during flight. Here, we test whether artificially induced wide-field motion generated through projected visual patterns elicits maneuvers in body orientation and flight position, in addition to stabilizing vision. To test this hypothesis, we present hummingbirds flying freely within a 1.2 m cylindrical visual arena with a virtual surround rotated at different speeds about its vertical axis. The birds responded robustly to these visual perturbations by rotating their heads and bodies with the moving visual surround, and by adjusting their flight trajectories, following the surround. Thus, similar to insects, hummingbirds appear to use optic flow cues to control flight maneuvers as well as to stabilize their visual inputs.


Identification of factors differentially associated with isolated impaired fasting glucose and isolated post-load impaired glucose tolerance: the Hong Kong Cardiovascular Risk Factor Study.
The use of fasting and post-prandial glucose levels in the classification of hyperglycaemic states often identifies distinct subjects, but the factors determining these intermediate-isolated glucose intolerant states are yet to be clearly elucidated in Chinese subjects. Representative subjects (n = 2769) were randomly recruited from the Hong Kong Chinese population and glycaemic status was determined using both fasting and 2h 75 g oral glucose tolerance test glucose levels. The relationship between the groups with isolated glucose intolerance and vascular risk factors was investigated using ANOVA and logistic regression analyses. Using either criterion, diabetes was identified in 265 (9.6%) subjects and glucose intolerance in 568 (20.5%) subjects. Of those 568, isolated impaired glucose tolerance (IGT) using the post-load criterion was identified in 49.5% and isolated impaired fasting glucose (IFG) in 30.5%. Ageing and hyperinsulinaemia were common determinants of IGT and IFG; with small hip circumference a marker of poorer early life development and being born in China rather than Hong Kong, a possible low birth weight marker was also associated with IFG. Hypertension, hypertriglyceridaemia and poor education were also associated with IGT. When we looked for factors differentially associated with these glucose intolerant states, female sex, greater hip circumference, high triglyceride levels, low fasting insulin levels, and not being born in China were independently associated with isolated IGT compared with isolated IFG. Despite common antecedents to the glucose intolerant states, isolated IFG appeared to be particularly associated with early life development, and isolated IGT was more strongly associated with obesity-related determinants such as hypertriglyceridaemia.


Nurse-led services.
Continuing our series of reports based on work submitted to the King's Fund database, the following article describes the implementation of nurse-led services in a variety of clinical settings. The initiatives show the need for multidisciplinary and patient involvement in the various stages of development.


Food control systems in Canada.
This paper provides an overview of the responsibilities and jurisdictional boundaries of Health Canada (HC) and Agriculture and Agri-Food Canada (AAFC) with regard to food regulation in Canada. It examines their interagency coordination within the federal structure and with other levels of government, industry, and the consumer. The international developments are considered with the North American Free Trade Agreement (NAFTA) and the Canada, United States Trade Agreement (CUSTA) being regarded as likely to have a significant future impact. The federal food safety and quality system is complex and fragmented. Federal food regulation comes under the jurisdiction of four federal departments: HC, AAFC, Industry Canada (IC), and Fisheries and Oceans Canada (FOC). All four departments are involved with inspection, surveillance, and the analysis of food sold in Canada. In addition, Canada's ten provincial and two territorial governments have provincial-, regional-, municipal-, and local-level governments that also have jurisdiction over food safety and quality. Consideration is first given to the main legislative provision covering food--the Federal Food and Drugs Act. This Act is administered by several of the Federal Government departments. The role of these departments is examined individually along with additional, more specific legal provisions for which responsibility is not divided (in particular, the Canada Agricultural Products [CAP] Act administered by AAFC, and the Consumer Packaging and Labeling Act [CPLA] administered by IC). The various reviews that have taken place in the recent past and those still in progress are considered, and the final part of this paper looks at the international developments that are likely to have a major impact on the future development of the Canadian food control system.


Design and Synthesis of a Zeolitic Organic Framework.
The development of novel zeolite-like materials with large channel windows and high stability is of importance but remains a tremendous challenge. Herein, we report the first example of a 3D covalent organic framework with zeolitic network, namely the zeolitic organic framework (ZOF). By combining two kinds of tetrahedral building blocks with fixed or relatively free bond angles, ZOF-1 with the zeolitic crb net has been successfully synthesized. Its structure was determined by the single-crystal 3D electron diffraction technique. Remarkably, ZOF-1 shows high chemical stability, large pore size (up to 16 Å), and excellent specific surface area (≈2785 m2 g-1 ), which is superior to its analogues with the same network, including traditional aluminosilicate zeolites and zeolitic imidazole frameworks. This study thus opens a new avenue to construct zeolite-like materials with pure organic frameworks and will promote their potential applications in adsorption and catalysis for macromolecules.