Using Remote Communication Technology in Insulin Pump Training: A Feasibility Study.
This feasibility study was designed to examine if remote communication technology can be used in the technical training of an insulin pump in adults with diabetes who were familiar with insulin pump therapy. Surveys were emailed to 69 individuals who purchased an insulin pump and had been trained by the manufacturer's diabetes educators. In consultation with providers, participants were given the choice of receiving training in a face-to-face meeting or via remote communication technology. The survey consisted of 27 questions asking participants' characteristics, device proficiency, confidence, and their satisfaction with the insulin pump and the training method. Differences between the 2 groups were examined using bivariate analyses. There were 17 participants in the remote group and 20 participants in the face-to-face group. Participants had a mean age of 40.9 ± 14.3 years, had diabetes for 24.3 ± 13.8 years, and used an insulin pump for 9.8 ± 4.9 years. The participants in both groups were not statistically different in age, diabetes history, years on insulin pump, device proficiency, confidence, or satisfaction with the training method. The remote group reported less graduate-level education (P < .05) and higher satisfaction scores with the insulin pump training (P < .05). Although this study has limitations associated with the small sample size and self-selection bias, the results suggest that remote communication technology may be an effective tool to provide technical training to adults who are familiar with insulin pump therapy. Additional research is required to determine the effectiveness of the remote insulin pump training.


Microbes to-go: slugs as source for Caenorhabditis elegans microbiota acquisition.
Research on the Caenorhabditis elegans microbiota only recently started, with little known about how C. elegans acquires its microbiota. Slugs live in the same habitat as C. elegans and are known vectors for the worm. Hence, we wondered how the passage through a slug affects the C. elegans gut microbiota and whether worms can acquire bacteria from the slug. Using fluorescently labelled microbiota and 16S rRNA gene amplicon sequencing, we evaluated microbiota persistence and acquisition in C. elegans after slug passage. We compared C. elegans gut microbiomes isolated from wild-caught slugs to the microbiomes of worms after experimental slug passage to compare similarities and differences in microbiome composition. We found that microbiota persists in C. elegans while passing the slug gut and that worms simultaneously acquire additional bacteria species from the slug. Although the amplicon sequencing variant (ASV) richness of worms from the experiment did not exceed the richness of worms that naturally occur in slugs, we found a high number of shared ASVs indicating the importance of commonly associated microbiota. We demonstrate that C. elegans can take advantage of its passage through the slug by acquiring new potential microbiota without losing its native microbiota.


Effects of lipoprotein lipase on uptake and transcytosis of low density lipoprotein (LDL) and LDL-associated alpha-tocopherol in a porcine in vitro blood-brain barrier model.
During the present study the contribution of lipoprotein lipase (LPL) to low density lipoprotein (LDL) holoparticle and LDL-lipid (alpha-tocopherol (alphaTocH)) turnover in primary porcine brain capillary endothelial cells (BCECs) was investigated. The addition of increasing LPL concentrations to BCECs resulted in up to 11-fold higher LDL holoparticle cell association. LPL contributed to LDL holoparticle turnover, an effect that was substantially increased in response to LDL-receptor up-regulation. The addition of LPL increased selective uptake of LDL-associated alphaTocH in BCECs up to 5-fold. LPL-dependent selective alphaTocH uptake was unaffected by the lipase inhibitor tetrahydrolipstatin but was substantially inhibited in cells where proteoglycan sulfation was inhibited by treatment with NaClO(3). Thus, selective uptake of LDL-associated alphaTocH requires interaction of LPL with heparan-sulfate proteoglycans. Although high level adenoviral overexpression of scavenger receptor BI (SR-BI) in BCECs resulted in a 2-fold increase of selective LDL-alphaTocH uptake, SR-BI did not act in a cooperative manner with LPL. Although the addition of LPL to BCEC Transwell cultures significantly increased LDL holoparticle cell association and selective uptake of LDL-associated alphaTocH, holoparticle transcytosis across this porcine blood-brain barrier (BBB) model was unaffected by the presence of LPL. An important observation during transcytosis experiments was a substantial alphaTocH depletion of LDL particles that were resecreted into the basolateral compartment. The relevance of LPL-dependent alphaTocH uptake across the BBB was confirmed in LPL-deficient mice. The absence of LPL resulted in significantly lower cerebral alphaTocH concentrations than observed in control animals.


A case of type 1 multiple endocrine neoplasia with esophageal stricture successfully treated with endoscopic balloon dilation and local steroid injection combined with surgical resection of gastrinomas.
In type 1 multiple endocrine neoplasia (MEN1), esophageal diseases association with excessive gastrin secretion in Zollinger-Ellison syndrome (ZES) sometimes develop. Here, we reported a case of MEN1/ZES, who developed dysphagia due to reflux esophagitis with severe esophageal stricture. Treatment for his esophageal stricture and ZES was discussed. A 43-year-old man with progressive dysphagia and diarrhea was referred to the teaching hospital. He had a history of recurrent duodenojejunal perforations despite the anti-secretory medication. Blood examinations revealed elevated serum gastrin, calcium, and parathyroid hormone. Upper gastrointestinal endoscopy demonstrated a severe esophageal stricture, multiple gastroduodenal ulcer scars, and a duodenal submucosal tumor. Enhanced computed tomography showed multiple hypervascular tumors within the pancreas and duodenum, suggestive of MEN1. Genetic examination demonstrated a pathogenic MEN1 mutation. Repetitive endoscopic esophageal dilatation with intralesional corticosteroid injection, coupled with pancreatoduodenectomy were performed to improve the patient's symptoms and to treat pancreatic tumors. The histology of multiple tumors in the duodenum and pancreas were all consistent with neuroendocrine tumors. His hypergastrinemia subsided and he remained asymptomatic in his gastrointestinal tract after these treatments. For esophageal stenosis in case of MEN1/ZES, anti-secretory therapy and endoscopic dilatation with corticosteroid injection could be recommended. However, in refractory cases with repetitive and/or severe complications due to high acid secretion, surgical treatment could be considered as an option.


An RNA binding protein promotes axonal integrity in peripheral neurons by destabilizing REST.
The RE1 Silencing Transcription Factor (REST) acts as a governor of the mature neuronal phenotype by repressing a large consortium of neuronal genes in non-neuronal cells. In the developing nervous system, REST is present in progenitors and downregulated at terminal differentiation to promote acquisition of mature neuronal phenotypes. Paradoxically, REST is still detected in some regions of the adult nervous system, but how REST levels are regulated, and whether REST can still repress neuronal genes, is not known. Here, we report that homeostatic levels of REST are maintained in mature peripheral neurons by a constitutive post-transcriptional mechanism. Specifically, using a three-hybrid genetic screen, we identify the RNA binding protein, ZFP36L2, associated previously only with female fertility and hematopoiesis, and show that it regulates REST mRNA stability. Dorsal root ganglia in Zfp36l2 knock-out mice, or wild-type ganglia expressing ZFP36L2 shRNA, show higher steady-state levels of Rest mRNA and protein, and extend thin and disintegrating axons. This phenotype is due, at least in part, to abnormally elevated REST levels in the ganglia because the axonal phenotype is attenuated by acute knockdown of REST in Zfp36l2 KO DRG explants. The higher REST levels result in lower levels of target genes, indicating that REST can still fine-tune gene expression through repression. Thus, REST levels are titrated in mature peripheral neurons, in part through a ZFP36L2-mediated post-transcriptional mechanism, with consequences for axonal integrity.


Pine needle abortion biomarker detected in bovine fetal fluids.
Pine needle abortion is a naturally occurring condition in free-range cattle caused by the consumption of pine needles from select species of cypress, juniper, pine, and spruce trees. Confirmatory diagnosis of pine needle abortion has previously relied on a combined case history of pine needle consumption and detection of isocupressic acid in a sample from the dam. Stable metabolites of isocupressic acid include agathic acid, dihydroagathic acid, and tetrahydroagathic acid, which have been shown to be present in the serum of mature animals for a few days following consumption of pine needles. As maternal serum is infrequently submitted for diagnosis of cattle abortions, a diagnostic assay capable of confirming isocupressic acid exposure in other matrices would be desirable. To the authors' knowledge, no previous investigations have indicated whether these stable metabolites of isocupressic acid cross the placenta or are detectable in fetal tissues. Therefore, the presence of agathic acid, dihydroagathic acid, and tetrahydroagathic acid was evaluated using gas chromatography-mass spectroscopy on fetal thoracic fluid and stomach contents collected from 2 aborted bovine fetuses with a recent herd history of pine needle consumption by the dams and a subsequent abortion outbreak in the herd. Only tetrahydroagathic acid was detected in the fetal thoracic fluid and fetal stomach contents. The current study encourages diagnosticians to collect fetal thoracic fluids to permit the detection of tetrahydroagathic acid in cases of suspected pine needle abortion.


[Clinical viewpoints of hemodynamics in cardiac arrhythmias and during anti-arrhythmia treatment].
1. Hemodynamics during cardiac arrhythmias: Cardiac syncopes can be caused by bradycardia (temporary asystole) or by tachycardia. However, tachycardia might be tolerated without causing such symptoms. The necessary compensatory mechanisms (as initiated from the heart, the circulatory system, and the metabolism) are incompletely understood in man. The tolerance of tachycardia depends on the underlying cardiac disease, heart rate, and duration of tachycardia, as well as on the efficiency of compensatory mechanisms. The aspects of tachycardia tolerance, presented here by hemodynamic analysis, include: atrial transport, ventricular tachycardia (arterial pressure, coronary flow, coronary reserve, extravascular resistance), syncopal ventricular tachycardia, supraventricular tachycardia, tachycardia in aortic valvular stenosis, the AFORMED phenomenon, arrhythmia effects on valvular heart disease, and perfusion of organic systems. 2. Hemodynamics during antiarrhythmic therapy: The cardiodepressive side effects inherent in virtually all antiarrhythmic (AA) drugs are complex, variable, and cannot be accurately differentiated as to their components by using conventional hemodynamic parameters. As a rule, this cardiodepression is effective only in cases of impaired myocardial function and/or increased vagal tone. These unwanted hemodynamic effects might influence LV-pump function directly (myocardium: negative inotrope) and indirectly (vasoactive, neurohumoral-reflectory: changes of pre and/or afterload, and of heart rate). The identification of the potentially participating negative inotropic action of the AA-induced cardiodepression, therefore, was accomplished using the elaborate method of analyzing the endsystolic pressure-volume relationship (conductance-catheter technique). The temporary balloon occlusion in the vena cava inferior was used to establish the equation of the isometric maxima. AA-induced alterations of the diastolic ventricular function used echocardiographic data for analysis.


Potassium Phthalocyanine, KPc: one-dimensional molecular stacks bridged by K+ ions.
We report the synthesis of potassium phthalocyanine (KPc) and its structural characterization by synchrotron X-ray powder diffraction. We find that while KPc adopts the beta-polymorphic structural type (monoclinic space group P21/a) common for many MPc solids, its structure is characterized by unique features. The K+ ions, which are statistically disordered over two symmetry-equivalent positions, reside in the intrastack spacing of the rodlike molecular assemblies and strongly bond equidistantly to selected N atoms of the two neighboring Pc rings along the chain direction with an unusual 5-fold coordination. The K+-stuffed slipped stacks of Pc units display much greater intrastack and slippage distances than those of other beta-MPc polymorphs. They may be thought as comprising disordered dimeric (Pc)22- units; this leads to electron pairing and is consistent with the observed nonmagnetic response of the system.


Conducting Interface in Oxide Homojunction: Understanding of Superior Properties in Black TiO2.
Black TiO2 nanoparticles with a crystalline core and amorphous-shell structure exhibit superior optoelectronic properties in comparison with pristine TiO2. The fundamental mechanisms underlying these enhancements, however, remain unclear, largely due to the inherent complexities and limitations of powder materials. Here, we fabricate TiO2 homojunction films consisting of an oxygen-deficient amorphous layer on top of a highly crystalline layer, to simulate the structural/functional configuration of black TiO2 nanoparticles. Metallic conduction is achieved at the crystalline-amorphous homointerface via electronic interface reconstruction, which we show to be the main reason for the enhanced electron transport of black TiO2. This work not only achieves an unprecedented understanding of black TiO2 but also provides a new perspective for investigating carrier generation and transport behavior at oxide interfaces, which are of tremendous fundamental and technological interest.


Neurologic complications of graft-versus-host disease.
BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.


The association of ABO and Rhesus blood groups with the occurrence of type 2 diabetes mellitus: A comparative cross-sectional study.
Type 2 diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated levels of glucose in circulation which result from insufficient insulin or insulin resistance. The blood group of an individual is thought to be genetically predetermined and plays a vital role in increasing susceptibility to DM for particular blood groups. Therefore, this study aimed to determine the association between ABO and Rhesus blood groups with type 2 DM. A comparative cross-sectional study was conducted on 326 participants (163 type 2 DM patients and 163 age and sex-matched healthy individuals). Socio-demographic data were collected using a semi-structured questionnaire while Clinical data were extracted from the patient chart. A blood sample was collected from each study participant for ABO and Rhesus blood grouping. Chi-square test, bivariable, and multivariable logistic regression analysis were employed to indicate the association between different blood group types and type 2 DM. The current result showed that blood group O had the highest frequency among all study participants followed by blood groups B, A, and AB. Blood groups B and A were more common in the type 2 DM group compared with the control group while blood groups O and AB were more frequent in the control group. A chi-square test indicated that the ABO blood group had a significant association with type 2 DM while the Rhesus blood group was not associated with type 2 DM. Moreover, logistic regression analysis showed that B and O blood groups had a significant association with type 2 DM while A and AB blood groups had no association. The findings of this study indicated that type 2 DM has an association with the ABO blood group and has no association with the Rhesus blood group. Individuals with blood group B have a higher risk of developing T2DM (type II DM) as compared to other ABO blood groups.


The Effects of Task Type on Time to Task Failure During Fatigue: A Modified Sørensen Test.
Understanding mechanisms of fatigue of the trunk extensors is important because fatigue is a major factor in predicting incidence of low back pain, but few studies have examined trunk extensor fatigue muscles using differing load types and measured the amplitude and frequency domain of the electromyographic signal to explain these differences. Sixteen healthy participants performed position- and force-matching fatigue tasks in a modified Sørensen test position. Time to task failure was significantly longer during the position-matching task compared to force-matching task (58.3 ± 6.6 min vs. 36.1 ± 5.4 min). This finding is the opposite of that commonly reported for the appendicular muscle, but the mean power frequency shifts and muscle activation patterns of the trunk and hip extensors did not explain this difference. The mean power frequency shifts and muscle activation patterns of the trunk and hip extensors did not explain this difference. The greater time to task failure during the position-matching task may reflect adaptation of the trunk extensor muscles to optimize maintaining specific joint angles more so than specific loads.


MSCHLMDA: Multi-Similarity Based Combinative Hypergraph Learning for Predicting MiRNA-Disease Association.
Accumulating biological and clinical evidence has confirmed the important associations between microRNAs (miRNAs) and a variety of human diseases. Predicting disease-related miRNAs is beneficial for understanding the molecular mechanisms of pathological conditions at the miRNA level, and facilitating the finding of new biomarkers for prevention, diagnosis and treatment of complex human diseases. However, the challenge for researchers is to establish methods that can effectively combine different datasets and make reliable predictions. In this work, we propose the method of Multi-Similarity based Combinative Hypergraph Learning for Predicting MiRNA-disease Association (MSCHLMDA). To establish this method, complex features were extracted by two measures for each miRNA-disease pair. Then, K-nearest neighbor (KNN) and K-means algorithm were used to construct two different hypergraphs. Finally, results from combinative hypergraph learning were used for predicting miRNA-disease association. In order to evaluate the prediction performance of our method, leave-one-out cross validation and 5-fold cross validation was implemented, showing that our method had significantly improved prediction performance compared to previously used methods. Moreover, three case studies on different human complex diseases were performed, which further demonstrated the predictive performance of MSCHLMDA. It is anticipated that MSCHLMDA would become an excellent complement to the biomedical research field in the future.


White Matter Hyperintensities on Brain Magnetic Resonance Imaging in People with Epilepsy: A Hospital-Based Study.
We aim to explore whether people with epilepsy have increased white matter hyperintensities (WMHs). Eligible patients were categorized into newly diagnosed epilepsy (NE) and chronic epilepsy (CE); the latter were subdivided to those treated with enzyme-inducing antiepileptic drugs (EIAEDs) with or without non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those with NEIAEDs only. WMHs were measured using age-related white matter changes (ARWMC) scale and compared between patients and healthy control group. Higher scores indicate greater WMH changes. The strengths of associations were estimated as incidence rate ratios (IRRs) with 95% confidence interval (CI). A total of 217 patients were included in the analysis, of whom 67 had NE, 45 had CE treated with NEIAEDs, and 105 had CE treated with EIAEDs. Age was positively associated with ARWMC score (IRR per year, 1.03; 95%CI, 1.03-1.04, P < 0.001). Compared with the healthy control group (n = 23), all patient groups had higher ARWMC score (P < 0.05). The difference was greatest in patients receiving EIAEDs (IRR, 2.13; 95%CI, 1.22-3.70, P = 0.007). WMHs tended to be observed in people with epilepsy, especially in those treated with EIAEDs. People with epilepsy with white matter changes should be evaluated for stroke risk, particularly if they are receiving EIAEDs.


Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly.
Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients' blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of FBN2 and ANKRD11 in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.


Astaxanthin and β-carotene in Helicobacter pylori-induced Gastric Inflammation: A Mini-review on Action Mechanisms.
Helicobacter pylori is a dominant bacterium living in the human gastric tissues. In H. pylori-infected tissues, the infiltrated inflammatory cells produce reactive oxygen species (ROS), leading to gastric inflammation with production of various mediators. According to numerous epidemiological studies, dietary carotenoids may prevent gastric inflammation due to their antioxidant properties. Recent studies showed that antioxidant and anti-inflammatory effects of astaxanthin and β-carotene may contribute to inhibition of H. pylori-induced gastric inflammation. Astaxanthin changes H. pylori-induced activation of T helper cell type 1 response towards T helper cell type 2 response in the infected tissues. Astaxanthin inhibits the growth of H. pylori. Even though astaxanthin reduces H. pylori-induced gastric inflammation, it does not reduce cytokine levels in the infected tissues. β-Carotene suppresses ROS-mediated inflammatory signaling, including mitogen-activated protein kinases and redox-sensitive transcription factors, and reduces expression of inflammatory mediators, including interleukin-8, inducible nitric oxide synthase, and cyclooxygenase-2 in the infected tissues. Therefore, consumption of astaxanthin- and β-carotene-rich foods may be beneficial to prevent H. pylori-induced gastric inflammation. This review will summarize anti-inflammatory mechanisms of astaxanthin and β-carotene in H. pylori-mediated gastric inflammation.


Modeling the effect of temperature on growth of Salmonella in chicken.
Growth data of Salmonella in chicken were collected at several isothermal conditions (10, 15, 20, 25, 28, 32, 35, 37, 42, and 45 degrees C) and were then fitted into primary models, namely the logistic model, modified Gompertz model and Baranyi model. Measures of goodness-of-fit such as mean square error, pseudo-R(2), -2 log likelihood, Akaike's information, and Sawa's Bayesian information criteria were used for comparison for these primary models. Based on these criteria, modified Gompertz model described growth data the best, followed by the Baranyi model, and then the logistic model. The maximum growth rates obtained from each primary model were then modeled as a function of temperature using the modified Ratkowsky model. Pseudo-R(2) values for this secondary model describing growth rate obtained from Baranyi, modified Gompertz, and logistic models were 0.999, 0.980, and 0.990, respectively. Mean square error values for corresponding models were 0.0002, 0.0008, and 0.0009, respectively. Both measures clearly show that the Baranyi model performed better than the modified Gompertz model or the logistic model.


Percutaneous valve stent insertion to correct the pulmonary regurgitation: an animal feasibility study.
Pulmonary regurgitation leads to progressive right ventricular dysfunction, susceptibility to arrhythmias, and sudden cardiac death. Percutaneous valve replacement has been developed in recent years, providing patients with an alternative option. Percutaneous pulmonary valve replacement has been recently introduced into clinical practice. The goal of this study was to evaluate the feasibility of percutaneous valve stent insertion to correct the pulmonary regurgitation in sheep using a cup-shaped valve stent. Pulmonary regurgitation was created by percutaneous cylindrical stent insertion in native pulmonary annulus of 8 sheep. One month after the initial procedure, the sheep with previous cylindrical stent implanted underwent the same implantation procedure of pulmonary valve stent. The valve stent consisted of a cup-shaped stent and pericardial valves. Hemodynamic assessments of the bioprosthetic pulmonary valve were obtained by echocardiography at immediately post-implant and at 2 months follow up. Successful transcatheter cylindrical stent insertion was performed in 7 sheep but failed in 1 sheep because the cylindrical stent was released to right ventricle outflow tract. After one month the 7 sheep with pulmonary regurgitation underwent valve stent implantation successfully. Echocardiography confirmed the stents were in desired position during the follow-up. No evidence of pulmonary valve insufficiency occurred in any animals. Echocardiography showed all heart function markers were normal. Percutaneous cylindrical stent insertion to induce significant pulmonary regurgitation in sheep was feasible, simple and reproducible. Percutaneous pulmonary valve stent implantation can reduce pulmonary regurgitation in a sheep model. Further development of animal model and clinical trials are warranted.


Detection of the hepatitis B virus (HBV) covalently-closed-circular DNA (cccDNA) in mice transduced with a recombinant AAV-HBV vector.
Hepatitis B Virus (HBV) persists in infected hepatocytes as an episomal covalently-closed-circular DNA mini-chromosome, called cccDNA. As the main nuclear transcription template, HBV cccDNA is a key replication intermediate in the viral life cycle. Little is known about the mechanisms involved in its formation, maintenance and fate under antiviral therapies. This is mainly due to the lack of small immune-competent animal models able to recapitulate the entire HBV replication cycle, including formation of HBV cccDNA. Here we report that HBV cccDNA can be detected by Southern blot analyses in the liver of C57BL6 mice transduced with AAV-HBV. HBV cccDNA persists in the liver of these animals together with the AAV-HBV episome. We also set up a PCR strategy to distinguish the HBV cccDNA from the AAV-HBV episome. These suggest that the AAV-HBV/mouse model might be relevant to test drugs targeting HBV cccDNA regulation and persistence.


The role of the gut microbiota in schizophrenia: Current and future perspectives.
Schizophrenia is a poorly understood chronic disease. Its pathophysiology is complex, dynamic, and linked to epigenetic mechanisms and microbiota involvement. Nowadays, correlating schizophrenia with the environment makes sense owing to its multidimensional implications: temporal and spatial variability. Microbiota involvement and epigenetic mechanisms are factors that are currently being considered to better understand another dimension of schizophrenia. This review summarises and discusses currently available information, focussing on the microbiota, epigenetic mechanisms, technological approaches aimed at performing exhaustive analyses of the microbiota, and psychotherapies, to establish future perspectives. The connection between the microbiota, epigenetic mechanisms and technological developments allows for formulating new approaches objectively oriented towards the development of alternative psychotherapies that may help treat schizophrenia. In this review, the gut microbiota and epigenetic mechanisms were considered as key regulators, revealing a potential new aetiology of schizophrenia. Likewise, continuous technological advances (e.g. culturomics), aimed at the microbiota-gut-brain axis generate new evidence on this concept.


[Effects of radiotherapy on lymphocyte populations in lung cancer].
The authors report on the results of the immune monitoring of a study population of 31 patients with lung cancer who were treated with radiotherapy. A synthetic thymic pentapeptide, thymopentin, was employed whose effect was evaluated on the immunological parameters analyzed. After radiotherapy, a considerable and homogeneous decrement was observed in several lymphocytic subsets (less sensible in activated T-cells), together with a progressive decrement in the helper/suppressor ratio, in the long run. Monocytes and null cells showed more radioresistance. Thymopentin had no influence on the tested immunological parameters up to 6 months after radiotherapy; later on, a slightly more balanced helper/suppressor ratio could be noticed in the surviving patients who had been treated with thymopentin.


[Ultrasound diagnosis of omphalocele during the first trimester of pregnancy (author's transl)].
Ventral defects in the fetus occur in 1/3200 to 1/10,000 deliveries. Prognosis for the newborn is mostly fatal since these anomalies are frequently combined with other congenital anomalies. A through ultrasound study of the fetus in its longitudinal and transverse diameter permits the antenatal diagnosis of this severe fetal anomaly. The earliest diagnosis of the fetal omphalocele in the first trimester of pregnancy is described in detail in this paper.


Improving uptake of Fracture Prevention drug treatments: a protocol for Development of a consultation intervention (iFraP-D).
Prevention of fragility fractures, a source of significant economic and personal burden, is hindered by poor uptake of fracture prevention medicines. Enhancing communication of scientific evidence and elicitation of patient medication-related beliefs has the potential to increase patient commitment to treatment. The Improving uptake of Fracture Prevention drug treatments (iFraP) programme aims to develop and evaluate a theoretically informed, complex intervention consisting of a computerised web-based decision support tool, training package and information resources, to facilitate informed decision-making about fracture prevention treatment, with a long-term aim of improving informed treatment adherence. This protocol focuses on the iFraP Development (iFraP-D) work. The approach to iFraP-D is informed by the Medical Research Council complex intervention development and evaluation framework and the three-step implementation of change model. The context for the study is UK fracture liaison services (FLS), which enact secondary fracture prevention. An evidence synthesis of clinical guidelines and Delphi exercise will be conducted to identify content for the intervention. Focus groups with patients, FLS clinicians and general practitioners and a usual care survey will facilitate understanding of current practice, and investigate barriers and facilitators to change. Design of the iFraP intervention will be informed by decision aid development standards and theories of implementation, behaviour change, acceptability and medicines adherence. The principles of co-design will underpin all elements of the study through a dedicated iFraP community of practice including key stakeholders and patient advisory groups. In-practice testing of the prototype intervention will inform revisions ready for further testing in a subsequent pilot and feasibility randomised trial. Ethical approval was obtained from North West-Greater Manchester West Research Ethics Committee (19/NW/0559). Dissemination and knowledge mobilisation will be facilitated through national bodies and networks, publications and presentations. researchregistry5041.


Immunomagnetic isolation of primordial germ cells and the establishment of embryonic germ cell lines in the mouse.
The stage-specific embryonic antigen 1 (SSEA-1) is a cell marker of primordial germ cells (PGCs). In the present study, it is shown that isolation and purification of PGCs from 8.5-11.5 days post coitum (dpc) embryos can be achieved by a immunomagnetic cell sorting method using SSEA-1 antibody-conjugated magnetic beads, and then the sorted PGCs can be used for long-term culture under strict culture conditions to derive embryonic germ (EG) cell lines. Five independent EG cell lines with male karyotypes have been established. They show both a strong alkaline phosphatase activity and expression of the SSEA-1 antigen, and are karyotypically stable with a modal number of chromosomes in more than 80% of the cells. One of the EG cell lines from 8.5-dpc embryos produced chimeras after injections of the cells into 8-cell host embryos. These procedures could provide a useful and simple method for isolation of undifferentiated cells from a heterogeneous cell population and for establishment of embryo-derived stem cell lines.


In-vessel composting of household wastes.
The process of composting has been studied using five different types of reactors, each simulating a different condition for the formation of compost; one of which was designed as a dynamic complete-mix type household compost reactor. A lab-scale study was conducted first using the compost accelerators culture (Trichoderma viridae, Trichoderma harzianum, Trichorus spirallis, Aspergillus sp., Paecilomyces fusisporus, Chaetomium globosum) grown on jowar (Sorghum vulgare) grains as the inoculum mixed with cow-dung slurry, and then by using the mulch/compost formed in the respective reactors as the inoculum. The reactors were loaded with raw as well as cooked vegetable waste for a period of 4 weeks and then the mulch formed was allowed to maturate. The mulch was analysed at various stages for the compost and other environmental parameters. The compost from the designed aerobic reactor provides good humus to build up a poor physical soil and some basic plant nutrients. This proves to be an efficient, eco-friendly, cost-effective, and nuisance-free solution for the management of household solid wastes.


Global decline of bumblebees is phylogenetically structured and inversely related to species range size and pathogen incidence.
Conservation biology can profit greatly from incorporating a phylogenetic perspective into analyses of patterns and drivers of species extinction risk. We applied such an approach to analyse patterns of bumblebee (Bombus) decline. We assembled a database representing approximately 43% of the circa 260 globally known species, which included species extinction risk assessments following the International Union fo Conservation of Nature Red List categories and criteria, and information on species traits presumably associated with bumblebee decline. We quantified the strength of phylogenetic signal in decline, range size, tongue length and parasite presence. Overall, about one-third of the assessed bumblebees are declining and declining species are not randomly distributed across the Bombus phylogeny. Susceptible species were over-represented in the subgenus Thoracobombus (approx. 64%) and under-represented in the subgenus Pyrobombus (approx. 6%). Phylogenetic logistic regressions revealed that species with small geographical ranges and those in which none of three internal parasites were reported (i.e. Crithidia bombi, Nosema spp. or Locustacarus buchneri) were particularly vulnerable. Bumblebee evolutionary history will be deeply eroded if most species from threatened clades, particularly those stemming from basal nodes, become finally extinct. The habitat of species with restricted distribution should be protected and the importance of pathogen tolerance/resistance as mechanisms to deal with pathogens needs urgent research.


Advances in improving the biotechnological application of oleaginous fungus Mortierella alpina.
Mortierella alpina is an oleaginous filamentous fungus with considerable lipid productivity, and it has been widely used for industrial production of arachidonic acid. The fermentation process of M. alpina is complicated and can be affected by various factors; therefore, a comprehensive knowledge of its metabolic characteristics and key factors governing lipid biosynthesis is required to further improve its industrial performance. In this review, we discuss the metabolic features and extracellular factors that affect lipid biosynthesis in M. alpina. The current progress in fermentation optimisation and metabolic engineering to improve lipid yield are also summarised. Moreover, we review the applications of M. alpina in the food industry and propose fermentation strategies for better utilisation of this genus in the future. In our opinion, the economic performance of M. alpina should be enhanced from multiple levels, including strains with ideal traits, efficient fermentation strategies, controllable fermentation costs, and competitive products of both high value and productivity. By reviewing the peculiarities of M. alpina and current progress to improve its suitability for biotechnological production, we wish to provide more efficient strategies for future development of M. alpina as a high-value lipid cell factory. KEY POINTS: • Understanding M. alpina metabolism is helpful for rational design of its fermentation processes. • Nitrogen source is a key point that affects PUFA's component and fermentation cost in M. alpina. • Dynamic fermentation strategy combined with breeding is needed to increase lipid yield in M. alpina.


[Diabetic emergencies].
Based on case reports pathogenesis and treatment of the following diabetic emergencies were discussed: 1. The hyperosmolar non-ketotic coma without or with only modest ketosis occurring mainly in type II diabetics and the severe ketoacidosis with or without disturbed consciousness occurring mainly in type I diabetics are the two forms of severe metabolic decompensation of diabetes mellitus. 2. Severe hypoglycaemia may be caused by treatment with sulfonylureas and insulin. 3. The most dangerous life threatening adverse effect of biguanides is lactic acidosis. The incidence of ketoacidosis is about 1-5% in type I diabetics with a mortality of 3-9%. Mortality rates of hyperosmolar non-ketotic comas are much higher, approaching 20-40%, and are explained by severe concomitant complications and older age. The most important triggering factors of diabetic coma are infections, insulin dispensing errors and non-compliance. Carefully instructing patients about the risks of loosing appetite and vomiting as early signs of ketoacidosis is essential. Adequate replacement of fluid, electrolyte and water are the most important therapeutical aspects of ketoacidosis and hyperosmolar non-ketotic coma. Early diagnosis and appropriate treatment of infection by antibiotics are important. Complication of therapy (hypokalemia, hypovolemia and rapid full of oncotic pressure) should be avoided by clinical and laboratory monitoring. Treatment of acidosis with bicarbonate has been found more dangerous than useful. Severe hypoglycaemia is the most important and most dangerous side effect of sulfonylurea and insulin. The incidence of severe hypoglycaemia under glibenclamide ist 3-5 fold higher than under treatment with tolbutamide or glibornurid. Glibenclamide should not be recommended anymore. Longterm experience of the therapeutic security of new sulfonylurea derivates like glimepirid is lacking. Blood-glucose-measurements in the afternoon are important for recognizing disposition to sulfonylurea hypoglycaemia, because at this time the blood-glucose-values tend to be lower than in the morning fasting state. Under insulin treatment the following risk factors for severe hypoglycaemia need to be considered: metabolic control in the near normal range, intensified treatment with rapidly decreasing HbA1c-levels, impaired renal function, unawareness o hypoglycaemia. When the renal function is impaired, biguanide treatment is not indicated because of the risk of lactic acidosis. Most of the diabetic emergency situations are avoidable by proper education of the patients.


Placebo interventions for nausea: a systematic review.
Expectancy often predicts nausea, but the extent to which placebo interventions can alter nausea is less clear. We conducted a systematic review to determine 1) if placebo interventions can affect nausea and 2) which features of these interventions are effective. Articles were identified via PsychInfo, Medline, and PubMed databases. We targeted instructional and conditioning interventions aimed at altering nausea via the placebo effect. Fourteen studies were identified, nine instructional and five conditioning. Many found evidence suggesting that placebo interventions could alter nausea, but a few found no evidence or 'reverse' effects. Effective interventions tended to be those that were aimed at participants with high initial expectancies, with evidence that combined or conditioning manipulations were more effective than instructions. These findings suggest that placebo interventions can alter nausea and that these may serve as a useful way of reducing the burden of nausea in practice.


Detection of Abrin by Electrochemiluminescence Biosensor Based on Screen Printed Electrode.
For the convenience of fast measurement in the outdoor environment, a portable electrochemiluminescence biosensor with the screen-printed electrode as the reaction center was developed, which possesses the characteristics of high sensitivity, small scale, simplified operation and so on, and has been used for in situ detection of abrin. First, combining with magnetic separation technique, the "biotin-avidin" method was used to immobilize the polyclonal antibody (pcAb) on the magnetic microspheres surface as the capture probe. Secondly, the Ru(bpy)₃2+-labeled monoclonal antibody (mcAb) was used as the specific electrochemiluminescence signal probe. Then, the "mcAb-toxin-pcAb" sandwich model was built to actualize the quantitative detection of abrin on the surface of the screen-printed electrode. The linear detection range was 0.5-1000 ng/mL; the regression equation was Y = 89.251lgX + 104.978 (R = 0.9989, n = 7, p < 0.0001); and the limit of detection (LOD) was 0.1 ng/mL. The sensing system showed high sensitivity, excellent specificity and good anti-interference ability, and could be used for the analysis of trace abrin in various environmental samples with good recovery and reproducibility. Compared with the traditional electrochemiluminescence sensing device, its miniaturization and portability gives it potential to satisfy the requirement of in situ detection.


2,4-Bis(4-propoxyphen-yl)-3-aza-bicyclo-[3.3.1]nonan-9-one.
In the title compound, C(26)H(33)NO(3), a crystallographic mirror plane bis-ects the mol-ecule (two C atoms, one O atom and one N atom lie on the mirror plane). The mol-ecule exists in a twin-chair conformation with equatorial orientations of the 4-propoxyphenyl groups. The dihedral angle between the 4-propoxyphenyl groups is 31.58 (3)°.


Characterization of the Pseudomonas aeruginosa T6SS PldB immunity proteins PA5086, PA5087 and PA5088 explains a novel stockpiling mechanism.
The bacterial type VI secretion system (T6SS) secretes many toxic effectors to gain advantage in interbacterial competition and for eukaryotic host infection. The cognate immunity proteins of these effectors protect bacteria from their own effectors. PldB is a T6SS trans-kingdom effector in Pseudomonas aeruginosa that can infect both prokaryotic and eukaryotic cells. Three proteins, PA5086, PA5087 and PA5088, are employed to suppress the toxicity of PldB-family proteins. The structures of PA5087 and PA5088 have previously been reported, but the identification of further distinctions between these immunity proteins is needed. Here, the crystal structure of PA5086 is reported at 1.90 Å resolution. A structural comparison of the three PldB immunity proteins showed vast divergences in their electrostatic potential surfaces. This interesting phenomenon provides an explanation of the stockpiling mechanism of T6SS immunity proteins.


Protein S deficiency presenting as deep vein thrombosis--a case report.
A rare case of spontaneous bilateral internal jugular vein (IJV) thrombosis is presented in absence of oral infection, malignancy, or intervention. Swelling of face, neck, and both upper limbs developed in a 30-year-old man 1 month before admission and after 4 weeks of use of nonpadded crutches. Computed tomography of the neck showed thrombus occluding both internal jugular veins extending to the opening of the superior vena cava. Protein S activity was found to be 30.3%, less than half of the lower limit of normal. Fibrinogen was 450 mg%, higher than normal. Protein C and antithrombin III were normal. The patient was treated conservatively, and discharged on aspirin 150 mg/day. Follow-up after 3 months showed no complications. It was concluded that the outcome in IJV thrombosis, caused by protein S deficiency, is usually good. The advantage of being aware of diagnosis is that physician can be more vigilant for potential complications and treat them earlier.


Levels of the antimicrobial proteins lactoferrin and chromogranin in the saliva of individuals with oral dryness.
Many individuals in an aging society experience oral dryness. Maintaining the flow of saliva and the presence of antimicrobial substances is important to maintain oral health. The inhibition of the secretion of antimicrobial substances could lead to oral dryness. The purpose of this study was to evaluate the antimicrobial substances lactoferrin and chromogranin A in the saliva of elderly individuals with oral dryness. The study included 25 controls and 28 participants with subjective oral dryness. The levels of lactoferrin and chromogranin A were determined in unstimulated whole saliva with an enzyme-linked immunosorbent assay method. The differences in secretion of lactoferrin and chromogranin A between the controls and the participants with oral dryness were analyzed with the Mann-Whitney U test (α=.05). The flow rate of lactoferrin and chromogranin A was lower in the group of participants with oral dryness (lactoferrin, 7.43 ±7.08 ng/min; chromogranin A, 0.24 ±0.24 ng/min) than in the control group (lactoferrin, 21.52 ±7.67 ng/min; chromogranin A, 0.97 ±0.69 ng/min) (P<.01). The ratio of both antimicrobial proteins to total protein was also lower in participants with oral dryness than in the controls. The results of this study indicated that the levels of lactoferrin and chromogranin A were lower in those with oral dryness. A reduction in the secretion of these antimicrobial substances may be associated with oral dryness.


Loss of predator species, not intermediate consumers, triggers rapid and dramatic extinction cascades.
Ecological networks are tightly interconnected, such that loss of a single species can trigger additional species extinctions. Theory predicts that such secondary extinctions are driven primarily by loss of species from intermediate or basal trophic levels. In contrast, most cases of secondary extinctions from natural systems have been attributed to loss of entire top trophic levels. Here, we show that loss of single predator species in isolation can, irrespective of their identity or the presence of other predators, trigger rapid secondary extinction cascades in natural communities far exceeding those generally predicted by theory. In contrast, we did not find any secondary extinctions caused by intermediate consumer loss. A food web model of our experimental system-a marine rocky shore community-could reproduce these results only when biologically likely and plausible nontrophic interactions, based on competition for space and predator-avoidance behaviour, were included. These findings call for a reassessment of the scale and nature of extinction cascades, particularly the inclusion of nontrophic interactions, in forecasts of the future of biodiversity.


Imaging diagnostics of renal trauma.
The aim of the study is presenting the diagnostic value of different imaging modalities in the evaluation of patients with renal injury. The material comprises a group of 16 patients with blunt abdominal trauma. Six of them were treated surgically. Plain abdominal radiography was performed in 9 patients, urography in 7, US examination in 16 patients and CT in 12 cases. The renal injuries in US were found in 16 cases, 7 of them were isolated and in 9 patients multi-organ injuries were found, with liver injury in 2 of them. The minor injuries were found in 8 cases. In other 8 cases severe renal injuries were found. The perirenal haematomas were visible as non-enhancing areas adjacent to kidney. The parenchymal laceration appeared as linear non-enhancing areas in the renal parenchyma. In the group of minor renal lesion in 3 cases the renal contusion was found and small parenchymal and subcapsular haematomas in 2 cases appearing as hyperdense subcapsular areas, without evident contrast enhancement. In 2 cases CT revealed perirenal extravasations of blood, appearing as perirenal masses (density of 50 HU), and not revealing contrast enhancement. In 2 cases in CT retroperitoneal haematomas were found. The absence of excretion was found in 2 cases, representing severe injury of the renal pedicle. In 3 cases the injury of ureteropelvic system with extravasations of the contrasted urine into perinephric area was found in CT and in urography. That was the most frequent urographic sign of renal laceration. In 3 cases axial sections revealed injuries of renal collecting system, with subtle extravasation of contrasted urine. In 2 other cases of extensive parenchymal injuries US examination revealed irregular areas of inhomogeneous reflectivity. Radiological evaluation of kidney in patients which sustained abdominal trauma is generally indicated in patients with hypotension < 90 mm Hg and hematuria. CT is preferred image method, enabling evaluation of the injury category. CT is essential in qualifying of patients for conservative or surgical management. USG is also useful in initial diagnosis, but usually precise renal evaluation requires additional CT examination.


A Case of Infantile Cardiac Rhabdomyoma Complicated by Tuberous Sclerosis.
We experienced a case with fetal cardiac tumor, which was diagnosed by prenatal ultrasonographic examination, and the diagnosis was confirmed after birth. A pregnancy woman of the 26th week of gestation was referred to our hospital for close examinations of fetal cardiac tumor. Ultrasonographic examinations revealed single homogeneous tumor with the diameter of 14 mm intracardiac space. The tumor was considered to emerge from the ventricular septum and to be occupied in left ventricle. Other cardiac abnormalities were not detected. The fetus was diagnosed to be complicated with the intracardiac tumor, and with the possible rhabdomyoma of heart. The serial ultrasonographic examinations revealed that the fetal cardiac function was normal. The size of the tumor gradually increased, although the fetal cardiac function revealed within normal range. The patient delivered a female infant weighing 2716g with the Apgar score of 9 and 10 at one and 5 minutes after delivery. The infant was confirmed to have cardiac tumors after examination by pediatric cardiologist, and the cardiac function of the infant was diagnosed as normal condition. The computed tomography of the head revealed the intracranial multiple calcification lesions, which indicated the symptoms of tuberous sclerosis.


Relationship between molar root fusion and localized periodontitis.
We investigated the relationship between molar root fusion and localized periodontitis in this study. A total of 143 individuals (1,109 molars) aged 23 to 68 years were examined for the presence of molar root fusion at diseased and healthy sites. Molar root fusions were diagnosed by periapical radiographs and clinical probing. Periodontal parameters measured included probing depth (PD), clinical attachment loss (CAL), gingival index (GI), and plaque index (PLI) around fused molars. Results indicated that the prevalence of molar root fusions in males and females was 15.2% (93/612) and 32.2% (160/497), respectively. The distribution of molars with root fusions occurs in the following order: maxillary second molars (51.8%), mandibular second molars (32.3%), maxillary first molars (5.7%), and mandibular first molars (0%). Statistically significant differences were observed between molar root fusions at healthy and diseased sites with respect to PLI, GI, PD, and CAL. The highest prevalence of molar root fusion was observed in females.


Solid state effects on exciton states and optical properties of PPV.
We perform ab initio calculations of optical properties for a typical semiconductor conjugated polymer, poly-para-phenylenevinylene, in both isolated chain and crystalline packing. In order to obtain results for excitonic energies and real-space wave functions we explicitly include electron-hole interaction within the density-matrix formalism. We find that the details of crystalline arrangement crucially affect the optical properties, leading to a richer exciton structure and opening nonradiative decay channels. This has implications for the optical activity and optoelectronic applications of polymer films.


Intracrine androgen biosynthesis in renal cell carcinoma.
Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression. Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume. We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01). Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.


Atlantoaxial tuberculosis: Outcome analysis.
Tuberculous (TB) spondylitis occurs in <1% of patients with TB. Atlantoaxial involvement is extremely rare amounting to 0.3%-1% cases of TB spondylitis. The management of this entity has been fluctuating with time. Various classifications and management protocols have also evolved. We present our experience in managing this entity in 8 patients. Retrospective follow-up study of eight patients with atlantoaxial TB over 2 years. They ranged in age from 14 to 33 years with male preponderance. Four required surgical intervention on initial presentation, 2 were successfully treated conservatively, and 2 had to undergo surgery after a trial of conservative management. All of them were started on antituberculous therapy (ATT) for 18 months. Patients were followed up for 8-29 months. Neck pain and restriction of neck movements were standard presenting features. All patients had pulmonary TB confirmed by sputum examination. Radiological investigations formed an integral part of the evaluation of disease, treatment plan, and prognosis. Improvement in symptoms has been documented in all eight. The involvement of the most mobile spinal segment and the potential cervicomedullary compression makes it a disease of utmost importance. Although ATT remains the mainstay of treatment, surgical intervention is needed for stabilizing the joint and decompressing the cervicomedullary junction. Strict adherence to medical advice and optimum surgical intervention tailored for each patient results in the successful management of the disease.


Visualization of Photoreceptors in Birdshot Chorioretinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy: A Pilot Study.
Adaptive optics scanning laser ophthalmoscopy (AOSLO) allows en face visualization of specific layers of the retina. This pilot study evaluated the ability of AOSLO to visualize photoreceptor integrity in patients with birdshot chorioretinopathy (BCR). A total of 16 consecutive patients with HLA-A29+ BCR were imaged using the prototype Apaeros retinal imaging system. Images of high quality were aligned with infrared reflectance photos and correlated with spectral domain optical coherence tomography (SD-OCT). Images of four eyes of three patients were of sufficient quality to allow posterior pole montage and point-to-point correlation with SD-OCT. Areas of photoreceptor disruption on SD-OCT were seen as patchy areas of loss on AOSLO, whereas areas of intact interdigitation zone and inner segment/outer segment junction correlated with normal appearing photoreceptors on AOSLO. Using AOSLO, we found one instance of subclinical photoreceptor disruption not seen on SD-OCT. Ultimately, there are unique challenges associated with imaging BCR patients using AOSLO.


Serum interleukin-6 in acute pancreatitis due to common bile duct stones. A reliable marker of necrosis.
In a prospective clinical study we have assessed the value of serum interleukin-6 in comparison with C-reactive protein in discriminating necrotizing from oedematous acute pancreatitis due to common bile duct stones in the first hours of disease. The study comprised 36 patients with acute biliary pancreatitis; inclusion criteria were admission in hospital within 48 hours from the onset of symptoms, availability of contrast enhanced CT scan within 72 hours from admission and presence of common bile duct stones at early ERCP. A sample of serum was taken at hospitalization and interleukin-6 and C-reactive protein were measured. Interleukin-6 levels were significantly higher in necrotizing pancreatitis, being closely related to the extension of necrosis. C-reactive protein showed low efficacy in detecting necrotizing forms, although its levels were higher than in oedematous. We conclude that serum interleukin-6 is a very reliable marker of necrosis in the first 48 hours of acute biliary pancreatitis.


Moiré Enhanced Potentials in Twisted Transition Metal Dichalcogenide Trilayers Homostructures.
The exploration of moiré superlatticesholds promising potential to uncover novel quantum phenomena emerging from the interplay of atomic structure and electronic correlation . However, the impact of the moiré potential modulation on the number of twisted layers has yet to be experimentally explored. Here, this work synthesizes a twisted WSe2 homotrilayer using a dry-transfer method and investigates the enhancement of the moiré potential with increasing number of twisted layers. The results of the study reveal the presence of multiple exciton resonances with positive or negative circularly polarized emission in the WSe2 homostructure with small twist angles, which are attributed to the excitonic ground and excited states confined to the moiré potential. The distinct g-factor observed in the magneto-optical spectroscopy is also shown to be a result of the confinement of the exciton in the moiré potential. The moiré potential depths of the twisted bilayer and trilayer homostructures are found to be 111 and 212 meV, respectively, an increase of 91% from the bilayer structure. These findings demonstrate that the depth of the moiré potential can be manipulated by adjusting the number of stacked layers, providing a promising avenue for exploration into highly correlated quantum phenomena.


Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients.
Among Asian countries, Pakistan has the highest rates of breast and ovarian cancer. To assess the contribution of the BRCA1 and BRCA2 germ line mutations to these high rates, we conducted the first study of 176 Pakistani breast and ovarian cancer patients, selected on family history and on age of diagnosis. Comprehensive BRCA mutation screening was performed using a range of techniques, including denaturing high-pressure liquid chromatography, single strand conformational polymorphism analysis and protein truncation test, followed by DNA sequencing. Thirty deleterious germ-line mutations were identified in the 176 families (17.0%), including 23 in BRCA1 and 7 in BRCA2. Four mutations, 185delAG, 185insA, S1503X and R1835X, were recurrent; these accounted for 52% of all identified BRCA1 mutations. Haplotype analyses suggested founder effects for 3 of these. The prevalence of BRCA1 or BRCA2 mutations was 42.8% for families with multiple cases of breast cancer, and was 50.0% for the breast/ovarian cancer families. The prevalence of mutations was 11.9% for single cases of early-onset breast cancer (< or =30 years) and was 9.0% for single cases of early-onset ovarian cancer (< or =45 years). Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer and early-onset breast and ovarian cancer cases in Pakistan.


CONTEXT BASED FOOD IMAGE ANALYSIS.
We are developing a dietary assessment system that records daily food intake through the use of food images. Recognizing food in an image is difficult due to large visual variance with respect to eating or preparation conditions. This task becomes even more challenging when different foods have similar visual appearance. In this paper we propose to incorporate two types of contextual dietary information, food co-occurrence patterns and personalized learning models, in food image analysis to reduce ambiguity in food visual appearance and improve food recognition accuracy. We evaluate our model on 1453 food images acquired by 45 participants in natural eating conditions. The result shows that incorporating contextual dietary information improves the food categorization accuracy by about 10%.


Impact of Fermentable Fibres on the Colonic Microbiota Metabolism of Dietary Polyphenols Rutin and Quercetin.
Dietary fibre and polyphenols are both metabolised to short-chain fatty acids (SCFAs) and phenolic acids (PA) by the colonic microbiota. These may alter microbiota growth/diversity, but their interaction is not understood. Interactions between rutin and raftiline, ispaghula or pectin were investigated in human faecal batch cultures (healthy participants; 19⁻33 years, 4 males, 6 females, BMI 18.4⁻27.4) after a low (poly)phenol diet three days prior to study. Phenolic acids were measured by gas chromatography-mass spectrometry and SCFAs by gas chromatography-flame ionisation after 2, 4, 6, and 24 h. Rutin fermentation produced Phenyl acetic acid (PAA), 4-Hydroxy benzoic acid (4-OHBA), 3-Hydroxy phenyl acetic acid (3-OHPAA), 4-Hydroxy phenyl acetic acid (4-OHPAA), 3,4-Dihydroxy phenyl acetic acid (3,4-diOHPAA), 3-Hydroxy phenyl propionic acid (3-OHPPA), and 4-Hydroxy phenyl propionic acid (4-OHPPA). 3,4-DiOHPAA and 3-OHPAA were predominant at 6 h (1.9 ± 1.8 µg/mL, 2.9 ± 2.5 µg/mL, and 0.05 ± 0.0 µg/mL, respectively) and 24 h (5.5 ± 3.3 µg/mL, 3.1 ± 4.2 µg/mL, and 1.2 ± 1.6 µg/mL). Production of all PA except 3-OHPPA and 4-OHPPA was reduced by at least one fibre. Inhibition of PA was highest for rutin (8-fold, p < 0.01), then pectin (5-fold, p < 0.01), and ispaghula (2-fold, p = 0.03). Neither rutin nor quercetin had a detectable impact on SCFA production. These interactions should be considered when assessing dietary polyphenols and potential health benefits.


Low-grade temporal gliomas: surgical strategy and long-term seizure outcome.
Low-grade gliomas (LGGs) are generally located in temporal lobe and cause medically-intractable seizure so that surgical treatment becomes inevitable. This study includes a retrospective analysis of our patients with temporal LGGs retrieved from our epilepsy surgery data base and tries to present appropriate surgical approach and long-term seizure and anti-epileptic drug (AED) outcomes. Fifty-three patients including children and adults underwent surgery on temporal lobe LGGs and 35 patients were reached to report seizure and AED outcomes. On the non-dominant temporal lobe, anterior temporal resection with hippocampectomy whether mesial structure are involved or not is the appropriate approach. On the dominant temporal lobe mesial structures should be respected. However, total resection of the tumor should be the goal of surgery. Mean follow-up period was 8.3 years and favorable seizure outcome was found to be 91.4%. Surgery decreased AED usage and mean number of AED significantly decreased. Children also benefited from surgery as adults. Surgical treatment of tumor-related epilepsy from temporal lobe controls seizures, and total removal should be the main goal of surgery as neuropsychological testing permit.


Histological diagnosis of gastric submucosal tumors: A pilot study of endoscopic ultrasonography-guided fine-needle aspiration biopsy vs mucosal cutting biopsy.
To compare the usefulness of endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) without cytology and mucosal cutting biopsy (MCB) in the histological diagnosis of gastric submucosal tumor (SMT). We prospectively compared the diagnostic yield, feasibility, and safety of EUS-FNAB and those of MCB based on endoscopic submucosal dissection. The cases of 20 consecutive patients with gastric SMT ≥ 1 cm in diameter. who underwent both EUS-FNAB and MCB were investigated. The histological diagnoses were gastrointestinal stromal tumors (n = 7), leiomyoma (n = 6), schwannoma (n = 2), aberrant pancreas (n = 2), and one case each of glomus tumor, metastatic hepatocellular carcinoma, and no-diagnosis. The tumors' mean size was 23.6 mm. Histological diagnosis was made in 65.0% of the EUS-FNABs and 60.0% of the MCBs, a nonsignificant difference. There were no significant differences in the diagnostic yield concerning the tumor location or tumor size between the two methods. However, diagnostic specimens were significantly more frequently obtained in lesions with intraluminal growth than in those with extraluminal growth by the MCB method (P = 0.01). All four SMTs with extraluminal growth were diagnosed only by EUS-FNAB (P = 0.03). No complications were found in either method. MCB may be chosen as an alternative diagnostic modality in tumors showing the intraluminal growth pattern regardless of tumor size, whereas EUS-FNAB should be performed for SMTs with extraluminal growth.


Modeling disease mutations by gene targeting in one-cell mouse embryos.
Gene targeting by zinc-finger nucleases in one-cell embryos provides an expedite mutagenesis approach in mice, rats, and rabbits. This technology has been recently used to create knockout and knockin mutants through the deletion or insertion of nucleotides. Here we apply zinc-finger nucleases in one-cell mouse embryos to generate disease-related mutants harboring single nucleotide or codon replacements. Using a gene-targeting vector or a synthetic oligodesoxynucleotide as template for homologous recombination, we introduced missense and silent mutations into the Rab38 gene, encoding a small GTPase that regulates intracellular vesicle trafficking. These results demonstrate the feasibility of seamless gene editing in one-cell embryos to create genetic disease models and establish synthetic oligodesoxynucleotides as a simplified mutagenesis tool.


Draft Genome Sequence of Aeribacillus pallidus Strain 8m3, a Thermophilic Hydrocarbon-Oxidizing Bacterium Isolated from the Dagang Oil Field (China).
The draft genome sequence of Aeribacillus pallidus strain 8m3, a thermophilic aerobic oil-oxidizing bacterium isolated from production water from the Dagang high-temperature oil field, China, is presented here. The genome is annotated to provide insights into the genomic and phenotypic diversity of the genus Aeribacillus.


Is a national program to prevent sickle cell disease possible?
There is no specific therapy for sickle cell disease, and there is no evidence that sickle hemoglobin screening by conventional methods will lead to a significant reduction in the number of children with sickle cell disease. Thus it follows that if there is to be a national program to prevent sickle cell disease, the only recourse is one based on prenatal diagnosis and selective abortion of affected embryos or fetuses. Present-day dire poverty and callous health care public policies lead to the inescapable conclusion that a concerted attempt to alleviate poverty and its consequent adverse effects on maternal, neonatal, and infant mortality should take precedence over, or at the least coincide with, a national program to prevent sickle cell disease. On the other hand, it is argued that a woman should have the right to decide whether or not she wishes to have a child with a genetic disorder, and that recent advances in research on prenatal diagnosis, particularly when supported by public funds, should be made available to all, and not just the affluent.


Bioinspired mechanically stable all-polysaccharide based scaffold for photosynthetic production.
We demonstrate the construction of water-stable, biocompatible and self-standing hydrogels as scaffolds for the photosynthetic production of ethylene using a bioinspired all-polysaccharidic design combining TEMPO-oxidised cellulose nanofibers (TCNF) and a cereal plant hemicellulose called mixed-linkage glucan (MLG). We compared three different molecular weight MLGs from barley to increase the wet strength of TCNF hydrogels, and to reveal the mechanisms defining the favourable interactions between the scaffold components. The interactions between MLGs and TCNF were revealed via adsorption studies and interfacial rheology investigations using quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that both the MLG solution stability and adsorption behaviour did not exactly follow the well-known polymer adsorption and solubility theories especially in the presence of co-solute ions, in this case nitrates. We prepared hydrogel scaffolds for microalgal immobilisation, and high wet strength hydrogels were achieved with very low dosages of MLG (0.05 wt%) to the TCNF matrix. The all-polysaccharic biocatalytic architectures remained stable and produced ethylene for 120 h with yields comparable to the state-of-the-art scaffolds. Due to its natural origin and biodegradability, MLG offers a clear advantage in comparison to synthetic scaffold components, allowing the mechanical properties and water interactions to be tailored.


Facilitating speech in the patient with a tracheostomy.
A tracheostomy tube decreases the ability of the patient to communicate effectively. The ability to speak provides an important improvement in the quality of life for a patient with a tracheostomy. In mechanically ventilated patients, speech can be provided by the use of a talking tracheostomy tube, using a cuff-down technique with a speaking valve, and using a cuff-down technique without a speaking valve. Speech can be facilitated in patients with a tracheostomy tube who are breathing spontaneously by use of a talking tracheostomy tube, by using a cuff-down technique with finger occlusion of the proximal tracheostomy tube, and with the use of a cuff-down technique with a speaking valve. Teamwork between the patient and the patient care team (respiratory therapist, speech-language pathologist, nurse, and physician) can result in effective restoration of speech in many patients with a long-term tracheostomy.


Impact of infection on glucose-dependent liver glucose uptake during TPN: interaction with insulin.
Chronic total parenteral nutrition (TPN) markedly augments net hepatic glucose uptake (NHGU). This adaptive increase is impaired by an infection despite accompanying hyperinsulinemia. In the nonadapted state, NHGU is dependent on the prevailing glucose levels. Our aims were to determine whether the adaptation to TPN alters the glucose dependence of NHGU, whether infection impairs this dependence, and whether insulin modulates the glucose dependence of NHGU during infection. Chronically catheterized dogs received TPN for 5 days. On day 3 of TPN, dogs received either a bacterial fibrin clot to induce a nonlethal infection (INF, n = 9) or a sterile fibrin clot (Sham, n = 6). Forty-two hours after clot implantation, somatostatin was infused. In Sham, insulin and glucagon were infused to match the level seen in Sham (9 +/- 1 microU/ml and 23 +/- 4 pg/ml, respectively). In infected animals, either insulin and glucagon were infused to match the levels seen in infection (25 +/- 2 microU/ml and 101 +/- 15 pg/ml; INF-HI; n = 5) or insulin was replaced to match the lower levels seen in Sham (13 +/- 2 microU/ml), whereas glucagon was kept elevated (97 +/- 9 pg/ml; INF-LO; n = 4). Then a four-step (90 min each) hyperglycemic (120, 150, 200, or 250 mg/dl) clamp was performed. NHGU increased at each glucose step in Sham (from 3.6 +/- 0.6 to 5.4 +/- 0.7 to 8.9 +/- 0.9 to 12.1 +/- 1.1 mg.kg(-1).min(-1)); the slope of the relationship between glucose levels and NHGU (i.e., glucose dependence) was higher than that seen in nonadapted animals. Infection impaired glucose-dependent NHGU in both INF-HI (1.3 +/- 0.4 to 2.9 +/- 0.5 to 5.5 +/- 1.0 to 7.7 +/- 1.6 mg.kg(-1).min(-1)) and INF-LO (0.5 +/- 0.7 to 2.2 +/- 0.6 to 4.2 +/- 1.0 to 5.8 +/- 0.8 mg.kg(-1).min(-1)). In summary, TPN augments glucose-dependent NHGU, the presence of infection decreases glucose-dependent NHGU, and the accompanying hyperinsulinemia associated with infection does not sustain the glucose dependence of NHGU.


Improvement in patient-reported outcomes after lung transplantation is not impacted by the use of extracorporeal membrane oxygenation as a bridge to transplantation.
Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation. The impact of preoperative ECMO on health-related quality of life (HRQL) and depressive symptoms after lung transplantation remains unknown, however. In a single-center prospective cohort study, we assessed HRQL and depressive symptoms before and at 3, 6, and 12 months after lung transplantation using the Short Form 12 Physical and Mental Component Scores (SF12-PCS and SF12-MCS), Airway Questionnaire 20-Revised (AQ20R), EuroQol 5D (EQ5D), and Geriatric Depression Scale (GDS). Changes in HRQL were quantified by segmented linear mixed-effects models controlling for age, sex, diagnosis, preoperative forced expiratory volume in 1 second, 6-minute walk distance, and Lung Allocation Score. We compared changes in HRQL among subjects bridged with ECMO, subjects hospitalized but not on ECMO, and subjects called in for transplantation as outpatients. Out of 189 subjects, 17 were bridged to transplantation with ECMO. In all groups, improvements in HRQL following lung transplantation exceeded the minimally clinically important difference using the SF12-PCS, AQ20R, EQ5D, and GDS. HRQL defined by SF12-MCS did not change after transplantation. Improvements were generally similar among the groups, except for EQ5D, which showed a trend toward less benefit in the outpatients, possibly due to their better HRQL before lung transplantation. Subjects ill enough to require ECMO as a bridge to lung transplantation appear to achieve similar improvements in HRQL and depressive symptoms as those who do not. It is reassuring to both providers and patients that lung transplantation provides substantial improvements in HRQL, even for those patients who are critically ill in the run up to transplantation.


Greater morphological and primary metabolic adaptations in roots contribute to phosphate-deficiency tolerance in the bread wheat cultivar Kenong199.
Phosphate (Pi) deficiency severely affects crop growth and productivity, including wheat, therefore it is necessary to develop cultivars with enhanced Pi-deficiency tolerance. However, the underlying mechanism of Pi-deficiency tolerance in wheat is still elusive. Two contrasting wheat cultivars, low-Pi tolerant Kenong199 (KN199) and low-Pi sensitive Chinese Spring (CS) were used to reveal adaptations in response to Pi deficiency at the morphological, physiological, metabolic, and molecular levels. KN199 was more tolerant to Pi deficiency than CS with significantly increased root biomass and R/S ratio. Root traits, the total root length, total root surface area, and total root volume, were remarkably enhanced by Pi deficiency in KN199. The shoot total P and soluble Pi concentrations of KN199 were significantly higher than those of CS, but not in roots. In KN199, high Pi level in shoots is a higher priority than that in roots under Pi deficiency. It was probably due to differentially regulation in the miR399-mediated signaling network between the shoots of the two cultivars. The Pi deficiency-induced root architecture adaptation in KN199 was attributed to the regulation of the hormone-mediated signaling (ethylene, gibberellin, and jasmonates). The expression of genes associated with root development and Pi uptake was enhanced in KN199. Some primary metabolites (amino acids and organic acids) were significantly accumulated in roots of KN199 under Pi deficiency. The low-Pi tolerant wheat cultivar KN199 possessed greater morphological and primary metabolic adaptations in roots than CS under Pi deficiency. The adaption and the underlying molecular mechanisms in wheat provide a better understanding of the Pi-deficiency tolerance and the strategies for improving Pi efficiency in wheat.


Noise reduction method for molecular interaction energy: application to in silico drug screening and in silico target protein screening.
We developed a new method to improve the accuracy of molecular interaction data using a molecular interaction matrix. This method was applied to enhance the database enrichment of in silico drug screening and in silico target protein screening using a protein-compound affinity matrix calculated by a protein-compound docking software. Our assumption was that the protein-compound binding free energy of a compound could be improved by a linear combination of its docking scores with many different proteins. We proposed two approaches to determine the coefficients of the linear combination. The first approach is based on similarity among the proteins, and the second is a machine-learning approach based on the known active compounds. These methods were applied to in silico screening of the active compounds of several target proteins and in silico target protein screening.


[Update on current care guidelines: Self-medication, Current Care Guideline].
Self-medication should always be temporary. Self-medication can be used to relief or treat many symptoms and conditions. In general self-medication is safe when used properly. However all medicines may cause adverse events or have interactions with other drugs. It is important to consider all used drugs and other self-medication products when new drugs are added to the medication list. Persons using the drugs as well as health care personnel should be aware of benefits and harms of drugs.The guideline has recommendations for 10 symptoms that are typically treated with self-medication.


Use of an enhanced bulk diffusion-based algorithm for phase separation of a ternary mixture.
Phase separation kinetics of two-dimensional ternary mixtures have been studied by means of a Monte Carlo approach. Standard Kawasaki kinetics are impractical to study the late stages of the segregation process at deep quenches. An extension of the accelerated algorithm for binary mixtures proposed by Marko and Barkema [Phys. Rev. E 52, 2522 (1995)] is presented to overcome this problem in a three-component system discretized with two coupled lattices. We study the domain growth and the scaling behavior over a wide range of quench depths. Computer performances of the Kawasaki and the accelerated schemes are compared.


The ShcA adaptor protein is a critical regulator of breast cancer progression.
Breast cancer affects 1 in 8 North American women throughout their lifetime and is the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease whose progression from hyperplasia to ductal carcinoma in situ and invasive carcinoma is regulated by the aberrant expression of multiple mediators; including growth factors, cytokines, chemokines and proteases that are produced both by the mammary tumor itself and the adjacent reactive stroma. These signals promote tumor cell proliferation, survival, establishment of a tumor vasculature, invasion and ultimately metastasis to secondary organs. Moreover, the ability of the tumor to create a state of local immune suppression allows tumor cells to evade clearance by the immune system. ShcA is an adaptor protein that relays extracellular signals downstream of receptor tyrosine kinases. Clinical studies suggest that activation of the ShcA signaling pathway is associated with poor patient prognosis. Moreover, recent studies with transgenic mouse models have clearly demonstrated the importance of tumor autonomous ShcA signaling, as well as signaling in cells comprising the tumor microenvironment, for the regulation of these biological processes, which contribute to breast cancer development and metastasis.


Dilaton-assisted dark matter.
A dilaton could be the dominant messenger between standard model fields and dark matter. The measured dark matter relic abundance relates the dark matter mass and spin to the conformal breaking scale. The dark matter-nucleon spin-independent cross section is predicted in terms of the dilaton mass. We compute the current constraints on the dilaton from LEP and Tevatron experiments, and the gamma-ray signal from dark matter annihilation to dilatons that could be observed by Fermi Large Area Telescope.


Aggregation-Induced Emission Materials that Aid in Pharmaceutical Research.
The in situ visualization of drugs can improve the understanding of their pharmacokinetics and mechanisms. Aggregation-induced emission (AIE) materials, which can aid in the visualization of drugs, are gradually being employed in pharmaceutical research due to their excellent fluorescence properties, good biocompatibility, and extremely high sensitivity. Herein, the progress of AIE materials in pharmaceutical research, including AIE carriers for drug delivery, AIE multifunctional prodrugs, and AIE compounds as bioactive reagents for theranostics is briefly described. Moreover, the opportunities and challenges of AIE materials in pharmaceutical research are discussed in depth. It is believed that versatile AIE materials hold great promise for the promotion of pharmacological research and can facilitate significant advancements in clinical fields.


Production of interleukin-1 (IL-1) and IL-1 inhibitor by human monocytes exposed to dengue virus.
Dengue hemorrhagic fever-dengue shock syndrome, the most severe manifestation of an acute dengue virus (DV) infection, is endemic in Southeast Asia. Antibody-dependent enhancement of DV growth in mononuclear phagocytes is thought to be the mechanism whereby preexisting dengue antibodies confer excess risk for this outcome. Interleukin-1 (IL-1) may play an important role in the pathogenetic mechanisms that cause dengue fever and shock. It was shown that both IL-1 and tumor necrosis factor-alpha are secreted from monocytes within 4 h after DV infection. However, there was no increase in IL-1 secretion by virus-stimulated monocytes from dengue fever patients compared with healthy controls. Significant amounts of IL-1 were secreted by DV-infected monocytes in the presence of aggregated immunoglobulin or immune complexes. In addition, a new 600-kDa IL-1 inhibitor from the supernatants of DV-infected monocytes was identified. This inhibitor may cause immunosuppression and influence the process of DV infection.


Ultrafast dynamics of the low-lying 3MLCT states of [Ru(bpy)2(dppp2)]2+.
The solvent dependence of the excited state dynamics of [Ru(bpy)(2)(dppp2)](2+) (bpy = 2,2'-bipyridine, dppp2 = pyrido[2',3':5,6]pyrazino[2,3-f][1,10]phenanthroline) were investigated using ultrafast transient absorption spectroscopy. In contrast to the "DNA light-switch" complex [Ru(bpy)(2)(dppz)](2+) (dppz = dipyrido[3,2-a:2',3'-c]phenzine), the structurally related [Ru(bpy)(2)(dppp2)](2+) exhibits discrete formation of the lowest-lying (3)MLCT(dis) (MLCT = metal-to-ligand charge transfer) state from the higher-energy (3)MLCT(prox) state in the picosecond time scale. In (3)MLCT(dis) and (3)MLCT(prox), the transferred electron is localized on the portion of the dppp2 ligand distal and proximal to the metal, respectively. The greater dipole moment of (3)MLCT(dis) compared to (3)MCLT(prox), together with the ability of the dppp2 ligand to hydrogen bond, results in a strong dependence of the kinetics of the interconversion process on solvent polarity, decreasing from 67 to 26 ps in CH(2)Cl(2) and CH(3)CN, respectively. Similarly, the lifetime of the emission of the lowest energy state of [Ru(bpy)(2)(dppp2)](2+) also decreases from 273 to 35 ns in the same solvents. In CH(3)CH(2)OH, both the rate of interconversion and the decay of (3)MLCT(dis) are significantly faster, 6.7 ps and 1.7 ns, respectively. Such dependence of the excited state properties is not observed for [Ru(bpy)(2)(dppz)](2+). The results are consistent with the relative stabilization of (3)MLCT(dis) of the dppp2 complex in CH(3)CN compared to CH(2)Cl(2) due to solvent polarity, which may be further stabilized by hydrogen bonding in CH(3)CH(2)OH.


FRUITFULL controls SAUR10 expression and regulates Arabidopsis growth and architecture.
MADS-domain transcription factors are well known for their roles in plant development and regulate sets of downstream genes that have been uncovered by high-throughput analyses. A considerable number of these targets are predicted to function in hormone responses or responses to environmental stimuli, suggesting that there is a close link between developmental and environmental regulators of plant growth and development. Here, we show that the Arabidopsis MADS-domain factor FRUITFULL (FUL) executes several functions in addition to its noted role in fruit development. Among the direct targets of FUL, we identified SMALL AUXIN UPREGULATED RNA 10 (SAUR10), a growth regulator that is highly induced by a combination of auxin and brassinosteroids and in response to reduced R:FR light. Interestingly, we discovered that SAUR10 is repressed by FUL in stems and inflorescence branches. SAUR10 is specifically expressed at the abaxial side of these branches and this localized activity is influenced by hormones, light conditions and by FUL, which has an effect on branch angle. Furthermore, we identified a number of other genes involved in hormone pathways and light signalling as direct targets of FUL in the stem, demonstrating a connection between developmentally and environmentally regulated growth programs.


Innate Invariant NKT Cell Recognition of HIV-1-Infected Dendritic Cells Is an Early Detection Mechanism Targeted by Viral Immune Evasion.
Invariant NKT (iNKT) cells are innate-like T cells that respond rapidly with a broad range of effector functions upon recognition of glycolipid Ags presented by CD1d. HIV-1 carries Nef- and Vpu-dependent mechanisms to interfere with CD1d surface expression, indirectly suggesting a role for iNKT cells in control of HIV-1 infection. In this study, we investigated whether iNKT cells can participate in the innate cell-mediated immune response to HIV-1. Infection of dendritic cells (DCs) with Nef- and Vpu-deficient HIV-1 induced upregulation of CD1d in a TLR7-dependent manner. Infection of DCs caused modulation of enzymes in the sphingolipid pathway and enhanced expression of the endogenous glucosylceramide Ag. Importantly, iNKT cells responded specifically to rare DCs productively infected with Nef- and Vpu-defective HIV-1. Transmitted founder viral isolates differed in their CD1d downregulation capacity, suggesting that diverse strains may be differentially successful in inhibiting this pathway. Furthermore, both iNKT cells and DCs expressing CD1d and HIV receptors resided in the female genital mucosa, a site where HIV-1 transmission occurs. Taken together, these findings suggest that innate iNKT cell sensing of HIV-1 infection in DCs is an early immune detection mechanism, which is independent of priming and adaptive recognition of viral Ag, and is actively targeted by Nef- and Vpu-dependent viral immune evasion mechanisms.


Retroperitoneal Laparoscopic Partial Nephrectomy for Tumors Larger than 7 cm in Renal Cell Carcinoma: Initial Experience of Single-Institution.
To report our initial experience dealing with retroperitoneal laparoscopic partial nephrectomy (LPN) for tumors larger than 7 cm in renal cell carcinoma (RCC). A total of 15 patients with malignant tumors larger than 7 cm underwent retroperitoneal LPN at our institution. Patient baseline demographics, perioperative outcomes, pathological characteristics, and estimated glomerular filtration rate (eGFR) were analyzed retrospectively in our collected database. The tumor size is 7.5 (7.1-9.0) cm. Nine (60.00%) patients, 4 (26.67%) patients, and 2 (13.33%) patients suffered from preoperative chronic kidney disease (CKD) at stage I, II, and III, respectively. The median operating time was 121 (90-330) minutes and the warm ischemia time (WIT) was 29 (12-45) minutes, with the estimated blood loss of 50 (10-1200) mL. The preoperative eGFR was 81.26 mL/min per 1.73 m2 (ranging from 56.15 to 140.47), eGFR on 1 and 30 days postoperative was 70.49 mL/min per 1.73 m2 (ranging from 50.32 to 137.73) and 75.13 mL/min per 1.73 m2 (ranging from 54.07 to 142.99), respectively. At last follow-up, the eGFR was 72.78 mL/min per 1.73 m2 (ranging from 51.28 to 137.86); no stage migration for CKD was observed. Major complications included 2 patients requiring blood transfusions and 1 patient performing renal vein suture as well as single leak. Our initial experience suggests that retroperitoneal LPN maybe a feasible, safe, and effective procedure for selected tumors larger than 7 cm in RCC, with the advantage of renal function preservation and acceptable major surgical complications. Tumor size might not be the contraindication of LPN in the treatment of selected tumors.


Impairment of T-cell control of Epstein-Barr virus infected B-cells in patients with adult T-cell leukemia.
The abilities of peripheral blood lymphocytes from 9 patients with adult T-cell leukemia (ATL) and 14 healthy control adults to cause regression of proliferating B-cell foci induced by Epstein-Barr virus (EBV) were examined. Marked regression of EBV-transformed B-cell foci was observed in lymphocytes from all 10 EBV-seropositive donors but with none of those of the 4 EBV-seronegative donors in the control group. The lymphocyte of all 9 patients with ATL, who were EBV-seropositive, caused little or no regression of B-cell foci like those of EBV-negative healthy donors. These results suggest that the absence of regression of EBV-induced B-cell proliferation observed in ATL patients is due to impairment of EBV-specific killer T-cell activities.


Long-Term Suppression of Circulating Proinflammatory Cytokines in Multiple Sclerosis Patients Following Autologous Haematopoietic Stem Cell Transplantation.
Autologous haematopoietic stem cell transplantation (AHSCT) is a therapeutic option for haematological malignancies, such as non-Hodgkin's lymphoma (NHL), and more recently, for autoimmune diseases, such as treatment-refractory multiple sclerosis (MS). The immunological mechanisms underlying remission in MS patients following AHSCT likely involve an anti-inflammatory shift in the milieu of circulating cytokines. We hypothesised that immunological tolerance in MS patients post-AHSCT is reflected by an increase in anti-inflammatory cytokines and a suppression of proinflammatory cytokines in the patient blood. We investigated this hypothesis using a multiplex-ELISA assay to compare the concentrations of secreted cytokine in the peripheral blood of MS patients and NHL patients undergoing AHSCT. In MS patients, we detected significant reductions in proinflammatory T helper (Th)17 cytokines interleukin (IL)-17, IL-23, IL-1β, and IL-21, and Th1 cytokines interferon (IFN)γ and IL-12p70 in MS patients from day 8 to 24 months post-AHSCT. These changes were not observed in the NHL patients despite similar pre-conditioning treatment for AHSCT. Some proinflammatory cytokines show similar trends in both cohorts, such as IL-8 and tumour necrosis factor (TNF)-α, indicating a probable treatment-related AHSCT response. Anti-inflammatory cytokines (IL-10, IL-4, and IL-2) were only transiently reduced post-AHSCT, with only IL-10 exhibiting a significant surge at day 14 post-AHSCT. MS patients that relapsed post-AHSCT exhibited significantly elevated levels of IL-17 at 12 months post-AHSCT, unlike non-relapse patients which displayed sustained suppression of Th17 cytokines at all post-AHSCT timepoints up to 24 months. These findings suggest that suppression of Th17 cytokines is essential for the induction of long-term remission in MS patients following AHSCT.


Improvements in the understanding and treatment of macular hole.
Recent innovations in macular imaging and surgery have provided important new information concerning the pathogenesis and treatment of idiopathic macular hole. New imaging data suggest that localized perifoveal vitreous detachment (an early stage of age-related posterior vitreous detachment) is the primary pathogenic event in idiopathic macular hole formation. Detachment of the posterior hyaloid from the pericentral retina exerts anterior traction on the foveola and localizes into the foveola the dynamic vitreous traction associated with ocular rotations. Optical coherence tomography has clarified the pathoanatomy of early macular hole stages, beginning with a foveal pseudocyst (stage 1A) and typically followed by disruption of the outer retina (stage 1B) before progressing to a full-thickness dehiscence (stage 2). The treatment of macular hole continues to evolve as modifications to the standard surgical procedure are proposed and evaluated. These innovations include the use of cytokine adjuvants, peeling of the internal limiting membrane, vital staining of the internal limiting membrane with indocyanine green dye, and variations in the length of postoperative face-down positioning.


State certification for school nurses.
State-specific credentialing of school nurses is generally equivalent to state teacher certification and is regulated by state departments of education. This certification establishes statewide employment standards for school nurses, as opposed to competency-based professional certification. Although more than half of all states currently have some type of credentialing for school nurses, it takes many different forms. The advantages of certification are pronounced but are surpassed by the barriers to its establishment. Considerations in establishing certification are presented along with analysis of the various forms of certification that exist in states that have school nurse certification.