Weaning from ventricular assist device support after recovery from left ventricular failure with or without secondary right ventricular failure.
Although complete myocardial recovery after ventricular assist device (VAD) implantation is rather seldom, systematic search for recovery is worthwhile because for recovered patients weaning from VADs is feasible and can provide survival benefits with long-term freedom from heart failure (HF) recurrence, even if a chronic cardiomyopathy was the primary cause for the drug-refractory HF necessitating left ventricular (LVAD) or biventricular support (as bridge-to-transplantation or definitive therapy) and even if recovery remains incomplete. LVAD patients explanted for myoacardial recovery compared to those transplanted from LVAD support showed similar survival rates and a significant proportion of explanted patients can achieve cardiac and physical functional capacities that are within the normal range of healthy controls. In apparently sufficiently recovered patients, a major challenge remains still the pre-explant prediction of the weaning success which is meanwhile reliably possible for experienced clinicians. In weaning candidates, the combined use of certain echocardiography and right heart catheterization parameters recorded before VAD explantation can predict post-weaning cardiac stability with good accuracy. However, in the absence of standardization or binding recommendations, the protocols for assessment of native cardiac improvement and also the weaning criteria differ widely among centers. Currently there are still only few larger studies on myocardial recovery assessment after VAD implantation. Therefore, the weaning practice relies mostly on small case series, local practice patterns, and case reports, and the existing knowledge, as well as the partially differing recommendations which are based mainly on expert opinions, need to be periodically systematised. Addressing these shortcomings, our review aims to summarize the evidence and expert opinion on the evaluation of cardiac recovery during mechanical ventricular support by paying special attention to the reliability of the methods and parameters used for assessment of myocardial recovery and the challenges met in both evaluation of recovery and weaning decision making.


Keratin 17 gene expression during the murine hair cycle.
Keratin 17 (K17) expression is currently considered to be associated with hyperplastic or malignant growth of epithelial cells. The functions of this keratin in normal skin physiology and the regulation of its gene expression, however, are still unclear. As one possible approach to further explore K17 functions, we have studied the differential patterns of mouse K17 (MK17) transcription during the murine hair cycle by means of in situ hybridization, using a digoxigenin-labeled riboprobe. Cycling hair follicles in the skin of C57BL/6 mice were found to be the only skin structures expressing MK17 under physiologic conditions. MK17 transcripts were constantly observed throughout all hair cycle stages in the suprainfundibular outer root sheath (ORS). The MK17 expression was also evident in the isthmus part of the ORS, where it was expressed weakly and was spatially restricted during telogen, with an increase in early anagen and stable expression during mid- and late anagen, localizing to the zone of so-called trichilemmal keratinization. In addition, in early anagen, a group of epithelial cells in or next to the bulge region stained weakly for MK17. With progressing anagen development, MK17 expression in this region increased and was consistently localized to keratinocytes at the advancing front of the emerging epithelial hair bulb. In mid- and late anagen, this zone of MK17 expression spread along the proximal ORS, with a maximal level of expression in the innermost cell layer of the ORS. Overall, these findings provide data on the MK17 expression profile of normal murine skin and demonstrate hair-cycle-dependent regulation of MK17 expression.


Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges.
Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis.


The evolution of sexual size dimorphism in the house finch. II. Population divergence in relation to local selection.
Recent colonization of ecologically distinct areas in North America by the house finch (Carpodacus mexicanus) was accompanied by strong population divergence in sexual size dimorphism. Here we examined whether this divergence was produced by population differences in local selection pressures acting on each sex. In a long-term study of recently established populations in Alabama, Michigan, and Montana, we examined three selection episodes for each sex: selection for pairing success, overwinter survival, and within-season fecundity. Populations varied in intensity of these selection episodes, the contribution of each episode to the net selection, and in the targets of selection. Direction and intensity of selection strongly differed between sexes, and different selection episodes often favored opposite changes in morphological traits. In each population, current net selection for sexual dimorphism was highly concordant with observed sexual dimorphism--in each population, selection for dimorphism was the strongest on the most dimorphic traits. Strong directional selection on sexually dimorphic traits, and similar intensities of selection in both sexes, suggest that in each of the recently established populations, both males and females are far from their local fitness optimum, and that sexual dimorphism has arisen from adaptive responses in both sexes. Population differences in patterns of selection on dimorphism, combined with both low levels of ontogenetic integration in heritable sexually dimorphic traits and sexual dimorphism in growth patterns, may account for the close correspondence between dimorphism in selection and observed dimorphism in morphology across house finch populations.


Risk factors associated with intracranial hemorrhage in neonates with persistent pulmonary hypertension on ECMO.
Up to 40% of infants with persistent pulmonary hypertension (PPHN) remains refractory to conventional therapies, and extracorporeal membrane oxygenation (ECMO) is offered as an effective support for this group. However, ECMO is a highly invasive and risky procedure with devastating complications such as intracranial hemorrhage (ICH). In this study, we aimed to determine the risk factors for ICH in infants with PPHN. A case-control study of patients admitted to the pediatric intensive care unit (PICU) with PPHN requiring ECMO support was conducted. The study was carried out at a 25-bed PICU in large urban tertiary care children's hospital. A total number of 32 subjects were studied. Patients with and without ICH during ECMO were evaluated for activated clotting time (ACT), heparin dosing, platelet count, coagulation profile such as activated partial thromboplastin time (aPTT), prothrombin time (PT), international normalized ratio (INR), fibrinogen level, vital signs including heart rate and mean arterial pressure (MAP), transfusion history, gestational age, and severity of pre-ECMO illness as possible risk factors. Low fibrinogen level (115 ± 13 mg/dl) and low platelet counts (37.4 ± 18.3 Thousand/μl) were associated with higher incidence of ICH (p = 0.009 and p = 0.005, respectively). Elevated MAP (69 ± 4.34 mmHg) was also noticed in ICH patients (p = 0.006). Results demonstrated that low fibrinogen level and low platelet count were associated with ICH in PPHN patients on ECMO. While on ECMO support, maintaining fibrinogen and platelet counts within normal ranges seems crucial to prevent ICH in PPHN patients. This is the first report identifying low fibrinogen level among the risk factors for ICH in infants with PPHN on ECMO support.


Optimization modeling of plant root architecture for water and phosphorus acquisition.
An optimization model is presented that examines the relationship between root architecture and multiple resource acquisition, specifically water and phosphorus in spatially heterogeneous environments. The basal root growth angle of an individual common bean plant, which determines the orientation and localization of the bulk of the root system, was modeled as the decision variable. The total payoff to the plant, the benefit obtained from water and phosphorus acquisition, minus the costs of spatial competition between roots, is given as a function of the (x,y) coordinates of the basal root in two-dimensional Cartesian space. We obtained a general solution and applied it to four unique environmental cases which are as follows: (1) the case of uniformly distributed water and phosphorus; (2) the case of localized shallow phosphorus; (3) the case of localized deep water; and (4) the case of shallow phosphorus and deep water. The general solution states that the optimal basal root growth angle will occur at the point where the total rate of change in the value of the resources acquired equals the total rate of change in cost that results from locating the root deeper in the soil. An optimizing plant locates its roots deeper in the soil profile until the marginal benefit exactly equals the marginal cost. The model predicts that the basal root angle of an optimizing plant will be shallower for Case 2 and deeper for Case 3, relative to the basal root angle obtained in the case of uniformly distributed water and phosphorus. The optimal basal root angle for Case 4 will depend on the marginal rate of substitution of water availability for phosphorus availability that occurs with depth. Empirical observations of bean root architecture in the greenhouse and in the field confirm model results and are discussed. In addition, the potential importance of phenotypic plasticity and phenotypic variation are discussed in relation to optimization of traits and adaptation to spatially heterogeneous environments.


Identification of self-consistent modulons from bacterial microarray expression data with the help of structured regulon gene sets.
Identification of bacterial modulons from series of gene expression measurements on microarrays is a principal problem, especially relevant for inadequately studied but practically important species. Usage of a priori information on regulatory interactions helps to evaluate parameters for regulatory subnetwork inference. We suggest a procedure for modulon construction where a seed regulon is iteratively updated with genes having expression patterns similar to those for regulon member genes. A set of genes essential for a regulon is used to control modulon updating. Essential genes for a regulon were selected as a subset of regulon genes highly related by different measures to each other. Using Escherichia coli as a model, we studied how modulon identification depends on the data, including the microarray experiments set, the adopted relevance measure and the regulon itself. We have found that results of modulon identification are highly dependent on all parameters studied and thus the resulting modulon varies substantially depending on the identification procedure. Yet, modulons that were identified correctly displayed higher stability during iterations, which allows developing a procedure for reliable modulon identification in the case of less studied species where the known regulatory interactions are sparse.


Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum.
Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial-lateral and a rostral-caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning.


Evidence for anomalous network connectivity during working memory encoding in schizophrenia: an ICA based analysis.
Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by "functional connectivity" analyses. We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct "normal" encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase. This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.


A secretory and histological study of the stomach before and after truncal vagotomy and pyloroplasty in duodenal ulcer patients.
In 10 patients with duodenal ulcer gastric secretion was studied after graded doses of pentagastrin before and 3 months after truncal vagotomy and pyloroplasty. In 6 patients carbacholine was also infused simultaneously with the greatest dose of pentagastrin after vagotomy. The histology of the gastric mucosa was studied in suction biopsies obtained from the corpus of the stomach before and 3 months after the operation. After truncal vagotomy with pyloroplasty the maximal pentagastrin-stimulated acid and pepsin secretion and the sensitivity of the parietal cells to pentagastrin were all reduced significantly. There was no significant increase in maximal pentagastrin-stimulated acid and pepsin secretion when carbacholine was added to pentagastrin. The average thickness of the gastric mucosa and the mean number of parietal cells per unit area of the stomach did not show any significant change, while the number of patients with deep gastritis increased significantly after vagotomy.


Apigenin Suppresses the IL-1β-Induced Expression of the Urokinase-Type Plasminogen Activator Receptor by Inhibiting MAPK-Mediated AP-1 and NF-κB Signaling in Human Bladder Cancer T24 Cells.
The urokinase-type plasminogen activator receptor (uPAR), a glycoprotein localized on the cell surface with a glycosylphosphatidylinositol anchor, plays a crucial role in cell invasion, and the metastasis of several cancers, including bladder cancer, and its expression are significantly negatively correlated with patient survival rates. Apigenin, a naturally produced phytochemical compound found in fruits, vegetables, and plant leaves, has been shown to mediate a variety of cancer-metastasis-related molecules in various cancers. The effect of apigenin on uPAR expression is still unknown. In this study, we examined the effects of apigenin on IL-1β-induced uPAR expression and investigated its potential mechanisms. We discovered in this study that IL-1β could remarkably induce uPAR expression in bladder cancer T24 cells and that apigenin-inhibited IL-1β could induce uPAR expression concentration-dependently. Interestingly, NF-κB and AP-1 transcription factors were critically required for IL-1β-induced high uPAR expression. Apigenin suppressed the transcriptional activity of both AP-1 and NF-κB by inhibiting ERK1/2 and JNK signaling pathways. These results suggest that apigenin can exert anti-invasion effects by inhibiting uPAR expression via mediating (ERK1/2, JNK)/AP-1 and (ERK1/2, JNK)/NF-κB signaling pathways in human T24 cells. Our present study generated novel and valuable biological insight into anti-invasion through treatment with a small native compound.


A randomized phase II study of gemcitabine and carboplatin with or without cediranib as first-line therapy in advanced non-small-cell lung cancer: North Central Cancer Treatment Group Study N0528.
The purpose of this study was to assess the safety and efficacy of gemcitabine and carboplatin with (arm A) or without (arm B) daily oral cediranib as first-line therapy for advanced non-small-cell lung cancer. A lead-in phase to determine the tolerability of gemcitabine 1000 mg/m on days 1 and 8, and carboplatin on day 1 at area under curve 5 administered every 21 days with cediranib 45 mg once daily was followed by a 2 (A):1 (B) randomized phase II study. The primary end point was confirmed overall response rate (ORR) with 6-month progression-free survival (PFS6) rate in arm A as secondary end point. Polymorphisms in genes encoding cediranib targets and transport were correlated with treatment outcome. On the basis of the safety assessment, cediranib 30 mg daily was used in the phase II portion. A total of 58 and 29 evaluable patients were accrued to arms A and B. Patients in A experienced more grade 3+ nonhematologic adverse events, 71% versus 45% (p = 0.01). The ORR was 19% (A) versus 20% (B) (p = 1.0). PFS6 in A was 48% (95% confidence interval: 35%-62%), thus meeting the protocol-specified threshold of at least 40%. The median overall survival was 12.0 versus 9.9 months (p = 0.10). FGFR1 rs7012413, FGFR2 rs2912791, and VEGFR3 rs11748431 polymorphisms were significantly associated with decreased overall survival (hazard ratio 2.78-5.01, p = 0.0002-0.0095). The trial did not meet its primary end point of ORR but met its secondary end point of PFS6. The combination with cediranib 30 mg daily resulted in increased toxicity. Pharmacogenetic analysis revealed an association of FGFR and VEGFR variants with survival.


Efficacy of Combined Magnetic Field Treatment on Spinal Fusion: A Review of the Literature.
Vertebral fractures place significant burdens on patients, caregivers, and the healthcare system at large. Nonunion is a frequent complication following vertebral fracture treatment, often resulting in significant patient pain and morbidity. Bone growth stimulators are an adjunct treatment modality proposed to increase rates of fracture healing. Combined magnetic field (CMF) bone growth stimulators have specifically been shown to increase union rates in patients with vertebral fractures. Certain populations, such as the elderly, postmenopausal women, and smokers, have demonstrated a preferentially greater response to CMF treatment. The present review focuses on the mechanism of action, efficacy, cost effectiveness, indications, contraindications, and safety of CMF treatment as an adjunct treatment for vertebral fractures. Future large high-quality investigations of adjunct CMF treatment for spine fusion patients focusing on patient-important outcomes are warranted.


Thermal treatment of landfill leachate and the emission control.
The main aim of this study was to develop an appropriate system for the thermal treatment of landfill leachate. In the initial phase of this study, characterization studies were conducted both for the waste disposed and leachate generated. For the thermal treatment of the landfill leachate two different incineration systems, namely a double-phase liquid waste incineration system and a new pilot-scale incineration system, were tested. During the experimental study, the capability of the new pilot-scale incineration system was proven to treat the landfill leachate. However, high concentrations of NOx were recorded. On the other hand, the experimental data, obtained during the testing period of the double-phase liquid waste incineration system, indicated that the fluidized bed incinerator provided an extra unit sufficient to complete the oxidation of partial products of combustion and organics carried from the initial incinerator. Therefore, lower gaseous emissions were noted. However, an agglomeration problem has occurred, due to the high concentrations of Na, Ca and K. It was concluded that considering the flexibility of the thermal processes, thermal treatment of leachate could successfully be applied to Odayeri landfill, as well as to many landfills, if proper gas treatment systems are applied.


A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma (DIPG).
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brainstem tumor that carries a universally fatal prognosis. Because surgical resection is not a viable treatment strategy and biopsy is not routinely performed, the availability of patient samples for research is limited. Consequently, efforts to study this disease have been challenged by a paucity of faithful disease models. To address this need, we describe here a protocol for the rapid processing of post-mortem autopsy tissue samples in order to generate durable patient-derived cell culture models that can be used in in vitro assays or in vivo orthotopic xenograft experiments. These models can be used to screen for potential drug targets and to study fundamental pathobiological processes within DIPG. This protocol can further be extended to analyze and isolate tumor and microenvironmental cells using Fluorescence-activated Cell Sorting (FACS), which enables subsequent analysis of gene expression, protein expression, or epigenetic modifications of DNA at the bulk cell or single cell level. Finally, this protocol can also be adapted to generate patient-derived cultures for other central nervous system tumors.


Low level constraints on dynamic contour path integration.
Contour integration is a fundamental visual process. The constraints on integrating discrete contour elements and the associated neural mechanisms have typically been investigated using static contour paths. However, in our dynamic natural environment objects and scenes vary over space and time. With the aim of investigating the parameters affecting spatiotemporal contour path integration, we measured human contrast detection performance of a briefly presented foveal target embedded in dynamic collinear stimulus sequences (comprising five short 'predictor' bars appearing consecutively towards the fovea, followed by the 'target' bar) in four experiments. The data showed that participants' target detection performance was relatively unchanged when individual contour elements were separated by up to 2° spatial gap or 200 ms temporal gap. Randomising the luminance contrast or colour of the predictors, on the other hand, had similar detrimental effect on grouping dynamic contour path and subsequent target detection performance. Randomising the orientation of the predictors reduced target detection performance greater than introducing misalignment relative to the contour path. The results suggest that the visual system integrates dynamic path elements to bias target detection even when the continuity of path is disrupted in terms of spatial (2°), temporal (200 ms), colour (over 10 colours) and luminance (-25% to 25%) information. We discuss how the findings can be largely reconciled within the functioning of V1 horizontal connections.


A study of the genetic basis of the sexual dimorphism for wing length in Drosophila melanogaster.
The genetic basis of a sexually dimorphic quantitative character in Drosophila melanogaster was investigated by means of two-way directional selection for increased and decreased differences between male and female wing length. The sex dimorphism (SD), defined as the mean wing length difference between the sexes, within families, provided the criterion for selection.-The two lines (High SD, Low SD) diverged rapidly during the 15 generations of selection, indicating the presence of extensive genetic variability for the genotype-sex interaction underlying the observed sexual dimorphism. There was evidence that genetic variability persisted in both lines when selection was relaxed. Most of the divergence between the two lines remained after 10 generations of relaxed selection.-The change in the level of sex dimorphism in the High line was due primarily to a decrease in male wing length; in the Low line most of the change in SD was the result of a decrease in female wing length. An overall reduction in wing length in both sexes in both lines is interpreted as an effect of inbreeding.-The distribution and nature of the genetic control underlying the SD characteristic of the two selection lines was investigated by chromosome substitution between selection lines using a marked inversion technique. The two lines differed by factors located on each of the three major chromosome pairs. Chromosome III had the greatest effect on the difference in SD level between lines, and showed an overall additive effect when present in homozygous versus heterozygous combination. Chromosome II had the least effect, with a significant dominance effect of the High II being evident when heterozygotes were compared with homozygotes. The effect of the X chromosome was intermediate. There was some evidence of interaction between non-homologous chromosomes.


Postdoctoral education in dentistry: preparing dental practitioners to meet the oral health needs of America in the 21st century.
There has been increasing interest in the organization and accreditation of Postdoctoral General Dentistry Programs (PGD). In addition, numerous national organizations have called for increases in the number of first postdoctoral year (PGY-1) positions and programs. At the same time there has been a movement to incorporate concepts of competency-based education into dental education programs in order to stress the outcomes of education rather then the process. These movements have coincided with an increased recognition that dental education will be affected by the changing demographics of our population, the emerging trends in health care delivery and financing, and the need for an increase in the number of primary care providers in dentistry, trained at an advanced level, who are capable of caring for an increasingly socially diverse and medically complex population in our country in the next century. This paper reviews the history of postdoctoral education programs in dentistry and medicine with a focus on PGD education, describes the changing health care environment in which future dental professionals will practice, and relates the dental postdoctoral experience to that in medicine. A strategy is presented for the dental profession to prepare dental practitioners with the competencies needed for the future and to create enough training opportunities to prepare these practitioners to care for the oral health needs of the nation. This proposal calls for a "National Consensus Development Conference on the Future of Postdoctoral Primary Care Education in Dentistry". This conference would define the strategies necessary to prepare dental practitioners with the competencies needed for the future and develop approaches to create enough training opportunities to prepare these practitioners to care for the oral health needs of the nation.


Investigating student collaborative problem-solving competency and science achievement with multilevel modeling: Findings from PISA 2015.
Collaborative problem-solving (CPS) competency is critical for 21st century students. However, reports from the Programme for International Student Assessment (PISA) 2015 have revealed significant deficiencies in this competency among young students globally, indicating a critical need for the cultivation of CPS skills. Therefore, it is essential for educators and researchers to examine the factors that influence CPS competency and understand the potential role of CPS in secondary education. The present study aims to investigate the relationship between collaboration dispositions and students' CPS competency as well as the relationships of CPS competency and inquiry-based science instruction (IBSI) with science achievement using the PISA 2015 data. A total of 408,148 students from 52 countries and economies (i.e., regions) were included in our analysis. Unlike most previous studies that only investigated one country at a time and neglected the multilevel data structure of PISA, this study provided a global view through adopting multilevel modeling to account for the cluster effect at the school and country levels. Our findings revealed that valuing relationship was positively associated with CPS, whereas valuing teamwork was negatively associated with CPS. Furthermore, CPS competency was found to be a dominant and positive predictor of science achievement among all study variables, underscoring the importance of integrating CPS into teaching practices to promote student success in science. Additionally, different IBSI activities show varying relationships with science achievement, indicating that caution should be taken when recommending any specific practices associated with IBSI to teachers.


In vitro evaluation of the performance of an oxygenator depending on the non-standard gas content of the inlet blood with special regard on CO2 elimination.
The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future.


Identification of pathways, gene networks, and paralogous gene families in Daphnia pulex responding to exposure to the toxic cyanobacterium Microcystis aeruginosa.
Although cyanobacteria produce a wide range of natural toxins that impact aquatic organisms, food webs, and water quality, the mechanisms of toxicity are still insufficiently understood. Here, we implemented a whole-genome expression microarray to identify pathways, gene networks, and paralogous gene families responsive to Microcystis stress in Daphnia pulex . Therefore, neonates of a sensitive isolate were given a diet contaminated with Microcystis to contrast with those given a control diet for 16 days. The microarray revealed 2247 differentially expressed (DE) genes (7.6% of the array) in response to Microcystis , of which 17% are lineage-specific (i.e., these genes have no detectable homology to any other gene in currently available databases) and 49% are gene duplicates (paralogues). We identified four pathways/gene networks and eight paralogous gene families affected by Microcystis . Differential regulation of the ribosome, including three paralogous gene families encoding 40S, 60S, and mitochondrial ribosomal proteins, suggests an impact of Microcystis on protein synthesis of D. pulex . In addition, differential regulation of the oxidative phosphorylation pathway (including the NADH:ubquinone oxidoreductase gene family) and the trypsin paralogous gene family (a major component of the digestive system in D. pulex ) could explain why fitness is reduced based on energy budget considerations.


Alpha-blocker therapy of hypertension. An unfulfilled promise.
For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. The introduction of additional agents of this class with properties different from prazosin provides slower onset of action, which should reduce the degree of first-dose and postural hypotension and a longer duration of action, which allows for once-a-day dosage. A summary of the published data on efficacy, side effects, and special properties of this class of agents indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.


Novel Li₂MnO₃ nanowire anode with internal Li-enrichment for use in a Li-ion battery.
Anode materials which undergo a conversion reaction can achieve larger specific capacities than conventional carbon-based materials. They can even achieve higher energy densities when used at low voltages. However, the large amounts of Li₂O generated in the interior of these structures when Li ions are inserted can cause volume expansion and mechanical fracturing from the inside out. This leads to a poor cycling performance and limits their commercial application. To overcome this limitation, we introduced Li ions into the interior of the cells of manganese oxide materials and successfully synthesized a novel Li-rich anode material (Li₂MnO₃). The reversible capacity reached 1279 mA h g(-1) after 500 cycles, much higher than that of pure MnO₂ or other commercial anodes. This optimization of the internal Li-enrichment and its application in Li₂MnO₃ nanowires used as low voltage anodes in Li-ion batteries have rarely been reported. Further investigations by X-ray diffraction and photoelectron spectroscopy suggested that the strategy of optimizing the internal Li-enrichment of this novel Li₂MnO₃ anode is a promising development for Li-ion batteries.


[Julian Huxley's transhumanism: a new religion for humanity].
In this article some works by Julian Huxley are analyzed with the intention of understanding the meaning that he gave to the word transhumanism. Huxley's intellectual search throughout his work as a scientist and as a humanist led him to transform his idea until he found the right word. The essence of his philosophical and religious concern is that he always looked for ways to transcend the limits of human nature. For the British biologist, the religious-scientific mission that supposes the belief in transhumanism leads to the conviction that the human being will be able to transcend his status as a species in order to concentrate all the fragments of his conscience in a total cosmic self-consciousness that gives fullness to the universal and unique substance of which it is a part.


Hematopoietic stem cells are not direct cytotoxic targets of natural killer cells.
Bone marrow (BM) transplants from one individual to an irradiated histoincompatible individual of the same species are rejected. In mice, the primary host barrier cells that recognize bone marrow grafts bearing hematopoietic histocompatibility antigens bear surface markers of natural killer (NK) lymphocytes. Because of the innate ability of NK cells to kill susceptible targets, it has been proposed that the cytotoxic bone marrow graft rejection. To test this hypothesis, we purified hematopoietic stem cells from mice and incubated them with purified populations of actively cytotoxic allogeneic and semisyngeneic NK cells, followed by analysis of the ability of the treated hematopoietic stem cells (HSCs) to rescue lethally irradiated syngeneic animals. Such rescue was unimpaired. Also, HSC allografts were transplanted into transgenic mice deficient in NK and killer T-cell cytotoxicity generated by expressing diphtheria toxin A chain under the control of granzyme A promoter. Allogeneic HSCs were susceptible to allogeneic restriction in these mice, implying that the effector functions of NK marker-positive cells do not require NK cell cytotoxicity.


Loop Electrosurgical Excision Procedure vs. Cold Knife Cone in Treatment of Cervical Intraepithelial Neoplasia: Review of 447 Cases.
Loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC) are often used for the treatment of high-grade cervical intraepithelial lesions. LEEP is an in-office procedure with less discomfort and fewer complications than CKC. However, concerns related to LEEP include the interpretability of the resection margins, positive margins, and the tissue fragmentation. Negative for dysplasia in LEEP or CKC specimens are not uncommon, which may be associated with lesion regression or interpretation errors. 447 cases with 259 LEEP and 188 CKC were included in this study. Patients with CKC were significantly older than patients with LEEP (38 vs. 31, p=0.0001). LEEP was associated with more tissue fragmentation (45.2% vs. 8.5%, p=0.0001) and un-interpretable surgical margins than CKC (10.4% vs. 2.7%, p=0.001). LEEP and CKC had similar positive surgical margin rate. 380 cases had both in-house biopsy and LEEP/CKC (219 LEEP and 161 CKC) specimens. Twenty four cases were negative for dysplasia on the LEEP/CKC (6.3%, 24/380), and the negative rates were similar between LEEP and CKC groups (6.8% vs. 5.6%, p=0.67). Reviewing the previous biopsy or cytology of the 24 negative cases confirmed high-grade squamous intraepithelial lesion (HSIL/CIN2+) in 22 cases, and the remaining 2 cases were misinterpretations of low-grade squamous intraepithelial lesion (LSIL/CIN1) in the biopsy or cytology. The negative rate was higher in cervical cytology only group comparing to cervical biopsy confirmed CIN2+ group (10.8% vs. 5.4%), but it was not statistically significant (p=0.15). The residual/recurrent rate for cervical dysplasia was only 2.9% (11/373).


The doctoring curriculum at the University of California, Davis School Of Medicine: leadership and participant roles for psychiatry faculty.
The authors describe in detail the 3-year model of the Doctoring curriculum plus an elective fourth-year Doctoring course at University of California, Davis School of Medicine (UCDSOM) and University of California, Los Angeles (UCLA) School of Medicine and the critical role for psychiatry faculty leadership and participation. The authors present a review of curricular materials and course operations for the different Doctoring courses for first-, second-, third-, and fourth-year curriculum. The authors describe the role of psychiatry faculty in both leadership and in group facilitation. The Doctoring curriculum offers case-based, small-group learning that relies heavily on standardized patients to teach core content around doctor-patient communication, ethics, behavioral medicine, and counseling approaches. There are frequent psychosocial issues woven in to these encounters. Psychiatry faculty members and other mental health professionals are well-prepared by virtue of their training to lead small group discussions and facilitate the supportive elements of the small groups in medical education. The Doctoring curriculum is both a biopsychosocial educational endeavor and a high-visibility leadership opportunity for the Department of Psychiatry. Other medical schools and departments of psychiatry may wish to pursue similar roles in their didactic programs.


Autonomic dysreflexia in multiple sclerosis.
Although autonomic dysreflexia (AD) is well documented in the spinal cord injury (SCI) population, its occurrence in persons with multiple sclerosis (MS) is not. A dense multiple sclerotic lesion in the spinal cord at or above the sixth thoracic level can cause interruption of descending inhibitory impulses and thus result in AD. A patient with MS presented to our facility with classic signs and symptoms of AD. We believe that lack of knowledge about the risks for this condition in MS led to a delay in diagnosis. Case report illustrates AD in a person with MS. A convenience survey was conducted among clinicians who provide care to people with MS. The survey looked at both awareness of, and experience with, AD in MS. Forty-five percent of the respondents indicated they were not aware of the potential risk for AD among MS patients. Only 10% indicated they were aware of MS patients in their practice who had experienced AD. Although AD is probably less common in MS than in SCI, this case does not appear to be unique. Knowledge of this potential life-threatening complication of MS seems to be limited.


Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
The development of chromosomal abnormalities (CAs) in the Philadelphia chromosome (Ph)-negative metaphases during imatinib (IM) therapy in patients with newly diagnosed chronic myecloid leukemia (CML) has been reported only anecdotally. We assessed the frequency and significance of this phenomenon among 258 patients with newly diagnosed CML in chronic phase receiving IM. After a median follow-up of 37 months, 21 (9%) patients developed 23 CAs in Ph-negative cells; excluding -Y, this incidence was 5%. Sixteen (70%) of all CAs were observed in 2 or more metaphases. The median time from start of IM to the appearance of CAs was 18 months. The most common CAs were -Y and + 8 in 9 and 3 patients, respectively. CAs were less frequent in young patients (P = .02) and those treated with high-dose IM (P = .03). In all but 3 patients, CAs were transient and disappeared after a median of 5 months. One patient developed acute myeloid leukemia (associated with - 7). At last follow-up, 3 patients died from transplantation-related complications, myocardial infarction, and progressive disease and 2 lost cytogenetic response. CAs occur in Ph-negative cells in a small percentage of patients with newly diagnosed CML treated with IM. In rare instances, these could reflect the emergence of a new malignant clone.


Toll-like receptors and myocardial ischemia/reperfusion, inflammation, and injury.
Cardiac ischemia/reperfusion (I/R) injury occurs in several important clinical contexts including percutaneous coronary interventions for acute myocardial ischemia, cardiac surgery in the setting of cardiopulmonary bypass, and cardiac transplantation. While the pathogenesis of I/R injury in these settings is multifactorial, it is clear that activation of the innate immune system and the resultant inflammatory response are important components of I/R injury. Toll-like receptor 4 (TLR4), originally identified as the sensor for bacterial lipopolysaccharide (LPS), has also been shown to serve as a sensor for endogenous molecules released from damaged or ischemic tissues. Accordingly, recent findings have demonstrated that TLR4 not only plays a central role as a mediator of cardiac dysfunction in sepsis, but also serves as a key mediator of myocardial injury and inflammation in the setting of I/R. Furthermore, TLR4 may play a role in the development of atherosclerotic lesions. Other studies have implicated TLR4 in the adverse remodeling that may occur after ischemic myocardial injury. This emerging body of literature, which is reviewed here, has provided new insight into the early molecular events that mediate myocardial injury and dysfunction in the setting of I/R injury.


Inoculation with Metal-Mobilizing Plant-Growth-Promoting Rhizobacterium Bacillus sp. SC2b and Its Role in Rhizoremediation.
A plant growth-promoting bacterial (PGPB) strain SC2b was isolated from the rhizosphere of Sedum plumbizincicola grown in lead (Pb)/zinc (Zn) mine soils and characterized as Bacillus sp. based on (1) morphological and biochemical characteristics and (2) partial 16S ribosomal DNA sequencing analysis. Strain SC2b exhibited high levels of resistance to cadmium (Cd) (300 mg/L), Zn (730 mg/L), and Pb (1400 mg/L). This strain also showed various plant growth-promoting (PGP) features such as utilization of 1-aminocyclopropane-1-carboxylate, solubilization of phosphate, and production of indole-3-acetic acid and siderophore. The strain mobilized high concentration of heavy metals from soils and exhibited different biosorption capacity toward the tested metal ions. Strain SC2b was further assessed for PGP activity by phytagar assay with a model plant Brassica napus. Inoculation of SC2b increased the biomass and vigor index of B. napus. Considering such potential, a pot experiment was conducted to assess the effects of inoculating the metal-resistant PGPB SC2b on growth and uptake of Cd, Zn and Pb by S. plumbizincicola in metal-contaminated agricultural soils. Inoculation with SC2b elevated the shoot and root biomass and leaf chlorophyll content of S. plumbizincicola. Similarly, plants inoculated with SC2b demonstrated markedly higher Cd and Zn accumulation in the root and shoot system, indicating that SC2b enhanced Cd and Zn uptake by S. plumbizincicola through metal mobilization or plant-microbial mediated changes in chemical or biological soil properties. Data demonstrated that the PGPB Bacillus sp. SC2b might serve as a future biofertilizer and an effective metal mobilizing bioinoculant for rhizoremediation of metal polluted soils.


Linear projection-based chemical exchange saturation transfer parameter estimation.
Isolated evaluation of multiparametric in vivo chemical exchange saturation transfer (CEST) MRI often requires complex computational processing for both correction of B0 and B1 inhomogeneity and contrast generation. For that, sufficiently densely sampled Z-spectra need to be acquired. The list of acquired frequency offsets largely determines the total CEST acquisition time, while potentially representing redundant information. In this work, a linear projection-based multiparametric CEST evaluation method is introduced that offers fast B0 and B1 inhomogeneity correction, contrast generation and feature selection for CEST data, enabling reduction of the overall measurement time. To that end, CEST data acquired at 7 T in six healthy subjects and in one brain tumor patient were conventionally evaluated by interpolation-based inhomogeneity correction and Lorentzian curve fitting. Linear regression was used to obtain coefficient vectors that directly map uncorrected data to corrected Lorentzian target parameters. L1-regularization was applied to find subsets of the originally acquired CEST measurements that still allow for such a linear projection mapping. The linear projection method allows fast and interpretable mapping from acquired raw data to contrast parameters of interest, generalizing from healthy subject training data to unseen healthy test data and to the tumor patient dataset. The L1-regularization method shows that a fraction of the acquired CEST measurements is sufficient to preserve tissue contrasts, offering up to a 2.8-fold reduction of scan time. Similar observations as for the 7-T data can be made for data from a clinical 3-T scanner. Being a fast and interpretable computation step, the proposed method is complementary to neural networks that have recently been employed for similar purposes. The scan time acceleration offered by the L1-regularization ("CEST-LASSO") constitutes a step towards better applicability of multiparametric CEST protocols in a clinical context.


[Interauricular right-left shunt: a serious complication of primary pulmonary arterial hypertension].
Primary pulmonary hypertension is a rare and generally progressive disease in which mild hypoxemia at rest, with lower PaO2 during exercise, is consistently reported. Severe hypoxemia at rest suggests the occurrence of a right to left intracardiac shunt, most often due to patency of a foramen ovale. Two cases are reported of primary pulmonary hypertension which rapidly developed severe hypoxemia at rest with worsening of pulmonary hypertension, from which interatrial communication was identified. The prognostic and therapeutic implications of this situation are discussed.


An investigation into the role of polymeric carriers on crystal growth within amorphous solid dispersion systems.
Using phase diagrams derived from Flory-Huggins theory, we defined the thermodynamic state of amorphous felodipine within three different polymeric carriers. Variation in the solubility and miscibility of felodipine within different polymeric materials (using F-H theory) has been identified and used to select the most suitable polymeric carriers for the production of amorphous drug-polymer solid dispersions. With this information, amorphous felodipine solid dispersions were manufactured using three different polymeric materials (HPMCAS-HF, Soluplus, and PVPK15) at predefined drug loadings, and the crystal growth rates of felodipine from these solid dispersions were investigated. Crystallization of amorphous felodipine was studied using Raman spectral imaging and polarized light microscopy. Using this data, we examined the correlation among several characteristics of solid dispersions to the crystal growth rate of felodipine. An exponential relationship was found to exist between drug loading and crystal growth rate. Moreover, crystal growth within all selected amorphous drug-polymer solid dispersion systems were viscosity dependent (η(-ξ)). The exponent, ξ, was estimated to be 1.36 at a temperature of 80 °C. Values of ξ exceeding 1 may indicate strong viscosity dependent crystal growth in the amorphous drug-polymer solid dispersion systems. We argue that the elevated exponent value (ξ > 1) is a result of drug-polymer mixing which leads to a less fragile amorphous drug-polymer solid dispersion system. All systems investigated displayed an upper critical solution temperature, and the solid-liquid boundary was always higher than the spinodal decomposition curve. Furthermore, for PVP-FD amorphous dispersions at drug loadings exceeding 0.6 volume ratio, the mechanism of phase separation within the metastable zone was found to be driven by nucleation and growth rather than liquid-liquid separation.


Site-directed mutagenesis of glutamate 166 in two beta-lactamases. Kinetic and molecular modeling studies.
The catalytic pathway of class A beta-lactamases involves an acyl-enzyme intermediate where the substrate is ester-linked to the Ser-70 residue. Glu-166 and Lys-73 have been proposed as candidates for the role of general base in the activation of the serine OH group. The replacement of Glu-166 by an asparagine in the TEM-1 and by a histidine in the Streptomyces albus G beta-lactamases yielded enzymes forming stable acyl-enzymes with beta-lactam antibiotics. Although acylation of the modified proteins by benzylpenicillin remained relatively fast, it was significantly impaired when compared to that observed with the wild-type enzyme. Moreover, the E166N substitution resulted in a spectacular modification of the substrate profile much larger than that described for other mutations of Omega-loop residues. Molecular modeling studies indicate that the displacement of the catalytic water molecule can be related to this observation. These results confirm the crucial roles of Glu-166 and of the "catalytic" water molecule in both the acylation and the deacylation processes.


The structural composition of the pulmonary acinus in the mouse. A scanning electron microscopical and developmental-biological analysis.
For analysis of the structural composition of the pulmonary acinus in the mouse, fixed lungs of adult mice were examined by scanning and transmission electron microscopy. The murine acinus proved to consist of one or two generations of rather short respiratory bronchioles and about three generations of alveolar ducts opening into alveolar sacs. The epithelial cells lining the respiratory bronchioles (except for a sharply demarcated zone in the initial portion of the first-order branch) have a cuboidal or squamous shape and are very probably of the same type as those lining the alveolar ducts and sacs, i.e., small and great alveolar cells and/or their precursor cells. Therefore, this respiratory bronchiole portion may be considered part of the respiratory unit or pulmonary acinus. The initial zone of the first-order branch is lined by columnar epithelium, i.e., bronchial epithelium (mainly Clara cells), and should be assigned to the bronchial system of the lung.


miR-873-5p Inhibits Cell Migration and Invasion of Papillary Thyroid Cancer via Regulation of CXCL16.
Papillary thyroid cancer (PTC) is the most common type of thyroid cancer with an increasing morbidity. MicroRNAs (miRNAs) play the pivotal roles in PTC occurrence and development. The aim of this study was to investigate the biological functions of miR-873-5p and its underlying molecular mechanisms in PTC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect miR-873-5p expressions in PTC tissues and cell lines. The target gene of miR-873-5p was predicted by TargetScan and confirmed by dual-luciferase reporter assay. Furthermore, cell proliferation, migration and invasion were assessed by CCK-8, wound healing assay and transwell assay, respectively. Additionally, the expressions of CXCL16, MMP1, MMP9 and MMP13 were measured by RT-qPCR and Western blot methods, and p65, Rel-B and their phosphorylation levels were examined by Western blot. We found that miR-873-5p expression was downregulated in PTC tissues and cell lines. Moreover, CXCL16 was identified as a target of miR-873-5p, and its expression was upregulated in PTC tissues and cells at both mRNA and protein levels. Functionally, overexpression of miR-873-5p inhibited PTC cell proliferation, migration and invasion, while co-transfection of CXCL16 overexpression plasmid reversed the anti-tumor behaviors induced by miR-873-5p. In addition, miR-873-5p overexpression suppressed the phosphorylation of p65 and Rel-B, and decreased the mRNA and protein expression of MMP1, MMP9 and MMP13, while overexpression of CXCL16 partially abrogated the effects of miR-873-5p. MiR-873-5p functions as a tumor suppressor in PTC by inhibiting the proliferation, migration and invasion of the PTC cells via targeting CXCL16. These findings might provide a potential novel target for the therapy of PTC.


Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine.
Migraine is a common neurovascular brain disorder characterised by recurrent attacks of severe headache that may be accompanied by various neurological symptoms. Migraine is thought to result from activation of the trigeminovascular system followed by vasodilation of pain-producing intracranial blood vessels and activation of second-order sensory neurons in the trigeminal nucleus caudalis. Calcitonin gene-related peptide (CGRP) is a mediator of neurogenic inflammation and the most powerful vasodilating neuropeptide, and has been implicated in migraine pathophysiology. Consequently, genes involved in CGRP synthesis or CGRP receptor genes may play a role in migraine and/or increase susceptibility. This study investigates whether variants in the gene that encodes CGRP, calcitonin-related polypeptide alpha (CALCA) or in the gene that encodes a component of its receptor, receptor activity modifying protein 1 (RAMP1), are associated with migraine pathogenesis and susceptibility. The single nucleotide polymorphisms (SNPs) rs3781719 and rs145837941 in the CALCA gene, and rs3754701 and rs7590387 at the RAMP1 locus, were analysed in an Australian Caucasian population of migraineurs and matched controls. Although we find no significant association of any of the SNPs tested with migraine overall, we detected a nominally significant association (p=0.031) of the RAMP1 rs3754701 variant in male migraine subjects, although this is non-significant after Bonferroni correction for multiple testing.


Stimulus-secretion coupling in beta-cells: modulation by pH.
We have examined the influence of changes in pH on the oscillatory pattern of electrical activity (EA) in the beta-cell by altering medium pH (pHo) and using permeable weak buffers to alter intracellular pH (pHi). A decrease in pH in the presence of glucose elicited depolarization to the active phase and constant spike activity, whereas an increase in pH elicited a decrease in spike activity or silent hyperpolarization. On inhibition of HCO3:Cl antiport by addition of DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonic acid), probenecid, or withdrawal of medium HCO-3, there was an increase in the duration of the active phase. A similar result was obtained on the inhibition of Na:H antiport by the addition of amiloride or the reduction of medium [Na+]. The influence of H+ and glucose has been proposed to decrease K+ permeability (PK). However, the influence of pH on 86Rb+ efflux was most effective at subthreshold or 4.2 mM glucose; only a moderate decrease in PK occurred at 8.3 mM glucose, and no effect was obtained at 16.7 mM glucose. Alteration of pHi, and not pHo, induces similar effects on glucose-induced electrical and secretory events. There is a clear dissociation between the influence of inhibitors of the Na:H and HCO3:Cl antiporters on the electrical and secretory events. DIDS and amiloride increased glucose-induced EA, but markedly inhibited the secretory response to glucose. It is evident that pH modulates the electrical events and cationic fluxes and ultimately influences the transduction of information to the mechanisms controlling the secretory process in the beta-cell.


[An overview of current research of the effect of foods on aging and stress].
The aging process is largely influenced by dietary factors. For example, caloric restriction can slow age-related functional deterioration and the onset or progression of age-related diseases, as well as prolong mean and maximum life span in laboratory animals. However, the dietary factors that affect the aging process comprise not only calories, but also various nutrients, such as proteins, carbohydrates, fats, and vitamins. Phytochemicals, which are found in plants, are non-nutritive, yet many phytochemicals are known to act as antioxidants and prevent diseases associated with free radical production. Furthermore, certain phytochemicals can help prevent or reduce the risk of cancer, inflammation, and cardiovascular disease by alteration of several signal transduction pathways in cells. Therefore, much focus is being placed on the effects of dietary phytochemicals on aging and stress response. This paper reviews recent advances in the study of two major dietary phytochemicals, resveratrol and curcumin, on aging and stress response.


Long-term consistency of personality traits of cattle.
Personality is often defined as the behaviour of individual animals that is consistent across contexts and over time. Personality traits may become unstable during stages of ontogeny from infancy to adulthood, especially during major periods of development such as around the time of sexual maturation. The personality of domesticated farm animals has links with productivity, health and welfare, but to our knowledge, no studies have investigated the development and stability of personality traits across developmental life stages in a mammalian farm animal species. Here, we describe the consistency of personality traits across ontogeny in dairy cattle from neonate to first lactation as an adult. The personality traits 'bold' and 'exploratory', as measured by behavioural responses to novelty, were highly consistent during the earlier (before and after weaning from milk) and later (after puberty to first lactation) rearing periods, but were not consistent across these rearing periods when puberty occurred. These findings indicate that personality changes in cattle around sexual maturation are probably owing to major physiological changes that are accelerated under typical management conditions at this time. This work contributes to the understanding of the ontogeny of behaviour in farm animals, especially how and why individuals differ in their behaviour.


[Antimicrobial chemotherapy in patients with pyo-septic diseases in intensive care units].
The analysis of the treatment of 900 patients with large festered wounds of various genesis and location for the period from 1973 to 1998 years in the intensive care department has shown, that infection of respiratory ways is encountered in 30% of cases (in patients with nonsporeforming anaerobic bacteria--in 11-12%), bacteriuria--in 70-80%, bacteriamia--in 75% of patients with sepsis. In acute pyogenous diseases of soft tissues microbes from the wounds in monoculture were isolated out in 83.3% of cases, associations of gram-positive and gram-negative bacteria--in 16.7%, in chronic pyogenous diseases of soft tissues--in 60 and 40% of cases, respectively. In sepsis associations of gram-positive and gram-negative microbes were isolated in 55.6% of cases. Most often (91%) pathogenic staphylococcus was found in hemocultures. Uring in 62% of cases contained association of gram-positive and gram-negative microorganisms, in sputum gram-positive microflora in monoculture (69%) prevailed. In the group of patients with peritonitis, phlegmon of the anterior abdominal wall, diabetic phlegmon and gangrene, crush syndrome the association of anaerobic and aerobic microflora (from 57.1 to 98.8%) prevailed in the wounds. Application of up-to-date antimicrobial means in the intensive care unit resulted in a decrease of mortality rate in sepsis and complicated course of wound infection up to 23%, and in anaerobic nonsporeforming infection--up to 15%.


Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma.
Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.


The Sensitivity of Endodontic Enterococcus spp. Strains to Geranium Essential Oil.
Enterococci are able to survive endodontic procedures and contribute to the failure of endodontic therapy. Thus, it is essential to identify novel ways of eradicating them from infected root canals. One such approach may be the use of antimicrobials such as plant essential oils. Enterococcal strains were isolated from endodontically treated teeth by standard microbiological methods. Susceptibility to antibiotics was evaluated by the disc-diffusion method. The minimal inhibitory concentration (MIC) of geranium essential oil was investigated by microdilution in 96-well microplates in Mueller Hinton Broth II. Biofilm eradication concentrations were checked in dentin tests. Geranium essential oil inhibited enterococcal strains at concentrations ranging from 1.8-4.5 mg/mL. No correlation was shown between resistance to antibiotics and the MICs of the test antimicrobials. The MICs of the test oil were lower than those found to show cytotoxic effects on the HMEC-1 cell line. Geranium essential oil eradicated enterococcal biofilm at concentrations of 150 mg/mL. Geranium essential oil inhibits the growth of endodontic enterococcal species at lower concentrations than those required to reach IC50 against the HMEC-1 cell line, and is effective against bacteria protected in biofilm at higher concentrations. In addition, bacteria do not develop resistance to essential oils. Hence, geranium essential oil represents a possible alternative to other antimicrobials during endodontic procedures.


Pure duplication 1q41-qter: further delineation of trisomy 1q syndromes.
Several authors have attempted to characterize the partial 1q trisomy syndrome, reporting clinical features such as mental retardation, macrocephaly, large fontanels, prominent forehead, broad flat nasal bridge, high-arched palate, micro/retrognathia, low-set ears, and cardiac defects. However, defining the partial trisomy 1q syndrome is difficult, because it is a rare chromosomal abnormality and in most instances the trisomy 1q is combined with partial monosomy of another autosomal segment. We report on the clinical and molecular cytogenetic study of a patient who presents pure partial 1q duplication. This is the first case of pure duplication 1q41-qter in the literature.


Cortical mechanisms for acquisition and performance of bimanual motor sequences.
We used functional magnetic resonance imaging to investigate the cortical mechanisms contributing to the acquisition and performance of a complex, bimanual motor sequence. To that aim, five subjects were trained on a difficult, asymmetrical finger opposition task. Their performance rate almost doubled in the course of training and approached the performance rate in an untrained, symmetrical finger opposition task. Before training, performance of the asymmetrical sequence was associated with activity in M1, premotor cortex, supplementary motor cortex, and parietal cortex. After training, performance of the asymmetrical sequence was associated mainly with activity in M1, and little activity outside M1 remained. The latter pattern of cortical activation resembled that observed during the execution of symmetrical sequences, which was unaffected by practice with the asymmetrical sequence. The activation pattern obtained with the symmetrical bimanual sequence was indistinguishable from the combined activation measured in contralateral hemispheres during unimanual control sequences. The data indicate that cortical regions previously implicated in the acquisition of difficult unimanual motor sequences also contribute to the acquisition of asymmetrical bimanual sequences. We found no evidence for an expansion of activity in M1 after acquisition of the asymmetrical sequence (while this has been reported after acquisition of unimanual sequences). In the context of existing literature, the data suggest that the acquisition of unimanual and bimanual motor sequences may rely on similar cortical mechanisms, but that the formation of long-term, procedural memories for the two types of sequences might at least in part depend on different mechanisms.


Marching into battle: synchronized walking diminishes the conceptualized formidability of an antagonist in men.
Paralleling behaviours in other species, synchronized movement is central to institutionalized collective human activities thought to enhance cooperation, and experiments demonstrate that synchrony has this effect. The influence of synchrony on cooperation may derive from an evolutionary history wherein such actions served to signal coalitional strength to both participants and observers-including adversaries. If so, then synchronous movement should diminish individuals' estimations of a foe's formidability. Envisioned physical size and strength constitute the dimensions of a representation that summarizes relative fighting capacity. Experiencing synchrony should therefore lead individuals to conceptualize an antagonist as smaller and weaker. We found that men who walked synchronously with a male confederate indeed envisioned a purported criminal as less physically formidable than did men who engaged in this task without synchronizing.


Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort.
The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients. A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves. High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03-1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively. This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.


Acceptance and commitment therapy improves exercise tolerance in sedentary women.
To test the efficacy of an acute intervention derived from acceptance and commitment therapy (ACT) for increasing high-intensity constant work rate (CWR) cycle exercise tolerance in a group of low-active women age 18-45 yr. The secondary goals were to examine whether ACT would reduce perceived effort and improve in-task affect during exercise and increase postexercise enjoyment. In a randomized controlled trial, 39 women were randomized to either the experimental (using ACT-based cognitive techniques and listening to music during the CWR exercise tests) or a control group (listening to music during the CWR exercise tests). Before (CWR-1) and after the intervention (CWR-2), participants completed a CWR cycle exercise test at 80% of maximal incremental work rate (Wmax) until volitional exhaustion. On average, ACT (n = 18) and control (n = 21) groups were matched for age, body mass index, weekly leisure activity scores, and Wmax (all P > 0.05). Exercise tolerance time (ETT) increased by 15% from CWR-1 to CWR-2 for the ACT group (392.05 ± 146.4 vs 459.39 ± 209.3 s; mean ± SD) and decreased by 8% (384.71 ± 120.1 vs 353.86 ± 127.9 s) for the control group (P = 0.008). RPE were lower (e.g., by 1.5 Borg 6-20 scale units at 55% of ETT, P ≤ 0.01) during CWR-2 in the ACT versus that in the control group. By contrast, ACT had no effect on in-task affect. Exercise enjoyment was higher after CWR-2 in the ACT group versus that in the control group (P < 0.001). An acute ACT intervention increased high-intensity ETT and postexercise enjoyment and reduced perceived effort in low-active women. Further investigations of ACT as an effective intervention for enhancing the established health benefits of high-intensity exercise need to be provided.


Quantitative Structure-Property Relationship Study for Prediction of Boiling Point and Enthalpy of Vaporization of Alkenes.
Quantitative structure-property relationships (QSPRs) models have been widely developed to derive a correlation between chemical structures of molecules to their known properties. In this study, QSPR models have been used on 91 alkenes to develop a robust model for the prediction of enthalpy of vaporization under standard condition (ΔH°vap/kJ.mol-1) and at normal temperature of boiling points (T˚bp /K) of alkenes. A training set of 81 structurally diverse alkenes was randomly selected and used to construct QSPR models. These models were optimized using backward-multiple linear regression (MLR) analysis. The genetic algorithm and multiple linear regression analysis (GA-MLR) were used to select the suitable descriptors derived from the Dragon software. The multicollinearity properties of the descriptors contributed in the QSPR models were tested and several methods were used for testing the predictive models power such as Leave-One-Out (LOO) cross-validation(Q2 LOO), the five-fold cross-validation techniques, external validation parameters (Q2F1, Q2F2, Q2F3), the concordance correlation coefficient (CCC) and the predictive parameter R2 m. The predictive ability of the models was found to be satisfactory, and the five descriptors in three blocks, namely connectivity, edge adjacency indices and 2D matrix-based descriptors could be used to predict the mentioned properties of alkenes.


Animal model of gluten induced enteropathy in mice.
The aim of our experiments was to produce a local T cell mediated immune response to gliadin in the mouse small intestine as a possible animal model of gluten sensitive enteropathy, coeliac disease. BALB/c and BDF1 mice were immunised systemically with gliadin in complete Freund's adjuvant. The jejunal mucosa was challenged by feeding a gluten containing diet, and villus and crypt lengths, crypt cell production rate, and intraepithelial lymphocyte counts were determined to assess mucosal cell mediated immunity. In some animals permeability and local immunity were modulated by concurrent intestinal anaphylaxis or a graft versus host reaction. There were no changes in the jejunal mucosa of BALB/c mice fed a gluten containing diet after having been parenterally immunized. When, however, mice were parenterally immunised with gliadin, fed a gluten containing diet, rendered hypersensitive to helminth antigen by infection with the nematode parasite Nippostrongylus brasiliensis, and challenged intravenously to produce intestinal anaphylaxis crypt cell production rate was significantly higher than in ovalbumin immunized controls at 12 days after parasite challenge. Finally, graft versus host reaction was induced in BDF1 mice that had been parenterally immunised with gliadin and were on a gluten containing diet. Two weeks later these mice had significantly longer crypts and a higher crypt cell production rate and intraepithelial lymphocyte count than control, unimmunized mice with graft versus host reaction. We conclude that active immunization with gliadin does not in itself produce intestinal cell mediated immunity to gliadin contained in the diet, or enteropathy. Additional factors, such as those occurring during intestinal anaphylaxis (increase intestinal permeability), or during graft versus host reaction (enhanced antigen presentation), seem to be necessary for the full expression of a jejunal mucosal reaction.


What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.
The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose. Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but "at-risk" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up. No significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings. The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.


Seed germination of Arabidopsis thaliana phyA/phyB double mutants is under phytochrome control.
We examined the photocontrol of seed germination in the phyA/phyB double mutants of Arabidopsis thaliana seeds. Dormant phyA/phyB seeds showed a red/far-red light (R/FR)-reversible induction of seed germination. This suggests the involvement of at least one other phytochrome, phyC, D, and/or E, in controlling seed germination. We designated this spectrally active phytochrome in phyA/phyB as phyX. The full reversibility of the R-induced germination by subsequent FR pulses, and the observation that the response is reversible by FR, even after a 3-h R treatment, indicates that this phyX response belongs to the low-fluence-response type. Thus, this phyX response is functionally related to phyB-mediated responses. However, in contrast to phyB-controlled seed germination, this phyX-mediated response needs a prolonged imbibition period and exhibits reversibility kinetics different from that needed for phyB. Furthermore, this phyX response requires a prolonged irradiation time and shows a fluence rate response dependency, showing a similarity to the high irradiance response of photomorphogenesis. Thus, phyX, with regard to its control of seed germination, is a functionally new phytochrome that shares some characteristics of both phyA- and phyB-mediated responses.


Effect of a linseed diet on lipogenesis, fatty acid composition and stearoyl-CoA-desaturase in rabbits.
The aim of the study was to examine the effect of a linseed diet on meat quality and on lipogenesis in rabbits. Twelve rabbits were fed a control or a linseed diet. There was no diet effect on growth, food consumption, carcass characteristics and meat ultimate pH and colour. Feeding the linseed diet increased the n-3 polyunsaturated fatty acids (PUFA) levels in perirenal and interscapular fats, in the Longissimus dorsi muscle and in the liver. The linseed diet produced lower linoleic acid/α-linolenic acid ratios in adipose tissues and in the Longissimus dorsi muscle, but not in the liver. Diet did not affect lipogenic enzyme activities in the Longissimus dorsi muscle, whereas the linseed diet decreased the lipogenic potential in perirenal and interscapular fats, and in the liver. Feeding rabbits with a high n-3 PUFA diet led to a decrease in the oxidative stability of perirenal fat and the Longissimus dorsi muscle, and to an inhibition of stearoyl-CoA-desaturase activity in liver and in adipose tissues, but not in muscle.


Evoluton of polygonal fracture patterns in lava flows.
Cooling-induced fractures, also known as columnar joints, divide basaltic lava flows into prismatic columns with polygonal cross sections. The regularity and symmetry of the fracture patterns have long fascinated naturalists. In view of the recent selection of two candidate nuclear waste sites in areas where polygonally fractured volcanic rocks are located, a better understanding of the fracture patterns is required. Field data indicate that the tetragonal networks at flow surfaces evolve systematically to hexagonal networks as the joints grow inward during solidification of lava. This evolution occurs by the gradual change of most orthogonal intersections to nonorthogonal intersections of about 120 degrees. The surface features and intersection geometries of columnar joints show that joint segments at any given level form sequentially yet harmoniously.


Comparison of computed tomography angiography and transesophageal echocardiography for evaluating aortic arch disease.
Aortic arch (AA) atheroma is a common source of artery-to-artery embolism. Identification of AA atherosclerotic disease is an important component of the embolic stroke workup. Transesophageal echocardiography (TEE) is the gold standard for AA evaluation, but it has associated risks and is not always readily available. Computed tomography angiography (CTA) is a rapid and noninvasive alternative. This study was conducted to compare the sensitivity and specificity of CTA and TEE for detecting AA disease. We performed a retrospective review of 250 consecutive patients at a tertiary stroke center who underwent both TEE and CTA within a 90-day period. We compared the presence and characteristics of AA plaques using a predetermined grading system for plaques in the ascending, transverse, and descending arch for both modalities (grades 1-4). Out of 750 AA segments (ascending, transverse, and descending AA in 250 patients), 494 were adequately imaged by CTA and TEE. The sensitivity of CTA in detecting grade 1-4 AA atheromas was 53%, and the specificity was 89%. For only high-grade atheromas, the specificity improved to 99%, but the sensitivity decreased to 23%. The negative predictive value of CTA for detection of AA atheromas was 60% (range 54%-65%) for all grades and 95% (range 92%-96%) for high-grade atheromas. CTA has a high negative predictive value for AA atheromas, especially for higher-grade atheromas, and thus may be a useful screening tool to exclude high-grade plaques, indicating a possible complementary role for CTA in detecting AA atheromas.


Concomitant use of prescription medications and dietary supplements in menopausal women: an approach to provider preparedness.
Dietary supplements are becoming increasingly popular as therapies for symptom relief among menopause-age women in the United States. However, a large gap exists between research in the concomitant use of prescription medications and dietary supplements and provider preparedness to guide patient decision making. Many menopausal women take prescription medications, over the counter medications, and herbs and dietary supplements for climactic symptoms or other health conditions. With any drug, there is the potential for interactions. Women taking medications with a narrow therapeutic index, such as anticoagulants, anticonvulsants, and drugs for the treatment of chronic diseases, are at particular risk. Patients should be queried regarding their use of dietary supplements when starting or stopping a prescription drug, or if unexpected reactions occur. When counseling patients, one must carefully consider the risks and benefits of each supplement and medication being taken by each individual.


Unilateral absence of latissimus dorsi muscle.
Latissimus dorsi (LD) is the broadest muscle of the back responsible for extension and adduction of shoulder. The authors report a case of isolated unilateral absence of the latissimus dorsi muscle observed during an ablative surgical procedure and flap reconstruction. The left LD muscle was completely absent in our patient and no tendon fibers belonging to this muscle could be observable on further dissection. The surrounding muscle anatomy was normal and in place suggesting a developmental etiology for its absence. Awareness of this possible variation is of importance in considering reconstructive options.


Functional genetic divergence in high CO2 adapted Emiliania huxleyi populations.
Predicting the impacts of environmental change on marine organisms, food webs, and biogeochemical cycles presently relies almost exclusively on short-term physiological studies, while the possibility of adaptive evolution is often ignored. Here, we assess adaptive evolution in the coccolithophore Emiliania huxleyi, a well-established model species in biological oceanography, in response to ocean acidification. We previously demonstrated that this globally important marine phytoplankton species adapts within 500 generations to elevated CO2 . After 750 and 1000 generations, no further fitness increase occurred, and we observed phenotypic convergence between replicate populations. We then exposed adapted populations to two novel environments to investigate whether or not the underlying basis for high CO2 -adaptation involves functional genetic divergence, assuming that different novel mutations become apparent via divergent pleiotropic effects. The novel environment "high light" did not reveal such genetic divergence whereas growth in a low-salinity environment revealed strong pleiotropic effects in high CO2 adapted populations, indicating divergent genetic bases for adaptation to high CO2 . This suggests that pleiotropy plays an important role in adaptation of natural E. huxleyi populations to ocean acidification. Our study highlights the potential mutual benefits for oceanography and evolutionary biology of using ecologically important marine phytoplankton for microbial evolution experiments.


Stochastic Self-Consistent Second-Order Green's Function Method for Correlation Energies of Large Electronic Systems.
The second-order Matsubara Green's function method (GF2) is a robust temperature-dependent quantum chemistry approach, extending beyond the random-phase approximation. However, until now the scope of GF2 applications was quite limited as they require computer resources that rise steeply with system size. In each step of the self-consistent GF2 calculation there are two parts: estimating of the self-energy from the previous step's Green's function and updating the Green's function from the self-energy. The first part formally scales as the fifth power of the system size, while the second has a much gentler cubic scaling. Here, we develop a stochastic approach to GF2 (sGF2), which reduces the fifth power scaling of the first step to merely quadratic, leaving the overall sGF2 scaling as cubic. We apply the method to linear hydrogen chains with up to 1000 electrons, showing that the approach is numerically stable, efficient, and accurate. The stochastic errors are very small, on the order of 0.1% or less of the correlation energy for large systems, with only a moderate computational effort. The first iteration of GF2 is an MP2 calculation that is done in linear scaling; hence we obtain an extremely fast stochastic MP2 (sMP2) method as a byproduct. While here we consider finite systems with large band gaps where at low temperatures effects are negligible, the sGF2 formalism is temperature dependent and general and can be applied to finite or periodic systems with small gaps at finite temperatures.


Three-Dimensional Printing in Cleft Care: A Systematic Review.
To determine the current applications of 3-dimensional (3D) printing in the care of patients with cleft lip and palate. We also reviewed 3D printing limitations, financial analysis, and future implications. Retrospective systematic review. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used by 3 independent reviewers. Articles were identified from Cochrane library, Ovid Medline, and Embase. Search terms included 3D printing, 3 dimensional printing, additive manufacturing, rapid prototyping, cleft lip, and cleft palate. Exclusion criteria included articles not in English, animal studies, reviews without original data, oral presentations, abstracts, opinion pieces, and articles without relevance to 3D printing or cleft lip and palate. Primary outcome measure was the purpose of 3D printing in the care of patients with cleft lip and palate. Secondary outcome measures were cost analysis and clinical outcomes. Eight-four articles were identified, and 39 met inclusion/exclusion criteria. Eleven studies used 3D printing models for nasoalveolar molding. Patient-specific implants were developed via 3D printing in 6 articles. Surgical planning was conducted via 3D printing in 8 studies. Eight articles utilized 3D printing for anatomic models/educational purposes. 3-Dimensional printed models were used for surgical simulation/training in 6 articles. Bioprinting was utilized in 4 studies. Secondary outcome of cost was addressed in 8 articles. 3-Dimensional printing for the care of patients with cleft lip and palate has several applications. Potential advantages of utilizing this technology are demonstrated; however, literature is largely descriptive in nature with few clinical outcome measures. Future direction should be aimed at standardized reporting to include clinical outcomes, cost, material, printing method, and results.


[Relationship of insight with depression and suicidal ideation in psychotic disorders].
The associations of insight into psychosis (i.e., awareness of illness) with clinical variables have been examined by a great number of studies. Most of these studies revealed that the level of insight is negatively correlated with psychotic symptoms but positively correlated with depression and suicidal ideation. The aim of this study was to test these findings in a Greek sample of patients. Forty-three outpatients (30 men and 13 women) with schizophrenia or delusional disorder being followed up at the Mental Health Centre of Kavala took part in the study. Patients with bipolar or schizoaffective disorder were excluded. Patients' mean age was 40.7 years and the mean duration of illness was 18.67 years. All participants were under treatment and clinically stable at the time of the study. We used the Positive and Negative Syndrome Scale (PANSS) for the assessment of positive and negative symptoms, the Schedule for the Assessment of Insight-Expanded (SAI-E) to assess the insight into psychosis, and the Montgomery-Asberg Depression Rating Scale (MADRS) for the evaluation of depression recording separately the score for item 10 as an estimate of suicidal ideation. All the scales used have been adapted to Greek population. We used Spearman rho coefficient to assess the strength of correlations between the scales because the distributions of some scores were not normal. In order to assess the predictive value of insight for depression and suicidal ideation, we used hierarchical linear regression analysis. Correlation coefficients between SAI-E and the clinical scales of psychopathology, depression and suicide ideation was statistically significant at the p<0.01 level. The correlations between the clinical scales and the three subscales of SAI-E were also significant at the aforementioned p level. The regression analysis showed that our model of positive and negative psychopathology and insight explained 47.4% of the variance of depression and 32.2% of the variance of suicidal ideation. The predictive value of insight was critically important, because only after the introduction of the SAI-E score in the analysis our regression models reached statistical significance. Taking into account its limitations regarding the sample size and the chronicity of the illness, our study confirms the positive correlation of insight with depression and suicidal ideation, offering support to the psychological model of insight.


[Doppler ultrasonic method of blood velocity measurement in Raynaud's phenomenon].
Ten patients, 3 males and 7 females, aging less then 50 years (M: 37), suffering from at least one year for a Raynaud's phenomenon surely not due to a costo-clavicular syndrome, were studied. A Doppler ultrasound evaluation was first done recording the pressure and the speed at the omeral, radial, ulnar, and digital arteries. The patients were then submitted to an angiography in general anaesthesia through puncture of the omeral artery and to screening tests to detect possible associated immunopathological diseases. In the patients affected by Raynaud's phenomenon the vascular lesions are generally distal to the omeral artery; the only surgical indication is a thoracic gangliectomy. Our experience shows that the Doppler velocimetry gives all the data necessary to check the efficacy of a pharmacological treatment and to state a correct surgical indication.


Identification and characterization of Heliothis virescens midgut membrane proteins binding Bacillus thuringiensis delta-endotoxins.
To investigate the specificity of Bacillus thuringiensis var. kurstaki strain HD1 insecticidal crystal proteins (ICP), we used membrane preparations obtained from the midgut of Heliothis virescens larvae to perform separate ligand-blot experiments with the three activated CryIA toxins. The CryIA(a) and the CryIA(b) toxins bind the same 170-kDa protein, but most likely at two different binding sites. The CryIA(c) toxin binds two proteins of molecular masses 140 kDa and 120 kDa. We also demonstrate that the binding proteins for each of the B. thuringiensis toxins are not part of a covalent complex. Although the 170-kDa protein is a glycoprotein, endoglycosidase treatment does not prevent the binding of the CryIA(a) or CryIA(b) toxin. This indicates that the sugars are not important for the binding of these toxins. A model for a protein complex binding the B. thuringiensis HD1 ICPs is presented. Our results support the idea that binding proteins on membranes of the gut epithelial cells of H. virescens larvea are important for the specificity of the bacterial toxins.