Immunological alteration & toxic molecular inductions leading to cognitive impairment & neurotoxicity in transgenic mouse model of Alzheimer's disease.
Inflammation is considered to be one of the crucial pathological factors associated with the development of Alzheimer's disease, although supportive experimental evidence remains undiscovered. Therefore, the current study was carried out to better understand and establish the pathophysiological involvement of chronic inflammation in a double transgenic mouse model of Alzheimer's disease. We analyzed amyloid-beta deposition, oxidative stress, biochemical, neurochemical and immunological markers in a 10month old (APΔE9) mouse model. Memory functions were assessed by behavioral testing followed by measurement of synaptic plasticity via extracellular field recordings. Substantial increases in amyloid-beta levels, beta-secretase activity, and oxidative stress, along with significant neurochemical alterations in glutamate and GABA levels were detected in the brain of APΔE9 mice. Interestingly, marked elevations of pro-inflammatory cytokines in whole brain lysate of APΔE9 mice were observed. Flow cytometric analysis revealed a higher frequency of CD4+ IL-17a and IFN-γ secreting T-cells in APΔE9 brain, indicating a robust T-cell infiltration and activation. Behavioral deficits in learning and memory tasks, along with impairment in long-term potentiation and associated biochemical changes in the expression of glutamatergic receptor subunits were evident. Thus, this study establishes the role by which oxidative stress, alterations in glutamate and GABA levels and inflammation increases hippocampal and cortical neurotoxicity resulting in the cognitive deficits associated with Alzheimer's disease.


Cell-mediated protection against pulmonary Yersinia pestis infection.
Pulmonary infection with the bacterium Yersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available. Antibody-mediated humoral immunity can protect mice against pulmonary Y. pestis infection, an experimental model of pneumonic plague. Little is known about the protective efficacy of cellular immunity. We investigated the cellular immune response to Y. pestis in B-cell-deficient microMT mice, which lack the capacity to generate antibody responses. To effectively prime pulmonary cellular immunity, we intranasally vaccinated microMT mice with live replicating Y. pestis. Vaccination dramatically increased survival of microMT mice challenged intranasally with a lethal Y. pestis dose and significantly reduced bacterial growth in pulmonary, splenic, and hepatic tissues. Vaccination also increased numbers of pulmonary T cells, and administration of T-cell-depleting monoclonal antibodies at the time of challenge abrogated vaccine-induced survival. Moreover, the transfer of Y. pestis-primed T cells to naive microMT mice protected against lethal intranasal challenge. These findings establish that vaccine-primed cellular immunity can protect against pulmonary Y. pestis infection and suggest that vaccines promoting both humoral and cellular immunity will most effectively combat pneumonic plague.


On the Role of DT-Diaphorase Inhibition in Aminochrome-Induced Neurotoxicity In Vivo.
Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity. In this study, a low dose of aminochrome (0.8 nmol) with or without the DT-diaphorase inhibitor dicoumarol (0.2 nmol) was injected into the left striatum of rats. Intrastriatal 6-hydroxydopamine (6-OHDA, 32 nmol) was used as a positive neurotoxin control in other rats. Two weeks later, there was significant loss in numbers of T-OH immunoreactive fibers in SNpc, also a loss in cell density in SNpc, and prominent apomorphine (0.5 mg/kg sc)-induced contralateral rotations in rats that had been treated with aminochrome, with aminochrome/dicoumarol, or with 6-OHDA. Findings demonstrate that neurotoxic aminochrome is able to exert neurotoxicity only when DT-diaphorase is suppressed-implying that DT-diaphorase is vital in normally suppressing toxicity of in vivo aminochrome, generated in the pathway towards neuromelanin formation.


[Research in medicine].
Research is defined as "seeking of knowledge, data, or the truth about something". Research in the field of medicine can be divided in "basic science" oriented and "patient oriented" research. The starting point of most research is one or a set of yet unanswered questions. The research question should be formulated precisely and in the field of patient oriented research the answer to the question should be clinically relevant. A research question includes the main occurrence relation, the determinant(s) and the outcome as well as the domain in which the relation will be investigated.


Residence Times from Molecular Dynamics Simulations.
In this work, efficient methods are proposed for the calculation, from molecular dynamics trajectories, of residence times (RTs) and related quantities. One of these was designed to obtain RT distributions, from which mean residence times (MRTs), residual time distributions, and mean residual times can be computed. This method does not require the assumptions and approximations made by the most commonly used methods. Its link to the most popular method in the literature is identified. It is shown how the much faster new method can be used as a replacement for the latter and the advantages of doing so. Also, a prescription for estimating the uncertainty in the MRTs obtained though the proposed method is provided. Another even faster method for the calculation of the MRTs, their uncertainties, and the mean residual times is also proposed. It yields exactly the same results as the first one but does not allow to obtain the mentioned distributions. Another very popular method, based on autocorrelation functions, for computing MRTs is analyzed in terms of its assumptions and approximations. An alternative, also based on autocorrelation functions, which is faster and requires fewer assumptions is presented. A prescription for the calculation of the uncertainty of the MRTs obtained with the latter method is also provided. In the literature, there are a few methods to discard short transient escapes. Here, an algorithm is suggested that is much faster than the most used one and allows a more integral treatment of the process. Also, it is more widely applicable because it is a preprocessing step that can be used in conjunction with any of the proposed methods mentioned above. The main disadvantage of these two approaches to discard brief escapes is that the maximum duration allowed for an escape to be considered transient appears as a parameter to be determined for the particular system under study. As an alternative, a parameter-free method of a similar character is also proposed to estimate the mean residence time of particles that reached a constant probability of leaving the region of interest.


Differentiation of WEHI-3B D+ myelomonocytic leukemia cells induced by ectopic expression of the protooncogene c-jun.
The product of the protooncogene c-jun is one of the components of the AP-1 transcription factor complex, which is involved in the control of cell proliferation and differentiation. To study the role of c-jun in leukemia cell growth and maturation, a plasmid (pMTJ11) was constructed that contained the rat c-jun complementary DNA under the control of the human metallothionein promoter and the neo gene. Murine myelomonocytic WEHI-3B D+ cells were transfected by electroporation with the linearized pMTJ11 plasmid and subsequently cloned in the presence of G-418. Exposure of these clones to cadmium resulted in a high level of expression of c-jun mRNA and protein, as demonstrated by Northern hybridization and Western blotting. When these clones were examined immediately after their establishment, expression of c-jun was accompanied by the appearance of a mature phenotype in many clones, as measured by the reduction of nitroblue tetrazolium and by the expression of Mac-1 (CD11b), a cell surface marker on differentiated cells. Morphological changes indicative of the differentiated state were also observed by staining. These findings indicate that expression of c-jun is capable of initiating the differentiation of WEHI-3B D+ cells in the absence of an external inducer of maturation. Furthermore, the expression of c-jun led to an enhancement of the induction of the differentiation of WEHI-3B D+ cells by retinoic acid, suggesting an involvement of c-jun in the retinoic acid signal transduction pathway.


Testosterone replacement in men.
To summarize recent findings related to the prevalence, epidemiology, diagnosis, and treatment of male hypogonadism. Population-based studies indicate that low testosterone levels predict development of type 2 diabetes mellitus, metabolic syndrome, and survival. Although a large clinical trial is needed to assess the long-term benefit-to-risk ratio, testosterone replacement therapy has been shown to have positive effects on sexual function, mood, body composition, muscle mass, and bone density. Due to its potential side effects, careful monitoring for safety is critical, mainly in old men. Testosterone replacement therapy is the mainstay of treatment for men with hypogonadism, treatment should be closely monitored in men over age 50.


Deciphering mechanisms of malathion toxicity under pulse exposure of the freshwater cladoceran Daphnia magna.
The organophosphate pesticide (OP) malathion is highly toxic to freshwater invertebrates, including the cladoceran Daphnia magna, a widely used test organism in ecotoxicology. To assess whether toxic effects of malathion are driven primarily by exposure concentration or exposure duration, D. magna was pulse exposed to equivalent integrated doses (duration × concentration): 3 h × 16 μg/L, 24 h × 2 μg/L, and 48 h × 1 μg/L. After recovery periods of 3 h, 24 h, and 48 h, the toxicity of malathion on different biological levels in D. magna was examined by analyzing the following endpoints: survival and immobilization; enzyme activities of acetylcholinesterase (AChE), carboxylesterase (CbE), and glutathione S-transferase (GST); and AChE gene expression. The results showed no difference in survival among equivalent integrated doses. Adverse sublethal effects were driven by exposure concentration rather than pulse duration. Specifically, short pulse exposure to a high concentration of malathion resulted in more immobilized daphnids, lower AChE and CbE activities, and a higher transcript level of AChE gene compared with long pulse exposure to low concentration. The expression of the AChE gene was up-regulated, indicating a compensatory mechanism to cope with enzyme inhibition. The study shows the need for obtaining a better understanding of the processes underlying toxicity under realistic exposure scenarios, so this can be taken into account in environmental risk assessment of pesticides.


Setting Mechanism of a CDHA Forming α-TCP Cement Modified with Sodium Phytate for Improved Injectability.
A calcium deficient hydroxyapatite (CDHA) forming cement with a bimodal grain size distribution, composed of α-TCP and fine grained CDHA at a weight ratio of 9:1, was modified by the addition of sodium phytate (IP6) in variable amounts ranging from 0.25 to 2 wt.%, related to the powder content. The injectability of the cement paste was drastically increased by the IP6 addition, independent of the amount of added IP6. Additionally, the cement paste viscosity during the first minutes decreased. These effects could be clearly related to a slightly more negative zeta potential. Furthermore, IP6 was shown to strongly retard the setting reaction, as can be seen both in the calorimetry and X-ray diffraction measurements. In addition, octacalcium phosphate (OCP) was identified as a further setting product. All measurements were performed at 23 °C and 37 °C to assess the effect of temperature on the setting reaction for both clinical handling by the surgeon and the final hardening in the bone defect.


Natural killer susceptibility is independent of HLA class I antigen expression on cell lines obtained from human solid tumors.
The susceptibility to natural killer (NK) cell-mediated cytotoxicity of 20 cell lines obtained from human solid tumors and their class I histocompatibility antigen (HLA) levels were studied in an attempt to determine whether major histocompatibility complex (MHC) products expressed on cells derived from human solid tumors influence NK susceptibility. The effect of interferon-gamma (IFN-gamma) treatment on these elements was also analyzed. The MHC class I (HLA-ABC, HLA-A and HLA-B) antigen levels and degree of NK lysis were very heterogeneous and no correlation was found on comparison. After treatment with IFN-gamma a marked decrease in NK susceptibility was observed in all the cell lines, including the control line K-562. However, the level of HLA class I expression was not modified in any of the lines with the exception of the K-562, which increased. In some cell lines the expression of HLA class I-like antigens. CDla, b and c, was also measured before and after IFN treatment; however, no correlation was found between CD1 levels and NK susceptibility. Consequently, from our results it is possible to conclude that HLA class I antigens do not play a decisive role in NK susceptibility of cell lines derived from human solid tumors and to suggest that molecules which are not HLA class I antigens but IFN-gamma inducible may confer NK resistance to these lines.


A Collaborative Approach for Surface Inspection Using Aerial Robots and Computer Vision.
Aerial robots with cameras on board can be used in surface inspection to observe areas that are difficult to reach by other means. In this type of problem, it is desirable for aerial robots to have a high degree of autonomy. A way to provide more autonomy would be to use computer vision techniques to automatically detect anomalies on the surface. However, the performance of automated visual recognition methods is limited in uncontrolled environments, so that in practice it is not possible to perform a fully automatic inspection. This paper presents a solution for visual inspection that increases the degree of autonomy of aerial robots following a semi-automatic approach. The solution is based on human-robot collaboration in which the operator delegates tasks to the drone for exploration and visual recognition and the drone requests assistance in the presence of uncertainty. We validate this proposal with the development of an experimental robotic system using the software framework Aerostack. The paper describes technical challenges that we had to solve to develop such a system and the impact on this solution on the degree of autonomy to detect anomalies on the surface.


An online tool for survival prediction of extrapulmonary small cell carcinoma with random forest.
Extrapulmonary small cell carcinoma (EPSCC) is rare, and its knowledge is mainly extrapolated from small cell lung carcinoma. Reliable survival prediction tools are lacking. A total of 3,921 cases of EPSCC were collected from the Surveillance Epidemiology and End Results (SEER) database, which form the training and internal validation cohorts of the survival prediction model. The endpoint was an overall survival of 0.5-5 years. Internal validation performances of machine learning algorithms were compared, and the best model was selected. External validation (n = 68) was performed to evaluate the generalization ability of the selected model. Among machine learning algorithms, the random forest model performs best on internal validation, whose area under the curve (AUC) is 0.736-0.800. The net benefit is higher than the TNM classification in decision curve analysis. The AUC of this model on the external validation cohort is 0.739-0.811. This model was then deployed online as a free, publicly available prediction tool of EPSCC (http://184.108.40.206:4399/). This study provides an excellent online survival prediction tool for EPSCC with machine learning and large-scale data. Age, TNM stages, and surgery (including potential performance status information) are the most critical factors for the prediction model.


The Task and Relational Dimensions of Online Social Support.
Online support groups are attractive to individuals suffering from various types of mental and physical illness due to their accessibility, convenience, and comfort level. Individuals coping with depression, in particular, may seek social support online to avoid the stigma that accompanies face-to-face support groups. We explored how task and relational messages created social support in online depression support groups using Cutrona and Suhr's social support coding scheme and Bales's Interaction Process Analysis coding scheme. A content analysis revealed emotional support as the most common type of social support within the group, although the majority of messages were task rather than relational. Informational support consisted primarily of task messages, whereas network and esteem support were primarily relational messages. Specific types of task and relational messages were associated with different support types. Results indicate task messages dominated online depression support groups, suggesting the individuals who participate in these groups are interested in solving problems but may also experience emotional support when their uncertainty is reduced via task messages.


A network including PU.1, Vav1 and miR-142-3p sustains ATRA-induced differentiation of acute promyelocytic leukemia cells - a short report.
Reduced expression of miR-142-3p has been found to be associated with the development of various subtypes of myeloid leukemia, including acute promyelocytic leukemia (APL). In APL-derived cells, miR-142-3p expression can be restored by all-trans retinoic acid (ATRA), which induces the completion of their maturation program. Here, we aimed to assess whether PU.1, essential for ATRA-induced gene transcription, regulates the expression of miR-142-3p in APL-derived cells and, based on the established cooperation between PU.1 and Vav1 in modulating gene expression, to evaluate the role of Vav1 in restoring the expression of miR-142-3p. ATRA-induced increases in PU.1 and Vav1 expression in APL-derived NB4 cells were counteracted with specific siRNAs, and the expression of miR-142-3p was measured by quantitative real-time PCR (qRT-PCR). The recruitment of PU.1 and/or Vav1 to the regulatory region of miR-142 was assessed by quantitative chromatin immunoprecipitation (Q-ChIP). Synthetic inhibitors or mimics for miR-142-3p were used to assess whether this miRNA plays a role in regulating the expression of PU.1 and/or Vav1. We found that the expression of miR-142-3p in differentiating APL-derived NB4 cells is dependent on PU.1, and that Vav1 is essential for the recruitment of this transcription factor to its cis-binding element on the miR-142 promoter. In addition, we found that in ATRA-treated NB4 cells miR-142-3p sustains agonist-induced increases in both PU.1 and Vav1. Our results suggest the existence of a Vav1/PU.1/miR-142-3p network that supports ATRA-induced differentiation in APL-derived cells. Since selective regulation of miRNAs may play a role in the future treatment of hematopoietic malignancies, our results may provide a basis for the development of new therapeutic strategies to restore the expression of miR-142-3p.


Multiple apocrine hidrocystomas: a case report.
Hidrocystomas are rare cystic lesions that form benign tumours of the sweat glands. In this report, a clinical case of multiple apocrine hidrocystomas on both the upper and lower eyelids, and on both the malar regions has been discussed. These lesions are less likely than the eccrine lesions to occur at the periorbital region.


Antiallergic effects of anti-interleukin-33 are associated with suppression of immunoglobulin light chain and inducible nitric oxide synthase.
We aimed to find novel genes that are significantly induced in allergic mice and that are significantly downregulated with anti-interleukin (IL) 33 treatment. Thirty-six mice were allocated into each of group A (intraperitoneal [i.p.]) sensitized and intranasally challenged to saline solution), group B (sensitized and challenged to ovalbumin), group C (sensitized and challenged with ovalbumin, and null treatment with i.p. saline solution), and group D (sensitized and challenged with ovalbumin, and treatment with anti-IL-33 i.p. injection). We counted the number of nose-scratching in 10 minutes, serum ovalbumin-specific immunoglobulin E (IgE), and titers of cytokines (IL-1, IL-4, IL-5, IL-10, IL-13) in bronchoalveolar lavage fluid. By using one whole lung from each mouse, we performed microarray analysis and real-time polymerase chain reaction. group D showed a significantly reduced nose-scratching events and lower serum ovalbumin-specific IgE compared with groups B and C. All the cytokines in the bronchoalveolar lavage fluid were significantly decreased after anti-IL-33 treatment. Microarray analysis revealed that group B (immunoglobulin free light chain [IgFLC], 89.1 times; nitric oxide synthase [NOS] 2, 11.5 times) and group C (IgFLC, 141.6 times; NOS2, 11.7 times) had significantly increased expression of IgFLC and NOS2 genes compared with group A. After anti-IL-33 treatment, group D showed significantly decreased expression of both IgFLC (49.3 times) and NOS2 (6.5 times). In real-time polymerase chain reaction, groups B and C had significantly increased expression of these genes (IgFLC, 10.4 times and 29 times, respectively; NOS2, 3.8 times and 4.5 times, respectively). After treatment, group D showed significantly decreased expression of IgFLC (5.0 times) and NOS2 (2.5 times). The antiallergic effect of anti-IL-33 can be explained by suppression of IgFLC and NOS2 in a murine model of allergic rhinitis.


Three-Dimensional-Printed Silica Aerogels for Thermal Insulation by Directly Writing Temperature-Induced Solidifiable Inks.
Silica aerogels are attractive materials for various applications due to their exceptional performances and open porous structure. Especially in thermal management, silica aerogels with low thermal conductivity need to be processed into customized structures and shapes for accurate installation on protected parts, which plays an important role in high-efficiency insulation. However, traditional subtractive manufacturing of silica aerogels with complex geometric architectures and high-precision shapes has remained challenging since the intrinsic ceramic brittleness of silica aerogels. Comparatively, additive manufacturing (3D printing) provides an alternative route to obtain custom-designed silica aerogels. Herein, we demonstrate a thermal-solidifying 3D printing strategy to fabricate silica aerogels with complex architectures via directly writing a temperature-induced solidifiable silica ink in an ambient environment. The solidification of silica inks is facilely realized, coupling with the continuous ammonia catalysis by the thermolysis of urea. Based on our proposed thermal-solidifying 3D printing strategy, printed objects show excellent shape retention and have a capacity to subsequently undergo the processes of in situ hydrophobic modification, solvent replacement, and supercritical drying. 3D-printed silica aerogels with hydrophobic modification show a super-high water contact angle of 157°. Benefiting from the low density (0.25 g·cm-3) and mesoporous silica network, optimized 3D-printed specimens with a high specific surface area of 272 m2·g-1 possess a low thermal conductivity of 32.43 mW·m-1·K-1. These outstanding performances of 3D-printed silica aerogels are comparable to those of traditional aerogels. More importantly, the thermal-solidifying 3D printing strategy brings hope to the custom design and industrial production of silica aerogel insulation materials.


Crystal structure of the galectin-9 N-terminal carbohydrate recognition domain from Mus musculus reveals the basic mechanism of carbohydrate recognition.
The galectins are a family of beta-galactoside-binding animal lectins with a conserved carbohydrate recognition domain (CRD). They have a high affinity for small beta-galactosides, but binding specificity for complex glycoconjugates varies considerably within the family. The ligand recognition is essential for their proper function, and the structures of several galectins have suggested their mechanism of carbohydrate binding. Galectin-9 has two tandem CRDs with a short linker, and we report the crystal structures of mouse galectin-9 N-terminal CRD (NCRD) in the absence and the presence of four ligand complexes. All structures form the same dimer, which is quite different from the canonical 2-fold symmetric dimer seen for galectin-1 and -2. The beta-galactoside recognition mechanism in the galectin-9 NCRD is highly conserved among other galectins. In the apo form structure, water molecules mimic the ligand hydrogen-bond network. The galectin-9 NCRD can bind both N-acetyllactosamine (Galbeta1-4GlcNAc) and T-antigen (Galbeta1-3GalNAc) with the proper location of Arg-64. Moreover, the structure of the N-acetyllactosamine dimer (Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc) complex shows a unique binding mode of galectin-9. Finally, surface plasmon resonance assay showed that the galectin-9 NCRD forms a homophilic dimer not only in the crystal but also in solution.


Prognosis of deferred non-culprit lesions according to fractional flow reserve in patients with acute coronary syndrome.
There are limited data on the prognosis of deferred non-culprit lesions in patients with acute coronary syndrome (ACS) based on fractional flow reserve (FFR). We aimed to investigate the prognosis of deferred non-culprit lesions in ACS patients, compared with deferred lesions in patients with stable coronary artery disease (SCAD), on the basis of FFR. The clinical outcomes of 449 non-culprit lesions (301 patients with ACS) were compared with 2,484 lesions (1,295 patients with SCAD) in which revascularisation was deferred on the basis of a high FFR (>0.80). The primary outcome was major adverse cardiac events (MACE), a composite of cardiac death, target vessel-related myocardial infarction (MI) and ischaemia-driven revascularisation. Among the ACS population, 65.8% presented with unstable angina and 34.2% with non-ST-segment elevation MI. Mean angiographic percent diameter stenosis and FFR of the deferred lesions were 39.3±15.0% and 0.92±0.06, respectively. During the median follow-up duration of 722.0 days, the deferred non-culprit lesions of ACS patients showed a significantly higher rate of MACE (3.8% vs. 1.6%, HRadj 2.97, 95% CI: 1.23-7.17, p=0.016), mainly driven by the higher rate of ischaemia-driven revascularisation (2.8% vs. 1.1%, HRadj 3.39, 95% CI: 1.29-8.92, p=0.013) than the deferred lesions in SCAD patients. Regardless of the range of FFR in the deferred lesions (0.81-0.85, 0.86-0.90, 0.91-0.95, and 0.95-1.00), non-culprit lesions of ACS showed a more than twofold higher rate of MACE than that of SCAD. In a multivariable marginal Cox model, ACS was the most powerful independent predictor of MACE (HRadj 2.74, 95% CI: 1.13-6.64, p=0.026). Compared to the deferred lesions of SCAD patients, deferred non-culprit lesions of ACS on the basis of FFR showed a higher rate of clinical events, regardless of FFR range.


True Dopers or Negligent Athletes? An Analysis of Anti-Doping Rule Violations Reported to the World Anti-Doping Agency 2010-2012.
The sanction that an athlete receives when an anti-doping rule violation has been committed depends on the specific circumstances of the case. Anti-doping tribunals decide on the final sanction, following the rules of the World Anti-Doping Code. To assess the athletes' degree of fault based on the length of sanctions imposed on them to feed policy-related discussions. Analysing data from the results management database of the World Anti-Doping Agency for anonymous information of anti-doping rule violations in eight selected sports covering the years 2010-2012. Four out of ten athletes who committed an anti-doping rule violation received a suspension that was lower than the standard. This is an indication that tribunals in many instances are not convinced that the athletes concerned were completely at fault, that mitigating circumstances were applicable, or that full responsibility of the suspected violation should not be held against them. Anabolic agents, peptide hormones, and hormone modulators lead to higher sanctions, as do combinations of several anti-doping rule violations. This first analysis of information from the World Anti-Doping Agency's results management database indicates that a large proportion of the athletes who commit anti-doping rule violations may have done this unintentionally. Anti-doping professionals should strive to improve this situation in various ways.


[Effects of synchronous treatment of bilateral scalp acupuncture and rehabilitation training on activities of daily life in patients with cerebral infarction at acute phase].
To observe the improvements of synchronous treatment of bilateral scalp acupuncture and rehabilitation training on activities of daily life in patients with cerebral infarction at acute phase, so as to compare the efficacy differences between scalp acupuncture at bilateral and affected side as well as differences between synchronous and non-synchronous treatment. Ninety patients of acute-phase cerebral infarction with motor dysfunction were randomly divided into three groups. The observation group was treated with synchronous treatment of scalp acupuncture at the Dingzhongxian (middle line of vertex), bilateral Dingnieqianxiexian (anterior oblique line of vertex-temporal) and bilateral Dingniehouxiexian (posterior oblique line of vertex-temporal) and rehabilitation training; the control group A was treated with synchronous treatment of affected scalp acupuncture at the Dingzhongxian, affected Dingnieqianxiexian and affected Dingniehouxiexian and rehabilitation training; the control group B was treated with bilateral scalp acupuncture for 4 h, followed by rehabilitation training. All the patients took the treatment once a day, and 6 days for a course of treatment for total of 4 courses. The modified Barthel index (MBI), activities of daily living (ADL) and Fugl-Meyer motor assessment (FMA) were used to perform efficacy assessment before treatment, in the 14th days of treatment and in the 28th days of treatment in three groups. After treatment, three indices at each time point were superior to those before the treatment in three groups (all P<0.01) ; the improvements of ADL and FMA in the observation group after 28 days of treatment were superior to those in the control group A and control group B (all P<0.05), and the improvement of MBI was superior to that in the control group B (P<0.05). The synchronous treatment of bilateral scalp acupuncture and rehabilitation training could significantly improve the activities of daily life and motor function in patients with cerebral infarction at acute phase, which is superior to scalp acupuncture at affected side and non-synchronous treatment.


Mammalian reproductive strategies: genes, photoperiod and latitude.
This paper considers how and why natural selection might promote or block the photoperiodic regulation of a mammal's reproduction. The factors most important in making this decision would seem to be the following: life expectancy, length of the female's cycle, feeding strategy, the presence or absence of survival mechanisms like hibernation, and the nature of the seasonal challenges offered by the mammal's habitat. A speculative scheme is offered for the potential utility of this type of regulation dependent upon life expectancy and latitude of residence.


The effects of training of morphological structure on spelling derived words by dyslexic adolescents.
This exploratory study aimed to determine the effects of explicit instruction about morphological structure on the spelling of derived words. A cross-sectional ability level-design was employed in order to determine differences in response to instruction between dyslexic students aged 13 + years and age-matched and spelling level matched control groups. The study was based on the word-pair paradigm (a base and derived word) and combined oral instruction with written materials. The intervention had a substantial impact in enhancing the spelling of derivations by the dyslexic adolescents. Their gains were appropriate for their spelling level, stable two months after the intervention, and generalized to untrained but analogous items in terms of structure and suffixation. Non-dyslexic younger participants matched in terms of spelling level also showed training and generalisation effects of the same size as their dyslexic counterparts, while the age-matched controls did not improve so much because of ceiling effects. It is proposed that morphological awareness constitutes a positive asset for dyslexic adolescents that can be used efficiently to counterbalance their severe phonological deficiencies.


Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance.
Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.


Mid-infrared spectroscopic imaging enabled by an array of Ge-filled waveguides in a microstructured optical fiber probe.
We demonstrate mid-infrared spectroscopic imaging using a unique optical fiber probe consisting of an array of Ge waveguide cores embedded in a silica fiber matrix. Biological tissue slices are characterized to illustrate its potential endoscopic uses. The fiber probe based transmission measurements show excellent agreement with the result obtained from standard Fourier Transform Infrared spectroscopy transmission measurements in the wavelength range of 3289.8 nm to 3383.3 nm, where fat and muscle tissues could be spectroscopically distinguished.


Vancomycin-Induced Modulation of Gram-Positive Gut Bacteria and Metabolites Remediates Insulin Resistance in iNOS Knockout Mice.
The role of oxidative and nitrosative stress has been implied in both physiology and pathophysiology of metabolic disorders. Inducible nitric oxide synthase (iNOS) has emerged as a crucial regulator of host metabolism and gut microbiota activity. The present study examines the role of the gut microbiome in determining host metabolic functions in the absence of iNOS. Insulin-resistant and dyslipidemic iNOS-/- mice displayed reduced microbial diversity, with a higher relative abundance of Allobaculum and Bifidobacterium, gram-positive bacteria, and altered serum metabolites along with metabolic dysregulation. Vancomycin, which largely depletes gram-positive bacteria, reversed the insulin resistance (IR), dyslipidemia, and related metabolic anomalies in iNOS-/- mice. Such improvements in metabolic markers were accompanied by alterations in the expression of genes involved in fatty acid synthesis in the liver and adipose tissue, lipid uptake in adipose tissue, and lipid efflux in the liver and intestine tissue. The rescue of IR in vancomycin-treated iNOS-/- mice was accompanied with the changes in select serum metabolites such as 10-hydroxydecanoate, indole-3-ethanol, allantoin, hippurate, sebacic acid, aminoadipate, and ophthalmate, along with improvement in phosphatidylethanolamine to phosphatidylcholine (PE/PC) ratio. In the present study, we demonstrate that vancomycin-mediated depletion of gram-positive bacteria in iNOS-/- mice reversed the metabolic perturbations, dyslipidemia, and insulin resistance.


Model-based imaging of damage with Lamb waves via sparse reconstruction.
Ultrasonic guided waves are gaining acceptance for structural health monitoring and nondestructive evaluation of plate-like structures. One configuration of interest is a spatially distributed array of fixed piezoelectric devices. Typical operation consists of recording signals from all transmit-receive pairs and subtracting pre-recorded baselines to detect changes, possibly due to damage or other effects. While techniques such as delay-and-sum imaging as applied to differential signals are both simple and capable of detecting flaws, their performance is limited, particularly when there are multiple damage sites. Here a very different approach to imaging is considered that exploits the expected sparsity of structural damage; i.e., the structure is mostly damage-free. Differential signals are decomposed into a sparse linear combination of location-based components, which are pre-computed from a simple propagation model. The sparse reconstruction techniques of basis pursuit denoising and orthogonal matching pursuit are applied to achieve this decomposition, and a hybrid reconstruction method is also proposed and evaluated. Noisy simulated data and experimental data recorded on an aluminum plate with artificial damage are considered. Results demonstrate the efficacy of all three methods by producing very sparse indications of damage at the correct locations even in the presence of model mismatch and significant noise.


Participation of mast cells in colitis inflammation induced by dextran sulfate sodium.
We investigated the participation of mast cells in colitis inflammation induced by dextran sulfate sodium (DSS). The damage score and myeloperoxidase (MPO) activity were measured to confirm the occurrence of colitis. Rat mast cell protease (RMPCP) II levels in the serum were estimated as an index of mast cell degranulation. Tissue RMCP I and RMCP II levels in the rectum were also measured as markers of the numbers of connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs), respectively. Administration of 4% DSS resulted in time-related increases in damage score, MPO activity and serum RMCP II levels, which were statistically significant at 7 and 11 days after treatment. Tissue RMCP I and RMCP II levels in the rectum were also increased significantly at 7 and 11 days, and 11 days, respectively after free drinking of 4% DSS. These results suggested that mast cells proliferated or the amount of protease per mast cell increased in the sites of inflammation induced by DSS, and that these mast cells may modulate the disorders observed in DSS-induced colitis.


The Cellular and Molecular Mechanisms Underlying Silver Nanoparticle/Chitosan Oligosaccharide/Poly(vinyl alcohol) Nanofiber-Mediated Wound Healing.
Wound healing is a complex pathophysiological process that occurs frequently in everyday pathology and remains a challenge during the treatment of trauma. Previously, we prepared silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNP) nanofibers via an electrospinning technique. These nanofibers promoted the proliferation of human skin fibroblasts (HSFs) and the expression of transforming growth factor TGF-β1 in the early stage of wound repair, although the specific mechanisms remain unclear. Therefore, considering that TGF-β1 has emerged as a major modulator of wound healing, the objective of this study was to further understand whether the molecular mechanisms responsible for PVA/COS-AgNP nanofiber-mediated wound healing include the TGF-β1/Smad signal transduction pathway. In this study, we used human skin fibroblasts (HSFs) to investigate the molecular and cellular mechanisms underlying PVA/COSAgNP nanofiber-mediated wound healing. Cell adhesion and proliferation experiments, immunofluorescence staining, hydroxyproline content measurements, flow cytometry, quantitative real-time PCR (qRT-PCR), and western blotting (WB) were used to analyze the wound healing mechanisms of human skin fibroblasts treated with various concentrations of PVA/COS-AgNP nanofibers and the combined application of silver nanofibers and SB431542 (an inhibitor of the TGF-β1 receptor kinase). Our study showed that PVA/COS-AgNP nanofibers markedly promoted fibroblast proliferation, collagen synthesis, and cell adherence. We also found that treating fibroblasts with PVA/COS-AgNP nanofibers stimulated cell cycle progression from G1 into the S and G2 phases, reducing the proportion of cells in the G0/G1 phase and inducing S and G2/M arrest. Importantly, the cell factors associated with the TGF-β1/Smad signal transduction pathway, such as TGF-β1, TGFβRI, TGFβRII, pSmad2, pSmad3, collagen I, collagen III, and fibronectin were also up-regulated. Moreover, this enhancing effect was markedly inhibited by the TGFβRI receptor inhibitor, SB431542. Therefore, the PVA/COS-AgNP nanofibers used to accelerate wound healing do so by activating the TGF-β1/Smad signal transduction pathway.


Glomerular Endothelium and its Impact on Glomerular Filtration Barrier in Diabetes: Are the Gaps Still Illusive?
Glomerular capillaries are lined with highly specialized fenestrated endothelium which are primarily responsible to regulate high flux filtration of fluid and small solutes. During filtration, plasma passes through the fenestrated endothelium and basement membrane before it reaches the slit diaphragm, a specialized type of intercellular junction that connects neighbouring podocytes. A PubMed search was done for recent articles on components of the glomerular filtration barrier such as glomerular endothelial cells, podocytes and glomerular basement membrane, and the effect of diabetes on these structures. Generally, the onset of kidney dysfunction in many diabetic patients is characterized by albuminuria/proteinuria, a pathophysiological event triggered by several factors including; (i) endothelial activation and shading of glycocalyx, (ii) loss of endothelial cell function, (ii) re-uptake of albumin by podocyte through a scavenger receptors and (iv) rearrangement of podocyte cytoskeleton. Howeover, as podocyte effacement does not always lead to proteinuria, the dynamic interplay between all constituents of the glomerular filtration barrier including podocytes, endothelial cells and the basement membrane may be fundamental for the effective filtration in healthy individuals. Thus, a putative cross-talk amongst podocytes, endothelial cells and the basement membrane in the homeostasis of glomerular function is envisaged. Although, the exact nature of this cross-talk remains to be clearly elucidated, it is possible that the interaction between: (i) glomerular endothelial cells and podocytes, (ii) glomerular endothelial cells and glomerular basement membrane, (iii) podocytes and glomerular basement membrane, and (iv) the simultaneous interaction amongst the three components collectively underpin effective filtration in healthy individuals. A comprehensive understanding of these different interactions still remains elusive. The elucidation of these multifaceted interactions will set the stage for greater understanding of the pathophysiology of kidney dysfunction.


[Localization of the multigene Lpm locus in chromosome 9 of the American mink].
The results of genetic study on linkage of Lpm locus with peptidase B gene are presented. Investigation of 111 offspring back-crosses shows that Lpm allotypes and allelic variants of peptidase B are inherited in concert. The frequency of recombination between the Lpm locus and peptidase B gene is 11 +/- 3% in male. Since it was earlier established that peptidase B gene is a marker of chromosome 9, our data indicate that the Lpm loci family is situated in the chromosome 9 of domestic mink.


Differential grandparental investment - the impact of phenotypic resemblance.
Differential grandparental investment is mainly explained as a result of paternity uncertainty. Phenotypic resemblance may be interpreted as an indicator of genetically relatedness. Consequently the present study focused on the impact of phenotypic resemblance on grandparental investment, i.e. solicitude, contact frequency and quality of relationship. 213 adults persons between the age 19 and 32 years (x = 25.5; SD = 3.4) were enrolled in the study. Data concerning grandparental investment during childhood were collected retrospectively using a 30 item questionnaire. Grandparental investment patterns differed significantly according grandparent category. In detail maternal grandmothers showed the highest contact frequency and the highest solicitude while - as to be expected - the paternal grandfather exhibited the lowest degree of investment. Grandparental investment was independent of grandparent category mainly influenced by residential distance. Phenotypic resemblance had an impact on grandparental investment independent of residential distance. This was first of all true of paternal grandfathers. An impact of phenotypic resemblance on grandparental investment patters can be assumed.


The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment with α1-adrenergic receptor blocker monotherapy: prospective analysis of elderly men.
Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron additional treatment in elderly male patients with persistent male LUTS, especially in OAB after monotherapy with α1-adrenergic blockers, is not fully understood. This study was conducted in male LUTS patients who were ≥ 65 years of age and had persistent OAB symptoms, regardless of whether they took an α1-adrenergic receptor blocker orally. Before and 12 weeks after mirabegron additional therapy (50 mg once daily), we evaluated the efficacy of this treatment using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), and changes in the maximum flow rate (Qmax) and post-void residual urine volume (PVR). We evaluated patients overall and divided into two groups by age: young-old (from 65 to 74 years old) and old-old (from 75 to 84 years old). Fifty men were enrolled in this study. Mirabegron additional therapy improved the total OABSS, total IPSS, and IPSS-quality of life (QOL) score. The voided volume (VV) and Qmax improved after treatment in patients overall. However, there was no significant change in PVR. The total OABSS, total IPSS, and IPSS-QOL score significantly improved in both of the young-old and old-old groups. However, a significant increasing of VV was detected in the young-old group. There were no significant differences in the Qmax or PVR in either group. Mirabegron additional therapy was effective for male patients whose persistent LUTS and particularly OAB was not controlled with α1-adrenergic receptor blocker monotherapy, and mirabegron did not have negative effects on voiding function. Additionally, mirabegron additional therapy was considered effective regardless of patient age. Trial registration number (TRN) trial registration number (TRN) and date of registration: ISRCTN16759097 in July 8, 2016.


Mental Health Among Black and Latinx Sexual Minority Adults Leading Up to and Following the 2016 U.S. Presidential Election: Results from a Natural Experiment.
Purpose: Multi-level hostility toward sexual minority (SM; includes, but is not limited to those identifying as gay, lesbian, bisexual, queer, or same-gender loving) and other minority populations (e.g., racial/ethnic) increased after the 2016 U.S. presidential election. This may generate stress and mental health problems among those groups, and particularly among SM people of color. This study assessed whether the mental health of Black and Latinx SM adults declined after the 2016 U.S. presidential election. Methods: Data were from a daily national probability survey (thus, mean changes in mental health outcomes over time may reflect population shifts in mental health) of Black and Latinx SM adults (N = 537), recruited 7 months before and 17 months after the November 8, 2016 election. Using a between-subjects design, spline-based regressions (spline set at election date), adjusted for sociodemographic characteristics, estimated four mental health outcomes (past-month number of "poor mental health" days and psychological distress, past-year suicidal ideation, and social wellbeing) as a function of survey completion date. Results: There was marked worsening in each of the mental health outcomes over the postelection period (past-month poor mental health days, B = 0.05, standard error [SE] = 0.02, p < 0.05; psychological distress, B = 0.28, SE = 0.14, p < 0.05; suicidal ideation, odds ratio = 1.13, 95% confidence interval >1.00-1.26, p < 0.05; and social wellbeing, B = -0.05, SE = 0.02, p < 0.05). None of the outcomes varied over the pre-election period. Conclusions: This study provides evidence of worsening mental health among Black and Latinx SM adults in the United States during the 1.5 years after the 2016 U.S. presidential election.


Alcohol, cytokines, and estrogen in the control of bone remodeling.
Alcohol has been identified as a risk factor for the development of osteoporosis. Chronic alcohol abuse has been shown to decrease bone mass and increase the incidence of fractures. Although the exact mechanism by which alcohol influences bone metabolism is not clear, it is likely a combination of both direct and indirect effects on bone cells. Alcohol has the potential to alter bone metabolism indirectly through its effects on gonadal hormones and through the secretion of cytokines shown to be critical factors in postmenopausal osteoporosis. Data are summarized here demonstrating that interleukin-1 and tumor necrosis factor play a direct causal role in the bone loss due to estrogen deficiency. In addition, studies are cited showing that these same cytokines are produced in alcohol-induced liver disease with the potential to enhance bone loss in post-menopausal women and in male patients. Although there are not yet data directly supporting the role of cytokines in bone loss due to alcohol consumption, the studies presented herein are intended to stimulate further research on the role of alcohol, estrogen, and cytokines in osteoporotic bone loss.


Diterpenoid alkaloids from the roots of Aconitum brachypodum Diels.
A new diterpenoid alkaloid, named bullatine H (1), along with 10 known diterpenoid alkaloids were isolated from the roots of Aconitum brachypodum Diels (Ranunculaceae). The structure of 1 was elucidated by analysis of its spectroscopic data. It should be noted that compound 1 is the first example with 11, 13-dioxygenated denudatine-type diterpenoid alkaloid isolated from Aconitum brachypodum.


Absence of autoregulation of cerebral blood flow during halothane and enflurane anesthesia.
The effects of halothane and enflurane anesthesia under conditions of normo-, hyper-, and hypocarbia on the autoregulation of cerebral blood flow (CBF) in the goat were evaluated. The goat was selected because of its unique arterial blood supply to the head and the development of a method by which CBF may be continuously measured. The study revealed that 1 MAC of halothane or enflurane anesthesia at normocarbia abolished cerebral autoregulation, CBF increasing or decreasing with increasing or decreasing peripheral blood pressure. Reduction of anesthesia to 0.5 MAC partially restored cerebral autoregulatory capability. The effect of 1 MAC and 0.5 MAC anesthesia on cerebral autoregulation of blood flow was potentiated by hypercarbia and antagonized by hypocarbia, indicating that the vascular response to blood CO2 fluctuations remained intact.


Toward high laser power beam manipulation with nanophotonic materials: evaluating thin film damage performance.
Nanophotonic materials enable unprecedented control of light-matter interactions, including the ability to dynamically steer or shape wavefronts. Consequently, nanophotonic systems such as metasurfaces have been touted as promising candidates for free-space optical communications, directed energy and additive manufacturing, which currently rely on slow mechanical scanners or electro-optical components for beam steering and shaping. However, such applications necessitate the ability to support high laser irradiances (> kW/cm2) and systematic studies on the high-power laser damage performance of nanophotonic materials and designs are sparse. Here, we experimentally investigate the pulsed laser-induced damage performance (at λ ∼ 1 µm) of model nanophotonic thin films including gold, indium tin oxide, and refractory materials such as titanium nitride and titanium oxynitride. We also model the spatio-thermal dissipation dynamics upon single-pulse illumination by anchoring experimental laser damage thresholds. Our findings show that gold exhibits the best laser damage resistance, but we argue that alternative materials such as transparent conducting oxides could be optimized to balance the tradeoff between damage resistance and optical tunability, which is critical for the design of thermally robust nanophotonic systems. We also discuss damage mitigation and ruggedization strategies for future device-scale studies and applications requiring high power beam manipulation.


Reducing state employee health insurance costs.
(1) States and their employees spent $30.7 billion on health insurance premiums for state employees in 2013. (2) State employee health plan cost-sharing arrangements and premiums vary widely by state. (3) Across all sectors, employer-provided health insurance costs doubled from 1992 to 2012.


Surgical Site Infection In Orthopaedic Surgery: Correlation Between Age, Diabetes, Smoke And Surgical Risk.
Surgical site infection is a common complication after orthopaedic surgery. It can be associated with increased morbidity rate and social cost. The accurate identification of risk factors is essential so that strategies to prevent these potentially devastating infections can be developed. We have conducted this study to determine the possible risk factors for the surgical site infections. We aimed at finding exhaustive evidence concerning the potential risk factors for infections in orthopaedic surgery. Between October 2009 and December 2011, we identified 84 patients with a superficial and/or deep surgical site infection and compared them with 203 uninfected patients (control group), taken out from a series of 486 patients. We considered the following risk factors: diabetes, BMI >30, ASA Score of 3 or 4, smoking and age. The most frequently performed operations of the 287 examined patients were the knee and hip arthroplasties (n = 32, 11.14%) and open fracture reductions (n = 178, 62.02%). Staphylococcus Aureus was the most common identified pathogen (n = 63, 75%). The analyses (preoperative and postoperative) of the infected patients showed them to have significantly high serum glucose levels in comparison with the control group (odds ratio = 8.7). We found a significant high rate of infection in patients smoking for more than 20 years (67 patients, 79.7%). The remaining variables (BMI, OR = 2.21; ASA score, OR = 1.3) showed no significant differences between the study group and controls. We also found a correlation between > 65-year-old patients and infections at the surgical site (61 patients, 72.6%). We found that there was correlation between diabetes, smoking and age as risk factors with the development of infection at the surgical site; other variables such as the ASA score and BMI are not relevant here (contrary to what is reported in literature). We believe that postoperative results can be improved considerably with a properly conducted antibiotic treatment, stringent glycemic control (achievable only with careful multidisciplinary management) and good compliance of patients.


Comparison of imaginal desensitisation with other behavioural treatments of pathological gambling. A two- to nine-year follow-up.
Of 120 pathological gamblers randomly allocated to imaginal desensitisation (ID) or to other behavioural procedures (60 to each group, all procedures administered over one week) 63 subjects were contacted two to nine years later. Twenty-six of the 33 who received ID reported control or cessation of gambling compared with 16 of 30 who received other behavioural procedures. This difference was significant, indicating ID had a specific effect additional to that of the other behavioural procedures. It is suggested the other procedures could be regarded as placebos. As the response at a mean of over five years to one week of ID is comparable with that reported to more intensive therapies, after briefer follow-up, it is suggested ID is a cost-effective therapy for pathological gambling, and is worth considering when resources are limited.


Communicative Informativeness in Aphasia: Investigating the Relationship Between Linguistic and Perceptual Measures.
Purpose Informativeness refers to how successfully a person is able to convey their intended message. This study explores the relationship between perceptual ratings of informativeness and selected linguistic measures of lexical and structural content. It considers which linguistic measures have ecological validity in terms of what listeners view as important. Method Two complex picture description samples from 20 people with aphasia were analyzed. Linguistic measures included number of correct information units (NCIU), percentage of correct information units, number of propositions (NP), propositional idea density (PID), and mean length of utterance in words (MLU-w). Eleven naïve listeners produced direct magnitude estimation (DME) ratings of informativeness. A correlational design was used to investigate the relationship between mean DME informativeness ratings and each of the linguistic measures. Results The 2 picture description samples elicited similar informativeness ratings. Positive significant correlations were identified between mean DME informativeness ratings and NCIU, percentage of correct information units, NP, and MLU-w; the strength of correlation differed across variables. No significant correlation was found between mean DME informativeness ratings and PID. Significant correlations were also seen between the linguistic variables, particularly between NP and PID as well as NP and MLU-w. Conclusions Overall, the linguistic measures corresponded to rated informativeness, highlighting their ecological validity. The strongest relationship was between NCIU and rated informativeness, emphasizing the importance of complete and accurate production of lexical information, particularly nouns. Less strong, but still significant, relationships were seen with variables looking at the efficiency of information giving and the connection of ideas within sentences. The importance of different types of informative measures is considered in relation to the elicitation stimuli.


Hypothalamic-Pituitary-Adrenocortical Axis Activity in Alcohol-Dependent Patients During Treatment with High-Dose Baclofen.
Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported to be affected in alcohol use disorder (AUD). It has been suggested that pharmacological relapse prevention in AUD might exert its effects partly by modulation of HPA axis activity. Here, we assessed the effects of high-dose treatment with baclofen on HPA axis activity in alcohol-dependent patients within a 24-week randomized, placebo-controlled trial (BACLAD study). Plasma levels of copeptin, adrenocorticotropic hormone (ACTH), and cortisol were measured at 3 timepoints in alcohol-dependent patients during the study. Corresponding plasma levels in healthy controls were assessed once. ACTH blood levels were significantly higher in the group of alcohol-dependent patients compared to controls. In patients receiving individually titrated high-dose baclofen, plasma cortisol levels decreased significantly, whereas no significant alterations were found in the placebo group. Our study underlines again the role of HPA axis alterations in AUD. Furthermore, a decrease in hormonal stress levels during treatment with high-dose baclofen might contribute to the relapse preventive effects of this compound.


[Chemical reactions in double-stranded nucleic acids. III. Synthesis of terminal inverted repeats of the IS1 element].
Three 35 bp-DNA duplexes have been assembled from synthetic oligonucleotides by means of DNA ligase or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide in two parallel series of experiments. The "top" strands of these duplexes correspond either to the imperfect (natural) or perfect terminal inverted repeats of the IS1. Tm of DNA duplexes composed of 2 to 6 different oligonucleotides were investigated by UV spectroscopy. It was shown that DNA ligase effectively joined oligonucleotides even under conditions of DNA duplex instability. However, there is a minimum duplex size (within the range of 9-15 bp) below which the enzymatic ligation is ineffective. Chemical assembly of duplexes took place only if the double helix was stable. The yield was 50% after two successive ligation cycles. Efficiency of the chemical ligation depends on the nature of the nucleotide units to be joined.


Taking HAART in the fight against HIV/AIDS.
Drug therapy for HIV/AIDS has come a long way since the 1980s when the focus was treating opportunistic infections that often accompany HIV. Today, caregivers target HIV itself with highly active (or highly aggressive) antiretroviral therapy (HAART) that interrupts viral replication.


[Simultaneous spectrophotometric determination of mixed colorants by artificial neural network].
The back propagation artificial neural network was applied to process spectrophotometric data of mixed colorants. By optimizing the network structure and parameters, the predication accuracy was enhanced. The method was used for simultaneous determination of mixed colorants in synthetic samples and drinks on sale with satisfactory results. Therefore, the artificial neural network may provide a new approach to determine the mixed colorants is drinks by spectrophotometry without any preliminary chemical separation.


Graphene oxide enabled self-assembly of silver trimolybdate nanowires into robust membranes for nanosolid capture and molecular separation.
A graphene oxide (GO) assisted self-assembly strategy for growing a silver trimolybdate nanowire membrane with capabilities of nanosolid capture and small molecule separation is reported. Thanks to the GO bridges and the accurate self-assembly process, the resulting membrane exhibits outstanding mechanical properties (can withstand 4300 times its weight) and impressively high porosity (97%). On the basis of the robustness and high porosity of the membrane, column-shaped filter apparatus has been fabricated, in which the membrane served as a self-standing permeation barrier to assess its permeability and practical application as a nanosolid filter and molecule filter. The permeability test of the membrane with pure water uncovers that the membrane exhibits fast permeability while driven by hydrostatic pressure only because of its significantly high porosity. The separation test of the membrane with P25 TiO2 solution, 13 nm Au solution, and yellow-emitting CdTe QDs reveals that all the tiny nanosolids are completely removed from the solution, which suggests that the membrane is an efficient nanosolid filter. Its efficiency is increased by the induction of surface collision from numerous nanowire barriers and the deposition of nanosolids on the nanowire surface. The separation test of the membrane with a mixed-dye solution reveals that sulfur containing methylene blue (MB) molecules are highly efficiently extracted under various chemical conditions, evidencing that the membrane is an ideal molecule filter too. Its high selectivity and high efficiency originated from the Ag-S bonding between the interlayered silver ions of the silver trimolybdate nanowire and the sulfur atom of MB molecules. Based on the above results, the silver trimolybdate nanowire membrane has been applied to purify drugs, which successfully removed sulbactam sodium impurity F from sulbactam sodium, demonstrating a purity increment from 98.92% to 99.93%. The present work should provide a significant step forward to bringing macroscopic 1D nanomaterial architectures much closer to real-world applications involving isolation and enrichment of catalyst reclamation, high-value chemical recovery, drug purification, and environmental remediation.


Controversies in Narcissism.
There has been a surge in interest in and research on narcissism and narcissistic personality disorder (NPD). Despite or because of this increased attention, there are several areas of substantial debate that surround the construct, including descriptions of grandiose and vulnerable dimensions or variants, questions regarding the existence of a consensual description, central versus peripheral features of narcissism, distinctions between normal and pathological narcissism, possible etiological factors, the role of self-esteem in narcissism, where narcissism should be studied, how it can be assessed, and its representation in diagnostic nosologies. We suggest that a failure to distinguish between grandiose (i.e., overtly immodest, self-centered, entitled, domineering) and vulnerable (e.g., self-centered, distrustful, neurotic, introverted) presentations of narcissism has led to a less cohesive and coherent literature and that trait-based models of personality and personality disorder can bring greater clarity to many of these important debates.


Influence of selective digestion of elastin and collagen on mechanical properties of human aortas.
There are two families of fibres taking part in the process of mechanical loads transfer, i.e. elastin and collagen fibres. Their number, spatial arrangement and specific properties determine the capacity of a blood vessels to resist mechanical loads resulting from the impact of blood on vessel walls. The purpose of the present paper is to define the load-bearing capacities of elastin and collagen scaffolds equivalent to natural fibre arrangements of human aorta and produced by selective digestion. Samples of thoracic human aortas were digested by using phosphate buffer of trypsin at pH 8.0 for 22 hours in order to degrade elastin and by autoclaving followed by incubation in 90% formic acid for 22 hours. The efficacy of digestion was assessed immunohistochemically. Mechanical properties of pre-stretched native and digested samples were determined by uniaxial tensile test. Samples subjected to autoclaving have been successfully deprived of both types of collagen and elastin has been intact. Treatment with trypsin caused a removal of elastin and the presence of type I and IV collagen was demonstrated. Digestion of aortic samples either by formic acid or trypsin has resulted significantly decreasing mechanical properties in comparison with native samples. Collagen and elastin scaffold-like stuctures have been effectively produced by selective digestion of thoracic human aorta and their contribution to the load-bearing process was evaluated. Isolated collagen network are more durable and stiffer and less deformable than elastin network, hence are responsible for load-bearing process at higher strain since the range of working of elastin is at lower strain values.


Mother-newborn contact in a randomized trial of kangaroo (skin-to-skin) care.
To describe the type and percent time of contact 0-48 hours postbirth for mother-preterm newborn (infant) dyads given kangaroo care (skin-to-skin) or standard care (controls). Randomized controlled trial with assignment by computerized minimization to kangaroo care (n = 48) or control (n = 43). Postpartum units and neonatal intensive-care units (NICU). Preterm infants 32 to less than 37 weeks gestation and their mothers. Kangaroo (skin-to-skin, SS) care (KC). Type and percent time of mother-infant contact (SS versus holding wrapped in blankets). Analyses were based on four groups: assignment for infants in each group to postpartum or NICU. For KC dyads, SS postpartum was 22.0%; SS NICU was 7.5%. KC wrapped holding postpartum was 11.6%; NICU was 1.8%. For control dyads, wrapped holding postpartum was 13.9%; NICU was 6.1%. Amount of SS was much less than expected. Reasons include unavailability of infants or mothers and hospital staff interrupting contact. However, KC postpartum dyads were held wrapped almost as often as control postpartum dyads. Total contact time for KC dyads (SS plus wrapped) was more than double that of controls. These data suggest that hospital and social supports for families are needed to facilitate early initiation of SS, prolonged periods of mother-infant SS contact, and reduction of maternal stress.


Blunt abdominal trauma in adults: role of CT in the diagnosis and management of visceral injuries. Part 1: liver and spleen.
Computed tomography is now widely used in the initial diagnostic workup of adult trauma victims with suspected intra-abdominal injuries. We review the role of CT in the detection and management of blunt visceral injuries in two parts. In the first part we discuss general aspects of performing CT in the setting of abdominal trauma and the diagnostic findings of intra-abdominal hemorrhage and blunt hepatic and splenic injuries. Hepatic and splenic injuries can be detected by means of CT with a high accuracy. The vast majority of hepatic injuries can be successfully managed conservatively, even when CT demonstrates parenchymal damage of more than three segments and major hemoperitoneum. Delayed complications, e. g., formation of biloma or a false aneurysm, can be readily detected on repeat CT studies, although they are quite uncommon. The outcome of conservative treatment of splenic injuries remains unpredictable because delayed splenic rupture may occur even when initial CT shows only minor parenchymal lesions and little or no intraperitoneal hemorrhage.


[Acid-soluble, non-histone proteins in rat liver chromatin. Interaction with DNA].
Some properties of nonhistone proteins of rat liver chromatin (Mr 40 +/- 1 and 41 +/- 1 KD) are described. These proteins are abundant in monomeric particles formed at the early steps of chromatin fragmentation by Ca2+,Mg2+-DNase. The proteins are not extracted from chromatin by 5% HClO4 and 1 M NaCl, but can be extracted by 0.4 n H2SO4 and 2 M NaCl. Study on proteins binding to DNA demonstrated that in 0.05 M NaCl these proteins are bound both to bovine satellite DNA and to the plasmid pBR 322 DNA.


[Some mechanisms of the action of oligonucleotides: stimulation of the immune system and decreased infection of the brain in tickborne encephalitis].
Morphological changes in the thymus, spleen, and brain are analyzed in white mice injected 16-component oligonucleotide (ON) pE16 complementary to the NS3 protein gene sequences of tickborne encephalitis (TBE) virus in doses of 1 to 0.001 nM. ON stimulated thymic and splenic cells. Besides the stimulating effect, injection of ON to mice infected with TBE enhanced the destruction of lymphocytes and boosted the macrophagal activity, which was paralleled by a decrease in the intensity of virus-specific injuries in the brain. Thus, the antiviral activity of ON may be due to not only the fact that it is complementary to the TBE virus genome, but to stimulation of the immune system, specifically, the thymus and T-related elements, as well.


Aberration free synthetic aperture second harmonic generation holography.
Second harmonic generation (SHG) microscopy is a valuable tool for optical microscopy. SHG microscopy is normally performed as a point scanning imaging method, which lacks phase information and is limited in spatial resolution by the spatial frequency support of the illumination optics. In addition, aberrations in the illumination are difficult to remove. We propose and demonstrate SHG holographic synthetic aperture holographic imaging in both the forward (transmission) and backward (epi) imaging geometries. By taking a set of holograms with varying incident angle plane wave illumination, the spatial frequency support is increased and the input and output pupil phase aberrations are estimated and corrected - producing diffraction limited SHG imaging that combines the spatial frequency support of the input and output optics. The phase correction algorithm is computationally efficient and robust and can be applied to any set of measured field imaging data.


Kinase mutations and imatinib mesylate response for 64 Taiwanese with advanced GIST: preliminary experience from Chang Gung Memorial Hospital.
Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutation of kit or platelet-derived growth factor receptor alpha (PDGFRA), which are therapeutic targets for imatinib. Results of 64 Taiwanese with advanced GIST treated with imatinib were reported. Between 2001 and May 2006, a prospective, non-randomized, and a single center trial containing 64 Taiwanese patients with advanced GIST treated with imatinib was conducted. Each tumor was investigated for mutations of kit or PDGFRA. The median follow-up time after imatinib administration was 16.1 months. 12 patients (18.8%) had complete response (CR), 24 (37.5%) had a partial response (PR), 12 stationary disease (18.8%), 16 progressive disease (25.0%). The 64 Taiwanese with advanced GIST had an estimated median survival of 48.0 months and 4-year survival rate for 76.1%. Kit mutation was found in 49 of 54 (90.7%) test patients and five of them had no mutation (9.3%). No PDGFRA mutant was identified. In 40 patients harboring kit exon 11 mutations, the CR and PR rates (ORR) were 57.5% , nine patients with tumors containing kit exon 9 mutation had ORR rates of 22.2%, and five patients with no mutation had ORR rates of 60.0% (not significant; P = 0.149). Activated mutation of kit constituted 90.7% genetic alteration of Taiwanese with advanced GIST and no PDGFRA mutation was detected. Imatinib induced a sustained objective response in more than half of Taiwan advanced GIST patients. ORR did not differ between patients whose GISTs had no mutation, kit exon 9, and 11 mutations.


Quality of life in the course of a one-year use of an advanced hybrid closed-loop system in adults with type 1 diabetes previously naïve to advanced diabetes technology.
To evaluate the effect of a one-year use of an advanced hybrid closed-loop (AHCL) system on the quality of life, level of anxiety, and level of self-efficacy in adults with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI) and naïve to advanced diabetes technology. A total of 18 participants of a previously published 3-month randomized trial (10 men, 8 women; age 40.9 ± 7.6 years) who were switched directly from MDI/BMG to AHCL completed 12 months of MiniMed 780G™system use (a 3-month randomized trial followed by a 9-month follow-up phase). At month 6 of the study, patients were switched from the sensor GS3 (Continuous Glucose Monitoring) system, powered by Guardian™ Sensor 3) to GS4. Quality of life was assessed using the Polish validated version of the 'QoL-Q Diabetes' questionnaire. The level of anxiety was evaluated with the use of the State-Trait Anxiety Inventory (STAI). Self-efficacy was assessed with the General Self-Efficacy Scale (GSES). Results were obtained at baseline and at the end of the study. Significant increase in QoL was reported in the global score (p=0.02, Cohen d=0.61) and in as many as 11 out of 23 analyzed areas of life: being physically active (p=0.02, Cohen d = 0.71); feeling well (p<.01, Cohen d = 0.73); feeling in control of my body (p<.01, Cohen d = 0.72); looking good (p<.01, Cohen d = 1.07); working (p<.01, Cohen d = 1.12); sleeping (p=0.01, Cohen d = 0.66); eating as I would like (p<.01, Cohen d = 0.79); looking after or being useful to others (p= 0.02, Cohen d = 0.65); being active with pets/animals (p<.01, Cohen d = 0.95); being spontaneous (p=0.02, Cohen d = 0.67); and doing "normal" things (p=0.02, Cohen d = 0.67). Both state (p=0.04, Cohen d = 0.56) and trait (p=0.02, Cohen d = 0.60) anxiety decreased while the general self-efficacy increased (p=0.03, Cohen d = 0.76). No participant stopped the use of the pump. Adult patients with T1D previously treated with MDI and naïve to modern technologies experienced significant improvement in their psychological well-being after transitioning to the AHCL system after 12 months of treatment.


Photothermal-Controlled Generation of Alkyl Radical from Organic Nanoparticles for Tumor Treatment.
The therapeutic properties of light are well known for photodynamic or photothermal therapy, which could cause irreversible photodamage to tumor tissues. Although photodynamic therapy (PDT) has been proved in the clinic, the efficacy is not satisfactory because of complicated tumor microenvironments. For example, the hypoxia in solid tumor has a negative effect on the generation of singlet oxygen. To address the hypoxia issues in PDT, leveraging alkyl radical is an available option due to the oxygen-independent feature. In this work, a new kind of organic nanoparticles (tripolyphosphate (TPP)-NN NPs) from porphyrin and radical initiator is developed. Under near-infrared light irradiation, TPP-NN NPs will split and release alkyl radical, which could induce obvious cytotoxicity both in normal and hypoxia environment. The photothermal-controlled generation of alkyl radical could significantly inhibit the growth of cervical cancer and show ignorable systemic toxicity. This activatable radical therapy opens up new possibilities for the application of PDT in hypoxia condition.


Effects of viscosity and surface moisture on bond strengths of resin-modified glass ionomers.
To evaluate the effects of surface moisture and material viscosity on the shear bond strength of resin-modified glass ionomers to dentin. Sixty human teeth were mounted in phenolic rings and ground to obtain flat facial and lingual dentin surfaces. The specimens were assigned to six treatment groups. Three groups were first conditioned with 10% polyacrylic acid. On one surface of each specimen, dentin was left visibly moist prior to application of the restorative material. On the opposite surface the dentin was dried, but not desiccated, after conditioning. For these three groups, Fuji II LC resin-modified glass ionomer was mixed at powder/liquid (P/L) ratios of 1.4, 3.0 and 3.6 and applied to the conditioned dentin in 2.5 mm diameter molds. The other three groups were treated with Vitremer primer. One surface of each specimen was "dry" and one surface was "moist" before primer application. Vitremer restorative material was mixed at P/L ratios of 2.2, 2.5 and 2.8 and applied to the primed surfaces. Shear bond strengths were measured using a universal testing machine. Data were subjected to three-way ANOVA and Tukey's multiple comparisons test. Mean shear bond strengths of the two materials ranged from 6.9 to 10.4 MPa and varied little regardless of the viscosity of the materials or the degree of surface moistness. The differences among viscosities and surface moistness were not statistically significant. IN this in vitro study, the shear bond strengths of two resin-modified glass ionomers were unaffected by the viscosity of the materials and the surface moisture of the dentin substrate.


Pd-Catalyzed Cyclocarbonylation of Allylic Alcohol under Benign Conditions with Ionic Liquid as Stabilizer.
Homogeneous palladium-catalyzed (Pd-catalyzed) cyclocarbonylation of unsaturated allylic alcohols and alkynols in the presence of hydrogen forms lactone products with important applications in the food, perfume, and polymer industry. In this work, the cyclocarbonylation of 2-methyl-3-buten-2-ol was studied for the first time using a very active Pd-DPEphos (bis[(2-diphenylphosphino)phenyl]ether) catalyst in the presence of the ionic liquid (IL) [BMIM]Cl (1-butyl-3-methylimidazolium chloride) in dichloromethane to selectively produce 4,4-dimethyl-γ-butyrolactone. The effect of different parameters such as temperature, gas partial pressures, time of reaction, substrate and ligand concentrations were investigated and found to provide optimal conditions for lactonization (95 °C, 28 bar (CO/H2/N2: 20/5/3)), 18 h, 0.1 M substrate, and 16 mol% DPEphos), which were significantly milder than previously reported systems for cyclocarbonylation. Importantly, the study further showed that presence of the IL in the reaction mixture provided stabilization of the catalyst system and prevented formation of Pd-black, which allowed reuse of the catalytic system in consecutive reactions after intermediate extraction of the lactone product.


Long-term follow-up of patients with birdshot retinochoroidopathy treated with systemic immunosuppression.
Birdshot retinochoroidopathy (BRC) is a rare uveitis syndrome of presumed autoimmune etiology. Therapy with systemic and periocular corticosteroids is of inconsistent efficacy, attendant with numerous potential long-term side effects. Corticosteroid-sparing strategies with agents such as cyclosporine A or azathioprine have been suggested for this disease. We retrospectively reviewed the medical charts of patients with BRC who were evaluated consecutively at a tertiary-care, referral-based North American uveitis clinic over a 15-year period. Eleven Caucasian patients (22 eyes) were diagnosed with BRC, representing approximately 1% of all cases seen at the uveitis clinic. HLA-A29 was positive in all 11 patients. We elected to treat five patients with azathioprine, methotrexate, cyclosporine A, mycophenolate mofetil, and/or IvIg, as well as systemic or periocular corticosteroid injections. The median period of follow-up for the five treated patients was six years (range: 8 months-13 years). Inflammation was reduced or stabilized in five of five patients. Although the definitive strategy for the management of BRC is unknown, control of intraocular inflammation and preservation of vision is possible with corticosteroid-sparing immunosuppressive agents.


Clinical neurology. Some applications of scanning by computer.
The use of averaging techniques permits a great increase in the resolution of time-locked waveforms in the electroencephologram. Averaged evoked potentials may be used to study sensory-sensory interactions and the effect of irritative and destructive lesions on the average evoked potential. More complex computations are possible once averages are derived, as was shown in the application of potential contour mapping, where considerable differences were noted between premature and newborn infants on the one hand and adults on the other. The flat, low voltage surface potential contour of the neonate was interpreted as reflecting a volume-conducted event having a distant, deep and midline source. Potential contour patterns in the adult were interpreted as showing predominantly neuronally propagated activity arising at the cortical surface.


Quality control in body composition measurements.
The principles of quality control (QC) are not new; they have always been with mankind. At the most fundamental level QC can be defined as a state of mind in which we continually strive to analyse what we are doing in order to produce a 'product' which our peers will judge to be 'better' . Paradoxically, this simple concept is expressed in many different ways within the multi-disciplinary team that makes up a body composition laboratory and very careful discussion is needed to ensure uniformity of technique and results. The situation is made even more difficult by the large range of equipment and techniques that are now available for the measurement of body composition. It is necessary to have a detailed understanding of the equipment and techniques and to have good communication within the group of workers. Good communication is essential to ensure that all members of the group have a clear understanding of the relevant guidelines and principles of QC and measurements, and to ensure that they are applied consistently throughout all the work of the laboratory. A detailed understanding of the equipment is necessary in order to define and implement simple tests that will monitor the most sensitive or troublesome features without imposing an undue burden upon the operator. There is a need for such tests to be automated as much as possible and, in general, there is a need for a more professional approach to the analysis of error and its propagation throughout an experiment. Inter comparisons of results between centres is a logical, but generally difficult requirement and some of the problems that arise would be simplified if equipment designs were more standardized. Finally, all these requirements need to be achieved within an environment that is continually changing with respect to the aims of the laboratory and the funding bodies.


Men, chronic illness and healthwork: accounts from male partners of women with endometriosis.
Currently dominant in medical discourse, the concept of self-management sees the responsibility for health and illness shift from the state to the individual. However, while this emphasis on individual responsibility and management has burgeoned, the role and status of partners and other family members in the management of chronic illness remains under-theorised. While self-management privileges individual responsibility for the management of chronic illness, the role of partners remains unclear. This paper utilises data from a study of heterosexual couples' experiences of living with the chronic gynaecological condition endometriosis to explore how male partners engage in its day-to-day management. In all, 22 couples participated in in-depth, semi-structured interviews with each partner interviewed separately (n = 44). Data were analysed thematically and dyadically, informed by an interpretivist relational approach. The paper utilises the concept of healthwork to describe the illness work, everyday life work, biographical work and emotion work men engaged in. The paper demonstrates how the conceptual value of healthwork is enhanced by incorporating an analysis of the emotional effort required in managing chronic illness. The paper illustrates the value of investigating the role of partners in managing chronic illness to provide a fuller account of the distributed and relational nature of healthwork.


Epidermal growth factor signaling induces behavioral quiescence in Caenorhabditis elegans.
The epidermal growth factor receptor (EGFR)/ErbB receptor tyrosine kinases regulate several aspects of development, including the development of the mammalian nervous system. ErbB signaling also has physiological effects on neuronal function, with influences on synaptic plasticity and daily cycles of activity. However, little is known about the effectors of EGFR activation in neurons. Here we show that EGF signaling has a nondevelopmental effect on behavior in Caenorhabditis elegans. Ectopic expression of the EGF-like ligand LIN-3 at any stage induces a reversible cessation of feeding and locomotion. These effects are mediated by neuronal EGFR (also called LET-23) and phospholipase C-gamma (PLC-gamma), diacylglycerol-binding proteins, and regulators of synaptic vesicle release. Activation of EGFR within a single neuron, ALA, is sufficient to induce a quiescent state. This pathway modulates the cessation of pharyngeal pumping and locomotion that normally occurs during the lethargus period that precedes larval molting. Our results reveal an evolutionarily conserved role for EGF signaling in the regulation of behavioral quiescence.


Comparative morphology of ultimate and walking legs in the centipede Lithobius forficatus (Myriapoda) with functional implications.
In the context of evolutionary arthopodial transformations, centipede ultimate legs exhibit a plethora of morphological modifications and behavioral adaptations. Many species possess significantly elongated, thickened, or pincer-like ultimate legs. They are frequently sexually dimorphic, indicating a role in courtship and mating. In addition, glandular pores occur more commonly on ultimate legs than on walking legs, indicating a role in secretion, chemical communication, or predator avoidance. In this framework, this study characterizes the evolutionarily transformed ultimate legs in Lithobius forficatus in comparison with regular walking legs. A comparative analysis using macro-photography, SEM, μCT, autofluorescence, backfilling, and 3D-reconstruction illustrates that ultimate legs largely resemble walking legs, but also feature a series of distinctions. Substantial differences are found with regard to aspects of the configuration of specific podomeres, musculature, abundance of epidermal glands, typology and distribution of epidermal sensilla, and architecture of associated nervous system structures. In consideration of morphological and behavioral characteristics, ultimate legs in L. forficatus primarily serve a defensive, but also a sensory function. Moreover, morphologically coherent characteristics in the organization of the ultimate leg versus the antenna-associated neuromere point to constructional constraints in the evolution of primary processing neuropils.


Fluorescence-based methods in the study of protein-protein interactions in living cells.
Multiprotein complexes partake in nearly all cell functions, thus the characterization and visualization of protein-protein interactions in living cells constitute an important step in the study of a large array of cellular mechanisms. Recently, noninvasive fluorescence-based methods using resonance energy transfer (RET), namely bioluminescence-RET (BRET) and fluorescence-RET (FRET), and those centered on protein fragment complementation, such as bimolecular fluorescence complementation (BiFC), have been successfully used in the study of protein interactions. These new technologies are nowadays the most powerful approaches for visualizing the interactions occurring within protein complexes in living cells, thus enabling the investigation of protein behavior in their normal milieu. Here we address the individual strengths and weaknesses of these methods when applied to the study of protein-protein interactions.


Secondary cytogenetic changes in acute promyelocytic leukemia--prognostic importance in patients treated with chemotherapy alone and association with the intron 3 breakpoint of the PML gene: a Cancer and Leukemia Group B study.
To examine, in newly diagnosed patients with acute promyelocytic leukemia (APL), the prognostic significance of secondary cytogenetic changes and the relationship between such changes and the two major promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) mRNA types. One hundred sixty-one patients with t(15;17)(q22;q11-12) enrolled onto Cancer and Leukemia Group B (CALGB) protocol 8461, a prospective study of cytogenetics in acute myeloid leukemia (AML), were studied. Eighty of these 161 patients were treated solely with chemotherapy and evaluated for response to treatment and survival. PML-RAR alpha mRNA type was determined using reverse transcriptase polymerase chain reaction (RT-PCR) in 56 patients. The incidence of secondary cytogenetic abnormalities was 32%. Among 80 patients treated with chemotherapy, the presence of a secondary chromosome abnormality was associated with longer complete remission (CR) duration (median, 29.9 v 15.7 months; P = .03) and longer event-free survival (EFS) duration (median, 17.0 v 12.2 months; P = .03). There was no difference in overall survival (P = .28). In a separate group of 56 patients with both cytogenetic and molecular data, 32 had the type L PML-RAR alpha transcript (intron 6 PML breakpoint). Of these 32 patients, four (12.5%) had chromosome changes in addition to t(15;17), whereas 12 of 20 patients (60%) with the type 5 PML-RAR alpha transcript (intron 3 PML breakpoint) had secondary cytogenetic changes (P < .001). (1) Secondary cytogenetic changes do not confer a poor prognosis in APL patients treated with anthracycline/cytarabine (Ara-C)-based chemotherapy; and (2) A highly significant relationship exists between the PML-RAR alpha 5 isoform (intron 3 PML genomic breakpoint) and secondary cytogenetic changes in APL.


Detection of soluble Fas mRNA using in situ reverse transcription-polymerase chain reaction.
Fas protein (Fas) is known to induce cell death by apoptosis in susceptible cells. Alternative splicing of the Fas gene produces soluble Fas protein (sFas), which is considered to block the function of Fas. The serum level of sFas is elevated in patients with various malignancies in a manner reflective of disease stage and tumor burden, but the precise cellular origin of sFas in vivo has not yet been clarified. To identify the cells that synthesize sFas mRNA on histologic specimens, we applied in situ reverse transcription-polymerase chain reaction (in situ RT-PCR) in 11 cases of gastric adenocarcinoma/metastatic lymph node. Furthermore, we studied the distribution of Fas using immunohistochemistry and Fas mRNA using in situ RT-PCR. In all primary tumors and 10 of 11 metastatic tumors, tumor cells expressed both Fas- and sFas mRNA. Lymphocytes infiltrated in the tumor tissues and the lymph nodes also revealed both mRNA signals. A clear correlation between the tissue distribution for Fas and its mRNA was also observed. These observations demonstrated that solid tumors in vivo can synthesize sFas mRNA and suggest that tumor cells are responsible in part for elevated sFas in human malignancies. However, the additional expression of sFas mRNA in tissue lymphocytes indicates the complex regulatory mechanisms of Fas-mediated apoptosis pathway in tumor pathogenesis and host defense. We also demonstrated that in situ RT-PCR can be a suitable method for in situ detection of alternatively spliced mRNA.


Blood-Blister Aneurysms of the Internal Carotid Artery in Tibetan and Han Populations : A Retrospective Observational Study.
Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin Scale, 0-2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients.


Mainstream wastewater treatment in integrated fixed film activated sludge (IFAS) reactor by partial nitritation/anammox process.
In this study the system based on the combination of biofilm and activated sludge (IFAS - integrated fixed film activated sludge) was tested and compared with a system that relies only on biofilm (MBBR - moving bed biofilm reactor) for nitrogen removal from municipal wastewater by deammonification process. By introduction of suspended biomass into MBBR the nitrogen removal efficiency increased from 36 ± 3% to 70 ± 4% with simultaneous 3-fold increase of nitrogen removal rate. Results of batch tests and continuous reactor operation showed that organotrophic nitrate reduction to nitrite, followed by anammox reaction contributed to this high removal efficiency. After sCOD/NH4-N ratio decreased from 1.8 ± 0.2 to 1.3 ± 0.1 removal efficiency decreased to 52 ± 4%, while still maintaining 150% higher removal rate, comparing to MBBR. Activity tests revealed that affinity of NOB to oxygen is higher than affinity of AOB with half-saturation constants of 0.05 and 0.41 mg/L, respectively.


Efficient synthetic approaches to the common scaffold of indole alkaloids.
Birch reductive alkylation of 2-aminobiphenyls affords access to highly functionalized polyenes that react through a Pd(II)-catalyzed oxidative amination cascade or through a double 1,4-addition process to provide the tetracyclic skeleton of indole alkaloids with up to four stereogenic centers created in a single-pot operation.