Role of quorum sensing in Sinorhizobium meliloti-Alfalfa symbiosis.
The ExpR/Sin quorum-sensing system of the gram-negative soil bacterium Sinorhizobium meliloti plays an important role in the establishment of symbiosis with its host plant Medicago sativa. A mutant unable to produce autoinducer signal molecules (sinI) is deficient in its ability to invade the host, but paradoxically, a strain lacking the quorum-sensing transcriptional regulator ExpR is as efficient as the wild type. We compared the whole-genome expression profile of the wild-type strain with strains missing one of the quorum-sensing regulatory components to identify genes controlled by the ExpR/Sin system throughout the different phases of the bacterial growth cycle, as well as in planta. Our analyses revealed that ExpR is a highly versatile regulator with a unique ability to show different regulatory capabilities in the presence or absence of an autoinducer. In addition, this study provided us with insight into the plant invasion defect displayed by the autoinducer mutant. We also discovered that the ExpR/Sin quorum-sensing system is repressed after plant invasion. Therefore, quorum sensing plays a crucial role in the regulation of many cell functions that ensures the successful invasion of the host and is inactivated once symbiosis is established.


Polarization dynamics in optical ground wire network.
We report the polarization dynamics in an optical ground wire (OPGW) network for a summer period and a fall period for what is believed to be the first time. To better observe the surrounding magnetic fields contribution to modulating the state of polarization (SOP) we installed a Faraday rotating mirror to correct reciprocal birefringence from quasi-static changes. We also monitored the OPGW while no electrical current was present in the towers' electrical conductors. The spectral analysis, the arc length mapped out over a given time interval on a Poincaré sphere, histograms of the arc length, and the SOP autocorrelation function are calculated to analyze the SOP changes. Ambient temperature changes, wind, Sun-induced temperature gradients, and electrical current all have a significant impact on the SOP drift in an OPGW network. Wind-generated cable oscillations and Sun-induced temperature gradients are shown to be the dominant slow SOP modulations, while Aeolian vibrations and electrical current are shown to be the dominant fast SOP modulations. The spectral analysis revealed that the electrical current gives the fastest SOP modulation to be 300 Hz for the sampling frequency of 1 KHz. This has set the upper speed limit for real-time polarization mode dispersion compensation devices.


[Nutritional evaluation of fatty acid compositions and the fat of Fujian characteristic snacks].
To analyze the fat and fatty acid composition of Fujian characteristic snacks, and to evaluate their nutritional value. The fat and fatty acid composition of Fujian characteristic snacks were analyzed by the national standards, and analyzed by statistics such as correlation analysis, nonparametric test and cluster analysis. The nutritional value of fatty acid was evaluated by unsaturated index(UI), atherogenic index(AI), thrombosis index(TI). The contents of crude fat and total fatty acid were 0.11-26.35 g/100 g and 0.08-17.85 g/100 g. The correlation coefficient r=0.915(P<0.01), crude fat and total fatty acid in poultry and livestock meats were higher than those in seafood(P<0.05). The main saturated fatty acids(SFA) were palmitic acid(21.80%-34.00%)and stearic acid(7.72%-21.45%), and the main unsaturated fatty acids(UFA)were oleic acid(5.38%-41.17%) and linoleic acid(2.99%-23.54%). The content of eicosapentaenoic acid(EPA) in fish noodle(0.71%) and docosahexaenoic acid(DHA) in fried fish roll, fish slide, fish noodles(0.41%, 2.12%, 1.59%)were far higher than other snacks. Polyunsaturated fatty acids/saturated fatty acids(PUFA/SFA)ratios were 0.10-0.69, there were 8 kinds of snacks with PUFA/SFA ratio value>0.4. The n-3 PUFA/n-6 PUFA ratios were 0.01-0.75, n-6 PUFA/n-3 PUFA ratios were 1.33-74.31. The n-6 PUFA/n-3 PUFA ratios of fish slide(1.33) and fish noodle(2.13) conform to the ideal ratio stipulated by the British Health Organization, and the ratio of flat food(6.36) conform to the recommended ratio of Food and Agriculture Organization. The SFA∶monounsaturated fatty acids(MUFA)∶PUFA ratios were 0.8∶1.0∶0.5-2.4∶1.0∶0.2, the ratios of pork zongzi, meat yan silk, spicy meat, pressed salted duck and fried oyster(1.2∶1.1∶0.5, 0.8∶1.0∶0.6, 1.0∶1.0∶0.7, 0.8∶1.0∶0.5 and 1.1∶1.1∶0.5) were close to 1∶1∶1. The UI of 15 snacks was 48.37-90.67. The AI was 0.40-1.44, and the TI was 0.97-2.32. When the distance scale was 9, snacks were divided into three categories, namely fish noodle, fish slide and others. Fish noodle was high EPA and DHA type, and fish slide was high DHA type. The fat and total fatty acid contents of the 15 snacks were wide, which were closely related to the raw materials and cooking style. Nutrition and health value of fish slide, fish noodles food, meat yan silk and spicy meat were high.


Isolation and Characterization of Anaephenes A-C, Alkylphenols from a Filamentous Cyanobacterium ( Hormoscilla sp., Oscillatoriales).
Three related new alkylphenols, termed anaephenes A-C (1-3), containing different side chains, were isolated from an undescribed filamentous cyanobacterium (VPG 16-59) collected in Guam. Our 16S rDNA sequencing efforts indicated that VPG 16-59 is a member of the marine genus Hormoscilla (Oscillatoriales). The structures of anaephenes A-C (1-3) were elucidated by spectroscopic methods, and compounds assayed for growth inhibitory activity against prokaryotic and eukaryotic cell lines. Anaephene B (2), possessing a terminal alkyne, displayed moderate activity against Bacillus cereus and Staphylococcus aureus with MIC values of 6.1 μg/mL. While 1 and 3 showed no pronounced activity in these assays, their structural features highlight the unusual biosynthetic capacity of this cyanobacterium and warrant further study.


Attended home titration of nasal continuous positive airway pressure therapy for obstructive sleep apnea.
Nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA) is usually titrated in a sleep laboratory with full polysomnographic monitoring until apneas, nonapneic desaturation, snoring, and microarousals are eliminated. This titration is sometimes done in the second half of the diagnostic sleep study or commonly on a separate second full night in the sleep laboratory. We performed NCPAP titration in the home in 17 patients with OSA previously documented by full polysomnography. Nasal CPAP was titrated at night in the patient's home by a registered nurse or polysomnography technician monitoring real-time recordings of heart rate, thoracic impedance, oxygen saturation, and pressure at the nasal mask on a four-channel recorder (EdenTec, Eden Prairie, Minn). Recordings of the nasal CPAP titration night were reviewed later by a physician. Apneas, hypopneas, and snoring were successfully eliminated in all patients. Mean nasal CPAP pressure was 10.3 +/- 3.2 cm H2O. At the time of a follow-up interview, 13 of 17 patients continued to be compliant with nasal CPAP therapy. The mean duration of therapy was 13.4 +/- 11.7 months with 7.23 mean hours of use for 6.76 nights per week. This compliance compares favorably with long-term home nasal CPAP compliance previously reported in patients titrated in our sleep laboratory. Home nasal CPAP titration resulted in about a $600 savings per patient.


Comparative anatomical distribution of serotonin 1A, 1D alpha and 2A receptor mRNAs in human brain postmortem.
The distribution of messenger ribonucleic acids (mRNA) for serotonin (5-HT) receptors of 1A, 2A and 1D alpha type (5-HT1A, 5-HT2A, and 5-HT1D alpha) was examined and compared in autoptic human brain by means of in-situ hybridization using cRNA probes, in those areas with the highest density of the receptors, as observed with binding techniques. The results showed that the 5-HT1A receptor mRNA was abundantly expressed in the layers II-VI of all cortical areas under examination, but the highest expression was found in the hippocampus, particularly in the granular cells of the dentate gyrus and in the pyramidal cell layer of the Hammon's horn. The 5-HT2A receptor mRNA was mainly present in the layers III-V of the cortex, with regional differences which were particularly marked in the striate area where the layer IV was specifically labeled. On the other hand, in the hippocampus, 5-HT2A receptor mRNA was restricted to the pyramidal cell layer of the CA1 field of the Hammon's horn. No expression of both 5-HT2A and 5-HT1D alpha receptors was detected in the caudate nucleus and in putamen where only a light labeling by means of the 5-HT1A receptor probe was detected. The 5-HT1D alpha receptor mRNA was found only in the CA3 field of the Hammon's horn. These findings confirm that 5-HT receptors are widely distributed in the brain, but that the different subtypes possess a selective localization in different neuronal populations which, in turn, may express one or more receptors. The regional differences may represent the anatomical substrate of different serotonergic functions and dysfunctions.


Evaluation of experimental myocardial infarction models via electromechanical mapping and magnetic resonance imaging.
The diagnostic characteristics of electromechanical mapping (EMM) were evaluated in porcine myocardial infarction (MI) models with the parallel application of cardiac magnetic resonance imaging (cMRI) from the aspect of different pathophysiology and localization. Balloon occlusion in the left anterior descending coronary artery (LAD balloon group) or coil deployment in the LAD (LAD coil group) or circumflex artery (Cx coil group) was applied percutaneously in 16 domestic pigs. Regional left ventricular viability data were captured via cMRI and EMM. The unipolar voltage (UV) value was significantly decreased in segments containing transmural and subendocardial late enhancement compared with viable segments in the LAD balloon, LAD coil, and Cx coil groups. Receiver operating characteristic analysis revealed area under the curve values of 0.809 and 0.691 in the LAD infarct territory, and 0.864 and 0.855 in the Cx infarct territory for the UV compared with cMRI viability results as transmural late enhancement or viable tissue and subendocardial late enhancement or viable tissue, respectively. In conclusion, the UV value detected the presence of scar tissue with differential transmural extent and which represented proper diagnostic features both in the reperfused and nonreperfused models. This data could provide additional benefit in the clinical use of EMM for diagnostic purposes.


Redox-sensitive YFP sensors for monitoring dynamic compartment-specific glutathione redox state.
Intracellular redox homeostasis is crucial for many cellular functions but accurate measurements of cellular compartment-specific redox states remain technically challenging. Genetically encoded biosensors including the glutathione-specific redox-sensitive yellow fluorescent protein (rxYFP) may provide an alternative way to overcome the limitations of conventional glutathione/glutathione disulfide (GSH/GSSG) redox measurements. This study describes the use of rxYFP sensors for investigating compartment-specific steady redox state and their dynamics in response to stress in human cells. RxYFP expressed in the cytosol, nucleus, or mitochondrial matrix of HeLa cells was responsive to the intracellular redox state changes induced by reducing as well as oxidizing agents. Compartment-targeted rxYFP sensors were able to detect different steady-state redox conditions among the cytosol, nucleus, and mitochondrial matrix. These sensors expressed in human epidermal keratinocytes HEK001 responded to stress induced by ultraviolet A radiation in a dose-dependent manner. Furthermore, rxYFP sensors were able to sense dynamic and compartment-specific redox changes caused by 100 μM hydrogen peroxide (H2O2). Mitochondrial matrix-targeted rxYFP displayed a greater dynamics of oxidation in response to a H2O2 challenge than the cytosol- and nucleus-targeted sensors, largely due to a more alkaline local pH environment. These observations support the view that mitochondrial glutathione redox state is maintained and regulated independently from that of the cytosol and nucleus. Taken together, our data show the robustness of the rxYFP sensors to measure compartmental redox changes in human cells. Complementary to existing redox sensors and conventional redox measurements, compartment-targeted rxYFP sensors provide a novel tool for examining mammalian cell redox homeostasis, permitting high-resolution readout of steady glutathione state and dynamics of redox changes.


Electrolysis and other local ablative treatments for non-resectable colorectal liver metastases.
The present paper is a review of the current ablative treatment options for the treatment of colorectal liver metastases. Cryotherapy, microwave coagulation therapy, radiofrequency ablation and laser-induced thermotherapy are discussed. Electrolysis, a novel non-thermal ablative treatment, is described. Potential benefits of electrolysis include the apparent ability to safely and effectively treat lesions abutting major hepatic structures and the lack of a systemic inflammatory reaction following electrolytic ablation. Further studies in animals and humans are needed to confirm this potential and to further refine the methods of electrolytic treatment of colorectal liver metastases.


Human leukocyte antigen-G in ankylosing spondylitis and the response after tumour necrosis factor-alpha blocker therapy.
To investigate the role of HLA-G in AS. Serum levels of soluble HLA-G (sHLA-G) were measured in 80 AS patients and 30 healthy controls. The expression of HLA-G on the peripheral blood mononuclear cell (PBMC) surface was investigated in the same 80 AS patients and 40 healthy controls by flow cytometry. The response of HLA-G after 3 months of TNF-alpha blocker therapy (adalimumab) was evaluated in 14 AS patients. We evaluated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), physical mobility, ESR and CRP levels. Serum levels of sHLA-G were significantly lower in 80 AS patients than 30 healthy controls [mean (s.d.) 22.47 (26.8) vs 34.78 (32.01) U/ml, P = 0.028], and correlated significantly with modified Schober index (r = 0.326; P = 0.009), chest expansion (r = 0.319; P = 0.011), lateral lumbar flexion (r = 0.377; P = 0.002), cervical rotation (r = 0.396; P = 0.004), whereas inversely correlated with fingertip-to-floor distance (r = -0.282; P = 0.026) and tragus-to-wall distance (r = -0.270; P = 0.031). The expression of HLA-G on PBMCs was significantly higher in 80 AS patients than 40 healthy controls [mean (s.d.) 18.5 (6.10)% vs 15.41 (4.84)%; P = 0.012], and correlated significantly with ESR (r = 0.421; P < 0.001) and CRP (r = 0.419; P < 0.001). The expression of HLA-G on PMBCs decreased significantly after 3 months of adalimumab therapy [third month vs baseline, 13.46 (5.38)% vs 19.87 (7.31)%; P = 0.016]. Lower serum levels of sHLA-G contribute to susceptibility to AS, and predispose to poor spinal mobility. The expression of HLA-G on PMBCs is up-regulated in AS, correlates with acute phase reactants and decreases after TNF-alpha blocker therapy, suggesting an index of disease activity.


Children favor punishment over restoration.
Why do people punish selfish behavior? Are they motivated to punish perpetrators of selfishness (retribution) or to compensate the victims of selfishness (restoration)? Developmental data can provide important insight into these questions by revealing whether punishment of selfishness is more retributive or restorative when it first emerges. Across two studies, we examined costly third-party intervention in 6- to 9-year-olds. In Study 1, children learned about a selfish actor who refused to share with a recipient. Children then chose to (1) punish the selfish actor by rejecting their payoff (retribution); (2) compensate the victim of selfishness by equalizing payoffs between the perpetrator and victim (restoration); or (3) do nothing. We found that children were more likely to punish than compensate in response to selfishness, suggesting that intervention in this context is more retributive than restorative. In Study 2, we tested third-party intervention in the face of generosity which, like selfishness, can lead to unequal outcomes. As in Study 1, children in this context could reject unequal payoffs, thereby depriving the recipient of the advantageous payoff but having no effect on the actor. Children could also use compensation in this context, equalizing the payoffs between actor and recipient. We found that children did not punish inequality that stemmed from generosity, suggesting that the retributive punishment in Study 1 was specifically targeting selfishness rather than inequality more generally. These results contribute to the debate on the function of third-party punishment in humans, suggesting that retributive motives toward selfish transgressors are privileged during ontogeny.


The isolation of the ectodomain of the alphavirus E1 protein as a soluble hemagglutinin and its crystallization.
Alphaviruses are isometric enveloped viruses approximately 70 nm in diameter. The viral surface contains 80 glycoprotein spikes arranged in a T = 4 lattice. Each of these spikes consists of three heterodimers of the viral membrane proteins E1 (approximately 49 kDa) and E2 (approximately 51 kDa). Cryoelectron microscopic analyses have shown that the spikes form a protein shell on the viral surface. We have made an attempt to isolate biologically active protein fragments from this surface and to grow crystals from such fragments. To this end membrane proteins were extracted with Nonidet-P40 from the Semliki Forest alphavirus and the proteins were separated from detergent by centrifugation. A protein complex containing the E1 and E2 molecules in quantitative yield was obtained by this procedure. This complex has the following properties: It sediments at approximately 30S, it chromatographs with an apparent molecular mass of approximately 580,000 Da during gel filtration, it cannot be dissociated by either nonionic detergents or 6 M urea, and at acid pH it is a highly active hemagglutinin. The data indicate that this 30S hemagglutinin complex, which has not been hitherto described for alphaviruses, may represent a variant form of the protein lattice present on the alphavirus surface. Cleavage of this complex by subtilisin selectively removes carboxy-terminal sequences from the E1 and E2 proteins, which contain the cytoplasmic and transmembrane segments of the proteins and a small part of their ectodomain. The remaining ectodomains are called E1DeltaS and E2DeltaS. This proteolysis also leads to dissociation of the 30S complex. The cleavage products accumulate in the form of a heterodimer of the E1DeltaS and E2DeltaS proteins. Treatment of the heterodimer with PNGase F leads to rapid removal of carbohydrate from the E2DeltaS protein and a dissociation of the complex into the constituent molecules, which can be separated by chromatography. The finding that the heterodimer and the purified E1DeltaS protein both function as hemagglutinin at acid pH indicates that the E1 protein represents the alphavirus hemagglutinin. We have obtained crystals of the E1DeltaS protein and are currently in the process of determining the atomic structure of this protein by the isomorphous replacement method.


Evidence for cross-species infections and cross-subtype mutations in influenza a matrix proteins.
The occurrence of swine H1N1 pandemic was unexpected because our previous focus was concentrated on highly pathogenic avian H5N1 outbreaks. The H1N1 pandemic means that cross-species infection and cross-subtype mutation is not as rare as we had previously thought, and the barriers between species and between subtypes are not strong for influenza A virus. In this study, we use ANOVA to determine if there are barriers between species and between subtypes in the matrix protein 1 family from influenza A virus. The results show that the inter-species/subtype variations are generally much smaller than the intra-species/subtype ones, indicating that the barriers between species and between subtypes are not strong for influenza A viruses, which provides statistical evidence for cross-species infections and cross-subtype mutations.


Thyroidectomy progressively renders the reproductive system of starlings (Sturnus vulgaris) unresponsive to changes in daylength.
If starlings (Sturnus vulgaris) are transferred to long days soon after being thyroidectomized, they show gonadal maturation but no subsequent photorefractoriness, suggesting a specific role for thyroid hormones in the development of photorefractoriness. This study tests an alternative hypothesis: that following thyroidectomy all gonadal responses to photoperiodic changes are progressively inhibited. Photoperiodic responses of starlings were examined at two different times after thyroidectomy. Transfer of thyroidectomized birds to long days 4 weeks after thyroidectomy caused testicular growth but at a slower rate than in intact birds, whereas, in thyroidectomized birds kept on short days, testicular growth was greater than in corresponding intact birds. Thirteen weeks after thyroidectomy, there was little or no response to an increase or a decrease in daylength in thyroidectomized birds, whereas intact birds showed marked testicular growth or regression respectively. The results support the hypothesis that the reproductive system gradually becomes unresponsive to changes in daylength during the weeks following thyroidectomy. This long-term effect may mean that earlier conclusions regarding the effects of thyroidectomy need to be reassessed.


Deregulated Ras signaling compromises DNA damage checkpoint recovery in S. cerevisiae.
The DNA damage checkpoint maintains genome stability by arresting the cell cycle and promoting DNA repair under genotoxic stress. Cells must downregulate the checkpoint signaling pathways in order to resume cell division after completing DNA repair. While the mechanisms of checkpoint activation have been well-characterized, the process of checkpoint recovery, and the signals regulating it, has only recently been investigated. We have identified a new role for the Ras signaling pathway as a regulator of DNA damage checkpoint recovery. Here we report that in budding yeast, deletion of the IRA1 and IRA2 genes encoding negative regulators of Ras prevents cellular recovery from a DNA damage induced arrest. The checkpoint kinase Rad53 is dephosphorylated in an IRA-deficient strain, indicating that recovery failure is not caused by constitutive checkpoint pathway activation. The ira1Δ ira2Δ recovery defect requires the checkpoint kinase Chk1 and the cAMP-dependent protein kinase (PKA) catalytic subunit Tpk2. Furthermore, PKA phosphorylation sites on the anaphase promoting complex specificity factor Cdc20 are required for the recovery defect, indicating a link between the recovery defect and PKA regulation of mitosis. This work identifies a new signaling pathway that can regulate DNA damage checkpoint recovery and implicates the Ras signaling pathway as an important regulator of mitotic events.


[Prognostic significance of auditory brainstem responses in full-term newborn infants with intracranial hemorrhages].
Auditory brainstem response (ABR) was recorded in 41 full-term newborn infants with intracranial hemorrhages (ICH; 10 infants with and 31 infants without neurological sequela) and the data were compared with those obtained in normal full-term newborn infants as controls. The wave-I peak latency was significantly prolonged in the non-sequela group than in the control group and in the sequela group than in the non-sequela group. The wave-III and wave-V peak latencies were significantly prolonged in the ICH group (sequela and non-sequela groups) than in the control group but did not significantly differ between the sequela and non-sequela group. The wave I-V interpeak latency did not significantly differ among the three groups. Among 10 infants in the sequela group, 9 had a V/I amplitude ratio (the amplitude of wave-I divided by the amplitude of wave- V) of less than 1.0. This suggests that the V/I amplitude ratio is of prognostic value in ICH infants.


Motivational influences on anaesthetists' use of practice guidelines.
With the proliferation of practice guidelines in anaesthesia comes the possibility that anaesthetists may, during the course of their work, commit 'violations' (actions that are not intended to cause harm to patients, but that deviate from guidelines). These may have a long-term impact on patient safety, and so there is a need to understand what makes anaesthetists decide to follow or deviate from guidelines. A questionnaire on the use of guidelines was completed by 629 College Fellows. This presented three anaesthetic scenarios, each of which involved a deviation from a guideline, and asked respondents to rate their beliefs about the likely outcome of the violation, the level of social approval they would have for violating, the amount of control they would have over violating, and the practice of their peers with regard to violating. In all three scenarios, beliefs about the outcome of violating and the amount of control over violating predicted respondents' self-reported likelihood that they would commit the violation. In two scenarios, beliefs about the practice of peers predicted violating. Level of social approval predicted violating in one scenario only. Anaesthetists' decisions to follow or deviate from guidelines are influenced by the beliefs they hold about the consequences of their actions, the direct or indirect influence of others, and the presence of factors that encourage or facilitate particular courses of action.


[Suicide and depression in the postmortem evaluation of disturbed neuronal activity].
The authors have reviewed the results of their postmortem neurohistological investigations related to the evaluation of impaired activity of brain structures relevant to pathophysiology of depression. Chronic changes in ribosomal DNA transcriptional activity have been indirectly suggested by the AgNOR staining method in neurons of the prefrontal limbic regions, the amygdala, the external globus pallidus, and the serotonergic dorsal raphe nucleus. The impact of processes leading to suicide has been clearly accentuated in contrast to the weak influence of unipolar-bipolar dichotomy. The present results support the view that suicide and depression constitute pathological phenomena with partially different neurobiology. They may be also relevant to forensic pathology.


Second natural history study of congenital heart defects. Aortic stenosis: echocardiography.
Recent advances in the field of echocardiography have made it possible to obtain a complete morphological and hemodynamic assessment of patients with aortic stenosis. Therefore, comprehensive two-dimensional and Doppler examinations were performed on patients with aortic stenosis returning for the Second Natural History Study of Congenital Heart Defects (NHS-2). Two hundred thirty-two patients with aortic stenosis underwent comprehensive two-dimensional and Doppler examinations. Of these, 96 were in the medically treated group, 49 had undergone aortic valve replacement, and 87 had had aortic valvotomy. The valve replacement group had a significantly smaller left ventricular diastolic cavity than did the medically treated group; both had smaller dimensions than the valvotomy group. There was no significant difference in left ventricular wall thickness or fractional shortening among the three groups. The valvotomy group had a significantly higher mean aortic valve gradient than did either the medically treated group or the valve replacement group. The degree of aortic regurgitation was more severe in the valvotomy group than in the other two groups. For all patients, there was a direct relation between the aortic valve gradient and the mean wall thickness and an inverse relation between the aortic valve mean gradient and fractional shortening. The only echocardiographic parameter that correlated with the presence or absence of symptomatology was the fractional shortening. These observations provide an objective measurement for assessing the status of the aortic valve and left ventricular response in patients with aortic stenosis returning for NHS-2. Limitations of echocardiography in this study are discussed.


α/β-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors.
In the brain, AMPA-type glutamate receptors are major postsynaptic receptors at excitatory synapses that mediate fast neurotransmission and synaptic plasticity. α/β-Hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor macromolecular complexes, but its physiological significance in the function of AMPA receptors (AMPARs) has remained unclear. The present study shows that overexpression of ABHD6 in neurons drastically reduced excitatory neurotransmission mediated by AMPA but not by NMDA receptors at excitatory synapses. Inactivation of ABHD6 expression in neurons by either CRISPR/Cas9 or shRNA knockdown methods significantly increased excitatory neurotransmission at excitatory synapses. Interestingly, overexpression of ABHD6 reduced glutamate-induced currents and the surface expression of GluA1 in HEK293T cells expressing GluA1 and stargazin, suggesting a direct functional interaction between these two proteins. The C-terminal tail of GluA1 was required for the binding between of ABHD6 and GluA1. Mutagenesis analysis revealed a GFCLIPQ sequence in the GluA1 C terminus that was essential for the inhibitory effect of ABHD6. The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6.


Serum tumor markers, hypoxia-inducible factor-1α HIF-1α and vascular endothelial growth factor, in patients with non- small cell lung cancer before and after intervention.
To explore changes in the serum tumor makers, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) level and their relations in patients with non-small cell lung cancer (NSCLC) before and after intervention. Forty patients with NSCLC and 40 healthy individuals undergoing physical examination in our hospital provided the observation and control groups. HIF-1α and VEGF levels in serum were detected by enzyme-linked immuno-sorbent assay (ELISA) in the observation group before and after intervention and in control group on the day of physical examination, along with serum carcino-embryonic antigen (CEA), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) levels in the observation group with a fully automatic biochemical analyzer. Clinical effects and improvement of life quality in the observation group were also evaluated. The total effective rate and improvement of life quality after treatment in observation group were 30.0% and 32.5%, respectively. Serum HIF-1α and VEGF levels in the control group were lower than that in observation group (p<0.01), but remarkably elevated after intervention (p<0.01). In addition, serum CEA, NSE and SCC levels were apparently lowered by treatment (p<0.01). Serum HIF-1α demonstrated a positive relation with VEGF level (p<0.01) and was inversely related with CEA, NSE and SCC levels (p<0.01). Significant correlations exist between marked increase of serum HIF-1α and VEGF levels and decrease of indexes related to hematological tumor markers in NSCLC patients after intervention.


Gestational trophoblastic disease: psychological aspects and fertility issues.
To evaluate the impact of a forced delay in childbearing during thefollow-up period on the perceived fertility of patients with gestational trophoblastic disease (GTD), and to investigate how women react to the monitoring period, with particular attention to fertility concerns, personal perceptions of the impact of GTD on reproductive outcomes, and psychological symptoms of depression and anxiety. Twenty women treated for GTD at San Raffaele Hospital, Milan, took part in the study. Depression, anxiety, and infertility-related stress were assessed using the Beck Depression Inventory-Short Form, the State-Trait Anxiety Inventory, and the Fertility Problem Inventory, respectively. A significant difference in depression levels was found between women with hydatiform mole and women with gestational trophoblastic neoplasia (p = 0.02). On the contrary, anxiety and depression levels did not vary on the basis of time elapsed since diagnosis, presence of children, and age (< 35 years). A significant correlation was also found between anxiety (state and trait) and depression (rho(s) = 0.62, p = 0.002 and rho(s) = 0.59, p = 0.005. respectively). There was no association between infertility-related stress and anxiety or depression or time elapsed since diagnosis. Additionally, such stress did not change between women with or without children. Women with GTD diagnosis should be followed by a multidisciplinary team so as to be supported in the disease's psychological aspects, too.


Criticism in a foreign language hurts less.
Understanding emotional resonances to social evaluations delivered in different languages may contribute to favourable social communication in today's increasingly internationalised world. The present study thus investigated the language-induced emotionality differences by presenting Chinese-English bilinguals with self-referential praising and criticising statements in both their native Chinese and foreign English languages and asking them to make their affective and cognitive judgments on the comments, namely, to rate how pleased they were by the comments and how truly the comments described their attributes. Results revealed that while criticism was rated more unpleasant than praise in both languages, the unpleasantness was reduced by the use of English as compared to Chinese. Intriguingly, no cross-language differences were found in the cognitive assessment. Our findings may shed light on facilitating affective social communication using different languages.


Drug resistance mutations among HIV-1 strains from antiretroviral-naive patients in Martinique, French West Indies.
We report on the frequency of genetic mutations associated with drug resistance in antiretroviral treatment-naive patients from Martinique (French West Indies), where zidovudine (ZDV) has been available since 1987 and where combination therapy developed simultaneously with its use in continental France. Genotypic resistance was studied in plasma HIV RNA from samples collected between 1988 and 1998 from 70 antiretroviral-naive study subjects, half presenting with either primary infection or documented seroconversion. A line probe assay (LIPA) was used to detect substitutions on the reverse transcriptase (RT) codons 41, 69, 70, 74, 184, and 215. Direct sequencing was used to complete the data for RT codons which were uninterpretable by LIPA. Of these patients, 17 harbored mutated viruses with one or more mutations in the RT gene codons analyzed. ZDV resistance mutations T215Y/F, M41L, and K70R were found in 2, 5, and 12 individuals, respectively. Mutant strains L74V (didanosine [ddI] and dideoxycytidine [ddC]) were detected in 3 patients and M184V (lamivudine/ddI/ddC) in 4 patients. However, pure mutant results at one or more codons of interest were observed in only 5 (7%; 95% confidence interval [CI], 1%-13%) patients, all involving ZDV resistance. One carried both mutations T215Y and M41L known to confer a high degree of phenotypic resistance to ZDV. Among a subgroup of 28 patients with a timepoint of infection after 1995, 24 [86%; approximately 95% CI, 73%-99%) presented with a wild-type pattern. The significance of the high prevalence of mixed patterns observed in drug-naive patients remains unclear. However, the frequency of primary mutant genotypes associated with high levels of drug resistance is low in Martinique and in this study we did not observe any currently increased tendency in this frequency.


[Suicide by a locomotive with unusual transport of suicide victims].
Two suicides are described in which the victims were transported for 400 m and 16 km (!) hanging from the locomotive's hook coupling. According to the Deutsche Bahn AG, it would be possible for a body caught on a coupling to be dragged for almost 600 km without being discovered. Upon discovery of such a body, the police must search long stretches of the railroad tracks.


[Detection carbamate pesticides residue in cucumber by immobilized acetyicholinesterase enzyme].
A novel method was described for detection carbamate pesticides residue in cucumber by immobilizing acetylcholinesterase enzyme in a micro-screen plate with 96 wells based on GA-BSA-gelatin gels. The concentrations of BSA, GA and gelatin in enzyme immobilization solution were optimized and the best concentrations were 5%, 0.5% and 0.1%, respectively. To analyze the pesticides residue 5g cucumber sample was homogenized with 10 mL acetone then an aliquot of 5mL extract was collected in a 10 mL test tube with a cap, into which 2g sodium chloride and 2mL dichloromethane were added in sequence. After shaking, 1 mL of the supernatant aliquot was evaporated by a blower in a small beaker and dissolved by 20% methanol-water solution then 50 microL was piped to a sample well. After incubation 10 minutes the absorbance was detected. The proposed method offered a rapid, simple and inexpensive means to in screen of batch samples. The minimum detection limit of this method was in a range of 0.1-0.2 mg/kg for cucumber samples.


Ketamine Augmentation of Exposure Response Prevention Therapy for Obsessive-compulsive Disorder.
Obsessive-compulsive disorder (OCD) is a disabling disease characterized by intrusive thoughts, with compulsions performed to lessen distress. Many patients with OCD do not respond to first-line intervention, such as serotonin reuptake inhibitors (SRIs) and exposure and response prevention (ERP) therapy. Previous studies have focused on the use of ketamine, a nonselective N-methyl D-aspartate receptor (NMDAR) antagonist, for treatment-resistant OCD. Research has shown that ketamine modulates NMDARs and gamma-aminobutyric acid receptors (GABAR), which are major pathways for contingency-learning, belief updating, and extinction learning. Here, we propose an augmented psychotherapy (AP) protocol combining ERP intervention with administration of ketamine. We describe the theory that NMDAR modulation might directly promote the therapeutic mechanisms involved in exposure and discuss the possibility that ketamine plasticity enhancement might potentiate extinction-based psychotherapy in the treatment of OCD.


[The role of estrogens in Parkinson's disease].
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder of the central nervous system. It has a high prevalence, which significantly increases with age. This disease significantly deteriorates the quality of life and, despite treatment, may lead to disability. For these reasons, PD is not only a medical problem, but also a social one. The neuropathological basis of Parkinson's disease is selective degeneration of dopaminergic neurons in the brain's substantia nigra, which results in an imbalance between neurotransmitters in the central nervous system, mainly between dopamine and acetylcholine. The basic symptoms of PD are tremor at rest, extrapyramidal rigidity, bradykinesia, and disturbances of postural reflexes. PD is described as a hypertonic- hypokinetic syndrome. It is also characterized by coexisting vegetative and psychopathological disturbances. In spite of considerable advances in knowledge about the mechanisms of dopaminergic neuron injury, the etiology and pathogenesis of PD are not yet well established. In this paper the authors briefly review agents which influence neurodegenerative processes of the extrapyramidal system based on available literature concerning clinical trials in Parkinson's disease. Since it is known that female sex hormones also influence dopaminergic transmission, special attention is paid to the potential role of estrogens as agents modulating the risk of PD occurrence and their neuroprotective action.


Architectural programming for the workplace and the careplace.
Sensitive planning and architectural design will impact long-term costs and daily operations. At the same time, the quality of the total environment has a direct impact on the patient, the family and the staff. These needs should be carefully balanced with the emotions of the patient, the care partner (parent, husband, wife or guardian) and those of the clinical team (physicians, nurses and staff). This article addresses the first step in the process; the master plan and then focuses in detail on one aspect of the architectural work referred to as architectural programming. The key to the process is selecting the best team of consultants, following the steps carefully, involving the client at every appropriate milestone along the way and asking the right questions. With this experienced team on board; following the proper steps, listening carefully to the answers and observing the daily process one can expect a successful product.


The roles of histidine kinases in sensing host plant and cell-cell communication signal in a phytopathogenic bacterium.
It has long been known that phytopathogenic bacteria react to plant-specific stimuli or environmental factors. However, how bacterial cells sense these environmental cues remains incompletely studied. Recently, three kinds of histidine kinases (HKs) were identified as receptors to perceive plant-associated or quorum-sensing signals. Among these kinases, HK VgrS detects iron depletion by binding to ferric iron via an ExxE motif, RpfC binds diffusible signal factor (DSF) by its N-terminal peptide and activates its autokinase activity through relaxation of autoinhibition, and PcrK specifically senses plant hormone-cytokinin and elicits bacterial responses to oxidative stress. These HKs are critical sensors that regulate the virulence of a Gram-negative bacterium, Xanthomonas campestris pv. campestris. Research progress on the signal perception of phytopathogenic bacterial HKs suggests that inter-kingdom signalling between host plants and pathogens controls pathogenesis and can be used as a potential molecular target to protect plants from bacterial diseases. This article is part of the theme issue 'Biotic signalling sheds light on smart pest management'.


Growth in Noonan syndrome.
Growth failure in Noonan syndrome is mainly postnatal of character and is dominated by slow maturation and late puberty. The postnatal early decline seems to be an intrinsic part of the syndrome. Reported adult heights are about -2 SD and are indicative of a secular trend.


A unique urinary metabolomic signature for the detection of pancreatic ductal adenocarcinoma.
Our study aimed to identify a urinary metabolite panel for the detection/diagnosis of pancreatic ductal adenocarcinoma (PDAC). PDAC continues to have poor survival outcomes. One of the major reasons for poor prognosis is the advanced stage of the disease at diagnosis. Hence, identification of a novel and cost-effective biomarker signature for early detection/diagnosis of PDAC could lead to better survival outcomes. Untargeted metabolomics was employed to identify a novel metabolite-based biomarker signature for PDAC diagnosis. Urinary metabolites from 92 PDAC patients (56 discovery cohort and 36 validation cohort) were compared with 56 healthy volunteers using 1 H nuclear magnetic resonance spectroscopy. Multivariate (partial-least squares discriminate analysis) and univariate (Mann-Whitney's U-test) analyses were performed to identify a metabolite panel which can be used to detect PDAC. The selected metabolites were further validated for their diagnostic potential using the area under the receiver operating characteristic (AUROC) curve. Statistical analysis identified a six-metabolite panel (trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone), which demonstrated high potential to diagnose PDAC, with AUROC of 0.933 and 0.864 in the discovery and validation cohort, respectively. Notably, the identified panel also demonstrated very high potential to diagnose early-stage (I and II) PDAC patients with AUROC of 0.897. These results demonstrate that the selected metabolite signature could be used to detect PDAC and will pave the way for the development of a urinary test for detection/diagnosis of PDAC.


Improved formulas for the estimation of renal depth in adults.
Commercial techniques are available to calculate effective renal plasma flow (ERPF) or glomerular filtration rate (GFR) based on the percent injected dose in the kidney 1-2 or 2-3 min post-injection; renal depth is estimated by the Tonnesen equations. Since the Tonnesen equations were derived from ultrasound measurements obtained at an oblique angle in sitting patients, we compared the renal depths obtained from the Tonnesen equations with the renal depth measured by computed tomography in supine patients, the most common position for radionuclide renography. The renal depth, height, weight, age and sex were determined for 126 patients undergoing CT scanning. Patients with obvious renal or abdominal pathology were excluded. The Tonnesen equations significantly underestimated renal depth. Using stepwise linear regression analysis, we derived a set of equations based on age, height and weight and applied these prospectively to a new set of 75 patients. In addition, a second set of equations were derived for the new data. There was no difference in the results for the two equations. We then pooled both studies and derived a combined set of equations: right renal depth (mm) = 153.1 weight/height + 0.22 age + 0.77 and left renal depth (mm) = 161.7 weight/height + 0.27 age - 9.4, where weight is in kilograms and height is in centimeters. The correlation coefficients were 0.81 and 0.83 for the right and left kidneys respectively with standard errors of the estimate of 10.2 and 10.1 mm. These equations provide a much better estimate of renal depth in the supine patient than the Tonnesen equations.


A comparison of patient and family caregiver prospective control over lung cancer.
This paper is a report of our secondary analysis of patient and family caregiver prospective control in lung cancer. Control beliefs underlie self-care in sickness and health. Self-care often involves 'shared' activities between the afflicted individual and caregiving family and friends. However, depending on how control is perceived, conflicts can occur in decision-making thus jeopardizing optimal self-care. We need to comprehend how control beliefs compare between patients and caregivers and how their control beliefs are linked with dealing with serious illness. Based on questionnaire data collected in our larger study between September 2005 and February 2009, we conducted exploratory comparative analyses of 304 patients' and caregivers' control beliefs in managing lung cancer. Eight 5-point response items captured prospective control. Exploratory factor analysis with promax rotation was conducted to compare dyadic perceptions on the dimensionality of prospective control. We also conducted exploratory correlations between control beliefs and smoking cessation, attributional reactions, caregiver helping and symptom reports. Principal component analysis identified the same factors for patients and caregivers: factor 1, Fate control and factor 2, Team control. Patient and caregiver 'Fate' and 'Team' control sub-scales were respectively associated with hope, caregiver helping and patient smoking cessation. Clinicians need to support, adapt or develop a philosophy of cancer care that is inclusive of partnerships, drawing on beliefs of patients and caregivers that controlling lung cancer is a team effort which in turn is tentatively linked to patient smoking cessation, positive emotions and caregiver helping.


Hepatic epithelioid hemangioendothelioma: A clinocopathological correlation.
Primary hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an incidence of <0.1 per 100,000. The clinical course is variable with variable outcomes. Due to its rarity, treatment protocols, prognostic and predictive factors are not well established underscoring the need for such a study. Pathologists' awareness of this entity, a meticulous morphologic examination coupled with immunohistochemistry can aid in accurate diagnosis.


Molecular systematics of the Malagasy babblers (Passeriformes: timaliidae) and warblers (Passeriformes: sylviidae), based on cytochrome b and 16S rRNA sequences.
The phylogenetic relationships of the Timaliidae (babblers) and Sylviidae (warblers) have long challenged ornithologists. We focus here on three Malagasy genera currently assigned to the Timaliidae, Mystacornis, Oxylabes, and Neomixis, and on their relationships with other babblers and warblers using the sequences of two mitochondrial genes (cytochrome b and 16S rRNA). Maximum parsimony analyses show that the Malagasy "babblers" are not related to any of the other African and Asian babblers. The genus Mystacornis is neither a babbler nor a warbler. The other Malagasy "babblers" are members of warbler groups (the monophyly of the Sylviidae is not demonstrated). Oxylabes madagascariensis and Hartertula flavoviridis (we recognize Hartertula as a genus for the species flavoviridis, previously Neomixis flavoviridis) constitute, with two presumed sylviine taxa, Thamnornis chloropetoides and Cryptosylvicola randrianasoloi, a warbler radiation endemic to the island of Madagascar. The other Neomixis species (tenella, striatigula, and viridis) belong to another warbler group comprising cisticoline taxa. These results show that the Timaliidae did not disperse to Madagascar. Rather, the island has been colonized, independently, by at least two clades of warblers, probably originating from Africa, where the Sylviidae radiation has been the most extensive.


Polylysine and polyamine stimulation of the phosphatidylinositol kinases of amphibian oocyte membranes.
Phosphatidylinositol kinase present in Xenopus laevis oocyte membranes catalyzes the formation of phosphatidylinositol 4-phosphate using phosphatidylinositol and ATP as substrates while the activity of a second enzyme, phosphatidylinositol-4-phosphate kinase, results in the synthesis of phosphatidylinositol 4,5-bisphosphate. Large (Mr greater than 20,000) homopolymers of L-lysine or L-ornithine can stimulate the activity of both of these enzymes by at least 2-fold at 10-20 microM concentrations. Under similar conditions poly-L-arginine fails to stimulate the reaction causing a partial inhibition. Smaller polylysine (25 lysines) or lysine-rich oligopeptides such as one corresponding to the last 14 amino acids of the carboxyl end of c-Ki-ras 2 protein produce appreciable stimulation of phosphatidylinositol but at concentrations of 300-500 microM. Spermine and spermidine at millimolar concentrations also stimulate exogenous phosphatidylinositol phosphorylation. The amino-glycoside antibiotic neomycin has a biphasic effect, stimulating the phosphatidylinositol kinase at concentrations below 0.5 mM and strongly inhibiting at higher concentrations. Polylysine also moderately stimulates the loss of radioactivity of phosphatidylinositol-4-[32P] phosphate observed in oocyte membranes. Polylysine and polyornithine do not change the apparent Km for ATP of the phosphatidylinositol kinase but increase the Vmax of the reaction.


Facile synthesis of nickel phosphate nanorods as biomimetic enzyme with excellent electrocatalytic activity for highly sensitive detection of superoxide anion released from living cells.
In this work, the superoxide dismutase (SOD) biomimetic enzyme based on nickel phosphate nanorods [Ni(PO4)NRs] was prepared by a simple and eco-friendly hydrothermal method. After further introduction of carboxylated multi-walled carbon nanotubes (C-MWCNTs), the obtained Ni(PO4)NRs/C-MWCNTs nanocomposites were utilized as the novel electrode materials to construct the electrochemical superoxide anion radicals (O2•-) biosensor with excellent electrical conductivity and unprecedented catalytic performance. The morphology of Ni(PO4)NRs/C-MWCNTs nanocomposite was examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Raman microscope, respectively. Under the optimum conditions, the proposed biosensor exhibits high sensitivity (5.67 × 104 μA/mM/cm2), low detection limit (0.097 μM at S/N = 3) and good selectivity to O2•-. In addition, the sensor can monitor O2•- released from MCF-7 cells with satisfactory results, which provides a great opportunity to apply it in the field of fundamental research and clinical diagnostics. Our results would promote Ni(PO4)NRs as the SOD biomimetic enzyme for designing biosensor and expand its various applications in biocatalysis and bioanalysis.


Effect of peroxide concentration and brushing on whitening clinical response.
This clinical trial compared the effects of hydrogen peroxide concentration and toothbrushing on clinical response to vital bleaching. Tooth bleaching was accomplished with a flexible, polyethylene strip coated with a hydrogen peroxide bleaching gel worn for 30 minutes twice daily over a 14-day period. A total of 36 subjects were randomized to 1 of 3 treatment groups: 5.3% hydrogen peroxide strip plus prebrushing, 6.5% hydrogen peroxide strip plus prebrushing, or 6.5% hydrogen peroxide strip without prebrushing. Two groups brushed with regular anticavity toothpaste immediately before bleaching, while the other group performed ad libitum brushing only. Tooth color was measured over a 14-day period using digital images of the anterior dentition. Over the 14-day treatment period, all 3 strip groups experienced highly significant (P < 0.001) whitening as evidenced by decreased yellowness (delta b*) and increased brightness (delta L*), as well as composite color change (delta E*) relative to baseline. Keeping brushing constant, the 6.5% hydrogen peroxide strip plus prebrushing group experienced a 31% to 60% improvement in whitening relative to the 5.3% hydrogen peroxide standard. Keeping concentration constant at 6.5% hydrogen peroxide, the prebrushing group experienced a directional 5% to 33% improvement in whitening relative to no prebrushing. All treatments were generally well tolerated. This study demonstrates that for strip-based delivery, increasing hydrogen peroxide concentration to 6.5% results in a significant improvement in efficacy with few tolerability trade-offs.


Interstitial adenosine concentration during norepinephrine infusion in isolated guinea pig hearts.
This study determined the effect of norepinephrine (NE) on cardiac interstitial fluid adenosine concentration [( ADO]isf). Isolated guinea pig hearts were perfused with a Krebs-Henseleit buffer solution. Radiolabeled albumin, sucrose, and adenosine were injected under control conditions and after 3 and 20 min of NE infusion to obtain multiple indicator dilution curves that were used to determine capillary transport parameters for adenosine. These parameters together with venous adenosine concentrations were used in a mathematical model to a calculate [ADO]isf. Capillary transport parameters were not changed significantly by NE infusion. Because of uncertainty regarding two model parameters, two sets of [ADO]isf values were calculated. One set used best-fit values obtained from indicator dilution curves, and a second set used parameters chosen to provide the highest [ADO]isf values consistent with indicator dilution curves. Venous adenosine concentrations were 1.9 +/- 0.4 nM under control conditions and 243 +/- 110 and 45 +/- 25 nM after 3 and 20 min of NE infusion, respectively. Calculated [ADO]isf was 2.6-9.4, 591-1,288, and 166-324 nM, respectively, under these same conditions. We conclude that NE infusion greatly increases [ADO]isf, and adenosine is responsible for most of the vasodilation at 3 min. The subsequent fall in venous concentration is due to a fall in [ADO]isf rather than to decreased capillary permeability. Vascular resistance remained low while [ADO]isf fell, which suggests that additional vasodilators are important during maintained NE infusion.


Comparison of the accuracy of bracket positioning between direct and digital indirect bonding techniques in the maxillary arch: a three-dimensional study.
When the indirect bonding technique was developed in 1972 by Silverman and Cohen, many authors wondered whether this technique would improve bracket positioning accuracy compared to the direct bonding technique. Studies have found little to no difference between them regarding positioning accuracy. Recently, technological advances have improved the indirect method by allowing the user to position the brackets virtually using software applications such as OrthoAnalyzer™. To the best of our knowledge, no studies have compared direct positioning to this new digital indirect technique. Thus, the aim of this study was to compare the accuracy of placement between the two techniques in the maxillary arch using two different bracket types: conventional twin brackets and self-ligating brackets. A secondary objective was to evaluate whether bracket type affected positioning accuracy. A maxillary arch of a patient was scanned by digital impression. Forty resin duplicates of this model were printed and then mounted on a mannequin head, on which 20 practitioners performed direct bonding using the aforementioned brackets. Later on, they performed a virtual indirect bonding of the same case virtually, with the digital impression superimposed to the patient's CBCT (cone-beam computed tomography). Afterwards, the direct bonded models were unmounted, scanned, and then superimposed to the indirect models. Differences in height, angulation and mesio-distal position of the brackets were evaluated. Regarding height, the differences between direct and indirect methods were not significant. Height difference was significantly greater for self-ligating brackets compared to conventional brackets. Regarding mesio-distal positioning, significant differences were noted for teeth 13 and 15 with self-ligating brackets (p-value = 0.019 and p-value = 0.043, respectively). The deviation was also greater for these brackets. Regarding angulation, the difference was significant on tooth 12 when using conventional brackets (p-value = 0.04) and on 12 and 22 when using self-ligating brackets (p-value = 0.09). There were no major significant differences between direct and indirect bonding. Differences were significant only on the laterals for of angulation, and on teeth 13 and 15 for mesio-distal centering. The bracket type seems to influence positioning accuracy, since self-ligating brackets had a larger deviation range than conventional brackets.


Economic assessment of a six-year project with extensive use of dental hygienists in the dental care of children: a pilot study.
The aim of the study was to assess the economic efficiency of an alternative division of labour based on an extensive use of dental hygienists combined with a reduced input of dentists. A test clinic was compared to a conventionally run public clinic in respect of dental and financial effects in the dental care of children. The study comprised 80 adolescents, born in 1975, in their 13th to 18th years. The assessment of economic efficiency was based on a cost/benefit analysis on the clinic level, in which the cost was defined as the difference between the test clinic and the control clinic in yearly running variable costs per child, and the benefit as the difference in the yearly caries increment multiplied by a value factor. The results showed statistically significant, lower caries incidence in the test group. Regression analyses, estimating a caries incidence function gave statistically significant explanation values for the variables "Caries prevalence" at 13 years of age' and 'Clinic'. The cost/benefit analysis showed a benefit/cost ratio of 1.48. The division of labour at the test clinic is discussed as a possible main factor for the outcome and suggests further experiments on a larger scale. The study can be regarded as a pilot, intended to be followed by a comprehensive study using a larger number of patients of different ages and more control clinics.


Endoscopic removal of a biliary Wallstent with a suture-cutting device in a patient with primary pancreatic lymphoma.
This report describes the case of a 74-year-old woman who had previously had a metal stent placed to relieve jaundice resulting from a pancreatic head tumor, suspected to be adenocarcinoma. The tumor was subsequently found to be a non-Hodgkin's large-cell lymphoma, which had shown a rapid response to chemotherapy without tumor recurrence in over 3 years since the diagnosis. She was referred for management of recurrent jaundice and cholangitis resulting from repeated metal stent occlusion, despite multiple endoscopic procedures and failed surgical removal. This report describes experience with the use of an endoscopic suture-cutting device to assist in the removal of the metal stent. It also highlights the need for proper patient selection before placement of biliary metal stents.


Conflict across representational gaps: Threats to and opportunities for improved communication.
Often, the senders and receivers of scientific communication have different knowledge bases. While such communication is essential for solving the complex social and technological problems that affect multiple stakeholders, a diversity of knowledge among communicators can create representational gaps (rGaps). rGaps occur when senders make assumptions that receivers do not, creating conflict over the meaning and value of the information communicated. Such conflict could, if managed, promote learning and innovation as communicators reconcile their assumptions. More often, however, rGaps cause conflict to transform from a debate that informs to an argument that divides. Managing rGap conflict so that it does not degrade communication requires relationship building to mitigate the negative by-products of persistent conflict while maintaining appropriate levels of cognitive distinctiveness among diverse stakeholders. Thus, we provide a framework for identifying and leveraging rGaps through managed conflict so that communication between those with different perspectives builds rather than burns bridges.


Essentials of anterior cruciate ligament rupture management.
Anterior cruciate ligament (ACL) rupture is a common knee injury and an understanding of current medical knowledge regarding its management is essential. Accurate and prompt diagnosis requires an awareness of injury mechanisms and risk factors, common symptoms and physical/radiologic findings. Early mobilization and physical therapy improves outcomes regardless of treatment modality. Many older patients regain sufficient stability and function after non-operative rehabilitation. Early ACL reconstruction is appropriate for younger patients and those who engage in activities requiring frequent pivoting and rapid direction changes. ACL surgery involves reconstruction of the torn ligament tissue with various replacement graft options, each with advantages and disadvantages. The guidance of a knowledgeable and experienced therapist is required throughout an intensive and prolonged rehabilitation course. Generally excellent outcomes and low complication rates are expected, but treatment does not prevent late osteoarthritis.


Conversion of trypsin to a copper enzyme: tyrosinase/catechol oxidase by chemical modification.
New active sites can be introduced into naturally occurring enzymes by the chemical modification of specific amino acid residues in concert with genetic techniques. Chemical strategies have had a significant impact in the field of enzyme design such as modifying the selectivity and catalytic activity which is very different from those of the corresponding native enzymes. Thus, chemical modification has been exploited for the incorporation of active site binding analogs onto protein templates and for atom replacement in order to generate new functionality such as the conversion of a hydrolase into a peroxidase. The introduction of a coordination complex into a substrate binding pocket of trypsin could probably also be extended to various enzymes of significant therapeutic and biotechnological importance. The aim of this study is the conversion of trypsin into a copper enzyme: tyrosinase by chemical modification. Tyrosinase is a biocatalyst (EC.184.108.40.206) containing two atoms of copper per active site with monooxygenase activity. The active site of trypsin (EC 126.96.36.199), a serine protease was chemically modified by copper (Cu(+2)) introduced p-aminobenzamidine (pABA- Cu(+2): guanidine containing schiff base metal chelate) which exhibits affinity for the carboxylate group in the active site as trypsin-like inhibitor. Trypsin and the resultant semisynthetic enzyme preparation was analysed by means of its trypsin and catechol oxidase/tyrosinase activity. After chemical modification, trypsin-pABA-Cu(+2) preparation lost 63% of its trypsin activity and gained tyrosinase/catechol oxidase activity. The kinetic properties (K(cat), K(m), K(cat)/K(m)), optimum pH and temperature of the trypsin-pABA-Cu(+2) complex was also investigated.


Phytosulfokine-alpha, a sulfated pentapeptide, stimulates the proliferation of rice cells by means of specific high- and low-affinity binding sites.
Peptide growth factors were isolated from conditioned medium derived from rice (Oryza sativa L.) suspension cultures and identified to be a sulfated pentapeptide [H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-Gln-OH] and its C-terminal-truncated tetrapeptide [H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-OH]. These structures were identical to the phytosulfokines originally found in asparagus (Asparagus officinalis L.) mesophyll cultures. The pentapeptide [phytosulfokine-alpha (PSK-alpha)] very strongly stimulated colony formation of rice protoplasts at concentrations above 10(-8) M, indicating a similar mode of action in rice of phytosulfokines. Binding assays using 35S-labeled PSK-alpha demonstrated the existence of both high- and low-affinity specific saturable binding sites on the surface of rice cells in suspension. Analysis of [35S]PSK-alpha binding in differential centrifugation fractions suggested association of the binding with a plasma membrane-enriched fraction. The apparent Kd values for [35S]PSK-alpha binding were found to be 1 x 10(-9) M for the high-affinity type and 1 x 10(-7) M for the low-affinity type, with maximal numbers of binding sites of 1 x 10(4) sites per cell and 1 x 10(5) sites per cell, respectively. Competition studies with [35S]PSK-alpha and several synthetic PSK-alpha analogs demonstrated that only peptides that possesses mitogenic activity can effectively displace the radioligand. These results suggest that a signal transduction pathway mediated by peptide factors is involved in plant cell proliferation.


Effects of musical tempo on physiological, affective, and perceptual variables and performance of self-selected walking pace.
[Purpose] This study investigated the effects of musical tempo on physiological, affective, and perceptual responses as well as the performance of self-selected walking pace. [Subjects] The study included 28 adult women between 29 and 51 years old. [Methods] The subjects were divided into three groups: no musical stimulation group (control), and 90 and 140 beats per minute musical tempo groups. Each subject underwent three experimental sessions: involved familiarization with the equipment, an incremental test to exhaustion, and a 30-min walk on a treadmill at a self-selected pace, respectively. During the self-selected walking session, physiological, perceptual, and affective variables were evaluated, and walking performance was evaluated at the end. [Results] There were no significant differences in physiological variables or affective response among groups. However, there were significant differences in perceptual response and walking performance among groups. [Conclusion] Fast music (140 beats per minute) promotes a higher rating of perceived exertion and greater performance in self-selected walking pace without significantly altering physiological variables or affective response.


Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.
To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. Serum FGF21 levels were measured at 6-15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24 kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24 kg/m2 ) and FGF21 levels (≥median and <median), a significant association was observed in those with higher BMI and FGF21 levels (odds ratio, 2.12; 95% CI: 1.41, 3.20) but not in those with either higher BMI or higher FGF21, with a significant additive interaction (relative excess risk due to interaction = 1.23; 95% CI: 0.27, 2.20). FGF21 was also correlated with unfavourable glucose and lipid biomarkers as well as adipokines. Elevated serum FGF21 levels in early pregnancy were associated with a higher risk of GDM, particularly among those with overweight/obesity.


Alcohol Consumption and Cardiovascular Disease Risk: Placing New Data in Context.
A clear link between excessive alcohol consumption and cardiovascular disease (CVD) has been established, but no consensus exists on the effects of moderate alcohol consumption on CVD. A lower risk of coronary heart disease and myocardial infarction among moderate drinkers compared to abstainers has been consistently observed in epidemiological studies and meta-analyses of these studies. However, ambiguity remains on the effect of alcohol on other CVDs and all-cause mortality. Short-term randomized controlled trials (RCT) have identified potentially beneficial effects of alcohol consumption on cardiovascular risk factors, but studies investigating genetic polymorphisms that influence alcohol consumption (i.e., Mendelian randomization) have yielded inconclusive results. To date, a long-term RCT providing causal evidence is lacking but urgently needed. Triangulation of evidence from different study designs, including long-term RCTs, pragmatic trials and the evaluation of policy measures, combined will lead to the best available evidence.


Quantification of metronidazole in human plasma using a highly sensitive and rugged LC-MS/MS method for a bioequivalence study.
A highly sensitive, selective and rugged method has been described for the quantification of metronidazole (MTZ) in human plasma by liquid chromatography-tandem mass spectrometry using metronidazole-d4 as the internal standard (IS). The analyte and the IS were extracted from 100 μL plasma by liquid-liquid extraction. The clear samples obtained were chromatographed on an ACE C18 (100 × 4.6 mm, 5 μm) column using acetonitrile and 10.0 mm ammonium formate in water, pH 4.00 (80:20, v/v) as the mobile phase. A triple quadrupole mass spectrometer system equipped with turbo ion spray source and operated in multiple reaction monitoring mode was used for the detection and quantification of MTZ. The calibration range was established from 0.01 to 10.0 μg/mL. The results of validation testing for precision and accuracy, selectivity, matrix effects, recovery and stability complied with current bioanalytical guidelines. A run time of 3.0 min permitted analysis of more than 300 samples in a day. The method was applied to a bioequivalence study with 250 mg MTZ tablet formulation in 24 healthy Indian males.


Unusually swift response of relapsed Burkitt leukemia to R-DHAP.
Burkitt leukemia (BL) represents a highly aggressive lymphoma characterized by proliferation rates of around 100%, and a frequent spread into the central nervous system. If standard frontline chemotherapy fails, the prognosis is usually dismal, and reports on successful effective salvage therapy strategies for patients with relapsed/refractory BL are scant. Here, we report on a 40-year-old female patient who suffered an early relapse of BL three months after the completion of frontline chemoimmunotherapy. Strikingly, after only one cycle of R-DHAP chemotherapy, the patient showed CR of BL enabling swift transition to a consolidating allogeneic stem cell transplantation. A 40-year-old previously healthy woman presented to the hospital with fatigue and incessant epistaxis, and a diagnosis of BL was made upon histological examination of a bone marrow biopsy. Treatment was initiated according to the GMALL 2002 B-NHL/ALL protocol, which could induce complete molecular remission. Nevertheless, three months after chemotherapy, the patient exhibited BL relapse in the bone marrow, and on Fluorodeoxyglucose (FDG)-PET-imaging. The relapse therapy was started with R-DHAP, and after only one cycle, the patient once again entered complete remission (CR) paving the way for allogeneic stem cell transplantation. Unfortunately, the patient again relapsed five months after transplantation prompting salvage therapy with R-DHAC and the execution of the second stem cell transplantation. However, one month after the second transplantation the patient presented with chemorefractory meningeosis leukemia resulting in the initiation of palliative care treatment. In summary, we report on rapid CR of relapsed BL after a single cycle of rituximab-DHAP. Given a paucity of clinical trials on the treatment of patients with r/r BL, we intend to highlight the potential efficacy of rituximab-DHAP as salvage therapy in those patients.


Calculating and updating nursing turnover costs.
A detailed study allowed FY 1988 nursing turnover costs to be calculated at four southeastern hospitals. These turnover costs were later updated using a procedure incorporating Consumer Price Index information. This procedure allows nurse administrators to determine and update turnover costs, to accurately evaluate the impact of nursing turnover, and to facilitate resource allocation.


Significance of 123I-MIBG scintigraphy as a pathophysiological indicator in the assessment of Parkinson's disease and related disorders: it can be a specific marker for Lewy body disease.
Recently, reliable and clear evidence for the usefulness of 123I-MIBG scintigraphy in the diagnosis of Parkinson's disease (PD) has been accumulated and it has become increasingly popular as one of the most accurate means of diagnosing the disease. PD, one of the most common neurodegenerative disorders, is characterized by resting tremor, rigidity, bradykinesia or akinesia, and postural instability. The disease is characterized pathologically by distinctive neuronal inclusions called Lewy bodies in many surviving cells of dopaminergic neurons of the substantia nigra pars compacta and other specific brain regions. Furthermore Lewy body type degeneration in the cardiac plexus has been observed in PD. In PD, cardiac MIBG uptake is reduced markedly even in the early disease stages; therefore, MIBG imaging can be used as an indicator of the presence of PD rather than disease severity. Other parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration demonstrate normal cardiac MIBG uptake or only mild reduction of MIBG uptake, indicating that MIBG imaging is a powerful method to differentiate PD from other parkinsonian syndromes. Dementia with Lewy bodies (DLB) also shows severe reduction of MIBG uptake, whereas Alzheimer's disease (AD) demonstrates normal MIBG uptake, permitting differentiation of DLB from AD using MIBG scintigraphy. In pure autonomic failure, which shares similar pathological findings with PD and is thought to be associated with diffuse loss of sympathetic terminal innervation, cardiac MIBG uptake also decreases markedly. Considering all the data together, marked reduction of cardiac MIBG uptake seems to be a specific marker of Lewy body disease and thus extremely useful in the differentiation from other diseases with similar symptoms without Lewy bodies.


[Contraceptive activity of RU486 and oral active prostaglandin combination].
The most used medical method for early pregnancy interruption associates the antiprogestin RU486 (Mifepristone) and an intramuscularly injected prostaglandin (Sulprostone) (Silvestre et al., New Engl. J. Med., 322, 1990, pp. 645-648). Misoprostol, an orally active PGE1 synthetic derivative, showed the same efficacy as Sulprostone in a trial including 100 patients. The medical characteristics and potential of the new method are briefly discussed.


The state of the union. Neuromuscular junction.
Synaptic differentiation is triggered by signals from the ingrowing axon and is shaped by information exchange between the presynaptic and postsynaptic cells. The central role of agrin in this process, and the identity of the signaling component of its receptor, have now been established.


Distribution of the human immunodeficiency virus coreceptors CXCR4 and CCR5 in fetal lymphoid organs: implications for pathogenesis in utero.
HIV entry into a cell requires the coordinate cell surface expression of CD4 and one of several chemokine coreceptors. Here we have examined the expression of the two most widely utilized HIV coreceptors, CXCR4 and CCR5, on various lymphoid tissues derived from the fetus. CXCR4 and CCR5 are differentially expressed on lymphocytes in different lymphoid organs, which may reflect the maturational and functional status of cells within the organ. The different levels of coreceptor expression on CD4+ cells in the various organs may directly affect the targeting of CXCR4- and CCR5-tropic strains of HIV toward different fetal lymphoid tissues during in utero infection.


'Full prosthetic jacket': external stenting of the renal vein.
Introduction: We present a case of positional compression of the left renal vein (LRV) after right nephrectomy and caval reconstruction, treated by external stenting using a reinforced vascular prosthesis.Case report: A 69-year-old female patient presented because of swelling of the left leg. A renal cell carcinoma (RCC) was visualized on computed tomography (CT) scan in the right kidney, with a thrombus occluding the inferior caval vein (ICV) and the right renal vein (RRV). A right nephrectomy was performed, with ligation of the already occluded ICV. Venotomy allowed thrombectomy of the ICV above the level of the renal veins. Venous return from the left kidney was secured by reconstruction of the confluence of the LRV and the ICV. Postoperatively, urinary output declined, leading to anuria and elevated levels of serum creatinine. With surgical exposition of the LRV, a flow of 387 mL/min was measured. After removal of exposition, flow in the LRV dropped to 51 mL/min. The positional compression was treated with a reinforced vascular PolyTetraFluoroEthylene (PTFE) prosthesis placed around the LRV.Discussion: Besides some reports on external stenting of the renal vein in the treatment of nutcracker syndrome (NS), this is the first report describing this technique outside this clinical entity.


The psychological typhoon eye effect during the COVID-19 outbreak in China: the role of coping efficacy and perceived threat.
The influence of COVID-19 on mental health problems has received considerable attention. However, only a few studies have examined the relationship between exposure to COVID-19 and mental health problems, and no empirical study has tested the mechanisms between them. We conducted a survey in 31 provinces of China during 3-13 March 2020 to test the effect of the exposure level on mental health problems. Our sample comprised 2987 participants who reported their perceived threat, coping efficacy, mental health problems and other demographic variables. Multiple mediators path analysis was used in the data analysis. The results showed that the level of exposure to COVID-19 in China was negatively associated with mental health problems, which confirmed the "Psychological Typhoon Eye" effect. Further analyses indicated that both perceived threat and coping efficacy partially mediated the relationship between them. However, coping efficacy explained the "Psychological Typhoon Eye" effect. Perceived threat mediated the positive relationship between exposure level and mental health problems. This study detected the psychological typhoon eye effect and demonstrated the mediating role of coping efficacy and perceived threat between exposure to COVID-19 and mental health problems. Our findings suggest that policy makers and psychological workers should provide enough psychological services to low-risk areas as the high-risk areas. An important means of alleviating mental health problems is to improve coping efficacy.


Aloe vera increases collagen fibres in extracellular matrix and mRNA expression of peroxiredoxin-6 in bovine ovarian cortical tissues cultured in vitro.
In vitro culture of ovarian tissue containing primordial follicles is an important tool to study the initiation of follicular populations and to develop efficient culture systems to support in vitro follicle growth. Considering that in vitro culture favours oxidative stress, it is very important to supplement culture medium with antioxidant substances such as Aloe vera extract. This study aims to evaluate the effects of different concentrations of Aloe vera on the distribution of collagen fibres in the extracellular matrix, follicular activation, development and survival in bovine ovarian cortical tissues cultured in vitro, as well as on expression of mRNAs for antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxiredoxin 6 (PRDX6) and glutathione peroxidase 1 (GPX1)]. To this end, ovarian cortical tissues were cultured for 6 days in α-MEM alone or supplemented with different concentrations of Aloe vera extract (1.0, 5.0, 10.0 or 50.0%). After culture, fragments were fixed and processed histologically to evaluate follicular morphology and activation, as well as the extracellular matrix by staining with picrosirius red. The levels of mRNA for SOD, CAT, PRDX6 and GPX1 in cultured ovarian tissues were evaluated by real-time polymerase chain reaction (PCR). Ovarian tissues cultured with 10.0 or 50.0% Aloe vera had higher percentages of collagen fibres than tissues cultured in control medium. A significant increase in developing follicles was observed in ovarian tissues cultured in α-MEM alone or supplemented with 10% Aloe vera when compared with fresh control or tissues cultured with 1.0% Aloe vera. Presence of Aloe vera did not influence the percentage of morphologically normal follicles when compared with control medium. Ovarian tissues cultured with 50.0% Aloe vera had higher percentages of morphologically normal follicles than those cultured with 10.0% Aloe vera. Furthermore, 10% Aloe vera significantly increased mRNA levels for PRDX6. In conclusion, 10.0% Aloe vera improves extracellular matrix distribution in cultured tissues and increases the expression of mRNA for PRDX6 after 6 days in vitro.


Minocycline as adjunctive treatment for major depressive disorder: Pooled data from two randomized controlled trials.
Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery-Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery-Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms - differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen's D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 - anxiety severity - differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen's D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status - differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen's D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.


Optimal Dietary and Plasma Magnesium Statuses Depend on Dietary Quality for a Reduction in the Risk of All-Cause Mortality in Older Adults.
The association between dietary or plasma magnesium (Mg) with diabetes incidence and with mortality in free-living elderly was investigated. A total of 1400 participants from the Taiwanese Nutrition Survey, aged ≥ 65 years, and diabetes-free from the 1999-2000 were assessed. The dietary intake and plasma Mg concentration were obtained through 24h dietary recall and health examination at baseline. Participants were classified by quartiles (Q) of dietary Mg or by the plasma Mg normal range (0.75-0.95 mmol/L). Dietary diversity score (DDS, range 1-6) represented the dietary quality. During 8 and 10 years, 231 incident diabetes cases and 475 deaths were identified. Cox's proportional-hazards regression was used to evaluate the association between Mg and health outcomes. The hazard ratios (95% confidence interval) for death in Q2 and Q3 of Mg intakes with DDS > 4 were 0.57 (0.44-0.74) and 0.59 (0.39-0.88), respectively, compared with the lowest intake and DDS ≤ 4 participants. Participants with normal and high plasma Mg in conjunction with high DDS had relative risks of 0.58 (0.37-0.89) and 0.46 (0.25-0.85) in mortality compared with low plasma Mg and lower DDS. Optimal dietary Mg intake and plasma Mg depend on dietary quality to reduce the mortality risk in older adults.


Large Fluorescence Enhancements of Fluorophore Ensembles with Multilayer Plasmonic Substrates: Comparison of Theory and Experimental Results.
Multilayer substrates consisting of a glass slide, silver mirror, silica layer, and silver nanoparticles were fabricated using magnetron sputtering. This new geometry of substrates with backplane mirror and dielectric photonic cavity produced large average fluorescence enhancements up to 190-fold. Fluorescence enhancements of five fluorescent probes were measured over the broad spectral range from 470 to 800 nm. Fluorescent probes were streptavidin conjugates attached to the substrate surface through a layer of biotinylated bovine serum albumin. The protein layers represent a common surface modification for surface-based bioassays such as immunoassays or molecular diagnostic assays. We found that optimal enhancement is dependent on the thickness of the dielectric layer separating the silver mirror and the silver nanoparticles and on the spectral range. We performed numerical calculations for enhancement in both the excitation and emission using finite element method (FEM) the results of which were in qualitative agreement with the experimental results. The described method for fabrication multilayered substrates and the results obtained with protein layers demonstrate great potential for the design of simple and ultrasensitive fluorometric bioassays with large optical amplifications compared to the standard approaches of enzyme-based bioassays with dielectric surfaces.


Substance Use in Adolescents and Young Adults With Inflammatory Bowel Diseases: An Exploratory Cluster Analysis.
Adolescents and young adults (AYAs) with chronic illnesses use substances at similar, if not greater, rates compared to healthy peers. The present study aimed to examine rates and patterns of tobacco use, marijuana use, and binge drinking in AYAs with inflammatory bowel diseases. We expected that substance use would be associated with poorer physical health, psychosocial functioning, and disease management. One hundred thirty-two AYAs completed a single set of surveys assessing demographics, disease activity, healthcare utilization, health-related quality of life (HRQoL), inflammatory bowel disease-specific self-efficacy, adherence barriers, disease management skills, and substance use in the last 30 days (eg, tobacco use, marijuana use, binge drinking). Exploratory cluster analyses, followed by chi-square tests and analyses of variance examined patterns of substance use and correlates of cluster membership. Four patterns emerged from the sample: Global Users (n = 17), Marijuana Users Engaging in Binge Drinking (n = 18), Exclusive Binge Drinkers (n = 21), and Global Abstainers (n = 76). Groups differed by age, gender, disease activity, healthcare utilization, HRQoL, self-efficacy, and adherence barriers with medium and large effect sizes (P < .05). Older age, male gender, active disease, at least 1 hospitalization in the past year, low self-efficacy, low HRQoL, and high adherence barriers were significantly more likely for those reporting multisubstance use. In addition, all those reporting both marijuana use and binge drinking also reported tobacco use. Future research ought to examine these associations longitudinally and throughout the transition to adult care.


Simple helium cryostat for Raman spectroscopy.
We describe a simple and inexpensive flowing gas helium cryostat which efficiently cools the surface of a sample and eliminates the need for good thermal contact between the sample and a substrate.


Oesophageal disorders: future developments.
Elicitation of the characteristic symptom patterns remains the primary approach to the diagnosis of gastro-oesophageal reflux disease, and this may be enhanced by developments in the use of high-resolution endoscopy and oesophageal biopsy. For future therapy, proton pump inhibitors and anti-reflux surgery may compete with reversible acid pump blockers, reflux inhibitor drugs and diverse luminally delivered physical anti-reflux therapies. Short-segment Barrett's oesophagus is known to be highly prevalent, but its impact on the risk of adenocarcinoma remains poorly defined. Biomarkers for Barrett's oesophagus have been proposed to aid in the stratification of cancer risk, and cytology may assume more importance in the future. Endoscopic surveillance for Barrett's oesophagus is widely practised, but more data are needed to demonstrate cost-effectiveness and a positive impact on mortality. Animal and limited human studies suggest that chemoprevention may become an important strategy in reducing the risk of adenocarcinoma. The ablation of Barrett's epithelium results in a reversal of Barrett's epithelium, albeit with an uncertain long-term outcome.


A Message from a Narrowed Internal Auditory Canal in a Patient with a Hyperpneumatized Petrous Bone.
Hyperpneumatization of the temporal bone (HPTB) is a rare finding, and its clinical impact is poorly described in literature. We report the case of a 34-year-old woman with no previous otologic condition, complaining of paroxysmal vertigo and right pulsatile tinnitus shortly after a first scuba diving session. Clinical neurotologic assessment found a right vestibular impairment. Cranial tomodensitometry showed a bilateral hyperpneumatization of the petrosal air cell system. Brain magnetic resonance imaging to rule out any retrocochlear pathology was normal, although the cochleo-vestibular nerve (CVN) appeared to be over lengthened in a narrowed internal auditory canal (IAC), especially on the right-hand side. Pain was alleviated by administration of a low-dose anti-epileptic drug. The clinical, neurological, and radiological findings evoked a right vestibulopathy generated by a limited compression of the CVN; HPTB appeared to contribute to the narrowing of the IAC, especially on the right-hand side.


The ecological validity of the Uniform Data Set 3.0 neuropsychological battery in individuals with mild cognitive impairment and dementia.
Objective: Ecological validity refers to the ability of neuropsychological measures to predict real world performance. Questions remain as to the ecological validity of commonly used measures, particularly regarding their relationships to global versus specific activities of daily living among those with neurodegenerative disease. We explored these issues through the lens of the Uniform Data Set 3.0 Neuropsychological battery (UDS3NB) in individuals with mild cognitive impairment and dementia. Method: UDS3NB and informant rated Functional Activities Questionnaire scales were evaluated from 2,253 individuals with mild cognitive impairment and dementia. Ordinal regression equations were used to explore the relationships of demographic and cognitive variables with overall and specific instrumental activities of daily living. Results: Delayed recall for visual and verbal material, and performance on trail making tests were consistent predictors of global and specific functions. Specific skills (i.e. naming or figure copy) showed differential relationships with specific activities, while phonemic fluency was not related to any particular activity. Conclusions: Measures in the UDS3NB predicted activities of daily living in individuals with MCI and dementia, providing initial support for the ecological validity of these tests. Specifically, measures that tap core deficits of Alzheimer's disease, such as delayed recall and sequencing/shifting, are consistent predictors of performance in daily tasks.


FAM122A, a new endogenous inhibitor of protein phosphatase 2A.
The regulation of the ubiquitously expressed protein phosphatase 2A (PP2A) is essential for various cellular functions such as cell proliferation, transformation, and fate determination. In this study, we demonstrate that the highly conserved protein in mammals, designated FAM122A, directly interacts with PP2A-Aα and B55α rather than B56α subunits, and inhibits the phosphatase activity of PP2A-Aα/B55α/Cα complex. Further, FAM122A potentiates the degradation of catalytic subunit PP2A-Cα with the increased poly-ubiquitination. In agreement, FAM122A silencing inhibits while its overexpression enhances cell growth and colony-forming ability. Collectively, we identify FAM122A as a new endogenous PP2A inhibitor and its physiological and pathophysiological significances warrant to be further investigated.


Transformation of Metal-Organic Frameworks into Stable Organic Frameworks with Inherited Skeletons and Catalytic Properties.
Metal-organic frameworks (MOFs) are an emerging class of porous materials with attractive properties, however, their practical applications are heavily hindered by their fragile nature. We report herein an effective strategy to transform fragile coordination bonds in MOFs into stable covalent organic bonds under mild annealing decarboxylative coupling reaction conditions, which results in highly stable organic framework materials. This strategy successfully endows intrinsic framework skeletons, porosity and properties of the parent MOFs in the daughter organic framework materials, which exhibit excellent chemical stability under harsh catalytic conditions. Therefore, this work opens a new avenue to synthesize stable organic framework materials derived from MOFs for applications in different fields.