Psychological interventions for acute pain after open heart surgery.
This is an update of a Cochrane review previously published in 2014. Acute postoperative pain is one of the most disturbing complaints in open heart surgery, and is associated with a risk of negative consequences. Several trials investigated the effects of psychological interventions to reduce acute postoperative pain and improve the course of physical and psychological recovery of participants undergoing open heart surgery. To compare the efficacy of psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention control in adults undergoing open heart surgery for pain, pain medication, psychological distress, mobility, and time to extubation. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and PsycINFO for eligible studies up to February 2017. We used the 'related articles' and 'cited by' options of eligible studies to identify additional relevant studies. We checked lists of references of relevant articles and previous reviews. We searched the ProQuest Dissertations and Theses Full Text Database, ClinicalTrials and the WHO International Clinical Trials Registry Platform to identify any unpublished material or ongoing trials. We also contacted the authors of primary studies to identify any unpublished material. In addition, we wrote to all leading heart centres in Germany, Switzerland, and Austria to check whether they were aware of any ongoing trials. Randomised controlled trials comparing psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery. Two review authors (SZ and SK) independently assessed trials for eligibility, estimated the risk of bias and extracted all data. We calculated effect sizes for each comparison (Hedges' g) and meta-analysed data using a random-effects model. We assessed the evidence using GRADE and created 'Summary of findings' tables. We added six studies to this update. Overall, we included 23 studies (2669 participants).For the majority of outcomes (two-thirds), we could not perform a meta-analysis since outcomes were not measured, or data were provided by one trial only.No study reported data on the number of participants with pain intensity reduction of at least 50% from baseline. Only one study reported data on the number of participants below 30/100 mm on the Visual Analogue Scale (VAS) in pain intensity (very low-quality evidence). Psychological interventions did not reduce pain intensity in the short-term interval (g 0.39, 95% CI -0.18 to 0.96, 2 studies, 104 participants, low-quality evidence), medium-term interval (g -0.02, 95% CI -0.24 to 0.20, 4 studies, 413 participants, moderate-quality evidence) or in the long-term interval (g 0.05, 95% CI -0.20 to 0.30, 2 studies, 200 participants, moderate-quality evidence).No study reported data on median time to re-medication or on number of participants re-medicated. Only two studies provided data on postoperative analgesic use in the short-term interval, showing that psychological interventions did not reduce the use of analgesic medication (g 1.18, 95% CI -2.03 to 4.39, 2 studies, 104 participants, low-quality evidence). Studies revealed that psychological interventions reduced mental distress in the medium-term (g 0.37, 95% CI 0.13 to 0.60, 13 studies, 1388 participants, moderate-quality evidence) and likewise in the long-term interval (g 0.32, 95% CI 0.10 to 0.53, 14 studies, 1586 participants, moderate-quality evidence). Psychological interventions did not improve mobility in the medium-term interval (g 0.23, 95% CI -0.22 to 0.67, 3 studies, 444 participants, low-quality evidence), nor in the long-term interval (g 0.09, 95% CI -0.10 to 0.28, 4 studies, 458 participants, moderate-quality evidence). Only two studies reported data on time to extubation, indicating that psychological interventions reduced the time to extubation (g 0.56, 95% CI 0.08 to 1.03, 2 studies, 154 participants, low-quality evidence).Overall, the very low to moderate quality of the body of evidence on the efficacy of psychological interventions for acute pain after open heart surgery cannot be regarded as sufficient to draw robust conclusions.Most 'Risk of bias' assessments were low or unclear. We judged selection bias (random sequence generation) and attrition bias to be mostly low risk for included studies. However, we judged the risk of selection bias (allocation concealment), performance bias, detection bias and reporting bias to be mostly unclear. In line with the conclusions of our previous review, there is a lack of evidence to support or refute psychological interventions in order to reduce postoperative pain in participants undergoing open heart surgery. We found moderate-quality evidence that psychological interventions reduced mental distress in participants undergoing open heart surgery. Given the small numbers of studies, it is not possible to draw robust conclusions on the efficacy of psychological interventions on outcomes such as analgesic use, mobility, and time to extubation respectively on adverse events or harms of psychological interventions.


[The study of 80 Hz auditory steady-state evoked potentials in patients with auditory neuropathy].
To investigate the character of 80 Hz auditory steady-state evoked potentials in auditory neuropathy (AN) patients and the correlation between it and ABR. The 80 Hz auditory steady-state evoked potentials and ABR to 95 dBnHL (1000 Hz) tone-pip stimuli were recorded from the scalp in patients with AN and normal subjects. The difference of the waveforms between AN ears and normal ears was compared. In 85.4% AN ears the 80 Hz auditory steady-state evoked potentials and ABR were simultaneously present. Their amplitudes were low or extremely low. The I and III waves of ABR were absent. The 80 Hz auditory steady-state evoked potentials and ABR were simultaneously absent, in 14.6% AN ears, but were present in all normal ears. The 80 Hz auditory steady-state evoked potentials and the V wave of ABR may come from the same brainstem sources.


A comparative study on the complications of conventional and end-to-side inserting pancreatojejunostomy after pancreaticoduodenectomy.
Pancreatico-digestive anastomosis is important in ensuring the safety of pancreaticoduodenectomy. This study compared the postoperative complications of a newly developed method of inserting end-to-side pancreaticojejunostomy with the conventional pancreaticojejunostomy after pancreaticoduodenectomy. From April 2012 to December 2015, 108 consecutive patients underwent pancreaticoduodenectomy at Kumamoto University Hospital. A modified child's reconstruction was performed with the inserting or conventional pancreaticojejunostomy. The clinical course and the incidence of postoperative complications were retrospectively evaluated. Five patients were excluded, four who underwent hepato-pancreatoduodenectomy and one who did not require pancreaticojejunostomy because of an atrophic pancreatic remnant. Of the 103 patients that were included in the analysis, 41 and 62 underwent surgery with the inserting and conventional methods, respectively. The incidence of postoperative Clavien-Dindo grade > II complications was similar in the two groups [36.6 % (15/41) vs 27.4 % (17/62)]. However, the rates of grade C postoperative pancreatic fistula [7.3 % (3/41) vs 0 % (0/62) P = 0.030] and re-operation for postoperative complications [14.6 % (6/41) vs 3.2 % (2/62), P = 0.034] were significantly higher in the inserting group than in the conventional group. There were no in-hospital deaths in either group. The conventional pancreaticojejunostomy is safer than the end-to-side inserting pancreaticojejunostomy, as the latter is associated with a risk of severe complications. Improvements in pancreatico-digestive anastomosis techniques are required.


Gender and health: a study of older unlike-sex twins.
The primary goal of this study was to assess gender differences in various measures of health conditions, symptoms, and self-rated health among older persons by comparing brothers and sisters in a sample of unlike-sex twins. All living pairs of unlike-sex twins born between 1906 and 1925 were identified through the Swedish Twin Registry and sent surveys assessing health and other factors. This population-based sample consisted of 605 twin pairs. Paired sample t tests were used to analyze gender differences in health-related measures, including a three-level measure of health problems based on physicians' ratings. Women had more total health conditions, not life-threatening health conditions, somewhat life-threatening cardiovascular conditions, and physical and psychological symptoms. Men had more very life-threatening health conditions and cardiovascular conditions. No gender differences were found in somewhat life-threatening health conditions, total cardiovascular conditions, or self-rated health. Important gender differences and similarities in health were found using an unlike-sex twin design that reduced variability due to background characteristics. This design also minimized problems caused by gender differences in survival. Research on gender and health in older persons requires more detailed approaches to address the complexity of this topic.


Laboratory Evaluation of Natural and Synthetic Aromatic Compounds as Potential Attractants for Male Mediterranean fruit Fly, Ceratitis capitata.
Ceratitis capitata, the Mediterranean fruit fly, is one of the most serious agricultural pests worldwide responsible for significant reduction in fruit and vegetable yields. Eradication is expensive and often not feasible. Current control methods include the application of conventional insecticides, leading to pesticide resistance and unwanted environmental effects. The aim of this study was to identify potential new attractants for incorporation into more environmentally sound management programs for C. capitata. In initial binary choice bioassays against control, a series of naturally occurring plant and fungal aromatic compounds and their related analogs were screened, identifying phenyllactic acid (7), estragole (24), o-eugenol (21), and 2-allylphenol (23) as promising attractants for male C. capitata. Subsequent binary choice tests evaluated five semisynthetic derivatives prepared from 2-allylphenol, but none of these were as attractive as 2-allylphenol. In binary choice bioassays with the four most attractive compounds, males were more attracted to o-eugenol (21) than to estragole (24), 2-allylphenol (23), or phenyllactic acid (7). In addition, electroantennography (EAG) was used to quantify antennal olfactory responses to the individual compounds (1-29), and the strongest EAG responses were elicited by 1-allyl-4-(trifluoromethyl)benzene (11), estragole (24), 4-allyltoluene (14), trans-anethole (9), o-eugenol (21), and 2-allylphenol (23). The compounds evaluated in the current investigation provide insight into chemical structure-function relationships and help direct future efforts in the development of improved attractants for the detection and control of invasive C. capitata.


HIS/RIS/PACS integration: getting to the gold standard.
The technology for acquiring, storing, retrieving, displaying, and distributing images has advanced dramatically in recent years. The push is toward enterprise-wide image management solutions, where digital images from radiology, cardiology, and other "ologies" are seamlessly linked with information from clinical information systems and other databases, and they are accessed seamlessly from a single point of end-user interaction. The "gold standard" of system integration would provide the platform for improved workflow, patient throughput and patient safety, as well as decreased cost. Unfortunately, the gold standard remains elusive in most healthcare environments, even those with new systems. One of the earliest issues that plagued the progress of hospital information system/radiology information systems/picture archiving and communication systems (HIS/RIS/PACS) integration was a matter of language between Health Level-7 (HL7) and DICOM. This barrier was solved by the broker--a software and hardware device that accepts HL7 messages from the RIS then translates, or maps, the data to produce DICOM messages for transmission to the PACS. Technologist workflow requires patient and exam information from the RIS to flow to the modality. The broker provides support for this by taking advantage of the DICOM Modality Worklist (DMWL). Two primary problems are inherent in most brokered configurations. Workflow is driven by paper, and RIS information flows in 1 direction only, which leads to duplicative databases. Overcoming the limitations of HIS/RIS/PACS connectivity requires industry accepted communication protocols/rules. To facilitate this, the Integrating the Health Care Enterprise (IHE) initiative was developed. The goal of IHE is to provide end-users improved access to critical patient and clinical information across all systems within the healthcare delivery network. While the IHE initiative began to facilitate more efficient, predictable, and functional integration between disparate systems, vendors still had technology hurdles to overcome. System integration continues to be significantly hampered, not by technology limitations, but instead by business and political issues. In response to these challenges, several vendors have begun to offer consolidated RIS/PACS solutions and/or HIS/RIS/PACS solutions. Consequently, the prospect of the gold standard appears to be on the horizon. Single vendor consolidated systems are not, however, feasible for deployment in many healthcare organizations, and they are not necessarily the panacea.


Clinical and ultrasound parameters in prediction of excessive hemorrhage during management of cesarean scar pregnancy.
During the management of cesarean scar pregnancy, gestational mass size >6 cm, uterine scar thickness <0.2 cm, peak systolic velocity >70 cm/s, and resistance index <0.35 are independent risk factors for excessive hemorrhage. The objective of this study was to investigate risk factors associated with excessive hemorrhage during the management of cesarean scar pregnancy (CSP). A retrospective case-control study was conducted, including 40 patients who experienced excessive bleeding and 80 controls without severe hemorrhage. Six parameters (two clinical and four ultrasound parameters) potentially related to excessive hemorrhage were analyzed. Single-variable statistical analyses showed that the case group had higher gestational age (74.1±23.6 days), higher pretreatment serum β-human chorionic gonadotropin (HCG) level (46,201±32,294 mIU/mL), larger gestational mass size (6.5±2.2 cm), thinner uterine scar thickness (0.17±0.12 cm), and richer peritrophoblastic perfusion (peak systolic velocity [PSV] 72.8±33.7 cm/s, resistance index [RI] 0.35±0.12), showing statistical significance compared with the control group. Further multivariable logistic regression analysis of the association between each of the risk factors and hemorrhage confirmed that increased gestational mass size and PSV were risk factors for hemorrhage (odds ratio [OR] 3.624, 95% confidence interval [CI] [1.179-11.138] and OR 1.062, 95% CI [1.007-1.121]) and increased uterine scar thickness and RI were protective factors against hemorrhage (OR 0.181, 95% CI [0.034-0.957] and OR 0.851, 95% CI [0.729-0.994]); however, there was no statistical significance between the two clinical parameters. Gestational mass size >6 cm, uterine scar thickness <0.2 cm, PSV >70 cm/s, and RI <0.35 are independent risk factors for excessive hemorrhage during the management of CSP.


Clinical and radiological outcomes after reverse shoulder arthroplasty in patients with failed deltoid or latissimus dorsi transfers. A review of ten cases.
The purpose of this study was to report clinical and radiological results of reverse shoulder arthroplasty (RSA) after failure of either a deltoid and/or a latissimus dorsi transfer. Between 2001 and 2011, ten patients (average age, 61 years) underwent primary RSA after a failed tendon transfer for irreparable postero-superior rotator cuff tear (five deltoid muscle transfers, four latissimus dorsi transfers and one both). Average follow-up was 48 months. Outcome measures included pain, range of motion and postoperative Constant-Murley score. Pain score improved significantly from a mean 8.3 to a mean 0.3. Mean shoulder elevation improved from 66 to 134°, and absolute Constant-Murley scores increased from 25.8 to 62.8 The mean improvement in external rotation was limited to 7.5°. Subjectively, six patients rated the result as much better and three rated it as better than before surgery. Failure of the tendon transfer with deterioration of the functional outcomes can be salvaged with a RSA with no impact on the expected outcome.


[Heavy metals in the soil of allotment gardens in industrialized post-flooded areas in the Opole region]].
The results of studies concerning the levels of heavy metals (chromium, zinc, cadmium, nickel and lead) in soils of allotment gardens in post-flooded industrialized areas of the Opole Region, conducted during the period 2000-2001 was presented. Spectrophotometric method was applied for the determination of heavy metals in soils. The results of the study show that the levels of chromium, zinc and cadmium in the soils examined are constantly decreasing. However, an opposite phenomenon is observed with respect to copper and lead, where an increase was noted in the number of samples exceeding the maximum allowable, concentration of these metals during the second year of the study. This suggests that there exist local sources of contamination with the above-mentioned elements.


Dopamine receptors mediating inhibition of the cyclic adenosine monophosphate generating system in the rat renal cortex.
1. In vitro addition of dopamine (DA) or of DA-1 receptor agonists increases 3'- 5'-cyclic adenosine monophosphate (cAMP) levels through the stimulation of DA-1 receptors. 2. Although receptor binding studies suggest the existence of DA-2 receptors in the renal cortex, the presence of DA receptors negatively coupled to cAMP generation (DA-2 effect) has not been so far characterized. 3. In this study we have shown that the addition of DA plus the selective DA-1 receptor antagonist SCH 23390 to membrane fractions of rat renal cortex decreased cAMP concentration below basal levels. 4. DA-2 receptor responses were also elicited with the DA-2 receptor agonists bromocriptine and quinpirole in the absence of SCH 23390. These inhibitory effects on cAMP generation were abolished by the DA-2 receptor antagonist 1-sulpiride. 5. The above findings are indicative of the existence in the rat renal cortex of DA-2 receptors showing an effect upon cAMP generation similar to that found in the brain and in several peripheral tissues.


Halide removal from waters by silver nanoparticles and hydrogen peroxide.
The objective of this study was to remove halides from waters by silver nanoparticles (AgNPs) and hydrogen peroxide (H2O2). The experimental parameters were optimized and the mechanism involved was also determined. The AgNP/H2O2 process proved efficacious for bromide and chloride removal from water through the selective precipitation of AgCl and AgBr on the AgNP surface. The optimal AgNP and H2O2 concentrations to be added to the solution were determined for the halide concentrations under study. The removal of Cl- and Br- anions was more effective at basic pH, reaching values of up to 100% for both ions. The formation of OH, O2-, radicals was detected during the oxidation of Ag(0) into Ag(I), determining the reaction mechanism as a function of solution pH. Moreover, the results obtained show that: i) the efficacy of the oxidation of Ag(0) into Ag(I) is higher at pH11, ii) AgNPs can be generated by the O2- radical formation, and iii) the presence of NaCl and dissolved organic matter (tannic acid [TAN]) on the solution matrix reduces the efficacy of bromide removal from the medium due to: i) precipitation of AgCl on the AgNP surface, and ii) the radical scavenger capacity of TAN. AgNPs exhausted can be regenerated by using UV or solar light, and toxicity test results show that AgNPs inhibit luminescence of Vibrio fischeri bacteria.


Ammonia recycled percolation as a complementary pretreatment to the dilute-acid process.
A two-stage dilute-acid percolation (DA) was investigated as a pretreatment method for switchgrass. With use of extremely low acid (0.078 wt% sulfuric acid) under moderate temperature (145-170 degrees C), hemicellulose in switchgrass was completely solubilized showing no sugar decomposition. The treated switchgrass contained about 70% glucan and 30% lignin. The high lignin content in the treated feedstock raises a concern that it may cause a high enzyme consumption because of irreversible adsorption of cellulase enzymes to lignin. This problem may be amplified in the SSF operation since it is usually run in fed-batch mode and the residual lignin is accumulated. The DA pretreatment was, therefore, combined with the ammonia recycled percolation (ARP) process that has been proven to be effective in delignification. The combined pretreatment essentially fractionated the switchgrass into three major components. The treated feedstock contained about 90% glucan and 10% lignin. The digestibility of these samples was consistently higher that that of DA treated samples. Further study on the interaction of cellulase with xylan and that with lignin has shown that the enzymatic hydrolysis of cellulose is inhibited by lignin as well as xylan. The external xylan was found to be a noncompetitive inhibitor to cellulose hydrolysis. The cellulase used in this study was proven to have the xylanase activity.


Take away their hammer: logical and ethical problems in Range and Cotton's "Reports of assent and permission in research with children: illustrations and suggestions.
Range and Cotton (1995) showed that many of the articles reviewed in their study did not include a line specifying institutional review board-approved procurement of informed parental permission and child assent for child research. Range and Cotton stated that the absence of the line suggests a lack of sensitivity to permission/assent issues, implied that many authors of the articles did not obtain permission/assent, and said those who did but did not report it were camouflaging those who did not. In this article, the logic of these points is refuted, the ethics of the Range and Cotton study are questioned, and its potential divisiveness is lamented.


Overexpression of a cell wall enzyme reduces xyloglucan depolymerization and softening of transgenic tomato fruits.
Xyloglucan xyloglucosyltransferase/endohydrolase (XTHs: EC 18.104.22.168 and/or EC 184.108.40.206) has been proposed to have a dual role integrating newly secreted xyloglucan chains into an existing wall-bound xyloglucan and restructuring existing cell wall material by catalyzing transglucosylation between previously wall bound xyloglucan molecules. In this work we generated transgenic tomatoes with altered levels of an XTH gene. These transgenic fruits showed significant overexpression of the XTH proteins in comparison with the wild type. Specific XET activity was approximately 4.33 fold higher in the transgenic fruits compared with the wild type fruits, although in both cases the activity decreased during fruit development. Cell wall hemicelluloses extracted with 24% KOH showed a depolymerization of total sugar and xyloglucan during ripening, although this depolymerization was much lower in the transgenic than in the wild type tomatoes. These results suggest that the increased XET activity in the transgenic plants was responsible for the lower xyloglucan depolymerization. Fruit softening, during ripening, was lower in the transgenic tomatoes, indicating that the xyloglucan structure is related with the softening mechanism and that XET is one of the enzymes involved in the process. We suggest that the role of XET during fruit growth and ripening could be related to the maintenance of the structural integrity of the cell wall and the decrease in activity during ripening might contribute to the fruit softening.


Congestive heart failure: how to evaluate efficacy of treatment.
Vasodilators are widely used in the therapy of congestive heart failure. Different mechanisms responsible for a failure of vasodilator therapy are discussed. Tolerance and/or diminished reabsorption or a less than optimal choice of the drug may be responsible for the lack of acute response. In addition, counter-regulation, mainly by the sympathetic nervous system, may decrease the drug effect. Furthermore, the initial beneficial effect of each vasodilator can be diminished with long-term therapy. Based on a clinical assessment and on invasive and noninvasive techniques a proposal is made as to how to treat an individual patient efficaciously.


Production of a Novel Superoxide Dismutase by Escherichia coli and Pichia pastoris and Analysis of the Thermal Stability of the Enzyme.
Previously, a new copper-zinc SOD (CuZnSOD) isolated from chestnut rose (Rosa roxburghii) with good stability was described. In this study, the biosynthetic approach was used to create recombinant CuZnSOD. RACE PCR was also used to amplify the full-length CuZnSOD gene from chestnut rose, and the ORF segment was expressed in E. coli BL21 and P. pastoris GS115. For characterization, the enzyme was isolated in two steps in E. coli and one step in P. pastoris. The biochemical properties of the two recombinant enzymes were similar, and their optimal reaction pH and temperature were 6.0 and 50°C, respectively. According to molecular dynamics simulation, the CuZnSOD showed high stability from 70 to 90°C, and eight amino acids are important for enzyme thermal stability at high temperatures. This study set the stage for industrial manufacture by filling gaps in the link between conformational changes and the thermal stability of the new CuZnSOD.


Phosphonothioate-Based Hydrogen Sulfide Releasing Reagents: Chemistry and Biological Applications.
Hydrogen sulfide (H2S) is a newly recognized gasotransmitter. Studies have demonstrated that the production of endogenous H2S and the exogenous administration of H2S can regulate many physiological and/or pathological processes. Therefore, H2S releasing agents (also known as H2S donors) are important research tools in advancing our understanding of the biology and clinical potential of H2S. Among currently available donors, GYY4137 is probably the most well-known and has been used in many studies in the past 10 years. Recently, a number of GYY4137 derivatives (e.g., phosphonothioate-based compounds) have been developed as H2S donors. In this review, we summarize the development and application of these donors, which include Lawesson's reagent, substituted phosphorodithioates, cyclic phosphorane analogs, and pH-controlled phosphonamidothioates (JK donors). These donors have advantages such as good water-solubility, slow and controllable H2S release capability, and a variety of reported biological activities. However, it should be noted that the detailed H2S release profiles and byproducts under real biological systems are still unclear for many of these donors. Only after we figure out these unknowns we will see better applications of these donors in H2S research and therapy.


Modifying phase I methodology to facilitate enrolment of molecularly selected patients.
Over the last decade, the focus of anticancer drug development has shifted from empirical cytotoxic chemotherapy to mechanism-defined molecularly targeted agents, for which appropriate patient selection at the earliest possible point in drug development is rational and critical to success. With the recently legislated "breakthrough product" definition in the U.S., it may be possible to plan a single trial for registration purposes to confirm a major clinical effect observed in phase I. However, most phase I trial designs remain excessively conservative and are driven by criteria developed for cytotoxic agents with the goal of identifying a "maximum tolerable dose" with acceptable risks to patients. This focus on empiric "most dose with acceptable risk" may be misguided for mechanism-targeting new agents, and this could lead to unnecessary delays, increased costs and even higher risk of missing important signals of activity and benefit. There is a compelling need to modify phase I trial designs to facilitate enrichment in molecularly selected patients who are the most likely to harbour disease driven by the targeted pathway and to avoid unjustified exclusions based on obsolete criteria so that the right subset of patients can participate. After discussion of the main inconsistencies of current phase I designs, we propose a new strategy to facilitate the inclusion of molecularly selected patients, in order to accelerate and mitigate risks in drug development as well as to increase the chance of benefit among trial participants.


Serum amyloid beta protein in young and elderly depression: a pilot study.
Depression may increase the risk of developing Alzheimer's disease (AD). Recent large cohort studies have also shown that a low plasma amyloid beta (Abeta)-42 level combined with a high Abeta40 level increases the risk of developing AD, suggesting plasma Abeta42/40 ratio as useful for identifying risk of developing mild cognitive impairment and AD. Although several studies have examined Abeta levels in the peripheral blood of elderly individuals with depression, results have been inconsistent. Furthermore, no results have been described for younger depression. Serum Abeta40, Abeta42 level and Abeta40/42 ratio were evaluated using enzyme-linked immunosorbent assay in 60 patients with major depressive disorder (MDD) and 60 healthy controls. The results were analyzed in two age groups (young, <60 years; elderly, >or=60 years). Serum Abeta40 level was significantly higher in young MDD patients compared to young controls (P < 0.001), but it was not significantly deferent in the elderly group. Serum Abeta42 level did not differ significantly in both young and elderly groups. Abeta40/42 ratio was significantly higher in both young (P < 0.001) and elderly (P < 0.001) patients with MDD compared to controls. Serum Abeta40/42 ratio was significantly higher in MDD patients than in controls, and this difference was seen for both elderly and young subjects. This may suggest that even young subjects with MDD undergo pathological changes in the very early stage of amyloid deposition.


Ultrafast Miniature Robotic Swimmers with Upstream Motility.
With the development of materials science and micro-nano fabrication techniques, miniature soft robots at millimeter or submillimeter size can be manufactured and actuated remotely. The small-scaled robots have the unique capability to access hard-to-reach regions in the human body in a noninvasive manner. To date, it is still challenging for miniature robots to accurately move in the diverse and dynamic environments in the human body (e.g., in blood flow). To effectively locomote in the vascular system, miniature swimmers with upstream swimming capability are required. Herein, we design and fabricate a miniature robotic swimmer capable of performing ultrafast swimming in a fluidic environment. The maximum velocity of the swimmer in water is 30 cm/s, which is 60 body lengths. Moreover, in a tubular environment, the swimmer can still obtain a swimming velocity of 17 cm/s. The swimmer can also perform upstream swimming in a tubular environment with a velocity of 5 cm/s when the flow speed is 10 cm/s. The ultrasound-guided navigation of the swimmer in a phantom mimicking a blood vessel is also realized. This work gives insight into the design of agile undulatory milliswimmers for future biomedical applications.


Synthesis and evaluation of novel 8,6-fused bicyclic peptidomimetic compounds as interleukin-1beta converting enzyme inhibitors.
Two novel 8,6-fused bicyclic peptidomimetic ring systems were synthesized utilizing olefin metathesis as the key reaction for the formation of the eight-membered ring. Both peptidomimetic scaffolds were further elaborated into potent ICE inhibitors, with numerous compounds exhibiting caspase-1 IC(50)s less than 10nM.


Postexposure Recovery and Analysis of Biological Agent in a Simulated Biothreat Scenario Using Tandem Mass Spectrometry.
Some pathogens and toxins have the potential to be used as weapons of mass destruction and instigate population-based fear. Rapid, sensitive, and unambiguous identification of biothreat agents is of paramount importance for confirmation of the event and to mitigate the direct and indirect damages to public health and resources. Although there are several potential dissemination scenarios to describe an attack with a biological weapon, artificially generated bioaerosol is of the greatest concern from a bioterrorism or warfare perspective, potentially capable of causing mass destruction to a civilian or military population by inhalation of toxic bioaerosol. The present investigation proposes methodologies for recovery of biological agent followed by an off-site unambiguous detection using tandem mass spectrometry, in a postattack situation. We envisaged a biothreat scenario wherein the polydispersed bioaerosol is disseminated in bulk over any geographical setting. The larger particles (>5 μm in diameter) of bioaerosol settle and bind to various surfaces depending on the geographical setting. Recovery of agent was optimized from foliage, sand, and glass in a simulated biothreat scenario using bovine serum albumin (BSA). The recovered agents were shown to be amenable to detection by a downstream tandem MS analysis. Applicability of the proposed methodology was demonstrated in validation experiments for the recovery and detection of toxin and bacterial agents. The use of cleaner matrices (foliage, exposed smooth surfaces, sand) is recommended for retrospective verification of agent in a biothreat scenario.


[Prevalence of congenital malformations at birth in Chilean maternity hospitals].
The Latin American Collaborative Study of Congenital Malformations (ECLAMC) is an epidemiological surveillance system operating in 11 South American countries since 1969. To analyze the Congenital Malformation prevalence rate at birth from 2001 to 2010 in Chilean Hospitals participating in ECLAMC. To compare these rates with those of the period 1982-1994. Review of the ECLAMC database, which contains information about 282.568 newborns, 2.110 of them stillbirths (0.75%) from 13 Maternity hospitals. In the study period, 10.925 newborns had congenital malformations (3.9 %). Their frequency was lower in live newborns than stillbirths (3.8 and 15.3%, respectively). Compared with the 1982-1994 period, congenital malformation prevalence rates at birth were higher. They stabilized in approximately 4 %, from 1985 to 2010. The prevalence of some anomalies such as Down syndrome increased significantly. On the other hand, there was a reduction in the prevalence of spina bifida and anencephaly. Prevalence rates of congenital malformations at birth remained stable in the last 18 years in Chilean Hospitals participating in ECLAMC. However the prevalence of some malformations such as Down syndrome, Polydactyly, anotia-microtia, syndactyly and cleft palate have increased. The prevalence rates of spina bifida and anencephaly have decreased.


The rs2619566, rs10260404, and rs79609816 Polymorphisms Are Associated With Sporadic Amyotrophic Lateral Sclerosis in Individuals of Han Ancestry From Mainland China.
The pathogenesis of sporadic amyotrophic lateral sclerosis (sALS) remains unknown; however, recent research suggests that genetic factors may play an important role. This study aimed at investigating possible genetic risk factors for the pathogenesis of sALS. In our previous study, we conducted a genome-wide association study (GWAS) in 250 sALS patients and 250 control participants of Han ancestry from mainland China (HACM) and retrospectively analyzed the previously reported candidate loci related with sALS including our GWAS investigated results. In this study, twenty-seven candidate loci that were most likely associated with sALS were selected for further analysis in an independent case/control population of 239 sALS patients and 261 control subjects of HACM ethnicity using sequenom massARRAY methodology and DNA sequencing. We discovered that the polymorphism rs2619566 located within the contactin-4 (CNTN4) gene, rs10260404 in the dipeptidyl-peptidase 6 (DPP6) gene, and rs79609816 in the inositol polyphosphate-5-phosphatase B (INPP5B) gene were strongly associated with sALS in subjects of HACM ethnicity. Subjects harboring the minor C allele of rs2619566 and the minor T allele of rs79609816 exhibited an increased risk for sALS development, while carriers of the minor C allele of rs10260404 showed a decreased risk of sALS development compared to the subjects of other genotypes. The polymorphisms of rs2619566, rs10260404, and rs79609816 may change or affect the splicing, transcription, and translation of CNTN4, DPP6, and INPP5B genes and may play roles in the pathogenesis of sALS roles in the pathogenesis of sALS.


Visual Signals in the Mammalian Auditory System.
Coordination between different sensory systems is a necessary element of sensory processing. Where and how signals from different sense organs converge onto common neural circuitry have become topics of increasing interest in recent years. In this article, we focus specifically on visual-auditory interactions in areas of the mammalian brain that are commonly considered to be auditory in function. The auditory cortex and inferior colliculus are two key points of entry where visual signals reach the auditory pathway, and both contain visual- and/or eye movement-related signals in humans and other animals. The visual signals observed in these auditory structures reflect a mixture of visual modulation of auditory-evoked activity and visually driven responses that are selective for stimulus location or features. These key response attributes also appear in the classic visual pathway but may play a different role in the auditory pathway: to modify auditory rather than visual perception. Finally, while this review focuses on two particular areas of the auditory pathway where this question has been studied, robust descending as well as ascending connections within this pathway suggest that undiscovered visual signals may be present at other stages as well.


Metal contamination and infiltration into the soil at refuse dump sites in Awka, Nigeria.
Awka has been the site of increased human activities since it became a state capital in 1991. Because refuse dumps have hitherto been a disregarded environmental menace in Nigeria, the authors sought to find out how much of the current environmental metal pollutant load comes from refuse dumps. They investigated the metal contamination of the refuse dumps in Awka. The authors collected four soil samples (from the surface and from depths of 0.45 m, 0.90 m, and 1.35 m) from 5 dumpsites digested with nitric acid and perchloric acid, and they analyzed iron, sodium, arsenic, lead, magnesium, potassium, cobalt, zinc, nickel, copper, chromium, and cadmium by using an atomic absorption spectrophotometer. Sites A and C showed the highest levels of arsenic (2300 mg/kg) and lead (2467 mg/kg), respectively. Site D had highest level of both iron (72,200 mg/kg) and sodium (3561 mg/kg), whereas Site E had the lowest level of lead (572 mg/kg). The metal levels exceed the limits set forth by the US Environmental Protection Agency. This study suggests that the refuse dumps in Awka may increase the level of environmental heavy metals in Nigeria.


[The prevalence of high-risk HPV infection in pregnant women from Morelos, México].
Some studies suggest the possibility that the physiological process of pregnancy modifies certain characteristics of the mother, increasing the risk of both, infection and persistence of infection with HPV. This association, however, has not been firmly established. This study seeks to determine the prevalence of oncogenic HPV infecton in a sample of pregnant Mexican women and its possible risk factors. A cross-sectional study was conducted using a sample of 274 pregnant women sought first level of care services during the year 2000 at the antenatal clinic of the Mexican Institute of Social Security (IMSS) in Cuernavaca, Morelos, Mexico. Samples of vaginal cells were obtained through self-collected specimens, for the high-risk HPV DNA test using the Hybrid Capture 2 test (HC2). A structured questionnaire was administered regarding sociodemographic, gynecologic, obstetric and sexual behavior characteristics. The mean age was 25.7 years. The average time of pregnancy when the study was conducted was 6 months. The principal risk factors associated with high-risk HPV infection were: ages between 20 and 29 (OR= 2.82; CI 95% 1.02-7.76)), age 30 and over (OR= 6.85,CI 95% 1.22-38.2); partners having sexual relations with other partners (OR= 2.05; CI 95% 1.2-3.7)); schooling less than 6 years (OR= 1.68 CI 95% 0.7-4.3); number of lifetime sexual partners > 2 (OR= 1.54 CI 95% 0.7-3.4); and current smoking (OR= 1.6 CI 95% 0.6-5.0). Our findings show a higher prevalence of high-risk HPV infection in pregnant women, more than double, that reported in studies of non-pregnant women. The associated risk factors are similar to those of the non-pregnant population. Follow-up in these women is recommended in order to evaluate the persistence or regression of the infection.


How Do Organic Vapors Swell Ultrathin Films of Polymer of Intrinsic Microporosity PIM-1?
Dynamic sorption of ethanol and toluene vapor into ultrathin supported films of polymer of intrinsic microporosity PIM-1 down to a thickness of 6 nm are studied with a combination of in situ spectroscopic ellipsometry and in situ X-ray reflectivity. Both ethanol and toluene significantly swell the PIM-1 matrix and, at the same time, induce persistent structural relaxations of the frozen-in glassy PIM-1 morphology. For ethanol below 20 nm, three effects were identified. First, the swelling magnitude at high vapor pressures is reduced by about 30% as compared to that of thicker films. Second, at low penetrant activities (below 0.3p/p0), films below 20 nm are able to absorb slightly more penetrant as compared with thicker films despite a similar swelling magnitude. Third, for the ultrathin films, the onset of the dynamic penetrant-induced glass transition Pg has been found to shift to higher values, indicating higher resistance to plasticization. All of these effects are consistent with a view where immobilization of the superglassy PIM-1 at the substrate surface leads to an arrested, even more rigid, and plasticization-resistant, yet still very open, microporous structure. PIM-1 in contact with the larger and more condensable toluene shows very complex, heterogeneous swelling dynamics, and two distinct penetrant-induced relaxation phenomena, probably associated with the film outer surface and the bulk, are detected. Following the direction of the penetrant's diffusion, the surface seems to plasticize earlier than the bulk, and the two relaxations remain well separated down to 6 nm film thickness, where they remarkably merge to form just a single relaxation.


Lactic acid bacteria: isolation-characterization approaches and industrial applications.
The current state-of-art research pertaining to lactic acid bacteria (LAB) calls for the screening and isolation of robust LAB strains to achieve holistic exploitation of LAB and their metabolites of marketable importance. Hence it is imperative to comprehend LAB sources, growth requisites, isolation and characterization strategies necessary for featured cataloging and appropriate culturing. This review comprehensively describes various growth media and biomasses used for supporting LAB sustenance, assay procedures needed for the isolation and characterization of LAB strains, and their application in diverse sectors. The various industrial patents and their summarized claims about novel LAB strains isolated and identified, methods and media (used for detection/screening, isolation, adaptation, culturing, preservation, growth improvement), the techniques and/or methodologies supporting LAB fermentation, and applications of produced industrial metabolites in various market scenarios are detailed.


Translation Initiation Factor eIF4E and eIFiso4E Are Both Required for Peanut stripe virus Infection in Peanut (Arachis hypogaea L.).
Peanut stripe virus (PStV) belongs to the genus Potyvirus and is the most important viral pathogen of cultivated peanut (Arachis hypogaea L.). The eukaryotic translation initiation factor, eIF4E, and its isoform, eIF(iso)4E, play key roles during virus infection in plants, particularly Potyvirus. In the present study, we cloned the eIF4E and eIF(iso)4E homologs in peanut and named these as PeaeIF4E and PeaeIF(iso)4E, respectively. Quantitative real-time PCR (qRT-PCR) analysis showed that these two genes were expressed during all growth periods and in all peanut organs, but were especially abundant in young leaves and roots. These also had similar expression levels. Yeast two-hybrid analysis showed that PStV multifunctional helper component proteinase (HC-Pro) and viral protein genome-linked (VPg) both interacted with PeaeIF4E and PeaeIF(iso)4E. Bimolecular fluorescence complementation assay showed that there was an interaction between HC-Pro and PeaeIF4E/PeaeIF(iso)4E in the cytoplasm and between VPg and PeaeIF4E/PeaeIF(iso)4E in the nucleus. Silencing either PeaeIF4E or PeaeIF(iso)4E using a virus-induced gene silencing system did not significantly affect PStV accumulation. However, silencing both PeaeIF4E and PeaeIF(iso)4E genes significantly weakened PStV accumulation. The findings of the present study suggest that PeaeIF4E and PeaeIF(iso)4E play important roles in the PStV infection cycle and may potentially contribute to PStV resistance.


Oocyte maturation is inhibited by adenosine in the presence of follicle-stimulating hormone.
Considerable evidence implicates cyclic 3', 5' adenosine monophosphate (AMP) in the maintenance of meiotic arrest of mammalian oocytes. Since this laboratory previously found that adenosine augmented follicle-stimulating hormone (FSH)-stimulated accumulation of cyclic AMP in oocyte-cumulus-complexes (OCC), in the present studies we investigated the possibility that adenosine inhibits maturation of oocytes. In rat OCC cultured in the presence of FSH, adenosine markedly inhibited oocyte maturation in a dose-dependent and biphasic manner. Maximum inhibition of oocyte maturation was seen with 1-30 microM adenosine in the presence of FSH, and half-maximal inhibition occurred with less than 0.3 microM adenosine. High levels of adenosine (100 microM) did not inhibit oocyte maturation in the presence of FSH. In the absence of FSH, adenosine showed little effect on oocyte maturation in the present studies, but increased the maximum inhibition of oocyte maturation produced by FSH approximately twofold. Like adenosine, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine 5'-monophosphate (AMP) also inhibited oocyte maturation; whereas adenine, guanosine, inosine, and hypoxanthine were inactive at equivalent levels. The metabolism-resistant adenosine analog (2-chloroadenosine) was as active an inhibitor as adenosine. Inhibition produced by the adenine nucleotides may have been direct or due to conversion to adenosine by extracellular nucleotidases. The concentration dependence and purine specificity for inhibition of oocyte maturation are characteristic of an adenosine receptor-mediated process, but direct evidence for such a mechanism was not shown. The effective concentration of adenosine for inhibition of oocyte maturation is within the range of reported levels of adenosine in biological tissues and fluids.(ABSTRACT TRUNCATED AT 250 WORDS)


Edoxaban treatment for pulmonary arterial thromboembolism associated with azygous vein aneurysm.
A 76-year-old woman, diagnosed 5 years previously with an asymptomatic mediastinal bronchogenic cyst, was referred to our department as the mass had grown slightly larger. Contrast-enhanced computed tomography and magnetic resonance imaging scans revealed an azygous vein aneurysm with a pulmonary arterial thromboembolism. The patient was treated with heparin for 5 days, and anticoagulation therapy with edoxaban was continued for 12 months. The thrombus resolved, and the aneurysm remained unchanged. An azygous vein aneurysm is a very rare condition that causes pulmonary arterial thromboembolism. Although surgical resection is indicated for patients with azygous vein aneurysms with a risk of rupture and pulmonary embolism, we chose anticoagulation therapy because of the patient's advanced age. This case suggests that the azygous vein aneurysm is one of the differential diagnoses for a mediastinal mass and that anticoagulation therapy can be the treatment of choice for pulmonary arterial thromboembolism with an azygous vein aneurysm.


Efficacy of antihypertensive treatment based on plasma renin activity: An open label observational study.
We investigated the extent of blood pressure (BP) reduction and control (<140/90 mmHg) in patients treated with appropriate or inappropriate drugs according to their plasma renin activity (PRA) level (natriuretic drugs and renin-angiotensin system blockers for low-renin and high-renin hypertension, respectively). One hundred and seventy Caucasian untreated hypertensive patients (61 females), aged 18-70 years, participated to the study. Patients with secondary hypertension, diabetes or established cardiovascular or renal disease were excluded. The physician prescribed an antihypertensive monotherapy chosen among all drug classes, unaware of patient's PRA levels. We compared effect of an inappropriate or appropriate drug, evaluating BP values after a month of treatment. Rate of BP control was not significantly higher in patients treated with an appropriate drug than the others (38% vs 29%, p=0.24). However, in a regression analysis, final diastolic BP (DBP) was lower in subjects treated with an appropriate drug (beta=-2.84, p=0.03). The present study does not clearly support the use of PRA in a general population of hypertensive patients to optimize BP control. However, the greater efficacy of a drug appropriate to PRA in reducing DBP may be clinically helpful in young hypertensive patients. Future studies are warranted to evaluate if PRA determination enhances the therapeutic success in patients with predominantly high values of DBP.


[The development of antibiotics resistance among Salmonella bacteria of animal origin in the Federal Republic of Germany and Berlin (West). 3rd Communication: 1972 Annual Report (author's transl)].
2273 Salmonella strains received from veterinary laboratories in the Federal Republic of Germany including Berlin (West) in 1972 were examined for their resistance against tetracyclines, ampicillin, chloramphenicol, kanamycin, nitrofurazone, and furazolidone. 13.3% of the strains studied were found to be resistant to one or more of these antibacterial substances. The proportion of resistant strains was 37.5% for S. typhimurium (excluding var. copenhagen), 3.1% for S. typhimurium var. copenhagen and 57% for S. panama. 79.8% of resistant strains were found to belong to these types. From 303 resistant strains found, resistance determinants were present in 87.4% to tetracyclines, in 37.2% to ampicillin, in 15.8% to chloramphenicol, in 4.6% to kanamycin, in 0.9% to furazolidone, and in 1.3% to nitrofurazone. 16 combinations of resistance determinants were found to occur 95.0% of strains transmitted resistance to E. coli K-12. A transmission of resistance determinants to furazolidone and nitrofurazone could not be demonstrated. Resistance patterns differed considerably from one serotype to another.


Extraction separation and electrothermal atomic absorption spectrometric determination of thallium in some sulfide minerals.
A method for thallium determination in some sulfide minerals (sphalerite, galena, orpiment and realgar) by electrothermal atomic absorption spectrometry has been proposed. Mineral samples were dissolved in a mixture of HNO3 and HCl. The effect of interfering elements (Zn, Pb and As) on the determination of Tl in the investigated minerals was studied. These investigations show that it is not possible to determine thallium directly from solutions obtained by dissolution of minerals in mineral acids, because these matrix elements tend to decrease the absorbance of thallium. Also, it was found that the investigated minerals contain iron that tends to increase the absorbance of thallium. Therefore, a method for extraction of thallium with isoamyl acetate from 10 mol/l HCl media was proposed. In these conditions, Zn, Pb and As remain in the inorganic phase, but iron and thallium are extracted into organic phase. Reextraction of iron from the organic layer was performed with 4 mol/l H2SO4. The determination of thallium was performed in the organic phase using Pd as modifier. The investigated sulfide minerals originated from different mines from the Republic of Macedonia. The relative standard-deviation range was between 2.20 to 3.92%. The detection limit of the method (calculated as 3SD of the blank) was found to be 0.05 microg/g.


Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.
A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.


The N terminus of the Escherichia coli transcription activator MalT is the domain of interaction with MalY.
The maltose system of Escherichia coli consists of a number of genes encoding proteins involved in the uptake and metabolism of maltose and maltodextrins. The system is positively regulated by MalT, its transcriptional activator. MalT activity is controlled by two regulatory circuits: a positive one with maltotriose as effector and a negative one involving several proteins. MalK, the ATP-hydrolyzing subunit of the cognate ABC transporter, MalY, an enzyme with the activity of a cystathionase, and Aes, an acetyl esterase, phenotypically act as repressors of MalT activity. By in vivo titration assays, we have shown that the N-terminal 250 amino acids of MalT contain the interaction site for MalY but not for MalK. This was confirmed by gel filtration analysis, where MalY was shown to coelute with the N-terminal MalT structural domain. Mutants in MalT causing elevated mal gene expression in the absence of exogenous maltodextrins were tested in their response to the three repressors. The different MalT mutations exhibited a various degree of sensitivity towards these repressors, but none was resistant to all of them. Some of them became nearly completely resistant to Aes while still being sensitive to MalY. These mutations are located at positions 38, 220, 243, and 359, most likely defining the interaction patch with Aes on the three-dimensional structure of MalT.


Anomalous diffusion of water in [BMIM][TFSI] room-temperature ionic liquid.
We have studied the self-diffusion properties of butyl-methyl-imidazolium bis(trifluoromethylsulfonyl)-imide ([BMIM][TFSI]) + water system. The self-diffusion coefficients of cations, anions, and water molecules were determined by pulsed field gradient NMR. These measures were performed with increased water quantity up to saturation (from 0.3 to 30 mol %). Unexpected variations have been observed. The self-diffusion coefficient of every species increases with the quantity of water but not in the same order of magnitude. Whereas very similar evolutions are observed for the anion and cation, the increase is 25 times greater for water molecules. We interpret our data by the existence of phase separation at microscopic scale.


Polyamine oxidase activity in peripheral blood of newborn infants with neonatal hyperbilirubinemia: is bilirubin an antioxidant?
Neonatal hyperbilirubinemia can be physiological and pathological and most frequently is a consequence of faster erythrocytes (RBC) hemolysis. Free unconjugated bilirubin is a highly toxic compound, especially for the central nervous system. The most abundant polyamines circulating in blood are spermidine (Spd) and spermine (Sp), which are mainly localized in RBC, where they control membrane permeability. Polyamine oxidase (PAO) exerts an important activity in the plasma and erythrocytes of newborn infants with hyperbilirubinemia, catalyzing the oxidative deamination of Sp and Spd, producing potentially toxic agents that induce apoptosis of mammalian cells. The present study investigated polyamine metabolism by measuring PAO activity in the blood of newborn infants with hyperbilirubinemia and explored the possible antioxidant function of bilirubin through monitoring malondialdehyde (MDA) levels. The study included 43 newborns, 10 in the control and 33 in the diseased group. Blood PAO activity and bilirubin and MDA levels were measured using spectrophotometric methods. Our results indicate that bilirubin, at physiologic concentrations, protects neonatal erythrocytes against oxidative stress. The positive correlation between PAO activity and MDA levels with high bilirubin concentrations (> 200 micromol/L) in newborn infants indicates that in pathological conditions, bilirubin cannot exert its antioxidant function. Investigating the function of polyamines in erythrocytes and the importance of PAO related to hemolysis and bilirubin synthesis is necessary to shed light on the functions of PAO and its metabolites on the permeability of the erythrocyte membrane.


Elderly gastrointestinal conditions increase sterol bioaccessibility in a plant sterol-enriched beverage: adaptation of the INFOGEST method.
Elderly people suffer from a higher cardiovascular risk. Thus, the fortification of foods with plant sterols (PSs), which have a cholesterol-lowering function, could be of great interest for this target group. To date, no studies have analyzed how the gastrointestinal conditions of the elderly affect PS bioaccessibility. Therefore, this study evaluated the impact of the adaptation of the gastric phase alone and in combination with the intestinal phase on sterol bioaccessibility. For this purpose, the standardized INFOGEST 2.0 method previously adapted for sterol bioaccessibility evaluation in healthy adults was applied to PS-enriched milk-based fruit beverages, examining changes in enzyme activity, incubation time, agitation and pH, based on elderly physiology. The results suggest that the specific gastrointestinal conditions of the elderly could increase absorption of PSs, since their bioaccessibility (%) in a PS-enriched milk-based fruit beverage was significantly increased compared with that in adults (14.95 ± 0.33 vs. 7.96 ± 0.26), also indicating that these conditions increase the bioaccessibility of the beverage's own cholesterol (61.25 ± 2.91 vs. 20.86 ± 2.79). These data support the recommendation of foods of this type for the elderly who can benefit from the increase in bioaccessibility of PSs to have an improved potential cholesterol lowering effect, thus decreasing their risk of cardiovascular disease. However, the performance of subsequent in vivo tests to confirm these results is necessary.


Dexamethasone, aldosterone and kallikrein release by isolated rat kidney.
1. The effect of D-aldosterone and dexamethasone on kallikrein release was studied in the isolated rat kidney perfused with modified Krebs-Henseleit buffer. 2. Animals received D-aldosterone or dexamethasone (10 microgram/100 g body weight) daily for 3 days. Their isolated kidneys were then perfused with the same steroids at rates of 2.0-2.5 microgram/min for 30 min. 3. Dexamethasone increased kallikrein release significantly (P less than 0.001) both in urine and in venous outflow. 4. D-Aldosterone had no significant effect on kallikrein release, either in urine or in venous outflow.


Effects of Consuming Preloads with Different Energy Density and Taste Quality on Energy Intake and Postprandial Blood Glucose.
Consumption of reduced energy dense foods and drink has the potential to reduce energy intake and postprandial blood glucose concentrations. In addition, the taste quality of a meal (e.g., sweet or savoury) may play a role in satiation and food intake. The objective of this randomised crossover study was to examine whether energy density and taste quality has an impact on energy intake and postprandial blood glucose response. Using a preload design, participants were asked to consume a sweet ("Cheng Teng") or a savoury (broth) preload soup in high energy density (HED; around 0.50 kcal/g; 250 kcal) or low energy density (LED; around 0.12 kcal/g; 50 kcal) in mid-morning and an ad libitum lunch was provided an hour after the preload. Participants recorded their food intake for the rest of the day after they left the study site. Energy compensation and postprandial blood glucose response were measured in 32 healthy lean males (mean age = 28.9 years, mean BMI = 22.1 kg/m²). There was a significant difference in ad libitum lunch intake between treatments (p = 0.012), with higher intake in sweet LED and savoury LED compared to sweet HED and savoury HED. Energy intake at subsequent meals and total daily energy intake did not differ between the four treatments (both p ≥ 0.214). Consumption of HED preloads resulted in a larger spike in postprandial blood glucose response compared with LED preloads, irrespective of taste quality (p < 0.001). Energy density rather than taste quality plays an important role in energy compensation and postprandial blood glucose response. This suggests that regular consumption of low energy-dense foods has the potential to reduce overall energy intake and to improve glycemic control.


Parathyroid-specific double knockout of Gq and G11 alpha-subunits leads to a phenotype resembling germline knockout of the extracellular Ca2+ -sensing receptor.
Germline knockout of the extracellular Ca2+ -sensing receptor (CaR) leads to a phenotype that includes severe hypercalcemia, hyperparathyroidism, relative hypocalciuria, skeletal abnormalities, retarded growth, and early postnatal death. To investigate the role of heterotrimeric G proteins in CaR signaling, we used cre/lox technology to delete the respective alpha-subunits of Gq and G11 selectively in parathyroid cells. Mice that were PTH-Cre(+/-); Gnaq(flox/flox); Gna11(-/-) (PTH-Galphaq/Galpha11 -double knockouts) were viable, but showed all the features of germline knockout of the CaR except hypocalcuria. Our results demonstrate the critical role of both Gq and G11 in mediating inhibition of PTH secretion by extracellular Ca2+.


CLINICALLY UNDETECTABLE OCCULT THYROID PAPILLARY CARCINOMA PRESENTING WITH CERVICAL LYMPH NODE METASTASIS.
Occult papillary thyroid carcinoma presented as isolated cervical lymphadenopathy without clinical and radiologic findings has been rarely reported. A 47 years old female patient admitted to otorhinolaryngology clinic with 4X3 cm sized cervical mass. Physical examination of the patient was noted as a nontender, firm, mobile lymph node at right lateral cervical region. There was no inflammatory or infection disease in the history of patients anamnesis and no abnormal value on laboratory tests. Ultrasound screening of the neck detected a lymph node with suspicious features for malignancy. Head and neck examination was normal and there is no evidence of a tumoral mass or nodule in the thyroid gland. Whole body scan of MRI showed no pathologic sign both in the neck and body. Excisional biopsy was performed and revealed a carcinoma with papillary morphology. Immunohistochemical staining features of the tumor confirmed a papillary carcinoma derived from the thyroid gland. Second look USG of the neck and thyroid was performed but it revealed no tumoral mass. The patient underwent total thyroidectomy with right functional and central lymph node dissection. Histological examination of the thyroid gland showed multicentric 2 mm sized, three foci of papillary carcinoma located in bilateral thyroid lobes and metastatic lymph nodes in the right side of the neck. A metastatic cervical lymph node can be evidence of a clinically undetected occult papillary thyroid carcinoma. Specific immunohistochemistry staining of specimen may lead to appropriate surgery and progression of carcinoma may be hindered by application of additional RAI therapy.


CTLA-4IG suppresses reactive oxygen species by preventing synovial adherent cell-induced inactivation of Rap1, a Ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells.
Oxidative stress contributes to the inflammatory properties of rheumatoid arthritis (RA) synovial T lymphocytes. This study was undertaken to investigate the mechanisms leading to production of reactive oxygen species (ROS) and oxidative stress in RA synovial T lymphocytes. ROS production in T lymphocytes from the peripheral blood (PB) of healthy donors and from the PB and synovial fluid (SF) of RA patients was measured by ROS-dependent fluorescence of 6-carboxy-2',7'-dichlorofluorescein. Rap1 GTPase activation was assessed by activation-specific probe precipitation. Proliferation of RA PB and SF T lymphocytes was assayed by 3H-thymidine incorporation. In some experiments, RA PB T cells were preincubated with autologous SF or with PB or SF adherent cells. Experiments were performed in the absence or presence of transwell membranes or CTLA-4Ig fusion proteins. Short- and long-term stimulations of healthy donor PB T lymphocytes were performed with inflammatory cytokines, in the absence or presence of activating anti-CD28 antibodies. T lymphocyte ROS production and Rap1 inactivation were mediated by cell-cell contact with RA synovial adherent cells, and this correlated with T cell mitogenic hyporesponsiveness. CTLA4-Ig blockade of synovial adherent cell signaling to CD28 T cells reversed the inhibition of Rap1 activity and prevented induction of ROS. Introduction of active RapV12 into T cells also prevented induction of ROS production. Coincubation of T cells with stimulating anti-CD28 antibodies and inflammatory cytokines synergistically increased T cell ROS production. Cell-cell contact between T cells and RA synovial adherent cells mediates Rap1 inactivation and subsequent ROS production in T lymphocytes following exposure to inflammatory cytokines. This process can be blocked by CTLA4-Ig fusion protein.


Ethics of Outbreaks Position Statement. Part 1: Therapies, Treatment Limitations, and Duty to Treat.
Outbreaks of disease, especially those that are declared a Public Health Emergency of International Concern, present substantial ethical challenges. Here we start a discourse (with a continuation of the dialogue in Ethics of Outbreaks Position Statement. Part 2: Family-Centered Care) concerning the ethics of the provision of medical care, research challenges and behaviors during a Public Health Emergency of International Concern with a focus on the proper conduct of clinical or epidemiologic research, clinical trial designs, unregistered medical interventions (including vaccine introduction, devices, pharmaceuticals, who gets treated, vulnerable populations, and methods of data collection), economic losses, and whether there is a duty of health care providers to provide care in such emergencies, and highlighting the need to understand cultural diversity and local communities in these efforts. Development of a Society of Critical Care Medicine position statement using literature review and expert consensus from the Society of Critical Care Medicine Ethics committee. The committee had representation from ethics, medical philosophy, critical care, nursing, internal medicine, emergency medicine, pediatrics, anesthesiology, surgery, and members with international health and military experience. Provision of therapies for patients who are critically ill or who have the potential of becoming critically ill, and their families, regarding medical therapies and the extent of treatments. Critically ill patients and their families affected by a Public Health Emergency of International Concern that need provision of medical therapies. Not applicable. Interventions by high income countries in a Public Health Emergency of International Concern must always be cognizant of avoiding a paternalistic stance and must understand how families and communities are structured and the regional/local traditions that affect public discourse. Additionally, the obligations, or the lack of obligations, of healthcare providers regarding the treatment of affected individuals and communities must also be acknowledged. Herein, we review such matters and suggest recommendations regarding the ethics of engagement in an outbreak that is a Public Health Emergency of International Concern.


2-D finite difference time domain model of ultrasound reflection from normal and osteoarthritic human articular cartilage surface.
Quantitative high-frequency ultrasonic evaluation of articular cartilage has shown a potential for the diagnosis of osteoarthritis, where the roughness of the surface, collagen and proteoglycan contents, and the density and mechanical properties of cartilage change concurrently. Experimentally, these factors are difficult to investigate individually and thus a numerical model is needed. The present study is the first one to use finite difference time domain modeling of pulse-echo measurements of articular cartilage. Ultrasound reflection from the surface was investigated with varying surface roughness, material parameters (Young's modulus, density, longitudinal, and transversal velocities) and inclination of the samples. The 2-D simulation results were compared with the results from experimental measurements of the same samples in an identical geometry. Both the roughness and the material parameters contributed significantly to the ultrasound reflection. The angular dependence of the ultrasound reflection was strong for a smooth cartilage surface but disappeared for the samples with a rougher surface. These results support the findings of previous experimental studies and indicate that ultrasound detects changes in the cartilage that are characteristic of osteoarthritis. In the present study there are differences between the results of the simulations and the experimental measurements. However, the systematic patterns in the experimental behavior are correctly reproduced by the model. In the future, our goal is to develop more realistic acoustic models incorporating inhomogeneity and anisotropy of the cartilage.


Pushing boundaries in paediatric intensive care: training as a paediatric retrieval nurse practitioner.
Traditionally in the UK, the transportation of the critically ill child to a paediatric intensive care unit has been carried out by a medically led team of doctors and nurses. However, in countries such as the USA and Canada, appropriately trained nurse practitioners have proven to be competent in the transportation of these vulnerable children. This nurse-led team model has also been shown to be successful in the speciality of neonatal care in the UK. The impact of changes in the National Health Service (NHS) has led to an increased demand for the transportation of the child requiring paediatric intensive or high-dependency care, the lifting of restrictions on nursing practice and the reduction of doctors' hours in keeping with the European Working Time Directive. This has led to one NHS Trust in the UK developing the role of paediatric retrieval nurse practitioners (RNP): nurses who lead the retrieval team. The purpose of this article is to describe a pilot initiative to develop the role of RNPs. The comprehensive process of recruitment, training and assessment of competency will be detailed. Personal reflection on the project will also explore the pertinent nursing issues around; role impact and definition, conflict and change management, communication, legislation and personal and professional growth. Recommendations for future initiatives will also be explored.


Molecular typing of native Bacillus thuringiensis isolates from diverse habitats in India using REP-PCR and ERIC-PCR analysis.
Bacillus thuringiensis is a bacterium of great agronomic and scientific interest. The subspecies of this bacterium colonize and kill a large variety of host insects and even nematodes, but each strain does so with a high degree of specificity. Therefore molecular typing and diversity analysis of B. thuringiensis has enormous importance for discrimination of strains isolated from different sources. In this study, 113 native B. thuringiensis isolates collected from diverse habitats and locations in India and 27 B. thuringiensis type strains obtained from the Bacillus Genetic Stock Centre (BGSC), Ohio State University, USA and used as reference, were analyzed for molecular typing. Genotypic data of 140 B. thuringiensis isolates and type strains was generated by using REP-PCR and ERIC-PCR primers and unweighted pair group method with arithmetic mean (UPGMA) analysis using NTSYSpc2.2 and grouped into 4 main clusters. All the groups have isolates from diverse origins. No group was found to represent any specific origin or location. The observed patterns of REP-PCR and ERIC-PCR pattern were discriminatory enough to reveal differences in the B. thuringiensis isolates and reference strains. The resolution power and marker index of the ERIC-PCR (RP 9.39, MI 6.34) was found to be higher than that of the REP-PCR (RP 6.20, MI 4.48). The REP-PCR and ERIC-PCR markers have been found to be useful for discrimination of B. thuringiensis isolates and reference strains. ERIC-PCR was the more informative of the two techniques. This study showed that the B. thuringiensis isolates collected from diverse habitats in India had a high degree of genetic diversity.


The expanding world of extracellular traps: not only neutrophils but much more.
The release of extracellular traps (ETs) is a recently described mechanism of innate immune response to infection. Although ETs have been intensely investigated in the context of neutrophil antimicrobial effector mechanisms, other immune cells such as mast cells, eosinophils, and macrophages can also release these structures. The different ETs have several features in common, regardless of the type of cells from which they originated, including a DNA backbone with embedded antimicrobial peptides, proteases, and histones. However, they also exhibit remarkable individual differences such as the type of sub-cellular compartments from where the DNA backbone originates (e.g., nucleus or mitochondria), the proportion of responding cells within the pool, and/or the molecular mechanism/s underlying the ETs formation. This review summarizes the knowledge accumulated in recent years regarding the complex and expanding world of ETs and their role in immune function with particular emphasis on the role of other immune cells rather than on neutrophils exclusively.


[Bronchial diffusion of new anti-pseudomonal beta-lactams. Clinical significance].
In treating severe respiratory infections due to Pseudomonas aeruginosa and in patients with cystic fibrosis, new anti-pseudomonal beta-lactams constitute a good alternative to the traditional aminoglycoside antibiotic therapy. Among several criteria for the choice of an antibiotic, estimation of intrabronchial levels is to be taken into account. The authors report the results of the study of a new semi-synthetic penicillin, apalcillin, and two cephalosporins (cefsulodin, ceftazidime), active in vitro against Pseudomonas; their penetration into respiratory secretions was evaluated in 48 patients, intubated, tracheostomized, or undergoing fiberoptic bronchoscopy. Antibiotic concentrations were measured by the microbiological procedure. Bronchial penetration of apalcillin was early and noticeable, reaching a bronchial peak representing 20% of the simultaneous seric concentration. The local levels of cefsulodin and of ceftazidime did not differ from those achieved with cephalosporins studied previously; the bronchial peak reached 5,6 micrograms/ml for both drugs 2 hours after administration; this bronchial level corresponded to 15 to 20% of the serum concentration. The clinical response could not be evaluated due to the severe underlying pathology which compromised the outcome of the disease in the patients of this study. However, at least for apalcillin, a significant correlation was noted between bronchial levels, susceptibility of bacteria isolated in patients, and eradication of susceptible organisms.


Association between generalized joint hypermobility and signs and diagnoses of temporomandibular disorders.
The aim of this study was to analyze whether generalized joint hypermobility (GJH) is a risk factor for temporomandibular disorders (TMD). We examined 895 subjects (20-60 yr of age) in a population-based cross-sectional sample in Germany for GJH according to the Beighton classification and for TMD according to the Research Diagnostic Criteria for TMD (RDC/TMD). After controlling for the effects of age, gender, and general joint diseases using multiple logistic regression analyses, hypermobile subjects (with four or more hypermobile joints on the 0-9 scale) had a higher risk for reproducible reciprocal clicking as an indicator for disk displacement with reduction (Odds Ratio (OR) = 1.68) compared with those subjects without hypermobile joints. Concurrently, subjects with four or more hypermobile joints had a lower risk for limited mouth opening (< 35 mm; OR = 0.26). The associations between GJH and reproducible reciprocal clicking or limited mouth opening were statistically significant in a trend test. No association was observed between hypermobility and myalgia/arthralgia (RDC/TMD Group I/IIIa). In conclusion, GJH was found to be associated with non-painful subtypes of TMD.


The prevalence of tardive dyskinesia.
A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team of trained raters employing a standard examination technique and rating scale. "Spontaneous" dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% among medical geriatric inpatients and ranged from 0 to 2% among psychiatric patients never exposed to neuroleptics. For samples of neuroleptic-treated patients, prevalence rates ranged from 13.3% among patients at a voluntary psychiatric hospital to 36.1% among state hospital patients. Logistic regression analyses revealed a large effect of age on tardive dyskinesia prevalence and an interaction of age with sex. Among younger subjects, men had higher rates; among subjects over age 40, rates were higher for women. Edentulousness and presence of other neurological disorders were possible contributors to high rates for the elderly. Even with control for age, sex and duration of neuroleptic exposure, prevalence differed markedly across study site.


Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection.
We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively.


Risk factors for infection after orthopaedic spine surgery at a high-volume institution.
Surgical site infections are associated with increased morbidity, mortality, and resource utilization. To identify risk factors for infection, the authors reviewed all orthopaedic spine operations at Duke University Medical Center from 2005 to 2010. Of the 3138 patients treated during the study period, 115 developed a surgical site infection (3.7%). Demographics, comorbidities, and perioperative blood glucose levels were analyzed in the infected and uninfected cohorts. History of myocardial infarction, congestive heart failure, renal disease, pneumonia, urinary tract infection, and diabetes mellitus (DM) were associated with a higher risk of infection. Notably, a diagnosis of DM nearly doubled the risk of infection. Even in patients without DM, perioperative blood glucose levels greater than 140 mg/dL doubled the risk of infection. The authors propose that strict blood glucose control in both DM and non-DM patients may significantly reduce the risk of infection after spinal surgery.


Off the couch and on the move: global public health and the medicalisation of nature.
In May 2004 the World Health Organization (WHO) officially launched the 'Global Strategy on Diet, Physical Activity and Health'. Lying at its heart is the recognition that many of the risk factors associated with non-communicable diseases, particularly poor diet and physical inactivity, have begun to move beyond the confines of the West. It was this apparent shift in the epidemiological boundaries of such diseases, along with fears over the so-called 'double burden' that they presented to some nations, that finally prompted the WHO to develop such a far reaching strategy. This paper adds to the on-going debate surrounding this important issue by drawing on the concepts of medicalisation, governmentality and the spatiality of scientific knowledge to explore one particular element of it: namely, the identification of nature as a setting for the promotion of physical activity. We adopt this perspective because we are concerned to understand the ways in which the knowledge and practice of the 'new' public health travels. As our analysis reveals, in many Western nations the natural environment has emerged as an important 'transactional zone' where the governmental imperative for the production of fit and active bodies coalesces with the individual desire to be healthy. However, while it is apparent that this physical activity discourse increasingly operates throughout the globe, there is less evidence of an equivalent discourse that promotes the health-related benefits of nature. We argue that this is significant because it helps us to recognise that contemporary public health discourse has a distinct geography.


[Coupling of immunomagnetic separation and polymerase chain reaction for the rapid detection of salmonellae in minced meat and chicken giblets].
Coupling of immunomagnetic separation and polymerase chain reaction was used after preenrichment for the rapid detection of salmonellae in minced meat and chicken giblets. The primers used are specific to the origin of DNA replication (oriC) on the Salmonella chromosome and produce a 163 bp DNA fragment. The method allowed a screening of Salmonella free samples within 24 hours. It detected 5 serovars when inoculated in minced meat at a contamination level of 1 to 4 cfu/g. Compared with the method L 00.00-20 of the Official Collection of Methods of Analysis according to section 35 of the German Law on Food and Commodities it showed a sensitivity of 94% and a specificity of 87.5% for the examination of chicken giblets (n = 45) and a specificity of 100% for the examination of minced meat (n = 63).


Effect of substance P and neurokinin A on rat parietal cell function.
In enzymatically dispersed enriched (76%) rat parietal cells we studied the effect of substance P on acid sequestration as indirectly measured by [14C]aminopyrine accumulation. Substance P (10(-8)-10(-5) M) had no effect on basal [14C]aminopyrine accumulation. Yet, the peptide reduced the response to histamine and to the postreceptor agonists forskolin and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP). Inhibition by substance P followed noncompetitive kinetics and reduced stimulated parietal cell function by up to 45% at 10(-5) M. The antagonist [D-Pro2, D-Trp7,9]-substance P at 10(-5) M partly reversed the inhibitory effect of substance P. Cholinergic stimulation of [14C]aminopyrine accumulation was not reduced by substance P. Neurokinin A, another tachykinin that is structurally related to substance P, was of comparable potency and efficacy in reducing [14C]aminopyrine accumulation in response to histamine, forskolin, and DBcAMP. Inhibition of forskolin- or DBcAMP-induced [14C]aminopyrine accumulation persisted in the presence of 10(-5) M ranitidine. Inhibition by substance P and neurokinin A of the response to histamine was not sensitive to pertussis toxin. Both tachykinins failed to reduce histamine- and forskolin-stimulated cAMP production. Our data suggest that substance P and neurokinin A exert a direct effect on rat parietal cells. They attenuate histamine-stimulated acid sequestration at an intracellular step that is distal to the adenylate cyclase and that does not involve pertussis toxin-sensitive GTP-binding proteins.


Reactions of substituted (1,3-butadiene-1,4-diyl)magnesium, 1,4-bis(bromomagnesio)butadienes and 1,4-dilithiobutadienes with ketones, aldehydes and PhNO to yield cyclopentadiene derivatives and N-Ph pyrroles by cyclodialkenylation.
1,4-Dilithiobutadiene derivatives 1, 1,4-bis(bromomagnesio)butadiene derivatives 2 and metallacyclic (1,3-butadiene-1,4-diyl)magnesium reagents 3 were prepared and their reactions with ketones, aldehydes, and PhNO were investigated. Multiply substituted cyclopentadienes and N-Ph pyrroles were formed by unprecedented reaction conditions. The carbonyl group of aldehydes and ketones was deoxygenated during the reaction and behaved formally as a one-carbon unit; the N==O moiety of PhNO was cleaved to afford N-Ph pyrrole derivatives. Furthermore, different reactivities among these three types of reagents 1, 2 and 3 were revealed. The 1,4-dilithium reagents 1 readily reacted with both aldehydes and ketones; the 1,4-dimagnesium reagents 2 reacted with aldehydes, but not ketones; the metallacyclopentadiene reagents of magnesium 3 showed higher reactivity and did react with ketones.


Dopaminergic neurons project to the nucleus accumbens regulates anxiety-like behaviors through dopamine D1 signaling.
Dopamine (DA) transmission is important in the regulation of mood and anxiety behaviors. However, how specific dopaminergic signaling pathways respond to anxiogenic stimuli as well as regulate behaviors remains unknown. To understand how DA regulates the animal behaviors under anxiety we performed retrograde labeling and c-Fos staining of midbrain DA neurons. Our c-Fos labeling results showed that DA neurons projected to nucleus accumbens (NAc) are activated in animals treated with the elevated plus-maze (EPM). Real-time measurement of DA release using fast scanning cyclic voltammetry (FSCV) in NAc of freely behaving mice showed that increased DA release and more DA transients in the close arms than the open arms in the EPM. Meanwhile, we also observed a reduction of DA level from the close arms to the open arms. Local infusion of DA D1 receptor antagonist, SCH23390 in the core of NAc, leads to an anxiolytic-like effect in the open-field and EPM. These anxiolytic effects were not observed in animals received D2 receptor antagonist sulpiride infusion in the core of NAc. Taken together, our results reveal a novel function of the mesolimbic DA pathway through the D1 receptor in the regulation of anxiety-like behaviors.


The Additive Effects of Cell Phone Use and Dental Hygiene Practice on Finger Muscle Strength: A Pilot Study.
Purpose: The purpose of this study was to determine strength of muscles involved with instrumentation (scaling) by dental hygienists and the additive effects of cellular (mobile) phone usage, as indicated by measurements of muscular force generation.Methods: A convenience sample of licensed dental hygienists currently in clinical practice (n=16) and an equal number of individuals not currently using devices/tools repetitively for work (n=16), agreed to participate in this pilot study. All participants completed a modified cell phone usage questionnaire to determine their use pattern and frequency. Upon completion of the questionnaire, participants' force production in six muscle groups was measured using a hand-held dynamometer. Descriptive statistics were used to analyze the data.Results: A total of 16 licensed dental hygienists (n=16) and 16 participants with no history of using tools/devices repetitively for work (n=16), comprised the experimental and control groups, repectively. The control group generated greater muscle force than the experimental group for the abductor pollicis longus (p=0.045). Significant differences were identified when comparing the low mobile phone users in the experimental group to the control group for the flexor pollicis brevis (p=0.031), abductor pollicis longus (p=0.031), and flexor digitorum (p=0.006), with the control group demonstrating higher muscle force. Years in clinical practice and mobile phone use was shown to have a significant effect on muscular force generation for the flexor pollicis brevis (F=3.645, df=3, p=0.020) and flexor digitorum (F=3.560, df=3, p=0.022); subjects who practiced dental hygiene the longest produced the least amount of muscle force.Conclusion: Results from this pilot study indicate there are no significant additive effects of cell phone use and dental hygiene practice on finger muscles used for instrumentation. However, results indicate that dental hygiene practice demonstrated significant effects on muscular strength as compared to individuals who do not use tools/devices repetitively for work. The small sample size may have impacted results and the study should be repeated with a larger sample.


Restraint stress-induced central monoaminergic & oxidative changes in rats & their prevention by novel Ocimum sanctum compounds.
Ocimum sanctum (OS) is known to possess various therapeutic properties. We have earlier isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating stress-induced central changes is unexplored. Thus, the present study was aimed to investigate the effect of these OS compounds on restraint stress (RS)-induced changes in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus of rats. RS was produced by immobilizing (restraining) the Sprague Dawley rats for a period of 2.5 h inside cylindrical steel tubes. The monoamine levels and the in vivo antioxidant status in brain regions were evaluated by HPLC-EC and spectrophotometric assays, respectively. RS significantly increased the dopamine levels in the frontal cortex and decreased in the striatum and hippocampus, and accompanied with selective increase of dopamine metabolites compared to the NS control group. The serotonin and its metabolite levels were significantly increased, while noradrenaline levels were decreased by RS in the three brain regions studied. The activities of superoxide dismutase and glutathione peroxidase in the frontal cortex and striatum were significantly increased by RS with decreased glutathione levels and increased lipid peroxidation. Pre-treatment with Ocimumoside A and B (40 mg/kg po) for a period of 3 days prevented the RS-induced changes with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg po) and antioxidant (Melatonin; 20 mg/kg ip) drugs, while, Ocimarin failed to modulate these changes. OS compounds per se had no effect on these parameters. The present findings showed the anti-stress potential of Ocimumoside A and B in relation to their simultaneous modulatory effects on the central monoaminergic and antioxidant systems implicating their therapeutic importance in stress-related disorders. Further studies are required to understand the mechanism of action of these compounds.


Limited Utility of Routine Tests Prior to Ophthalmologic Surgery: An Observational Study in a Japanese Hospital.
Routine preoperative testing for low-risk surgeries without a clinical indication should be avoided; however, such tests are still frequently performed in Japan. This study was performed to assess the impact of routine preoperative tests in low-risk surgery in a Japanese medical setting. We performed a retrospective chart review to examine the utility of routine tests with respect to anesthetic management and postoperative complications in all patients aged ≥ 18 years whom ophthalmologists consulted with anesthesiologists before ophthalmologic surgery under general anesthesia. During the 10-year study period, 1,234 anesthetic consultations and 1,211 routine preoperative tests (laboratory tests, chest X-rays, and electrocardiograms) were performed in Toyama University Hospital. In total, 59 patients (4.8% of the study population) canceled surgery after a battery of preoperative evaluation. Among them, 10 patients had incidental abnormalities that necessitated additional tests, and only three patients (0.2%) canceled surgery. In-hospital postoperative complications developed in nine patients (0.7%) whose routine test results made it difficult to predict development of these adverse events. No severe life-threatening events were noted in this survey. Routine tests prior to eye surgery for adults were of low value for perioperative management and prediction of development of in-hospital complications in this Japanese medical setting. Anesthesiologists and ophthalmologists should selectively order preoperative tests based on the medical interview and physical examination.


Thrombotic and Infectious Risks of Parenteral Nutrition in Hospitalized Pediatric Inflammatory Bowel Disease.
Malnutrition is common in inflammatory bowel disease (IBD), requiring timely and sufficient nutritional supplementation. In patients hospitalized for active disease, symptoms and/or altered intestinal function hinder enteral nutrition feasibility. In this scenario, parenteral nutrition (PN) is used. We aimed (1) to assess the frequency of PN use between 1997 and 2012 among hospitalized pediatric patients with IBD, (2) to determine the risk of in-hospital thrombus and infection associated with PN, and (3) to identify predictors of thrombus and infection in pediatric IBD hospitalizations utilizing PN. We performed a cross-sectional analysis of pediatric patients hospitalized between 1997 and 2012. We used the Kids' Inpatient Database (KID) to identify pediatric patients (≤18 years of age) with Crohn's disease (CD) or ulcerative colitis (UC), PN exposure, and primary outcomes including thrombus and infection. We used multivariable regression to identify risk factors for outcomes of interest. Parenteral nutrition was utilized in 3732 (12%) of 30,914 IBD hospitalizations. Three percent of PN patients experienced a thrombotic complication, and 5.5% experienced an infectious complication. Multivariate analysis showed PN as an independent risk factor for thrombus (odds ratio [OR], 4.3; 95% confidence interval [CI], 3.2-5.6) and infection (OR, 3.8; 95% CI, 3.1-4.6). Surgery was an independent risk factor for thrombus (OR, 2.0; 95% CI, 1.4-2.7) and infection (OR, 2.5; 95% CI, 2.0-3.1) in hospitalizations exposed to PN. Hospitalized pediatric IBD patients, particularly surgical, receiving PN are at increased risk for thrombosis and infection. Clinicians must balance these risks with the benefits of PN.