Glycine/Serine polymorphism at position 38 influences KCNE1 subunit's modulatory actions on rapid and slow delayed rectifier K+ currents.
KCNE1 encodes a modulator of KCNH2 and KCNQ1 delayed rectifier K(+) current channels. KCNE1 mutations might cause long QT syndrome (LQTS) by impairing KCNE1 subunit's modulatory actions on these channels. There are major and minor polymorphismic KCNE1 variants whose 38(th) amino acids are glycine and serine [KCNE1(38G) and KCNE1(38S) subunits], respectively. Despite its frequent occurrence, the influence of this polymorphism on the K(+) channels' function is unclear. Patch-clamp recordings were obtained from human embryonic kidney -293T cells. KCNH2 channel current density in KCNE1(38S)-transfected cells was smaller than that in KCNE1(38G)-transfected cells by 34%. The voltage-sensitivity of the KCNQ1 channel current in KCNE1(38S)-transfected cells was lowered compared to that in KCNE1(38G)-transfected cells, with a +13mV shift in the half-maximal activation voltage. KCNH2 channel current density or KCNQ1 channel voltage-sensitivity was not different between KCNE1(38G)-transfected cells and cells transfected with both KCNE1(38G) and KCNE1(38S). Moreover, the KCNH2 channel current in KCNE1(38S)-transfected cells was more susceptible to E4031, a QT prolonging drug and a condition with hypokalemia, than that in KCNE1(38G)-transfected cells. Homozygous inheritance of KCNE1(38S) might cause a mild reduction of the delayed rectifier K(+) currents and might thereby increase an arrhythmogenic potential particularly in the presence of QT prolonging factors. By contrast, heterozygous inheritance of KCNE1(38G) and KCNE1(38S) might not affect the K(+) currents significantly. (Circ J 2014; 78: 610-618).


Awake perception is associated with dedicated neuronal assemblies in the cerebral cortex.
Neural activity in the sensory cortex combines stimulus responses and ongoing activity, but it remains unclear whether these reflect the same underlying dynamics or separate processes. In the present study, we show in mice that, during wakefulness, the neuronal assemblies evoked by sounds in the auditory cortex and thalamus are specific to the stimulus and distinct from the assemblies observed in ongoing activity. By contrast, under three different anesthetics, evoked assemblies are indistinguishable from ongoing assemblies in the cortex. However, they remain distinct in the thalamus. A strong remapping of sensory responses accompanies this dynamic state change produced by anesthesia. Together, these results show that the awake cortex engages dedicated neuronal assemblies in response to sensory inputs, which we suggest is a network correlate of sensory perception.


Cytochrome c mediates electron transfer between ubiquinol-cytochrome c reductase and cytochrome c oxidase by free diffusion along the surface of the membrane.
Ubiquinol oxidase can be reconstituted from ubiquinol-cytochrome c reductase (Complex III) and cytochrome c oxidase (Complex IV) whose endogenous phosphatidylcholine and phosphatidylethanolamine have been replaced by dimyristoylglycerophosphocholine. Phase transition of the lipid has no effect on Complex III and Complex IV activities assayed separately, but ubiquinol oxidase activity rapidly decreases as the temperature is lowered through the phase transition. A spin-labelled yeast cytochrome c derivative has been synthesized. Binding of the cytochrome c to liposomes demonstrates that only cardiolipin is involved under the conditions used for the ubiquinol oxidase experiments. In liposomes consisting of cardiolipin and dimyristoylglycerophosphocholine, e.s.r. (electron-spin-resonance) measurements show that rotational diffusion of cytochrome c is slowed in the gel phase of the latter lipid. We propose that the cytochrome c pool is bound to cardiolipin molecules, whose lateral and rotational diffusion in the bilayer is adequate to account for electron-transport rates.


PTOV1 enables the nuclear translocation and mitogenic activity of flotillin-1, a major protein of lipid rafts.
PTOV1 is a mitogenic protein that shuttles between the nucleus and the cytoplasm in a cell cycle-dependent manner. It consists of two homologous domains arranged in tandem that constitute a new class of protein modules. We show here that PTOV1 interacts with the lipid raft protein flotillin-1, with which it copurifies in detergent-insoluble floating fractions. Flotillin-1 colocalized with PTOV1 not only at the plasma membrane but, unexpectedly, also in the nucleus, as demonstrated by immunocytochemistry and subcellular fractionation of endogenous and exogenous flotillin-1. Flotillin-1 entered the nucleus concomitant with PTOV1, shortly before the initiation of the S phase. Protein levels of PTOV1 and flotillin-1 oscillated during the cell cycle, with a peak in S. Depletion of PTOV1 significantly inhibited nuclear localization of flotillin-1, whereas depletion of flotillin-1 did not affect nuclear localization of PTOV1. Depletion of either protein markedly inhibited cell proliferation under basal conditions. Overexpression of PTOV1 or flotillin-1 strongly induced proliferation, which required their localization to the nucleus, and was dependent on the reciprocal protein. These observations suggest that PTOV1 assists flotillin-1 in its translocation to the nucleus and that both proteins are required for cell proliferation.


Comparison of running energetics in male and female domestic fowl.
Carbon dioxide production (VCO2) and end-exercise venous lactate concentration were compared in intensively-trained, mature male and female domestic fowl running on a treadmill for 10-min periods at maximal and sub-maximal work loads. The relationship between VCO2 and running speed was linear and had the same slope in male and female birds. However the maximum sustainable running speed of the males was approximately twice that in the females and the maximum weight-specific VCO2 was 60% higher in males. End-exercise venous lactate concentration rose significantly above resting at work loads above 75% maximum in females, but only at work loads above 95% maximum in fully-trained males. The results indicate a greater work capability in male than in female birds in the conditions of the experiments.


Differential effect of coformycin on the cell cycle traverse of normal and simian virus 40-transformed human fibroblasts.
Normal and simian virus 40-transformed human embryonic lung fibroblasts in culture were exposed to 3.5 microM coformycin (CF). This treatment resulted in almost complete inhibition of adenosine deaminase activity in both cell lines and retarded the progress of the fibroblasts through the cell cycle, as measured by the rate of cell proliferation. There was a marked difference, however, in the effect of CF on the traverse of different segments of the cell cycle. In normal fibroblasts, CF rapidly but transiently inhibited cell entry into visible stages of mitosis and delayed the progress through S and G2. In transformed fibroblasts, the effects of CF on the cell cycle included an early acceleration of the cell entry into visible mitosis and prolongation of this phase of the cell cycle. These results indicate that inhibition of adenosine deaminase can have different effects on the traverse of the critical segments of the cell cycle in normal and transformed cells.


Dopamine D2 receptors in WFS1-neurons regulate food-seeking and avoidance behaviors.
The selection and optimization of appropriate adaptive responses depends on interoceptive and exteroceptive stimuli as well as on the animal's ability to switch from one behavioral strategy to another. Although growing evidence indicate that dopamine D2R-mediated signaling events ensure the selection of the appropriate strategy for each specific situation, the underlying neural circuits through which they mediate these effects are poorly characterized. Here, we investigated the role of D2R signaling in a mesolimbic neuronal subpopulation expressing the Wolfram syndrome 1 (Wfs1) gene. This subpopulation is located within the nucleus accumbens, the central amygdala, the bed nucleus of the stria terminalis, and the tail of the striatum, all brain regions critical for the regulation of emotions and motivated behaviors. Using a mouse model carrying a temporally controlled deletion of D2R in WFS1-neurons, we demonstrate that intact D2R signaling in this neuronal population is necessary to regulate homeostasis-dependent food-seeking behaviors in both male and female mice. In addition, we found that reduced D2R signaling in WFS1-neurons impaired active avoidance learning and innate escape responses. Collectively, these findings identify a yet undocumented role for D2R signaling in WFS1-neurons as a novel effector through which dopamine optimizes appetitive behaviors and regulates defensive behaviors.


Entity/quality-based logical definitions for the human skeletal phenome using PATO.
This paper describes an approach to providing computer-interpretable logical definitions for the terms of the Human Phenotype Ontology (HPO) using PATO, the ontology of phenotypic qualities, to link terms of the HPO to the anatomic and other entities that are affected by abnormal phenotypic qualities. This approach will allow improved computerized reasoning as well as a facility to compare phenotypes between different species. The PATO mapping will also provide direct links from phenotypic abnormalities and underlying anatomic structures encoded using the Foundational Model of Anatomy, which will be a valuable resource for computational investigations of the links between anatomical components and concepts representing diseases with abnormal phenotypes and associated genes.


Isolation of human splenic macrophages and lymphocytes by countercurrent centrifugal elutriation.
Certain tissues, such as the spleen, are rich sources of mononuclear phagocytes (MP); however, separating the phagocytes from tissues and removing the contaminating cells have been difficult. We report here a method for the extraction and purification of human splenic MP that employs gentle homogenization of splenic fragments with a Tenbroeck tissue homogenizer, controlled digestion with purified collagenase to free MP from splenic stroma, incubation with DNase to dissociate cell clumps and purification by countercurrent centrifugal elutriation (CCE). With homogenization and enzymatic digestion most of the splenic nonspecific-esterase-positive cells are freed into suspension as determined by morphometric analysis of 2 micron sections from plastic embedded spleen stained for alpha-naphthyl butyrate esterase (ANB). Overall cell recovery after homogenization and enzyme treatment is 56 +/- 7%; no selective cell loss occurs as determined by differential cell counts at each purification step. CCE of up to 3 X 10(9) treated spleen cells results in recovery of 63 +/- 6% of the elutriated cells and separates nearly 50% of the recovered MP into enriched fractions. These MP are morphologically intact as determined by light and electron microscopy and are actively phagocytic. Highly purified (96%) autologous splenic lymphocytes are a useful by-product of this separation technique.


Language Matters: It Is Time We Change How We Talk About Addiction and its Treatment.
The way we communicate about addiction, its treatment, and treatment outcomes matters to individuals affected by addiction, their families, and communities. Stigmatizing language can worsen addiction-related stigma and outcomes. Although non-professional terminology may be used by individuals with addiction, the role of clinicians, educators, researchers, policymakers, and community and cultural leaders is to actively work toward destigmatization of addiction and its treatment, in part through the use of non-stigmatizing language. Role-modeling better approaches can help us move away from the inaccurate, outdated view of addiction as a character flaw or moral failing deserving of punishment, and toward that of a chronic disease requiring long-term treatment. Non-stigmatizing, non-judgmental, medically-based terminology and the adoption of person-first language can facilitate improved communication as well as patient access to and engagement with addiction care. Person-first language, which shifts away from defining a person through the lens of disease (eg, the term "a person with addiction" is recommended over the terms "addict" or "addicted patient"), implicitly acknowledges that a patient's life extends beyond a given disease. While such linguistic changes may seem subtle, they communicate that addiction, chronic pain and other diseases are only one aspect of a person's health and quality of life, and can promote therapeutic relationships, reduce stigma and health and disparities in addiction care. This article provides examples of stigmatizing terms to be avoided and recommended replacements to facilitate the dialogue about addiction in a more intentional, therapeutic manner.


Cost-Utility Analysis of Pembrolizumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small Cell Lung Cancer With Different PD-L1 Expression Levels.
To evaluate the cost-utility of pembrolizumab versus chemotherapy as the first-line setting for metastatic non-small cell lung cancer (NSCLC) from the US health care system perspective, a Markov model was developed to compare the lifetime cost and effectiveness of pembrolizumab versus chemotherapy for untreated metastatic NSCLC, based on the clinical data derived from phase III randomized controlled trial (KEYNOTE-042; ClinicalTrials.gov; NCT02220894). Weibull distribution was fitted to simulate the parametric survival functions. Drug costs were collected from official websites, and utility values were obtained from published literature. Total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed as primary output indicators. The impact of different PD-L1 expression levels on ICER was also evaluated. One-way and probabilistic sensitivity analyses were performed to assess the model uncertainty. Compared with chemotherapy, patients treated with pembrolizumab provided an additional 1.13, 1.01, and 0.59 QALYs in patients with PD-L1 expression levels of ≥50%, ≥20%, and ≥1%, with corresponding incremental cost of 53,784, 47,479, and 39,827, respectively. The resultant ICERs of pembrolizumab versus chemotherapy were 47,596, 47,184, and 68,061/QALY, in three expression levels of PD-L1, respectively, all of which did not exceed the WTP threshold of 180,000/QALY. Probability sensitivity analysis outcome supported that pembrolizumab exhibited evident advantage over chemotherapy to be cost-effective. One-way sensitivity analysis found that ICERs were most sensitive to utility value of pembrolizumab in progression survival state. All the adjustment of parameters did not qualitatively change the result. For treatment-naive, metastatic NSCLC patients with PD-L1+, pembrolizumab was estimated to be cost-effective compared with chemotherapy for all PD-L1 expression levels at a WTP threshold of 180,000/QALY in the context of the US health care system.


An open evaluation of triple antibiotic therapy including vancomycin for febrile bone marrow transplant recipients with severe neutropenia.
Infectious complications still represent a major problem in patients submitted to bone marrow transplant (BMT); approximately 40% of febrile episodes are associated with infection and one-third of these are bacteremias. Opinions about the best appropriate empiric regimens are based on evaluation of cost, potential for adverse side-effects, development of bacterial resistance, prevalent nosocomial infections. In order to assess the clinical and microbiological effectiveness of an aggressive approach, we performed a prospective open study in 72 neutropenic febrile BMT patients, employing a triple antibiotic association including amikacin 500 mg x 8h, ceftazidime 2 g x 8 h, vancomycin 500 mg x 8 h as first-line empiric treatment. For the purpose of this study, a lasting return of temperature to normal and complete disappearance of either clinical or bacteriological signs of infection without any modification of therapy was considered as success; the persistence of fever after 72 hours or a protocol change was considered as failure. Eighty episodes were enrolled during the course of the study; bacteriological evidence of infection was obtained in 23 (28.7%) febrile episodes. Median duration of antibiotic administration and of febrile episodes were 5 and 2 days respectively. Overall response rate based on clinical responses was 87% and 91% in microbiological documented infections. Death due to sepsis nor toxicity were observed. This triple antibiotic combination appears to be a very effective regimen for the empiric treatment of febrile episodes in severely neutropenic BMT recipients.


[Improving home auto-control in diabetic children: reducing atherogenic risk].
Insulin-dependent Diabetes (IDDM) is a major endocrine abnormality in children and the greatest morbi-mortality problems for diabetic patients are those related to cardiovascular complications (macro-microangiopaties), where kept hyperlipidemia and hyperglucemia play a fundamental patogenic role. The programs for optimization of home autocontrol have reduced frequent metabolic derangements. The aim of this study was to analyze the metabolic control state and its relationships with plasma lipids and atherogenic ratios in diabetic patients that were submitted to a program for optimization of home autocontrol of this illness. Blood samples were taken fom 49 IDDM, aged 10.53 +/- 0.51 (+/- SEM) years old, with a mean evolution period of 4.34 +/- 0.38 years, at the begining of the program (Stage I) and 6 months later (Stage II). Biochemical Analysis: Total Cholesterol (TC), cholesterol joined to high density lipoprotein (HDLc), Triglycerides (TG) and Phospholipids (Ph) were measured by microspectrphotometric methods. Cholesterol joined to very low and low density lipoproteins (VLDLc and LDLc, respectively) were calculated by Friedwald's formula. Apoproteins A and B (Apo A and Apo B) were measured using Mancini's method, Glycemia levels (Gly) by peroxidase's method, Glycosilated Serum Protein (GSP) by colormetric's method and Glycosilated haemoglobine (HbA1c) by chromatographic separation using cationic interchange microcolumns. 65% of the patients showed a significant decrease in plasma levels of Gly, GSP and HbA1c percentage between Stages I and II (Favourable Metabolic Control).(ABSTRACT TRUNCATED AT 250 WORDS)


Fighting the TB dragon.
As the battle to stem the transmission of tuberculosis rages, OSHA and the CDC have joined forces to increase awareness of this adversary and improve occupational safety practices.


Selection of talented female gymnasts, aged 8 to 11, on the basis of motor abilities with special reference to balance: a retrospective study.
Our aim is to propose a selection procedure on the basis of motor abilities. Within this scope, we have particularly studied balance as one of the selection criteria for young female gymnasts. We have used the combination of two standardized tests: the beam-walking test and the stork-standing test. Four groups of young females (aged 8 to 11 years) were tested. The results indicate that the talented group (n = 23, those participating in national training) has better balance in comparison to the control group (n = 37), gymnasts only participating at club level) and the average group (n = 32, girls not taking part in gymnastics). The results are independent of age, height, and weight, which justify the conclusion that balance is stabilized before the age of 8 years. The fourth group (n = 192) are girls who took part in the selection procedure in 1979 and 1980. We divided this group in 1981 into a non-selected group (n = 121), a discharged, selected young talented group (n = 42), a selected young talented group (n = 16), and an older talented group (n = 13). We discuss the results of these groups at the time of the selection procedure. The two talented groups show better results on the balance tests than the discharged, selected group and the non-selected group. There is no relationship to the results of the total selection test. The results indicate that these tests can be used as one of the selection criteria within the selection procedure for young female gymnasts.


Impact of a school-based hygiene promotion and sanitation intervention on pupil hand contamination in Western Kenya: a cluster randomized trial.
Handwashing with soap effectively reduces exposure to diarrhea-causing pathogens. Interventions to improve hygiene and sanitation conditions in schools within low-income countries have gained increased attention; however, their impact on schoolchildren's exposure to fecal pathogens has not been established. Our trial examined whether a school-based water, sanitation, and hygiene intervention reduced Escherichia coli contamination on pupils' hands in western Kenya. A hygiene promotion and water treatment intervention did not reduce risk of E. coli presence (relative risk [RR] = 0.92, 95% confidence interval [CI] = 0.54-1.56); the addition of new latrines to intervention schools significantly increased risk among girls (RR = 2.63, 95% CI = 1.29-5.34), with a non-significant increase among boys (RR = 1.36, 95% CI = 0.74-2.49). Efforts to increase usage of school latrines by constructing new facilities may pose a risk to children in the absence of sufficient hygiene behavior change, daily provision of soap and water, and anal cleansing materials.


Pseudocholinesterase activity of human whole blood, bank blood, and blood protein solutions.
Pseudocholinesterase (E.C. 220.127.116.11) activity was measured in plasma of whole blood, bank blood, and several commercially available blood protein solutions by means of a colorimetric assay technique at 25 degrees C, pH 7.7, and with butyrylthiocholine as substrate (Merckotest-R No. 3337). Activity of whole blood was 5.79 plus or minus 0.20 U x ml-1, of bank blood 4.53 plus or minus 0.27 U x ml-1, and of two human serum solutions (Biseko-R, Seretin-R) 3.05 plus or minus 0.13 and 3.04 plus or minus 0.22 U x ml-1, respectively (mean plus or minus S.E.M.). The other blood protein solutions contained no clinically significant esterase activity. Since transfusion of blood plasma has been suggested for treatment of cholinesterase deficiency and postoperative suxamethonium-induced muscle paralysis, an in-vitro attempt was carried out to correlate the amount of plasma necessary and the rise of pseudocholinesterase activity in the recipient's blood: A large amount of blood has to be transfused to yield a comparatively small increase in esterase activity. Thus, considering the potential hazards of blood transfusion, this treatment does not seem to be advisable.


Lupus nephritis reoccurs following transplantation in the lupus prone mouse.
The incidence and pathomechanism of recurrent lupus nephritis (RLN) after transplantation is not clearly understood. Burning out of the autoimmune process or local immunoregulatory mechanisms in the kidney may be responsible for the low incidence of recurrence. These mechanisms cannot be investigated in human subjects, due to post-transplant immunosuppression. To investigate the pathomechanisms of RLN, male and female kidneys were transplanted from FAS deficient lupus prone (LPR) or control (FAS intact) MRL mice into either LPR or MRL recipients. Urinary protein and blood urea were assessed. Double negative (DN) lymphocyte proliferation was determined by flow cytometry. Two months after transplantation inflammatory infiltration of the glomerular, vascular and interstitial compartments were determined. Renal function as demonstrated by blood urea levels was normal in MRL recipients, but elevated in LPR recipients, independent of the donor strain. Paralleling functional results, inflammatory infiltration was mild or absent in MRL recipients of MRL grafts, and mild to moderate in MRL recipients of LPR grafts, suggesting that kidney removal from the autoimmune (LPR) environment significantly reduced inflammation. Graft infiltration was most severe in LPR recipients: grafts were similarly inflamed independent of the donor. All LPR recipients had significantly less CD4+ Th cells versus MRL mice. Transplantation of LPR grafts into MRL recipients reduced CD4+ Th cell percentage, accompanied by a slight induction of lupus autoantibody production. Our results demonstrate that lupus nephritis is not kidney specific in the LPR model with recurrence after transplantation in the absence of immunosuppression.


Evolutionary responses to global change in species-rich communities.
Evolution in nature occurs in the proverbial tangled bank. The species interactions characterizing this tangled bank can be strongly affected by global change and can also influence the fitness and selective effects of a global change on a focal population. As a result, species interactions can influence which traits will promote adaptation and the magnitude or direction of evolutionary responses to the global change. First, we provide a framework describing how species interactions may influence evolutionary responses to global change. Then, we highlight case studies that have explicitly manipulated both a global change and the presence or abundance of interacting species and used either experimental evolution or quantitative genetics approaches to test for the effects of species interactions on evolutionary responses to global change. Although still not frequently considered, we argue that species interactions commonly modulate the effects of global change on the evolution of plant and animal populations. As a result, predicting the evolutionary effects of the multitude of global changes facing natural populations requires both community ecology and evolutionary perspectives.


Effectiveness of web-based education on Kenyan and Brazilian adolescents' knowledge about HIV/AIDS, abortion law, and emergency contraception: findings from TeenWeb.
Little evidence is available about the utility of web-based health education for students in low resource settings. This paper reports results from an evaluation of the TeenWeb project, a multi-year, web-based health education intervention implemented in two urban settings: Nairobi, Kenya (N=1178 school students) and Rio de Janeiro, Brazil (N=714 school students). A quasi-experimental, school-based pre-test/post-test design was implemented at each study site to determine if easy access to web-based reproductive health information, combined with intellectual "priming" about reproductive health topics, would result in improved knowledge and attitudes about topics such as condom use, access to HIV testing, emergency contraception and abortion laws. Students in web-access schools completed one web-based module approximately every 6-8 weeks, and in return, had access to the Internet for at least 30 min after completing each module. Although students were encouraged to access project-supplied web-based health information, freedom of web navigation was an incentive, so they could choose to access other Internet content instead. Most measures showed statistically significant differences between students in "web" and "comparison" conditions at post-test, but only about half of the differences were in the hypothesized direction. Results of an embedded experiment employing more directed feedback tripled the likelihood of correctly reporting the duration of emergency contraception effectiveness. Review of URL logs suggests that the modest results were due to inadequate exposure to educational materials. Future intervention should focus on teen's purposeful searching for health information when they are in personal circumstances of unmet health needs.


Blood supply to the human spinal cord: part I. Anatomy and hemodynamics.
The arterial network that supplies the human spinal cord, which was once thought to be similar to that of the brain, is in fact much different and more extensive. In this article, the authors attempt to provide a comprehensive review of the literature regarding the anatomy and known hemodynamics of the blood supply to the human spinal cord. Additionally, as the medical literature often fails to provide accurate terminology for the arteries that supply the cord, the authors attempt to categorize and clarify this nomenclature. A complete understanding of the morphology of the arterial blood supply to the human spinal cord is important to anatomists and clinicians alike.


Sustainable approaches to the management of plant-parasitic nematodes and disease complexes.
Physical, chemical, and biological factors of soil may reduce damage caused by plant-parasitic nematodes. Suppression of plant-parasitic nematodes is particularly challenging in soils in which there are short crop sequences, sequential susceptible host crops, or infestations of multiple nematode species. In southern Indiana, a watermelon production system involving rotations with soybean and corn does not suppress Meloidogyne incognita, but several aspects of such systems can be modified to reduce nematode damage in an integrated management approach. Cash crops with resistance to M. incognita can be used to reduce population densities of M. incognita. Small grains as cover crops can be replaced by cover crops with resistance to M. incognita or by crops with biofumigation potential. Mycorrhizal fungal inoculations of potting mixes during transplanting production of watermelon seedlings may improve early crop establishment. Other approaches to nematode management utilize soil suppressiveness. One-year rotations of soybean with corn neither reduced the soil-borne complex of sudden death syndrome (SDS) nor improved soybean root health over that in soybean monoculture. Reduced tillage combined with crop rotation may reduce the activity of soil-borne pathogens in some soils. For example in a long-term trial, numbers of Heterodera glycines and severity of foliar SDS symptoms were reduced under minimum tillage. Thus, sustainable management strategies require holistic approaches that consider entire production systems rather than focus on a single crop in its year of production.


Analgesic Effect of Valerian Root and Turnip Extracts.
Medicinal plants are considered as one of the important sources of chemical substances with therapeutic effects. This study aimed to compare the analgesic effects of alcoholic extract of valerian root and turnip in rats. Fifty female Wistar rats weighing 190 g were divided into 5 equal groups of control (subcutaneous injection of 2.5% formalin in the right foot), sham (subcutaneous injection of 2.5% formalin+distilled water), experimental 1 (subcutaneous injection of 2.5% formalin+200 mg/kg turnip extract), experimental 2 (subcutaneous injection of 2.5% formalin 2+200 mg/kg valerian root extract) and experimental 3 (subcutaneous injection of 2.5% formalin+200 mg/kg turnip extract+200 mg/kg valerian root extract). The time duration of 0-5 and 16-60 minutes after injection of formalin were respectively considered as acute and chronic phases. Injection of distilled water and the extracts was conducted 30 minutes before assessing the analgesic effects. A significant decrease in pain score in the acute phase was observed in the group received valerian root extract compared to the control group. Also, a significant reduction in pain score was noted in the acute and chronic phases of the group receiving simultaneous administration of valerian root and turnip extracts when compared to the control group. Simultaneous use of valerian root and turnip extracts is recommended for analgesic effects in both acute and chronic phases of the pain.


Boundary genes in regulation and evolution of secondary growth.
Many extant land plants display secondary growth originating in a lateral meristem known as vascular cambium. A conspicuous product of secondary growth is wood which dominates terrestrial ecosystem biomass. Despite the economic and ecological significance of the process the underlying molecular mechanism are still poorly understood. We have recently shown that members of the LBD transcription factor family play function in control of secondary growth. Here we propose a mechanistic model of LBD regulatory roles. We also show how these roles may be linked to evolutionary changes in level and pattern of wood formation that provide structural and functional innovations in wood anatomy in relation to species growth habit and biology.


Four-quadrant gratings moiré fringe alignment measurement in proximity lithography.
This paper aims to deal with a four-quadrant gratings alignment method benefiting from phase demodulation for proximity lithography, which combines the advantages of interferometry with image processing. Both the mask alignment mark and the wafer alignment mark consist of four sets of gratings, which bring the convenience and simplification of realization for coarse alignment and fine alignment. Four sets of moiré fringes created by superposing the mask alignment mark and the wafer alignment mark are highly sensitive to the misalignment between them. And the misalignment can be easily determined through demodulating the phase of moiré fringe without any external reference. Especially, the period and phase distribution of moiré fringes are unaffected by the gap between the mask and the wafer, not excepting the wavelength of alignment illumination. Disturbance from the illumination can also be negligible, which enhances the technological adaptability. The experimental results bear out the feasibility and rationality of our designed approach.


Neural network predictions of (α,n) reaction cross sections at 18.5±3 MeV using the Levenberg-Marquardt algorithm.
In recent developments, artificial neural networks (ANNs) have demonstrated their capability to predict reaction cross-sections based on experimental data. Specifically, for predicting (α,n) reaction cross-sections, we meticulously fine-tuned the neural network's performance by optimizing its parameters through the Levenberg-Marquardt algorithm. The effectiveness of this approach is corroborated by notable correlation coefficients; an R-value of 0.90928 for overall correlation, 0.98194 for validation, 0.99981 for testing, and 0.94116 for the comprehensive network prediction. We conducted a rigorous comparison between the results and theoretical computations derived from the TALYS 1.95 nuclear code to validate the predictive accuracy. The mean square error value for artificial neural network results is 7620.92, whereas for TALYS 1.95 calculations, it has been found to be 50,312.74. This comprehensive evaluation process validates the reliability of the ANN based on the Levenberg-Marquardt algorithm in approximating the reaction sections, thus demonstrating its potential for comprehensive investigations. These recent developments confirm the feasibility of using ANN models to gain insight into (α,n) reaction cross-sections.


ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists Number 36, July 2002. Obstetric analgesia and anesthesia.
Labor results in severe pain for many women. There is no other circumstance in which it is considered acceptable for a person to experience untreated severe pain, amenable to safe intervention, while under a physician's care. In the absence of a medical contraindication, maternal request is a sufficient medical indication for pain relief during labor. Pain management should be provided whenever it is medically indicated. The purpose of this document is to help obstetrician-gynecologists understand the available methods of pain relief to facilitate communication with their colleagues in the field of anesthesia, thereby, optimizing patient comfort while minimizing the potential for maternal and neonatal morbidity and mortality.


Bilateral total hip arthroplasty in siblings with Stickler Syndrome.
Stickler Syndrome is an infrequent autosomal dominant connective tissue disorder. The most prevalent mutation affects type II collagen gene and results in abnormalities in cartilage, vitreous and nucleus pulposus. Orthopaedic manifestations include joint hyper- mobility and pain with early development of secondary osteoarthritis. The condition has a predilection for the femoral head and patients usually present in their third to fourth decade with secondary hip arthritis. We report on two siblings with Stickler Syndrome who presented with hip osteoarthritis in their third decade of life and underwent staged bilateral total hip arthroplasties (THA). The patients experienced pain relief and improved quality of life after surgery.


Effect of inhibitors of plant cell division on mammalian tumor cells in vitro.
We studied the activity of 14 compounds, all of which have been shown to interfere in plant cell division, in two animal tumor cell cultures, EL-4 and L1210. Four compounds [propham, chlorpropham, bensulide S-(O,O-diisopropylphosphorodithioate) ester of N-(2-mercaptoethyl)benzenesulfonamide), and siduron] had a 50% inhibitory dose less than 10(-4) M; six [2,3,5-triiodobenzoic acid, (2,4-dichlorophenoxy)acetic acid, bromacil, (2,4,5-trichlorophenoxy)acetic acid, naptalam, and (4-chloro-2-methylphenoxy)acetic acid] had a 50% inhibitory dose between 10(-4) and 10(-3) M, and the remaining four 2,3:4,6-di-O-isopropylidene-2-keto-L-gulonate, eptam, maleic hydrazide, and 4-(methylsulfonyl)-2,6-dinitro-N,N,-dipropylaniline] had a 50% inhibitory dose at higher than 10(-3) M. There was a significant correlation between the effect on the two cell lines as well as between the inhibition of cell proliferation and that of thymidine and leucine uptake. More detailed study of cell proliferation and leucine and thymidine uptake for bensulide and 2,3,5-triiodobenzoic acid revealed a dose-response pattern of inhibition starting shortly after exposure of the cells to the compounds. These results indicate that some inhibitors of plant cell division are capable of inhibiting the proliferation of animal tumor cells.


Birth Cohort Differences in Sexual Identity Development Milestones Among HIV-Negative Gay and Bisexual Men in the United States.
The coming-out process for gay and bisexual men (GBM) involves crossing sexual identity development (SID) milestones: (1) self-awareness of sexual attraction to the same sex, (2) self-acceptance of an identity as gay or bisexual, (3) disclosure of this sexual identity to others, and (4) having sex with someone of the same sex. We examined trends in SID milestones by birth cohort in a 2015 U.S. national sample of GBM (n = 1,023). Birth cohort was independent of when men first felt sexually attracted to someone of the same sex (median age 11 to 12). However, with the exception of age of first same-sex attraction, older cohorts tended to pass other milestones at later ages than younger cohorts. Latent class analysis (LCA) of SID milestone patterns identified three subgroups. The majority (84%) began sexual identity development with same-sex attraction around the onset of puberty (i.e., around age 10) and progressed to self-identification, same-sex sexual activity, and coming out-in that order. The other two classes felt same-sex attraction during teen years (ages 12.5 to 18.0) but achieved the remaining SID milestones later in life. For 13% of men, this was during early adulthood; for 3% of men, this was in middle adulthood. Findings highlight the need to monitor ongoing generational differences in passing SID milestones.


Implementing stroke care in a lower-middle-income country: results and recommendations based on an implementation study within the Nepal Stroke Project.
Globally, the majority of strokes affect people residing in lower- and lower-middle-income countries (LMICs), but translating evidence-based knowledge into clinical practice in regions with limited healthcare resources remains challenging. As an LMIC in South Asia, stroke care has remained a healthcare problem previously unaddressed at a national scale in Nepal. The Nepal Stroke Project (NSP) aims to improve acute stroke care in the tertiary healthcare sector of Nepal. We hereby describe the methods applied and analyze the barriers and facilitators of the NSP after 18 months. The NSP follows a four-tier strategy: (1) quality improvement by training healthcare professionals in tertiary care centers; (2) implementation of in-hospital stroke surveillance and quality monitoring system; (3) raising public awareness of strokes; and (4) collaborating with political stakeholders to facilitate public funding for stroke care. We performed a qualitative, iterative analysis of observational data to analyze the output indicators and identify best practices. Both offline and online initiatives were undertaken to address quality improvement and public awareness. More than 1,000 healthcare professionals across nine tertiary care hospitals attended 26 stroke-related workshops conducted by Nepalese and international stroke experts. Monthly webinars were organized, and chat groups were made for better networking and cross-institutional case sharing. Social media-based public awareness campaigns reached more than 3 million individuals. Moreover, live events and other mass media campaigns were instituted. For quality monitoring, the Registry of Stroke Care Quality (RES-Q) was introduced. Collaboration with stakeholders (both national and international) has been initiated. We identified six actions that may support the development of tertiary care centers into essential stroke centers in a resource-limited setting. We believe that our experiences will contribute to the body of knowledge on translating evidence into practice in LMICs, although the impact of our results must be verified with process indicators of stroke care.


[Assessment of electrical conductivity in the points of mastoid region of the head in patients with blood circulation disorders in vertebrobasilar vessels].
The conductivity of the points of mastoid region of the head in 145 patients with blood circulation disorders in vertebrobasilar vessels has been measured to determine reliability of electropuncture diagnostics in patients with such a condition. The measured indices significantly differentiated from indices of the control group. The method also showed the significant difference among groups of patients varied by severity of the pathological process. It enables to discern the pathology and substantiate the use of method.


Repeat posterior fossa exploration for patients with persistent or recurrent idiopathic trigeminal neuralgia.
Patients with trigeminal neuralgia (TN) and persistent or recurrent facial pain after microvascular decompression (MVD) typically undergo less invasive procedures in the hope of providing pain relief. The outcomes and risks of repeat posterior fossa exploration (PFE) for these patients are not clearly understood. From September 2000 to November 2006, 29 patients (14 men, 15 women) underwent repeat PFE. The mean number of surgeries per patient at the time of repeat PFE was 3.2 (range 1-6). The mean follow-up duration after surgery was 33.7 months. Compression of the trigeminal nerve was noted in 24 patients (83%) by an artery (13 patients, 45%), vein (4 patients, 14%), or Teflon (7 patients, 24%). Four patients (14%) who underwent operations elsewhere had incorrect cranial nerves decompressed at their first surgery. Only MVD was performed in 18 patients (62%) and a partial nerve section (PNS) was performed in 11 patients (38%). An excellent facial pain outcome (no pain, no medications required) was achieved and maintained for 80% and 75% of patients at 1 and 3 years after surgery, respectively. Patients with Burchiel Type 1 TN were pain free without medications (91% at 1 year and 85% at 3 years) more frequently than patients with Burchiel Type 2 TN (27% at both 1 and 3 years; hazard ratio = 5.4, 95% confidence interval 1.4-21.1, p = 0.02). Fifteen patients (52%) had new or increased facial numbness. Two patients (7%) developed anesthesia dolorosa; both had undergone PNS. Two patients (7%) had hearing loss after surgery. Repeat PFE for patients with idiopathic TN has facial pain outcomes that are comparable with both percutaneous needle-based techniques and stereotactic radiosurgery. Patients with persistent or recurrent TN should be considered for repeat PFE, especially if other less invasive surgeries have not relieved their facial pain.


Comparative studies of the antilipolytic effect of insulin and adenosine in the perifused isolated fat cell.
Insulin and adenosine are both antilipolytic when studied in the epinephrine-stimulated perifused isolated fat cell. Submaximal combinations of insulin plus adenosine are additive but not synergistic. The polypeptide hormone insulin produces an antilipolytic effect which manifests itself as a "lag" in restoration of epinephrine-stimulated lipolysis after removal of the insulin. No such lag is observed with the non-peptide, small molecular weight adenosine. Herein, we demonstrate the antilipolytic effect of two distinct, physiologically important agents in the perifused isolated fat cell.


Effects of dietary interventions on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones.
The aim of this study is to investigate the effects of dietary factors on 24-hour urine parameters in patients with idiopathic recurrent calcium oxalate stones. A total of 108 of idiopathic recurrent calcium oxalate stones were included in the study. A 24-hour urinalysis was performed and metabolic abnormalities were measured for all of the patients. All of the patients were given specialized diets for their 24-hour urine abnormalities. At the end of first month, the same parameters were examined in another 24-hour urinalysis. Hyperoxaluria, hypernatruria, and hypercalciuria were found in 84 (77%), 43 (39.8%), and 38 (35.5%) of the patients, respectively. The differences between the oxalate, sodium, volume, uric acid, and citrate parameters before and after the dietary intervention were significant (p < 0.05). The calcium parameters were not significantly different before and after the intervention. We found that oxalate, sodium, volume, uric acid, and citrate-but not calcium-abnormalities in patients with recurrent calcium oxalate stones can be corrected by diet. The metabolic profiles of idiopathic calcium oxalate stone patients should be evaluated and the appropriate dietary interventions should be implemented to decrease stone recurrence.


Transmission line model for simulation of guided-wave defect signals in piping.
A simple transmission line model for analytically simulating the guided-wave signal reflected from a volumetric defect of arbitrary shape in piping is described. In the model, the guided-wave interaction with a defect is treated as the one-dimensional problem of plane wave reflection from a boundary of multilayered media of different acoustic impedances in a transmission line. Results of simulation show good qualitative agreement with experimentally measured signals.


Optical nanomanipulations of malignant cells: controlled cell damage and fusion.
Specifically targeting and manipulating living cells is a key challenge in biomedicine and in cancer research in particular. Several studies have shown that nanoparticles irradiated by intense lasers are capable of conveying damage to nearby cells for various therapeutic and biological applications. In this work ultrashort laser pulses and gold nanospheres are used for the generation of localized, nanometric disruptions on the membranes of specifically targeted cells. The high structural stability of the nanospheres and the resonance pulse irradiation allow effective means for controlling the induced nanometric effects. The technique is demonstrated by inducing desired death mechanisms in epidermoid carcinoma and Burkitt lymphoma cells, and initiating efficient cell fusion between various cell types. Main advantages of the presented approach include low toxicity, high specificity, and high flexibility in the regulation of cell damage and cell fusion, which would allow it to play an important role in various future clinical and scientific applications.


Multivariate analysis of male reproductive function in Inpp5b-/- mice reveals heterogeneity in defects in fertility, sperm-egg membrane interaction and proteolytic cleavage of sperm ADAMs.
Past work indicated that sperm from mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b have reduced ability to fertilize eggs in vitro and reduced epididymal proteolytic processing of the sperm protein A Disintegrin and A Metalloprotease 2 (ADAM2). On the basis of these data, our central working hypothesis was that reduced ADAM cleavage would correlate with reduced sperm-egg binding and fusion and in turn with reduced male fertility in Inpp5b(-/-) mice. Multiple endpoints of reproductive functions [mating trials, in vitro fertilization (IVF) assays and ADAM2 and ADAM3 cleavage] were investigated on a male-by-male basis, with pair-wise correlation analysis used to assess the relationships between these various parameters. Motile sperm from Inpp5b(-/-) mice showed significantly reduced fertilization of zona pellucida-free eggs due to reduced binding to the egg plasma membrane and subsequent fusion. Localization of a mouse sperm protein required for gamete fusion, IZUMO1, appears normal in Inpp5b-null sperm. To our surprise and differing from previous reports, we found that ADAM cleavage was only modestly impaired in numerous Inpp5b-null males and varied between individual animals. Performance in mating trials also differed from past reports. The pair-wise correlation analysis revealed that ADAM2 and ADAM3 cleavage was positively correlated, suggesting that processing of these proteins occurs by related/identical mechanisms, but otherwise, there were few correlations between the reproductive endpoints examined here. Nevertheless, this work provides detailed analysis of the Inpp5b(-/-) phenotype and also a blueprint for multivariate analysis to examine relationships between molecular characteristics and in vitro and in vivo physiological functions.


Automated fiber tract reconstruction for surgery planning: Extensive validation in language-related white matter tracts.
Diffusion MRI and tractography hold great potential for surgery planning, especially to preserve eloquent white matter during resections. However, fiber tract reconstruction requires an expert with detailed understanding of neuroanatomy. Several automated approaches have been proposed, using different strategies to reconstruct the white matter tracts in a supervised fashion. However, validation is often limited to comparison with manual delineation by overlap-based measures, which is limited in characterizing morphological and topological differences. In this work, we set up a fully automated pipeline based on anatomical criteria that does not require manual intervention, taking advantage of atlas-based criteria and advanced acquisition protocols available on clinical-grade MRI scanners. Then, we extensively validated it on epilepsy patients with specific focus on language-related bundles. The validation procedure encompasses different approaches, including simple overlap with manual segmentations from two experts, feasibility ratings from external multiple clinical raters and relation with task-based functional MRI. Overall, our results demonstrate good quantitative agreement between automated and manual segmentation, in most cases better performances of the proposed method in qualitative terms, and meaningful relationships with task-based fMRI. In addition, we observed significant differences between experts in terms of both manual segmentation and external ratings. These results offer important insights on how different levels of validation complement each other, supporting the idea that overlap-based measures, although quantitative, do not offer a full perspective on the similarities and differences between automated and manual methods.


Cholinergic leukocytes in sepsis and at the neuroimmune junction in the spleen.
The spleen is a key participant in the pathophysiology of sepsis and inflammatory disease. Many splenocytes exhibit a cholinergic phenotype, but our knowledge regarding their cholinergic biology and how they are affected by sepsis is incomplete. We evaluated effects of acute sepsis on the spleen using the cecal ligation and puncture (CLP) model in C57BL/6 and ChATBAC-eGFP mice. Quantification of cholinergic gene expression showed that choline acetyltransferase and vesicular acetylcholine transporter (VAChT) are present and that VAChT is upregulated in sepsis, suggesting increased capacity for release of acetylcholine (ACh). High affinity choline transporter is not expressed but organic acid transporters are, providing additional mechanisms for release. Flow cytometry studies identified subpopulations of cholinergic T and B cells as well as monocytes/macrophages. Neither abundance nor GFP intensity of cholinergic T cells changed in sepsis, suggesting that ACh synthetic capacity was not altered. Spleens have low acetylcholinesterase activity, and the enzyme is localized primarily in red pulp, characteristics expected to favor cholinergic signaling. For cellular studies, ACh was quantified by mass spectroscopy using d4-ACh internal standard. Isolated splenocytes from male mice contain more ACh than females, suggesting the potential for gender-dependent differences in cholinergic immune function. Isolated splenocytes exhibit basal ACh release, which can be increased by isoproterenol (4 and 24 h) or by T cell activation with antibodies to CD3 and CD28 (24 h). Collectively, these data support the concept that sepsis enhances cholinergic function in the spleen and that release of ACh can be triggered by stimuli via different mechanisms.


Role of NF kappa B activator Act1 in CD40-mediated signaling in epithelial cells.
CD40, a cell surface receptor in the tumor necrosis factor receptor family, first identified and functionally characterized on B lymphocytes, is also expressed on epithelial and other cells and is now thought to play a more general role in immune regulation. Overexpression of the NF kappa B activator 1 (Act1) leads to the activation of both NF kappa B and Jun kinase in epithelial cell lines. Endogenous Act1 is recruited to the CD40 receptor in human intestinal (HT29) and cervical (HeLa) epithelial cells upon stimulation with CD40 ligand, indicating that Act1 is involved in this signaling pathway. Act1 also interacts with tumor necrosis factor receptor-associated factor 3, a component involved in CD40-activated pathway. Furthermore, transfection of Act1 into C33A cervical epithelial cells, which do not express it, renders these cells sensitive to CD40 ligand-induced NF kappa B activation and protects them from CD40 ligand-induced apoptosis. We conclude that Act1 plays an important role in CD40-mediated signaling in epithelial cells.


Phosphate Deficiency Induces the Jasmonate Pathway and Enhances Resistance to Insect Herbivory.
During their life cycle, plants are typically confronted by simultaneous biotic and abiotic stresses. Low inorganic phosphate (Pi) is one of the most common nutrient deficiencies limiting plant growth in natural and agricultural ecosystems, while insect herbivory accounts for major losses in plant productivity and impacts ecological and evolutionary changes in plant populations. Here, we report that plants experiencing Pi deficiency induce the jasmonic acid (JA) pathway and enhance their defense against insect herbivory. Pi-deficient Arabidopsis (Arabidopsis thaliana) showed enhanced synthesis of JA and the bioactive conjugate JA-isoleucine, as well as activation of the JA signaling pathway, in both shoots and roots of wild-type plants and in shoots of the Pi-deficient mutant pho1 The kinetics of the induction of the JA signaling pathway by Pi deficiency was influenced by PHOSPHATE STARVATION RESPONSE1, the main transcription factor regulating the expression of Pi starvation-induced genes. Phenotypes of the pho1 mutant typically associated with Pi deficiency, such as high shoot anthocyanin levels and poor shoot growth, were significantly attenuated by blocking the JA biosynthesis or signaling pathway. Wounded pho1 leaves hyperaccumulated JA/JA-isoleucine in comparison with the wild type. The pho1 mutant also showed an increased resistance against the generalist herbivore Spodoptera littoralis that was attenuated in JA biosynthesis and signaling mutants. Pi deficiency also triggered increased resistance to S. littoralis in wild-type Arabidopsis as well as tomato (Solanum lycopersicum) and Nicotiana benthamiana, revealing that the link between Pi deficiency and enhanced herbivory resistance is conserved in a diversity of plants, including crops.


[Biological action and complex-forming properties of a macrotetrolide antibiotic complex].
Macrotetrolide antibiotic complexes containing 60-80 per cent of nonactin were studied and their high antibacterial activity was shown. The macrotetrolides had a disintegrating effect on the bacterial membrane, which was evident from induction of the protoplast lysis and release of low-molecular compounds from the bacterial cells. The complex-forming properties of nonactin with respect to the ammonium, potassium and sodium ions were investigated in vitro. The selectivity level with respect to the ammonium ions was higher. Nonactin incorporated into an artificial membrane provided a linear dependence of the delta mV on the ammonium chloride concentration within the ranges of 10(-1)-10(-5) M.


An Observational Assessment of Anesthesia Capacity in Madagascar as a Prerequisite to the Development of a National Surgical Plan.
The global lack of anesthesia capacity is well described, but country-specific data are needed to provide country-specific solutions. We aimed to assess anesthesia capacity in Madagascar as part of the development of a Ministry of Health national surgical plan. As part of a nationwide surgical safety quality improvement project, we surveyed 19 of 22 regional hospitals, representing surgical facilities caring for 75% of the total population. The assessment was divided into 3 areas: anesthesia workforce density, infrastructure and equipment, and medications. Data were obtained by semistructured interviews with Ministry of Health officials, hospital directors, technical directors, statisticians, pharmacists, and anesthesia providers and through on-site observations. Interview questions were adapted from the World Health Organization Situational Analysis Tool and the World Federation of Societies of Anaesthesiologists International Standards for Safe Practice of Anaesthesia. Additional data on workforce density were collected from the 3 remaining regions so that workforce density data are representative of all 22 regions. Anesthesia physician workforce density is 0.26 per 100,000 population and 0.19 per 100,000 outside of the capital region. Less than 50% of hospitals surveyed reported having a reliable electricity and oxygen supply. The majority of anesthesia providers work without pulse oximetry (52%) or a functioning vaporizer (52%). All the hospitals surveyed had very basic pediatric supplies, and none had a pediatric pulse oximetry probe. Ketamine is universally available but more than 50% of hospitals lack access to opioids. None of the 19 regional hospitals surveyed was able to completely meet the World Federation of Societies of Anaesthesiologists' standards for monitoring. Improving anesthesia care is complex. Capacity assessment is a first step that would enable progress to be tracked against specific targets. In Madagascar, scale-up of the anesthesia workforce, investment in infrastructure and equipment, and improvement in medication supply-chain management are needed to attain minimal international standards. Data from this study were presented to the Ministry of Health for inclusion in the development of a national surgical plan, together with recommendations for the needed improvements in the delivery of anesthesia.


Progesterone receptor modulator CDB-2914 down-regulates proliferative cell nuclear antigen and Bcl-2 protein expression and up-regulates caspase-3 and poly(adenosine 5'-diphosphate-ribose) polymerase expression in cultured human uterine leiomyoma cells.
The present study was conducted to evaluate the effects of the progesterone receptor modulator CDB-2914 on proliferative activity and apoptosis in cultured human uterine leiomyoma cells. Isolated leiomyoma cells were subcultured in phenol red-free DMEM supplemented with 10% fetal bovine serum for 120 h and then stepped down to serum-free conditions for 12, 24, 48, and 96 h in the absence or presence of graded concentrations of CDB-2914 (10(-9), 10(-8), 10(-7), and 10(-6) M). The number of viable cultured leiomyoma cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazodium bromide assay. Proliferating cell nuclear antigen (PCNA) expression was evaluated by immunocytochemistry and Western blot analysis. Apoptosis was examined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) assay. Caspase-3, cleaved poly(ADP-ribose) polymerase (PARP), and Bcl-2 expression were assessed by Western blot analysis. Compared with untreated control cultures, treatment with CDB-2914 decreased the number of viable cultured leiomyoma cells and the PCNA-positive rate in those cells and increased the TUNEL-positive rate in cultured leiomyoma cells in a dose-dependent manner. Western blot analysis revealed that treatment with CDB-2914 significantly decreased the expression of PCNA and Bcl-2 protein and increased the expression of cleaved caspase-3 and cleaved PARP in a dose-dependent manner compared with untreated control cultures. These results suggest that CDB-2914 inhibits the proliferation of cultured leiomyoma cells by down-regulating PCNA expression and induces apoptosis by up-regulating cleaved caspase-3 and PARP expression and down-regulating Bcl-2 protein expression in those cells.


A technology-assisted life of recovery from psychosis.
Developments in digital health technologies have the potential to expedite and strengthen the path towards recovery for people with psychosis. This perspective piece provides a snapshot of how a range of digital technologies can be deployed to support a young adult's efforts to cope with schizophrenia-spectrum illness. In conjunction with a day in the life of this individual, we provide examples of innovations in digital health research designed for this clinical population, as well as brief summaries of the evidence supporting the usability, feasibility, or effectiveness of each approach. From early detection to ongoing symptom management and vocational rehabilitation, this day-in-the-life vignette provides an overview of the ways in which digital health innovations could be used in concert to augment, scaffold, and enhance schizophrenia-spectrum illness management and recovery.


[Burn injuries to military personnel during the Six Day War].
About 2500 soldiers were injured during the Six Day War (June 1967) of whom 115 suffered from burns. In 34 of them 15% or more of their body surface was involved and 11 died. Typical features of these burn cases were supplementary injuries, a high rate of infection, and long periods of hospitalization. Prophylactic antibiotics were not useful. The general condition of many deteriorated during the first week after injury, indicating the importance of treating severe burns in specialized facilities.


A microfluidic gradient device for drug screening with human iPSC-derived motoneurons.
We developed a microfluidic gradient device to utilize as a drug screening system with human induced pluripotent stem cell (hiPSC)-derived motoneurons. The microfluidic channel was asymmetrically designed to generate the concentration gradients and a micropillar array was used to trap and culture the motoneuron spheroids containing motoneurons for 9 days. We optimized the concentration gradients in the microfluidic device using a computational fluid dynamics (CFD) model. We also observed that the motoneuron spheroid-derived neurite network was generated in response to the concentration gradients of riluzole in the microfluidic device. Therefore, this microfluidic gradient device could be useful for screening of various drugs for neurological disease applications.


[Endovascular treatment in diseases of the thoracic aorta].
To determine whether endovascular treatment of thoracic aorta conditions can be an effective alternative approach to surgical repair. July 1997 to February 1999, eighteen patients (16 men and 2 women; 58.6 +/- 14.8 years) presenting with different kinds of descending aorta conditions were selected for the endovascular treatment. All patients exhibited severe comorbid pulmonary and/or cardiovascular medical conditions which increased surgical risk. All implants were performed in the operating room under fluoroscopic and TEE guidance. Clinical and imaging follow-up was performed 1, 3, 6 and 12 months later. The endovascular treatment was successful in 17 cases. No deaths or major complications occurred. No leakage was evident at post-procedure angiography. The patients were discharged after 6 +/- 4 days. MRI or CT study performed before hospital discharge showed aneurysms exclusion in 16 patients. In the four cases of dissection, thrombosis of the false lumen was evident since the first follow-up study. In the group of patients (11 cases) with 6 months follow-up, the diameters of stented aortic segments decreased. No late leakage was observed and thrombosis was complete in all cases. The natural history of aortic aneurysms and dissection is progressive toward dilation and aortic rupture. Surgery of descending thoracic aorta is burdened with a mortality of 8-12% in elective cases and over 50% in emergency cases or aortic dissection. The endovascular treatment of aortic conditions was introduced in clinical practice in 1991 and literature data show that it is effective, with lower mortality and morbidity rates than surgical treatment. Our results stress the feasibility and effectiveness of endovascular procedure in the treatment of complex thoracic aorta conditions even in high risk patients. Thus, endovascular treatment of thoracic aorta can be considered an effective alternative approach to conventional surgery.


A Proposal for a Genome Similarity-Based Taxonomy for Plant-Pathogenic Bacteria that Is Sufficiently Precise to Reflect Phylogeny, Host Range, and Outbreak Affiliation Applied to Pseudomonas syringae sensu lato as a Proof of Concept.
Taxonomy of plant pathogenic bacteria is challenging because pathogens of different crops often belong to the same named species but current taxonomy does not provide names for bacteria below the subspecies level. The introduction of the host range-based pathovar system in the 1980s provided a temporary solution to this problem but has many limitations. The affordability of genome sequencing now provides the opportunity for developing a new genome-based taxonomic framework. We already proposed to name individual bacterial isolates based on pairwise genome similarity. Here, we expand on this idea and propose to use genome similarity-based codes, which we now call life identification numbers (LINs), to describe and name bacterial taxa. Using 93 genomes of Pseudomonas syringae sensu lato, LINs were compared with a P. syringae genome tree whereby the assigned LINs were found to be informative of a majority of phylogenetic relationships. LINs also reflected host range and outbreak association for strains of P. syringae pathovar actinidiae, a pathovar for which many genome sequences are available. We conclude that LINs could provide the basis for a new taxonomic framework to address the shortcomings of the current pathovar system and to complement the current taxonomic system of bacteria in general.


Proteomic characterization of the cellular response to chemopreventive triterpenoid astragaloside IV in human hepatocellular carcinoma cell line HepG2.
Triterpenoids are implicated in the chemoprevention of various cancers. Current challenge is to define the molecular mechanism underlying the chemopreventive activity of triterpenoids. This study was designed to characterize the intracellular proteins regulated by astragaloside IV, the major active triterpenoid in Radix Astragali. Upon the treatment with astragaloside IV, human hepatocellular carcinoma HepG2 cells were evaluated for the colonogenic survival and anchorage-independent growth. The cellular proteins of treated and untreated cells were resolved by 2-D polyacrylamide gel electrophoresis. The protein spots mostly altered by drug treatment were identified by mass spectrometry and subsequently verified by Western blotting using specific antibodies and RT-PCR technique using specific DNA primers. We found that astragaloside IV attenuated the colonogenic survival and anchorage-independent growth of cancer cells. Based on the proteomic profiles, top 14 upregulated and 13 down-regulated protein spots were subjected to mass spectrometric analysis. As an example, Vav3.1 belongs to the oncogene Vav family, which is implicated in tumorigenesis. Vav3.1 expression was down-regulated by astragaloside IV in a dose- and time-dependent manner. Down-regulation of Vav3.1 was highly correlated with the suppression of cell malignant transform. Thus, astragaloside IV may elicit anticancer activity via down-regulating the expression of oncogenes such as Vav3.1.


Treatment of capitellar osteochondritis dissecans with a tendon graft: a case report.
A 14-year-old girl who was engaged in farming was admitted with the complaints of right elbow pain and limited range of motion in the elbow joint. Plain radiograph revealed capitellar osteochondritis dissecans. After the loose fragment was removed from the capitellum and the defect was curetted, a palmaris longus tendon graft harvested from the same hand was implanted into the capitellar defect. Elbow joint was immobilized for three weeks. Magnetic resonance imaging showed that tendon graft was successfully adapted into defect. The range of motion was preserved and she had no pain in the elbow joint. In conclusion, we suggest that tendon autograft can be used in the treatment of capitellar osteochondritis dissecans.


Rational design of 5-aminolevulinic acid derivatives aimed at improving photodynamic therapy.
5-aminolevulinic acid (ALA) is the first intermediate in heme biosynthesis and is therefore a precursor of protoporphyrin IX (PpIX). PpIX is used as an endogenous photosensitizer in photodynamic therapy (PDT). Several chemical modifications have been made, both on the amino and carboxyl groups of ALA to induce higher PpIX production and photosensitisation. Esterification of ALA with aliphatic lineal and cyclic alcohols was found to reduce the amount of ALA required for photosensitization. Esterification by aliphatic alcohols with carbohydrate chains equal or lower than C4 leads to porphyrin accumulation lower than ALA, whereas equal or longer than C6 chains leads to greater synthesis of porphyrin. A branch point in the alcohol located next to the site of ester cleavage limits access of the esters to the esterase active site, resulting in lower PpIX production. ALA esters of the polyethylenglycol family can induce high levels of PpIX, with some selectivity for endothelial cells toward tumor cells. On the basis of the differential expression of some aminopeptidases in tumor vasculature when compared to normal vasculature, some ALA-pseudopeptides were synthesized. In a rational design of ALA derivatives, the transport mechanism of these aminoacids into the cell is central. Due to the similar characteristics between ALA and GABA transport, a novel approach for designing new ALA derivatives which could penetrate more easily into tumoral cells, would be to take into account the structures of the inhibitors of GABA transport.


Single-Cell Probe Force Studies to Identify Sox2 Overexpression-Promoted Cell Adhesion in MCF7 Breast Cancer Cells.
The replacement of the cantilever tip by a living cell in Atomic Force Microscopy (AFM) experiments permits the direct quantification of cell-substrate and cell-cell adhesion forces. This single-cell probe force measurement technique, when complemented by microscopy, allows controlled manipulation of the cell with defined location at the area of interest. In this work, a setup based on two glass half-slides, a non-fouling one with bacterial S-layer protein SbpA from L. sphaericus CMM 2177 and the second with a fibronectin layer, has been employed to measure the adhesion of MCF7 breast cancer cells to fibronectin films (using SbpA as control) and to other cells (symmetric vs. asymmetric systems). The measurements aimed to characterize and compare the adhesion capacities of parental cells and cells overexpressing the embryonic transcription factor Sox2, which have a higher capacity for invasion and are more resistant to endocrine therapy in vivo. Together with the use of fluorescence techniques (epifluorescence, Total Internal Fluorescence Microscopy (TIRF)), the visualization of vinculin and actin distribution in cells in contact with fibronectin surfaces is enabled, facilitating the monitoring and quantification of the formation of adhesion complexes. These findings demonstrate the strength of this combined approach to assess and compare the adhesion properties of cell lines and to illustrate the heterogeneity of adhesive strength found in breast cancer cells.


In vivo MRI volumetric measurement of prostate regression and growth in mice.
Mouse models for treatment of late-stage prostate cancer are valuable tools, but assessing the extent of growth of the prostate and particularly its regression due to therapeutic intervention or castration is difficult due to the location, small size and interdigitated anatomy of the prostate gland in situ. Temporal monitoring of mouse prostate regression requires multiple animals and examination of histological sections. Initially, T2-weighted magnetic resonance imaging (MRI) was performed on normal year-old C57/BL6 mice. Individual mice were repeatedly imaged using inhalation anesthesia to establish the reproducibility of the method and to follow hormone manipulation of the prostate volume. Subsequently, MRI fat signal was suppressed using a chemical shift-selective (CHESS) pulse to avoid signal contamination and enhance discrimination of the prostate. High field (7T) MRI provides high resolution (117 x 117 microm in plane), highly reproducible images of the normal mouse prostate. Despite long imaging times, animals can be imaged repeatedly to establish reliability of volume measurements. Prostate volume declines following castration and subsequently returns to normal with androgen administration in the same animal. CHESS imaging allowed discrimination of both the margins of the prostate and the dorsal-lateral lobes of the prostate (DLP) from the ventral lobes (VP). Castration results in a 40% reduction in the volume of the DLP and a 75% reduction in the volume of the VP. MRI assessment of the volume of the mouse prostate is precise and reproducible. MRI improves volumetric determination of the extent of regression and monitoring of the same mouse over time during the course of treatment is possible. Since assessing groups of animals at each time point is avoided, this improves the accuracy of the measurement of any manipulation effect and reduces the number of animals required.


Tunable wrinkling pattern in annular graphene under circular shearing at inner edge.
This work is concerned with the wrinkling phenomenon observed in an annular graphene sheet under circular shearing at its inner edge. By performing molecular mechanics simulations on the aforementioned loaded annular graphene sheet, it is observed that the unusual wrinkles formed are confined to within an annulus that hugs the perimeter of the inner radius. This confined wrinkling pattern is in contrast to the wrinkling patterns that spread throughout rectangular graphene sheets under tension or shear. The present wrinkling pattern is characterized by a wave number and wrinkle profile. The wave number at the bifurcation wrinkle is found to depend only on the inner radius of the annular graphene and it increases almost linearly with increasing inner radius. The orientation of these developed waves is found to be at a constant angle and independent from the radii ratio of annular graphene. The wrinkle profile in terms of wave amplitude and wavelength depends on the magnitude of the circular shearing. The predictable formation of wrinkles in annular graphene can be exploited for applications in nano-force sensors, tunable magnetic or electronic devices, as well as patterned stretchable electronics.


Ocular surface disease in patients with glaucoma or ocular hypertension treated with either BAK-preserved latanoprost or BAK-free travoprost.
The preservative benzalkonium chloride (BAK) may adversely affect ocular surface health. This study evaluated symptoms of ocular surface disease (OSD) in patients previously treated with a BAK-preserved therapy to lower their intraocular pressure, who either continued that therapy or switched to a BAK-free therapy. Eligible adult patients with ocular hypertension or open-angle glaucoma that had been controlled with BAK-preserved latanoprost 0.005% monotherapy (Xalatan ®) for at least one month and had a score of ≥ 13 (0 = none, 100 = most severe) on the Ocular Surface Disease Index (OSDI) questionnaire were entered into this prospective, double-masked, randomized, active-controlled, multicenter trial. By random assignment, patients either continued with BAK-preserved latanoprost 0.005% or transitioned to BAK-free travoprost 0.004% (Travatan Z ® ophthalmic solution). OSDI scores were assessed again after six and 12 weeks. For the 678 evaluable patients, mean change in OSDI score from baseline to week 12 favored the travoprost 0.004% BAK-free group, but was not statistically different between groups (P = 0.10). When patients with mild OSD at baseline were assessed after 12 weeks, the mean OSDI score was significantly lower (P = 0.04) in the BAK-free travoprost 0.004% group (score = 11.6 ± 10.8 units) than in the BAK-preserved latanoprost 0.005% group (score = 14.4 ± 11.9 units), and a significantly larger percentage (P < 0.01) improved to normal OSDI scores in the BAK-free travoprost 0.004% group (62.9% of group) than in the BAK-preserved latanoprost 0.005% group (47.0% of group). Patients pretreated with BAK-preserved latanoprost 0.005% for >24 months were significantly more likely (P = 0.03) to improve to a normal OSDI score after 12 weeks if they were switched to BAK-free travoprost 0.004% (47.9% of group) than if they remained on BAK-preserved latanoprost 0.005% (33.9% of group). Switching from BAK-preserved latanoprost 0.005% to BAK-free travoprost 0.004% yielded significant improvements in symptoms of OSD in patients with glaucoma or ocular hypertension.


Atrial Fibrillation, Neurocognitive Decline and Gene Expression After Cardiopulmonary Bypass.
Atrial fibrillation and neurocognitive decline are common complications after cardiopulmonary bypass. By utilizing genomic microarrays we investigate whether gene expression is associated with postoperative atrial fibrillation and neurocognitive decline. Twenty one cardiac surgery patients were prospectively matched and underwent neurocognitive assessments pre-operatively and four days postoperatively. The whole blood collected in the pre-cardiopulmonary bypass, 6 hours after-cardiopulmonary bypass, and on the 4th postoperative day was hybridized to Affymetrix Gene Chip U133 Plus 2.0 Microarrays. Gene expression in patients who developed postoperative atrial fibrillation and neurocognitive decline (n=6; POAF+NCD) was compared with gene expression in patients with postoperative atrial fibrillation and normal cognitive function (n=5; POAF+NORM) and patients with sinus rhythm and normal cognitive function (n=10; SR+NORM). Regulated genes were identified using JMP Genomics 4.0 with a false discovery rate of 0.05 and fold change of >1.5 or <-1.5. Eleven patients developed postoperative atrial fibrillation. Six of these also developed neurocognitive decline. Of the 12 patients with sinus rhythm, only 2 developed neurocognitive decline. POAF+NCD patients had unique regulation of 17 named genes preoperatively, 60 named genes six hours after cardiopulmonary bypass, and 34 named genes four days postoperatively (P<0.05) compared with normal patients. Pathway analysis demonstrated that these genes are involved in cell death, inflammation, cardiac remodeling and nervous system function. Patients who developed postoperative atrial fibrillation and neurocognitive decline after cardiopulmonary bypass may have differential genomic responses compared to normal patients and patients with only postoperative atrial fibrillation, suggesting common pathophysiology for these conditions. Further exploration of these genes may provide insight into the etiology and improvements of these morbid outcomes.


Two low-molecular-weight Ca2+-binding proteins isolated from squid optic lobe by phenothiazine--Sepharose affinity chromatography.
We have isolated two Ca2+-binding proteins from squid optic lobes, each of which is also able to bind phenothiazines in a Ca2+-dependent manner. These proteins have each been purified and partly characterized. One of the proteins corresponds to calmodulin, in that it has a similar amino acid content to bovine brain calmodulin, including a single residue of trimethyl-lysine, it co-migrates with bovine calmodulin both on alkaline-urea- and on sodium dodecyl sulphate (SDS)/polyacrylamide-gel electrophoresis, and will activate calmodulin-dependent phosphodiesterase. The second protein has the same subunit molecular weight as calmodulin, as determined by SDS/polyacrylamide-gel electrophoresis, Mr 17 000, but migrates more slowly than this protein on alkaline-urea-gel electrophoresis. It has an amino acid composition distinct from calmodulin, containing no trimethyl-lysine, its CNBr fragments migrate on alkaline gels in a pattern distinct from those of calmodulin and it shows little ability to activate phosphodiesterase. The u.v.-absorption spectra of the proteins indicate the absence of tryptophan and the presence of a high phenylalanine/tyrosine ratio in each. Both proteins also bind 3-4 calcium ions/mol at 0.1 mM-free Ca2+ and each binds chlorpromazine in a Ca2+-dependent manner.


Brominated flame retardants in matched serum samples from Swedish first-time mothers and their toddlers.
Tri-decabrominated diphenyl ethers and 21 other flame retardants were determined in matched serum samples from 24 Swedish mothers (Uppsala county) and their toddlers (11-15 months of age). The median concentrations of individual polybrominated diphenyl ethers (PBDEs) ranged from 0.036 to 0.95 ng/g lipid in mothers and from 0.057 to 1.5 ng/g lipid in toddlers. BDE-209 was detected in all but one sample. BDE-153 was the predominant congener in the mothers while in toddlers, BDE-209 was found in the highest concentrations. The levels of BDE-47, -100, -207, -208, and -209 in toddlers were significantly higher (p < 0.05) than those in their mothers. Dechlorane Plus (anti- and syn-) and α- and β-tetrabromoethylcyclohexane were detected in a few (2-4) serum samples from both mothers and toddlers. This study also reports concentrations of α-HBCD and eight emerging brominated flame retardants (EBFRs) in the standard reference material serum (SRM 1958, NIST). Lack of correlations between the matched serum samples indicate different exposure routes for octa-decaBDEs in mothers versus toddlers. Congener-to-congener correlations within the mother or toddler cohorts suggest diet as an important exposure pathway for tetra-nonaBDEs for mothers, breastfeeding as a predominant exposure pathway for tetra-hexaBDEs, and dust for octa-decaBDEs for toddlers.


[Analysis of judicial sentences against neurosurgeons resolved in second court of justice in Spain in the period from 1995 to 2007].
With the aim of identifying the factors related to sentences against neurosurgeons, we have analyzed all the sentences issued in the second court of justice in Spain against neurosurgeons in the period from 1995 to 2007. Of a total of 1899 sentences of the second or last appeal, during the period from 1995 to 2007 issued in Spain, 61 were chosen which fulfill the criteria to be included in our study. 25 variables were included on the record of compiled data. A complete descriptive and comparative study was elaborated, as well as an analysis of the type of suits, circumstances, and professionals involved. In a third of the cases, complete malpraxis was identified. In regards to the sentences, they were absolved in approximately half the cases, resolved with one fifth of the cases being penal, and four fifths with compensation. Indemnity quantities range from 60,000 to 600,000euro. Deficiency of information or consent was noted in 17% of lawsuits. 62.5% of operations in our sample were on the anatomic region of the vertebral column followed in frequency by the cranial region with 28.6%. Consequences of surgical procedure included major permanent sequelae in 40% of the cases and death in 22%. It is wise to invest time to deal with patients, including the verbal informed consent, which must be confirmed by the written informed consent form. It is also important to leave a written proof of medical praxis, both related to surgical records and to diagnosis and follow-up of the patient. Procedures with a lower life-threatening risk should not be underestimated, since they comprise the greatest demanded group. The greatest amount of demands is related to economic reimbursement, especially in private practice.


Dynamics of Increasing IFN-γ Exposure on Murine MH-S Cell-Line Alveolar Macrophage Phagocytosis of Streptococcus pneumoniae.
Previous investigations have demonstrated that activation with the type II interferon, IFN-γ, downregulates alveolar macrophage (AM) phagocytosis of Streptococcus pneumoniae. While these studies have shown clear effects at discrete time points, the kinetics of the macrophage response to IFN-γ over time, with respect to pneumococcal phagocytosis, have not been shown. Here, we describe these kinetics in the murine MH-S AM cell-line, a well-established model useful for investigations of AM phenotype and function. We measure binding and internalizing rates of S. pneumoniae following exposure to increasing durations of physiologic levels of IFN-γ. When MH-S murine alveolar macrophage (mAM) were exposed to IFN-γ for increasing durations of time, from 0 to 6 days before inoculation with the type II S. pneumoniae, D39, exposure for 6 h transiently reduced bacterial binding by 50%, which was temporarily restored at 2 and 3 days of exposure. Bacterial internalization was also reduced shortly following initial exposure, however, internalization continued to fall to less than 5% that of IFN-γ naïve controls after 6 days of exposure. These data may help explain otherwise contradictory reports from the literature regarding timing between infections and reductions in macrophage function.


Sprint Specificity of Isolated Hamstring-Strengthening Exercises in Terms of Muscle Activity and Force Production.
To train hamstring muscle specifically to sprint, strengthening programs should target exercises associated with horizontal force production and high levels of hamstring activity. Therefore, the objectives of this study were to analyze the correlation between force production capacities during sprinting and hamstring strengthening exercises, and to compare hamstring muscle activity during sprinting and these exercises. Fourteen track and field regional level athletes performed two maximal 50-m sprints and six strengthening exercises: Nordic hamstring exercises without and with hip flexion, Upright-hip-extension in isometric and concentric modalities, Standing kick, and Slide-leg-bridge. The sprinting horizontal force production capacity at low (F0) and high (V0) speeds was computed from running velocity data. Hamstring muscle performances were assessed directly or indirectly during isolated exercises. Hamstring muscle electromyographic activity was recorded during all tasks. Our results demonstrate substantially large to very large correlations between V0 and performances in the Upright-hip-extension in isometric (rs = 0.56; p = 0.040), Nordic hamstring exercise without hip flexion (rs = 0.66; p = 0.012) and with 90° hip flexion (rs = 0.73; p = 0.003), and between F0 and Upright-hip-extension in isometric (rs = 0.60; p = 0.028) and the Nordic hamstring exercise without hip flexion (rs = 0.59; p = 0.030). However, none of the test exercises activated hamstring muscles more than an average of 60% of the maximal activation during top-speed sprinting. In conclusion, training programs aiming to be sprint-specific in terms of horizontal force production could include exercises such as the Upright-hip-extension and the Nordic hamstring exercise, in addition to maximal sprinting activity, which is the only exercise leading to high levels of hamstring muscle activity.


Bioproduction of ferric sulfate used during heavy metals removal from sewage sludge.
Toxic metals removal from wastewater sewage sludge can be achieved through microbial processes involving Acidithiobacillus ferrooxidans. The oxidation of ferrous ions by A. ferrooxidans, cultured in sewage sludge filtrate, was studied in both batch and continuous flow stirred tank reactors. Sewage sludge filtrate containing natural nutrients (phosphorus and nitrogen) was recovered as effluent following the dehydration of a primary and secondary sludge mixture. Batch and continuous flow stirred tank reactor tests demonstrated that A. ferrooxidans were able to grow and completely oxidize ferrous iron in a culture medium containing more than 80% (v v(-1)) sewage sludge filtrate with 10 g Fe(II) L(-1) added. Toxic levels were reached when total organic carbon in the sewage sludge filtrate exceeded 250 mg L(-1). The ferric iron solution produced in the sludge filtrate by A. ferrooxidans was used to solubilize heavy metals in primary and secondary sludge. The solubilization of Cu, Cr, and Zn yielded 71, 49, and 80%, respectively. This is comparable with the yield percentages obtained using a FeCl(3) solution. The cost of treating wastewater sewage sludge by bioproducing a ferric ion solution from sewage sludge is three times less expensive than the conventional method requiring a commercial ferric chloride solution.


Two-step conversion surgery after failed laparoscopic adjustable gastric banding. Comparison between laparoscopic Roux-en-Y gastric bypass and laparoscopic gastric sleeve.
Despite its worldwide popularity, laparoscopic adjustable gastric banding (LAGB) requires revisional surgery for failures or complications, in 20-60% of cases. The purpose of this study was to compare in terms of efficacy and safety, the conversion of failed LAGB to laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy. (LSG). The bariatric database of our institution was reviewed to identify patients who had undergone conversion of failed LAGB to LRYGB or to LSG, from November 2007 to June 2012. A total of 108 patients were included. Of these, 74 (68.5%) underwent conversion to LRYGB and 34 to LSG. All of the procedures were performed in 2-stage and laparoscopically. The mean follow-up for the LRYGB group was 29.1±17.9 months while for the LSG patients was 24.2±14.3 months. The mean body mass index (BMI) prior LRYGB and LSG was 45.6±7.8 and 47.5±5.6 (P = .09), respectively. Postoperative complications occurred in 16.2% of the LRYGB patients and in 2.9% of the LSG group (P = .04). Mean percentage of excess weight loss was 59.9%±16.2% and 70.2%±16.7% in LRYGB, and it was 52.2%±11.4% and 59.9%±14.4% in LSG at 12 months (P = .007) and 24 months (P = .01) after conversion. In this series, LRYGB and LSG are both effective and adequate revisional procedure after failure of LAGB. While LRYGB seems to ensure greater weight loss at 24 months follow-up, LSG is associated with a lower postoperative morbidity.


The rhesus monkey analogue of human lymphocyte antigen-G is expressed primarily in villous syncytiotrophoblasts.
The human placenta expresses the nonclassical major histo-compatibility complex (MHC) class I molecule, human lymphocyte antigen (HLA)-G, which may contribute to the establishment of maternal-fetal immune tolerance. Although the HLA-G ortholog of the rhesus monkey, Mamu-G, is a pseudogene, another nonclassical MHC class I locus, Mamu-AG, is expressed in the rhesus monkey placenta. Mamu-AG encodes MHC class I A locus-related molecules that exhibit all the characteristics of human HLA-G, including limited polymorphism and a truncated cytoplasmic domain. We have examined MHC class I glycoprotein and Mamu-AG mRNA expression in the rhesus placenta and in cultured trophoblasts. Immunocytochemical analysis of rhesus placental tissues with the W6/32 monoclonal antibody demonstrated a high level of MHC class I expression in villous syncytiotrophoblasts, whereas villous cytotrophoblasts were largely MHC class I negative. Only low levels of MHC class I expression were seen in extravillous cytotrophoblasts of cell columns and the trophoblastic shell. In situ hybridization demonstrated that Mamu-AG mRNAs were expressed at a high level in first-trimester villous syncytiotrophoblasts. MHC class I and Mamu-AG expression was significantly up-regulated during in vitro culture and differentiation of freshly isolated villous cytotrophoblasts into syncytiotrophoblasts. Preferential Mamu-AG expression in syncytiotrophoblasts suggests that rhesus monkey MHC class I-bearing trophoblasts could potentially interact with maternal peripheral blood lymphocytes rather than with uterine decidual lymphocytes as has been proposed for human trophoblasts.


Dose-dependent responses of avian daily rhythms to artificial light at night.
Recent studies have shown that animals are affected by night-time light exposure. Light is a continuous variable, but our knowledge on how individuals react to different light intensities during the night is limited. We therefore determined the relationship between night light intensity and the behaviour and physiology of great tits (Parus major). We measured daily activity patterns and melatonin levels in 35 males exposed to five different light intensities and found strong, dose-dependent effects. Activity onset was increasingly advanced, and activity offset delayed with higher light intensities. Furthermore, night-time activity increased and melatonin levels measured at midnight decreased with higher intensities. In this experimental study, we demonstrate for the first time dose-dependent effects of artificial light at night on birds' daily activity patterns and melatonin levels. Our results imply that these effects are not limited to a certain threshold, but emerge even when nocturnal light levels are slightly increased. However, in a natural area, these effects may be limited as artificial light levels are commonly low; light intensities drop rapidly with distance from a light source and birds can avoid exposure to light at night. Future studies should thus focus on examining the impact of different intensities of light at night in the wild.


Refinement of embolic stroke model in rats: Effect of post-embolization anesthesia duration on arterial blood pressure, cerebral edema and mortality.
Injection of a clot into the internal carotid artery is an experimental model of ischemic stroke that is considered to closely mimic embolic stroke in humans. In this model, the common carotid artery typically remains temporarily occluded to permit time for stabilization of the clot in the middle cerebral artery. However, the associated lengthening of the anesthesia duration could affect arterial blood pressure and stroke outcome. We refined the model by examining how increasing isoflurane anesthesia duration from 30 to 60 min after clot embolization affects mortality, infarct volume, edema, blood-brain barrier permeability, and the 8-h post-ischemic time course of blood pressure, which has not been reported previously in this model. We found that arterial pressure increased after discontinuing anesthesia in both embolized groups and that the increase was greater than in the corresponding non-embolized sham-operated rats. At 24 h, the group with 60-min post-ischemia anesthesia exhibited greater brain water content and a greater ipsilateral-to-contralateral ratio of extravasated Evans blue dye. Mortality was greater in the 60-min group, but infarct volume among survivors was not different from that in the 30-min anesthesia group. This study refines the embolic stroke model by demonstrating the importance of minimizing the duration of anesthesia after embolization. These data indicate that early discontinuation of isoflurane anesthesia after clot embolization permits an earlier hypertensive response that limits edema formation and mortality without significantly affecting infarct volume in survivors, thereby decreasing the required number of animals.