Role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy.
Chronic complications of diabetes mellitus e.a. diabetic nephropathy, neuropathy and retinopathy develop in at least 30-50% of patients with both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes, and are the major cause of increased morbidity and mortality. The ultimate consequences of diabetes complications include renal failure, foot ulceration and amputation, and blindness. The magnitude of the problem and its economic impact make extremely important to understand the natural history of chronic diabetes complications and to identify more successful preventive and therapeutic options. The pathogenesis of diabetes complications involves multiple mechanisms. The importance of vascular component is well recognized in diabetic retinopathy, which is primarily a vascular disease, as well as diabetic nephropathy developing as a result of complex interplay between hemodynamic and metabolic factors. The importance of vascular versus non-vascular mechanisms in the pathogenesis of diabetic neuropathy remains a subject of debate. Studies in animal and cell culture models revealed that such mechanisms as increased aldose reductase activity, non-enzymatic glycation/glycoxidation, activation of protein kinase C, impaired growth factor support, enhanced oxidative/nitrosative stress, and its downstream effectors such as mitogen-activated protein kinase activation, inflammatory response, endothelin-1 overexpression and impaired Ca(++) signaling, play an important role in all three tissue-targets for diabetes complications i.e. kidney, retina and peripheral nerve. Evidence for important role of the downstream effector of free radical and oxidant-induced DNA injury, poly(ADP-ribose) polymerase activation, is emerging. This review describes recent studies addressing the role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy.


Automatic synchronization of functional electrical stimulation and robotic assisted treadmill training.
This work presents a means to automatically synchronize two promising gait training technologies to address gait deficits in stroke survivors: functional electrical stimulation using intramuscular electrodes (FES-IM) and the Lokomat robotic gait orthosis. A system of hardware and software was developed to achieve the automatic synchronization. A series of bench tests were performed to verify the feasibility and reliability of automatic synchronization. The bench tests showed that automatic synchronization of FES-IM to the Lokomat gait cycle was feasible and reliable. Automatic synchronization was more consistent than manually triggered stimulation (10-fold smaller standard deviation of latency), and produced no early or missed stimulations across 634 strides. Automatic synchronization had greater accuracy than manually triggered stimulation, producing stimulation timed to an accuracy of 2.5% of one gait cycle duration (heel strike to heel strike = 100).


Cardiovascular Risk Reduction is Important for Improving Patient and Graft Survival After Ligation and Bypass Surgery for Popliteal Artery Aneurysm.
To report outcomes following ligation and bypass (LGB) surgery for popliteal artery aneurysm (PAA) and study factors influencing patient and graft survival. A retrospective review of patients undergoing LGB surgery for PAA between September 1999 and August 2012 at a tertiary referral vascular unit was performed. Primary graft patency (PGP), primary-assisted graft patency (PAGP), and secondary graft patency (SGP) rates were calculated using survival analyses. Patient, graft aneurysm-free survival (GAFS), aneurysm reperfusion-free survival (ARFS), and amputation-free survival (AFS) rates were also calculated. Log-rank testing and Cox proportional hazards modeling were used to perform univariate and multivariate analysis of influencing factors, respectively. Eighty-four LGB repairs in 69 patients (mean age 71.3 years, 68 males) were available for study. The 5-year PGP, PAGP, SGP, and patient survival rates were 58.1%, 84.4%, 85.2%, and 81.1%, respectively. On multivariate analysis, the principal determinants of PGP were urgency of operation ( P = .009) and smoking status ( P = .019). The principal determinants of PAGP were hyperlipidemia status ( P = .048) and of SGP were hyperlipidemia ( P = .042) and cerebrovascular disease (CVD) status ( P = .045). The principal determinants of patient survival were previous myocardial infarction ( P = .004) and CVD ( P = .001). The 5-year GAFS, ARFS, and AFS rates were 87.9%, 91.6%, and 96.1%, respectively. This study has shown that traditional cardiovascular risk factors, such as a smoking and ischemic heart disease, are the most important predictors of early graft failure and patient death following LGB surgery for PAA.


Sildenafil (Viagra) evokes retinal arteriolar dilation: dual pathways via NOS activation and phosphodiesterase inhibition.
Sildenafil (Viagra; Pfizer, New York, NY), a selective phosphodiesterase type-5 (PDE5) inhibitor, is widely used to treat impotence by improving penile blood flow via elevation of cGMP. However, its effect on ocular circulation is controversial and whether retinal arterioles are responsive to this drug remains unclear. In this study, the direct reaction of retinal arterioles to sildenafil was examined and the signaling pathway underlying this vasomotor activity was probed. Retinal arterioles from porcine eyes were isolated, cannulated, and pressurized without flow. Diameter changes in response to sildenafil were recorded using videomicroscopic techniques. Retinal arterioles (67 +/- 2 microm) dilated dose dependently to sildenafil (1 ng/mL to 1 microg/mL). This dilation was inhibited by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the guanylyl cyclase inhibitor 1H- [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), the extracellular signal-regulated kinase (ERK) pathway inhibitor PD98059, the nonselective potassium channel blocker tetraethylammonium (TEA), and the selective adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel blocker glibenclamide. The vasodilation elicited by the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was inhibited by ODQ and TEA but was insensitive to PD98059. In the presence of L-NAME, the addition of SNAP (1 microM) produced modest vasodilation and the inhibited sildenafil response was subsequently restored. The restored dilation was insensitive to PD98059 but was blocked by TEA. Activation of NO synthase, through ERK signaling, leading to NO production and subsequent guanylyl cyclase activation and K(ATP) channel opening is the major vasodilatory pathway for sildenafil in retinal arterioles. Moreover, the elevated cGMP, from endogenous or exogenous NO, plays a permissive role for sildenafil to exert vasodilation through inhibition of the PDE5 pathway independent of ERK signaling.


Multiomics Reveals Induction of Neuroblastoma SK-N-BE(2)C Cell Death by Mitochondrial Division Inhibitor 1 through Multiple Effects.
Mitochondrial division inhibitor 1 (Mdivi-1) is a well-known synthetic compound aimed at inhibiting dynamin-related protein 1 (Drp1) to suppress mitochondrial fission, making it a valuable tool for studying mitochondrial dynamics. However, its specific effects beyond Drp1 inhibition remain to be confirmed. In this study, we employed integrative proteomics and phosphoproteomics to delve into the molecular responses induced by Mdivi-1 in SK-N-BE(2)C cells. A total of 3070 proteins and 1945 phosphorylation sites were identified, with 880 of them represented as phosphoproteins. Among these, 266 proteins and 97 phosphorylation sites were found to be sensitive to the Mdivi-1 treatment. Functional enrichment analysis unveiled their involvement in serine biosynthesis and extrinsic apoptotic signaling pathways. Through targeted metabolomics, we observed that Mdivi-1 enhanced intracellular serine biosynthesis while reducing the production of C24:1-ceramide. Within these regulated phosphoproteins, dynamic dephosphorylation of proteasome subunit alpha type 3 serine 250 (PSMA3-S250) occurred after Mdivi-1 treatment. Further site-directed mutagenesis experiments revealed that the dephosphorylation-deficient mutant PSMA3-S250A exhibited a decreased cell survival. This research confirms that Mdivi-1's inhibition of mitochondrial division leads to various side effects, ultimately influencing cell survival, rather than solely targeting Drp1 inhibition.


Difference in glucose sensitivity of liver glycolysis and glycogen synthesis. Relationship between lactate production and fructose 2,6-bisphosphate concentration.
Incubation of isolated rat hepatocytes from fasted rats with 0-6 mM-glucose caused an increase in [fructose 2,6-bisphosphate] (0.2 to about 5 nmol/g) without net lactate production. A release of 3H2O from [3-3H]glucose was, however, detectable, indicating that phosphofructokinase was active and that cycling occurred between fructose 6-phosphate and fructose 1,6-bisphosphate. A relationship between [fructose 2,6-bisphosphate] and lactate production was observed when hepatocytes were incubated with [glucose] greater than 6 mM. Incubation with glucose caused a dose-dependent increase in [hexose 6-phosphates]. The maximal capacity of liver cytosolic proteins to bind fructose 2,6-bisphosphate was 15 nmol/g, with affinity constants of 5 X 10(6) and 0.5 X 10(6) M-1. One can calculate that, at 5 microM, more than 90% of fructose 2,6-bisphosphate is bound to cytosolic proteins. In livers of non-anaesthetized fasted mice, the activation of glycogen synthase was more sensitive to glucose injection than was the increase in [fructose 2,6-bisphosphate], whereas the opposite situation was observed in livers of fed mice. Glucose injection caused no change in the activity of liver phosphofructokinase-2 and decreased the [hexose 6-phosphates] in livers of fed mice.


Innate Intracellular Antiviral Responses Restrict the Amplification of Defective Virus Genomes of Parainfluenza Virus 5.
During the replication of parainfluenza virus 5 (PIV5), copyback defective virus genomes (DVGs) are erroneously produced and are packaged into "infectious" virus particles. Copyback DVGs are the primary inducers of innate intracellular responses, including the interferon (IFN) response. While DVGs can interfere with the replication of nondefective (ND) virus genomes and activate the IFN-induction cascade before ND PIV5 can block the production of IFN, we demonstrate that the converse is also true, i.e., high levels of ND virus can block the ability of DVGs to activate the IFN-induction cascade. By following the replication and amplification of DVGs in A549 cells that are deficient in a variety of innate intracellular antiviral responses, we show that DVGs induce an uncharacterized IFN-independent innate response(s) that limits their replication. High-throughput sequencing was used to characterize the molecular structure of copyback DVGs. While there appears to be no sequence-specific break or rejoining points for the generation of copyback DVGs, our findings suggest there are region, size, and/or structural preferences selected for during for their amplification.IMPORTANCE Copyback defective virus genomes (DVGs) are powerful inducers of innate immune responses both in vitro and in vivo They impact the outcome of natural infections, may help drive virus-host coevolution, and promote virus persistence. Due to their potent interfering and immunostimulatory properties, DVGs may also be used therapeutically as antivirals and vaccine adjuvants. However, little is known of the host cell restrictions which limit their amplification. We show here that the generation of copyback DVGs readily occurs during parainfluenza virus 5 (PIV5) replication, but that their subsequent amplification is restricted by the induction of innate intracellular responses. Molecular characterization of PIV5 copyback DVGs suggests that while there are no genome sequence-specific breaks or rejoin points for the generation of copyback DVGs, genome region, size, and structural preferences are selected for during their evolution and amplification.


The proteomic dataset for bone marrow derived human mesenchymal stromal cells: Effect of in vitro passaging.
Bone-marrow derived mesenchymal stromal cells (BMSCs) have been in clinical trials for therapy. One major bottleneck in the advancement of BMSC-based products is the challenge associated with cell isolation, characterization, and ensuring cell fitness over the course of in vitro cell propagation steps. The data in this report is part of publications that explored the proteomic changes following in vitro passaging of BMSCs [4] and the molecular heterogeneity in cultures obtained from different human donors [5], [6].The methodological details involving cell manufacturing, proteome harvesting, protein identification and quantification as well as the bioinformatic analyses were described to ensure reproducibility of the results.


Use of the isolator 1.5 microbial tube for culture of synovial fluid from patients with septic arthritis.
Synovial fluid specimens obtained from patients with arthritis were plated onto solid media (conventional cultures) or inoculated into an Isolator 1.5 microbial tube (Isolator cultures), and the yield and time to detection of organisms were compared. Overall, 144 specimens obtained from 137 patients were processed, and 31 (21.5%) cultures obtained from 29 patients were positive by at least one method. Staphylococcus aureus was isolated from 12 patients, Streptococcus pneumoniae and Kingella kingae were isolated from 4 patients each, group G streptococci were isolated from 3 patients, Staphylococcus epidermidis and members of the family Enterobacteriaceae were isolated from 2 patients each, and Streptococcus mitis and Peptostreptococcus prevotii were isolated from 1 patient each. Overall, the causative organism was detected in 31 of 31 (100.0%) Isolator cultures and 24 of 31 (77.4%) conventional cultures (P < 0.02). Twenty-nine of 31 (93.5%) positive Isolator cultures and 20 of 24 (83.3%) conventional cultures were positive by the second day of incubation. Among the 24 cultures positive by both methods, higher numbers of CFU per milliliter were detected with the Isolator system in 13 cultures and with conventional cultures in 2 cultures (P < 0.002). Inoculation of synovial fluid into an Isolator 1.5 microbial tube improves the recovery of organisms causing septic arthritis.


Mucosal eosinophilia: prevalence and racial/ethnic differences in symptoms and endoscopic findings in adults over 10 years in an urban hospital.
Eosinophilic esophagitis is a chronic inflammatory disease with mucosal accumulation of eosinophils. There is a paucity of data among racial/ethnic groups other than white patients. To determine if racial/ethnic differences exist in clinical presentation, endoscopic appearance, and biopsy results in adult patients (age ≥18 y) with mucosal eosinophilia and examine the prevalence of mucosal eosinophilia at an urban hospital over a 10-year period. Pathology reports searched at Temple University Hospital 2000 to 2009; key words: "eosinophils", "esophagus", and "biopsy". Clinical and endoscopic records reviewed on patients with ≥15 eosinophils/high power field. A total of 64 adults (average age, 41 y; 62% male patients; 81% white, 12% black, and 6% Hispanic). White patients were significantly younger (P=0.03). Adult mucosal eosinophilia diagnosis increased by 833% (3 in 2000 to 25 in 2009); black/Hispanic diagnosis increased by 500% (1 in 2000 to 5 in 2009). Solid food dysphagia was more common among white patients (72% vs. 0.33%, P=0.02). Reflux symptoms were more common in black/Hispanic patients (42% vs. 22%, P=0.16). Normal endoscopy (42% vs. 13%, P=0.04) and reflux changes (41% vs. 21%, P=0.16) were more common in black/Hispanic patients. Furrows (42% vs. 8%, P=0.04) and rings (46% vs. 0%, P=0.002) were more common in white patients. Average eosinophil counts did not vary between groups. Mucosal eosinophilia presents with significant differences between racial/ethnic groups in age at onset, symptoms at presentation, and endoscopic features. Differences may reflect different phenotypes of the same disease or separate disease entities.


Immunoproteomic identification of antigenic salivary biomarkers detected by Ixodes ricinus-exposed rabbit sera.
Ixodes ricinus, the primary vector of tick-borne disease in Europe, is currently expanding its distribution area and its activity in many countries. Antibody responses to tick salivary antigens have been proposed as an alternative marker of exposure to tick bites. However, the identification of the I. ricinus corresponding antigens remains elusive. Using rabbits artificially exposed to I. ricinus and 2 other European tick species (Rhipicephalus sanguineus and Dermacentor reticulatus) as controls, a cross-comparison of IgG profiles was performed against protein salivary gland extracts (pSGE) from these 3 tick species using immunoblots. Immunoblot analysis highlighted a singularity in the immune patterns according to tick species exposure and pSGE antigen source. Two protein bands were detected against I. ricinus pSGE only in rabbits exposed to I. ricinus bites. An immunoproteomic approach based on a fluorescence detection method was developed to unambiguously identify corresponding antigenic spots on 2-D gels. Among the unique I. ricinus salivary antigenic proteins detected by sera from rabbits exposed to this tick species, I. ricinus calreticulin was identified. Although tick calreticulin was previously proposed as a potential antigenic marker following exposure to ticks (particularly in North American tick species), the present study suggested that Ixodes calreticulin does not appear to be cross-recognized by the 2 other tick genera tested. Additional experiments are needed to confirm the use of I. ricinus calreticulin salivary protein as a potential discriminant antigenic biomarker to Ixodes tick exposure.


Recognizing Degenerative Aging as a Treatable Medical Condition: Methodology and Policy.
It is becoming increasingly clear that in order to accomplish healthy longevity for the population, there is an urgent need for the research and development of effective therapies against degenerative aging processes underlying major aging-related diseases, including heart disease, neurodegenerative diseases, type 2 diabetes, cancer, pulmonary obstructive diseases, as well as aging-related complications and susceptibilities of infectious communicable diseases. Yet, an important incentive for the research and development of such therapies appears to be the development of clinically applicable and scientifically grounded definitions and criteria for the multifactorial degenerative aging process (or "senility" using the existing ICD category), underlying those diseases, as well as for the safety and effectiveness of interventions against it. Such generally agreed definitions and criteria are currently absent. The devising of such criteria is important not only for the sake of their scientific value and their utility for the development of therapeutic solutions for the aging population, but also to comply with and implement major existing national and international programmatic and regulatory requirements. Some methodological suggestions and potential pitfalls for the development of such criteria are examined.


Postnatal maturation of excitation-contraction coupling in rat ventricle in relation to the subcellular localization and surface density of 1,4-dihydropyridine and ryanodine receptors.
To better understand excitation-contraction coupling in cardiac muscle, we investigated the main Ca2+ channels involved in that process in adult and neonatal rat ventricle. Voltage-dependent (L-type) Ca2+ channels and sarcoplasmic reticulum Ca2+ release channels were labeled by means of [3H] (+)-PN200-110 and [3H]ryanodine, respectively. The number of [3H]ryanodine binding sites (per gram tissue) increased more than that of [3H] (+)-PN200-110 binding sites over the postnatal period (2.1-fold versus 1.35-fold, respectively). After equilibration of microsomal fractions in density gradient, ryanodine receptors were characterized by a heavy distribution pattern that did not change appreciably between days 1 and 30 after birth. In neonatal tissue, 1,4-dihydropyridine receptors were found mainly in low-density subfractions, together with other sarcolemmal constituents, whereas in adult tissue, they were recovered predominantly in high-density subfractions, together with ryanodine receptors. Thus, after birth, and in parallel with the development of T tubules, there was a progressive concentration of L-type Ca2+ channels in junctional structures of high equilibrium density, where they were situated close to the Ca2+ release channels of the sarcoplasmic reticulum. In adult ventricle, L-type channels were, on an average, threefold more abundant in T tubules than in external sarcolemma. In parallel mechanical studies, we found that the inhibitory action of ryanodine on systolic contraction was much more pronounced in adult than in neonatal right ventricle, and that, conversely, neonatal tissue was more sensitive that adult tissue to inhibitors of L-type channels. We conclude that, in view of the presumed mechanism of Ca2+ release from the sarcoplasmic reticulum, that is, Ca(2+)-induced Ca2+ release, the predominant localization in adult rat ventricle of the major Ca2+ entry pathway in the vicinity of the Ca2+ release pathway is of great functional significance. Furthermore, owing to the relative stoichiometry of Ca2+ entry and Ca2+ release channels in junctional structures (about 1:9), a physical link between these channels is not likely to be involved in the modulation of Ca2+ release from the sarcoplasmic reticulum in cardiac muscle.


Modulatory Effect of Rosmarinic Acid on H2O2-Induced Adaptive Glycolytic Response in Dermal Fibroblasts.
Oxidative stress induces the adaptive response and alteration of energy metabolism across human cell types. Dermal fibroblasts shift their energy system to overload anaerobic glycolysis when exposed to sub-lethal hydrogen peroxide (H2O2). However, oxidative stress levels in the cells can be depleted by antioxidants, and such cellular changes can therefore be modulated. The present study aimed to investigate the modulatory effect of rosmarinic acid (a polyphenol antioxidant) against H2O2-induced reactive oxygen species (ROS) and the glycolytic adaptive response in fibroblasts. The results showed that H2O2 caused a significant ROS increase in the cells, and pre-treatment with rosmarinic acid (5-50 µM) decreased ROS significantly in the presence of glutathione. Rosmarinic acid modulated the adaptive response in H2O2-treated cells by decreasing glucose consumption and lactate production. The rosmarinic acid also recovered intracellular ATP and decreased NADPH production via the pentose phosphate pathway. Several glycolytic enzymes, including hexokinase-2 (HK-2), phosphofructokinase-2 (PFK-2), and lactate dehydrogenase A (LDHA), were downregulated in cells treated with rosmarinic acid. Furthermore, the key antioxidant enzymes: glutathione-disulfide reductase (GSR), glutathione peroxidase-1 (GPx-1), and peroxiredoxin-1 (Prx-1) and redox protein thioredoxin-1 (Trx-1) were upregulated in treated cells compared to control cells. To sum up, the rosmarinic acid could be used as an antioxidant against H2O2-induced adaptive responses in fibroblasts by modulating glucose metabolism, glycolytic genes, and GSH production. The present work indicates that rosmarinic acid holds promise in cell-based research applications for combating ROS and enhancing dermal fibroblast health.


Stability of human stromal-derived factor-1alpha (CXCL12alpha) after blood sampling.
Stromal-derived factor 1-alpha (SDF-1alpha, or CXCL12alpha) is a major chemokine that controls adult stem cell trafficking. Little is known about its stability after blood sampling, but this is a crucial issue for clinical studies of this molecule. In a study of six subjects, we found total human plasma SDF-1alpha concentrations to be stable for 120 min when the blood is placed on ice immediately after sampling.


Mortality risk score prediction in an elderly population using machine learning.
Standard practice for prediction often relies on parametric regression methods. Interesting new methods from the machine learning literature have been introduced in epidemiologic studies, such as random forest and neural networks. However, a priori, an investigator will not know which algorithm to select and may wish to try several. Here I apply the super learner, an ensembling machine learning approach that combines multiple algorithms into a single algorithm and returns a prediction function with the best cross-validated mean squared error. Super learning is a generalization of stacking methods. I used super learning in the Study of Physical Performance and Age-Related Changes in Sonomans (SPPARCS) to predict death among 2,066 residents of Sonoma, California, aged 54 years or more during the period 1993-1999. The super learner for predicting death (risk score) improved upon all single algorithms in the collection of algorithms, although its performance was similar to that of several algorithms. Super learner outperformed the worst algorithm (neural networks) by 44% with respect to estimated cross-validated mean squared error and had an R2 value of 0.201. The improvement of super learner over random forest with respect to R2 was approximately 2-fold. Alternatives for risk score prediction include the super learner, which can provide improved performance.


SSP1, a gene necessary for proper completion of meiotic divisions and spore formation in Saccharomyces cerevisiae.
During meiosis, a diploid cell undergoes two rounds of nuclear division following one round of DNA replication to produce four haploid gametes. In yeast, haploid meiotic products are packaged into spores. To gain new insights into meiotic development and spore formation, we followed differential expression of genes in meiotic versus vegetatively growing cells in the yeast Saccharomyces cerevisiae. Our results indicate that there are at least five different classes of transcripts representing genes expressed at different stages of the sporulation program. Here we describe one of these differentially expressed genes, SSP1, which plays an essential role in meiosis and spore formation. SSP1 is expressed midway through meiosis, and homozygous ssp1 diploid cells fail to sporulate. In the ssp1 mutant, meiotic recombination is normal but viability declines rapidly. Both meiotic divisions occur at the normal time; however, the fraction of cells completing meiosis is significantly reduced, and nuclei become fragmented soon after meiosis II. The ssp1 defect does not appear to be related to a microtubule-cytoskeletal-dependent event and is independent of two rounds of chromosome segregation. The data suggest that Ssp1 is likely to function in a pathway that controls meiotic nuclear divisions and coordinates meiosis and spore formation.


[Effect of Fe3+ ions on Thiobacillus ferrooxidans oxidation of ferrous oxide at various temperatures].
The inhibition of the rate of ferrous iron oxidation by Thiobacillus ferrooxidans with ferric ions was shown to depend on their concentration, the temperature of the medium, and the phase of the cultural growth. Ferrous iron oxidation was inhibited with ferric ions both at low (below 1.0 g/l) and high (ca. 10 g/l) concentrations, the process being temperature dependent: the rate of inhibition decreased with a fall of the temperature. The bacterium was most sensitive to unfavourable Fe3+ concentrations at 8-26 degrees C during the lag phase; Fe2+ oxidation was inhibited during the exponential phase of growth only at 26 degrees C. The Ki for Fe3+ at 27, 10 and 5 degrees C were 3.09-3.39, 11.4-22.8 and 46.0 g/l Fe3+, respectively. Therefore, the affinity of the enzyme for the inhibitor Fe3+ decreases with a fall of the temperature.


Light-emitting diodes as an illumination source for plants: a review of research at Kennedy Space Center.
The provision of sufficient light is a fundamental requirement to support long-term plant growth in space. Several types of electric lamps have been tested to provide radiant energy for plants in this regard, including fluorescent, high-pressure sodium, and metal halide lamps. These lamps vary in terms of spectral quality, which can result in differences in plant growth and morphology. Current lighting research for space-based plant culture is focused on innovative lighting technologies that demonstrate high electrical efficiency and reduced mass and volume. Among the lighting technologies considered for space are light-emitting diodes (LEDs). The combination of red and blue LEDs has proven to be an effective lighting source for several crops, yet the appearance of plants under red and blue lighting is purplish gray, making visual assessment of plant health difficult. Additional green light would make the plant leaves appear green and normal, similar to a natural setting under white light, and may also offer psychological benefits for the crew. The addition of 24% green light (500-600 nm) to red and blue LEDs enhanced the growth of lettuce plants compared with plants grown under cool white fluorescent lamps. Coincidentally, these plants grown under additional green light would have the additional aesthetic appeal of a green appearance.


MicroRNA-related genetic variants in iron regulatory genes, dietary iron intake, microRNAs and lung cancer risk.
Genetic variations in MicroRNA (miRNA) binding sites may alter structural accessibility of miRNA binding sites to modulate risk of cancer. This large-scale integrative multistage study was aimed to evaluate the interplay of genetic variations in miRNA binding sites of iron regulatory pathway, dietary iron intake and lung cancer (LC) risk. The interplay of genetic variant, dietary iron intake and LC risk was assessed in large-scale case-control study. Functional characterization of the validated SNP and analysis of target miRNAs were performed. We found that the miRNA binding site SNP rs1062980 in 3' UTR of Iron-Responsive Element Binding protein 2 gene (IREB2) was associated with a 14% reduced LC risk (P value = 4.9×10 - 9). Comparing to AA genotype, GG genotype was associated with a 27% reduced LC risk. This association was evident in males and ever-smokers but not in females and never-smokers. Higher level of dietary iron intake was significantly associated with 39% reduced LC risk (P value = 2.0×10 - 8). This association was only present in individuals with AG + AA genotypes with a 46% reduced risk (P value = 1.0×10 - 10), but not in GG genotype. The eQTL-analysis showed that rs1062980 significantly alters IREB2 expression level. Rs1062980 is predicted to alter a miR-29 binding site on IREB2 and indeed the expression of miR-29 is inversely correlated with IREB2 expression. Further, we found that higher circulating miR-29a level was significantly associated with 78% increased LC risk. The miRNA binding site SNP rs1062980 in iron regulatory pathway, which may alter the expression of IREB2 potentially through modulating the binding of miR-29a, together with dietary iron intake may modify risk of LC both individually and jointly. These discoveries reveal novel pathway for understanding lung cancer tumorigenesis and risk stratification.


Photo-, Thermo-, Electrochromic, Erasable Inkless Printing, Ions Detection, and UV Detector Properties of Viologen Compounds Based on Homomolybdate/Keggin POMs.
Three POMs-based viologen compounds with different structures were successfully constructed under solvothermal and hydrothermal conditions, [Cu(1,4-cby)2(H2O)0.5(β-Mo8O26)0.5]·C3H7NO·3H2O (1), [H2(1,4-cby)2]·(β-Mo8O26) (2) (1,4-cby·Cl = 1-(4-carboxybenzyl)-4,4'-bipyridine chloride), [H2(1,4-cbyy)2]·(SiMo12O40) (3) (1,4-cbyy·Cl = 1-(4-cyanobenzyl)-4,4'-bipyridine chloride). Compound 1 is a structure with the number "eight-like" metal-organic chain with Cu as the nodes, and compounds 2 and 3 are fascinating structures connected by hydrogen bonding interactions. More importantly, compounds 1-3 exhibit a good response to both light and electricity and the thermal response of compound 1 was also studied. The reasons for the response of compounds 1-3 to external stimuli were analyzed through methods such as UV-Vis, EPR, and XPS. In addition, the transient photocurrent response results of compounds 1-3 are the same as those obtained from kinetic calculations. Meanwhile, the coated filter paper based on compound 3 has been successfully applied in erasable inkless printing and anti-counterfeiting, the test paper of 3 can also detect metal ions, and the films based on compounds 1-3 are a flexible and portable ultraviolet (UV) detector.


Conserved deployment of genes during odontogenesis across osteichthyans.
Odontogenesis has only been closely scrutinized at the molecular level in the mouse, an animal with an extremely restricted dentition of only two types and one set. However, within osteichthyans many species display complex and extensive dentitions, which questions the extent to which information from the mouse is applicable to all osteichthyans. We present novel comparative molecular and morphological data in the rainbow trout (Oncorhynchus mykiss) that show that three genes, essential for murine odontogenesis, follow identical spatial-temporal expression. Thus, at all tooth bud sites, epithelial genes Pitx-2 and Shh initiate the odontogenic cascade, resulting in dental mesenchymal Bmp-4 expression, importantly, including the previously unknown formation of replacement teeth. Significantly, this spatial-temporal sequence is the same for marginal and lingual dentitions, but we find notable differences regarding the deployment of Pitx-2 in the developing pharyngeal dentition. This difference may be highly significant in relation to the theory that dentitions may have evolved from pharyngeal tooth sets in jawless fishes. We have provided the first data on operational genes in tooth development to show that the same signalling genes choreograph this evolutionary stable event in fishes since the osteichthyan divergence 420 Myr ago, with the identical spatial-temporal expression as in mammals.


Penile curvature: an update for management from 20 years experience in a high volume centre.
Our aim was to review the literature and discuss about penile curvature in order to have an update for management after 20 years experience in the field.Penile curvature may be congenital or acquired. Congenital penile curvature is a relatively uncommon condition that may present in late adolescent or early adult life. The incidence is estimated to be 0.6 %. On the other side, acquired penile curvature has an overall prevalence of 0.5-13%. Three main factors seem to increase the risk of developing an acquired penile curvature, often related to Peyronie's disease: penile traumatism, genetic and familiar conditions and a history of diseases of the genital tract. In treating Peyronie's disease, no medical therapy is fully effective, and surgery remains the gold standard in cases of severe deformity and/or erectile disfunction. Peyronie's disease is associated with significant psychological stress for patients and their partners. Appropriate treatment should be individualized and tailored to the patient's goals and expectations. There is not the 'best' surgical technique and outcomes are satisfactory when proper treatment decisions are made.


Effect of Crown Angulation of Maxillary Incisor on Effective Arch Perimeter.
It has been postulated that crown angulation and inclination has potential space implication within the arch. With the insight of space implication of the axial relations of teeth, cases of genuine tooth size discrepancies can be dealt with improved stability. This in vitro study was designed to investigate and quantify the influence of angulation and inclination of maxillary incisors on the effective arch perimeter. Acrylic teeth were arranged over typhodont frame with spaced maxillary anterior segment. Known value of tip and torque in increments were incorporated to maxillary incisors through bracket positioning and corresponding consumption of the interdental spaces were measured using coordinate measuring machine. Study revealed that increase in maxillary incisor crown angulation by 1o results in consumption of approximately 0.012 mm of arch perimeter. Similarly, there is a consumption of 0.021 mm of arch perimeter with each degree increase in labial crown inclination. The knowledge of the space implication can be included in the space analysis during the orthodontic treatment planning. Depending upon the amount of space discrepancy, an accurate degree of required alteration in the axial relation of one or more teeth can be planned.


Case Report: Infectious Diseases in Pilgrims Visiting the Holy Land.
Every year Christian pilgrims from around the world visit the holy sites located around the Sea of Galilee. Some become ill during their stay with infectious diseases that were acquired in their country of origin, and are hospitalized at Poriya Medical Center. They pose a diagnostic challenge due to language barriers, the rarity of these infections in Israel, and the fact that diagnostic tests are not readily available. All patient records from 2015 of Holy Land tourists hospitalized at Poriya Medical Center were screened for the diagnosis of imported zoonotic diseases that are not commonly diagnosed in Israel. Three patients who were on a Holy Land tour were hospitalized during 2015 with laboratory-confirmed diagnostically challenging zoonotic infectious diseases: a 91-year-old priest from Ethiopia diagnosed with relapsing fever due to Borrelia recurrentis, an 85-year-old retired mountaineer from New Hampshire diagnosed with human granulocytic anaplasmosis, and a 57-year-old farmer from central Brazil diagnosed with leptospirosis. These case reports emphasize the importance of considering imported zoonotic infectious diseases and obtaining appropriate diagnostic tests when treating Holy Land travelers to Israel.


Management of new oral anticoagulants related life threatening or major bleedings in real life: a brief report.
Although new oral anticoagulants (NOAs) have been marketed in many countries, concern exists about the management of bleedings related to these drugs due to the lack of specific antidotes. The aim of our study was to report on real life management of NOAs-related life-threatening or major bleedings. We report data from consecutive cases of NOAs related major bleedings admitted to 4 hospitals since NOAs became marketed in Italy. We treated 8 patients, 4 males, with mean age 84 ± 7 years, 7 of whom were on dabigatran and one on rivaroxaban. The indication for NOA was atrial fibrillation. All bleedings were spontaneous and involving the gastro-intestinal tract. At the time of bleeding all patients had a drop in hemoglobin levels over 20 g/L. Creatinine clearance was ≤30 mL/min in 4 patients. All patients received general supportive measures, 4 of 8 patients were transfused with packed red cells and one patient received platelet transfusion. Three patients were treated with tranexamic acid and one patient on dabigatran received 4-factor prothrombin complex concentrate (PCC) with bleeding cessation, although coagulation parameters were not corrected. The median time for normalization of coagulation parameters was 3 days (range 1-6 days). All patients were discharged alive and NOAs were discontinued. In NOAs related major gastro-intestinal bleeding general supportive measures seem to be effective for the majority of patients. Despite promoting bleeding cessation, 4-factor PCC does not reverse abnormal coagulation parameters.


MicroRNA-204-5p targets SOX11 to regulate the inflammatory response in spinal cord injury.
The purpose of this study was to investigate whether microRNA-204-5p can regulate the inflammatory response of spinal cord injury (SCI) by targeting SOX11. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-204-5p in patients with SCI. The mouse SCI model was established to detect the recovery of the grip strength of the upper and lower limbs. Then, the expression of microRNA-204-5p in these mice with SCI was detected by qRT-PCR, and the levels of the inflammatory factors Toll-like receptor 4 (TLR4) and iNOS were examined by Western blot. Subsequently, microRNA- 204-5p was overexpressed in the mouse SCI model using lentivirus, and the changes in mouse grip strength and the inflammatory factor levels were observed. SOX11 was then searched as the target gene of microRNA-204-5p through bioinformatics analysis, and its expression in patients or mice with SCI was examined using qRT-PCR. SOX11 expression was again detected after the overexpression or knockdown of microRNA-204-5p in cells. The binding of microRNA-204-5p to SOX11 was verified by dual-luciferase reporting assay. After microRNA-204-5p and SOX11 were co-overexpressed in cells, the levels of TLR4 and iNOS were analyzed. Furthermore, the changes in the grip strength were observed in mice with SCI after simultaneous up-regulation of microRNA-204-5p and SOX11. Micro-204-5p level was conspicuously decreased in the population with SCI. And the SCI mouse model showed that the upper and lower limb strength conspicuously decreased and began to recover after 7 days. During the seven days, microRNA-204-5p level in the SCI mice decreased with time, while the levels of the inflammatory cytokines TLR4 and iNOS conspicuously increased. After microRNA-204-5p was overexpressed in SCI mice, their upper and lower limb strength was conspicuously restored, while the levels of TLR4 and iNOS were also remarkably decreased. The bioinformatics analysis revealed that there exist some binding sites between microRNA-204-5p and SOX11, and we found that SOX11 expression was conspicuously enhanced in the plasma of the SCI patients. Meanwhile, the SOX11 level in SCI mice was also conspicuously increased, and it was time-dependent. The expression of SOX11 was decreased after the upregulation of microRNA-204-5p, while the opposite result was observed after the downregulation of microRNA-204-5p. In addition, the result of the dual-luciferase reporter gene assay revealed that microRNA-204-5p could bind to SOX11 in a targeted manner. Meanwhile, the up-regulation of SOX11 was partially relieved by the inhibitory effect of microRNA-204-5p on TLR4 and iNOS. Moreover, the simultaneous overexpression of SOX11 and microRNA-204-5p partially reversed the impact of the up-regulated microRNA-204-5p alone on the recovery of the upper and lower limb strength in SCI mice. The low expression of microRNA-204-5p in patients with SCI can affect the levels of the inflammatory cytokines TLR4 and iNOS and improve SCI by targeting SOX11.


[Fluorophotometry by instillation. II. Effect of beta-blocker eyedrops in the normal subject].
The effects of various drugs on the human aqueous humor flow were studied by the fluorophotometric method of Yablonski (topical fluorescein instillation). The effect of the beta-adrenergic blocker (Timolol) on aqueous humor flow and on intra-ocular pressure has been studied in ten normal eyes on the Fluorotron Master. We found that the acute decrease in intra-ocular pressure was equal to 1.39 +/- 0.44 microliter.min-1 for the Timolol treated eyes, and equal to 2.79 +/- 0.57 microliter.min-1 for the untreated eyes (Placebo). The difference between Timolol and Placebo was statistically significant (Student t-tested, and Wilcoxon W-tested). The fluorophotometric method is superior to the tonographic method by giving a more favorable condition to study the facility of outflow in steady physiological state. Our results are in good agreement with other authors and show Timolol to have little or no effect on the facility of outflow.


Increased incidence of postoperative infections associated with peritoneal dialysis in renal transplant recipients.
Infection is a frequent postoperative complication in renal transplant recipients. However, little information is available concerning the effect of pretransplantation dialysis modality on posttransplantation complications including infection. We therefore evaluated the effect of hemodialysis (HD) versus peritoneal dialysis (PD) on the incidence of postoperative infection as well as several other posttransplantation outcomes. A retrospective analysis was performed using medical records covering the period 30 days after transplantation of 156 dialysis patients who underwent renal transplantation at a single center during a 22-month period. Of these patients, 103 received only HD, 32 received only PD, 13 received PD in the past and HD immediately before transplantation (PH/HD), and 8 received HD in the past and PD immediately before transplantation (HD/PD). The presence of culture-proven infection, types of infecting organisms, length of initial hospital stay, and incidence of rejection during the first 30 days after transplantation were determined for each patient. All groups were similar with regard to age, race, gender, underlying disease, donor type, incidence of delayed graft function, and perioperative antibiotic prophylaxis. There were more infectious complications within 30 days after transplantation in patients on PD just prior to transplantation (PD and HD/PD) than in HD patients (67.5% vs. 25.9%, P<0.00001). When types of infectious organisms were assessed, PD patients were found to have a greater incidence of infections with microorganisms that colonize human skin (P<0.0001). The median length of hospital stay was 3 days longer for PD patients and 6.5 days longer for HD/PD patients than for patients receiving HD (P=0.01 and 0.04), and PD and HD/PD patients were more likely to have an episode of rejection than HD patients (P=0.02). Renal replacement therapy with PD immediately before transplantation negatively affects outcome as compared with HD, predisposing patients to a greater incidence of postoperative infections and rejection and a longer hospital stay. Further study in a randomized controlled trial may help determine how adjustment of the dialysis method can optimize transplantation outcome.


GroEL-assisted refolding of adrenodoxin during chemical cluster insertion.
Chemical reconstitution of recombinant bovine adrenal mitochondrial apoadrenodoxin was carried out in the presence of the nonhomologous chaperone protein GroEL and of the cochaperone GroES, both in the presence and in the absence of ATP. The approach used here was different from the one characterizing studies on chaperone activity, as we used an adrenodoxin apoprotein, devoid of the cluster iron and sulfide, rather than a denaturant-unfolded form of the protein, and catalytic amounts of the chaperone proteins. A possible scaffolding role for two bacterial sulfur transferases, namely, rhodanese from Azotobacter vinelandii and a rhodanese-like sulfurtransferase from Escherichia coli, was also investigated in the absence of the enzyme substrates. The extent and the rate of adrenodoxin refolding following cluster insertion was measured by spectroscopy and by monitoring the activity recovery in a NADPH-cytochrome c reduction assay. These measurements were carried out on the unresolved reaction mixture and on the adrenodoxin-containing fraction obtained by HPLC fractionation of the reconstitution mixture at different reaction times. The rate and extent of cluster insertion and activity recovery were substantially improved by addition of GroEL and increased with increasing the GroEL/apoadrenodoxin ratio. GroES and ATP had no effect by themselves, and did not enhance the effect of GroEL. A. vinelandii rhodanese, the E. coli sulfurtransferase, and bovine serum albumin had no effect on the rate and yield of chemical reconstitution. The accelerated chemical reconstitution of apoadrenoxin in the presence of GroEL is therefore attributable to a scaffolding effect of this protein.


Protein phosphatase type 1 in mammalian cell mitosis: chromosomal localization and involvement in mitotic exit.
We have examined the role of protein phosphatase type 1 (PP-1) in mammalian cell mitosis. Immunofluorescence using anti-PP-1 antibodies revealed that PP-1, which is mainly localized in the cytoplasm of G1 and S phase cells, accumulates in the nucleus during G2 phase and intensely colocalizes with individual chromosomes at mitosis. This increase in nuclear PP-1 in G2/M cells was confirmed by immunoblotting on subcellular fractions. Microinjection of neutralizing anti-PP-1 antibodies before division blocked cells at metaphase, whereas injection of PP-1 in one pole of an anaphase B cell accelerated cytokinesis and the reflattening of the injected cell. These results reveal a specific cell cycle-dependent redistribution of PP-1 and its involvement in reversing p34cdc2-induced effects after mid-mitosis in mammalian cells.


[Repeat surgery for recurrent thyroid cancer in children].
Repeat surgery for recurrent thyroid carcinoma was carried out in 110 out of 662 (16.6%) children followed up at the Republican Thyroid Cancer Center, Minsk, in 1990-2000. Age varied 4.2-15 years (average 11.8 yrs). Papillary carcinoma was diagnosed in 94.4%, follicular type--5.1%, and medullary thyroid carcinoma--0.5%. Repeat surgery was indicated in cases of involvement of the regional lymph nodes of the neck. In 4 cases, lymph node metastases were associated with relapsing tumor surviving in the remaining thyroid tissue. Repeat surgery was required to remove the remnants of thyroid tissue in 12 cases of lung involvement. Risk of relapse is determined by the nature of primary intervention, and the best results are achieved when total thyroidectomy and bilateral dissection of neck lymph nodes are performed.


CD4-IgG binding threshold for inactivation of human immunodeficiency virus type 1.
The stoichiometry of human immunodeficiency virus type 1 (HIV-1) inactivation by soluble receptor CD4-IgG hybrid dimers (CD4-IgG) was examined. The extent of HIV-1 inactivation was measured in a sensitive plaque-forming assay, and the corresponding level of CD4-IgG binding was determined by immunofluorescence of infected cells. Ninety percent virus inactivation occurred at relatively low levels of CD4-IgG binding (10% of the saturating level). At even lower binding levels (1.4% of maximum binding), virus survival was 44%. Over a broad range of binding conditions, the survival curve followed a model in which viruses binding more than a threshold level of CD4-IgG were completely inactivated, while viruses binding less remained infectious. The data indicate that CD4-IgG binding to 1.4% of gp120 binding sites equals the threshold for inactivation. Thus, virus inactivation can begin when 3 CD4-IgG (of approximately 216 gp120 sites) bind per virion.


Characterization of encephalomyocarditis virus isolated from aborted swine fetuses.
Characteristics of 2 encephalomyocarditis virus (EMCV) isolates (MN-25 and MN-30) recovered from aborted swine fetuses were examined along with 2 other swine isolates (NVSL-MDV and NVSL-PR) and a reference ATCC strain (VR-129). All 5 EMCV isolates were found to be serologically related by cross testing, using serum neutralization and fluorescent antibody assays. Hemagglutination (HA) properties of the 5 isolates were compared, using 5 diluents. The MN-25 and NVSL-MDV strains had HA activity with guinea pig RBC in all 5 diluents, whereas MN-30, NVSL-PR, and VR-129 had HA activity only in KCl-borate buffer. The HA ability with RBC of various animal species was examined, using KCl-borate diluent. All virus isolates had high HA titer (1:512 to 1:2,048) with guinea pig, rat, and horse RBC and lower HA titer (1:16 to 1:64) with sheep RBC. The MN-25 and NVSL-MDV isolates agglutinated dogs RBC, whereas MN-30, NVSL-PR, and VR-129 strains did not. Viral replication was evident in 8 of 10 cell lines tested, although infectivity titers of each virus varied by cell line used. Plaque-forming ability was similar for all 5 isolates, but plaque size was different by virus and cell culture used. Virus isolates were found to be stable after being heated at 56 C and subjected to a wide range of pH. A viral polypeptide pattern difference for all 5 isolates was not found by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS)


Iminium ion catalysis: use of the alpha-effect in the acceleration of the Diels-Alder reaction.
The alpha-effect can be used in the acceleration of the Diels-Alder reaction between a series of dienes and electron deficient dienophiles using iminium ion catalysis, providing a novel molecular scaffold capable of performing this class of catalytic process.


Similar effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on depressive disorder in heart failure patients: A 12-week randomized controlled trial.
Heart failure related depression is recently increased worldwide. Heart failure (HF) disease is identified as a critical cause of increasing morbidity, hospital readmission, and mortality. The most important purpose of treatment of HF disease is to relief disease problems, improve functional performance, and achieve better quality of life. This study was proposed to evaluate the effects of low to moderate-intensity exercise program vs moderate-intensity continuous exercise program on the level of depressive disorder in heart failure patients. 12-week randomized controlled trial. Sixty nine HF patients with mild to moderate level of depression and ejection fraction <40% were examined before and after 12-week intervention. Their age was ranged from 40 to 60 years. Patients were randomly classified into 3 groups. Group I (n = 23) received low to moderate intensity exercise program (LMIEP), group II (n = 23) received moderate-intensity exercise program (MICEP), and group III (n = 23) did not receive any exercise program (Non-exercised group). All patients were instructed to conduct home-based exercise with their pharmacological therapy. The level of depression was evaluated before and after 12 weeks of the intervention program. The 3 study groups were associated with significant decrease of depression level (P < .05). Significant differences were exhibited between the 3 groups in favor to both exercise programs (P < .05) with non-significant differences between the 2 exercise programs (P > .05). Both exercise programs had positive effects in reducing the severity of depression in HF patients. Low to moderate and moderate-intensity exercise programs should be proposed for depression illness specially patients with heart failure.


Functional interactions between GTP cyclohydrolase I and tyrosine hydroxylase in Drosophila.
Tyrosine hydroxylase requires the regulatory cofactor, tetrahydrobiopterin, for catecholamine biosynthesis. Because guanosine triphosphate cyclohydrolase I is the rate limiting enzyme for the synthesis of this cofactor, it has a key role in catecholamine production. We show that GTP cyclohydrolase and tyrosine hydroxylase (TH) are co-localized in the Drosophila central nervous system. Mutations in the Punch locus, which encodes GTP cyclohydrolase, reduce TH activity; addition of cofactor to crude extracts could not fully rescue this activity in all mutant strains. The decrease in TH activity and the inability to increase it with added cofactor is not due to loss or decreased production of TH protein. We found that TH co-immunoprecipitated with GTP cyclohydrolase when wild type head extracts were incubated with anti-GTP cyclohydrolase antibody. We suggest that regulation of TH by its cofactor may require its association with GTP cyclohydrolase, and that the ability of GTP cyclohydrolase to associate with TH and its role in tetrahydrobiopterin synthesis may be separable functions of this enzyme. These results have important implications for understanding catecholamine-related neural diseases and designing strategies for gene therapy.


Give Me a Straight Answer: Response Ambiguity Diminishes Likability.
Across nine experiments (eight preregistered) involving Western and Asian samples, we showed that people providing ambiguous (vs. specific) responses to questions in various social scenarios are seen as less likable. This is because, depending on the social context, response ambiguity may be interpreted as a way to conceal the truth and as a sign of social disinterest. Consequently, people reported lower inclination to befriend or date individuals who appeared to provide ambiguous responses. We also identified situations in which response ambiguity does not harm likability, such as when the questions are sensitive and the responder may need to "soften the blow." A final exploratory study showed that response ambiguity also impacts personality perceptions-individuals providing ambiguous responses are judged as less warm, less extraverted, less gullible, and more cautious. We discuss theoretical implications for the language psychology and person perception literatures and practical implications for impression management and formation.


[Ultrastructural demonstration of 3 beta-hydroxysteroid dehydrogenase activity using potassium ferricyanide].
Sections of Rat and Amphibian adrenocortical tissue fixed in a mixture of 1% formaldehyde and 0.25% glutaraldehyde, are incubated in a medium containing namely a 3 beta-hydroxysteroid (substrate), NAD, potassium ferricyanide (hydrogen acceptor) and copper sulfate. A hyaloplasmic copper ferrocyanide precipitate is observed in the immediate vicinity of the smooth endoplasmic reticulum membranes, or in close contact with them. This reaction, which does not occur in media lacking the substrate or containing cyanoketone, is a result of 3 beta-hydroxysteroid dehydrogenase activity. Problems concerning the precise localization of this enzyme are discussed.


Cardiac tamponade during pregnancy due to primary lung cancer: A case report.
We report a rare case of cardiac tamponade caused by lung cancer in a pregnant woman. A 32-year-old multiparous pregnant woman was admitted to the hospital at 15 weeks of gestation with a persistent cough and dyspnea. Transthoracic echocardiography revealed a pericardial effusion with evidence of tamponade physiology. Computed tomography (CT) revealed a massive pericardial effusion and a left lung tumor. Pericardial tamponade was successfully treated using pericardiocentesis. She was diagnosed with lung adenocarcinoma stage IVB based on bronchoscopic lung biopsy, which showed adenocarcinoma and CT, which showed brain metastasis. Pregnancy was terminated at 18 weeks of gestation, followed by molecular-targeted therapy with alectinib hydrochloride and whole-brain irradiation. 24 months after treatment initiation the patient is alive without disease progression. Although pericardial tamponade caused by a malignant tumor during pregnancy is a rare and serious life-threatening condition, appropriate diagnosis and prompt treatment can improve maternal prognosis.


[Electrophysiological study of 5,6-dihydroxytryptamine effect on defensive reflex conditioning in the snail].
The role of serotonin in expression of membrane properties of identified neurons was studied during defensive reflex conditioning using the neurotoxic analogue of serotonin 5,6-dihydroxytryptamine (5,6-DHT). The defensive reflex conditioning in snails was destroyed on the second day after second injection of 5,6-DHT. Through the 1st weeks after second injection of 5,6-DHT the snails were learned but worse than snails after injection of saline solution. This result shows the recovery of snail's learning ability within 2 weeks after the second injection of 5,6-DHT. It was found that injection of 5,6-DHT prevented the decrease of membrane and threshold potentials of command neurons during defensive reflex conditioning as compared with the snails injected with 5,6-DHT without learning.


Genetically engineered angiogenic cell sheets using magnetic force-based gene delivery and tissue fabrication techniques.
A major limitation in tissue engineering is the insufficient formation of blood vessels in implanted tissues, resulting in reduced cell density and graft size. We report here the fabrication of angiogenic cell sheets using a combination of two magnetic force-based techniques which use magnetite cationic liposomes (MCLs), magnetofection and magnetic cell accumulation. A retroviral vector encoding an expression cassette of vascular endothelial growth factor (VEGF) was labeled with MCLs, to magnetically attract the particles onto a monolayer of mouse myoblast C2C12 cells, for gene delivery. MCL-mediated infection increased transduction efficiency by 6.7-fold compared with the conventional method. During the fabrication of the tissue constructs, MCL-labeled cells were accumulated in the presence of a magnetic field to promote the spontaneous formation of a multilayered cell sheet. VEGF gene-engineered C2C12 (C2C12/VEGF) cell sheets, constructed using both magnetic force-based techniques, were subcutaneously transplanted into nude mice. Histological analyses revealed that on day 14 the C2C12/VEGF cell sheet grafts had produced thick tissues, with a high-cell density, and promoted vascularization. This suggests that the method described here represents a powerful strategy in tissue engineering.


Detection of Escherichia coli O157:H7 in the beef marketed in Malaysia.
Twelve strains of Escherichia coli O157:H7 were isolated from 9 of 25 beef samples purchased from retail stores in Malaysia. These strains produced Shiga toxin 2 with or without Shiga toxin 1 and had the eae gene and a 60-MDa plasmid. The antibiograms and the profiles of the arbitrarily primed PCR of the strains were diverse, suggesting that the strains may have originated from diverse sources.


[Applications of genetically modified animals].
The first transgenic animals, mice, were obtained in 1980. The techniques of gene transfer had to be adapted to obtain transgenic animals with an acceptable yield in about fifteen species. When the yield is low (low rate of random integration and targeted integration via homologous recombination), genetic modifications must be achieved in intermediate cells able to participate to the development of chimeric transgenic animals (ES cells, EG cells, iPS obtained by the dedifferentiation of somatic cells) or in somatic cells used as nuclear donor to generate transgenic clones. Various tools make possible a marked increase of homologous recombination efficiency (meganucleases and ZFN), or a gene inactivation at the genome level (direct or conditional knock out) or at the mRNA level (interfering RNAs). Vectors allow a more reliable transgene expression. Genetically modified animals are used mainly to obtain information on biological functions and human diseases. Transgenic animals produce recombinant pharmaceutical proteins in milk and soon in egg white. Pig organs adapted to be tolerated by patients might be tested in humans in five years. The projects based on the use of transgenesis to improve animal production are presently few. Transgenic salmon with accelerated growth might be on the market when their possible escape in oceans will be controlled.


Bleeding complications after basilar artery fibrinolysis with tissue plasminogen activator.
Fibrinolysis with local intraarterial urokinase infusion for basilar artery thrombosis has been associated with a low rate of spontaneous symptomatic cerebral hemorrhage, even when patients have been treated late in the course of symptoms. Because urokinase is presently unavailable in the United States, this study was undertaken to determine the frequency of spontaneous cerebral hemorrhage in basilar artery fibrinolysis performed with tissue plasminogen activator (tPA). In a retrospective review of our initial experience with cerebral fibrinolysis for acute stroke using intraarterial tPA, four cases of basilar thrombosis were identified. Doses of the fibrinolytic agent and heparin, angiographic findings, clinical courses, and bleeding complications for these patients were determined. These results were compared with those from a prior study of 20 similar consecutive patients treated with urokinase. Symptom duration before treatment was unlimited. Intraarterial doses of tPA were 20 to 50 mg. Patients received full systemic anticoagulation with heparin. Complete basilar artery recanalization was achieved in 75% of patients. Two patients treated with tPA had angioplasty and stent placement for related high-grade stenosis. Spontaneous symptomatic cerebral hemorrhage occurred in three (75%) of the four tPA-treated patients and in three (15%) of the 20 urokinase-treated patients. The cerebral hemorrhage complication rate for intraarterial fibrinolysis with tPA was very high in cases of basilar artery thrombosis at the doses we used. Protocol adjustments should be considered.


Organic acids and protein compounds causing the photoluminescence properties of natural rubber membranes and the quenching phenomena from Au nanoparticle incorporation.
Natural rubber membranes were fabricated using latex from Hevea brasiliensis trees (clone RRIM 600) by casting, and controlling the time and temperature of thermal treatment. Three temperatures were used: 65, 80 and 120 °C and the corresponding annealing times of 6, 8, 10 and 12 h. The centrifugation of the latex produces the constituent phases: solid rubber (F1), serum or protein components (F2) and bottom fraction (F3). The photoluminescence properties could be correlated with organic acid components of latex. Natural rubber membranes were used as the active substrate (reducing agent) for the incorporation of colloidal Au nanoparticles synthesized by in situ reduction at different times. The intensity of photoluminescence bands assigned to the natural rubber decreases with the increase in amount of nanoparticles present on the membrane surface. It can be assumed that Au nanoparticles may be formed by reduction of the Au cation reacting with functional groups that are directly related to photoluminescence properties. However, the quenching of fluorescence may be attributed to the formation of a large amount of metal nanostructures on the natural rubber surface.


Trait impulsivity as an endophenotype for bipolar I disorder.
Impulsivity, conceptualized as impairment in planning and poor attentional and inhibitory control, is a key feature of bipolar disorder. Familial risk for bipolar disorder is known to affect inhibitory control but its impact on the attentional and planning dimensions of impulsivity is still unclear. We administered the Barratt Impulsiveness Scale, version 11 (BIS-11) to 54 euthymic individuals with DSM-IV bipolar I disorder, 57 of their clinically unaffected siblings, and 49 healthy comparison subjects. Groups were compared on the attentional (rapid shifts in attention/impatience with complexity), motor (acting impetuously), and non-planning (absence of weighing upon long-term consequences of actions) subscales of the BIS-11, and on total BIS-11 score. To investigate functional implications of trait impulsivity, total BIS-11 score was examined in relation to current psychosocial functioning and criminal history. Individuals with bipolar I disorder had elevated scores compared to healthy comparison subjects on BIS-11 total score and all three subscales (p < 0.0001). Unaffected siblings had elevated BIS-11 total score (p = 0.0037), motor (p = 0.0027), and non-planning (p = 0.0379) subscales in comparison to unrelated healthy controls. Total BIS-11 score was negatively associated with global assessment of functioning (GAF) score (β = -0.32, p < 0.0001). Our results suggest that impulsivity is sensitive to familial liability for the illness, making it a potential endophenotype for bipolar disorder.


Quality improvement methodology can reduce hospitalisation for abscess management.
Abscesses are a common reason for ED visits. While many are drained in the ED, some require drainage in the operating room (OR). We observed that a higher percentage of patients at our institution in Columbus, Ohio, were admitted to the hospital with abscesses for incision and drainage (I&D) in the OR than other institutions, including paediatric institutions. Our aim was to decrease hospitalisations for abscess management. A multidisciplinary team convened to decrease hospitalisation for patients with abscesses and completed multiple 'Plan-Do-Study-Act' cycles, including increasing I&Ds performed in the ED. Other interventions included implementation of a clinical pathway, training of procedure technicians (PT), updating the electronic medical record (EMR), credentialing advanced practice nurses in sedation and individual follow-up with providers for admitted patients. Data were analysed using statistical process control charts. Gross average charges were assessed. Admissions for I&D decreased from 26.3% to 13.7%. Abscess drainage in the ED improved from 79.3% to 96.5%. Mean length of stay decreased from 19.5 to 11.5 hours for all patients. Patients sedated increased from 3.3% to 18.2%. The number of repeat I&Ds within 30 days decreased from 4.3% to 1.7%. We decreased hospitalisations for abscess I&D by using quality improvement methodology. The most influential intervention was an initiative to increase I&Ds performed in the ED. Additional interventions included expanded training of PTs, implementation of a clinical pathway, updating the EMR, improving interdepartmental communication and increasing sedation providers.


Effects of a multilamellar emulsion on glucocorticoid-induced epidermal atrophy and barrier impairment.
Skin atrophy is one of the most frequent side-effects of the topical glucocorticoid. Skin barrier impairment has also been reported as a steroid-induced side effect. Although there have been various studies on preventing or minimizing this atrophogenic effect, little has been reported about preventing barrier impairment. This study was performed to determine the effects of a multilamellar emulsion (MLE) that had a well-ordered lamellar structure on the steroid-induced barrier impairment and epidermal atrophy. To confirm these effects of MLE, 0.05% clobetasol-17-propionate (CP) and 0.05% clobetasol-17-propionate in MLE (MLE/CP) were topically applied to both flanks of hairless mice for 9 days. The topically applied CP induced a significant impairment of the epidermal permeability barrier, and MLE/CP also did not have a preventive effect on this change. However, skinfold thickness studies and histological studies showed that MLE/CP significantly reduced the steroid-induced atrophy. The topical application of MLE/CP was also shown to have a preventive effect on the steroid-induced increase of the stratum corneum (SC) surface pH. In addition, the electron microscopic findings showed relatively well-conserved lamellar bilayers in the skin treated with MLE, as compared to CP only. The results showed that the topical application of MLE immediately after CP treatment prevented the glucocorticoid-induced transepidermal water loss values increase. Light microscopy measurements showed that the skin treated with MLE immediately after CP treatment for 1 week had a slightly lower decline of skin thickness than did the CP-treated skin. These results suggest that MLE should be effective for preventing glucocorticoid-induced epidermal atrophy and for repairing the barrier impairment.


Binary and Hybrid Work-Condition Maps for Interactive Exploration of Ergonomic Human Arm Postures.
Ergonomics of human workers is one of the key elements in design and evaluation of production processes. Human ergonomics have a major impact on productivity as well as chronic health risks incurred by inappropriate working postures and conditions. In this paper we propose a novel method for estimating and communicating the ergonomic work condition called Binary Work-Condition Map, which provides a visualized feedback about work conditions of different configurations of an arm. The map is of binary nature and is derived by imposing the desired thresholds on considered ergonomic and safety related criteria. Therefore, the suggested arm postures in the map guarantee that all considered criteria are satisfied. This eliminates the ambiguity compared to state-of-the-art maps that uses continuous scales derived from weighted sum of multiple ergonomics criteria. In addition, to combine the advantages of both the binary map and the continuous map, we additionally propose a Hybrid Work-Condition Map that rules out unsuitable workspace with the binary map approach and renders the suitable workspace with the continuous map approach. The proposed approach was tested in simulation for various tasks and conditions. In addition, we conducted subjective evaluation experiments to compare the proposed methods with the state-of-the art method regarding the usability. The results indicated that the binary map is simpler to use, while the hybrid map is a good tradeoff between the binary and the continuous map. In selecting the map, strong points of each map should be considered with respect to the requirements of a specific application and task.


[Parent assessment of outpatient child and adolescent mental health services].
Parent assessment of outpatient child and adolescent mental health services (CAMHS) is now part of the Norwegian quality indicator system. This national survey included a validated questionnaire that assessed three aspects of care from a parental perspective. Questionnaires were mailed to 17,080 parents of children and adolescents receiving care from CAMHS on an outpatient basis between 1 September and 31 December 2006. Two postal reminders were sent and telephone interviews were conducted with a sample of non-respondents. 7 906 (46%) parents returned a completed questionnaire. Three scales about treatment providers, treatment outcome and information/influence were identified (scales scored 0 to 100 where 100 represent the best experiences). The parents were most satisfied with the treatment providers (national mean 75). The national mean for the treatment outcome was 72 and for the scale concerning information and patients' possibilities to influence decisions the mean score was 59. The clinic scores varied considerably; the score for information and influence varied most (48-68). Few scores were however significantly different from the national average. Most parents have good experience with the CAMHS. The scale concerning information and influence has the greatest potential for improvement. Several CAMHS had higher scores for all aspects of parent experience and may have useful information to convey to other clinics.


[1R-(1α,2α,4α,5β,6α,7α)]-4-Benzoyl-oxymethyl-5,6-dihy-droxy-3,8-dioxa-tricyclo-[18.104.22.168]octan-5-yl acetate (3-deacetyl-crotepoxide) from Kaempferia rotunda Val.
The title compound, C(16)H(16)O(7), isolated from Kaempferia rotunda rhizomes, features a six-membered cyclo-hexane ring that adopts a twisted-boat conformation owing to the presence of two adjacent epoxide attachments that lock in four of the six axial positions. The CH(3)CO(2)- and HO- substituents occupy equatorial positions. However, the bond angles at the ring carbon connected to the C(6)H(5)CO(2)CH(2)- substituent deviate signifcantly from the idealized tetra-hedral angles as the carbon atom is part of an epoxide ring. In the crystal, the molecules are linked into chains by O-H⋯O hydrogen bonds.


Dual-Mode Fluorescence/Ultrasound Imaging with Biocompatible Metal-Doped Graphene Quantum Dots.
Sonography offers many advantages over standard methods of diagnostic imaging due to its non-invasiveness, substantial tissue penetration depth, and low cost. The benefits of ultrasound imaging call for the development of ultrasound-trackable drug delivery vehicles that can address a variety of therapeutic targets. One disadvantage of the technique is the lack of high-precision imaging, which can be circumvented by complementing ultrasound contrast agents with visible and, especially, near-infrared (NIR) fluorophores. In this work, we, for the first time, develop a variety of lightly metal-doped (iron oxide, silver, thulium, neodymium, cerium oxide, cerium chloride, and molybdenum disulfide) nitrogen-containing graphene quantum dots (NGQDs) that demonstrate high-contrast properties in the ultrasound brightness mode and exhibit visible and/or near-infrared fluorescence imaging capabilities. NGQDs synthesized from glucosamine precursors with only a few percent metal doping do not introduce additional toxicity in vitro, yielding over 80% cell viability up to 2 mg/mL doses. Their small (<50 nm) sizes warrant effective cell internalization, while oxygen-containing surface functional groups decorating their surfaces render NGQDs water soluble and allow for the attachment of therapeutics and targeting agents. Utilizing visible and/or NIR fluorescence, we demonstrate that metal-doped NGQDs experience maximum accumulation within the HEK-293 cells 6-12 h after treatment. The successful 10-fold ultrasound signal enhancement is observed at 0.5-1.6 mg/mL for most metal-doped NGQDs in the vascular phantom, agarose gel, and animal tissue. A combination of non-invasive ultrasound imaging with capabilities of high-precision fluorescence tracking makes these metal-doped NGQDs a viable agent for a variety of theragnostic applications.


Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses.
To identify new regulators of antiviral innate immunity, we completed the first genome-wide gene silencing screen assessing the transcriptional response at the interferon-β (IFNB1) promoter following Sendai virus (SeV) infection. We now report a novel link between WNT signaling pathway and the modulation of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR)-dependent innate immune responses. Here we show that secretion of WNT2B and WNT9B and stabilization of β-catenin (CTNNB1) upon virus infection negatively regulate expression of representative inducible genes IFNB1, IFIT1 and TNF in a CTNNB1-dependent effector mechanism. The antiviral response is drastically reduced by glycogen synthase kinase 3 (GSK3) inhibitors but restored in CTNNB1 knockdown cells. The findings confirm a novel regulation of antiviral innate immunity by a canonical-like WNT/CTNNB1 signaling pathway. The study identifies novel avenues for broad-spectrum antiviral targets and preventing immune-mediated diseases upon viral infection.


Differentiation of two distinct K conductances in the basolateral membrane of turtle colon.
The K conductance of the basolateral membrane of turtle colon was measured in amphotericin-treated cell layers under a variety of ionic conditions. Changing the composition of the bathing solutions changed not only the magnitude but also the physical properties of the basolateral K conductance. The results are consistent with the notion that altered ionic environments can lead to changes in the relative abundance of two different populations of K channels in the basolateral membrane, which can be differentiated on the basis of pharmacological specificity, ion selectivity, and tracer kinetics. In the following article (Germann, W. J., S. A. Ernst, and D. C. Dawson, 1986, Journal of General Physiology, 88:253-274), we present evidence consistent with the hypothesis that one of these conductances was due to the same channels that give rise to the normal resting basolateral K conductance of the transporting cells, while the other was associated with experimental maneuvers that led to extreme swelling of the epithelial cells.


Surface Structure of Hydroxyapatite from Simulated Annealing Molecular Dynamics Simulations.
The surface structure of hydroxyapatite (HAP) is crucial for its bioactivity. Using a molecular dynamics simulated annealing method, we studied the structure and its variation with annealing temperature of the HAP (100) surface. In contrast to the commonly used HAP surface model, which is sliced from HAP crystal and then relaxed at 0 K with first-principles or force-field calculations, a new surface structure with gradual changes from ordered inside to disordered on the surface was revealed. The disordering is dependent on the annealing temperature, Tmax. When Tmax increases up to the melting point, which was usually adopted in experiments, the disordering increases, as reflected by its radial distribution functions, structural factors, and atomic coordination numbers. The disordering of annealed structures does not show significant changes when Tmax is above the melting point. The thickness of disordered layers is about 10 Å. The surface energy of the annealed structures at high temperature is significantly less than that of the crystal structure relaxed at room temperature. A three-layer model of interior, middle, and surface was then proposed to describe the surface structure of HAP. The interior layer retains the atomic configurations in crystal. The middle layer has its atoms moved and its groups rotated about their original locations. In the surface layer, the atomic arrangements are totally different from those in crystal. In particular for the hydroxyl groups, they move outward and cover the Ca(2+) ions, leaving holes occupied by the phosphate groups. Our study suggested a new model with disordered surface structures for studying the interaction of HAP-based biomaterials with other molecules.


Effects of medium-chain triglyceride feeding on glucose homeostasis in the newborn rat.
The mechanism of the profound hypoglycemia that develops in newborn rats during a fast of 16-h beginning at birth has been investigated. This fasting hypoglycemia was completely reversed by giving oral medium-chain fatty acids (MCT). The rise in blood glucose induced by MCT feeding was not secondary to a decreased uptake of glucose by peripheral tissues because [6-3H]glucose turnover rate was increased in MCT-fed neonates. Several lines of evidence strongly suggest that MCT feeding was associated with a stimulation of hepatic gluconeogenesis. 1) The rate of [6-3H]glucose turnover was enhanced after MCT feeding. 2) A fivefold increase in the conversion of labeled lactate into glucose was observed in vivo after MCT feeding. 3) The rise in blood glucose induced by MCT feeding was totally suppressed by an inhibitor of gluconeogenesis (3-mercaptopicolinate). Despite their utilization for glucose synthesis, blood levels of lactate, alanine, and pyruvate were increased two- to threefold after MCT feeding. When MCT feeding was given in association with dichloroacetate, an activator of pyruvate dehydrogenase (PDH), no increase in blood lactate, alanine, and pyruvate was observed and the rise in glycemia was prevented. This suggested that hyperketonemia due to MCT feeding could decrease the oxidation of 3-carbon glucose precursors in peripheral tissues, secondary to an inhibition of PDH, and thus enhanced their release in blood. These data indicate that MCT feeding stimulates glucose production in the newborn rat, both by increasing the availability of gluconeogenic precursors and by a direct effect on hepatic gluconeogenesis.


X-ray imaging inside the focal spot of polycapillary optics using the coded aperture concept.
We present a method for x-ray imaging of objects inside the focal spot of polycapillary optics that resolves details smaller than the focal spot dimensions. This method employs coded aperture imaging, in which the micro-structure of polycapillary optics is treated as the coding pattern. Projection of the object is decoded from a magnified x-ray image of the polycapillary structure which is specifically sharpened by the object. Field of view can be extended by scanning the object across the focal spot.


[Responsible cancer screening].
In the Netherlands, national screening programs for breast and cervical cancer are operating, whilst that for colorectal cancer is in preparation. In the meantime, experimental studies have been conducted into the effectiveness of prostate and lung cancer screening. Death from these five types of cancer is reduced by these screening investigations. However, these screening programmes also have disadvantages, such as unnecessary referral for definitive diagnosis in the hospital. The average hospital would receive on a yearly basis via screening 156 referrals of women with breast cancer, 79 for cervical cancer and nearly 1100 persons for colorectal cancer. n average general practice encounters annually 3 positive screening results for breast cancer, almost 1 referral for cervical carcinoma or an early stage thereof, and every two years a patient with CIN III. For colorectal cancer around 22 referrals can be expected yearly, of which 8 will have adenoma or cancer.


TNF-alpha promoter polymorphisms and extended HLA and TNF-alpha haplotypes in Koreans based on 100 families.
We investigated five single-nucleotide polymorphism (SNP) sites of tumor necrosis factor-alpha (TNF-alpha) promoter, the distribution of five-locus TNF-alpha haplotypes, and extended human leukocyte antigen (HLA)/TNF-alpha haplotypes in 200 parents from 100 unrelated Korean families. TNF-alpha SNPs were typed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and PCR restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of -1031C, -863A, -857T, -308A, and -238A alleles were 0.185, 0.145, 0.140, 0.060, and 0.040, respectively. The allele frequencies in Koreans were similar to those of Japanese. A total of five TNF-alpha haplotypes (-1031/-863/-857/-308/-238) were detected in 196 parents: TCCGG (frequency 0.617), CACGG (0.143), TCTGG (0.143), TCCAG (0.061), and CCCGA (0.036). Five most common extended HLA/TNF-alpha haplotypes (frequencies >0.020) accounted for 16% (63/392) of the total haplotypes. A total of 223 HLA haplotypes and 239 HLA/TNF-alpha haplotypes were detected, indicating that most HLA haplotypes are exclusively associated with particular TNF-alpha haplotypes.


Ultrasound evaluation of amniotic fluid volume: methods and clinical accuracy.
Ultrasound evaluation of amniotic fluid volume (AFV) is frequently used to detect fetuses at high risk for an adverse outcome - an event that is often correlated with AFV abnormalities. As is well known, ultrasound is a non invasive procedure, which makes it ideal for application on a very large scale: in practice, it can be used for routine monitoring of all pregnancies and, not infrequently, for repeat AFV determination in those cases where there is the suspect of amniotic fluid abnormalities. Sonographic quantification of AFV, whether it is performed through a simple visual estimation or through biometric measurement of one or more amniotic fluid pockets, can never represent a true "quantitative" method and its actual reliability has not consistently been proved by scientific evidence. Moreover, even though ultrasound AFV evaluation is indispensable in the management of high-risk pregnancies, there is no consensus on which ultrasound index is the most accurate in predicting perinatal morbidity and mortality. The sonographer can evaluate AFV by directly observing amniotic fluid pockets and his experience is crucial for a high reliability of the procedure. When pathological AFV changes are present, especially if the examination is performed by a not so expert sonographer, biometric measurements (Single Deepest Pocket, Amniotic Fluid Index, Two-Diameter Pocket) with their respective reference ranges might be helpful in confirming the diagnosis of oligohydramnios or hydramnios. A complete review of all tests performances and confidences is made by the Authors.


Immunologic aspects of the nonobese diabetic (NOD) mouse. Abnormalities of cellular immunity.
Experiments were performed on 12-wk-old nonobese diabetic (NOD) mice to investigate the immunologic background of the condition, using ICR mice as controls. The results indicate the following: (1) absolute decreases in number of T lymphocytes, (2) depression of natural killer activity, (3) normal responsiveness in delayed type hypersensitivity and functional depression of killer T cells against allogeneic tumors, (4) diminished resistance to herpes virus infection, and (5) enhanced production of polyclonal antibodies to T cell-dependent antigens. These features are similar to those noted in other autoimmune diseases of man and in their experimental models in laboratory animals. Elucidation of the pathogenetic mechanism of autoimmune diabetes mellitus in NOD mice, therefore, may contribute to the diagnosis, treatment, and prevention of a wide variety of autoimmune diseases.


Less repair of pyrimidine dimers and single-strand breaks in genes by scid cells.
Severe combined immunodeficient (Scid) mice have a mutation in the catalytic subunit of the DNA binding protein kinase that is involved in repair of double-strand breaks in DNA. To determine if the protein also influences repair of single-strand breaks, we examined the ability of Scid cells to repair lesions introduced by ultraviolet light and gamma-ray irradiation. DNA repair was measured both in total genomic DNA and in specific genes from murine Scid and wildtype fibroblast cell lines. The removal of pyrimidine dimers and repair of strand breaks in genes was measured using quantitative Southern blot analyses. After ultraviolet irradiation, there was no significant difference in the repair of photoproducts in bulk DNA between Scid and wildtype cells, as measured by cellular survival and unscheduled DNA synthesis. However, deficient repair was evident in genes, where Scid cells had 25-50% less repair in the c-myc and dihydrofolate reductase genes. After gamma-irradiation, Scid fibroblasts had 20-35% less repair of DNA breaks in immunoglobulin kappa and heavy constant genes than wildtype cells. The data suggest that intact DNA-PK enzyme is needed for the efficient operation of cellular repair of pyrimidine dimers and single-strand breaks in genes, as well as in its established role in rejoining double-strand breaks.


Photonic microwave frequency divider with a tunable division ratio and harmonic suppression capability.
A photonic microwave frequency divider that is capable to realise tunable high order frequency division, is presented. It is based on injecting an RF phase modulated optical signal into an off-the-shelf DFB laser operating at period-N state. Optical frequency components with a frequency separation of 1/N times the input RF signal frequency are generated by the DFB laser. An optical bandpass filter can be employed to select two optical frequency components to be detected by a photodetector to obtain a divide-by-N RF signal without harmonic components. The proposed frequency divider can be operated over a wide frequency range and has high reconfigurability as it is free of electrical components. Experimental results demonstrate the realisation of frequency division operation with a tunable 1/2 to 1/5 division ratio for different input RF signal frequencies of 8 to 20 GHz by adjusting the DFB laser forward bias current. Over 35 dB harmonic component suppression is demonstrated. A proof-of-concept experiment is also set up to show the frequency divider based on an optically injected semiconductor laser is capable to operate at a high input RF signal frequency of 50 GHz and has a tunable high order division ratio of 1/2 to 1/8.


Synthesis and characterization of heterobimetallic (Pd/B) Nindigo complexes and comparisons to their homobimetallic (Pd2, B2) analogues.
Reactions of Nindigo-BF2 complexes with Pd(hfac)2 produced mixed complexes with Nindigo binding to both a BF2 and a Pd(hfac) unit. These complexes are the first in which the Nindigo ligand binds two different substrates, and provide a conceptual link between previously reported bis(BF2) and bis(Pd(hfac)) complexes. The new Pd/B complexes have intense near IR absorption near 820 nm, and they undergo multiple reversible oxidations and reductions as probed by cyclic voltammetry experiments. The spectral, redox, and structural properties of these complexes are compared against those of the corresponding B2 and Pd2 complexes with the aid of time-dependent density functional calculations. In all cases the low-energy electronic transitions are ligand-centered π-π* transitions, but the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies--and hence the absorption wavelength as well as the oxidation and reduction potentials--are significantly modulated by the moieties bound to the Nindigo ligand.


Global municipal solid waste infrastructure: Delivery and forecast of uncontrolled disposal.
Proper management and treatment of municipal solid waste (MSW) plays a central role towards the reduction or elimination of uncontrolled disposal and the achievement of United Nations (UN) Sustainable Development Goals (SDGs) with the reduction of its vast adverse environmental and health impacts. Despite that, till now, there has never been a quantitative analysis of the progress in waste management infrastructure delivery worldwide. In this paper, we provide valuable insights regarding the progress in new MSW infrastructure delivery based on a dataset of 1764 projects from 156 countries, for the period 2014-2019. We also estimate the magnitude of uncontrolled waste disposal practices worldwide by estimating the gap between the current MSW infrastructure delivery and actual changes in MSW generation. Our results show that the new capacity delivered during the six years period amounted to 243 million metric tonnes (Mt) (40 million Mt per year), out of which 45% was delivered in high-income countries, 37.5% in the People's Republic of China and 17.5% in the rest of the world, mainly through thermal treatment (~57%) and landfilling (8%). The average allocated per capita budget of these projects during this period is about US$14, equivalent to US$2.33 (cap*year)-1. Our main conclusion is that the share of uncontrolled disposal will continue to rise at least until 2028, reaching almost 730 million Mt per year. Evidently, the global community continues to face a serious challenge towards the implementation of the UN SDG 12, target 12.4 by 2020. The analysis demonstrates that infrastructure delivery must increase by four folds to eliminate uncontrolled disposal practices.


The prediction of benzo[a]pyrene clearance by rat liver and lung from enzyme kinetic data.
The metabolic clearance of circulating benzo[a]pyrene (B[a]P) by liver and lung of control and 3-methylcholanthrene (3MC)-pretreated rats was predicted according to the perfusion-limited model from apparent enzyme kinetic constants determined in microsomal incubations. These predictions were tested in isolated organs perfused at normal organ flow. From microsomal incubations the apparent enzyme kinetic constants of B[a]P metabolism were determined. The apparent Km of liver microsomes was decreased 100 times by pretreatment with 3MC, while the Km of lung microsomes remained at about 0.2 microM. Maximal velocity of B[a]P metabolism was much greater in microsomes from liver than in those from lung of both control and 3MC-pretreated rats. Liver was found to have a far greater capacity for B[a]P metabolism (intrinsic free clearance) than lung. However, this large disparity was not evident in the predicted clearances. Perfused organs had B[a]P clearances very close to those predicted from the model. At normal (in vivo) organ flows, control rat lung had a clearance of 1.0 +/- 0.1 ml/min, whereas liver had a clearance of 5.9 +/- 0.2 ml/min. Corresponding clearances in organs from 3 MC-pretreated rats were 8.9 +/- 0.5 and 6.7 +/- 0.6 ml/min for lung and liver, respectively. Small discrepancies between predicted and observed values could not be explained by non-uniform distribution of B[a]P or shunting of flow. These results suggest that enzyme kinetic data can be used to assess accurately the ability of lung and liver to clear xenobiotic compounds such as B[a]P and that, despite the great disparity in their metabolic capacity, under certain conditions these two organs may function equally well in the removal of circulating compounds from the blood.


A study of phagocytosis in the ameba Chaos chaos.
The process of phagocytosis was investigated by observing the interactions between the ameba Chaos chaos and its prey (Paramecium aurelia), by studying food cup formation in the living cell, and by studying the fine structure of the newly formed cup using electron microscopy of serial sections. The cytoplasm surrounding the food cup was found to contain structures not seen elsewhere in the ameba. The results are discussed in relation to the mechanisms which operate during food cup formation.


ADP secretion and subsequent P2Y12 receptor signalling play a crucial role in thrombin-induced ERK2 activation in human platelets.
Stimulating human platelets with thrombin induces the activation of the extracellular signal-regulated kinase 2 (ERK2). We demonstrate that this effect is highly dependent on ADP secretion and P2Y12 receptor signalling. AR-C69931MX (10 microM), a specific antagonist of the Gi-coupled P2Y12 ADP receptor, inhibits ERK2 activation induced by thrombin. Antagonists of the Gq-coupled P2Y1 ADP receptor, A3P5P (500 microM) and MRS2179 (100 microM), have no effect. ADP and its more potent analogue 2-methylthio-ADP alone (both up to 100 microM) do not induce ERK2 activation. Furthermore, we show that the inhibitory effect of AR-C69931MX on ERK2 activation induced by 0.1 U/ml thrombin as well as on platelet aggregation can be bypassed by epinephrine (1 and 10 microM), whereas epinephrine alone has no effect. Epinephrine acts on platelets mainly via alpha(2A)-adrenergic receptors, which, like P2Y12 receptors, couple to inhibitory G proteins. In addition, 2-methylthio-ADP as well as epinephrine provoke ERK2 activation at a thrombin concentration that alone has no detectable effect (0.05 U/ml). Thromboxane A2 (TXA2), which, like ADP, is released by activated platelets, acts as a positive feedback mediator. Stimulating the Gq-coupled TXA2 -receptor with U46619 (10 microM), which leads to ADP secretion and P2Y12 receptor-dependent platelet aggregation, also induces P2Y12-related ERK2 activation. The inhibition of U46619-induced ERK2 activation and platelet aggregation by AR-C69931MX are also rescued by epinephrine. Pretreatment with aspirin inhibits ERK2 activation induced by 0.1 U/ml thrombin, but has no effect at high concentrations of thrombin. The combination of U46619 and thrombin, at concentrations which alone have no effect, provokes ERK2 activation, suggesting that thrombin and released TXA2 act synergistically. Our data indicate that both primary signalling through Gq, which evokes ADP secretion, as well as subsequent coupling via Gi by the P2Y12 receptor are required for ERK2 activation.