Large-sample Bayesian posterior distributions for probabilistic sensitivity analysis.
In probabilistic sensitivity analyses, analysts assign probability distributions to uncertain model parameters and use Monte Carlo simulation to estimate the sensitivity of model results to parameter uncertainty. The authors present Bayesian methods for constructing large-sample approximate posterior distributions for probabilities, rates, and relative effect parameters, for both controlled and uncontrolled studies, and discuss how to use these posterior distributions in a probabilistic sensitivity analysis. These results draw on and extend procedures from the literature on large-sample Bayesian posterior distributions and Bayesian random effects meta-analysis. They improve on standard approaches to probabilistic sensitivity analysis by allowing a proper accounting for heterogeneity across studies as well as dependence between control and treatment parameters, while still being simple enough to be carried out on a spreadsheet. The authors apply these methods to conduct a probabilistic sensitivity analysis for a recently published analysis of zidovudine prophylaxis following rapid HIV testing in labor to prevent vertical HIV transmission in pregnant women.


Characterization of viral particles isolated from primary cultures of human breast cancer cells.
The association of human breast cancer with sequences similar to the mouse mammary tumor virus (MMTV) has been shown, but convincing evidence for the presence of viral particles in breast tumors has been lacking. We have described the complete proviral structure of a retrovirus in human breast cancer. This provirus, designated as human mammary tumor virus (HMTV), was 95% homologous to MMTV and revealed features of a replication-competent virus. We have therefore investigated the production of viral particles in primary cultures of human breast cancer (MSSM). Cells isolated from ascites or pleural effusions of patients with metastatic breast cancer contained viral sequences in their DNA, expressed Env protein, and showed retroviral particles by electron microscopy. Viral particles from culture media exhibited morphologic features of beta-retroviruses sedimenting at buoyant densities of 1.12 to 1.18 g/mL in sucrose gradients and showed reverse transcriptase activity. cDNA sequences from virion RNA were synthesized, amplified, and sequenced and all the virion genes were detected and 70% of the virion RNA was sequenced. The sequence homologies were, respectively, 85% to 95% compared with the MMTV and HMTV proviruses we have previously described. These results clearly show that breast cancer cells in primary cultures produced HMTV viral particles that are similar to the mouse virus and which may play a role in human breast cancer pathogenesis.


PTH levels correlate with mental performance in CAPD.
Nervous system dysfunction remains a major cause of disability in patients with end stage renal disease. The mechanisms remain unclear, but elevated levels of parathyroid hormone (PTH) have been proposed to act as a neurotoxin in uremia. Previous studies have mainly used electroencephalographic techniques to assess mental performance in patients in dialysis. This study utilized the trail test A and the Pennsylvania bimanual dexterity work sample to evaluate mental performance of patients in CAPD and to correlate their performance with parathyroid hormone levels. Ten male patients from the same CAPD unit, with comparable dialysis dose, underwent standardized testing. Subjects had a mean +/- SE age of 50.8 +/- 3.66 years and had been on CAPD for a mean of 42.4 +/- 12.2 months. Each used 10-12 liters of dialysis per day, with a mean peritoneal dialysis index of 1.04 +/- 0.05 and Kt/V (UN/wk) of 2.35 +/- 0.39. Mental performance of patients with lower intact PTH levels 151.7 +/- 20.8 ng/ml (Group 1) was 34.4 +/- 2.8 min in the trail test A and patients with the higher PTH-mm level (414.0 +/- 21.4 ng/ml) was 58.2 +/- 10.8 min (p = 0.06). Whereas the bi-manual dexterity test was completed in 7.27 +/- 0.5 min by Group 1 and in 11.1 +/- 0.2 by Group 2 (p = 0.003). This study favors the hypothesis that PTH levels may be associated with the impaired mental performance observed in patients with end stage renal disease.


Wastewater nutrient removal in a mixed microalgae-bacteria culture: effect of light and temperature on the microalgae-bacteria competition.
The aim of this study was to evaluate the effect of light intensity and temperature on nutrient removal and biomass productivity in a microalgae-bacteria culture and their effects on the microalgae-bacteria competition. Three experiments were carried out at constant temperature and various light intensities: 40, 85 and 125 µE m-2 s-1. Other two experiments were carried out at variable temperatures: 23 ± 2°C and 28 ± 2°C at light intensity of 85 and 125 µE m-2 s-1, respectively. The photobioreactor was fed by the effluent from an anaerobic membrane bioreactor. High nitrogen and phosphorus removal efficiencies (about 99%) were achieved under the following operating conditions: 85-125 µE m-2 s-1 and 22 ± 1°C. In the microalgae-bacteria culture studied, increasing light intensity favoured microalgae growth and limited the nitrification process. However, a non-graduated temperature increase (up to 32°C) under the light intensities studied caused the proliferation of nitrifying bacteria and the nitrite and nitrate accumulation. Hence, light intensity and temperature are key parameters in the control of the microalgae-bacteria competition. Biomass productivity significantly increased with light intensity, reaching 50.5 ± 9.6, 80.3 ± 6.5 and 94.3 ± 7.9 mgVSS L-1 d-1 for a light intensity of 40, 85 and 125 µE m-2 s-1, respectively.


Selective sp3 C-H activation of ketones at the beta position by Ir(I). Origin of regioselectivity and water effect.
The reaction of the cationic (PNP)Ir(I)(cyclooctene) complex (1) (PNP = 2,6-bis-(di-tert-butylphosphinomethyl)pyridine) with 2-butanone or 3-pentanone results in the selective, quantitative activation of a beta C-H bond, yielding O,C-chelated complexes. Calculations show that the selectivity is both kinetically (because of steric reasons in the rate determingin step (RDS)) and thermodynamically controlled, the latter as a result of carbonyl oxygen coordination in the product. The RDS is formation of the eta2-C,H intermediates from the complexed ketone intermediates. Water has a strong influence on the regioselectivity, and in its presence, reaction of 1 with 2-butanone gives also the alpha terminal C-H activation product. Computational studies suggest that water can stabilize the terminal alpha C-H activation product by hydrogen bonding, forming a six-membered ring with the ketone, as experimentally observed in the X-ray structure of the acetonyl hydride aqua complex.


Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to.
Calorie restriction (CR), which deactivates the nutrient-sensing mTOR pathway, slows down aging and prevents age-related diseases such as type II diabetes. Compared with CR, rapamycin more efficiently inhibits mTOR. Noteworthy, severe CR and starvation cause a reversible condition known as "starvation diabetes." As was already discussed, chronic administration of rapamycin can cause a similar condition in some animal models. A recent paper published in Science reported that chronic treatment with rapamycin causes a diabetes-like condition in mice by indirectly inhibiting mTOR complex 2. Here I introduce the notion of benevolent diabetes and discuss whether starvation-like effects of chronic high dose treatment with rapamycin are an obstacle for its use as an anti-aging drug.


Mouse Retinal Whole Mounts and Quantification of Vasculature Protocol.
Angiogenesis is the formation of new blood vessels from a pre-existing vascular bed. It is a multi-step process beginning with enzymatic degradation of the capillary basement membrane, followed by endothelial cell (EC) proliferation, migration, tube formation, assembly of a new basement membrane, and pericyte stabilization. Aberrant angiogenesis plays a major role in the pathogenesis of many diseases. The regulation of this complex process is an important therapeutic target. Success in this pursuit, however, requires the development of in vivo angiogenesis models that provide a reliable and facile platform for mechanistic studies of angiogenic regulation as well as drug development and testing (Carmeliet and Jain, 2011). Postnatal development of mouse retinal vasculature offers a unique and powerful in vivo angiogenesis model because, unlike other species, mice undergo extensive angiogenesis-dependent maturation of their retinal vessels after birth. As such, this model is also very useful for the mechanistic study of embryonic vascularization (Stahl et al., 2010; Adini et al., 2003). This protocol describes the steps involved in the whole mount processing of mouse eyes for visualization of the retinal vasculature.


Morpho-physiological and biochemical characterization of African spider plant (Gynandropsis gynandra (L.) Briq.) genotypes under drought and non-drought conditions.
The African spider plant (Gynandropsis gynandra (L.) Briq.) is a nutrient-dense, climate-resilient indigenous vegetable with a C4 carbon fixation pathway. Understanding African spider plant drought tolerance mechanisms is essential for improving its performance in water-stressed areas. The objective of this study was to evaluate the stress tolerance potential of African spider plant accessions based on thirteen morphological, physiological, and biochemical traits under three different water treatment regimes. Eighteen accessions were evaluated over two growing seasons in the greenhouse using a split-split plot design with four replications and three water treatment-regimes namely optimum (100% field capacity), intermediate drought (50% field capacity) and, severe drought (30% field capacity). The results revealed that water regime had a significant effect (P< 0.01) on the accessions for the traits studied. A significant reduction across most of the studied traits was observed under drought conditions. However, proline content in all the accessions significantly rose under drought conditions. The principal component analysis revealed a considerable difference in the performance of the 18 African spider plant accessions under optimum and drought stress conditions. Several morphological and physiological parameters, including days to 50% flowering (r = 0.80), leaf length (r = 0.72), net photosynthesis (r = 0.76) and number of leaves per plant (r = 0.79), were positively associated with leaf yield under drought conditions. Cluster analysis categorized the 18 accessions and 13 measured parameters into 4 clusters, with cluster-1 exhibiting greater drought tolerance for most of the studied traits, and cluster-4 having the most drought-sensitive accessions. Among the accessions tested, accessions L3 and L5 demonstrated excellent drought tolerance and yield performance under both conditions. As a result, these accessions were selected as candidates for African spider plant drought tolerance breeding programs. These findings will serve as the foundation for future studies and will aid in improving food and nutrition security in the face of drought.


Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly complicated by the onset of acute myeloid leukemia.
We herein describe the case of a 62-year-old woman who presented with anemia and an 8-month history of weight loss. Bone marrow aspiration showed increased myeloblasts. The histopathology findings of biopsy specimens of the right cervical lymph node and intestinal mass indicated B-lymphoproliferative disorder (B-LPD) with Hodgkin lymphoma-like morphologic features and polymorphous diffuse large B-cell lymphoma (DLBCL), respectively. In addition, both types of lymphoma cells were positive for Epstein-Barr virus (EBV)-encoded small RNA-1. The patient was diagnosed with EBV-associated B-LPD and simultaneous acute myeloid leukemia (AML). This is the first case of a patient diagnosed with simultaneous EBV-positive DLBCL of the elderly and AML.


Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat.
Recent studies indicate that decreased central dopamine is associated with diet-induced obesity in humans and in animal models. In the current study, the authors assessed the hypothesis that diet-induced obesity reduces mesolimbic dopamine function. Specifically, the authors compared dopamine turnover in this region between rats fed a high-fat diet and those consuming a standard low-fat diet. The authors also assessed behavioral consequences of diet-induced obesity by testing the response of these animals in a conditioned place paradigm using amphetamine as a reinforcer and in an operant conditioning paradigm using sucrose reinforcement. Results demonstrate that animals consuming a high-fat diet, independent of the development of obesity, exhibit decreased dopamine turnover in the mesolimbic system, reduced preference for an amphetamine cue, and attenuated operant responding for sucrose. The authors also observed that diet-induced obesity with a high-fat diet attenuated mesolimbic dopamine turnover in the nucleus accumbens. These data are consistent with recent hypotheses that the hormonal signals derived from adipose tissue regulate the activity of central nervous system structures involved in reward and motivation, which may have implications for the treatment of obesity and/or addiction.


Providing Orthopaedic Care for the Incarcerated: Obstacles and Challenges.
Scant information on healthcare delivery to inmates is available in the medical literature. Healthcare provision to inmates has different rules than that for the general population and presents particular challenges for orthopaedic surgeons because of the nature of this population and restrictions imposed by their confinement. This population is typically of a lower socioeconomic status and is less well educated, has accumulated injuries over a lifetime, and has a considerable prevalence of communicable and blood-borne diseases, along with a high prevalence of smoking and high-risk behavior, such as drug-seeking, abuse, and self-inflicted injury. These variables add levels of complexity of care, including the determination of medical necessity for orthopaedic referral, the logistics of transportation and follow-up, access to durable medical equipment and ancillary services, and the choices the orthopaedic provider must make to optimize care within these limitations.


Toluene solubilization induces different modes of mixed micelle growth.
The effect of toluene solubilization on the size and mobility of Triton X100 (TX100) micelles and TX100/sodium dodecyl sulfate (SDS) mixed micelles was studied by turbidimetry, dynamic light scattering, and capillary electrophoresis. Micelle growth due to toluene solubilization was observed for both surfactant systems; however, two different modes of growth were seen. Mixed micelles in 0.1 M NaCl are spherical (apparent diameter d(app) = 8 nm) and remain so while taking up 3 mM toluene, with a volume increase per micelle of deltaV(m) = 50 nm3. In 0.5 M NaCl, the large d(app) of both nonionic and mixed micelles (14 and 24 nm, respectively) indicate ellipsoidal or rodlike shapes, and their large increases in d(app) upon addition of 3 mM toluene thus correspond to elongational growth, with the same deltaV(m) = 50 nm3. Further addition of toluene to TX100/SDS in 0.5 M NaCl results in a dramatic increase in micelle size followed by an unexpected bimodal size distribution. The addition of excess toluene leads to the formation of ca. 140 nm toluene droplets, stabilized mainly by monomers of the high critical micelle concentration surfactant, SDS. These microemulsions coexist with the smaller (20 nm) swollen mixed micelles.


Morphogenetic studies on the neural crest of hynobius larvae using vital staining and India ink labeling methods.
The neural crest cells of hynobius larvae during the morphogenesis of the neural crest were studied with the following methods: the region of the primordial neural crest was first determined by vital stainings, and then the movement of individual neural crest cells was traced with India ink labeling. The cytoarchitecture and the fine structure of neural crest cells were further observed by light, transmission and scanning electron microscopy. The primordium of the neural crest is located in the area extending from the lateral part of the neural plate to the medial part of the neural fold. RAVEN (1931) suggested that the lateral part of the neural fold was a part of the primordial neural crest. The result of our vital staining shows that it is the primordial epidermal ectoderm. The morphogenesis of the neural crest was found to proceed as follows: at first both neural folds moved to the dorsal mid line of larva, then contacted and fused to each other. The primordial neural crest cells in the neural folds became polygonal, and these cells from both folds mixed and formed a neural crest cell mass. In this process they lost their junctional apparatuses. When larvae developed at the tail bud stage, the cells in the lateral part of the neural crest extended their cytoplasmic processes and began to migrate.


Dynamics in a room-temperature ionic liquid: a computer simulation study of 1,3-dimethylimidazolium chloride.
The transport properties and solvation dynamics of model 1,3-dialkylimidazolium chloride melt at 425 K is studied using molecular-dynamics simulations. Long trajectories of a large system have been generated and quantities such as the self-diffusion coefficient of ions, shear viscosity, and ionic conductivity have been calculated. Interestingly, the diffusion of the heavier cation is found to be faster than the anion, in agreement with experiment. The interaction model is found to predict a higher viscosity and lower electrical conductivity compared to experimental estimates. Analysis of the latter calculations points to correlated ion motions in this melt. The solvation time correlation function for dipolar and ionic probes studied using equilibrium simulations exhibits three time components, which include an ultrafast (subpicosecond) part as well as one with a time constant of around 150 ps. The ultrafast solvent relaxation is ascribed to the rattling of anions in their cage, while the slow component could be related to the reorientation of the cations as well as to ion diffusion.


Detection of specific bacterial antigen in urine of patients infected with Bacteroides fragilis.
An indirect enzyme-linked immunosorbent assay was developed to detect specific Bacteroides fragilis antigen(s) in human urine. Specimens collected within 72 hr of a positive culture were centrifuged, dialyzed, and treated with Tween 20, polyethylene glycol, and bovine serum albumin. Goat hyperimmune gamma-globulin to B. fragilis strain ATCC 23745 was added and incubated, and supernatants were tested for antibody activity to polysaccharide-protein antigen of the same organism. Mean +/- SD results, reported as percentage inhibition of control values and interpreted blindly, were as follows: 29 normal subjects, 9.8% +/- 6.0%; 22 patients with Enterobacteriaceae bacteremia, 6.0% +/- 5.1%; six patients with nonbacteremic infections due to B. fragilis, 22.3% +/- 10.3%; and nine patients with B. fragilis bacteremia, 28.7% +/- 10.2%. Three of six nonbacteremic patients and eight of nine bacteremic patients yielded values greater than 2 SD of control values. None of 22 patients with Enterobacteriaceae bacteremia was falsely positive (specificity, 100%).


Host Bias in Diet-Source Microbiome Transmission in Wild Cohabitating Herbivores: New Knowledge for the Evolution of Herbivory and Plant Defense.
It is commonly understood that dietary nutrition will influence the composition and function of the animal gut microbiome. However, the transmission of organisms from the diet-source microbiome to the animal gut microbiome in the natural environment remains poorly understood, and elucidating this process may help in understanding the evolution of herbivores and plant defenses. Here, we investigated diet-source microbiome transmission across a range of herbivores (insects and mammals) living in both captive and wild environments. We discovered a host bias among cohabitating herbivores (leaf-eating insects and deer), where a significant portion of the herbivorous insect gut microbiome may originate from the diet, while in deer, only a tiny fraction of the gut microbiome is of dietary origin. We speculated that the putative difference in the oxygenation level in the host digestion systems would lead to these host biases in plant-source (diet) microbiome transmission due to the oxygenation living condition of the dietary plant's symbiotic microbiome. IMPORTANCE We discovered a host bias among cohabitating herbivores (leaf-eating insects and deer), where a significant portion of the herbivorous insect gut microbiome may originate from the diet, while in deer, only a tiny fraction of the gut microbiome is of dietary origin. We speculated that the putative difference in the oxygenation level in the host digestion systems would lead to these host biases in plant-source (diet) microbiome transmission due to the oxygenation living condition of the dietary plant's symbiotic microbiome. This study shed new light on the coevolution of herbivory and plant defense.


Is genetic information relevantly different from other kinds of non-genetic information in the life insurance context?
Within the medical, legal and bioethical literature, there has been an increasing concern that the information derived from genetic tests may be used to unfairly discriminate against individuals seeking various kinds of insurance; particularly health and life insurance. Consumer groups, the general public and those with genetic conditions have also expressed these concerns, specifically in the context of life insurance. While it is true that all insurance companies may have an interest in the information obtained from genetic tests, life insurers potentially have a very strong incentive to (want to) use genetic information to rate applicants, as individuals generally purchase their own cover and may want to take out very large policies. This paper critically focuses on genetic information in the context of life insurance. We consider whether genetic information differs in any relevant way from other kinds of non-genetic information required by and disclosed to life insurance companies by potential clients. We will argue that genetic information should not be treated any differently from other types of health information already collected from those wishing to purchase life insurance cover.


Perceptual behavior: recurrence analysis of a haptic exploratory procedure.
Various object properties are perceptible by wielding. We asked whether the dynamics of wielding differed as a function of the to-be-perceived property. Wielding motions were analyzed to determine if they differed under the intention to perceive or not perceive rod length (experiment 1), to perceive object height versus object width (experiment 2), and to perceive the length forward of where the rod was grasped versus the position of the grasp (experiment 3). Perceiving these different properties is known to depend on different components of the object's inertia tensor. Analyses of the subtle recurrent patterns in the phase space of the hand motions revealed differences in wielding across the different perceptual intentions. Haptic exploratory procedures may exhibit distinct exploratory dynamics.


Enzymatic hydrolysates of soy protein promote the physicochemical stability of mulberry anthocyanin extracts in food processing.
Soy protein papain hydrolysate (SPAH) and soy protein pepsin hydrolysate (SPEH) were used as protective agents for mulberry anthocyanin extracts (MAEs) to inhibit its color fading and enhance the anthocyanin stability at pH 6.3. Both SPAH and SPEH showed a significant protective effect on total anthocyanins in MAEs solutions. 1.0 mg/mL of SPEH presented the best protective effect on MAEs by increasing its half-life from 1.8 to 5.7 days. SPAH/SPEH-cyaniding-3-O-glucoside (C3G) interactions were investigated at pH 6.3 by fluorescence, Fourier-transform infrared spectroscopy (FT-IR), and Circular Dichroism (CD). Their association was mainly driven by hydrophobic interactions, and SPEH showed a higher binding affinity for C3G than SPAH, with a KA value of 2.62 × 105 M-1 at 300 K. The second structures of SPAH and SPEH were altered by C3G, with a decrease in the β-sheets and an increase in the turns and random coils.


Suppression of Endothelial Cell FAK Expression Reduces Pancreatic Ductal Adenocarcinoma Metastasis after Gemcitabine Treatment.
Despite substantial advances in the treatment of solid cancers, resistance to therapy remains a major obstacle to prolonged progression-free survival. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with a high level of liver metastasis. Primary PDAC is highly hypoxic, and metastases are resistant to first-line treatment, including gemcitabine. Recent studies have indicated that endothelial cell (EC) focal adhesion kinase (FAK) regulates DNA-damaging therapy-induced angiocrine factors and chemosensitivity in primary tumor models. Here, we show that inducible loss of EC-FAK in both orthotopic and spontaneous mouse models of PDAC is not sufficient to affect primary tumor growth but reduces liver and lung metastasis load and improves survival rates in gemcitabine-treated, but not untreated, mice. EC-FAK loss did not affect primary tumor angiogenesis, tumor blood vessel leakage, or early events in metastasis, including the numbers of circulating tumor cells, tumor cell homing, or metastatic seeding. Phosphoproteomics analysis showed a downregulation of the MAPK, RAF, and PAK signaling pathways in gemcitabine-treated FAK-depleted ECs compared with gemcitabine-treated wild-type ECs. Moreover, low levels of EC-FAK correlated with increased survival and reduced relapse in gemcitabine-treated patients with PDAC, supporting the clinical relevance of these findings. Altogether, we have identified a new role of EC-FAK in regulating PDAC metastasis upon gemcitabine treatment that impacts outcome. These findings establish the potential utility of combinatorial endothelial cell FAK targeting together with gemcitabine in future clinical applications to control metastasis in patients with pancreatic ductal adenocarcinoma.


Entropy-based method for assessing the influence of genetic markers and covariates on hypertension: application to Genetic Analysis Workshop 18 data.
Many complex diseases are related to genetics, and it is of great interest to evaluate the association between single-nucleotide polymorphisms (SNPs) and disease outcome. The association of genetics with outcome can be modified by covariates such as age, sex, smoking status, and membership to the same pedigree. In this paper, we propose a block entropy method to separate two classes of SNPs, for which the association with hypertension is either sensitive or insensitive to the covariates. We also propose a consistency entropy method to further reduce the number of SNPs that might be associated with the outcome. Based on the data provided by the organizers of Genetic Analysis Workshop 18, we calculated the block entropies for six different blocking strategies. Using block entropy and consistency entropy, we identified 230 SNPs on chromosome 9 that are most likely to be associated with the outcome and whose associations with hypertension are sensitive to the covariates.


Is alexithymia related to negative symptoms of schizophrenia? A preliminary longitudinal study.
Alexithymic features are close to anhedonia, blunted affect, and alogia that are also characteristics of the negative symptoms of schizophrenia. This study aimed to evaluate whether alexithymia is associated with negative symptoms and is related to the change of schizophrenic symptoms over time. A consecutive sample of 29 schizophrenic outpatients was evaluated at baseline and at 3, 6, and 12 months during appropriate treatment. They completed the Positive and Negative Syndrome Scale, the Montgomery and Asberg Depression Rating Scale, the Global Assessment of Functioning Scale, and the 20-item Toronto Alexithymia Scale at any time points. The psychiatric scale scores showed significant symptom improvement over time but were unrelated to the alexithymia score that was instead stable over time. Hierarchical regression showed that the 20-item Toronto Alexithymia Scale at baseline was the sole predictor of alexithymia at 12 months, after controlling for psychopathology and psychological functioning. Alexithymia was unrelated to negative symptoms, suggesting it is an independent and separate construct from schizophrenia. As expected, the negative symptoms were associated instead with illness-related aspects of depression and psychosocial functioning. Caution should be expressed in generalization mainly because this study is limited by the small sample size.


Origin of tokamak density limit scalings.
The onset criterion for radiation driven islands [P. H. Rebut and M. Hugon, Plasma Physics and Controlled Nuclear Fusion Research 1984: Proc. 10th Int. Conf. London, 1984, (IAEA, Vienna, 1985), Vol. 2] in combination with a simple cylindrical model of tokamak current channel behavior is consistent with the empirical scaling of the tokamak density limit [M. Greenwald, Nucl. Fusion 28, 2199 (1988)]. Many other unexplained phenomena at the density limit are consistent with this novel physics mechanism.


Validation of claims-based diagnostic codes for idiopathic thrombotic thrombocytopenic purpura in a commercially-insured population.
It was the purpose of the present study to validate administrative claims codes for idiopathic thrombotic thrombocytopenic purpura (TTP) in a commercially-insured US population. Patients with at least one medical claim with ICD-9 code 446.6X between 1/1/2001 and 5/31/2008 were identified in the HealthCore Integrated Research Database (HIRD). A chart abstraction form was developed to enable case determination for patients identified by the claims code. Two clinical experts, not involved in the design of the study, reviewed the abstracted medical record data and determined whether definite evidence supporting the diagnosis of TTP was present. The positive predictive value (PPV) of the claims coding algorithm for cases assessed by both reviewers was computed. The claims algorithm was further refined and the PPV of the refined algorithm was computed. One hundred eighty-nine abstracted charts were reviewed by two clinical experts; 86 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 45.5% [86/189; 95% confidence interval (CI), 38.3-52.9%]). Refinement of the claims algorithm first included the use of plasma exchange treatment, resulting in 103 potential cases, of which 67 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 65.0%; 95% CI, 55.0-74.2%). Further refinement of the claims algorithm ruled out alternative diagnoses that may mimic TTP; 34 were assessed to have definite evidence supporting the diagnosis of TTP (PPV 72.3% [34/47; 95% CI, 57.4-84.4%]).Our findings demonstrate the difficulty of confirming the diagnosis of rare disorders that lack definite diagnostic criteria, and indicate that more complex claims coding algorithms are necessary for identifying these disorders.


Isolation and confirmation of viral nervous necrosis (VNN) disease in golden grey mullet (Liza aurata) and leaping mullet (Liza saliens) in the Iranian waters of the Caspian Sea.
The present study was conducted on 428 moribund mullet fish samples to isolate and identify the causative agent of a mysterious acute mortality which recently occurred in wild mullets in Iranian waters of Caspian Sea, suspected to be due to viral nervous necrosis (VNN) disease. Disease investigation was carried out employing various diagnostic procedures such as virology, bacteriology, parasitology, haematology, histopathology, IFAT, IHC and nested RT-PCR. Brain and eye samples of affected fishes were collected in sterile conditions and then kept at -80°C for cell culture isolation and nested RT-PCR detection of the causative agent. Other tissue samples were also collected and fixed for histopathology, IHC and EM examinations. CPE was observed in cell cultures at 6days after inoculation. Nine samples were found positive with virological assay. Nested RT-PCR, performed on suspected tissues and CPE positive samples, showed that about 21 tissue samples and all the CPE positive samples were positive for VNN virus (VNNV). IFAT was selected as a confirmatory method for detecting the presence of Betanodavirus antigen, cell culture isolation results and nested RT-PCR findings. Moreover, VNNV particles with 25-30nm in diameter were also visualized in the infected brain and retina. In pathogenicity studies, guppy fishes bathed in VNNV-infected tissue culture (10(-4) TCID50) showed clinical signs similar to naturally infected mullet after 15days post infection (dpi), with mortality rates reaching up to 100% at 30dpi. Affected organ samples as examined by cell culture isolation, IFAT, IHC and histopathology, revealed the presence of VNNV in the guppy fishes. In conclusion, it was confirmed that VNNV was the main causative agent for the disease outbreak in mullet fish in the Caspian Sea, and this is such first official report of VNN disease from Iran.


Dietary supplementation with α-tocopherol reduces neuroinflammation and neuronal degeneration in the rat brain after kainic acid-induced status epilepticus.
Vitamin E (as α-tocopherol, α-T) is proposed to alleviate glia-mediated inflammation in neurological diseases, but such a role in epilepsy is still elusive. This study investigated the effect of α-T supplementation on glial activation, neuronal cell death and oxidative stress of rat brain exposed to kainate-induced seizures. Animals were fed for 2 weeks with a α-T-enriched diet (estimated intake of 750 mg/kg/day) before undergoing status epilepticus. Compliance to supplementation was demonstrated by the remarkable increase in brain α-T. Four days after seizure, brain α-T returned to baseline and lipid peroxidation markers decreased as compared to non-supplemented rats. Status epilepticus induced a lower up-regulation of astrocytic and microglial antigens (GFAP and MHC II, respectively) and production of pro-inflammatory cytokines (IL-1β and TNF-α) in supplemented than in non-supplemented animals. This anti-inflammatory effect was associated with a lower neuronal cell death. In conclusion, α-T dietary supplementation prevents oxidative stress, neuroglial over-activation and cell death occurring after kainate-induced seizures. This evidence paves the way to an anti-inflammatory and neuroprotective role of α-T interventions in epilepsy.


Polydimethylsiloxane permeability-based method for the continuous and specific detection of hydrogen sulfide.
Hydrogen sulfide (H(2)S) is known to play a physiological role in processes as diverse as vasodilation, maintenance of vascular tone, neurotransmission, and immune response. The multitude of physiological functions in which H(2)S is involved warrants the development of useful methods for its detection. Here, we introduce a simple and continuous H(2)S detection method that exploits the relatively high polydimethylsiloxane (PDMS) permeability of H(2)S in comparison to other thiols typically encountered in the cellular milieu. In this method, 96-well inserts constructed of PDMS act as an H(2)S-permeable membrane, eliminating nonspecific thiol detection. This design also makes it possible to use virtually any available thiol-specific probe such as Ellman's reagent which was used here to detect H(2)S once it crossed the PDMS membrane. Utilizing this method, a detection limit of 9.2 ± 1.9 ppb(m) (parts per billion (by mole) or ~0.51 μM in 1.6 mL of buffer) free H(2)S (detected as solution sulfide) was achieved. In addition, the assay was used to determine K(M) and V(max) for natural substrates of cystathionine γ-lyase (CSE), the main enzyme responsible for H(2)S production in peripheral tissues. The K(M) and V(max) of CSE for cysteine were 3.79 ± 2.07 mM and 0.37 ± 0.02 nmol H(2)S/min, respectively. K(M) and V(max) for homocysteine were 6.90 ± 1.78 mM and 1.10 ± 0.19 nmol H(2)S/min, respectively. In addition, the assay was used to examine the potential for a direct interaction of H(2)S and NO. The levels of detected H(2)S decreased in the presence of NO under normoxia but not under anoxia indicating that H(2)S does not react with NO but with N(2)O(3) likely formed in the hydrophobic environment of PDMS.


Radiation cell survival and growth delay studies in multicellular spheroids of small-cell lung carcinoma.
The radiation sensitivity of two small-cell lung carcinoma cell lines growing as multicellular spheroids in static culture was determined using clonogenic cell survival and growth delay as endpoints. Growth delay determination suggested that clonogenic cell kill was less than was obtained by direct assay of cell survival. Recovery from potentially lethal damage was assayed in one line (HC12) but was not demonstrable, and clonogenic cell survival decreased with time in treated spheroids with diameters greater than 300 microns which contained a hypoxic cell population. Microscopic examination of the treated spheroids showed the emergence of an abnormal giant-cell population, and the progressive clonogenic cell loss that occurred after treatment was thought to be due to oxygen and nutrient deprivation of the remaining viable cells by this doomed cell population. Correction of the growth delay measurements for changes in cell size and clonogenic cell population allowed correlation of the growth delay and cell survival data.


Scientometrics of anesthetic drugs and their techniques of administration, 1984-2013.
The aim of this study was to assess progress in the field of anesthetic drugs over the past 30 years using scientometric indices: popularity indices (general and specific), representing the proportion of articles on a drug relative to all articles in the field of anesthetics (general index) or the subfield of a specific class of anesthetics (specific index); index of change, representing the degree of growth in publications on a topic from one period to the next; index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 58 topics were assessed during six 5-year periods from 1984 to 2013. Our analysis showed that during 2009-2013, out of seven anesthetics with a high general popularity index (≥2.0), only two were introduced after 1980, ie, the inhaled anesthetic sevoflurane and the local anesthetic ropivacaine; however, only sevoflurane had a high index of expectations (12.1). Among anesthetic adjuncts, in 2009-2013, only one agent, sugammadex, had both an extremely high index of change (>100) and a high index of expectations (25.0), reflecting the novelty of its mechanism of action. The index of ultimate success was positive with three anesthetics, ie, lidocaine, isoflurane, and propofol, all of which were introduced much longer than 30 years ago. For the past 30 years, there were no new anesthetics that have produced changes in scientometric indices indicating real progress.


Tumor recurrence of keratinocyte carcinomas judged appropriate for Mohs micrographic surgery using Appropriate Use Criteria.
The use of Mohs micrographic surgery (MMS) has increased greatly to treat basal cell and cutaneous squamous cell carcinomas (keratinocyte carcinoma [KC]), and consensus-based Appropriate Use Criteria (AUC) were developed to identify tumors for which MMS is appropriate. We sought to compare recurrence rates after different treatments in tumors judged appropriate for MMS. We used data from an observational prospective cohort study and retrospectively categorized consecutive tumors as appropriate for MMS according to the AUC. Among appropriate tumors, we used survival analyses to compare 5-year recurrence rates after treatments. Among tumors appropriate for MMS (N = 1483), adjusted 5-year recurrence rates were 2.9% (range, 1.4-4.3%) after MMS, 5.5% (range, 3.1-7.9%) after excision, 4.0% (range, 0.6-7.2%) after destruction, and 5.9% (range, 1.5-10.2%) after other treatments. In tumors treated only with MMS or excision (the most similar subgroups), the adjusted hazard ratio of 5-year recurrence after MMS was 0.6 (95% confidence interval, 0.3-1.0; P = .06). This study is limited by its uncertain generalizability, lack of randomization, and unmeasured characteristics. The AUC identified tumors for which recurrence would be less common after MMS than after excision, but the absolute difference in recurrence rates was small.


Lowering effects of a preparation containing fibres and lactulose on glucose and insulin levels in obesity.
The short-term metabolic effects of a dietary supplementation of biscuits containing raw fibre and lactulose (Fiberlac, Bracco) on circadian glucose, insulin and amino acid concentrations were studied in 10 obese patients in a crossover comparison. The biscuits (3 at breakfast, 4 at lunch and 4 at evening meal; approximately 10 g total dietary fibre, 2 g raw fibre, 8.25 g lactulose) were randomly substituted for an equicaloric part of a diet containing 20-22 kcal per kg ideal body weight under strict medical surveillance. Blood glucose in response to meal, as well as mean concentration throughout the day was lower during fibre supplementation. Also mean insulin was halved, and the insulin response to meals was blunted by 100-250 pmol/L. The plasma amino acid response to meals was increased, possibly in relation to decreased insulinemia. The data show a remarkable metabolic effect of the preparation in obese patients, without any further dietary restriction. The clinical effects and compliance remain to be determined in long-term studies, and in other states of glucose-intolerance, e.g. liver cirrhosis.


[Multicenter study of a slow-release theophylline: armophylline].
In a co-operative study involving 10 centres, 95 asthmatic patients were treated with Armophylline, a new slow-release theophylline for a period of 1 to 3 months. Eighty per cent of the patients receiving the drug in doses of 11 to 15 mg/kg/day immediately had adequate blood theophylline levels (7-20 mcg/ml). There was a significant decrease in dyspnoea and number of asthmatic attacks and a significant increase in FEV1 and FEV1/VC ratio. The drug was usually well tolerated. Side-effects, such as insomnia, headache or digestive disorders were, as a rule, mild.


Parasites, politics and public science: the promotion of biological control in Western Australia, 1900-1910.
Biological control of arthropods emerged as a scientific enterprise in the late nineteenth century and the orchard industry of California was an early centre of expertise. In 1900, as the Australian colonies prepared for federation, each had a government entomologist attached to its agriculture department. The hiring of George Compere from California by the Western Australian Department of Agriculture began a controversial chapter in the early history of biological control that was linked to a late, local popularization of acclimatization. Compere became known as the 'travelling entomologist' and for a decade brought 'parasites' of pest insects from overseas and released them in Perth. His antagonistic disciplinary rhetoric and inflated claims for the 'parasite theory' created conflict with his counterparts in the eastern states. The resulting inter-state entomological controversy was played out in the press, revealing the political use of science for institutional and even state identity. It is a story of transnational exchanges, chance discoveries and popular public science: popular because of the promise of a simple, natural solution to agricultural insect pests and because of the public nature of the disputes it generated between the experts. This microcosm contributes to the global historiography of acclimatization, biological control, scientific exposition and the professionalization of agricultural science.


Sun Protection Beliefs among Hispanics in the US.
Purpose. We reviewed the literature on sun protection beliefs in Hispanics living in the United States to explore what challenges are faced by area of research. Method. A review of PubMED, PsycINFO, and CINAHL databases was performed. Studies were published in peer-reviewed journals (in all years available) and written in English. The search terms used were ["skin cancer" OR "sun protection"] AND ["Latino" OR "Hispanic"] AND "beliefs." Eligible papers were included in the final analysis after meeting the following inclusion criteria: (1) the records had to quantitatively examine and report sun protection beliefs in Hispanics, (2) the number of Hispanic participants in the sample had to be clearly specified, and (3) studies reporting differences in sun protection beliefs between Hispanics and other racial and ethnic groups were included in the review. Results. Of the 92 articles identified, 11 met inclusion criteria and addressed sun protection beliefs regarding skin cancer seriousness and susceptibility, and benefits and barriers of sun protection and skin cancer risk behaviors. Characteristics of studies and results were examined. Conclusion. There is insufficient evidence to determine a pattern of sun protection beliefs among Hispanics in the United States. More quality studies are needed which focus on sun protection beliefs in Hispanics.


Differences in chronotropic and inotropic responses of canine atrial muscle and SA node pacemaker activity to adenosine and ACh.
The right atrium isolated from the dog heart was perfused through the cannulated sinus node artery with heparinized arterial blood led from a support dog anesthesized with 30 mg/Kg of sodium pentobarbital. When adenosine was administered into the sinus node artery, negative chronotropic and inotropic effects were dose-relatedly induced. The threshold dose for inducing the negative ones was 0.3 mug. Even a large dose level of 100 mug of adenosine did not cause sinus arrest although a profound sinus deceleration was induced. Adenosine action was suppressed by treatment with caffeine both in chronotropism and in inotropism. On the other hand, ACh induced only negative inotropic effect at a dose range of 0.01-0.03 mug. At 0.1 mug, ACh produced a significantly negative chronotropic effect. A large amount of 3-10 mug of ACh usually caused sinus arrest. Atropine treatment inhibited a negative chronotropic effect much more readily than a negative inotropic one. Although ACh action was enhanced by physostigmine, the difference of threshold doses remained unchanged even after physostigmine treatment. From these results, either adenosine or ACh depresses both SA nodal pacemaker activity and atrial contractile force and there may be the difference of receptor density for ACh between the SA node and atrial tissue.


[Anti-inflammatory molecule, Clara cell 10 kilodalton protein and respiratory diseases].
Clara cell 10 kilodalton protein(CC10) is the major product of non-ciliated bronchiolar epithelial cells (Clara cells) and is identical with uteroglobin and urinary protein 1(P-1). CC10/uteroglobin is a homodimer consisting of 70 amino acid subunits arranged in an antiparallel fashion and connected by two disulfide bonds. CC10/uteroglobin shows an anti-inflammatory property including inhibition of phospholipase A2 and phospholipase C. We analyzed the epitope of monoclonal antibodies(mAbs) to human CC10/P-1. TY-5, TY-7 and TY-8 recognized alpha 1-, alpha 2- and alpha 3-helix of CC10, respectively. The combination of TY-1 and TY-2 are most suitable for ELISA, while TY-5 and TY-7 are very good for immunoblot and immunohistochemical analysis. Circulating CC10 levels are increased in sarcoidosis and decreased in asthma. Bronchoalveolar lavage CC10 levels are increased in sarcoidosis patients with a good outcome. The use of these mAbs is a powerful tool to investigate the clinical roles of CC10. CC10 is a regulator of the inflammatory process in respiratory diseases.


Overall Survival of Patients with Aggressive Thyroid Cancer on Fine-Needle Aspiration Biopsy Examination. A Tertiary Romanian Center Experience.
Anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PTDC) and lymphoma are aggressive forms of neoplasia. Although all carry a poor prognosis there is an important heterogeneity of overall survival (OS) between individual patients. The decision of total thyroidectomy is often based on fine-needle aspiration biopsy (FNAB) which has important limitations in this setting. Our aim was to assess the OS of aggressive thyroid cancer diagnosed on FNAB in a single university center. We retrospectively reviewed all the ATC, PDTC and lymphoma cases diagnosed on FNAB during 2007-2013 (15 cases). All FNAB examinations were performed by the same specialized pathologist. Data on demographics, laboratory tests, imaging studies, FNAB/pathology reports, treatment and survival time were recorded. All patients had serum calcitonin levels under 5 pg/mL. Five patients had total thyroidectomy. The OS was 2.2 (0.6, 18.5) months. The survival rate at 3 and 12 months was 46.6% and 33.3% respectively. There were no significant differences between ATC and PDTC/lymphoma patients for age, TSH, largest tumoral diameter and cervical lymph involvement. Patients with ATC (8 cases) had a median OS of 0.8 months, significantly shorter than 6 months for patients with PDTC/lymphoma (7 cases). Patients treated with total thyroidectomy had a median OS of 20 months compared with 1.87 months for patients without surgical intervention (p=0.06). The differences between groups and the heterogeneity of individual cases suggest that a diagnosis of aggressive thyroid cancer on FNAB should not preclude the surgical intervention. The decision to operate should be based on accurate imaging rather than on discouraging FNAB result.


Someone to rely on: the impact of social support on self-perceived health in Slovene elderly.
Aiming at highlighting the importance of social networking for health of elderly, the association between social support and self-perceived health (SPH) was assessed in Slovenia. Data from three consecutive cross-sectional surveys on health behaviour in Slovenia (2008, 2012 and 2016), for 4599 elderly, aged 65-75 years, were pooled. Association between poor SPH (PSPH) and social support (taking into account also existence of extended personal social network (EPSN)), adjusted for confounders, was analysed by multiple logistic regression. The PSPH odds were statistically significantly higher in single/divorced/living in extramarital partnership/widowed, all without EPSN (OR = 2.99; p = 0.005), and single/divorced with EPSN (OR = 1.49; p = 0.053) in comparison to married with EPSN. Irrespective of gender, socio-economic status or health-related factors, elderly with low level of social support were more likely to perceive their health as poor/very poor. Public health measures to reduce isolation of elderly should be included in the action plan in the frame of the Longevity strategy.


Assessment of Tomato (Solanum lycopersicum L.) Producers' Exposure Level to Pesticides, in Kouka and Toussiana (Burkina Faso).
To assess producers' exposure level to pesticides in vegetable production in Burkina Faso, a study was carried out in 2016 and 2017 among 30 tomato producers in the municipalities of Kouka and Toussiana. Eighteen (18) commercial formulations were identified, with more than 50% of pesticides destined for cotton production. Eleven active substances have been identified and the most frequently used are λ-cyhalothrin (35%), acetamiprid (22%) and profenofos (13%). The most commonly used chemical families are pyrethroids (28%) and organophosphates (18%). The study revealed a low level of training for producers, a high use of pesticides according to the Frequency Treatment Indicator, and a very low level of protection used by producers. The Health Risk Index shows that active substances such as methomyl, λ-cyhalothrin and profenofos present very high risk to operators' health. Based on the UK-POEM model, the predictive exposure levels obtained varied from 0.0105 mg/kg body weight/day to 1.7855 mg/kg body weight/day, which is several times higher than the Acceptable Operator Exposure Level. However, the study also shows that exposure can be greatly reduced if the required Personal Protective Equipment is worn. Producers' awareness and training on integrated pest management are necessary to reduce the risks linked to the pesticides use in Burkina Faso.


Definite familial multiple system atrophy with unknown genetics.
Multiple system atrophy (MSA) is an oligodendrogliopathy of presumably sporadic origin, characterized by prominent α-synuclein inclusions with neuronal multisystem degeneration, although a few Mendelian pedigrees have been reported. Here we report two familial cases of MSA of unknown genetic background. One patient was diagnosed as a possible MSA-C (cerebellar dysfuntion) case, and the other as clinically possible MSA-P (parkinsonism), which turned out to be definite MSA, based on a detailed autopsy. The neuropathology showed extensive deposition of α-synuclein in the glia as well as in the neurons located in the cerebral cortices and hippocampal systems, although neither multiplication of the SNCA gene or mutations in COQ2 gene were identified in the family concerned.


Diagnostic challenges in meningioma.
Advances in molecular profiling and the application of advanced imaging techniques are currently refreshing diagnostic considerations in meningioma patients. Not only technical refinements but also sophisticated histopathological and molecular studies have the potential to overcome some of the challenges during meningioma management. Exact tumor delineation, assessment of tumor growth, and pathophysiological parameters were recently addressed by "advanced" MRI and PET. In the field of neuropathology, high-throughput sequencing and DNA methylation analysis of meningioma tissue has greatly advanced the knowledge of molecular aberrations in meningioma patients. These techniques allow for more reliable prediction of the biological behavior and clinical course of meningiomas and subsequently have the potential to guide individualized meningioma therapy. However, higher costs and longer duration of full molecular work-up compared with histological assessment may delay the implementation into clinical routine.This review highlights the diagnostic challenges of meningiomas from both the neuroimaging as well as the neuropathological side and presents the latest scientific achievements and studies potentially helping in overcoming these challenges. It complements the recently proposed European Association of Neuro-Oncology guidelines on treatment and diagnosis of meningiomas by integrating data on nonstandard imaging and molecular assessments most likely impacting the future.


Sleep restriction alters children's positive emotional responses, but effects are moderated by anxiety.
An abundance of cross-sectional research links inadequate sleep with poor emotional health, but experimental studies in children are rare. Further, the impact of sleep loss is not uniform across individuals and pre-existing anxiety might potentiate the effects of poor sleep on children's emotional functioning. A sample of 53 children (7-11 years, M = 9.0; 56% female) completed multimodal, assessments in the laboratory when rested and after two nights of sleep restriction (7 and 6 hr in bed, respectively). Sleep was monitored with polysomnography and actigraphy. Subjective reports of affect and arousal, psychophysiological reactivity and regulation, and objective emotional expression were examined during two emotional processing tasks, including one where children were asked to suppress their emotional responses. After sleep restriction, deleterious alterations were observed in children's affect, emotional arousal, facial expressions, and emotion regulation. These effects were primarily detected in response to positive emotional stimuli. The presence of anxiety symptoms moderated most alterations in emotional processing observed after sleep restriction. Results suggest inadequate sleep preferentially impacts positive compared to negative emotion in prepubertal children and that pre-existing anxiety symptoms amplify these effects. Implications for children's everyday socioemotional lives and long-term affective risk are highlighted.


c-Myc blazing a trail of death: coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc.
TRAIL ligand induces selectively apoptosis in tumor cells by binding to two death receptors (DR4 and DR5) and holds promise as a potential therapeutic agent against cancer. While it has been known for long time that TRAIL receptors are commonly expressed in wide variety of normal tissues, it is not well understood why TRAIL kills tumor cells but leaves normal cells unharmed. The prototypic oncogene c-Myc promotes the cell cycle and simultaneously primes activation of the Bcl-2 family controlled mitochondria apoptosis pathway. A striking reflection of the c-Myc-dependent apoptotic sensitization is the dramatic c-Myc-induced vulnerability of cells to TRAIL and other death receptor ligands. Here we summarize the recent findings regarding the death mechanisms of TRAIL/TRAIL receptor system and the connection of c-Myc to the mitochondrial apoptosis pathway, focusing on our work that couples c-Myc via Bak to the TRAIL death receptor pathway. Finally, we present a mitochondria-priming model to explain how c-Myc-Bak interaction amplifies the TRAIL-induced caspase 8-Bid pathway to induce full-blown apoptosis. We discuss the implications of these findings for understanding the selective cytotoxicity of TRAIL and for the therapeutic exploitation of the death receptor pathway.


Incorporating evidence from pharmacologic and pharmacogenetic studies of atypical antipsychotic drugs into advanced psychiatric nursing practice.
To present a conceptual framework for incorporating pharmacologic findings and pharmacogenetic evidence related to atypical antipsychotic drugs (AADs) into advanced psychiatric nursing practice. Three evidence domains lend important information about differential AAD response. These include the pharmacology of AADs, the molecular genetics of metabolizing enzymes, and the molecular genetics of neurotransmitter receptor drug targets. These evidence domains can be incorporated into nursing practice decisions related to medication planning, patient and family education, and medication monitoring processes. The central focus of the framework is patient outcomes, which include medication adherence, tolerability of the AADs, and demonstrated clinical effectiveness.


Two-photon imaging of a magneto-fluorescent indicator for 3D optical magnetometry.
We developed an optical method to visualize the three-dimensional distribution of magnetic field strength around magnetic microstructures. We show that the two-photon-excited fluorescence of a chained donor-bridge-acceptor compound, phenanthrene-(CH2)12-O-(CH2)2-N,N-dimethylaniline, is sensitive to ambient magnetic field strength. A test structure is immersed in a solution of the magneto-fluorescent indicator and a custom two-photon microscope maps the fluorescence of this compound. The decay kinetics of the electronic excited state provide a measure of magnetic field that is insensitive to photobleaching, indicator concentration, or local variations in optical excitation or collection efficiency.


abFASP-MS: affinity-based filter-aided sample preparation mass spectrometry for quantitative analysis of chemically labeled protein complexes.
Affinity purification coupled to 1-D gel-free liquid chromatography mass spectrometry (LC-MS) is a well-established and widespread approach for the analyses of noncovalently interacting protein complexes. In this study, two proteins conjugated to a streptavidin-binding peptide and hemagglutinin double tag were expressed in the respective Flp-In HEK293 cell lines: green fluorescent protein (SH-GFP) and TANK binding kinase 1 (SH-TBK1_MOUSE). Fluorescent anti-HA immunoblots revealed that the expression level of SH-GFP was ∼50% lower than that of SH-TBK1_MOUSE. Subsequently, the input material was normalized to obtain a similar quantity of purified SH-tagged proteins. Optimization of the release of protein complexes from the anti-HA-agarose with different eluting agents was then assessed. With respect to the total number of protein groups identified in the purified complexes, elution with 2% SDS surpassed both 100 mM glycine and 100 mM formic acid. Relative quantitation of the purified protein complexes using TMT 6-plex reagents confirmed the higher efficiency of the 2% SDS elution followed by filter-aided sample preparation (FASP). The data presented in this study provide a new application of FASP to quantitative MS analysis of affinity-purified protein complexes. We have termed the approach abFASP-MS, or affinity-based filter-aided sample preparation mass spectrometry.


Differences in Some Kinematic Parameters between Two Qualitatively Different Groups of Pole Vaulters.
The basic aim of this research was to determine the differences of kinematic parameters in two qualitatively different groups of young pole vaulters. With this purpose, a research was conducted in which the video records from a competition were acquired. The sample of entities (N = 71) consisted of successful vaults of 30 pole vaulters, whose attempts were recorded at the European Junior Championship in Novi Sad, held on 23-26th July 2009. The examinees performed the vaults as a part of the elimination competition for the finals, and during the final part of the competition. The age of examinees was from 17 to 19 years, and the span of their best results was from 4.70 to 5.30 meters. The kinematic analysis was conducted according to the standards of APAS procedure (Ariel Performance Analysis System, USA), determining 25 kinematic variables necessary for further analysis. The entities (vaults) were divided into two categories (qualitative classes) based on the expert knowledge. Group 1 consisted of successful vaults up to 4.90 m (N = 46), while group 2 consisted of successful vaults whose height was more than 4.90 m (N = 25). The discrimination analysis determined the parameters differentiating the vaults of different quantitative classes. Also, it was confirmed that the result efficiency in pole vault was primarily determined by the variables defined by motor abilities, as well as the indicators determining the vault performance technique.


Difficulties or mistakes in diagnosing type 1 diabetes mellitus in children? The consequences of delayed diagnosis.
Delayed diagnosis is one of the causes of diabetic ketoacidosis (DKA) development in many children with new-onset of type 1 diabetes mellitus (T1DM). of the study was to analyse difficulties in diagnosing T1DM and establish if delayed recognition is the main risk factor of diabetic ketoacidosis (DKA) in children with newly diagnosed T1DM. Retrospective analysis of 335 children with new-onset T1DM, aged below 17 years and living in the Pomeranian region of Poland, was carried out. The delay in diagnosis was recognized if the patient was not diagnosed on the first visit because of omission, wrong interpretation of symptoms, exclusive treatment of additional diabetic signs or concomitant diseases. Difficulties in diagnosing T1DM were found in 54 cases (16.12%). The initial diagnosis was wrongly categorized as respiratory system infection (46.3%), perineal candidiasis (16.6%), gastroenteritis (16.6%), urinary tract infection (11.1%), stomatitis (11.1%), appendicitis (3.7%). Duration of symptoms (mean 14 days) and glycated haemoglobin level did not significantly correspond with diagnostic delay. DKA was significantly more frequent in children with delayed diagnosis - 33 patients (61.11%) (p=0.0005). The infection preceding diagnosis of T1DM, more common among children with delayed recognition, did not affect the duration of symptoms or affect characteristicly more frequent DKA development in children with diagnostic delay. No significant associations between diagnostic delay and duration of diabetic symptoms as well as glycated haemoglobin level exclude possibility of delayed diagnosis because of slow development of diabetic symptoms. Significantly more frequent DKA development in children with delayed recognition, irrespective of infection preceding diagnosis, and no confirmation that younger patient's age predisposes to quick increase of DKA point out that the main risk factor for DKA development in the research group was diagnostic delay.


A density functional study of C1-C4 alkyl adsorption on Cu(111).
To better understand the nature of alkyl intermediates often invoked in reactions involving hydrocarbon reactants and products, the adsorption of linear and branched C(1)-C(4) alkyls on Cu(111) at 1/4 ML and 1/9 ML coverages was studied using density functional theory. The adsorption energy and site preference are found to be coverage-dependent, and both direct alkyl-alkyl interactions and changes in the Cu electronic structure play a role in these trends. It was found that methyl strongly prefers the hollow sites, the branched alkyls strongly prefer the top site, and the linear C(2)-C(4) alkyls have weak site preferences that change with coverage. To explain these differences, rationalize alkyl adsorption trends, and predict the binding energy of other alkyls, a simple model was developed in which the binding energy is fit as a linear function of the number of C-Cu and C-H-Cu interactions as well as the C-H bond energy in the corresponding alkane. Site preference can be understood as a compromise between C-Cu interactions and C-H-Cu interactions. Density of states analysis was used to gain a molecular-orbital understanding of the bonding of alkyls to Cu(111).


Concurrent Implicit Adaptation to Multiple Opposite Perturbations.
Simultaneous adaptation to opposite visuomotor perturbations is known to be difficult. It has been shown to be possible only in situations where the two tasks are associated with different contexts, being either a different colored background, a different area of workspace, or a different follow-through movement. However, many of these elements evoke explicit mechanisms that could contribute to storing separate (modular) memories. It remains to be shown whether simultaneous adaptation to multiple perturbations is possible when they are introduced in a fully implicit manner. Here, we sought to test this possibility using a visuomotor perturbation small enough to eliminate explicit awareness. Participants (N = 25) performed center-out reaching movements with a joystick to five targets located 72° apart. Depending on the target, visual feedback of cursor position was either veridical (one target) or could be rotated by +5 or -5° (two targets each). After 300 trials of adaptation (60 to each target), results revealed that participants were able to fully compensate for each of the imposed rotations. Moreover, when veridical visual feedback was restored, participants exhibited after-effects that were consistent with the rotations applied at each target. Questionnaires collected immediately after the experiment confirmed that none of the participants were aware of the perturbations. These results speak for the existence of implicit processes that can smoothly handle small and opposite visual perturbations when these are associated with distinct target locations.


Oral health after breast cancer treatment in postmenopausal women.
Oral health can affect a patient's general health and quality of life. Given the increase in breast cancer survival rates, investigations of factors influencing the quality of life of survivors have gained importance. Therefore, the objective of our study was to characterize oral health in postmenopausal breast cancer survivors. We conducted a matched case-control study. Forty-eight women who survived breast cancer (age 62.1±9.1 years) and 48 healthy controls (age 61.8±8.6 years) were included. For each case and control, a complete oral evaluation chart was completed. The prevalence of chronic periodontal disease was 98% in breast cancer survivors and 87% in controls. The breast cancer survivors had a median of 16 remaining teeth, whereas controls had a median of 22 remaining teeth (p = 0.03). The percentage of sites with gingival bleeding was 16.05% (0-100%) in breast cancer survivors and 0% (0-72%) in controls (p = 0.04). Chronic periodontal disease and tooth loss were highly prevalent in postmenopausal breast cancer survivors. To improve survivors' quality of life, a preventive oral health evaluation should be available prior to cancer treatment.


Imaging the fate of implanted bone marrow stromal cells labeled with superparamagnetic nanoparticles.
Bone marrow stromal cells (MSCs) are pluripotent progenitor cells that have the capacity to migrate toward lesions and induce or facilitate site-dependent differentiation in response to environmental signals. In animals with a cortical photochemical lesion, the fate of rat MSCs colabeled with magnetic iron-oxide nanoparticles (Endorem) and bromodeoxyuridine (BrdU) was studied. MSCs were either grafted intracerebrally into the contralateral hemisphere of adult rat brain or injected intravenously. In vivo MRI was used to track their fate; Prussian blue staining and transmission electron microscopy (TEM) confirmed the presence of iron-oxide nanoparticles inside the cells. During the first week posttransplantation, the transplanted cells migrated to the lesion site and populated the border zone of the damaged cortical tissue. The implanted cells were visible on MR images as a hypointense area at the injection site and in the lesion. The hypointense signal persisted for more than 50 days. The presence of BrdU-positive and iron-containing cells was confirmed by subsequent histological staining. Three to 4 weeks after injection, <3% of MSCs around the lesion expressed the neuronal marker NeuN. Our study demonstrates that a commercially available contrast agent can be used as a marker for the long-term noninvasive MR tracking of implanted cells.


Biomechanical properties of normal and varicose internal spermatic veins.
To investigate possible differences in biomechanical properties between varicose spermatic veins and controls. During surgery on 12 patients for grade 3 left-sided varicocele testis, 2 cm of the vein was obtained for comparison with: (i) samples of the left internal spermatic vein taken from the same anatomical localization from 8 patients without scrotal disease, and (ii) samples from the right internal spermatic vein from 7 other patients also without scrotal disease. The biomechanical properties of ring-shaped venous specimens were investigated by loading the specimen at a constant deformation rate until rupture. The relative amounts of collagen in the specimens were determined as the contents of hydroxyproline. There was a significant difference between varicocele testis/right spermatic vein in UC (unit collagen), F-max (maximum strength), Strain (ultimate extensibility) and E-fail (relative failure energy), but not in LD (diameter) and Tan-a (stiffness of the specimen). There were no significant differences between left and right spermatic vein in LD, UC, F-max, Strain, Tan-a and E-fail. There was a significant difference in LD between varicocele testis/left spermatic vein, but no relationship in UC, F-max, Strain, Tan-a and E-fail. Biomechanical analyses of the spermatic veins from patients operated for varicocele seem to support the hypothesis that a difference in biomechanical properties plays a part in the development of varicocele because a significant increase in extensibility of varicocele samples was found compared with normal right spermatic vein samples.


Hospitalization risk among patients with Mpox infection-a propensity score matched analysis.
Monkeypox (Mpox) is a reemerging, neglected viral disease. By May 2023, worldwide Mpox cases surpassed 87,000. Predictive factors for hospitalization with Mpox are lacking. We aim to compare clinical characteristics and outcomes in hospitalized and nonhospitalized patients with Mpox infection. A multicenter retrospective case-control cohort of patients with Mpox infection. We performed a propensity score match analysis from a global health network (TrinetX). We compare clinical characteristics and outcomes between hospitalized and nonhospitalized patients with Mpox. Of 1477 patients, 6% were hospitalized, 52% required an ED visit, and 29% received treatment at urgent care. After propensity score matching, 80 patients remained in each group. Hospitalizations were more common among Black persons (51% versus 33%, p = 0.01), people with HIV (50% versus 20%, p < 0.0001), and those with proctitis (44% versus 12.5%, p < 0.001). Independent predictive factors of hospitalization in our cohort for Mpox included people who are Black with a diagnosis of HIV, severe proctitis, pain requiring opioids, and elevated lactate dehydrogenase. Greater recognition of factors associated with increased risk of Mpox severity and hospitalization is paramount.


Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives.
To find potential α-glucosidase inhibitors, indolo[1,2-b]isoquinoline derivatives (1-20) were screened for their α-glucosidase inhibitory effects. All derivatives presented potential α-glucosidase inhibitory effects with IC50 values of 3.44 ± 0.36~41.24 ± 0.26 μM compared to the positive control acarbose (IC50 value: 640.57 ± 5.13 μM). In particular, compound 11 displayed the strongest anti-α-glucosidase activity, being ~186 times stronger than acarbose. Kinetic studies found that compounds 9, 11, 13, 18, and 19 were all reversible mix-type inhibitors. The 3D fluorescence spectra and CD spectra results revealed that the interaction between compounds 9, 11, 13, 18, and 19 and α-glucosidase changed the conformational changes of α-glucosidase. Molecular docking and molecular dynamics simulation results indicated the interaction between compounds and α-glucosidase. In addition, cell cytotoxicity and drug-like properties of compound 11 were also investigated.


AKT and GSK-3 are necessary for direct ezrin binding to NHE3 as part of a C-terminal stimulatory complex: role of a novel Ser-rich NHE3 C-terminal motif in NHE3 activity and trafficking.
Basal activity of the BB Na(+)/H(+) exchanger NHE3 requires multiprotein complexes that form on its C terminus. One complex stimulates basal NHE3 activity and contains ezrin and phosphoinositides as major components; how it stimulates NHE3 activity is not known. This study tested the hypothesis that ezrin dynamically associates with this complex, which sets ezrin binding. NHE3 activity was reduced by an Akti. This effect was eliminated if ezrin binding to NHE3 was inhibited by a point mutant. Recombinant AKT phosphorylated NHE3 C terminus in the domain ezrin directly binds. This domain (amino acids 475-589) is predicted to be α-helical and contains a conserved cluster of three serines (Ser(515), Ser(522), and Ser(526)). Point mutations of two of these (S515A, S515D, or S526A) reduced basal NHE3 activity and surface expression and had no Akti inhibition. S526D had NHE3 activity equal to wild type with normal Akti inhibition. Ezrin binding to NHE3 was regulated by Akt, being eliminated by Akti. NHE3-S515A and -S526D did not bind ezrin; NHE3-S515D had reduced ezrin binding; NHE3-S526D bound ezrin normally. NHE3-Ser(526) is predicted to be a GSK-3 kinase phosphorylation site. A GSK-3 inhibitor reduced basal NHE3 activity as well as ezrin-NHE3 binding, and this effect was eliminated in NHE3-S526A and -S526D mutants. The conclusions were: 1) NHE3 basal activity is regulated by a signaling complex that is controlled by sequential effects of two kinases, Akt and GSK-3, which act on a Ser cluster in the same NHE3 C-terminal domain that binds ezrin; and 2) these kinases regulate the dynamic association of ezrin with NHE3 to affect basal NHE3 activity.


Biventricular pacing improves quality of life and exercise tolerance in patients with heart failure and intraventricular conduction delay.
Biventricular pacing improves left ventricular dysynchrony, leading to improvement in congestive heart failure symptoms. The extent of placebo effect, the predictors of response and the long term benefits are unknown. Forty-five patients with symptomatic congestive heart failure underwent implantation of a biventricular pacing system over a 30-month period (age 65 10 years, 37 men). Patients underwent implantation of a biventricular pacemaker or implantable defibrillator one month or longer after stabilization of congestive heart failure on maximal medical therapy, including angiotensin-converting enzyme inhibitors in 84% of patients and beta-blockers in 56% of patients. Three patients had New York Heart Association (NYHA) class II heart failure, 34 had NYHA class III and eight had NYHA class IV. Cardiomyopathy was ischemic in 31 patients, dilated in 12 and the result of other causes in two. The left ventricular ejection fraction was 19 5%. Implantation of the biventricular pacing system was successful in 38 of 45 patients (84%). Two patients had successful implantation with a second attempt, and one patient had an epicardial lead implant. Lead dislodgement occurred in four patients, with successful repositioning in all. During a mean follow-up of 10 7 months, the Minnesota Living with Heart Failure Questionnaire quality of life index score improved from 62 16 to 42 22 at one month (P<0.001), but subsequently returned to intermediate levels (55 26 at three months, 48 26 at six months and 56 34 at one year, P=0.50). In seven patients with deferred device activation, quality of life scores also improved by 10 15 points from baseline to one month with VDI 35 pacing, and improved a further 15 20 points with left ventricular lead activation. The mean NYHA class fell from 3.1 0.5 at baseline to 2.7 0.7 at one month (P=0.006) and remained stable thereafter (2.8 0.9 at three months, 2.8 0.9 at six months). Six patients died during follow-up, one patient had a cardiac transplantation and subsequently died, one patient had a successful cardiac transplantation and one patient underwent insertion of a left ventricular assist device. Death occurred due to progressive heart failure in five patients, sudden death occurred in one patient and a noncardiovascular cause resulted in the death of one patient. An analysis of NYHA responders (NYHA class improvement of 1 or more at last follow-up, 44% of patients) and quality of life responders (score improvement of 10 or more at last follow-up, 57% patients) did not show any difference in age, sex, heart failure etiology, QRS width, ejection fraction or baseline NYHA class. Biventricular pacing improves quality of life and NYHA class in patients with advanced heart failure and intraventricular conduction delay. The attenuated benefit seen over time may be related to initial placebo effect or simple dual- chamber pacing, or the natural history of the underlying disease. Identification of patients most likely to respond to biventricular pacing was not possible.


Ramus graft and 1-stage implant placement: a case report.
Althougth hard-tissue grafting protocols have typically recommended a 6-month healing period before placement of any dental implants at the graft site, it may be possible to secure an onlay graft to a wide but shallow alveolar ridge using implants that are then submerged and allowed to osseointegrate. This approach has the advantage of expediting treatment and making it less traumatic for the patient. A case is described in which a portion of an edentulous mandible was augmented with ramus bone secured with 2 dental implants.


Comparison of complications attributable to enteral and parenteral nutrition in predicted severe acute pancreatitis: a systematic review and meta-analysis.
Enteral nutrition (EN) reduces infectious complications and mortality compared with parenteral nutrition (PN) in patients with predicted severe acute pancreatitis. However, to date the complications attributable to the administration of EN and PN in this patient group have not been comprehensively studied. The aim of the study was to systematically review the complications related to the use of nutrition in patients with predicted severe acute pancreatitis receiving EN v. PN. The Cochrane Library, MEDLINE and Scopus were searched. Randomised controlled trials (RCT) of EN v. PN in predicted severe acute pancreatitis were selected. Pooled estimates of complications were expressed as OR with corresponding 95 % CI. Data from five RCT were meta-analysed. Diarrhoea occurred in six of ninety-two (7 %) patients receiving PN and twenty-four of eighty-two (29 %) patients receiving EN (OR 0.20; 95 % CI 0.09, 0.43; P < 0.001). Hyperglycaemia developed in twenty-one of ninety-two (23 %) patients receiving PN and nine of eighty-two (11 %) receiving EN (OR 2.59; 95 % CI 1.13, 5.94; P = 0.03). Given a significant reduction in infectious complications and mortality associated with the use of EN over PN that has been consistently demonstrated in previous studies, the former should be the treatment of choice in acute pancreatitis. Further clinical studies should investigate the strategies to mitigate the complications of enteral tube feeding in patients with acute pancreatitis.


Serologic evidence for exposure to Rickettsia rickettsii in eastern Arizona and recent emergence of Rocky Mountain spotted fever in this region.
During 2002 through 2004, 15 patients with Rocky Mountain spotted fever (RMSF) were identified in a rural community in Arizona where the disease had not been previously reported. The outbreak was associated with Rickettsia rickettsii in an unexpected tick vector, the brown dog tick (Rhipicephalus sanguineus), which had not been previously associated with RMSF transmission in the United States. We investigated the extent of exposure to R. rickettsii in the local area through serologic evaluations of children and dogs in 2003-2004, and in canine sera from 1996. Antibodies to R. rickettsii at titers > or = 32 were detected in 10% of children and 70% of dogs in the outbreak community and 16% of children and 57% of dogs in a neighboring community. In comparison, only 5% of canine samples from 1996 had anti-R. rickettsii antibodies at titers > or = 32. These results suggest that exposures to RMSF have increased over the past 9 years, and that RMSF may now be endemic in this region.


Dysplastic Patellofemoral Joints Lead to a Shift in Contact Forces: A 3D-Printed Cadaveric Model.
The distribution of contact forces across the dysplastic patellofemoral joint has not been adequately quantified because models cannot easily mimic the dysplasia of both the trochlea and the patella. Thus, the mechanical consequences of surgical treatments to correct dysplasia cannot be established. The objective of this study was to quantify the contact mechanics and kinematics of normal, mild, and severely dysplastic patellofemoral joints using synthetic mimics of the articulating surfaces on cadavers. We tested the hypothesis that severely dysplastic joints would result in significantly increased patellofemoral contact forces and abnormal kinematics. Controlled laboratory study. Patellofemoral dysplasia was simulated in 9 cadaveric knees by replacing the native patellar and trochlear surfaces with synthetic patellar and trochlear implants. For each knee, 3 synthetic surface geometries (normal, showing no signs of dysplasia; mild, exemplifying Dejour type A; and severe, exemplifying Dejour type B) were randomized for implantation and testing. Patellar kinematics and the sum of forces acting on the medial and lateral patellar facets were computed for each knee and for each condition at 10° increments from 0° to 70° of flexion. A pronounced lateral shift in the weighted center of contact of the lateral facet occurred for severely dysplastic knees from 20° to 70° of flexion. Compared with normal geometries, lateral patellar facet forces exhibited a significant increase only with mild dysplasia from 50° to 70° of flexion and with severe dysplasia at 70° of flexion. No measurable differences in medial patellar facet mechanics or joint kinematics occurred. Our hypothesis was rejected: Severely dysplastic joints did not result in significantly increased patellofemoral contact forces and abnormal kinematics in our cadaveric simulation. Rather, severe dysplasia resulted in a pronounced lateral shift in contact forces across the lateral patellar facet, while changes in kinematics and the magnitude of contact forces were not significant. Including dysplasia of both the patella and trochlea is required to fully capture the mechanics of this complex joint. The pronounced lateralization of contact force in severely dysplastic patellofemoral joints should be considered to avoid cartilage overload with surgical manipulation.


Synthesis and properties of oligodeoxynucleotides containing the analogue 2'-deoxy-4'-thiothymidine.
The 2'-deoxythymidine analogue 2'-deoxy-4'-thiothymidine has been incorporated, using standard methodology, into a series of dodecadeoxynucleotides containing the EcoRV restriction endonuclease recognition site (GATATC). The stability of these oligodeoxynucleotides and their ability to act as substrates for the restriction endonuclease and associated methylase have been compared with a normal unmodified oligodeoxynucleotide. No problems were encountered in the synthesis despite the presence of a potentially oxidisable sulfur atom in the sugar ring. The analogue had very little effect on the melting temperature of the self-complementary oligoeoxynucleotides so synthesised and all had a CD spectrum compatible with a B-DNA structure. The oligodeoxynucleotide containing one analogue in each strand within the recognition site, adjacent to the bond to be cleaved (i.e. GAXATC, where X is 2'-deoxy-4'-thiothymidine), was neither a substrate for the endonuclease nor was recognized by the associated methylase. When still within the recognition hexanucleotide but two further residues removed from the site of cleavage (i.e. GATAXC), the oligodeoxynucleotide was a poor substrate for both the endonuclease and methylase. Binding of the oligodeoxynucleotide to the endonuclease was unaffected but the kcat value was only 0.03% of the value obtained for the parent oligodeoxynucleotide. These results show that the incorporation of 2'-deoxy-4'-thionucleosides into synthetic oligodeoxynucleotides may shed light on subtle interactions between proteins and their normal substrates and may also show why 2'-deoxy-4'-thiothymidine itself is so toxic in cell culture.


Fate of transplanted bone marrow derived mesenchymal stem cells following spinal cord injury in rats by transplantation routes.
This research was performed to investigate the differences of the transplanted cells' survival and differentiation, and its efficacy according to the delivery routes following spinal cord injury. Allogenic mesenchymal stem cells (MSCs) were transplanted intravenously (IV group) or intralesionally (IL group) at post-injury 1 day in rats. Behavioral improvement, engraftment and differentiation of the transplanted cells and the expression of neurotrophic factors of the transplanted groups were analyzed and compared with those of the control group. At 6 weeks post-injury, the mean BBB motor scales in the control, IV and IL groups were 6.5 ± 1.8, 11.1 ± 2.1, and 8.5 ± 2.8, respectively. Regardless of the delivery route, the MSCs transplantation following spinal cord injuries presented better behavioral improvement. The differentiations of the engrafted cells were different according to the delivery routes. The engrafted cells predominantly differentiated into astrocytes in the IV group and on the other hand, engrafted cells of the IL group demonstrated relatively even neural and glial differentiation. The expressions of neuronal growth factor were significantly higher in the IL group (mean relative optical density, 2.4 ± 0.15) than those in the control (2.16 ± 0.04) or IV group (1.7 ± 0.23). Transplantation of MSCs in the early stage of spinal cord injury gives a significant clinical improvement. However, the fate of the transplanted MSCs and expression of neuronal growth factors are different along the transplantation route.


Seismological constraints on the crustal structures generated by continental rejuvenation in northeastern China.
Crustal rejuvenation is a key process that has shaped the characteristics of current continental structures and components in tectonic active continental regions. Geological and geochemical observations have provided insights into crustal rejuvenation, although the crustal structural fabrics have not been well constrained. Here, we present a seismic image across the North China Craton (NCC) and Central Asian Orogenic Belt (CAOB) using a velocity structure imaging technique for receiver functions from a dense array. The crustal evolution of the eastern NCC was delineated during the Mesozoic by a dominant low seismic wave velocity with velocity inversion, a relatively shallow Moho discontinuity, and a Moho offset beneath the Tanlu Fault Zone. The imaged structures and geochemical evidence, including changes in the components and ages of continental crusts and significant continental crustal growth during the Mesozoic, provide insight into the rejuvenation processes of the evolving crust in the eastern NCC caused by structural, magmatic and metamorphic processes in an extensional setting. The fossil structural fabric of the convergent boundary in the eastern CAOB indicates that the back-arc action of the Paleo-Pacific Plate subduction did not reach the hinterland of Asia.


Cytosol androgen binding in submandibular gland and kidney of the normal mouse and the mouse with testicular feminization.
Androgen binding was investigated in the cytosol of the submandibular gland and the kidney from normal mice, mice with testicular feminization (Tfm), and carriers of the Tfm gene. In both tissues from normal mice an androgen-binding complex was observed from birth throughout life that could not be detected in Tfm animals at any age. This complex was precipitated at 35 and 40% saturation with ammonium sulfate in the kidney and the submandibular gland, respectively, and had an approximate sedimentation coefficient of 8S in the submandibular gland and 10S in the kidney. In both tissues of the normal female, the apparent dissociation constants (Kd) for testosterone and dihydrotestosterone were about 1 nM, and the binding capacity averaged 20 fmol-mg protein-1. The number of binding sites in preparations from Tfm carriers was intermediate between that in the Tfm and the normal female . In 0.5M KCl the 8S receptor of normal submandibular gland sediments at about 3S, and the 10S receptor of normal kidney sediments at about 4.5S. In the submandibular gland, binding of approximate 3S size was also observed. The latter was present in Tfm animals as well as in normal mice, it precipitated at 70% saturation with ammonium sulfate, and it was detectable from birth. In the kidney the only low molecular weight binding for androgen was about 4.5S in size.


Brominated and chlorinated flame retardants in Lake Ontario, Canada, lake trout (Salvelinus namaycush) between 1979 and 2004 and possible influences of food-web changes.
Concentrations of non-polybrominated diphenyl ether (PBDE) brominated (hexabromocyclododecane [HBCD], 1,2-bis[2,4,6-tribromophenoxy]ethane [BTBPE], and pentabromoethylbenzene [PEB]) and chlorinated (Dechlorane Plus [DP] as well as short- and medium-chain chlorinated paraffins [SCCP and MCCP, respectively]) flame retardants were evaluated in archived Lake Ontario, Canada, lake trout (Salvelinus namaycush) samples collected between 1979 and 2004. Polybrominated diphenyl ethers also were analyzed to provide a point of reference for comparison to previous studies. Concentrations of the dominant PBDE congeners (BDEs 28, 47, 99, 100, 153, and 154) increased significantly from 1979 until the mid-1990s, then either leveled off or decreased significantly between 1998 and 2004, a result that corresponds to those of previous studies. In contrast, BDE 209 increased approximately fourfold between 1998 and 2004. The temporal trends of the non-PBDE flame retardants varied, with sum (sigma) HBCD and DP showing significant overall decreases; BTBPE, sigmaSCCP, and sigmaMCCP showing parabolic trends; and PEB showing no overall change during the study period. Because many of the non-PBDE chemicals may be used as replacements for penta- and octa-BDE mixtures, these results will provide a baseline to evaluate future usage patterns. Possible changes in food-web structure, evaluated through stable nitrogen isotopes (delta15N), may be influencing our interpretations of contaminant trends in lake trout and are hypothesized to be partially responsible for the observed decrease in concentrations of BDEs 28, 47, 99, 100, 153, and 154 between 1998 and 2004. Retrospective analyses evaluating temporal trends in stable isotope values at the base of the food web, however, are recommended to test this hypothesis further.


Simple yet effective analysis of waveguide mode symmetry: generalized eigenvalue approach based on Maxwell's equations.
Particular waveguide structures and refractive index distribution can lead to specified degeneracy of eigenmodes. To obtain an accurate understanding of this phenomenon, we propose a simple yet effective approach, i.e., generalized eigenvalue approach based on Maxwell's equations, for the analysis of waveguide mode symmetry. In this method, Maxwell's equations are reformulated into generalized eigenvalue problems. The waveguide eigenmodes are completely determined by the generalized eigenvalue problem given by two matrices (M, N), where M is 6 × 6 waveguide Hamiltonian and N is a constant singular matrix. Close examination shows that N usually commute with the corresponding matrix of a certain symmetry operation, thus the waveguide eigenmode symmetry is essentially determined by M, in contrast to the tedious and complex procedure given in the previous work [Opt. Express25, 29822 (2017)10.1364/OE.25.029822]. Based on this new approach, we discuss several symmetry operations and the corresponding symmetries including chiral, parity-time reversal, rotation symmetry, wherein the constraints of symmetry requirements on material parameters are derived in a much simpler way. In several waveguides with balanced gain and loss, anisotropy, and geometrical symmetry, the analysis of waveguide mode symmetry based on our simple yet effective approach is consistent with previous results, and shows perfect agreement with full-wave simulations.


Nonsteady dynamics at the dynamic depinning transition in the two-dimensional Gaussian random-field Ising model.
With large-scale Monte Carlo simulations, we investigate the nonsteady relaxation at the dynamic depinning transition in the two-dimensional Gaussian random-field Ising model. The dynamic scaling behavior is carefully analyzed, and the transition fields as well as static and dynamic exponents are accurately determined based on the short-time dynamic scaling form. Different from the usual assumption, two distinguished growth processes of spatial correlation lengths for the velocity and height of the domain wall are found. Thus, the universality class of the depinning transition is established, which significantly differs from that of the quenched disorder equation but agrees with that of the recent experiment as well as other simulations works. Under the influence of the mesoscopic time regime, the crossover from the second-order phase transition to the first-order one is confirmed in the weak-disorder regime, yielding an abnormal disorder-dependent nature of the criticality.


Action of the highly purified, membrane-bound enzyme phosphatidylserine decarboxylase Escherichia coli toward phosphatidylserine in mixed micelles and erythrocyte ghosts in the presence of surfactant.
Phosphatidylserine decarboxylase, Escheichia coli, was purified to near-homogeneity by the procedure of Dowhan, W., Wickner, W. T., and Kennedy, E. P. ((1974) J. Biol. Chem. 249, 3079-3084) and assayed by following the production of CO2 using gas chromatography. The purified enzyme has an absolute requirement for the surfactant Triton X-100. The function of Triton in the assay is evaluated and a kinetic scheme describing the action of this membrane-bound enzyme in the micellar system provided by the surfactant is presented. According to this scheme, the enzyme first binds to a mixed micelle, composed of phosphatidylserine and Triton, where the dissociation constant is KSA. The enzyme, now part of the mixed micelle, then binds the substrate phosphatidylserine in its active site and this binding is related to the Michaelis constant, KMB. KSA, expressed as the sum of the molar concentrations of Triton and phosphatidylserine, is about 0.04 M. KMB, expressed as the mole fraction of phosphatidylserine in the mixed micelles, is about 0.03. Phosphatidylserine decarboxylase activity toward phosphatidylserine in human erythrocyte ghosts was also determined. The amount of phsophatidylserine converted to phosphatidylethanolamine and CO2 was found to be related to the amount of phosphatidylserine solubilized from the membrane by Triton X-100. In the absence of Triton, no significant activity of the enzyme toward the ghosts was detected even after subjecting the ghosts to lyophilization, homogenization, or sonication.