Finding the biologically optimal alignment of multiple sequences.
Deterministic annealing, which is derived from statistical physics, is a method for obtaining the global optimum in parameter space. During the annealing process, starting from high temperatures which are then lowered, deterministic annealing deterministically find the (global) optimum at each temperature. Thus, deterministic annealing is expected to be more computationally efficient than stochastic sampling strategies to obtain the global optimum. We propose to apply the deterministic annealing technique to the problem of efficiently finding the biologically optimal alignment of multiple sequences. We take a strategy based on probabilistic models for aligning multiple sequences. That is, we train a probabilistic model using given training sequences and obtain their alignment by parsing, i.e. searching for the most likely parse of each sequence and gaps using the trained parameters of the model. In this scenario, we propose a new stochastic model, which is simple enough to be suited to multiple sequence alignment and, unlike existing stochastic models, say a profile hidden Markov model (HMM), allows us to use similarity scores between symbols (or a symbol and a gap). We further present a learning algorithm for our simple model by combining deterministic annealing with an expectation-maximization (EM) algorithm. We emphasize that our approach is time-efficient, even if the training is done through an annealing process. In our experiments, we used actual protein sequences whose three-dimensional (3D) structures are determined and which are all aligned based on their 3D structures. We compared the results obtained by our approach with those by other existing approaches. Experimental results clearly showed that our approach gave the best performance, in terms of the similarity to the structurally determined alignment, among the approaches tested. Experimental results further indicated that our approach was ten times more efficient in terms of actual computation time than a competing method.


Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome.
This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22)(q34;q11) in chronic leukemia myeloid and acute lymphoblastic leukemia patients. Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II). A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME). Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.


Omission of adjuvant radiotherapy following breast-conserving surgery for elderly women with early-stage pure mucinous breast carcinoma.
We aimed to ascertain population-based practice patterns and survival outcomes of postoperative radiotherapy following breast conserving-surgery (BCS) in elderly women (aged ≥65 years) with early-stage pure mucinous breast carcinoma (PMBC). Patients aged ≥65 years diagnosed with T1-2N0 and hormone receptor-positive PMBC between 1990 and 2010 were identified from the Surveillance, Epidemiology, and End Results database. Binomial logistic regression, Kaplan-Meier method, Multivariate Cox proportional hazards models, and propensity score matching (PSM) were used for statistical analysis. We enrolled 3416 patients, including 1225 (35.9%) and 2191 (64.1%) in the no-radiotherapy and radiotherapy cohorts, respectively. The percentage of patients receiving postoperative radiotherapy following BCS was significantly lower after 2004 (59.5% between 2004 and 2010), relative to that before 2004 (71.1% between 1990 and 2003; P < 0.001). Before PSM, the 10-year breast cancer-specific survival (BCSS) rates were 98.1 and 93.2% for patients with and without postoperative radiotherapy (log-rank test, P < 0.001), respectively. In the PSM cohort, receiving postoperative radiotherapy was associated with better BCSS rates, with 10-year BCSS rates of 97.6 and 94.5% in patients with and without postoperative radiotherapy, respectively (log-rank test, P = 0.001). Multivariate Cox proportional analysis indicated that receiving postoperative radiotherapy was an independent factor associated with better BCSS before (P < 0.001) and after PSM (P = 0.001), relative to those not receiving postoperative radiotherapy. This study shows a decreasing utilization of postoperative radiotherapy following BCS of elderly PMBC patients over time. However, postoperative radiotherapy following BCS should be administered for elderly women with PMBC owing to independent association with better survival.


An evaluation on the effect of the copayment waiver policy for Korean hospitalized children under the age of six.
In January 2006, the Korean government implemented a copayment waiver policy for hospitalized children under the age of 6 years to reduce the economic burden on patients. This policy was implemented from 2006 to 2007 in Korea and involved hospitalized children under the age of 6 years. The goal of this study is to evaluate the effect of the copayment waiver policy on health insurance beneficiaries. The change in medical service utilization before and after the policy implementation was analyzed using data from the national health insurance corporation (NHIC) and compared with medical aid beneficiaries who were already exempt from copayment. The "difference in difference" method was applied to determine the net effect of the copayment waiver policy. The net effect of policy implementation on NHIC beneficiaries was unclear by the "difference in difference" method because the number of inpatient days and hospital expenditure after policy implementation showed opposite results. The copayment waiver policy did not decrease the intensity of health care utilization when compared with the medical aid beneficiaries group. Among the NHIC beneficiaries, patients who utilized medical services for fatal disease and those with the low premiums group were more affected by the policy. The net effect of copayment waiver policy remains unclear. Therefore, further studies are needed to determine the effects of policies implemented to reduce the economic burden on patients, such as the herein-described copayment waiver policy.


The nature of potassium chloride-induced relaxations of the rat anococcygeus muscle.
1. The nature of KCl-induced relaxations of the rat anococcygeus muscle was investigated. 2. The relaxations were mimicked by other K+ salts, but not by NaCl. 3. The muscle was more susceptible to the relaxant effects of KCl than the contractile effects. 4. Addition of ouabain (100 micron) had no effect on the relaxations. 5. The relaxations were abolished by tetrodotoxin (5 microgram/ml), procaine (500 micron), and by section of the inhibitory nerves. 6. The results suggest that KCl-induced relaxations are due to stimulation of the inhibitory nerves by K+.


On the existence of a perennial river in the Harappan heartland.
The legendary river Saraswati of Indian mythology has often been hypothesized to be an ancient perennial channel of the seasonal river Ghaggar that flowed through the heartland of the Bronze Age Harappan civilization in north-western India. Despite the discovery of abundant settlements along a major paleo-channel of the Ghaggar, many believed that the Harappans depended solely on monsoonal rains, because no proof existed for the river's uninterrupted flow during the zenith of the civilization. Here, we present unequivocal evidence for the Ghaggar's perennial past by studying temporal changes of sediment provenance along a 300 km stretch of the river basin. This is achieved using 40Ar/39Ar ages of detrital muscovite and Sr-Nd isotopic ratios of siliciclastic sediment in fluvial sequences, dated by radiocarbon and luminescence methods. We establish that during 80-20 ka and 9-4.5 ka the river was perennial and was receiving sediments from the Higher and Lesser Himalayas. The latter phase can be attributed to the reactivation of the river by the distributaries of the Sutlej. This revived perennial condition of the Ghaggar, which can be correlated with the Saraswati, likely facilitated development of the early Harappan settlements along its banks. The timing of the eventual decline of the river, which led to the collapse of the civilization, approximately coincides with the commencement of the Meghalayan Stage.


Figure-ground organization in real and subjective contours: a new ambiguous figure, some novel measures of ambiguity, and apparent distance across regions of figure and ground.
This study was designed to assess the effects of organization, luminance contrast, sector angle, and orientation on a new, highly ambiguous Cs-keyhole figure. Organization and contrast were the most important factors, and sector angle also influenced figure-ground relationships. There was no significant effect of orientation, nor was there any significant interaction between any of the factors. Several new measures of figure-ground organization were developed, such as ambiguity ratios based on reaction times and on ratings of the strength of perceived organizations, providing new quantitative measures of figure-ground relationships. Distances measured across figural regions appeared smaller than equal distances across the ground in the new reversible figure, and also in Rubin's classic vase-face figure presented in real and subjective contours. Inducing a perceptual set to see a particular organization in a reversible figure influenced the apparent distance across that organization. Several possible explanations of the observed effects are considered: (1) an instance of Emmert's law, based on the difference in apparent depth of figure and ground; (2) an aspect of the Müller-Lyer illusion; (3) a feature-detector model of contour attraction; (4) a natural set or predisposition to see a figure as smaller; and (5) framing effects. The first two explanations appear the most promising.


Cognitive intermediate phenotype and genetic risk for psychosis.
Intermediate phenotypes (IPs) are defined as measurable liability traits underlying complex phenotypes, posited to be more genetically tractable than the phenotypes themselves. Here we review evidence for cognition as an IP of psychosis, and highlight topical advances in the literature: first, heritability estimation of cognitive abilities using genomewide complex-trait analysis; second, evidence that cognition lies upstream to schizophrenia liability; third, use of polygenic risk scores rather than single genetic variants to examine genetic overlap between cognitive IPs and schizophrenia; and fourth, use of cognitive IPs for schizophrenia risk gene discovery and functional characterization. We end with future directions in using cognitive IPs to study genetic risk of psychosis, including methodological refinements and shifting research focus from identifying IPs to using them.


Endocrine cells in human intestine: an immunocytochemical study.
The regional and topographic distribution of endocrine cells in the human intestine was examined by immunohistochemistry. The frequency of endocrine cells was greatest in the small intestine with the rectum next in order. The duodenum and jejunum harbored a large number of different endocrine cell types; the spectrum of cell types gradually narrowed distally in the intestine. 5-Hydroxytryptamine-containing enterochromaffin cells were present in all regions of the intestine and comprised the single largest endocrine cell population. In addition, a minor proportion of these cells contained substance P. The second largest cell population consisted of the glicentin cells, which were notably numerous in the ileum and colon. The somatostatin cells also occurred throughout the digestive tract. Cells storing cholecystokinin, motilin, secretin, or gastric inhibitory polypeptide were more numerous in the proximal and middle small intestine than distally. Gastrin cells were few and occurred in the proximal duodenum only. Other cells in the small intestine reacted with antiserum directed against the common C-terminus of gastrin and cholecystokinin. The number of these cells greatly exceeded the sum of cells reactive to gastrin-specific or cholecystokinin-specific antisera. Cells displaying beta-endorphin, pro-gamma-melanocyte-stimulating hormone, or beta-lipotropin immunoreactivity, or a combination of these, were found in the small intestine. Cells storing neurotensin, glicentin, substance P, or pro-gamma-melanocyte-stimulating hormone increased in number distally in the small intestine. Enterochromaffin cells, glicentin cells, and somatostatin cells were the predominant endocrine cell types in the colon and rectum. The majority of the glicentin-immunoreactive cells also contained glucagon and pancreatic polypeptide-like immunoreactivity. Endocrine cells in the large intestine often possessed basal processes.


Electrochemical biosensor evaluation of the interaction between DNA and metallo-drugs.
Electrochemical techniques were used to study the interaction between a panel of antiproliferative metallo-drugs and double-stranded DNA immobilized on screen-printed electrodes as a model of the analogous interaction occurring in solution. The propensity of a given metal drug to interact with DNA was measured as a function of the decrease of guanine oxidation signal, which was detected by square wave voltammetry. Estimates of variations in experimental parameters, such as the concentration of complexes, time following dissolution (ageing time) and the presence of chloride, are provided.


Species loss and nitrogen pollution alter litter decomposition dynamics in coastal salt marshes.
Litter decomposition is a central ecosystem function because dead plant biomass plays a critical role in carbon storage, the nitrogen (N) cycle, and as food/habitat for animals and microorganisms. In the face of global change, interactions between organisms that participate in litter decomposition are likely to change due to species loss and N pollution. To understand how these global change factors may interact to alter litter decomposition, we manipulated the detritivore community and N concentrations in a coastal salt marsh for 2 years. We chose to manipulate densities of a dominant, detritivorous snail (Melampus bidentatus) because its population size is expected to decline due to climate change, yet its impact on litter decomposition has not been tested in the field. We measured litter decomposition rates, detritivore densities, and the N concentrations of sediment and litter. We found that endogenous N enrichment (N added live plants before decomposition), exogenous N enrichment (N added to decomposing plants) and higher densities of Melampus increased litter decomposition rates. Linear mixed models further revealed that snails, other detritivores, and soil NH4+ were the best predictors of litter mass loss in the middle stages of decomposition. Notably, exogenous N added to litter already enriched with N further increased mass loss but did not increase litter %N. Our study reveals how global change in the form species loss and N pollution can have palpable impacts on carbon cycling and ecosystem function.


Facile Fabrication of Multi-hierarchical Porous Polyaniline Composite as Pressure Sensor and Gas Sensor with Adjustable Sensitivity.
A multi-hierarchical porous polyaniline (PANI) composite which could be used in good performance pressure sensor and adjustable sensitivity gas sensor has been fabricated by a facile in situ polymerization. Commercial grade sponge was utilized as a template scaffold to deposit PANI via in situ polymerization. With abundant interconnected pores throughout the whole structure, the sponge provided sufficient surface for the growth of PANI nanobranches. The flexible porous structure helped the composite to show high performance in pressure detection with fast response and favorable recoverability and gas detection with adjustable sensitivity. The sensing mechanism of the PANI/sponge-based flexible sensor has also been discussed. The results indicate that this work provides a feasible approach to fabricate efficient sensors with advantages of low cost, facile preparation, and easy signal collection.


Atomic sites and stability of Cs+ captured within zeolitic nanocavities.
Zeolites have potential application as ion-exchangers, catalysts and molecular sieves. Zeolites are once again drawing attention in Japan as stable adsorbents and solidification materials of fission products, such as (137)Cs(+) from damaged nuclear-power plants. Although there is a long history of scientific studies on the crystal structures and ion-exchange properties of zeolites for practical application, there are still open questions, at the atomic-level, on the physical and chemical origins of selective ion-exchange abilities of different cations and detailed atomic structures of exchanged cations inside the nanoscale cavities of zeolites. Here, the precise locations of Cs(+) ions captured within A-type zeolite were analyzed using high-resolution electron microscopy. Together with theoretical calculations, the stable positions of absorbed Cs(+) ions in the nanocavities are identified, and the bonding environment within the zeolitic framework is revealed to be a key factor that influences the locations of absorbed cations.


Circadian variations of adenosine level in blood and liver and its possible physiological significance.
The role of adenosine as a possible physiological modulator was explored by measuring its concentration in different tissues during a 24-hour period. Initially the circadian variations of adenosine and other purine compounds such as inosine, hypoxanthine, uric acid and adenine nucleotides were studied in the rat blood. A daily cyclic response was observed, with low levels of adenosine from 08.00 - 20.00 h, followed by an increase from this time on. Inosine and hypoxanthine levels were elevated during the day and low at night. The uric acid changes observed indicate that the decrease in purine catabolism coincides with a decrease in inosine and hypoxanthine levels and an increase in adenosine. The blood adenine nucleotides, energy charge and phosphorylation potential remained constant during the day and showed oscillatory changes during the night. Similar studies were made in the liver, a primary source of circulating purines. Liver adenosine was high during the night while inosine and hypoxanthine remained low along the 24 hours. The results suggest that liver purine metabolism might participate in the maintenance and renewal of the blood purine pool and in the energy state of erythrocytes in vivo.


Synergistic impact of heat-ultrasound treatment on the properties and digestibility of Sagittaria sagittifolia L. starch-phenolic acid complexes.
The current research investigated the multi-scale structural interactions between arrowhead starch (AS) and phenolic acids, such as ferulic acid (FA) and gallic acid (GA) to identify the mechanism of anti-digestion effects of starch. AS suspensions containing 10 % (w/w) GA or FA were subjected to physical mixing (PM) followed by heat treatment at 70 °C for 20 min (HT) and a synergistic heat-ultrasound treatment (HUT) for 20 min using a dual-frequency 20/40 KHz system. The synergistic HUT significantly (p < 0.05) increased the dispersion of phenolic acids in the amylose cavity, with GA showing a higher complexation index than FA. XRD analysis showed a typical V-type pattern for GA, indicating the formation of an inclusion complex, while peak intensities decreased for FA following HT and HUT. FTIR revealed sharper peaks possibly of amide bands in the ASGA-HUT sample compared to that of ASFA-HUT. Additionally, the emergence of cracks, fissures, and ruptures was more pronounced in the HUT-treated GA and FA complexes. Raman spectroscopy provided further insight into the structural attributes and compositional changes within the sample matrix. The synergistic application of HUT led to increased particle size in the form of complex aggregates, ultimately improving the digestion resistance of the starch-phenolic acid complexes.


Case report of a spontaneous pneumothorax after the recovery from COVID-19 pneumonia: A delayed complication.
This case demonstrates pneumothorax as a consequence of COVID-19 and emphasizes the significance of follow-up of the COVID-19 patients.


Phosphorus removal from secondary wastewater effluent using copper smelter slag.
This study investigated the use of copper smelter slag for the removal of phosphorus from secondary wastewater effluent through batch tests. The media was physically and chemically characterized and showed presence of Fe2O3 (45.22%), SiO2 (14.98%), Al2O3 (3.21%), CaO (1.99%), SO3 (1.77%) and MgO (1.33%). Scanning electron microscopy monographs revealed smooth and flat surface and no heterogeneity on the surface of the slag with visible micro pores before the experiment and less visible after the experiment. The point of zero charge of the media was 5.0. Equilibrium was reached after 4 h at 29.5 ± 0.71% phosphorus removal efficiency and media dosage of 0.4/100 mL. The kinetic data was best described by Pseudo second order equation. More than one mechanisms were involved in the adsorption of phosphorus onto copper smelter slag as suggested by multi-linearity of intra particle diffusion model. Ninety seven percent (97.5 ± 0.0%) removal efficiency was achieved at an equilibrium dosage of 160 gL-1. The equilibrium isotherm was described better by Langmuir equation with observed maximum adsorption capacity of 0.16 mg P g-1 media and the experimental maximum adsorption capacity was 0.26 mg P g-1 media. Regeneration studies showed low performance with maximum efficiency of 11.7% revealed during the first regeneration trial therefore low practical benefits. Copper smelter slag is a poor adsorbent for phosphorus and further studies on the media should be conducted.


Synthesis, characterization, and intracellular delivery of reducible heparin nanogels for apoptotic cell death.
Reducible heparin nanogels cross-linked with disulfide linkages were developed for efficient cellular uptake of therapeutic heparin to induce apoptotic cell death. The heparin nanogels were synthesized by forming nanocomplexes between thiolated heparin and poly(ethylene glycol) in a selected organic solvent, and subsequently producing intermolecular disulfide bonds between thiolated heparin molecules by ultrasonication. The resultant heparin nanogels had a stable structure with an average diameter of 248.7+/-26.8nm in aqueous solution. However, they rapidly disintegrated and released free heparin molecules under reductive environments, such as intracellular cytosol, through the cleavage of disulfide cross-links within their network structure. Confocal laser scanning microscopy and flow cytometric analysis revealed that these heparin nanogels significantly inhibited proliferation of mouse melanoma cells by inducing caspase-mediated apoptotic cell death. The present study suggested that the reducible heparin nanogels exhibiting a remarkable apoptotic activity could be potentially applied for cancer cell targeted delivery when combined with various therapeutic and diagnostic agents.


Recalcitrant course of bullous pemphigoid indicating coexisting hypereosinophilic syndrome: A case report and literature review.
As dermatologists, we must be aware that even limited localized lesions may signal a life-threatening condition, for which early diagnosis and treatment can improve the prognosis. Bullous pemphigoid is an autoimmune disorder characterized by blister formation. Hypereosinophilic syndrome is a myeloproliferative disorder featuring papules, nodules, urticarial lesions, and blisters. The coexistence of these disorders may highlight the involvement of common molecular and cellular factors. Here, we describe a 16-year-old patient with hypereosinophilic syndrome and bullous pemphigoid.


Delta opioid agonists inhibit proliferation of highlypurified murine CD4+ and CD8+ T-cells.
A substantial body of evidence demonstrates that opiates and opioid peptides modulate immune function. The present study used highly purified murine CD4+ and CD8+ T-cells to determine the effects of delta opioid receptor (DOR) agonists on proliferation. Splenic T-cells, obtained from male or female C57BL/6 or CD1 mice, were separated by a fluorescence activated cell sorter. Cells were stimulated to proliferate in serum free medium by cross-linking the T-cell receptor using plate-coated anti-CD3-epsilon, 3H-thymidine uptake was determined at 48 hours. Previous experiments had shown that deltorphin and [D-Ala2]-met-enkephalinamide (DAME), at concentrations from 10(-11) to 10(-7) M, dose dependently inhibited the proliferation of CD4+ and CD8+ T-cells obtained from female C57BL/6 or CD1 mice. Similarly, the experiments herein demonstrate that proliferation of CD4+ T-cells from female CD1 mice was inhibited by 2,5 DPDP-enkephalin (DPDP-E), in direct relation to dose. In contrast, the anti-proliferative response of cells from C57BL/6 mice demonstrated an inverse relationship to dose. At 10(-11) M, the most effective dose of DPDP-E studied, 3H-thymidine uptake was inhibited by 50%. The selective DOR antagonist, naltrindole (10(-12) M), abolished this. DAME was used to compare the effects of DOR agonists on CD8+ T-cells from both strains of female mice. 3H-Thymidine uptake was dose-dependently inhibited to a similar degree in both strains; 10(-7) M DAME maximally reduced proliferation by 70%. DAME had similar effects on both CD8+ and CD4+ T-cells from male mice, and its inhibitory effect was markedly attenuated after 72 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


Adhesive Enrichment and Membrane Turnover at the Heart of Cardiopharyngeal Induction.
Differential inductive signaling during asymmetric division of progenitor cells specifies the heart lineage in Ciona intestinalis. In this issue of Developmental Cell, Cota and Davidson (2015) show that differential induction is mediated by FGF receptor regionalization, resulting from asymmetric cell-matrix adhesion and reduced mitotic turnover of polarized Caveolin-rich membrane domains.


Early Versus Delayed Lead Extraction in Patients With Infected Cardiovascular Implantable Electronic Devices.
This study sought to assess the impact of early versus delayed lead extraction in patients with an infected cardiovascular implantable electronic device (CIED). CIED infections are associated with poor outcomes. Prior studies have demonstrated improved survival with CIED extraction compared with antibiotic therapy alone. The impact of timing of CIED extraction has not been well characterized. All infected CIED extraction cases at our medical center from 2006 to 2019 were reviewed. Patients were divided into 2 groups based on the presence of bacteremia or isolated pocket infection. We assessed the in-hospital morbidity and 1-year mortality for early versus delayed lead extraction, using hospitalization day 7 as cutoff. Of 233 patients who underwent CIED extraction, 127 patients had bacteremia and 106 patients had pocket infection. Delayed extraction (15.2 days) in bacteremic patients was associated with septic shock (odds ratio [OR]: 5.39; 95% confidence interval [CI]: 1.23 to 23.67; p = 0.026), acute kidney injury (OR: 5.61; 95% CI: 2.15 to 14.63; p < 0.001), respiratory failure (OR: 5.52; 95% CI: 1.25 to 24.41; p = 0.024), and decompensated heart failure (OR: 3.32; 95% CI: 1.10 to 10.05; p = 0.033). Locally infected patients with delayed extraction (10.7 days) were associated with acute kidney injury (OR: 3.45; 95% CI: 1.11 to 10.77; p = 0.033) and respiratory failure (OR: 10.29; 95% CI: 1.26 to 83.93; p = 0.030). Delayed CIED extraction in both groups was associated with increased 1-year mortality. Delayed infected CIED extraction is associated with worse outcomes. This underscores the importance of early detection and a strategy for prompt management including lead extraction.


Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control.
Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert a significant role in the survival, growth, and immune development of neonatal calves. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 (241.3 pg/mL) production induced by PMA (p < 0.05), while increasing IL-10 production (45.3 pg/mL), in comparison to PMA control (441.1 and 12.5 pg/mL, respectively). Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-κB activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration and intestinal score, and suppressed IL-6 (142.0 pg/mL) production during S. typhimurium infection, in comparison to control animals (215.2 pg/mL). These results suggest the immunomodulatory activity of bovine colostrum and its potential applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models.


Current microfluidic platforms for reverse engineering of cornea.
According to the World Health Organization, corneal blindness constitutes 5.1% of global blindness population. Surgical outcomes have been improved significantly in the treatment of corneal blindness. However, corneal transplantation is limited by global shortage of donor tissue, prompting researchers to explore alternative therapies such as novel ocular pharmaceutics to delay corneal disease progression. Animal models are commonly adopted for investigating pharmacokinetics of ocular drugs. However, this approach is limited by physiological differences in the eye between animals and human, ethical issues and poor bench-to-bedside translatability. Cornea-on-a-chip (CoC) microfluidic platforms have gained great attention as one of the advanced in vitro strategies for constructing physiologically representative corneal models. With significant improvements in tissue engineering technology, CoC integrates corneal cells with microfluidics to recapitulate human corneal microenvironment for the study of corneal pathophysiological changes and evaluation of ocular drugs. Such model, in complement to animal studies, can potentially accelerate translational research, in particular the pre-clinical screening of ophthalmic medication, driving clinical treatment advancement for corneal diseases. This review provides an overview of engineered CoC platforms with respect to their merits, applications, and technical challenges. Emerging directions in CoC technology are also proposed for further investigations, to accentuate preclinical obstacles in corneal research.


Photoecology of the coral Leptoseris fragilis in the Red Sea twilight zone (an experimental study by submersible).
Depth-dependent photoadaptational responses of the Red Sea zooxanthellate coral (Leptoseris fragilis) were studied down to 160 m from the research submersible GEO. Light saturation curves for photosynthesis revealed, with I C=1-2, I K=10.9 and I sat=20 μE·cm-2·sec-1, the lowest values of photokinetic parameters ever reported for a symbiotic coral. In summer, positive net production occurs only around noon at approx. 100m depth. Biomass parameters of corals at 100-135 m are negatively correlated with depth in algal cell density, protein, chlorophyll and carotenoid but not in pigment ratios or cell based pigment content. Coral size decreased with depth. Corals transplanted from 110-120 m original depth to 40, 70, 90 and 160 m showed high survival after one year. O2-production and dark O2-uptake increased with decreasing transplantation depth. After one year, transplants at 70 and 90 m but not at 40 m had higher algae density and pigment concentrations. The host light-harvesting systems described by Schlichter, Fricke and Weber (1986) are partially destroyed in 40 m but not in 70 and 90 m transplants. Different light exposures alter P-I-responses (P max, I C, I K, I sat) but not biomass parameters, indicating molecular or biochemical adaptation. The coraal's optimal light fields lie between 70 to 90 m. Its exceptional bathymetric distribution is linked with the newly discovered host light-harvesting systems which probably enhance photosynthetic performance in a dim environment.


Effect of anthraquinone-laxatives on the proliferation and urokinase secretion of normal, premalignant and malignant colonic epithelial cells.
Even though 1,8-dihydroxyanthraquinone (DHA)-laxatives have been implicated in colon carcinogenesis, the available information is still inconclusive. The aim of this study was to demonstrate the effect of the DHA-laxatives, danthrone, rhein, aloe-emodin and sennidine, on colorectal tumour cells. In SW480 carcinoma cultures, dose-dependent induction of urokinase secretion into the medium was the predominant effect. Simultaneously, cell numbers were decreased by DHA-aglycones, but not by sennoside or the biphenylic laxative bisacodyl. DNA synthesis was not similarly reduced: 0.4-4 microM danthrone and sennidine even stimulated 5-bromo-2'-desoxyuridine (BrdU) uptake into DNA. When uptake was normalised to cell number, danthrone and sennidine doubled BrdU uptake/10(6) cells, 18 microM rhein and 0.7 microM aloe-emodin induced increases of 37 and 50%, respectively. This may at least partially be due to selective resistance of S-phase cells to DHA-caused cell loss. In VACO235 adenoma cells, sennidine and aloe-emodin did not affect urokinase secretion, but stimulated growth. Both cell numbers and DNA synthesis were increased. In contrast to SW480 carcinoma cells, VACO235 cells were also sensitive to sennoside and bisacodyl. No effects of DHA were observed in normal colorectal epithelial cells. The biological effects were preceeded by specific phosphorylation of cellular proteins with molecular weights of 110, 78, 63, 57 kDa, indicating the specific induction of a cellular signalling cascade by the laxatives.


Patterns of contraceptive use before and after an abortion: results from a nationally representative survey of women undergoing an abortion in France.
Using a large national survey of women undergoing an abortion in France, we explore their contraceptive use surrounding an abortion. The study comprised a representative sample of 7541 women undergoing an abortion in 2007. We compared their use of contraception before and after the abortion and examined the factors associated with the prescription of a very effective method (IUD, hormonal methods) after the procedure. Sixty-six percent of women were using contraception in the month they conceived. A third of women reported the same use of contraception before and after the abortion, 54% were prescribed a more effective method, while 14% changed to a less effective or no method at all. After the abortion, 77% of women were prescribed a very effective contraceptive. Abortion offers an opportunity to improve contraceptive uptake and a chance for providers to adjust their prescriptions according to the difficulties women experience in their use of contraceptives.


Corrigendum: Long Noncoding RNA NONHSAT079852.2 Contributes to GBM Recurrence by Functioning as a ceRNA for has-mir-10401-3p to Facilitate HSPA1A Upregulation.
[This corrects the article DOI: 10.3389/fonc.2021.636632.].


Serum and 24-hour urinary tests cost-effectiveness in stone formers.
To assess the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers. This study analyzes the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers. The sensitivity and specificity, false positive, and negative results of the tests are extracted from diagnostic kits used in the laboratories of the target community. To accurately infer the results, a simulation based on 1000 people was used through 22 standard laboratory tests (Additional File 2), including calcium, oxalate, phosphate, uric acid, sulfate, potassium, sodium, citrate, and magnesium in 24-hour urine; and calcium, creatinine, Vit D, uric acid, and intact parathyroid hormone (PTH) in serum. The incremental cost-effectiveness ratio (ICER) was calculated and compared for each diagnostic test versus other diagnostic tests according to the incremental cost required for correct diagnoses of stone causes. Urinary uric acid, citrate, and serum potassium constitute the cost-effectiveness boundary curve in this study. This means that other diagnostic tests are not cost-effective compared to these three tests in terms of indexing at least one item of cost and effectiveness. The ICER index for each correct diagnosis with the urinary uric acid test was $ 1.25 per diagnosis, the most cost-effective test compared to serum potassium and urinary citrate. The simplified blood and 24-hour urine metabolic evaluation, including urinary uric acid, citrate, and serum potassium, constitute the cost-effectiveness boundary curve. The most cost-effective test was urinary uric acid measurement.


Best evidence topic report. Intra-articular corticosteroid injections in acute rheumatoid monoarthritides.
A short cut review was carried out to establish whether intra-articular corticosteroid injections were effective at reducing pain in patients with acute rheumatoid monoarthritis. Altogether 215 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.


Synergy between vinorelbine and afatinib in the inhibition of non-small cell lung cancer progression by EGFR and p53 signaling pathways.
Currently, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were approved for the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutation. However, some lung cancer patients fail to respond and eventually develop drug resistance. Therefore, new therapeutic strategies are needed to improve the outcomes for substantial clinical benefit. Here we aimed to explore the combination of vinorelbine with the second EGFR-TKI afatinib in NSCLC cells with or without EGFR mutation. The three cells of H1975, HCC827, and H460 were assessed for the combination of vinorelbine and afatinib. Vinorelbine combined with afatinib synergistically inhibited the three lung cancer cells growth without aggravating adverse effect on the normal lung cells. The combination of low doses of vinorelbine and afatinib suppressed the cancer cell proliferation by cell colony formation assay and significantly induced cell apoptosis. The anti-apoptotic proteins Bcl-xL and Bcl-2 showed significant reduction after the drug combination treatment, while the pro-apoptotic protein Bax as well as apoptosis indicators cytochrome C and cleaved PARP were observed a notable increasing. EGFR downstream pathways including AKT, ERK, JNK, and p38 were highly active and p53 was inactive in the three lung cancer cells, favoring tumor growth. The low doses of vinorelbine plus afatinib blocked the phosphorylation of AKT, ERK, JNK, and p38, but restored the expression of p53. Our findings suggested that the combination of vinorelbine and afatinib could be recommended as a therapeutic regimen for treatment of NSCLC with or without EGFR mutation.


Future challenges for parasitology: vector control and one health in the Americas.
"One Health" is a term that encapsulates and underscores the inherent interrelatedness of the health of people, animals, and the environment. Vector-borne infections are central in one health. Many arthropod vectors readily feed on humans and other animals, serving as an ideal conduit to move pathogens between a wide spectrum of potential hosts. As ecological niches flux, opportunities arise for vectors to interact with novel species, allowing infectious agents to broaden both geographic and host ranges. Habitat change has been linked to the emergence of novel human and veterinary disease agents, and can dramatically facilitate expansion opportunities by allowing existing vector populations to flourish and by supporting the establishment of new pathogen maintenance systems. At the same time, control efforts can be hindered by the development of parasiticide and pesticide resistance, foiling efforts to meet these challenges. Using examples drawn from representative diseases important in one health in the Americas, including rickettsial infections, Lyme borreliosis, Chagas disease, and West Nile virus, this paper reviews key aspects of vector-borne disease maintenance cycles that present challenges for one health in the Americas, including emergence of vector-borne disease agents, the impact of habitat change on vector-borne disease transmission, and the complexities faced in developing effective control programs. Novel strategies will be required to effectively combat these infections in the future if we are to succeed in the goal of fostering an environment which supports healthy animals and healthy people.


Impact of fetal presentation on neurodevelopmental outcome in a trial of preterm vaginal delivery: a nationwide, population-based record linkage study.
To assess the risk of adverse neurodevelopmental outcomes at the age of four after an attempted vaginal delivery according to the fetal presentation in birth. This retrospective record linkage study evaluated the risks of cerebral palsy, epilepsy, intellectual disability, autism spectrum disorder, attention-deficit/hyperactivity disorder, and speech, visual, and auditory disabilities among preterm children born after an attempted vaginal breech delivery. The control group comprised children born in a cephalic presentation at the same gestational age. This study included 23 803 singleton deliveries at gestational weeks 24 + 0-36 + 6 between 2004 and 2014. From 1629 women that underwent a trial of vaginal breech delivery, 1122 (66.3%) were converted to emergency cesarean sections. At extremely preterm and very preterm gestations (weeks 24 + 0-31 + 6), no association between a trial of vaginal breech delivery and neurodevelopmental delay occurred. At gestational weeks 32 + 0-36 + 6, the risks of visual disability (aOR 1.67, CI 1.07-2.60) and autism spectrum disorders (aOR 2.28, CI 1.14-4.56) were increased after an attempted vaginal breech delivery as compared to vaginal cephalic delivery. A trial of vaginal breech delivery at extremely preterm and very preterm gestations appears not to increase the risk of adverse neurodevelopmental outcomes at the age of four. In moderate to late preterm births, a trial of vaginal breech delivery was associated with an increased risk of visual impairment and autism spectrum disorders compared to children born in cephalic presentation. A trial of vaginal preterm breech delivery requires distinctive consideration and careful patient selection.


Methane excretion in the growing pig.
Total methane excretion (CH4 in breath + flatus) was measured in two experiments with thirty-six castrated male pigs (Danish Landrace) during the growth period from 20 to 120 kg live weight (LW). In Expt A, twenty-eight pigs were fed on a commercial diet alternately at high (HFL; metabolizable energy (ME) 1234 (SE 41) kJ/kg LW 0.75) or low (LFL; ME 784 (SE 31) kJ/kg LW 0.75) feed levels in different weight classes. In Expt B, eight pigs were constantly fed on a semi-purified diet at HFL without (-oil) or with 90 g soya-bean oil/kg diet (+oil) corresponding to daily intakes of ME of 1339 (SE 11) and 1413 (SE 8) kJ/kg LW 0.75 respectively. CH4 excretion was measured during 24 h respiration trials in open-air-circulation chambers. About 1 litre CH4 was excreted per day at 20-25 kg LW increasing to a maximum of 12 litres at 120 kg LW, which corresponded to no more than 1.2% of dietary gross energy. In Expt A, CH4 excretion increased linearly with LW, while in Expt B the increase was linear until about 70 kg LW, when it reached a plateau. On average LFL reduced CH4 excretion by 23% compared with HFL. When related to dry matter (DM) intake, however, the pigs on LFL excreted 3.1 litres CH4/kg dietary DM and those on HFL 2.5 litres CH4/kg dietary DM, the difference being significant (P less than 0.05). In Expt B the inclusion of soya-bean oil in the basal diet (+oil) reduced CH4 excretion by 26% compared with the diet without oil (-oil).(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of the pulmonary origin of bronchoconstrictor vagal tone.
1. In anaesthetized spontaneously breathing cats, the sensory component of the vagal nerves was sectioned at the level of nodose ganglion, using a method described previously (Mei, 1966; Mei & Dussardier, 1966).2. The strength of the Hering-Breuer reflex (inhibitory ratio, i.e. T(1)/T(0)) provided a test for effectiveness of section of vagal afferents, particularly respiratory afferents. On the other hand, by studying the cardiac and bronchomotor effects induced by electrical stimulation of the supranodose portion of the vagal nerve, it was possible to test the integrity of the efferent vagal component.3. Unilateral right sensory vagotomy was followed by a 29% reduction in total pulmonary resistance.4. Section of the contralateral sensory vagal component (sensory bivagotomy), produced a weak supplementary effect (total decrease of total pulmonary resistance: 31%).5. No additive bronchomotor effect could be observed after the bilateral section of efferent vagal fibres (total bivagotomy).6. In intact cats, blockade of the two vagal nerves by procaine induced a decrease in pulmonary resistance similar to those produced by the sensory bivagotomy (23%). This bronchodilatator effect was concomitant with a complete disappearance of the C wave of the compound vagal potential.7. Intravenous injection of phenyl diguanide, immediately after the blockade of the C vagal fibres by procaine did not modify bronchomotor tone. This result confirms that the C pulmonary afferents, which are activated by phenyl diguanide, are mainly involved in this mechanism.8. The pulmonary irritant receptors seem to play a minor role. In fact, the I.V. administration of histamine under the same conditions, provides evidence that the corresponding neurones (small sized myelinated fibres) are potent during the procaine application.9. From these results, it appears that bronchoconstrictor vagal tone has an exclusive peripheral origin and that pulmonary endings, in particular those connected with non-medullated fibres, are probably involved in this mechanism.


Platelet surface antigens: analysis by monoclonal antibodies. I. Antibodies. I. Immunological and biochemical studies.
Monoclonal antibodies were produced against human platelets. Four antibodies (PA1, PA2, PA3 and PA4) reacted specifically with platelets and megakaryocytes, but not with peripheral blood lymphocytes, granulocytes, erythrocytes or monocytes. The antibodies belonged to the mouse IgG subclass 2a (PA1, PA2, PA3), or 1 (PA4) respectively. PA1 and PA4 did not precipitate, their antigens have not yet fully been characterized. PA3 was directed against the glycoprotein (Gp) complex IIb/IIIa; PA2 precipitated Gp IIb/IIIa, and, in addition, Gp Ia. PA4 revealed specificity against the human platelet alloantigen Zw(a).


Physiological effects of two driving pressure-based methods to set positive end-expiratory pressure during one lung ventilation.
During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEPINCREMENTAL) or by stepwise decrease after a lung recruiting manoeuvre (PEEPDECREMENTAL). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEPINCREMENTAL or PEEPDECREMENTAL strategy to match the lowest ∆P. In the PEEPINCREMENTAL group, PEEP was stepwise titrated from ZEEP up to 16 cm H2O, whereas in the PEEPDECREMENTAL group PEEP was decrementally titrated, starting from 16 cm H2O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39-55]% to 35 [28-42]% in the PEEPINCREMENTAL and from 45 [37-58]% to 33 [25-45]% in the PEEPDECREMENTAL group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEPDECREMENTAL than in the PEEPINCREMENTAL group (8 [7-11] vs 10 [9-11] cm H2O; p = 0.03). In the PEEPDECREMENTAL group the PaO2/ FIO2 ratio increased significantly after intervention (from 140 [99-176] to 186 [152-243], p < 0.001). Both the PEEPINCREMENTAL and the PEEPDECREMENTAL strategies were able to decrease intraoperative shunt, but only PEEPDECREMENTAL improved oxygenation and lowered intraoperative ΔP.Clinical trial number NCT03635281; August 2018; "retrospectively registered".


A multicenter study of the clinical characteristics of usual-type vulvar intraepithelial neoplasia in China.
To investigate clinical characteristics of usual-type vulvar intraepithelial neoplasia (uVIN) in China. A retrospective review of the records of 64 patients with uVIN was performed at 3 academic hospitals between 2004 and 2010. Patients were assigned to a younger (≤40 years) or an older (>40 years) group. Clinical characteristics of lesions were described and analyzed. Mean patient age was 40.6 years. There was a high proportion of incidental findings (34%), multifocal lesions (64%), variegated lesions (59%), and multiple neoplastic lesions in the lower genital tract (20%). As patient age increased, so did numbers of patients reporting pain (P<0.05). Longer time between symptom onset and uVIN diagnosis, and more multifocal lesions were noted in the older group (P<0.05). Whereas younger patients often presented with cervical intraepithelial neoplasia and uVIN, older patients often presented with intraepithelial neoplasia at uncommon locations (e.g. vagina, anus, and periurethral region) (P<0.05). No differences between the groups were found regarding gross appearance or anatomic location of uVIN lesions (P>0.05). Age-specific differences were noted in location of neoplastic lesions in the lower genital tract and time to diagnosis of uVIN. However, the clinical features of uVIN lesions were heterogeneous and non-age specific.


Prepubertal Environmental Enrichment Prevents Dopamine Dysregulation and Hippocampal Hyperactivity in MAM Schizophrenia Model Rats.
Schizophrenia (SCZ) is a neurodevelopmental disorder with a progressive, prolonged course. Early prevention for SCZ is promising but overall lacks support from preclinical evidence. Previous studies have tested environmental enrichment (EE) in certain models of SCZ and discovered a broadly beneficial effect in preventing behavioral abnormalities relevant, yet not specific, to the disorder. Nonetheless, whether EE can prevent dopamine (DA) dysregulation, a hallmark of psychosis and SCZ, had not been tested. Using the MAM (methylazoxymethanol acetate) rat model of schizophrenia and saline-treated control animals, we investigated the long-term electrophysiological effects of prepubertal (postnatal day 21-40) EE on DA neurons, pyramidal neurons in the ventral hippocampus, and projection neurons in the basolateral amygdala. Anxiety-related behaviors in the elevated plus maze and locomotor responses to amphetamine were also analyzed. Prepubertal EE prevented the increased population activity of DA neurons and the associated increase in locomotor response to amphetamine. Prepubertal EE also prevented hyperactivity in the ventral hippocampus but did not prevent hyperactivity in the basolateral amygdala. Anxiety-like behaviors in MAM rats were not ameliorated by prepubertal exposure to EE. Twenty-day prepubertal EE is sufficient to prevent DA hyperresponsivity in the MAM model, measured by electrophysiological recordings and locomotor response to amphetamine. This effect is potentially mediated by normalizing excessive firing in the ventral hippocampus without affecting anxiety-like behaviors and basolateral amygdala firing. This study identified EE as a useful preventative approach that may protect against the pathophysiological development of SCZ.


Unsupervised grammar induction of clinical report sublanguage.
Clinical reports are written using a subset of natural language while employing many domain-specific terms; such a language is also known as a sublanguage for a scientific or a technical domain. Different genres of clinical reports use different sublaguages, and in addition, different medical facilities use different medical language conventions. This makes supervised training of a parser for clinical sentences very difficult as it would require expensive annotation effort to adapt to every type of clinical text. In this paper, we present an unsupervised method which automatically induces a grammar and a parser for the sublanguage of a given genre of clinical reports from a corpus with no annotations. In order to capture sentence structures specific to clinical domains, the grammar is induced in terms of semantic classes of clinical terms in addition to part-of-speech tags. Our method induces grammar by minimizing the combined encoding cost of the grammar and the corresponding sentence derivations. The probabilities for the productions of the induced grammar are then learned from the unannotated corpus using an instance of the expectation-maximization algorithm. Our experiments show that the induced grammar is able to parse novel sentences. Using a dataset of discharge summary sentences with no annotations, our method obtains 60.5% F-measure for parse-bracketing on sentences of maximum length 10. By varying a parameter, the method can induce a range of grammars, from very specific to very general, and obtains the best performance in between the two extremes.


Construction of recombinant Mip-FlaA dominant epitope vaccine against Legionella pneumophila and evaluation of the immunogenicity and protective immunity.
Legionnaires' disease, a kind of systemic disease with pneumonia as the main manifestation, is caused by Legionella pneumophila (L. pneumophila). In order to prevent the disease, we optimized Mip and FlaA, the virulence factors of L. pneumophila, to design recombinant Mip-FlaA dominant epitope vaccine against the pathogen. Firstly, the coding sequences of mip and flaA were optimized by DNAStar software and Expasy protein analysis system, and then, the tertiary structure and function of recombinant Mip-FlaA were predicted by PHYRE2 Protein Fold Recognition Server. After that, the optimized mip, flaA and mip-flaA were cloned, expressed and purified, and the proteins were used as dominant epitope vaccines to immunize BABL/c mice. Moreover, the IgG titers, histological changes in lung and the level of TNF-α, IFN-γ, IL-6 and IL-1β were detected to reflect the immunogenicity and protective immunity of the vaccines. The results of SDS-PAGE and Western blot proved the recombinant Mip-FlaA was successfully expressed. ELISA results of IgG titers and these cytokines showed Mip-FlaA group was capable to induce the strongest immune response, compared to PBS, Mip and FlaA groups. In addition, histopathology analysis demonstrated the mice immunized with Mip-FlaA showed better immune protection. Therefore, the work indicated that the above-described biological tools were useful in optimization of epitope vaccine. Antigenic characterization and immune protection of recombinant Mip-FlaA would be of great value in understanding the immunopathogenesis of the disease and in developing possible vaccine against the pathogen.


An alternative approach to evaluating, measuring, and comparing domestic and international health institutions: insights from social science theories.
This article introduces the benefits of applying social science theories discussing institutional stasis and change to better measure, explain, and compare elite behavior within health administration and decentralization processes. A new comparative method based on these theories is introduced, as well as methods for collecting and analyzing data. A literature review of health governance, health system governance, and path dependency and institutional change theory was conducted to reveal the limitations of health governance approaches explaining elite behavior. Next, path dependency and institutional change theory was applied to case studies in order to demonstrate their utility in explaining institutional stasis and change. Current approaches to analyzing and comparing elite behavior in the health governance frameworks are limited in their ability to accurately explain the willingness of elites to pursue more efficient institutional and policy designs. Current indicators measuring elite behavior are also too static, failing to account for periodic resistance to change and the conditions for it. By applying path dependency and institutional change theory, the policy community can obtain greater insight into the willingness and thus capacity of institutions to pursue innovations while developing alternative analytic frameworks and databases that better measure and predict this process.


Congenital aneurysms of the deep veins of the lower extremities.
This is a report of our experience with seven children with congenital aneurysms of the deep veins of the lower extremities. All the patients had various clinical features of angiodysplasia. With the use of ascending functional phlebography the patients were divided into two groups: four patients with fusiform aneurysms and three patients with saccular aneurysms. Patients in group 1 had venous reflux and a mild degree of venous insufficiency, which were surgically treated. Three patients with saccular aneurysms (group 2) showed no signs of venous insufficiency and are still being carefully followed. Anatomic and functional assessment of the deep venous system by ascending functional phlebography is essential for planning an appropriate treatment for this rare clinical entity.


The analysis of contact sampling data.
Use of the chi-square statistic for investigating interspecific association has been incorrectly applied to the contact sampling method because of an invalid probability argument. The usual method of calculating expected frequencies leads to a large overestimation and hence bias towards negative association. A correct method of analysis is presented and discussed.


Lipid dependence of diadinoxanthin solubilization and de-epoxidation in artificial membrane systems resembling the lipid composition of the natural thylakoid membrane.
In the present study, the solubility and enzymatic de-epoxidation of diadinoxanthin (Ddx) was investigated in three different artificial membrane systems: (1) Unilamellar liposomes composed of different concentrations of the bilayer forming lipid phosphatidylcholine (PC) and the inverted hexagonal phase (H(II) phase) forming lipid monogalactosyldiacylglycerol (MGDG), (2) liposomes composed of PC and the H(II) phase forming lipid phosphatidylethanolamine (PE), and (3) an artificial membrane system composed of digalactosyldiacylglycerol (DGDG) and MGDG, which resembles the lipid composition of the natural thylakoid membrane. Our results show that Ddx de-epoxidation strongly depends on the concentration of the inverted hexagonal phase forming lipids MGDG or PE in the liposomes composed of PC or DGDG, thus indicating that the presence of inverted hexagonal structures is essential for Ddx de-epoxidation. The difference observed for the solubilization of Ddx in H(II) phase forming lipids compared with bilayer forming lipids indicates that Ddx is not equally distributed in the liposomes composed of different concentrations of bilayer versus non-bilayer lipids. In artificial membranes with a high percentage of bilayer lipids, a large part of Ddx is located in the membrane bilayer. In membranes composed of equal proportions of bilayer and H(II) phase forming lipids, the majority of the Ddx molecules is located in the inverted hexagonal structures. The significance of the pigment distribution and the three-dimensional structure of the H(II) phase for the de-epoxidation reaction is discussed, and a possible scenario for the lipid dependence of Ddx (and violaxanthin) de-epoxidation in the native thylakoid membrane is proposed.


In vitro and in vivo safety of aqueous extracts of Graptopetalum paraguayense E. Walther.
Graptopetalum paraguayense E. Walther, a widely consumed vegetable in Taiwan, has many biological effects and has been used in folk medicine to alleviate hepatic disorders, exert diuretic effects, and relieve pain and infections. However, little data exist regarding its safety. Two genotoxicity assays were performed: chromosomal aberration of Chinese hamster ovary (CHO-K1 cells) (in vitro) and micronucleus assay in mice (in vivo). Acute oral toxicity and 28-day repeated feeding toxicity tests were performed by oral gavage in Sprague-Dawley (SD) rats. GWE did not increase micronucleus ratios in vivo, and by chromosome aberration assay, GWE was safe up to 1.2mg/ml with regard to clastogenicity. Chromatid breakage was observed at high concentrations (2.5 and 5.0mg/ml) of GWE. GWE had no acute lethal effect at the maximum dose (5g/kg bw) in rats. In the 28-day study, there were no adverse effects on body weight, feed consumption, hematology, blood biochemical parameters, organ weight, or pathology. The acute toxicity study showed that the LD(50) of GWE was greater than the tested dose (up to 1g/kg bw) in SD rats. In the subacute toxicity study, the no observed adverse effect level (NOAEL) of GWE in rats was 1g/kg bw. The in vivo study of mammalian erythrocyte micronuclei confirmed the Ames test results, demonstrating that GWE has no mutagenicity. High doses of GWE require further examination due to its clastogenic potential.


Atenolol and short umbilical cords.
Umbilical cord length may be a function of fetal movement. Agents that cause decreased fetal movement may cause short umbilical cords. This investigation examined the effect of the beta-blocker atenolol on umbilical cord length in rabbits. Fetuses of rabbits treated with atenolol had significantly shorter cords than control animals (p less than or equal to 0.0005). Since short cords are associated with problems in labor, low Apgar scores, and abruption, we recommend careful surveillance of mothers and fetuses who are given beta-blocking agents in the first 30 weeks of pregnancy.


Selective conversion of cellulose to levulinic acid via microwave-assisted synthesis in ionic liquids.
A highly selective approach to produce levulinic acid from cellulose was developed via microwave-assisted synthesis in SO3H-functionalized ionic liquids (SFILs). The effects of reaction conditions and ionic liquid structures on the yield of levulinic acid have been investigated, where the highest yield of 55.0% was obtained. The catalytic activities of SFILs depend on the anions and decrease in the order: HSO4->CH3SO3->H2PO4-, which is in good agreement with their acidity order. The SFILs are efficient catalysts for cellulose conversion into levulinic acid and the subsequent esterification, which facilitates the separation of product and reuse of ionic liquids.


Changes in thymidine kinase activity during differentiation of HL-60 leukemic cells.
Induction of granulocyte maturation in HL-60 leukemic cells by DMSO (1.2%) or RA (1 microM) is accompanied by a 50-60% decrease in cellular thymidine kinase activity. Similarly, the differentiation of HL-60 cells into monocyte-macrophage phenotype by the addition of PMA is paralleled by a 60-80% suppression of thymidine kinase specific activity. Measurement of thymidine kinase kinetic parameters shows that the Vmax decreases from 0.7 pmol/min in control cells to 0.43 pmol/min in PMA-treated cells and to 0.38 pmol/min in RA-treated cells. The Km of the enzyme is not affected by either inducing agent and remains at 2.1 microM. Studies with PMA analogs suggest that thymidine kinase modulation is coupled to HL-60 differentiation.


Sperm release from oviduct epithelial binding is controlled hormonally by peri-ovulatory graafian follicles.
To avoid inappropriate conclusions being drawn from the extensive use of in vitro preparations of sperm-oviduct epithelial binding, it is recalled that events in the genital tract of mammals are regulated by the gonads, primarily by their changing secretion of steroid hormones. Key observations from in vivo models are used to emphasise the dynamic interactions between viable sperm cells and the caudal (distal) portion of the oviduct isthmus, the site of the functional sperm reservoir. These include (1) pre-ovulatory arrest and epithelial binding of intact sperm cells and thereby suppression of completion of capacitation, (2) peri-ovulatory activation and release from binding of discrete sub-populations of competent spermatozoa, and (3) post-ovulatory liberation of large numbers of spermatozoa. These observations underline the influence of endocrine regulation of sperm binding and release by peri-ovulatory Graafian follicles, a point brought out by the enhanced sperm release prompted by diverse treatments with solutions of progesterone. In the light of this evidence, the suitability of in vitro preparations for clarifying physiological events should be questioned, especially if myosalpingeal catecholamines diffusing out of the autonomic nervous system contribute to sperm activation and/or release. None of this is to infer that sperm cells themselves are without influence on their epithelial binding reaction(s). Nor is it to suggest that in vitro models of sperm-oviduct binding are without relevance to the development of sperm evaluation technologies. However, pre-ovulatory sperm-epithelial binding and a regulated peri-ovulatory release should be seen as vital tactics in the overall strategy of achieving successful monospermic fertilisation.


Behavioral interaction of adenosine and methylxanthines on central purinergic systems.
Mice implanted with chronic indwelling cannulae were injected in the lateral cerebral ventricle with adenosine (ADO); an adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA); a potent adenosine uptake inhibitor, papaverine (PAP); and a methylxanthine, 3-isobutyl-1-methylxanthine (IBMX). All drugs produced dose-related decreases in spontaneous locomotor activity and the order of potency for locomotor depression was: NECA much greater than IBMX greater than ADO, PAP. Further, the behavioral interaction of i.p. injections of caffeine with drug-induced locomotor depression was examined at a dose of caffeine which had no effect on locomotor activity when given alone. Caffeine antagonized the depressant effects of NECA at all doses. However, doses of IBMX producing only behavioral depression, in combination with caffeine, elicited pronounced behavioral stimulation. At higher doses of ADO and PAP, caffeine antagonized their depressant effects whereas at the lower doses of ADO and PAP in combination with caffeine there was behavioral stimulation. These results suggest there is a complex behavioral interaction between methylxanthines and central purinergic systems.


Genome-wide comparative chromosome maps of Arvicola amphibius, Dicrostonyx torquatus, and Myodes rutilus.
The subfamily Arvicolinae consists of a great number of species with highly diversified karyotypes. In spite of the wide use of arvicolines in biological and medicine studies, the data on their karyotype structures are limited. Here, we made a set of painting probes from flow-sorted chromosomes of a male Palearctic collared lemming (Dicrostonyx torquatus, DTO). Together with the sets of painting probes made previously from the field vole (Microtus agrestis, MAG) and golden hamster (Mesocricetus auratus, MAU), we carried out a reciprocal chromosome painting between these three species. The three sets of probes were further hybridized onto the chromosomes of the Eurasian water vole (Arvicola amphibius) and northern red-backed vole (Myodes rutilus). We defined the diploid chromosome number in D. torquatus karyotype as 2n = 45 + Bs and showed that the system of sex chromosomes is X1X2Y1. The probes developed here provide a genomic tool-kit, which will help to investigate the evolutionary biology of the Arvicolinae rodents. Our results show that the syntenic association MAG1/17 is present not only in Arvicolinae but also in some species of Cricetinae; and thus, should not be considered as a cytogenetic signature for Arvicolinae. Although cytogenetic signature markers for the genera have not yet been found, our data provides insight into the likely ancestral karyotype of Arvicolinae. We conclude that the karyotypes of modern voles could have evolved from a common ancestral arvicoline karyotype (AAK) with 2n = 56 mainly by centric fusions and fissions.


Retinoic acid modulates prolactin receptor expression and prolactin-induced STAT-5 activation in breast cancer cells in vitro.
Two recent papers demonstrate that prolactin plays an important role in the induction and progression of mammary tumours. Retinoids have been shown to be potent inhibitors of breast carcinogenesis. We studied expression of prolactin receptor mRNA in human breast cancer cell lines MCF-7, SKBR-3, T47D and BT-20 treated with and without retinoids using Northern blot and a quantitative polymerase chain reaction (PCR) method. In all cell lines, all-trans- and 9-cis-retinoic acid, as well as the retinoic acid receptor gamma (RAR-gamma) selective agonists CD2325 and CD437 (1 microM), were able to down-regulate prolactin receptor. After 1 h, a significant reduction was detectable and maximal effect was achieved after 24 h of treatment. Pretreatment with retinoic acid also reduced the prolactin-/prolactin receptor-dependent signal transduction and activation of transcription 5 (STAT-5) activation in T47D cells. Cycloheximide failed to abrogate the retinoic acid-induced decline in prolactin receptor mRNA levels, indicating that this effect was not dependent upon continuing protein synthesis. Similarly, no change in the stability of prolactin receptor mRNA was observed during 12 h of retinoic acid treatment. In conclusion, our results demonstrate that retinoids are able to inhibit the expression of prolactin receptor message, which encodes an important growth factor receptor in breast cancer cells. This action could be responsible for the anti-tumour effects of retinoids.


Synthesis, structure elucidation, DNA-PK, PI3K, anti-platelet and anti-bacteria activity of linear 5, 6, and 10-substituted-2-morpholino-chromen-oxazine-dione and angular 3, 4, 6-substituted-8-morpholino-chromen-oxazine-2,10-dione.
Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3-benzoxazine rings is not well documented and there is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds 14a-i and angular compounds 16a-e were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic 10-13 with freshly prepared Ph3P(SCN)2. 2-Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted-chromen-oxazine-2,10-dione 15a-f and 17 were synthesised from the reaction of the corresponding oxazines 14 and 16 with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound 13b showed moderate PI3Kγ (IC50 = 5.56 μM) and PI3Kα (IC50 = 14.7 μM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione 17a showed isoform selective PI3Kδ activity with IC50 = 5.08 μM with non-DNA-PK ≥ 100 μM. Consequently compound 17a can be considered as a selective PI3Kδ inhibitor with non-DNA-PK at compound concentrations ≥100 μM.


Evidence that the bZIP domains of the Jun transcription factor bind to DNA as monomers prior to folding and homodimerization.
The Jun oncoprotein belongs to the AP1 family of transcription factors that is collectively engaged in diverse cellular processes by virtue of their ability to bind to the promoters of a wide spectrum of genes in a DNA sequence-dependent manner. Here, using isothermal titration calorimetry, we report detailed thermodynamics of the binding of bZIP domain of Jun to synthetic dsDNA oligos containing the TRE and CRE consensus promoter elements. Our data suggest that binding of Jun to both sites occurs with indistinguishable affinities but with distinct thermodynamic signatures comprised of favorable enthalpic contributions accompanied by entropic penalty at physiological temperatures. Furthermore, anomalously large negative heat capacity changes observed provoke a model in which Jun loads onto DNA as unfolded monomers coupled with subsequent folding and homodimerization upon association. Taken together, our data provide novel insights into the energetics of a key protein-DNA interaction pertinent to cellular signaling and cancer. Our study underscores the notion that the folding and dimerization of transcription factors upon association with DNA may be a more general mechanism employed in protein-DNA interactions and that the conventional school of thought may need to be re-evaluated.


Risk factors associated with a school-related outbreak of serogroup C meningococcal disease.
An outbreak of Neisseria meningitidis sero-group C disease occurred in four eighth grade students and in a younger sibling of another eighth grade student attending an intermediate school (seventh and eighth grades) in Santa Clara County, CA. Four cases had onset within 3 days in January, 1989, with the fifth case occurring approximately 10 days later. A case-control study was performed to determine risk factors associated with serogroup C meningococcal infection (disease or carriage) in this eighth grade class. Students were more likely to be infected if they had had a preceding viral-like respiratory illness characterized by fever (odds ratio (OR) 5.3, P = 0.03) or cough (OR 5.1, P = 0.048). A ski trip (OR 6.3, P = 0.01) and a poster-making session for a school dance (OR 3.7, P = 0.08) were identified as possible settings for a common exposure. Spending time with two specific students during lunchtime or outside of school was associated with an increased risk of infection (OR 7.0, P = 0.054; OR 5.8, P = 0.04).


Neurologic disorders of neonatal foals.
Neurologic examination of the neonatal foal is quite different from the process used to examine older foals and adult horses. Abnormal neurologic signs are best appreciated in the context of a detailed knowledge of general neonatal medicine and awareness of nor-mal foal behavior and milestones of development. A systematic approach to neurologic examination is provided. The results of such examination are used to localize a lesion or lesions in the nervous system. Descriptions and treatment strategies are given for most common and important neonatal neurologic diseases.


[Blount's disease in its infantile form. Apropos of 16 cases].
The authors report 16 cases of tibia vara in children. They insist on: the difficult diagnosis of that pathology at the beginning, the early surgery (simple osteotomy) give a complete restoration, in neglected cases they recommend to elevate the medial condyle of the tibia with bone grafting, a tibial osteotomy and an epiphysiodesis of the lateral tibial condyle and proximal fibula.


Foliar uptake and metal(loid) bioaccessibility in vegetables exposed to particulate matter.
At the global scale, high concentrations of particulate matter (PM) enriched with metal(loid)s are currently observed in the atmosphere of urban areas. Foliar lead uptake was demonstrated for vegetables exposed to airborne PM. Our main objective here was to highlight the health risk associated with the consumption of vegetables exposed to foliar deposits of PM enriched with the various metal(loid)s frequently observed in the atmosphere of urban areas (Cd, Sb, Zn and Pb). Leaves of mature cabbage and spinach were exposed to manufactured mono-metallic oxide particles (CdO, Sb2O3 and ZnO) or to complex process PM mainly enriched with lead. Total and bioaccessible metal(loid) concentrations were then measured for polluted vegetables and the various PM used as sources. Finally, scanning electronic microscopy coupled with energy dispersive X-ray microanalysis was used to study PM-phyllosphere interactions. High quantities of Cd, Sb, Zn and Pb were taken up by the plant leaves. These levels depended on both the plant species and nature of the PM, highlighting the interest of acquiring data for different plants and sources of exposure in order to better identify and manage health risks. A maximum of 2% of the leaf surfaces were covered with the PM. However, particles appeared to be enriched in stomatal openings, with up to 12% of their area occupied. Metal(loid) bioaccessibility was significantly higher for vegetables compared to PM sources, certainly due to chemical speciation changes. Taken together, these results confirm the importance of taking atmospheric PM into account when assessing the health risks associated with ingestion of vegetables grown in urban vegetable crops or kitchen gardens.


Comparison of technology-based cooperative learning with technology-based individual learning in enhancing fundamental nursing proficiency.
The aim of nursing education is to prepare students with critical thinking, high interests in profession and high proficiency in patient care. Cooperative learning promotes team work and encourages knowledge building upon discussion. It has been viewed as one of the most powerful learning methods. Technology has been considered an influential tool in teaching and learning. It assists students in gathering more information to solve the problems and master skills better. The purpose of this study was to compare the effect of technology-based cooperative learning with technology-based individual learning in nursing students' critical thinking in catheterization knowledge gaining, error discovering, skill acquisitions, and overall scores. This study used a pretest-posttest experimental design. Ninety-eight students were assigned randomly to one of two groups. Questionnaires and tests were collected at baseline and after completion of intervention. The results of this study showed that there was no significant difference in related catheterization skill performance. However, the remaining variables differed greatly between the two groups. CONCLUSIONS AND APPLICATIONS: This study's findings guide the researchers and instructors to use technology-based cooperative learning more appropriately. Future research should address the design of the course module and the availability of mobile devices to reach student-centered and learn on the move goals.


The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy.
The intravenous anesthetics which are commonly used for electroconvulsive therapy (ECT) possess dose-dependent anticonvulsant properties. Since the clinical efficacy of ECT depends on the induction of a seizure of adequate duration, it is important to determine the optimal dose of the hypnotic for use during ECT. We compared the duration of seizure activity and cognitive recovery profiles after different doses of methohexital, propofol, and etomidate administered to induce hypnosis prior to ECT. Ten outpatients with major depressive disorders receiving maintenance ECT participated in this prospective, randomized, cross-over study. Patients were premedicated with glycopyrrolate, 0.2 mg intravenously (i.v.), and labetalol, 20-30 mg i.v., and hypnosis was induced with an i.v. bolus injection of methohexital or propofol (0.75, 1.0, and 1.5 mg/kg), or etomidate (0.15, 0.2, and 0.3 mg/kg), administered over 10-15 s. Adequate muscle paralysis was achieved with succinylcholine, 1.0-1.4 mg/kg i.v. Each patient's seizure threshold was determined prior to enrollment in the study and the electrical stimulus variables were kept constant throughout the study period. After delivery of a bilateral electrical stimulus, the duration of the resulting electroencephalographic (EEG) and motor seizures were recorded. A total of 90 ECT treatments were evaluated. The durations of EEG and motor seizures were longest after etomidate and shortest after propofol. There were no significant dose-related differences in motor and EEG seizure durations (means +/- SD) after the low, intermediate, and high doses of etomidate of 44 +/- 11 and 77 +/- 19, 43 +/- 10 and 76 +/- 34, 42 +/- 16 and 78 +/- 56 s, respectively. Conversely, both methohexital and propofol, 0.75, 1.0, and 1.5 mg/kg, produced dose-dependent decreases in motor and EEG seizure durations (i.e., 37 +/- 10 and 58 +/- 12, 36 +/- 8 and 62 +/- 24, and 29 +/- 13 and 48 +/- 20 for methohexital; 34 +/- 15 and 56 +/- 29, 31 +/- 8 and 50 +/- 17, and 20 +/- 6 and 33 +/- 12 for propofol, respectively). The awakening times were similar, regardless of the hypnotic or dose administered.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolation and enrichment of Stro-1 immunoselected mesenchymal stem cells from adult human bone marrow.
The availability of mesenchymal stem cells (MSCs) or skeletal stem cells (SSCs) is vital to many of the tissue engineering strategies currently being developed for repairing bone and cartilage. One difficulty with using this cell population is that SSCs represent only a small fraction of the cells available from an individual patient's bone marrow sample, typically less than 1 in 10,000. Therefore, methods have been devised to enrich the proportion of MSCs obtained from a bone marrow sample using hybridoma cell lines to generate antibodies to cell surface antigens specific for MSCs. Stro-1 is the most widely targeted of these cell surface antigens. The protocol described overleaf is used to isolate and enrich the Stro-1 positive fraction of cells from a bone marrow aspirate to provide a sample enriched for MSCs for use in both in vitro and in vivo studies.


Outcomes of the UAMS summer undergraduate research program to increase diversity in research and health professions.
The University of Arkansas for Medical Sciences (UAMS) Summer Undergraduate Research Program (SURP) aims to increase diversity in research and health-related careers. The SURP provides underrepresented minority (URM) and disadvantaged students with research, mentoring, and networking experiences; real-life surgical observations; and simulated cardiovascular demonstrations. A postprogram survey was developed to assess program outcomes and explore ways of improving the program to stimulate URM and disadvantaged students' interest in research and health-related careers. This is a report of those postprogram survey findings. Using a survey research design, an online survey was emailed to participants (n = 88). Data were collected for 6 weeks beginning March 2020. There were 37 multiple-choice and open-ended questions regarding education, career choices, and program experiences. Responses were downloaded to statistical software for analyses. Quantitative data were analyzed using descriptive statistics. Major themes were identified for qualitative data. Responses were received from 44.3% (n = 39) of former SURP participants. Overall, 59% stated that the SURP influenced their career goals. When asked about mentor-mentee relationships, 69.3% responded that their interactions were excellent or good; 61.5% maintained contact with their mentor after the SURP. Finally, 79% indicated their SURP experience was excellent or good, and 84.6% would recommend the SURP to others. The SURP has been successful at providing URM and disadvantaged students with positive research experiences and long-term mentor-mentee relationships and has influenced educational and/or career goals. Programs that expose URM and disadvantaged students to basic, clinical, and/or translational research are beneficial for stimulating interest in research and health-related careers.NEW & NOTEWORTHY Mentor-mentee relationships were extremely beneficial as many of the former participants maintained contact with their summer mentor after the program ended. This assessment also revealed that exposing underrepresented and minority students to research has a long-lasting effect on career and educational goals.


Comparison of condylar displacement after sagittal split ramus osteotomy depending on the glenoid fossa depth.
This study aimed to evaluate the relationship between postoperative condylar displacement (PCD) after sagittal split ramus osteotomy (SSRO) and the glenoid fossa depth. A total of 29 patients who underwent computed tomography (CT) before surgery (T0), immediately after (T1), and 6 months after (T2) surgery were studied. The fossa depth was measured, and the amount of displaced condylar center and axis were evaluated on CT at T0, T1, and T2 using three-dimensional analysis software. PCD and the fossa depth relationship was investigated by Pearson's correlation analysis. The fossa depth varied from 3.9 mm to 12.0 mm, and the mean value was 8.15 ± 1.60 mm. The condylar center was displaced by 1.12 ± 0.66 mm at T1 compared with it at T0. The amount of displaced condylar center negatively correlated with the fossa depth (r = -0.424, p = 0.001). The displacement of the condylar center between T0 and T2 was 0.85 ± 0.51 mm. The amount of condylar center displacement between T0 and T1 showed a positive correlation with it between T0 and T2 (r = 0.481, p < 0.001). In conclusion, more attention is needed in patients with small fossa depth during condylar repositioning after SSRO and postoperative management to minimize complications.


Beyond the particular case of circuits with geometrically distributed components for approximation of fractional order models: Application to a new class of model for power law type long memory behaviour modelling.
In the literature, fractional models are commonly approximated by transfer functions with a geometric distribution of poles and zeros, or equivalently, using electrical Foster or Cauer type networks with components whose values also meet geometric distributions. This paper first shows that this geometric distribution is only a particular distribution case and that many other distributions (an infinity) are in fact possible. From the networks obtained, a class of partial differential equations (heat equation with a spatially variable coefficient) is then deduced. This class of equations is thus another tool for power law type long memory behaviour modelling, that solves the drawback inherent in fractional heat equations that was proposed to model anomalous diffusion phenomena.


BOLD fMRI Correlation Reflects Frequency-Specific Neuronal Correlation.
The brain-wide correlation of hemodynamic signals as measured with BOLD fMRI is widely studied as a proxy for integrative brain processes. However, the relationship between hemodynamic correlation structure and neuronal correlation structure remains elusive. We investigated this relation using BOLD fMRI and spatially co-registered, source-localized MEG in resting humans. We found that across the entire cortex BOLD correlation reflected the co-variation of frequency-specific neuronal activity. Resolving the relation between electrophysiological and hemodynamic correlation structures locally in cortico-cortical connection space, we found that this relation was subject specific and even persisted on the centimeter scale. At first sight, this relation was strongest in the alpha to beta frequency range (8-32 Hz). However, correcting for differences in signal-to-noise ratios across electrophysiological frequencies, we found that the relation extended over a broad frequency range from 2 to 128 Hz. Moreover, we found that the frequency with the tightest link to BOLD correlation varied across cortico-cortical space. For every cortico-cortical connection, we show which specific correlated oscillations were most related to BOLD correlations. Our work provides direct evidence for the neuronal origin of BOLD correlation structure. Moreover, our work suggests that, across the brain, BOLD correlation reflects correlation of different types of neuronal network processes and that frequency-specific electrophysiological correlation provides information about large-scale neuronal interactions complementary to BOLD fMRI.


Stimulation of ketogénesis after glycogen depletion by nicotinic acid in perfused rat liver.
Treatment with nicotinic acid produced an enhancement of ketone bodies production from endogenous, substrates, either oleate or octanotate. The enhancement was accounted for by an increase of acetoacetate synthesis. These results suggest that the increase of acetoacetate production may be due to the enhancement of extramitochondrial ketogenesis as a consequence of the inhibition of lipogenesis.


Repeated oxytocin treatment during abstinence inhibited context- or restraint stress-induced reinstatement of methamphetamine-conditioned place preference and promoted adult hippocampal neurogenesis in mice.
Propensity to relapse, even after long-term abstinence, is a crucial feature of methamphetamine (METH) abuse. We and other laboratories have reported that acute treatment of oxytocin (OXT), a hormone and neuropeptide, could inhibit reinstatement of METH seeking in animal studies. However, the effects of repeated OXT treatment on METH reinstatement as well as underlying mechanisms are still unclear. In the present study, the effects of repeated OXT treatment during abstinence on context- or restraint stress-induced reinstatement were investigated using the mice conditioned place preference (CPP) paradigm. After three intermittent injections of METH (2 mg/kg, i.p.) to induce CPP, mice received a daily bilateral intra-hippocampus injection of OXT (0.625, 1.25 or 2.5 μg) for 8 consecutive days before the context- or restraint stress-induced reinstatement test. Meanwhile, adult hippocampal neurogenesis (AHN) level was detected using immunostaining. To further clarify the role of AHN underlying OXT's effects on METH-CPP reinstatement, temozolomide (TMZ, 25 mg/kg, i.p.) was employed to deplete AHN prior to OXT treatment. The data showed that repeated OXT treatment (1.25 and 2.5 μg, intra-hippocampus) significantly inhibited both context- and restraint stress-induced METH-CPP reinstatement and concomitantly promoted AHN in a dose-dependent manner. Notably, TMZ pre-treatment markedly abolished all the above-mentioned effects of OXT, suggesting that AHN was closely involved in OXT's inhibition on reinstatement induced by both triggers. Taken together, the present study indicated that repeated OXT treatment during abstinence could inhibit both context- and restraint stress-induced METH-CPP reinstatement possibly by promoting AHN in mice, which provided a better understanding for OXT's beneficial effects on METH addiction.


Theoretical evaluation of flotation performance of carboxyl hydroxamic acids with different number of polar groups on the surfaces of diaspore (010) and kaolinite (001).
The adsorption behaviors of three carboxyl hydroxamic acids on diaspore (010) and kaolinite (001) have been studied by density functional theory (DFT) and molecular dynamics (MD) method. The results indicated that carboxyl hydroxamic acids could adsorb on diaspore surface by ionic bonds and hydrogen bonds, and adsorb on kaolinite surface by hydrogen bonds. The models of carboxyl hydroxamic acids adsorbed on diaspore and kaolinite surfaces are proposed.


A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome.
To investigate whether physical trauma may precipitate the onset of fibromyalgia syndrome (FMS). A case-control study was carried out to compare fibromyalgia out-patients with controls attending non-rheumatology out-patient clinics. One hundred and thirty-six FMS patients and 152 age- and sex-matched controls completed a postal questionnaire about any physical trauma in the 6 months before the onset of their symptoms. Fifty-three (39%) FMS patients reported significant physical trauma in the 6 months before the onset of their disease, compared with only 36 (24%) of controls (P<0.007). There was no significant difference between FMS patients who had a history of physical trauma and those who did not have physical trauma with regard to age, sex, disease duration, employment status and whether their job at onset was manual. Physical trauma in the preceding 6 months is significantly associated with the onset of FMS.


Surgery in Acute Metastatic Spinal Cord Compression: Timing and Functional Outcome.
Background: Patients with metastatic spinal cord compression (MSCC) may experience long-term functional impairment. It has been established that surgical decompression improves neurological outcomes, but the effect of early surgery remains uncertain. Our objective was to evaluate the impact of early versus late surgery for acute MSCC due to spinal metastases (SM). Methods: We retrospectively reviewed a consecutive cohort of all patients undergoing surgery for SMs at our institution. We determined the prevalence of acute MSCC; the time between acute neurological deterioration as well as between admission and surgery (standard procedure: decompression and instrumentation); and neurological impairment graded by the ASIA scale upon presentation and discharge. Results: We screened 693 patients with surgery for spinal metastasis; 140 patients (21.7%) had acute MSCC, defined as neurological impairment corresponding to ASIA grade D or lower, acquired within 72 h before admission. Non-MSCC patients had surgery for SM-related cauda equina syndrome, radiculopathy and/or spinal instability. Most common locations of the SM in acute MSCC were the thoracic (77.9%) and cervical (10.7%) spine. Per standard of care, acute MSCC patients underwent surgery including decompression and instrumentation, and the median time from admission to surgery was 16 h (interquartile range 10-22 h). Within the group of patients with acute MSCC, those who underwent early surgery (i.e., before the median 16 h) had a significantly higher rate of ASIA improvement by at least one grade at discharge (26.5%) compared to those who had late surgery after 16 h (10.1%; p = 0.024). Except for a significantly higher sepsis rate in the late surgery group, complication rates did not differ between the late and early surgery subgroups. Conclusions: We report data on the largest cohort of patients with MSCC to date. Early surgery is pivotal in acute MSCC, substantially increasing the chance for neurological improvement without increasing complication rates. We found no significant impact when surgery was performed later than 24 h after admission. These findings will provide the framework for a much-needed prospective study. Until then, the treatment strategy should entail the earliest possible surgical intervention.


Effects of anorexia on mortality among older adults receiving home care: an observation study.
We describe the prevalence of secondary anorexia in a population of older people living in community and receiving home care. In addition, we examined the relationship between secondary anorexia and mortality. We analyzed data from a large collaborative observational study group, the Italian Silver Network Home Care project, that collected data on patients admitted to home care programs. A total of twelve Home Health Agencies participated in such project evaluating the implementation of the Minimum Data Set for Home Care (MDS-HC) instrument. A total of 2757 patients were enrolled in the present study. The main outcome measures were the prevalence of anorexia, weight loss and survival. More than 25% (744 subjects) of the study sample suffered from anorexia. During a mean follow-up of 10 months from initial MDS-HC assessment, 468 patients (17%) died. There was uneven distribution of the risk. After adjusting for age, gender and for all other possible risk factors for death (living alone, physical and cognitive disability, behavior problems, urinary incontinence, pressure ulcer, hearing impairment, congestive heart failure, hypertension, depression, diabetes, renal failure, cancer), subjects with anorexia were more likely to die relative to patients without anorexia (RR, 1.83; 95% CI 1.45-2.31). Even though the risk of mortality was higher among subjects suffering from anorexia and weight loss, the anorexia per se was associated with higher risk compared with subjects without anorexia (RR, 1.45; 95% CI 1.01-2.19). Anorexia is associated with a significant higher risk of all-cause mortality. The present findings support the possibility that anorexia has an independent effect on survival even among old people receiving home care.