Tunable strong exciton-plasmon-exciton coupling in WS2-J-aggregates-plasmonic nanocavity.
A coupling system is proposed to active control of strong exciton-plasmon-exciton coupling, which consists of a silver nanoprism separated from a monolayer WS2 by J-aggregates. The scattering spectrum of the hybrid system calculated by the finite-difference time-domain (FDTD) method is well reproduced by the coupled oscillator model theory. The calculation results show that strong couplings among WS2 excitons, J-aggregate excitons, and localized surface plasmon resonances (LSPRs) are achieved in the hybrid nanostructure, and result in three plexciton branches. We further analyze the exciton-plasmon-exciton coupling behaviors and obtain the weighting efficiencies of the original modes in three plexciton branches. The strong couplings between two different excitons and LSPRs can be active manipulated by tuning the temperature or the concentration of J-aggregates. The proposed systems make up a simple platform for the dynamic control of exciton-plasmon-exciton couplings and have potential applications in optical modulators at the nanoscale.


Imbedding quality improvement into all aspects of nursing practice.
Influencing nurses to accept and implement best practice and continuous quality improvement into everyday nursing activities and to change practice is a significant challenge for any nursing service. Quality improvement is often considered by clinicians to be yet another task to be added to their already busy workloads. This paper describes the attempts of one large metropolitan tertiary teaching hospital to imbed quality improvement and best practice across the spectrum of its nursing service and to foster a culture of quality within clinical practice and documentation. It outlines the methods used by one hospital to enshrine best practice into all nursing activities and to minimize variations in practice throughout the hospital through the use of its nursing clinical information system.


Polyunsaturated Fatty Acid Biosynthesis Involving Δ8 Desaturation and Differential DNA Methylation of FADS2 Regulates Proliferation of Human Peripheral Blood Mononuclear Cells.
Polyunsaturated fatty acids (PUFAs) are important for immune function. Limited evidence indicates that immune cell activation involves endogenous PUFA synthesis, but this has not been characterised. To address this, we measured metabolism of 18:3n-3 in quiescent and activated peripheral blood mononuclear cells (PBMCs), and in Jurkat T cell leukaemia. PBMCs from men and women (n = 34) were incubated with [1-13C]18:3n-3 with or without Concanavalin A (Con. A). 18:3n-3 conversion was undetectable in unstimulated PBMCs, but up-regulated when stimulated. The main products were 20:3n-3 and 20:4n-3, while 18:4n-3 was undetectable, suggesting initial elongation and Δ8 desaturation. PUFA synthesis was 17.4-fold greater in Jurkat cells than PBMCs. The major products of 18:3n-3 conversion in Jurkat cells were 20:4n-3, 20:5n-3, and 22:5n-3. 13C Enrichment of 18:4n-3 and 20:3n-3 suggests parallel initial elongation and Δ6 desaturation. The FADS2 inhibitor SC26196 reduced PBMC, but not Jurkat cell, proliferation suggesting PUFA synthesis is involved in regulating mitosis in PBMCs. Con. A stimulation increased FADS2, FADS1, ELOVL5 and ELOVL4 mRNA expression in PBMCs. A single transcript corresponding to the major isoform of FADS2, FADS20001, was detected in PBMCs and Jurkat cells. PBMC activation induced hypermethylation of a 470bp region in the FADS2 5'-regulatory sequence. This region was hypomethylated in Jurkat cells compared to quiescent PBMCs. These findings show that PUFA synthesis involving initial elongation and Δ8 desaturation is involved in regulating PBMC proliferation and is regulated via transcription possibly by altered DNA methylation. These processes were dysregulated in Jurkat cells. This has implications for understanding the regulation of mitosis in normal and transformed lymphocytes.


Nephrolithiasis in pregnancy.
Although the anatomical and physiological changes of normal pregnancy may predispose to kidney stone formation, it remains an uncommon occurrence. Correct diagnosis is often difficult. Ultrasonography has become the primary radiological diagnostic tool, with a limited excretory urogram only necessary in complicated cases. Nephrolithiasis during pregnancy occurs more frequently during the later stages of gestation, in multiparas, and without a difference in laterality. Conservative management with bed rest, hydration and analgesia can result in spontaneous passage of most stones in gravidas. Past experience of several groups suggests that cystoscopy and/or surgery can usually be done safely when absolutely necessary. Pre-existing stone disease can increase the incidence of maternal urinary tract infections by 10-20%. The most common obstetric complications of stones during gestation is premature labour induced by renal colic. Most drugs normally used to treat stone disease are contraindicated in gestation. Known inhibitors of stone formation are present in gestation and may partially explain why the incidence of stones is not increased in this hypercalciuric state.


Do testosterone levels relate to aggression in elderly men with dementia?
The aim of this study was to determine if testosterone and estrogen levels correlate with aggression in older men with dementia. Plasma total and free testosterone and estrogen levels and scores for behavioral disturbances, in particular aggression, were measured in 50 elderly males who had a diagnosis of dementia. Aggression was analyzed separately from agitation. Pearson correlations were calculated to determine the association between testosterone and estrogen and aggression. Linear regression analyses determined the influence of hormone levels on aggression, controlling for age, medical burden, and dementia severity. Free testosterone levels showed significant positive correlations with measures of aggression. Estrogen levels showed significant negative correlations with measures of aggression.


[Construct a wireless clinical information system on the basis of the original information system].
This article describes how to construct a integrated wireless clinical information system based on the original information system. It is constructed on the basis of the hospital HIS through the middle ware which provides a data-interaction platform for all the existing data and the data which would be added in future for various information management systems. The software system adopts the Web Service technology in information services. The SOAP protocol is applied to the data interaction between the foreground and the background. The mode of the network structure is "Wireless Switchboard + Intelligence antenna". Relying on the wireless network, the handheld data terminal and the barcode, the network information can be extended to the patient bedsides and the mobile medical personnels.


A Statistical Description of Plant Shoot Architecture.
Plant architectures can be characterized statistically by their spatial density function, which specifies the probability of finding a branch at each location in the territory occupied by a plant. Using high-precision 3D scanning, we analyzed 557 plant shoot architectures, representing three species, grown across three to five environmental conditions, and through 20-30 developmental time points. We found two elegant properties in the spatial density functions of these architectures: all functions could be nearly modified in one direction without affecting the density in orthogonal directions (called "separability"), and all functions shared the same underlying shape, aside from stretching and compression (called "self-similarity"). Surprisingly, despite their striking visual diversity, we discovered that all architectures could be described as variations on a single underlying function: a Gaussian density function truncated at roughly two SDs. We also observed systematic variation in the spatial density functions across species, growth conditions, and time, which suggests functional specialization despite following the same general design form.


Anterior Maxillary Segmental Distraction Osteogenesis for Treatment of Maxillary Hypoplasia in Patients With Repaired Cleft Palate.
This study is to present experiences of using anterior maxillary segmental distraction osteogenesis (AMSDO) with internal distractors for treatment of maxillary hypoplasia in patients with repaired cleft palate. A total of 42 patients of maxillary hypoplasia with repaired cleft palate were included in this study, and underwent AMSDO. Cephalometric analysis and speech quality assessments were performed to evaluate the changes after AMSDO and its long-term effect on stability. All cases had successfully accomplished AMSDO. The average SNA (°), NA-FH (°), ANS-PNS (millimeter), and Overjet (millimeter) have change to 80.41°, 89.51°, 55.64 mm, and 2.52 mm, respectively (P < 0.01). Maxillary advancement has reached 13.80 mm on average (ranging from 10.0 mm to 20.0 mm). Speech quality assessment demonstrated that nasal resonance, speech articulation, nasal emission, intelligibility, and velopharyngeal function did not get worse after AMSDO. AMSDO has unique advantages as follows: can effectively correct maxillary hypoplasia in patients with repaired cleft palate; can create a space for postoperative orthodontic treatment to solve the crowding teeth situation; the postoperative velopharyngeal function and speech quality show no significant change. The results shown AMSDO is an effective and appropriate treanment for curing maxillary hypoplasia in patients with repaired cleft palate.


Revisiting the role of hematopoietic stem cell transplantation in chronic lymphocytic leukemia.
Since the advent of hematopoietic stem cell transplantation more than 40 years ago, numerous methods of transplantation have been developed, modified and improved upon. Although hematopoietic stem cell transplantation has been used in a variety of malignant diseases since then, its use in the treatment of chronic lymphocytic leukemia has recently started to gain interest. Patients with chronic lymphocytic leukemia are generally elderly, and because of its relatively benign course, they were not considered suitable candidates for hematopoietic stem cell transplantation. Nonetheless, there have been marked improvements in transplantation techniques, including better conditioning regimens that have decreased treatment-related morbidity and mortality. In this article, the authors review the most recent data on hematopoietic stem cell transplantation in chronic lymphocytic leukemia as well as the change in risk stratification based on newer prognostic factors and its impact on treatment decisions in chronic lymphocytic leukemia.


Nesiritide in pulmonary hypertension.
We present the case of a patient with severe symptomatic pulmonary hypertension due to rheumatic mitral valve disease who was refractory to traditional therapies, including prostacyclin. Therapy with continuous nesiritide infusion resulted in significant and sustained decreases in pulmonary vascular resistance, an improvement in renal function, and the maintenance of euvolemia.


Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.
Cognitive disorders are mental health disorders that can affect cognitive ability. Surgery and anesthesia have been proposed to increase the incidence of cognitive dysfunction, including declines in memory, learning, attention and executive function. Tau protein is a microtubule-associated protein located in the axons of neurons and is important for microtubule assembly and stability; its biological function is mainly regulated by phosphorylation. Phosphorylated tau protein has been associated with cognitive dysfunction mediated by disrupting the stability of the microtubule structure. There is an increasing consensus that anesthetic drugs can cause cognitive impairment. Herein, we reviewed the latest literature and compared the relationship between tau protein and cognitive impairment caused by different anesthetics. Our results substantiated that tau protein phosphorylation is essential in cognitive dysfunction caused by anesthetic drugs, and the possible mechanism can be summarized as "anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment".


Laser Doppler imaging through tissues phantoms by using self-mixing interferometry with a laser diode.
Laser Doppler imaging has been widely used for the evaluation of cutaneous blood flow. We report on how the self-mixing interferometry configuration with a laser diode is explored for what is believed to be the first time to generate flow maps. The experiment was carried out by sensing the laser intensity power spectrum at each pixel as the laser was scanned over a model that mimics the properties of skin and circulating blood.


Readmission and mortality in patients discharged with a diagnosis of medical observation and evaluation (Z03*-codes) from an acute admission unit in Denmark: a prospective cohort study.
We assessed the 30-day risk of readmission and mortality among patients receiving an International Classification of Diseases 10th edition diagnosis of medical observation and evaluation (Z03*) following admission to an acute medical admission unit (AMAU), stratified on any further specification of diagnosis during hospital stay. We used Central Denmark's (Midt)-Electronic Patient Journal to identify patients with a Z03*-diagnosis among patients admitted to the AMAU, Aarhus University Hospital Nørrebrogade from April 2012 to March 2013, and noted any specification of diagnosis. Patients were followed from hospital discharge until death, emigration, or completion of 30 days follow-up. Of 409 patients with an initial Z03* diagnosis at the AMAU, 55% (n = 226) received a more specific discharge diagnosis after transferral to other departments. Among patients discharged to home with a Z03*-diagnosis, 30% were readmitted within 30 days, while the corresponding figure was 23% for patients receiving a specific diagnosis (p = 0.06). In contrast, corresponding figures for 30-day mortality were 3% for Z03*-diagnosed patients and 10% for those who obtained a specific diagnosis (p = 0.003). Patients diagnosed with Z03* at hospital discharge have a substantially lower 30-day mortality, but a higher readmission-rate, compared to patients who obtain a specific diagnosis during the entire hospital stay.


Enantioselective Construction of Tertiary C-O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols.
An efficient method for the enantioselective construction of tertiary C-O bond via asymmetric allylic substitution of racemic vinylethylene carbonates with water and alcohols has been developed. Under the cooperative catalysis system of an in situ generated chiral palladium complex and boron reagent in mild conditions, the process allowed rapid access to valuable tertiary alcohols and ethers in high yields with complete regioselectivities and high enantioselectivities. This protocol represented the first example of direct enantioselective formation of a tertiary C-O bond with water as an oxygen donor. The synthetic utilities of the process have been demonstrated by the elaboration of the products into key intermediates of biologically relevant agents, and chiral tertiary cyclic ethers could also be provided through the sequential reactions of the allylic etherification and ring-closing metathesis.


Comparison of the Peripheral Reactive Hyperemia Index with Myocardial Perfusion Reserve by 82Rb PET/CT in HIV-Infected Patients.
After the introduction of antiretroviral therapy (ART) the life expectancy of patients infected with human immunodeficiency virus (HIV) is now approaching that of the general population and the importance of non-AIDS co-morbidities is increasing. Specifically, the risk of coronary artery disease (CAD) seems to be higher in HIV-infected patients and an accurate risk prediction of CAD is of high importance for optimal long term treatment. In this study, we assessed the correlation of the endoPAT, which is an office-based CVD screening tool with the myocardial perfusion reserve by 82-rubidium PET/CT. We measured the reactive hyperemia index, which is a measure of the endothelial responsiveness, by the use of an endoPAT device (Itamar Medical, Caesarea, Israel) in 48 ART treated HIV-infected patients with high CD 4 cell counts and viral suppression (HIV-RNA < 20 copies/mL), who had previously undergone measurement of the myocardial perfusion reserve by 82-rubidium PET/CT for study purposes. We found an inverse correlation between the reactive hyperemia index and the myocardial perfusion reserve which most likely indicates different vascular physiology. This study did not find evidence to suggest the immediate implementation of the reactive hyperemia index as a screening tool for early coronary artery disease in well-treated HIV-infected patients pending further validation in larger prospective studies.


Elucidating the initial dynamics of electron photodetachment from atoms in liquids using variably-time-delayed resonant multiphoton ionization.
We study the photodetachment of electrons from sodium anions in room temperature liquid tetrahydrofuran (THF) using a new type of three-pulse pump-probe spectroscopy. Our experiments use two variably-time-delayed pulses for excitation in what is essentially a resonant 1+1 two-photon ionization: By varying the arrival time of the second excitation pulse, we can directly observe how solvent motions stabilize and trap the excited electron prior to electron detachment. Moreover, by varying the arrival times of the ionization (excitation) and probe pulses, we also can determine the fate of the photoionized electrons and the distance they are ejected from their parent Na atoms. We find that as solvent reorganization proceeds, the second excitation pulse becomes less effective at achieving photoionization, and that the solvent motions that stabilize the excited electron following the first excitation pulse occur over a time of approximately 450 fs. We also find that there is no spectroscopic evidence for significant solvent relaxation after detachment of the electron is complete. In combination with the results of previous experiments and molecular dynamics simulations, the data provide new insight into the role of the solvent in solution-phase electron detachment and charge-transfer-to-solvent reactions.


A cellular lineage analysis of the chick limb bud.
The chick limb bud has been used as a model system for studying pattern formation and tissue development for more than 50 years. However, the lineal relationships among the different cell types and the migrational boundaries of individual cells within the limb mesenchyme have not been explored. We have used a retroviral lineage analysis system to track the fate of single limb bud mesenchymal cells at different times in early limb development. We find that progenitor cells labeled at stage 19-22 can give rise to multiple cell types including clones containing cells of all five of the major lateral plate mesoderm-derived tissues (cartilage, perichondrium, tendon, muscle connective tissue, and dermis). There is a bias, however, such that clones are more likely to contain the cell types of spatially adjacent tissues such as cartilage/perichondrium and tendon/muscle connective tissue. It has been recently proposed that distinct proximodistal segments are established early in limb development; however our analysis suggests that there is not a strict barrier to cellular migration along the proximodistal axis in the early stage 19-22 limb buds. Finally, our data indicate the presence of a dorsal/ventral boundary established by stage 16 that is inhibitory to cellular mixing. This boundary is demarcated by the expression of the LIM-homeodomain factor lmx1b.


Effect of phorbol myristate acetate on cultured tumor cells derived from different stages of avian sarcoma virus (ASV)-induced neoplastic growth.
We have investigated the action of the tumor promoter phorbol 12-myristate-13-acetate (PMA) on avian sarcoma cells cultured from avian sarcoma virus (ASV)-induced tumors at various stages of growth and on normal chicken embryo fibroblasts (CEF). We found that exposure to PMA (30 ng/ml) led to decreased expression of the malignant phenotype of avian sarcoma cells which had been derived from progressively-growing or regressing neoplasms. For example, treatment with PMA caused inhibition of growth of cultured avian tumor cells as well as decreased synthesis of DNA and protein. In addition, such treatment resulted in reduced expression of pp60src kinase activity. Direct inoculation of PMA into growing avian sarcomas led to an enhancement of the tumor regression which occurs in this system as a consequence of a strong cell-mediated, anti-tumor immune response.


Quantitative risk assessment of noroviruses in drinking water based on qualitative data in Japan.
Noroviruses are one of the major causes of viral gastroenteritis in Japan. A quantitative risk assessment was conducted to evaluate the health risk caused by this virus in drinking water. A Monte Carlo analysis was used to calculate both the probability of infection and the disease burden using disability-adjusted life years (DALYs). The concentration of noroviruses in tap water was estimated based on qualitative data and a most probable number (MPN) method with an assumed Poisson lognormal distribution. This numerical method was evaluated using two sets of available count data of Cryptosporidium: that collected from a river and that found in tap water in Japan. The dose-response relationships for noroviruses were estimated using assumed ID50 (10 or 100). The annual risk was higher than the US-EPA acceptable level (10(-4) [infection/ person-year]) but around the WHO level (10(-6) [DALYs/ person-year]). As suggested by others, since microbial concentrations are generally lognormally distributed, the arithmetic mean was directly related to the annual risk, suggesting that the arithmetic mean is more useful in representing the degree of microbial contamination than the geometric mean.


Biosynthesis of Oxytetracycline by Streptomyces rimosus: Past, Present and Future Directions in the Development of Tetracycline Antibiotics.
Natural tetracycline (TC) antibiotics were the first major class of therapeutics to earn the distinction of 'broad-spectrum antibiotics' and they have been used since the 1940s against a wide range of both Gram-positive and Gram-negative pathogens, mycoplasmas, intracellular chlamydiae, rickettsiae and protozoan parasites. The second generation of semisynthetic tetracyclines, such as minocycline and doxycycline, with improved antimicrobial potency, were introduced during the 1960s. Despite emerging resistance to TCs erupting during the 1980s, it was not until 2006, more than four decades later, that a third--generation TC, named tigecycline, was launched. In addition, two TC analogues, omadacycline and eravacycline, developed via (semi)synthetic and fully synthetic routes, respectively, are at present under clinical evaluation. Interestingly, despite very productive early work on the isolation of a Streptomyces aureofaciens mutant strain that produced 6-demethyl-7-chlortetracycline, the key intermediate in the production of second- and third-generation TCs, biosynthetic approaches in TC development have not been productive for more than 50 years. Relatively slow and tedious molecular biology approaches for the genetic manipulation of TC-producing actinobacteria, as well as an insufficient understanding of the enzymatic mechanisms involved in TC biosynthesis have significantly contributed to the low success of such biosynthetic engineering efforts. However, new opportunities in TC drug development have arisen thanks to a significant progress in the development of affordable and versatile biosynthetic engineering and synthetic biology approaches, and, importantly, to a much deeper understanding of TC biosynthesis, mostly gained over the last two decades.


Double Sweeping: Highly Effective Sample Preconcentration Using Cationic and Anionic Micelles and Its Application to a Multiple Enzyme Activity Assay.
In conventional microfluidic bioassays, short optical path length and extremely small quantities of analytes sometimes can significantly reduce detectability. Various sample preconcentration techniques have been reported for improving the detectability of bioassays. In the present study, we developed a novel preconcentration technique, "double sweeping", utilizing cationic and anionic micelles simultaneously. Microscopic observations demonstrated that double sweeping enabled a sample solution, which initially filled a capillary, to be focused into an extremely narrow band. Initially, the sample molecules are swept from cathode to anode, or anode to cathode, based on conventional sweeping with an anionic or cationic micellar solution, respectively. Then, the fronts of the swept bands collide with each other in the capillary and halt at the interface between the bands. The sample molecules in the micellar solutions continue to move toward the interface because of the electrophoretic migration of the micelles, which results in further focusing and suppression of the band broadening due to molecular diffusion. We demonstrated that higher preconcentration efficiency was achieved using double sweeping than using conventional sweeping. In addition, double sweeping was successfully incorporated into a multiple enzyme activity assay using an arrayed reagent-release capillary, resulting in simple, rapid, simultaneous, and highly sensitive assays of caspase-3, alkaline phosphatase, and trypsin.


Challenges Associated With Applying Physiologically Based Pharmacokinetic Modeling for Public Health Decision-Making.
The development and application of physiologically based pharmacokinetic (PBPK) models in chemical toxicology have grown steadily since their emergence in the 1980s. However, critical evaluation of PBPK models to support public health decision-making across federal agencies has thus far occurred for only a few environmental chemicals. In order to encourage decision-makers to embrace the critical role of PBPK modeling in risk assessment, several important challenges require immediate attention from the modeling community. The objective of this contemporary review is to highlight 3 of these challenges, including: (1) difficulties in recruiting peer reviewers with appropriate modeling expertise and experience; (2) lack of confidence in PBPK models for which no tissue/plasma concentration data exist for model evaluation; and (3) lack of transferability across modeling platforms. Several recommendations for addressing these 3 issues are provided to initiate dialog among members of the PBPK modeling community, as these issues must be overcome for the field of PBPK modeling to advance and for PBPK models to be more routinely applied in support of public health decision-making.


New developments in the treatment of hypoplastic left heart syndrome.
In the current decade, the prognosis of newborns with hypoplastic left heart syndrome, previously considered a uniformly fatal condition, has dramatically improved through refinement of rapidly evolving treatment strategies. These strategies include various modifications of staged surgical reconstruction, orthotopic heart transplantation, and hybrid palliation using ductal stenting and bilateral pulmonary artery banding. The variety of treatment approaches are based on different surgical philosophies, and each approach has its unique advantages and disadvantages. Nonetheless, multiple experienced centers have reported improved outcomes in each one of those modalities. The purpose of this review is to outline recent developments in the array of currently available management strategies for neonates with hypoplastic left heart syndrome. Because the vast majority of deaths in this patient population occur within the first months of life, the focus of the review will be evaluation of the impact of these management strategies on survival in the neonatal and infant periods.


In vitro analysis of fetal fibroblast collagenolytic activity.
Tissue repair in the rabbit fetus is remarkably rapid and occurs without significant inflammation or excessive collagen deposition. The objective of this study was to compare the ability of rabbit fetal and adult fibroblasts to express the matrix metalloproteinases which are thought to be critical to scar tissue remodeling. In vitro, both fetal and adult rabbit fibroblasts express procollagenase messenger RNA in a constitutive manner. Mechanical disruption of fetal fibroblast monolayers caused a twofold increase in procollagenase mRNA. In contrast, the adult rabbit fibroblast procollagenase mRNA remained unchanged. The mRNA data correlated well with enzyme protein levels. Quantitation by immunoprecipitation showed a 2.3-fold increase in fetal fibroblast procollagenase protein after mechanical injury, whereas the level in adult rabbit fibroblasts remained unchanged. However, it was noted that the constitutive levels of procollagenase mRNA and protein were higher in adult fibroblasts. Analysis of enzyme activity, by means of a fluorogenic substrate, showed that adult fibroblasts had 2.2 times more collagenase activity compared with fetal cells. After mechanical injury, the fetal fibroblast collagenase activity increased 1.3-fold compared with 1.7-fold in the adult fibroblasts. In contrast, fetal fibroblast gelatinase activity was 1.25 times greater than in adult cells and increased 1.4-fold after mechanical injury, whereas the adult profile remained unchanged. Immunolocalization studies indicated that 1 hour after mechanical injury, procollagenase was produced primarily by fibroblasts along the mechanical injury ridge. By 4 hours after injury, the ridge cells began to migrate out into the open area and procollagenase was noted in adjacent cells of both adult and fetal origin. By 12 and 18 hours, all cells throughout the monolayer were expressing procollagenase. These findings show that in vitro fetal fibroblasts actually had lower levels of procollagenase, but higher levels of gelatinase compared with adult fibroblasts. The increased gelatinase expression may explain why fetal wounds do not have excessive collagen accumulation and heal without a visible scar.


Optical modelling of a supplementary tunable air-spaced goggle lens for rodent eye imaging.
Aberration variations severely degrade retinal imaging in small animal eyes. Previously, the approach of a goggle lens with a matching corneal index was proposed to overcome the on-axis resolution limit of static imaging systems, which allows the use of the full eye pupil. But this technique didn't address the problem of the large power variation, and the ensuing aberration on and off-axis, when dealing with small animal eyes. In this study, we present the concept of a tunable goggle lens, designed to compensate individual ocular aberration for different rodent eye powers. Ray tracing evidences that lens-fitted goggles permit, not only to adjust individual eyes power, but also to surpass conventional adaptive correction technique over large viewing angle, provided a minimum use of two spaced liquids. We believe that the overlooked advantage of the 3D lens function is a seminal finding for further technological advancements in widefield retinal imaging.


Helicobacter pylori infection and disease: from humans to animal models.
Informative and tractable animal models that are colonized by well-defined microbial pathogens represent ideal systems for the study of complex human diseases. Helicobacter pylori colonization of the stomach is a strong risk factor for peptic ulceration and distal gastric cancer. However, gastritis has no adverse consequences for most hosts and emerging evidence suggests that H. pylori prevalence is inversely related to gastroesophageal reflux disease and allergic disorders. These observations indicate that eradication may not be appropriate for certain populations due to the potentially beneficial effects conferred by persistent gastric inflammation. Animal models have provided an invaluable resource with which to study H. pylori pathogenesis and carcinogenesis, and have permitted the development of a focused approach to selectively target human populations at high-risk of disease.


[Management of acute complications in sickle cell disease ].
Acute complications in sickle cell disease are a major and life-long cause for hospital referral. The most frequent events are painful acute vaso-occlusive crisis involving the limbs and back, and acute chest syndrome. Acute vaso-occlusive crisis is a therapeutic emergency because of the very high level of pain. Acute chest syndrome may be potentially fatal and must be adequately searched for and treated. Sickle cell patients are susceptible to pneumococcal infections notably, but any infection may favour vaso-occlusive crisis. Triggers of sickle cell vase occlusion must be tracked and corrected, if possible. Moderate crisis can be managed at home, but referral is necessary as soon as opiates are needed and/or if acute chest syndrome is suspected. Additional treatments besides opiates include co analgesics, oxygen, hydration, physiotherapy. Blood transfusion may be required but is not systematic. Acute spleen sequestration occurs in young children and requires immediate hospital referral for transfusion.


Induction of beta-amyloid-containing polypeptides in hippocampus: evidence for a concomitant loss of synaptic proteins and interactions with an excitotoxin.
Long-term cultures of brain slices were used to test if the lysosomotropic agent chloroquine induces beta-amyloid-related peptides in hippocampus and if such effects are accompanied by other manifestations of brain aging. Chloroquine administration resulted in the appearance of a carboxyl-terminal fragment of the beta-amyloid precursor protein (APP); the 27-kDa antigen was detectable after 24 h, increased rapidly for 6-10 days, and was eliminated upon drug washout. Immunocytochemical analyses showed that beta-amyloid immunoreactivity accumulated in the perikarya of pyramidal neurons, primarily in the form of punctate bodies. These effects were accompanied by a correlated loss (and recovery) of the presynaptic marker synaptophysin and by a delayed reduction of postsynaptic glutamate receptors, while cytoskeletal proteins were unchanged. Acute administration of chloroquine had no evident effects on synaptic responses but prolonged applications caused a decrease in the maximum amplitude of field potentials. Finally, a brief pretreatment with the excitotoxin kainic acid had little effect with regard to APP fragments or synaptophysin, but altered the events following from a subsequent infusion of chloroquine. Buildup of the 27-kDa APP fragment and loss of synaptophysin were more rapid and, more importantly, did not reverse upon washout of chloroquine. These findings indicate that lysosomal dysfunction in hippocampus results in the accumulation of a particular APP fragment and suggest that this event, or a variable correlated with it, is linked to the loss of synaptic proteins. They also raise the possibility that certain aspects of brain aging reflect a synergism between lysosomal disturbances and excitotoxicity.


Acetic acid formation in Escherichia coli fermentation.
Acetic acid formation in Escherichia coli fermentation has been studied in continuous cultures. Experimental results suggest that the limited capacity of the oxidative metabolism (perhaps the limited capacity of TCA cycle) may be responsible for acetic acid formation. At low growth rates, both anabolic and catabolic requirements may be satisfied by the oxidative metabolism. However, at high growth rates these two demands may exceed the capacity of the oxidative metabolism alone. It is proposed that under these circumstances, E. coli reorganizes the oxidative metabolism to first meet the anabolic requisition and then supply the necessary amount of energy using both the remaining capacity of the oxidative metabolism and acetic acid formation metabolism. Escherichia coli selects acetic acid synthesis as the aerobic energy source because it generates the second largest amount of ATP and NADH(2). According to our proposition, acetic acid formation could be reduced by decreasing the anabolic requirement, i.e., reducing glucose uptake, or by increasing the capacity of the oxidative metabolism. These two approaches were experimentally confirmed by observing reduced acetic acid formation by reducing the glucose uptake with a yeast extract addition and enhancing the capacity of oxidative metabolism with a methionine addition.


Finite element prediction of endosteal and periosteal bone remodelling in the turkey ulna: effect of remodelling signal and dead-zone definition.
Bone remodelling is the adaptation of bone mass in response to localized changes in loading conditions. The nature of the mechanical signal governing remodelling, however, remains the subject of continued investigation. The aims of this study were to use an iterative finite element (FE) bone remodelling technique to explore the effect of different remodelling signals in the prediction of bone remodelling behaviour. A finite element model of the turkey ulna, following that of Brown et al., was analysed using the ABAQUS package. The model was validated against the static predictions of the Brown et al. study. A bone remodelling technique, based on swelling algorithms given by Taylor and Clift, was then applied to predict the dramatic change in loading conditions imposed. The resulting changes in FE mid-shaft bone geometry were compared with the remodelling observed experimentally and showed good agreement. The tensile principal stress was found to be the best remodelling signal under the imposed conditions. Localized sensitivities in the remodelling patterns were found, however, and the definition of the dead zone was modified as a result. Remodelling with the new dead-zone definition showed that both the tensile principal stress and the tensile principal strain produced the remodelling patterns that agreed most closely with experiment.


Perceived benefits of and barriers to exercise and stage of exercise adoption in young adults.
College students (N = 432) completed questionnaires assessing current exercise participation, intention to become more active, perceived benefits of exercise, and perceived barriers to exercise. Confirmatory factor analyses of the benefit and barrier items suggested that a model containing 4 benefit factors (social, psychological, body image, and health) and 4 barrier factors (time-effort, social, physical effects, and specific obstacles) fit better than other models with fewer factors. Subscales derived from these factors revealed specific differences across participants who were categorized into 1 of 4 stages of exercise adoption. These findings confirm the multidimensional nature of perceived benefits of and barriers to exercise. Implications for the promotion and maintenance of exercise are discussed.


Low antibody response against tuberculous glycolipid (TBGL) in elderly gastrectomised tuberculosis patients.
To evaluate differences in anti-tuberculous glycolipid (TBGL) antibody titers in patients who developed tuberculosis (TB) with and without gastrectomy, 11 gastrectomised patients who developed TB after surgery (GS-TB), 19 TB patients without any other complications (TB), 12 gastrectomised patients who did not develop TB after surgery (GS) and 27 healthy subjects (H) with normal findings on chest X-ray were evaluated, although there were no differences in the clinical findings at admission between the TB and GS-TB groups. The assay used here allowed us to find low anti-TBGL antibody titers in GS-TB patients.


Lipid Emulsion Added to a Liquid High-Carbohydrate Diet and Voluntary Running Exercise Reduce Lipogenesis and Ameliorate Early-Stage Hepatic Steatosis in Mice.
Background: The use of parenteral nutrition formulas is often associated with the development of hepatic steatosis. We have shown previously that the addition of a lipid emulsion (LE) rich in n-6 (ω-6) fatty acids (FAs) ameliorated triglyceride (TG) accumulation in the livers of nonobese mice fed a high-carbohydrate diet (HCD) for 5 wk. However, it remains unclear how rapidly this condition develops and whether it can be prevented by LE with or without a running wheel for voluntary exercise (Exe).Objective: We investigated in an 8-d study whether mice develop steatosis and whether the administration of LE with or without Exe reduces the concentration of total FAs and prevents an increase in the expression of genes in the liver associated with lipogenesis.Methods: Male C57BL/6 mice aged 5 wk were randomized into 5 groups: standard feed pellet (SFP); a liquid HCD (77% of total energy from carbohydrates and 0.5% from fat); HCD + Exe; HCD + 13.5% LE (67% carbohydrates and 13.5% fat); or HCD + 13.5% LE + Exe. Hepatic TG concentration, lipogenic genes, and total FAs were measured on day 8.Results: Oil Red O staining and TG quantification showed hepatic TG accumulation on day 8; the addition of 13.5% LE either with or without Exe suppressed the TG accumulation compared with HCD (P < 0.005). With the use of quantitative reverse transcriptase-polymerase chain reaction analysis, the expression concentrations of lipogenic genes [ATP-citrate lyase, acetyl coenzyme A carboxylase 1, FA synthase (Fasn), and stearoyl coenzyme A desaturase 1 (Scd1)] in the HCD + 13.5% LE group were 26-60% of HCD (P < 0.01) and 11-38% of HCD in the HCD + 13.5% LE + Exe group (P < 0.001), with interactions for Fasn and Scd1 (P < 0.05). With the use of gas chromatography-mass spectrometry analysis, the HCD + 13.5% LE group had lower monounsaturated fatty acids (38.7% of HCD) but higher polyunsaturated fatty acids (164% of HCD) (P < 0.001).Conclusions: In short-term studies designed to resemble the early dynamic stage of the development of hepatic steatosis, the addition of 13.5% LE to a liquid HCD reduced hepatic lipogenesis. Exe exerted an independent protective effect and interacted with LE to further reduce the expression of Scd1.


The Accountable Care Workforce: Bridging the Health Divide in North Carolina.
Accountable care communities form as health care entities partner with communities to more fully address population health. This partnership requires an adaptable, boundary spanning, and diverse workforce, as well as flexible regulatory and governing structures that adapt to changing payment models, task shifting, and new roles in health care.


The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells.
Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid cells, suggesting that the capacity to repair the induced DNA lesion is present.


Responses in Growth and Anatomical Traits of Two Subtropical Tree Species to Nitrogen Addition, Drought, and Their Interactions.
Nitrogen (N) deposition and drought are two major stressors that influence tree growth and propagation. However, few studies have investigated their interactions. In this study, saplings of the two co-occurring species Ormosia pinnata (leguminous) and Schima superba (non-leguminous) were cultivated under two N addition rates (0 and 80 kg N ha-1 year-1) with well-watered (WW, 80% of field capacity), moderate drought (MD, 60% of field capacity), and severe drought conditions (SD, 40% of field capacity). We examined their growth, as well as multiple anatomical and non-structural carbohydrate (NSC) responses, after 2 years. Results revealed that N addition significantly promoted the growth of MD-stressed S. superba, whereas no significant effect was detected in O. pinnata. Decreased leaf water potential (both Ψmd and Ψpd) was also observed with N addition for both species under MD, but not under SD. Furthermore, the application of N positively impacted drought adaptive responses in the stem xylem of S. superba, showing decreased stem xylem vessel diameter (D H), theoretical hydraulic conductivity (K th), and increased vessel frequency (VF) upon drought under N addition; such impacts were not observed in O. pinnata. Regarding leaf anatomy, N addition also caused drought-stressed S. superba to generate leaves with a lower density of veins (VD) and stomata (SD), which potentially contributed to an enhanced acclimation to drought. However, the same factors led to a decrease in the palisade mesophyll thickness (PMT) of SD-stressed O. pinnata. Moreover, N addition increased the xylem soluble sugar and starch of MD-stressed O. pinnata, and decreased the xylem soluble sugar under SD for both species. The results suggest that N addition does not consistently modify tree growth and anatomical traits under variable water availability. S. superba appeared to have a greater capacity to be more adaptable under the future interactive effects of N addition and drought due to major modifications in its anatomical traits.


Comparative analysis of nonverbal interpersonal communication of schizophrenics and normals.
The nonverbal communications of schizophrenics and normals in dyadic interactions were analyzed and compared. Twelve purposively selected women were videotaped in normal-normal, normal-schizophrenic, and schizophrenic-schizophrenic communication acts for 30 minutes. Using a PLATO IV computer program and a modified Kendon Kinesic Notation System, a priori sets of nonverbal behaviors were recorded at 1-second intervals. Frequency and duration scores for the sets of nonverbal behaviors with corresponding communication meanings were totaled. A nested analysis of variance showed that the three groups differed significantly (p less than .05) in engagement and defensiveness and that the normal interactors were the least imitative of the three groups. An analysis and description of the patterns of nonverbal communication also revealed differences, lending support to the theory of dysjunctive schizophrenic communication.


Smallholders' knowledge about healing goat gastrointestinal parasite infections with wild plants in southern DR Congo.
Gastrointestinal parasite (GIP) infections control has an important role to play in increasing livestock production from a limited natural resource base and to improve animal health and welfare. This study aimed to collect indigenous knowledge and identify wild plants locally used by goat smallholders of three territories of Haut-Katanga province for treating signs of gastrointestinal parasitism. Ethnoveterinary surveys were conducted by semi-structured interviews and a bibliographic screening of the biological activities relating to cited plants was carried out. Our interviews showed that ethnosemantic diagnoses of GIP diseases are based on signs. Eighty-seven informants reported that 27 plant species from 15 families, dominated by Fabaceae (29.6%) and Lamiaceae (18.5%) were commonly used in their goats treatment. Among these plants, five species with palmately compound leaves were considerably more used. From those, we noted a substitution of Vitex congolensis De Wild. and T. Durand (Lamiaceae) by Oldfieldia dactylophylla (Welw. Ex Oliv.) J. Leonard (Picrodendraceae) and of Vitex mombassae Vatke by Vitex madiensis Oliv. Subsp. Milanjiensis (Britten) F. White. Roots (46.9%), leaves (28.0%) and seeds (12.5%) were the most frequently used plant organs, and maceration is applied for most of the medicinal preparations (62.2%). Recipes were administered by oral route, for GIP 1) prevention (33.3%), by macerating the ground plant material in drinking water for 2 weeks at the start of each season (dry and rainy); and 2) treatment (66.7%). According to the literature, some of these plants have few or no studies investigating their anthelmintic activity. The cited plants are worth investigating further as they could constitute an effective alternative strategy in maintaining animal productivity. Studies on the biological activity of these plants can also provide indications of promising leads for extracts that could be developed into commercial standardized medications.


The plantar calcaneal spur: a review of anatomy, histology, etiology and key associations.
The plantar calcaneal spur (PCS) is a bony outgrowth from the calcaneal tuberosity and has been studied using various methods including cadavers, radiography, histology and surgery. However, there are currently a number of discrepancies in the literature regarding the anatomical relations, histological descriptions and clinical associations of PCS. Historically, authors have described the intrinsic muscles of the foot and/or the plantar fascia as attaching to the PCS. In this article we review the relationship between the PCS and surrounding soft tissues as well as examining the histology of the PCS. We identify a number of key associations with PCS, including age, weight, gender, arthritides, plantar fasciitis and foot position; these factors may function as risk factors in PCS formation. The etiology of these spurs is a contentious issue and it has been explained through a number of theories including the degenerative, inflammatory, traction, repetitive trauma, bone-formers and vertical compression theories. We review these and finish by looking clinically at the evidence that PCS causes heel pain.


Inhaled and nasal corticosteroid use and the risk of fracture.
Studies of the risk of fracture associated with inhaled corticosteroids are inconclusive and are limited to short-term effects. We assessed whether long-term use increases this risk. We conducted a case control study nested within a population-based cohort of all Quebec elderly dispensed respiratory medications and followed for at least 4 years during 1988-2001. There were 9,624 new cases of fracture of the hip or upper extremities and 191,622 age-matched control subjects (mean age of 81 years). The rate of any such fracture for current inhaled corticosteroid use was not elevated (rate ratio [RR], 0.97; 95% confidence interval [CI], 0.92-1.03). For upper-extremity fracture, the rate increased by 12% (RR, 1.12; 95% CI, 1.04-1.19) with every 1,000-microg increase in the daily dose of inhaled corticosteroids, but not for hip fracture (RR, 0.97; 95% CI, 0.88-1.07). Among subjects followed for over 8 years, the rate of hip fracture was only elevated with daily doses of more than 2,000 microg of inhaled corticosteroids (RR, 1.61; 95% CI, 1.04-2.50). The rate was not elevated at any dose of nasal corticosteroids. In conclusion, the long-term use of inhaled and nasal corticosteroids at the usual recommended doses is not associated with a risk of fracture in older patients with respiratory disease.


Needles in a Haystack: Tracking City-Scale Moving Vehicles from Continuously Moving Satellite.
In recent years, the satellite videos have been captured by moving satellite platforms. In contrast to consumers, movies, and common surveillance videos, satellite videos can record the snapshots of city-scale scenes. In a broad fieldof-view of satellite videos, each moving target would be very tiny and usually composed of several pixels in frames. Even worse, the noise signals also exist in the video frames, and the background of the video frames subpixel-level and uneven moving thanks to the motion of satellites. We argue that it is a novel type of computer vision task since previous technologies are unable to detect such tiny moving vehicles efficiently. This paper proposes a novel framework that can identify small moving vehicles in satellite videos. In particular, we offer a novel detecting algorithm based on the local noise modeling. We differentiate the potential vehicle targets from noise patterns by an exponential probability distribution. Subsequently, a multi-morphologicalcue based discrimination strategy is designed to distinguish correct vehicle targets from the existing noises further. Another significant contribution is to introduce a series of evaluation protocols to measure the performance of tiny moving vehicle detection systematically. We annotate satellite videos manually to test our algorithms under different evaluation criterions. The proposed algorithm is also compared with the state-of-the-art baselines, which demonstrates the advantages of our framework over the benchmarks. Besides, the dataset would be downloaded from http://first.authour.github.com.


Thermo-reversible protein fibrillar hydrogels as cell scaffolds.
Hen egg white lysozyme has been exposed to various physical and chemical denaturing environments and the physical properties of the resulting gels have been examined and their potential for use as tissue engineering scaffolds has been explored. Transparent, self-supporting fibrillar hydrogels were obtained when lysozyme was heated at low pH, while opaque, particulate gels were obtained at high pH. No increase in viscosity was observed for lysozyme at pH 7 unless the native state was disrupted by reducing the disulfide bridges. This was achieved by adding 20 mM of the reductant dithiothreitol (DTT). Under these conditions the macroscopic critical gelation concentration, C(gel), was found to be approximately 3.0 mM and mechanical spectra obtained as a function of temperature revealed that the gelling and melting temperatures increased with increasing lysozyme concentration. The mechanical strength of the hydrogel measured as the plateau elastic modulus shows a scaling behavior of G(e) approximately c2.43 for concentrations > or = C(gel), which is in good agreement with the theoretical prediction for densely cross-linked semi-flexible networks. Infrared spectroscopy showed that an alpha-helix to beta-sheet molecular transition occurred during heating resulting in beta-sheet rich fibrils forming through the self-assembly of beta-sheet rich denaturated proteins. Cryo-transmission electron microscopy shows these fibres (6 nm in diameter) exist as single entities at low concentration, and at C(gel) associate to form the junctions of a well defined regular network. Our preliminary cell culture experiments show the gel matrix promotes cell spreading, attachment and proliferation; indicating our lysozyme hydrogels are cytocompatible and they provide a viable support for the cells.


Carbon-fiber alternative to the commercial gating surrogate for the Varian Truebeam™.
In this study we present the Tracking Accessory 3 (TA3) as an alternative to the commercial gating block (GB) surrogate for the Varian Truebeam™ gating system (TGS). The TGS requires three visible reflectors to track the surrogate, presenting an opportunity for a surrogate to be made with less material and thus smaller dosimetric footprint than the commercial four reflector model. Relative dose and depth dose profiles below the TA3 and the GB were measured with radiosensitive film. Accuracy and reproducibility of the detected motion amplitude for three TA3s and one GB were determined using a respiratory phantom with surrogate to determine the camera's tracking volume. Clinical performance was evaluated prospectively in 10 breast cancer patients treated with deep inspiration breath hold monitored with TA3 and compared to previously published results. Non-parametric statistics were applied to test for significance. Surface doses were increased up to 94% and 187% for the TA3 and GB, respectively, compared to no surrogate. The surface area influenced by at least 25% increase in dose was 12 cm2 and 105 cm2 for the TA3 and GB, respectively. The water equivalent thickness of the surrogates was found to be 1 mm for the TA3 and 3 mm for GB. The difference in measured amplitude were <0.2 mm for TA3 compared to the GB. The TA3s and GB were detected at all extremes of the clinically relevant tracking volume of the TGS. Clinical performance showed no significant differences. The TA3 caused less surface dose increase compared to the commercial GB. In the tested range all surrogates measured motion amplitude within 0.2 mm of reference value, which is not a clinically relevant difference. The TA3 showed no significant differences in clinical performance to similarly positioned surrogates.


A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans.
Fetal membrane rupture is associated with increased expression of matrix metalloproteinase-9 (MMP-9) and matrix degradation. We have determined the functional significance of a variable number tandem repeat and a single nucleotide polymorphism (SNP) in the MMP-9 gene on promoter activity and their association with preterm premature rupture of membranes (PPROM). The 14 CA-repeat allele was a stronger promoter than the 20 CA-repeat allele in amnion epithelial cells and WISH amnion-derived cells, but in THP-1 monocyte/macrophage cells the 14 and 20 CA-repeat alleles had similar activities. An SNP at -1562 did not significantly affect promoter activity. A case-control study of African American neonates revealed that the 14 CA-repeat allele was more common in newborns delivered of mothers who had PPROM than in those delivered at term. There was no association between the -1562 SNP and PPROM. We conclude that there are cell host-dependent differences in MMP-9 promoter activity related to CA-repeat number and that fetal carriage of the 14 CA-repeat allele is associated with PPROM in African Americans.


Quality of life and living with cancer: findings from the European social survey (2014) special module on the social determinants of health.
This study is a comparison of quality of life (QOL) of current and previous cancer victims with people who never had experienced cancer in samples from the general population from the 19 countries in the European Social Survey (ESS) 2014. The study was based on the ESS 2014 with representative samples from 19 countries. QOL was measured by combining two questions on happiness and life satisfaction into a QOL scale. Multilevel modelling was used to examine whether the relationship between cancer status and QOL varies between countries in general and by welfare state regimes in particular. People with cancer at the time of the interview, showed lower general QOL than both people who previously have had cancer and people who never have experienced cancer. The unadjusted and the adjusted odds ratios (ORs) for poor QOL were respectively, OR = 2.38, (2.07, 2.74) and OR = 1.98, (1.71, 2.30). The difference between the 'Never' and the 'Previously' groups was minor but statistical significant. The welfare state classification was a strong predictor of country differences in QOL, but there was no significant statistical interaction effect between cancer status and the welfare state classification. The study also replicated well-documented findings on differences in QOL by education and social support. The QOL of people with a cancer disease is significantly impaired. People who previously have had cancer, scored only slightly lower on the QOL scale than people who never had experienced cancer. We found evidence indicating that these differences may vary between the countries, but this variation cannot be explained by the welfare state classification.


Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer.
The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated: 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V(45 Gy) = 98% and V(42.75 Gy) = 100%. Compared with WP 3DCRT, IMRT reduced bladder V(45 Gy) by 78%, rectum V(45 Gy) by 48%, and small bowel V(45 Gy) by 232 cm3. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V(45 Gy) by 90%, rectum V(45 Gy) by 54% and small bowel V(45 Gy) by 455 cm3 compared with EF 3DCRT. In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.


Alternative pathway complement activation in rheumatoid arthritis.
Serum and synovial fluid (SF) levels of the complement components C3, C5, factor B (B), properdin (P), beta 1H and C3b inactivator (C3bINA), and EDTA-plasma and SF concentrations of C3d and Ba were measured in 40 rheumatoid arthritis (RA) and 5 patients with osteoarthritis. Decreased SF concentration of B and P and increased levels of Ba showed that increased alternative pathway turnover occurred in RA. Reduced SF C3bINA concentrations occurred, but levels of beta 1H were not reduced. The results showed that alternative pathway turnover was dependent upon C3 turnover, but failed to support the notion that levels of C3bINA or beta 1H control alternative pathway turnover in RA.


Porcine adipose tissue-derived mesenchymal stem cells retain their proliferative characteristics, senescence, karyotype and plasticity after long-term cryopreservation.
We and others have provided evidence that adipose tissue-derived mesenchymal stem cells (ASCs) can mitigate rat cardiac functional deterioration after myocardial ischemia, even though the mechanism of action or the relevance of these findings to human conditions remains elusive. In this regard, the porcine model is a key translational step, because it displays heart anatomic-physiological features that are similar to those found in the human heart. Towards this end, we wanted to establish the cultural characteristics of porcine ASCs (pASCs) with or without long-term cryostorage, considering that allogeneic transplantation may also be a future option. Compared to fresh pASCs, thawed cells displayed 90-95% viability and no changes in morphological characteristics or in the expression of surface markers (being pASCs characterized by positive markers CD29(+); CD90(+); CD44(+); CD140b(+); CD105(+); and negative markers CD31(-); CD34(-); CD45(-) and SLA-DR(-); n = 3). Mean population doubling time was also comparable (64.26±15.11 hours to thawed cells vs. 62.74±18.07 hours to fresh cells) and cumulative population doubling increased constantly until Passage 10 (P10) in the entire cell population, with a small and gradual increase in senescence (P5, 3.25%±0.26 vs. 3.47%±0.32 and P10, 9.6%±0.29 vs. 10.67%±1.25, thawed vs. fresh; SA-β-Gal staining). Chromosomal aberrations were not observed. In addition, under both conditions pASCs responded to adipogenic and osteogenic chemical cues in vitro. In conclusion, we have demonstrated the growth characteristics, senescence, and the capacity of pASCs to respond to chemical cues in vitro and have provided evidence that these properties are not influenced by cryostorage in 10% DMSO solution.


[Paternal age and pregnancy issues. The CECOS experience].
From a collaborative study of the French "Federation des CECOS" who collected the follow up of 11,535 pregnancies, the effect of parental age on the offspring is studied. A significant influence of the donor's age is demonstrated for the occurrence of trisomy 21 (37.4 +/- 7.8 vs 34.5 +/- 6.0; p < 0.05).


Endoscopic ultrasound-guided tissue sampling of small subepithelial tumors of the upper gastrointestinal tract with a 22-gauge core biopsy needle.
Background and study aims The optimal approach to small subepithelial tumors (SETs) of the upper gastrointestinal tract remains inconclusive. The aim of this study was to evaluate endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for less invasive tissue sampling of small SETs of the upper gastrointestinal tract. Patients and methods In this prospective observational study patients with small ( ≤ 3 cm) SETs of the upper gastrointestinal tract were eligible and underwent EUS-FNB with a 22-gauge core biopsy needle. The main outcome measure was the diagnostic yield. The number of obtained core biopsies was also assessed. Results Twenty patients were included. The mean SET size was 16 mm (range 10 - 27 mm). EUS-FNB was technically feasible in all cases and no complications were observed. The diagnostic yield was 75 %. Core biopsy specimens were obtained in only 25 % of cases. Conclusion EUS-FNB with a 22-gauge core biopsy needle of small SETs can achieve a definite diagnosis in the majority of cases. However, because core samples cannot regularly be obtained, EUS-FNB seems not to be convincingly superior to standard EUS-FNA in this setting.


Growth and carcass quality of prolific crossbred lambs fed silage with fish meal or different amounts of concentrate.
Sixty Romanov x Dorset (RVDP) and sixty Romanov x Suffolk (RVSU) male lambs were used in a 2 x 5 factorial arrangement of treatments including two breed crosses and five diets to determine the effect of breed crosses on performance and to compare growth and carcass characteristics of lambs. Diets consisted of an all-silage diet, silage supplemented with 100 g of fish meal.animal-1.d-1, or silage supplemented daily with concentrate at either 200 g or 400 g per animal, or ad libitum intake. Lambs were fed from an initial weight of 23 kg to a slaughter weight of 45 kg. There was no interaction (P > .10) between diet and breed for any parameter measured. Silage DMI was decreased (P < .05) by supplementation, but total DMI was similar among diets. The ADG was increased by fish meal and concentrate supplementation, with higher (P < .05) ADG observed with ad libitum access to concentrate. Lambs that had ad libitum access to concentrate had an improved gain:feed and required less time to reach market weight but had more carcass fat than lambs fed other diets. Lambs fed only silage had a higher percentage of carcass with poorer muscling than others. The highest percentage of carcasses with excellent to good muscling, normal fat covering, and grades A1 and A2 was obtained with fish meal supplementation. Lambs from the RVSU-crossbreed had better ADG than RVDP lambs but carcass quality of RVDP lambs was better than that of RVSU lambs.(ABSTRACT TRUNCATED AT 250 WORDS)


Statistical characterization of the charge state and residue dependence of low-energy CID peptide dissociation patterns.
Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg- and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides, a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from singly charged peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s) in multiply protonated peptides. Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages N-terminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and may be useful in algorithm development that employs improved models to predict fragment ion intensities.


The natural compound benzoxazolin-2(3H)-one selectively retards cell cycle in lettuce root meristems.
Benzoxazolin-2(3H)-one (BOA) is a natural plant product that is phytotoxic to target plant species, inhibiting germination and growth and causing oxidative damage. We investigated its effects on the root meristems of seedlings of lettuce (Lactuca sativa) by means of light and transmission electron microscopy, flow cytometry, and conventional determination of mitotic index. Flow cytometry analyses and mitotic index showed a retard of cell cycle in BOA-treated meristems with selective activity at G2/M checkpoint.


How Do the Locking Screws Lock? A Micro-CT Study of 3.5-mm Locking Screw Mechanism.
To quantify the amount of the screw head thread and the plate hole thread connection in two 3.5 mm locking plates: Locking Compression Plate (LCP) and Polyaxial Locking System (PLS). A micro - CT scan of a screw head - plate hole connection was performed pre- and post destructive tests. Tests were performed on bone surrogates in a fracture gap model. The 3.5 LCP and 3.5 PLS plates, with 3 perpendicular screws per segment were used in a destructive static test. The 3.5 PLS plates with mono- and polyaxial screws were compared in a cyclic fatigue tests in two orthogonal directions. Pre - and post - test scan datasets were compared. Each dataset was converted into serial images depicting sections cut orthogonally to locking screw axis. The amount of engagement was detected through automated image postprocessing. The mean amount of the thread connection for the LCP was 28.85% before and 18.55% after destructive static test. The mean amount of the connection for the PLS was 16.20% before and 14.55% after destructive static test. When inserted monoaxially, the mean amount of the connection for the PLS screws was 14.4% before and 19.24% after destructive cyclic test. The mean amount of the connection for the polyaxial inserted PLS screws when loaded against plate thickness was 2.99% before and 2.08% after destructive cyclic test. The mean amount of the connection for the polyaxial inserted PLS screws when loaded against plate width was 3.36% before and 3.93% after destructive cyclic test. The 3D visualization of the thread connection showed that the initial interface points between screw head and plate hole are different for both LCP and PLS after the destructive testing. Depending on the type of applied force, there was either loss or increase of the contact. Micro-CT offers news possibilities in locking implant investigation. It might be helpful in better understanding the nature of locking mechanism and prediction of possible mode of failure in different systems.


A Readily Accessible Chiral NNN Pincer Ligand with a Pyrrole Backbone and Its Ni(II) Chemistry: Syntheses, Structural Chemistry, and Bond Activations.
A new class of chiral C2-symmetric N-donor pincer ligands, 2,5-bis(2-oxazolinyldimethylmethyl)pyrroles (PdmBox)H, was synthesized starting from the readily available ethyl 2,2-dimethyl-3-oxobutanoate (1). The synthesis of the ligand backbone was achieved by oxidative enole coupling with CuC12 followed by Paal-Knorr-type pyrrole synthesis. The corresponding protioligands (RPdmBox)H (R = iPr: 5a; Ph: 5b) were obtained by condensation with amino alcohols and subsequent zinc-catalyzed cyclization. Reaction of the lithiated ligands with [NiCl2(dme)] yielded the corresponding square-planar nickel(II) complexes [(RPdmBox)NiCl] (6a/b). Salt metathesis of 6a with the corresponding alkali or cesium salts in acetone led to the formation of air- and moisture-stable [(iPrPdmBox)NiX] (X = F (7), X = Br (8), X = I (9), X = N3 (10), X = OAc (11). Furthermore, the conversion of [(iPrPdmBox)NiF] (7) with hydride transfer reagents such as PhSiH3 led to the stable hydrido species [(iPrPdmBox)NiH] (27), the stoichiometric transformations of which were studied. Treatment of 6a with organometallic reagents such as ZnEt2, PhLi, PhC≡CLi, NsLi, or (4FBn)2Mg(THF)2 gave the corresponding alkyl, alkynyl, or aryl complexes. The availability of the new nonisomerizable PdmBox pincer ligands allowed the comparative study of their ligation to square-planar complexes as helically twisted spectator ligands as opposed to the enforced planar rigidity of their iso-PmBox analogues and the way this influences the reactivity of the Ni complexes.


Activation of local innate immune signal induces periodontitis in microbiota-dependent manner.
Periodontitis is a chronic inflammatory disease. Both inflammation and dysbiosis have been implicated in periodontitis development. However, the relationship between local inflammation and dysbiosis, and the precise roles of local inflammation in periodontitis are not well-elucidated. In present study, we explored the role of local inflammation in periodontitis. We established a periodontitis model by administration of Pam3CSK4 to local oral area and compared the difference of outcome between local and systemic administration. We monitored the pro-inflammatory cytokine expression, local inflammation and alveolar bone loss. We also evaluated the dysbiosis, NF-κB activation. Local but not systemic administration of Pam3CSK4-induced pro-inflammatory cytokines productions and finally resulted in periodontitis. Pam3CSK4 caused dysbiosis and promoted Porphyromonas gingivalis growth. The bacterial growth and NF-κB activation were required for Pam3CSK4-induced periodontitis. We evaluated the effect of local inflammation by inducing TLR2 activation on dysbiosis and periodontitis. Activation of local innate immune signal induces periodontitis in microbiota-dependent manner.


Evaluation of four portable blood glucose meters in diabetic and non-diabetic dogs and cats.
Monitoring of an animal's blood glucose concentration is critical for diagnostic and therapeutic decisions. Over the past few decades, portable blood glucose meters (PBGMs) have been used to monitor blood glucose concentrations in animals. Recently, new and improved PBGMs have been made available on the market. The purpose of this study was to evaluate four PBGMs for use in dogs and cats. A total of 155 venous blood samples of dogs and 85 venous blood samples of cats were tested using four PBGMs. Control solutions from manufacturers were used to determine the precision of each meter. The coefficient of variation was calculated to determine precision during a set of replicates. Pearson's correlation analysis, Passing-Bablok regression, and Bland-Altman analysis were used to determine the accuracy of four PBGMs against the hexokinase reference method. Error grid analysis was used to evaluate clinical relevance. All PBGMs, except CERA-PET®, were clinically acceptable for monitoring blood glucose concentrations; AlphaTrak® and VetMate® appeared to be the most accurate ones, demonstrating that to use PBGMs for glucose monitoring, it is important to understand the strengths or limitations of each meter. The difference in results between the PBGMs and the reference method increased at high glucose concentration ranges, which were also affected by the hematocrit. Although readings of the PBGMs and the reference method varied across glycemic ranges (low, normal, and high glucose concentrations), most PBGMs were clinically acceptable for monitoring blood glucose concentrations in dogs and cats.


Non-persistence to antiretroviral therapy among adults receiving HIV medical care in the United States.
Not taking medicine over a specific period of time-non-persistence to antiretroviral therapy (ART)-may be associated with higher HIV-viral load. However, national estimates of non-persistence among U.S. HIV patients are lacking. We examined the association between non-persistence and various factors, including sustained HIV-viral suppression (VS) stratified by adherence, and assessed reasons for non-persistence using Medical Monitoring Project (MMP) data. MMP conducts clinical and behavioral surveillance among cross-sectional representative samples of adults receiving HIV care in the U.S. We analyzed weighted MMP interview and medical record abstraction data collected between 6/2011-5/2015 from 18,423 patients self-reporting ART use. We defined non-persistence as a self-initiated decision to not take ART for ≥2 consecutive days in the past 12-months, non-adherence as missing ≥1 ART dose during the past 3-days and sustained VS as all HIV-viral loads documented in medical record during the past 12-months as undetectable or <200 copies/mL. We used Rao-Scott chi-square tests to examine the association between non-persistence and sociodemographic, behavioral, clinical, and medication-related factors. We examined the association between non-persistence and sustained VS, stratified by adherence, and present prevalence ratios (PRs) with 95% confidence intervals (CIs). Reasons for non-persistence were assessed. Overall, 7% of patients reported non-persistence. Drug use, depression and medication side effects were associated with non-persistence (P < 0.01). Non-persistence was associated with the lack of sustained VS (PR: .66, CI:63-.70); this association did not differ by adherence level. However, VS was lower among the non-persistent/adherent compared with the persistent/non-adherent [51% (CI:47-54) versus 61% (CI:36-46), P < 0.01]. The most prevalent reason for non-persistence was treatment fatigue (38%). Though few persons in HIV care reported non-persistence, our findings suggest that non-persistence is associated with lack of sustained VS, regardless of adherence. Routine screening for non-persistence during clinical appointments and counseling for those at risk for non-persistence may help improve clinical outcomes.


AIDS appearance in children is associated with the velocity of disease progression in their mothers.
Thirty-four human immunodeficiency virus type 1 (HIV-1)-infected mother-child pairs were studied from delivery, and the association between velocity of disease progression in mothers and age at AIDS appearance in their children was analyzed. Four maternal disease stages were defined, and the velocity of HIV-1 progression was calculated. Maternal clinical conditions at delivery and intervals before starting zidovudine in women and children were included in the analysis. The relative risk of the child's developing AIDS for mother's disease progression of 1 stage/year was 3.004 (95% confidence interval, 1.37-6.58, P = .006) in stepwise analysis. A maternal CD4+ cell count < or = 400/mm3 appeared to be associated with a rapid disease course in both women and children. Thus, the faster HIV-1 progressed in the mother, the quicker AIDS developed in her baby. This suggests that HIV-1 strains with comparable virulence develop in mother-child pairs, perhaps because of their similar genetically driven immune responses.


Geomatics and public health.
Geomatics technology has tremendous potential to address public health issues particularly under the present circumstances of global climate change and climate or technology induced human migration, which result in an increase in the geographical extent and re-emergence of vector-borne diseases. The authors present an overview of the science of geomatics, describe the potential impacts of climate change on vector-borne diseases and review the applications of remote sensing for disease vector surveillance.


Might Reinfibulation be Medically Plausible in Carefully Screened Cases?
In light of the relational account of autonomy and the modern (holistic and phenomenological) account of health, this paper examines ethical justifications for ̳consensual' reinfibulation. Significant and constant discomfort in the body following deinfibulation might make a case for reinfibulation (considered as medical treatment in the traditional sense of the term). In any other case, the following requirements should be met for reinfibulation to be considered medically plausible: a) strong evidence that reinfibulation could help effectively improve woman's relational well-being, b) insignificant complications are expected, c) congruence between first-order and second-order autonomy or -in the context of political liberalism- strong second-order autonomy, d) an -open door‖ for the woman to exit an oppressive context, e) rigorous scrutiny of woman's psychology, and f) woman's practical wisdom to organize her identity-related values, find a balance between her extreme emotions and realize her own goal of meaningful life in accordance with her own conception of the good. Conclusively, in carefully screened cases and individually judged requests for reinfibulation, it should not be ruled out that, after having been conducted a multi-disciplinary in- depth investigation at social, psychological and medical level may be met conditions that make a case for reinfibulation.


Professional Identity Formation: A Role for Patients as Mentors.
Medical education should foster professional identity formation, but there is much to be learned about how to support learners in developing their professional identity. This study examined the role that patients can play in supporting professional identity development during the University of British Columbia Interprofessional Health Mentors Program (HMP), a longitudinal preclinical elective in which patients, or their caregivers, act as mentors and educate students about their lived experience of a chronic condition or disability. The authors interviewed 18 medical residents in 2016, 3 to 4 years after they completed the HMP. Professional identity was explored by asking participants how the HMP had influenced their ideas about the ideal physician and the kind of doctor they aspire to become. The authors analyzed the data using the identify status paradigm as a conceptual framework. The authors identified 7 themes: patient as more than disease, patient as autonomous, patient as expert, doctor as partner, doctor as collaborator, self-aware doctor, and empathic doctor. They found firm commitments to patient partnership, interprofessional collaboration, and holistic care for patients rooted in the exploration of professional values that was prompted by patient mentors during HMP. Patient mentors can help medical students begin to construct their professional identity during the preclinical period by supporting exploration of and commitment to the professional values that society expects of physicians.


A fast small-sample kernel independence test for microbiome community-level association analysis.
To fully understand the role of microbiome in human health and diseases, researchers are increasingly interested in assessing the relationship between microbiome composition and host genomic data. The dimensionality of the data as well as complex relationships between microbiota and host genomics pose considerable challenges for analysis. In this article, we apply a kernel RV coefficient (KRV) test to evaluate the overall association between host gene expression and microbiome composition. The KRV statistic can capture nonlinear correlations and complex relationships among the individual data types and between gene expression and microbiome composition through measuring general dependency. Testing proceeds via a similar route as existing tests of the generalized RV coefficients and allows for rapid p-value calculation. Strategies to allow adjustment for confounding effects, which is crucial for avoiding misleading results, and to alleviate the problem of selecting the most favorable kernel are considered. Simulation studies show that KRV is useful in testing statistical independence with finite samples given the kernels are appropriately chosen, and can powerfully identify existing associations between microbiome composition and host genomic data while protecting type I error. We apply the KRV to a microbiome study examining the relationship between host transcriptome and microbiome composition within the context of inflammatory bowel disease and are able to derive new biological insights and provide formal inference on prior qualitative observations.


Colon sparing resection versus extended colectomy for left-sided obstructing colon cancer with caecal ischaemia or perforation: a nationwide study from the French Surgical Association.
It is not known whether patients with obstructive left colon cancer (OLCC) with caecal ischaemia or diastatic perforation (defined as a blowout of the caecal wall related to colonic overdistension) should undergo a (sub)total colectomy (STC) or an ileo-caecal resection with double-barrelled ileo-colostomy. We aimed to compare the results of these two strategies. From 2000 to 2015, 1220 patients with OLCC underwent surgery by clinicians who were members of the French Surgical Association. Of these cases, 201 (16%) were found to have caecal ischaemia or diastatic perforation intra-operatively: 174 patients (87%) underwent a STC (extended colectomy group) and 27 (13%) an ileo-caecal resection with double-end stoma (colon-sparing group). Outcomes were compared retrospectively. In the extended colectomy group, 95 patients (55%) had primary anastomosis and 79 (45%) had a STC with an end ileostomy. In the colon-sparing group, 10 patients (37%) had simultaneous resection of their primary tumour with segmental colectomy and an anastomosis which was protected by a double-barrelled ileo-colostomy. The demographic data for the two groups were comparable. Median operative time was longer in the STC group (P = 0.0044). There was a decrease in postoperative mortality (7% vs 12%, P = 0.75) and overall morbidity (56% vs 67%, P = 0.37) including surgical (30% vs 40%, P = 0.29) and severe complications (17% vs 27%, P = 0.29) in the colon-sparing group, although these differences did not reach statistical significance. Cumulative morbidity included all surgical stages and the rate of permanent stoma was 66% and 37%, respectively, with no significant difference between the two groups. Overall survival and disease-free survival were similar between the two groups. The colon-sparing strategy may represent a valid and safe alternative to STC in OLCC patients with caecal ischaemia or diastatic perforation.


Pain and pharmacologic pain management in long-stay nursing home residents.
Previous studies estimate that >40% of long-stay nursing home (NH) residents experience persistent pain, with 20% of residents in pain receiving no analgesics. Strengthened NH surveyor guidance and improved pain measures on the Minimum Data Set 3.0 were introduced in March 2009 and October 2010, respectively. This study aimed to provide estimates after the important initiatives of (1) prevalence and correlates of persistent pain; and (2) prevalence and correlates of untreated or undertreated persistent pain. We identified 1,387,405 long-stay residents in U.S. NHs between 2011 and 2012 with 2 Minimum Data Set assessments 90 days apart. Pain was categorized as persistent (pain on both assessments), intermittent (pain on either assessment), or none. Pharmacologic pain management was classified as untreated pain (no scheduled or as needed medications received) or potentially undertreated (no scheduled received). Modified Poisson models adjusting for resident clustering within NHs provided adjusted prevalence ratios (APRs) estimates and 95% confidence intervals (CIs). The prevalence of persistent and intermittent pain was 19.5% and 19.2%, respectively, but varied substantially by age, sex, race and ethnicity, cognitive impairment, and cancer. Of residents in persistent pain, 6.4% and 32.0% were untreated and undertreated, respectively. Racial and ethnic minorities (non-Hispanic blacks vs whites, APR = 1.19, 95% CI: 1.13-1.25) and severely cognitively impaired residents (severe vs no/mild APR = 1.51, 95% CI: 1.44-1.57) had an increased prevalence of untreated and undertreated pain. One in 5 NH residents has persistent pain. Although this estimate is greatly improved, many residents may be undertreated. The disturbing disparities in untreated and undertreated pain need to be addressed.


Histopathology and ultrastructural examination of optic nerve sheath biopsies after optic nerve sheath decompression with and without mitomycin.
We chose to compare histologically and ultrastructurally changes in the optic nerve sheath after optic nerve sheath decompression, initially after a second surgery and after treatment with mitomycin-C. The mechanism by which optic nerve sheath decompression alleviates papilledema can be further understood in consideration of the results. Tissue was obtained by biopsy from 3 first-time surgical and 4 reoperative cases with and without mitomycin-C in patients with idiopathic intracranial hypertension. The sheaths were fixed in a mixture of 2% paraformaldehyde and 2% glutaraldehyde, osmicated and dehydrated in a series of ethanol, and finally embedded in epon. Tissue blocks were sectioned at 1 microm and stained with both PPD and toluidine blue. Thin sections were examined by transmission electron microscopy. Normal meningeal tissue obtained at the time at optic nerve sheath decompression consisted mainly of collagen, closely packed and roughly parallel to the axis of the optic nerve. Collagen deposition seen in scar tissue after secondary optic nerve sheath decompression was extremely disorganized and irregular, with the individual fibers laid down seemingly at random. There was little sense of layering or of parallel arrays. Mitomycin-C appeared to influence collagen deposition in such a way that the collagen was more regularly packed and more closely resembled unoperated tissue. The regular well-organized collagen packing seen in normal sheath tissue is disrupted and replaced by less organized but compact scar tissue after optic nerve sheath decompression. With mitomycin use, more regular collagen packing closely approximating that found in unoperated sheath occurs. This configuration of fibers lends support for the filtration mechanism of optic nerve sheath decompression in treating papilledema.


Mechanisms of Dominant Electrophysiological Features of Four Subtypes of Layer 1 Interneurons.
Neocortical layer 1 (L1) consists of the distal dendrites of pyramidal cells and GABAergic interneurons (INs) and receives extensive long-range "top-down" projections, but L1 INs remain poorly understood. In this work, we systematically examined the distinct dominant electrophysiological features for four unique IN subtypes in L1 that were previously identified from mice of either gender: Canopy cells show an irregular firing pattern near rheobase; neurogliaform cells are late-spiking, and their firing rate accelerates during current injections; cells with strong expression of the α7 nicotinic receptor (α7 cells), display onset (rebound) bursting; vasoactive intestinal peptide (VIP) expressing cells exhibit high input resistance, strong adaptation, and irregular firing. Computational modeling revealed that these diverse neurophysiological features could be explained by an extended exponential-integrate-and-fire neuron model with varying contributions of a slowly inactivating K+ channel, a T-type Ca2+ channel, and a spike-triggered Ca2+-dependent K+ channel. In particular, we show that irregular firing results from square-wave bursting through a fast-slow analysis. Furthermore, we demonstrate that irregular firing is frequently observed in VIP cells because of the interaction between strong adaptation and a slowly inactivating K+ channel. At last, we reveal that the VIP and α7 cell models resonant with alpha/theta band input through a dynamic gain analysis.SIGNIFICANCE STATEMENT In the neocortex, ∼25% of neurons are interneurons. Interestingly, only somas of interneurons reside within layer 1 (L1) of the neocortex, but not of excitatory pyramidal cells. L1 interneurons are diverse and believed to be important in the cortical-cortex interactions, especially top-down signaling in the cortical hierarchy. However, the electrophysiological features of L1 interneurons are poorly understood. Here, we systematically studied the electrophysiological features within each L1 interneuron subtype. Furthermore, we build computational models for each subtype and study the mechanisms behind these features. These electrophysiological features within each subtype should be incorporated to elucidate how different L1 interneuron subtypes contribute to communication between cortexes.


Migraine disability awareness campaign in Asia: migraine assessment for prophylaxis.
This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). A total of 2782 patients (72% females; mean age 38.1 15.1 years) finished the study.Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries.Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school,work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains underdiagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study.


Stagnation and complex flow in ruptured cerebral aneurysms: a possible association with hemostatic pattern.
OBJECT Histopathological examination has revealed that ruptured cerebral aneurysms have different hemostatic patterns depending on the location of the clot formation. In this study, the authors investigated whether the hemostatic patterns had specific hemodynamic features using computational fluid dynamics (CFD) analysis. METHODS Twenty-six ruptured middle cerebral artery aneurysms were evaluated by 3D CT angiography and harvested at the time of clipping. The hemostatic patterns at the rupture points were assessed by means of histopathological examination, and morphological parameters were obtained. Transient analysis was performed, and wall shear stress-related hemodynamic parameters and invariant Q (vortex core region) were calculated. The morphological and hemodynamic parameters were compared among the hemostatic patterns. RESULTS Hematoxylin and eosin staining of the aneurysm wall showed 13 inside-pattern, 9 outside-pattern, and 4 other-pattern aneurysms. Three of the 26 aneurysms were excluded from further analysis, because their geometry models could not be generated due to low vascular CT values. Mann-Whitney U-tests showed that lower dome volume (0.04 cm3 vs 0.12 cm3, p = 0.014), gradient oscillatory number (0.0234 vs 0.0289, p = 0.023), invariant Q (-0.801 10-2/sec2 vs -0.124 10-2/sec2, p = 0.045) and higher aneurysm formation indicator (0.986 vs 0.963, p = 0.041) were significantly related to inside-pattern aneurysms when compared with outside-pattern aneurysms. CONCLUSIONS Inside-pattern aneurysms may have simpler flow patterns and less flow stagnation than outside-pattern aneurysms. CFD may be useful to characterize the hemostatic pattern of ruptured cerebral aneurysms.