Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib.
Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child-Pugh A, 83% performance status (PS) ≥1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3-4.9) months, resulting from 4.6 (3.3-5.7) months for 123 progressors, 7.3 (6.0-10.0) months in 77 with adverse effects, and 1.8 (1.6-2.4) months in 60 decompensated patients (P < 0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 (4.6-7.1) months, which was dependent on reasons of discontinuation (P = 0.004), PS (P < 0.001), macrovascular invasion (P < 0.001), and extrahepatic metastases (P < 0.002). Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second-line therapy.


An orthopedist's guide to shoulder ultrasound: a systematic review of examination protocols.
The utilization of musculoskeletal ultrasound has expanded within the setting of the orthopedic clinic as a cost-effective, point-of-care diagnostic tool for shoulder pathology. In experienced hands, ultrasound exhibits capabilities equivalent to that of magnetic resonance imaging in the diagnosis of many shoulder diseases including full-thickness and partial-thickness rotator cuff tears. Although similarly effective in identifying additional shoulder disease processes, major obstacles to its widespread use include user dependence and intrinsic limitation to extra-articular diagnosis. The purpose of this review is to present a step-by-step guide of how to perform a comprehensive shoulder examination and to discuss the appropriate use, economic benefit and implementation of ultrasound within the clinic. A systematic search (June 2016) of PubMed, Scopus, and EMBASE databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for literature presenting shoulder ultrasound examination protocols. Included studies were peer-reviewed articles or academic society endorsed protocols presenting comprehensive sonographic examinations of the adult shoulder. Papers with limited or single structure examination descriptions, non-English language, and publication dates before 1980 were excluded. Final papers meeting criteria were secondarily screened for publication after 2005 to reflect the current state of ultrasound imaging. The search yielded 1,725 unique articles with 17 studies meeting final selection criteria. Information from identified studies was summarized to formulate a 4-part shoulder examination protocol, including steps most pertinent to orthopedic in-office diagnoses. In agreement with previous studies, the inexperienced orthopedic surgeon can be quickly trained to expert level proficiency in shoulder ultrasound diagnosis. Using an established protocol, a comprehensive, yet effective shoulder ultrasound examination can be performed within ten minutes. Further, ultrasound provides opportunity to off-set costs through the engagement of revenue generating activity for the orthopedic practice.


Tuberculosis-Human Immunodeficiency Virus (HIV) co-infection in Ethiopia: a systematic review and meta-analysis.
Human Immunodeficiency Virus (HIV) and Tuberculosis (TB) are the double burden diseases of the world. The African continent takes a great share of TB-HIV cases worldwide. This study was aimed to determine the prevalence of TB-HIV co-infection in Ethiopia, using a meta-analysis based on a systematic review of published articles. An electronic search was conducted in databases including PubMed, HINARI, EMBASE, Cochrane library and Google Scholar to extract the articles. Articles published between 1995 and November 2017 had been searched for using different keywords. The analysis was performed using MetaXL software and R statistical software (version 3.2.3). Our searches returned a total of (n = 26,746) records from 30 articles of which 21 were cross-sectional, 7 were retrospectives and 2 were prospective studies. The range of prevalence of TB-HIV co-infection was found to be from 6 to 52.1% with random effects pooled prevalence of 22% (95% CI 19-24%) and with substantial heterogeneity chi-square (X2) = 746.0, p < 0.001, (I2 = 95.84%). Our analysis indicated that the prevalence of TB-HIV co-infection is high in Ethiopia with substantial regional variation. An integrated, facility-based and community-based effort towards the prevention, early detection and management of cases should be further strengthened throughout the country to mitigate the double burden disease.


Nucleation instability in supercooled Cu-Zr-Al glass-forming liquids.
Few general models representing certain classes of real glass-forming systems play a special role in computer simulations of supercooled liquid and glasses. Recently, it was shown that one of the most widely used model glassformers-the Kob-Andersen binary mixture-crystalizes in quite lengthy molecular dynamics simulations, and moreover, it is in fact a very poor glassformer at large system sizes. Thus, our understanding of crystallization stability of model glassformers is far from complete due to the fact that relatively small system sizes and short time scales have been considered so far. Here we address this issue for two embedded atom models intensively used last years in numerical studies of Cu-Zr-(Al) bulk metallic glasses. Exploring the structural evolution of Cu64.5Zr35.5 and Cu46Zr46Al8 alloys at continuous cooling and isothermal annealing, we observe that both systems nucleate in sufficiently lengthy simulations, although critical nucleation time for the latter is an order of magnitude higher than that for the former. We show that Cu64.5Zr35.5 is actually unstable to crystallization for large system sizes (N > 20 000). Both systems crystallize with the formation of tetrahedrally close packed Laves phases of different types. We argue that nucleation instability of the simulated Cu64.5Zr35.5 alloy is due to the fact that its composition is very close to that for the stable Cu2Zr compound with a C15 Laves phase structure.


[The use of screens in the anti-tsetse campaign in the forest zone].
After preliminary studies on the ecodistribution of Glossina palpalis s.l. in the sleeping sickness focus of Vavoua (Ivory Coast) trials with screens impregnated with decamethrine were carried out. Artificial supports for insecticide present several advantages: less pollution, less costly, simplicity, facility of use by local personnel, possibility of re-use, integration with other methods. On the other hand, its action based on the attraction of flies which come into contact with the screen is relatively slow, particularly in obtaining a complete interruption of reproduction. The technique is compared with other control methods as the use of biconical traps and selective spraying along borders. Its action can be improved by the addition of attractive host odours or sex pheromones.


Micro-scale technologies propel biology and medicine.
Historically, technology has been central to new discoveries in biology and progress in medicine. Among various technologies, microtechnologies, in particular, have had a prominent role in the revolution experienced by the life sciences in the last few decades, which will surely continue in the years to come. In this Perspective, we illustrate how microtechnologies, with a focus on microfluidics, have evolved in trends/waves to tackle the boundary of knowledge in the life sciences. We provide illustrative examples of technology-enabled biological breakthroughs and their current and future use in clinics. Finally, we take a closer look at the translational process to understand why the incorporation of new micro-scale technologies in medicine has been comparatively slow so far.


Lipocalin 2, a Regulator of Retinoid Homeostasis and Retinoid-mediated Thermogenic Activation in Adipose Tissue.
We have recently characterized the role of lipocalin 2 (Lcn2) as a new adipose-derived cytokine in the regulation of adaptive thermogenesis via a non-adrenergic pathway. Herein, we explored a potential non-adrenergic mechanism by which Lcn2 regulates thermogenesis and lipid metabolism. We found that Lcn2 is a retinoic acid target gene, and retinoic acid concurrently stimulated UCP1 and Lcn2 expression in adipocytes. Lcn2 KO mice exhibited a blunted effect of all-trans-retinoic acid (ATRA) on body weight and fat mass, lipid metabolism, and retinoic acid signaling pathway activation in adipose tissue under the high fat diet-induced obese condition. We further demonstrated that Lcn2 is required for the full action of ATRA on the induction of UCP1 and PGC-1α expression in brown adipocytes and the restoration of cold intolerance in Lcn2 KO mice. Interestingly, we discovered that Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue. Moreover, Lcn2 deficiency abolished the ATRA effect on RBP4 expression in adipocytes. All the data suggest that the decreased retinoid level and action are associated with impaired retinol transport and storage in adipose tissue in Lcn2 KO mice. We conclude that Lcn2 plays a critical role in regulating metabolic homeostasis of retinoids and retinoid-mediated thermogenesis in adipose tissue.


Augmented Self-Association by Electrostatic Forces in Thienopyrrole-Fused Thiadiazoles that Contain an Ester instead of an Ether Linker.
During the self-assembly of π-conjugated molecules, linkers and substituents can potentially add supportive noncovalent intermolecular interactions to π-stacking interactions. Here, we report the self-assembly behavior of thienopyrrole-fused thiadiazole (TPT) fluorescent dyes that possess ester or ether linkers and dodecyloxy side chains in solution and the condensed phase. A comparison of the self-association behavior of the ester- and ether-bridged compounds in solution using detailed UV-vis, fluorescence, and NMR spectroscopic studies revealed that the subtle replacement of the ether linkers by ester linkers leads to a distinct increase in the association constant (ca. 3-4 fold) and the enthalpic contribution (ca. 3 kcal mol-1 ). Theoretical calculations suggest that the ester linkers, which are in close proximity to one another due to the π-stacking interactions, induce attractive electrostatic forces and augment self-association. The self-assembly of TPT dyes into well-defined 1D clusters with high aspect ratios was observed, and their morphologies and crystallinity were investigated using SEM and X-ray diffraction analyses. TPTs with ester linkers exhibit a columnar liquid crystalline mesophase in the condensed phase.


Control and controllability of microswimmers by a shearing flow.
With the continuing rapid development of artificial microrobots and active particles, questions of microswimmer guidance and control are becoming ever more relevant and prevalent. In both the applications and theoretical study of such microscale swimmers, control is often mediated by an engineered property of the swimmer, such as in the case of magnetically propelled microrobots. In this work, we will consider a modality of control that is applicable in more generality, effecting guidance via modulation of a background fluid flow. Here, considering a model swimmer in a commonplace flow and simple geometry, we analyse and subsequently establish the efficacy of flow-mediated microswimmer positional control, later touching upon a question of optimal control. Moving beyond idealized notions of controllability and towards considerations of practical utility, we then evaluate the robustness of this control modality to sources of variation that may be present in applications, examining in particular the effects of measurement inaccuracy and rotational noise. This exploration gives rise to a number of cautionary observations, which, overall, demonstrate the need for the careful assessment of both policy and behavioural robustness when designing control schemes for use in practice.


Resolution of venous thrombosis using a novel oral small-molecule inhibitor of P-selectin (PSI-697) without anticoagulation.
P-selectin inhibition has been shown to decrease thrombogenesis in multiple animal species. In this study, we show that a novel oral small-molecule inhibitor of P-selectin, PSI-697, promotes thrombus resolution and decreases inflammation in a baboon model of venous thrombosis. Experimental groups consisted of the following: 1) primates receiving a single oral dose of PSI-697 (30 mg/kg) daily starting three days pre-iliac vein balloon occlusion, and continued for six days; 2) primates receiving a single treatment dose of a low-molecular-weight-heparin (LMWH) (1.5 mg/kg) daily starting one day pre-iliac balloon occlusion, and continued for six days; and 3) primates receiving a single oral dose of a vehicle control daily starting three days pre-iliac vein balloon occlusion, and continued for six days. Animals receiving PSI-697, although thrombosed after balloon deflation, demonstrated greater than 80% vein lumen opening over time, with no opening (0%) for vehicle control (p < 0.01). LMWH opening evident after balloon deflation slightly deteriorated over time compared to PSI-697. PSI-697 therapy also significantly decreased vein wall inflammation determined by magnetic resonance venography (MRV). Importantly, this beneficial opening occurred without measured anticoagulation. Animals receiving PSI-697 demonstrated significantly increased plasma D-dimer levels versus LMWH and control animals six hours post thrombus induction (p < 0.01). This study is the first to demonstrate the effectiveness of oral P-selectin inhibition to modify venous thrombogenesis, increase vein lumen opening, and decrease inflammation in a large animal model.


"Small Hepatocytes" in the Liver.
Mature hepatocytes (MHs) in an adult rodent liver are categorized into the following three subpopulations based on their proliferative capability: type I cells (MH-I), which are committed progenitor cells that possess a high growth capability and basal hepatocytic functions; type II cells (MH-II), which possess a limited proliferative capability; and type III cells (MH-III), which lose the ability to divide (replicative senescence) and reach the final differentiated state. These subpopulations may explain the liver's development and growth after birth. Generally, small-sized hepatocytes emerge in mammal livers. The cells are characterized by being morphologically identical to hepatocytes except for their size, which is substantially smaller than that of ordinary MHs. We initially discovered small hepatocytes (SHs) in the primary culture of rat hepatocytes. We believe that SHs are derived from MH-I and play a role as hepatocytic progenitors to supply MHs. The population of MH-I (SHs) is distributed in the whole lobules, a part of which possesses a self-renewal capability, and decreases with age. Conversely, injured livers of experimental models and clinical cases showed the emergence of SHs. Studies demonstrate the involvement of SHs in liver regeneration. SHs that appeared in the injured livers are not a pure population but a mixture of two distinct origins, MH-derived and hepatic-stem-cell-derived cells. The predominant cell-derived SHs depend on the proliferative capability of the remaining MHs after the injury. This review will focus on the SHs that appeared in the liver and discuss the significance of SHs in liver regeneration.


Critical changes in hypothalamic gene networks in response to pancreatic cancer as found by single-cell RNA sequencing.
Cancer cachexia is a devastating chronic condition characterized by involuntary weight loss, muscle wasting, abnormal fat metabolism, anorexia, and fatigue. However, the molecular mechanisms underlying this syndrome remain poorly understood. In particular, the hypothalamus may play a central role in cachexia, given that it has direct access to peripheral signals because of its anatomical location and attenuated blood-brain barrier. Furthermore, this region has a critical role in regulating appetite and metabolism. To provide a detailed analysis of the hypothalamic response to cachexia, we performed single-cell RNA-seq combined with RNA-seq of the medial basal hypothalamus (MBH) in a mouse model for pancreatic cancer. We found many cell type-specific changes, such as inflamed endothelial cells, stressed oligodendrocyes and both inflammatory and moderating microglia. Lcn2, a newly discovered hunger suppressing hormone, was the highest induced gene. Interestingly, cerebral treatment with LCN2 not only induced many of the observed molecular changes in cachexia but also affected gene expression in food-intake decreasing POMC neurons. In addition, we found that many of the cachexia-induced molecular changes found in the hypothalamus mimic those at the primary tumor site. Our data reveal that multiple cell types in the MBH are affected by tumor-derived factors or host factors that are induced by tumor growth, leading to a marked change in the microenvironment of neurons critical for behavioral, metabolic, and neuroendocrine outputs dysregulated during cachexia. The mechanistic insights provided in this study explain many of the clinical features of cachexia and will be useful for future therapeutic development.


Comparison of Direct Patient Care Costs and Quality Outcomes of the Teaching and Nonteaching Hospitalist Services at a Large Academic Medical Center.
To compare costs of care and quality outcomes between teaching and nonteaching hospitalist services, while testing the assumption that resident-driven care is more expensive. Records of inpatients with the top 20 Medicare Severity Diagnosis-Related Groups admitted to the University Teaching Service (UTS) and nonteaching hospitalist service (NTHS) at Houston Methodist Hospital from 2014-2015 were analyzed retrospectively. Direct costs of care, length of stay (LOS), in-hospital mortality (IHM), 30-day readmission rate (30DRR), and consultant utilization were compared between the UTS and NTHS. Propensity score matching and case mix index (CMI) were used to mitigate differences in baseline characteristics. To compare outcomes between matched groups, the Wilcoxon rank sum test and chi-square test were used. A sensitivity analysis was conducted using multivariable regression analysis. From the overall study population of 8,457 patients, 1,041 UTS and 3,123 NTHS patients were matched. CMI was 1.07 for each group. The UTS had lower direct costs of care per case ($5,028 vs. $5,502, P = .006), lower LOS (4.7 vs. 5.2 days, P = .0002), and lower consultant utilization (1.0 vs. 1.6, P ≤ .0001) versus the NTHS. The UTS and NTHS 30DRR (17.2% vs. 19.3%, P = .110) and IHM (2.9% vs. 3.7%, P = .206) were comparable. The multivariable regression analysis validated the matched data and identified an incremental cost savings of $333/UTS patient. Patients of an academic hospitalist service had significantly shorter LOS, fewer consultants, and lower direct care costs than comparable patients of a nonteaching service.


Airway management in maxillofacial trauma: do we really need tracheostomy/submental intubation.
There are various techniques available for airway management in patients with maxillofacial trauma. Patients with panfacial injuries may need surgical airway access like submental intubation or tracheostomy, which have their associated problems. We have been managing these types of cases by a novel technique, i.e, intraoperative change of nasotracheal to orotracheal intubation. To review our experience about various techniques for the airway management in patient with maxillofacial trauma. To analyse the possibility of using nasotracheal intubation and intraoperative change of nasotracheal to orotracheal intubation in panfacial fractures. In a tertiary care centre four hundred eighty seven patients of maxillofacial injuries, operated over a period of 2 years were reviewed in relation to age, sex, mode of injury, type of facial fractures, methods of airway management and their associated complications. Young patients with male predominance is the most common affected population. Panfacial fracture is the most common type of injury (39.83%) among facial fractures. Airway was managed with intraoperative change of nasotracheal to orotracheal intubation in 33.05% of the patients whereas submental intubation or tracheostomy was done in 8.62% of the patients. Nasal route for endotracheal intubation is not a contraindication in the presence of nasal fractures, base of skull fractures and CSF leak. By changing the nasotracheal intubation to orotracheal intubation intraoperatively in cases panfacial fractures, most of the tracheostomies and submental intubations can be avoided.


Rapid and near-complete resolution of moyamoya vessels in a patient with moyamoya disease treated with superficial temporal artery-middle cerebral artery bypass.
Several groups have reported partial resolution of moyamoya vessels following surgical revascularization in pediatric patients, but angiographic documentation of near-complete resolution has been poor. We report here a case of a 5-year-old boy who underwent bilateral superficial temporal artery-middle cerebral artery bypass combined with unilateral encephaloduroarteriosynangiosis who demonstrated near-complete resolution of moyamoya vessels and a dramatic improvement in cerebral perfusion as measured by xenon-enhanced CT. The resolution of moyamoya networks may serve as an indicator of successful surgical revascularization.


Distinct Molecular Effects of Angiotensin II and Angiotensin III in Rat Astrocytes.
It is postulated that central effects of angiotensin (Ang) II may be indirect due to rapid conversion to Ang III by aminopeptidase A (APA). Previously, we showed that Ang II and Ang III induced mitogen-activated protein (MAP) kinases ERK1/2 and stress-activated protein kinase/Jun-terminal kinases (SAPK/JNK) phosphorylation in cultured rat astrocytes. Most importantly, both peptides were equipotent in causing phosphorylation of these MAP kinases. In these studies, we used brainstem and cerebellum astrocytes to determine whether Ang II's phosphorylation of these MAP kinases is due to the conversion of the peptide to Ang III. We pretreated astrocytes with 10 μ M amastatin A or 100 μ M glutamate phosphonate, selective APA inhibitors, prior to stimulating with either Ang II or Ang III. Both peptides were equipotent in stimulating ERK1/2 and SAPK/JNK phosphorylation. The APA inhibitors failed to prevent Ang II- and Ang III-mediated phosphorylation of the MAP kinases. Further, pretreatment of astrocytes with the APA inhibitors did not affect Ang II- or Ang III-induced astrocyte growth. These findings suggest that both peptides directly induce phosphorylation of these MAP kinases as well as induce astrocyte growth. These studies establish both peptides as biologically active with similar intracellular and physiological effects.


Autoradiographic localization of voltage-dependent sodium channels on the mouse neuromuscular junction using 125I-alpha scorpion toxin. II. Sodium distribution on postsynaptic membranes.
A radioiodinated alpha-scorpion toxin (toxin II from Androctonus australis Hector) (alpha ScTx) was used as a probe for EM autoradiography to study the distribution of voltage-dependent sodium channels (Na+ channel) on the postsynaptic side of the mouse neuromuscular junction. Silver grain distribution was analyzed by the cross-fire method to assess the relative Na+ channel density in each membrane domain measured by stereology. This analysis showed that the maximum Na+ channel density was located on the edge of the synaptic gutter, where it reached about twice the mean density in the postsynaptic fold membrane. Na+ channel densities have been calculated using ACh receptor (AChR) density in fold crests as reference. Sodium channel density on the edge of the synaptic gutter was estimated at about 5000/microns 2. Sodium channel distribution in the postsynaptic folds was compared to AChR distribution using density distribution analysis (Fertuck and Salpeter, 1976). The results confirmed that, as already observed by immunogold labeling (Flucher and Daniels, 1989), there are no Na+ channels on fold crests. Na+ channels are located in the rest of the fold membrane (bottom) and may be distributed according to two possible models. In the first, density would be uniformly high, although lower than on the gutter edge. In the second, density would decrease from the crest border, where the value was that of the gutter edge, to the fold end, where the value would be 50% lower. Based on the latter model, which was the "best-fit model," we propose that the postsynaptic membrane includes two domains. The first is the fold crest, which contains almost exclusively AChRs. This domain is devoted to reception-transduction of the chemical signal. The second includes both the fold bottom membrane and the perisynaptic membrane. Sodium channel density is highest along the crest border and decreases moving away. Its functions are the integration of postsynaptic potentials and generation-conduction of the muscle action potential.


The plant DNA polymerase theta is essential for the repair of replication-associated DNA damage.
Safeguarding of genome integrity is a key process in all living organisms. Due to their sessile lifestyle, plants are particularly exposed to all kinds of stress conditions that could induce DNA damage. However, very few genes involved in the maintenance of genome integrity are indispensable to plants' viability. One remarkable exception is the POLQ gene, which encodes DNA polymerase theta (Pol θ), a non-replicative polymerase involved in trans-lesion synthesis during DNA replication and double-strand break (DSB) repair. The Arabidopsis tebichi (teb) mutants, deficient in Pol θ, have been reported to display severe developmental defects, leading to the conclusion that Pol θ is required for normal plant development. However, this essential role of Pol θ in plants is challenged by contradictory reports regarding the phenotypic defects of teb mutants and the recent finding that rice (Oryza sativa) null mutants develop normally. Here we show that the phenotype of teb mutants is highly variable. Taking advantage of hypomorphic mutants for the replicative DNA polymerase epsilon, which display constitutive replicative stress, we show that Pol θ allows maintenance of meristem activity when DNA replication is partially compromised. Furthermore, we found that the phenotype of Pol θ mutants can be aggravated by modifying their growth conditions, suggesting that environmental conditions impact the basal level of replicative stress and providing evidence for a link between plants' responses to adverse conditions and mechanisms involved in the maintenance of genome integrity.


Tropical freshwater ecosystems have lower bacterial growth efficiency than temperate ones.
Current models and observations indicate that bacterial respiration should increase and growth efficiency (BGE) should decrease with increasing temperatures. However, these models and observations are mostly derived from data collected in temperate regions, and the tropics are under-represented. The aim of this work was to compare bacterial metabolism, namely bacterial production (BP) and respiration (BR), bacterial growth efficiency (BGE) and bacterial carbon demand (BCD) between tropical and temperate ecosystems via a literature review and using unpublished data. We hypothesized that (1) tropical ecosystems have higher metabolism than temperate ones and, (2) that BGE is lower in tropical relative to temperate ecosystems. We collected a total of 498 coupled BP and BR observations (N total = 498; N temperate = 301; N tropical = 197), calculated BGE (BP/(BP+BR)) and BCD (BP+BR) for each case and examined patterns using a model II regression analysis and compared each parameter between the two regions using non-parametric Mann-Whitney U test. We observed a significant positive linear regression between BR and BP for the whole dataset, and also for tropical and temperate data separately. We found that BP, BR and BCD were higher in the tropics, but BGE was lower compared to temperate regions. Also, BR rates per BP unit were at least two fold higher in the tropics than in temperate ecosystems. We argue that higher temperature, nutrient limitation, and light exposure all contribute to lower BGE in the tropics, mediated through effects on thermodynamics, substrate stoichiometry, nutrient availability and interactions with photochemically produced compounds. More efforts are needed in this study area in the tropics, but our work indicates that bottom-up (nutrient availability and resource stoichiometry) and top-down (grazer pressure) processes, coupled with thermodynamic constraints, might contribute to the lower BGE in the tropics relative to temperate regions.


Research Weaving: Visualizing the Future of Research Synthesis.
We propose a new framework for research synthesis of both evidence and influence, named research weaving. It summarizes and visualizes information content, history, and networks among a collection of documents on any given topic. Research weaving achieves this feat by combining the power of two methods: systematic mapping and bibliometrics. Systematic mapping provides a snapshot of the current state of knowledge, identifying areas needing more research attention and those ready for full synthesis. Bibliometrics enables researchers to see how pieces of evidence are connected, revealing the structure and development of a field. We explain how researchers can use some or all of these tools to gain a deeper, more nuanced understanding of the scientific literature.


Guanidinium analogues as probes of the squid axon sodium pore. Evidence for internal surface charges.
We have investigated the reduction of steady state sodium channel currents by a monovalent and a divalent guanidinium analogue. The amount of block by the divalent compound at a constant membrane potential was dramatically reduced by an increase in the internal salt concentration. Channel block by the monovalent molecule was a less steep function of salt concentration. These results would be expected if there were negative charges near the sodium pore that produced a local accumulation of the cationic blocking ions. According to this view, the ionic strength dependence of block results from changes in surface potential. The divalent blocker would be expected to be more sensitive to ionic strength owing to its larger valence. Our results can be quantitatively described by a simple ionic double-layer model with an effective surface charge density of about -1 e/250 A2 in the vicinity of the pore.


Optimization of Patterned Surfaces for Improved Superhydrophobicity through Cost-Effective Large-Scale Computations.
The pattern design of superhydrophobic surfaces can be significantly aided by computations that predict the Cassie-Baxter (CB) to Wenzel (W) transition, which is responsible for the break-down of superhydrophobic behavior. We present a computational framework for the optimization of patterned surfaces based on the energy barriers of the CB-W transitions which comprises the following elements: (a) design of structured surface patterns, for example, arrays of pillars, with parameterized geometric features such as size, pitch, slope, and roundness. (b) Computation of the wetting states with a modified Young-Laplace equation that facilitates the introduction of solid/liquid interactions for complex surface patterns and has significantly lower computational cost than other commonly used methods, such as the volume-of-fluid, phase-field, and so forth. (c) Incorporation of the modified Young-Laplace in the simplified string method, allowing the calculation of the minimum energy paths of wetting transitions which, apart from the energy barriers, also reveal the transition mechanisms (CB failure modes). (d) Accommodation of large-scale problems with good parallel performance and scalability on multicore-distributed memory systems using fast iterative solvers and the Message Passing Interface communication protocol. We demonstrate the computational framework with a shape optimization study of inverted conical frustum pillars. The optimization objective function is the resistance to the CB-W transition, which is quantified by the energy barrier-a relatively large energy barrier suggests improved superhydrophobicity. We also report the parallel performance, in terms of parallel speedup for problems ranging from three hundred thousands to 12 million degrees of freedom, solved using up to 40 processing cores.


Diagnosis and treatment of deep vein thrombosis.
Deep vein thrombosis and pulmonary embolism are important clinical disorders that affect patients in many medical and surgical specialties. In North America, deep vein thrombosis results in hospitalization of up to 600,000patients per year. Pulmonary embolism is also a serious problem that occurs in more than 500,000patients per year, of whom approximately 200,000will die. Almost half of those patients who die will be terminally ill or suffer an incurable disease, but the remainder of the deaths occur in patients who other- wise could have recovered completely.'


[Conditions for reciprocal conversion of oligomeric forms of heart mitochondrial creatine kinase].
A procedure for purifying creatine kinase from bovine heart mitochondria, including enzyme extraction from mitochondria with salt solutions, concentration on cellulose phosphate gel and gel filtration on Sephacryl S-300 has been developed. Using ultracentrifugation in a sucrose density gradient and gel filtration, it was demonstrated that mitochondrial creatine kinase is present in solution as a mixture of two main forms, i. e., an octamer and a dimer. The distribution of the oligomeric forms is not influenced by changes in the ionic strength from 0.02 to 0.25, temperature (5-20 degrees C), freezing-thawing and the nature of monovalent anions (Cl-, NO3-, CH3COO-) and cations (Na+, K+) present in the medium. At pH 6.0, the predominant form is the octamer; an increase in pH induces its dissociation. An equilibrious mixture of the creatine kinase reaction substrates in the presence of Mg2+ also causes octamer dissociation; no dissociation is observed in the absence of Mg2+ or in the presence of one of the substrates. The non-working couple of substrates, Mg-ADP and creatine, causes dissociation of the octamer in the presence of Cl-, but not of CH3COO-. It is assumed that the dissociating effect of the substrates is due to conformational changes in the subunits concomitant with the formation of the creatine kinase active center in the course of catalysis. At physiological concentrations of nucleotide substrates, the degree of octamer dissociation depends on pH, creatine phosphate/creatine ratio and Pi. It is assumed that the above factors may regulate the reversible conversion of the octamer into the dimer in vivo.


1,25-Dihydroxyvitamin D deficiency is associated with preterm birth in African American and Caucasian women.
Vitamin (vit) D deficiency and preterm birth (PTB) are more prevalent among African American (AA) women compared to caucasian (Cau) women. Because vit D is important in regulating cell-mediated immune responses, vit D insufficiency or deficiency during pregnancy may enhance inflammation in pregnant women and increase the risk of PTB. In this study, circulatory levels of 25-hydroxy (OH) and 1,25-dihydroxy (OH)2 vit D were measured using chemiluminescence and radioimmunoassay techniques, respectively, in AA (n = 108) and Cau (n = 84) women who delivered at term and preterm. The results from this study suggest that the serum levels of the 25-(OH) vit D concentrations tend to decrease (P = .06) in the Cau women who delivered at preterm compared to those delivering at term. However, the 25-(OH) vit D levels in Cau and AA between term and preterm deliveries were not significantly different. The serum levels of 1,25-(OH)2 vit D were found to be significantly lower in AA women compared to Cau women (P < .02) at term, and in the Cau (P < .01) and AA (P < .04) women delivering at preterm compared to those delivering at term. One-way analysis of variance demonstrated that 1,25-(OH)2 vit D levels were significantly lower in participants delivering at preterm (<34 weeks and between 34 and 37 weeks) compared to those delivering at term (>37 weeks).These results suggest that low levels of serum 1,25-(OH)2 vit D are associated with PTB, and vit D can potentially be used as a novel diagnostic marker in the detection of PTB.


Relationship between parity and clinical and biological features in patients with systemic sclerosis.
To assess the influence of parity on the clinical and biological features of systemic sclerosis (SSc). We recorded the following clinical and biological data of 100 consecutive women with SSc: age, disease duration before diagnosis, cutaneous extension of sclerosis according to LeRoy's classification, pulmonary involvement, and antinuclear antibodies. We compared these features to the number and sex of children who were born before SSc onset. Date of birth of the first children was systematically recorded. Patients with limited SSc had more children before SSc onset than patients with diffuse SSc (2.4 +/- 1.8 vs 1.7 +/- 1.5; p < 0.05). The interval between first birth and SSc onset was shorter for patients with limited SSc than for patients with diffuse SSc (11.0 +/- 9.9 vs 23.5 +/- 14.5 yrs; p < 0.01). Patients with pulmonary fibrosis had more children than patients without pulmonary fibrosis (2.5 +/- 1.9 vs 2.0 +/- 1.6; p < 0.05). Age at first birth was significantly higher when the child was a girl than a boy (26.8 +/- 7.5 vs 22.9 +/- 5.3 yrs; p < 0.05). The interval between the first birth and SSc onset was shorter when the child was a girl than a boy (16.2 +/- 9.6 vs 25.4 +/- 13.4 yrs; p < 0.05). Pregnancy related microchimerism could be preferentially associated with limited SSc and pulmonary fibrosis. Microchimerism may be facilitated in cases in which the fetus is female.


Understanding postoperative fatigue.
Performance characteristics of the central nervous, cardiovascular, respiratory and muscular systems in man postoperatively have received little investigative attention, despite the well known syndrome of postoperative fatigue. The impairmen in perception and psychomotor skills that has been shown to result from caloric restriction, bedrest, sedation and sleep deprivation suggests that a similar deficit may occur after surgical procedures. After a simple elective surgical procedure, maximal oxygen uptake decreases and the adaptability of heart rate to submaximal workloads is impaired. Similar deleterious effects on cardiorespiratory performance have been documented with starvation and bedrest; an understanding of cardiorespiratory performance postoperatively awaits further investigation. Maximal muscular force of contraction is also impaired by caloric restriction and bedrest, suggesting that similar effects may be seen in the postoperative state, although this has not been studied. A better understanding of the syndrome of postoperative fatigue could be achieved by a descriptive analysis of physiologic performance postoperatively. Such descriptive data could form the basis for objective evaluation of therapeutic measures intended to improve performance, such as nutritional supplementation and pharmacologic intervention. The observation that exercise with the patient in the supine position may decrease the impairment in maximal aerobic power otherwise expected in immobilized patients suggests that controlled exercise therapy may be of value in reducing physiologic impairment postoperatively.


Decreased metabolic uptake in tuberculous pericarditis indicating response to antituberculosis therapy on FDG PET/CT.
Early diagnosis and adequate treatment of tuberculosis are important for disease control and prevention of complication. However, diagnosing disease is frequently delayed because of difficulties of bacilli isolation or reproduction in cultures, and also, the decision of the efficiency of treatment sometimes can be impossible. FDG PET has become a promising imaging modality in the field of infection and inflammation, especially for the extension and severity of disease. Here, we describe an unusual case of tuberculous pericarditis that shows marked increased FDG uptake on initial scan, with decreasing metabolic activity on follow-up scan indicating response to antituberculosis therapy.


Linkage analysis of chromosome 1q markers in 136 prostate cancer families. The Cancer Research Campaign/British Prostate Group U.K. Familial Prostate Cancer Study Collaborators.
Prostate cancer shows evidence of familial aggregation, particularly at young ages at diagnosis, but the inherited basis of familial prostate cancer is poorly understood. Smith et al. recently found evidence of linkage to markers on 1q, at a locus designated "HPC1," in 91 families with multiple cases of early-onset prostate cancer. Using both parametric and nonparametric methods, we attempted to confirm this finding, in 60 affected related pairs and in 76 families with three or more cases of prostate cancer, but we found no significant evidence of linkage. The estimated proportion of linked families, under a standard autosomal dominant model, was 4%, with an upper 95% confidence limit of 31%. We conclude that the HPC1 locus is responsible for only a minority of familial prostate cancer cases and that it is likely to be most important in families with at least four cases of the disease.


Nutritional interventions for survivors of childhood cancer.
Childhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases. The primary aim of this review was to assess the efficacy of a range of nutritional interventions designed to improve the nutritional intake of childhood cancer survivors, as compared to a control group of childhood cancer survivors who did not receive the intervention. Secondary objectives were to assess metabolic and cardiovascular risk factors, measures of weight and body fat distribution, behavioural change, changes in knowledge regarding disease risk and nutritional intake, participants' views of the intervention, measures of health status and quality of life, measures of harm associated with the process or outcomes of the intervention, and cost-effectiveness of the intervention We searched the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 3), MEDLINE/PubMed (from 1945 to April 2013), and Embase/Ovid (from 1980 to April 2013). We ran the search again in August 2015; we have not yet fully assessed these results, but we have identified one ongoing trial. We conducted additional searching of ongoing trial registers - the International Standard Randomised Controlled Trial Number register and the National Institutes of Health register (both screened in the first half of 2013) - reference lists of relevant articles and reviews, and conference proceedings of the International Society for Paediatric Oncology and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (both 2008 to 2012). We included all randomised controlled trials (RCTs) that compared the effects of a nutritional intervention with a control group which did not receive the intervention in this review. Participants were childhood cancer survivors of any age, diagnosed with any type of cancer when less than 18 years of age. Participating childhood cancer survivors had completed their treatment with curative intent prior to the intervention. Two review authors independently selected and extracted data from each identified study, using a standardised form. We assessed the validity of each identified study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE criteria to assess the quality of each trial. Three RCTs were eligible for review. A total of 616 participants were included in the analysis. One study included participants who had been treated for acute lymphoblastic leukaemia (ALL) (275 participants). Two studies included participants who had all forms of paediatric malignancies (266 and 75 participants). All participants were less than 21 years of age at study entry. The follow-up ranged from one month to 36 months from the initial assessment. All intended outcomes were not evaluated by each included study. All studies looked at different interventions, and so we were unable to pool results. We could not rule out the presence of bias in any of the studies.There was no clear evidence of a difference in calcium intake at one month between those who received the single, half-day, group-based education that focused on bone health, and those who received standard care (mean difference (MD) 111.60, 95% confidence interval (CI) -258.97 to 482.17; P = 0.56, low quality evidence). A regression analysis, adjusting for baseline calcium intake and changes in knowledge and self-efficacy, showed a significantly greater calcium intake for the intervention as compared with the control group at the one-month follow-up (beta coefficient 4.92, 95% CI 0.33 to 9.52; P = 0.04). There was statistically significant higher, self-reported milk consumption (MD 0.43, 95% CI 0.07 to 0.79; P = 0.02, low quality evidence), number of days on calcium supplementation (MD 11.42, 95% CI 7.11 to 15.73; P < 0.00001, low quality evidence), and use of any calcium supplementation (risk ratio (RR) 3.35, 95% CI 1.86 to 6.04; P < 0.0001, low quality evidence), with those who received this single, face-to-face, group-based, health behaviour session.There was no clear evidence of a difference in bone density Z-scores measured with a dual-energy X-ray absorptiometry (DEXA) scan at 36 months follow-up (MD -0.05, 95% CI -0.26 to 0.16; P = 0.64, moderate quality evidence) between those who received calcium and vitamin D supplementation combined with nutrition education and those who received nutrition education alone. There was also no clear evidence of a difference in bone mineral density between the intervention and the control group at the 12-month (median difference -0.17, P = 0.99) and 24-month follow-up (median difference -0.04, P = 0.54).A single multi-component health behaviour change intervention, focusing on general healthy eating principles, with two telephone follow-ups brought about a 0.17 lower score on the four-point Likert scale of self-reported junk food intake compared with the control group (MD -0.17, 95% CI -0.33 to -0.01; P = 0.04, low quality evidence); this result was statistically significant. There was no clear evidence of a difference between the groups in the self-reported use of nutrition as a health protective behaviour (MD -0.05, 95% CI -0.24 to 0.14; P = 0.60, low quality evidence). Due to a paucity of studies, and the heterogeneity of the studies included in this review, we are unable to draw conclusions regarding the effectiveness of nutritional interventions for use with childhood cancer survivors. Although there is low quality evidence for the improvement in health behaviours using health behaviour change interventions, there remains no evidence as to whether this translates into an improvement in dietary intake. There was also no evidence that the studies reduced the risk of cardiovascular and metabolic disorders in childhood cancer survivors, although no evidence of effect is not the same as evidence of no effect. This review highlights the need for further well designed trials to be implemented in this population.


Optimization of rhabdomyosarcoma disseminated disease assessment by flow cytometry.
Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. Circulating tumor cells in peripheral blood or disseminated to bone marrow, a concept commonly referred to as minimal residual disease (MRD), are thought to be key to the prediction of metastasis and treatment efficacy. To date, two MRD markers, MYOD and MYOGENIN, have been tested; however, MRD detection continues to be challenging mainly owing to the closeness of the detection limit and the discordance of both markers in some samples. Therefore, the addition of a third marker could be useful for more accurate MRD assessment. The PAX3 gene is expressed during embryo development in all myogenic precursor cells in the dermomyotome. As RMS cells are thought to originate from these muscle precursor cells, they are expected to be positive for PAX3. In this study, PAX3 expression was characterized in cancer cell lines and tumors, showing wide expression in RMS. Detection sensitivities by quantitative polymerase chain reaction (qPCR) of the previously proposed markers, MYOD and MYOGENIN, were similar to that of PAX3, thereby indicating the feasibility of its detection. Interestingly, the flow cytometry experiments supported the usefulness of this technique in the quantification of MRD in RMS using PAX3 as a marker. These results indicate that flow cytometry, albeit in some cases slightly less sensitive, can be considered a good approach for MRD assessment in RMS and more consistent than qPCR, especially owing to its greater specificity. Furthermore, fluorescence-activated cell sorting permits the recovery of cells, thereby providing material for further characterization of circulating or disseminated cancer cells.


Biomedical research involving patients with disorders of consciousness: ethical and legal dimensions.
THE DIRECTIVE 2001/20/UE AND THE RESEARCH INVOLVING PATIENTS WITH DOCS: Research involving patients with disorders of consciousness (DOCs) deserves special ethical and legal attention because of its Janus-faced nature. On the one hand, it raises concerns about the risk to expose the involved subjects to disproportionate risks not respecting their individual dignity, particularly their right to be cared for; on the other hand, research is an essential tool in order to improve the clinical condition of patients with DOCs. The present paper concerns the ethical and legal dimensions of biomedical research involving patients with disorders of consciousness. In particular, it focuses on informed consent to experimental treatments, which is a challenging issue both from an ethical and legal point of view. The first part reads the Directive 2001/20/EU in the light of the experimentation of patients with DOCs, and suggests a revision in order to better assess the issue of informed consent. THE PARTICULAR CASE OF INFORMED CONSENT FOR OBSERVATIONAL STUDIES OF NON-COMMUNICATIVE PATIENTS: The second part presents an informed consent form for studies through video-recording of patients unable to communicate their own consent. This form has been elaborated by the bioethics unit of the project "Review of the nosography of vegetative states: application of methods of behavioral analysis to individuals in coma or vegetative state" developed at the Italian National Institute of Health. RELEVANCE OF THE SUGGESTED FORM: The paper describes the conceptual framework of the form for informed consent to studies through video-recoding, which is a relevant example of what issues should be included in an informed consent for any type of studies through video-recording of patients unable to express their own consent. The article has been sent on November the 7th 2013, before the adoption of the Regulation (EU) no. 536/2014 (and consequent abrogation of the Directive 2001/20/EU) and the release of the new edition of the Italian Code of Medical Ethics.


Amelioration effects of the soybean lecithin-gallic acid complex on iron-overload-induced oxidative stress and liver damage in C57BL/6J mice.
Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored. This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded. In vitro, free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo, C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques. In vitro, SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC50 values equal to 24.92 and 128.36 μg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%). These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.


The extracellular matrix of the lung and airway responsiveness in asthma.
The extracellular matrix is the main determinant of the structure and of mechanical behaviour of the lung. The extracellular matrix is also responsible for the mechanical interdependence between airway and parenchyma due to the alveolar attachments to the airways. Asthma is characterized by bronchial hyperresponsiveness, airway remodelling and inflammation, and an altered extracellular matrix may play a role in all these functional and structural abnormalities. The excessive airway narrowing observed in asthma may be related to the altered viscoelastic properties of lung parenchyma and airway wall, determining a decrease in the mechanical load opposing the airways' smooth muscle contraction. Indeed, an altered extracellular matrix deposition in asthma in humans, has been demonstrated. In addition, in the asthmatic lung, the matrix seems to contribute to airway inflammation, airway remodelling, and to those alterations of the smooth muscle function of the airway and morphology typical of asthma.


[A comparison of several convenient methods of estimating effective energy in X-ray computed tomography].
The measurement of half-value layers (HVLs) and effective energy in X-ray computed tomography (CT) using conventional nonrotating methods is regarded as a highly challenging task, as it necessitates the use of a nonrotating X-ray tube and the assistance of service engineers. Several convenient methods have been proposed to circumvent this limitation; however, to the best of our knowledge, there are no reports that provide a comparative study on the accuracy of each method. This prompted us to compare the accuracy and practicality of each method. Effective energy was calculated using four methods: lead shielding, copper pipe, localization, and inner-metal center-air ratio (IMCAR). The accuracy of each method for the measurement of effective energy in X-ray CT was evaluated and compared with the conventional nonrotating method. The differences in the effective energy were 0.0 to 0.6 keV (0.0% to 1.1%) for lead shielding, -2.2 to -0.6 keV (1.4% to 4.3%) for copper pipe, 4.7 to 16.7 keV (9.9% to 31.4%) for localization, and -7.4 to -0.3 keV (0.6% to 17.5%) for the IMCAR method. The results indicate that the lead shielding method is the most accurate and practical method of estimating effective energy in X-ray CT.


Dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in a patient with acquired reactive perforating collagenosis.
Bullous pemphigoid (BP) is a common autoimmune blistering disorder with unknown etiology. Recently, increasing numbers of BP cases which developed under the medication with dipeptidyl peptidase-4 inhibitors (DPP4i), widely used antihyperglycemic drugs, have been reported in published works. Here, we report a case of DPP4i (teneligliptin)-associated BP that developed in a 70-year-old Japanese man. Interestingly, the patient had acquired reactive perforating collagenosis (ARPC), which is also known to be associated with the onset of BP. In the present case, clinical, histopathological and immunological findings suggested that DPP4i rather than ARPC was associated with the onset of BP.


Maintenance of blood pressure in normotensive dogs by endothelin.
The role of endothelin (ET)-1 in blood pressure homeostasis and the interaction with the renin-angiotensin system (RAS) was investigated in normotensive conscious dogs. ETA receptors were blocked by LU-135252 (1-30 mg/kg); trandolapril (2 mg/kg) or losartan (10 mg/kg) was used to inhibit the RAS. LU-135252 in oral doses of 3-30 mg/kg significantly reduced mean arterial pressure (MAP) by approximately 10 mmHg maximally, whereas trandolapril or losartan were without any effect. MAP reduction was more pronounced when LU-135252 was combined with either losartan (-15.5 +/- 3.2 mmHg; 2 h postadministration; P < 0.05) or trandolapril (-30.9 +/- 3.6 mmHg; P < 0.05). When endogenous nitric oxide (NO) generation was blocked but NO concomitantly infused, this synergistic effect on MAP was prevented. The data show that ET-1 contributes to the maintenance of blood pressure via ETA receptors. Furthermore, ET-1 and ANG II play a prominent role in the control of blood pressure by opposing the effects of NO. The pronounced blood pressure fall after combined blockade of ETA receptors and the RAS may be mediated by an enhanced release of NO.


Enzymatic decolorization of anthraquinone and diazo dyes using horseradish peroxidase enzyme immobilized onto various polysulfone supports.
In this study, covalent immobilization of the horseradish peroxidase (HRP) onto various polysulfone supports was investigated. For this purpose, different polysulfones were methacrylated with methacryloyl chloride, and then, nonwoven fabric samples were coated by using solutions of these methacrylated polysulfones. Finally, support materials were immersed into aquatic solution of HRP enzyme for covalent immobilization. Structural analysis of enzyme immobilization onto various polysulfones was confirmed with Fourier transform infrared spectroscopy, atomic force microscopy, and proton nuclear magnetic resonance spectroscopy. Decolorization of textile diazo (Acid Black 1) and anthraquinone (Reactive Blue 19) dyes was investigated by UV-visible spectrophotometer. Covalently immobilized enzyme has been used seven times in freshly prepared dye solutions through 63 days. Dye decolorization performance of the immobilized systems was observed that still remained high (70%) after reusing three times. Enzyme activities of immobilized systems were determined and compared to free enzyme activity at different conditions (pH, temperature, thermal stability, storage stability). Enzyme activities of immobilized systems and free enzyme were also investigated at the different temperatures and effects of temperature and thermal resistance for different incubation time at 50 °C. In addition, storage activity of free and immobilized enzymes was determined at 4 °C at different incubation days.


Correlation Between Delivery Mode and Pelvic Organ Prolapse Evaluated by Four-Dimensional Pelvic Floor Ultrasonography.
BACKGROUND This study explored symptoms and signs of pelvic organ prolapse (POP) evaluated by 4-dimensional pelvic floor ultrasonography and analyzed the relationship between delivery mode and POP. MATERIAL AND METHODS A total of 578 women who underwent 4-dimensional transperineal ultrasound were enrolled in this study. Obstetric history together with other clinical information were gathered from clinical questionnaires and gynecologists. Patients were thereafter classified into 4 groups: women with normal vaginal delivery, women with forceps delivery, women with cesarean, and nullipara women. We assessed symptoms and signs of POP among these 4 groups by use of 2 evaluation methods. The first method was clinical assessment applying International Continence Society (ICS) pelvic organ prolapse quantification (POP-Q). The second method was the use of ultrasonography in the quantification of anterior, middle, and posterior compartment prolapse. RESULTS Nulliparae women exhibited the lowest probability of POP (POP-Q: cystocele of 15.6%, uterine prolapse of 11.1%, rectocele of 20.0%; ultrasound exam: 6.7%, 8.9%, 13.3% in sequence), while women with forceps delivery had the highest probability of POP (POP-Q: 59.6%, 50.8%, 63.2% in sequence; ultrasound exam: 45.6%, 52.6%, 42.1% in sequence). Regarding the correlation between POP and delivery mode, the adjusted odds ratio was 2.40 (95%CI: 1.301~4.590) and 3.20 (95%CI: 1.651~6.121) in the normal vaginal delivery group and forceps group, respectively, compared with the cesarean group. CONCLUSIONS Four-dimensional pelvic floor ultrasonography can be used as a preferred method in evaluating POP. Regarding the relationship between delivery mode and POP, there is a significant correlation between vaginal delivery and POP.


Nephrotic state substantially enhances apparent mycophenolic acid clearance .
; Several factors may decrease plasma protein binding of mycophenolic acid (MPA), the active compound of mycophenolate mofetil (MMF), and potentially enhance its clearance. It is unclear if MMF dose adjustments are required for the treatment of steroid-resistant nephrotic syndrome (SRNS). Therapeutic drug monitoring of MPA levels is not widely utilized in the treatment of steroid-resistant nephrotic syndrome (SRNS). In this retrospective cohort study, the authors measured 182 MPA predose trough levels (1 - 45/patient, HPLC/MS/MS) in 10 patients aged 0.9 - 18 years with SRNS treated with MMF. Apparent MPA clearances (CL/F) were calculated from the dose/estimated AUC. Anthropomorphic data, blood parameters, and proteinuria levels were collected from electronic health records. We compared all parameters with apparent MPA clearance, including albumin level, microalbuminuria, proteinuria, triglycerides, cystatin C, and estimated glomerular filtration rate (eGFR), analyzed by nonlinear regression analysis. Median apparent clearance was 22.63 L/h (IQR 17.1, 32.47). Significant correlations were found between MPA Cl/F and serum albumin (r = -0.47), microalbuminuria (+0.54), triglycerides (+0.33), and cholesterol (+0.32). CL/F increased from a minimum of 2.4 L/h for the highest albumin levels to a maximum of 59.9 for albumin levels < 25 g/L. Similarly, the apparent MPA clearance increased significantly with higher triglycerides and lower hematocrit. This study confirms a significant increase of the apparent clearance of MPA with low serum albumin, microalbuminuria, proteinuria, high triglycerides, and low hematocrit. The 20-fold increase of the apparent clearance suggests that MMF unresponsiveness in the nephrotic state may be related to MPA underexposure. .


Reasons for entering treatment reported by initially treatment-resistant patients with substance use disorders.
Many individuals with substance use disorders are resistant to entering formal treatment, despite the negative consequences that plague their own lives and the lives of concerned significant others (CSOs). Community Reinforcement and Family Training (CRAFT) has been developed as an effective strategy for helping family members who are concerned about the alcohol/drug use of a loved one who refuses to seek treatment. The present study explored reasons and feelings that played a part in these resistant individuals' (identified patients [IPs]) decision to begin treatment. Written statements and feelings of 36 initially treatment-refusing IPs, who were engaged into treatment via their CRAFT-trained CSOs, were examined upon entering treatment. Self-report forms assessed three complementary domains about entering treatment: (1) feelings about coming for treatment, (2) important reasons for entering treatment, and (3) reasons for entering treatment narratives. It was shown that the occurrences of self-reported positive emotions and statements that expressed a positive wish for change outweighed negative feelings and statements. Although conceivably these CRAFT-exposed IPs may have provided different responses than other treatment-seeking populations, the current study's strong IP reports of positive feelings, reasons, and narrative statements regarding treatment entry nonetheless address potential concerns that treatment-refusing IPs might only enter treatment if felt coerced by family members and while experiencing salient negative feelings overall.


Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD.
Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.


Simulation of light transport in scintillators based on 3D characterization of crystal surfaces.
In the development of positron emission tomography (PET) detectors, understanding and optimizing scintillator light collection is critical for achieving high performance, particularly when the design incorporates depth-of-interaction (DOI) encoding or time-of-flight information. Monte-Carlo simulations play an important role in guiding research in detector designs and popular software such as GATE now include models of light transport in scintillators. Although current simulation toolkits are able to provide accurate models of perfectly polished surfaces, they do not successfully predict light output for other surface finishes, for example those often used in DOI-encoding detectors. The lack of accuracy of those models mainly originates from a simplified description of rough surfaces as an ensemble of micro-facets determined by the distribution of their normal, typically a gaussian distribution. The user can specify the standard deviation of this distribution, but this parameter does not provide a full description of the surface reflectance properties. We propose a different approach based on 3D measurements of the surface using atomic force microscopy. Polished and rough (unpolished) crystals were scanned to compute the surface reflectance properties. The angular distributions of reflectance and reflected rays were computed and stored in look-up tables (LUTs). The LUTs account for the effect of incidence angle and were integrated in a light transport model. Crystals of different sizes were simulated with and without reflector. The simulated maximum light output and the light output as a function of DOI showed very good agreement with experimental characterization of the crystals, indicating that our approach provides an accurate model of polished and rough surfaces and could be used to predict light collection in scintillators. This model is based on a true 3D representation of the surface, makes no assumption about the surface and provides insight on the optical behaviour of rough crystals that can play a critical role in optimizing the design of PET detectors. This approach is also compatible with existing simulation toolkits and next steps include the implementation in GATE.


Different human cervical carcinoma cell lines show similar transcription patterns of human papillomavirus type 18 early genes.
Transcription of human papillomavirus type 18 (HPV18) DNA in the human cervical carcinoma cell lines HeLa, C4-1 and SW756 was studied by nucleotide sequence analysis of HPV18-positive cDNA clones isolated from a HeLa, C4-1 and SW756 cDNA library, respectively, and the cDNA sequences were used to predict the potential encoded proteins. The cDNA clones from all three cell lines were found to be derived from virus-cell fusion transcripts in which 3'-terminal host cell sequences (different for each cell line) were spliced to 5'-terminal exon sequences from the HPV18 E6-E7-E1 region. Three different types of cDNA clones can be distinguished according to the splicing patterns observed in the 5' terminal HPV18 sequences. They carry as potential protein-coding regions the HPV18 specific open reading frames E6 and E6* (generated by splicing and identical with E6 up to the E6* splice junction), E7 and E1 (only in HeLa). Translation of specific cellular genes from the chimeric viral-cellular transcripts seems to be unlikely. The mapping of the 5'-ends of the virus-cell fusion transcripts indicates that transcription is initiated at a viral promoter. The similar patterns of HPV18 transcription in the three different cervical carcinoma cell lines suggest a functional role of HPV18 early genes for the malignant phenotype of these cells.


An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation.
The development of the mononuclear phagocyte system requires macrophage colony-stimulating factor (CSF-1) signaling through the CSF-1 receptor (CSF1R, CD115). We examined the effect of an antibody against CSF1R on macrophage homeostasis and function using the MacGreen transgenic mouse (csf1r-enhanced green fluorescent protein) as a reporter. The administration of a novel CSF1R blocking antibody selectively reduced the CD115(+)Gr-1(neg) monocyte precursor of resident tissue macrophages. CD115(+)Gr-1(+) inflammatory monocytes were correspondingly increased, supporting the view that monocytes are a developmental series. Within tissue, the antibody almost completely depleted resident macrophage populations in the peritoneum, gastrointestinal tract, liver, kidney, and skin, but not in the lung or female reproductive organs. CSF1R blockade reduced the numbers of tumor-associated macrophages in syngeneic tumor models, suggesting that these cells are resident type macrophages. Conversely, it had no effect on inflammatory monocyte recruitment in models, including lipopolysaccharide-induced lung inflammation, wound healing, peritonitis, and severe acute graft-versus-host disease. Depletion of resident tissue macrophages from bone marrow transplantation recipients actually resulted in accelerated pathology and exaggerated donor T-cell activation. The data indicate that CSF1R signaling is required only for the maturation and replacement of resident-type monocytes and tissue macrophages, and is not required for monocyte production or inflammatory function.


Second Near-Infrared Aggregation-Induced Emission Fluorophores with Phenothiazine Derivatives as the Donor and 6,7-Diphenyl-[1,2,5]Thiadiazolo[3,4-g]Quinoxaline as the Acceptor for In Vivo Imaging.
Traditional organic fluorophores generally have hydrophobic conjugated backbones and exhibit an aggregation-caused quenching emission property, which limits greatly their applications in the biological field. Aggregation-induced emission (AIE) fluorophores can breakthrough this shortcoming and are more promising in biological imaging. In this paper, we synthesized three novel donor-acceptor-donor-type second near-infrared (NIR-II) fluorophores and studied their geometric and electronic structures and photophysical properties by both theoretical and experimental studies. All the three fluorophores had typical AIE characteristics, and their emission wavelength spanned the traditional near-infrared and NIR-II regions. They exhibited much stronger fluorescence after being encapsulated in polymer nanoparticles (NPs) than in solutions, and the fluorophore-loaded NPs had desirable biosafety and significant tumor accumulation, indicating that they have great application potentials in tumor detection.


Meta-analysis in genome-wide association studies.
The advent of genome-wide association studies has allowed considerable progress in the identification and robust replication of common gene variants that confer susceptibility to common diseases and other phenotypes of interest. These genetic effect sizes are almost invariably moderate to small in magnitude and single studies, even if large, are underpowered to detect them with confidence. Meta-analysis of many genome-wide association studies improves the power to detect more associations, and to investigate the consistency or heterogeneity of these associations across diverse datasets and study populations. In this review, we discuss the key methodological issues in the set-up, information gathering and processing, and analysis of meta-analyses of genome-wide association datasets. We illustrate, as an example, the application of meta-analysis methods in the elucidation of common genetic variants associated with Type 2 diabetes. Finally, we discuss the prospects and caveats for future application of meta-analysis methods in the genome-wide setting.


Isolate-dependent growth, virulence, and cell wall composition in the human pathogen Aspergillus fumigatus.
The ubiquitous fungal pathogen Aspergillus fumigatus is a mediator of allergic sensitization and invasive disease in susceptible individuals. The significant genetic and phenotypic variability between and among clinical and environmental isolates are important considerations in host-pathogen studies of A. fumigatus-mediated disease. We observed decreased radial growth, rate of germination, and ability to establish colony growth in a single environmental isolate of A. fumigatus, Af5517, when compared to other clinical and environmental isolates. Af5517 also exhibited increased hyphal diameter and cell wall β-glucan and chitin content, with chitin most significantly increased. Morbidity, mortality, lung fungal burden, and tissue pathology were decreased in neutropenic Af5517-infected mice when compared to the clinical isolate Af293. Our results support previous findings that suggest a correlation between in vitro growth rates and in vivo virulence, and we propose that changes in cell wall composition may contribute to this phenotype.


Application of law to the childhood obesity epidemic.
Childhood obesity is in important respects a result of legal policies that influence both dietary intake and physical activity. The law must shift focus away from individual risk factors alone and seek instead to promote situational and environmental influences that create an atmosphere conducive to health. To attain this goal, advocates should embrace a population-wide model of public health, and policymakers must critically examine the fashionable rhetoric of consumer choice.


Resveratrol mitigate structural changes and hepatic stellate cell activation in N'-nitrosodimethylamine-induced liver fibrosis via restraining oxidative damage.
Resveratrol, a polyphenol, found in skin of red grapes, peanuts and berries possesses anti-inflammatory, anti-carcinogenic and lipid modulation properties. Here, we demonstrate in vivo antifibrotic activity of resveratrol in a mammalian model, wherein hepatic fibrosis was induced by N'-nitrosodimethylamine (NDMA) administration. Apart from being a potent hepatotoxin, NDMA is a known mutagen and carcinogen, as well. To induce hepatic fibrosis, rats were administered NDMA (i.p.) in 10mg/kgb.wt thrice/week for 21 days. Another group of animals received resveratrol supplement (10mg/kgb.wt) subsequent to NDMA administration and were sacrificed weekly. The changes in selected biomarkers were monitored to compare profibrotic effects of NDMA and antifibrotic activity of resveratrol. The selected biomarkers were: sera transaminases, ALP, bilirubin, liver glycogen, LPO, SOD, protein carbonyl content, ATPases (Ca(2+), Mg(2+), Na(+)/K(+)) and hydroxyproline/collagen content. Alterations in liver architecture were assessed by H&E, Masson's trichrome and reticulin staining of liver biopsies. Immuno-histochemistry and immunoblotting were employed to examine expression of α-SMA. Our results demonstrate that during NDMA-induced liver fibrosis transaminases, ALP, bilirubin, hydroxyproline and liver collagen increases, while liver glycogen is depleted. The decline in SOD (>65%) and ATPases, which were concomitant with the elevation in MDA and protein carbonyls, strongly indicate oxidative damage. Fibrotic transformation of liver in NDMA-treated rats was verified by histopathology, immuno-histochemistry and immunoblotting data, with the higher expressivity of α-SMA-positive HSCs being most established diagnostic immuno-histochemical marker of HSCs. Resveratrol-supplement refurbished liver architecture by significantly restoring levels of biomarkers of oxidative damage (MDA, SOD, protein carbonyls and membrane-bound ATPases). Therefore, we conclude that antifibrotic effect of resveratrol is due to restrained oxidative damage and down-regulation of α-SMA, which inhibits HSC activation to obstruct liver fibrosis.


Guarana (Paullinia cupana) but Not Low-Dose Caffeine Improves Cycling Time-Trial Performance Versus Placebo.
Guarana (GUA) seed extract, containing caffeine (CAF) and additional bioactive compounds, may positively affect mental performance, but evidence regarding exercise is limited. This investigation assessed acute GUA ingestion compared with CAF on endurance performance. Eleven endurance-trained noncyclists and cyclists (V˙O2peak = 49.7 ± 5.9, 60.4 ± 4.6 ml·kg·min-1) completed a double-blind, crossover experiment after ingesting (a) 100 mg CAF, (b) 500 mg GUA (containing 130 mg CAF), or (c) placebo (P) prior to 60-min fixed cycling workload (FIX) + 15-min time trial. Oxygen uptake, heart rate, respiratory exchange ratio, blood glucose, and lactate were not different (p ≥ .052) during FIX. A significant interaction (p = .042) for perceived exertion was observed at 50-min FIX with lower rating (p = .023) for GUA versus CAF but not compared with P. Work accumulated over 15-min time trial was greater (p = .038) for GUA versus P due to higher early (1-11 min) work outputs. Work performance favored (effect size = 0.18; 95% confidence interval [0.003, 0.355], p = .046) GUA (241.4 ± 39.9 kJ) versus P (232.1 ± 46.6 kJ), but CAF (232.3 ± 43.9) was not different from GUA (effect size = 0.19; 95% confidence interval [-0.022, 0.410], p = .079) or P. Postexercise strength loss was not attenuated with GUA (-5.6 ± 8.5%) or CAF (-8.3 ± 9.4%) versus P (-10.3 ± 5.1%). Acute GUA ingestion improved work performance relative to P, but effects were trivial to small and unrelated to altered substrate oxidation or muscular strength. Ergogenicity may involve central mechanisms reducing perceived effort with GUA (containing 130 mg caffeine). Due to issues related to identical matching of dosage, whether GUA confers additional benefits beyond its CAF content cannot be determined at present.


Advances in studies on acupuncture abstinence.
Acupuncture abstinence includes mainly abstaining from smoking, drinking and drug using by means of acupuncture therapy. In this paper, the curative effect, the stimulation methods, the therapeutic course, the psychological, demography and other factors on the therapeutic effect, and the progress in acupuncture abstinence are briefly introduced, and its development tendency is prospected. It is found that the therapeutic effects of acupuncture abstinence are not lower than those of other abstinence therapies. It is simple and easy to be performed, with little pain, little injury and little side-effects, inhibiting withdrawal syndrome, thus well accepted by the patients. It could be used if other withdrawal therapies show no apparent therapeutic effects.


Application Settings versus Fixed Photomultiplier Tube Voltages for Optimal Cytometer Stability over Time, and Effect on Reusing a Compensation Matrix.
In flow cytometry, a compensation matrix is commonly reused over time, especially in clinical laboratories, to save time and reagents. However, generating a same-day compensation matrix is considered the best practice by many experts. BD Biosciences developed Cytometer Setup and Tracking software to deliver proper instrument characterization, performance tracking, and stability. BD's "Application Settings" enable daily cytometer adjustments of photomultiplier tube (PMT) settings to correct for day-to-day variations in instrument performance. Here, we investigated if using Application Settings would improve data stability over time, including the impact on data stability when reusing a compensation matrix. We consecutively analyzed peripheral blood mononuclear cell (PBMC) aliquots from a single healthy donor together with 8-peak Rainbow beads and daily compensation controls (22 runs in total over 6.5 months). We found larger variation within both PBMC subset quantifications and median fluorescence intensity (MFI) levels when using Application Settings (i.e., daily adjusted PMTs) compared to fixed PMT voltages (both with the same Day 0 compensation matrix applied). This larger variation was partly due to errors in compensation, but was also seen for Rainbow beads MFI data (not impacted by compensation), and thus likely produced by imprecise adjustments of PMTs by Applications Settings. Notably, the larger variation observed with Application Settings was most pronounced on a few days of the experiment with very large deviations, whereas on most days Application Settings and Fixed PMTs performed similar. The present results call for caution in using Application Settings in longitudinal studies, especially if also reusing a compensation matrix. In contrast, reusing a compensation matrix over time with fixed PMT voltages yielded stable results comparable with running same-day compensation controls. © 2020 International Society for Advancement of Cytometry.


Impact of Language and Ethnicity on Pediatric Tracheostomy Outcomes.
To compare outcomes after tracheostomy between children from Spanish- and English-speaking families. Prospective cohort study. Tertiary care children's hospital. All children <18 years of age who had a tracheostomy placed between 2014 and 2020 were included. Comorbidities and postsurgical outcomes were compared between (1) children whose families preferred speaking Spanish or identified as Hispanic/Latino and (2) children from English-language or non-Hispanic families. A total of 339 children met inclusion, with 11% (37/339) from families identifying Spanish as their primary language and 33% (112/339) identifying as Hispanic. Spanish-speaking families were more likely to have tracheostomy-dependent children with cardiac conditions (65% vs 42%, P = .008) and high complexity (72% vs 49%, P = .007). Outcomes were similar regardless of language preference, with 45% (153/339) still tracheostomy dependent, 28% (94/339) decannulated, and 6.8% (23/339) deceased at a median follow-up of 1.77 years (interquartile range, 0.65-3.43). Severe neurocognitive disabilities were similar between Spanish- and English-language families (P > .05). Spanish language was not associated with times to decannulation or death in univariate or multiple regression models. A sensitivity analysis of self-identified Hispanic or Latino patients did not show significant differences for time to decannulation, death, or neurocognitive disability rates (P > .05). Spanish language and Hispanic ethnicity appear to have minimal impact on pediatric tracheostomy outcomes.


The relationship of Injury Severity Score and Glasgow Coma Score to rehabilitative potential in patients suffering traumatic brain injury.
The predictive utility of the Injury Severity Score (ISS) and Glasgow Coma Score (GCS) in relation to rehabilitative potential and functional outcome in traumatic brain injury (TBI) is untested. The purpose of this study was to define the relationship of ISS and GCS to rehabilitative potential using the functional independence measure (FIM) score. Trauma and inpatient rehabilitation (IR) registries were queried for demographic, disposition, and injury scoring data. FIM scores at admission (A) and discharge (D) were assessed including IR FIM gain (G). Analysis of variance was used to examine the relationship of ISS and GCS to FIM with predictive utility investigated through bivariate analysis. Of 5488 patients admitted to a Level I trauma center (1999-2000) 1437 suffered TBI with 285 (20%) entering IR. Compared with low-ISS patients the high-ISS patients had significantly lower FIM-A and FIM-D, but FIM-G was static. GCS results were similar, excluding FIM-G which was significantly higher for GCS < or = 8 compared with GCS > 8. Bivariate analysis revealed no ISS correlation with FIM-G (r = 0.16) and a weak GCS correlation (FIM-G r = -0.15). As prospective predictive measures ISS and GCS correlate weakly with rehabilitative potential in TBI patients. Severely injured patients including those with severe TBI have a rehabilitative gain toward functional independence that is similar to that of when compared with those less severely injured.


Integrating live cells with semiconductor devices: A biocompatibility assay.
There is increasing interest in the development of small hybrid cell-semiconductor systems for the non-invasive evaluation of the physiological state of a cell population. These miniature devices can be used in many areas of biomedical applications, ranging from basic research to drug screening during cancer chemosensitivity testing in clinics. A prerequisite for the biological and medical application of these devices is that cells retain their functional and growth properties when in contact with the semiconductor sensor material. The sensor surface is usually coated with dielectric silicon dioxide (SiO2 ) or a silicon nitride layer (Si3 N4 ); therefore, cellular adhesion to these materials and cellular viability on these surfaces are of crucial im-portance. This is especially true for bone cells that are sensitive to the surface microstructure. Therefore, we investigated the short-term (1-7 days) behavior of model bone cells (MG63 human osteosarcoma cells) grown on silicon samples coated with SiO2 . Cell adhesion and morphology were evaluated by scanning electron microscopy (SEM) 1 day after seeding and cell pro-liferation was evaluated by Alamar Blue assay at 2, 3 and 7 days after seeding. No adverse cellular reactions could be detected with these assays suggesting that the tested substrate is suitable for the hybrid cell-semiconductor systems that test bone tumor chemosensitivity.


Physical rehabilitation of central facial palsy: A survey of current multidisciplinary practice.
Purpose: The role of allied health practitioners providing physical rehabilitation of central facial palsy (CFP) is minimally reported in the literature. This study explores current practice and the roles, attitudes and perceptions of allied health professionals (AHPs) working with people with CFP.Method: An electronic survey was distributed to speech-language pathologists (SLPs), occupational therapists and physiotherapists. Responses (n = 78) were analysed using qualitative and quantitative methods.Result: SLPs often lead management of CFP; however, their role is not clearly defined nor well recognised. Several barriers were identified which prevent AHPs from providing consistent specialist rehabilitation to people with CFP. These included a lack of training, no clear delegation of role, limited evidence and lack of resources.Conclusion: Survey respondents viewed CFP to be within SLP scope of practice; although, ownership of management varies between countries and professions. Most SLPs recognise the negative impact of CFP and feel a sense of responsibility to provide assessment and treatment of this impairment, but many barriers to doing so have been identified. Suggestions to improve access to rehabilitation for people with CFP included increased access to training for SLPs, more evidence, clinical practice guidelines and more clinical resources. Further research is required to ensure people suffering from CFP can access services that provide skilled management of their impairment.


Electron microscopic examination of the extracellular polymeric substances in anaerobic granular biofilms.
Scanning electron microscopy revealed that collapsed extracellular polymeric substances (EPS) surrounded bacteria present in granular sludge. Treatment of granular sludge with whole-cell antiserum and staining with polycationic ferritin demonstrated that bacteria were enveloped by extensive EPS. Antibody stabilization permitted a visualization of the EPS which more closely resembled its natural hydrated state. The EPS was seen to completely fill the intercellular spaces in the microcolonies. Both pure and mixed microcolonies were observed to be enclosed by EPS. The presence of these large amounts of EPS indicates that this extracellular layer is important in maintaining the structural integrity of granular sludge.


Carcinoids of unknown origin: comparative analysis with foregut, midgut, and hindgut carcinoids.
Carcinoids are rare neuroendocrine tumors typically arising in the gastrointestinal tract. A significant percentage of these tumors present as metastatic disease of unknown primary site. The aim of this study was to better define the functional and clinical characteristics of carcinoids of unknown primary (CUP) site. This study examines the hormonal activity, clinical characteristics, and survival of 434 patients with carcinoids originating in the foregut, midgut, hindgut, or unknown location. The 143 patients with CUP were compared with the other groups with regard to presenting characteristics, diagnostic tests and therapeutic modalities used, hormonal activity, and survival. The hormone levels (urinary 5-hydroxyindoleacetic acid and serotonin, serum and platelet serotonin) of CUP were not significantly different from midgut carcinoids with metastatic disease. Although survival with CUP was shorter than with carcinoids with identified primaries (10-year survivals of 22% vs 62%, 50%, and 48% for foregut, midgut, and hindgut, respectively), the survival curve for CUP was quite similar to that of patients with midgut carcinoids with distant disease (10-year survival of 22% vs 28%). CUP are similar to midgut carcinoids presenting with metastatic disease with regard to hormone production and survival. Like other carcinoids, CUP can be an indolent disease process with gradual progression over decades.


Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia: a systematic review.
In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88-95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54-97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. HPA-1a antibody level has the potential to predict the severity of FNAIT.


Fast physical random number generator using amplified spontaneous emission.
We report a 12.5 Gb/s physical random number generator (RNG) that uses high-speed threshold detection of the spectrally-sliced incoherent light produced by a fiber amplifier. The system generates a large-amplitude, easily measured, fluctuating signal with bandwidth that is constrained only by the optical filter and electrical detector used. The underlying physical process (spontaneous emission) is inherently quantum mechanical in origin, and therefore cannot be described deterministically. Unlike competing optical RNG approaches that require photon counting electronics, chaotic laser cavities, or state-of-the-art analog-to-digital converters, the system employs only commonly available telecommunications-grade fiber optic components and can be scaled to higher speeds or multiplexed into parallel channels. The quality of the resulting random bitstream is verified using industry-standard statistical tests.


Cross-sectoral communication by bringing together patient with cancer, general practitioner and oncologist in a video-based consultation: a qualitative study of oncologists' and nurse specialists' perspectives.
Shared care models in the field of cancer aim to improve care coordination, role clarification and patient satisfaction. Cross-sectoral communication is pivotal. Involvement of patients may add to intended mechanisms.A randomised controlled trial 'The Partnership Study' tested the effect of bringing together patient, general practitioner (GP) and oncologist for a consultation conducted by video. As part of the process evaluation, this study aimed to explore experiences, attitudes and perspectives of the oncological department on sharing patient consultations with GPs using video. Four semistructured interviews with five oncologists and four nurse specialists were conducted in February 2020. We focused on the informants' experiences and reflections on the potential of future implementation of the concept 'inviting the GP for a shared consultation by video'. The analyses were based on an inductive, open-minded, hermeneutic phenomenological approach. A total of six overall themes were identified: structuring consultation and communication, perceptions of GP involvement in cancer care, stressors, making a difference, alternative ways of cross-sector communication and needs for redesigning the model. The concept made sense and was deemed useful, but solving the many technical and organisational problems is pivotal. Case-specific tasks and relational issues were targeted by pragmatically rethinking protocol expectations and the usual way of communication and structuring patient encounters. Case selection was discussed as one way of maturing the concept. This Danish study adds new insight into understanding different aspects of the process, causal mechanisms as well as the potential of future implementation of video-based tripartite encounters. Beyond solving the technical problems, case selection and organisational issues are important. Acknowledging the disruption of the usual workflow, the introduction of new phases of the usual encounter and the variety of patient-GP relationships to be embraced may help to better understand and comply with barriers and facilitators of communication and sharing. NCT02716168.