Adsorption of Stearic Acid at the Iron Oxide/Oil Interface: Theory, Experiments, and Modeling.
Improved friction performance is an important objective of equipment manufacturers for meeting improved energy efficiency demands. The addition of friction-reducing additives, or friction modifiers (FMs), to lubricants is a key part of the strategy. The performance of these additives is related to their surface activity and their ability to form adsorbed layers on the metal surface. However, the extent of surface coverage (mass per unit area) required for effective friction reduction is currently unknown. In this article, we show that full coverage is not necessary for significant friction reduction. We first highlight various features of surface adsorption that can influence the surface coverage, packing, and free energy of adsorption of organic FMs on iron oxide surfaces. Using stearic acid in heptane and hexadecane as model lubricant formulations, we employ a combination of experiments and molecular dynamics (MD) simulations to show how the dimerization of acid molecules in the bulk solvent and the crystallographic orientation of the surface modifies surface adsorption. In addition, we show that the solvent can strongly influence the adsorption kinetics, and MD simulations reveal that hexadecane tends to align on the surface, increasing the energy barrier for the adsorption of stearic acid to the surface. Furthermore, we present a combined approach using MD and molecular thermodynamic theory to calculate adsorption isotherms for stearic acid on iron oxide surfaces, which agrees well with experimental data obtained with a quartz crystal microbalance (QCM). Our results suggest that while the friction of systems lubricated with organic FMs decreases with increasing coverage, complete coverage of the surface is neither practically achievable nor necessary for effective friction reduction for the systems and conditions studied here.


Enzyme-linked immunosorbent assay for coronaviruses HCV 229E and MHV 3.
The antigenic relationship between human cornonavirus strain 229E (HCV 229E) and mouse hepatitis virus strain 3 (MHV 3) was studied by means of the indirect form of enzyme-linked immunosorbent assay (ELISA). A cross-reaction was found with hyprimmune rabbit sera between HCV 229E and MHV 3 which may be due to the adherence of bovine serum componeants from tissue culture media, which were present on virus particles even after extensive purification. No cross-reaction was observed with immune sera absorbed with bovine serum, or with HCV 229E grown in tissue culture without serum. This indirect ELISA with HCV 229E may prove to be useful for studies with human sera.


Shear thickening of F-actin networks crosslinked with non-muscle myosin IIB.
The material properties of cytoskeletal F-actin networks facilitate a broad range of cellular behaviors, whereby in some situations cell shape is preserved in the presence of force and, at other times, force results in irreversible shape change. These behaviors strongly suggest that F-actin networks can variably deform elastically or viscously. While a significant amount is known about the regulation of the elastic stiffness of F-actin networks, our understanding of the regulation of viscous behaviors of F-actin networks is largely lacking. Here, we study the rheological behavior of F-actin networks formed with heavy meromyosin non-muscle IIB (NMMIIB). We show that NMMIIB quenched with ADP crosslinks F-actin into networks that, for sufficient densities, display stress stiffening behavior. By performing a series of creep tests, we show that densely crosslinked actin/NMMIIB-ADP networks undergo viscous deformation over a wide range of stresses, ranging from 0.001 to 10 Pa. At high stresses, networks that stress stiffen are also observed to shear thicken, whereby the effective viscosity increases as a function of stress. Shear thickening results in a reduction in the extent of irreversible, viscous deformation in actin/NMMIIB-ADP networks at high stresses compared to that expected for a linear viscoelastic material. Thus, viscous deformation contributes less to the overall mechanical response at high levels of applied force. Our results indicate mechanisms by which the fluid-like nature of the actomyosin cytoskeleton can be reduced under high load.


Efficacy of a T Cell-Biased Adenovirus Vector as a Zika Virus Vaccine.
Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a T-cell response. In a highly lethal challenge in an interferon α/β receptor knockout mice, 80% of Ad5 vaccinated animals and 33% of Ad4 vaccinated animals survived a lethal ZIKV challenge, whereas no animals in the sham vaccinated group survived. In an infection model utilizing immunocompetent C57BL/6 mice that were immunized and then treated with a blocking anti-IFNAR-1 antibody immediately before ZIKV challenge, 100% of Ad4-prM-E and Ad5-prM-E vaccinated mice survived. This indicates that Ad4-prM-E vaccination is protective without the development of detectable anti-ZIKV antibodies. The protection seen in these highly lethal mouse models demonstrate the efficacy of Ad vectored vaccines for use against ZIKV.


Understanding the interface of six-shell cuboctahedral and icosahedral palladium clusters on reduced graphene oxide: experimental and theoretical study.
Studies on noble-metal-decorated carbon nanostructures are reported almost on a daily basis, but detailed studies on the nanoscale interactions for well-defined systems are very rare. Here we report a study of reduced graphene oxide (rGOx) homogeneously decorated with palladium (Pd) nanoclusters with well-defined shape and size (2.3 ± 0.3 nm). The rGOx was modified with benzyl mercaptan (BnSH) to improve the interaction with Pd clusters, and N,N-dimethylformamide was used as solvent and capping agent during the decoration process. The resulting Pd nanoparticles anchored to the rGOx-surface exhibit high crystallinity and are fully consistent with six-shell cuboctahedral and icosahedral clusters containing ~600 Pd atoms, where 45% of these are located at the surface. According to X-ray photoelectron spectroscopy analysis, the Pd clusters exhibit an oxidized surface forming a PdO(x) shell. Given the well-defined experimental system, as verified by electron microscopy data and theoretical simulations, we performed ab initio simulations using 10 functionalized graphenes (with vacancies or pyridine, amine, hydroxyl, carboxyl, or epoxy groups) to understand the adsorption process of BnSH, their further role in the Pd cluster formation, and the electronic properties of the graphene-nanoparticle hybrid system. Both the experimental and theoretical results suggest that Pd clusters interact with functionalized graphene by a sulfur bridge while the remaining Pd surface is oxidized. Our study is of significant importance for all work related to anchoring of nanoparticles on nanocarbon-based supports, which are used in a variety of applications.


Effects of a single dose of erythropoietin on motor function and cognition after focal brain ischemia in adult rats.
We tested the influence of erythropoietin (EPO), a basic cytokine in erythropoiesis regulation, on the process of motor function and cognition after focal brain ischemia induced by a local application of endothelin. Endothelin-1 (ET-1) induced short lasting strong vasoconstriction, with described impact on the structure and on the function of neuronal cells. Neurological description of motor function and Morris water maze test (the swimming test is one of most widely used methods for studying cognitive functions in rodents) were used to study the process of learning and memory in three-month-old male albino Wistar rats (n=52). Both tests were performed one week before, and three weeks after ischemia induction (endothelin application on the cortex in the area of a. cerebri media dx.). Experimental group received i.p. injection of EPO (5,000 IU/kg body weight, 10 min before endothelin application). Control group of animals received one i.p. injection of saline at the dose of 1 ml/kg body weight at the same time. Only sham surgery was performed in the third group of animals. Rats with EPO pretreatment before the experimental lesion exhibited significantly better motor and cognitive function then those with saline injection. No significant changes in the motor and cognitive function were found in the third group of rats (sham operated controls).


Complications of intraoperative radiofrequency ablation of liver metastases.
Intraoperative radiofrequency ablation (IRFA) of liver metastases can be used to treat patients with complex tumours that are unsuitable for parenchymal resection alone. This systematic review assesses the frequency, patterns and severity of complications associated with this procedure. We carried out a bibliographic search on MEDLINE focused on IRFA for liver metastases, excluding hepatocarcinomas, and on intraoperative use, excluding percutaneous application. Thirty papers published between 1999 and 2007 were analysed. They covered a total of 2822 patients and 1755 IRFA procedures. The indications and techniques for IRFA differ from those for percutaneous treatment, as do associated results and complications. Specific complications associated with IRFA, such as liver abscesses, biliary stenoses and vascular thromboses, are directly correlated with the indications and associated procedures. Published results should be interpreted with caution as IRFA can be used alone or combined with parenchymal resection. Specific complications related to IRFA are rare, especially for lesions of <35 mm in size located far from a main biliary duct, when additional septic procedures are not used. A lesion-by-lesion approach based on the benefit : risk ratio should therefore be used in the process of making surgical decisions. Combining resection with IRFA leads to higher morbidity, especially in difficult patients with numerous bilateral lesions, but may be necessary to achieve R0 (microscopically negative margins) outcomes.


The p58-positive pre-golgi intermediates consist of distinct subpopulations of particles that show differential binding of COPI and COPII coats and contain vacuolar H(+)-ATPase.
We have studied the structural and functional properties of the pre-Golgi intermediate compartment (IC) in normal rat kidney cells using analytical cell fractionation with p58 as the principal marker. The sedimentation profile (sediterm) of p58, obtained by analytical differential centrifugation, revealed in steady-state cells the presence of two main populations of IC elements whose average sedimentation coefficients, s(H)=1150+/-58S ('heavy') and s(L)=158+/-8S ('light'), differed from the s-values obtained for elements of the rough and smooth endoplasmic reticulum. High resolution analysis of these subpopulations in equilibrium density gradients further revealed that the large difference in their s-values was mainly due to particle size. The 'light' particle population contained the bulk of COPI and COPII coats, and redistribution of p58 to these particles was observed in transport-arrested cells, showing that the two types of elements are also compositionally distinct and have functional counterparts in intact cells. Using a specific antibody against the 16 kDa proteolipid subunit of the vacuolar H(+)-ATPase, an enrichment of the V(o )domain of the ATPase was observed in the p58-positive IC elements. Interestingly, these elements could contain both COPI and COPII coats and their density distribution was markedly affected by GTP(&ggr;)S. Together with morphological observations, these results demonstrate that, in addition to clusters of small tubules and vesicles, the IC also consists of large-sized structures and corroborate the proposal that the IC elements contain an active vacuolar H(+)-ATPase.


Multicenter Evaluation of the Portrait Staph ID/R Blood Culture Panel for Rapid Identification of Staphylococci and Detection of the mecA Gene.
Bloodstream infections are a leading cause of morbidity and mortality in the United States and are associated with increased health care costs. We evaluated the Portrait Staph ID/R blood culture panel (BCP) multiplex PCR assay (Great Basin Scientific, Salt Lake City, UT) for the rapid and simultaneous identification (ID) of Staphylococcus aureus, Staphylococcus lugdunensis, and Staphylococcus species to the genus level and the detection of the mecA gene directly from a positive blood culture bottle. A total of 765 Bactec bottles demonstrating Gram-positive cocci in singles or clusters were tested during the prospective trial at 3 clinical sites. The Portrait Staph ID/R BCP results were compared with results from conventional biochemical and cefoxitin disk methods performed at an independent laboratory. Discordant ID and mecA results were resolved by rpoB gene sequencing and mecA gene sequencing, respectively. A total of 658 Staphylococcus species isolates (S. aureus, 211 isolates; S. lugdunensis, 3 isolates; and Staphylococcus spp., 444 isolates) were recovered from monomicrobial and 33 polymicrobial blood cultures. After discrepant analysis, the overall ratios of Portrait Staph ID/R BCP positive percent agreement and negative percent agreement were 99.4%/99.9% for Staphylococcus ID and 99.7%/99.2% for mecA detection.


Effect of banana consumption on faecal microbiota: a randomised, controlled trial.
Banana is a widely consumed fruit, which contains considerable amounts of potential prebiotic indigestible carbohydrates. In our randomised, controlled trial we aimed to evaluate the in vivo prebiotic effect of banana consumption on faecal microbiota. Thirty-four healthy women participated in the study, having Body Mass Index (BMI) 24-30 kg/m(2), age 19-45 years, without history of gastrointestinal disease and no antibiotic and other medication use two months prior the initiation and during the study. All women were asked to maintain their usual dietary habits for 60 days and they were randomly assigned to consume twice a day a pre-meal snack, either one medium banana, or one cup of banana-flavoured drink or one cup of water (control group). Stool samples were collected at baseline, on days 30 and 60 of intervention for enumeration of total anaerobes, bifidobacteria and lactobacilli by plate count techniques, as well as for pH and short chain fatty acids (SCFAs) measurement. Gastrointestinal symptoms were also recorded. Mean bifidobacterial levels were increased only in the banana group both at 30 and 60 days of intervention, but this change did not reach a statistical significance. No significant overall differences in the total concentrations and molar ratios of SCFAs were detected according to dietary intervention. Analysis of the gastrointestinal symptoms records revealed significantly lower bloating levels in the banana group, compared to controls, at 26-35 days (p = 0.009) and 51-60 days (p = 0.010). Banana consumption had also no adverse effects on evacuation patterns. We concluded that daily consumption of bananas is a well-tolerated eating behaviour, which may induce bifidogenesis in healthy women experiencing body weight problems.


BoNT-A efficacy in high frequency migraine: an open label, single arm, exploratory study applying the PREEMPT paradigm.
In this open label, single-arm trial we evaluated the efficacy of onabotulinum toxin-A in the prevention of high-frequency episodic migraine (8-14 migraine days/month). We enrolled 32 high-frequency episodic migraine subjects (age 44.8 ± 11.9 years, 11.0 ± 2.2 migraine days, 11.5 ± 2.1 headache days, 7 females). After a 28-day baseline period, subjects underwent 4 subsequent onabotulinum toxin-A treatments according to the phase III research evaluating migraine prophylaxis therapy (PREEMPT) paradigm, 12-weeks apart. The primary outcome was the reduction of monthly migraine days from baseline in the 12-week period following the last onabotulinum toxin-A treatment. Onabotulinum toxin-A reduced monthly migraine days by 3.68 days (-33.1%, p < 0.01). Thirty-nine percent of the patients experienced a ≥50% reduction in monthly migraine days. Onabotulinum toxin-A also reduced the number of headache days (-33.9%, p < 0.01) and the intake of acute medications (-22.9%, p = 0.03). Disability and quality of life (QoL) scores improved markedly (migraine disability assessment (MIDAS) -41.7%; migraine specific questionnaire (MSQ) -31.7%, p < 0.01). The findings suggest that, when administered according to the PREEMPT paradigm, onabotulinum toxin-A is effective in the prevention of high-frequency episodic migraine.Trial Registration: NCT04578782.


[The characteristics of the early postoperative period in patients with organic hyperinsulinism].
An analysis of the postoperative period in 34 patients with organic hyperinsulinism has shown that its severity and duration is determined first of all by postoperative pancreatitis with its symptoms observed in all the patients. The severity of this complication can be decreased by shorter duration of the operation which can be achieved by the introduction of more reliable new methods of diagnosis of the disease as well as by using a plasma scalpel for operating on the pancreas which can make the operation less traumatic.


Alkoxysilane-Mediated Decoration of Si Nanowires Vertical Arrays with Au Nanoparticles as Improved SERS-Active Platforms.
The search for improved transducers to fabricate better-performing (bio)sensors is a challenging but rewarding endeavor aiming to better diagnose and treat diseases. In this paper, we report on the decoration of a dense vertical array of ultrathin silicon nanowires (Si NWs), produced by metal-assisted chemical etching, with 20 nm gold nanoparticles (Au NPs) for surface-enhanced Raman scattering (SERS) applications. To optimize the production of a uniform 3D SERS active platform, we tested different Si NW surface functionalizations with various alkoxysilanes before Au decoration. Scanning electron microscopy investigations confirm that Au NPs decorate both bare and (3-glycidiloxypropyl)trimethoxysilane (GPTMS)-modified Si NWs with a high surface coverage uniformity. The SERS response of the decorated NWs was probed using a model dye system (methylene blue; MB) at 633 and 785 nm excitation wavelengths. The GPTMS-modified NWs present the highest enhancements of 2.9 and 2.6 for the 450 cm-1 and 1625 cm-1 peaks under 785 nm excitation and of 10.8 and 5.3 for the 450 cm-1 and 1625 cm-1 peaks under 633 nm excitation. These results demonstrate the perspective role of Si NWs decorated with Au NPs as a low-cost 3D SERS platform.


Calculation of x-ray grid characteristics by Monte Carlo methods.
The performance of x-ray grids has generally been evaluated experimentally. A theoretical method has been developed by which photon histories are generated by Monte Carlo methods. The probability of penetrating the grid is calculated for each photon escaping from the object towards the detector. The scatter transmission of the grid is determined as the average of these individual probabilities. Results for linear and cross grids are in good agreement with measurements. The method is applicable to arbitrary irradiation and grid parameters. The dependence of scatter transmission values on the irradiation parameters is shown. Grids with linear and zigzag strip patterns are compared in order to demonstrate that even grids that cannot at present be manufactured can nevertheless be evaluated.


LRP5 competes for SPOP binding to enhance tumorigenesis mediated by Daxx and PD-L1 in prostate cancer.
Genetic factors coordinate with environmental factors to drive the pathogenesis of prostate adenocarcinoma (PRAD). SPOP is one of the most mutated genes and LRP5 mediates lipid metabolism that is abnormally altered in PRAD. Here, we investigated the potential cross-talk between SPOP and LRP5 in PRAD. We find a negative correlation between SPOP and LRP5 proteins in PRAD. SPOP knockdown increased LRP5 protein while SPOP overexpression resulted in LRP5 reduction that was fully rescued by proteasome inhibitors. LRP5 intracellular tail has SPOP binding site and the direct interaction between LRP5 and SPOP was confirmed by Co-IP and GST-pulldown. Moreover, LRP5 competed with Daxx for SPOP-mediated degradation, establishing a dynamic balance among SPOP, LRP5 and Daxx. Overexpression of LRP5 tail could shift this balance to enhance Daxx-mediated transcriptional inhibition, and inhibit T cell activity in a co-culture system. Further, we generated human and mouse prostate cancer cell lines expressing SPOP variants (F133V, A227V, R368H). SPOP-F133V and SPOP-A227V have specific effects in up-regulating the protein levels of PD-1 and PD-L1. Consistently, SPOP-F133V and SPOP-A227V show robust inhibitory effects on T cells compared to WT SPOP in co-culture. This is further supported by the mouse syngeneic model showing that SPOP-F133V and SPOP-A227V enhance tumorigenesis of prostate cancer in in-vivo condition. Taken together, our study provides evidence that SPOP-LRP5 crosstalk plays an essential role, and the genetic variants of SPOP differentially modulate the expression and activity of immune checkpoints in prostate cancer.


Chan chan: andean alternative of the preindustrial city.
I have discussed Chan Chan in terms of its political and economic characteristics because state organization had a pervasive impact on the growth and structure of the settlement. In this sense the capital of Chimor resembles Cuzco the Inca capital (1). Both metropolitan centers served as seats of Andean empires governed by noble classes headed by members of royal dynasties. Each state relied on a system of labor taxation and controlled the production, collection, and redistribution of goods. These political and economic institutions gave the sites distinctive but parallel forms. First, the settlements were large, containing a great deal of monumental architecture, but size and construction do not reflect substantial populations because building was done by nonresident work forces. Second, the urban proletariat were relatively few in numbers and composed of retainers or service personnel at Cuzco, as well as craftsmen and artisans at Chan Chan. Third, civic facilities were intended to serve the aristocracy and the state, not the common citizenry because these were governmental, not folk or popular, centers. And, fourth, palaces tied up a great amount of urban space because each monarch built his own seat of government during life and this became a monument to his name after death. In conclusion, I cannot say Chan Chan and Cuzco are necessarily typical of other prehistoric population centers in the region because these centers are little studied. I can, however, say Chan Chan was distinct from the preindustrial cities of Europe and Mesopotamia, but this is not surprising because the capital of Chimor was the product of distinctly Andean cultural institutions.


Standardizing data exchange for clinical research protocols and case report forms: An assessment of the suitability of the Clinical Data Interchange Standards Consortium (CDISC) Operational Data Model (ODM).
Efficient communication of a clinical study protocol and case report forms during all stages of a human clinical study is important for many stakeholders. An electronic and structured study representation format that can be used throughout the whole study life-span can improve such communication and potentially lower total study costs. The most relevant standard for representing clinical study data, applicable to unregulated as well as regulated studies, is the Operational Data Model (ODM) in development since 1999 by the Clinical Data Interchange Standards Consortium (CDISC). ODM's initial objective was exchange of case report forms data but it is increasingly utilized in other contexts. An ODM extension called Study Design Model, introduced in 2011, provides additional protocol representation elements. Using a case study approach, we evaluated ODM's ability to capture all necessary protocol elements during a complete clinical study lifecycle in the Intramural Research Program of the National Institutes of Health. ODM offers the advantage of a single format for institutions that deal with hundreds or thousands of concurrent clinical studies and maintain a data warehouse for these studies. For each study stage, we present a list of gaps in the ODM standard and identify necessary vendor or institutional extensions that can compensate for such gaps. The current version of ODM (1.3.2) has only partial support for study protocol and study registration data mainly because it is outside the original development goal. ODM provides comprehensive support for representation of case report forms (in both the design stage and with patient level data). Inclusion of requirements of observational, non-regulated or investigator-initiated studies (outside Food and Drug Administration (FDA) regulation) can further improve future revisions of the standard.


Predictors for 30-Day and 90-Day Hospital Readmission Among Patients With Opioid Use Disorder.
To identify the incidence, characteristics, and predictors for 30 and 90-day readmission among acutely hospitalized patients with opioid use disorder (OUD). This retrospective, cohort study evaluated consecutive adults with OUD admitted to an academic medical center over a 5-year period (10/1/11 to 9/30/16). Multivariable logistic regression was used to determine independent predictors for 30 and 90-day readmissions based on pertinent admission, hospital, and discharge variables collected via chart review and found to be different (with a P < 0.10) on univariate analysis. Among the 470 adults (mean age 43.1 ± 12.8 years, past heroin use 77.9%; admission opioid agonist therapy use [buprenorphine 22.6%; methadone 27.0%]; medical [vs surgical] admission 75.3%, floor [vs ICU] admission 93.0%, in-hospital mortality 0.9%), 85 (18.2%) and 151 (32.1%) were readmitted within 30 and 90 days, respectively. Among the 90-day readmitted patients, median time to first readmission was 26 days. Buprenorphine use (vs no use) at index hospital admission was independently associated with reduced 30-day (odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24-0.93) and 90-day (OR 0.57, 95% CI 0.34-0.96) readmission; prior heroin (vs prescription opioid) use was associated with reduced 90-day readmission (OR 0.59, 95% CI 0.37-0.94) and length of hospital stay was associated with both greater 30-day (OR 1.02, 95% CI 1.01-1.05) and 90-day (OR 1.04, 95% CI 1.01-1.06) readmission rates. Among patients with OUD taking buprenorphine at the time of hospital admission, 30-day and 90-day hospital readmission was reduced by 53% and 43%, respectively.


MEANSP: How Many Channels Are Needed to Predict the Performance of a SMR-Based BCI?
Predicting whether a particular individual would reach an adequate control of a Brain-Computer Interface (BCI) has many practical advantages. On the one hand, participants with low predicted performance could be trained with specifically designed sessions and avoid frustrating experiments; on the other hand, planning time and resources would be more efficient; and finally, the variables related to an accurate prediction could be manipulated to improve the prospective BCI performance. To this end, several predictors have been proposed in the literature, most of them based on the power estimation of EEG signals at the specific frequency bands. Many of these studies evaluate their predictors in relatively small datasets and/or using a relatively high number of channels. In this manuscript, we propose a novel predictor called MEANSP to predict the performance of participants using BCIs that are based on the modulation of sensorimotor rhythms. This novel predictor has been positively evaluated using only 2, 3, 4 or 5 channels. MEANSP has shown to perform as well as or better than other state-of-the-art predictors. The best sets of different number of channels are also provided, which have been tested in two different settings to prove their robustness. The proposed predictor has been successfully evaluated using two large-scale datasets containing 150 and 80 participants, respectively. We also discuss predictor thresholds for users to expect good performance in feedback experiments and show the advantages in comparison to a competing algorithm.


[Alternative treatment possibilities of atopic diseases].
Families of children with atopic diseases often seek so-called alternative treatment as supplementation, not as real alternative to clinical medicine (complementary instead of alternative treatment). Clinical studies on the efficiency of acupuncture in the treatment of bronchial asthma gave contradictory results. The author's own uncontrolled experience in asthmatic children using a simple acupuncture scheme is rather good and a controlled clinical trial seems justified. In atopic dermatitis treatment comprises a mixture of acupuncture, homeopathy and dietary regimes and the therapeutic results have to be viewed against the possibility of spontaneous remissions. A controlled clinical trial seems impossible.


Discontinuous locomotion and prey sensing in the leech.
The medicinal leech, Hirudo verbana, is an aquatic predator that utilizes water waves to locate its prey. However, to reach their prey, the leeches must move within the same water that they are using to sense prey. This requires that they either move ballistically towards a pre-determined prey location or that they account for their self-movement and continually track prey. We found that leeches do not localize prey ballistically. Instead, they require continual sensory information to track their prey. Indeed, in the event that the prey moves, leeches will approach the prey's new location. While leeches need to continually sense water disturbances to update their percept of prey location, their own behavior is discontinuous--prey involves switching between swimming, crawling and non-locomoting. Each of these behaviors may allow for different sensory capabilities and may require different sensory filters. Here, we examined the sensory capabilities of leeches during each of these behaviors. We found that while one could expect the non-locomoting phases to direct subsequent behaviors, crawling phases were more effective than non-locomotor phases for providing direction. During crawling bouts, leeches adjusted their heading so as to become more directed towards the stimulus. This was not observed during swimming. Furthermore, in the presence of prey-like stimuli, leeches crawled more often and for longer periods of time.


Subwavelength metallic cavities with high-Q resonance modes.
Metallic cavities have been extensively studied to realize small-volume nanocavities and nanolasers. However cavity-resonance quality (Q) factors of nanolasers observed up to now remain low (up to ∼500) due to metal optical absorption. In this paper, we report the observation of highest Q factors of 9000 at low temperature and ∼6000 near room temperature in a metallic cavity with a probe of sub-bandgap emission of Si-doped GaAs. We analyze the temperature dependence of cavity-mode resonance wavelengths and show that the refractive-index term dominates the measured temperature dependence. We also show that this refractive-index term is cavity-mode dependent and the fitting procedure offers a new method to identify cavity modes. We simulate the metallic cavity with finite-element method and attribute the high-Q cavity mode to a whispering gallery optical mode. This mode is shown to have isotropic polarization dependence of the output emission, which is preferable for quantum information applications.


Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant - National Healthcare Safety Network, March 1-August 1, 2021.
Nursing home and long-term care facility residents live in congregate settings and are often elderly and frail, putting them at high risk for infection with SARS-CoV-2, the virus that causes COVID-19, and severe COVID-19-associated outcomes; therefore, this population was prioritized for early vaccination in the United States (1). Following rapid distribution and administration of the mRNA COVID-19 vaccines (Pfizer-BioNTech and Moderna) under an Emergency Use Authorization by the Food and Drug Administration (2), observational studies among nursing home residents demonstrated vaccine effectiveness (VE) ranging from 53% to 92% against SARS-CoV-2 infection (3-6). However, concerns about the potential for waning vaccine-induced immunity and the recent emergence of the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant† highlight the need to continue to monitor VE (7). Weekly data reported by the Centers for Medicaid & Medicare (CMS)-certified skilled nursing facilities or nursing homes to CDC's National Healthcare Safety Network (NHSN)§ were analyzed to evaluate effectiveness of full vaccination (2 doses received ≥14 days earlier) with any of the two currently authorized mRNA COVID-19 vaccines during the period soon after vaccine introduction and before the Delta variant was circulating (pre-Delta [March 1-May 9, 2021]), and when the Delta variant predominated¶ (Delta [June 21-August 1, 2021]). Using 17,407 weekly reports from 3,862 facilities from the pre-Delta period, adjusted effectiveness against infection for any mRNA vaccine was 74.7% (95% confidence interval [CI] = 70.0%-78.8%). Analysis using 33,160 weekly reports from 11,581 facilities during an intermediate period (May 10-June 20) found that the adjusted effectiveness was 67.5% (95% CI = 60.1%-73.5%). Analysis using 85,593 weekly reports from 14,917 facilities during the Delta period found that the adjusted effectiveness was 53.1% (95% CI = 49.1%-56.7%). Effectiveness estimates were similar for Pfizer-BioNTech and Moderna vaccines. These findings indicate that mRNA vaccines provide protection against SARS-CoV-2 infection among nursing home residents; however, VE was lower after the Delta variant became the predominant circulating strain in the United States. This analysis assessed VE against any infection, without being able to distinguish between asymptomatic and symptomatic presentations. Additional evaluations are needed to understand protection against severe disease in nursing home residents over time. Because nursing home residents might remain at some risk for SARS-CoV-2 infection despite vaccination, multiple COVID-19 prevention strategies, including infection control, testing, and vaccination of nursing home staff members, residents, and visitors, are critical. An additional dose of COVID-19 vaccine might be considered for nursing home and long-term care facility residents to optimize a protective immune response.


Maternal docosahexaenoic acid supplementation during pregnancy and visual evoked potential development in term infants: a double blind, prospective, randomised trial.
To test the hypothesis that maternal docosahexaenoic acid (DHA) supplementation during pregnancy enhances maturation of the visual evoked potential (VEP) in healthy term infants. One hundred women were supplemented with either fish oil capsules rich in DHA (n = 50) or placebo capsules (n = 50) from week 15 of pregnancy until delivery. Total fatty acids in red blood cells and plasma were measured at weeks 15, 28, and 40 of pregnancy and at delivery in umbilical cord blood. Infant visual pathway development was assessed using VEPs recorded to flash stimuli shortly after birth and to both flash and pattern-reversal stimuli at 50 and 66 weeks post-conceptional age (PCA). Maternal supplementation did not significantly elevate the level of DHA in umbilical cord blood. Moreover, there were no significant differences in any of the VEP measures observed between supplementation groups. However, maturity of the pattern-reversal VEP at 50 and 66 weeks PCA was associated with DHA status of the infants at birth. Infants with higher DHA status, both as a concentration and as a percentage of total fatty acids, showed shorter P100 peak latencies of the pattern-reversal VEP than those with lower DHA status. Maternal DHA supplementation during pregnancy did not enhance VEP maturation in healthy term infants. However, these results show an association between the DHA status of infants at term and early postnatal development of the pattern-reversal VEP, suggesting that DHA status itself may influence maturation of the central visual pathways.


Heme oxygenase-1 in pregnancy and cancer: similarities in cellular invasion, cytoprotection, angiogenesis, and immunomodulation.
Pregnancy can be defined as a "permissible" process, where a semi-allogeneic fetus and placenta are allowed to grow and survive within the mother. Similarly, in tumor growth, antigen-specific malignant cells proliferate and evade into normal tissues of the host. The microenvironments of the placenta and tumors are amazingly comparable, sharing similar mechanisms exploited by fetal or cancer cells with regard to surviving in a hypoxic microenvironment, invading tissues via degradation and vasculogenesis, and escaping host attack through immune privilege. Heme oxygease-1 (HO-1) is a stress-response protein that has antioxidative, anti-apoptotic, pro-angiogenic, and anti-inflammatory properties. Although a large volume of research has been published in recent years investigating the possible role(s) of HO-1 in pregnancy and in cancer development, the molecular mechanisms that regulate these "yin-yang" processes have still not been fully elucidated. Here, we summarize and compare pregnancy and cancer development, focusing primarily on the function of HO-1 in cellular invasion, cytoprotection, angiogenesis, and immunomodulation. Due to the similarities of both processes, a thorough understanding of the molecular mechanisms of each process may reveal and guide the development of new approaches to prevent not only pregnancy disorders; but also, to study cancer.


Pathways between caregiver body mass index, the home environment, child nutritional status, and development in children with severe acute malnutrition in Malawi.
Children with severe acute malnutrition (SAM) remain vulnerable after treatment at nutritional rehabilitation units (NRUs). The objective was to assess the concurrent pathways in a hypothesized model between caregiver body mass index (BMI), the home environment, and child nutritional status, and development (gross motor, fine motor, language, and social domains) in children with SAM following discharge from inpatient treatment. Structural equation modelling (SEM) was performed with data from a cluster-randomized controlled trial at the Moyo Nutritional Rehabilitation and Research Unit in Blantyre, Malawi. This approach was undertaken to explore simultaneous relationships between caregiver BMI, the home environment (Home Observation for Measurement of the Environment Inventory scores), child nutritional status (anthropometric indicators including weight-for-age z-scores [WAZ]), and child development (Malawi Developmental Assessment Tool (MDAT) z-scores as a latent variable) in children with SAM. These data were collected at participants' homes six months after discharge from NRU treatment. This analysis included 85 children aged 6-59 months with SAM and their caregivers recruited to the trial at the NRU and followed up successfully six months after discharge. The model with WAZ as the nutritional indicator fit the data according to model fit indices (χ2 = 28.92, p = 0.42). Caregiver BMI was predictive of better home environment scores (β = 0.23, p = 0.03) and child WAZ (β = 0.30, p = 0.005). The home environment scores were positively correlated with MDAT z-scores (β = 0.32, p = 0.001). Child nutritional status based on WAZ was also correlated with MDAT z-scores (β = 0.37, p<0.001). This study demonstrates that caregiver BMI could ultimately relate to child development in children with SAM, through its links to the home environment and child nutritional status.


How to design multi-target drugs.
Despite improved rational drug design and a remarkable progress in genomic, proteomic and high-throughput screening methods, the number of novel, single-target drugs has fallen far behind expectations during the past decade. Multi-target drugs multiply the number of pharmacologically relevant target molecules by introducing a set of indirect, network-dependent effects. Parallel with this, the low-affinity binding of multi-target drugs eases the constraints of druggability and significantly increases the size of the druggable proteome. These effects tremendously expand the number of potential drug targets and introduce novel classes of multi-target drugs with smaller side effects and toxicity. Here, the authors review the recent progress in this field, compare possible network attack strategies and propose several methods to find target-sets for multi-target drugs.


Mathematical Modeling of Yarn Dynamics in a Generalized Twisting System.
Twisting is an important process to form a continuous yarn from short fibres and to determine the structure and properties of the resultant yarn. This paper proposes a new theoretical model of yarn dynamics in a generalized twisting system, which deals with two important phenomena simultaneously, that is, twist generation and twist propagation. Equations of yarn motion are established and the boundary value problems are numerically solved by Newton-Raphson method. The simulation results are validated by experiments and a good agreement has been demonstrated for the system with a moving rigid cylinder as the twisting element. For the first time, influences of several parameters on the twisting process have been revealed in terms of twist efficiency of the moving rigid cylinder, propagation coefficients of twist trapping and congestion. It was found that the wrap angle and yarn tension have large influence on the twisting process, and the yarn torsional rigidity varies with the twisting parameters.


Massachusetts General Physicians Organization's quality incentive program produces encouraging results.
Physicians are increasingly becoming salaried employees of hospitals or large physician groups. Yet few published reports have evaluated provider-driven quality incentive programs for salaried physicians. In 2006 the Massachusetts General Physicians Organization began a quality incentive program for its salaried physicians. Eligible physicians were given performance targets for three quality measures every six months. The incentive payments could be as much as 2 percent of a physician's annual income. Over thirteen six-month terms, the program used 130 different quality measures. Although quality-of-care improvements and cost reductions were difficult to calculate, anecdotal evidence points to multiple successes. For example, the program helped physicians meet many federal health information technology meaningful-use criteria and produced $15.5 million in incentive payments. The program also facilitated the adoption of an electronic health record, improved hand hygiene compliance, increased efficiency in radiology and the cancer center, and decreased emergency department use. The program demonstrated that even small incentives tied to carefully structured metrics, priority setting, and clear communication can help change salaried physicians' behavior in ways that improve the quality and safety of health care and ease the physicians' sense of administrative burden.


Impact of gynecological screening in Lynch syndrome carriers with an MSH2 mutation.
Lifetime risk of developing endometrial cancer in Lynch syndrome carriers is very high and females are also at an increased risk of developing ovarian cancer. The aim of the study was to determine the impact of gynecological screening in MSH2 mutation carriers. Gynecological cancer incidence and overall survival was compared in female mutation carriers who received gynecological screening (cases) and in matched controls. Controls were randomly selected from non-screened mutation carriers who were alive and disease-free at the age the case entered the screening program. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in controls (p = 0.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (p = 0.17). Two of three deaths in the screened group were the result of ovarian cancer. Mean survival in the screened group was 79 years compared to 69 years in the control group (p = 0.11), likely associated with concomitant colonoscopy screening. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing.


Early pastoral economies along the Ancient Silk Road: Biomolecular evidence from the Alay Valley, Kyrgyzstan.
The Silk Road was an important trade route that channeled trade goods, people, plants, animals, and ideas across the continental interior of Eurasia, fueling biotic exchange and key social developments across the Old World. Nestled between the Pamir and Alay ranges at a baseline elevation of nearly 3000m, Kyrgyzstan's high Alay Valley forms a wide geographic corridor that comprised one of the primary channels of the ancient Silk Road. Recent archaeological survey reveals a millennia-long history of pastoral occupation of Alay from the early Bronze Age through the Medieval period, and a stratified Holocene sequence at the site of Chegirtke Cave. Faunal remains were recovered from test excavations as well as surface collection of material from recent marmot activity. Although recovered specimens were highly fragmented and mostly unidentifiable using traditional zooarchaeological methods, species identification via collagen mass fingerprinting (ZooMS) coupled with sex and first-generation hybrid identification through ancient DNA enabled preliminary characterization of the animal economy of Alay herders. Our new results indicate primary reliance on sheep at Chegirtke Cave (ca. 2200 BCE), with cattle and goat also present. The discovery of a large grinding stone at a spatially associated Bronze or Iron Age habitation structure suggests a mixed agropastoral economic strategy, rather than a unique reliance on domestic animals. Radiocarbon-dated faunal assemblages from habitation structures at nearby localities in the Alay Valley demonstrate the presence of domestic horse, as well as Bactrian camel during later periods. The current study reveals that agropastoral occupation of the high-mountain Alay corridor started millennia before the formal establishment of the Silk Road, and posits that ZooMS, when paired with radiocarbon dates and ancient DNA, is a powerful and cost-effective tool for investigating shifts in the use of animal domesticates in early pastoral economies.


Structural properties of silkworm small heat-shock proteins: sHSP19.9 and sHSP20.8.
sHSP20.8 and sHSP19.9 are silkworm small-heat shock proteins (sHSPs) comprising a number of polypeptides of molecular sizes of several tens of kilodaltons as subunits. The structural properties of sHSPs were investigated. sHSP19.9 was found to be aggregated by itself during incubation at 60 degrees C. Aggregation was suppressed in the presence of dithiothreitol and at high ionic strength. In contrast, sHSP20.8 was not aggregated. Aggregation of sHSP19.9 was partially suppressed by sHSP20.8 and in the presence of catalase as a target protein. Based on changes in small-angle X-ray scattering, it is possible that the molecular size of sHSP19.9 is larger than that of sHSP20.8, and that their molecular sizes increase with increasing temperature in a reversible, biphasic manner. sHSPs did not protect catalase from thermal inactivation, but protected it from precipitation by forming a soluble complex. sHSP20.8 and sHSP19.9 with dithiothreitol were stable against lyophilization, autoclaving at 120 degrees C, and boiling.


Neck involvement in early carcinoma of tongue. Is elective neck dissection warranted?
To evaluate need of elective neck dissection in patients with early oral tongue cancer, and to see the pattern of involvement of different lymph node levels. Ninety four patients with T1-T2, N0 squamous cell carcinoma of the oral tongue were treated with a partial glossectomy and an elective modified radical neck dissection. Thirty two patients had T1 and 62 patients had T2 lesion. In patients with T1 carcinoma, 9 out of 32 had metastases (28%), whereas in patients with T2 carcinoma, 21 out of 62 showed metastases(34%).Thus, the overall rate of occult lymph node metastases was high(32%). In our study skip metastases to level III was seen in only in 2 patients (6%) but there was no skip metastases seen involving level IV or V. The overall micrometastases rate in our patients (32%) warrants elective neck dissection in early cases also. The incidence of metastases to level IV and V from T1-T2 oral tongue cancer is low so these lymph nodes should be removed only when there is intraoperative suspicion of extensive metastases in levels I, II or III., otherwise supraomohyoid neck dissection is sufficient.


Review of 109 cases of primary malignant orofacial lesions seen at a Nigerian Tertiary Hospital.
Orofacial malignancy is a growing health issue common in developing regions of the world. Presentation patterns are myriad with geographic variations. Advanced stage owing to late presentation constitutes a significant public health burden. The site and type of the lesions are valuable in diagnosis and patient management. This study aims to review cases of primary orofacial malignancies at the OAUTHC Dental Hospital. The objective of the study was to determine the prevalence of histologically diagnosed orofacial malignancies, the relative frequencies, types and site of distribution. Records of patients with orofacial malignancies at the OAUTHC, Dental Hospital over a period of 10 years (January 2008-December 2017) were reviewed, demographic data (age, gender and site), history of tobacco use were retrieved and entered into a pro forma. The data obtained were analysed with STATA 11. Statistical significance was set at P < 0.05. Of 375, 109 cases of neoplasms seen were primary malignant tumours, with prevalence rate of 29.1%. There were 71 (65.1%) males and 38 (34.9%) females (male:female ratio of 1.87:1), mean age (48.7 ± 19.3 years) and range (4-94 years). Affected sites were mandible (41, 37.6%), maxilla (39, 35.8%), palate (17, 15.6%) and others. Lesions were mainly squamous cell carcinomas (SCC: 46, 42.2%), salivary gland adenocarcinomas (SGAs, 25, 22.9%) including 8 (32%) cases of adenoid cystic carcinoma (ACC). Others were odontogenic carcinoma (18, 16.5%) and lymphoma (8, 7.3%). Most specimen analysed were hard tissues (n = 63, 57.8%). Thirty-four (73.9%) cases of SCC and 66 (60.6%) cases of primary malignancies were in the 5th-9th decades of life. This was statistically significant at P = 0.000. SCC was more prevalent than salivary and odontogenic carcinomas. ACC and mucoepidermoid carcinoma were two most common SGAs. Metastatic tumours to the jaws are rare.


[Erysipelas today].
Erysipelas is a form of cellulitis and a bacterial infection affecting the most superficial layers of the skin which is caused by group A--hemolytic Streptococcus. The symptoms of erysipelas usually arise quite suddenly and they are often accompanied by fever, chill and shivering. The affected skin is distinguished from other forms of cellulitis by well-defined, raised edge. The affected skin is red, swollen and may be finely dimpled (like an orange skin). TREATMENT OF ERYSIPELAS: Uncomplicated erysipelas can be treated on an outpatient basis. Indications for hospitalization include a severe clinical picture and socioeconomics factors. Most patients suffering from erysipelas in Belgrade are treated at the Institute of Infectious and Tropical Diseases, and the aim of this study was to analyze patients treated during 2002 and 2003, in order to determine characteristics of erysipelas at the beginning of the XXI century. During the studied period, we treated 60 patients (26.7%) of all registrated erysipelas cases in Belgrade. The male/female ratio was 1:1.6. Prevalence was higher during the summer months. In most cases, the severity and the need for hospitalization were recognized at the beginning; therefore, 74% of patients were hospitalized during the first five days from the onset of nonspecific signs of illness. Laboratory tests showed mild leukocytosis (med 12.05 x 10/9/l), with predominant neutrophils (74.8%) and increased fibrinogen (med 5.4 g/l). Predisposing factors were present in 83.3% of cases; of them, in 35% of cases this was not the first episode of this illness. In 85% of cases erysipelas of the leg was established, and it was the most frequent localization of all.


Analysis of dark albedo features on a southern polar dune field of Mars.
We observed 20-200 m sized low-albedo seepage-like streaks and their annual change on defrosting polar dunes in the southern hemisphere of Mars, based on the Mars Orbiter Camera (MOC), High Resolution Stereo Camera (HRSC), and High Resolution Imaging Science Experiment (HiRISE) images. The structures originate from dark spots and can be described as elongated or flowlike and, at places, branching streaks. They frequently have another spotlike structure at their end. Their overall appearance and the correlation between their morphometric parameters suggest that some material is transported downward from the spots and accumulates at the bottom of the dune's slopes. Here, we present possible scenarios for the origin of such streaks, including dry avalanche, liquid CO(2), liquid H(2)O, and gas-phase CO(2). Based on their morphology and the currently known surface conditions of Mars, no model interprets the streaks satisfactorily. The best interpretation of only the morphology and morphometric characteristics is only given by the model that implies some liquid water. The latest HiRISE images are also promising and suggest liquid flow. We suggest, with better knowledge of sub-ice temperatures that result from extended polar solar insolation and the heat insulator capacity of water vapor and water ice, future models and measurements may show that ephemeral water could appear and flow under the surface ice layer on the dunes today.


[Is the surgeon still the main prognosis factor?].
Assessment of surgeon's influence on the results of cancer surgery is complex. Investigation field is extremely large and should differentiate surgeon's impact from the one of surgery. This can result in major differences in the rate of postoperative complications and deaths, in the indication and use of technically difficult surgeries, and also in long-term results. The surgeon's impact is correlated with his activity volume for each type of major procedures and is independent from hospital activity volume. It persists independently of major progresses in hospital organization and process standardization. Data from the literature confirm the prognosis importance of the surgeon in cancer outcome. In the future, the timely implementation of established, evidence-based guidelines and checklists programs could prevent large number of deaths and complications and reduce the surgeon specific impact.


Efficacy of electrolyzed oxidizing water and lactic acid on the reduction of Campylobacter on naturally contaminated broiler carcasses during processing.
Campylobacter is the most commonly reported gastrointestinal bacterial pathogen in humans in many developed countries. During slaughter of broiler flocks, it is difficult to avoid contamination of broiler carcasses. This study aimed to quantify Campylobacter contamination on broiler carcasses at 5 points in the slaughter processing during the slaughter of a Campylobacter-colonized flock by real-time PCR and conventional enumeration. In addition, the decontamination effect of neutral electrolyzed oxidizing (EO) water and 1.5% lactic acid (pH 2.0) were evaluated. During processing, the Campylobacter counts on the carcasses declined toward the end of the processing line. The log counts on the carcasses as determined by quantitative real-time PCR (qPCR), decreased from 9.37 after scalding to 8.08 after the last cooling step. Enumeration of the campylobacters on plates revealed the same trend, although the counts per carcass were generally 3 logs lower. After scalding, a mean of 6.86 log cfu/carcass were counted, which decreased to 4.83 log cfu/carcass after the last cooling step. Submerging carcasses after scalding in EO water gave a significant reduction of 1.31 log cfu/carcass by enumeration on plates and a not significant reduction of 0.53 log cfu/carcass by qPCR. Treatment of the carcasses after the inside-outside bird washer led to reductions from 0.09 to 0.91 log cfu/carcass, although not significant. After submerging the carcasses in a 1.5% lactic acid solution, significant reductions of 1.62 and 1.24 log cfu/carcass by qPCR and enumeration, respectively, were observed. Spraying the carcasses with lactic acid led to nonsignificant reductions of 0.68 log cfu/carcass determined by qPCR and 0.26 log cfu/carcass by enumeration. Both EO water and lactic acid seem promising for implementation in poultry processing plants.


Microbicidal cationic proteins of rabbit alveolar macrophages: amino acid composition and functional attributes.
We purified two microbicidal cationic proteins, MCP-1 and MCP-2, from rabbit alveolar macrophages. MCP-1 was remarkably rich in arginine (25.5 mol%) and half cystine (18.7 mol%) residues and constituted approximately 1.5% of the total protein content of Freund adjuvant-elicited alveolar macrophages. MCP-2 was approximately half as abundant as MCP-1 and contained relatively less arginine (14.9 mol%) and half cystine (9.8 mol%). The amino acid compositions of MCP-1 and MCP-2 resembled those reported for the lysosomal cationic proteins of rabbit granulocytes, but were distinct from those of any known histone. MCP-1 (1 microgram/ml) killed 99.6% of Candida albicans in 20 min, whereas MCP-2 killed approximately 80% under similar conditions. Both proteins rapidly suppressed O2 consumption by C. albicans and induced a rapid loss of intracellular 86Rb+. Although more information is needed about the biological origin, distribution, and roles of macrophage microbicidal proteins, it seems likely that MCP-1 and MCP-2 contribute to the microbicidal efficacy of rabbit alveolar macrophages.


Somatic mutation detection using various targeted detection assays in paired samples of circulating tumor DNA, primary tumor and metastases from patients undergoing resection of colorectal liver metastases.
Assessing circulating tumor DNA (ctDNA) is a promising method to evaluate somatic mutations from solid tumors in a minimally-invasive way. In a group of twelve metastatic colorectal cancer (mCRC) patients undergoing liver metastasectomy, from each patient DNA from cell-free DNA (cfDNA), the primary tumor, metastatic liver tissue, normal tumor-adjacent colon or liver tissue, and whole blood were obtained. Investigated was the feasibility of a targeted NGS approach to identify somatic mutations in ctDNA. This targeted NGS approach was also compared with NGS preceded by mutant allele enrichment using synchronous coefficient of drag alteration technology embodied in the OnTarget assay, and for selected mutations with digital PCR (dPCR). All tissue and cfDNA samples underwent IonPGM sequencing for a CRC-specific 21-gene panel, which was analyzed using a standard and a modified calling pipeline. In addition, cfDNA, whole blood and normal tissue DNA were analyzed with the OnTarget assay and with dPCR for specific mutations in cfDNA as detected in the corresponding primary and/or metastatic tumor tissue. NGS with modified calling was superior to standard calling and detected ctDNA in the cfDNA of 10 patients harboring mutations in APC, ATM, CREBBP, FBXW7, KRAS, KMT2D, PIK3CA and TP53. Using this approach, variant allele frequencies in plasma ranged predominantly from 1 to 10%, resulting in limited concordance between ctDNA and the primary tumor (39%) and the metastases (55%). Concordance between ctDNA and tissue markedly improved when ctDNA was evaluated for KRAS, PIK3CA and TP53 mutations by the OnTarget assay (80%) and digital PCR (93%). Additionally, using these techniques mutations were observed in tumor-adjacent tissue with normal morphology in the majority of patients, which were not observed in whole blood. In conclusion, in these mCRC patients with oligometastatic disease NGS on cfDNA was feasible, but had limited sensitivity to detect all somatic mutations present in tissue. Digital PCR and mutant allele enrichment before NGS appeared to be more sensitive to detect somatic mutations.


Epoxyeicosatrienoic acids are part of the VEGF-activated signaling cascade leading to angiogenesis.
Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid to epoxyeicosatrienoic acid (EET) regioisomers, which activate several signaling pathways to promote endothelial cell proliferation, migration, and angiogenesis. Since vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, we assessed a possible role of EETs in the VEGF-activated signal transduction cascade. Stimulation with VEGF increased CYP2C promoter activity in endothelial cells and enhanced CYP2C8 mRNA and protein expression resulting in increased intracellular EET levels. VEGF-induced endothelial cell tube formation was inhibited by the EET antagonist 14,15-epoxyeicosa-5(Z)-enoicacid (14,15-EEZE), which did not affect the VEGF-induced phosphorylation of its receptor or basic fibroblast growth factor (bFGF)-stimulated tube formation. Moreover, VEGF-stimulated endothelial cell sprouting in a modified spheroid assay was reduced by CYP2C antisense oligonucleotides. Mechanistically, VEGF stimulated the phosphorylation of the AMP-activated protein kinase (AMPK), which has also been linked to CYP induction, and the overexpression of a constitutively active AMPK mutant increased CYP2C expression. On the other hand, a dominant-negative AMPK mutant prevented the VEGF-induced increase in CYP2C RNA and protein expression in human endothelial cells. In vivo (Matrigel plug assay) in mice, endothelial cells were recruited into VEGF-impregnated plugs; an effect that was sensitive to 14,15-EEZE and the inclusion of small interfering RNA directed against the AMPK. The EET antagonist did not affect responses observed in plugs containing bFGF. Taken together, our data indicate that CYP2C-derived EETs participate as second messengers in the angiogenic response initiated by VEGF and that preventing the increase in CYP expression curtails the angiogenic response to VEGF.


Air Pollution and the microvasculature: a cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA).
Long- and short-term exposures to air pollution, especially fine particulate matter (PM(2.5)), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature. Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000-2002). Long-term outdoor concentrations of PM(2.5) were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM(2.5). These relationships were observed in a joint exposure model with -0.8 µm (95% confidence interval [CI] -1.1 to -0.5) and -0.4 µm (95% CI -0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m(3)) and short-term (9 µg/m(3)) PM(2.5) levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a -0.7 µm decrease (95% CI -1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM(2.5) concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM(2.5). Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease. Please see later in the article for the Editors' Summary.


Mitochondrial genetics in Bakers' yeast: a molecular mechanism for recombinational polarity and suppressiveness.
Recombinational polarity and suppressiveness are two well-known but puzzling cytoplasmic genetic phenomena in bakers' yeast, Saccharomyces cerevisiae. Little progress has been made in characterizing the underlying molecular mechanisms of these phenomena. In this paper we describe a molecular model for recombinational polarity that is compatible with the available genetic evidence. The model stresses the role of small deletions and excision/repair processes in otherwise canonical recombinational events. According to the model, both phenomena require recombination and may share mechanistic elements.


Comparative fitness analysis of D-cycloserine resistant mutants reveals both fitness-neutral and high-fitness cost genotypes.
Drug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for six decades without significant appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We therefore investigated why Mycobacterium tuberculosis fails to become resistant to D-cycloserine. To address this question, we employed a combination of bacterial genetics, genomics, biochemistry and fitness analysis in vitro, in macrophages and in mice. Altogether, our results suggest that the ultra-low rate of emergence of D-cycloserine resistance mutations is the dominant biological factor delaying the appearance of clinical resistance to this antibiotic. Furthermore, we also identified potential compensatory mechanisms able to minimize the severe fitness costs of primary D-cycloserine resistance conferring mutations.


Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints.
Yazıcı S, Güneş S, Kurtuluş-Çokboz M, Kemer Ö, Baranlı G, Aşık-Akman S, Can D. Allergen variability and house dust mite sensitivity in pre-school children with allergic complaints. Turk J Pediatr 2018; 60: 41-49. The increase in the prevalence of allergic diseases in pre-school children who are often at home may be due to an increase in house dust mite sensitivity, which is rarely expected in this age group. In our study, it was aimed to investigate allergen sensitivities, especially house dust mite sensitivity in pre-school children with allergic disease complaints by skin prick test (SPT). Two hundred and twenty children admitted to the Pediatric Allergy and Asthma Clinic of Balıkesir University between October 2015 and October 2016 diagnosed with asthma, allergic rhinitis, food allergy, atopic dermatitis or urticaria were involved in the retrospective cross-sectional study. Allergen groups used in SPT were Dermatophagoides farina (Derf), Dermatophagoides pteronyssinus (Der p), Alternaria alternata, cat epithelium, pollen mixture and food mixture. Average age of the 220 patients was 2.98 years (2.75-3.21). SPT was positive in 55.9% of patients. Sixteen percent were monosensitized and 73.8% were polysensitized. Seventy two children (32.7%) were sensitive to Der f and 67 (30.4%) were sensitive to Der p. There was no difference between SPT positivity and gender (p > 0.05). Ninty-five children were diagnosed with asthma, 38 with asthma and allergic rhinitis, 63 with food allergy and 24 with urticaria and/or atopic dermatitis. SPT positivity was significantly higher in the asthma and allergic rhinitis group than other groups. As the age increased, significant increases in the sensitivities of Der f (p < 0.01), Der p (P < 0.01) and A. alternata (p < 0.05) and a significant decrease for food panel sensitivity (p < 0.01) were detected. Even though skin and food allergies were included in our study, house dust mite sensitivity was found much higher than other studies reporting ranges between 3.5-23% in children of the same age group with mainly respiratory complaints. It is concluded that the probable reasons for this increase, especially geographical features, should be investigated in different areas and in larger number of studies.


Transportation mechanism for vanillin uptake through fungal plasma membrane.
Protoplasts of the basidiomycete, Fomitopsis palustris (formerly Tyromyces palustris), were utilized to study a function of the fungal plasma membrane. Fungal protoplasts exhibited metabolic activities as seen with intact mycelial cells. Furthermore, the uptake of certain compounds into the protoplast cells was quantitatively observed by using non-radioactive compounds. Vanillin was converted to vanillyl alcohol and vanillic acid as major products and to protocatechuic acid and 1,2,4-trihydroxybenzene as trace products by protoplasts prepared from F. palustris. Extracellular culture medium showed no activity responsible for the redox reactions of vanillin. Only vanillic acid was detected in the intracellular fraction of protoplasts. However, the addition of disulfiram, an aldehyde dehydrogenase inhibitor, caused an intracellular accumulation of vanillin, strongly suggesting that vanillin is taken up by the cell, followed by oxidation to vanillic acid. The addition of carbonylcyanide m-chlorophenylhydrazone, which dissipates the pH gradient across the plasma membrane, inhibited the uptake of either vanillin or vanillic acid into the cell. Thus, the fungus seems to possess transporter devices for both vanillin and vanillic acid for their uptake. Since vanillyl alcohol was only observed extracellularly, the reduction of vanillin was thought to be catalyzed by a membrane system.


Hypofractionated radiotherapy for localized prostate cancer.
This article gives an overview on the current status of hypofractionated radiotherapy in the treatment of prostate cancer with a special focus on the applicability in routine use. Based on a recently published systematic review the German Society of Radiation Oncology (DEGRO) expert panel added additional information that has become available since then and assessed the validity of the information on outcome parameters especially with respect to long-term toxicity and long-term disease control. Several large-scale trials on moderate hypofractionation with single doses from 2.4-3.4 Gy have recently finished recruiting or have published first results suggestive of equivalent outcomes although there might be a trend for increased short-term and possibly even long-term toxicity. Large phase 3 trials on extreme hypofractionation with single doses above 4.0 Gy are lacking and only very few prospective trials have follow-up periods covering more than just 2-3 years. Until the results on long-term follow-up of several well-designed phase 3 trials become available, moderate hypofractionation should not be used in routine practice without special precautions and without adherence to the highest quality standards and evidence-based dose fractionation regimens. Extreme hypofractionation should be restricted to prospective clinical trials.


A decade beyond the economic recession: A study of health-related lifestyles in urban and rural Spain (2006-2017).
The 2008 economic recession may have affected health-related indicators differently depending on the living environment. We analyze health-related indicators in Spain using data from four Spanish health surveys (2006, 2011, 2014, and 2017, 95 924 individuals aged ≥16 years). In 2006-2011, physical activity decreased among men and women, while in 2006-2017, physical activity only decreased among urban women. Daily vegetable intake, except in rural women, increased in 2006-2011 but decreased in 2006-2017 in all groups. Smoking decreased among urban women in 2006-2011 and 2006-2014 but only decreased among men, and even increased among rural women, in 2006-2017. In 2006-2017, obesity increased among men and urban women, good self-rated health status increased in all groups and flu vaccination declined. Blood pressure and cholesterol control decreased in urban women in 2006-2011 but increased in 2006-2017 in all groups, as well as mammographic and cytological control. Our findings highlight the differential impact of the economic recession on health-related lifestyles according to sex and place of residence, underscoring the need for targeted health policies to address evolving health disparities over time.


Distributed cognition and social brains: reductions in mushroom body investment accompanied the origins of sociality in wasps (Hymenoptera: Vespidae).
The social brain hypothesis assumes the evolution of social behaviour changes animals' ecological environments, and predicts evolutionary shifts in social structure will be associated with changes in brain investment. Most social brain models to date assume social behaviour imposes additional cognitive challenges to animals, favouring the evolution of increased brain investment. Here, we present a modification of social brain models, which we term the distributed cognition hypothesis. Distributed cognition models assume group members can rely on social communication instead of individual cognition; these models predict reduced brain investment in social species. To test this hypothesis, we compared brain investment among 29 species of wasps (Vespidae family), including solitary species and social species with a wide range of social attributes (i.e. differences in colony size, mode of colony founding and degree of queen/worker caste differentiation). We compared species means of relative size of mushroom body (MB) calyces and the antennal to optic lobe ratio, as measures of brain investment in central processing and peripheral sensory processing, respectively. In support of distributed cognition predictions, and in contrast to patterns seen among vertebrates, MB investment decreased from solitary to social species. Among social species, differences in colony founding, colony size and caste differentiation were not associated with brain investment differences. Peripheral lobe investment did not covary with social structure. These patterns suggest the strongest changes in brain investment--a reduction in central processing brain regions--accompanied the evolutionary origins of eusociality in Vespidae.


Ergonomic risk associated with assisting in minimally invasive surgery.
Given the physical risks associated with performing laparoscopic surgery, ergonomics to date has focused on the primary minimally invasive surgeon. Similar studies have not extended to other operating room staff. Simulation of the assistant's role as camera holder and retractor during a Nissen fundoplication allowed investigation of the ergonomic risks involved in these tasks. Seven subjects performed camera navigation and retraction tasks using a box trainer on an operating room table that simulated an adult patient in low lithotomy position. Each subject stood on force plates at the simulated patient's left side. A laparoscope was introduced through a port into the training box with four 2-cm circles as rear-panel targets located in relation to the assistant as distal superior, proximal superior, distal inferior, and proximal inferior target effects. The subjects held the camera with their left hand, pointing it at a target. The task was to match the target to a circle overlaid on the monitor. Simultaneously, a grasper in the right hand grasped and pulled a panel-attached band. A minute signal moved the subject to the next target. Each trial had three four-target repetitions (phase effect). The subjects performed two separate trials: one while holding the camera from the top and one while holding it from the bottom (grip effect). A 4 x 3 x 2 (target x phase x grip) repeated-measures design provided statistics. Dividing the left force-plate vertical ground reaction forces (VGRF) by the total VGRF from both plates provided a weight-loading ratio (WLR). The WLR significantly increased (p < 0.005) with proximal targets (2 by 80% and 4 by 79%). The WLR decreased 75%, 74%, and 71% over time. No difference existed between the grip strategies (grip effect, p > 0.5). A high-risk ergonomic situation is created by the assistant's left or caudal leg disproportionately bearing 70-80% of body weight over time. A distance increase between the camera head location and the camera holder increases ergonomic risk. The phase effect was interpreted as a compensatory rebalancing to reduce ergonomic risk. Ergonomic solutions minimizing ergonomic risks associated with laparoscopic assistance should be considered.


Computational-weighted Fourier single-pixel imaging via binary illumination.
Single-pixel imaging has the ability to generate images at nonvisible wavelengths and under low light conditions and thus has received increasing attention in recent years. Fourier single-pixel imaging (FSI) utilizes deterministic basis patterns for illumination to greatly improve the quality of image reconstruction. However, the original FSI based on grayscale Fourier basis illumination patterns is limited by the imaging speed as the digital micro-mirror devices (DMD) used to generate grayscale patterns operate at a low refresh rate. In this paper, a new approach is proposed to increase the imaging speed of DMD-based FSI without reducing the imaging spatial resolution. In this strategy, the grayscale Fourier basis patterns are split into a pair of grayscale patterns based on positive/negative pixel values, which are then decomposed into a cluster of binary basis patterns based on the principle of decimalization to binary. These binary patterns are used to illuminate the imaged object. The resulting detected light intensities multiply the corresponding weighted decomposed coefficients and are summed, and the results can be used to generate the Fourier spectrum for the imaged object. Finally, an inverse Fourier transform is applied to the Fourier spectrum to obtain the object image. The proposed technique is verified by a computational simulation and laboratory experiments. Both static and dynamic imaging experiments are carried out to demonstrate the proposed strategy. 128 × 128 pixels dynamic scenes at a speed of ~9 frames-per-second are captured under 22 KHz projection rate using a DMD. The reported technique accelerates the imaging speed for DMD-based FSI and provides an alternative approach to improve FSI efficiency.


Differential patterns of Batrachochytrium dendrobatidis infection in relict amphibian populations following severe disease-associated declines.
Global amphibian biodiversity has declined dramatically in the past 4 decades, and many amphibian species have declined to near extinction as a result of emergence of the amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd). However, persistent or recovering populations of several amphibian species have recently been rediscovered, and such populations may illustrate how amphibian species that are highly susceptible to chytridiomycosis may survive in the presence of Bd. We conducted field surveys for Bd infection in 7 species of Costa Rican amphibians (all species that have declined to near extinction but for which isolated populations persist) to characterize infection profiles in highly Bd-susceptible amphibians post-decline. We found highly variable patterns in infection, with some species showing low prevalence (~10%) and low infection intensity and others showing high infection prevalence (>80%) and either low or high infection intensity. Across sites, infection rates were negatively associated with mean annual precipitation, and infection intensity across sites was negatively associated with mean average temperatures. Our results illustrate that even the most Bd-susceptible amphibians can persist in Bd-enzootic ecosystems, and that multiple ecological or evolutionary mechanisms likely exist for host-pathogen co-existence between Bd and the most Bd-susceptible amphibian species. Continued monitoring of these populations is necessary to evaluate population trends (continuing decline, stability, or population growth). These results should inform efforts to mitigate impacts of Bd on amphibians in the field.


Computed Tomographic Evaluation of Posttreatment Soft-Tissue Changes by Using a Lymphedema Scoring System in Patients with Oral Cancer.
This study aimed to evaluate posttreatment soft-tissue changes in patients with oral cancer with computed tomography (CT). To accomplish that purpose, a scoring system was established, referring to the criteria of lower leg lymphedema (LE). One hundred and six necks in 95 patients who underwent oral oncologic surgery with neck dissection (ND) were analyzed retrospectively using routine follow-up CT images. A two-point scoring system to evaluate soft-tissue changes (so-called "LE score") was established as follows: Necks with a "honeycombing" appearance were assigned 1 point. Necks with "taller than wide" fat lobules were assigned 1 point. Necks with neither appearance were assigned 0 points. Comparisons between patients with LE score ≥1 and LE score = 0 at 6 months postoperatively were performed using the Fisher exact test for discrete variables and the Mann-Whitney U test for continuous variables. Univariate predictors associated with posttreatment changes (i.e., LE score ≥1 at 6 months postoperatively) were entered into a multivariate logistic regression analysis. Values of p < 0.05 were considered to indicate statistical significance. The occurrence of the posttreatment soft-tissue changes was 32%. Multivariate logistic regression analysis showed that postoperative radiation therapy (RT) and bilateral ND were potential risk factors of posttreatment soft-tissue changes on CT images. Sequential evaluation of "honeycombing" and the "taller than wide" appearances on routine follow-up CT revealed the persistence of posttreatment soft-tissue changes in patients who underwent oral cancer treatment, and those potential risk factors were postoperative RT and bilateral ND.


Non-vertebrate melatonin.
Melatonin has been detected in bacteria, eukaryotic unicells, macroalgae, plants, fungi and various taxa of invertebrates. Although precise determinations are missing in many of these organisms and the roles of melatonin are still unknown, investigations in some species allow more detailed conclusions. Non-vertebrate melatonin is not necessarily circadian, and if so, not always peaking at night, although nocturnal maxima are frequently found. In the cases under study, the major biosynthetic pathway is identical with that of vertebrates. Mimicking of photoperiodic responses and concentration changes upon temperature decreases have been studied in more detail only in dinoflagellates. In plants, an involvement in photoperiodism seems conceivable but requires further support. No stimulation of flowering has been demonstrated to date. A participation in antioxidative protection might be possible in many aerobic non-vertebrates, although evidence for a contribution at physiological levels is mostly missing. Protection from stress by oxidotoxins or/and extensions of lifespan have been shown in very different organisms, such as the dinoflagellate Lingulodinium, the ciliate Paramecium, the rotifer Philodina and Drosophila. Melatonin can be taken up from the food, findings with possible implications in ecophysiology as well as for human nutrition and, with regard to high levels in medicinal plants, also in pharmacology.


Morbidity Related Groups (MRG) for Epidemiological Analysis in Outpatient Treatment.
Each patient in outpatient treatment is assigned per quarter and corresponding physician to a case group that is strongly related to the morbidity (Morbidity Related Group, MRG). MRG is defined by the drug group on a four character level in the international anatomic-therapeutic-chemical (ATC) classification with the largest costs as an indicator for the severity of the drug treatment. Using severity levels we get a risk adjustment with respect to age and polypharmacy as an indicator for multimorbidity and treatment intensity. By application of MRG groups we generate a patient type classification in relation to physicians and a distance structure of the medical disciplines.


High-dose ketorolac affects adult spinal fusion: a meta-analysis of the effect of perioperative nonsteroidal anti-inflammatory drugs on spinal fusion.
Meta-analysis of literature. To evaluate the effect of perioperative nonsteroidal anti-inflammatory drugs (NSAIDs) on the success rate of adult spinal fusion. NSAIDs are commonly used to treat postsurgical orthopedic pain. Studies on animal models have shown a significant inhibiting effect of NSAIDs on osteogenesis process, on which spinal fusion also depends. Recently, great interest has been shown in the effect of NSAIDs on the success rate of adult spinal fusion. Clinical trials have tested the effect of perioperative NSAIDs in spinal fusion procedures. A cumulative result of these studies would give more credit to the final conclusions. A systematic search of electronic databases and references from eligible articles was conducted. Comparative studies reporting on the results of primary spinal fusion including treatment group of NSAIDs perioperatively were regarded eligible. A pooled estimate of effect size was produced using both random and fixed effect model. Five retrospective comparative studies (n = 1403 participants) were included in the present study. The mean age of these patients was more than 40 years and none of them had NSAIDs for longer than 14 days following spinal fusion surgery. High-dose ketorolac showed a statistically significant adverse effect on spinal fusion (P = 0.001, RR = 2.87, 95% CI = 1.53 = - 5.38) with no statistical heterogeneity (I = 3%, P = 0.38), whereas normal-dose NSAIDs (ketorolac, diclofenac sodium, celecoxib, or rofecoxib) did not appear to produce inferior results than the no-NSAIDs group (P = 0.30, RR = 1.39, 95% CI = 0.74 - 2.61) with no statistical heterogeneity (I² = 0%, P = 0.50). Although randomized controlled trials would be optimal for meta-analyses, the data of this review revealed that short-time (<14 days) exposure to normal-dose NSAIDs (ketorolac, diclofenac sodium, celecoxib, or rofecoxib) were safe after spinal fusion, whereas short-time (<14 days) exposure to high-dose ketorolac increased the risk of nonunion, which meant that the effect of perioperative NSAIDs on spinal fusion might be dose-dependent. Further studies would be needed to find out whether long-time exposure to normal-dose NSAIDs could also increase the risk of nonunion and which type of NSAIDs would like to have a worse effect on spinal fusion.


Effects of the polysaccharide fraction of Urtica fissa on castrated rat prostate hyperplasia induced by testosterone propionate.
A crude polysaccharide fraction of Urtica fissa roots and stems (UFP) was obtained by water extraction and ultrafiltration, and its effect on castrated rat prostate hyperplasia induced by testosterone propionate was evaluated by the volume index, wet and dry weight index and histopathological tests. Results showed that the crude polysaccharide fraction significantly inhibited prostatic hyperplasia in animal models at doses of 62.5, 125, 250 mg/kg body wt. (administered orally). Treatment with UFP at 62.5 mg/kg body wt. decreased the volume index by 32%, the wet weight index by 17% and the dry weight index by 23%, respectively. In the high-dose group (UFP at 250 mg/kg body wt.), the indexes of volume, wet weight and dry weight decreased further by 37%, 25% and 33%, respectively. Histopathological examination showed that proliferation of prostatic epithelial cells and fibrotic tissues were significantly inhibited.


Pain, Agitation, and Delirium Guidelines: Interprofessional Perspectives to Translate the Evidence.
Societal guidelines exist for the management of pain, agitation, and delirium (PAD) in critically ill patients. This contemporary practice aims for a more awake and interactive patient. Institutions are challenged to translate the interrelated multivariable concepts of PAD into daily clinical practice and to demonstrate improvement in quality outcomes. An interdisciplinary goal-directed approach shows outcomes in high-acuity surgical critical care during the early stages of implementation. This study was a prospective preintervention and postintervention design. A formal PAD clinical practice guideline targeting standardized assessment and "light" levels of sedation was instituted. All mechanically ventilated patients admitted to a 24-bed surgical intensive care unit (ICU) at an academic medical center during a 6-month period were included (3 months before and 3 months after implementation). Sedation and agitation were measured using the Richmond Agitation Sedation Scale (RASS), pain measured using a Behavioral or Numeric Pain Scale (NPS/BPS), and delirium using the Confusion Assessment Method for the Intensive Care Unit. Total ventilator days with exposure to continuous opioid or sedative infusions and total ICU days where the patient received a physical activity session exercising out of bed were recorded. There were 106 patients (54 at preintervention and 52 at postintervention). Mean percentage of RASS scores between 0 to -1 increased from 38% to 50% postintervention (P < .02). Mean percentage of NPS/BPS scores within the goal range (<5 for BPS and <3 for NPS) remained stable, 86% to 83% (P = .16). There was a decrease in use of continuous narcotic infusions for mechanically ventilated patients. This was reported as mean percentage of total ventilator days with a continuous opioid infusing: 65% before implementation versus 47% after implementation (P < .01). Mean percentage of ICU days with physical activity sessions increased from 24% to 41% (P < .001). Overall mean ventilator-free days and ICU length of stay were 5.4 to 4.5 days (P = .29) and 11.75 to 9.5 days (P = .20), respectively. Measureable patient outcomes are achievable in the early stages of PAD guideline initiatives and can inform future systems-level organizational change. Pain, agitation, and delirium assessment tools form the foundation for clinical implementation and evaluation. High-acuity surgical critical care patients can achieve more time at goal RASS, decreased ventilator days, and less exposure to continuous opioid infusions, all while maintaining stable analgesia.


Estimating the lifelong health impact and financial burdens of different types of lung cancer.
Owing to the high mortality and rapidly growing costs related to lung cancer, it is worth examining the health benefits of prevention for major types of lung cancer. This study attempts to quantify the quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures of patients with different pathological types of lung cancer. A national cohort consisting of 66,535 patients with pathologically verified lung cancer was followed for 13 years (1998-2010) to obtain the survival function, which was further extrapolated to lifetime. Between 2011 and 2012, EuroQol 5-dimension questionnaires were used to measure the quality of life (QoL) for 1,314 consecutive, cross-sectional samples. After multiplying the lifetime survival function by the utility values of QoL, we estimated the QALE and loss-of-QALE. We also collected the monthly healthcare expenditures, which included National Health Insurance-reimbursed and out-of-pocket direct medical costs, for 2,456 patients from 2005 to 2012. These values were multiplied by the corresponding survival probabilities to calculate lifetime healthcare expenditures after adjustments with medical care inflation rates and annual discount rates. The QALE for patients with small cell lung cancer, squamous cell carcinoma, and adenocarcinoma were 1.21, 2.37, and 3.03 quality-adjusted life year (QALY), with the corresponding loss-of-QALE of 13.69, 12.22, and 15.03 QALY, respectively. The lifetime healthcare expenditures were US$ 18,455 ± 1,137, 20,599 ± 1,787, and 36,771 ± 1,998, respectively. The lifelong health impact and financial burdens in Taiwan are heavier for adenocarcinoma than for squamous cell carcinoma. The cost-effectiveness of prevention programs could be directly compared with that of treatment strategies to improve patient value. And the methodology could be applied to other chronic diseases for resources planning of healthcare services.


Epigallocatechin 3-O-gallate induces 67 kDa laminin receptor-mediated cell death accompanied by downregulation of ErbB proteins and altered lipid raft clustering in mammary and epidermoid carcinoma cells.
Since the administration of synthetic medicines is associated with drug resistance and undesired side effects, utilization of natural compounds could be an alternative and complementary modality to inhibit or prevent the development of tumors. Epigallocatechin 3-O-gallate (EGCG, 1), the major flavan component of green tea, and genistein (2), a soy isoflavonoid, are known to have chemopreventive and chemotherapeutic effects against cancer. This study demonstrated that both flavonoids inhibit cell proliferation, an effect enhanced under serum-free conditions. Compound 1, but not 2, induced downregulation of ErbB1 and ErbB2 in mammary and epidermoid carcinoma cells, and its inhibitory effect on cell viability was mediated by the 67 kDa laminin receptor (67LR). While 1 was superior in inducing cell death, 2 was more efficient in arresting the tumor cells in the G2/M phase. Furthermore, number and brightness analysis revealed that 1 decreased the homoclustering of a lipid raft marker, glycosylphosphatidylinositol-anchored GFP, and it also reduced the co-localization between lipid rafts and 67LR. The main conclusion made is that the primary target of 1 may be the lipid raft component of the plasma membrane followed by secondary changes in the expression of ErbB proteins. Compound 2, on the other hand, must have other unidentified targets.


Computational fluid dynamic studies of leukocyte adhesion effects on non-Newtonian blood flow through microvessels.
The study of the effect of leukocyte adhesion on blood flow in small vessels is of primary interest to understand the resistance changes in venular microcirculation. Available computational fluid dynamic studies provide information on the effect of leukocyte adhesion when blood is considered as a homogeneous Newtonian fluid. In the present work we aim to understand the effect of leukocyte adhesion on the non-Newtonian Casson fluid flow of blood in small venules; the Casson model represents the effect of red blood cell aggregation. In our model the blood vessel is considered as a circular cylinder and the leukocyte is considered as a truncated spherical protrusion in the inner side of the blood vessel. The cases of single leukocyte adhesion and leukocyte pairs in positions aligned along the same side, and opposite sides of the vessel wall are considered. The Casson fluid parameters are chosen for cat blood and human blood and comparisons are made for the effects of leukocyte adhesion in both species. Numerical simulations demonstrated that for a Casson fluid with hematocrit of 0.4 and flow rate Q = 0.072 nl/s, a single leukocyte increases flow resistance by 5% in a 32 microns diameter and 100 microns long vessel. For a smaller vessel of 18 microns, the flow resistance increases by 15%.