Ionic hydration-induced evolution of decane-water interfacial tension.
Building a connection between the variations in interfacial tension and the microstructure of the oil-water interface is still very challenging. Here, we employ a molecular dynamics method to study the effect of monovalent ions on the decane-water interfacial tension and reveal the relationship between ionic hydration and the variation of interfacial tension. Our results indicate that interfacial tension presents a non-monotonic dependence on the ionic concentrations owing to the distinctive adsorption characteristics of ions. At low ionic concentrations, the hydration of the discrete ions at the interface causes an enhancement in the virial term of the interfacial tension, resulting in an increase of the interfacial tension with increasing ionic concentrations. At high ionic concentrations, the ion pairs at the interface weaken the ionic hydration, thus the virial term of the interfacial tension decreases and the interfacial tension decreases slightly. In addition, the kinetic energy term of interfacial tension increases only with increasing temperature, while the virial term decreases with an increase in either temperature or pressure on account of the weakening ionic hydration; therefore, the increase of temperature and pressure induces different degrees of the decrease in the interfacial tension owing to the major contribution of the virial term, particularly at high ionic concentrations.


Therapy of deep vein thrombosis.
Adequate anticoagulation treatment in patients with deep vein thrombosis reduces the risk of thrombus extension or embolization to less than 5%. Thrombolytic treatment may possibly prevent subsequent postthrombotic syndrome. Heparin is the initial treatment of choice for most patients with deep vein thrombosis. The dose is adjusted according to the results of tests such as the whole blood clotting time, thrombin clotting time, activated partial thromboplastin time or plasma heparin concentration. The most commonly used test is the activated partial thromboplastin time which should be maintained at 1 1/2 to two times the control level. Initially the test should be performed two to three times daily and when optimal adjustment has been established, clotting studies are required only at 24-hour intervals. In general, treatment with intravenous heparin should be continued for seven to ten days. Thereafter, for secondary prophylaxis, treatment with oral anticoagulants is carried out for six to eight weeks for symptomatic lower leg thrombosis, for twelve weeks in the case of proximal venous thrombosis and pulmonary embolism. Oral anticoagulant therapy with warfarin should be given overlapping the last few days of heparin with the dose adjusted to prolong the prothrombin time to 1.3 to 1.5 times control. Initially, the prothrombin time should be monitored weekly, thereafter at intervals of two to three weeks. If oral anticoagulant therapy is contraindicated, secondary prophylaxis with subcutaneous heparin given twice daily in doses sufficient to prolong the activated partial thromboplastin time to 1 1/2 times control is an effective and safe alternative. The major side effect of oral anticoagulant therapy, as well as that of heparin, is bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparative Cost of Early Infant Male Circumcision by Nurse-Midwives and Doctors in Zimbabwe.
The 14 countries that are scaling up voluntary male medical circumcision (VMMC) for HIV prevention are also considering early infant male circumcision (EIMC) to ensure longer-term reductions in HIV incidence. The cost of implementing EIMC is an important factor in scale-up decisions. We conducted a comparative cost analysis of EIMC performed by nurse-midwives and doctors using the AccuCirc device in Zimbabwe. Between August 2013 and July 2014, nurse-midwives performed EIMC on 500 male infants using AccuCirc in a field trial. We analyzed the overall unit cost and identified key cost drivers of EIMC performed by nurse-midwives and compared these with costing data previously collected during a randomized noninferiority comparison trial of 2 devices (AccuCirc and the Mogen clamp) in which doctors performed EIMC. We assessed direct costs (consumable and nonconsumable supplies, device, personnel, associated staff training, and waste management costs) and indirect costs (capital and support personnel costs). We performed one-way sensitivity analyses to assess cost changes when we varied key component costs. The unit costs of EIMC performed by nurse-midwives and doctors in vertical programs were US$38.87 and US$49.77, respectively. Key cost drivers of EIMC were consumable supplies, personnel costs, and the device price. In this cost analysis, major cost drivers that explained the differences between EIMC performed by nurse-midwives and doctors were personnel and training costs, both of which were lower for nurse-midwives. EIMC unit costs were lower when performed by nurse-midwives compared with doctors. To minimize costs, countries planning to scale up EIMC should consider using nurse-midwives, who are in greater supply than doctors and are the main providers at the primary health care level, where most infants are born.


Predictors of Cognitive Behavioral Therapy for Insomnia (CBTi) Outcomes in Active-Duty U.S. Army Personnel.
Cognitive behavioral therapy for insomnia (CBTi) is well established as the first-line treatment for the management of chronic insomnia. Identifying predictors of response to CBTi should enable the field to efficiently utilize resources to treat those who are likely to respond and to personalize treatment approaches to optimize outcomes for those who are less likely to respond to traditional CBTi. Although a range of studies have been conducted, no clear pattern of predictors of response to CBTi has emerged. The purpose of this study was to examine the impact and relative importance of a comprehensive group of pretreatment predictors of insomnia outcomes in 99 active-duty service members who received in-person CBTi in a randomized clinical trial. Results indicated that higher levels of baseline insomnia severity and total sleep time predicted greater improvements on the Insomnia Severity Index (ISI) following treatment. Higher depression symptoms and a history of head injury predicted a worse response to treatment (i.e., smaller improvements on the ISI). Clinically meaningful improvements, as measured by the reliable change index (RCI), were found in 59% of the sample. Over and above baseline insomnia severity, only depressive symptoms predicted this outcome. Future studies should examine if modifications to CBTi based on these predictors of response can improve outcomes.


A case report on late presentation of occult dural lesions.
Occult dural injuries are rare and can occur as a result of major or minor head injury. These injuries usually manifest with cerebrospinal fluid rhinorrhea alone, or with meningitis and cerebral abscess, sometimes many years after the original injury. We present a case of occult dural injury with endocranial complications which occurred in a 34 year old man, with a history of head injury forty-three years ago. The patient presented with a triad of findings; meningitis, CSF rhinorrhoea and pneumocephalus. He was managed conservatively with intravenous antibiotics and observation and made a full recovery. The presence of acute endocranial symptoms and particularly these three findings in a patient with a previous history of head injury, no matter how long it had been should raise suspicion of the presence of an occult dural injury. It need to retain a high index of suspicion for occult dural injury in patients who present with endocranial symptoms of unknown origin, especially if there is a previous history of head injury.


Long-term follow-up with I-CARE phakic IOLs.
To evaluate visual quality and postoperative results as well adverse events in myopic patients undergoing I-CARE anterior-chamber angle-supported phakic intraocular lens (IOL) implantation. A retrospective, non-randomised, case series. Data on 29 eyes (16 patients) receiving I-CARE phakic IOL for high myopia (-11.66±3.3) were analysed. The IOLs were implanted between 2003 and 2006 at the Department of Ophthalmology, Medical University, Graz, Austria. The mean follow-up was 51.7±16 months (17-78 months). The authors measured uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA); patients underwent slit-lamp examination, corneal topography, Scheimpflug imaging and measurement of endothelial cells (EC). The mean UCVA and BCSVA were 0.63 and 0.94 decimal after 1 year. Endothelial cell loss was the most serious adverse event observed. The mean EC loss was 2%, 9%, 17%, 21%, 33% and 47% after 1 year (n=17), 2 years (n=20), 3 years (n=17), 4 years (n=17), 5 years (n=12) and 6 years (n=3), respectively. Eight IOL explantations were made due to severe EC loss 3-6 years after implantation. Other serious complications included one patient with Urrets-Zavalia Syndrome (one eye). Implantation of the I-CARE phakic-IOL is not a safe method for the correction of high myopia due to serious endothelial cell loss that might occur in a high number of patients. Patients with these IOLs should be followed up at least every 6 months, and the IOL should be explanted, once the EC count drops to less than 2000 cells/mm(2).


Exhaustive differentiation of alloreactive CD8+ T cells: critical for determination of graft acceptance or rejection.
The precise role that CD8+ T cells play in the rejection and acceptance of different types of allograft is unclear and has been shown to vary between donor-recipient combinations. The response of adoptively transferred CD8+ T cells reactive to the donor alloantigen H2Kb was examined after transplantation of H2Kb liver, kidney, and heart grafts in mice. After transfer of 6 x 10(6) alloreactive CD8+ T cells to T-cell depleted syngeneic mice spontaneous long-term acceptance of liver grafts was observed, whereas kidney and heart grafts were acutely rejected. Within 5 days of liver transplantation, we found that the entire H2Kb-reactive T-cell pool was stimulated to proliferate and differentiate into memory or effector cells that were detectable within lymphoid tissues as well as the liver graft itself. However, despite the generation of effector or memory T cells, liver allografts were accepted, which correlated with the exhaustion or deletion of such cells. In contrast, although activation and proliferation of H2Kb-reactive CD8+ T cells was observed after transplantation of heart or kidney grafts, unactivated, H2Kb-reactive CD8+ T cells were still present in the spleen even long term. Interestingly, differences in the effector function of liver and kidney graft infiltrating donor-reactive CD8+ T cells were not detected after adoptive transfer into immunodeficient mice, despite a reduction in Th1-type cytokines within liver grafts. The rapid and extensive initial activation and differentiation of donor-reactive CD8+ T cells that occurs after liver transplantation leads to clonal exhaustion or deletion of the alloreactive CD8+ T-cell repertoire resulting in spontaneous tolerance induction.


Physical and verbal aggressive behavior and COMT genotype: Sensitivity to the environment.
Catechol-O-methyltransferase (COMT) genotype has been implicated as a vulnerability factor for several psychiatric diseases as well as aggressive behavior, either directly, or in interaction with an adverse environment. The present study aimed at investigating the susceptibility properties of COMT genotype to adverse and favorable environment in relation to physical and verbal aggressive behavior. The COMT Val158Met polymorphism was genotyped in a Swedish population-based cohort including 1,783 individuals, ages 20-24 years (47% males). A significant three-way interaction was found, after correction for multiple testing, between COMT genotype, exposure to violence, and parent-child relationship in association with physical but not verbal aggressive behavior. Homozygous for the Val allele reported lower levels of physical aggressive behavior when they were exposed to violence and at the same time experienced a positive parent-child relationship compared to Met carriers. Thus, susceptibility properties of COMT genotype were observed in relation to physical aggressive behavior supporting the hypothesis that COMT genotypes are modifying the sensitivity to environment that confers either risk or protection for aggressive behavior. As these are novel findings, they warrant further investigation and replication in independent samples. © 2016 Wiley Periodicals, Inc.


p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain.
The possible involvement of p38 mitogen-activated protein kinase activation in spinal cord and dorsal root ganglion (DRG) cells in the development of peripheral neuropathic pain has been explored. Ligation of the L5 spinal nerve (SNL) on one side in adult rats produces an early onset and long-lasting mechanical allodynia. This lesion results in activation of p38 in the L5 segment of the spinal cord, most prominently in the ipsilateral dorsal horn, starting soon after the lesion (<1 d) and persisting for >3 weeks. The activated p38 in the spinal cord is restricted entirely to microglia; phospho-p38 colocalizes only with the microglial marker OX-42 and not with either the neuronal marker neuronal-specific nuclear protein or the astrocyte marker GFAP. In contrast, SNL induces a delayed (>3 d) activation of p38 in the L5 DRG that occurs predominantly in neurons. Continuous injection of the p38 inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) via the intrathecal route, starting before the SNL surgery, reduces SNL-induced mechanical allodynia from day 1 to day 10, with maximal effects at early time points. Post-treatment with SB203580 starting on day 1 or on day 10 after surgery also reduces established mechanical allodynia. Because the reduction in neuropathic pain by p38 inhibition occurs before the appearance of p38 activation in DRG neurons, p38 activation in spinal cord microglia is likely to have a substantial role in the earliest phase of neuropathic pain. Coactivation of p38 in DRG neurons and spinal microglia may contribute to later phases of neuropathic pain.


Virome Analysis of Aphid Populations That Infest the Barley Field: The Discovery of Two Novel Groups of Nege/Kita-Like Viruses and Other Novel RNA Viruses.
Aphids (order Hemiptera) are important insect pests of crops and are also vectors of many plant viruses. However, little is known about aphid-infecting viruses, particularly their diversity and relationship to plant viruses. To investigate the aphid viromes, we performed deep sequencing analyses of the aphid transcriptomes from infested barley plants in a field in Japan. We discovered virus-like sequences related to nege/kita-, flavi-, tombus-, phenui-, mononega-, narna-, chryso-, partiti-, and luteoviruses. Using RT-PCR and sequence analyses, we determined almost complete sequences of seven nege/kitavirus-like virus genomes; one of which was a variant of the Wuhan house centipede virus (WHCV-1). The other six seem to belong to four novel viruses distantly related to Wuhan insect virus 9 (WhIV-9) or Hubei nege-like virus 4 (HVLV-4). We designated the four viruses as barley aphid RNA virus 1 to 4 (BARV-1 to -4). Moreover, some nege/kitavirus-like sequences were found by searches on the transcriptome shotgun assembly (TSA) libraries of arthropods and plants. Phylogenetic analyses showed that BARV-1 forms a clade with WHCV-1 and HVLV-4, whereas BARV-2 to -4 clustered with WhIV-9 and an aphid virus, Aphis glycines virus 3. Both virus groups (tentatively designated as Centivirus and Aphiglyvirus, respectively), together with arthropod virus-like TSAs, fill the phylogenetic gaps between the negeviruses and kitaviruses lineages. We also characterized the flavi/jingmen-like and tombus-like virus sequences as well as other RNA viruses, including six putative novel viruses, designated as barley aphid RNA viruses 5 to 10. Interestingly, we also discovered that some aphid-associated viruses, including nege/kita-like viruses, were present in different aphid species, raising a speculation that these viruses might be distributed across different aphid species with plants being the reservoirs. This study provides novel information on the diversity and spread of nege/kitavirus-related viruses and other RNA viruses that are associated with aphids.


Effects of transients in LIGO suspensions on searches for gravitational waves.
This paper presents an analysis of the transient behavior of the Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) suspensions used to seismically isolate the optics. We have characterized the transients in the longitudinal motion of the quadruple suspensions during Advanced LIGO's first observing run. Propagation of transients between stages is consistent with modeled transfer functions, such that transient motion originating at the top of the suspension chain is significantly reduced in amplitude at the test mass. We find that there are transients seen by the longitudinal motion monitors of quadruple suspensions, but they are not significantly correlated with transient motion above the noise floor in the gravitational wave strain data, and therefore do not present a dominant source of background noise in the searches for transient gravitational wave signals. Using the suspension transfer functions, we compared the transients in a week of gravitational wave strain data with transients from a quadruple suspension. Of the strain transients between 10 and 60 Hz, 84% are loud enough that they would have appeared above the sensor noise in the top stage quadruple suspension monitors if they had originated at that stage at the same frequencies. We find no significant temporal correlation with the suspension transients in that stage, so we can rule out suspension motion originating at the top stage as the cause of those transients. However, only 3.2% of the gravitational wave strain transients are loud enough that they would have been seen by the second stage suspension sensors, and none of them are above the sensor noise levels of the penultimate stage. Therefore, we cannot eliminate the possibility of transient noise in the detectors originating in the intermediate stages of the suspension below the sensing noise.


Electrical Mapping of Silver Nanowire Networks: A Versatile Tool for Imaging Network Homogeneity and Degradation Dynamics during Failure.
Electrical stability and homogeneity of silver nanowire (AgNW) networks are critical assets for increasing their robustness and reliability when integrated as transparent electrodes in devices. Our ability to distinguish defects, inhomogeneities, or inactive areas at the scale of the entire network is therefore a critical issue. We propose one-probe electrical mapping (1P-mapping) as a specific simple tool to study the electrical distribution in these discrete structures. 1P-mapping has allowed us to show that the tortuosity of the voltage equipotential lines of AgNW networks under bias decreases with increasing network density, leading to a better electrical homogeneity. The impact of the network fabrication technique on the electrical homogeneity of the resulting electrode has also been investigated. Then, by combining 1P-mapping with electrical resistance measurements and IR thermography, we propose a comprehensive analysis of the evolution of the electrical distribution in AgNW networks when subjected to increasing voltage stresses. We show that AgNW networks experience three distinctive stages: optimization, degradation, and breakdown. We also demonstrate that the failure dynamics of AgNW networks at high voltages occurs through a highly correlated and spatially localized mechanism. In particular the in situ formation of cracks could be clearly visualized. It consists of two steps: creation of a crack followed by propagation nearly parallel to the equipotential lines. Finally, we show that current can dynamically redistribute during failure, by following partially damaged secondary pathways through the crack.


Ginsenoside Re promotes human sperm capacitation through nitric oxide-dependent pathway.
The regulation of sperm capacitation is important for successful fertilization. Ginsenosides, the biologically effective components of ginseng, have been found to enhance intracellular nitric oxide (NO) production and the latter has recently been indicated to play a significant role in modulation of sperm functions. We investigated the effect of Ginsenoside Re on human sperm capacitation in vitro and the mechanism by which the Ginsenosides play their roles. Spermatozoa were separated by Percoll and incubated with 0, 1, 10, or 100 microM of Ginsenoside Re. The percentages of spontaneous and lysophosphatidylcholine (LPC)-induced acrosome reaction (AR), as a measure of sperm capacitation, were assayed with fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA). The intracellular cGMP level was measured by [(3)H] cGMP radioimmunoassay system. The results showed that the percentages of both spontaneous and LPC-induced AR and intracellular cGMP level were significantly enhanced by Ginsenoside Re with a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside Re. And pretreatment with a NOS inhibitor N(omega)-nitro-l-arginine methyl ester (L-NAME, 100 microM) or a NO scavenger N-acetyl-l-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside Re. Furthermore, the AR-inducing effect of Ginsenoside Re was significantly reduced in the presence of the soluble guanylate cyclase inhibitor LY83583 or cGMP-dependent protein kinase (PCK) inhibitor KT5823, whereas addition of the cGMP analogue 8-Br-cGMP significantly increased the AR of human spermatozoa. Data suggested that Ginsenoside Re is beneficial to sperm capacitation and AR, and that the effect is accomplished through NO/cGMP/PKG pathway.


Health Benefits of Fennel, Rosemary Volatile Oils and their Nano-Forms in Dyslipidemic Rat Model.
Dyslipidemia is a major health problem that may lead to cardiovascular diseases (CVDs). In the present research, a biological experiment was run on dyslipidemic rats to study the health benefits of the volatile oils (VOs) of fennel and rosemary in its original and nano-form using chitosan as carrier. Rats were divided into 6 groups; normal control, dyslipidemic control and 4 test groups with dyslipidemia and treated by VOs of fennel and rosemary and their respective nano-forms separately. Glucose tolerance test was carried out after 4 weeks. Parameters reflecting oxidative stress/antioxidant plasma catalase, malondialdehyde (MDA) and blood uric acid, were assessed. Plasma lipid profile and tumor necrosis factor alpha (TNF-α) as inflammatory biomarker were determined. Liver and kidney function were assessed as determinant of the safety of the different VO forms. Twenty four hour urinary volume was measured to assess creatinine clearance and to evaluate the possible diuretic activity of the VOs. Dyslipidemic control rats showed dyslipidemia, increased CVDs risk, liver dysfunction, elevated MDA and TNF-α with marked increase in blood sugar after half an hour of glucose ingestion compared to normal control. Treatment with the four VOs forms improved the majority of the biochemical parameters. All treatment showed cardio and hepato- protective effect and safety towards kidney and blood sugar. Oxidative stress and inflammatory biomarkers were significantly improved by the different treatments; both VO forms of fennel were more efficient in ameliorating inflammation.


Comparing the efficacy of continuous and pulsed ultrasound therapies in patients with lateral epicondylitis: A double-blind, randomized, placebo-controlled study.
The aim of this study was to investigate the efficacy of continuous and pulsed ultrasound therapies in lateral epicondylitis. A total of 51 patients (18 males, 33 females; mean age: 46.52±6.16 years; range, 27 to 64 years) who were diagnosed with lateral epicondylitis between February 2013 and October 2014 were included. The patients were randomized to either continuous ultrasound (n=17), pulsed ultrasound (n=17), or placebo (n=17) groups. First group received 10 sessions of continuous ultrasound therapy. The second group received 10 sessions of pulsed ultrasound therapy in a ratio of 1:4. The third group received 10 sessions of placebo treatment. The pain levels of the patients were evaluated using Visual Analog Scale (VAS). The muscle strength was evaluated using a dynamometer. For functional evaluation, Duruöz's Hand Index (DHI) and Patient-Rated Tennis Elbow Evaluation (PRTEE) scales were used. Assessments were made at baseline, at the end of therapy, and one month after therapy. The thickness of the common extensor tendon was also measured using ultrasonic imaging at baseline and at the end of therapy. At the end of the study, there was a statistically significant improvement in the rest and activation VAS scores, and DHI and PRTEE scores in both continuous and pulsed ultrasound therapy groups, compared to placebo (p<0.05). However, no superiority was found between the continuous and pulsed ultrasound therapy groups (p>0.05). A statistically significant reduction in the common extensor tendon thickness was found only in the pulsed ultrasound therapy group (p<0.05). Our study results show that both continuous and pulsed ultrasound applications are effective in the treatment of lateral epicondylitis.


Tenascin-R (J1 160/180 inhibits fibronectin-mediated cell adhesion--functional relatedness to tenascin-C.
Cell adhesion and neurite outgrowth on fibronectin is a multistep process modulated by different extra- and intracellular signals. Fibronectin-mediated cell attachment and spreading can be affected in a negative way by tenascin-C, an extracellular matrix glycoprotein expressed in a temporally and spacially restricted manner during early morphogenesis. Tenascin-R (J1-160/180), consisting of two major isoforms of 160 kDa (tenascin-R 160) and 180 kDa (tenascin-R 180) in mammals, is an extracellular matrix glycoprotein of the central nervous system that shares high structural homologies with tenascin-C. Here we show that in relation to fibronectin-mediated adhesion, the two extracellular matrix molecules are also functionally closely related. When offered as mixed substrata with other extracellular matrix molecules, the two tenascin-R isoforms and tenascin-C derived from mouse brain selectively inhibit fibronectin-dependent cell adhesion and neurite outgrowth, and affect cell morphology of different mesenchymal and neural cells. This effect is partially due to interactions at the substrate level that result in a steric hindrance and/or conformational change of the cell binding sites of the fibronectin molecule. In addition, tenascin-R 180 and tenascin-C interact with cells by an RGD- and beta 1 integrin-independent mechanism, leading to cell rounding and detachment from such substrata. The expression of tenascin-R and tenascin-C in the nervous system at times and locations where fibronectin-mediated cellular processes take place may be related to the role of inhibitory signals in the extracellular matrix in the regulation of cell migration and differentiation in general.


Light scattering in disordered honeycomb photonic lattices near the Dirac points.
We address Anderson localization in disordered honeycomb photonic lattices and show that the localization process is strongly affected by the spectral position of the input wavepacket within the first Brillouin zone of the lattice. In spite of the fact that in regular lattices expansion of the beam is much stronger for excitation near the Dirac points-where light exhibits conical diffraction-than for excitation at the center of the Brillouin zone-where light exhibits normal diffraction-we found that disorder leads to pronounced Anderson localization even around the Dirac points. We found that for the same disorder level the width of the averaged output intensity distribution for excitations around the Dirac points may be substantially larger than that for excitations at the center of the Brillouin zone.


Distinct Particle Morphologies Revealed through Comparative Parallel Analyses of Retrovirus-Like Particles.
The Gag protein is the main retroviral structural protein, and its expression alone is usually sufficient for production of virus-like particles (VLPs). In this study, we sought to investigate-in parallel comparative analyses-Gag cellular distribution, VLP size, and basic morphological features using Gag expression constructs (Gag or Gag-YFP, where YFP is yellow fluorescent protein) created from all representative retroviral genera: Alpharetrovirus, Betaretrovirus, Deltaretrovirus, Epsilonretrovirus, Gammaretrovirus, Lentivirus, and Spumavirus. We analyzed Gag cellular distribution by confocal microscopy, VLP budding by thin-section transmission electron microscopy (TEM), and general morphological features of the VLPs by cryogenic transmission electron microscopy (cryo-TEM). Punctate Gag was observed near the plasma membrane for all Gag constructs tested except for the representative Beta- and Epsilonretrovirus Gag proteins. This is the first report of Epsilonretrovirus Gag localizing to the nucleus of HeLa cells. While VLPs were not produced by the representative Beta- and Epsilonretrovirus Gag proteins, the other Gag proteins produced VLPs as confirmed by TEM, and morphological differences were observed by cryo-TEM. In particular, we observed Deltaretrovirus-like particles with flat regions of electron density that did not follow viral membrane curvature, Lentivirus-like particles with a narrow range and consistent electron density, suggesting a tightly packed Gag lattice, and Spumavirus-like particles with large envelope protein spikes and no visible electron density associated with a Gag lattice. Taken together, these parallel comparative analyses demonstrate for the first time the distinct morphological features that exist among retrovirus-like particles. Investigation of these differences will provide greater insights into the retroviral assembly pathway. Comparative analysis among retroviruses has been critically important in enhancing our understanding of retroviral replication and pathogenesis, including that of important human pathogens such as human T-cell leukemia virus type 1 (HTLV-1) and HIV-1. In this study, parallel comparative analyses have been used to study Gag expression and virus-like particle morphology among representative retroviruses in the known retroviral genera. Distinct differences were observed, which enhances current knowledge of the retroviral assembly pathway.


Structure investigations of group 13 organometallic carboxylates.
The octet-compliant group 13 organometallics with highly polarized bonds in the metal coordination sphere exhibit a significant tendency to maximize their coordination number through the formation of adducts with a wide range of neutral donor ligands or by self-association to give aggregates containing tetrahedral and higher coordinated aluminium centres, and even in some cases molecular complexes equilibrate with ionic species of different coordination numbers of the metal centre. This work provides a comprehensive overview of the structural chemistry landscape of the group 13 carboxylates. Aside from a more systematic approach to the general structural chemistry of the title compounds, the structure investigations of [R2M(μ-O2CPh)]2-type benzoate complexes (where M = B, Al and Ga) and their Lewis acid-base adducts [(R2M)(μ-O2CPh)(py-Me)] are reported. DFT calculations were also performed to obtain a more in-depth understanding of both the changes in the bonding of group 13 organometallic carboxylate adducts with a pyridine ligand.


Immunocytochemical expression of growth factors by odontogenic jaw cysts.
To determine the immunocytochemical pattern of expression of transforming growth factor (TGF) alpha, epidermal growth factor (EGF), and TGF beta in the three most common types of odontogenic jaw cyst. Growth factor expression was detected in paraffin wax sections of odontogenic cysts (27 odontogenic keratocysts, 10 dentigerous cysts, and 10 radicular cysts) using a streptavidin-biotin peroxidase technique with monoclonal antibodies directed against TGF alpha (clone 213-4.4) and TGF beta (clone TB21) and a polyclonal antibody directed against EGF (Z-12). The epithelial linings of all cysts showed reactivity for TGF alpha which was mainly localised to basal and suprabasal layers. Odontogenic keratocyst linings expressed higher levels of TGF alpha than those of dentigerous and radicular cysts, with 89% (24/27) of odontogenic keratocysts exhibiting a strong positive reaction compared with 50% (five of 10) of dentigerous and radicular cysts, respectively. EGF reactivity was similar in all cyst groups, weaker than that for TGF alpha and predominantly suprabasal. TGF alpha and EGF were also detected in endothelial cells, fibroblasts and inflammatory cells within the cyst walls. The most intense TGF beta staining in odontogenic cysts was extracellular within the fibrous tissue capsules, irrespective of cyst type. These results, together with previous studies of EGF receptor, indicate differential expression of TGF alpha, EGF and their common receptor between the different types of odontogenic cyst, suggesting that these growth factors (via autocrine or paracrine, or both, pathways) may be involved in their pathogenesis.


Independent component analysis of microarray data in the study of endometrial cancer.
Gene microarray technology is highly effective in screening for differential gene expression and has hence become a popular tool in the molecular investigation of cancer. When applied to tumours, molecular characteristics may be correlated with clinical features such as response to chemotherapy. Exploitation of the huge amount of data generated by microarrays is difficult, however, and constitutes a major challenge in the advancement of this methodology. Independent component analysis (ICA), a modern statistical method, allows us to better understand data in such complex and noisy measurement environments. The technique has the potential to significantly increase the quality of the resulting data and improve the biological validity of subsequent analysis. We performed microarray experiments on 31 postmenopausal endometrial biopsies, comprising 11 benign and 20 malignant samples. We compared ICA to the established methods of principal component analysis (PCA), Cyber-T, and SAM. We show that ICA generated patterns that clearly characterized the malignant samples studied, in contrast to PCA. Moreover, ICA improved the biological validity of the genes identified as differentially expressed in endometrial carcinoma, compared to those found by Cyber-T and SAM. In particular, several genes involved in lipid metabolism that are differentially expressed in endometrial carcinoma were only found using this method. This report highlights the potential of ICA in the analysis of microarray data.


Towards an IMU Evaluation Framework for Human Body Tracking.
Existing full-body tracking systems, which use Inertial Measurement Units (IMUs) as sensing unit, require expert knowledge for setup and data collection. Thus, the daily application for human body tracking is difficult. In particular, in the field of active and assisted living (AAL), tracking human movements would enable novel insights not only into the quantity but also into the quality of human movement, for example by monitoring functional training. While the current market offers a wide range of products with vastly different properties, literature lacks guidelines for choosing IMUs for body tracking applications. Therefore, this paper introduces developments towards an IMU evaluation framework for human body tracking which compares IMUs against five requirement areas that consider device features and data quality. The data quality is assessed by conducting a static and a dynamic error analysis. In a first application to four IMUs of different component consumption, the IMU evaluation framework convinced as promising tool for IMU selection.


Low-variance RNAs identify Parkinson's disease molecular signature in blood.
The diagnosis of Parkinson's disease (PD) is usually not established until advanced neurodegeneration leads to clinically detectable symptoms. Previous blood PD transcriptome studies show low concordance, possibly resulting from the use of microarray technology, which has high measurement variation. The Leucine-rich repeat kinase 2 (LRRK2) G2019S mutation predisposes to PD. Using preclinical and clinical studies, we sought to develop a novel statistically motivated transcriptomic-based approach to identify a molecular signature in the blood of Ashkenazi Jewish PD patients, including LRRK2 mutation carriers. Using a digital gene expression platform to quantify 175 messenger RNA (mRNA) markers with low coefficients of variation (CV), we first compared whole-blood transcript levels in mouse models (1) overexpressing wild-type (WT) LRRK2, (2) overexpressing G2019S LRRK2, (3) lacking LRRK2 (knockout), and (4) and in WT controls. We then studied an Ashkenazi Jewish cohort of 34 symptomatic PD patients (both WT LRRK2 and G2019S LRRK2) and 32 asymptomatic controls. The expression profiles distinguished the four mouse groups with different genetic background. In patients, we detected significant differences in blood transcript levels both between individuals differing in LRRK2 genotype and between PD patients and controls. Discriminatory PD markers included genes associated with innate and adaptive immunity and inflammatory disease. Notably, gene expression patterns in levodopa-treated PD patients were significantly closer to those of healthy controls in a dose-dependent manner. We identify whole-blood mRNA signatures correlating with LRRK2 genotype and with PD disease state. This approach may provide insight into pathogenesis and a route to early disease detection.


Trichophytin reactions in children with tinea capitis.
Of 52 patients with proved Trichophyton tonsurans infection of the scalp, 16 had an inflammatory reaction to this infection (kerion), while the rest had only slight scaling and broken hairs (black dot ring-worm). Each patient was tested with trichophytin antigen to determine whether cell-mediated immunity (CMI) was responsible for the differences in these different clinical presentations. Fifteen of 16 with kerion had a 48-hour reaction greater than 10 mm, while none of the 36 with noninflammatory (black dot) tinea capitis had a similar response. This suggests that the patient's immune response (CMI) may be responsible for kerion infections of the scalp and that therapy could be directed initially toward suppressing this reaction.


Burst-mode gain switched technique for high peak and average optical energy extraction.
The optical performance of a cw PIE CO(2) laser has been substantially improved through the adoption of a burst-mode gain switching technique. The approach has provided a doubling of the average beam power extractable from the device. With appropriate optimization, the process could possibly permit the attainment of pulsed energy extraction in the kilohertz range, and with average optical powers within the several tens of kilowatt category.


The Diagnostic Apathia Scale predicts the ability to return to work following depression or anxiety.
The aim of this study was to evaluate the validity of a new apathy rating scale in predicting the ability to return to work (RTW) in patients with depression or anxiety a year after discharge from a psychiatric hospital. We evaluated 56 patients with depression or anxiety, who participated in an on-going randomised clinical trial using RTW as primary outcome. The degree of apathy was measured by the Diagnostic Apathia Scale, which contains six items covering the following neuropsychological symptoms: concentration/memory problems, difficulties in decision making, lassitude, tiredness/fatigue, insomnia, and reduced ability to work and engage in personal interests. The scale was analysed for psychometric validity (scalability) and for its ability to predict RTW. Finally, the predictive validity of the Diagnostic Apathia Scale regarding RTW was compared with scales measuring severity of depression/anxiety symptoms, disability, and psychological well-being. The Diagnostic Apathia Scale displayed sufficient scalability, that is, the total score was a psychometrically valid measure of apathy. Only the Diagnostic Apathia Scale, and not the scales measuring severity of symptoms, disability, or psychological well-being, had predictive validity regarding RTW. Thus, 76% with 'clinically significant apathy' at baseline were unable to RTW versus 50% of the patients without apathy (p<0.05). The Diagnostic Apathia Scale was found to have an acceptable predictive validity in terms of patients' ability to RTW 1 year after discharge from hospitalisation for depression or anxiety.


Shallot aphids, Myzus ascalonicus, in strawberry: biocontrol potential of three predators and three parasitoids.
The parasitization capacity of 3 parasitoids and the predation capacity of 3 predators towards the shallot aphid, Myzus ascalonicus Doncaster (Homoptera: Aphididae), on strawberry, Fragaria x ananassa Duchesne (Rosales: Rosaceae) cv. Honeoye, were examined in laboratory experiments. In Petri dish assays, both Aphidius colemani Viereck (Hymenoptera: Aphidiidae) and A. ervi Haliday readily stung shallot aphids, with no significant difference in stinging frequency between the two species. A. ervi induced a significantly higher mortality (79.0 ± 7.2%) in terms of stung aphids compared with A. colemani (55.3 ± 4.1%); however, only a minor fraction (2.7 ± 1.8% and 7.1 ± 3.1%, respectively) of the killed aphids resulted in formation of mummies, presumably due to a physiological response to parasitism. The low percentage of mummification precludes the use of either Aphidius species in anything but inundative biocontrol. In similar set-ups, Aphelinus abdominalis (Dalman) (Hymenoptera: Aphelinidae) killed almost half (49.6 ± 5.3%) of the exposed aphids through host feeding. In addition, 23.2 ± 7.3% of non-host-fed aphids developed into mummified aphids, and 38.1 ± 13.2% of non-host-fed aphids died from other parasitoid-induced causes. However, the host feeding rate was reduced to only 1.2 ± 0.8%, and no significant parasitization mortality was observed on strawberry plants, suggesting that host plants interfered with A. abdominalis activity. This parasitoid does not, therefore, seem to be suited to either inoculative or inundative biocontrol of shallot aphids in strawberry. The three predators studied were the green lacewing, Chrysoperla carnea Steph. (Neuroptera: Chrysopidae), the two-spotted lady beetle, Adalia bipunctata L. (Coleoptera: Coccinellidae), and the gall midge Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae). Third instars of all 3 predators readily preyed upon the shallot aphid in Petri dish set-ups with significant differences in daily predation (34.62 ± 3.45, 25.25 ± 3.18, and 13.34 ± 1.45, respectively). Further studies on A. bipunctata revealed that the larvae maintained their daily predation capacity (32.0 ± 6.3) on strawberry plants. About 60% of already ovipositing A. bipunctata refrained from laying any eggs on the first day after transfer to set-ups with combinations of shallot or peach-potato aphids, Myzus persicae (Sulzer) (Homoptera: Aphididae), and strawberry or sweet pepper leaves. The aphid species and the plant species did not, however, have a significant influence on the number of females laying eggs, the average number of eggs laid during the first day being 6.37±1.28 per female. Adult lady beetles had a significant preference for odor from controls without plants over odors from uninfested strawberry or pepper plants, but they showed no preference for either of the plant species, whether infested with aphids or not. The predation capacity of A. bipunctata on shallot aphids holds promise for its use in inundative biocontrol, and the results on egg laying cues suggests that inoculative biocontrol may be possible, although further studies will be needed for a complete evaluation.


Phenotypic and genetic heterogeneity of lactic acid bacteria isolated from "Alheira", a traditional fermented sausage produced in Portugal.
The aim of this study was to evaluate the phenotypic and genetic heterogeneity of lactic acid bacteria (LAB) isolated from "Alheira", a fermented sausage produced in Portugal. LAB were identified to genus and species level by phenotypic characteristics, using genus or species-specific primers and sequencing of the gene encoding 16S rRNA. Two-hundred and eighty-three isolates were grouped into 14 species. Lactobacillus plantarum was isolated from all sausages and Enterococcusfaecalis from most of the samples. Low numbers of Lactobacillus paraplantarum, Lactobacillus brevis, Lactobacillus rhamnosus, Lactobacillus sakei, Lactobacillus zeae, Lactobacillus paracasei, Leuconostoc mesenteroides, Pediococcus pentosaceus, Pediococcus acidilactici, Weissella cibaria, Weissella viridescens and Enterococcus faecium were recorded. The genetic heterogeneity of L. plantarum and E. faecalis strains were determined by numerical analysis of DNA banding patterns obtained by RAPD-PCR. Strains of L. plantarum and E. faecalis were different from different producers. This study forms the basis from which starter cultures could be selected for production of "Alheira".


Discovering and Summarizing Relationships Between Chemicals, Genes, Proteins, and Diseases in PubChem.
The literature knowledge panels developed and implemented in PubChem are described. These help to uncover and summarize important relationships between chemicals, genes, proteins, and diseases by analyzing co-occurrences of terms in biomedical literature abstracts. Named entities in PubMed records are matched with chemical names in PubChem, disease names in Medical Subject Headings (MeSH), and gene/protein names in popular gene/protein information resources, and the most closely related entities are identified using statistical analysis and relevance-based sampling. Knowledge panels for the co-occurrence of chemical, disease, and gene/protein entities are included in PubChem Compound, Protein, and Gene pages, summarizing these in a compact form. Statistical methods for removing redundancy and estimating relevance scores are discussed, along with benefits and pitfalls of relying on automated (i.e., not human-curated) methods operating on data from multiple heterogeneous sources.


Maintaining the 'good maternal body': expressing milk as a way of negotiating the demands and dilemmas of early infant feeding.
To report a descriptive study of early infant feeding experiences focusing on ACCOUNTS OF WOMEN WHO EXPRESSED MILK EXTENSIVELY IN THE FIRST FEW WEEKS POSTPARTUM. Relatively little is known about the reasons for expressing milk following healthy term births. Evidence indicates it is an increasingly common practice during early infant feeding in Westernized countries. A more comprehensive understanding of this practice will help midwives and nurses assist mothers negotiate early feeding challenges. Qualitative data were collected in two phases in the first few weeks postpartum. Audio-diary and semi-structured interview data from seven British women who extensively expressed milk in the first month postpartum were analysed. These data were drawn from a larger qualitative longitudinal study which took place in 2006-2007. Themes, discursive constructions and discourses are identified through the use of a feminist informed analysis. The practice of expressing was employed as a solution to managing the competing demands and dilemmas of early breastfeeding and ensuring the continued provision of breast milk, thereby deflecting potential accusations of poor mothering. In addition, the practice may afford a degree of freedom to new mothers. The need to maintain the 'good maternal body' can account for the motivation to express milk, although there may be reasons to be cautious about promoting expression as a solution to breastfeeding difficulties. Education for health professionals, which emphasizes the complexities and contradictions of mothering and which challenges prescriptive notions of 'good mothering' could better support new mothers in their feeding 'choices'.


Expression and distribution of phosphodiesterase isoenzymes in the human male urethra.
To investigate the expression and distribution of phosphodiesterase (PDE) isoenzymes PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A in human urethral tissue. Specimens of penile urethra were obtained from male subjects who had undergone male-to-female sex reassignment surgery. Using immunohistochemistry (immunofluorescence), the occurrence of PDE1A, PDE2A, PDE4A, PDE4B, and PDE5A, the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide was examined in urethral sections. Cytosolic supernatants prepared from isolated human urethral tissue were subjected to Western blot analysis using specific anti-PDE antibodies. Immunosignals specific for PDE1A, 4A, 4B, and 5A were observed in the urethral smooth musculature. The smooth muscle bundles were seen innervated by slender nerve fibers, characterized by the expression of the neuronal nitric oxide synthase, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. The expression of the PDE isoenzymes mentioned was confirmed by Western blotting. The results provide evidence for a significance of both the cyclic adenosine monophosphate and cyclic guanosine monophosphate signaling in the control of human urethral smooth muscle. The selective inhibition of PDE isoenzymes might represent a pharmacologic option to influence the function of smooth musculature in the human outflow region.


An Enzyme-Directed Imidazoquinoline Activated by Drug Resistance.
Drug efflux and enzymatic drug degradation are two cellular mechanisms that contribute to drug resistance in many cancers. Herein, we report the synthesis and in vitro activity of a pro-immunostimulant that exploits both processes in tandem to selectively confer cancer-mediated immunogenicity. We demonstrate that an imidazoquinoline pro-immunostimulant is inactive until it is selectively metabolized to an active immunostimulant by an endogenous α-mannosidase enzyme expressed within multidrug-resistant cancer cells. Following conversion, the immunostimulant is transported to the extracellular space via drug efflux, resulting in the activation of model bystander immune cells. Taken together, these results suggest that enzyme-directed immunostimulants can couple immunogenicity to these mechanisms of drug resistance. We name this process bystander-assisted immunotherapy, and envision that it could be advanced to treat drug-resistant diseases that rely on enzymatic degradation or drug efflux to persist.


Anomalous thermomechanical properties of a self-propelled colloidal fluid.
We use numerical simulations to compute the equation of state of a suspension of spherical self-propelled nanoparticles in two and three dimensions. We study in detail the effect of excluded volume interactions and confinement as a function of the system's temperature, concentration, and strength of the propulsion. We find a striking nonmonotonic dependence of the pressure on the temperature and provide simple scaling arguments to predict and explain the occurrence of such anomalous behavior. We explicitly show how our results have important implications for the effective forces on passive components suspended in a bath of active particles.


Quantitative analysis of syndecan-1 expression in dysplasia and squamous cell carcinoma of the oral cavity.
Decreased expression of syndecan-1 has been reported in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity and appears to correlate with decreasing histological differentiation and poor clinical outcome. Assays of syndecan-1 expression to date have utilized manual microscopic analysis with qualitative grading of immunohistochemical staining intensity, which may introduce observer bias. We evaluated syndecan-1 expression in dysplasia and squamous cell carcinoma (SCCA) of the oral cavity, using a novel automated cellular imaging system that incorporates both staining intensity as well as the percentage of positively stained cells to yield a quantitative value for syndecan-1 expression. We performed a quantitative immunohistochemical analysis of syndecan-1 expression using an automated cellular image analysis system. We analyzed specimens from cases of mild dysplasia (N = 55), moderate dysplasia (N = 38), severe dysplasia (N = 25), carcinoma in situ (CIS) (N = 43), and SCCA of the oral cavity (N = 45), using normal mucosal epithelium (N = 21) as a positive control. The SCCA specimens were further subdivided by degree of differentiation. We retrospectively reviewed patient charts to identify tumor stage at diagnosis, recurrence, and disease-specific survival. Syndecan-1 expression was significantly greater in normal controls than in specimens of mild, moderate, or severe dysplasia, CIS, or invasive SCCA (P < .05). Syndecan-1 expression did not differ significantly among specimens of mild, moderate, or severe dysplasia, CIS or SCCA. There was no significant difference in syndecan-1 expression between specimens from patients with no evidence of disease at 3 years follow-up and patients with local, regional, or distant recurrence. Syndecan-1 expression does not appear to be useful as a marker of differentiation or as a prognostic indicator in dysplasia and SCCA of the oral cavity. The search for a suitable and reliable marker of biological aggressiveness is ongoing.


A Life-Cycle Model of Human Social Groups Produces a U-Shaped Distribution in Group Size.
One of the central puzzles in the study of sociocultural evolution is how and why transitions from small-scale human groups to large-scale, hierarchically more complex ones occurred. Here we develop a spatially explicit agent-based model as a first step towards understanding the ecological dynamics of small and large-scale human groups. By analogy with the interactions between single-celled and multicellular organisms, we build a theory of group lifecycles as an emergent property of single cell demographic and expansion behaviours. We find that once the transition from small-scale to large-scale groups occurs, a few large-scale groups continue expanding while small-scale groups gradually become scarcer, and large-scale groups become larger in size and fewer in number over time. Demographic and expansion behaviours of groups are largely influenced by the distribution and availability of resources. Our results conform to a pattern of human political change in which religions and nation states come to be represented by a few large units and many smaller ones. Future enhancements of the model should include decision-making rules and probabilities of fragmentation for large-scale societies. We suggest that the synthesis of population ecology and social evolution will generate increasingly plausible models of human group dynamics.


The influence of metals on the expression of surface antigens on human lymphocytes in vitro.
Metals have different effects on the immune functions. Through the experimental in vitro model, we studied the changes in the activation and co-stimulatory surface markers in human lymphocytes cultivated with selected metal salts. Whole human blood was cultivated with cadmium (Cd) or zinc (Zn) sulfate for 18 hours. The number of lymphocytes positive for activation and co-stimulatory markers was evaluated by flow cytometry. Elevation of the CD69 and CD23 markers as well as higher expression of CD28 was found in cultures of lymphocytes incubated with Cd. In cultures incubated with Zn, minor elevation of the HLA-DR antigen expression was observed in comparison to Cd-treated cell cultures. Decrease of CD3 expression was observed after cultivation with both Cd and Zn salts. Cd and Zn exhibit different effects on the expression of human surface activation antigens and co-stimulatory molecules. Cd in non-toxic concentrations stimulated expression of early activation molecules and therefore could change the early phase of immune response. This was not the case for Zn, where the results were similar to untreated cell cultures.


Fear of falling and gait variability in older adults: a systematic review and meta-analysis.
Fear of falling (FOF) and increased gait variability are both independent markers of gait instability. There is a complex interplay between both entities. The purposes of this study were (1) to perform a qualitative analysis of all published studies on FOF-related changes in gait variability through a systematic review, and (2) to quantitatively synthesize FOF-related changes in gait variability. A systematic Medline literature search was conducted in May 2014 using the Medical Subject Heading (MeSH) terms "Fear" OR "fear of falling" combined with "Accidental Falls" AND "Gait" OR "Gait Apraxia" OR "Gait Ataxia" OR "Gait disorders, Neurologic" OR "Gait assessment" OR "Functional gait assessment" AND "Self efficacy" OR "Self confidence" AND "Aged" OR "Aged, 80 and over." Systematic review and fixed-effects meta-analysis using an inverse-variance method were performed. Of the 2184 selected studies, 10 observational studies (including 5 cross-sectional studies, 4 prospective cohort studies, and 1 case-control study) met the selection criteria. All were of good quality. The number of participants ranged from 52 to 1307 older community-dwellers (26.2%-85.0% women). The meta-analysis was performed on 10 studies with a total of 999 cases and 4502 controls. In one study, the higher limits of the effect size's confidence interval (CI) were lower than zero. In the remaining studies, the higher limits of the CI were positive. The summary random effect size of 0.29 (95% CI 0.13-0.45) was significant albeit of small magnitude, and indicated that gait variability was overall 0.29 SD higher in FOF cases compared with controls. Our findings show that FOF is associated with a statistically significant, albeit of small magnitude, increase in gait variability.


The wonderful colors of the hematoxylin-eosin stain in diagnostic surgical pathology.
The hematoxylin-eosin (H&E) stain has stood the test of time as the standard stain for histologic examination of human tissues. This simple dye combination is capable of highlighting the fine structures of cells and tissues. Most cellular organelles and extracellular matrix are eosinophilic, while the nucleus, rough endoplasmic reticulum, and ribosomes are basophilic. This review discusses the spectrum, intensity, and texture of colors observed in H&E-stained slides to illustrate their value in surgical pathology diagnosis. Changes in color of the nuclei occur in the presence of nuclear pseudoinclusions (such as papillary thyroid carcinoma) or inclusions (such as viral infection, surfactant, immunoglobulin, and biotin). The color of the cytoplasm of spindly cells can provide clues to their nature, such as basophilic (fibroblast), eosinophilic (smooth muscle and others), and amphophilic (myofibroblast). Eosinophilic globules have diagnostic value for sclerosing polycystic adenosis of salivary gland, low-grade B-cell lymphoma, solid pseudopapillary tumor of pancreas, and inclusion body fibromatosis. Eosinophilic granules are characteristic of granular cells (lysosome-rich), oncocytic cells (mitochondria-rich), and cells with secretory products (including neuroendocrine cells). Eosinophilic crystals can be diagnostic of lymphoma/plasmacytoma and crystal-storing histiocytosis. Basophilic granules or inclusions are diagnostic of acinic cell carcinoma and malakoplakia (Michaelis-Gutmann bodies). Yellow or brown inclusions are characteristic of hyalinizing trabecular adenoma of thyroid (yellow bodies), brown bowel syndrome, and malignant melanoma. Extracellular eosinophilic deposits can be produced by many conditions, but amyloid and monoclonal immunoglobulin deposition disease are important considerations. Extracellular basophilic deposits may be seen in small cell carcinoma and systemic lupus erythematosus, but they differ in that the former is blue (nuclear material) while the latter is purple (nuclear material plus immunoglobulin).


Chronically impaired endothelial vasoreactivity following oversized endovascular introducer sheath placement in porcine iliac arteries: implications for endovascular therapy.
The conventional endovascular aortic aneurysm procedure entails the placement of oversized introducer sheaths in relatively normal ileofemoral arteries to allow the delivery and deployment of endovascular prosthesis. Endoluminal manipulation with passage of oversized endoluminal devices can lead to endothelial denudation, resulting in impaired cellular function. The purpose of this study was to assess the time course of endothelial function with vasoreactivity following oversized endovascular sheath insertion ranging from 1 day to 16 weeks in normal porcine iliac arteries. Following oversized introducer sheath placement in bilateral iliac arteries, vasoreactivity was tested using both endothelium-dependent and -independent vasodilators. Intravascular ultrasonography showed a significant reduction in the luminal area at 12 and 16 weeks. This was similarly supported by morphometric analysis, which showed increased medial thickness with an elevated intima to media ratio at the same time course. Endothelium-dependent relaxation to bradykinin, calcium ionophore A23187, serotonin, and adenosine diphosphate all uniformly displayed attenuated endothelial dysfunction at all time points when compared with the control group. In contrast, endothelium-independent relaxation showed a decreased vasoresponsiveness at 4 weeks. In conclusion, this study underscored the detrimental and chronic endothelial dysfunction in a normal artery caused by oversized introducer sheath placement. Chronically impaired endothelial function may play a role leading to iliofemoral artery thrombosis or late occlusion, which were well-recognized adverse events following endovascular aneurysm procedures. Our study underscores the importance of appropriate patient selection to minimize potential sheath oversize and endograft device miniaturization to avoid vessel wall injury and maintain vasoreactivity.


Prostate-specific antigen is a new favorable prognostic indicator for women with breast cancer.
Prostate-specific antigen (PSA) is thought to be produced exclusively by prostatic epithelial cells and is currently used as a tumor marker of prostatic adenocarcinoma. We recently found that 30% of breast cancers contain PSA immunoreactivity (IR-PSA). To examine the prognostic value of PSA in female breast cancer, we measured IR-PSA in tumor cytosols of 174 breast cancer patients and classified the breast cancers as either PSA positive or PSA negative based on an IR-PSA cutoff level of 0.03 ng/mg. IR-PSA was present in 27% of the patients. IR-PSA presence was associated with early disease stage, small tumors, and estrogen receptor-positive tumors. We used the Cox proportional hazards regression model to analyze survival of patients in association with PSA status and found that patients with IR-PSA-positive tumors had a reduced risk for relapse and death in univariate analysis (P = 0.02 and 0.06, respectively) and a reduced risk for relapse in multivariate analysis (P = 0.03). Further analysis indicated that the effect of IR-PSA on relapse-free survival was evident in node-positive or estrogen receptor-negative patients. Our study suggests that IR-PSA is an independent favorable prognostic marker for breast cancer and may be used to identify a subgroup of estrogen receptor-negative and/or node-positive patients who have good prognoses.


Examining the boundaries of tailoring: the utility of tailoring versus targeting mammography interventions for two distinct populations.
Health messages can be generic, targeted to population subsets or tailored for individual recipients. There has been little examination of which populations need tailored interventions or whether tailored and targeted interventions differ in important ways. We used data from a mammography intervention study in two distinct populations to simulate a comparison of individually tailored versus targeted interventions. Tailored intervention content was based on individual recipients' interview responses. Targeted intervention content was based on composite group responses. For more than 60% in each population group, about two-thirds of tailored message content was a good match with content of the targeted intervention generated by composite group responses; roughly one-third of the content was 'not a good' fit for their intervention needs. Tailored interventions for more than 80% of subjects in each population differed in at least some way from those generated for all other population group members. This simulation is a first step in quantifying the contribution of individual tailoring over group targeting. Future research should examine whether a targeted intervention that is mostly a 'good' match results in behavioral outcomes similar to those of individually tailored interventions and whether particular differences in tailored versus targeted interventions yield significantly more favorable intervention outcomes.


Disparities for latino children in the timely receipt of medical care.
It is not known whether Latino children, the largest minority population in the United States, experience disparities in the timeliness of their access to health care. We compared timeliness of care among Latino, white, and African American children. cross-sectional cohort from the 2000 Medical Expenditure Panel Survey. children with a usual source of care. timeliness of care was assessed using parent reports of their child's 1) routine care, 2) illness care, 3) phone help, and 4) experiencing of a brief wait time. multiple logistic regression was used to determine the adjusted odds of not always receiving timely medical care. Four-thousand one-hundred twenty children were included. Latino children were less likely to always (P < .05) receive timely care compared with whites and African Americans, respectively, in 3 areas: routine care, phone help, and brief wait time. Multiple regression revealed decreased relative risks (RR, 95% CI) of always receiving timely medical care for Latinos in the same areas: routine care, compared with whites (0.88, 0.79-0.98) and African Americans (0.81, 0.70-0.93); phone help, compared with whites (0.84, 0.76-0.92) and African Americans (0.86, 0.76-0.960); and brief wait time, compared with whites (0.71, 0.65-0.80) and African Americans (0.81, 0.70-0.92). With parental survey language in the model, Latinos experienced decreased timeliness of care for routine care compared with African Americans (0.85, 0.72-0.98); phone help compared with whites (0.87, 0.77-0.96); and brief wait times compared with whites (0.79, 0.71-0.87). Latino children experience marked disparities in obtaining timely medical care, only some of which is associated with language differences.


Ruthenium-indolizinone complexes as a new class of metalated heterocyclic compounds: insight into unconventional alkyne activation pathways, revelation of unexpected electronic properties and exploration of medicinal application.
The two series of ruthenium-indolizinone complexes prepared by Ru-mediated cyclization of pyridine-tethered alkynes represent the first examples of metalated indolizinone complexes. Joint experimental-theoretical investigation suggests an unconventional 5-endo-dig cyclization pathway as their formation mechanism. They also exhibit moderate cytotoxicity against several human cancer cell lines.


Frequency based design of modal controllers for adaptive optics systems.
This paper addresses the problem of reducing the effects of wavefront distortions in ground-based telescopes within a "Modal-Control" framework. The proposed approach allows the designer to optimize the Youla parameter of a given modal controller with respect to a relevant adaptive optics performance criterion defined on a "sampled" frequency domain. This feature makes it possible to use turbulence/vibration profiles of arbitrary complexity (even empirical power spectral densities from data), while keeping the controller order at a moderate value. Effectiveness of the proposed solution is also illustrated through an adaptive optics numerical simulator.


Changes in brain alpha-adrenergic receptors after alpha-methyldopa administration to spontaneously hypertensive rats.
The hypotensive action of methyldopa has been linked to production of the metabolites methyldopamine and methylnorepinephrine in brain. We have studied the effect of long-term (72 hour) intravenous infusions of methyldopa to awake restrained spontaneously hypertensive rats and normotensive Wistar-Kyoto control animals to look for differences in hypotensive effect, differences in concentrations of natural and alpha-methylated catecholamines, and differences in alpha 1 and alpha 2-adrenergic receptor populations. Results described here indicate that hypertensive rats have a greater reduction in blood pressure and a larger increase in hypothalamic and brain stem methylnorepinephrine concentrations than do the normotensive animals. The methylnorepinephrine concentration reached a plateau value in hypothalamus in both strains while pons and medulla showed progressive, dose-related increases in concentration. These regional and strain differences in the metabolism of alpha-methyldopa suggest that the production of methylnorepinephrine in brain stem nuclei is most correlated with the hypotensive action of methyldopa. alpha 2 Agonist binding (p-amino-clonidine) declined in both hypothalamus and brain stem, and the fall was greater in hypertensive than in normotensive rats. alpha 1-Adrenergic receptor binding (prazosin) was increased, again more in hypertensive than in normotensive rats. The down regulation of alpha 2-adrenergic receptors and the up regulation of alpha 1-adrenergic receptors are compatible with increased alpha 2-adrenergic agonist presynaptic inhibition of catecholamine release with resultant postsynaptic alpha 1-adrenergic receptor supersensitivity. Spontaneously hypertensive rats showed greater methylnorepinephrine production, larger up regulation of alpha 1-adrenergic receptors, and greater down regulation of alpha 2-adrenergic receptors than did the normotensive animals; these changes may be physiological markers for the greater antisympathetic action of methyldopa in hypertensive animals.


Development and validation of an immunosensor for monocyte chemotactic protein 1 using a silicon photonic microring resonator biosensing platform.
We report the development of an optical immunosensor for the detection of monocyte chemotactic protein 1 (MCP-1) in serum samples. MCP-1 is a cytokine that is an emerging biomarker for several diseases/disorders, including ischemic cardiomyopathy, fibromyalgia, and some cancers. The detection of MCP-1 was achieved by performing a sandwich immunoassay on a silicon photonic microring resonator sensor platform. The resonance wavelengths supported by microring sensors are responsive to local changes in the environment accompanying biomarker binding. This technology offers a modularly multiplexable approach to detecting analyte localization in an antibody-antigen complex at the sensor surface. The immunosensor allowed the rapid detection of MCP-1 in buffer and spiked human serum samples. An almost 2 order of magnitude linear range was observed, between 84.3 and 1582.1pg/mL and the limits of blank and detection were determined to be 0.3 and 0.5pg/mL, respectively. The platform's ability to analyze MCP-1 concentrations across a clinically-relevant concentration range was demonstrated. A silicon photonic immunosensor technology was applied to the detection of clinically-relevant concentrations of MCP-1. The performance of the sensor was validated through a broad dynamic range and across a number of suggested clinical cut-off values. Importantly, the intrinsic scalability and rapidity of the technology makes it readily amenable to the simultaneous detection of multiplexed biomarker panels, which is particularly needed for the clinical realization of inflammatory diagnostics.


Isolation of Arabidopsis ahg11, a weak ABA hypersensitive mutant defective in nad4 RNA editing.
The phytohormone abscisic acid (ABA) plays pivotal roles in the regulation of developmental and environmental responses in plants. Identification of cytoplasmic ABA receptors enabled the elucidation of the main ABA signalling pathway, connecting ABA perception to either nuclear events or the action of several transporters. However, the physiological functions of ABA in cellular processes largely remain unknown. To obtain greater insight into the ABA response, genetic screening was performed to isolate ABA-related mutants of Arabidopsis and several novel ABA-hypersensitive mutants were isolated. One of those mutants--ahg11--was characterized further. Map-based cloning showed that AHG11 encodes a PPR type protein, which has potential roles in RNA editing. An AHG11-GFP fusion protein indicated that AHG11 mainly localized to the mitochondria. Consistent with this observation, the nad4 transcript, which normally undergoes RNA editing, lacks a single RNA editing event conferring a conversion of an amino acid residue in ahg11 mutants. The geminating ahg11 seeds have higher levels of reactive-oxygen-species-responsive genes. Presumably, partial impairment of mitochondrial function caused by an amino acid conversion in one of the complex I components induces redox imbalance which, in turn, confers an abnormal response to the plant hormone.


Detection of evoked acetylcholine release in mouse brain slices.
The study of transmitter interactions in reward and motor pathways in the brain, including the striatum, requires methodology to detect stimulus-driven neurotransmitter release events. Such methods exist for dopamine, and have contributed to the understanding of local and behavioral factors that regulate dopamine release. However, factors that regulate release of another key transmitter in these pathways, acetylcholine (ACh), are unresolved, in part because of limited temporal and spatial resolution of current detection methods. We have optimized a voltammetric method for detection of local stimulus-evoked ACh release using enzyme-coated carbon-fiber microelectrodes and fast-scan cyclic voltammetry. These electrodes are based on the detection of H2O2 generated by the actions of acetylcholine esterase and choline oxidase, and reliably respond to ACh in a concentration-dependent manner. Methods for enzyme coating were optimized for mechanical stability that allowed for their use in ex vivo brain slices. We report here the first quantitative assessment of extracellular ACh concentration after local electrical stimulation in dorsal striatum in slices from control mice. The selective detection of ACh under these conditions was confirmed by showing that the response detected in the control slices was absent in slices from mice bred to lack ACh synthesis in the forebrain. These electrodes represent a new tool to study ACh and ACh-dopamine interactions with micrometer spatial resolution.


Mapping Plasmodium falciparum Mortality in Africa between 1990 and 2015.
Malaria control has not been routinely informed by the assessment of subnational variation in malaria deaths. We combined data from the Malaria Atlas Project and the Global Burden of Disease Study to estimate malaria mortality across sub-Saharan Africa on a grid of 5 km2 from 1990 through 2015. We estimated malaria mortality using a spatiotemporal modeling framework of geolocated data (i.e., with known latitude and longitude) on the clinical incidence of malaria, coverage of antimalarial drug treatment, case fatality rate, and population distribution according to age. Across sub-Saharan Africa during the past 15 years, we estimated that there was an overall decrease of 57% (95% uncertainty interval, 46 to 65) in the rate of malaria deaths, from 12.5 (95% uncertainty interval, 8.3 to 17.0) per 10,000 population in 2000 to 5.4 (95% uncertainty interval, 3.4 to 7.9) in 2015. This led to an overall decrease of 37% (95% uncertainty interval, 36 to 39) in the number of malaria deaths annually, from 1,007,000 (95% uncertainty interval, 666,000 to 1,376,000) to 631,000 (95% uncertainty interval, 394,000 to 914,000). The share of malaria deaths among children younger than 5 years of age ranged from more than 80% at a rate of death of more than 25 per 10,000 to less than 40% at rates below 1 per 10,000. Areas with high malaria mortality (>10 per 10,000) and low coverage (<50%) of insecticide-treated bed nets and antimalarial drugs included much of Nigeria, Angola, and Cameroon and parts of the Central African Republic, Congo, Guinea, and Equatorial Guinea. We estimated that there was an overall decrease of 57% in the rate of death from malaria across sub-Saharan Africa over the past 15 years and identified several countries in which high rates of death were associated with low coverage of antimalarial treatment and prevention programs. (Funded by the Bill and Melinda Gates Foundation and others.).


Experiences of problems in individuals with hypersensitivity to odours and chemicals.
The purpose of the study was to describe how individuals with hypersensitivity to odours and chemicals handle their problems. One group of patients we often encounter consists of those with upper and lower respiratory problems who also have a pronounced sensitivity to odours and chemicals. Earlier studies have shown that these symptoms can be related to sensory hyperreactivity (SHR). This hyperreactivity is characterised by respiratory tract symptoms triggered by odours and chemicals, along with high sensitivity to inhaled capsaicin and a positive score on the chemical sensitivity scale for SHR. However, there is still a lack of studies in which SHR sufferers describe their situations in their own words. The study was conducted using a qualitative approach. Eight individuals with confirmed SHR were selected from a population-based epidemiological study and interviewed. A qualitative content analysis was performed on the data. Four themes emerged from the data analysis: Limitations in one's life situation, Lack of understanding from others, Concern that the symptoms will develop into a serious disease and Disparagement of one's own personal experience. The results show how individuals manage their daily lives with the help of various strategies, how they relate to other people, how they cope with their concerns and the fact that they sometimes choose to disparage their own experience of their problems. The results indicate that people with SHR experience limitations in their life situations. These limitations consist of the adjustments they make to avoid triggering factors. To improve care, nurses need to know how people experience SHR and how they cope with their hypersensitivity to odours and chemicals.


Pathophysiological and hygienic aspects of hand-arm vibration.
A review of current knowledge on the pathophysiological and hygienic aspects of the hand-arm vibration syndrome is given. Hemodynamic measurements indicate that the primary factor in vibration-induced white finger is an increase in the peripheral resistance of finger circulation that is present after local and general cooling. The reason for this increase is not known, but it is postulated that an excessive affinity of vasoactive substances for the efferent receptors exists, this affinity being potentiated during local cooling of the digits. So far, the hygienic rating of hazardous vibration in individual work phases is of limited value in diagnosing possible cases, but this rating does provide guidelines for general risk assessment. A consideration of several factors, eg, intermittency of the work, duration of daily exposure, impact of vibration, individual physiological responses, climate, etc, might improve the accuracy of the rating, but the influence of these factors on the development of the vibration syndrome is still poorly understood. Of various preventive measures, only those that significantly reduce vibration will be beneficial in the long run.


The cost of deep sleep: Environmental influences on sleep regulation are greater for diurnal lemurs.
Primates spend almost half their lives asleep, yet we know little about how evolution has shaped variation in the duration or intensity of sleep (i.e., sleep regulation) across primate species. Our objective was to test hypotheses related to how sleeping site security influences sleep intensity in different lemur species. We used actigraphy and infrared videography to generate sleep measures in 100 individuals (males = 51, females = 49) of seven lemur species (genera: Eulemur, Lemur, Propithecus, and Varecia) at the Duke Lemur Center in Durham, NC. We also generated experimental data using sleep deprivation for 16 individuals. This experiment used a pair-wise design for two sets of paired lemurs from each genus, where the experimental pair experienced a sleep deprivation protocol while the control experienced normal sleeping conditions. We calculated a sleep depth composite metric from weighted z scores of three sleep intensity variables. We found that, relative to cathemeral lemurs, diurnal Propithecus was characterized by the deepest sleep and exhibited the most disruptions to normal sleep-wake regulation when sleep deprived. In contrast, Eulemur mongoz was characterized by significantly lighter sleep than Propithecus, and E. mongoz showed the fewest disruptions to normal sleep-wake regulation when sleep deprived. Security of the sleeping site led to greater sleep depth, with access to outdoor housing linked to lighter sleep in all lemurs that were studied. We propose that sleeping site security was an essential component of sleep regulation throughout primate evolution. This work suggests that sleeping site security may have been an important factor associated with the evolution of sleep in early and later hominins.


How far did we get? How far to go? A European survey on postgraduate courses in evidence-based medicine.
Over the past decade, evidence-based medicine (EBM) has gained recognition as a means to improve the quality of health care provision. However, little is known about learning opportunities to acquire EBM-associated skills. The EUebm-Unity partnership explored current educational activities for EBM practice for doctors across Europe. We surveyed organizations offering postgraduate EBM courses across Europe inquiring about their course programme, teaching content and strategies, and interest in a Europe-wide curriculum in EBM. One hundred and fifty-six organizers in eight European countries reported 403 courses that had started first-time from 1996 to 2006. Despite a steady increase, in absolute terms, the frequency of courses was low and varied from 1 first-time offering of a course per 640 doctors (Spain) to 1 first-time offering per 5600 doctors (Austria) over 10 years. Most adopted the McMaster EBM teaching concept of small group, problem-based learning focussing on interventions, diagnostic tests and guidelines, and included efforts to link EBM to patient care. Teaching staff consisted of doctors from academic and non-academic settings, supported by methodologists. Efforts to formally integrate EBM in postgraduate activities were only partially successful. Most organizations welcomed a standardized European qualification in EBM. A limitation of the survey is the lack of follow-up information about the continuation of courses following the first-time offering. All countries offer some EBM courses with varying teaching intensity. Learning opportunities are insufficient to ensure widespread dissemination of knowledge and skills. Most countries welcome more efforts to develop inexpensive and feasible educational activities at a postgraduate level.


Anti-HIV-1 Activity Prediction of Novel Gp41 Inhibitors Using Structure-Based Virtual Screening and Molecular Dynamics Simulation.
The fusion of viral and host cell membranes is mediated using gp41 subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein. As the HIV-1 enters the host cells, the two helical regions (HR1 and HR2) in the ectodomain of gp41 form a six-helix bundle, which carries the target and viral cell membranes to close proximity. Steps of this process serve as attractive targets for developing HIV-1 fusion inhibitors. Identification of some novel HIV fusion inhibitors with the goal of blocking the formation of the six-helix bundle was accomplished by computer-aided drug design techniques. A virtual screening strategy was employed to recognize small molecules presumably able to bind the gp41 at the internal interface of the NHR helices at the core native viral six-helix. This study was carried out in two stages. In the first stage, a library of more than seven thousand compounds was collected from ZINC, PubChem and BindingDB databases and protein data bank. Key contacts of known inhibitors with gp41 binding site residues were considered as the collecting criteria. In the second stage series of filtering processes were performed on this library in subsequent steps to find the potential gp41 inhibitors. The filtering criteria included pharmacokinetic and ADMET properties as well as in silico anti-HIV-1 prediction. Molecular docking simulation was carried out to identify interactions of the filtered molecules with the key residues in the gp41 binding site. Finally, molecular dynamics simulation indicates the superior inhibitory ability of three selected compounds over the known gp41inhibitor, NB-64.


Cause of death in Washington state veterans hospitalized with acute coronary syndromes in the veterans health administration.
In the United States, relatively little is known about cause of death in individuals who die prior to or after hospital discharge for acute coronary syndromes (ACS). The purpose of this report was to compare baseline patient characteristics according to whether the underlying cause of death was cardiac or non-cardiac. We linked cause of death information from Washington State death records to the Department of Veterans Affairs (VA) External Peer Review Program ACS registry. From 524 individuals who were hospitalized for ACS in veterans hospitals located in Washington State or Oregon, we identified 136 individuals who according to VA death records died during the years 2003 to 2005. Of these, 117 (86%) were found in Washington State death records. Sociodemographic variables, as well as underlying and secondary causes of death, were obtained from Washington State death records provided by the Washington State Department of Health. Clinical variables, including medical histories, presentation on admission, and in-hospital death were extracted from the VA ACS registry. Somewhat surprisingly, only 52% of veterans died of cardiac causes when only the underlying cause of death was used. However, when secondary causes of death were added to the definition, the proportion that died of cardiac causes increased to 81%. Patient characteristics were similar in the two groups, although small numbers limited the ability to detect statistically significant differences. These preliminary findings suggest that it is important to consider secondary causes as well as the underlying one when classifying deaths as cardiac or non-cardiac.


Comparison between non-modulation four-sided and two-sided pyramid wavefront sensor.
Based on the diffraction theory the paper analyzes non-modulation Pyramid wavefront sensor (PWFS, namely, four-sided pyramid) and two-sided pyramid wavefront sensor (TSPWFS), and expresses the detected signals as a function of the measured wavefront. The expressions of the detected signals show that non-modulation PWFS and TSPWFS hold the same properties of both slope and direct phase sensors. We compare both sensors working in slope and phase sensing by theory and numerical simulations. The results demonstrate that the performance of TSPWFS excels that of PWFS. Additionally, the influence of interference between adjacent pupils is discussed.


Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma.
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL). CD8 TIL were abundant in ccRCC, but they were phenotypically distinct and both functionally and metabolically impaired. ccRCC CD8 TIL were unable to efficiently uptake glucose or perform glycolysis and had small, fragmented mitochondria that were hyperpolarized and generated large amounts of ROS. Elevated ROS was associated with downregulated mitochondrial SOD2. CD8 T cells with hyperpolarized mitochondria were also visible in the blood of ccRCC patients. Importantly, provision of pyruvate to bypass glycolytic defects or scavengers to neutralize mitochondrial ROS could partially restore TIL activation. Thus, strategies to improve metabolic function of ccRCC CD8 TIL may promote the immune response to ccRCC.


Associations between dietary amino acid intakes and blood concentration levels.
Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations. Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results. Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might be related to physiological AA status, particularly for the essential AAs. However, these results should be further evaluated and confirmed in large-scale prospective studies.


Birth of projection neurons in adult avian brain may be related to perceptual or motor learning.
Projection neurons that form part of the motor pathway for song control continue to be produced and to replace older projection neurons in adult canaries and zebra finches. This is shown by combining [3H]thymidine, a cell birth marker, and fluorogold, a retrogradely transported tracer of neuronal connectivity. Species and seasonal comparisons suggest that this process is related to the acquisition of perceptual or motor memories. The ability of an adult brain to produce and replace projection neurons should influence our thinking on brain repair.


Decision-support tool for prevention and control of Rift Valley fever epizootics in the Greater Horn of Africa.
In East Africa, Rift Valley fever (RVF) usually occurs as explosive epizootics with prolonged inter-epidemic periods on the order of 8 to 10 years. The episodic nature of the disease and the rapid evolution of outbreaks create special challenges for its mitigation and control. Following the events of the 2006 and 2007 RVF outbreak in East Africa, decision-makers assembled their collective experiences in the form of a risk-based decision support tool to help guide responses in future emergencies. The premise of the tool is that a series of natural events are indicative of the increasing risk of an outbreak and that actions should be matched to this evolving risk profile. In this manner, investment in prevention and control can be qualitatively optimized. The decision support tool is a living document written through stakeholder input. This publication captures the current tool as an example of risk-based decision support.


A target-mediated fuel-initiated molecular machine for high-sensitive fluorescence assay of the ZIKV gene via strand displacement reaction-based signal recovery and cycling amplification.
Zika virus (ZIKV) is a serious threat to human health due to its widespread human arboviral infections, and early diagnosis is one of the keys to preventing infections from spreading, but there is a lack of highly sensitive and specific detection. In this work, a target-mediated fuel-initiated molecular machine was proposed for the high-sensitive fluorescence assay of the ZIKV gene via strand displacement reaction-based signal recovery and cycling amplification. The molecular machine was prepared by modifying AuNP surfaces with specially designed lock-like DNAs (LLDs). The LLDs assembled with a hairpin DNA (H1) and a fluorescent aDNA can be opened under the trigger of the ZIKV gene and the strand displacement reactions are further initiated with the help of the DNA fuel (H2), which results in the release of the aDNAs and ZIKV genes from the AuNPs, causing the recovery of the fluorescence signal and the cyclic amplification of the gene. The target-mediated fuel-initiated molecular machines output an amplified fluorescence signal with the enhancement of 360%, and possess good sensitivity for detecting the ZIKV gene in serum with a linear calibration curve from 100 pM to 1 fM and a low limit of detection of 0.90 fM. The molecular machines can differentiate the ZIKV gene from the single base mismatched DNA obviously and show good recovery of ZIKV gene detection, which demonstrates the good specificity, reproducibility and reliability of the highly sensitive assay for the early detection of the virus.


Noninvasive device to produce and maintain an erection-like state.
In 35 men with organic impotence we have tested a noninvasive device which uses a vacuum to produce an erection-like state and rubber bands to maintain this state. The subjects were first evaluated to determine the cause of their impotence and to establish that it had an organic basis. Using this device 32 of the 35 subjects achieved penile rigidity sufficient for vaginal penetration. Subjects were studied with the rubber bands constricting the base of the penis for thirty minutes. During that period, blood flow continued, but at a less than normal rate. Of 30 men followed up from eight to twenty-two months, 24 use the device regularly and report that they are satisfied. Four subjects have not yet tried to use it, and 1 no longer needs it. One man was dissatisfied because the rigidity begins to decrease after five to ten minutes of sexual activity, even though it did not change over a thirty-minute period when originally tested in the laboratory. Ecchymoses of the penis, probably due to excess vacuum, developed in 3 subjects. In 8 other men petechiae of the skin of the penis developed on one or more occasions. These ecchymoses and petechiae were painless and disappeared without treatment. No other complications occurred. The vacuum device appears to be a safe and inexpensive way for an impotent man to make the penis rigid enough to engage in sexual intercourse.