Magnetoencephalography (MEG) and other neurophysiological investigations.
Cortical generators of epileptic and certain physiological activity can be localized noninvasively by magnetoencephalography (MEG). MEG detects weak magnetic fields produced by the postsynaptic currents of pyramidal cortical cells in sulcal walls. Unlike EEG, MEG signals are not distorted by edema or bone defects, and unlike fMRI, abnormal hemodynamics do not alter the MEG. The patient's head is centered inside a helmet housing over a hundred magnetic field sensors. Cortical generators of MEG signals are determined with a useful spatial resolution and an excellent time resolution, which enable tracking of brain activity in successive points of, for example, an epileptic network. MEG sources can be co-registered and visualized on magnetic resonance images (MRI). MEG is highly sensitive for the detection of interictal epileptic discharges, and present techniques allow some degree of head movements enabling ictal recordings also. MEG is also useful for localizing the somatosensory, visual, and language areas before tailored surgery in the vicinity of eloquent cortex. In conjunction with other noninvasive modalities MEG provides nonredundant data in one-third of epilepsy surgery patients. Clinical MEG utilization is mainly focused on presurgical localization of the epileptogenic zone and eloquent cortex in epilepsy surgery candidates, including patients with Landau-Kleffner syndrome. However, MEG is also an excellent noninvasive tool to study the source distribution in childhood epilepsy syndromes and epileptic encephalopathies.


Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication.
The current outbreak of Ebola virus (EBOV) in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC) demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.


Brain growth deficits following a single day of alcohol exposure in the neonatal rat.
Alcohol (7.5 g/kg) was administered to neonatal rats in a single day via artificial rearing procedures, being given in four consecutive feedings spaced two hours apart on either postnatal day 4, 5, or 6. These single days of alcohol exposure resulted in high peak blood alcohol concentrations (mean peak BACs of 380, 439 and 460 mg/dl, respectively) and significantly restricted brain weight when measured on postnatal day 10. The cerebellum was affected more than total brain, forebrain or brain stem. Additionally, growth of the cerebellum was more stunted by alcohol exposure on either day 4 or 5 than when the alcohol exposure occurred on day 6. Small but significant delays in body growth occurred 1-2 days after the alcohol exposure for each group. The interference with brain growth following high BACs for a short period of time has important clinical and experimental implications related to binge drinking and the mechanisms underlying alcohol-induced effects on the developing brain.


The effect of pH on the interaction of substrates and effector to yeast and rabbit muscle pyruvate kinase.
The interaction of fructose 1,6-bisphosphate, phosphoenolpyruvate and ADP with pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 220.127.116.11) from yeast and rabbit muscle has been studied as a function of pH utilizing the quenching of protein fluorescence at 330 nm by these ligands. Both the muscle and the yeast pyruvate kinase interact with either ADP or phosphoenolpyruvate with similar affinity, indicating that the substrate-binding sites for these two isozymes are similar. The major difference between the yeast and muscle isozymes is their affinity with fructose 1,6-bisphosphate. Fructose 1,6-bisphosphate interacts with the yeast isozyme in orders of magnitude more strongly than with the muscle isozyme. Moreover, the affinity of fructose 1,6-bisphosphate to the yeast isozyme is strongly pH-dependent, while the interaction of fructose 1,6-bisphosphate with the muscle isozyme is independent of pH. The data indicate that yeast pyruvate kinase undergoes a conformational change as the pH is increased from 6.0 to 8.5.


Long-term survival of two patients with inoperable post-irradiation osteosarcoma treated with carbon-ion radiotherapy: a case report.
Curative treatment of inoperable post-irradiation sarcoma is often challenging, especially using radiotherapy, wherein curative dose administration is difficult because the organs around the tumor have already been irradiated during the first cancer treatment. Carbon-ion radiotherapy (C-ion RT) might be useful in the treatment of post-irradiation sarcomas because it allows re-irradiation with high-dose localization properties and also demonstrates higher cytotoxic effects on radioresistant tumors compared with X-rays. This study presents the long-term survival of two patients with inoperable post-irradiation pelvic osteosarcoma treated with C-ion RT after uterine cervical cancer treatment. The durations from prior radiotherapy to the diagnosis of post-irradiation osteosarcoma were 112.8 and 172.2 months, respectively. Both patients received 70.4 Gy (relative biological effectiveness) in 16 fractions of C-ion RT, and chemotherapy was performed before and after C-ion RT. Both patients achieved a complete response 1 year after the initiation of C-ion RT. However, one patient developed single lung metastasis 12.6 months after the initiation of C-ion RT and underwent thoracoscopic lobectomy. After 63.7 and 89.0 months from the initiation of C-ion RT, respectively, the patients were alive with no evidence of local recurrence, other distant metastasis, or fatal toxicities. The study findings suggest that C-ion RT is a suitable treatment option for inoperable post-irradiation osteosarcoma.


Surface Acoustic Wave Resonators With Hetero Acoustic Layer (HAL) Structure Using Lithium Tantalate and Quartz.
This article reports a new concept of surface-acoustic-wave (SAW) resonator, which uses shear horizontal (SH) wave confined in a thin LiTaO3 (LT) layer supported by a quartz (Qz) substrate. The LT layer is 35-50°YX LT, and the quartz substrate is 35-60°Y90°X Qz. A negative temperature coefficient of frequency (TCF) of the SH SAW in the LT layer is compensated by the quartz substrate, which shows a wide range of positive TCF depending on the crystalline orientation. Excellent TCFs of 2 and -10 ppm/°C were measured for the series and parallel resonance frequencies, respectively. The strong confinement of the SH SAW in the LT layer results in the best level of resonance characteristics ever reported. The measured impedance ratio reached 84 dB. On the other hand, spurious waves other than the SH SAW are not confined in the LT layer due to the unique properties of quartz, which results in spurious-free characteristics throughout a wide frequency range.


Absence of CD36 alters systemic vitamin A homeostasis.
Fatty acid translocase (CD36) is a scavenger receptor with multiple ligands and diverse physiological actions. We recently reported that alcohol-induced hepatic retinoid mobilization is impaired in Cd36-/- mice, leading us to hypothesize that CD36 has a novel role in hepatic vitamin A mobilization. Given the central role of the liver in systemic vitamin A homeostasis we also postulated that absence of CD36 would affect whole-body vitamin A homeostasis. We tested this hypothesis in aging wild type and Cd36-/- mice, as well as mice fed a vitamin A-deficient diet. In agreement with our hypothesis, Cd36-/- mice accumulated hepatic retinyl ester stores with age to a greater extent than wild type mice. However, contrary to expectations, Cd36-/- mice consuming a vitamin A-deficient diet mobilized hepatic retinoid similar to wild type mice. Interestingly, we observed that Cd36-/- mice had significantly reduced white adipose tissue retinoid levels compared to wild type mice. In conclusion, we demonstrate that the absence of CD36 alters whole-body vitamin A homeostasis and suggest that this phenotype is secondary to the impaired chylomicron metabolism previously reported in these mice.


Descriptions and Reflections on the Cognitive Apprenticeship Model of Psychotherapy Training & Supervision.
This paper offers a detailed description of a Cognitive Apprenticeship Model for psychotherapy training and supervision. This form of training has been utilized in a novel psychotherapy training program developed for psychiatric trainees, enrolled in a specialized psychotherapy scholars track, embedded in an adult psychiatric residency training program. The paper offers new elaborations of the model, reflections on the apprenticeship supervision and implementation, and clinical lessons learned. The four dimensions of this model include: (1) acquisition of psychotherapy content knowledge; (2) an application of the Cognitive Apprenticeship Model of Supervision, utilizing modeling, coaching, scaffolding, articulation, reflection and exploration as essential aids in structuring a live, real-time supervisory experience; (3) sequencing of clinical psychotherapy training activities; and (4) use of situated learning and communities of practice, as important components of psychotherapy training. The article also discusses an apprentice method of psychotherapy supervision including the intake, working through, and termination phases, Barriers impeding apprenticeship supervision and implementation, and reflections on participant experiences are discussed. This approach may be valuable to others considering the development or evolution of psychotherapy training programs for psychiatrists, psychologists, social workers, or other mental health professionals.


Fractional anisotropy values detect pyramidal tract involvement in multiple system atrophy.
Pathological studies have shown remarkable pyramidal tract involvement in multiple system atrophy (MSA), while clinical pyramidal signs are relatively rare. We investigated the fractional anisotropy (FA) values to assess the degree of pyramidal tract involvement in MSA, in comparison with amyotrophic lateral sclerosis (ALS) and controls. Furthermore, we compared FA values between MSA patients with or without clinical pyramidal signs and controls, and between MSA patients with or without positive conventional MRI findings and controls. We evaluated FA values in the internal capsule, corona radiate and whole pyramidal tract using visualized tractography of 65 subjects (20 probable MSA patients, 28 age-matched ALS patients, and 17 age-matched healthy controls) using a 3.0T magnetic resonance system. The FA values in the internal capsule, corona radiate, and whole pyramidal tract were significantly lower in MSA patients than in controls and were at a level similar to those of ALS patients. In addition, low FA values were prominent in MSA patients, even in those with short duration of illness, lacking precentral gyrus hyperintensity in FLAIR images, and without pyramidal signs. FA values could identify pyramidal tract degeneration even in patients with early phase MSA and those without clinical pyramidal signs or abnormal MRI findings. More extensive degeneration of the pyramidal tract occurs in MSA than so far believed.


Ex Vivo Porcine Arterial and Chorioallantoic Membrane Acoustic Angiography Using Dual-Frequency Intravascular Ultrasound Probes.
The presence of blood vessels within a developing atherosclerotic plaque has been found to be correlated with increased plaque vulnerability and ensuing cardiac events, however, detection of coronary intraplaque neovascularization poses a significant challenge in the clinic. We describe here a new in vivo intravascular ultrasound imaging method using a dual-frequency transducer to visualize contrast flow in microvessels with high specificity. This method uses a specialized transducer capable of exciting contrast agents at a low frequency (5.5 MHz) while detecting their nonlinear superhamonics at a much higher frequency (37 MHz). In vitro evaluation of the approach was performed in a microvascular phantom to produce 3-D renderings of simulated vessel patterns and to determine image quality metrics as a function of depth. Furthermore, we describe the ability of the system to detect microvessels both ex vivo using porcine arteries and in vivo using the chorioallantoic membrane of a developing chicken embryo with optical confirmation. Dual-frequency contrast-specific imaging was able to resolve vessels similar in size to those found in vulnerable atherosclerotic plaques at clinically relevant depths. The results of this study add to the support for further evaluation and translation of contrast-specific imaging in intravascular ultrasound for the detection of vulnerable plaques in atherosclerosis.


The effect of unimanual performance on speed of verbalization.
Male college students (N = 20) named colors under two levels of difficulty while turning a wheel with one hand. The hand used was found to be unrelated to naming time. In a second experiment, 24 male college students performed a dowel-balancing task while repeating a simple sentence and while remaining silent. Verbalization was found to be unrelated to hand used while dowel-balancing. The results failed to replicate and extend earlier findings.


Composite cylinder models of DNA: application to the electrostatics of the B-Z transition.
We develop and test a Poisson-Boltzmann model of the electrostatics of the B-Z transition of DNA. Starting from the detailed geometries of the two forms, we compute at each radius the fractions of DNA matter, of volume forbidden (for nonpoint-like ions), and of volume accessible to the center of ions. These radial distributions are incorporated in a composite cylinder model; availability to ions (porosity) and the dielectric constant at each radial distance are then obtained. The phosphate charge is distributed with cylindrical symmetry on two layers at the appropriate radial distances. The porous sheath, between the axis and the charge distribution, provides much more room for ions in B-DNA than in Z-DNA. By using previously developed methods, the Poisson-Boltzmann problem of such cylinders is easily solved. The computational load is small, so that results can be obtained for a large set of salt concentrations and for a number of ionic radii. The variation of the electrostatic free energy difference with salt concentration compares favorably with the experimental value (it is half as large). There is also qualitative agreement with experiments on supercoiled DNA, including a maximum of the free energy difference at submolar salt concentrations. The results for this cylinder with porous sheath are in line with those of the earlier simple planar model and of a plain cylinder with sheath, which is also presented here. They are thus insensitive to details of the model. They support the proposition that the main electrostatic feature of the B-Z transition is the better immersion of the B-DNA phosphates into the solution. They also give confidence in the validity of the Poisson-Boltzmann approach, despite the large salt concentrations involved. Prior studies using an approach based on the potential of mean force are discussed.


The bidirectional relationship between NAFLD and type 2 diabetes: A prospective population-based cohort study.
To explore the bidirectional relationship between NAFLD and type 2 diabetes and the possible directions of the main effect. 30 633 participants from the Jinchang cohort were enrolled. Firstly, cox proportional hazards regression model was used to assess the unidirectional causality between NAFLD and prediabetes and type 2 diabetes. Secondly, cross-lag path analysis model was conducted to estimate the bidirectional relationship between NAFLD and prediabetes and type 2 diabetes, and to determine the direction of the main effects. Finally, potential effect modifications were also considered by age, sex, hyperlipidemia, and overweight/obesity. We found that NAFLD increased the risk of prediabetes and type 2 diabetes with adjusted HR (95%CI) of 1.355(95%CI: 1.255-1.462) and 1.898(95%CI: 1.415-2.545), respectively. Prediabetes and type 2 diabetes also increased the risk of NAFLD, with adjusted HR (95%CI) of 1.245(95%CI: 1.115-1.392) and 1.592(95%CI: 1.373-1.846), respectively. Cross-lag path analysis showed that NAFLD significantly affected the incidence of prediabetes (β = 0.285, P < 0.001), while the effect on type 2 diabetes was not statistically significant. The effect of prediabetes and type 2 diabetes on the risk of NAFLD was weak, and the path coefficients were 0.076 and 0.037, respectively. Stratified analyses showed similar results. This study provides evidence that there was a bidirectional causal association between NAFLD and type 2 diabetes, and the progression from NAFLD through prediabetes to type 2 diabetes may be the main pathway.


[Influence of Xinqin tablets on guinea-pig nasal hypersensitivity].
To study the influence of Xinqin tablets on guinea-pig nasal hypersensitivity. 2,4-Toluene Diisocyanate (TDI) was selected as antigen and used in nose to establish guinea-pig allergic rhinitis. The effects of Xinqin tablets on symptoms of nasal hypersensitivity in guinea-pigs, histamine content of nasal mucosa and activity of nitric oxide synthase (NOS) were examined. Xinqin tablets could significantly relieve the pathological symptoms of nasal hypersensitivity in guinea-pig, reduce histamine content of nasal mucosa and inhibit the activity of nitric oxide synthase. Xinqin tablets have significant effect on nasal hypersensitivity, and prevent the occurrence of allergic rhinitis.


Synthesis and structure-activity relationships of pyrazine-pyridine biheteroaryls as novel, potent, and selective vascular endothelial growth factor receptor-2 inhibitors.
There is much evidence that direct inhibition of the kinase activity of vascular endothelial growth factor receptor-2 (VEGFR-2) will result in the reduction of angiogenesis and the suppression of tumor growth. Palladium-catalyzed C-C bond, C-N bond formation reactions were used to assemble various pyrazine-pyridine biheteroaryls as potent VEGFR-2 inhibitors. Among them, 4-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-ylamino}-butan-1-ol (39) and N-{5-[6-(3-chloro-phenylamino)-pyrazin-2-yl]-pyridin-3-yl}-N',N'-dimethyl-ethane-1,2-diamine (41) exhibited the highest kinase selectivity against fibroblast growth factor receptor kinase, platelet-derived growth factor receptor kinase, and glycogen synthase kinase-3. All of these compounds showed good cellular potency to inhibit VEGF-stimulated proliferation of human umbilical vein endothelial cells (HUVEC) but with modest effects on the unstimulated growth of HUVEC. The low inhibition of these compounds to the growth of tumor cell lines, such as HeLa, HCT-116, and A375 further confirms that these VEGFR-2 inhibitors are not cytotoxic agents. The in vivo antitumor activity of 39 and 41 were demonstrated in the A375 human melanoma xenograft nude mice model. Molecular modeling (QSAR analysis) was conducted in an attempt to rationalize the observed structure-activity relationship.


Drinking to toxicity: college students referred for emergency medical evaluation.
In 2009, a university adopted a policy of emergency department transport of students appearing intoxicated on campus. The objective was to describe the change in ED referrals after policy initiation and describe a group of students at risk for acute alcohol-related morbidity. A retrospective cohort of university students during academic years 2007-2011 (September-June) transported to local ED's was evaluated. Data were compared 2 years prior to initiation of the policy and 3 years after and included total number of ED transports and blood or breath alcohol level. 971 Students were transported to local ED's. The mean number of yearly transports 2 years prior to policy initiation was 131 and 3 years after was 236 (56 % increase, p < 0.01). 92 % had a blood or breath alcohol level obtained. The mean alcohol level was 193 mg/dL. Twenty percent of students had alcohol levels greater than 250 mg/dL. Adoption of a university alcohol policy was followed by a significant increase in ED transports of intoxicated students. College students identified as intoxicated frequently drank to toxicity.


Evaluation of sequential testing strategies using non-amplified and amplified methods for detection of Chlamydia trachomatis in endocervical and urine specimens from women.
Nucleic acid amplification tests (NAAT) are more sensitive than other methods for the diagnosis of Chlamydia trachomatis (CT) genital infections. Two unique sequential testing strategies that employed two different commercial NAAT methods to detect CT in a population of women with widely varying infection risk were evaluated. Specimens from 504 women aged 15 to 75 years were studied. Two endocervical swabs and a urine sample were collected from each woman. One swab was initially tested using the Access enzyme immunoassay (EIA) (Beckman). An aliquot from the EIA extraction was subsequently amplified using the COBAS AMPLICOR CT assay (PCR) (Roche). The second swab was initially tested using the PACE 2 CT hybridization assay (Gen-Probe). An aliquot was pipetted off prior to performing the PACE 2 assay and also amplified using the AMP-CT assay (TMA) (Gen-Probe). Urine samples were tested for CT using both NAAT methods. True CT infections were defined as any woman that was confirmed to be positive on both NAAT results from endocervical swabs. The results of all other CT assays were compared against this expanded gold standard. 28 women were confirmed to have CT infection giving an overall prevalence of 5.6%; low-risk women had a rate of 1.3% while high-risk women had a rate of 9.8%. NAAT methods have a higher sensitivity for detecting CT cervicitis when swabs are tested compared to urine. The positive predictive value of NAAT is decreased when testing low risk women. Limited automation makes it difficult to test a high volume of samples (i.e., > 100 swabs and/or urines) using either of these NAAT methods and continue to provide same day results. Laboratories performing CT testing must define the female population served so that appropriate diagnostic strategies can be employed.


Barley malt wort fermentation by exopolysaccharide-forming Weissella cibaria MG1 for the production of a novel beverage.
The growing interest of governments and industry in developing healthy and natural alternative foods and beverages that will fulfil the consumer drive towards a healthy lifestyle and clean-label, natural diet has led to an increase in traditional lactic acid bacteria fermentation research. In particular, this research aims to address the organoleptic modulation of beverages using in situ-produced bacterial polysaccharides. Weissella cibaria MG1 is capable of producing exopolysaccharides (dextran) and oligosaccharides (glucooligosaccharides) during sucrose-supplemented barley-malt-derived wort fermentation. Up to 36·4 g l(-1) of dextran was produced in an optimized system, which improved the rheological profile of the resulting fermentate. Additionally, small amounts of organic acids were formed, and ethanol remained below 0·5% (v/v), the threshold volume for a potential health claim designation. The results suggest that the cereal fermentate produced by W. cibaria MG1 could be potentially used for the production of a range of novel, nutritious and functional beverages. Using conventional raw materials and traditional processes, novel LAB-fermented beverages can be produced representing an innovative mechanism towards fulfilling the aim to decrease government and personal costs as well as potentially ameliorating consumer lifestyle regarding dietary-related disease.


Merlin inhibits Wnt/β-catenin signaling by blocking LRP6 phosphorylation.
Merlin, encoded by the NF2 gene, is a tumor suppressor that acts by inhibiting mitogenic signaling and is mutated in Neurofibromatosis type II (NF2) disease, although its molecular mechanism is not fully understood. Here, we observed that Merlin inhibited Wnt/β-catenin signaling by blocking phosphorylation of LRP6, which is necessary for Wnt signal transduction, whereas mutated Merlin in NF2 patients did not. Treatment with Wnt3a enhanced phosphorylation of Ser518 in Merlin via activation of PAK1 in a PIP2-dependent manner. Phosphorylated Merlin dissociated from LRP6, allowing for phosphorylation of LRP6. Tissues from NF2 patients exhibited higher levels of β-catenin, and proliferation of RT4-D6P2T rat schwannoma cells was significantly reduced by treatment with chemical inhibitors of Wnt/β-catenin signaling. Taken together, our findings suggest that sustained activation of Wnt/β-catenin signaling due to abrogation of Merlin-mediated inhibition of LRP6 phosphorylation may be a cause of NF2 disease.


The neurotoxicity of misonidazole and its relationship to dose, half-life and concentration in the serum.
Misonidazole has been given to a total of 87 patients. Neurotoxicity has occurred--convulsions with the higher doses and peripheral neuropathy with the lowern ones. The data from 34 patients receiving 4--7 doses has been analysed. Peripheral neuropathy is related to the total tissue exposure. By monitoring serum levels and controlling the total dose given, convulsions are avoidable and peripheral neuropathy restricted to a low and acceptable level.


A graphical approach to the identification and estimation of causal parameters in mortality studies with sustained exposure periods.
In observational cohort mortality studies with prolonged periods of exposure to the agent under study, independent risk factors for death commonly determine subsequent exposure to the study agent. For example, in occupational mortality studies, date of termination of employment is both a determinant of subsequent exposure to the chemical agent under study (since terminated individuals receive no further exposure) and an independent risk factor for death (since disabled individuals tend to leave employment). When a risk factor determines subsequent exposure and is determined by previous exposure, standard analyses that estimate age-specific mortality rates as a function of cumulative exposure can underestimate the true effect of exposure on mortality, whether or not one adjusts for the risk factor in the analysis. This observation raises the question, "Which, if any, empirical population parameter can be causally interpreted as the true effect of exposure in observational mortality studies?" In answer, we offer a graphical approach to the identification and estimation of causal parameters in mortality studies with sustained exposure periods. We reanalyze the mortality experience of a cohort of arsenic-exposed copper smelter workers using our approach and compare our results with those obtained using standard methods. We find an adverse effect of arsenic exposure on all cause and lung cancer mortality, which standard methods failed to detect. The analytic approach introduced in this paper may be necessary to control bias in any epidemiologic study in which there exists a risk factor which both determines subsequent exposure and is determined by previous exposure to the agent under study.


Urinary proteomics reveals association between pediatric nephrolithiasis and cardiovascular disease.
To study (1) the differences in the relative abundance of urinary proteins between children with kidney stones (RS) and hypercalciuria, hypocitraturia, normal metabolic work-up, and healthy controls (HC); (2) the association of these proteins with various diseases. Quantitative proteomic comparison of pooled urine from RS (N = 30, 24 females, mean age 12.95 ± 4.03 years) versus age- and gender-matched HC, using mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest were selected using the following criteria: (1) ≥ 5 spectral counts; (2) ≥ twofold difference in spectral counts; and (3) ≤ 0.05 p value for the Fisher's Exact Test. Of the 1813 proteins identified, 229 met the above criteria, with 162 proteins up-regulated in the RS group and 67 up-regulated in HC. The largest group of proteins (30 out of 229) was found to be associated with cardiovascular disease (CVD). Of those, 16 were involved in coagulation, fibrinolysis, and adhesion, 10 in inflammation, 5 in lipid transport and metabolism, and 4 in oxidative stress. All except two were exclusively found in children with hypercalciuria and hypocitraturia, and were not seen in children with normal metabolic work-up. Using a proteomic approach, we found a significant association between hypercalciuric and hypocitraturic nephrolithiasis and CVD in children. The shared risk factors among both diseases are endothelial dysfunction and atherosclerosis caused by abnormal coagulation, adhesion, disturbance of lipid transport and metabolism, oxidative stress and inflammation. Further understanding of the pathophysiological link between nephrolithiasis and CVD is necessary for developing new therapeutic targets.


Differentiation between high-grade gliomas and solitary brain metastases: a comparison of five diffusion-weighted MRI models.
To compare the diagnostic performance of neurite orientation dispersion and density imaging (NODDI), mean apparent propagator magnetic resonance imaging (MAP-MRI), diffusion kurtosis imaging (DKI), diffusion tensor imaging (DTI) and diffusion-weighted imaging (DWI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs). Patients with previously untreated, histopathologically confirmed HGGs (n = 20) or SBMs (n = 21) appearing as a solitary and contrast-enhancing lesion on structural MRI were prospectively recruited to undergo diffusion-weighted MRI. DWI data were obtained using a q-space Cartesian grid sampling procedure and were processed to generate parametric maps by fitting the NODDI, MAP-MRI, DKI, DTI and DWI models. The diffusion metrics of the contrast-enhancing tumor and peritumoral edema were measured. Differences in the diffusion metrics were compared between HGGs and SBMs, followed by receiver operating characteristic (ROC) analysis and the Hanley and McNeill test to determine their diagnostic performances. NODDI-based isotropic volume fraction (Viso) and orientation dispersion index (ODI); MAP-MRI-based mean-squared displacement (MSD) and q-space inverse variance (QIV); DKI-generated radial, mean diffusivity and fractional anisotropy (RDk, MDk and FAk); and DTI-generated radial, mean diffusivity and fractional anisotropy (RD, MD and FA) of the contrast-enhancing tumor were significantly different between HGGs and SBMs (p < 0.05). The best single discriminative parameters of each model were Viso, MSD, RDk and RD for NODDI, MAP-MRI, DKI and DTI, respectively. The AUC of Viso (0.871) was significantly higher than that of MSD (0.736), RDk (0.760) and RD (0.733) (p < 0.05). NODDI outperforms MAP-MRI, DKI, DTI and DWI in differentiating between HGGs and SBMs. NODDI-based Viso has the highest performance.


Des-aspartate-angiotensin I exerts antiviral effects and attenuates ICAM-1 formation in rhinovirus-infected epithelial cells.
The high frequency of rhinovirus (RV) infection and the lack of an effective treatment, underline the importance of research on novel anti-rhinoviral agents. The present study investigated the effects of des-aspartate-angiotensin I (DAA-I) on the survival of RV14-infected H1HeLa cells; and the early inflammatory processes in RV14-infected A549 lung epithelial cells. The study rationale was based on earlier findings showing that DAA-I is an effective anti-inflammatory agent, and that symptoms and severity of rhinoviral infection are related to the underling inflammation. RV14 concentration dependently caused the death of H1HeLa cells and DAA-I, at concentrations of 10⁻¹⁰ to 10⁻¹² M, attenuated the lethal action of RV14 indicating that that DAA-I exerts antiviral action. Unlike its action on H1HeLa cells, RV14 did not cause apparent cytopathic effect on A549 cells, and these cells were used to study the antiviral action of DAA-I. RV14 induced overexpression of ICAM-1, E-selectin and overproduction of superoxide in A549 cells, and DAA-I attenuated the three increases to basal level at concentrations of 10⁻¹⁰ to 10⁻¹² M. Losartan, an angiotensin AT₁ receptor antagonist, blocked the inhibitory action of DAA-I on superoxide overproduction indicating that the AT₁ receptor mediates the action of DAA-I. The present data represent a novel demonstration of the antiviral action of an angiotensin peptide, and a possible involvement of the renin angiotensin system in viral infection. Indeed the angiotensin AT₁ receptor has been reported to be obligatory for the development of virus-induced myocardial injury through the proinflammatory action of angiotensin II via the NF-κB/cytokine pathway.


Social comparison effects on brand addiction: A mediating role of materialism.
This research explores the role of materialism, and social comparison to brand addiction in relation to compulsive buying. A structural equation modeling was used to analyze data through partial least squares by collecting online data in Vietnam. The research findings explain social comparison is an antecedent leading to addictive behavior. Materialism mediates and increases the addictive behavior when consumers are significantly impacted by social comparison. In addition, brand addiction leads to word-of-mouth and willingness to pay premium price when consumers are set under social comparison and materialistic tendency. The managerial and theoretical application is also provided in this research.


Vascular endothelial growth factor gene-460 C/T polymorphism is a biomarker for prostate cancer.
To use the Bst U I polymorphism as a genetic marker in the search for the association between patients with prostate cancer and normal control subjects. The formation or progression of prostate cancer is presumed to be associated with a polymorphism of the vascular endothelial growth factor (VEGF) gene. The most frequently seen polymorphism is Bst U I (C to T) located at the -460th nucleotide upstream of the VEGF gene. A normal control group of 119 healthy people and 96 patients with prostate cancer were examined. The polymorphism was seen after polymerase chain reaction-based restriction analysis. The analysis revealed significant differences between normal individuals and patients with cancer (P <0.001). Also, the distribution of the "TT" homozygote in the patient group was greater than that in the control group. The odds ratio per copy of the "T" allele was 2.3 (95% confidence interval 1.4 to 3.8) and was 2.2 (95% CI 1.3 to 3.8) when adjusted for age. No statistically significant differences in clinical stage or grade were found. We also categorized the 54 patients who received hormonal therapy into response and nonresponse groups, but no statistically significant differences between these two groups were revealed (P = 0.110, Fisher's exact test). The Bst U I polymorphism of the VEGF gene is a suitable genetic marker of prostate cancer but cannot be used in the prediction of the outcome of patients who have received hormonal therapy.


Full six-dimensional nonadiabatic quantum dynamics calculation for the energy pooling reaction O(2)(a (1)Delta)+O(2)(a (1)Delta)-->O(2)(b (1)Sigma)+O(2)(X (3)Sigma).
Six new potential energy surfaces of four singlet states and two triplet states for the title oxygen molecule reaction along with the spin-orbit coupling among them have been constructed from the complete active space second-order perturbation theory with a 6-311+G(d) basis. Accurate integral cross sections are calculated with a full six-dimensional nonadiabatic time-dependent quantum wave packet method. The thermal rate constant based on the integral cross sections agrees well with the result of the experimental measurements, and the intersystem crossing effects are also discussed in this electronic energy-transfer process.


Intraoperative changes in coronary resistance during aortic valve replacement.
Coronary vascular resistance was investigated in 10 patients undergoing aortic valve replacement using continuous constant-pressure coronary perfusion at 32 degrees C. After coronary flow was initiated, resistance was low but increased steadily until it reached a certain resting level. The plateau was attained faster after a short period of anoxia than after a longer period. The initial postischemic resistance was dependent on the duration preceding anoxia, being of the same magnitude after short and moderate periods of anoxia but significantly higher after a long period. This resistance difference between the groups lasted for the whole perfusion. The total coronary resistance and flow reached a plateau in 30 minutes, while resistance increased threefold but flow decreased to half of the initial postanoxia flow. Our results indicate the importance of initiating coronary perfusion soon after aortic cross-clamping to avoid increase in the initial vascular resistance and subsequent inadequate myocardial flow.


Face processing in adolescents with autistic disorder: the inversion and composite effects.
Two experiments with upright and inverted face and object images were carried out to investigate whether face processing in autism is more feature-based than in individuals with typical development. Participants were 17 high-ability adolescents with autistic disorder (16-24 years), 24 typically developing children (9-10 years) and 16 adults (18-33 years). In Experiment 1, a normal inversion effect was found for the adolescents with autism in a standard face recognition paradigm with reduced memory demands, except for a subgroup with low social intelligence who were not better in recognizing upright relative to inverted photographs of faces. In Experiment 2, the group with autism did not show the composite effect like the adult group did: they recognized face halves as well in aligned composite faces as in non-aligned composite faces. The results on the inversion task suggest that most adolescents with autism form a normal configuration-based face representation, but the absence of the composite effect indicates that they are less prone to use the contextual information of the face in a visual-search task.


[Scapholunate synostoses within the framework of congenital carpal synostoses].
Modality of appearance in fetal life. Racial (certain) and congenital (probable) predisposing factors. X-ray discovery of radioscapholunate fusion after minor sprain of the wrist in a young 22 year old woman otherwise without past history. Functional study of the wrist. Analysis of six similar observations reported to date.


Compartments of roots and mature leaves are key hubs in the connectivity of tea-plant mycobiomes and are influenced by environmental factors and host age.
Understanding the tripartite consortium of crop, mycobiome, and environment is necessary to advance smart farming. Owing to their life cycle of hundreds of years, tea plants are excellent models for studying these entwined relationships; however, observations on this globally important cash crop with numerous health benefits are still rudimentary. Here, the fungal taxa along the soil-tea plant continuum in tea gardens of different ages in famous high-quality tea-growing regions in China were characterized using DNA metabarcoding. Using machine learning, we dissected the spatiotemporal distribution, co-occurrence patterns, assembly, and their associations in different compartments of tea-plant mycobiomes, and further explored how these potential interactions were driven by environmental factors and tree age, and how they influenced the market prices of tea. The results revealed that Compartment niche differentiation was the key driving force behind variation in the tea-plant mycobiome. The mycobiome of roots had the highest specific proportion and convergence and almost did not overlap with the soil. The enrichment ratio of developing leaves to root mycobiome increased with increasing tree age, while mature leaves showed the highest value in the Laobanzhang (LBZ) tea garden with top market prices and displayed the strongest depletion effect on mycobiome association along the soil-tea plant continuum. The balance between determinism and stochasticity in the assembly process was co-driven by compartment niches and life cycle variation. Fungal guild analysis showed that altitude indirectly affected market prices of tea by mediating the abundance of the plant pathogen. The relative importance of plant pathogen and ectomycorrhizae could be used to assess the age of tea. Biomarkers were mainly distributed in soil compartments, and Clavulinopsis miyabeana, Mortierella longata, and Saitozyma sp. may affect the spatiotemporal dynamics of tea-plant mycobiomes and their ecosystem services. Soil properties (mainly total potassium) and tree age indirectly affected the developing leaves via positively influencing the mycobiome of mature leaves. In contrast, the climate directly and significantly drove the mycobiome composition of the developing leaves. Moreover, the proportion of negative correlations in the co-occurrence network positively regulated tea-plant mycobiome assembly, which significantly affected the market prices of tea in the structural equation model with network complexity as hub. These findings indicate that mycobiome signatures play pivotal roles in the adaptive evolution and fungal disease control of tea plants and can help develop better agricultural practices that focus on both plant health and financial profits, and provide a new strategy for assessing tea quality grade and age.


ZFPL1, a novel ring finger protein required for cis-Golgi integrity and efficient ER-to-Golgi transport.
The Golgi apparatus occupies a central position within the secretory pathway, but the molecular mechanisms responsible for its assembly and organization remain poorly understood. We report here the identification of zinc finger protein-like 1 (ZFPL1) as a novel structural component of the Golgi apparatus. ZFPL1 is a conserved and widely expressed integral membrane protein with two predicted zinc fingers at the N-terminus, the second of which is a likely ring domain. ZFPL1 directly interacts with the cis-Golgi matrix protein GM130. Depletion of ZFPL1 results in the accumulation of cis-Golgi matrix proteins in the intermediate compartment (IC) and the tubulation of cis-Golgi and IC membranes. Loss of ZFPL1 function also impairs cis-Golgi assembly following brefeldin A washout and slows the rate of cargo trafficking into the Golgi apparatus. Effects upon Golgi matrix protein localization and cis-Golgi structure can be rescued by wild-type ZFPL1 but not mutants defective in GM130 binding. Together, these data suggest that ZFPL1 has an important function in maintaining the integrity of the cis-Golgi and that it does so through interactions with GM130.


Synthesis of 3-(2, 8, 9-trioxa-5-aza-1-germatricyclo [22.214.171.124] undecane-1-yl)-3-(4-hydroxyl-3-methoxyphenyl)-propionic acid and its inhibitory effect on the cervical tumor U14 in vitro and in vivo.
In this study, the novel germatrane compound, 3-(2, 8, 9-trioxa-5-aza-1- germatricyclo [126.96.36.199] undecane-1-yl)-3-(4-hydroxy-3- methoxyphenyl)-propionic acid (1), has been synthesized and its activities against cervical tumor U14 were evaluated in vitro and in vivo. The results have demonstrated that the compound posed significant inhibition on U14 tumor with IC(50) values of 48.57 mg/L in cell-based assay and tumor inhibitory rates of 38.50%, 47.17% and 64.02% (from low dose to high dose) in animal experiment.


Structural characterization of sulfated glycosaminoglycans by fast atom bombardment mass spectrometry: application to heparin fragments prepared by chemical synthesis.
We report herein the results of f.a.b.-m.s. experiments conducted on synthetic fragments of glycosaminoglycans, one of them representing the pentasaccharidic sequence present in heparin and responsible for the binding to antithrombin III, and the others being related to this sequence. The results indicate that f.a.b.-m.s. can be very useful for the structural analysis of sulfated glycosaminoglycans. The relatively small amounts of sample required enable molecular characterization at physiologically significant levels. In contrast to the chondroitin sulfates, the heparin saccharides analyzed and reported here do not provide sequence information. The data indicate that glycosidic rupture is not a process competing with the much more facile loss of N-sulfite residues. Dominating the spectra are a series of molecular-weight-related ions (distributed to indicate the associated countercation composition), and fragments related directly to sulfite elimination. This f.a.b.-induced, facile loss of sulfite may impose limitations in molecular-weight analysis for the larger oligomers.


Comparison of total urinary oestrogens and total serum oestriol in pregnancy.
The total oestrogens detected by fluorescence in 24-h urine and the concentration of total oestriol detected in serum by radioimmunoassay were estimated in 51 women during the second half of pregnancy. The statistical analysis showed a linear regression between urinary excretion and serum concentration according to the equation y = -2.89 + 2.82x (y = serum oestriol). The correlation coefficient over all pairs of estimations (N =567) was r = 0.69, which is very highly significant (P less than 0.0001). The analysis of the individual pregnancies showed that the linear correlation coefficient was significant (P less than 0.05) in 35 cases, poorly significant (0.05 less than P less than 0.1) in 3 cases and not significant (P less than 0.1) in 5 cases. The correlation could not be calculated in 8 cases because the number of estimations was too small. These values were compared empirically (normal/pathological). There was agreement in 6 cases and no agreement in 2 cases. The results show on the one hand that the radioimmunological estimation of total oestriol in serum can be used in the same way as urinary excretion of oestrogens for monitoring the feto-placental unit. On the other hand, the study confirms that a "simple" fluorimetric Kober-Ittrich method can give at least the same clinical information as a radioimmunoassay of relatively high cost. It may be concluded indirectly from the results that a considerable diurnal rhythm or substantial day-to-day fluctuation in the production of oestriol are unlikely.


Babesia bovis: computer simulation of the relationship between the tick vector, parasite, and bovine host.
Components contributing to the survival of Babesia bovis in its tick vector (Boophilus microplus) and bovine host were identified and their relationship simulated with an interactive BASIC computer program. Estimates for major independent variables (host-finding success, feeding success, filial infection rate, recovery rate) were derived from published laboratory and field data. Values for dependent variables (tick burden, inoculation rate, tick and bovine infection rates) were calculated during successive tick generations until equilibrium conditions were reached. The simulation was used to predict the effects of alternate disease control strategies. Babesiosis outbreaks were associated with simulated daily infestations of approximately two to eight engorged ticks. Below this range, B. bovis parasites disappeared, while above it all cattle were infected during the period of calfhood resistance (through 9 months of age). The babesial inoculation rate was most unstable over the above range due to instability in tick populations and tick infection rates. The risk of babesiosis outbreaks among older, less resistant cattle was also greatest over this range. The optimum daily infestation was eight to nine engorged ticks. This level would maintain herd immunity to babesiosis without causing significant physiologic stress to the bovine host. The difficulty in maintaining ecological and immunological stability at low infestation rates discourages "strategic dipping" as a means of maintaining herd immunity to babesiosis. Introduction of tick-resistant cattle provided a more effective means of reducing the risk of babesiosis outbreaks. The economic implications of computer-simulated babesiosis control alternatives should be analyzed. The validity of simulation parameters should be confirmed by field studies on the relationship between tick burdens and the babesial inoculation rate. These studies would be greatly facilitated by development of an assay system for the detection of babesiae in field-collected ticks.


L-Leucinamide hydrogensquarate: spectroscopic and structural elucidation.
The hydrogensquarate [LeuNH(2)] (HSq) of L-leucinamide has been synthesized and its structure has been determined by single crystal X-ray diffraction. A three dimensional network is formed by hydrogen bonds with participation of the O=C-NH(2) function, the hydrogensquarate ion and the N(+)H(3) group [NH(2)...O=C((Sq)) (2.840 and 2.749 A), ((Sq))OH...O=C(NH(2)) (2.618 A), NH(3) (+)...O=C((Sq)) (3.246, 2.804 and 2.823 A)], respectively. A theoretical approximation of the electronic structure was carried out by means of ab initio UMP2 and MP2 level of theory at the 6-311++G** basis set. The IR-spectroscopic assignment in the solid-phase was obtained by linear-polarized IR-spectroscopy of oriented samples as colloid suspensions in a nematic host and application of the reducing-difference procedure for the interpretation of polarized IR-spectra.


An efficient protocol for the solid-phase synthesis of glycopeptides under microwave irradiation.
A standardized and smooth protocol for solid-phase glycopeptides synthesis under microwave irradiation was developed. Double activation system was proved to allow for highly efficient coupling of Tn-Ser/Thr and bulky core 2-Ser/Thr derivatives. Versatility and robustness of the present strategy was demonstrated by constructing a Mucine-1 (MUC1) fragment and glycosylated fragments of tau protein. The success of this approach relies on the combination of microwave energy, a resin consisting totally of polyethylene glycol, a low excess of sugar amino acid and the "double activation" method.


Oligonucleotide-based therapies for cystic fibrosis.
In the clinically successful era of CFTR modulators and Theratyping, 10-20% of individuals with cystic fibrosis (CF) may develop disease due to CFTR mutations that remain undruggable. These individuals produce low levels of CFTR mRNA and/or not enough protein to be rescued with modulator drugs. Alternative therapeutic approaches to correct the CFTR defect at the mRNA level using nucleic acid technologies are currently feasible; e.g., oligonucleotides platforms, which are being rapidly developed to correct genetic disorders. Drug-like properties, great specificity, and predictable off-target effects by design make oligonucleotides a valuable approach with fewer clinical and ethical challenges than genomic editing strategies. Together with personalized and precision medicine approaches, oligonucleotides are ideal therapeutics to target CF-causing mutations that affect only a few individuals resilient to modulator therapies.


The adaptive ARMA analysis of EMG signals.
In this study, Adaptive auto regressive-moving average (A-ARMA) analysis of EMG signals recorded on the ulnar nerve region of the right hand in resting position was performed. A-ARMA method, especially in the calculation of the spectrums of stationary signals, is used for frequency analysis of signals, which give frequency response as sharp peaks and valleys. In this study, as the result of A-ARMA method analysis of EMG signals frequency-time domain, frequency spectrum curves (histogram curves) were obtained. As the images belonging to these histograms were evaluated, fibrillation potential widths of the muscle fibers of the ulnar nerve region of the people (material of the study) were examined. According to the degeneration degrees of the motor nerves, 22 people had myopathy, 43 had neuropathy, and 28 were normal.


Activation of Mg(2+)-dependent DNAzymes based on AP site-containing triplex for specific melamine recognition.
Based on melamine binding-triggered triplex formation and subsequent activation of Mg(2+)-dependent DNAzymes, a novel strategy for DNAzyme regulation was proposed and developed for melamine recognition.


Totally implantable venous access device placement by interventional radiologists: are prophylactic antibiotics necessary?
To determine the rate of early infection for totally implantable venous access devices (TIVADs) placed without antibiotic prophylaxis. A list of patients who underwent TIVAD placement in 2009 was obtained from the patient archiving and communication system (PACS). This list was cross-referenced to all patients who underwent TIVAD removal from January 1, 2009, through January 30, 2010, to identify TIVADs that were removed within 30 days of placement. Retrospective chart review was performed to record patient demographics, including age, sex, cancer diagnosis, and indication for removal. Concurrent antibiotic therapy, chemotherapy, and laboratory data before and within 30 days of placement were recorded. Central line-associated bloodstream infections (CLABSIs) were identified using U.S. Centers for Disease Control and Prevention (CDC) criteria. There were 1,183 ports placed and 13 removed. CLABSIs occurred in seven (0.6%) patients within 30 days of placement. At the time of TIVAD placement, 81 (7%) patients were receiving antibiotics incidental to the procedure. One patient who received an antibiotic the day of implantation developed a CLABSI. Chemotherapy was administered to 148 (13%) patients on the day of placement. The rate of early infection without antibiotic prophylaxis before TIVAD placement in the interventional radiology suite is < 1%. Based on these data, use of prophylactic antibiotics for TIVAD placement is not recommended.


Novel induction therapy transoral surgery treatment paradigm with risk-adapted adjuvant therapy for squamous cell carcinoma of the head and neck - Mature clinical and functional outcomes.
Induction chemotherapy in head and neck squamous cell carcinoma (HNSCCA) has principally been studied prior to radiation therapy. We evaluated pre-operative induction therapy followed by surgery followed by risk-adapted adjuvant therapy. This report details the mature 5-year survival statistics, clinical and functional outcomes. An IRB-approved single institution prospective phase II clinical trial from October 2012 to November 2016 was conducted for patients with transorally-resectable American Joint Committee on Cancer 7th ed. stage III/IV HNSCCA. Patients were treated once weekly for six weeks with a multi-drug induction regimen of carboplatin, paclitaxel and daily lapatinib followed by transoral surgery and neck dissection. Patients were then stratified based on pathologic response to either observation or adjuvant therapy. Survival statistics and functional patient outcomes were analyzed. Specifically, peri-operative outcomes were analyzed and compared to a matched surgical cohort. 38/40 enrolled patients completed trial therapy. Median hospital stay was 3 days with 9/38 patients receiving a PEG (median 46 days). Median NPO status was 1 day, with a median return to a regular diet in 16 days. Mean patient weight was well preserved from pretreatment to 1 year after surgery (85.1 kg (95% CI 79.6-90.7) vs 83.1 kg (95% CI 77.7-88.6 kg) respectively). Of the 38 patients who completed trial therapy; DSS, PFS and OS were 100%, 97% and 97% respectively with median follow up of 4.9 years (3.33-7.25). Transoral surgery was feasible following this novel induction regimen with excellent peri-operative, functional and longterm survival outcomes.


Mast cell population density, blood vessel density and histamine content in normal human skin.
Mast cell population density was determined in normal skin from two regions of the arm of several healthy men and compared with blood vessel density and histamine concentration in the same sites. Mast cell and blood vessel counts were made in 1--1.5 micrometer thick plastic sections, by light microscopy and tissue-histamine concentrations were determined by automated fluorimetric analysis. Statistically significant correlations were found between mast cell counts, blood vessel counts and histamine content in skin from the upper arm but no similar correlations were obtained in the forearm. Anatomical differences between the two sites may have been the cause of this discrepancy. Wide variations in mast cell counts and blood vessel density were found in different sections from the same biopsy samples which confirms the notion that dermal mast cells are unevenly distributed. Analysis of variance of the mast cell counts showed that the variance between sections from different blocks from the same biopsy samples was greater than the variance between adjacent biopsies. There was also a marked variation in the histamine content between biopsy samples from sites only 2 cm apart in the same subject.


Structural perspective on the formation of ribonucleoprotein complex in negative-sense single-stranded RNA viruses.
Negative-sense single-stranded RNA viruses (NSRVs) possess a ribonucleoprotein (RNP) complex composed of viral polymerase and genomic RNA surrounded by viral nucleoprotein. The RNP facilitates virus replication, transcription, and assembly. To date, a large body of structural work, through crystallography and electron microscopy (EM) analysis, has been performed to aid understanding the molecular mechanism of RNP formation in NSRVs, and provides great potential for the discovery of antiviral agents targeting viral RNP formation.


Behavioral effects of cyclic changes in serotonin during the human menstrual cycle.
Many cyclic changes during the menstrual cycle (temperature, depression, motor activity, pain sensitivity, etc.) are closely paralleled by changes in brain serotonin level. These changes, in turn, are associated with peripheral hormone levels which are comparatively regular and easily measured. Their measurement may be useful both in predicting behavior and in accounting for atypical menstrual-related behavior.


Lack of anodic capacitance causes power overshoot in microbial fuel cells.
Power overshoot commonly makes the performance evaluation of microbial fuel cells (MFCs) inaccurate. Here, three types of carbon with different capacitance (ultracapacitor activated carbon (UAC), plain activated carbon (PAC) and carbon black (CB)) rolled on stainless steel mesh (SSM) as anodes to investigate the relationship between overshoot and anodic capacitance. It was not observed in all cycles of UAC-MFCs (from Cycle 2 to 4) due to the largest abiotic capacitance (Cm(abiotic)) of 2.1F/cm(2), while this phenomenon was eliminated in PAC-MFCs (Cm(abiotic)=1.6 F/cm(2)) from Cycle 3 and in CB-MFCs (Cm(abiotic)=0.5F/cm(2)) from Cycle 4, indicated that the Cm(abiotic) of the anode stored charges and functioned as electron shuttle to overcome the power overshoot. With bacterial colonization, the transient charge storage in biofilm resulted in a 0.1-0.4F/cm(2) increase in total capacitance for anodes, which was the possible reason for the elimination of power overshoot in PAC/CB-MFCs after multi cycle acclimation.


Comparison of Completion Thyroidectomy and Primary Total Surgery for Differentiated Thyroid Cancer: A Meta-Analysis.
The aim of this study was to compare the complication rates between completion thyroidectomy and primary total thyroidectomy for differentiated thyroid cancer (DTC). PubMed, the Web of Knowledge, and the China Journal Net were searched for studies concerning the treatment of DTC published in 1990-2014. A meta-analysis was performed to compare the effects of different treatments. 7 studies with a total of 1,208 patients were included. There were no statistically significant differences regarding the presence of temporary recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, temporary hypocalcemia, permanent hypocalcemia, hematoma, and wound infection. Completion thyroidectomy can be performed with acceptable morbidity in select cases of DTC who could not be properly diagnosed perioperatively or who recurred after less than total thyroidectomy.


Effect of aerobic exercise alone or combined with Mediterranean diet on dry eye in obese hypertensive elderly.
Lifestyle modification is a newly recommended complementary treatment for dry eye (DE) disorder. To investigate the effect of a 6-month high-intensity interval aerobic exercise (HIIAE) (conducted 30 min, 3 times weekly) alone or combined with a caloric-restriction approach, the Mediterranean diet (MD), on DE parameters in obese hypertensive elderly. This is a randomized controlled trial included sixty obese hypertensive elderly with DE based on university-based hospital recruitment. Elderly were randomly assigned to the experimental group (n = 30 elderly received HIIAE plus MD) and control group (n = 30 elderly received only HIIAE). Besides anthropometry (abdominal circumference, body weight, and body mass index) and blood pressure (measured in systole and diastole), DE parameters (tear film break-up time, DE scoring system, ocular surface disability index questionnaire, Schirmer's test, and Oxford grading system) were evaluated. Significant improvements in anthropometry, blood pressure, and DE parameters were higher in the experimental group than in the control group. Aging-related DE symptoms and signs can be prevented and/or treated with HIIAE alone or combined with MD in obese hypertensive elderly with DE disorder.


A new survival status prediction system for severe trauma patients based on a multiple classifier system.
Severe trauma patients are those who have several injuries implying a death risk. Prediction systems consider the severity of these injuries to predict whether the patients are likely to survive or not. These systems allow one to objectively compare the quality of the emergency services of trauma centres across different hospitals. However, even the most accurate existing prediction systems are based on the usage of a single model. The aim of this paper is to combine several models to make the prediction, since this methodology usually improves the performance of single models. The two currently used prediction systems by the Hospital of Navarre, which are based on logistic regression models, besides the C4.5 decision tree are combined to conform our proposed multiple classifier system. The quality of the method is tested using the major trauma registry of Navarre, which stores information of 462 trauma patients. A 10x10-fold cross-validation model is applied using as performance measures the specificity, sensitivity and the geometric mean between the two former ones. The results are supported by the usage of the Mann-Whitney's U statistical test. The proposed method provides 0.8908, 0.6703 and 0.7661 for sensitivity, specificity and geometric mean, respectively. It slightly decreases the sensitivity of the currently used systems but it notably increases the specificity, which implies a large enhancement on the geometric mean. The same behaviour is found when it is compared versus four classical ensemble approaches and the random forest. The statistical analysis supports the quality of our proposal, since the obtained p-values are less than 0.01 in all the cases. The obtained results show that the multiple classifier systems is the best choice among the considered methods to obtain a trade-off between sensitivity and specificity.


Selection of an M184V mutation in the cerebrospinal fluid of a treatment-naive HIV-infected individual starting darunavir-based therapy.
Here, we describe a newly diagnosed HIV-1-infected patient, in whom shortly after the initiation of a darunavir-based regimen, the HIV-1 virus exclusively mutated in the cerebrospinal fluid (CSF), leading to an increase in CSF HIV-1 RNA load and neurological complaints.


Upper Airway Length is Predictive of Obstructive Sleep Apnea in Syndromic Craniosynostosis.
Midfacial hypoplasia is a characteristic feature of the syndromic craniosynostoses and predisposes these patients to developing obstructive sleep apnea (OSA). The purpose of this study was to identify anatomic factors associated with airway obstruction in patients with syndromic craniosynostoses. This was a retrospective cohort study. The authors enrolled a study sample composed of patients with syndromic craniosynostoses. The predictor variables were age, gender, body mass index (BMI), syndromic diagnosis, and parameters of upper airway length and size measured on lateral cephalograms. To control for age, upper airway length was corrected for differences in patient height. The outcome variable was OSA status (present or absent). Descriptive, bivariate, and regression statistics were computed. For all analyses, a P value less than or equal to .05 was considered statistically significant. The sample was composed of 50 patients with a mean age of 10.3 ± 0.6 years, 50% were boys, and 24 (48%) had OSA. Patients with and without OSA did not differ statistically in age, gender, BMI, or syndromic diagnosis. Those with OSA had increased upper airway length (P = .016), decreased posterior airway space (P = .001), and more severe midfacial retrusion (P = .022) compared to patients without OSA. After adjusting for covariates, the odds ratio for OSA was 32.9 in patients with an upper airway longer than 45.3 mm per meter of height (P = .018), and for every 1-mm decrease in posterior airway space, the risk of OSA increased by 30% (P = .022). Patients with syndromic craniosynostosis and OSA have a longer upper airway, smaller posterior airway space, and more severe midfacial retrusion than those without OSA.


Interaction of secretin5-27 and its analogues with hormone receptors on pancreatic acini.
The C-terminal tricosapeptide of secretin (S5-27) and two analogues, one with asparagine replacing aspartic acid in position 15 (15-Asn-S5--27) and one with lysine replacing aspartic acid in position 15 (15-Lys-S5-27) were tested for their abilities to interact with hormone receptors on pancreatic acinar cells. In interacting with the receptors which prefer vasoactive intestinal peptide (vasoactive intestinal peptide-preferring receptors), the apparent affinity of 15-Asn S5-27 was equal to that of 15-Lys-S5-27 and was greater than that of S5-27. In interacting with secretin-preferring receptors, the apparent affinity of 15-Asn-S5--27 was equal to that of S5-27 and was greater than that of 15-Lys-S5-27. In interacting with the secretin-preferring receptors each of the secretin fragments was approximately 2% as effective as secretin in causing an increase in cellular cyclic AMP. None of these fragments was able to cause a detectable increase in cyclic AMP mediated by the vasoactive intestinal peptide-preferring receptors. The dose vs. response curves for the action of secretin and vasoactive intestinal peptide on cellular cyclic AMP and on amylase secretion as well as the pattern of effects of secretin fragments on these actions indicated that the increase in amylase secretion caused by vasoactive intestinal peptide and secretin is mediated exclusively by the vasoactive intestinal peptide-preferring receptors. Furthermore, occupation of approximately 50% of the vasoactive intestinal peptide-preferring receptors is sufficient to cause maximal stimulation of amylase secretion.


Measure of Caregiver Attention-Deficit/Hyperactivity Disorder Knowledge Is Responsive to Decision Aid on Treatment for Attention-Deficit/Hyperactivity Disorder.
Adapt and test a measure of knowledge for caregivers of children with attention-deficit/hyperactivity disorder (ADHD) and evaluate the impact of the information component of a decision aid (DA) on participant knowledge. A set of seven knowledge items were created based on prior knowledge measures and clinical guidelines. As part of a larger cross-sectional survey study of caregivers of children diagnosed with ADHD, caregivers were randomized to one of two arms: 1) a DA arm, where participants reviewed the information component of the Cincinnati Children's Hospital's DA, and 2) a control arm, where participants were not shown a DA. All participants completed the seven knowledge items. Knowledge items were assessed for difficulty, quality of distractors, acceptability, and redundancy. Total knowledge scores (0-100) for the DA and control arm were compared. Caregivers were assigned to the DA arm (n = 243) or the control arm (n = 260). All 7 knowledge items were retained as no items were too difficult or too easy, all response options were used, there were little missing data, and no items were redundant. The overall knowledge score was normally distributed, and almost covered the full range of scores (5-100). Those who received the DA component had higher knowledge scores (M=68, SD=23) than those who did not receive the DA component (M=60, SD=19, P < .01, d=0.4). The Caregiver ADHD Knowledge (CAKe) measure was acceptable and demonstrated construct validity as those who were assigned to review the DA component demonstrated greater knowledge than those who were not assigned to review the DA component.


Lipoplastic lymphadenopathy presenting as an ovarian mass: a case report.
Lipoplastic lymphadenopathy is a pathological condition wherein accumulations of intranodal fat result in lymph node enlargement and may mimic abdominal, pelvic, and retroperitoneal neoplasms, particularly lymphomas. The pathology appears to be different from lipomatosis in that benign, mature adipocytes and lipids are located within lymph nodes, rather than deposited in body cavities. The case of a 49-year-old woman presenting as an ovarian neoplasm is presented as an example of the pathology and its ability to masquerade as other neoplasms. The etiology of lipoplastic lymphadenopathy is unclear although associated causes are suggested. The difficulties of radiological examination of this case and others makes open lymph node biopsy important for the final diagnosis.


Serial single-cell genomics reveals convergent subclonal evolution of resistance as early-stage breast cancer patients progress on endocrine plus CDK4/6 therapy.
Combining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for metastatic estrogen receptor positive (ER+) breast cancer patients but its value in earlier stage patients is unclear. We examined evolutionary trajectories of early-stage breast cancer tumors, using single cell RNA sequencing (scRNAseq) of serial biopsies from the FELINE clinical trial (#NCT02712723) of endocrine therapy (letrozole) alone or combined with the CDK inhibitor ribociclib. Despite differences in subclonal diversity evolution across patients and treatments, common resistance phenotypes emerged. Resistant tumors treated with combination therapy showed accelerated loss of estrogen signaling with convergent up-regulation of JNK signaling through growth factor receptors. In contrast, cancer cells maintaining estrogen signaling during mono- or combination therapy showed potentiation of CDK4/6 activation and ERK upregulation through ERBB4 signaling. These results indicate that combination therapy in early-stage ER+ breast cancer leads to emergence of resistance through a shift from estrogen to alternative growth signal-mediated proliferation.


A novel midstream urine-collection device reduces contamination rates in urine cultures amongst women.
To evaluate a novel urine-collection device (UCD) that automatically collects a midstream urine (MSU) sample, and compare contamination rates to those of the conventional MSU sampling method, as the contamination of urine samples for microbiological analysis in women leads to diagnostic ambiguity and unnecessary costs, and may result in part from an incorrect collection procedure. In all, 2823 women from four centres, most from antenatal clinics, were randomized to two urine-collection methods: conventional MSU collection and collection with a novel MSU UCD (the Whiz, JBOL Ltd, Oxford, UK). Semi-quantitative growth and user acceptability were compared between the collection methods. MSU samples collected with the UCD had significantly fewer mixed growth samples (9% vs 14%, P = 0.001; 36% relative reduction), significantly fewer heavy mixed growth samples (1.2% vs 3.0%, P = 0.004; 60% relative reduction) and required significantly fewer re-tests (11% vs 16%, P = 0.002; 31% relative reduction). There were more samples with clinically insignificant growth than the conventional MSU group (86% vs 82%, P = 0.005). Those using the UCD preferred it to the conventional method (67.5%) and experienced significantly less spillage during sample collection (27% vs 46%, P = 0.001; relative reduction 41%). The UCD reduced contamination rates in urine samples and improved the predictive value of the urine culture in a manner acceptable to patients and staff.


Unilateral ovarian metastasis from renal clear cell carcinoma.
Ovarian metastases of renal origin are rarely reported in the literature and pose a diagnostic problem because they are usually diagnosed at a distance from the primary cancer. We report a case of unilateral ovarian metastasis from clear cell renal cell carcinoma fifteen years after nephrectomy in a fifty-six-year-old patient who underwent surgery for an abdominopelvic mass. The diagnosis of ovarian metastases can be made at the same time as the diagnosis of the primary cancer or at a distance from it, with an interval ranging from a few months to years later. In the case of our patient, the ovarian metastasis was diagnosed fifteen years after the nephrectomy. Ovarian metastases are exceptional secondary localizations of renal cancer, they can be unilateral or bilateral, and are usually discovered several years after the renal tumor.


Continuous humidification enhances postoperative recovery in laryngeal cancer patients undergoing tracheotomy.
To investigate the effects of perioperative continuous humidification on patients with laryngeal cancer undergoing tracheotomy. Eighty patients with laryngeal cancer underwent tracheotomy in our hospital were selected as the subjects and divided into the observation group and the control group according to random table method. Patients in the control group were given routine tracheotomy care, including regular open endotracheal suction, tracheotomy nursing, oral care, dietary intervention, etc., while those in the observation group were given continuous airway humidification on the basis of the control group. The differences in sputum pH, viscosity, comfort, cough frequency, and respiratory ventilation were compared between the two groups at three postoperative time points. The incidence of complications such as pulmonary infection, bloody sputum and sputum crust, and the improvement of clinical symptoms were compared between the two groups. The sputum pH of patients in the observation group was higher than that in the control group at the 4th and 7th postoperative days (P<0.001). The observation group showed significantly lower percentage of grade 3 viscous sputum and higher comfort scores than the control group at the 7th postoperative day (P=0.020, P<0.001). The observation group showed lower cough frequency and higher airway patency than the control group at the 4th and 7th postoperative days (P<0.001, P<0.001, P<0.001, P=0.007). Perioperative continuous airway humidification in patients with laryngeal cancer undergoing tracheotomy could reduce sputum consistency and cough frequency, improve comfort and respiratory patency of patients, and has positive significance in accelerating their postoperative rehabilitation.


Multigene Engineering in Rice Using High-Capacity Agrobacterium tumefaciens BIBAC Vectors.
The high-capacity binary bacterial artificial chromosome (BIBAC) vector system permits the insertion of large fragments of DNA, up to 150 kb, into plants via Agrobacterium-mediated transformation. Here, we describe an optimized protocol for transformation of japonica rice (Oryza sativa L.) using this system. Calli derived from mature embryos are transformed using Agrobacterium strain LBA4404 that carries the BIBAC vector and the super-virulent helper plasmid pCH32. Transformed calli are then regenerated using optimized media and tested for transgene integration by PCR, GUS assay, and Southern blot analyses.


Community acquired fungemia caused by Candida pulcherrima: diagnostic contribution of MALDI-TOF mass spectrometry.
Community-onset candidemia constitute a distinct clinical entity the incidence of which is increasing. Contribution of non-albicans Candida species is rising. We describe here the first reported case of community acquired fungemia due to Candida pulcherrima. Identification to the species level was performed by MALDI-TOF mass spectrometry. Treatment with fluconazole was successful. This case confirms the pathogenic role of C. pulcherrima and the contribution of MALDI-TOF mass spectrometry for identification of rare Candida species.


Manganese Oxide Nanoparticles Inhibit the Growth of Subcutaneous U-87MG Glioblastoma Xenografts in Immunodeficient Mouse.
Our previous study demonstrated that manganese oxide nanoparticles (MnO NP) selectively destroyed U-87MG and U251 human glioblastoma cells in vitro. MnO NP were synthesized and studied by electron microscopy. Their antitumor properties were studied in vivo on the model of immunodeficient SCID mice with subcutaneous xenografts of U-87MG human glioblastoma. The mice were injected subcutaneously with MnO NP in doses of 0.96 and 1.92 mg/kg (calculated for Mn) 3 days a week over 3 weeks. In was shown that MnO NP in these doses significantly suppressed the growth of U-87MG glioblastoma xenografts: on day 21 from the start of the treatment, the tumor growth inhibition index was 61.1 and 99.22%, respectively. These results indicate the necessity of the further studies of MnO NP as a potential oncolytic agent for the therapy of human glioblastomas.


CAMP chemotherapy for metastatic non-oat cell bronchogenic carcinoma. A 7-year experience (1975-1981) with 160 patients.
Between January 1975 and December 1981, 160 patients with metastatic non-oat cell bronchogenic carcinoma (MNOBC) were treated with cyclophosphamide, doxorubicin, methotrexate, and procarbazine (CAMP), or with a CAMP-like regimen. Forty-two (26%) of these patients demonstrated an objective response to the chemotherapy with a median survival of 61 weeks. Thirty-nine (24%) patients had stable disease (SD) with a median survival of 45 weeks. Seventy-nine patients (49.4%) were nonresponders with a median survival of 15 weeks. There was a significant difference in survival times between the responders and the SD patients, and between the responders and SD patients and the nonresponders. Responses were seen in 11% of the patients with squamous cell carcinoma and in 37% of the patients with adenocarcinoma. There was a significant difference in the response and SD categories in favor of adenocarcinoma over squamous cell carcinoma. Once a response was achieved, the median survival of the patients with adenocarcinoma was not significantly longer than that of the patients with squamous cell carcinoma.


Mucosal vaccination increases local chemokine production attracting immune cells to the stomach mucosa of Helicobacter pylori infected mice.
Vaccination is an attractive approach for the prevention of Helicobacter pylori infection and disease. In a mouse model, infection induces an accumulation of dendritic cells, macrophages, granulocytes, and B- and T cells to the stomach mucosa, which is further heightened when the infection is preceded by a mucosal immunization. We have studied the chemokines and chemokine receptors guiding infection- and vaccination-induced immune cells to the stomach and their relation to protection against H. pylori infection in mice. C57BL/6 mice were immunized sublingually with H. pylori lysate antigens and cholera toxin adjuvant or left unimmunized, and then challenged with live H. pylori bacteria. Stomach tissue was taken at 3, 7, 14 and 21 days after challenge and bacterial colonization, chemokine and chemokine receptor gene expression, and influx of cells into the stomach mucosa were evaluated. RT-PCR array screening revealed differential expression of a broad range of chemokine and chemokine receptor genes between immunized and unimmunized mice. A significant upregulation of chemokines known to attract, among other cells, eosinophils (CCL8), T cells (CXCL10, CXCL11) and neutrophils (CXCL2, CXCL5) and of their cognate receptors CCR3, CXCR3 and CXCR2, preceded or coincided with vaccine-induced protection, which was first evident 7 days after infection and was then sustained at the later time-points. Consistent with the increase in chemokines and chemokine receptors flow cytometric analysis indicated a sequential accumulation of CD4(+) T cells, eosinophils, neutrophils and CD103(+) dendritic cells in the gastric lamina propria of immunized mice. This study provides insights into vaccination-induced chemokines that guide the influx of protective immune cells into the stomach of H. pylori infected mice.


Does angioplasty improve the quality of life for claudicants?: A prospective study.
This study aims to analyze the impact of percutaneous transluminal angioplasty (PTA) for claudication on patients' quality of life (QOL). The patients in this study included 108 claudicants, 74 men and 34 women, with a median age of 67 years (range 40-87 years), who were assessed prior to and at 1, 3, and 6 months following PTA. This is the first report to demonstrate that the previously well-documented improvements in the clinical indicators of lower-limb ischemia are accompanied by improvements in individual QOL domains and in overall global QOL. These findings are detectable within a month following PTA and last at least 6 months. The results of this study may go some way to provide proof of efficacy for the procedure and thus help justify the recently questioned widespread use of PTA in clinical practice.


Phylogeny of Euclidieae (Brassicaceae) based on plastome and nuclear ribosomal DNA data.
Euclidieae, a morphologically diverse tribe in the family Brassicaceae (Cruciferae), consists of 29 genera and more than 150 species distributed mainly in Asia. Prior phylogenetic analyses on Euclidieae are inadequate. In this study, sequence data from the plastid genome and nuclear ribosomal DNA of 72 species in 27 genera of Euclidieae were used to infer the inter- and intra-generic relationships within. The well-resolved and strongly supported plastome phylogenies revealed that Euclidieae could be divided into five clades. Both Cymatocarpus and Neotorularia are polyphyletic in nuclear and plastome phylogenies. Besides, the conflicts of systematic positions of three species of Braya and two species of Solms-laubachia s.l. indicated that hybridization and or introgression might have happened during the evolutionary history of the tribe. Results from divergence-time analyses suggested an early Miocene origin of Euclidieae, and it probably originated from the Central Asia, Pamir Plateau and West Himalaya. In addition, multiple ndh genes loss and pseudogenization were detected in eight species based on comparative genomic study.


Vaccine failures in the epidemiology and control of measles.
Data were employed from confirmed measles case reports and an immunization survey to estimate the apparent effectiveness of measles vaccine in Los Angeles County in 1976. We evaluated the age-specific proportions of our case load arising from persons erroneously thought to possess immunity. Thirty five per cent of our cases claimed to have had prior measles vaccination, and over 60 per cent of these reported having written records. Since community measles control programs rely on immunization records as the principal screening tool, the shortcomings observed need to be recognized.


Association between physical partner violence, posttraumatic stress, childhood trauma, and suicide attempts in a community sample of women.
Our objective was to estimate the prevalence of intimate partner violence (IPV) and to explore its association with childhood maltreatment, substance misuse, posttraumatic stress, and suicidal behavior in a representative community sample of women. IPV was operationalized as a "physical attack or beating by a spouse, boyfriend, or live-in partner." We surveyed 637 women in Memphis, Tennessee, by telephone survey. Sixteen percent reported ever experiencing IPV by a male partner, and 75% endorsed multiple assaultive acts. Of abused women, 5.9% met current PTSD diagnostic criteria, and an additional 11.8% were assessed with subthreshold symptoms. Abused women were more likely than other women to be divorced, to have less than 13 years education, to endorse high levels of childhood victimization, to have abused drugs and alcohol, and to have attempted suicide. Twenty-three percent of IPV+ (abused) women reported a suicide attempt at some time in their lives compared with 3% of IPV- (nonabused) women (p < .0001). Further, multiple logistic regression analysis showed that childhood sexual and emotional abuse and low educational attainment were the only significant predictors of IPV. These results suggest that in women who endorse IPV, careful inquiry of past abuse, trauma-related symptoms, suicidal behavior, and drug use may be important, so that interventions can be both timely and appropriate.


Evaluating the feasibility and potential efficacy of a brief eTherapy for binge-eating disorder: A pilot study.
For those with binge-eating disorder (BED), access to evidence-based, face-to-face treatment is often constrained by clinician availability and high treatment costs. Emerging evidence suggests online therapy (eTherapy) may navigate these barriers and reduce binge-eating symptomatology; however, less evaluation has been done in those with BED, particularly with briefer programs targeting early change. This study investigated the feasibility and potential efficacy of a brief, supported eTherapy in those with BED or subthreshold BED. Participants were 19 women with BED who completed a four-session eTherapy. This was a single-arm, pre-post intervention study, with participants completing weekly content and attending telehealth sessions. Key outcomes were assessed by the Eating Disorder Examination Questionnaire-Short (EDE-QS): objective binge episode days, loss of control over eating days, and eating disorder (ED) psychopathology via a total EDE-QS score. Generalized and linear mixed models showed significantly reduced loss of control over eating days and ED psychopathology. Program feasibility was high, with strong program adherence and a below average attrition rate. Pilot results support the feasibility and potential efficacy of a brief, behavioral-focused eTherapy program in reducing ED pathology in those with BED. Future research should further investigate findings in an adequately powered randomized controlled trial. This study suggests that a brief, behavioral-focused online therapy, guided by non-expert clinicians, can be successfully administered to those with binge-eating disorder (BED) and may be efficacious at reducing eating disorder and other related symptomatology. Brief eTherapies that are effective, accessible, and rapidly available may facilitate earlier intervention in illness and improve treatment outcomes for individuals who experience this common and distressing disorder.


Evaluation of the antioxidant activity, genotoxic, and cytotoxic effects of the ethanolic leaves extract of Abutilon hirtum (Lam.) Sweet using in vitro assays.
Abutilon hirtum (Lam.) Sweet belongs to the Malvaceae family and is a perennial shrub commonly known as Indian mallow, which is distributed in tropical regions and many different areas in Saudi Arabia. A. hirtum is an economically and a medicinally useful plant in different zones of the world for healing various diseases. The current research explores the in vitro antioxidant characteristics and cytotoxic and genotoxic potential effects of the ethanolic leaf extract of A. hirtum (LEAH). Mitotic index (MI), micronucleus (MN), and chromosomal aberration (CA) tests were performed in Allium cepa, and MTT assays were performed using human dermal fibroblast, adult (HDFa) and breast cancer (MCF7) cell lines. The comet assay was used to assess the genotoxic effect of LEAH. The antioxidant activity of LEAH was evaluated by DPPH and superoxide anion free radical scavenging assays. The results revealed that the cytotoxic effects of LEAH on Allium cepa were significantly changed in an inverse relationship with MI (general average for 3 times 0.275) and a direct relationship with MNs and CAs against concentration and treatment time, for highest concentration 1.351 mg/ml were 0.74 and 1.81 respectively. In addition, the MTT test revealed a dose-dependent cytotoxic impact, with the % cell viability decreasing as the concentration of LEAH increased, the lowest % cell viability (19.54) and highest inhibition (80.46) were obtained with 4.40 mg/ml of LEAH. In general, the results indicated that A. hirtum has a damaging effect at high doses; however, a cell safe effect, and a strong antioxidant and DNA protective effect at carefully calculated doses was observed. This provides credibility to justify its general therapeutic activity. Moreover, future studies should identify bioactive molecules and their molecular mechanisms responsible for potential therapies.


Effects of citrate on hexavalent chromium reduction by structural Fe(II) in nontronite.
Previous studies have shown that organic ligands could influence Cr(VI) reduction by aqueous Fe2+ and pyrite. In this study, the effects of citrate on Cr(VI) reduction by structural Fe(II) in nontronite (NAu-2) were investigated at pH 6. Our results showed that the presence of citrate decreased the rate but increased the amount of Cr(VI) reduction. The decreased rate was likely due to competitive sorption of citrate and anionic dichromate (Cr2O7-) to NAu-2 surface sites, because sorption of dichromate appeared to be the first step for subsequent Cr(VI) reduction. The increased amount of Cr(VI) reduction was likely because citrate served as an additional electron donor to reduce Cr(VI) through ligand-metal electron transfer in the presence of soluble Fe3+, which was possibly derived from dissolution of reduced NAu-2. Soluble Cr(III)-citrate complex was a possible form of reduced Cr(VI) when citrate was present. Without citrate, nanometer-sized Cr2O3 particles were the product of Cr(VI) reduction. Our study highlights the importance of citrate on Cr(VI) reduction and immobilization when iron-rich smectite is applied to treat Cr(VI) contaminant in organic carbon rich environments.


Serum iron, vitamin B12 and folic acid levels in Parkinson's disease.
We aimed to investigate possible associations between systemic iron metabolism deficiency and Parkinson's disease, and also to research any possible correlations between stage of the disease and vitamin B12 and folic acid levels. 33 male and 27 female patients diagnosed with idiopathic Parkinson's disease and 22 male and 20 female age- and sex-matched controls were enrolled in the study. Having the diagnosis of secondary Parkinsonism or Parkinson plus syndromes, and for the females, not being in the menopausal stage were considered as exclusion criteria. Recordings of blood samples of both groups collected after 8 h fasts were assessed in terms of serum iron, ferritin levels and iron-binding capacity, vitamin B12 and folic acid levels. The Hoehn and Yahr scale was used to determine the stage of the disease. No statistically significant difference was found with respect to mean serum iron, median serum ferritin levels and median serum iron-binding capacity between the groups. A statistically significant but inverse correlation was found between symptoms' duration and serum iron and ferritin levels. There was no statistically significant difference between the groups with respect to vitamin B12 and folic acid levels. However, a statistically significant but inverse correlation was determined between the patients' vitamin B12 levels and the Hoehn and Yahr scores. As Parkinson's disease progresses, serum iron, ferritin and vitamin B12 levels may decrease. The lower levels of these parameters may be the cause of the progression or may be the result of it.


Collegial ethics: supporting our colleagues.
The goal of collegial ethics is to actively support our colleagues and to develop the skills needed to do so. While collegial interactions are key for our careers, there is little or no training in this. Many of our actions and reactions with our colleagues are instinctive. Human nature has evolved to be self-protective, but many evolved and automatic responses to others are not always in the best interests of our society or of us. Developing courage and a style of supportive language, avoiding destructive acts, and adhering to the golden rule will improve our relationships and provide a more positive environment for all.


Effects of oral pyridoxine upon plasma and 24-hour urinary oxalate levels in normal subjects and stone formers with idiopathic hypercalciuria.
The effect of pyridoxine hydrochloride, 200 mg/day (0.97 mmol/day) for 3 weeks, upon plasma and urinary oxalate has been determined in ten normal subjects and seven patients with idiopathic hypercalciuria while both groups were on low-oxalate diets. Patients had higher basal urinary oxalate levels than normal subjects. In normal subjects pyridoxine administration decreased plasma oxalate levels and raised urinary oxalate. The patients showed no change in either plasma or urinary oxalate.


Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells.
Despite the obvious importance of epithelial stem cells in tissue homeostasis and tumorigenesis, little is known about their specific location or biological characteristics. Using 3H-thymidine labeling, we have identified a subpopulation of corneal epithelial basal cells, located in the peripheral cornea in a region called limbus, that are normally slow cycling, but can be stimulated to proliferate in response to wounding and to a tumor promotor, TPA. No such cells can be detected in the central corneal epithelium, suggesting that corneal epithelial stem cells are located in the limbus. A comparison of various types of epithelial stem cells revealed a common set of features, including their preferred location, pigment protection, and growth properties, which presumably play a crucial role in epithelial stem cell function.


Precision medicine: Vinpocetine as a potential treatment for GABRG2-related epilepsy.
Pathogenic variants of the GABRG2 gene, encoding a GABAA receptor subunit, have been associated with various epileptic syndromes and drug-resistant epilepsy. Vinpocetine has been previously reported efficacious in a patient harboring a GABRB3 pathogenic variant, encoding another GABAA receptor subunit. We describe a patient with GABRG2-related drug-resistant epilepsy who improved after vinpocetine treatment. An 8-year-old boy with a family history of epilepsy was diagnosed with early onset absence epilepsy at 6 months of age and was treated unsuccessfully with sodium valproate and ethosuximide. At 6 years of age, he developed generalized tonic-clonic seizures and increasing absences despite lamotrigine add-on as well as learning difficulties. Brain MRI was normal and video-EEG telemetry showed multiple myoclonic absences. An epilepsy gene panel analysis showed a GABRG2 pathogenic variant, c.254 T > A p.(Ile85Lys) (NM_198903.2), inherited from the proband's father. Seizures were resistant to several medications. After treatment with vinpocetine add-on, the patient showed a dramatic initial response, further reduction of seizures, and improvement of his cognitive functions. This case illustrates that vinpocetine could be considered in drug-resistant epilepsies related to GABRG2 in accordance with the principles of precision medicine.


The relationship between high-sensitivity C-reactive protein and ApoB, ApoB/ApoA1 ratio in general population of China.
Inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) is considered as a major predictor of cardiovascular events. Apolipoprotein B (ApoB) directly reflects the number of plasma atherogenic lipoproteins, and may play a major role in vascular inflammation. We aimed to assess whether an association between ApoB and hsCRP exists and, furthermore, to examine whether ApoB is more predictive of the inflammatory status than other cardiovascular risk factors. This was a cross-sectional study, with 511 apparently healthy adult subjects enrolled. Waist circumference (WC), body mass index (BMI), and blood pressure (BP) were measured. Plasma glucose levels, hsCRP, lipid profile, and insulin were collected after 10-14 h fasting. From the lowest to the highest quartile of hsCRP, the values for BMI, WC, BP, HOMA-IR, insulin, glucose level, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), ApoB and the ApoB/apolipoprotein A1 (ApoA1) ratio were increased as the hsCRP level increased (P < 0.01), and high-density lipoprotein cholesterol (HDL-C) and ApoA1 levels declined as hsCRP level increased (P < 0.0001). Pearson's correlation analysis demonstrated that hsCRP correlated with all variables (P < 0.01), except for total cholesterol (TC) (P = 0.154) and LDL-C (P = 0.087). According to forward stepwise regression analysis with hsCRP as the dependent variable, WC was the only variable entered the regression model. ApoB level correlated with hsCRP level but was not the major determinant of hsCRP. WC was stronger than other cardiovascular risk factors in the associations with hsCRP. Abdominal obesity rather than atherogenic dyslipidemia was the primary cause of chronic inflammatory status.