Christine: a case study of literacy acquisition by an adult with developmental disabilities.
Christine, an adult with developmental disabilities, had no history of education. A nonreader, she began to receive literacy tutoring at age 35. In 7 years she was educated through an eclectic approach that primarily entailed echo reading of brief passages, such as sentences and stories. She moved from holistic recognition of print to an ability to respond to instruction about analysis of some features of print, thereby gaining insights into decoding and spelling. This approach contrasts with literacy instruction that teaches adults with developmental disabilities to memorize small units of decontextualized print (letter-sound correspondences or survival words) before reading full text. Implications for facilitating literacy in adults with developmental disabilities by using contextually supported reading instruction are explored.


Facile Co-Electrodeposition Method for High-Performance Supercapacitor Based on Reduced Graphene Oxide/Polypyrrole Composite Film.
A facile co-electrodeposition method has been developed to fabricate reduced graphene oxide/polypyrrole (rGO/PPy) composite films, with sodium dodecyl benzene sulfonate as both a surfactant and supporting electrolyte in the precursor solution. The introduction of rGO into the PPy films forms porous structure and enhances the conductivity across the film, leading to superior electrochemical performance. By controlling the deposition time and rGO concentration, the highest area capacitance can reach 411 mF/cm2 (0.2 mA/cm2) for rGO/PPy films, whereas optimized specific capacitance is as high as 361 F/g (0.2 mA/cm2). All of the composite films exhibit excellent rate capability (at least 175 F/g at the current density of 12 mA/cm2) compared with pure PPy film (only 12 F/g at the current density of 12 mA/cm2). The rGO/PPy composite exhibits excellent cycling stability that maintains 104% of its initial capacitance after cycling for 2000 cycles and 80% for 5000 cycles. The two-electrode solid-state supercapacitor (SC) based on rGO/PPy composite electrodes demonstrates good rate performance, excellent cycling stability, as well as a high area capacitance of 222 mF/cm2. The solid-state planar SC based on the rGO/PPy composite exhibits an area capacitance of 9.4 mF/cm2, demonstrating great potential for fabrication of microsupercapacitors.


Phase equilibria and structure of dry and hydrated egg lecithin.
The behavior of purified egg lecithin in water has been investigated in relation to the quantity of water present and the temperature. The complete binary phase diagram of egg lecithin-water is presented as well as X-ray diffraction data on selected mixtures. Dry egg lecithin is present in at least partially crystalline form until about 40 degrees C. Above this temperature it forms a "wax-like" phase up to about 88 degrees C. From 88 to 109 degrees C it forms a viscous isotropic phase which gives face-centered cubic spacings by X-ray analysis. Above 110 degrees C its texture is "neat" and the structure is assumed to be lamellar until its final melting point at 231 degrees C. Hydrated lecithin forms (except for a small zone of cubic phase at low water concentrations and high temperature) a lamellar liquid crystalline phase. This phase contains up to 45% water at 20 degrees C. Mixtures containing more water separate into two phases, the lamellar liquid crystalline phase and water. In the melting curve of hydrated lecithin a eutectic is noted at about 16% water and the cubic phase seen when less water is present disappears at this composition of the mixture. These facts, along with previous vapor pressure measurements, suggest that there is a structural change at about 16% water. X-ray diffraction studies of lecithin at 24 degrees C and calculations from these data suggest that the reason for this may be the presence of a "free water layer" when more than 16% water is present.


Lower pre-ART intra-participant HIV-1 pol diversity may not be associated with virologic failure in adults.
Identifying pre-ART factors associated with the emergence of HIV-1 drug resistance is critical for optimizing strategies to prevent virologic failure. A previous study reported that lower pre-ART HIV-1 pol diversity was associated with higher risk of virologic failure in HIV-1-infected children. To investigate this association in adults, we measured HIV-1 diversity with deep sequencing in pre-ART samples from adults with well-characterized virologic outcomes in a study (A5142) of initial ART conducted by the AIDS Clinical Trials Group (ACTG). We identified 22 cases in ACTG A5142 who experienced virologic failure with drug resistance mutations in RT and 44 matched controls who did not experience virologic failure. cDNA was synthesized from plasma HIV-1 RNA. Each cDNA molecule was tagged with a unique primer ID and RT codons 41-103 were amplified and deep sequenced. Sequences with the same tag were aligned and a consensus was generated to reduce PCR and sequencing errors. Diversity was calculated by measuring average pairwise distance (APD) of the consensus sequences. An exact conditional logistic regression model with percent APD as the risk factor estimated the odds ratio for VF and the corresponding 95% confidence interval. Consensus single-genome sequences and diversity estimates of pol were obtained for pre-ART samples from 21 cases and 42 controls. The median (IQR) pre-ART percent APD was 0.71 (0.31-1.13) in cases and 0.58 (0.32-0.94) in controls. A possible trend was found for higher diversity being associated with greater risk of virologic failure in adults (OR = 2.2 per one percent APD increase, 95% CI = [0.8, 7.2]; p = 0.15). This study in adults suggests there is a positive association between higher pre-ART pol diversity and the risk of virologic failure in adults rather than an inverse relationship reported in children.


Simian immunodeficiency virus-induced CD4+ T cell deficits in cytokine secretion profile are dependent on monkey origin.
Facets of the immune response early after human immunodeficiency virus (HIV) infection influence the course of disease. In the simian immunodeficiency virus (SIV)-rhesus monkey system, a global dysfunction of CD4(+) T cell cytokine secretion was reported to develop early after infection [McKay PF, Barouch DH, Schmitz JE, Veazey RS, Gorgone DA, Lifton MA, Williams KC, and Letvin NL: J Virol 2003;77:4695-4702]. Because differences have been found in SIV pathogenesis depending on the origin of the monkeys, we investigated the correlation between animal background, defined by country of origin (India or China), and circulating T cell cytokine secretion as well as cycling ability within the first 3 mo of SIV infection. An early loss of CD4(+) T cells that produce interferon (IFN)-gamma and interleukin (IL)-2, those that produce IFN-gamma but not tumor necrosis factor (TNF)-alpha, as well as those that do not express IFN-gamma but can express IL-2 or TNF-alpha, was observed in animals of Indian, but not of Chinese, origin after SIV infection. After infection CD4(+) T cells in Chinese macaques developed an increased proliferating pool of T cells compared with Indian animals. These data reveal host diversity in the global effects of SIV infection on functional subsets of immune cells, which can add to a better understanding of differences observed in populations from diverse ethnic origins.


Diffusion-weighted MR imaging for the regional characterization of liver tumors.
To determine if diffusion-weighted (DW) magnetic resonance (MR) imaging with measurements of the apparent diffusion coefficient (ADC), pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction can be used to differentiate between viable tumor and fibrous and necrotic regions within malignant liver tumors. The prospective study was approved by the institutional review board, and informed consent was obtained from all patients. Forty-eight patients with 51 malignant tumors were assessed. MR images of the liver were obtained by using DW imaging with 11 b factors (0-500 sec/mm(2)) and gadolinium-enhanced three-dimensional gradient-echo T1-weighted imaging. Tumors were segmented into viable tumor and fibrous and necrotic regions according to the enhancement pattern after injection of a nonspecific gadolinium chelate and, in surgically removed lesions, results of histopathologic correlation. The ADC, pure diffusion coefficient, perfusion-related diffusion coefficient, and perfusion fraction were calculated, and values were compared between viable tumor and fibrous and necrotic regions with the Kruskal-Wallis test followed by the Dunn multiple comparison test. The pure diffusion coefficient differed significantly between regions of viable tumor tissue and fibrosis (1.16 × 10(-3) mm(2)/sec ± 0.29 and 1.48 × 10(-3) mm(2)/sec ± 0.31, respectively; P = .016) and between regions of viable tumor tissue and necrosis (1.70 × 10(-3) mm(2)/sec ± 0.49, P = .002). There was a significantly lower perfusion fraction in necrotic regions (14% ± 6) than in viable tumor regions (21% ± 8, P = .005), but the perfusion fraction of the fibrous regions (21% ± 7) did not differ significantly from that of the other two regions. ADCs and perfusion-related diffusion coefficients did not differ significantly among the three regions. Results of this study show that viable tumor regions in malignant liver tumors can be differentiated from fibrous and necrotic regions with use of the pure diffusion coefficient but not with the other diffusion parameters.


Type VI Secretion System Dynamics Reveals a Novel Secretion Mechanism in Pseudomonas aeruginosa.
The type VI secretion system (T6SS) inhibits the growth of neighboring bacterial cells through a contact-mediated mechanism. Here, we describe a detailed characterization of the protein localization dynamics in the Pseudomonas aeruginosa T6SS. It has been proposed that the type VI secretion process is driven by a conformational-change-induced contraction of the T6SS sheath. However, although the contraction of an optically resolvable TssBC sheath and the subsequent localization of ClpV are observed in Vibrio cholerae, coordinated assembly and disassembly of TssB and ClpV are observed without TssB contraction in P. aeruginosa These dynamics are inconsistent with the proposed contraction sheath model. Motivated by the phenomenon of dynamic instability, we propose a new model in which ATP hydrolysis, rather than conformational change, generates the force for secretion.IMPORTANCE The type VI secretion system (T6SS) is widely conserved among Gram-negative bacteria and is a central determinant of bacterial fitness in polymicrobial communities. The secretion system targets bacteria and secretes effectors that inhibit the growth of neighboring cells, using a contact-mediated-delivery system. Despite significant homology to the previously characterized Vibrio cholerae T6SS, our analysis reveals that effector secretion is driven by a distinct force generation mechanism in Pseudomonas aeruginosa The presence of two distinct force generation mechanisms in T6SS represents an example of the evolutionary diversification of force generation mechanisms.


Optimizing cochlear implant speech performance.
Results of studies performed in our laboratory suggest that cochlear implant recipients understand speech best if the following speech processor parameters are individually chosen for each person: minimum and maximum stimulation levels on each electrode in the speech processor program (MAP), stimulation rate, and speech coding strategy. If these and related parameters are chosen to make soft sounds (from approximately 100 to 6,000 Hz) audible at as close to 20 dB hearing level as possible and loud sounds not too loud, recipients have the opportunity to hear speech in everyday life situations that are of key importance to children who are learning language and to all recipients in terms of ease of communication.


Not all mind wandering is created equal: dissociating deliberate from spontaneous mind wandering.
In two large samples we show a dissociation between trait-level tendencies to mind-wander spontaneously (unintentionally) and deliberately (intentionally). Participants completed online versions of the Mind Wandering Spontaneous (MW-S) and the Mind Wandering Deliberate (MW-D) self-report scales and the Five Facet Mindfulness Questionnaire (FFMQ). The results revealed that deliberate and spontaneous mind wandering were uniquely associated with some factors of the FFMQ. Notably, while the MW-D and the MW-S were positively associated with each other, the MW-D was uniquely positively associated with the 'Non-Reactivity to Inner Experience' factor of the FFMQ, whereas the MW-S was uniquely negatively associated with this factor. We also showed that conflating deliberate and spontaneous mind wandering can result in a misunderstanding of how mind wandering is related to other traits. We recommend that studies assessing individual differences in mind wandering should distinguish between deliberate and spontaneous subtypes of mind wandering to avoid possibly erroneous conclusions.


(68)Ga-DOTATATE PET/CT imaging in carotid body tumor.
Imaging modalities like Doppler ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging are routinely used in the diagnosis of carotid body tumors. Ga-DOTATATE PET/CT is another promising noninvasive technique in the diagnosis of carotid body tumors. We present F-FDG PET/CT and Ga-DOTATATE PET/CT in a 30-year-old man with carotid body tumor.


The plasticity of posterior communicating artery influences on the outcome of white matter injury induced by chronic cerebral hypoperfusion in rats.
This study was performed to identify which factors are involved in the development of white matter lesions induced by chronic cerebral hypoperfusion in rats. Male Wistar and Sprague-Dawley (SD) rats (250-270 g) were subjected to the permanent occlusion of bilateral common carotid arteries (BCCAO). The regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry and the plasticity of the posterior communicating artery (PcomA) was visualized by transcardiac perfusion of latex solution. For the histological examination, Klüver-Barrera staining was used to evaluate white matter damage. When compared with SD rats, Wistar rats showed lower rCBF after BCCAO, as well as thinner PcomAs. Moreover, 21 days after BCCAO, Wistar rats showed marked vacuolation of white matter in the optic tract, whereas SD rats had an almost intact optic tract. These results suggest that the plasticity of the PcomA and the reduction of rCBF in Wistar rats are important factors in the development of BCCAO-induced white matter lesions.


Road Traffic Noise, Air Pollutants, and the Prevalence of Cardiovascular Disease in Taichung, Taiwan.
Background: A few studies have investigated the interaction between exposure to road traffic noise, air pollutants, and cardiovascular disease (CVD), but their results were inconsistent. This cross-sectional study investigated whether road traffic noise, particulate matter with dynamic diameter less than 10 μm (PM10) and nitrogen dioxides (NO₂) exposure were independently associated with the risk of CVD. Methods: We recruited 663 volunteers who had been living near main roads for more than three years in 2008. Information concerning the subjects' home addresses was combined with noise measurements at 42 locations and annual average of air pollutants from 2 monitoring stations to estimate individual exposure. Multivariate logistic regression was used to calculate the odds ratio (OR) for diagnosed CVD, adjusting for potential confounders and co-exposure. Results: Only per 5-dBA increase in road traffic noise was significantly associated with elevated risk of CVD (adjusted OR = 2.23, 95% confidence interval (CI) = 1.26⁻3.93) in the single-exposure models. Such association was aggravated (adjusted OR = 2.96, 95% CI = 1.41⁻6.23) after adjustment for total traffic and PM10 or NO₂ in the two-exposure models. Conclusions: Road traffic noise exposure may be associated with the increasing prevalence of CVD. No synergistic association was observed between co-exposure to noise and air pollutants and the risk of CVD.


Age-related abnormalities of oxidoreductase activity and mitochondria in rat hippocampal formation.
The activity of oxidoreductases in the hippocampal formation of young adult (3-month old) and aged (24-month old) Wistar rats was compared by histochemical methods. A decreased activity of NADH-diaphorase and dehydrogenases involved in the Krebs cycle and glycolysis as well as an increased activity of glucose-6-phosphate dehydrogenase were demonstrated in the hippocampal nerve cells of aged rats. The activity of oxidoreductases in the glial cells of aged rats was increased. Degenerative changes in scattered mitochondria were seen ultrastructurally. No significant differences in the relative volume fraction of mitochondria in the presynaptic axon terminals and dendrites were found between young adult and aged rats.


GLUT4 Expression in Adipocytes Regulates De Novo Lipogenesis and Levels of a Novel Class of Lipids With Antidiabetic and Anti-inflammatory Effects.
Adipose tissue (AT) regulates systemic insulin sensitivity through multiple mechanisms, and alterations in de novo lipogenesis appear to contribute. Mice overexpressing GLUT4 in adipocytes (AG4OX) have elevated AT lipogenesis and enhanced glucose tolerance despite being obese and having elevated circulating fatty acids. Lipidomic analysis of AT identified a structurally unique class of lipids, branched fatty acid esters of hydroxy-fatty acids (FAHFAs), which were elevated in AT and serum of AG4OX mice. Palmitic acid esters of hydroxy-stearic acids (PAHSAs) are among the most upregulated FAHFA families in AG4OX mice. Eight PAHSA isomers are present in mouse and human tissues. PAHSA levels are reduced in insulin resistant people, and levels correlate highly with insulin sensitivity. PAHSAs have beneficial metabolic effects. Treatment of obese mice with PAHSAs lowers glycemia and improves glucose tolerance while stimulating glucagon-like peptide 1 and insulin secretion. PAHSAs also reduce inflammatory cytokine production from immune cells and ameliorate adipose inflammation in obesity. PAHSA isomer concentrations are altered in physiological and pathophysiological conditions in a tissue- and isomer-specific manner. The mechanisms most likely involve changes in PAHSA biosynthesis, degradation, and secretion. The discovery of PAHSAs reveals the existence of previously unknown endogenous lipids and biochemical pathways involved in metabolism and inflammation, two fundamental physiological processes.


Association of betaine with blood pressure in dialysis patients.
Mechanisms underlying elevated blood pressure in dialysis patients are complex as a variety of non-traditional factors are involved. We sought to explore the association of circulating betaine, a compound widely distributed in food, with blood pressure in dialysis patients. We used baseline data of an ongoing cohort study involving patients on hemodialysis. Plasma betaine was measured by high performance liquid chromatography in 327 subjects. Blood pressure level was determined by intradialytic ambulatory blood pressure monitoring. The mean age of the patients was 52.6 ± 11.9 years, and 58.4% were male. Average interdialytic ambulatory systolic and diastolic blood pressure were 138.4 ± 22.7 mm Hg and 84.4 ± 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 μmol/L. Multiple linear regression analysis revealed significant associations of betaine with both systolic blood pressure (β = -3.66, P = .003) and diastolic blood pressure (β = -2.00, P = .004). The associations persisted even after extensive adjustment for cardiovascular covariates. Subgroup analysis revealed that the association between betaine and blood pressure was mainly limited to female patients. Our data suggest that alteration of circulating betaine possibly contributes to blood pressure regulation in these patients.


Advances in differential diagnosis and management of growth hormone deficiency in children.
Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000-10,000 live births and can be due to multiple causes, some of which are yet to be determined. Establishing the correct diagnosis remains key in children with short stature, as initiating treatment with recombinant human GH can help them attain their genetically determined adult height. During the past two decades, our understanding of the benefits of continuing GH therapy throughout the transition period from childhood to adulthood has increased. Improvements in transitional care will help alleviate the consequent physical and psychological problems that can arise from adult GHD, although the consequences of a lack of hormone replacement are less severe in adults than in children. In this Review, we discuss the differential diagnosis in children with GHD, including details of clinical presentation, neuroimaging and genetic testing. Furthermore, we highlight advances and issues in the management of GHD, including details of transitional care.


The Therapeutic Targeting of HGF/c-Met Signaling in Hepatocellular Carcinoma: Alternative Approaches.
The poor prognosis of hepatocellular carcinoma (HCC), one of the most devastating cancers worldwide, is due to frequent recurrence and metastasis. Among the metastatic factors in the tumor microenvironment, hepatocyte growth factor (HGF) has been well known to play critical roles in tumor progression, including HCC. Therefore, c-Met is now regarded as the most promising therapeutic target for the treatment of HCC. However, there are still concerns about resistance and the side effects of using conventional inhibitors of c-Met, such as tyrosine kinase inhibitors. Recently, many alternative strategies of c-Met targeting have been emerging. These include targeting the downstream effectors of c-Met, such as hydrogen peroxide-inducible clone 5 (Hic-5), to block the reactive oxygen species (ROS)-mediated signaling for HCC progression. Also, inhibition of endosomal regulators, such as PKCε and GGA3, may perturb the c-Met endosomal signaling for HCC cell migration. On the other hand, many herbal antagonists of c-Met-dependent signaling, such as saponin, resveratrol, and LZ-8, were identified. Taken together, it can be anticipated that more effective and safer c-Met targeting strategies for preventing HCC progression can be established in the future.


Direct peroral cholangioscopy for diagnosis of bile duct lesions using an I-SCAN ultraslim endoscope: a pilot study.
Background and study aims I-SCAN is a computed virtual chromoendoscopy (CVC) system designed to enhance surface and vascular patterns. In this study, we evaluated the usefulness of direct peroral cholangioscopy (POC) using I-SCAN compared with a conventional white-light image (WLI) to diagnose bile duct lesions. Patients and methods Patients with mucosal lesions in the bile duct detected during direct POC were enrolled prospectively. The quality of endoscopic visualization and the visual diagnosis were assessed using I-SCAN and WLI modes, respectively, during direct POC. Results A total of 20 patients (9 malignant and 11 benign lesions) underwent I-SCAN to evaluate lesions in the bile duct using direct POC. The quality of endoscopic visualization using direct POC with I-SCAN was significantly higher than that of WLI for surface structure (P = 0.04), surface microvascular architecture (P = 0.01), and margins (P = 0.02). Overall diagnostic accuracy of the visual diagnosis was not different between I-SCAN and WLI (90.0 % vs. 75.0 %; P = 0.20). Conclusion Direct POC using CVC by I-SCAN seems to be helpful for evaluating mucosal lesions of the bile duct, without the interference from bile. UMIN000021009.


Translational diffusion of cumene and 3-methylpentane on free surfaces and pore walls studied by time-of-flight secondary ion mass spectrometry.
Mobility of molecules in confined geometry has been studied extensively, but the origins of finite size effects on reduction of the glass transition temperature, T(g), are controversial especially for supported thin films. We investigate uptake of probe molecules in vapor-deposited thin films of cumene, 3-methylpentane, and heavy water using secondary ion mass spectrometry and discuss roles of individual molecular motion during structural relaxation and glass-liquid transition. The surface mobility is found to be enhanced for low-density glasses in the sub-T(g) region because of the diffusion of molecules on pore walls, resulting in densification of a film via pore collapse. Even for high-density glasses without pores, self-diffusion commences prior to the film morphology change at T(g), which is thought to be related to decoupling between translational diffusivity and viscosity. The diffusivity of deeply supercooled liquid tends to be enhanced when it is confined in pores of amorphous solid water. The diffusivity of molecules is further enhanced at temperatures higher than 1.2-1.3 T(g) irrespective of the confinement.


Smoothing It Out: Military Health Care Supply Chain in Transition.
Health care provision in the US can be characterized by its ongoing consolidation of systems and facilities in its efforts to achieve clinical and business integration. An important goal in health care systems is integration to reduce fragmentation and gain value. Functional integration has a long history of association with clinical performance. Supply chain can dramatically support the goals of cost avoidance, improved clinical outcomes, and buffer the system from external dependencies. This paper examines the efforts by the Department of Defense to consolidate the medical supply chain and explores lessons for and from the civilian health sector supply chain.


The highly diverse antiphage defence systems of bacteria.
Bacteria and their viruses have coevolved for billions of years. This ancient and still ongoing arms race has led bacteria to develop a vast antiphage arsenal. The development of high-throughput screening methods expanded our knowledge of defence systems from a handful to more than a hundred systems, unveiling many different molecular mechanisms. These findings reveal that bacterial immunity is much more complex than previously thought. In this Review, we explore recently discovered bacterial antiphage defence systems, with a particular focus on their molecular diversity, and discuss the ecological and evolutionary drivers and implications of the existing diversity of antiphage defence mechanisms.


Field evaluation of a novel synthetic odour blend and of the synergistic role of carbon dioxide for sampling host-seeking Aedes albopictus adults in Rome, Italy.
Despite the expanding worldwide distribution of Aedes albopictus and its increasing relevance as arboviral vector, current methods to collect adult specimens are not optimal. Improved approaches are thus needed to monitor their density and pathogen infections, and to establish baseline data for control interventions. A widely used device is the BG-Sentinel (BG-trap) which mostly targets host-seeking females attracted by release of CO2 and/or a synthetic odour blend (the BG lure). We compared the attractiveness of this blend to that of the Mbita (MB5) lure, a new synthetic blend of proven efficiency in attracting Afrotropical malaria vectors, and evaluated the additional effect of CO2 to the two odour baits. We carried out 6x6 Latin square experiments in two Ae. albopictus-infested areas in Rome, baiting the BG-traps as follows: CO2, BG lure, MB5 lure, BG lure + CO2, MB5 lure + CO2, no bait. CO2 was derived from yeast-fermented sugar. Overall, 949 females and 816 males were collected. Baited traps collected significantly more females than unbaited ones. Traps baited with either lures in combination with CO2 were more effective than those baited with CO2 alone. No significant differences were observed in female captures between traps baited with any of the two lures, nor between the two lures, independently from the addition of CO2. The use of BG lure + CO2 significantly increased males catches compared to unbaited traps. The results suggest a broad significance of the MB5 lure for sampling medically important mosquito species and highlight the high efficacy of the combination of lures + CO2 for female Ae. albopictus and of BG lure + CO2 for males, leading to consider CO2 as an essential additional cue for the sampling of this species.


Effects of Age and Size on Xylem Phenology in Two Conifers of Northwestern China.
The climatic signals that directly affect the trees can be registered by xylem during its growth. If the timings and duration of xylem formation change, xylogenesis can occur under different environmental conditions and subsequently be subject to different climatic signals. An experimental design was applied in the field to disentangle the effects of age and size on xylem phenology, and it challenges the hypothesis that the timings and dynamics of xylem growth are size-dependent. Intra-annual dynamics of xylem formation were monitored weekly during the growing seasons 2013 and 2014 in Chinese pine (Pinus tabulaeformis) and Qilian juniper (Juniperus przewalskii) with different sizes and ages in a semi-arid region of northwestern China. Cell differentiation started 3 weeks earlier in 2013 and terminated 1 week later in 2014 in small-young pines than in big-old pines. However, differences in the timings of growth reactivation disappeared when comparing the junipers with different sizes but similar age. Overall, 77 days were required for xylem differentiation to take place, but timings were shorter for older trees, which also exhibited smaller cell production. Results from this study suggest that tree age does play an important role in timings and duration of growth. The effect of age should also be considered to perform reliable responses of trees to climate.


Isolating the spectra of cluster ion isomers using Ar-"tag" -mediated IR-IR double resonance within the vibrational manifolds: Application to NO2- *H2O.
We demonstrate a method for isolating the vibrational predissociation spectra of different structural isomers of mass-selected cluster ions based on a population-labeling double resonance scheme. This involves a variation on the "ion dip" approach and is carried out with three stages of mass selection in order to separate the fragment ion signals arising from a fixed-frequency population-monitoring laser and those generated by a scanned laser that removes population of species resonant in the course of the scan. We demonstrate the method on the Ar-tagged NO(2) (-)H(2)O cluster, where we identify the spectral patterns arising from two isomers. One of these structures features accommodation of the water molecule in a double H-bond arrangement, while in the other, H(2)O attaches in a single ionic H-bond motif where the nominally free OH group is oriented toward the N atom of NO(2) (-). Transitions derived from both the NO(2) (-) and H(2)O constituents are observed for both isomers, allowing us to gauge the distortions suffered by both the ion and solvent molecules in the different hydration arrangements.


[Diagnosis and treatment of carotid body paragangliomas. Presentation of 9 cases and review of the literature].
Carotid body paragangliomas (CBP) are relatively rare tumors arising from the carotid body paraganglion. Clinical signs and images are necessary to establish the diagnosis. Surgery is the preferred method of treatment, paying special attention to the carotid artery. Nine patients with carotid body tumors were identified, three of them with complicated diagnosis. One patient is treated with radiotherapy. Out of the eight surgical patients, three preserved the whole arterial structure, the external carotid artery is resected in two patients, the carotid artery is replaced (safen graft, gore tex prosthesis) in other two patients, and the common carotid was tied in the remaining patient. Our objective is to show the decisions taken in the patients from our casuistic, comparing them to the literature data. We conclude that the diagnosis may be deceptive, and that the attitude forward the carotid is variable, always being prepared to do arterial replacement techniques.


[Use of various technics in the classification of hematopoietic system tumors].
A comparison of three groups classified according to three different methods (89, 91, und 278 cases respectively) confirmed that the main oncological features of haematopoietic tissue tumours should be sought in their cytological-histological properties.--The spectrum of methods employed (histochemistry, immunohistology, electron microscopy) may in individual cases underpin the decision-making process especially when the appearance of tumour cells has been altered by advanced anaplasia. Partial results of these methods judged in isolation may, however, be conductive to wrong interpretation. That is why special significance should be attached to thin sections of tissue stained according to Giemsa as they combine the advantage of histology with those of cytology.--In the basic classification the pathologist can do with the conventional haematological classes of tumours (granulocytic, histiomonocytic, lymphocytic, erythrocytic, megakaryocytic, mixed, and unclassifiable). In the lymphocytic series it was necessary to proceed not only according to immaturity but also according to the blastic transformation of the initial elements.--The principal outstanding problem is that of a positive mutual distinction between blastically transformed lymphocytes and between those and cells of the reticulum.


[Income and assets of the middle and old age Mexican population].
The purpose of this article is to describe the amount and types of income and assets that the middle and old age population receive and own in Mexico. We use data from the Mexican Health and Aging Study (MHAS) 2001; a prospective panel study with national representation of individuals aged 50 and older. The results confirm the hypotheses of the paper: that the distributions of income and wealth are biased in favor of certain groups, in particular those highly educated; that the majority of the wealth of individuals is in non-financial form; that family help is an important source of income; and that the association between wealth and health is positive in general, which is consistent with the international literature for other countries. In addition, we find that wealth is more equitably distributed than income. We conclude that the wealth indicator offers an additional dimension of analysis than income, with potential to contribute to studies of well-being of the population of middle and old age in Mexico.


Enhancing outcomes in an indicated drug prevention program for high-risk youth.
This study examined the net effects of refining a high school-based indicated drug prevention program. The Personal Growth Class (PGC), tailored to meet the needs of high-risk youth, was designed to increase control of drug use, school performance, and emotional well-being. The program integrates social support and life-skills training. Process evaluation revealed the need for program enhancements to address underestimated levels of depression, anger, and suicidal behaviors prevalent among high-risk youth and to ensure that core content was being emphasized consistently. Youth participating in Late cohorts received the refined PGC with enhanced skills training. Study participants (N = 280) were youth, primarily ages fifteen to-seventeen, at high-risk for school failure or dropout. Indicators of emotional well-being (e.g., depression, stress, anger, self-esteem, personal control), drug involvement, and school performance were compared for Late versus Early cohorts. Regression analyses revealed the Late versus Early cohorts showed significantly greater decreases in hard drug use, depression, perceived stress, and anger, and greater increases in self-esteem. The results support arguments that effective indicated prevention programs should target specific high-risk youth employing strategies to counteract the multifaceted risk factors they experience and enhance needed protective factors.


Unilateral versus bilateral injections of botulinum toxin in patients with adductor spasmodic dysphonia.
Both unilateral and bilateral thyroarytenoid muscle injections of Botox provide effective management of voice symptoms in patients with adductor spasmodic dysphonia; however, the preferred injection technique has not been established. In this study, 16 patients were treated with unilateral injections (72 injections total) and 33 patients were managed with bilateral injections (133 injections total). Individual assignments to injection type were based on treatment previously received and dose was adjusted according to the patient's previous treatment response. An optimal treatment included a benefit lasting 3 months or more with side effects lasting 2 weeks or less. Compared to patients receiving bilateral injections, those receiving unilateral injections more frequently noted a benefit of 3 months or more (p = 0.03), side effects of 2 weeks or less duration (p = 0.03), as well as both a 3-month benefit and a 2-week or less side effect (p = 0.0004). Injection type had no effect on optimal Botox dosing with repeat injections. Successive unilateral injections at the same dose were more likely (p = 0.012) than successive bilateral injections to produce the same or longer duration of benefit. We conclude that a unilateral injection routine has a more optimal and consistent treatment effect/side effect profile.


Humidity affects relative ion abundance in direct analysis in real time mass spectrometry of hexamethylene triperoxide diamine.
Unstable explosive hexamethylene triperoxide diamine (HMTD) is dangerous in quantity and benefits from the minimal sampling handling associated with atmospheric pressure chemical ionization for mass spectral analysis. Seasonal variation observed in HMTD mass spectra suggested a humidity dependence. Therefore, direct analysis in real time (DART) ionization mass spectra were acquired at a range of humidity values. An enclosure was designed to fit around the ion source and mass spectrometer inlet at atmospheric pressure. The enclosure was supplied with controlled amounts of humidified air from a test atmosphere generator to create programmable conditions for ambient analysis. The relative abundance and fragmentation of analyte ions were observed to change reliably with changing humidity values and, to a lesser degree, temperature. Humidity at such plasma-based ion sources should be regulated to avoid ∼90% shifts in relative ion abundance and provide stability and reproducibility of HMTD analysis.


Effect of misoprostol versus oxytocin during caesarean section: a systematic review and meta-analysis.
The efficacy of misoprostol versus oxytocin for reducing blood loss during caesarean section remains unclear. To conduct a meta-analysis comparing the efficacy of misoprostol with that of oxytocin in reducing blood loss during caesarean section. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov for randomised controlled trials (RCTs) using the keywords 'misoprostol', 'oxytocin' and 'caesarean section'. Refereed publications examining the efficacy of misoprostol and oxytocin for reducing blood loss during caesarean section. Two of the authors independently abstracted data from original articles. A fixed-effects or random-effects model was used, depending on the heterogeneity of the data, to estimate the risk ratio (RR), risk difference (RD) or weighted mean difference (WMD) with 95% confidence intervals (95% CIs). A total of 646 pregnant women were included in this analysis. There was a significant difference in estimated blood loss between the misoprostol and the oxytocin groups (WMD-64.09; 95% CI-119.86--8.31). However, differences in haemoglobin levels (WMD-0.04; 95% CI-0.18-0.10), additional oxytocic therapy requirements (RD .03; 95% CI -0.04-0.10) and blood transfusion requirements (RD 0.00; 95% CI-0.03-0.02) between the two groups failed to reach statistical significance. The incidence of postoperative shivering/pyrexia was significantly higher in the misoprostol group, compared with the oxytocin group (RR 3.23; 95% CI 1.41-7.39). The results suggest that misoprostol is as effective as oxytocin for reducing blood loss during caesarean section. However, further research into treatment strategies is needed.


Chemical and in vitro study of the potential of 3-(aryl)-2-sulfanylpropenoic acids and their Zn(II) complexes as protective agents against cadmium toxicity.
The free H(2)xspa ligands [xspa = pspa, Clpspa, tspa or fspa where p = 3-(phenyl), Clp = 3-(2-chlorophenyl), t = 3-(2-thienyl), f = 3-(2-furyl) and spa = 2-sulfanylpropenoato], their Zn(II) complexes of formula [HQ](2)[Zn(xspa)(2)] (HQ = diisopropylammonium) and the Cd(II) equivalents were prepared and characterized by elemental analysis and by IR, Raman and NMR ((1)H, (13)C) spectroscopy. X-Ray studies of the crystal structures of [HQ](2)[Zn(pspa)(2)], [HQ](2)[Zn(Clpspa)(2)], [HQ](2)[Zn(tspa)(2)] and [HQ](2)[Zn(fspa)(2)] show that the zinc atom is coordinated to two O atoms and two S atoms of the ligands in a distorted tetrahedral ZnO(2)S(2) environment. In the structures of [HQ](2)[Cd(pspa)(2)] and [HQ](2)[Cd(Clpspa)(2)] the cadmium atom is coordinated to three S atoms and two carboxylato O atoms of the ligands in a distorted trigonal bipyramidal environment. The interchange of ligands between Zn(II) and Cd(II) was studied by (113)Cd NMR spectroscopy. The in vitro protective effect of H(2)xspa and their Zn(II) complexes against Cd toxicity was investigated using the human hepatocarcinoma HepG2 cell line and the pig renal proximal tubule LLC-PK1 cell line. The incorporation of Zn(II) was found to be relevant in the case of H(2)pspa, with an increase observed in the cell viability of the LCC-PK1 cells with respect to the value for the free ligand.


Early introduction of very small amounts of multiple foods to infants: A randomized trial.
We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods. Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837). A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant. Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached.


Effect of Coadministration of Lidocaine on the Pain and Pharmacokinetics of Intramuscular Amikacin in Children With Multidrug-Resistant Tuberculosis: A Randomized Crossover Trial.
Currently recommended treatment for multidrug-resistant (MDR) tuberculosis (TB) includes 4-8 months of an injectable medication, which is poorly tolerated. We evaluated the impact of coadministering lidocaine on pain and pharmacokinetics of intramuscular injections of amikacin in children with MDR-TB. Children 8-18 years of age, receiving amikacin for MDR-TB treatment in Cape Town, South Africa, were eligible for this randomized crossover trial. Participants received a 15 mg/kg dose of intramuscular amikacin with and without additional lidocaine (0.2-0.4 mg/kg) on different days and were randomized to the order of the treatments (the sequence). Participants and staff completing evaluations were blinded to sequence. Samples were drawn predose, and at 1, 2, 4, 6 and 8 hours postdose for measurement of plasma amikacin concentrations. Pain was assessed by participants using the Wong Baker FACES pain scale (0-5) predose, immediately after the injection and then at 30 and 60 minutes. Pharmacokinetic measures were calculated using noncompartmental analysis. Twelve children were included, median age 11.5 years (interquartile range [IQR], 9.9-13.4 years). Participant-reported pain scores immediately after the amikacin injection were lower when lidocaine was coadministered: 1.0 (IQR, 0.5-2.0) with lidocaine versus 2.5 (1.0-4.0) without lidocaine (P = 0.004). The median area under the concentration time curve0-8 and median maximum plasma concentration of amikacin were 109.0 μg × h/mL (IQR, 84.7-121.3) and 36.7 μg/mL (IQR, 34.1-40.5) with lidocaine compared with 103.3 μg × h/mL (IQR, 81.7-135.0; P = 0.814) and 34.1 μg/mL (IQR, 35.6-46.4; P = 0.638) without lidocaine, respectively. The coadministration of lidocaine resulted in reduced pain immediately after the injection and did not alter amikacin area under the concentration time curve or maximum plasma concentration.


Neurological Outcome of Early versus Late Surgery Following Cervical Spinal Cord Injury.
Background There are numerous retrospective studies and a few prospective studies to determine the neurologic outcome after early versus late surgical treatment for cervical spinal cord injury. Objective To compare the neurological outcome between early (within 72 hours after injury) and delayed (≥ 72 hours after injury) surgery in patients with cervical spinal injury. Method This is a retrospective analysis of the neurological outcome of early versus late surgery following cervical spinal cord trauma. Patients meeting appropriate inclusion criteria were divided into an early or a late surgical treatment group. The neurologic outcomes and other complications were recorded up to six months of follow-up. Result Overall, there was a significant difference in neurological status at presentation and at follow-up (p < 0.001). However, there was no statistically significant difference between the early versus late surgery groups (p-value 0.261) in terms of neurological outcome. Complications were found to be higher among those undergoing posterior surgical approach (OR = 23.75; 95% CI 2.65, 212.98) than those with anterior or combined approach (p=0.005). However, multivariate analysis of these variables failed to show any statistically significant difference between the two groups. Conclusion The timing of surgery does not alter the neurological outcomes and the development of complications significantly. The American Spinal Cord Injury Association (ASIA) status at the time of presentation is found to be the single most important factor correlating with the neurological outcome.


Tonofilament-desmosome complex in induced regenerated epidermis in senile elastosis. An electron microscopic study.
This paper presents the ultramicroscopic structure of the epidermis in senile elastosis, and compares it with the structure of an induced regenerated specimen in the same layers. In the regenerated specimen it was found that tonofilament-desmosome complexes have been replaced by a regular twist of villous processes. Such a substitution influences the structure and function of keratinocytes. Newly-formed structures may be established even 10 years after the induction.


Association Between Tooth Loss, Body Mass Index, and All-Cause Mortality Among Elderly Patients in Taiwan.
To date, the effect of tooth loss on all-cause mortality among elderly patients with a different weight group has not been assessed. This retrospective cohort study evaluated the data obtained from a government-sponsored, annual physical examination program for elderly citizens residing in Taipei City during 2005 to 2007, and follow-up to December 31, 2010. We recruited 55,651 eligible citizens of Taipei City aged ≥ 65 years, including 29,572 men and 26,079 women, in our study. Their mortality data were ascertained based on the national death files. The number of missing teeth was used as a representative of oral health status. We used multivariate Cox proportional hazards regression analysis to determine the association between tooth loss and all-cause mortality. After adjustment for all confounders, the hazard ratios (HRs) of all-cause mortality in participants with no teeth, 1 to 9 teeth, and 10 to 19 teeth were 1.36 [95% confidence interval (CI): 1.15-1.61], 1.24 (95% CI: 1.08-1.42), and 1.19 (95% CI: 1.09-1.31), respectively, compared with participants with 20 or more teeth. A significant positive correlation of body mass index (BMI) with all-cause mortality was found in underweight and overweight elderly patients and was represented as a U-shaped curve. Subgroup analysis revealed a significant positive correlation in underweight (no teeth: HR = 1.49, 95% CI: 1.21-1.83; 1-9 teeth: HR = 1.23, 95% CI: 1.03-1.47; 10-19 teeth: HR = 1.20, 95% CI: 1.06-1.36) and overweight participants (no teeth: HR = 1.37, 95% CI: 1.05-1.79; 1-9 teeth: HR = 1.27, 95% CI: 1.07-1.52). The number of teeth lost is associated with an increased risk of all-cause mortality, particularly for participants with underweight and overweight.


Breaking the boundaries: collaborating to develop a model ventilator training program.
Changes in the health care system have created new opportunities for acute care nurses to establish collaborative relationships with their rehabilitation partners. When a rehabilitation facility decided to establish a ventilator weaning rehabilitation program, an acute care facility joined forces with the institution to develop an educational plan for the nursing staff. The development and implementation of the educational program as well as the collaborative relationship established between the two facilities are highlighted in this continuing education article.


Intrapericardial left-sided ectopic thyroid mass supplied by the left circumflex artery.
Intrapericardial left-sided ectopic thyroid tissue is a rare entity. We report a 47-year old female patient with an intrapericardial mass mounting the left atrial wall. Two prominent vessels, both originating from the left circumflex artery (LCX), supplied the tumour. Owing to the compression of the left atrium and the left upper pulmonary vein, the patient was highly symptomatic with exertional dyspnoea and ventricular extrasystoles. Histopathological examination showed regressive thyroid adenoma with no signs of malignancy. Complete resection was feasible. The evaluation of thyroid hormone levels was not indicative for diagnosis. Postoperative hormone substitution appeared to be unnecessary.


Iodine deficiency in pregnant women of Lahore.
To know extent of iodine deficiency (ID), role of thyroid enlargement (goiter) as marker of ID and current status of iodized salt intake in pregnant women of Lahore. A cross sectional study was carried out at Institute of Chemistry, University of the Punjab, during March 2002 to September 2005. Pregnant women (n = 254) during first trimester attending antenatal clinic participated voluntarily. Iodine intake status was determined by urinary iodine (UI) excretion. UI excretion ranged from 34 to 142 microg/L and median value was 67 microg/L. According to international criteria, 202 (79.5%) pregnant women were iodine deficient (UI < 100 microg/L) mostly (68.8%) of mild (UI: 50-99 microg/L) degree. Moderate iodine deficiency (MID; UI < 50 microg/L) was found in 63 (24.8%) pregnant women. Among all pregnant women 80 (31.5%) had slightly visible goiter and only 87 (34.2%) were currently taking iodized salt. The difference in UI excretion between goitrous and non-goitrous pregnant women was not significant. Among iodized salt users percentage of women with MID was less, though not significant, as compared to non-users (20.7% Vs 26.9%). About one-fourth of pregnant women screened in this study are moderately iodine deficient in Lahore. These women and their neonates are at increased risk of iodine deficiency disorders. Goiter is not a good indicator of low iodine intake while iodized salt consumption is beneficial in this regard.


Likability of targets and distractors in facial recognition.
Target and distractor likability were examined in two studies of face memory. Subjects studied faces that had been rated by others as likable or unlikable . The test required subjects to identify the previously studied face in an array of four faces, where the distractor faces were either likable or unlikable . Overall, unlikable targets were more readily recognized than likable targets. In Experiment 2, distractor likability appeared to have little effect on correct recognition when response bias was ruled out. However, in Experiment 2, arrays involving all new faces showed that likable faces were more apt to be falsely identified as targets. In general, these results seem more in accord with an interpretation based on distinctiveness instead of affective responses.


Single-cell RNA-seq with spike-in cells enables accurate quantification of cell-specific drug effects in pancreatic islets.
Single-cell RNA-seq (scRNA-seq) is emerging as a powerful tool to dissect cell-specific effects of drug treatment in complex tissues. This application requires high levels of precision, robustness, and quantitative accuracy-beyond those achievable with existing methods for mainly qualitative single-cell analysis. Here, we establish the use of standardized reference cells as spike-in controls for accurate and robust dissection of single-cell drug responses. We find that contamination by cell-free RNA can constitute up to 20% of reads in human primary tissue samples, and we show that the ensuing biases can be removed effectively using a novel bioinformatics algorithm. Applying our method to both human and mouse pancreatic islets treated ex vivo, we obtain an accurate and quantitative assessment of cell-specific drug effects on the transcriptome. We observe that FOXO inhibition induces dedifferentiation of both alpha and beta cells, while artemether treatment upregulates insulin and other beta cell marker genes in a subset of alpha cells. In beta cells, dedifferentiation and insulin repression upon artemether treatment occurs predominantly in mouse but not in human samples. This new method for quantitative, error-correcting, scRNA-seq data normalization using spike-in reference cells helps clarify complex cell-specific effects of pharmacological perturbations with single-cell resolution and high quantitative accuracy.


Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction.
Plasma free fatty acids (FFA) play important physiological roles in skeletal muscle, heart, liver and pancreas. However, chronically elevated plasma FFA appear to have pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral and hepatic insulin resistance and, while the precise action in the liver remains unclear, a model to explain the role of raised FFA in the development of skeletal muscle insulin resistance has recently been put forward. Over 30 years ago, Randle proposed that FFA compete with glucose as the major energy substrate in cardiac muscle, leading to decreased glucose oxidation when FFA are elevated. Recent data indicate that high plasma FFA also have a significant role in contributing to insulin resistance. Elevated FFA and intracellular lipid appear to inhibit insulin signalling, leading to a reduction in insulin-stimulated muscle glucose transport that may be mediated by a decrease in GLUT-4 translocation. The resulting suppression of muscle glucose transport leads to reduced muscle glycogen synthesis and glycolysis. In the liver, elevated FFA may contribute to hyperglycaemia by antagonizing the effects of insulin on endogenous glucose production. FFA also affect insulin secretion, although the nature of this relationship remains a subject for debate. Finally, evidence is discussed that FFA represent a crucial link between insulin resistance and beta-cell dysfunction and, as such, a reduction in elevated plasma FFA should be an important therapeutic target in obesity and type 2 diabetes.


Influence of seabed on very low frequency sound recorded during passage of merchant ships on the New England shelf.
An examination of the received spectrogram levels of about twenty merchant ship recordings on two vertical line arrays deployed on the New England continental shelf during the Seabed Characterization Experiment 2017 has identified an acoustic feature that can be attributed to the group velocities of modes 1 and 2 being equal at a frequency f=F. The observation of such a feature is a result of βnm(2πF)=∞, where βnm is the waveguide invariant for modes n and m. For the New England Mudpatch, the average value of F is about 24.5 Hz. An effective seabed model is inferred from a feature inversion method that has a deep sediment layer which lies between 190 m and 290 m beneath the seafloor with sound speeds on the order of 1810 m/s. This effective sediment model appears to be consistent with a previous seismic survey on the New England shelf that identified a deep low speed layer about 250 m beneath the water sediment interface.


[The progress and strategy of molecular diagnosis for human genetic diseases].
Recently, the human genome project has progressed and the responsible genes for many diseases have been discovered. Molecular diagnosis based on gene analysis techniques has developed. In this paper, the methods in molecular diagnosis were explained, taking as examples of several pediatric neurological diseases such as GM1- gangliosidosis, fragile X syndrome and congenital myotonic dystrophy. Next, we stressed the importance of the study on the gene function in related to the gene mutation. Finally the strategy to establish the molecular diagnosis of polygenic diseases, such as mental retardation and autism, was considered.


Glioma grading prediction using multiparametric magnetic resonance imaging-based radiomics combined with proton magnetic resonance spectroscopy and diffusion tensor imaging.
To evaluate the efficacy of three-dimensional (3D) segmentation-based radiomics analysis of multiparametric MRI combined with proton magnetic resonance spectroscopy (1 H-MRS) and diffusion tensor imaging (DTI) in glioma grading. A total of 100 patients with histologically confirmed gliomas (grade II-IV) were examined using conventional MRI, 1 H-MRS, and DTI. Tumor segmentations of T1-weighted imaging (T1WI), contrast-enhanced T1WI (T1WI+C), T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC) mapping, and fractional anisotropy (FA) mapping were performed. In total, 396 radiomics features were extracted and reduced using basic tests and least absolute shrinkage and selection operator (LASSO) regression. The selected features of each sequence were combined, and logistic regression with ten-fold cross-validation was applied to develop the grading model. Sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) were compared. The model developed from the training set was applied to the test set to measure accuracy. One optimal grading quantitative parameter was selected for each 1 H-MRS and DTI analysis. A radiomics nomogram model including radiomics signature, quantitative parameters, and clinical features was developed. T1WI+C exhibited the highest grading efficacy among single sequences (AUC, 0.92; sensitivity, 0.89; specificity, 0.85), but the efficacy of the combined model was higher (AUC, 0.97; sensitivity, 0.94; specificity, 0.91). The AUCs of all models exhibited high accuracy, and no significant differences were observed in AUCs between the training and test sets. The visualized nomogram was developed based on the combined radiomics signature and choline (Cho)/N-acetyl aspartate (NAA) from 1 H-MRS. Multiparametric MRI can be used to predict the pathological grading of high-grade gliomas (HGGs) and low-grade gliomas (LGGs) by combining radiomics features with quantitative parameters. The visualized nomogram may provide an intuitive assessment tool in clinical practice. This trial was not registered, as it was a retrospective study and was approved by the local institutional review board.


Antioxidative and anti-inflammatory activities of paeoniflorin and oxypaeoniflora on AGEs-induced mesangial cell damage.
Paeonia suffruticosa, an important traditional herbal medicine, has been reported to prevent the pathogenesis of diabetic nephropathy through modulating advanced glycation end products-induced inflammatory and oxidative stress responses. However, little was known about the protective effect of the two major compounds in P. suffruticosa, paeoniflorin and oxypaeoniflora, on advanced glycation end products-induced mesangial cell damage. In the present study, we investigated the protective activities of paeoniflorin and oxypaeoniflora on advanced glycation end product-induced oxidative stress and inflammation in mesangial cells HBZY-1. The IC50 values of paeoniflorin and oxypaeoniflora for inhibiting 2,2'-azinobis-(3-thylbenzothiazoline-6-sulfonic acid) formation were 4.197 × 10-4 M and 1.002 × 10-4 M, respectively. The pretreatment with paeoniflorin and oxypaeoniflora (10-8-10-4 M) significantly increased advanced glycation end product-induced glutathione peroxidase and catalase activities. In the coculture system of HBZY-1 and macrophages, paeoniflorin and oxypaeoniflora could inhibit remarkably the migration of macrophages. Furthermore, paeniflorin and oxypaeniflora attenuated markedly advanced glycation end products-induced inflammation cytokines interleukin-6 and monocyte chemoattractant protein-1 levels in ELISA and western blot analysis in a dose-dependent manner. Taken together, our data provided the reliable evidence that paeniflorin and oxypaeniflora were able to attenuate advanced glycation end products-induced oxidative damage and inflammation in mesangial cells. Paeniflorin and oxypaeniflora might therefore have a beneficial effect in the treatment of diabetic nephropathy.


Granulosa cell apoptosis by impairing antioxidant defense system and cellular integrity in caprine antral follicles post malathion exposure.
Toxicological studies have demonstrated the exposure-risk relationship of several pesticides on reproduction of living organisms. To evaluate the role of malathion as a reproductive toxicant, this study aims at assessing the cytological and biochemical changes in the granulosa cells after malathion exposure in dose (1 nM, 10 nM, 100 nM) and time (4 h, 6 h, 8 h) dependent manner. Histomorphological analysis, fluorescence assay, apoptosis quantification, and terminal deoxynucleotidyl transferase d-UTP mediated nick end labeling (TUNEL) assay were done to determine cytological changes, whereas antioxidant enzyme assays were done to measure the oxidative stress in malathion treated ovarian antral follicles. Histological studies exhibited the occurrence of highly condensed or marginated chromatin with fragmented nucleus, pyknosis, loss of membrane integrity, increased empty spaces, and vacuolization in malathion treated granulosa cells. Ethidium bromide/acridine orange (EB/AO) fluorescence staining demonstrated a significant increase in incidence and percentage of apoptosis after malathion exposure (p < 0.001), both between and within the groups. Malathion exposure also resulted in increased DNA fragmentation and decline in both antioxidant enzymes activity namely catalase (CAT) and superoxide dismutase (SOD) in granulosa cells of antral follicles. Moreover, there was found a significant negative correlation between the apoptosis incidence and the level of antioxidant enzymes activity, SOD (r = -0.73 p < 0.01) and CAT (r = -0.80 p < 0.01), in malathion treated ovarian antral follicles. Thus, highlighting the role of DNA fragmentation and declining antioxidant level as a possible mechanism underlying malathion induced reproductive toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1944-1954, 2016.


Sex differences in basal and cocaine-induced alterations in PKA and CREB proteins in the nucleus accumbens.
Alterations in protein kinase (PKA) protein levels have been implicated in the regulation of responses to and development of cocaine addiction. However, the contribution of differences in PKA intracellular cascade to the known sex differences in responses to cocaine is not well understood. This study examined whether there are intrinsic or cocaine-induced alterations in PKA-mediated responses, such as phosphorylation of cyclic AMP response element binding protein, in male and female rats. To this end, protein levels of PKA and phosphorylated CREB (pCREB) in the caudate putamen (CPu) and nucleus accumbens (NAc) of male and female rats were measured basally or after acute (one 30-mg/kg intraperitoneal injection) or chronic (twice-daily 15-mg/kg injections for 14 days) cocaine administration. Behavioral responses to both cocaine administration paradigms were also studied. Similar to previous findings, ambulatory, rearing, and stereotypic activities were higher in female rats after acute cocaine administration. Sex differences in cocaine-induced responses were also observed after chronic cocaine administration: While males developed a robust sensitization in ambulatory activities to cocaine, females developed tolerance in cocaine-induced rearing and stereotypic activities. In the basal group, females had significantly higher PKA protein levels in the NAc. Regardless of the cocaine administration paradigm, PKA protein levels in the NAc were higher overall in females than in males. Furthermore, after cocaine administration, while pCREB protein levels in male rats were induced for a longer amount of time than in female rats, the magnitude of change on pCREB levels were higher in female than male rats. However, in the CPu, no sex differences in PKA or pCREB protein levels were observed either in the basal group or after acute or chronic cocaine administration. Taken together, these findings suggest that sex differences in basal and cocaine-induced alterations in the PKA signaling regulation in the NAc may contribute to sex differences in the psychomotor responses to cocaine.


[Research and application of microcontroller system for target controlled infusion].
This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.


Parametric and nonparametric FDR estimation revisited.
Nonparametric and parametric approaches have been proposed to estimate false discovery rate under the independent hypothesis testing assumption. The parametric approach has been shown to have better performance than the nonparametric approaches. In this article, we study the nonparametric approaches and quantify the underlying relations between parametric and nonparametric approaches. Our study reveals the conservative nature of the nonparametric approaches, and establishes the connections between the empirical Bayes method and p-value-based nonparametric methods. Based on our results, we advocate using the parametric approach, or directly modeling the test statistics using the empirical Bayes method.


Nutritional complexity in children with ADHD related morbidities in China: A cross-sectional study.
To assess the general and nutritional health of children with attention deficit/ hyperactivity disorder (ADHD). The National Multicenter Sleep Research Database for 23791 school-age children in grades 1-6 from 9 cities in China was accessed. Children with a specialist diagnosis of ADHD or not (non-ADHD) in 2005 were studied. National anthropometric growth standards for children aged 2-18 years classified children as underweight, wasted, stunted (short stature presumed nutritional), or overweight/obesity. Independent variables were preterm birth, sleep quality and prior disease and ADHD was the dependent variable. Binary logistic regression models were developed along with interaction analyses for associated disorder or disease on overweight/obesity, and stunted. Some 18731 records were analyzed for 808 children with ADHD. The comparative prevalences for ADHD with non-ADHD children were stunted 9.8% vs 5.9% (p<0.001) and overweight/ obesity (32.6% vs 29.6%, p=0.002) respectively. ADHD boys were more often underweight (7.5% vs 5.3%, p=0.027), but not in girls. ADHD likelihood Odds Ratios, ORs (with 95%CI) were for premature birth 1.838, (1.393-2.423), allergic diseases 1.915 (1.526-2.399), otitis media 1.54 (1.118- 2.146), tonsillar or adenoid hypertrophy1.662 (1.348-2.050), gastroesophageal reflux 3.008(1.792-1.792-5.049), and sleep disorder 2.201(1.847-2.623) were ADHD risk factors. Only poor sleep quality and ADHD exhibited an interaction for stunted with OR=0.409 (0.233-0.719). Compromised and complex nutritional health in ADHD children challenges clinical nutrition with a range of health problems, albeit coherent with the needed nutritional emphasis in the 'first 1000 days'.


Selective effects of enucleation and transfer of heterologous nuclei on cytoplasmic organelles in Amoeba proteus.
The ultrastructural changes in the cytoplasm of lethal hybrids obtained by nuclear transplantation between different strains of Amoeba proteus were compared with those of enucleated amebae. It was found that, whereas the Golgi complex and glycocalyx degenerated first in enucleated cells, mitochondria and endosymbiotes became abnormal first in the hybrids. The selective effects are attributed to the presence of nucleic acids in the mitochondria and endosymbiotes and hence to the different interactions they would have with the nuclear genome.


The mitochondrial transcription factor TFAM in neurodegeneration: emerging evidence and mechanisms.
The mitochondrial transcription factor A, or TFAM, is a mitochondrial DNA (mtDNA)-binding protein essential for genome maintenance. TFAM functions in determining the abundance of the mitochondrial genome by regulating packaging, stability, and replication. More recently, TFAM has been shown to play a central role in the mtDNA stress-mediated inflammatory response. Emerging evidence indicates that decreased mtDNA copy number is associated with several aging-related pathologies; however, little is known about the association of TFAM abundance and disease. In this Review, we evaluate the potential associations of altered TFAM levels or mtDNA copy number with neurodegeneration. We also describe potential mechanisms by which mtDNA replication, transcription initiation, and TFAM-mediated endogenous danger signals may impact mitochondrial homeostasis in Alzheimer, Huntington, Parkinson, and other neurodegenerative diseases.


Case report: Novel junctional sarcoplasmic reticulum protein 1 intergenic region-anaplastic lymphoma kinase fusion in a patient with lung adenocarcinoma responds to alectinib.
Novel anaplastic lymphoma kinase (ALK) fusions are still being discovered in non-small cell lung cancer (NSCLC). Most patients with ALK+ NSCLC respond favorably to ALK tyrosine kinase inhibitors. In this case report, we identified a novel nonreciprocal ALK fusion, namely, junctional sarcoplasmic reticulum protein 1 (JSRP1) intergenic region-ALK fusion (Jintergenic: A20) via next-generation sequencing in a female patient initially diagnosed with stage IV B lung adenocarcinoma. Further examination of biopsy specimen and analysis of clinical samples by a multidisciplinary team confirmed the diagnosis of ALK+ NSCLC. At the 2- and 4-months follow-up after receiving alectinib, the patient responded rapidly, implying that alectinib had a remarkable therapeutic effect. We identified a novel JSRP1 intergenic region-ALK fusion as a carcinogenic mutation that responds to alectinib, thereby expanding the spectrum of ALK fusion partners in ALK + NSCLC. This study may help clinicians detect oncogenic mutations and provide timely treatment to patients with ALK+ NSCLC.


Epstein-Barr virus-related cutaneous necrotizing vasculitis in a girl heterozygous for factor V Leiden.
Necrotizing vasculitides are basically characterized by vessel wall neutrophil infiltration and necrosis and they can occur as a primary process or secondary to an underlying disease. Although Henoch-Schönlein purpura (HSp) is the more frequent primary vasculitis in childhood, sometimes it has to be distinguished from other secondary vasculitides induced by infections, drugs, vaccines, or immune-mediated disorders. We report a case of a 14-year-old girl with cutaneous necrotizing vasculitis, appearing in the course of acute Epstein-Barr virus infection. Physical examination revealed highly aching erythematous-purple lesions with reticular edges localized on the back of feet. Pain was non-responsive to ibuprofen and required administration of tapentadol and pregabalin. The patient was also heterozygous for factor V Leiden that might have contributed to the development of cutaneous painful lesions. To our knowledge this is the first documented pediatric case of necrotizing vasculitis associated with acute EBV infection in a girl heterozygous for factor V Leiden. In this patient the severity of skin manifestations might have been influenced by the concomitant factor V Leiden, which gave rise to hypercoagulability and occlusive vasculopathy with markedly severe pain, a symptom rather infrequent in other childhood vasculitides.


Effect of dopamine on vascular reactivity in near-term lamb carotids: role of the endothelium.
Many neonates are diagnosed with hypotension in the first 24 hr of life. Those with severe hypotension are often given high doses of dopamine at 10 to 20 microg/kg/min. This study examined the hypothesis that dopamine, a vasoactive drug commonly used in the neonatal intensive care unit, alters vascular reactivity. Vascular reactivity was measured by comparing 5HT dose-response characteristics in untreated near-term lamb common carotid arteries and arteries treated with 15 microg/kg/min of dopamine. The authors found that dopamine pretreatment for 60 min significantly potentiated 5HT-induced contractile tone by approximately 100% ( p < .05). This observed increase in tone was accompanied by a significant decrease in the affinity of 5HT to its receptor ( p < .05), suggesting an activation of a separate contractile pathway, or a mechanism downstream from agonist-receptor binding. Interestingly, an increase in contractility was observed only in endothelium-intact arteries. In arteries with denuded endothelium, dopamine pretreatment resulted in a small but significant decrease in tone compared to control arteries ( p < .05), suggesting a vasodilatory mechanism unmasked by endothelium removal. Although multiple mechanisms can increase vascular resistance, these data described the in vitro effects of high doses of dopamine on vascular tone as well as the role of the endothelium in dopaminemediated vasoconstriction.


Gene set enrichment analysis and ingenuity pathway analysis of metastatic clear cell renal cell carcinoma cell line.
In recent years, genome-wide RNA expression analysis has become a routine tool that offers a great opportunity to study and understand the key role of genes that contribute to carcinogenesis. Various microarray platforms and statistical approaches can be used to identify genes that might serve as prognostic biomarkers and be developed as antitumor therapies in the future. Metastatic renal cell carcinoma (mRCC) is a serious, life-threatening disease, and there are few treatment options for patients. In this study, we performed one-color microarray gene expression (4×44K) analysis of the mRCC cell line Caki-1 and the healthy kidney cell line ASE-5063. A total of 1,921 genes were differentially expressed in the Caki-1 cell line (1,023 upregulated and 898 downregulated). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) approaches were used to analyze the differential-expression data. The objective of this research was to identify complex biological changes that occur during metastatic development using Caki-1 as a model mRCC cell line. Our data suggest that there are multiple deregulated pathways associated with metastatic clear cell renal cell carcinoma (mccRCC), including integrin-linked kinase (ILK) signaling, leukocyte extravasation signaling, IGF-I signaling, CXCR4 signaling, and phosphoinositol 3-kinase/AKT/mammalian target of rapamycin signaling. The IPA upstream analysis predicted top transcriptional regulators that are either activated or inhibited, such as estrogen receptors, TP53, KDM5B, SPDEF, and CDKN1A. The GSEA approach was used to further confirm enriched pathway data following IPA.


Sickle cell disease and perioperative considerations: review and retrospective report.
To review the current literature on sickle cell disease (SCD) and patient management in the perioperative setting and to retrospectively evaluate the treatment and complications of oral and maxillofacial surgical patients with SCD treated in the Regional Medical Center at Memphis. A literature review was performed, with the main search criteria of SCD, anesthesia, and oral and maxillofacial surgery. In addition, a retrospective record analysis was performed of patients with SCD seen at the Regional Medical Center over 9 years. Criteria recorded included the procedure, type of anesthesia, use of intravenous fluids, thermoregulation (use of warm fluids and blankets covering the patient), supplemental oxygen, antibiotic prophylaxis, and postoperative complications. In total, 33 clinic visits were reviewed, with 29 patients and 21 procedures performed. Patients were managed quite differently each time, with no consistent protocol. Intravenous fluids were used in only 9 of 21 procedures, supplemental oxygen was recorded for 11 of 21 patients, and preoperative antibiotics were given to 14 of 21 patients. A small sample and the lack of an established protocol did not provide significant statistics. Patients with SCD are at risk for various perioperative complications, and it is imperative that the surgeons be educated and prepared so they can effectively manage these patients. No significant complications were found through the outpatient treatment of patients with SCD in this analysis. It may be concluded that treating patients with SCD in the outpatient setting is not contraindicated and may be a safe alternative to inpatient treatment or no treatment at all.


Sex-dependent aberrant PFC development in the adolescent offspring rats exposed to variable prenatal stress.
Adolescence is a remarkable period of brain development. Prenatal stress can increase the risk of various neuropsychiatric disorders. This research investigated neurochemical and behavioural changes in the offspring rats (especially adolescences) who were treated with repeated variable prenatal stress (PNS) during the third week of gestation. The study tested the concentration of brain-derived neurotrophic factor (BDNF), cluster of differentiation 68 (CD68), synaptotagmin-1(Syt-1), 5-hydroxytryptamine (5-HT), dopamine (DA), glucocorticoid receptors (GRs) and oestrogen receptors (ERs) in the PFC (prefrontal cortex). We also tested prepulse inhibition (PPI) of the acoustic startle reflex (ASR) (a measure of sensorimotor gating). The main results were as follows: PNS increased the BDNF and CD68 concentrations in adolescent females, and increased the Syt-1 concentration in adolescent males. The increases in BDNF/CD68 concentration (in females) and Syt-1/DA concentration (in males) with age were disturbed by PNS, and PNS changed the sex differences in CD68 concentration in adolescence and disturbed the sex differences in the Syt-1 concentration (in adolescence) and DA concentration (in adults). In conclusion, we found that PNS lead to Sex-dependent aberrant PFC development, and might accelerate the development of the adolescent PFC, and so that lessened the age difference (between adolescence and adulthood) and the sex difference.


A crossover study on lipid and weight changes associated with olanzapine and risperidone.
The results from case-control and retrospective studies revealed that olanzapine might be associated with more increased risks of metabolic dysfunction than risperidone. The crossover design can minimize the influence of individual variation in metabolic profiles and demographic variables, such as age, sex, concomitant medication use and personal life styles. We design a crossover study to evaluate the metabolic effect of olanzapine and risperidone. Fifteen schizophrenic patients were shifted from olanzapine and risperidone or from risperidone and olanzapine due to poor treatment response. The body weights, lipid profiles and fasting glucose levels were assessed before medication switch and 3 months after crossover. In the seven patients taking risperidone at the time of inclusion (risperidone-first group), after shifting to olanzapine, there was a significant increase in triglyceride level (p=0.048) and body weight (p=0.008). In the other eight patients (olanzapine-first group), after shift to risperidone, there was a decrease in triglyceride level (p=0.009), body weight (p=0.049) and body mass index (BMI; p=0.04). When comparing the metabolic profiles in all patients after olanzapine and after risperidone (irrespective of the order of treatment), the mean triglyceride level (p=0.001), body weight (p=0.001) and BMI (p=0.015) were significantly higher in patients receiving olanzapine than in those receiving risperidone. Furthermore, there was a small increase in total cholesterol level (p=0.091) and a small decrease in high-density lipoprotein (HDL) level (p=0.061) in olanzapine group, but the differences did not reach a significant level. There was no significant difference between olanzapine and risperidone in fasting glucose and low-density lipoprotein (LDL). This study confirms that elevated levels of triglyceride and body weight could be associated with the use of olanzapine as compared with risperidone. The changes in body weights and lipid profiles should be closely monitored in patients during treatment with atypical antipsychotic drugs.


Adaptive defence-related changes in the metabolome of Sorghum bicolor cells in response to lipopolysaccharides of the pathogen Burkholderia andropogonis.
Plant cell suspension culture systems are valuable for the study of complex biological systems such as inducible defence responses and aspects of plant innate immunity. Perturbations to the cellular metabolome can be investigated using metabolomic approaches in order to reveal the underlying metabolic mechanism of cellular responses. Lipopolysaccharides from the sorghum pathogen, Burkholderia andropogonis (LPSB.a.), were purified, chemically characterised and structurally elucidated. The lipid A moiety consists of tetra- and penta-acylated 1,4'-bis-phosphorylated disaccharide backbone decorated by aminoarabinose residues, while the O-polysaccharide chain consists of linear trisaccharide repeating units of [→2)-α-Rha3CMe-(1 → 3)-α-Rha-(1 → 3)-α-Rha-(1 → ]. The effect of LPSB.a. in triggering metabolic reprogramming in Sorghum bicolor cells were investigated using untargeted metabolomics with liquid chromatography coupled to mass spectrometry detection. Cells were treated with LPSB.a. and the metabolic changes monitored over a 30 h time period. Alterations in the levels of phytohormones (jasmonates, zeatins, traumatic-, azelaic- and abscisic acid), which marked the onset of defence responses and accumulation of defence-related metabolites, were observed. Phenylpropanoids and indole alkaloids as well as oxylipins that included di- and trihydroxyoctadecedienoic acids were identified as signatory biomarkers, with marked secretion into the extracellular milieu. The study demonstrated that sorghum cells recognise LPSB.a. as a 'microbe-associated molecular pattern', perturbing normal cellular homeostasis. The molecular features of the altered metabolome were associated with phytohormone-responsive metabolomic reconfiguration of primary and secondary metabolites originating from various metabolic pathways, in support of defence and immunity.


Cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis A virus infected fibroblasts.
The role of Natural Killer (NK) cells, Lymphokine Activated Killer (LAK) cells and the induction of cytokines in the hepatocellular injury of hepatitis A were studied in vitro using a 51Cr release assay in hepatitis A virus (HAV) infected MRC-5 cells (MRC-HAV). When fresh peripheral mononuclear cells (PBMC) from healthy, anti-HAV antibody (-) and (+) human donors, or patients with acute hepatitis A were used as effector cells, MRC-HAV were lysed more extensively than uninfected cells. Similarly, in models using recombinant interleukin-2 (rIL-2) pretreated PBMC from HAV antibody (-) and (+) donors or patients with hepatitis A as effector cells, MRC-HAV were lysed more extensively than uninfected MRC. Both fresh PBMC and rIL-2 pretreated PBMC from anti-HAV antibody (+) donor lysed MRC-HAV cells more effectively than PBMC collected from anti-HAV antibody (-) patients. PBMC from patients with hepatitis A during the acute phase demonstrated more severe lysis of both uninfected MRC and MRC-HAV target cells. However, MRC-HAV lysis was enhanced to a greater degree. In an attempt to identify which cells were involved in cell lysis, cytotoxicity assays were performed by separating PBMC by cell sorter using monoclonal antibodies against all T cells, NK and B-cell fractions and culturing each with supplemental rIL-2. The NK cell fraction selectively destroyed MRC-HAV, but the lytic activity of both the pan T-cell and B-cell fractions was too weak to demonstrate any significant difference. Therefore, NK-LAK cells appeared to play a more significant role in cytolysis than did T-LAK cells. Morphologic observations of cellular damage were accomplished with PBMC obtained from healthy anti-HAV antibody (+) donors. PBMC were suspended in media containing rIL-2 and incubated for 4 days on monolayers of uninfected MRC and MRC-HAV. IFN-alpha and IFN-gamma in the supernatant of the cultured media were simultaneously assayed. Severe damage to HAV-infected cells was observed. Moreover, strong induction of IFN-alpha and IFN-gamma was found with high levels measured in the supernatant. Therefore, it is likely that non-specific immune mechanisms involving NK and LAK cells play a central role in hepatocellular damage prior to the initiation of damage due to Cytotoxic T Lymphocytes (CTL).


Differentiation of Essential Oils Using Nanofluidic Protein Post-Translational Modification Profiling.
Current methods for the authentication of essential oils focus on analyzing their chemical composition. This study describes the use of nanofluidic protein post-translational modification (PTM) profiling to differentiate essential oils by analyzing their biochemical effects. Protein PTM profiling was used to measure the effects of four essential oils, copaiba, mandarin, Melissa, and turmeric, on the phosphorylation of MEK1, MEK2, and ERK1/2 in the MAPK signaling pathway; Akt and 4EBP1 in the pI3K/Akt/mTOR signaling pathway; and STAT3 in the JAK/STAT signaling pathway in cultured HepG2 cells. The gain or loss of the phosphorylation of these proteins served as direct read-outs for the positive or negative regulatory effects of essential oils on their respective signaling pathways. Furthermore, protein PTM profiling and GC-MS were employed side-by-side to assess the quality of the essential oils. In general, protein PTM profiling data concurred with GC-MS data on the identification of adulterated mandarin, Melissa, and turmeric essential oils. Most interestingly, protein PTM profiling data identified the differences in biochemical effects between copaiba essential oils, which were indistinguishable with GC-MS data on their chemical composition. Taken together, nanofluidic protein PTM profiling represents a robust method for the assessment of the quality and therapeutic potential of essential oils.


Risk of Cardiovascular Disease in an Aging HIV Population: Where Are We Now?
With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population. The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking), toxicities associated with cumulative exposure to some antiretroviral agents, together with persistent chronic inflammation, and immune activation associated with HIV infection. Tools are available to calculate an individual's predicted risk of CVD and should be incorporated in the regular follow-up of HIV-infected patients. Targeted interventions to reduce this risk must be recommended, including life-style changes and medical interventions that might include changes in antiretroviral therapy.


Catalase catalyzes of peroxynitrite-mediated phenolic nitration.
Catalase catalyzed the peroxynitrite-mediated nitration of 4-hydroxyphenylacetic acid. The curve for the pH dependence of nitration was similar to that for the reaction between peroxynitrite and phenol. Cyanide, azide, and 3-amino-1,2,4-triazole inhibited the nitration in a dose-dependent way. When catalase was mixed with peroxynitrite, Compound I was detected as an intermediate. Because azide was an electron donor for the peroxidatic action of catalase, and because 3-amino-1,2,4-triazole inhibited catalase activity by binding with Compound I, peroxynitrite-mediated phenolic nitration was probably accompanied by Compound I formation. Both catalase and superoxide dismutase protected Escherichia coli from peroxynitrite toxicity.


The fixed combination of valerian and hops (Ze91019) acts via a central adenosine mechanism.
The aim of the study was to demonstrate competition between caffeine and a fixed valerian/hop extract combination (Ze91019) by the central adenosine mechanism. EEG was used to describe the action of caffeine on the central nervous system after oral administration (200 mg) in healthy volunteers. In addition to caffeine, the volunteers (16 in each group) received either placebo or verum (2 and 6 tablets containing the valerian/hop extract). The EEG responses were recorded every 30 min thereafter. The verum medication was capable of reducing (2 tablets) or inhibiting (6 tablets) the arousal induced by caffeine. This pharmacodynamic action was observed 60 minutes after oral administration, indicating not only competition between the antagonist caffeine and the partial agonist, i. e., the valerian/hop extract but also bio-availability of the compound(s) responsible for the agonistic action. In conclusion, the valerian/hop extract acts via a central adenosine mechanism which is possibly the reason for its sleep-inducing and -maintaining activity.


The Co-Twin Control Design: Implementation and Methodological Considerations.
Establishing causal relationships in observational studies is an important step in research and policy decision making. The association between an exposure and an outcome can be confounded by multiple factors, often making it hard to draw causal conclusions. The co-twin control design (CTCD) is a powerful approach that allows for the investigation of causal effects while controlling for genetic and shared environmental confounding factors. This article introduces the CTCD and offers an overview of analysis methods for binary and continuous outcome and exposure variables. Tools for data simulation are provided, along with practical guidance and accompanying scripts for implementing the CTCD in R, SPSS, and Stata. While the CTCD offers valuable insights into causal inference, it depends on several assumptions that are important when interpreting CTCD results. By presenting a broad overview of the CTCD, this article aims to equip researchers with actionable recommendations and a comprehensive understanding of the design's strengths and limitations.


Orthostatic headaches without CSF leak in postural tachycardia syndrome.
Four women age 17 to 28 years presented with orthostatic headaches as the most prominent feature of their symptom complex. None had CSF leak or intracranial hypotension. Autonomic studies showed evidence of orthostatic intolerance with tachycardia in all cases. Treatment of orthostatic intolerance, mainly with volume expansion, was only partially effective. Orthostatic headaches are not always caused by CSF leak or supine intracranial hypotension. Occasionally they may be the major clinical manifestation of postural tachycardia syndrome or orthostatic intolerance.


Sensitivity of cultured human and mouse fibroblasts to trichothecenes.
Cultured human diploid fibroblasts and a cloned permanent line of Swiss mouse fibroblasts (3T3) have been adapted to a biological assay of trichothecenes and other toxic fungal metabolites both in purified form and as crude extracts. The assays are carried out in multi-well tissue culture trays with serial dilutions of toxins in 200 microL volumes of medium. Cells are cultured with the toxins for 3-4 days, fixed, and stained, providing a permanent record of results. The sensitivity of the assay ranges from 0.1 ng/mL (20 pg/assay) for T-2 toxin on mouse fibroblasts to no detectable toxicity at 5 micrograms/mL for cis-zearalenone and verrucarol. Human skin fibroblasts exhibit patterns of relative sensitivities similar to that observed with mouse fibroblasts, but the absolute sensitivities are much greater with mouse fibroblasts because they can be cultured at much lower cell densities.


Changes in serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy.
The clinical significance of serum apolipoprotein A-1 levels as an indicator of hepatic protein synthesis after hepatectomy was investigated. A total of 50 patients who had undergone hepatectomy at our department from 1997 to 1999 were selected for this study. The serum levels of apolipoprotein A-1, indocyanine green dye retention at 15 minutes, lectin-cholesterol acyltransferase, prealbumin, and high-density lipoprotein cholesterol were measured in these patients preoperatively and on postoperative days 7 and 14. The type of hepatic resection conducted was partial resection in 13 cases, subsegmentectomy in 13 cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the patients tolerated the operation, and none of the cases had any severe complications, such as liver failure. In most cases, the serum apolipoprotein A-1 levels decreased on postoperative day 7 and recovered by day 14. There were no significant differences in the changes in apolipoprotein A-1 levels between patients with the individual types of operative procedures. The serum apolipoprotein A-1 levels showed significant correlations with the serum high-density lipoprotein cholesterol, lectin-cholesterol acyltransferase and prealbumin levels on postoperative days 7 and 14; however, there was no significant correlation with the indocyanine green retention test. When the cases were divided into three groups according to the serum level of apolipoprotein A-1 on postoperative day 7 (group A: over 81 mg/dl, group B: 61-80 mg/dl, group C: under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin-cholesterol acyltransferase and high-density lipoprotein cholesterol levels in group C were significantly lower than those in group A on postoperative day 7. On the basis of these results, it is suggested that the pattern of changes in the serum apolipoprotein A-1 levels may be a good indicator of the hepatic protein synthetic ability during the perioperative period after hepatectomy.


Canine pancreatic polypeptide complementary deoxyribonucleic acid sequence: pancreatic polypeptide and insulin messenger ribonucleic acid distribution in the lobes of the pancreas.
The structure of the canine prepropancreatic polypeptide (preproPP) cDNA was determined. The nucleotide sequence conservation between human and canine preproPP is very high for the signal peptide (82%) and the region coding for the 36 amino acid pancreatic polypeptide (PP) (92%). The overall sequence homology for the C-terminal portion of proPP containing the icosapeptide and a C-terminal extension peptide is only 63% whereas the 3'-untranslated regions of human and canine PP mRNA share 73% homology after alignment for maximal homology. The only sequence conservation in icosapeptide is the region coding for the last 10 amino acids of the icosapeptide. Comparison of PP immunoactivity and PP mRNA concentrations in extracts of the developmentally distinct uncinate process and splenic lobes of the canine pancreas revealed the same ratio of mRNA concentrations (16 +/- 6.5) and PP peptide concentrations (18 +/- 7.0) in the uncinate process compared to the splenic lobe (n = 6). However, a similar comparison of insulin C-peptide (CP) immunoactivity and insulin mRNA concentration revealed a smaller ratio of CP immunoactivity (0.37 +/- 0.05) than insulin mRNA (0.58 +/- 0.10) between the same lobes (P less than 0.0074, n = 6). This increased steady state CP concentration relative to insulin mRNA in splenic lobe compared to the uncinate process was not observed for PP peptide and mRNA.