Expression of basigin, an inducer of matrix metalloproteinases, in the rat ovary.
The extensive tissue remodeling that occurs during follicular development, ovulatory rupture, and the formation and regression of the corpus luteum (CL) requires local degradation of the extracellular environment by matrix metalloproteinases (MMPs). This report characterizes the expression pattern of basigin (Bsg), a putative regulator of MMP induction, in the rat ovary. An induced superovulation model (eCG/hCG) was used in immature rats to evaluate Bsg expression profiles in ovaries collected during the follicular phase, the preovulatory period, and the luteal lifespan. Levels of Bsg mRNA were unchanged through follicular growth (0-48 h post-eCG) and increased during postovulatory luteinization (24 and 48 h post-hCG; P < 0.01). Bsg expression persisted into pseudopregnancy (4-8 days post-hCG) and after functional luteal regression (12 days post-hCG). The profile of Bsg expression during regression of the CL was examined using a model of induced luteolysis. Both functional and structural regression was associated with a decline in Bsg expression levels. Bsg mRNA and protein localized to the theca of preovulatory follicles (12 h post-hCG) and formative and functional CL (24 h-8 days post-hCG). Bsg expression profiles in the induced ovulation and CL regression models were similar to observations made in naturally cycling mature rats. In the cycling ovary, Bsg signaling localized to newly forming CL, the theca of preovulatory follicles, and appeared to be lower in CL from previous estrous cycles. A putative regulatory mechanism of Bsg expression was identified using an in vitro model; treatment of cultured granulosa cells with hCG significantly augmented Bsg mRNA expression levels. The processes of ovulation and luteogenesis may be facilitated by Bsg expression and its induction or regulation of the MMPs.


Provider-Level Variation in Treatment Planning of Radiation Oncology Procedures in the United States.
Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them. The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non-facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population. Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, P < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, P < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, P < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, P = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, P = .02). Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.


A socio-technical approach to improving retail energy efficiency behaviours.
In recent years, the UK retail sector has made a significant contribution to societal responses on carbon reduction. We provide a novel and timely examination of environmental sustainability from a systems perspective, exploring how energy-related technologies and strategies are incorporated into organisational life. We use a longitudinal case study approach, looking at behavioural energy efficiency from within one of the UK's leading retailers. Our data covers a two-year period, with qualitative data from a total of 131 participants gathered using phased interviews and focus groups. We introduce an adapted socio-technical framework approach in order to describe an existing organisational behavioural strategy to support retail energy efficiency. Our findings point to crucial socio-technical and goal-setting factors which both impede and/or enable energy efficient behaviours, these include: tensions linked to store level perception of energy management goals; an emphasis on the importance of technology for underpinning change processes; and, the need for feedback and incentives to support the completion of energy-related tasks. We also describe the evolution of a practical operational intervention designed to address issues raised in our findings. Our study provides fresh insights into how sustainable workplace behaviours can be achieved and sustained over time. Secondly, we discuss in detail a set of issues arising from goal conflict in the workplace; these include the development of a practical energy management strategy to facilitate secondary organisational goals through job redesign.


Total heart replacement using dual intracorporeal continuous-flow pumps in a chronic bovine model: a feasibility study.
Continuous-flow pumps are small, simple, and respond physiologically to input variations, making them potentially ideal for total heart replacement. However, the physiological effects of complete pulseless flow during long-term circulatory support without a cardiac interface or with complete cardiac exclusion have not been well studied. We evaluated the feasibility of dual continuous-flow pumps as a total artificial heart (TAH) in a chronic bovine model. Both ventricles of a 6-month-old Corriente crossbred calf were excised and sewing rings attached to the reinforced atrioventricular junctions. The inlet portions of 2 Jarvik 2000 pumps were positioned through their respective sewing rings at the mid-atrial level and the pulseless atrial reservoir connected end-to-end to the pulmonary artery and aorta. Pulseless systemic and pulmonary circulations were thereby achieved. Volume status was controlled, and systemic and pulmonary resistance were managed pharmacologically to keep mean arterial pressures at 100+/-10 mmHg (systemic) and 20+/-5 mmHg (pulmonary) and both left and right atrial pressures at 15+/-5 mmHg. The left pump speed was maintained at 14,000 rpm and its output autoregulated in response to variations in right pump flow, systemic and pulmonary pressures, fluid status, and activity level. Hemodynamics, end-organ function, and neurohormonal status remained normal. These results suggest the feasibility of using dual continuous-flow pumps as a TAH.


Analysis of Volatile Components in Rosa roxburghii Tratt. and Rosa sterilis Using Headspace-Solid-Phase Microextraction-Gas Chromatography-Mass Spectrometry.
Volatile organic compounds (VOCs) and flavor characteristics of Rosa roxburghii Tratt. (RR) and Rosa sterilis (RS) were analyzed using headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS). The flavor network was constructed by combining relative odor activity values (ROAVs), and the signature differential flavor components were screened using orthogonal partial least squares discriminant analysis (OPLS-DA) and random forest (RF). The results showed that 61 VOCs were detected in both RR and RS: 48 in RR, and 26 in RS. There were six key flavor components (ROAVs ≥ 1) in RR, namely nonanal, ethyl butanoate, ethyl hexanoate, (3Z)-3-hexen-1-yl acetate, ethyl caprylate, and styrene, among which ethyl butanoate had the highest contribution, whereas there were eight key flavor components (ROAVs ≥ 1) in RS, namely 2-nonanol, (E)-2-hexenal, nonanal, methyl salicylate, β-ocimene, caryophyllene, α-ionone, and styrene, among which nonanal contributed the most to RS. The flavor of RR is primarily fruity, sweet, green banana, and waxy, while the flavor of RS is primarily sweet and floral. In addition, OPLS-DA and RF suggested that (E)-2-hexenal, ethyl caprylate, β-ocimene, and ethyl butanoate could be the signature differential flavor components for distinguishing between RR and RS. In this study, the differences in VOCs between RR and RS were analyzed to provide a basis for further development and utilization.


Recommended curriculum for subspecialty training in transplant infectious disease on behalf of the American Society of Transplantation Infectious Diseases Community of Practice Educational Initiatives Working Group.
The American Society of Transplantation Infectious Diseases (ID) Community of Practice has established an education workgroup to identify core components of a curriculum for training specialists in transplant ID. Clinical, laboratory, and research training form the triad of components on which an additional year of ID training, dedicated to the care of solid organ and hematopoietic stem cell transplant recipients, should be based. The recommended training environment would have access to adequate numbers of transplant patients, along with qualified faculty committed to teaching specialized fellows in this area. The learning objectives for both inpatient and outpatient clinical training are presented. The laboratory component requires trainees to attain expertize in utilizing and interpreting cutting-edge diagnostics used in transplant medicine. The research component may involve basic science, and translational or clinical research individualized to the trainee. Finally, suggestions for evaluation of both the fellows and the training program are provided.


Widely contrasting outcomes from the use of tris(pentafluorophenyl)bismuth or pentafluorophenylsilver as oxidants in the reactions of lanthanoid metals with N,N'-diarylformamidines.
Reactions of lanthanoid metals with tris(pentafluorophenyl)bismuth or pentafluorophenylsilver and two widely disparate formamidines, N,N'-bis(2,6-difluorophenyl)formamidine (DFFormH) and N,N'-bis(2,6-diisopropylphenyl)formamidine (DippFormH) have been investigated as possible redox transmetallation/protolysis (RTP) syntheses of lanthanoid formamidinates. Thus, [Ln(DFForm)3(thf)] (Ln = Lu, 1, Yb, 2, Tm, 3, Er, 4, Ho, 5, Dy, 6; thf = tetrahydrofuran), [Ln(DFForm)3(thf)2] (Ln = Tb, 7, Gd, 8, Sm, 9, Nd, 10), and [Yb(DippForm)2(thf)2]·2thf (11) complexes were obtained from an excess of lanthanoid metals, [Bi(C6F5)3]·0.5diox (diox = 1,4-dioxane) and the appropriate formamidine. Reaction of neodymium and [Bi(C6F5)3]·0.5diox with the bulkier DippFormH in thf resulted in C-F activation and formation of [Nd(DippForm)2F(thf)2] (12) and o-HC6F4O(CH2)4N(Dipp)CH[double bond, length as m-dash]N(Dipp) (Dipp = 2,6-di-isopropylphenyl). Although the reaction of erbium and [Bi(C6F5)3]·0.5diox with DippFormH was not complete after one week (by 19F NMR), use of [Hg(C6F5)2] instead of [Bi(C6F5)3]·0.5diox resulted in C-F activation and formation of [Er(DippForm)2F(thf)] (13) and o-HC6F4O(CH2)4N(Dipp)CH[double bond, length as m-dash]N(Dipp) in two days. Attempted RTP reactions between lanthanoid metals, AgC6F5 and DFFormH in thf gave [Ag2(DFForm)2]·3thf (14), except in the case of ytterbium. All other lanthanoid metals required activation by I2 (2%) before lanthanoid complex formation could be achieved. From these reactions, lanthanoid formamidinates, [Ln(DFForm)2(solv)I] (Ln = Lu, 15, Tm, 16, Er, 17, Tb, 18, Gd, 19), [Ln(DFForm)3(py)] (Ln = Er, 17a, Tb, 18a; py = pyridine), and [Nd(DFForm)3(thf)2]·thf (10) were obtained. Where two types of lanthanoid formamidinates [Ln(DFForm)3(py)] and [Ln(DFForm)2(solv)I] were obtained from the Ln metals activated by I2, they could not be separated on preparative scale. From Yb, the peroxide-bridged complex, [Yb2(DippForm)2(O2)2(py)4] (20) was surprisingly isolated. Thus [Bi(C6F5)3]·0.5diox has potential as an oxidative replacement for diarylmercurials in RTP syntheses of lanthanoid formamidinates but [AgC6F5(py)] does not.


Patterns of noncompliance in adolescent field-based accelerometer research.
The primary purpose of this study was to investigate patterns of noncompliance in an adolescent field based accelerometer study. A further purpose was to investigate the effect of a cost efficient strategy (SMS reminder message) on the compliance of adolescents The research carried out in 2010 involved 117 second level students (12.41 ± .53 yrs) from 4 schools in a rural Irish town. The Actigraph accelerometer data were processed over 7 days to determine compliance level. Students were more likely to remove their monitor in the evening period than at any other time, however if students removed their monitor after school it remained unworn for a significantly longer duration than in any other time period. Students who received a SMS message were significantly more likely (P = .008) to wear their monitor in the morning than those that did not. Sending an SMS message each morning is effective for improving the number of students wearing monitors to school. The after school period is a critical period for nonwear time and should be targeted in future studies wishing to improve compliance.


Multi-colour light emission from InGaN nanowires monolithically grown on Si substrate by MBE.
InGaN nanostructures are among the most promising candidates for visible solid-state lighting and renewable energy sources. To date, there is still a lack of information about the influence of the growth conditions on the physical properties of these nanostructures. Here, we extend the study of InGaN nanowires growth directly on Si substrates by plasma-assisted molecular beam epitaxy. The results of the study showed that under appropriate growth conditions a change in the growth temperature of just 10 °C leads to a significant change in the structural and optical properties of the nanowires. InGaN nanowires with the areas containing 4%-10% of In with increasing tendency towards the top are formed at the growth temperature of 665 °C, while at the growth temperatures range of 655 °C-660 °C the spontaneously core-shell NWs are typically presented. In the latter case, the In contents in the core and the shell are about an order of magnitude different (e.g. 35% and 4% for 655 °C, respectively). The photoluminescence study of the NWs demonstrates a shift in the spectra from blue to orange in accordance with an increase of In content. Based on these results, a novel approach to the monolithic growth of InxGa1-xN NWs with multi-colour light emission on Si substrates by setting a temperature gradient over the substrate surface is proposed.


Immunohistochemistry of the circadian clock in mouse and human vascular tissues.
The circadian clock is a molecular network that controls the body physiological rhythms. In blood vessels, the circadian clock components modulate vascular remodeling, blood pressure, and signaling. The goal in this study was to determine the pattern of expression of circadian clock proteins in the endothelium, smooth muscle, and adventitia of the vasculature of human and mouse tissues. Immunohistochemistry was performed in frozen sections of mouse aorta, common carotid artery, femoral artery, lung, and heart at 12 AM and 12 PM for Bmal1, Clock, Npas2, Per and other clock components. Studies of expression were also assessed in human saphenous vein both by immunoblotting and immunohistochemistry. In this study, we identified the expression of Bmal1, Clock, Npas, Per1, Cry1, and accessory clock components by immunohistochemical staining in the endothelium, smooth muscle and adventitia of the mouse vasculature with differing temporal and cellular profiles depending on vasculature and tissue analyzed. The human saphenous vein also exhibited expression of clock genes that exhibited an oscillatory pattern in Bmal1 and Cry by immunoblotting. These studies show that circadian clock components display differences in expression and localization throughout the cardiovascular system, which may confer nuances of circadian clock signaling in a cell-specific manner.


Developing nutritional component chrysin as a therapeutic agent: Bioavailability and pharmacokinetics consideration, and ADME mechanisms.
Chrysin is a promising naturally occurring flavonoid mainly found in honey and propolis. Although chrysin's biological activities have been demonstrated and the mechanism of actions has been determined using in vitro and in vivo models, results from the current clinical studies were largely negative. A potential reason for chrysin's low efficacy in humans is poor oral bioavailability. In this paper, we reviewed the preclinical and clinical pharmacokinetics studies of chrysin and analyzed the mechanism of poor in vivo efficacy with emphasis on its bioavailability and ADME mechanism. Low aqueous solubility, rapid metabolism mediated by UGTs and SULT, efficient excretion through efflux transporters including BCRP and MRP2 are the major reasons causing poor systemic bioavailability for chrysin. However, because of efficient enterohepatic recycling facilitated by phase II metabolism and efflux, chrysin's bioavailability in the low GI tract is high. Thus, chrysin can be ideal for treating diseases in the terminal ileum and colon (e.g., carcinoma, local infection) since it is localized in the lower GI tract with limited delivery to other organs.


Neuroanatomy of body weight control: lessons learned from leptin.
Rather than arising from the passive accumulation of excess calories, obesity is a state in which the biologically defended level of body fat stores increases due to defects in the homeostatic process that matches food intake and energy expenditure over time. By deleting leptin receptors from distinct brain regions and neuronal subsets, researchers are beginning to identify the neuroanatomical substrates responsible for this regulation. In this issue of the JCI, Scott et al. demonstrate that loss of leptin receptors in a subset of hindbrain neurons increases food intake in mice, but, unlike what is observed when leptin receptors are deleted from hypothalamic neurons, these mice compensate by increasing energy expenditure and hence do not become obese. Although many brain areas can regulate energy intake and/or energy expenditure, it is likely that only a small subset of neurons actively matches the two over time. It is vital to clarify how this works if we are to improve our understanding of obesity pathogenesis and options available for its treatment.


The unusual quadruple bonding of nitrogen in ThN.
Nitrogen has five valence electrons and can form a maximum of three shared electron-pair bonds to complete its octet, which suggests that its maximum bond order is three. With a joint anion photoelectron spectroscopy and quantum chemistry investigation, we report herein that nitrogen presents a quadruple bonding interaction with thorium in ThN. The quadruple Th≣N bond consists of two electron-sharing Th-N π bonds formed between the Th-6dxz/6dyz and N 2px/2py orbitals, one dative Th←N σ bond and one weak Th←N σ bonding interaction formed between Th-6dz2 and N 2s/2pz orbitals. The ThC molecule has also been investigated and proven to have a similar bonding pattern as ThN. Nonetheless, due to one singly occupied σ-bond, ThC is assigned a bond order of 3.5. Moreover, ThC has a longer bond length as well as a lower vibrational frequency in comparison with ThN.


The interface of primary and oncology specialty care: from symptoms to diagnosis.
Symptomatic individuals presenting to their primary care providers may need further evaluation and/or testing to determine whether a cancer is present. A number of issues arise in determining who needs further testing, what tests are needed, which specialists need to be involved, and how the testing can be organized and supported within a specific health-care system within a timely, coordinated, and cost-efficient manner. This article explores the challenges in the interface of primary care providers and specialists, includes evidence from prior research, and proposes research opportunities to understand and improve this phase of care.


Ex vivo comparison of single-layer and double-layer laparoscopic closure of equine bladders with 2 types of barbed sutures.
To compare laparoscopic single-layer versus double-layer closure of experimental, full-thickness incisions in adult equine urinary bladders using unidirectional and bidirectional barbed suture. Experimental, ex vivo, surgical study. Thirty adult equine cadaver urinary bladders. Bladders were randomly divided into 5 groups (n = 6): intact controls, bladders sutured with unidirectional or bidirectional barbed suture in a single-layer closure, and bladders sutured with unidirectional or bidirectional barbed suture in a double-layer closure. A 5-cm apical incision was created in each bladder assigned to a suture group, prior to closure in a laparoscopic trainer. After suturing, bursting pressures (BPs) were determined by filling the bladders with saline to failure. Continuous variables were compared among groups using generalized linear modeling with post hoc testing between groups, and categorical variables were compared using Fisher's exact test. Significance was set at P < .05. No difference in BP was detected between treatment groups, all failing at pressures lower than those of intact bladders. The 95% confidence interval for BPs exceeded a physiologically relevant threshold of 30 mm Hg after single-layer or double-layer closure. Irrespective of treatment group, surgical time decreased with experience, and the rate of reduction was greater for the single-layer than the double-layer closures. In this ex vivo study, both closure techniques and both suture types appeared to be acceptable for laparoscopic closure of the urinary bladder in adult horses.


[Immunomodulating effect of lysozyme in acute cold stress].
It was shown that lysozyme (1 or 5 mg/kg) injection in Wistar rats cooled immersially caused potent immune modulating, antioxidant and hepatoprotector effects. Lysozyme effect was due to heavy erythrocytes and by cytokines induced in spleen (with glass-adhesion at 32-37 degrees C).


[Functional dimorphism in satellite chromosomes in hamadryas baboons].
Dimorphism of satellite chromosomes observed in bone marrow of female as well as male Papio hamadryas, and in continuous cultures of the monkey haemopoetic cells is described. Most frequently the observed dimorphism is expressed in different lengths of satellite arms. The structural dimorphism of satellite chromosomes seen in Macaca, Papio and other genera may seem to originate from different degrees of functional activity of these chromosomes. The active homologue is longer since its satellite arm is less spiralized.


Engineered truncations in the Drosophila mastermind protein disrupt Notch pathway function.
The phenotypes and genetic interactions associated with mutations in the Drosophila mastermind (mam) gene have implicated it as a component of the Notch signaling pathway. However, its function and site of action within many tissues requiring Notch signaling have not been thoroughly investigated. To address these questions, we have constructed truncated versions of the Mam protein that elicit dominant phenotypes when expressed in imaginal tissues under GAL4-UAS regulation. By several criteria, these effects appear to phenocopy loss of function for the Notch pathway. When expressed in the notum, truncated Mam results in failure of lateral inhibition within proneural clusters and perturbations in cell fate specification within the sensory organ precursor cell lineage. Expression in the wing is associated with vein thickening and margin defects, including nicking and bristle loss. The truncation-associated wing margin phenotypes are modified by mutations in Notch and Wg pathway genes and are correlated with depressed expression of wg, cut, and vg. These data support the idea that Mam truncations have lost key effector domains and therefore behave as dominant-negative proteins. Coexpression of Delta or an activated form of Notch suppresses the effects of the Mam truncation, suggesting that Mam can function upstream of ligand-receptor interaction in the Notch pathway. This system should prove useful for the investigation of the role of Mam within the Notch pathway.


Antioxidant and cytotoxic activities of Caesalpinia pulcherrima wood.
Antioxidant and cytotoxic activities of the methanolic and aqueous extracts of Caesalpinia pulcherrima wood were studied in in vitro models. Both extracts exhibited strong antioxidant activity, as evidenced by the low IC50 values in both 1,1-diphenyl-2-picryl hydrazyl (DPPH), nitric oxide and superoxide scavenging methods; the values were found to be less or comparable to those of gallic acid, the standard used. To determine the cytotoxic activity, extracts were tested for toxic effects to brine shrimp larvae. In this assay, the methanolic extract had little effect, but aqueous extract was relatively toxic. The antioxidant and cytotoxic activities may be attributed to the total phenolic content in the wood.


Structure of the complex between the cytosolic chaperonin CCT and phosducin-like protein.
The three-dimensional structure of the complex formed between the cytosolic chaperonin CCT (chaperonin containing TCP-1) and phosducin (Pdc)-like protein (PhLP), a regulator of CCT activity, has been solved by cryoelectron microscopy. Binding of PhLP to CCT occurs through only one of the chaperonin rings, and the protein does not occupy the central folding cavity but rather sits above it through interactions with two regions on opposite sides of the ring. This causes the apical domains of the CCT subunits to close in, thus excluding access to the folding cavity. The atomic model of PhLP generated from several atomic structures of the homologous Pdc fits very well with the mass of the complex attributable to PhLP and predicts the involvement of several sequences of PhLP in CCT binding. Binding experiments performed with PhLP/Pdc chimeric proteins, taking advantage of the fact that Pdc does not interact with CCT, confirm that both the N- and C-terminal domains of PhLP are involved in CCT binding and that several regions suggested by the docking experiment are indeed critical in the interaction with the cytosolic chaperonin.


Clinical T Category of Non-Small Cell Lung Cancers: Prognostic Performance of Unidimensional versus Bidimensional Measurements at CT.
Purpose To compare the prognostic performances of clinical T categorization between the longest diameter and average diameter at CT in patients who underwent surgical resection of non-small cell lung cancers (NSCLCs). Materials and Methods This study retrospectively determined clinical T categories based on the longest diameter (clinical Tlongest) and average diameter (clinical Taverage) in 1153 patients, including 651 men (median age, 67 years; interquartile range [IQR], 60-72 years) and 502 women (median age, 63 years; IQR, 55-70 years) who underwent preoperative chest CT and subsequent resection of NSCLCs (clinical T1 to clinical T4; N0M0) between 2009 and 2015. Prognostic performances for disease-free survival (DFS) were compared between clinical Tlongest and clinical Taverage by using the Harrell concordance indexes and Student t test. The effect of the average diameter on clinical T category shifts (downstaging) was also investigated by using the McNemar-Bowker test. Results Concordance indexes did not significantly differ between clinical Tlongest (0.72; 95% confidence interval [CI]: 0.67, 0.76) and clinical Taverage (0.70; 95% CI: 0.64, 0.75) (P = .12 for the comparison). In the clinical T1 subgroup analysis, concordance indexes were 0.77 (95% CI: 0.71, 0.83) for clinical Tlongest and 0.75 (95% CI: 0.69, 0.81) for clinical Taverage (P = .17 for the comparison). Use of the clinical Taverage resulted in significant downstaging in all clinical T categories (P < .001). Conclusion The prognostic performance of clinical T categorization was not significantly different between the longest and average diameter measurements. Clinical T categorization based on the longest tumor diameter at CT was demonstrated to be sufficient for risk stratification of surgically treated non-small cell lung cancers. © RSNA, 2019 Online supplemental material is available for this article.


The quality of life of people in chronic pain: developing a pain and discomfort module for use with the WHOQOL.
This article reports the development of a pain and discomfort module (PDM) designed to assess the full impact of quality of life (QoL) relating to chronic pain, which could be used with the generic World Health Organisation Quality of Life Assessment (WHOQOL). First, cognitive interviewing was completed with nine participants with chronic pain, for 108 items representing 10 pain-specific facets of QoL. Sixty-eight QoL items and 16 importance questions on pain were relevant, comprehensive, comprehensible and acceptable to users, and were confirmed to assess their purported concepts. Secondly, these items were pilot tested using a cross-sectional survey of 216 people with chronic pain, to investigate the preliminary psychometric properties of the PDM, and reduce its items statistically. All new facets were important to those with chronic pain. Sixteen items within four facets of pain relief, anger and frustration, vulnerability/fear/worry, and uncertainty were retained, and demonstrated acceptable to good internal consistency reliability (α = 0.77-0.85). The PDM is a self-administered, multidimensional subjective assessment of pain-related QoL, with potential to evaluate pain-relieving interventions, identify sufferer's needs, and for survey use.


Streamlined analysis of pooled genotype data in SNP-based association studies.
Several groups have developed methods for estimating allele frequencies in DNA pools as a fast and cheap way for detecting allelic association between genetic markers and disease. To obtain accurate estimates of allele frequencies, a correction factor k for the degree to which measurement of allele-specific products is biased is generally applied. Factor k is usually obtained as the ratio of the two allele-specific signals in samples from heterozygous individuals, a step that can significantly impair throughput and increase cost. We have systematically investigated the properties of k through the use of empirical and simulated data. We show that for the dye terminator primer extension genotyping method we have applied, the correction factor k is substantially influenced by the dye terminators incorporated, but also by the terminal 3' base of the extension primer. We also show that the variation in k is large enough to result in unacceptable error rates if association studies are conducted without regard to k. We show that the impact of ignoring k can be neutralized by applying a correction factor k(max) that can be easily derived, but this at the potential cost of an increase in type I error. Finally, based upon observed distributions for k we derive a method allowing the estimation of the probability pooled data reflects significant differences in the allele frequencies between the subjects comprising the pools. By controlling the error rates in the absence of knowledge of the appropriate SNP-specific correction factors, each approach enhances the performance of DNA pooling, while considerably streamlining the method by reducing time and cost.


Identification and release kinetics of peptides from tilapia skin collagen during alcalase hydrolysis.
Collagen from tilapia skin was extracted and confirmed as type I collagen. Collagen was then hydrolyzed with alcalase for 4 h and the released peptides were identified. The structure-activity relationship of collagen-released peptides showed that proline at position C3 played a key role in improving ACE inhibitory activity, while proline at position C2 had a negative effect. Collagen peptide release kinetics showed that with the extension of time, the number of peptides increased dramatically at first, decreased, and then tended to be stable. This indicated that collagen peptides mainly originated from primary enzymolysis at the first stage and began to undergo secondary hydrolysis in the second stage. Afterwards, secondary enzymolysis was dominant at the third stage and finally remained stable at final two stages. Understanding the pattern of collagen peptide release kinetics might offer a powerful approach in the collagen-peptide food processing industry to better control food safety and quality.


White matter hyperintensities, cortisol levels, brain atrophy and continuing cognitive deficits in late-life depression.
Cerebrovascular changes and glucocorticoid mediated hippocampal atrophy are considered relevant for depression-related cognitive deficits, forming putative treatment targets. This study examined the relative contribution of cortisol levels, brain atrophy and white matter hyperintensities to the persistence of cognitive deficits in older adults with depression. Thirty-five people aged > or =60 years with DSM-IV major depression and twenty-nine healthy comparison controls underwent magnetic resonance imaging (MRI) and were followed up for 18 months. We analysed the relationship between baseline salivary cortisol levels, whole brain, frontal lobe and hippocampal volumes, severity of white matter hyperintensities and follow-up cognitive function in both groups by testing the interaction between the groups and these biological measures on tests of memory, executive functions and processing speed in linear regression models. Group differences in memory and executive function follow-up scores were associated with ratings of white matter hyperintensities, especially of the deep white matter and periventricular regions. Compared with healthy controls, participants with depression scoring within the third tertile of white matter hyperintensities dropped two and three standard deviations in executive function and memory scores respectively. No biological measure related to group differences in processing speed, and there were no significant interactions between group and cortisol levels, or volumetric MRI measures. White matter hyperintensities, rather than cortisol levels or brain atrophy, are associated with continuing cognitive impairments in older adults with depression. The findings suggest that cerebrovascular disease rather than glucocorticoid-mediated brain damage are responsible for the persistence of cognitive deficits associated with depression in older age.


Endothelial EphA receptor stimulation increases lung vascular permeability.
Mediators of angiogenesis such as VEGFs and angiopoietins may regulate pulmonary vascular permeability under normal and pathological conditions. Ephrin family receptor tyrosine kinases are expressed in the vasculature and also regulate angiogenesis under some circumstances, but whether they also modulate lung vascular permeability is unknown. We hypothesized that stimulation of lung endothelial EphA receptors with ephrin-a1 ligand would alter pulmonary vascular permeability and tested this idea in vivo and in vitro. We found that ephrin-a1 ligand and EphA2 receptors are expressed in distal normal lung vasculature and that their expression is increased in injured lung, suggesting a link to mechanisms of increased permeability. Intravenous injection of ephrin-a1 caused a large increase in the leakage of labeled albumin into the lungs of rats within 30 min (293 +/- 27 vs. 150 +/- 6 ng/mg dry lung, P < 0.01), along with histological evidence of the formation of endothelial disruptions. In cultured lung vascular endothelial cells, stimulation with ephrin-a1 increased monolayer permeability by 44% (P < 0.01), a permeability change similar to that seen with VEGF stimulation of the same cells. Ephrin-a1 stimulation in vivo and in vitro was associated with histological evidence for disruptions of tight and adherens junctions. These observations describe a novel role for ephrin-a1 and EphA receptors in the regulation of vascular permeability in the lung.


PKM2, a Central Point of Regulation in Cancer Metabolism.
Aerobic glycolysis is the dominant metabolic pathway utilized by cancer cells, owing to its ability to divert glucose metabolites from ATP production towards the synthesis of cellular building blocks (nucleotides, amino acids, and lipids) to meet the demands of proliferation. The M2 isoform of pyruvate kinase (PKM2) catalyzes the final and also a rate-limiting reaction in the glycolytic pathway. In the PK family, PKM2 is subjected to a complex regulation by both oncogenes and tumour suppressors, which allows for a fine-tone regulation of PKM2 activity. The less active form of PKM2 drives glucose through the route of aerobic glycolysis, while active PKM2 directs glucose towards oxidative metabolism. Additionally, PKM2 possesses protein tyrosine kinase activity and plays a role in modulating gene expression and thereby contributing to tumorigenesis. We will discuss our current understanding of PKM2's regulation and its many contributions to tumorigenesis.


Septal and lateral wall localization of PBP5, the major D,D-carboxypeptidase of Escherichia coli, requires substrate recognition and membrane attachment.
The distribution of PBP5, the major D,D-carboxypeptidase in Escherichia coli, was mapped by immunolabelling and by visualization of GFP fusion proteins in wild-type cells and in mutants lacking one or more D,D-carboxypeptidases. In addition to being scattered around the lateral envelope, PBP5 was also concentrated at nascent division sites prior to visible constriction. Inhibiting PBP2 activity (which eliminates wall elongation) shifted PBP5 to midcell, whereas inhibiting PBP3 (which aborts divisome invagination) led to the creation of PBP5 rings at positions of preseptal wall formation, implying that PBP5 localizes to areas of ongoing peptidoglycan synthesis. A PBP5(S44G) active site mutant was more evenly dispersed, indicating that localization required enzyme activity and the availability of pentapeptide substrates. Both the membrane bound and soluble forms of PBP5 converted pentapeptides to tetrapeptides in vitro and in vivo, and the enzymes accepted the same range of substrates, including sacculi, Lipid II, muropeptides and artificial substrates. However, only the membrane-bound form localized to the developing septum and restored wild-type rod morphology to shape defective mutants, suggesting that the two events are related. The results indicate that PBP5 localization to sites of ongoing peptidoglycan synthesis is substrate dependent and requires membrane attachment.


Downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes.
Dysregulation of lipid metabolism in skeletal muscle is involved in the development of insulin resistance. Mutations in lipin-1, a key lipid metabolism regulator leads to significant systemic insulin resistance in fld mice. However, the function of lipin-1 on lipid metabolism and insulin sensitivity in skeletal muscle is still unclear. Herein we demonstrated that downregulation of lipin-1 in C2C12 myotubes by siRNA transfection suppressed insulin action, characterized by reduced insulin stimulated Akt phosphorylation and glucose uptake. Correspondingly, decreased lipin-1 expression was observed in palmitate-induced insulin resistance in C2C12 myotubes, suggested that lipin-1 might play a role in the etiology of insulin resistance in skeletal muscle. The insulin resistance induced by lipin-1 downregulation was related to the disturbance of lipid homeostasis. Lipin-1 silencing reduced intracellular DAG and TAG levels, but elevated ceramide accumulation in C2C12 myotubes. Moreover, the impaired insulin stimulated Akt phosphorylation and glucose uptake caused by lipin-1 silencing could be blocked by the pretreatment with SPT inhibitor myriocin, ceramide synthase inhibitor FB1, or PP2A inhibitor okadaic acid, suggested that the increased ceramide accumulation might be responsible for the development of insulin resistance induced by lipin-1 silencing in C2C12 myotubes. Meanwhile, decreased lipin-1 expression also impaired mitochondrial function in C2C12 myotubes. Therefore, our study suggests that lipin-1 plays an important role in lipid metabolism and downregulation of lipin-1 induces insulin resistance by increasing intracellular ceramide accumulation in C2C12 myotubes. These results offer a molecular insight into the role of lipin-1 in the development of insulin resistance in skeletal muscle.


Combination of FDG PET/CT and contrast-enhanced MSCT in detecting lymph node metastasis of esophageal cancer.
Lymph node metastasis is believed to be a dependent negative prognostic factor of esophageal cancer. To explore detection methods with high sensitivity and accuracy for metastases to regional and distant lymph nodes in the clinic is of great significance. This study focused on clinical application of FDG PET/CT and contrast-enhanced multiple-slice helical computed tomography (MSCT) in lymph node staging of esophageal cancer. One hundred and fifteen cases were examined with enhanced 64-slice-MSCT scan, and FDG PET/CT imaging was conducted for neck, chest and upper abdomen within one week. The primary lesion, location and numbers of metastatic lymph nodes were observed. Surgery was performed within one week after FDG PET/CT detection. All resected lesions were confirmed histopathologically as the gold standard. Comparative analysis of the sensitivity, specificity, and accuracy based on FDG PET/CT and MSCT was conducted. There were 946 lymph node groups resected during surgery from 115 patients, and 221 were confirmed to have metastasis pathologically. The sensitivity, specificity, accuracy of FDG PET/CT in detecting lymph node metastasis were 74.7%, 97.2% and 92.0%, while with MSCT they were 64.7%, 96.4%, and 89.0%, respectively. A significance difference was observed in sensitivity (p=0.030), but not the others (p>0.05). The accuracy of FDG PET/CT in detecting regional lymph node with or without metastasis were 91.9%, as compared to 89.4% for MSCT, while FDG PET/CT and MSCT values for detecting distant lymph node with or without metastasis were 94.4% and 94.7%. No significant difference was observed for either regional or distant lymph node metastasis. Additionally, for detecting para-esophageal lymph nodes metastasis, the sensitivity of FDG PET/CT was 72%, compared with 54.7% for MSCT (p=0.029). FDG PET/CT is more sensitive than MSCT in detecting lymph node metastasis, especially for para-esophageal lymph nodes in esophageal cancer cases, although no significant difference was observed between FDG PET/CT and MSCT in detecting both regional and distant lymph node metastasis. However, enhanced MSCT was found to be of great value in distinguishing false negative metastatic lymph nodes from FDG PET/CT. The combination of FDG PET/CT with MSCT should improve the accuracy in lymph node metastasis staging of esophageal cancer.


Design and evaluation of self-nanoemulsifying drug delivery system of flutamide.
Flutamide (FLT) is an antiandrogen drug for the treatment of prostate cancer. It has the drawback of poor water solubility and needs enhancement of its dissolution rate in simulated gastric fluids. Hence, it is prepared as self-nanoemulsifying drug delivery systems (SNEDDS) with an aim to enhance its dissolution rate. The objectives of the study are to develop SNEDDS of FLT and to characterize for particle size, self-nanoemulsification, and dissolution enhancement. Solubility of FLT was determined in various oils, surfactants, and cosurfactants. Sesame oil was selected as an oil phase, Tween 20 as surfactant, and PEG400 as cosurfactant due to their higher solubilization effect. Various formulations were prepared by simple mixing followed by vortexing. From studies, the optimized SNEDDS formulation was composed of FLT (8.04% w/w), sesame oil (24.12% w/w), Tween 20 (53.38% w/w), and PEG400 (14.46% w/w). The selected SNEDDS could be self-emulsified without precipitation upon simple mixing. The mean particle size of the SNEDDS was 148.7 nm and percent drug content was 99.66. The dissolution rate of FLT from SNEDDS was faster and higher in three different dissolution media such as 2% sodium lauryl sulfate (97.85%), simulated gastric fluid (0.1 N HCl containing 0.5% Tween 20) (95.71%), and simulated intestinal fluid (pH 6.8 buffer) (96.21%).


Blazed-binary diffractive elements with periods much larger than the wavelength
Blazed-binary optical elements with only binary ridges or pillars are diffractive components that mimic standard blazed-echelette diffractive elements. We report on the behavior of one-dimensional blazed-binary optical elements with local periods much larger than the wavelength. For this purpose, an approximate model based on both scalar and electromagnetic theory is proposed. The model is tested against electromagnetic-theory computational results obtained for one-dimensional blazed-binary gratings with large periods. An excellent agreement is obtained, showing that the model is able to predict quantitatively the wavelength and the incidence-angle dependences of the diffraction efficiency of blazed-binary structures.


Urban air pollution and emergency admissions for asthma in four European cities: the APHEA Project.
A study was undertaken to assess the combined association between urban air pollution and emergency admissions for asthma during the years 1986-92 in Barcelona, Helsinki, Paris and London. Daily counts were made of asthma admissions and visits to the emergency room in adults (age range 15-64 years) and children (< 15 years). Covariates were short term fluctuations in temperature and humidity, viral epidemics, day of the week effects, and seasonal and secular trends. Estimates from all the cities were obtained for the entire period and separately by warm or cold seasons using Poisson time-series regression models. Combined associations were estimated using meta-analysis techniques. Daily admissions for asthma in adults increased significantly with increasing ambient levels of nitrogen dioxide (NO2) (relative risk (RR) per 50 micrograms/m3 increase 1.029, 95% CI 1.003 to 1.055) and non-significantly with particles measured as black smoke (RR 1.021, 95% CI 0.985 to 1.059). The association between asthma admissions and ozone (O3) was heterogeneous among cities. In children, daily admissions increased significantly with sulphur dioxide (SO2) (RR 1.075, 95% CI 1.026 to 1.126) and non-significantly with black smoke (RR 1.030, 95% CI 0.979 to 1.084) and NO2, though the latter only in cold seasons (RR 1.080, 95% CI 1.025 to 1.140). No association was observed for O3. The associations between asthma admissions and NO2 in adults and SO2 in children were independent of black smoke. The evidence of an association between air pollution at current urban levels and emergency room visits for asthma has been extended to Europe. In addition to particles, NO2 and SO2--by themselves or as a constituent of a pollution mixture--may be important in asthma exacerbations in European cities.


Structure of the Atmosphere of Venus up to 110 Kilometers: Preliminary Results from the Four Pioneer Venus Entry Probes.
The four Pioneer Venus entry probes transmitted data of good quality on the structure of the atmosphere below the clouds. Contrast of the structure below an altitude of 50 kilometers at four widely separated locations was found to be no more than a few degrees Kelvin, with slightly warmer temperatures at 30 degrees south latitude than at 5 degrees or 60 degrees north. The atmosphere was stably stratified above 15 or 20 kilometers, indicating that the near-adiabatic state is maintained by the general circulation. The profiles move from near-adiabatic toward radiative equilibrium at altitudes above 40 kilometers. There appears to be a region of vertical convection above the dense cloud deck, which lies at 47.5 to 49 kilometers and at temperature levels near 360 K. The atmosphere is nearly isothermal around 100 kilometers (175 to 180 K) and appears to exhibit a sizable temperature wave between 60 and 70 kilometers. This is where the 4-day wind is believed to occur. The temperature wave may be related to some of the wavelike phenomena seen in Mariner 10 ultraviolet photographs.


Self-healable, super tough graphene oxide-poly(acrylic acid) nanocomposite hydrogels facilitated by dual cross-linking effects through dynamic ionic interactions.
Here we propose a facile, one-pot in situ free radical polymerization strategy to prepare self-healable, super tough graphene oxide (GO)-poly(acrylic acid) (PAA) nanocomposite hydrogels by using Fe3+ ions as a cross-linker. The 3-dimensional network structure of the GO-PAA nanocomposite hydrogels is facilitated by dual cross-linking effects through dynamic ionic interactions: (i) the first cross-linking points are Fe3+ ions creating ionic cross-linking among PAA chains; (ii) the second cross-linking points are GO nanosheets linking PAA chains through Fe3+ coordination. When the GO-PAA nanocomposite hydrogels are under stretching conditions, the ionic interactions among PAA chains can dynamically break and recombine to dissipate energy, while the GO nanosheets coordinated to the PAA chains maintain the configuration of the hydrogels and work as stress transfer centers transferring the stress to the polymer matrix. In this regard, the GO-PAA nanocomposite hydrogels exhibit superior toughness (tensile strength = 777 kPa, work of extension = 11.9 MJ m-3) and stretchability (elongation at break = 2980%). Furthermore, after being treated at 45 °C for 48 h, the cut-off GO-PAA nanocomposite hydrogels exhibit good self-healing properties (tensile strength = 495 kPa, elongation at break = 2470%). The self-healable, super tough GO-PAA nanocomposite hydrogels lay a basis for developing advanced soft materials holding potential applications in modern biomedical engineering and technology.


Sit-to-stand measurement for in-home monitoring using voxel analysis.
We present algorithms to segment the activities of sitting and standing, and identify the regions of sit-to-stand (STS) transitions in a given image sequence. As a means of fall risk assessment, we propose methods to measure STS time using the 3-D modeling of a human body in voxel space as well as ellipse fitting algorithms and image features to capture orientation of the body. The proposed algorithms were tested on ten older adults with ages ranging from 83 to 97. Two techniques in combination yielded the best results, namely the voxel height in conjunction with the ellipse fit. Accurate STS time was computed on various STSs and verified using a marker-based motion capture system. This application can be used as part of a continuous video monitoring system in the homes of older adults and can provide valuable information to help detect fall risk and enable early interventions.


Lhermitte - Duclos disease with syrinx: case report and literature review.
Lhermitte-Duclos disease is typified by a hamartomatous lesion of the cerebellum. It is usually seen in females. The usual presentation is of raised intracranial pressure along with cerebellar signs. We report an 18-year-old female patient who presented to us with history of headache and gait ataxia and was observed to have Lhermitte-Duclos disease with cervical cord syrinx on imaging. To our knowledge this is the fifth case of Lhermitte-Duclos disease with syringomyelia in the pediatric age group. The treatment of this condition is decompression of the lesion. Malignant transformation never occurs and the prognosis is excellent.


Long-Term Follow-Up of Adults with Gender Identity Disorder.
The aim of this study was to re-examine individuals with gender identity disorder after as long a period of time as possible. To meet the inclusion criterion, the legal recognition of participants' gender change via a legal name change had to date back at least 10 years. The sample comprised 71 participants (35 MtF and 36 FtM). The follow-up period was 10-24 years with a mean of 13.8 years (SD = 2.78). Instruments included a combination of qualitative and quantitative methods: Clinical interviews were conducted with the participants, and they completed a follow-up questionnaire as well as several standardized questionnaires they had already filled in when they first made contact with the clinic. Positive and desired changes were determined by all of the instruments: Participants reported high degrees of well-being and a good social integration. Very few participants were unemployed, most of them had a steady relationship, and they were also satisfied with their relationships with family and friends. Their overall evaluation of the treatment process for sex reassignment and its effectiveness in reducing gender dysphoria was positive. Regarding the results of the standardized questionnaires, participants showed significantly fewer psychological problems and interpersonal difficulties as well as a strongly increased life satisfaction at follow-up than at the time of the initial consultation. Despite these positive results, the treatment of transsexualism is far from being perfect.


Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer.
This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by β-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and β-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16-9.17, p = 0.03). β-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62-50.91, p = 0.13) to 15.52 (95% CI = 2.94-82.38, p = 0.001) by β-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed β-catenin in combination with reduced NME1 expression.


2D-Material-Assisted GaN Growth on GaN Template by MOCVD and Its Exfoliation Strategy.
The production of freestanding membranes using two-dimensional (2D) materials often involves techniques such as van der Waals (vdW) epitaxy, quasi-vdW epitaxy, and remote epitaxy. However, a challenge arises when attempting to manufacture freestanding GaN by using these 2D-material-assisted growth techniques. The issue lies in securing stability, as high-temperature growth conditions under metal-organic chemical vapor deposition (MOCVD) can cause damage to the 2D materials due to GaN decomposition of the substrate. Even when GaN is successfully grown using this method, damage to the 2D material leads to direct bonding with the substrate, making the exfoliation of the grown GaN nearly impossible. This study introduces an approach for GaN growth and exfoliation on 2D material/GaN templates. First, graphene and hexagonal boron nitride (h-BN) were transferred onto the GaN template, creating stable conditions under high temperatures and various gases in MOCVD. GaN was grown in a two-step process at 750 and 900 °C, ensuring exfoliation in cases where the 2D materials remained intact. Essentially, while it is challenging to grow GaN on 2D material/GaN using only MOCVD, this study demonstrates that with effective protection of the 2D material, the grown GaN can endure high temperatures and still be exfoliated. Furthermore, these results support that vdW epitaxy and remote epitaxy principle are not only possible with specific equipment but also applicable generally.


Trends in adolescent smoking initiation in the United States: is tobacco marketing an influence?
To compare recent trends in smoking initiation by adolescents with trends in inflation-adjusted cigarette pricing and tobacco marketing expenditures. We examined smoking initiation trends in demographic subgroups of adolescents aged 14-17 years during the decade 1979-1989. Data on cigarette pricing and tobacco marketing expenditures were adjusted for inflation and plotted over this same period. Large population surveys, United States. 140,975 ever-smokers aged 17-38 when surveyed in 1992 or 1993, who reported on age of smoking initiation during the decade 1979-1989. Initiation rate was calculated as the number in an age group who reported starting to smoke regularly in a year, divided by the number of never-smokers at the start of the year. Trends were evaluated by linear and quadratic models. From 1979 to 1984, adolescent initiation rates decreased, but increased thereafter, particularly among males, whites, and those who, as adults, reported never having graduated from high school. Cigarette price increased throughout the decade as did tobacco marketing expenditures, especially for coupons, value-added items, and promotional allowances. Availability of cheaper cigarettes is not likely to be a cause of increased smoking initiation by adolescents. Although other influences cannot be ruled out, we suspect that the expanded tobacco marketing budget, with its increased emphasis on tactics that may be particularly pertinent to young people, affected adolescent initiation rates.


Insights into IL-29: Emerging role in inflammatory autoimmune diseases.
Interleukin-29 (IL-29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL-29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL-29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL-29. The information collected revealed the regulatory role of IL-29 and may give important implications for its potential in clinical treatment.


The basic difference in catalyses by serine and cysteine proteinases resides in charge stabilization in the transition state.
Besides the mechanistic similarities, in particular acylenzyme formation, kinetic investigations and X-ray diffraction studies have revealed some differences between the mechanisms of serine and cysteine proteinases: general base-catalysis in acylation, catalytic contribution by oxyanion binding, and a negatively charged catalytic triad in serine proteinases, but not in cysteine proteinases. In this paper we point out that all these differences are related and connected with the mode of stabilization of the zwitterionic species developing in the transition state of the reactions. In the case of serine proteinases this charge separation requires facilitation by the oxyanion binding and the negative charge of the catalytic triad. On the other hand cysteine proteinases do not require such contributions as they are capable of stabilizing the ion-pair even in the ground state of the reaction. Therefore, cysteine proteinases, in contrast to serine proteinases, may be regarded as "activated" enzymes.


Distribution and ontogeny of SP, CGRP, SOM, and VIP in chick sensory and sympathetic ganglia.
The distribution and ontogeny of four neuropeptides in developing chick lumbosacral sensory and sympathetic ganglia were studied using immunohistochemical techniques. Antibodies to two of these peptides, substance P (SP) and calcitonin gene-related peptide (CGRP), stained small neurons in the medial part of the dorsal root ganglia from embryonic Day 5 and Day 10, respectively, whereas neurons in the lateral part of the ganglia were negative; this distribution persisted throughout development. Both sets of neurons apparently send fibers to the dorsal horn of the spinal cord: SP to laminae I and II, and CGRP to lamina I, suggesting that the SP- and CGRP-positive sensory neurons are nociceptive or thermoreceptive. This correlation between the presence of SP or CGRP in a neuron and a particular functional modality thus provides evidence for a functional distinction between the mediodorsal and ventrolateral zones that are apparent during the development of chick dorsal root ganglia. Moreover, this study suggests that the type of neuron that develops within the dorsal root ganglion correlates with its position within the ganglion. In contrast to SP and CGRP, somatostatin (SOM) and vasoactive intestinal polypeptide (VIP) immunoreactivities were not seen in the lumbosacral sensory ganglia at any stage during development. However, both were present in sympathetic ganglia: SOM from embryonic Day 4.5 and VIP from embryonic Day 10. VIP immunoreactivity persisted throughout development in a large number of sympathetic neurons, but the number of cells with SOM immunoreactivity decreased from embryonic Day 10 onward. SOM therefore appears to be present only transiently in most chick lumbosacral sympathetic cells.


ATP13A2 facilitates HDAC6 recruitment to lysosome to promote autophagosome-lysosome fusion.
Mutations in ATP13A2 cause Kufor-Rakeb syndrome, an autosomal recessive form of juvenile-onset atypical Parkinson's disease (PD). Recent work tied ATP13A2 to autophagy and other cellular features of neurodegeneration, but how ATP13A2 governs numerous cellular functions in PD pathogenesis is not understood. In this study, the ATP13A2-deficient mouse developed into aging-dependent phenotypes resembling those of autophagy impairment. ATP13A2 deficiency impaired autophagosome-lysosome fusion in cultured cells and in in vitro reconstitution assays. In ATP13A2-deficient cells or Drosophila melanogaster or mouse tissues, lysosomal localization and activity of HDAC6 were reduced, with increased acetylation of tubulin and cortactin. Wild-type HDAC6, but not a deacetylase-inactive mutant, restored autophagosome-lysosome fusion, antagonized cortactin hyperacetylation, and promoted lysosomal localization of cortactin in ATP13A2-deficient cells. Mechanistically, ATP13A2 facilitated recruitment of HDAC6 and cortactin to lysosomes. Cortactin overexpression in cultured cells reversed ATP13A2 deficiency-associated impairment of autophagosome-lysosome fusion. PD-causing ATP13A2 mutants failed to rescue autophagosome-lysosome fusion or to promote degradation of protein aggregates and damaged mitochondria. These results suggest that ATP13A2 recruits HDAC6 to lysosomes to deacetylate cortactin and promotes autophagosome-lysosome fusion and autophagy. This study identifies ATP13A2 as an essential molecular component for normal autophagy flux in vivo and implies potential treatments targeting HDAC6-mediated autophagy for PD.


Doppler angle estimation using AR modeling.
The transit time spectrum broadening effect has long been explored for Doppler angle estimation. Given acoustic beam geometry, the Doppler angle can be derived based on the mean Doppler frequency and the Doppler bandwidth. Spectral estimators based on the fast Fourier transform (FFT) are typically used. One problem with this approach is that a long data acquisition time is required to achieve adequate spectral resolution, with typically 32-128 flow samples being needed. This makes the method unsuitable for real-time two-dimensional Doppler imaging. This paper proposes using an autoregressive (AR) model to obtain the Doppler spectrum using a small number (e.g., eight) of flow samples. The flow samples are properly selected, then extrapolated to ensure adequate spectral resolution. Because only a small number of samples are used, the data acquisition time is significantly reduced and real-time, two-dimensional Doppler angle estimation becomes feasible. The approach was evaluated using both simulated and experimental data. Flows with various degrees of velocity gradient were simulated, with the Doppler angle ranging from 20 degrees to 75 degrees. The results indicate that the AR method generally provided accurate Doppler bandwidth estimates. In addition, the AR method outperformed the FFT method at smaller Doppler angles. The experimental data for Doppler angles, ranging from 33 degrees to 72 degrees, showed that the AR method using only eight flow samples had an average estimation error of 3.6 degrees, which compares favorably to the average error of 4.7 degrees for the FFT method using 64 flow samples. Because accurate estimates can be obtained using a small number of flow samples, it is concluded that real-time, two-dimensional estimation of the Doppler angle over a wide range of angles is possible using the AR method.


An evaluation of shear bond strength of self-etch adhesive on pre-etched enamel: an in vitro study.
To determine the shear bond strength of self-etch adhesive G-bond on pre-etched enamel. Thirty caries free human mandibular premolars extracted for orthodontic purpose were used for the study. Occlusal surfaces of all the teeth were flattened with diamond bur and a silicon carbide paper was used for surface smoothening. The thirty samples were randomly grouped into three groups. Three different etch systems were used for the composite build up: group 1 (G-bond self-etch adhesive system), group 2 (G-bond) and group 3 (Adper single bond). Light cured was applied for 10 seconds with a LED unit for composite buildup on the occlusal surface of each tooth with 8 millimeters (mm) in diameter and 3 mm in thickness. The specimens in each group were tested in shear mode using a knife-edge testing apparatus in a universal testing machine across head speed of 1 mm/ minute. Shear bond strength values in Mpa were calculated from the peak load at failure divided by the specimen surface area. The mean shear bond strength of all the groups were calculated and statistical analysis was carried out using one-way Analysis of Variance (ANOVA). The mean bond strength of group 1 is 15.5 Mpa, group 2 is 19.5 Mpa and group 3 is 20.1 Mpa. Statistical analysis was carried out between the groups using one-way ANOVA. Group 1 showed statistically significant lower bond strength when compared to groups 2 and 3. No statistical significant difference between groups 2 and 3 (p < 0.05). Self-etch adhesive G-bond showed increase in shear bond strength on pre-etched enamel.


Comparing robotic, laparoscopic and open cystectomy: a systematic review and meta-analysis.
To conduct a systematic review and meta-analysis comparing outcomes between Open Radical Cystectomy (ORC), Laparoscopic Radical Cystectomy (LRC) and Robot-assisted Radical Cystectomy (RARC). RARC is to be compared to LRC and ORC and LRC compared to ORC. A systematic review of the literature was conducted, collating studies comparing RARC, LRC and ORC. Surgical and oncological outcome data were extracted and a meta-analysis was performed. Twenty-four studies were selected with total of 2,104 cases analyzed. RARC had a longer operative time (OPT) compared to LRC with no statistical difference between length of stay (LOS) and estimated blood loss (EBL). RARC had a significantly shorter LOS, reduced EBL, lower complication rate and longer OPT compared to ORC. There were no significant differences regarding lymph node yield (LNY) and positive surgical margins (PSM.) LRC had a reduced EBL, shorter LOS and increased OPT compared to ORC. There was no significant difference regarding LNY. RARC is comparable to LRC with better surgical results than ORC. LRC has better surgical outcomes than ORC. With the unique technological features of the robotic surgical system and increasing trend of intra-corporeal reconstruction it is likely that RARC will become the surgical option of choice.


IMPROVED TEMPERATURE-GRADIENT INCUBATOR AND THE MAXIMAL GROWTH TEMPERATURE AND HEAT RESISTANCE OF SALMONELLA.
An improved all-metal temperature-gradient incubator produces its gradient by means of a bar permanently installed in a near-vertical position with its lower end in a cool constant-temperature water bath and with thermostatically controlled heaters near its top. Bolts hold the incubator in contact with the temperature-gradient bar, and polyurethane foam insulates the entire assemblage during use. Maximal growth temperatures of 34 representative strains of Salmonella were found to be between 43.2 and 46.2 C. In an agar medium with an initial level of 10(6) cells per milliliter, no strain survived 50 C for 48 hr. S. senftenberg 775W showed no greater heat resistance at or near 48 C than did other species or other S. senftenberg strains. However, it was considerably more resistant than other strains at 55 C.


Generalized optimal current patterns and electrical safety in EIT.
There are a number of constraints which limit the current and voltages which can be applied on a multiple drive electrical imaging system. One obvious constraint is to limit the maximum ohmic power dissipated in the body. Current patterns optimizing distinguishability with respect to this constraint are singular functions of the difference of transconductance matrices with respect to the power norm (the optimal currents of Isaacson). If one constrains the total current (L1 norm) the optimal patterns are pair drives. On the other hand if one constrains the maximum current on each drive electrode (an L(infinity) norm), the optimal patterns have each drive channel set to the maximum source or sink current value. In this paper we consider appropriate safety constraints and discuss how to find the optimal current patterns with those constraints.


Use of a balloon-expandable metallic stent to relieve malignant urethral obstruction in a cat.
A 19-year-old neutered male domestic shorthair cat was evaluated because of signs of urinary tract obstruction. Physical examination findings were consistent with urethral obstruction, and a mass could be palpated in the region of the bladder neck. Abdominal ultrasonography and thoracic radiography revealed a mass in the trigone of the urinary bladder and a solitary mass in the left caudal lung lobe. Cytologic examination of the urine sediment, samples obtained by means of traumatic urethral catheterization, and fine-needle aspirates of the bladder mass did not result in a diagnosis. A balloon-expandable metallic stent was placed in the proximal portion of the urethra to relieve the malignant obstruction. After stent placement, the cat had signs of urinary incontinence and detrusor atony, both of which resolved with medical treatment. The cat was euthanized 1 month after stent placement because of progressive azotemia. Histologic examination of necropsy samples revealed grade III urothelial carcinoma and papillary pulmonary adenocarcinoma. Findings suggested that stent placement may be a viable palliative treatment in cats with malignant urinary obstruction.


Cholinergic depletion reduces plasticity of barrel field cortex.
This experiment examines the impact of the cholinergic input from the basal forebrain on the plasticity of the vibrissa-related somatosensory cortex. Newborn rat pups received intraventricular injections of the cholinergic immunotoxin IgG192-saporin, after bilateral removal of the C-line whisker follicles. Compared with saline-injected control animals, unilateral injections of 0.1 microg IgG192-saporin decreased the number of cholinergic neurons on the toxin injected side by 78% in the basal nucleus of Meynert and the vertical limb of the diagonal band of Broca, 80% in the magnocellular preoptic nucleus and the horizontal limb of the diagonal band of Broca, and 54% in the medial septal nucleus. Neuronal loss contralateral to the toxin was approximately half that on the ipsilateral side. The size of the C and D row barrels were compared from tangential sections through the barrel field. In control animals, D row barrels expanded into C row territory, giving a ratio of areas for D/C barrels of 2.03. Depletion of the cholinergic neurons reduced the expansion of D row barrels and hence decreased the D/C ratio, with a greater reduction on the toxin-treated side (1.43, P <0.005) compared with the contralateral side (1.64, P <0.05). This study implicates the basal forebrain cholinergic projection in somatosensory cortical plasticity.


Memantine effects on verbal memory in fragile X-associated tremor/ataxia syndrome (FXTAS): a double-blind brain potential study.
Older FMR1 premutation carriers may develop fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder manifesting cognitive deficits that often subsequently progress to dementia. To date, there is no specific treatment available for FXTAS. Studies have demonstrated the premutation-associated overactivation of glutamatergic receptors in neurons. Memantine, a NMDA receptor antagonist approved for treatment of Alzheimer's disease, thus was tested in the first placebo-controlled, double-blind, randomized clinical trial in FXTAS. Prior event-related brain potential (ERP) studies in FXTAS found reduced N400 repetition effect, a glutamate-related electrophysiological marker of semantic priming, and verbal memory processes. This substudy of the randomized clinical trial of memantine in FXTAS sought to use the N400 repetition effect to evaluate effects of chronic memantine treatment on verbal memory. Subsequent recall and recognition memory tests for the experimental stimuli were administered to characterize verbal memory. Data from 41 patients who completed the 1-year memantine trial (21 on memantine) and also completed longitudinal ERP studies were analyzed. Results showed treatment-associated benefits on both cued-recall memory and N400 repetition effect amplitude. Importantly, improvement in cued recall was positively correlated with amplitude increase of the N400 repetition effect. The placebo group, in contrast, displayed a significant reduction of the N400 repetition effect after 1 year. These results suggest that memantine treatment may have beneficial effects on verbal memory in FXTAS. Additional studies of memantine, perhaps in combination with other therapeutic agents, appear warranted, as symptomatic treatments and neuroprotective treatments are both needed for this recently recognized neurodegenerative disorder.


The Full Outline of UnResponsiveness (FOUR) Score and Its Use in Outcome Prediction: A Scoping Review of the Pediatric Literature.
The Full Outline of UnResponsiveness (FOUR) score is a neurologic assessment score. Its benefit over pre-existing scores is its evaluation of brainstem reflexes and respiratory pattern. Our goal was to perform a scoping systematic review of the literature on the application of the FOUR score within pediatric patients. Six databases were searched and 2 reviewers independently screened the results. The initial search yielded 1709 citations; ultimately, 6 studies composed of 571 pediatric patients were used. Four studies examined interobserver reliability of the FOUR score and found it to be good to excellent. All 6 studies demonstrated equivalency of the FOUR score and Glasgow Coma Scale (GCS) in predicting outcome. The existing literature suggests the FOUR score is equivalent to GCS in outcome prediction in pediatric patients; its true superiority over the GCS has not yet been established. It displays good to excellent inter-rater reliability among physicians and nurses.


Proinflammatory stimuli control N-acylphosphatidylethanolamine-specific phospholipase D expression in macrophages.
Palmitoylethanolamide (PEA) is an endogenous lipid amide that modulates pain and inflammation by engaging peroxisome proliferator-activated receptor type-α. Here, we show that the proinflammatory bacterial endotoxin lipopolysaccharide (LPS) decreases PEA biosynthesis in RAW264.7 macrophages by suppressing the transcription of N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD), which catalyzes the production of PEA and other lipid amides. Using a luciferase reporter construct and chromatin immunoprecipitation, we further show that LPS treatment reduces acetylation of histone proteins bound to the NAPE-PLD promoter, an effect that is blocked by the histone deacetylase inhibitor trichostatin A. The transcription factor Sp1 is involved in regulating baseline NAPE-PLD expression but not in the transcriptional suppression induced by LPS. The ability of LPS to down-regulate PEA biosynthesis is impaired in peritoneal macrophages from mutant NAPE-PLD-deficient mice, in which PEA is produced through a compensatory mechanism distinct from NAPE-PLD. Moreover, NAPE-PLD-deficient mice fail to mount a normal inflammatory reaction in response to carrageenan administration in vivo. Our findings suggest that proinflammatory stimuli suppress NAPE-PLD expression and PEA biosynthesis in macrophages and that this effect might contribute to the inflammatory response.


Body perception in newborns.
Body ownership and awareness has recently become an active topic of research in adults using paradigms such as the "rubber hand illusion" and "enfacement" [1-11]. These studies show that visual, tactile, postural, and anatomical information all contribute to the sense of body ownership in adults [12]. While some hypothesize body perception from birth [13], others have speculated on the importance of postnatal experience [14, 15]. Through studying body perception in newborns, we can directly investigate the factors involved prior to significant postnatal experience. To address this issue, we measured the looking behavior of newborns presented with visual-tactile synchronous and asynchronous cues, under conditions in which the visual information was either an upright (body-related stimulus; experiment 1) or inverted (non-body-related stimulus; experiment 2) infant face. We found that newborns preferred to look at the synchronous condition compared to the asynchronous condition, but only when the visual stimulus was body related. These results are in line with findings from adults and demonstrate that human newborns detect intersensory synchrony when related to their own bodies, consistent with the basic processes underlying body perception being present at birth.


Stress management in the Federal Bureau of Investigation: principles for program development.
Images from the destruction of the Alfred P. Murrah Federal Building in Oklahoma City, the compound in Waco, Texas, the World Trade Center in New York City, Pan Am Flight 103 over Lockerbie, Scotland, and the American Embassy in Nairobi, Kenya, burned themselves into the public's consciousness as disasters viewed from a distance. Many law enforcement officers and rescue workers experienced those images firsthand. Headlines flash in newspapers, and sound bites blare on the airwaves as many law enforcement professionals suffer in silence. With increasing frequency, such major critical incidents, as well as smaller-scale events such as shootings, accidents, and personal tragedies--which all emergency response personnel encounter throughout their careers--encroach on their daily lives and may cause intense stress reactions. Managers within the Federal Bureau of Investigation (FBI) commit to mitigating the ill effects of stressors on fellow employees. The FBI's Behavioral Science Unit and the Employee Assistance Unit work together to teach FBI employees a three-step process--how to recognize, understand, and cope with the stress in their lives. Given the alarming increase in violence, terrorism, and related crimes, there exists a myriad of organizations as well as other law enforcement agencies which could benefit from a similar formula. This paper describes how the FBI operationalizes stress management.


Discrete Neural Correlates for the Recognition of Negative Emotions: Insights from Frontotemporal Dementia.
Patients with frontotemporal dementia have pervasive changes in emotion recognition and social cognition, yet the neural changes underlying these emotion processing deficits remain unclear. The multimodal system model of emotion proposes that basic emotions are dependent on distinct brain regions, which undergo significant pathological changes in frontotemporal dementia. As such, this syndrome may provide important insight into the impact of neural network degeneration upon the innate ability to recognise emotions. This study used voxel-based morphometry to identify discrete neural correlates involved in the recognition of basic emotions (anger, disgust, fear, sadness, surprise and happiness) in frontotemporal dementia. Forty frontotemporal dementia patients (18 behavioural-variant, 11 semantic dementia, 11 progressive nonfluent aphasia) and 27 healthy controls were tested on two facial emotion recognition tasks: The Ekman 60 and Ekman Caricatures. Although each frontotemporal dementia group showed impaired recognition of negative emotions, distinct associations between emotion-specific task performance and changes in grey matter intensity emerged. Fear recognition was associated with the right amygdala; disgust recognition with the left insula; anger recognition with the left middle and superior temporal gyrus; and sadness recognition with the left subcallosal cingulate, indicating that discrete neural substrates are necessary for emotion recognition in frontotemporal dementia. The erosion of emotion-specific neural networks in neurodegenerative disorders may produce distinct profiles of performance that are relevant to understanding the neurobiological basis of emotion processing.


Direct synthesis of CsPbX3 perovskite nanocrystal assemblies.
Inorganic CsPbX3 (X = Cl, Br, I) perovskite nanocrystals (NCs) possess many advantageous optoelectronic properties, making them an attractive candidate for light emitting diodes, lasers, or photodetector applications. Such perovskite NCs can form extended assemblies that further modify their bandgap and emission wavelength. In this article, a facile direct synthesis of CsPbX3 NC assemblies that are 1 μm in size and are composed of 10 nm-sized NC building blocks is reported. The direct synthesis of these assemblies with a conventional hot-injection method of the NCs is achieved through the judicious selection of the solvent, ligands, and reaction stoichiometry. Only under selective reaction conditions where the surface ligand environment is tuned to enhance the hydrophobic interactions between ligand chains of neighbouring NCs is self-assembly achieved. These assemblies possess narrow and red-shifted photoluminescence compared to their isolated NC counterparts, which further expands the colour gamut that can be rendered from inorganic perovskites. This is demonstrated through simple down-converting light emitters.


Cardiac Remodeling and Disease Progression in Patients With Repaired Coarctation of Aorta and Aortic Stenosis.
Valvulo-arterial impedance (Zva) is used for assessment of left ventricular (LV) global pressure load in patients with aortic stenosis (AS) and impaired arterial compliance. Because patients with repaired coarctation of aorta (COA) have impaired arterial compliance, we hypothesized that COA patients with greater than or equal to moderate AS (AS-COA group) will have higher Zva, symptomatic progression, and cardiovascular events, as compared to non-COA patients with similar AS severity (AS group). Propensity matching (1:1) of 71 AS-COA and 71 AS patients based on age, sex, body mass index, and aortic valve mean gradient (cohort 1). Of 172 patients, 117 patients (AS-COA [n=62]; AS [n=55]) underwent aortic valve replacement, cohort 2. Cohort 1 was used to assess the relationship between preoperative Zva, cardiac remodeling, and symptomatic progression, while cohort 2 was used to assess the relationship between postoperative Zva, LV mass index regression (reduction in LV mass index after aortic valve replacement), and cardiovascular events. The AS-COA group had higher Zva (4.2±0.6 versus 3.5±0.4 mm Hg/mL·m2, P<0.001), more advanced cardiac remodeling, and higher 5-year incidence of symptomatic progression (85% versus 51%, P<0.001). Preoperative Zva was independently associated with cardiac remodeling (r=0.66, P<0.001) and symptomatic progression (hazard ratio, 1.06 [1.02-1.10], per mm Hg/mL·m2 increase in Zva). The AS-COA group had higher postoperative Zva (3.3±0.5 versus 2.4±0.4 mm Hg/mL·m2, P<0.001), less robust LV mass index regression at 1-year post-aortic valve replacement, and higher 5-year incidence of cardiovascular events. Postoperative Zva was independently associated with LV mass index regression (r=-0.46, P<0.001) and cardiovascular events (hazard ratio, 1.06 [1.02-1.10], per mm Hg/mL·m2 increase in Zva). Adults with AS-COA had higher LV global pressure load, cardiac remodeling, symptomatic progression, and cardiovascular events as compared to non-COA patients with similar severity of AS. Zva can identify patients at risk for adverse outcomes, and perhaps should be used for risk stratification with regards to timing of aortic valve replacement.


Depressive-like states heighten the aversion to painful stimuli in a rat model of comorbid chronic pain and depression.
Chronic pain and depression are two complex states with sensory/somatic and emotional components, and they may mutually exacerbate one another in conditions of comorbidity, leading to a poorer prognosis. The authors have evaluated the sensory and emotional components in a rat model combining chronic constriction injury (CCI, a model of chronic neuropathic pain) with unpredictable chronic mild stress (CMS, an experimental model of depression). In addition, the phosphorylation/activation of the extracellular signal-regulated kinases 1 and 2 and neuronal density was also evaluated in the anterior cingulate cortex. Four groups were tested: sham-control, sham-CMS, CCI-control, and CCI-CMS. CMS selectively heightens aversion to painful experiences in animals subjected to CCI, as measured in the place escape/avoidance test at 20, 25, and 30 min (CCI-CMS (mean±SEM): 75.68±3.32, 66.75±4.70, 77.54±3.60 vs. CCI-control: 44.66±6.07, 43.17±6.92, 52.83±5.92, respectively), in conjunction with an increase in the accumulation of phosphorylation/activation of the extracellular signal-regulated kinases (CCI-CMS: 4.17±0.52 vs. sham-control: 0.96±0.05) and a decrease in neuronal density in the anterior cingulate cortex. In contrast, chronic pain did not exacerbate the characteristic profile of depression (anhedonia and behavioral despair) in rats subjected to CMS. Furthermore, depression enhances the perception of some specific modalities of sensorial pain such as cold allodynia but has no influence on mechanical threshold. These findings support the theory that depression leads to emotional dysfunction in the interpretation of pain in patients suffering chronic pain. In addition, combined animal models of pain-depression may provide a valuable tool to study the comorbidity of pain and depression.


Quick screen of patients' numeracy and document literacy skills: the factor structure of the Newest Vital Sign.
The Newest Vital Sign (NVS) is a survey designed to measure general health literacy whereby an interviewer asks six questions related to information printed on a nutritional label from an ice cream container. It enables researchers to evaluate several health literacy dimensions in a short period of time, including document literacy, comprehension, quantitative literacy (numeracy), application, and evaluation. No study has empirically examined which items belong to which latent dimensions of health literacy in the NVS using factor analysis. Identifying the factor structure of the NVS would enable health care providers to choose appropriate intervention strategies to address patients' health literacy as well as improve their health outcomes accordingly. This study aimed to explore the factor structure of the NVS that is used to assess multiple dimensions of health literacy. A cross-sectional study administering the NVS in a face-to-face manner was conducted at two family medicine clinics in the USA. One hundred and seventy four individuals who participated were at least 20 years old, diagnosed with type 2 diabetes, prescribed at least one oral diabetes medicine, and used English as their primary language. Exploratory factor analysis and confirmatory factor analysis were conducted to investigate the factor structure of the NVS. Numeracy and document literacy are two dimensions of health literacy that were identified and accounted for 63.05% of the variance in the NVS. Internal consistency (Cronbach's alpha) of the NVS were 0.78 and 0.91 for numeracy and document literacy, respectively. Numeracy and document literacy appropriately represent the factor structure of the NVS and may be used for assessing health literacy in greater detail for patients with type 2 diabetes.


Ribonucleotides incorporated by the yeast mitochondrial DNA polymerase are not repaired.
Incorporation of ribonucleotides into DNA during genome replication is a significant source of genomic instability. The frequency of ribonucleotides in DNA is determined by deoxyribonucleoside triphosphate/ribonucleoside triphosphate (dNTP/rNTP) ratios, by the ability of DNA polymerases to discriminate against ribonucleotides, and by the capacity of repair mechanisms to remove incorporated ribonucleotides. To simultaneously compare how the nuclear and mitochondrial genomes incorporate and remove ribonucleotides, we challenged these processes by changing the balance of cellular dNTPs. Using a collection of yeast strains with altered dNTP pools, we discovered an inverse relationship between the concentration of individual dNTPs and the amount of the corresponding ribonucleotides incorporated in mitochondrial DNA, while in nuclear DNA the ribonucleotide pattern was only altered in the absence of ribonucleotide excision repair. Our analysis uncovers major differences in ribonucleotide repair between the two genomes and provides concrete evidence that yeast mitochondria lack mechanisms for removal of ribonucleotides incorporated by the mtDNA polymerase. Furthermore, as cytosolic dNTP pool imbalances were transmitted equally well into the nucleus and the mitochondria, our results support a view of the cytosolic and mitochondrial dNTP pools in frequent exchange.


Significance of a Posttranslational Modification of the PilA Protein of Geobacter sulfurreducens for Surface Attachment, Biofilm Formation, and Growth on Insoluble Extracellular Electron Acceptors.
Geobacter sulfurreducens, an anaerobic metal-reducing bacterium, possesses type IV pili. These pili are intrinsic structural elements in biofilm formation and, together with a number of c-type cytochromes, are thought to serve as conductive nanowires enabling long-range electron transfer (ET) to metal oxides and graphite anodes. Here, we report that a posttranslational modification of a nonconserved amino acid residue within the PilA protein, the structural subunit of the type IV pili, is crucial for growth on insoluble extracellular electron acceptors. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry of the secreted PilA protein revealed a posttranslational modification of tyrosine-32 with a moiety of a mass consistent with a glycerophosphate group. Mutating this tyrosine into a phenylalanine inhibited cell growth with Fe(III) oxides as the sole electron acceptor. In addition, this amino acid substitution severely diminished biofilm formation on graphite surfaces and impaired current output in microbial fuel cells. These results demonstrate that the capability to attach to insoluble electron acceptors plays a crucial role for the cells' ability to utilize them. The work suggests that glycerophosphate modification of Y32 is a key factor contributing to the surface charge of type IV pili, influencing the adhesion of Geobacter to specific surfaces.IMPORTANCE Type IV pili are bacterial appendages that function in cell adhesion, virulence, twitching motility, and long-range electron transfer (ET) from bacterial cells to insoluble extracellular electron acceptors. The mechanism and role of type IV pili for ET in Geobacter sulfurreducens is still a subject of research. In this study, we identified a posttranslational modification of the major G. sulfurreducens type IV pilin, suggested to be a glycerophosphate moiety. We show that a mutant in which the glycerophosphate-modified tyrosine-32 is replaced with a phenylalanine has reduced abilities for ET and biofilm formation compared with those of the wild type. The results show the importance of the glycerophosphate-modified tyrosine for surface attachment and electron transfer in electrode- or Fe(III)-respiring G. sulfurreducens cells.


Adiponectin receptor fragmentation in mouse models of type 1 and type 2 diabetes.
The protein hormone adiponectin regulates glucose and fatty acid metabolism by binding to two PAQR-family receptors (AdipoR1 and AdipoR2). Both receptors feature a C-terminal segment which is released by proteolysis to form a freely circulating C-terminal fragment (CTF) found in the plasma of normal individuals but not in some undefined diabetes patients. The AdipoR1-CTF344-376 is a competitive inhibitor of tumor necrosis factor α cleavage enzyme (TACE) but it contains a shorter peptide domain (AdipoR1 CTF351-362) that is a strong non-competitive inhibitor of insulin-degrading enzyme (IDE). The link between adiponectin receptor fragmentation and diabetes pathology is unclear but could lead to new therapeutic strategies. We therefore investigated physiological variations in the concentrations of CTF in non-obese diabetic (NOD/ShiLtJ) mice and C57BL/6 mice with diet-induced obesity (DIO) as models of diabetes types 1 and 2, respectively. We tested for changes in adiponectin receptor signaling, immune responses, disease progression, and the abundance of neutralizing autoantibodies. Finally, we administered exogenous AdipoR1-CTF peptides either containing or lacking the IDE-binding domain. We observed the more pronounced CTF shedding in the TACE-active NOD mice, which represents an inflammatory autoimmune phenotype, but fragmentation was also observed to a lesser extent in the DIO model. Autoantibodies to CTF were detected in both models. Neither exogenous CTF peptide affected IgG-CTF plasma levels, body weight or the conversion of NOD mice to diabetes. The pattern of AdipoR1 fragmentation and autoantibody production under physiological conditions of aging, DIO, and autoimmune diabetes therefore provides insight into the association adiponectin biology and diabetes.


Localization of methadone in the brain of young rats by computer-assisted autoradiography.
The distribution of systemically administered [14C]methadone in the brain of 21-day-old rats was examined by computer-assisted autoradiography. Methadone binding differed 2.5-fold across the more than 90 neural structures examined, with the dentate nucleus having the highest levels and lamina I of the anterior parietal cortex the lowest. Since a full normal probability plot demonstrated that the binding was distributed normally across brain structures (r = 0.99), binding classes were defined in terms of 0.5 standard deviation units from the mean. In addition to marked binding differences between neuronal structures, there were prominent laminar differences in the cerebral cortex, hippocampus, superior colliculus and cerebellar cortex. These highly specific patterns of methadone localization were specifically related to the opioid receptor because naloxone blocked the antinociceptive effects of methadone on the hot-plate test and abolished the distribution of methadone binding in the central nervous system. The relatively high levels of methadone binding in layers III and V of neocortex, sensory relay nuclei, inferior olive, pontine nuclei, cerebellar nuclei and cerebellar molecular layer suggest that the constellation of physiological and neurobehavioral sequelae of perinatal opioid exposure result from specific binding at multiple sites involved in sensory, motor and integrative information processing.


The National Football Head and Neck Injury Registry. 14-year report on cervical quadriplegia, 1971 through 1984.
Data on cervical spine injuries resulting from participation in football have been compiled by a national registry. Analysis of epidemiologic data and cinematographic documentation clearly demonstrated that the majority of cervical fractures and dislocations were due to axial loading. On the basis of this observation, rule changes banning both deliberate "spearing" and the use of the top of the helmet as the initial point of contact in making a tackle were implemented at the high school and college level. Subsequently, a marked decrease in cervical spine injury rates has occurred. The occurrence of permanent cervical quadriplegia decreased from 34 in 1976 to five in the 1984 season. It is suggested that axial loading of the cervical spine is also responsible for the catastrophic injuries in diving, rugby, ice hockey, and gymnastics. Implementation of appropriate changes in playing techniques and/or equipment modifications could possibly reduce the incidence of cervical spine injuries in these activities.


[The classification of chronic pancreatitis].
To make the II Marseilles Classification of Pancreatitis more applicable to everyday clinical practice, a new systemic approach is suggested basing on clinical, laboratory, CT and ultrasound evidence. Upon examination of 182 chronic sufferers with pancreatitis, interstitial--edematous, parenchymatous, fibrous--sclerotic (indurative), hyperplastic (pseudotumorous) and cystic variants of the disease were established in 34.6%, 30%, 21.1%, 4.4% and 9.9%, respectively. Clinical features typical for each variant of the disease and most common complications are reviewed.