A systematic review of the effectiveness of interventions using the Common Sense Self-Regulatory Model to improve adherence behaviours.
This systematic review assessed the effectiveness of the Common Sense Self-Regulatory Model in the design of interventions to improve adherence behaviours. Of nine eligible studies, six reported improvements in adherence behaviours and three showed moderate to large effects on return to work and lifestyle recommendations. Four studies stated how Common Sense Self-Regulatory Model constructs were addressed in the intervention and five measured illness perceptions as outcomes. Evidence was found for targeting cure/control perceptions in studies aimed at improving adherence behaviours. Future studies need to measure illness perceptions pre- and post-intervention to enable mediational analyses to assess the effect of Common Sense Self-Regulatory Model interventions on improving health outcomes.


Mitochondrial DNA phylogeny in Eastern and Western Slavs.
To resolve the phylogeny of certain mitochondrial DNA (mtDNA) haplogroups in eastern Europe and estimate their evolutionary age, a total of 73 samples representing mitochondrial haplogroups U4, HV*, and R1 were selected for complete mitochondrial genome sequencing from a collection of about 2,000 control region sequences sampled in eastern (Russians, Belorussians, and Ukrainians) and western (Poles, Czechs, and Slovaks) Slavs. On the basis of whole-genome resolution, we fully characterized a number of haplogroups (HV3, HV4, U4a1, U4a2, U4a3, U4b, U4c, U4d, and R1a) that were previously described only partially. Our findings demonstrate that haplogroups HV3, HV4, and U4a1 could be traced back to the pre-Neolithic times ( approximately 12,000-19,000 years before present [YBP]) in eastern Europe. In addition, an ancient connection between the Caucasus/Europe and India has been revealed by analysis of haplogroup R1 diversity, with a split between the Indian and Caucasus/European R1a lineages occurring about 16,500 years ago. Meanwhile, some mtDNA subgroups detected in Slavs (such as U4a2a, U4a2*, HV3a, and R1a1) are definitely younger being dated between 6,400 and 8,200 YBP. However, robust age estimations appear to be problematic due to the high ratios of nonsynonymous to synonymous substitutions found in young mtDNA subclusters.


Turnover of newly synthesized cytochromes P-450scc and P-45011 beta and adrenodoxin in bovine adrenocortical cells in monolayer culture: effect of adrenocorticotropin.
The turnover of newly synthesized cytochromes P-450scc and P-45011 beta, and adrenodoxin was investigated in bovine adrenocortical cells in primary monolayer cultures. Cells were pulse-radiolabeled with [35S]methionine, and specific newly synthesized enzymes were immunoisolated at various times following labeling and quantitated. Adrenocorticotropin (ACTH) treatment did not alter the average turnover rate of total cellular proteins or that of total mitochondrial proteins. The half-life of total cellular proteins of control and ACTH-treated cells was determined to be 20.5 and 23 h, respectively. The half-life of mitochondrial proteins of control and ACTH-treated cells was determined to be 42.5 and 44 h, respectively. The turnover rate of newly synthesized cytochrome P-450scc was approximately the same as total mitochondrial protein (t1/2 = 38 h), and was unchanged by ACTH treatment (t1/2 = 42 h). ACTH treatment did not greatly alter the turnover rate of adrenodoxin. The half-life of adrenodoxin from control and ACTH-treated cells was determined to be 20 and 17 h, respectively. However, ACTH treatment appeared to increase the half-life of cytochrome P-45011 beta from 16 h in control cells to 24 h in treated cells. The differential rate of turnover of mitochondrial proteins studied here supports the contention that mitochondria are subject to heterogeneous degradation. It appears that chronic treatment of bovine adrenocortical cells in culture with ACTH leads to increased steroidogenic capacity, primarily as a result of increased synthesis of steroidogenic enzymes, although, as shown for cytochrome P-45011 beta, ACTH action might also increase steroidogenic capacity by increasing the half-life of this steroid hydroxylase.


Porphyrins in erythrocytes and blood plasma: preliminary studies with qualitative thin-layer chromatography.
1. A simple chromatographic method for the study of porphyrins in erythrocytes and blood plasma, requiring little technician time, is described. The findings in adults and neonates are presented as well as those from severely ill patients. 2. The regular occurrence of uro-, copro- and proto-porphyrin in erythrocytes is deomonstrable as well as sporadic occurrence of tri-, penta-, hexa- and hepta-carboxylic porphyrin. The method gives, however, irregular values for protoporphyrin, which seems to occur in a more labile form in some subjects than in others; this is especially the case in erythropoietic protoporphyria. 3. In blood plasma, uroporphyrin occurs regularly, and coproporphyrin less regularly. Protoporphyrin and penta- to hepta-carboxylic porphyrin are found only occasionally.


Up-regulated desaturase and elongase gene expression promoted accumulation of polyunsaturated fatty acid (PUFA) but not long-chain PUFA in Lates calcarifer, a tropical euryhaline fish, fed a stearidonic acid- and γ-linoleic acid-enriched diet.
The limited activity of Δ6 fatty acid desaturase (FAD6) on α-linolenic (ALA, 18:3n-3) and linoleic (LA, 18:2n-6) acids in marine fish alters the long-chain (≥C(20)) polyunsaturated fatty acid (LC-PUFA) concentration in fish muscle and liver when vegetable oils replace fish oil (FO) in aquafeeds. Echium oil (EO), rich in stearidonic acid (SDA, 18:4n-3) and γ-linoleic acid (GLA, 18:3n-6), may enhance the biosynthesis of n-3 and n-6 LC-PUFA by bypassing the rate-limiting FAD6 step. Nutritional and environmental modulation of the mechanisms in LC-PUFA biosynthesis was examined in barramundi, Lates calcarifer , a tropical euryhaline fish. Juveniles were maintained in either freshwater or seawater and fed different dietary LC-PUFA precursors present in EO or rapeseed oil (RO) and compared with FO. After 8 weeks, growth of fish fed EO was slower compared to the FO and RO treatments. Irrespective of salinity, expression of the FAD6 and elongase was up-regulated in fish fed EO and RO diets, but did not lead to significant accumulation of LC-PUFA in the neutral lipid of fish tissues as occurred in the FO treatment. However, significant concentrations of eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), but not docosahexaenoic acid (DHA, 22:6n-3), appeared in liver and, to a lesser extent, in muscle of fish fed EO with marked increases in the phospholipid fraction. Fish in the EO treatment had higher EPA and ARA in their liver phospholipids than fish fed FO. Endogenous conversion of dietary precursors into neutral lipid LC-PUFA appears to be limited by factors other than the initial rate-limiting step. In contrast, phospholipid LC-PUFA had higher biosynthesis, or selective retention, in barramundi fed EO rather than RO.


Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.
Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry. 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72). When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors. In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.


The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes.
Combined phylogenetic and chromosomal location studies suggest that the orphan receptor RDC1 is related to CXC chemokine receptors. RDC1 provides a co-receptor function for a restricted number of human immunodeficiency virus (HIV) isolates, in particular for the CXCR4-using HIV-2 ROD strain. Here we show that CXCL12, the only known natural ligand for CXCR4, binds to and signals through RDC1. We demonstrate that RDC1 is expressed in T lymphocytes and that CXCL12-promoted chemotaxis is inhibited by an anti-RDC1 monoclonal antibody. Concomitant blockade of RDC1 and CXCR4 produced additive inhibitory effects in CXCL12-induced T cell migration. Furthermore, we provide evidence that interaction of CXCL12 with RDC1 is specific, saturable, and of high affinity (apparent KD approximately 0.4 nM). In CXCR4-negative cells expressing RDC1, CXCL12 promotes internalization of the receptor and chemotactic signals through RDC1. Collectively, our data indicate that RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12.


Chrysoviruses in Magnaporthe oryzae.
Magnaporthe oryzae, the fungus that causes rice blast, is the most destructive pathogen of rice worldwide. A number of M. oryzae mycoviruses have been identified. These include Magnaporthe oryzae. viruses 1, 2, and 3 (MoV1, MoV2, and MoV3) belonging to the genus, Victorivirus, in the family, Totiviridae; Magnaporthe oryzae. partitivirus 1 (MoPV1) in the family, Partitiviridae; Magnaporthe oryzae. chrysovirus 1 strains A and B (MoCV1-A and MoCV1-B) belonging to cluster II of the family, Chrysoviridae; a mycovirus related to plant viruses of the family, Tombusviridae (Magnaporthe oryzae. virus A); and a (+)ssRNA mycovirus closely related to the ourmia-like viruses (Magnaporthe oryzae. ourmia-like virus 1). Among these, MoCV1-A and MoCV1-B were the first reported mycoviruses that cause hypovirulence traits in their host fungus, such as impaired growth, altered colony morphology, and reduced pigmentation. Recently we reported that, although MoCV1-A infection generally confers hypovirulence to fungi, it is also a driving force behind the development of physiological diversity, including pathogenic races. Another example of modulated pathogenicity caused by mycovirus infection is that of Alternaria alternata chrysovirus 1 (AaCV1), which is closely related to MoCV1-A. AaCV1 exhibits two contrasting effects: Impaired growth of the host fungus while rendering the host hypervirulent to the plant, through increased production of the host-specific AK-toxin. It is inferred that these mycoviruses might be epigenetic factors that cause changes in the pathogenicity of phytopathogenic fungi.


Seasonal assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Bremen using personal monitoring.
The study was designed to determine seasonal differences in personal exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) for nonsmokers in Bremen, Germany. The subjects were office workers, either living and working in smoking locations or living and working in nonsmoking locations. One hundred and twenty four randomly selected nonsmoking subjects collected air samples close to their breathing zone by wearing personal monitors for 24 h or, in some cases, for 7-day periods during the winter of 1999. The investigation was repeated in the summer with 126 subjects, comprised of as many of the studied winter population (89 subjects) as possible. Saliva cotinine analyses were undertaken to verify the nonsmoking status of the subjects. Subjects wore one personal monitor while at work and one while away from the workplace on weekdays, and a third monitor at the weekend. Collected air samples were analysed for RSP, nicotine, 3-ethenylpyridine (3-EP) and ETS particles. The latter were estimated using ultraviolet absorbance (UVPM), fluorescence (FPM) and solanesol (SolPM) measurements. ETS exposure was consistently higher in the winter than in the summer, this pattern being particularly evident for subjects both living and working with smokers. The highest median 24-h time weighted average (TWA) concentrations of ETS particles (SolPM, 25 microg m(-3)) and nicotine (1.3 microg m(-3)) were recorded for subjects performing weekday monitoring during the winter. These were significantly higher than equivalent levels of ETS particles (SolPM, 2.4 microg m(-3)) and nicotine (0.26 microg m(-3)) determined during the summer. There were no appreciable differences between winter and summer percent workplace contributions to median TWA ETS particle and nicotine weekday concentrations, the workplace in Bremen, in general, contributing between 35% and 61% of reported median concentrations. Workers, on average, spent one-third of their time at work during a weekday, indicating that concentrations were either comparable or higher in the workplace than in the home and other locations outside the workplace. Median 24-h weekend ETS particle and nicotine concentrations for smoking locations were not significantly different from equivalent weekday levels during the winter, but were significantly lower during the summer. Based upon median 24-h TWA SolPM and nicotine concentrations for the winter, extrapolated to 1 year's ETS exposure, those subjects both living and working in smoking locations (the most highly exposed group) would potentially inhale 13 cigarette equivalents/year (CEs/y). However, based on a similar extrapolation of summer measurements, the same group of subjects would potentially inhale between 1.3 and 1.9 CEs/y. The most highly exposed subjects in this study, based upon 90th percentile concentrations for those both living and working in smoking locations during the winter, would potentially inhale up to 67 CEs/y in the winter and up to 22 CEs/y in the summer. This clearly demonstrates that seasonal effects should be taken into account in the design and interpretation of ETS exposure studies. Air sampling over a 7-day period was shown to be technically feasible, and subsequent RSP, ETS particle and nicotine levels determined by 7-day monitoring were not found to be significantly different from equivalent levels determined by 24-h monitoring. However, the longer sampling period resulted in the collection of an increased quantity of analytes, which improved the limits of quantitation (LOQ) and allowed a more accurate determination of low level ETS exposure. This was reflected by a reduced percentage of data falling below the LOQ for 7-day monitoring compared with 24-h monitoring. The use of a liquid chromatographic method with tandem mass spectrometric detection for saliva cotinine measurement afforded a greatly improved LOQ and greater accuracy at low concentrations compared with the radioimmunoassay (RIA) method used in previous studies by these authors. In this study, 17 subjects out of 180 tested (9.4%) were found to have saliva cotinine levels exceeding the selected threshold of 25 ng ml(-1) used to discriminate between smokers and nonsmokers.


Fluoride concentration in ground water and prevalence of dental fluorosis in Ethiopian Rift Valley: systematic review and meta-analysis.
The concentration of fluoride in ground drinking water greater than the world health organization standard value imposes a serious health, social and economic problem in developing countries. In the Ethiopian Rift Valley where deep wells are the major source of drinking water, high fluoride level is expected. Though many epidemiological studies on fluoride concentration and its adverse effects have been conducted in the region, the result is highly scattered and needs systematically summarized for better utilization. This research is aimed at estimating the pooled level of fluoride concentration in ground drinking water and the prevalence of dental fluorosis among Ethiopian rift valley residences. Cochrane library, MEDLINE/PubMed and Google scholar databases were searched for studies reporting the mean concentration of fluoride in ground water and prevalence of dental fluorosis in Ethiopian Rift valley. Search terms were identified by extracting key terms from reviews and selected relevant papers and review medical subject headings for relevant terms. The mean fluoride level in ground water and the prevalence of dental fluorosis were pooled from eleven and nine primary studies conducted in Ethiopian Rift Valley respectively. The pooled mean level of fluoride in ground water therefore was 6.03 mg/l (95% CI; 4.72-7.72, p < 0.001) and the pooled prevalence of dental fluorosis among residents in Ethiopian rift valley was 32% (95% CI: 25, 39%, p < 0.001), 29% (95% CI: 22, 36%, p < 0.001) and 24% (95% CI: 17, 32%, p < 0.001 for mild, moderate and sever dental fluorosis respectively. The overall prevalence of dental fluorosis is 28% (95% CI, 24, 32%, p < 0.001). Though, the concentration level varies across different part of the rift valley region, still the level of fluoride in ground drinking water is greater than the WHO standard value (1.5 mg/l). Relatively high-level pooled prevalence of dental fluorosis was also seen in Ethiopian rift valley. Therefore, further studies covering the temperature, exposure time and other intake path ways with large sample size is recommended. Interventional projects should be implemented to decrease the concentration of fluoride in the ground drinking water source.


Predators as stressors? Physiological and reproductive consequences of predation risk in tropical stonechats (Saxicola torquata axillaris).
Tropical birds usually lay smaller clutches and are less likely to initiate a second brood than their temperate-zone relatives. This reduction in annual fecundity is generally explained as an adaptation either to higher rates of nest predation or to a more limited food supply concurrent with higher adult survival in the tropics. However, the physiological parameters associated with lower annual fecundity in tropical birds have not been well investigated. We compared the annual fecundity, behaviour and a number of physiological parameters of stonechat parents feeding fledged juveniles in territories with and without fiscal shrikes, a predator on adult and fledged birds. Stonechat pairs in territories with shrikes were less likely to initiate a second brood and delayed successive broods compared to pairs in territories without shrikes. After fledging of their young, males showed a greater propensity than females to initiate distraction calls after a human intrusion into their territory and, therefore, invested more in the defence of their young. In territories with shrikes stonechat males had higher initial plasma corticosterone levels and lower body conditions than males in territories without shrikes, suggesting that they were chronically stressed. In contrast, the females from both types of territory had low initial plasma corticosterone levels. We conclude that shrike presence might account for the delay in initiation of a second brood and the reduction in the tendency to initiate a second brood. Whether these effects are mediated by the elevated levels of corticosterone remains to be demonstrated.


Interventions for treating fractures of the patella in adults.
Fractures of the patella (kneecap) account for around 1% of all human fractures. The treatment of these fractures can be surgical or conservative (such as immobilisation with a cast or brace). There are many different surgical and conservative interventions for treating fractures of the patella in adults. To assess the effects (benefits and harms) of interventions (surgical and conservative) for treating fractures of the patella in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (2 May 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 4), MEDLINE (1946 to April Week 4 2014), Ovid MEDLINE In-Process & Other Non-Indexed Citations (2 May 2014), Embase (1980 to 2014 Week 17), LILACS (1982 to 2 May 2014), trial registers and references lists of articles. Randomised controlled trials (RCTs) or quasi-RCTs that evaluated any surgical or conservative intervention for treating adults with fractures of the patella were eligible for inclusion. The primary outcomes were patient-rated knee function and knee pain, and major adverse outcomes. At least two review authors independently selected eligible trials, assessed risk of bias and cross-checked data extraction. Where appropriate, results of comparable trials were pooled. We included five small trials involving 169 participants with patella fractures. Participant age ranged from 16 to 76 years. There were 68 females and 100 males; the gender of one participant was not reported. Two trials were conducted in China and one each in Finland, Mexico and Turkey.All five trials compared different surgical interventions. Two trials compared biodegradable versus metallic implants for treating displaced patella fractures; one trial compared patellectomy with advancement of vastus medialis obliquus versus simple patellectomy for treating comminuted patella fractures; and two trials compared percutaneous osteosynthesis (both procedures were 'novel' and one used a new device) versus open surgery for treating displaced patella fractures. All the trials had design flaws, such as lack of assessor blinding, which put them at high risk of bias, potentially limiting the reliability of their findings. No trial reported on health-related quality of life, return to previous activity or cosmetic appearance.Very low quality evidence from two trials (48 participants) comparing biodegradable versus metallic implants indicated little difference between the two interventions at two-year follow-up in the numbers of participants with occasional knee pain (1/23 versus 2/24), incurring adverse events (3/24 versus 1/24) or with reduced knee motion (2/23 versus 2/24). Neither trial reported patient-rated knee function scores. In one trial, as per routine practice, metallic implants were removed one year after surgery (four participants). The other trial did not report on this aspect.Very low quality evidence from one trial (28 participants) indicated that compared with simple patellectomy, patellectomy with advancement of vastus medialis obliquus surgery for treating comminuted patella fractures resulted in more participants with a 'good' result based on a subjectively rated score (12/12 versus 11/16; risk ratio (RR) 1.42, 95% confidence interval (CI) 1.01 to 2.01), fewer participants experiencing knee pain (5/12 versus 13/16; RR 3.11, 95% CI 1.01 to 9.60) and more participants with unlimited activity and no loss in quadriceps strength at four-year follow-up. The only adverse event reported was a patellar tendon subluxation in the simple patellectomy group.Neither trial comparing percutaneous osteosynthesis (using novel devices or methods) versus open surgery reported on patient-rated knee function scores. Very low quality evidence from two trials (93 participants) showed that percutaneous osteosynthesis improved knee pain measured using visual analogue scale (0 to 10 where 10 is worst pain) at one month (mean difference (MD) -2.24, 95% CI -2.80 to -1.68) and at up to three months (MD -1.87, 95% CI -2.45 to -1.29). This effect did not persist at six months (very low quality evidence from one trial). Very low quality evidence from the two trials showed significantly fewer participants with adverse events (loss of reduction, infection, hardware complications, delayed wound healing) after percutaneous surgery (8/47 versus 28/46; RR 0.28, 95% CI 0.14 to 0.55). Very low quality evidence from the two trials indicated better clinician-rated knee function scores after percutaneous fixation at two to three months and 12 months follow-up; however, the between-group difference was not clinically important at 24 months. Very low quality evidence showed a lower incidence of hardware removal in the percutaneous group at two years; however, the results in the two trials were heterogeneous and the reasons for removal were not given in detail. There is very limited evidence from RCTs about the relative effects of different surgical interventions for treating fractures of the patella in adults. There is no evidence from RCTs evaluating the relative effects of surgical versus conservative treatment or different types of conservative interventions.Based on very low quality evidence, biodegradable implants seem to be no better than metallic implants for displaced patellar fractures; patellectomy with vastus medialis obliquus advancement may give better results than simple patellectomy for comminuted patellar fractures; and two novel methods of percutaneous osteosynthesis may give better results than conventional open surgery. However, until conclusive evidence becomes available, treatment options must be chosen on an individual patient basis, carefully considering the relative benefits and harms of each intervention and patient preferences. Further randomised trials are needed, but in order to optimise research effort, these should be preceded by research that aims to identify priority questions.


Crystal structure of Zebrafish interferons I and II reveals conservation of type I interferon structure in vertebrates.
Interferons (IFNs) play a major role in orchestrating the innate immune response toward viruses in vertebrates, and their defining characteristic is their ability to induce an antiviral state in responsive cells. Interferons have been reported in a multitude of species, from bony fish to mammals. However, our current knowledge about the molecular function of fish IFNs as well as their evolutionary relationship to tetrapod IFNs is limited. Here we establish the three-dimensional (3D) structure of zebrafish IFNϕ1 and IFNϕ2 by crystallography. These high-resolution structures offer the first structural insight into fish cytokines. Tetrapods possess two types of IFNs that play an immediate antiviral role: type I IFNs (e.g., alpha interferon [IFN-α] and beta interferon [IFN-β]) and type III IFNs (lambda interferon [IFN-λ]), and each type is characterized by its specific receptor usage. Similarly, two groups of antiviral IFNs with distinct receptors exist in fish, including zebrafish. IFNϕ1 and IFNϕ2 represent group I and group II IFNs, respectively. Nevertheless, both structures reported here reveal a characteristic type I IFN architecture with a straight F helix, as opposed to the remaining class II cytokines, including IFN-λ, where helix F contains a characteristic bend. Phylogenetic trees derived from structure-guided multiple alignments confirmed that both groups of fish IFNs are evolutionarily closer to type I than to type III tetrapod IFNs. Thus, these fish IFNs belong to the type I IFN family. Our results also imply that a dual antiviral IFN system has arisen twice during vertebrate evolution.


Nonbifurcating Carotid Artery: A Case Report with a Review of Embryogenesis.
BACKGROUND Vascular anomalies of the carotid vessels can be attributed to false embryogenesis. A rare variant called a nonbifurcating carotid artery (NBCA) exists, where typical carotid bifurcation is not recognizable with its typical branches of the external carotid artery (ECA) and internal carotid artery (ICA). This paper describes a case of this anomaly and reviews the embryogenesis of the carotid arteries for explanation. CASE REPORT A 66-year-old man received a routine health examination at our hospital. Initial carotid ultrasound indicated an absence of bifurcation in the right cervical carotid artery, and magnetic resonance imaging of the brain indicated an absence of the proximal cervical segment of the right ICA, with a remnant arterial stump at the expected bifurcation level. No evidence of the carotid bulb was identified. The common carotid artery seemed to continue cranially in the trunk of the ECA, where it exhibited extracranial branches. After distributing these branches, the carotid artery coursed medially at the C2 level, where it ascended into the carotid canal to become the petrosal segment of the ICA. This carotid anomaly was labelled an NBCA. No aberrant intracranial arteries were derived from the NBCA in this case. CONCLUSIONS In this case, the arterial stump was considered a remnant from agenesis of the right ICA. We assumed that the NBCA most likely developed because of false regression of the third embryogenic aortic arch with persistence of the second aortic arch.


Hydrogen-rich saline protects against ultraviolet B radiation injury in rats.
Exposure of skin to solar ultraviolet (UV) radiation induces photo-damage. Ultraviolet B (UVB) is the major component of UV radiation which induces the production of reactive oxygen species (ROS) and plays an important role in photo-damage. Hydrogen gas reduces ROS and alleviates inflammation. In this study, we sought to demonstrate that hydrogen-rich saline has the effect on skin injuries caused by UVB radiation. UVB radiation was irradiated on female C57BL/6 rats to induce skin injury. Hydrogen-rich saline and nitrogen-rich saline were administered to rats by intraperitoneal injection. Skin damage was detected by microscope after injury. UVB radiation had a significant affection in tumor necrosis factor alpha, interleukin (IL)-1β and IL-6 levels, tissue superoxide dismutase, malondialdehyde and nitric oxide activity. Hydrogen-rich saline had a protective effect by altering the levels of these markers and relieved morphological skin injury. Hydrogen-rich saline protected against UVB radiation injury, possibly by reducing inflammation and oxidative stress.


Advances in Flexible Metallic Transparent Electrodes.
Transparent electrodes (TEs) are pivotal components in many modern devices such as solar cells, light-emitting diodes, touch screens, wearable electronic devices, smart windows, and transparent heaters. Recently, the high demand for flexibility and low cost in TEs requires a new class of transparent conductive materials (TCMs), serving as substitutes for the conventional indium tin oxide (ITO). So far, ITO has been the most used TCM despite its brittleness and high cost. Among the different emerging alternative materials to ITO, metallic nanomaterials have received much interest due to their remarkable optical-electrical properties, low cost, ease of manufacturing, flexibility, and widespread applicability. These involve metal grids, thin oxide/metal/oxide multilayers, metal nanowire percolating networks, or nanocomposites based on metallic nanostructures. In this review, a comparison between TCMs based on metallic nanomaterials and other TCM technologies is discussed. Next, the different types of metal-based TCMs developed so far and the fabrication technologies used are presented. Then, the challenges that these TCMs face toward integration in functional devices are discussed. Finally, the various fields in which metal-based TCMs have been successfully applied, as well as emerging and potential applications, are summarized.


Annual incidence rate of infectious diseases estimated from sentinel surveillance data in Japan.
The estimation of incidence rates of infectious diseases based on the sentinel surveillance data is rather rare. We attempted to estimate these in 2000 in Japan by the surveillance data, and to evaluate their biases. We used the incidences of influenza-like illness and 12 pediatric diseases in each of the sentinel medical institutions in Japan based on surveillance data in 2000. The incidence in all medical institutions was estimated under the assumption that the sentinel medical institutions were randomly selected. The possible bias of this estimate was evaluated in comparison with the hypothetical true incidence obtained as the total incidence in all medical institutions estimated by a regression model using the numbers of all disease outpatients per day from the National Survey of Medical Care Institutions of Japan. The estimated annual incidence rate was 75.6 (95% confidence interval: 72.3-78.7) per 1,000 population in influenza-like illness, and ranged from 1.1 (95% confidence interval: 1.0-1.2) to 285.2 (95% confidence interval: 270.2-300.3) per 1,000 population aged 0-19 years among 12 pediatric diseases. The ratio of the estimated incidence to the hypothetical true one was 1.06-1.26 among influenza-like illness and the 12 pediatric diseases. The incidence rates of influenza-like illness and pediatric diseases in 2000 in Japan were estimated from sentinel surveillance data. The rates obtained provide some useful but not always accurate information. Thus, further research is necessary.


Breast Tumor Prognostic Characteristics and Biennial vs Annual Mammography, Age, and Menopausal Status.
Screening mammography intervals remain under debate in the United States. To compare the proportion of breast cancers with less vs more favorable prognostic characteristics in women screening annually vs biennially by age, menopausal status, and postmenopausal hormone therapy (HT) use. This was a study of a prospective cohort from 1996 to 2012 at Breast Cancer Surveillance Consortium facilities. A total of 15,440 women ages 40 to 85 years with breast cancer diagnosed within 1 year of an annual or within 2 years of a biennial screening mammogram. We updated previous analyses by using narrower intervals for defining annual (11-14 months) and biennial (23-26 months) screening. We defined less favorable prognostic characteristics as tumors that were stage IIB or higher, size greater than 15 mm, positive nodes, and any 1 or more of these characteristics. We used log-binomial regression to model the proportion of breast cancers with less favorable characteristics following a biennial vs annual screen by 10-year age groups and by menopausal status and current postmenopausal HT use. Among 15,440 women with breast cancer, most were 50 years or older (13,182 [85.4%]), white (12,063 [78.1%]), and postmenopausal (9823 [63.6%]). Among 2027 premenopausal women (13.1%), biennial screeners had higher proportions of tumors that were stage IIB or higher (relative risk [RR], 1.28 [95% CI, 1.01-1.63]; P=.04), size greater than 15 mm (RR, 1.21 [95% CI, 1.07-1.37]; P=.002), and with any less favorable prognostic characteristic (RR, 1.11 [95% CI, 1.00-1.22]; P=.047) compared with annual screeners. Among women currently taking postmenopausal HT, biennial screeners tended to have tumors with less favorable prognostic characteristics compared with annual screeners; however, 95% CIs were wide, and differences were not statistically significant (for stage 2B+, RR, 1.14 [95% CI, 0.89-1.47], P=.29; size>15 mm, RR, 1.13 [95% CI, 0.98-1.31], P=.09; node positive, RR, 1.18 [95% CI, 0.98-1.42], P=.09; any less favorable characteristic, RR, 1.12 [95% CI, 1.00-1.25], P=.053). The proportions of tumors with less favorable prognostic characteristics were not significantly larger for biennial vs annual screeners among postmenopausal women not taking HT (eg, any characteristic: RR, 1.03 [95% CI, 0.95-1.12]; P=.45), postmenopausal HT users after subdividing by type of hormone use (eg, any characteristic: estrogen+progestogen users, RR, 1.16 [95% CI, 0.91-1.47]; P=.22; estrogen-only users, RR, 1.14 [95% CI, 0.94-1.37]; P=.18), or any 10-year age group (eg, any characteristic: ages 40-49 years, RR, .1.04 [95% CI, 0.94-1.14]; P=.48; ages 50-59 years, RR, 1.03 [95% CI, 0.94-1.12]; P=.58; ages 60-69 years, RR, 1.07 [95% CI, 0.97-1.19]; P=.18; ages 70-85 years, RR, 1.05 [95% CI, 0.94-1.18]; P=.35). Premenopausal women diagnosed as having breast cancer following biennial vs annual screening mammography are more likely to have tumors with less favorable prognostic characteristics. Postmenopausal women not using HT who are diagnosed as having breast cancer following a biennial or annual screen have similar proportions of tumors with less favorable prognostic characteristics.


Compression garments: no enhancement of high-intensity exercise in hot radiant conditions.
To establish the thermal and performance effects of wearing a lower-body graduated compression garment (GCG) in a hot environment (35.2°C ± 0.1°C) with a representative radiant heat load (~800 W/m²) in contrast to a control (running shorts) and sham condition (a compression garment 1 size larger than that recommended by the manufacturer), with the latter included to establish any placebo effect. Eight participants (mean ± SD; age 21 ± 2 y, height 1.77 ± 0.06 m, mass 72.8 ± 7.1 kg, surface area, 1.89 ± 0.10 m²) completed 3 treadmill tests at a fixed speed for 15 min followed by a self-paced 5-km time trial. Performance (completion time) and pacing (split time), thermal responses (aural, skin, and mean body temperature, cardiac frequency), and perceptual responses (rating of perceived exertion [RPE], thermal sensation, thermal comfort) were measured. Performance in the compression group was not different than in either sham or control at any stage (P > .05); completion time 26.08 ± 4.08, 26.05 ± 3.27, and 25.18 ± 3.15 min, respectively. At the end of the 5-km time trial, RPE was not different; it was 19 ± 1 across conditions. In general, thermal and perceptual responses were not different, although the radiant heat load increased site-specific skin temperature (quadriceps) in the garment conditions. GCG did not enhance performance in a hot environment with a representative radiant heat load. The sham treatment did not benefit perception. GCG provided no evidence of performance enhancement.


Early and persistent up-regulated expression of renal cortical osteopontin in experimental hydronephrosis.
The mechanical disturbance after unilateral ureteral obstruction (UUO) is a nonimmune stimulus that is capable of eliciting a florid macrophage infiltration of the kidney and subsequent post-inflammatory renal scarring. Osteopontin has potential chemoattractant activity and, for this reason, we delineated the kinetics of its expression in the renal cortex of rats with UUO. Whole body X-irradiation and reversal of UUO were utilized as interventional maneuvers to give additional pathobiological insight into this protein's role in the response of the kidneys to ureteral obstruction. Increased osteopontin mRNA levels in obstructed kidneys versus contralateral unobstructed specimens were evident as early as 4 hours after UUO and steadily increased at 12, 24, 48, and 96 hours after UUO. Both X-irradiation and reversal of UUO failed to significantly modulate renal cortical osteopontin mRNA expression at all of the above time points. Paralleling the increments in renal cortical osteopontin mRNA levels were significant elevations in the cortical renal interstitial macrophage number, which was significantly diminished by previous X-irradiation but not reversal of UUO. Focal labeling of osteopontin was noted in both tubular and Bowman's capsular epithelium in obstructed kidneys as early as 4 hours after UUO, whereas, in the contralateral unobstructed specimens, there was only faint staining in Bowman's capsule. By 96 hours after UUO, obstructed kidneys exhibited intense, diffuse staining for osteopontin in both tubules and Bowman's capsule. Osteopontin's immunolocalization was not modulated by X-irradiation or reversal of UUO. These data support the contention that osteopontin is involved in the accumulation of macrophages within the peritubular and periglomerular interstitium in the obstructed renal cortex.


The prevalence of atopic dermatitis in Puerto Rican school children.
Atopic dermatitis is a common inflammatory disease of the skin that usually begins in childhood and its diagnosis depends on clinical criteria. Recent reports have indicated that the worldwide prevalence of atopic dermatitis is increasing. The objective of this study was to determine the prevalence of atopic dermatitis in schoolchildren between the ages of six and seven in two school districts in Puerto Rico. The Laughter questionnaire, developed to determine the prevalence of atopic dermatitis in schoolchildren was translated and validated in Spanish. A population-based prevalence survey was conducted among second grade students in the districts of Guaynabo and Humacao, Puerto Rico. The prevalence of atopic dermatitis was determined by sex, school type (private or public), and geographical location (urban or rural) using the questionnaire. Ninety-two percent (92 %) of the eligible schools participated in the study. A total of 2,393 questionnaires were distributed with a response rate of 53 %. The prevalence of atopic dermatitis among the population surveyed was 24.8%. The prevalence of atopic dermatitis by sex or geographic location was not significantly different (p>0.05). An excess of atopic dermatitis was observed in private schools (31.0%) when compared to public schools (19.9%). The effect remained after controlling potential confounders (POR Mantel-Haenszel = 1.37; 95%CI: 1.07 - 1.42). This study presents evidence of a significant public health problem in Puerto Rico. The prevalence of atopic dermatitis in Puerto Rico is high and possibly a large percentage (70%) of the patients is not been diagnosed.


White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.
White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.


Do not resuscitate, brain death, and organ transplantation: Islamic perspective.
Muslim patients and families are often reluctant to discuss and accept fatal diagnoses and prognoses. In many instances, aggressive therapy is requested by a patient's family, prolonging the life of the patient at all costs. Islamic law permits the withdrawal of futile treatment, including life support, from terminally ill patients allowing death to take its natural course. "Do not resuscitate" is permitted in Islamic law in certain situations. Debate continues about the certainty of brain death criteria within Islamic scholars. Although brain death is accepted as true death by the majority of Muslim scholars and medical organizations, the consensus in the Muslim world is not unanimous, and some scholars still accept death only by cardiopulmonary criteria. Organ transplantation has been accepted in Islamic countries (with some resistance from some jurists). Many fatwas (decrees) of Islamic Jurisprudence Councils have been issued and allowed organs to be donated from living competent adult donor; and from deceased (cadavers), provided that they have agreed to donate or their families have agreed to donate after their death (usually these are brain-dead cases). A clear and well-defined policy from the ministry of health regarding do not resuscitate, brain death, and other end-of-life issues is urgently needed for all hospitals and health providers in most (if not all) Muslim and Arab countries.


Nanoscale View of Amyloid Photodynamic Damage.
A combination of time-resolved optical spectroscopy and nanoscale imaging has been used to study the complex binding to amyloids of a photocatalyst that selectively photo-oxygenates pathogenic aggregates, as well as the consequences of its irradiation. Correlative atomic force microscopy (AFM) and fluorescence microscopy reveals topography-dependent binding of the dye to model β-lactoglobulin fibers, which may also explain the observed difference in their response to photodegradation. We provide direct evidence of the photosensitization of singlet oxygen by the photocatalyst bound to amyloid fibers by direct detection of its NIR phosphorescence. The effect of singlet oxygen at the molecular level brings about nanoscale morphological changes that can be observed with AFM at the single-fiber level. We also find differential response of two α-synuclein mutants to photodamage, which can be rationalized by the presence of amino acids susceptible to photo-oxygenation. Overall, our results help to unravel some of the complexity associated with highly heterogeneous amyloid populations and contribute to the development of improved phototherapeutic strategies for amyloid-related disorders.


Structure-Function Relationships of Temporomandibular Retrodiscal Tissue.
It is estimated that 2% to 4% of the US population will seek treatment for temporomandibular joint (TMJ) symptoms, typically occurring with anterior disc displacement. The temporomandibular retrodiscal tissue (RDT) has been postulated to restrict pathologic disc displacement. To elucidate RDT function, understanding regional RDT biomechanics and ultrastructure is required. No prior biomechanical analysis has determined regional variations in RDT properties or associated biomechanical outcomes with regional variations in collagen and elastin organization. The purpose of this study was to determine direction- and region-dependent tensile biomechanical characteristics and regional fibrillar arrangement of porcine RDT. Incremental stress relaxation experiments were performed on 20 porcine RDT specimens, with strain increments from 5% to 50%, a ramp-strain rate of 2% per second, and relaxation periods of 2.5 min. Tensile characteristics were determined between temporal and condylar regions and anteroposterior and mediolateral directions. RDT preparations were imaged using second-harmonic generation (SHG) microscopy for both collagen and elastin. Young's modulus showed significant differences by region ( P < 0.001) and strain ( P < 0.001). Young's modulus was <1 MPa from 5% to 20% strain, before increasing from 20% to 50% strain to a maximum of 2.9 MPa. Young's modulus trended higher in the temporal region and mediolateral direction. Instantaneous and relaxed moduli showed no significant difference by region or direction. Collagen arrangement was most organized near the disc boundary, with disorganization increasing posteriorly. Elastin was present at the disc boundary and RDT mid-body. Porcine RDT demonstrated region- and strain-dependent variations in tensile moduli, associated with regional differences in collagen and elastin. The small tensile moduli suggest that the RDT is not resistive to pathologic disc displacement. Further biomechanical analysis of the RDT is required to fully define RDT functional roles. Understanding regional variations in tissue stiffness and ultrastructure for TMJ components is critical to understanding joint function and for the long-term goal of improving TMJ disorder treatment strategies.


Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction.
While glucose control is recommended by professional societies for patients with hyperglycemia hospitalized with acute myocardial infarction (AMI), enthusiasm for glucose lowering is tempered, in part, by concerns of inducing hypoglycemia. Yet, whether episodic hypoglycemia that occurs as a result of glucose-lowering therapy is harmful in patients with AMI is unknown. To determine whether the mortality risk associated with hypoglycemic events is similar in patients who develop hypoglycemia spontaneously and those who develop it as a result of insulin therapy. Retrospective cohort study using data from Health Facts, a contemporary database of patients hospitalized across the United States in 40 hospitals between January 1, 2000, and December 31, 2005. Of all the patients in the database, 7820 patients were hospitalized with AMI and were hyperglycemic on admission (glucose level > or = 140 mg/dL). Patients were stratified based on whether they developed a hypoglycemic event (random glucose level < 60 mg/dL) during subsequent hospitalization. Logistic regression models were used to evaluate the association between hypoglycemia and in-hospital mortality within subgroups of patients who were and were not treated with insulin therapy. All-cause in-hospital mortality. Among patients treated or not treated with insulin, those with hypoglycemia were older and had more comorbidity. Hypoglycemia was associated with increased mortality in patients not treated with insulin (18.4% [25/136] mortality in patients with hypoglycemia vs 9.2% [425/4639] in those without hypoglycemia; P<.001), but not in those treated with insulin (10.4% [36/346] mortality in patients with hypoglycemia vs 10.2% [276/2699] in those without hypoglycemia; P = .92). After multivariable adjustment, there was a significant interaction between hypoglycemia and insulin therapy (P value for interaction = .01). Hypoglycemia was a predictor of higher mortality in patients who were not treated with insulin (odds ratio, 2.32 [95% confidence interval, 1.31-4.12] vs patients without hypoglycemia), but not in patients treated with insulin (odds ratio, 0.92 [95% confidence interval, 0.58-1.45] vs patients without hypoglycemia). While hypoglycemia was associated with increased mortality in patients with AMI, this risk was confined to patients who developed hypoglycemia spontaneously. In contrast, iatrogenic hypoglycemia after insulin therapy was not associated with higher mortality risk.


High-resolution anorectal manometry: An expensive hobby or worth every penny?
Introduced approximately 10 years ago, high-resolution manometry catheters have fostered interest in anorectal manometry. This review, which accompanies two articles in this issue of Neurogastroenterology and Motility, reviews the methods, clinical indications, utility, and pitfalls of anorectal manometry and revisits the American Gastroenterological Association (AGA) Medical Position Statement on Anorectal Testing Techniques, which was last published in 1999. High-resolution manometry provides a refined assessment of the anorectal pressure profile, obviates the need for station pull-through maneuvers, and minimizes movement artifacts. In selected cases, this refined assessment may be useful for identifying structural abnormalities or anal weakness. However, many manometry patterns that were previously regarded as abnormal are also observed in a majority of healthy patients, which substantially limits the utility of manometry for identifying defecatory disorders. It is our impression that most conclusions of the AGA medical position statement from 1999 remain valid today. High-resolution techniques have not substantially affected the number of publications on or management of anorectal disorders. The ongoing efforts of an international working group to standardize techniques for anorectal manometry are welcome. Although high-resolution manometry is more than an expensive hobby, improvements in catheter design and further research to rigorously define and evaluate these techniques are necessary to determine if they are worth every penny.


Effect of bupropion extended release on negative emotion processing in major depressive disorder: a pilot functional magnetic resonance imaging study.
Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing. Functional magnetic resonance imaging (fMRI) scans and clinical ratings were obtained for 10 patients with DSM-IV-TR-defined major depressive disorder (mean [SD] age = 41 [+/- 7] years, mean [SD] Hamilton Rating Scale for Depression [HAM-D] score = 21 [+/- 4]) before and after 8 weeks of treatment with bupropion XL. The fMRI sessions were conducted during administration of the Emotional Oddball Task; scans were obtained while subjects viewed emotional distracters and performed an attentional executive function task. The primary outcome was fMRI activations evoked by the emotional distracters. The first baseline fMRI scan was performed in December 2004, and the last posttreatment scan was in March 2005. Treatment with bupropion XL was associated with improvements in HAM-D and Clinical Global Impressions scale ratings (p < .05). Treatment reduced fMRI activation during emotional distracters in several regions including right orbital frontal cortex, left dorsomedial prefrontal cortex, right ventromedial prefrontal cortex, right anterior cingulate cortex, right inferior frontal cortex, right amygdala/parahippocampal area, right caudate, right fusiform gyrus, and left posterior cingulate. In addition, changes in fMRI activation in the amygdala correlated with improvements on the HAM-D (p < .05). Treatment increased activation to attentional targets in the following regions: right middle and inferior frontal gyri, right caudate, and bilateral precuneus. Despite the limitations of a small sample size and the lack of a placebo control group, this study demonstrated that bupropion XL therapy for 8 weeks may attenuate emotion-induced, blood-oxygen-level-dependent (BOLD) activation responses in the amygdala and related brain regions. Such attenuation may be associated with a positive clinical response in depression. Bupropion XL also improved activation in the executive-function neural network. These fMRI surrogate markers offer promise for studying antidepressant and neurocognitive effects of existing and novel therapies.


1D and 2D annotation enrichment: a statistical method integrating quantitative proteomics with complementary high-throughput data.
Quantitative proteomics now provides abundance ratios for thousands of proteins upon perturbations. These need to be functionally interpreted and correlated to other types of quantitative genome-wide data such as the corresponding transcriptome changes. We describe a new method, 2D annotation enrichment, which compares quantitative data from any two 'omics' types in the context of categorical annotation of the proteins or genes. Suitable genome-wide categories are membership of proteins in biochemical pathways, their annotation with gene ontology terms, sub-cellular localization, presence of protein domains or membership in protein complexes. 2D annotation enrichment detects annotation terms whose members show consistent behavior in one or both of the data dimensions. This consistent behavior can be a correlation between the two data types, such as simultaneous up- or down-regulation in both data dimensions, or a lack thereof, such as regulation in one dimension but no change in the other. For the statistical formulation of the test we introduce a two-dimensional generalization of the nonparametric two-sample test. The false discovery rate is stringently controlled by correcting for multiple hypothesis testing. We also describe one-dimensional annotation enrichment, which can be applied to single omics data. The 1D and 2D annotation enrichment algorithms are freely available as part of the Perseus software.


Effects of quorum sensing signal molecules on the hydrogen peroxide resistance against planktonic Pseudomonas aeruginosa.
The effects of quorum sensing signal molecules in Pseudomonas aeruginosa, N-butanoyl-L-homoserinelactone (C4-HSL) and N-(3-oxododecanoyl)-L-homoserinelactone (3-oxo-C12-HSL) on planktonic cell resistance against hydrogen peroxide were studied. In P. aeruginosa JP2 cells with the deletion of lasI and rhlI, the viable cell concentration decreased with time and was reduced by about 4 log after 2 h of 7.5 mM H2O2 treatment, while only a 2-log reduction was found for the wild type P. aeruginosa PAO1 cells. When cultured with 20% PAO1 spent medium, P. aeruginosa JP2 showed similar hydrogen peroxide resistance to that seen in P aeruginosa PAO1. Culturing with 20% JP2 spent medium or with 10 microM C4-HSL and 20 microM 3-oxo-C12-HSL did not affect P aeruginosa JP2 cell susceptibility to hydrogen peroxide. Although both 20% PAO1 and JP2 spent media reacted with H2O2 and reduced H2O2 to 50% of the strength of the original concentration, the remaining H2O2 was still sufficient to kill P. aeruginosa JP2. These results indicate that the difference in cell resistance against H2O2 between P. aeruginosa PAO1 and JP2 was related to the existence of gene products of the lasI and rhlI systems. However, adding synthetic homoserine lactones alone did not increase P. aeruginosa JP2 cell resistance to H2O2 as seen in the experiments adding PAO1 spent medium. Determination of the detailed relation between cascade regulation in P. aeruginosa and its cell resistance to H2O2 will require further investigation.


Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster.
Ribosomes can read through stop codons in a regulated manner, elongating rather than terminating the nascent peptide. Stop codon readthrough is essential to diverse viruses, and phylogenetically predicted to occur in a few hundred genes in Drosophila melanogaster, but the importance of regulated readthrough in eukaryotes remains largely unexplored. Here, we present a ribosome profiling assay (deep sequencing of ribosome-protected mRNA fragments) for Drosophila melanogaster, and provide the first genome-wide experimental analysis of readthrough. Readthrough is far more pervasive than expected: the vast majority of readthrough events evolved within D. melanogaster and were not predicted phylogenetically. The resulting C-terminal protein extensions show evidence of selection, contain functional subcellular localization signals, and their readthrough is regulated, arguing for their importance. We further demonstrate that readthrough occurs in yeast and humans. Readthrough thus provides general mechanisms both to regulate gene expression and function, and to add plasticity to the proteome during evolution. DOI: http://dx.doi.org/10.7554/eLife.01179.001.


Noise Mitigation During Pile Driving Efficiently Reduces Disturbance of Marine Mammals.
Acoustic monitoring of harbor porpoises (Phocoena phocoena L., 1758) indicated a strongly reduced disturbance by noise emitted by pile driving for offshore wind turbine foundations insulated by a big bubble curtain (BBC). This newly developed noise mitigation system was tested during construction of the offshore wind farm Borkum West II (North Sea). Because porpoise activity strongly corresponded to the sound level, operation of the new system under its most suitable configuration reduced the porpoise disturbance area by ~90%. Hence, for the first time, a positive effect of a noise mitigation system during offshore pile driving on an affected marine mammal species could be demonstrated.


Background differences in baseline and stimulated MMP levels influence abdominal aortic aneurysm susceptibility.
Evidence has demonstrated profound influence of genetic background on cardiovascular phenotypes. Murine models in Marfan syndrome (MFS) have shown that genetic background-related variations affect thoracic aortic aneurysm formation, rupture, and lifespan of mice. MFS mice with C57Bl/6 genetic background are less susceptible to aneurysm formation compared to the 129/SvEv genetic background. In this study, we hypothesize that susceptibility to abdominal aortic aneurysm (AAA) will be increased in 129/SvEv mice versus C57Bl/6 mice. We tested this hypothesis by assessing differences in aneurysm size, tissue properties, immune response, and MMP expression. Mice of C57Bl/6 or 129/SvEv background underwent AAA induction by periaortic application of CaCl2. Baseline aortic diameters, tissue properties and MMP levels were measured. After aneurysm induction, diameters, MMP expression, and immune response (macrophage infiltration and bone marrow transplantation) were measured. Aneurysms were larger in 129/SvEv mice than C57Bl/6 mice (83.0% ± 13.6 increase compared to 57.8% ± 6.4). The aorta was stiffer in the 129/SvEv mice compared to C57Bl/6 mice (952.5 kPa ± 93.6 versus 621.4 kPa ± 84.2). Baseline MMP-2 and post-aneurysm MMP-2 and -9 levels were higher in 129/SvEv aortas compared to C57Bl/6 aortas. Elastic lamella disruption/fragmentation and macrophage infiltration were increased in 129/SvEv mice. Myelogenous cell reversal by bone marrow transplantation did not affect aneurysm size. These data demonstrate that 129/SvEv mice are more susceptible to AAA compared to C57Bl/6 mice. Intrinsic properties of the aorta between the two strains of mice, including baseline expression of MMP-2, influence susceptibility to AAA.


Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions.
We have advocated the idea of agonist therapy for treating cocaine addiction. This strategy involves administration of stimulant-like medications (eg, monoamine releasers) to alleviate withdrawal symptoms and prevent relapse. A major limitation of this approach is that many candidate medicines possess significant abuse potential because of activation of mesolimbic dopamine (DA) neurons in central nervous system reward circuits. Previous data suggest that serotonin (5-HT) neurons can provide an inhibitory influence over mesolimbic DA neurons. Thus, it might be predicted that the balance between DA and 5-HT transmission is important to consider when developing medications with reduced stimulant side effects. In this article, we discuss several issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we discuss evidence supporting the existence of a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Then we summarize studies that have tested the hypothesis that 5-HT neurons can dampen the effects mediated by mesolimbic DA. For example, it has been shown that pharmacological manipulations that increase extracellular 5-HT attenuate stimulant effects produced by DA release, such as locomotor stimulation and self-administration behavior. Finally, we discuss our recently published data about PAL-287 (naphthylisopropylamine), a novel non-amphetamine DA-/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers might be useful therapeutic adjuncts for the treatment of cocaine and alcohol addiction, obesity, and even attention deficit disorder and depression.


Risk factors associated with short dental implant success: a long-term retrospective evaluation of patients followed up for up to 9 years.
This multicenter study aimed to identify the different implant- and patient-related risk factors for long-term short dental implant success. Through a retrospective chart review of three centers, patient information regarding demographic variables, smoking habits, history of periodontitis, systemic diseases, and medications in addition to the parameters for short implant placement including implant manufacturer, design, anatomical location, diameter and length, and type of placement was collected. For statistical analysis, univariate regression models were used at the implant and patient levels. A total of 460 short implants placed in 199 patients followed up for up to 9 years were reviewed. Survival rates of the short implants were 95.86% and 92.96% and success rates were 90% and 83.41% for implant- and patient-based analysis, respectively. Peri-implantitis was reported as the primary cause of short dental implant failure (34/46, 73.91%). Univariate regression models revealed that female sex was strongly related to short implant success. In addition, smoking and history of periodontitis were found to have a significant negative influence on short implant success at the implant and patient levels. Taken together, these results support the use of short implants as a predictable longterm treatment option; however, smoking and history of periodontitis are suggested to be the potential risk factors for short implant success. Therefore, clinicians need to assess these potential risk factors and make treatment decisions accordingly.


Preparing the ground for the 'paperless hospital': a case study of medical records management in a UK outpatient services department.
The purpose of the study was to understand the preparations for the introduction of electronic patient record systems (EPRs) within the outpatient services department of a large acute hospital based in the UK. In particular, one of the main aims of the study was to examine in detail the likely impact of EPRs on the working practices of healthcare workers, their expectations regarding the impact of EPRs within the department and other sociotechnical aspects of the management of patient information. Twenty-seven semi-structured interviews were undertaken with staff in a variety of roles that deal with the management of medical records. The interviews focused on the organisation of the medical records department and current problems (e.g., missing records). In addition, the interviews contained questions about the specific role of medical records supervisors in the administration of records, as well as pathways and expectations about EPRs more generally. The data from the interviews was analysed using a mixture of thematic and template analysis and coded using constructs from a sociotechnical model of information system implementation and adoption. The findings show that despite severe delays to the nationally led (NPfIT) roll-out of EPRs and associated IT infrastructure within the UK, staff attitudes within the department were broadly positive about the potential of future EPRs to deliver efficiencies (e.g., improved workflow within the department, reduced reliance on paper-based systems). One of the main influences on attitudes towards the type of EPRs that should exist within outpatients was prompted by negative reactions to the way in which NPfIT systems had been managed and attempted to be introduced in the past. A strong commitment to end-user involvement in EPRs design, together with a rejection of NPfIT, appears to have shaped attitudes towards future expectations of the adoption of new EPRs within the department. In addition, staff do not believe that a rapid change to 'paperless' working is likely to be possible. Our findings provide further evidence that there is a need to treat the implementation of EPRs not simply as an exercise in technical system delivery, but as a larger process of sociotechnical systems change. We conclude the paper with some guidelines, the aim of which is to provide guidance regarding EPRs implementation and adoption informed by sociotechnical principles and ideas.


Comparison of phenotypic and genotypic tropism determination in triple-class-experienced HIV patients eligible for maraviroc treatment.
Determination of HIV-1 tropism is a pre-requisite to the use of CCR5 antagonists. This study evaluated the potential of population genotypic tropism tests (GTTs) in clinical practice, and the correlation with phenotypic tropism tests (PTTs) in patients accessing routine HIV care. Forty-nine consecutive plasma samples for which an original Trofile(TM) assay was performed were obtained from triple-class-experienced patients in need of a therapy change. Viral tropism was defined as the consensus of three or more tropism calls obtained from the combination of two independent population PTT assays (Trofile Biosciences, San Francisco, CA, USA, and Virco, Beerse, Belgium), population GTTs and GTTs based on ultra-deep sequencing. If no consensus was reached, a clonal PTT was performed in order to finalize the tropism call. This two-step approach allowed the definition of a reference tropism call. According to the reference tropism result, 35/49 samples were CCR5 tropic (R5) (patients eligible for maraviroc treatment) and 14/49 were assigned as non-R5 tropic. The non-R5 samples [patients not eligible for maraviroc treatment according to the FDA/European Medicines Agency (EMEA) label] group included both the CXCR4 (X4) samples and the dual and mixed CCR5/CXCR4 (R5/X4) samples. Compared with Trofile(TM) population PTTs, population GTTs showed a higher sensitivity (97%) and a higher negative predictive value (91%), but almost equal specificity and an equal positive predictive value. In line with recent reports from clinical trial data, our data support the use of population genotypic tropism testing as a tool for tropism determination before the start of maraviroc.


An un-commissioned randomized, placebo-controlled double-blind study to test the effect of deep sea fish oil as a pain reliever for dogs suffering from canine OA.
An un-commissioned randomized, double-blinded, placebo controlled clinical study was planned using a deep sea fish oil product for pets. Seventy-seven client-owned dogs with osteoarthritis were randomly assigned to supplement the food with either the fish oil product or corn (=placebo) oil. Our main outcome variables were force platform variables peak vertical force (PVF) and impulse, the validated Helsinki Chronic Pain Index (HCPI) and the use of rescue NSAIDs. Secondary outcome variables were a locomotion visual analog scale (VAS), a Quality of life VAS, a comparative questionnaire, a veterinary assessment, owners' final assessment of outcome and guessing the product given. When comparing the two test groups at the end of the trial (16 weeks) there was no significant difference in any of the main outcome variables but owners of dogs that had taken fish oil were significantly happier with the treatment at the end visit and did significantly better at guessing what group their dogs had been in, compared to the placebo group. When comparing variables within the fish oil group as change from baseline to trial end, there were significant positive changes in PVF, HCPI, NSAID use, Quality of life VAS, as well as in all three scores in the comparative questionnaire (locomotion, every-day situations, and skin & coat). There were similar positive trends in force platform impulse and in the veterinary assessment variables, although they did not reach significance. Within the placebo group there were significant positive changes only in the HCPI and a significant deterioration according to veterinary assessment. When compared to placebo, there was not a major statistically significant benefit in using deep sea fish oil as a pain reliever in our study population of dogs suffering from osteoarthritis. However, the fish oil treated patients improved significantly in many of the variables, when comparing baseline values to the study-end values within the group, indicating a true but small relief in symptoms. Deep sea fish oil supplementation could be considered a part of the multimodal pain relieving approach currently recommended for dogs suffering from OA, especially for individuals that do not tolerate anti-inflammatory drugs.


Relationships between technique and bat speed, post-impact ball speed, and carry distance during a range hitting task in cricket.
The ability of a batsman to clear the boundary is a major contributor to success in modern cricket. The aim of this study was to identify technique parameters characterising those batsmen able to generate greater bat speeds, ball launch speeds, and carry distances during a range hitting task in cricket. Kinematic data were collected for 20 batsmen ranging from international to club standard, and a series of ball launch, bat-ball impact, and technique parameters were calculated for each trial. A stepwise multiple linear regression analysis found impact location on the bat face in the medio-lateral and longitudinal directions and bat speed at impact to explain 68% of the observed variation in instantaneous post-impact ball speed. A further regression analysis found the X-factor (separation between the pelvis and thorax segments in the transverse plane) at the commencement of the downswing, lead elbow extension, and wrist uncocking during the downswing to explain 78% of the observed variation in maximum bat speed during the downswing. These findings indicate that players and coaches should focus on generating central impacts with the highest possible bat speed. Training and conditioning programmes should be developed to improve the important kinematic parameters shown to generate greater bat speeds, particularly focussing on increased pelvis to upper thorax separation in the transverse plane.


Comparative proteomics reveals human pluripotent stem cell-derived limbal epithelial stem cells are similar to native ocular surface epithelial cells.
Limbal epithelial stem cells (LESCs) are tissue-specific stem cells responsible for renewing the corneal epithelium. Acute trauma or chronic disease affecting LESCs may disrupt corneal epithelial renewal, causing vision threatening and painful ocular surface disorders, collectively referred to as LESC deficiency (LESCD). These disorders cannot be treated with traditional corneal transplantation and therefore alternative cell sources for successful cell-based therapy are needed. LESCs derived from human pluripotent stem cells (hPSCs) are a prospective source for ocular surface reconstruction, yet critical evaluation of these cells is crucial before considering clinical applications. In order to quantitatively evaluate hPSC-derived LESCs, we compared protein expression in native human corneal cells to that in hPSC-derived LESCs using isobaric tag for relative and absolute quantitation (iTRAQ) technology. We identified 860 unique proteins present in all samples, including proteins involved in cell cycling, proliferation, differentiation and apoptosis, various LESC niche components, and limbal and corneal epithelial markers. Protein expression profiles were nearly identical in LESCs derived from two different hPSC lines, indicating that the differentiation protocol is reproducible, yielding homogeneous cell populations. Their protein expression profile suggests that hPSC-derived LESCs are similar to the human ocular surface epithelial cells, and possess LESC-like characteristics.


The impact of elective diagnostic laparoscopy in chronic abominal disorders.
Diagnostic laparoscopy has become an integral part of general surgical procedures with the recent advancements in laparoscopic technology. Since surgeons are more oriented in viewing and dissection of different intra-abdominal areas and are proficient in the definitive management of complications in the procedures, diagnostic laparoscopy may be better off in the hands of surgeons. Laparoscopy has proved to be an important tool in final minimally invasive exploration for selected medical patients with chronic abdominal disorders, the diagnosis of which remains uncertain despite employing the requisite laboratory and non-invasive imaging investigations. This retrospective study was done to evaluate the accuracy of elective diagnostic laparoscopy in patients with chronic abdominal disorders and its impact on the management of these patients. The records of 35 patients, admitted to Riyadh Medical Complex with chronic abdominal disorders and referred to the author by physicians for elective diagnostic laparoscopy from 1999 through 2004, were evaluated for the accuracy and impact of this procedure in the further management of these patients. All 35 patients were investigated by the referring physician. Investigations included hematology, biochemistry, radiology, ascitic fluid analysis, endoscopic and imaging studies and the Mantoux test. These investigations suggested abdominal tuberculosis in 22 patients and intra-abdominal malignancy in 13 patients. They were referred for elective diagnostic laparoscopy and tissue biopsy. Diagnostic laparoscopy confirmed the diagnosis in all patients suspected of malignancy. In patients with suspected abdominal tuberculosis, the laparoscopic diagnosis and biopsy revealed tuberculosis (16 patients), liver cirrhosis (2 patients), Crohn's disease (1 patient), and metastatic carcinoma of terminal ileum (1 patient). In 2 patients the procedure did not reveal any specific pathology. The accuracy of the preoperative investigations for those suspected to have abdominal tuberculosis was 71 %. There was 100% impact of diagnostic laparoscopy on the management of all 35 patients since, in the 2 patients with negative laparoscopy, at least tuberculosis and malignancy were excluded. Diagnostic laparoscopy in the hands of surgeons proved to have an impact as an investigation technique, where the diagnosis remained uncertain after the laboratory and non-invasive investigations, of selected medical patients with chronic abdominal disorders. It is a minimally invasive procedure which has a high percentage of accuracy in diagnosis and impact in the further management of selected patients.


Adaptability to changes in temporal structure is fornix-dependent.
Recognition memory deficits, even after short delays, are sometimes observed following hippocampal damage. One hypothesis links the hippocampus with processes in updating contextual memory representation. Here, we used fornix transection, which partially disconnects the hippocampal system, and compares the performance of fornix-transected monkeys with normal monkeys on two versions of a delayed-matching-to-position task with short delays. Spatial recognition memory was affected by fornix transection only when the temporal structure of the task changed across trials, while differences in motor control, motivation, perception, or short-term memory were not critical. We attributed the deficit to a compromised ability in tracking changes in task temporal structure.


Melatonin protects against oxidative damage and restores expression of GLUT4 gene in the hyperthyroid rat heart.
To understand the mechanism of cardiovascular dysfunction in the hyperthyroid condition, the role of oxidative stress was examined in rats treated with 3,5,3'-triiodo-l-thyronine (T3). Treatment of rats daily with T3 (8 microg/100 g BW) for 15 days resulted in an increase in heart weight to body weight ratio, which was ameliorated by antioxidants, melatonin (2 mg/100 g BW) or vitamin E (4 mg/100 g BW). Both melatonin and vitamin E also inhibited rises of lipid peroxidation and hydroxyl radical generation and prevented the inhibition of Cu,Zn-superoxide dismutase in the hypertrophic heart. The expression of the glucose transporter, GLUT4, was reduced in response to T3, which was completely restored by melatonin and partially by vitamin E. However, neither antioxidant prevented down regulation of peroxisome proliferator-activated receptor-alpha in the hyperthyroid heart. Furthermore, the reduced level of myocyte enhancer factor-2, a regulator of GLUT4 transcription was restored completely by melatonin and partially by vitamin E treatment. Glucose uptake in hypertrophic left ventricular cells was also restored by these antioxidants. The expression of B-type natriuretic peptide, a marker of heart failure, was significantly increased by T3 and ameliorated by melatonin or vitamin E treatments. In general, the beneficial effects of melatonin given as a co-treatment with T3 were better than those induced by vitamin E. These data show that melatonin ameliorates hypertrophic growth of the myocardium induced by hyperthyroidism and provide an insight into the mechanism of reactive oxygen species-mediated down regulation of metabolically important genes such as GLUT4 in the heart.


Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials.
The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.


Adaptive strategies and pathogenesis of Clostridium difficile from in vivo transcriptomics.
Clostridium difficile is currently the major cause of nosocomial intestinal diseases associated with antibiotic therapy in adults. In order to improve our knowledge of C. difficile-host interactions, we analyzed the genome-wide temporal expression of C. difficile 630 genes during the first 38 h of mouse colonization to identify genes whose expression is modulated in vivo, suggesting that they may play a role in facilitating the colonization process. In the ceca of the C. difficile-monoassociated mice, 549 genes of the C. difficile genome were differentially expressed compared to their expression during in vitro growth, and they were distributed in several functional categories. Overall, our results emphasize the roles of genes involved in host adaptation. Colonization results in a metabolic shift, with genes responsible for the fermentation as well as several other metabolic pathways being regulated inversely to those involved in carbon metabolism. In addition, several genes involved in stress responses, such as ferrous iron uptake or the response to oxidative stress, were regulated in vivo. Interestingly, many genes encoding conserved hypothetical proteins (CHP) were highly and specifically upregulated in vivo. Moreover, genes for all stages of sporulation were quickly induced in vivo, highlighting the observation that sporulation is central to the persistence of C. difficile in the gut and to its ability to spread in the environment. Finally, we inactivated two genes that were differentially expressed in vivo and evaluated the relative colonization fitness of the wild-type and mutant strains in coinfection experiments. We identified a CHP as a putative colonization factor, supporting the suggestion that the in vivo transcriptomic approach can unravel new C. difficile virulence genes.


Life cycle assessment of roads: Exploring research trends and harmonization challenges.
The transparency, heterogeneity and hypotheses considered in the calculation of the environmental impacts of roads are still barriers to the identification of low-carbon solutions. To overcome this problem, this study presents an analysis of 94 papers obtained in a systematic literature review of the Scopus, Science Direct, Mendeley, Springer Link, and Web of Science databases. From a total of 417 road case studies, only 18% were found to be fully transparent, reproducible, and likely to present reliable results. The road design parameters of the speed limit were provided in 11% of the cases, and the average annual daily traffic data were provided in 42%. Limited data were found for the dimensions of road elements such as the number (77%) and width of lanes (33%), shoulders (15%), footpaths (5%), berms (1%) and foreslope (4%). The source of the life cycle inventory was presented in 57% of the case studies, impact assessment method was indicated in 22%, and the software utilized was listed in 50%. A lack of information was noted in the description of the types of materials employed in road projects. In addition, the large heterogeneity in the definitions of the functional unit, system boundary and in the reference study period of repair, replacement, rehabilitation or end-of-life for both flexible and rigid pavement does not support the identification of the most environmentally friendly solutions. Based on the results of the analysis, several recommendations for design parameters and life cycle assessment aspects are proposed to support a harmonized calculation of the environmental impacts of road projects.


Metabolomic changes in CSF of migraine patients measured with 1H-NMR spectroscopy.
Migraine is a common episodic brain disorder. Treatment options and diagnosis are hampered by an incomplete understanding of disease pathophysiology and the lack of objective diagnostic markers. The aim of this study was to identify biochemical differences characteristic for different subtypes of migraine in cerebrospinal fluid (CSF) of migraine patients using an exploratory 1H-NMR-based metabolomics approach. CSF was obtained, in between migraine attacks, via lumbar puncture from patients with hemiplegic migraine, migraine with aura, migraine without aura, and healthy controls. Metabolite concentrations were measured by quantitative 1H-NMR spectroscopy. Multivariate data analysis was used to find the optimal set of predictors, generalized linear models (GLM) were used to ascertain the differential significance of individual metabolites. In CSF samples from 18 patients with hemiplegic migraine, 38 with migraine with aura, 27 migraine without aura, and 43 healthy controls, nineteen metabolites were identified and quantified. Hemiplegic migraine patients could be discriminated from healthy controls using supervised multivariate modelling with 2-hydroxybutyrate and 2-hydroxyisovalerate as the most discriminant metabolites. Univariate GLM analysis showed 2-hydroxybutyrate to be lower in hemiplegic migraine compared with healthy controls; no significant differences were observed for other metabolites. It was not possible to discriminate migraine with and without aura from healthy controls based on their metabolic profile. Using an exploratory 1H-NMR metabolomics analysis we identified metabolites that were able to discriminate hemiplegic migraine patients from healthy controls. The lower levels of 2-hydroxybutyrate found in patients with hemiplegic migraine could indicate a dysregulation of the brain's energy metabolism. An experimental confirmation in vitro or in animal models will be required to confirm or discard this hypothesis. Migraine with and migraine without aura patients did not reveal a metabolic profile different from healthy controls.


Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet.
This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.


Prescribing patterns of medicines in chronic kidney disease patients on maintenance hemodialysis.
To study medicine prescribing pattern for chronic kidney disease (CKD) patients on maintenance hemodialysis. This prospective observational study was conducted in hemodialysis unit of a teaching hospital with adult CKD patients on maintenance hemodialysis. Patients' clinical profile, drug-use pattern, and medication-related problem data were captured in a structured case report form and the data were analyzed descriptively. Adherence level was assessed by Morisky Medication-Taking Adherence Scale 4-item. Data from 100 patients recruited over 6 months have been analyzed. The median (interquartile range [IQR]) age was 51 (42-57) years; 57% were male, mean [standard deviation (SD)] urea level was 160.11 (70.32) mg/dL, mean (SD) creatinine level was 8.73 (5.29) mg/dL. A large number (46%) were suffering from diabetic nephropathy. The common comorbidities were anemia (89%) followed by hypertension (85%). The median (IQR) number of drugs per prescription was 10 (9-13), with the bulk being cardiovascular drugs (23.41%) followed by gastrointestinal drugs (15.76%) and vitamins (12.29%). The median (IQR) number of potential drug-drug interaction per prescription was 2 (2-3). The incidence of adverse drug reactions (ADRs) was 46% with hyponatremia being most common (32%), followed by hypoglycemia (16%) and hypokalemia (10%). Adherence level was low in the majority (64%) of patients. There is a high incidence of polypharmacy along with significant medication-related problems such as high drug-drug interactions/prescription, high incidence of ADRs, and low adherence.


Galectin-1 overexpression in nasopharyngeal carcinoma: effect on survival.
Galectin-1 overexpression is significantly correlated with the survival rate of patients with nasopharyngeal carcinoma (NPC). Immunohistochemical analysis of galectin-1 expression might be useful for identifying patients with a high risk of distant metastasis and for prompting timely adjuvant systemic therapy for patients with aggressive NPC. We examined the effect of galectin-1 on the survival rate of patients with NPC. A total of 124 patients diagnosed between 1998 and 2002 with NPC without distant metastasis were enrolled in this single-center historical prospective cohort study. Immunohistochemical analysis was used to correlate the galectin-1 expression score in the cytoplasm and the survival rate of patients with NPC. Patients with NPC who overexpressed galectin-1 in cytoplasm showed more aggressive tumor growth and significantly shorter disease-specific survival (DSS) (p = 0.0037) and distant metastasis-free survival (DMFS) (p = 0.0006) than patients with NPC who did not overexpress galectin-1. Multivariate analysis showed that galectin-1 overexpression remained prognostically independent for DSS (p = 0.031, hazard ratio = 1.821), and DMFS (p = 0.005, hazard ratio = 2.417), together with the advanced III-IV stages.


Coccidioidomycosis complicating solid organ transplantation.
Coccidioidomycosis is the most common endemic mycosis to cause disease in solid-organ transplant patients in North America. Underlying renal and liver disease, T-lymphocyte suppression from antirejection medication, and activation of immunomodulating viruses, such as cytomegalovirus, all increase the risk for coccidioidomycosis among these patients. About one half of all cases are the result of reactivation of previously acquired coccidioidal infection and occur during the first year after transplantation. Although disseminated infection is common, most cases manifest pulmonary symptoms. Culture of pulmonary secretions from bronchoscopy is frequently diagnostic. Serologic tests are particularly useful for identifying patients who are at high risk for reactivating coccidioidomycosis posttransplantation. Amphotericin B and azoles are the mainstay of therapy. Although there are no established approaches to preventing coccidioidomycosis among these patients, studies are underway examining the use of prophylactic azole antifungals with documented prior coccidioidal infection.


The active methanotrophic community in hydromorphic soils changes in response to changing methane concentration.
Methanotrophic communities were studied in several periodically water-saturated gleyic soils. When sampled, each soil had an oxic upper layer and consumed methane from the atmosphere (at 1.75 ppmv). In most gleyic soils the K(m(app)) values for methane were between 70 and 800 ppmv. These are higher than most values observed in dry upland soils, but lower than those measured in wetlands. Based on cultivation-independent retrieval of the pmoA-gene and quantification of partial pmoA gene sequences, type II (Alphaproteobacteria) methanotrophs of the genus Methylocystis spp. were abundant (> 10(7) pmoA target molecules per gram of dry soil). Type I (Gammaproteobacteria) methanotrophs related to the genera Methylobacter and Methylocaldum/Methylococcus were detected in some soils. Six pmoA sequence types not closely related to sequences from cultivated methanotrophs were detected as well, indicating that diverse uncultivated methanotrophs were present. Three Gleysols were incubated under different mixing ratios of (13)C-labelled methane to examine (13)C incorporation into phospholipid fatty acids (PLFAs). Phospholipid fatty acids typical of type II methanotrophs, 16:0 and 18:1omega7c, were labelled with (13)C in all soils after incubation under an atmosphere containing 30 ppmv of methane. Incubation under 500 ppmv of methane resulted in labelling of additional PLFAs besides 16:0 and 18:1omega7c, suggesting that the composition of the active methanotrophic community changed in response to increased methane supply. In two soils, 16:1 PLFAs typical of type I methanotrophs were strongly labelled after incubation under the high methane mixing ratio only. Type II methanotrophs are most likely responsible for atmospheric methane uptake in these soils, while type I methanotrophs become active when methane is produced in the soil.