bluuebunny/crossref_metadata_2025 huggingface dataset:
Opicapone: a short lived and very long acting novel catechol‐O‐methyltransferase inhibitor following multiple dose administration in healthy subjects
Authors: Rocha José Francisco , Almeida Luis , Falcão Amílcar , Palma P. Nuno , Loureiro Ana I. , Pinto Roberto , Bonifácio Maria João , Wright Lyndon C. , Nunes Teresa , Soares‐da‐Silva Patrício
Published: January 2013

Aims

The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol‐O‐methyltransferase (S‐COMT) activity following repeated doses of opicapone.

Methods

This randomized, placebo‐controlled, double‐blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days.

Results

Opicapone was well tolerated. Its systemic exposure increased in an approximately dose‐proportional manner with an apparent terminal half‐life of 1.0 to 1.4 h. Sulphation was the main metabolic pathway. Opicapone metabolites recovered in urine accounted for less than 3% of the amount of opicapone administered suggesting that bile is likely the main route of excretion. Maximum S‐COMT inhibition (Emax) ranged from 69.9% to 98.0% following the last dose of opicapone. The opicapone‐induced S‐COMT inhibition showed a half‐life in excess of 100 h, which was dose‐independent and much longer than plasma drug exposure. Such a half‐life translates into a putative underlying rate constant that is comparable with the estimated dissociation rate constant of the COMT–opicapone complex.

Conclusion

Despite its short elimination half‐life, opicapone markedly and sustainably inhibited erythrocyte S‐COMT activity making it suitable for a once daily regimen.
A phase I study of panobinostat (LBH589) in patients with primary myelofibrosis (PMF) and post‐polycythaemia vera/essential thrombocythaemia myelofibrosis (post‐PV/ET MF)
Authors: Mascarenhas John , Lu Min , Li Timmy , Petersen Bruce , Hochman Tsivia , Najfeld Vesna , Goldberg Judith D. , Hoffman Ronald
Published: January 2013

Panobinostat (LBH589), a novel histone deacetylase inhibitor (HDACi), was evaluated in a phase I study of patients with primary myelofibrosis (PMF) and post‐essential thrombocythaemia/polycythaemia vera‐related myelofibrosis (Post‐ET/PV MF). Eighteen patients (PMF 56%; Post‐PV MF 28%; Post‐ET MF 17%) were treated in three cohorts at oral doses of (i) 20, (ii) 30, and (iii) 25 mg three times weekly consecutively. Reversible thrombocytopenia was the dose‐limiting toxicity. Five patients (two in Dose Cohort 1, one in Dose Cohort 2 and two in Dose Cohort 3) received six or more cycles and were evaluable for response assessment. After the sixth cycle, three of these five patients achieved clinical improvement (CI) with 100% reduction in palpable splenomegaly from baseline, and two patients experienced stable disease. Panobinostat therapy was also associated with improvement in the degree of anaemia in two of the five patients. Of the three patients who achieved CI after six cycles, one patient achieved a near complete remission after 15 cycles of treatment and another patient had resolution of marrow fibrosis after 16 cycles. We conclude that panobinostat is a well‐tolerated, clinically active treatment for MF patients, regardless of JAK2 V617F status, and most effective when given at low doses over long periods of time.
Positive feedback loop and synergistic effects between hypoxia‐inducible factor‐2α and stearoyl–CoA desaturase‐1 promote tumorigenesis in clear cell renal cell carcinoma
Authors: Zhang Yujian , Wang Hui , Zhang Jin , Lv Jianwei , Huang Yiran
Published: January 2013

Adapting to hypoxic stress is pivotal in tumor progression and determining tumor malignancy. The transcriptional factor hypoxia‐inducible factor (HIF) is crucial in modulating tumorous hypoxic responses through altering cell energy metabolism, which includes the modification of glucose and lipid metabolism‐associated gene expression. Stearoyl–CoA desaturase‐1 (SCD1) is the main isoform of SCDs, the rate‐limiting enzymes in the biosynthesis of monounsaturated fatty acids from saturated fatty acids, which is extensively activated in cancer progression. In this study, we found that SCD1 and HIF‐2α were overexpressed in human clear cell renal cell carcinoma (ccRCC) tissues and ccRCC cell lines, and were upregulated in the 786‐0 ccRCC cell line under hypoxia. Knockdown of SCD1 or HIF‐2α impacted the other's expression. Enhancing SCD1 resulted in HIF‐2α upregulation, which could be blocked by inhibiting the PI3K/Akt pathway. Deficiency of SCD1 or HIF‐2α in 768‐0 cells led to apoptosis, less colony formation ability, and decreased cell migration. More obvious effects were observed in 786‐0 cells with double SCD1 and HIF‐2α knockdown. These results indicate a PI3K/Akt‐mediated loop between SCD1 and HIF‐2α that mutually enhances their protein levels. Both SCD1 and HIF‐2α are critical to promoting tumorigenesis by synergistically acting on maintaining cell survival, triggering cell migration, and enhancing the colony formation ability of cancer cells.
A systematic review of interventions to promote social support and parenting skills in parents with an intellectual disability
Authors: Wilson S. , McKenzie K. , Quayle E. , Murray G.
Published: January 2013

The family support needs of parents with an intellectual disability (ID) are relatively unknown. This paper reviewed two types of intervention for parents with ID: those designed to strengthen social relationships and those teaching parenting skills. A literature search was conducted using electronic databases and a limited number of evaluative studies were found. The evidence for interventions aimed at strengthening social relationships was inconclusive; although positive changes were observed, there were limitations in study design which restricted the generalizability of the results. The evidence for parental skills teaching suggested that behavioural based interventions are more effective than less intensive forms such as lesson booklets and the provision of normal services, although these studies also had limitations. There is a need for further large scale controlled studies in this area to provide clearer evidence and to explore additional factors relating to child, parent and family which may impact on outcomes.
Short‐form versions of theParental‐CaregiversPerceptionsQuestionnaire and theFamilyImpactScale
Authors: Thomson William Murray , Foster Page Lyndie A. , Gaynor Wanda N. , Malden Penelope E.
Published: January 2013

Objective

To develop short‐form versions of theParental‐CaregiversPerceptionsQuestionnaire (P‐CPQ) andFamilyImpactScale (FIS).

Methods

Pretest/post‐test clinical studies involved parent‐completed questionnaires (theP‐CPQand theFIS) before and some weeks after dental care (under general anaesthesia) for early childhood caries (ECCs) in consecutive clinical samples fromWellington andAuckland. Deriving the short‐form versions used only the baseline data from theWellington sample (N = 195), whereas their evaluation used both baseline and follow‐up data from theAuckland sample (N = 144 followed up). Item impact analysis was used to identify the 8 and 16 items with the greatest impact. An eight‐item short‐formFISversion was obtained in the same way.

Results

In theWellington sample,Cronbach's α for the full, 16‐ and 8‐itemP‐CPQscales was 0.92, 0.89 and 0.82, respectively, and it was 0.88 and 0.85 for the full and eight‐itemFIS. Cross‐sectional concurrent validity in theWellington sample was acceptable for all short forms. Examining their responsiveness in theAuckland sample, large decreases post‐treatment were observed in the short‐formP‐CPQscores which were similar in relative magnitude to those seen with the full version. The full and short‐formFISscale scores showed moderate decreases.

Conclusions

The reliability, validity and responsiveness of the short‐form versions were acceptable in these settings with children suffering from severeECC; however, before they can be treated as definitive measures for use in health services research to determine the effects of clinical interventions forECC, their test‐retest reliability should be examined and further validation undertaken.
Interleukin‐27 promotes inflammatory and neuroprotective responses in microglia
Authors: Kawanokuchi Jun , Takeuchi Hideyuki , Sonobe Yoshifumi , Mizuno Tetsuya , Suzumura Akio
Published: January 2013

Objectives

Interleukin‐27 (IL‐27) is released by antigen‐presenting cells including macrophages, dendritic cells and microglia, and negatively regulates IL‐17‐producing T helper (Th17) cells, which play key pathogenic roles in multiple sclerosis. As the effects of IL‐27 on cells in the central nervous system are unclear, we have examined the effects of IL‐27 on microglia to uncover the roles of IL‐27 in immune responses of the central nervous system.

Methods

The effects of IL‐27 on microglial production of cytokines, neurotrophic factors and antigen‐presentation related molecules were examined using reverse transcription polymerase chain reaction analyses and enzyme‐linked immunosorbent assays. The effects of IL‐27 on microglial antigen‐presenting function were also assessed using coculture assays of microglia and myelin oligodendrocyte glycoprotein peptide 35–55‐specific T cells.

Results

We showed that IL‐27 induces inflammatory and neuroprotective responses effects in microglia. IL‐27 enhanced the production of nitric oxide and such pro‐inflammatory cytokines as tumor necrosis factor‐α and IL‐6 in lipopolysaccharide‐activated microglia; these effects were not observed in unstimulated microglia, suggesting that IL‐27 acts as an amplifier rather than an initiator of microglial neuroinflammation. IL‐27 also enhanced microglial antigen presentation to promote Th1 polarization and suppress Th17 cell development by increasing IL‐12 levels and reducing IL‐23 levels. Furthermore, IL‐27 increased microglial production of nerve growth factor, glial cell line‐derived neurotrophic factor and brain‐derived neurotrophic factor.

Conclusions

Our data suggest the therapeutic potential of IL‐27 and microglia for multiple sclerosis through Th17 cell suppression and neurotrophic factor production.
Corneal endothelial changes after selective laser trabeculoplasty
Authors: Ong Keith , Ong Lillian , Ong Leonard
Published: January 2013

Background

Whitish spots are sometimes noted in the corneal endothelium after selective laser trabeculoplasty. To evaluate the corneal endothelium after selective laser trabeculoplasty, corneal specular microscopy was performed.

Design

Prospective observational study in a private practice.

Participants

Fifteen consecutive patients with open‐angle glaucoma undergoing selective laser trabeculoplasty in February 2012 had their corneal endothelium examined with specular microscopy before and after treatment.

Methods

Selective laser trabeculoplasty was done with 50 ± 5 shots to 180 degrees of meshwork using 0.3–0.9 mJ of power to achieve the reaction of a hint of microbubbles in 80% of laser shots.

Main Outcome Measures

Corneal specular microscopy photographs (0.25 × 0.54 mm) were taken prior to, immediately after and 1 month after selective laser trabeculoplasty. These photographs were assessed and graded.

Results

Of the 15 patients, three showed numerous, four showed few and eight showed no increase of dark spots after selective laser trabeculoplasty. All the dark spots resolved by 1 month.

Conclusion

The effect of selective laser trabeculoplasty on the corneal endothelium may be transient, and long‐term effects are probably negligible in normal corneas. However, in compromised corneas and corneas with pigment deposits on endothelium, there may be a risk of corneal endothelial compromise, especially after repeated selective laser trabeculoplasty. Larger and longer term studies with histopathological evaluation would be useful to evaluate the effect of selective laser trabeculoplasty on normal and subnormal corneal endothelium. Until further studies are done, it would be wise to minimize the number and energy of laser shots.
Giant cell arteritis incidence: analysis by season and year in mid‐Atlantic United States
Authors: Kisza Krystian , Murchison Ann P , Dai Yang , Bilyk Jurij R , Eagle Ralph C , Sergott Robert , Savino Peter J
Published: January 2013

Background

Evaluate the incidence of biopsy‐proven giant cell arteritis for seasonal or annual variability in the Mid‐Atlantic United States.

Design

Retrospective chart review of all patients undergoing temporal artery biopsy from 1994 to 2011.

Participants

The charts of 744 patients were reviewed, and 215 patients were diagnosed with giant cell arteritis based on positive temporal artery biopsy results.

Methods

All results between 1994 and 2011 were reviewed. Giant cell arteritis incidence data were evaluated by year, season and month for any trends or cyclic patterns.

Main Outcome Measure

Incidence of biopsy‐proven giant cell arteritis.

Results

The majority of patients were female (74%) and over the age of 60 (98.6%). The diagnosis of biopsy‐proven giant cell arteritis was found in 215 of 744 (28.9%) patients. The incidence of biopsy‐proven giant cell arteritis by year varied, with the peak incidence in 1996. The monthly incidence peaked in July and had a trough in October. However, Poisson regression analysis did not show any statistically significant trend over time or cyclic pattern to the incidence by year, season or month.

Conclusions

The incidence of biopsy‐proven giant cell arteritis in the population studied did not have any significant cyclic pattern over the last 17 years. The highest incidence by month was noted in July with a trough in October. However, this was not a significant pattern by month or season to support infectious or periodic environmental factors inciting giant cell arteritis.
FGF18 accelerates osteoblast differentiation by upregulating Bmp2 expression
Authors: Nagayama Tomoko , Okuhara Shigeru , Ota Masato S. , Tachikawa Noriko , Kasugai Shohei , Iseki Sachiko
Published: January 2013

Fibroblast growth factor (FGF) signaling is involved in skeletal development. Among total 22 FGFs, it is suggested that FGF18 functions in promotion of osteoblast differentiation. In order to elucidate the mechanism of FGF18‐dependent acceleration of osteogenesis, we implanted rhFGF18 soaked beads over mouse fetal coronal sutures using ex‐utero surgery. The coronal suture area comprises the peripheries of the developing frontal and parietal bones, separated by the sutural mesenchyme. rhFGF18 accelerated osteogenesis by promoting connection of the frontal and parietal bone domains, resulting in elimination of the sutural mesenchyme. Expression of Fgf receptors, Fgfr1, ‐2 and ‐3 involved in skeletal development, was maintained or upregulated in the developing bone domains, consistent with enhanced osteogenesis. Bone morphogenetic protein (Bmp) 2 was specifically upregulated in the skeletogenic layer and the application of Bmp antagonist, rmNoggin, inhibited rhFGF18‐dependent upregulation of osteoblast markers. These results suggest that FGF18 accelerates osteogenesis by upregulation of Bmp2 as well as maintenance or upregulation of Fgfr1, ‐2 and ‐3 expression in osteoblasts.
The forensic analysis of foodborne bacterial pathogens in the age of whole‐genome sequencing
Authors: Wilson Mark R. , Allard Marc W. , Brown Eric W.
Published: January 2013

The forensic evaluation of bacterial pathogens presents new challenges to the forensic science community. This review examines bacterial pathogens as objects of forensic comparison, focusing on their nucleic acid sequences as an important aspect of the comparison process. Because of the clonal propagation of most bacterial pathogens, a phylogenetic approach to understanding the diversity and using this understanding to address common forensic questions is explored. As a general phylogenetic framework is now employed in human mitochondrial DNA analysis, we will use the relevant concepts and approaches common in this area to develop this approach further. We also address the impact of the current ease and prevalence of whole‐genome DNA sequence analysis in the forensic comparison process.
Systematic review and meta‐analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer
Authors: Beaton C. , Twine C. P. , Williams G. L. , Radcliffe A. G.
Published: January 2013

Aim

Lymph node (LN) metastases are present in up to 17% of early colorectal cancers (pT1). Identification of associated histopathological factors would enable counselling of patients regarding this risk.

Method

Pubmed and Embase were employed utilizing the terms ‘early colorectal cancer’, ‘lymph node metastasis’, ‘submucosal invasion’, ‘lymphovascular invasion’, ‘tumour budding’ and ‘histological differentiation’. Analysis was performed using REVIEW MANAGER 5.1.

Results

Twenty‐three cohort studies including 4510 patients were analysed. There was a significantly higher risk of LN metastasis with a depth of submucosal invasion > 1 mm than with lesser degrees of penetration (OR 3.87, 95% CI 1.50–10.00, P = 0.005). Lymphovascular invasion was significantly associated with LN metastasis (OR 4.81, 95% CI 3.14–7.37, P < 0.00001). Poorly differentiated tumours had a higher risk of LN metastasis compared with well or moderately differentiated tumours (OR 5.60, 95% CI 2.90–10.82, P < 0.00001). Tumour budding was found to be significantly associated with LN metastasis (OR 7.74, 95% CI 4.47–13.39, P < 0.001).

Conclusion

Meta‐analysis of the current literature demonstrates that in early colorectal cancer a depth of submucosal invasion by the primary tumour of > 1 mm, lymphovascular invasion, poor differentiation and tumour budding are significantly associated with LN metastasis.
Is a liquid‐based cytology more sensitive than a conventional Pap smear?
Authors: Sigurdsson K.
Published: January 2013

K. Sigurdsson  Is a liquid‐based cytology more sensitive than a conventional Pap smear?

Background:  The comparative sensitivity of liquid‐based cytology (LBC) test and conventional Papanicolaou (Pap) smears is controversial.

Material and methods:  This study analyses the distribution of cytology, histology, colposcopy and large loop excision of the transformation zone among women screened in Iceland with LBC at the Cancer Detection Clinic in Reykjavik and with a conventional Pap smear outside the Detection Clinic in 2007–2011. The study material included 42 654 LBC tests from 20 439 women and 103 909 Pap smears from 61 574 women. The period 2000–2004 is used to correct for potential bias as a result of unequal distribution of the studied parameters between the study sites before the introduction of LBC.

Results:  The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears, increased detection of low‐grade squamous intraepithelial lesion (LSIL)/atypical cytology and referrals to colposcopy, and an increased detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) irrespective of age. LBC increased significantly the detection rates of high‐grade squamous intraepithelial lesion or worse (HSIL+) cytology and CIN3+ histology only in women under 40 years of age. Taking into consideration the unequal prevalence of the studied parameters between the study sites in 2000–2004 indicated, however, that LBC only affected the rate of inadequate and low‐grade cytology tests under the age of 40 years. Positive predictive values for CIN2+ were not significantly different between the tests.

Conclusions:  The study results support the view that LBC is no more sensitive than Pap smears for the detection of HSIL+ and CIN2+ irrespective of age. LBC decreased the rate of inadequate smears, but increased the rate of low‐grade cytology under the age of 40 years and decreased the total rate of abnormal smears over the age of 40 years.
Physical function measurements predict mortality in ambulatory older men
Authors: De Buyser Stefanie L. , Petrovic Mirko , Taes Youri E. , Toye Kaatje R. C. , Kaufman Jean‐Marc , Goemaere Stefan
Published: January 2013

Background

To assess and compare the predictive value of physical function measurements (PFMs) for all‐cause mortality in older men and to evaluate the Timed Up and Go test (TUG) as a predictor in subjects with underlying comorbidity.

Design

Observational study of a population‐based sample of 352 ambulatory older men aged 71–86 at study baseline. The Rapid disability rating scale‐2, 36‐Item short form health survey, Grip strength, Five times sit‐to‐stand test, Standing balance, and TUG were determined at baseline. Associations with all‐cause mortality were assessed using Cox proportional hazard analyses. Age, Body mass index (BMI), smoking status, education, physical activity and cognitive status were included as confounders. Follow‐up exceeded 15 years. Comorbidity status was categorized into cardiovascular disease, chronic obstructive pulmonary disease (COPD) and diabetes mellitus.

Results

All examined PFMs were associated with all‐cause mortality. TUG was the best predictor (adjusted HR per SD increase = 1·58, 95% CI = 1·40–1·79, P < 0·001) for global mortality and continued to be predictive in subjects with cardiovascular disease (adjusted HR per SD increase = 1·80, 95% CI = 1·40–2·33, P < 0·001).

Conclusions

The assessment of physical functioning is important in the evaluation of older persons. We encourage the use of the TUG as a reliable, quick and feasible screening tool in clinical settings.
Are Commodity Prices Driven by Fundamentals?
Authors: De Meo Emanuele
Published: January 2013

Physical scarcity is hardly sufficient to explain commodity price swings. However, despite of clues of commodity market inefficiency in the last decade, excess volatility in commodity markets emerges only under strong assumptions. When we allow for non‐stationarity in commodity prices and time variation in commodity‐specific risk premia, evidence of commodity market inefficiency becomes significantly weaker. Moreover, there is some evidence of commodity‐specific regime changes in commodity markets, with negligible or even positive correlation between efficiency and market liquidity.
Rapid loss of response after withdrawal of treatment with azacitidine: a case series in patients with higher‐risk myelodysplastic syndromes or chronic myelomonocytic leukemia
Authors: Voso Maria Teresa , Breccia Massimo , Lunghi Monia , Poloni Antonella , Niscola Pasquale , Finelli Carlo , Bari Alessia , Musto Pellegrino , Zambello Renato , Fianchi Luana , Alimena Giuliana , Leone Giuseppe
Published: January 2013

In patients with myelodysplastic syndromes (MDS), the likelihood of having a sustained response to azacitidine is increased by maximizing treatment duration. This is important as prognosis postrelapse is poor. There is also the concern that early termination of treatment may result in rapid disease progression. We reviewed outcomes in 13 patients who discontinued azacitidine (decitabine in one patient) while still responding to the treatment. Most patients rapidly relapsed; median time to progression was 5.4 months. Reasons for treatment discontinuation included comorbidities, infections, and patient choice. These findings illustrate the risk of prematurely terminating azacitidine therapy in MDS.
The fine structure of the dopaminergic innervation of area 10 of macaque prefrontal cortex
Authors: Martin Kevan A. C. , Spühler Isabelle A.
Published: January 2013

In common with other areas of the prefrontal cortex, activity in frontopolar area 10 is probably modulated by dopamine. We studied the dopaminergic innervation of monkey prefrontal area 10 by immunostaining with tyrosine hydroxylase (TH) antibodies. TH‐positive axons in layer 3 were examined by electron microscopy of series of ultrathin sections. TH‐positive boutons containing vesicles were sparse (2 × 10−4 per μm3) and the majority (94%, n = 52) had no identifiable synaptic specialization, which supports the hypothesis that dopamine is released non‐synaptically and raises the question of whether the local microenvironment surrounding the boutons is special. Compared with unlabelled boutons TH‐positive boutons had a higher proportion of their perimeter in contact with dendritic shafts and were more often in continuous contact with pairs of pre‐ and postsynaptic structures. However, this may result from exclusion from sites preferred by glutamatergic and GABAergic synapses as the density of all synapses in the closer vicinity was no different from any randomly selected site in the neuropil. This quantitative ultrastructural study presents basic features of the dopaminergic innervation in prefrontal area 10 and provides a more detailed understanding of the structural basis of dopamine signalling in the cortex.
The use of a tongue tie alters laryngohyoid position in the standing horse
Authors: Chalmers H. J. , Farberman A. , Bermingham A. , Sears W. , Viel L.
Published: January 2013

Reasons for performing study

The use of tongue ties in racing is common, yet there are few data to support their efficacy. In order to make appropriate recommendations for clinical practice and policy on tongue ties, data documenting their effect on upper airway structure are necessary.

Objectives

To determine the effect of a tongue tie on the resting laryngohyoid position of the standing horse.

Study design

Experimental study.

Methods

Twelve normal Standardbred horses were subjected to ultrasonographic measures of laryngohyoid position during 3 phases of tack application: Phase I – halter and lead; Phase II – bit, bridle, harness and check applied; and Phase III – as in Phase II but with the tongue tie added.

Results

Compared to Phase I, during Phase III with the application of a tongue tie a significant difference between lingual process position was noted both rostrally and caudally (P<0.001 and P<0.001), such that the tongue tie resulted in an increase in lingual process depth. The tongue tie in Phase III resulted in a decrease in depth of the thyroid cartilage and basihyoid bone compared to the Phase I location (P = 0.007 and P = 0.0047).

Conclusion

The use of a tongue tie has a significant effect on the basihyoid and thyroid cartilage positions in the standing horse.

Potential relevance

This is the first report documenting a difference in laryngohyoid morphology following the application of a tongue tie, providing evidence that the use of a tongue tie has a measurable effect on upper airway structure. The functional implications of this finding are yet to be elucidated.
Inhibition of UV‐induced uric acid production using Allopurinol prevents suppression of the contact hypersensitivity response
Authors: Leighton Sarah , Kok Lai‐Fong , Halliday Gary M. , Byrne Scott N.
Published: January 2013

Exposure to solar ultraviolet (UV) radiation suppresses adaptive immune responses. This contributes to skin carcinogenesis but may protect from some autoimmune diseases. However, the molecular changes occurring within UV‐exposed skin that precipitate the downstream events leading to immune suppression are not fully understood. Using a combination of in vitro and in vivo mouse models, we have discovered that UV induces significant cutaneous production of immune suppressive uric acid. The ability of UV‐induced uric acid to inhibit a contact hypersensitivity response was successfully blocked by the gout‐treating drug Allopurinol. Up‐regulation of NLRP3 mRNA by UV was also found to be dependent on UV‐induced uric acid. This suggested that the target of UV‐induced uric acid included proteins involved in the formation and activation of the NLRP3‐inflammasome. However, in contrast to NLRP3, the adaptor protein ASC, which is required for formation of the NLRP3‐inflammasome, was significantly down‐regulated. Furthermore, this down‐regulation was not dependent on UV‐induced uric acid production because Allopurinol treatment failed to prevent the reduction in ASC. Hence, our results identify uric acid as an important molecule involved in sterile UV‐induced inflammation and immune suppression. UV‐induced uric acid may therefore offer a unique therapeutic target for preventing and treating skin cancer.
Unfolding dynamics of the mucin SEA domain probed by force spectroscopy suggest that it acts as a cell‐protective device
Authors: Pelaseyed Thaher , Zäch Michael , Petersson Åsa C. , Svensson Frida , Johansson Denny G. A. , Hansson Gunnar C.
Published: January 2013

MUC1 and other membrane‐associated mucins harbor long, up to 1 μm, extended highly glycosylated mucin domains and sea urchin sperm protein, enterokinase and agrin (SEA) domains situated on their extracellular parts. These mucins line luminal tracts and organs, and are anchored to the apical cell membrane by a transmembrane domain. The SEA domain is highly conserved and undergoes a molecular strain‐dependent autocatalytic cleavage during folding in the endoplasmic reticulum, a process required for apical plasma membrane expression. To date, no specific function has been designated for the SEA domain. Here, we constructed a recombinant protein consisting of three SEA domains in tandem and used force spectroscopy to assess the dissociation force required to unfold individual, folded SEA domains. Force–distance curves revealed three peaks, each representing unfolding of a single SEA domain. Fitting the observed unfolding events to a worm‐like chain model yielded an average contour length of 32 nm per SEA domain. Analysis of forces applied on the recombinant protein revealed an average unfolding force of 168 pN for each SEA domain at a loading rate of 25 nN·s−1. Thus, the SEA domain may act as a breaking point that can dissociate before the plasma membrane is breached when mechanical forces are applied to cell surfaces.
Evidence of current impact of climate change on life: a walk from genes to the biosphere
Authors: Peñuelas Josep , Sardans Jordi , Estiarte Marc , Ogaya Romà , Carnicer Jofre , Coll Marta , Barbeta Adria , Rivas‐Ubach Albert , Llusià Joan , Garbulsky Martin , Filella Iolanda , Jump Alistair S.
Published: January 2013

We review the evidence of how organisms and populations are currently responding to climate change through phenotypic plasticity, genotypic evolution, changes in distribution and, in some cases, local extinction. Organisms alter their gene expression and metabolism to increase the concentrations of several antistress compounds and to change their physiology, phenology, growth and reproduction in response to climate change. Rapid adaptation and microevolution occur at the population level. Together with these phenotypic and genotypic adaptations, the movement of organisms and the turnover of populations can lead to migration toward habitats with better conditions unless hindered by barriers. Both migration and local extinction of populations have occurred. However, many unknowns for all these processes remain. The roles of phenotypic plasticity and genotypic evolution and their possible trade‐offs and links with population structure warrant further research. The application ofomictechniques to ecological studies will greatly favor this research. It remains poorly understood how climate change will result in asymmetrical responses of species and how it will interact with other increasing global impacts, such as N eutrophication, changes in environmental N : P ratios and species invasion, among many others. The biogeochemical and biophysical feedbacks on climate of all these changes in vegetation are also poorly understood. We here review the evidence of responses to climate change and discuss the perspectives for increasing our knowledge of the interactions between climate change and life.
Effects of grazing on grassland soil carbon: a global review
Authors: McSherry Megan E. , Ritchie Mark E.
Published: January 2013

Soils of grasslands represent a large potential reservoir for storingCO2, but this potential likely depends on how grasslands are managed for large mammal grazing. Previous studies found both strong positive and negative grazing effects on soil organic carbon (SOC) but explanations for this variation are poorly developed. Expanding on previous reviews, we performed a multifactorial meta‐analysis of grazer effects onSOCdensity on 47 independent experimental contrasts from 17 studies. We explicitly tested hypotheses that grazer effects would shift from negative to positive with decreasing precipitation, increasing fineness of soil texture, transition from dominant grass species with C3to C4photosynthesis, and decreasing grazing intensity, after controlling for study duration and sampling depth. The six variables of soil texture, precipitation, grass type, grazing intensity, study duration, and sampling depth explained 85% of a large variation (±150 g m−2 yr−1) in grazing effects, and the best model included significant interactions between precipitation and soil texture (P = 0.002), grass type, and grazing intensity (P = 0.012), and study duration and soil sampling depth (P = 0.020). Specifically, an increase in mean annual precipitation of 600 mm resulted in a 24%decreasein grazer effect size on finer textured soils, while on sandy soils the same increase in precipitation produced a 22%increasein grazer effect onSOC. Increasing grazing intensity increasedSOCby 6–7% on C4‐dominated and C4–C3mixed grasslands, but decreasedSOCby an average 18% in C3‐dominated grasslands. We discovered these patterns despite a lack of studies in natural, wildlife‐dominated ecosystems, and tropical grasslands. Our results, which suggest a future focus on why C3vs. C4‐dominated grasslands differ so strongly in their response ofSOCto grazing, show that grazer effects onSOCare highly context‐specific and imply that grazers in different regions might be managed differently to help mitigate greenhouse gas emissions.
The role of patients and their relatives in ‘speaking up’ about their own safety – a qualitative study of acute illness
Authors: Rainey Helen , Ehrich Kathryn , Mackintosh Nicola , Sandall Jane
Published: January 2013

Background

Poor recognition of and response to acute illness in hospitalized patients continues to cause significant harm despite the implementation of safety strategies such as early warning scores. Patients and their relatives may be able to contribute to their own safety by speaking up about changes in condition, but little is known about the factors that influence this. This study examined the experiences and views of patients and their relatives to determine the potential for involvement in promoting their own safety.

Methods

This data set is drawn from a wider ethnographic study of the management of the acutely ill patient in hospital. Thirteen patients and seven relatives from two medical settings in two UK NHS Trusts were interviewed. Thematic analysis identified factors likely to influence patients' and their relatives' ability to contribute to the management of deterioration.

Results

All patients interviewed had experienced their acute illness within the context of a long‐term health problem. Speaking up was influenced by the ability to recognize changes in clinical condition, self‐monitoring, confidence and trust, and culture and system of health care. When patients or relatives did raise concerns, health‐care staff had a mediating effect on their comfort with and the effectiveness of speaking up.

Implications

Safety strategies based on patient involvement must take account of the complexities of acute illness. Those that promote partnership may be more acceptable to patients, their families and staff than those that promote challenging behaviour and may ultimately prove to be most safe and effective.
Predictive factors for pulp necrosis in traumatized primary incisors: a longitudinal study
Authors: Aldrigui Janaina Merli , Cadioli Isabela Caparelli , Mendes Fausto Medeiros , Antunes José Leopoldo Ferreira , Wanderley Marcia Turolla
Published: January 2013

Background

This study aimed to assess factors associated with occurrence of pulp necrosis (PN) in traumatized primary incisors, which may contribute to the prognosis of this outcome.

Design

Data were collected by single examiner through the analysis of clinical files of traumatized patients. The occurrence of PN in traumatized teeth was the evaluated outcome. Poisson regression analysis was applied to calculate the relative risk (RR) and the respective 95% confidence interval.

Results

Five hundred and twenty‐one files were assessed, summing up 727 traumatized primary incisors. The proportion of teeth affected by PN was 23.8%. Multiple regression analysis indicated the following factors as positively associated with PN: trauma with displacement, pulp exposure fracture, self‐report of pain, yellow, grey and brown crown discoloration, internal root resorption, and bone loss. Trauma in 4‐ to 5‐year old and more than 5‐year‐old children, pulp canal obliteration, and external root resorption with bone formation were negatively associated with PN.

Conclusions

Teeth that suffered more aggressive injuries, pain, some types of discoloration, and other radiographic findings (for instance, internal root resorption) are positively associated with the occurrence of PN. On the other hand, trauma in older children, canal obliteration, or external resorption show less probability of PN.
Cutaneous scrotal metastasis: origins and clinical characteristics of visceral malignancies that metastasize to the scrotum
Authors: Hoyt Brian S. , Cohen Philip R.
Published: January 2013

Cutaneous metastases occur in about 10% of patients with cancer, occasionally presenting as the initial sign of internal malignancy. Most often cutaneous metastases are an indicator of advanced cancer and are associated with a poor prognosis. The scrotum is a rare site of cutaneous metastasis, and metastatic tumor to the scrotum can be mistaken for other skin lesions. We reviewed the published literature regarding patients who developed cutaneous metastasis to the scrotum. We summarized the clinical characteristics of these men, including primary tumor sites, age at diagnosis, treatment regimens, interval between diagnosis of primary tumor and subsequent metastasis, and outcomes. We extensively searched the PubMed medical database for papers on visceral malignancies with metastasis to the scrotum. We limited our definition to solid organ tumors; thus lymphomas, sarcomas, and melanomas of the scrotum were excluded. We identified 29 patients who developed scrotal metastases from visceral cancers. The colon/rectum (34%), prostate (28%), and lung (14%) were the most frequent sites of tumor origin. The prognosis for these patients is poor: mean patient survival was only four months after diagnosis of metastatic skin lesions. Cutaneous metastasis to the scrotum is a rare manifestation of internal malignancies that most often represents an advanced and/or progressive cancer associated with a poor prognosis. Treatment is often unsuccessful, and the mean patient survival following scrotal metastasis is <4 months.
Stevens–Johnson syndrome and toxic epidermal necrolysis in sub‐Saharan Africa: a multicentric study in four countries
Authors: Saka Bayaki , Barro‐Traoré Fatou , Atadokpédé Felix A. , Kobangue Léon , Niamba Pascal Antoine , Adégbidi Hugues , Yedomon Hubert G. , Traoré Adama , Pitché Vincent P.
Published: January 2013

Objective

The purpose of this study was to document the clinical profile, etiologies, and outcomes of Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in hospitals in four sub‐Saharan African countries.

Patients and methods

A retrospective study on cases of SJS/TEN treated in dermatology departments and/or intensive care units in four sub‐Saharan African countries (Benin, Burkina Faso, Central African Republic, and Togo) from 2000 to 2010. The study focuses on variables such as age, sex, type of SJS/TEN, epidermal detachment of the skin surface, HIV status, drug(s) involved, and outcomes (death and sequelae).

Results

This study identified 177 cases of SJS/TEN from 2000 to 2010: 129 with SJS; 37 TEN; and 11 overlapping SJS/TEN. The average age of patients was 32.3 ± 15.4 years, and the sex ratio (M/F) was 0.6. HIV serology was positive in 69 (54.8%) of the 126 patients tested. Antibacterial sulfonamides (38.4%) were the most commonly used drugs followed by nevirapine (19.8%) and tuberculosis drugs (5.6%). We recorded 22 deaths (i.e. six cases of SJS, 15 of TEN, and one of overlapping SJS/TEN). Of the 22 patients who died, 16 were infected with HIV; among them, seven had an opportunistic infection (four cases of cerebral toxoplasmosis and three of pulmonary tuberculosis). Twenty‐seven cases of sequelae were noted with a large part of eye complications.

Conclusion

This study has highlighted: (i) the high proportion of patients infected with HIV among patients who had SJS/TEN in sub‐Saharan Africa; (ii) the high frequency of antiretroviral drugs as new SJS/TEN causes in sub‐Saharan Africa; and (iii) the impact of HIV infection on morbidity and mortality of these affections.
Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma)
Authors: Mantovani Lucia , Zauli Stefania , Sarno Oriele , Querzoli Patrizia , Corazza Monica , Virgili Annarosa
Published: January 2013

A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow‐up, the patient is relapse‐free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment.
Generalized anxiety disorder, subthreshold anxiety and anxiety symptoms in primary headache
Authors: Lucchetti Giancarlo , Peres Mario F. P. , Lucchetti Alessandra L. G. , Mercante Juliane P. P. , Guendler Vera Z. , Zukerman Eliova
Published: January 2013

Aims

The aim of the present study was to evaluate the association between generalized anxiety disorder, subthreshold anxiety (SubAnx) and anxiety symptoms in the prevalence of primary headache.

Methods

This cross‐sectional study evaluated 383 people from a Brazilian low‐income community. One‐year prevalence rates of migraine, chronic migraine and tension‐type headache were calculated. Anxiety symptoms were then separated into the following groups (based on DSM‐IV criteria): no anxiety criteria; one anxiety criterion; two anxiety criteria; and generalized anxiety disorder (GAD). The control group (no headaches) was compared with headache sufferers for each anxiety group using an adjusted model controlled for confounding factors.

Results

GAD was present in 37.0% of participants and SubAnx in 16.6%. Those with SubAnx had a 2.28‐fold increased chance of having migraine; 3.83‐fold increased chance of having chronic migraine, a 5.94‐fold increased chance of having tension‐type headache and a 3.27‐fold increased chance of having overall headache. Some anxiety criteria (irritability, difficulty with sleep, concentration problems, muscle tension and fatigue) had similar prevalence to International Classification of Headache Disorders (ICHD‐II) headache criteria such as unilateral pain and nausea for migraine and chronic migraine.

Conclusion

Headache sufferers seem to have a high prevalence of anxiety symptoms and SubAnx. In addition, the presence of two or more anxiety criteria (not necessarily fulfilling all the criteria for GAD) was associated with having a headache disorder.
‘Every Father is a Superhero to his Children’: The Gendered Politics of the (Real) Fathers 4 Justice Campaign
Authors: Jordan Ana
Published: January 2013

Fathers' rights groups have been characterised by some feminist academics as part of an anti-feminist ‘backlash’, responding to a perceived crisis of masculinity through a problematic politics of fatherhood aimed at (re)asserting control over women and children. This article analyses the construction of gender and masculinity/ies within fathers' rights groups, specifically, the UK-based pressure group, (Real) Fathers 4 Justice. The article explores the construction of power-laden gender identity/ies within (Real) Fathers 4 Justice and, in doing so, contributes to understanding the logic and implications of fathers' rights perspectives. The analysis is based on in-depth interviews conducted with members of the group. The qualitative case study is used to explore critically the (gender) politics of fathers' rights. It is argued that the interviewees (re)construct multiple masculinities: bourgeois-rational masculinity, new man/new father masculinity and hypermasculinity. These masculinity frames intersect with broader constructions of gender and need to be understood in evaluating the perspectives of fathers' rights groups which are complex in terms of their implications for gender politics broadly conceived. Overall, it is argued that each of the masculinity frames can be problematic, as they reinforce existing gendered binaries.
Price Discovery in the Treasury‐Bill When‐Issued Market
Authors: Mercer Jeffrey M. , Moore Mark E. , Whitby Ryan J. , Winters Drew B.
Published: January 2013

When‐issued (i.e., forward) trading in T‐bills yet to be auctioned provides a unique environment for examining price discovery. Because T‐bills are auctioned in a sealed‐bid process, when‐issued traders cannot observe the spot market price. Yet the forward price must ultimately converge on the auction outcome price. Our results indicate that traders in the when‐issued market “discover” the ultimate auction price. Little evidence is found that standard order flow variables contribute to price discovery. Instead, the ability to observe a few trades with relatively small volume in the when‐issued market is sufficient to discover the auction price resulting from the sealed‐bid process.
Outcome favorability as a boundary condition to voice effect on people's reactions to public policymaking
Authors: Wu Xuan‐Na , Wang Er‐Ping
Published: January 2013

Regarding people's reactions to public policymaking, an organizational justice framework has been introduced. Although these studies showed a link between fairness perceptions and attitudes toward public policy and authority, results concerning more behavioral consequences and the moderation of outcome favorability are less clear. The present research explored the voice effect on people's reactions to public policymaking, as well as outcome favorability as a boundary condition to it. Two different settings and use of different designs (a scenario and an experiment) yielded convergent results that people's reactions to public policymaking were more favorable when they had voice than they did not and outcome favorability moderated the voice effect. More precisely, the voice effect was stronger when the outcome was unfavorable than favorable.
Shocks and social protection in the Horn of Africa: analysis from the Productive Safety Net programme in Ethiopia
Authors: Béné Christophe , Devereux Stephen , Sabates‐Wheeler Rachel
Published: January 2013

Using panel data from the Ethiopian Productive Safety Net Program, this paper explores the degree to which this social protection programme has been successful in protecting its beneficiaries against the various shocks that have affected the Horn of Africa in the recent past. The analysis suggests that although the PSNP has managed to improve households’ food security and wellbeing, the positive effects of the programme are not robust enough to shield recipients completely against the impacts of severe shocks.