bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood donation and risk of polycythemia vera
Authors: Edgren Gustaf , Nyrén Olof , Hultcrantz Malin , Nielsen Kaspar Rene , Pedersen Ole B.V. , Björkholm Magnus , Rostgaard Klaus , Hjalgrim Henrik 
Published: February 2016

BACKGROUNDIt has been suggested that blood donors could have an increased risk of polycythemia vera (PV). However, no study has assessed whether frequent donors have a higher PV risk than less frequent donors.STUDY DESIGN AND METHODSFrom the Scandinavian Donations and Transfusions (SCANDAT2) database, we established a cohort of blood donors who had donated whole blood at least once between 1980 and 2012. Within this cohort we first assessed the risk of PV, comparing the donors to the general population using standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs). To assess the association between frequency of blood donation and risk of PV we then conducted a case‐control study nested within the cohort, where we compared prior donation activity among donors who were diagnosed with PV and matched controls. Here odds ratios (ORs) were used as measures of relative risk comparing donors with different donation frequency.RESULTSAmong 1.4 million donors in the cohort a total of 271 donors developed PV, yielding a SIR of 1.00 (95% CI, 0.89‐1.13) compared to the general population. The nested case‐control study showed no association between donation frequency and risk of PV. The OR of PV comparing donors who had made at least 33 donations in the period from 3 to 22 years before diagnosis of the case, to donors with one to eight donations in the same period was 1.01 (95% CI, 0.51‐1.97).CONCLUSIONSWe find no evidence of excess risk of PV among blood donors or of an association between donation frequency and PV risk.
Seasonal dynamics of ground cover in Cirsium arvense – a basis for estimating grazing losses and economic impacts
Authors: Bourdôt G W , Hurrell G A , Trolove M , Saville D J 
Published: February 2016

SummaryAnalysis of the economics of managing Cirsium arvense in grazed pastures worldwide has been hampered by a lack of data on the within‐year seasonal dynamics of the weed and its impact on the yield of palatable herbage. To redress this, the seasonal pattern in within‐patch percentage ground cover of the weed was determined from measurements on 39 dairy and 66 sheep and/or beef cattle farms in New Zealand during 2009–2010 and 2010–2011. This pattern was then scaled using farmer estimates of peak whole‐farm cover to derive mean monthly covers for dairy, beef, sheep/beef, sheep and deer farms. These monthly covers corresponded, respectively, to mean annual percentage covers of 2.7, 1.7, 3.0, 5.9 and 2.9% and to mean annual percentage losses in pasture growth (palatable herbage yield) of 3.6, 2.3, 4.0, 7.8 and 3.9%. The latter, in combination with 2011–2012 farm statistics, revealed that C. arvense caused a national loss in pastoral farm gross revenue in New Zealand in 2011–2012 of $685 million ($446 m dairy, $233 m sheep/beef, $6 m deer). Beyond the scope of this paper, the monthly covers and their corresponding monthly losses in pasture growth provide a basis for modelling the economic impacts of C. arvense and its management at a farm scale. More generally, the analytical method that we have developed is appropriate for evaluating the economic impact of any weed in a grazed pasture, particularly those exhibiting pronounced seasonal patterns in occupancy, such as annuals and deciduous perennials.
Comparative study of quality of life and psychosocial characteristics in patients with psoriasis and leg ulcers
Authors: Kouris Anargyros , Christodoulou Christos , Efstathiou Vasiliki , Tsatovidou Revekka , Torlidi‐Kordera Evangelia , Zouridaki Eftychia , Kontochristopoulos George 
Published: February 2016

AbstractPsoriasis and leg ulcers have a marked impact on the patient's quality of life and represent a life‐long burden for affected patients. The aim of this study is to compare the quality of life, anxiety and depression, self‐esteem, and loneliness in patients with psoriasis and leg‐ulcer patients. Eighty patients with leg ulcers, eighty patients with psoriasis, and eighty healthy controls were included in this study. The quality of life, depression and anxiety, loneliness of the patient, and self‐esteem were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), the UCLA loneliness Scale (UCLA‐Version 3), and the Rosenberg's Self‐esteem Scale (RSES), respectively. The DLQI score among patients with psoriasis was 12.74 ± 4.89 and leg ulcer patients was 13.28 ± 2.57. The patients with psoriasis presented statistically significant higher anxiety (9.87 ± 4.56) than both leg ulcer patients (8.26 ± 2.82) and controls (6.45 ± 1.89), while leg ulcer patients also presented higher anxiety than controls. Regarding self‐esteem, although there were no significant differences between the patients with psoriasis (15.25 ± 3.20) and the ones with leg ulcers (15.89 ± 2.93), they both presented statistically significant lower self‐esteem scores than control group (18.53 ± 3.04). The patients with psoriasis presented statistically significant higher levels of loneliness and social isolation (46.18 ± 6.63) compared to leg ulcer patients (43.73 ± 5.68) than controls (42.49 ± 3.41). Psoriasis and leg ulcers are long‐term skin diseases associated with significant impairment of the patient's quality of life, anxiety, and self‐esteem, which are frequently under‐recognized.
Effects of tretinoin on wound healing in aged skin
Authors: de Campos Peseto Danielle , Carmona Erica Vilaça , Silva Kellyn Cristina da , Guedes Flavia Roberta Valente , Hummel Filho Fernando , Martinez Natalia Peres , Pereira José Aires , Rocha Thalita , Priolli Denise Gonçalves 
Published: February 2016

AbstractAged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid‐Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing.
Inositol 1,4,5‐trisphosphate receptors and their protein partners as signalling hubs
Authors: Prole David L. , Taylor Colin W. 
Published: February 2016

AbstractInositol 1,4,5‐trisphosphate receptors (IP3Rs) are expressed in nearly all animal cells, where they mediate the release of Ca2+ from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca2+ signals allows selective regulation of diverse physiological responses. Interactions of IP3Rs with other proteins contribute to the specificity and speed of Ca2+ signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3Rs, facilitate their regulation by multiple signalling pathways and direct the Ca2+ that they release to specific targets. We suggest that IP3Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca2+ signals.
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Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow
Authors: Hartley Geoffrey L. , Watson Cody L. , Ainslie Philip N. , Tokuno Craig D. , Greenway Matthew J. , Gabriel David A. , O'Leary Deborah D. , Cheung Stephen S. 
Published: February 2016

Key points
Reductions in cerebral blood flow (CBF) may be implicated in the development of neuromuscular fatigue; however, the contribution from hypocapnic‐induced reductions (i.e. ) in CBF versus reductions in CBF per se has yet to be isolated.
We assessed neuromuscular function while using indomethacin to selectively reduce CBF without changes in and controlled hyperventilation‐induced hypocapnia to reduce both CBF and .
Increased corticospinal excitability appears to be exclusive to reductions in but not reductions in CBF, whereas sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF independent of changes in .
These findings suggest that changes in CBF and have distinct roles in modulating neuromuscular function.
AbstractAlthough reductions in cerebral blood flow (CBF) may be involved in central fatigue, the contribution from hypocapnia‐induced reductions in CBF versus reductions in CBF per se has not been isolated. This study examined whether reduced arterial (), independent of concomitant reductions in CBF, impairs neuromuscular function. Neuromuscular function, as indicated by motor‐evoked potentials (MEPs), maximal M‐wave (Mmax) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in ten males (29 ± 10 years) during three separate conditions: (1) cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg kg−1) to selectively reduce CBF by 28.8 ± 10.3% (estimated using transcranial Doppler ultrasound) without changes in end‐tidal (); (2) controlled iso‐oxic hyperventilation‐induced reductions in (Hypocapnia), = 30.1 ± 4.5 mmHg with related reductions in CBF (21.7 ± 6.3%); and (3) isocapnic hyperventilation (Isocapnia) to examine the potential direct influence of hyperventilation‐mediated activation of respiratory control centres on CBF and changes in neuromuscular function. Change in MEP amplitude (%Mmax) from baseline was greater in Hypocapnia tha in Isocapnia (11.7 ± 9.8%, 95% confidence interval (CI) [2.6, 20.7], P = 0.01) and Indomethacin (13.3 ± 11.3%, 95% CI [2.8, 23.7], P = 0.01) with a large Cohen's effect size (d ≥ 1.17). Although not statistically significant, cVA was reduced with a moderate effect size in Indomethacin (d = 0.7) and Hypocapnia (d = 0.9) compared to Isocapnia. In summary, increased corticospinal excitability – as reflected by larger MEP amplitude – appears to be exclusive to reduced , but not reductions in CBF per se. Sub‐optimal voluntary output from the motor cortex is moderately associated with decreased CBF, independent of reduced .
Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis
Authors: Deng S. , Pan W. , Liao W. , de Hoog G. S. , Gerrits van den Ende A. H. G. , Vitale R. G. , Rafati H. , Ilkit M. , Van der Lee A. H. , Rijs A. J. M. M. , Verweij P. E. , Seyedmousavi S. 
Published: February 2016

ABSTRACT

Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungi
Cladophialophora bantiana
,
Rhinocladiella mackenziei
, and
Exophiala dermatitidis.
Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Our
in vitro
studies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the order
Chaetothyriales
. Further
in vivo
studies and clinical investigations to elucidate and confirm these observations are warranted.
Amino Acid Substitutions Account for Most MexS Alterations in Clinical
nfxC
Mutants of Pseudomonas aeruginosa
Authors: Richardot Charlotte , Juarez Paulo , Jeannot Katy , Patry Isabelle , Plésiat Patrick , Llanes Catherine 
Published: February 2016

ABSTRACT

Multidrug-resistant mutants of
Pseudomonas aeruginosa
that overproduce the active efflux system MexEF-OprN (called
nfxC
mutants) have rarely been characterized in the hospital setting. Screening of 221 clinical strains exhibiting a reduced susceptibility to ciprofloxacin (a substrate of MexEF-OprN) and imipenem (a substrate of the negatively coregulated porin OprD) led to the identification of 43 (19.5%)
nfxC
mutants. Subsequent analysis of 22 nonredundant mutants showed that, in contrast to their
in vitro
-selected counterparts, only 3 of them (13.6%) harbored a disrupted
mexS
gene, which codes for the oxidoreductase MexS, whose inactivation is known to activate the
mexEF-oprN
operon through a LysR-type regulator, MexT. Nine (40.9%) of the clinical
nfxC
mutants contained single amino acid mutations in MexS, and these were associated with moderate effects on resistance and virulence factor production in 8/9 strains. Finally, the remaining 10 (45.5%)
nfxC
mutants did not display mutations in any of the regulators known to control
mexEF-oprN
expression (the
mexS
,
mexT
,
mvaT
, and
ampR
genes), confirming that other loci are responsible for pump upregulation in patients. Collectively, these data demonstrate that
nfxC
mutants are probably more frequent in the hospital than previously thought and have genetic and phenotypic features somewhat different from those of
in vitro
-selected mutants.
Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host
Authors: Mesa-Arango Ana C. , Rueda Cristina , Román Elvira , Quintin Jessica , Terrón María C. , Luque Daniel , Netea Mihai G. , Pla Jesus , Zaragoza Oscar 
Published: February 2016

ABSTRACT

We have morphologically characterized
Candida tropicalis
isolates resistant to amphotericin B (AmB). These isolates present an enlarged cell wall compared to isolates of regular susceptibility. This correlated with higher levels of β-1,3-glucan in the cell wall but not with detectable changes in chitin content. In line with this, AmB-resistant strains showed reduced susceptibility to Congo red. Moreover, mitogen-activated protein kinases (MAPKs) involved in cell integrity were already activated during regular growth in these strains. Finally, we investigated the response elicited by human blood cells and found that AmB-resistant strains induced a stronger proinflammatory response than susceptible strains. In agreement, AmB-resistant strains also induced stronger melanization of
Galleria mellonella
larvae, indicating that the effect of alterations of the cell wall on the immune response is conserved in different types of hosts. Our results suggest that resistance to AmB is associated with pleiotropic mechanisms that might have important consequences, not only for the efficacy of the treatment but also for the immune response elicited by the host.
5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2′-Deoxycytidine
Authors: Rawson Jonathan M. O. , Daly Michele B. , Xie Jiashu , Clouser Christine L. , Landman Sean R. , Reilly Cavan S. , Bonnac Laurent , Kim Baek , Patterson Steven E. , Mansky Louis M. 
Published: February 2016

ABSTRACT

5-Azacytidine (5-aza-C) is a ribonucleoside analog that induces the lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1) by causing predominantly G-to-C transversions during reverse transcription. 5-Aza-C could potentially act primarily as a ribonucleotide (5-aza-CTP) or as a deoxyribonucleotide (5-aza-2′-deoxycytidine triphosphate [5-aza-dCTP]) during reverse transcription. In order to determine the primary form of 5-aza-C that is active against HIV-1, Illumina sequencing was performed using proviral DNA from cells treated with 5-aza-C or 5-aza-dC. 5-Aza-C and 5-aza-dC were found to induce highly similar patterns of mutation in HIV-1 in terms of the types of mutations observed, the magnitudes of effects, and the distributions of mutations at individual sequence positions. Further, 5-aza-dCTP was detected by liquid chromatography–tandem mass spectrometry in cells treated with 5-aza-C, demonstrating that 5-aza-C was a substrate for ribonucleotide reductase. Notably, levels of 5-aza-dCTP were similar in cells treated with equivalent effective concentrations of 5-aza-C or 5-aza-dC. Lastly, HIV-1 reverse transcriptase was found to incorporate 5-aza-CTP
in vitro
at least 10,000-fold less efficiently than 5-aza-dCTP. Taken together, these data support the model that 5-aza-C enhances the mutagenesis of HIV-1 primarily after reduction to 5-aza-dC, which can then be incorporated during reverse transcription and lead to G-to-C hypermutation. These findings may have important implications for the design of new ribonucleoside analogs directed against retroviruses.
Characterization of SlyA in Shigella flexneri Identifies a Novel Role in Virulence
Authors: Weatherspoon-Griffin Natasha , Wing Helen J. 
Published: February 2016

ABSTRACT

The SlyA transcriptional regulator has important roles in the virulence and pathogenesis of several members of the
Enterobacteriaceae
family, including
Salmonella enterica
serovar Typhimurium and
Escherichia coli
. Despite the identification of the
slyA
gene in
Shigella flexneri
nearly 2 decades ago, as well as the significant conservation of SlyA among enteric bacteria, the role of SlyA in
Shigella
remains unknown. The genes regulated by SlyA in closely related organisms often are absent from or mutated in
S. flexneri
, and consequently many described SlyA-dependent phenotypes are not present. By characterizing the expression of
slyA
and determining its ultimate effect in this highly virulent organism, we postulated that novel SlyA-regulated virulence phenotypes would be identified. In this study, we report the first analysis of SlyA in
Shigella
and show that (i) the
slyA
gene is transcribed and ultimately translated into protein, (ii)
slyA
promoter activity is maximal during stationary phase and is negatively autoregulated and positively regulated by the PhoP response regulator, (iii) the exogenous expression of
slyA
rescues transcription and virulence-associated deficiencies during virulence-repressed conditions, and (iv) the absence of
slyA
significantly decreases acid resistance, demonstrating a novel and important role in
Shigella
virulence. Cumulatively, our study illustrates unexpected parallels between the less conserved
S. flexneri
and
S
. Typhimurium
slyA
promoters as well as a unique role for SlyA in
Shigella
virulence that has not been described previously in any closely related organism.
Flagellar Cap Protein FliD Mediates Adherence of Atypical Enteropathogenic Escherichia coli to Enterocyte Microvilli
Authors: Sampaio Suely C. F. , Luiz Wilson B. , Vieira Mônica A. M. , Ferreira Rita C. C. , Garcia Bruna G. , Sinigaglia-Coimbra Rita , Sampaio Jorge L. M. , Ferreira Luís C. S. , Gomes Tânia A. T. 
Published: February 2016

ABSTRACT

The expression of flagella correlates with different aspects of bacterial pathogenicity, ranging from adherence to host cells to activation of inflammatory responses by the innate immune system. In the present study, we investigated the role of flagella in the adherence of an atypical enteropathogenic
Escherichia coli
(aEPEC) strain (serotype O51:H40) to human enterocytes. Accordingly, isogenic mutants deficient in flagellin (FliC), the flagellar structural subunit; the flagellar cap protein (FliD); or the MotAB proteins, involved in the control of flagellar motion, were generated and tested for binding to differentiated Caco-2 cells. Binding of the aEPEC strain to enterocytes was significantly impaired in strains with the
fliC
and
fliD
genes deleted, both of which could not form flagella on the bacterial surface. A nonmotile but flagellated MotAB mutant also showed impaired adhesion to Caco-2 cells. In accordance with these observations, adhesion of aEPEC strain 1711-4 to Caco-2 cells was drastically reduced after the treatment of Caco-2 cells with purified FliD. In addition, incubation of aEPEC bacteria with specific anti-FliD serum impaired binding to Caco-2 cells. Finally, incubation of Caco-2 cells with purified FliD, followed by immunolabeling, showed that the protein was specifically bound to the microvillus tips of differentiated Caco-2 cells. The aEPEC FliD or anti-FliD serum also reduced the adherence of prototype typical enteropathogenic, enterohemorrhagic, and enterotoxigenic
E. coli
strains to Caco-2 cells. In conclusion, our findings further strengthened the role of flagella in the adherence of aEPEC to human enterocytes and disclosed the relevant structural and functional involvement of FliD in the adhesion process.
Pathophysiological Mechanisms in Gaseous Therapies for Severe Malaria
Authors: Kayano Ana Carolina A. V. , Dos-Santos João Conrado K. , Bastos Marcele F. , Carvalho Leonardo J. , Aliberti Júlio , Costa Fabio T. M. 
Published: February 2016

ABSTRACTOver 200 million people worldwide suffer from malaria every year, a disease that causes 584,000 deaths annually. In recent years, significant improvements have been achieved on the treatment of severe malaria, with intravenous artesunate proving superior to quinine. However, mortality remains high, at 8% in children and 15% in adults in clinical trials, and even worse in the case of cerebral malaria (18% and 30%, respectively). Moreover, some individuals who do not succumb to severe malaria present long-term cognitive deficits. These observations indicate that strategies focused only on parasite killing fail to prevent neurological complications and deaths associated with severe malaria, possibly because clinical complications are associated in part with a cerebrovascular dysfunction. Consequently, different adjunctive therapies aimed at modulating malaria pathophysiological processes are currently being tested. However, none of these therapies has shown unequivocal evidence in improving patient clinical status. Recently, key studies have shown that gaseous therapies based mainly on nitric oxide (NO), carbon monoxide (CO), and hyperbaric (pressurized) oxygen (HBO) alter vascular endothelium dysfunction and modulate the host immune response to infection. Considering gaseous administration as a promising adjunctive treatment against severe malaria cases, we review here the pathophysiological mechanisms and the immunological aspects of such therapies.