Tag Archives: PLoS

Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death.

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Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death.

PLoS One. 2014;9(2):e88521

Authors: Op den Dries S, Sutton ME, Karimian N, de Boer MT, Wiersema-Buist J, Gouw AS, Leuvenink HG, Lisman T, Porte RJ

Abstract
BACKGROUND: Livers derived from donation after circulatory death (DCD) are increasingly accepted for transplantation. However, DCD livers suffer additional donor warm ischemia, leading to biliary injury and more biliary complications after transplantation. It is unknown whether oxygenated machine perfusion results in better preservation of biliary epithelium and the peribiliary vasculature. We compared oxygenated hypothermic machine perfusion (HMP) with static cold storage (SCS) in a porcine DCD model.
METHODS: After 30 min of cardiac arrest, livers were perfused in situ with HTK solution (4°C) and preserved for 4 h by either SCS (n = 9) or oxygenated HMP (10°C; n = 9), using pressure-controlled arterial and portal venous perfusion. To simulate transplantation, livers were reperfused ex vivo at 37°C with oxygenated autologous blood. Bile duct injury and function were determined by biochemical and molecular markers, and a systematic histological scoring system.
RESULTS: After reperfusion, arterial flow was higher in the HMP group, compared to SCS (251±28 vs 166±28 mL/min, respectively, after 1 hour of reperfusion; p = 0.003). Release of hepatocellular enzymes was significantly higher in the SCS group. Markers of biliary epithelial injury (biliary LDH, gamma-GT) and function (biliary pH and bicarbonate, and biliary transporter expression) were similar in the two groups. However, histology of bile ducts revealed significantly less arteriolonecrosis of the peribiliary vascular plexus in HMP preserved livers (>50% arteriolonecrosis was observed in 7 bile ducts of the SCS preserved livers versus only 1 bile duct of the HMP preserved livers; p = 0.024).
CONCLUSIONS: Oxygenated HMP prevents arteriolonecrosis of the peribiliary vascular plexus of the bile ducts of DCD pig livers and results in higher arterial flow after reperfusion. Together this may contribute to better perfusion of the bile ducts, providing a potential advantage in the post-ischemic recovery of bile ducts.

PMID: 24551114 [PubMed – in process]

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Predictors of progression in albuminuria in the general population: results from the PREVEND cohort.

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Predictors of progression in albuminuria in the general population: results from the PREVEND cohort.

PLoS One. 2013;8(5):e61119

Authors: Scheven L, Halbesma N, de Jong PE, de Zeeuw D, Bakker SJ, Gansevoort RT

Abstract
BACKGROUND: Urinary albumin excretion is known to be independently associated with progression of renal and cardiovascular disease. The aim of this study was to identify predictors for progression in albuminuria in the general population.
METHODS: Data were used of the first 4 screening rounds of a community-based prospective cohort study (PREVEND). Included were 5,825 subjects that at baseline had no known renal disease or macroalbuminuria. Subjects were defined as having progressive albuminuria when they belonged to the quintile of subjects with highest absolute increase in urinary albumin excretion per year and a urinary albumin excretion during the last screening in which they participated of ≥150 mg/24 h. Change in urinary albumin excretion per year was calculated as last available urinary albumin excretion minus baseline UAE divided by follow-up time.
RESULTS: During 9.3 years follow-up 132 subjects had progressive albuminuria. These subjects were significantly older, more often of male gender and had a worse cardiovascular risk profile. In a multivariable model, testing baseline values, significant predictors of progressive albuminuria were male gender (OR 2.23; p<0.001), age (OR 1.03; p<0.001), BMI (OR 1.06; p = 0.02) and baseline albuminuria (OR 5.71; p<0.001). Based on these findings a risk score was made to estimate a subject’s risk for progressive albuminuria.
CONCLUSION: A high baseline albuminuria is by far the most important predictor of progressive albuminuria. Thus, screening for baseline albuminuria will be more important than screening for cardiovascular risk factors in order to identify subjects at risk for progressive albuminuria.

PMID: 23723966 [PubMed – indexed for MEDLINE]

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Immune modulation by different types of β2→1-fructans is toll-like receptor dependent.

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Immune modulation by different types of β2→1-fructans is toll-like receptor dependent.

PLoS One. 2013;8(7):e68367

Authors: Vogt L, Ramasamy U, Meyer D, Pullens G, Venema K, Faas MM, Schols HA, de Vos P

Abstract
INTRODUCTION: β2→1-fructans are dietary fibers. Main objectives of this study were 1) to demonstrate direct signalling of β2→1-fructans on immune cells, 2) to study whether this is mediated by the pattern recognition receptors Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain-containing proteins (NODs), and 3) to relate the observed effects to the chain length differences in β2→1-fructans.
METHODS: Four different β2→1-fructan formulations were characterised for their chain length profile. Human peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with β2→1-fructans, and production of IL-1Ra, IL-1β, IL-6, IL-10, IL-12p70, and TNF-α was analysed. Reporter cells for TLRs and NODs were incubated with β2→1-fructans and analysed for NF-κB/AP-1 activation.
RESULTS: Cytokine production in human PBMCs was dose- and chain length-dependent. Strikingly, short chain enriched β2→1-fructans induced a regulatory cytokine balance compared to long chain enriched β2→1-fructans as measured by IL-10/IL-12 ratios. Activation of reporter cells showed that signalling was highly dependent on TLRs and their adapter, myeloid differentiation primary response protein 88 (MyD88). In human embryonic kidney reporter cells, TLR2 was prominently activated, while TLR4, 5, 7, 8, and NOD2 were mildly activated.
CONCLUSIONS: β2→1-fructans possess direct signalling capacity on human immune cells. By activating primarily TLR2, and to a lesser extent TLR4, 5, 7, 8, and NOD2, β2→1-fructan stimulation results in NF-κB/AP-1 activation. Chain length of β2→1-fructans is important for the induced activation pattern and IL-10/IL-12 ratios.

PMID: 23861894 [PubMed – indexed for MEDLINE]

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Psychosis-proneness and neural correlates of self-inhibition in theory of mind.

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Psychosis-proneness and neural correlates of self-inhibition in theory of mind.
PLoS One. 2013;8(7):e67774
Authors: van der Meer L, Groenewold NA, Pijnenborg M, Aleman A
Abstract
Impaired Theo… Continue reading

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Clinical implications of non-steatotic hepatic fat fractions on quantitative diffusion-weighted imaging of the liver.

Clinical implications of non-steatotic hepatic fat fractions on quantitative diffusion-weighted imaging of the liver.

PLoS One. 2014;9(2):e87926

Authors: Dijkstra H, Handayani A, Kappert P, Oudkerk M, Sijens PE

Abstract
Diffusion-weighted imaging (DWI) is an important diagnostic tool in the assessment of focal liver lesions and diffuse liver diseases such as cirrhosis and fibrosis. Quantitative DWI parameters such as molecular diffusion, microperfusion and their fractions, are known to be affected when hepatic fat fractions (HFF) are higher than 5.5% (steatosis). However, less is known about the effect on DWI for HFF in the normal non-steatotic range below 5.5%, which can be found in a large part of the population. The aim of this study was therefore to evaluate the diagnostic implications of non-steatotic HFF on quantitative DWI parameters in eight liver segments. For this purpose, eleven healthy volunteers (2 men, mean-age 31.0) were prospectively examined with DWI and three series of in-/out-of-phase dual-echo spoiled gradient-recalled MRI sequences to obtain the HFF and T2*. DWI data were analyzed using the intravoxel incoherent motion (IVIM) model. Four circular regions (ø22.3 mm) were drawn in each of eight liver segments and averaged. Measurements were divided in group 1 (HFF≤2.75%), group 2 (2.75< HFF ≤5.5%) and group 3 (HFF>5.5%). DWI parameters and T2* were compared between the three groups and between the segments. It was observed that the molecular diffusion (0.85, 0.72 and 0.49 ×10(-3) mm(2)/s) and T2* (32.2, 27.2 and 21.0 ms) differed significantly between the three groups of increasing HFF (2.18, 3.50 and 19.91%). Microperfusion and its fraction remained similar for different HFF. Correlations with HFF were observed for the molecular diffusion (r = -0.514, p<0.001) and T2* (-0.714, p<0.001). Similar results were obtained for the majority of individual liver segments. It was concluded that fat significantly decreases molecular diffusion in the liver, also in absence of steatosis (HFF≤5.5%). Also, it was confirmed that fat influences T2*. Determination of HFF prior to quantitative DWI is therefore crucial.

PMID: 24505333 [PubMed – in process]

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Variant B Cell Receptor Isotype Functions Differ in Hairy Cell Leukemia with Mutated BRAF and IGHV Genes.

Variant B Cell Receptor Isotype Functions Differ in Hairy Cell Leukemia with Mutated BRAF and IGHV Genes.
PLoS One. 2014 Jan 3;9(1):e86556
Authors: Weston-Bell NJ, Forconi F, Kluin-Nelemans HC, Sahota SS
Abstract
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Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination.

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Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination.
PLoS One. 2013;8(6):e66125
Authors: Gefenaite G, Tacken M, Bos J, Stirbu-Wagner I, Korevaar JC, Stolk RP… Continue reading

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Human FXR Regulates SHP Expression through Direct Binding to an LRH-1 Binding Site, Independent of an IR-1 and LRH-1.

Human FXR Regulates SHP Expression through Direct Binding to an LRH-1 Binding Site, Independent of an IR-1 and LRH-1.

PLoS One. 2014;9(2):e88011

Authors: Hoeke MO, Heegsma J, Hoekstra M, Moshage H, Faber KN

Abstract
BACKGROUND: Farnesoid X receptor/retinoid X receptor-alpha (FXR/RXRα) is the master transcriptional regulator of bile salt synthesis and transport in liver and intestine. FXR is activated by bile acids, RXRα by the vitamin A-derivative 9-cis retinoic acid (9cRA). Remarkably, 9cRA inhibits binding of FXR/RXRα to its response element, an inverted repeat-1 (IR-1). Still, most FXR/RXRα target genes are maximally expressed in the presence of both ligands, including the small heterodimer partner (SHP). Here, we revisited the FXR/RXRα-mediated regulation of human SHP.
METHODS: A 579-bp hSHP promoter element was analyzed to locate FXR/chenodeoxycholic acid (CDCA)- and RXRα/9cRA-responsive elements. hSHP promoter constructs were analyzed in FXR/RXRα-transfected DLD-1, HEK293 and HepG2 cells exposed to CDCA, GW4064 (synthetic FXR ligand) and/or 9cRA. FXR-DNA interactions were analyzed by in vitro pull down assays.
RESULTS: hSHP promoter elements lacking the previously identified IR-1 (-291/-279) largely maintained their activation by FXR/CDCA, but were unresponsive to 9cRA. FXR-mediated activation of the hSHP promoter was primarily dependent on the -122/-69 region. Pull down assays revealed a direct binding of FXR to the -122/-69 sequence, which was abrogated by site-specific mutations in a binding site for the liver receptor homolog-1 (LRH-1) at -78/-70. These mutations strongly impaired the FXR/CDCA-mediated activation, even in the context of a hSHP promoter containing the IR-1. LRH-1 did not increase FXR/RXRα-mediated activation of hSHP promoter activity.
CONCLUSION: FXR/CDCA-activated expression of SHP is primarily mediated through direct binding to an LRH-1 binding site, which is not modulated by LRH-1 and unresponsive to 9cRA. 9cRA-induced expression of SHP requires the IR-1 that overlaps with a direct repeat-2 (DR-2) and DR-4. This establishes for the first time a co-stimulatory, but independent, action of FXR and RXRα agonists.

PMID: 24498423 [PubMed – in process]

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Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children.

Clinical Epidemiology of Bocavirus, Rhinovirus, Two Polyomaviruses and Four Coronaviruses in HIV-Infected and HIV-Uninfected South African Children.

PLoS One. 2014;9(2):e86448

Authors: Nunes MC, Kuschner Z, Rabede Z, Madimabe R, Van Niekerk N, Moloi J, Kuwanda L, Rossen JW, Klugman KP, Adrian PV, Madhi SA

Abstract
BACKGROUND: Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV), human rhinovirus (hRV), polyomavirus-WU (WUPyV) and -KI (KIPyV) and human coronaviruses (CoV)-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI).
METHODS: Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age) hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B.
RESULTS: At least one of these viruses were identified in 274 (53.0%) of 517 and in 509 (54.0%) of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7%) and -uninfected children (32.0%), followed by CoV-OC43 (12.2%) and hBoV (9.5%) in HIV-infected; and by hBoV (13.3%) and WUPyV (11.9%) in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002) and CoV-OC43 (12.2% vs. 3.6%; p<0.001) were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children).
CONCLUSIONS: We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a synergetic role of viral co-infections in the pathogenesis of childhood LRTI.

PMID: 24498274 [PubMed – in process]

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Opinions of youngsters with congenital below-elbow deficiency, and those of their parents and professionals concerning prosthetic use and rehabilitation treatment.

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Opinions of youngsters with congenital below-elbow deficiency, and those of their parents and professionals concerning prosthetic use and rehabilitation treatment.
PLoS One. 2013;8(6):e67101
Authors: Vasluian… Continue reading

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“Timed up & go”: a screening tool for predicting 30-day morbidity in onco-geriatric surgical patients? A multicenter cohort study.

“Timed up & go”: a screening tool for predicting 30-day morbidity in onco-geriatric surgical patients? A multicenter cohort study.

PLoS One. 2014;9(1):e86863

Authors: Huisman MG, van Leeuwen BL, Ugolini G, Montroni I, Spiliotis J, Stabilini C, Carino ND, Farinella E, de Bock GH, Audisio RA

Abstract
OBJECTIVE: To determine the predictive value of the “Timed Up & Go” (TUG), a validated assessment tool, on a prospective cohort study and to compare these findings to the ASA classification, an instrument commonly used for quantifying patients’ physical status and anesthetic risk.
BACKGROUND: In the onco-geriatric surgical population it is important to identify patients at increased risk of adverse post-operative outcome to minimize the risk of over- and under-treatment and improve outcome in this population.
METHODS: 280 patients ≥70 years undergoing elective surgery for solid tumors were prospectively recruited. Primary endpoint was 30-day morbidity. Pre-operatively TUG was administered and ASA-classification was registered. Data were analyzed using multivariable logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (95%-CI). Absolute risks and area under the receiver operating characteristic curves (AUC’s) were calculated.
RESULTS: 180 (64.3%) patients (median age: 76) underwent major surgery. 55 (20.1%) patients experienced major complications. 50.0% of patients with high TUG and 25.6% of patients with ASA≥3 experienced major complications (absolute risks). TUG and ASA were independent predictors of the occurrence of major complications (TUG:OR 3.43; 95%-CI = 1.14-10.35. ASA1 vs. 2:OR 5.91; 95%-CI = 0.93-37.77. ASA1 vs. 3&4:OR 12.77; 95%-CI = 1.84-88.74). AUCTUG was 0.64 (95%-CI = 0.55-0.73, p = 0.001) and AUCASA was 0.59 (95%-CI = 0.51-0.67, p = 0.04).
CONCLUSIONS: Twice as many onco-geriatric patients at risk of post-operative complications, who might benefit from pre-operative interventions, are identified using TUG than when using ASA.

PMID: 24475186 [PubMed – in process]

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Stability of Lysozyme in Aqueous Extremolyte Solutions during Heat Shock and Accelerated Thermal Conditions.

Stability of Lysozyme in Aqueous Extremolyte Solutions during Heat Shock and Accelerated Thermal Conditions.

PLoS One. 2014 Jan 23;9(1):e86244

Authors: Avanti C, Saluja V, van Streun EL, Frijlink HW, Hinrichs WL

Abstract
The purpose of this study was to investigate the stability of lysozyme in aqueous solutions in the presence of various extremolytes (betaine, hydroxyectoine, trehalose, ectoine, and firoin) under different stress conditions. The stability of lysozyme was determined by Nile red Fluorescence Spectroscopy and a bioactivity assay. During heat shock (10 min at 70°C), betaine, trehalose, ectoin and firoin protected lysozyme against inactivation while hydroxyectoine, did not have a significant effect. During accelerated thermal conditions (4 weeks at 55°C), firoin also acted as a stabilizer. In contrast, betaine, hydroxyectoine, trehalose and ectoine destabilized lysozyme under this condition. These findings surprisingly indicate that some extremolytes can stabilize a protein under certain stress conditions but destabilize the same protein under other stress conditions. Therefore it is suggested that for the screening extremolytes to be used for protein stabilization, an appropriate storage conditions should also be taken into account.

PMID: 24465983 [PubMed – in process]

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Porphyromonas Gingivalis and E-coli Induce Different Cytokine Production Patterns in Pregnant Women.

Porphyromonas Gingivalis and E-coli Induce Different Cytokine Production Patterns in Pregnant Women.

PLoS One. 2014 Jan 22;9(1):e86355

Authors: Faas MM, Kunnen A, Dekker DC, Harmsen HJ, Aarnoudse JG, Abbas F, De Vos P, Van Pampus MG

Abstract
OBJECTIVE: Pregnant individuals of many species, including humans, are more sensitive to various bacteria or their products as compared with non-pregnant individuals. Pregnant individuals also respond differently to different bacteria or their products. Therefore, in the present study, we evaluated whether the increased sensitivity of pregnant women to bacterial products and their heterogeneous response to different bacteria was associated with differences in whole blood cytokine production upon stimulation with bacteria or their products.
METHODS: Blood samples were taken from healthy pregnant and age-matched non-pregnant women and ex vivo stimulated with bacteria or LPS from Porphyromonas Gingivalis (Pg) or E-coli for 24 hrs. TNFα, IL-1ß, IL-6, IL-12 and IL-10 were measured using a multiplex Luminex system.
RESULTS: We observed a generally lower cytokine production after stimulation with Pg bacteria or it’s LPS as compared with E-coli bacteria. However, there was also an effect of pregnancy upon cytokine production: in pregnant women the production of IL-6 upon Pg stimulation was decreased as compared with non-pregnant women. After stimulation with E-coli, the production of IL-12 and TNFα was decreased in pregnant women as compared with non-pregnant women.
CONCLUSION: Our results showed that cytokine production upon bacterial stimulation of whole blood differed between pregnant and non-pregnant women, showing that the increased sensitivity of pregnant women may be due to differences in cytokine production. Moreover, pregnancy also affected whole blood cytokine production upon Pg or E-coli stimulation differently. Thus, the different responses of pregnant women to different bacteria or their products may result from variations in cytokine production.

PMID: 24466049 [PubMed – in process]

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Adiponectin Expression Protects against Angiotensin II-Mediated Inflammation and Accelerated Atherosclerosis.

Adiponectin Expression Protects against Angiotensin II-Mediated Inflammation and Accelerated Atherosclerosis.
PLoS One. 2014 Jan 22;9(1):e86404
Authors: van Stijn CM, Kim J, Barish GD, Tietge UJ, Tangirala RK
Abstract
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Stressful Events and Continued Smoking and Continued Alcohol Consumption during Mid-Pregnancy.

Stressful Events and Continued Smoking and Continued Alcohol Consumption during Mid-Pregnancy.

PLoS One. 2014 Jan 20;9(1):e86359

Authors: Beijers C, Ormel J, Meijer JL, Verbeek T, Bockting CL, Burger H

Abstract
AIM: to examine whether the severity of different categories of stressful events is associated with continued smoking and alcohol consumption during mid-pregnancy. Also, we explored the explanation of these associations by anxiety and depressive symptoms during pregnancy. Finally, we studied whether the severity of stressful events was associated with the amount of cigarettes and alcohol used by continued users.
METHOD: we conducted a cross-sectional analysis using data from a population-based prospective cohort study. Pregnant women were recruited via midwifery practices throughout The Netherlands. We analyzed women who continued smoking (n = 113) or quit (n = 290), and women who continued alcohol consumption (n = 124) or quit (n = 1403) during pregnancy. Smoking, alcohol consumption, and perceived severity of stressful events were measured at 19 weeks of gestation. The State Trait Anxiety Inventory and the Edinburgh Postnatal Depression Scale were filled out at 14 weeks of gestation. Odds ratios were calculated as association measures and indicated the relative increase for the odds of continuation of smoking and alcohol consumption for the maximum severity score compared to the minimum score.
FINDINGS: SEVERITY OF THE FOLLOWING STRESSFUL EVENT CATEGORIES WAS ASSOCIATED WITH CONTINUED ALCOHOL CONSUMPTION: ‘conflict with loved ones’ (OR = 10.4, p<0.01), ‘crime related’ (OR = 35.7, p<0.05), ‘pregnancy-specific’ (OR = 13.4, p<0.05), and the total including all events (OR = 17.2, p<0.05). Adjustment for potential confounders (age, parity and educational level) did not notably change the estimates. There was no association of anxiety and depressive symptoms with continued smoking or alcohol consumption. No associations emerged for continued smoking and severity of stressful events. The amount of cigarettes and alcohol consumption among continued users was not associated with severity of stressful events.
CONCLUSIONS: Our findings may be relevant for health care providers, in particular midwives and general practitioners. The impact of stressful events may be considered when advising pregnant women on smoking and alcohol consumption.

PMID: 24466052 [PubMed – in process]

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Preferred and Actual Relative Height among Homosexual Male Partners Vary with Preferred Dominance and Sex Role.

Preferred and Actual Relative Height among Homosexual Male Partners Vary with Preferred Dominance and Sex Role.

PLoS One. 2014 Jan 22;9(1):e86534

Authors: Valentova JV, Stulp G, Třebický V, Havlíček J

Abstract
Previous research has shown repeatedly that human stature influences mate preferences and mate choice in heterosexuals. In general, it has been shown that tall men and average height women are most preferred by the opposite sex, and that both sexes prefer to be in a relationship where the man is taller than the woman. However, little is known about such partner preferences in homosexual individuals. Based on an online survey of a large sample of non-heterosexual men (N = 541), we found that the majority of men prefer a partner slightly taller than themselves. However, these preferences were dependent on the participant’s own height, such that taller men preferred shorter partners, whereas shorter men preferred taller partners. We also examined whether height preferences predicted the preference for dominance and the adoption of particular sexual roles within a couple. Although a large proportion of men preferred to be in an egalitarian relationship with respect to preferred dominance (although not with respect to preferred sexual role), men that preferred a more dominant and more “active” sexual role preferred shorter partners, whereas those that preferred a more submissive and more “passive” sexual role preferred taller partners. Our results indicate that preferences for relative height in homosexual men are modulated by own height, preferred dominance and sex role, and do not simply resemble those of heterosexual women or men.

PMID: 24466136 [PubMed – in process]

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Deficits in facial emotion recognition indicate behavioral changes and impaired self-awareness after moderate to severe traumatic brain injury.

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Deficits in facial emotion recognition indicate behavioral changes and impaired self-awareness after moderate to severe traumatic brain injury.
PLoS One. 2013;8(6):e65581
Authors: Spikman JM, Milders MV, Viss… Continue reading

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Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands.

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Meningococcal serogroup A, C, W₁₃₅ and Y conjugated vaccine: a cost-effectiveness analysis in the Netherlands.

PLoS One. 2013;8(5):e65036

Authors: Hepkema H, Pouwels KB, van der Ende A, Westra TA, Postma MJ

Abstract
BACKGROUND: In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in subjects of 12 months of age and above.
OBJECTIVES: To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine.
METHODS: A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER) was estimated for the current disease incidence and for a scenario when herd immunity is lost.
RESULTS: Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving.
CONCLUSIONS: Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity.

PMID: 23741448 [PubMed – indexed for MEDLINE]

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Source discrimination in adults with attention deficit hyperactivity disorder.

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Source discrimination in adults with attention deficit hyperactivity disorder.
PLoS One. 2013;8(5):e65134
Authors: Fuermaier AB, Tucha L, Koerts J, Aschenbrenner S, Weisbrod M, Lange KW, Tucha O
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Galectin-9 activates and expands human T-helper 1 cells.

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Galectin-9 activates and expands human T-helper 1 cells.

PLoS One. 2013;8(5):e65616

Authors: Gooden MJ, Wiersma VR, Samplonius DF, Gerssen J, van Ginkel RJ, Nijman HW, Hirashima M, Niki T, Eggleton P, Helfrich W, Bremer E

Abstract
Galectin-9 (Gal-9) is known for induction of apoptosis in IFN-γ and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-γ positive T-cells in a sarcoma mouse model and in food allergy, suggesting that Gal-9 can have diametric effects on T-cell immunity. Here, we aimed to delineate the immunomodulatory effect of Gal-9 on human resting and ex vivo activated peripheral blood lymphocytes. Treatment of resting lymphocytes with low concentrations of Gal-9 (5-30 nM) induced apoptosis in ∼60% of T-cells after 1 day, but activated the surviving T-cells. These viable T-cells started to expand after 4 days with up to 6 cell divisions by day 7 and an associated shift from naïve towards central memory and IFN-γ producing phenotype. In the presence of T-cell activation signals (anti-CD3/IL-2) Gal-9 did not induce T-cell expansion, but shifted the CD4/CD8 balance towards a CD4-dominated T-cell response. Thus, Gal-9 activates resting T-cells in the absence of typical T-cell activating signals and promotes their transition to a TH1/C1 phenotype. In the presence of T-cell activating signals T-cell immunity is directed towards a CD4-driven response by Gal-9. Thus, Gal-9 may specifically enhance reactive immunological memory.

PMID: 23741502 [PubMed – indexed for MEDLINE]

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