Propionibacterium acnes promotes Th17 and Th17/Th1 responses in acne patients

Propionibacterium acnes is a Gram-positive commensal bacterium thought to be involved in the pathogenesis of acne vulgaris. Although the ability of P. acnes in the initiation of pro-inflammatory responses is well documented, little is known about adaptive immune responses to this bacterium. The observation that infiltrating immune cells consist mainly of CD4(+) T cells in the perifollicular space of early acne lesions suggests that helper T cells may be involved in immune responses caused by the intra-follicular colonization of P. acnes. A recent report showing that P. acnes can induce IL-17 production by T cells suggests that acne might be a T helper type 17 (Th17)-mediated disease. In line with this, we show in this work that, in addition to IL-17A, both Th1 and Th17 effector cytokines, transcription factors, and chemokine receptors are strongly upregulated in acne lesions. Furthermore, we found that, in addition to Th17, P. acnes can promote mixed Th17/Th1 responses by inducing the concomitant secretion of IL-17A and IFN-γ from specific CD4(+) T cells in vitro. Finally, we show that both P. acnes-specific Th17 and Th17/Th1 cells can be found in the peripheral blood of patients suffering from acne and, at lower frequencies, in healthy individuals. We therefore identified P. acnes-responding Th17/Th1 cells as, to our knowledge, a previously unreported CD4(+) subpopulation involved in inflammatory acne.

Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters

OBJECTIVE To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. MATERIALS AND METHODS Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19-52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. RESULTS The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. CONCLUSIONS One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Metal Artifact Reduction in Pelvic Computed Tomography With Hip Prostheses: Comparison of Virtual Monoenergetic Extrapolations From Dual-Energy Computed Tomography and an Iterative Metal Artifact Reduction Algorithm in a Phantom Study.

OBJECTIVE The aim of this study was to directly compare metal artifact reduction (MAR) of virtual monoenergetic extrapolations (VMEs) from dual-energy computed tomography (CT) with iterative MAR (iMAR) from single energy in pelvic CT with hip prostheses. MATERIALS AND METHODS A human pelvis phantom with unilateral or bilateral metal inserts of different material (steel and titanium) was scanned with third-generation dual-source CT using single (120 kVp) and dual-energy (100/150 kVp) at similar radiation dose (CT dose index, 7.15 mGy). Three image series for each phantom configuration were reconstructed: uncorrected, VME, and iMAR. Two independent, blinded radiologists assessed image quality quantitatively (noise and attenuation) and subjectively (5-point Likert scale). Intraclass correlation coefficients (ICCs) and Cohen κ were calculated to evaluate interreader agreements. Repeated measures analysis of variance and Friedman test were used to compare quantitative and qualitative image quality. Post hoc testing was performed using a corrected (Bonferroni) P < 0.017. RESULTS Agreements between readers were high for noise (all, ICC ≥ 0.975) and attenuation (all, ICC ≥ 0.986); agreements for qualitative assessment were good to perfect (all, κ ≥ 0.678). Compared with uncorrected images, VME showed significant noise reduction in the phantom with titanium only (P < 0.017), and iMAR showed significantly lower noise in all regions and phantom configurations (all, P < 0.017). In all phantom configurations, deviations of attenuation were smallest in images reconstructed with iMAR. For VME, there was a tendency toward higher subjective image quality in phantoms with titanium compared with uncorrected images, however, without reaching statistical significance (P > 0.017). Subjective image quality was rated significantly higher for images reconstructed with iMAR than for uncorrected images in all phantom configurations (all, P < 0.017). CONCLUSIONS Iterative MAR showed better MAR capabilities than VME in settings with bilateral hip prosthesis or unilateral steel prosthesis. In settings with unilateral hip prosthesis made of titanium, VME and iMAR performed similarly well.

Endothelial- and Platelet-Derived Microparticles Are Generated During Liver Resection in Humans.

BACKGROUND Cell-derived plasma microparticles (<1.5 μm) originating from various cell types have the potential to regulate thrombogenesis and inflammatory responses. The aim of this study was to test the hypothesis that microparticles generated during hepatic surgery co-regulate postoperative procoagulant and proinflammatory events. METHODS In 30 patients undergoing liver resection, plasma microparticles were isolated, quantitated, and characterized as endothelial (CD31+, CD41-), platelet (CD41+), or leukocyte (CD11b+) origin by flow cytometry and their procoagulant and proinflammatory activity was measured by immunoassays. RESULTS During liver resection, the total numbers of microparticles increased with significantly more Annexin V-positive, endothelial and platelet-derived microparticles following extended hepatectomy compared to standard and minor liver resections. After liver resection, microparticle tissue factor and procoagulant activity increased along with overall coagulation as assessed by thrombelastography. Levels of leukocyte-derived microparticles specifically increased in patients with systemic inflammation as assessed by C-reactive protein but are independent of the extent of liver resection. CONCLUSIONS Endothelial and platelet-derived microparticles are specifically elevated during liver resection, accompanied by increased procoagulant activity. Leukocyte-derived microparticles are a potential marker for systemic inflammation. Plasma microparticles may represent a specific response to surgical stress and may be an important mediator of postoperative coagulation and inflammation.

Comparison of Routine Brain Imaging at 3 T and 7 T.

OBJECTIVE The aim of this study was to compare quantitative and semiquantitative parameters (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], image quality, diagnostic confidence) from a standard brain magnetic resonance imaging examination encompassing common neurological disorders such as demyelinating disease, gliomas, cerebrovascular disease, and epilepsy, with comparable sequence protocols and acquisition times at 3 T and at 7 T. MATERIALS AND METHODS Ten healthy volunteers and 4 subgroups of 40 patients in total underwent comparable magnetic resonance protocols with standard diffusion-weighted imaging, 2D and 3D turbo spin echo, 2D and 3D gradient echo and susceptibility-weighted imaging of the brain (10 sequences) at 3 T and 7 T. The subgroups comprised patients with either lesional (n = 5) or nonlesional (n = 4) epilepsy, intracerebral tumors (n = 11), demyelinating disease (n = 11) (relapsing-remitting multiple sclerosis [MS, n = 9], secondary progressive MS [n = 1], demyelinating disease not further specified [n = 1]), or chronic cerebrovascular disorders [n = 9]). For quantitative analysis, SNR and CNR were determined. For a semiquantitative assessment of the diagnostic confidence, a 10-point scale diagnostic confidence score (DCS) was applied. Two experienced radiologists with additional qualification in neuroradiology independently assessed, blinded to the field strength, 3 pathology-specific imaging criteria in each of the 4 disease groups and rated their diagnostic confidence. The overall image quality was semiquantitatively assessed using a 4-point scale taking into account whether diagnostic decision making was hampered by artifacts or not. RESULTS Without correction for spatial resolution, SNR was higher at 3 T except in the T2 SPACE 3D, DWI single shot, and DIR SPACE 3D sequences. The SNR corrected by the ratio of 3 T/7 T voxel sizes was higher at 7 T than at 3 T in 10 of 11 sequences (all except for T1 MP2RAGE 3D).In CNR, there was a wide variation between sequences and patient cohorts, but average CNR values were broadly similar at 3 T and 7 T.DCS values for all 4 pathologic entities were higher at 7 T than at 3 T. The DCS was significantly higher at 7 T for diagnosis and exclusion of cortical lesions in vascular disease. A tendency to higher DCS at 7 T for cortical lesions in MS was observed, and for the depiction of a central vein and iron deposits within MS lesions. Despite motion artifacts, DCS values were higher at 7 T for the diagnosis and exclusion of hippocampal sclerosis in mesial temporal lobe epilepsy (improved detection of the hippocampal subunits). Interrater agreement was 69.7% at 3 T and 93.3% at 7 T. There was no significant difference in the overall image quality score between 3 T and 7 T taking into account whether diagnostic decision making was hampered by artifacts or not. CONCLUSIONS Ultra-high-field magnetic resonance imaging at 7 T compared with 3 T yielded an improved diagnostic confidence in the most frequently encountered neurologic disorders. Higher spatial resolution and contrast were identified as the main contributory factors.

Evaluation of residential bioaerosol concentrations and their related health effects

Limited research has been conducted on the collection of bioaerosols and their health effects on individuals in the El Paso area. A year long study was conducted in the region to evaluate indoor bioaerosol concentrations (Mota et al., unpublished data). As part of the study, air samples were collected during each season for a year from 38 homes from the El Paso area. The main objective of the study was to assess seasonality differences in bioaerosol concentrations. The air samples were then cultured and analyzed for bacterial and fungal concentrations. As a supplement to that study, a health questionnaire was given during each seasonal air sampling to the participating resident to complete regarding their health status. The aim of this study was to evaluate the health questionnaire and assess any associations between the collected bioaerosol concentrations and the self-reported respiratory symptoms of the participating home residents. Symptom frequencies were tabulated and basic descriptive statistics, along with logistic regressions, were conducted on the relationship between “High” reporters of symptoms and bioaerosol concentrations and environmental factors. The most commonly reported symptoms by homeowners were nasal symptoms and allergies. In addition, there was evidence to support an association between indoor respirable bacteria concentrations and homeowners that report greater than or equal to 8 respiratory symptoms (OR=1.10, p=0.045). Smoking status, indoor humidity and season also displayed associations with homeowners that report greater than or equal to 8 respiratory symptoms (OR=3.3, p=0.045; OR=71.0, p=0.030; OR=7.2, 3.2, p=0.001, 0.008). With such a strong association, future assessment of symptoms, bioaerosol concentrations and environmental factors is needed to further establish their relationship. ^

Factorial structure and reliability of a perceived influence on selection of a specialized plan of studies, IPEP, in secondary school students of Chillan, Chile

To evaluate these factors, the scale of perceived influences on the election of a specialized plan of studies, IPEP, was built and in this study its factorial structure and reliability were evaluated. The instrument was applied to 115 students, chosen by quote sampling. They were students of a subsidized private secondary school from the city of Chillan, Chile. An exploratory factorial analysis identified eight factors in the scale IPEP: Academic projection, Personal development, Maintenance of the social environment, Academic requirements, Satisfaction of others' expectations, Vocational information, Image of the plan and Family pressure. The results present an initial factorial structure, that empirically and theoretically adequate, whose factors were reliable and conceptually useful. These factors distinguish psychogenic and sociogenic aspects of the vocational process, and allow to initiate diagnostic and investigative actions in relation to this early vocational election that is established in secondary schools of the Chilean educational system

Factorial structure and reliability of a perceived influence on selection of a specialized plan of studies, IPEP, in secondary school students of Chillan, Chile

To evaluate these factors, the scale of perceived influences on the election of a specialized plan of studies, IPEP, was built and in this study its factorial structure and reliability were evaluated. The instrument was applied to 115 students, chosen by quote sampling. They were students of a subsidized private secondary school from the city of Chillan, Chile. An exploratory factorial analysis identified eight factors in the scale IPEP: Academic projection, Personal development, Maintenance of the social environment, Academic requirements, Satisfaction of others' expectations, Vocational information, Image of the plan and Family pressure. The results present an initial factorial structure, that empirically and theoretically adequate, whose factors were reliable and conceptually useful. These factors distinguish psychogenic and sociogenic aspects of the vocational process, and allow to initiate diagnostic and investigative actions in relation to this early vocational election that is established in secondary schools of the Chilean educational system

Factorial structure and reliability of a perceived influence on selection of a specialized plan of studies, IPEP, in secondary school students of Chillan, Chile

To evaluate these factors, the scale of perceived influences on the election of a specialized plan of studies, IPEP, was built and in this study its factorial structure and reliability were evaluated. The instrument was applied to 115 students, chosen by quote sampling. They were students of a subsidized private secondary school from the city of Chillan, Chile. An exploratory factorial analysis identified eight factors in the scale IPEP: Academic projection, Personal development, Maintenance of the social environment, Academic requirements, Satisfaction of others' expectations, Vocational information, Image of the plan and Family pressure. The results present an initial factorial structure, that empirically and theoretically adequate, whose factors were reliable and conceptually useful. These factors distinguish psychogenic and sociogenic aspects of the vocational process, and allow to initiate diagnostic and investigative actions in relation to this early vocational election that is established in secondary schools of the Chilean educational system

Exploring the link between sustainability reporting and sustainability management: a conceptual framework.

Sustainability managementand Sustainability Reporting (SR) practices have dramatically increased during the last two decades, raising important questions about the relationship between internal practices and external communication. Previous literature on SR has almost exclusively highlighted the role of institutional and stakeholder pressures in driving its adoption. However, as surveys among reporters also identify internal benefits of SR, its full role for company-level sustainability management remains unclear. In order to address this question, we develop a framework accounting for four SR configurations, stemming from different levels of relative importance of external and internal motives for SR. A multiple case study involving four large Spanish companies serves to illustrate the framework and to identify company-level factors that act both as enablers and barriers of SR internal relevance. We conclude that motivations for SR, along with such internal factors, decisively influence its contribution to sustainability management.

Inhibition of proteasomal degradation by the Gly-Ala repeat of Epstein–Barr virus is influenced by the length of the repeat and the strength of the degradation signal

The Gly-Ala repeat (GAr) of the Epstein–Barr virus nuclear antigen-1 is a transferable element that inhibits in cis ubiquitin/proteasome-dependent proteolysis. We have investigated this inhibitory activity by using green fluorescent protein-based reporters that have been targeted for proteolysis by N end rule or ubiquitin-fusion degradation signals, resulting in various degrees of destabilization. Degradation of the green fluorescent protein substrates was inhibited on insertion of a 25-aa GAr, but strongly destabilized reporters were protected only partially. Protection could be enhanced by increasing the length of the repeat. However, reporters containing the Ub-R and ubiquitin-fusion degradation signals were degraded even in the presence of a 239-aa GAr. In accordance, insertion of a powerful degradation signal relieved the blockade of proteasomal degradation in Epstein–Barr virus nuclear antigen-1. Our findings suggest that the turnover of natural substrates may be finely tuned by GAr-like sequences that counteract targeting signals for proteasomal destruction.

Structure and function of pectic enzymes: Virulence factors of plant pathogens

The structure and function of Erwinia chrysanthemi pectate lysase C, a plant virulence factor, is reviewed to illustrate one mechanism of pathogenesis at the molecular level. Current investigative topics are discussed in this paper.

Older plasma lipoproteins are more susceptible to oxidation: a linking mechanism for the lipid and oxidation theories of atherosclerotic cardiovascular disease.

Increases in plasma cholesterol are associated with progressive increases in the risk of atherosclerotic cardiovascular disease. In humans plasma cholesterol is contained primarily in apolipoprotein B-based low density lipoprotein (LDL). Cells stop making the high-affinity receptor responsible for LDL removal as they become cholesterol replete; this slows removal of LDL from plasma and elevates plasma LDL. As a result of this delayed uptake, hypercholesterolemic individuals not only have more LDL but have significantly older LDL. Oxidative modification of LDL enhances their atherogenicity. This study sought to determine whether increased time spent in circulation, or aging, by lipoprotein particles altered their susceptibility to oxidative modification. Controlled synchronous production of distinctive apolipoprotein B lipoproteins (yolk-specific very low density lipoproteins; VLDLy) with a single estrogen injection into young turkeys was used to model LDL aging in vivo. VLDLy remained in circulation for at least 10 days. Susceptibility to oxidation in vitro was highly dependent on lipoprotein age in vivo. Oxidation, measured as hexanal release from n-6 fatty acids in VLDLy, increased from 13.3 +/- 5.5 nmol of 2-day-old VLDLy per ml, to 108 +/- 17 nmol of 7-day-old VLDLy per ml. Oxidative instability was not due to tocopherol depletion or conversion to a more unsaturated fatty acid composition. These findings establish mathematically describable linkages between the variables of LDL concentration and LDL oxidation. The proposed mathematical models suggest a unified investigative approach to determine the mechanisms for acceleration of atherosclerotic cardiovascular disease risk as plasma cholesterol rises.

High Value Lies, Ugly Truths, and the First Amendment

Lying has a complicated relationship with the First Amendment. It is beyond question that some lies – such as perjury or pretending to be a police officer – are not covered by the First Amendment. But it is equally clear that some lies, even intentionally lying about military honors, are entitled to First Amendment protection. U.S. v. Alvarez, 132 S. Ct. 2537 (2012). To date, however, both Supreme Court doctrine and academic commentary has taken for granted that any constitutional protection for lies is purely prophylactic – it protects the liar to avoid chilling truthful speech. This Article is the first to argue, contrary to conventional wisdom, that certain types of lies paradoxically advance the values underlying the First Amendment. Our framework is descriptively novel and doctrinally important insofar as we provide the first comprehensive post-Alvarez look at the wide range of lies that may raise First Amendment issues. Because there was no majority opinion in Alvarez, there is uncertainty about which standard of constitutional scrutiny should apply to protected lies, an issue we examine at length. Moreover, our normative claim is straightforward: when a lie has intrinsic or instrumental value it should be treated differently from other types of lies and warrant the greatest constitutional protection. Specifically, we argue that investigative deceptions – lies used to secure truthful factual information about matters of public concern – deserve the utmost constitutional protection because they advance the underling purposes of free speech: they enhance political discourse, help reveal the truth, and promote individual autonomy. A prototypical investigative deception is the sort of misrepresentation required in order for an undercover journalist, investigator, or activist to gain access to information or images of great political significance that would not be available if the investigator disclosed her reporting or political objectives. Tactical use of such lies have a long history in American journalism and activism, from Upton Sinclair to his modern day heirs. Using the proliferation of anti-whistleblower statutes like Ag Gag laws as an illustrative example, we argue that investigative deceptions are a category of high value lies that ought to receive rigorous protection under the First Amendment. At the same time, we recognize that not all lies are alike and that in other areas, the government regulation of lies serves legitimate interests. We therefore conclude the Article by drawing some limiting principles to our theory.