Treatment of Acne Vulgaris With Salicylic Acid Chemical Peel and Pulsed Dye Laser: A Split Face, Rater-Blinded, Randomized Controlled Trial

Introduction: Pulsed dye laser (PDL) has been used to treat acne lesions and scar erythema by interrupting superficial vasculature. Salicylic acid chemical peels are employed chiefly due to their lipophilic, comedolytic, and anti-inflammatory properties. Although studies have looked at peels and laser therapy independently in acne management, we examined these treatments in combination. Our primary objective was to evaluate the safety and efficacy of concurrent use of salicylic acid peels with PDL versus salicylic acid peels alone in the treatment of moderate to severe acne vulgaris.Methods: Adult patients with moderate to severe acne were included. Subjects received a total of 3 treatments at 3-week intervals. Per randomized split-face treatment, at week 0, one half of the subject’s face was treated with PDL (595 nm) followed by whole face application of a 30% salicylic acid peel. At weeks 3 and 6, the treatments were repeated. At 0 and 9 weeks, patients were assessed with the Global Evaluation Acne (GEA) scale and Dermatology Life Quality Index (DLQI) questionnaire.Results: Nineteen subjects were enrolled, and 18 completed the study. Significant improvement in acne was seen in both the combined (laser and peel) and chemical peel alone treatment arms (P < .0005 and P = .001). Using the GEA scale score, compared to week 0, the mean difference in acne improvement at week 9 was -1.61 in the combination therapy group versus -1.11 in the peel only group. Based on the GEA scale scoring, a statistically significant greater difference in acne improvement was seen, from week 0 to week 9, in the combination treatment group compared with the peel only group (P = .003).Conclusion: While acne subjects had significant benefit from the salicylic acid peel alone, they experienced greater significant benefit from PDL treatment used in conjunction with salicylic acid peels. The adjunctive utilization of PDL to salicylic acid peel therapy can lead to better outcomes in acne management

The Customary International Law Game

Structural realists in political science and some rationalist legal scholars argue that customary international law cannot affect state behavior: that it is “epiphenomenal.” This article develops a game theoretic model of a multilateral prisoner’s dilemma in the customary international law context that shows that it is plausible that states would comply with customary international law under certain circumstances. Our model shows that these circumstances relate to: (i) the relative value of cooperation versus defection, (ii) the number of states effectively involved, (iii) the extent to which increasing the number of states involved increases the value of cooperation or the detriments of defection, including whether the particular issue has characteristics of a commons problem, a public good, or a network good, (iv) the information available to the states involved regarding compliance and defection, (v) the relative patience of states in valuing the benefits of long-term cooperation compared to short-term defection, (vi) the expected duration of interaction, (vii) the frequency of interaction, and (viii) whether there are also bilateral relationships or other multilateral relationships between the involved states. This model shows that customary international law is plausible in the sense that it may well affect state behavior where certain conditions are met. It shows what types of contexts, including malleable institutional features, may affect the ability of states to produce and comply with customary international law. This article identifies a number of empirical strategies that may be used to test the model

Dietary strategies of Pleistocene Pongo sp. and Homo erectus on Java (Indonesia)

During the Early to Middle Pleistocene, Java was inhabited by hominid taxa of great diversity. However, their seasonal dietary strategies have never been explored. We undertook geochemical analyses of orangutan (Pongo sp.), Homo erectus and other mammalian Pleistocene teeth from Sangiran. We reconstructed past dietary strategies at subweekly resolution and inferred seasonal ecological patterns. Histologically controlled spatially resolved elemental analyses by laser-based plasma mass spectrometry confirmed the preservation of authentic biogenic signals despite the effect of spatially restricted diagenetic overprint. The Sr/Ca record of faunal remains is in line with expected trophic positions, contextualizing fossil hominid diet. Pongo sp. displays marked seasonal cycles with ~3 month-long strongly elevated Sr/Ca peaks, reflecting contrasting plant food consumption presumably during the monsoon season, while lower Sr/Ca ratios suggest different food availability during the dry season. In contrast, omnivorous H. erectus shows low and less accentuated intra-annual Sr/Ca variability compared to Pongo sp., with δ13C data of one individual indicating a dietary shift from C4 to a mix of C3 and C4 plants. Our data suggest that H. erectus on Java was maximizing the resources available in more open mosaic habitats and was less dependent on variations in seasonal resource availability. While still influenced by seasonal food availability, we infer that H. erectus was affected to a lesser degree than Pongo sp., which inhabited monsoonal rain forests on Java. We suggest that H. erectus maintained a greater degree of nutritional independence by exploiting the regional diversity of food resources across the seasons

Evaluation of the effect of patient education on rates of falls in older hospital patients: Description of a randomised controlled trial

Background. Accidental falls by older patients in hospital are one of the most commonly reported adverse events. Falls after discharge are also common. These falls have enormous physical, psychological and social consequences for older patients, including serious physical injury and reduced quality of life, and are also a source of substantial cost to health systems worldwide. There have been a limited number of randomised controlled trials, mainly using multifactorial interventions, aiming to prevent older people falling whilst inpatients. Trials to date have produced conflicting results and recent meta-analyses highlight that there is still insufficient evidence to clearly identify which interventions may reduce the rate of falls, and falls related injuries, in this population. Methods and design. A prospective randomised controlled trial (n = 1206) is being conducted at two hospitals in Australia. Patients are eligible to be included in the trial if they are over 60 years of age and they, or their family or guardian, give written consent. Participants are randomised into three groups. The control group continues to receive usual care. Both intervention groups receive a specifically designed patient education intervention on minimising falls in addition to usual care. The education is delivered by Digital Video Disc (DVD) and written workbook and aims to promote falls prevention activities by participants. One of the intervention groups also receives follow up education training visits by a health professional. Blinded assessors conduct baseline and discharge assessments and follow up participants for 6 months after discharge. The primary outcome measure is falls by participants in hospital. Secondary outcome measures include falls at home after discharge, knowledge of falls prevention strategies and motivation to engage in falls prevention activities after discharge. All analyses will be based on intention to treat principle. Discussion. This trial will examine the effect of a single intervention (specifically designed patient education) on rates of falls in older patients in hospital and after discharge. The results will provide robust recommendations for clinicians and researchers about the role of patient education in this population. The study has the potential to identify a new intervention that may reduce rates of falls in older hospital patients and could be readily duplicated and applied in a wide range of clinical settings. Trial Registration. ACTRN12608000015347

Reducing falls in older adults recently discharged from hospital: A systematic review and meta-analysis

Background: Older adults are known to have increased falls rates and functional decline following hospital discharge, with substantial economic healthcare costs. This systematic review aimed to synthesise the evidence for effective falls prevention interventions in older adults recently discharged from hospital. Methods: Literature searches of six databases of quantitative studies conducted from 1990 to June 2017, reporting falls outcomes of falls prevention interventions for community-dwelling older adults discharged from hospital were included. Study quality was assessed using a standardised JBI critical appraisal tool (MAStARI) and data pooled using Rev-Man Review Manager® Results: Sixteen studies (total sample size N= 3,290, from eight countries, mean age 77) comprising 12 interventions met inclusion criteria. We found home hazard modification interventions delivered to those with a previous falls history (1 study), was effective in reducing the number of falls (RR 0.63, 95%CI 0.43, 0.93, Low GRADE evidence). Home exercise interventions (3 studies) significantly increased the proportion of fallers (OR 1.74, 95%CI 1.17, 2.60, Moderate GRADE evidence), and did not significantly reduce falls rate (RR 1.27, 95%CI 0.99, 1.62, Very Low GRADE evidence) or falls injury rate (RR1.16, 95%CI, 0.83,1.63, Low GRADE evidence). Nutritional supplementation for malnourished older adults (1 study) significantly reduced the proportion of fallers (HR 0.41, 95% CI 0.19, 0.86, Low GRADE evidence). Conclusion: The recommended falls prevention interventions for older adults recently discharged from hospital are to provide home hazard minimisation particularly if they have a recent previous falls history and consider nutritional supplementation if they are malnourished

Concurrent Oral 9 - Rheumatoid Arthritis: Aetiopathogenesis [OP59-OP64]: OP59. The Value of Interleukin-17 Serum Level in Rheumatoid Arthritis Immunopathogenesis

Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P < 0.001), tender (16.7 ± 2.0 vs 8.4 ± 1.1; P < 0.01) and swollen (12.3 ± 2.3 vs 3.9 ± 0.8; P < 0.01) joint count, DAS28 (5.0 ± 0.4 vs 2.8 ± 0.2 P < 0.01) were significantly higher compare to group1. It was found that in group2 the higher T-lymphocyte amount (CD3) was due to CD4 higher quantity, at the same time CD8 amount was significantly lower (22.2 ± 1.5% vs 28.4 ± 1.7%, P < 0.05) compare to group1. This caused the immunoregulative index increasing and indicated in the lost of autoimmune process regulation, including B-lymphocytes (CD19) activation. The CD154 expression was significantly lower in the group2 (3.4 ± 0.4% vs 10.8 ± 2.8%, P < 0.05) compare to group1. The difference in autoimmune reaction indices wasn't significant between groups except antibody-producing B-lymphocytes (13.7 ± 1.5% vs 8.5 ± 1.0%, P < 0.05) and IgM RF serum level (2.9 ± 0.3 U/ml vs 1.6 ± 0.5 U/ml, P < 0.05), which were significantly higher in group1. The IL-17 level had a positive correlative connections with DAS28 (r = 0.7; P < 0.05), circulative immune complex level (r = 0.38; P < 0.05), anti-CCP antibodies (r = 0.4; P < 0.05), IgM RF (r = 0.41; P < 0.05), CD4 (r = 0.38; P < 0.05) and negative correlative connection with CD8 (r = -0.39; P < 0.05). Conclusions: The importance of IL-17 value in immuno-inflammatory and autoimmune reactions development through T-lymphocytes activation in RA pathogenesis was confirmed. Thus the influence on T-depended immuno-inflammatory reaction products synthesis could be a new therapeutic target of RA patients' management. Disclosure statement: All authors have declared no conflicts of interes

Tailored education for older patients to facilitate engagement in falls prevention strategies after hospital discharge—A pilot randomized controlled trial

Background The aims of the study were to evaluate the effect of providing tailored falls prevention education in hospital on: i) engagement in targeted falls prevention behaviors in the month after discharge: ii) patients’ self-perceived risk and knowledge about falls and falls prevention strategies after receiving the education. Methods A pilot randomized controlled trial (n = 50): baseline and outcome assessments conducted by blinded researchers. Participants: hospital inpatients 60 years or older, discharged to the community. Participants were randomized into two groups. The intervention was a tailored education package consisting of multimedia falls prevention information with trained health professional follow-up, delivered in addition to usual care. Outcome measures were engagement in falls prevention behaviors in the month after discharge measured at one month after discharge with a structured survey, and participants’ knowledge, confidence and motivation levels before and after receiving the education. The feasibility of providing the intervention was examined and falls outcomes (falls, fall-related injuries) were also collected. Results Forty-eight patients (98%) provided follow-up data. The complete package was provided to 21 (84%) intervention group participants. Participants in the intervention group were significantly more likely to plan how to safely restart functional activities [Adjusted odds ratio 3.80, 95% CI (1.07, 13.52), p = 0.04] and more likely to complete other targeted behaviors such as completing their own home exercise program [Adjusted odds ratio 2.76, 95% CI (0.72, 10.50), p = 0.14] than the control group. The intervention group was significantly more knowledgeable, confident and motivated to engage in falls prevention strategies after receiving the education than the control group. There were 23 falls (n = 5 intervention; n = 18 control) and falls rates were 5.4/1000 patient days (intervention); 18.7/1000 patient days (control). Conclusion This tailored education was received positively by older people, resulted in increased engagement in falls prevention strategies after discharge and is feasible to deliver to older hospital patients. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; ACTRN12611000963921 on 8th November 2011

Phosphorylation of Serine 248 of C/EBPα Is Dispensable for Myelopoiesis but Its Disruption Leads to a Low Penetrant Myeloid Disorder with Long Latency

BACKGROUND: Transcription factors play a key role in lineage commitment and differentiation of stem cells into distinct mature cells. In hematopoiesis, they regulate lineage-specific gene expression in a stage-specific manner through various physical and functional interactions with regulatory proteins that are simultanously recruited and activated to ensure timely gene expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is such a factor and is essential for the development of granulocytic/monocytic cells. The activity of C/EBPα is regulated on several levels including gene expression, alternative translation, protein interactions and posttranslational modifications, such as phosphorylation. In particular, the phosphorylation of serine 248 of the transactivation domain has been shown to be of crucial importance for granulocytic differentiation of 32Dcl3 cells in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Here, we use mouse genetics to investigate the significance of C/EBPα serine 248 in vivo through the construction and analysis of Cebpa(S248A/S248A) knock-in mice. Surprisingly, 8-week old Cebpa(S248A/S248A) mice display normal steady-state hematopoiesis including unaltered development of mature myeloid cells. However, over time some of the animals develop a hematopoietic disorder with accumulation of multipotent, megakaryocytic and erythroid progenitor cells and a mild impairment of differentiation along the granulocytic-monocytic lineage. Furthermore, BM cells from Cebpa(S248A/S248A) animals display a competitive advantage compared to wild type cells in a transplantation assay. CONCLUSIONS/SIGNIFICANCE: Taken together, our data shows that the substitution of C/EBPα serine 248 to alanine favors the selection of the megakaryocytic/erythroid lineage over the monocytic/granulocytic compartment in old mice and suggests that S248 phosphorylation may be required to maintain proper hematopoietic homeostasis in response to changes in the wiring of cellular signalling networks. More broadly, the marked differences between the phenotype of the S248A variant in vivo and in vitro highlight the need to exert caution when extending in vitro phenotypes to the more appropriate in vivo context