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BACKGROUND Eyebrows are an important esthetic feature of the face. In cosmetic surgery, knowledge about the patient's preference of eyebrow apex position is important to achieve agreeable esthetic results. AIM To study the preference of eyebrow apex positions on the different facial shapes in the Malaysian population. METHODS A frontal view photograph of a female model was morphed into oval, square, round, and long facial shapes. Four types of brow apex were created on each facial shape, A. above the midpupil (A-MP), B. above the lateral limbus (A-LL), C. halfway between the lateral limbus and lateral canthus (A-HF) and D. above the lateral canthus (A-LC). Out of the four brow apexes, the respondent selected one esthetically appealing brow apex for each facial shape. A total of 441 Malaysians completed the survey questionnaire. Differences in preference between the ethnic groups were analyzed by the chi-square test. RESULTS The majority of Malaysian Chinese (MC) and Malaysian Indians (MI) subjects found A-LL as attractive on the oval (MC-73%, MI-52%), square (MC-42%, MI-42%), round (MC-45%, MI-40%) and long (MC-39%, MI-44%) shape, but the Malaysian Malays preferred more the A-HF on long (42%) and round (42%) face. While the Malaysian Indians least preferred the A-MP on the oval (4%), square (5%), round (6%), and long (5%). A significant difference in preference of apex position was observed between MC versus MI and MC versus MM in both oval and square faces. On the round face, the difference was noted between all the ethnic groups. However, on the long face, a significant difference was noted only between MI and MM. CONCLUSIONS Significant interethnic differences exist in the preference of eyebrow apex position on the facial shapes.

The acceleration of biological aging is a risk factor for Alzheimer's disease (AD). Here, we performed weighted gene co-expression network analysis (WGCNA) to identify modules and dysregulated genesinvolved in biological aging in AD.We performed WGCNA to identify modules associated with biological clocks and hub genes of the module with the highest module significance. In addition, we performed differential expression analysis and association analysis with AD biomarkers.WGCNA identified five modules associated with biological clocks, with the module designated as "purple" showing the strongest association. Functional enrichment analysis revealed that the purple module was related to cell migration and death. Ten genes were identified as hub genes in purple modules, of whichNetwork analysis identified genes associated with biological clocks, which suggests the genetic architecture underlying biological aging in AD.Examine links between Alzheimer's disease (AD) peripheral transcriptome and biological aging changes.Weighted gene co-expression network analysis (WGCNA) found five modules related to biological aging.Among the hub genes of the module

Victims of injustice are prominent protagonists in efforts to resist injustice. I argue that they have a duty to do so. Extant accounts of victims’ duties primarily cast these duties as self-regarding duties (say, of Kantian self-respect) or duties based on collective identities and commitments. I provide an account of victims’ duties to resist injustice that is grounded in the duty to assist. I argue that victims are epistemically privileged with respect to injustice and are therefore uniquely positioned to assist fellow victims. Primarily, they discharge this duty through testimony: victims alert other actors to the need for assistance and initiate and coordinate resistance efforts. I briefly provide an account of oppression that ranges from persecution to structural injustice. Through the examples of torture and ‘manterrupting’, I illustrate the duty and its limits. I outline shortcomings in victims’ epistemic privilege and explore means by which these can be overcome. I respond to objections from demandingness and fairness, arguing that victims have an essential, albeit circumscribed, role to play in defeating injustice.

Background Pharmacologic stress testing is utilized in preference to exercise stress echocardiography (ESE) for cardiac risk evaluation in potential renal transplant recipients due to the perceived lower feasibility of ESE for achieving adequate workload and target heart rate (THR) in this population. Methods Consecutive patients referred for cardiac risk evaluation prior to potential kidney transplantation were evaluated. All patients attempted ESE before pharmacologic testing was considered. Treadmill ESE utilized BRUCE protocol to maximum capacity. THR was defined as >85% of the maximum predicted heart rate (220-age). Functional capacity was assessed by metabolic equivalents (METs) and the rate pressure product (RPP). Results Of 535 patients (349 male, age 56±11), 372(70%) reached THR. Mean METs were 10±3 with 531(99%) achieving ≥4 METs and 87% ≥7 METs. Mean RPP was 25 821±5820 bpm×mm Hg (83% achieving >20 000 bpm×mm Hg). On multivariate analysis, independent predictors of failure to reach THR were rate-control medication and diabetes; failure to reach 7 METs: females, diabetics, age≥65, and previous cardiac disease; failure to reach RPP>20 000: rate-control medication. There were 97% of ESE completed to physiologic endpoints. Conclusion In unselected potential renal transplant candidates, cardiac assessment by ESE is well tolerated, with 9-in-10 exercising to satisfactory functional capacity. ESE should be considered a feasible alternative to pharmacologic testing in this population.

Aim: To use continuous glucose monitoring to examine the effects of insulin initiation with glargine, with or without glulisine, on glycaemic variability and glycaemia in a cohort of people with Type 2 diabetes receiving maximum oral hypoglycaemic agents in primary healthcare. Methods: We conducted a post hoc analysis of continuous glucose monitoring data from 89 participants at baseline and at 24 weeks after insulin commencement. Indicators of glycaemic variability (standard deviation, J-index and mean amplitude of glycaemic excursion) and glycaemia (HbA, mean glucose, area under the glucose-time curve) were assessed. Multi-level regression analysis was used to identify the predictors of change. Results: Complete glycaemic variability data were available for 78 participants. Of these participants, 41% were women, their mean (sd) age was 59.2 (10.4) years, the median (interquartile range) diabetes duration was 10.4 (6.5, 13.3) years and the median (interquartile range) baseline HbA was 82.5 (71.6, 96.7) mmol/mol [9.7 (8.7, 11.0)%]. At baseline, BMI correlated negatively with standard deviation (r = -0.30) and mean amplitude of glycaemic excursion (r = -0.26), but not with J-index; HbA correlated with J-index (r = 0.61) but not with mean amplitude of glycaemic excursion and standard deviation. After insulin initiation the mean (sd) glucose level decreased [from 12.0 (3.0) to 8.5 (1.6) mmol/l; P < 0.001], as did the median (interquartile range) J-index [from 66.9 (47.7, 95.1) to 36.9 (27.6, 49.8) mmol/l; P < 0.001]. Baseline HbA correlated with a greater J-index reduction (r = -0.45; P < 0.001). The mean amplitude of glycaemic excursion and standard deviation values were unchanged. The baseline temporal profile, showing elevated postprandial morning glucose levels, was unchanged after insulin initiation, despite an overall reduction in glycaemia. Conclusion: Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability in adults with Type 2 diabetes receiving maximum oral hypoglycaemic agents. The most significant postprandial excursions were seen in the morning, which identifies prebreakfast as the most effective target for short-acting insulin therapy. What's new?: We report the largest study to date of glycaemic variability using continuous glucose monitoring in people with Type 2 diabetes of long duration, before and after commencement of insulin therapy. Data were obtained in the primary care setting, which is where the majority of patients with Type 2 diabetes are treated in countries such as the UK and Australia. Insulin initiation reduced hyperglycaemia but did not alter glycaemic variability. The largest postprandial excursions were related to breakfast, suggesting that this time point should be targeted when intensifying treatment with rapid-acting insulin or other agents.

This article engages in democratic theory and transnational politics by examining exile political representation, a long-standing but underexplored instance of transnational politics. It argues that in order to be valid -- which is distinct from being democratically legitimate -- a representative claim involves three elements: authorisation of the putative representative by her putative constituents, the putative representative acting in the interests of her putative constituents, and the putative representative being held accountable. The article considers the extent to which these elements can be satisfied through informal means and in the non-ideal circumstances surrounding exile politics. It argues that political representation should be regarded as a scalar concept and representative claims should be regarded as being more or less valid. It concludes by identifying the mechanisms that may render exiles' representative claims more valid, and suggests other democratically legitimate or desirable roles that they can play in the political communities they have left.

Amidated kyotorphin (l-Tyr-l-Arg-NH2; KTP-NH2) causes analgesia when systemically administered. The lipophilic ibuprofen-conjugated derivative of KTP-NH2 has improved analgesic efficacy. However, fast degradation by peptidases impacts negatively in the pharmacodynamics of these drugs. In this work, selected derivatives of KTP and KTP-NH2 were synthesized to combine lipophilicity and resistance to enzymatic degradation. Eight novel structural modifications were tested for the potential to transverse lipid membranes and to evaluate their efficacy in vivo. The rationale behind the design of the pool of the eight selected molecules consisted in the addition of individual group at the N-terminus, namely the tert-butyloxycarbonyl (Boc), γ-aminobutyric acid (GABA), acetyl, butanoyl, and propanoyl or in the substitution of the tyrosine residue by an indole moiety and in the replacement of the peptidic bond by a urea-like bond in some cases. All the drugs used in the study are intrinsically fluorescent, which enables the use of spectrofluorimetry to sample the drugs in the permeation assays. The results show that the BOC and indolyl derivatives of KTP-NH2 have maximal ability to permeate membranes with concomitant maximal analgesic power. Overall, the results demonstrate that membrane permeation is correlated with analgesic efficacy. However, this is not the only factor accounting for analgesia. KTP-NH2 for instance has low passive permeation but is known to have central action. In this case, hypothetical transcytosis over the blood-brain barrier seems to depend on dipeptide transporters. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 1–10, 2015.

Regulatory T cells (Tregs) are a specialized subset of CD4 T cells that have an indispensable role in maintaining immune homeostasis and tolerance. Although studies in mice and humans have clearly highlighted that the absence of these cells results in severe autoimmunity and inflammation, increased Treg numbers and/or function is not always beneficial. This is best exemplified in certain cancers where increased Tregs promote cancer progression by interfering with immune surveillance. Conversely, in other types of cancers that have an inflammatory component, Tregs can inhibit cancer progression by dampening inflammation. In this review article, we provide a historical perspective of the discovery of Tregs, followed by a summary of the existing literature on the role of Tregs in malignancy.

Tr1 cells are non-Foxp3-expressing regulatory CD4(+) T cells that execute suppressor functions by secreting the anti-inflammatory cytokine IL-10. Differentiation of this T-cell subset is facilitated by the heterodimeric cytokine IL-27, which can activate transcription factors such as c-Maf and Ahr to positively regulate the differentiation of Tr1 cells and their IL-10 production. In this issue of the European Journal of Immunology, an alternate transcriptional network regulated by IL-27 to induce IL-10 production in Tr1 cells is reported by Iwasaki et al. [Eur. J. Immunol. 2013. 43: 1063-1073]. This study shows that IL-27 initiates tandem activation of the transcription factors STAT3 and Egr-2 to induce il10 in Tr1 cells in a Blimp1-dependent fashion. These findings indicate a c-Maf/Ahr independent mechanism that activates IL-10 production by Tr1 cells and suggest that Il10 induction may depend on both the cytokine environment and the molecular context. Thus, Tr1 cells may be another example of the remarkable plasticity of CD4(+) T cells and indeed may not constitute a separate lineage of CD4(+) T cells but rather represent a developmental endpoint of several T helper cell differentiation pathways.

Streptomyces are a major group of soil bacteria that produce wide range of bioactive compounds including antibiotics. Daunorubicin is a chemotherapeutic agent for treatment of certain types of cancer, which is produced as a secondary metabolite by S. peucetius. Owing to the significance of this drug in treating cancer, understanding the molecular mechanism of its biosynthesis will assist in the genetic manipulation of this strain for better drug yields. Additionally, the knowledge can also be applied to design hybrid antibiotics that can be made in vivo by transferring genes from one Streptomyces species to another. Biosynthesis of daunorubicin in S. peucetius is accomplished by the function of 30 enzyme-coding genes in a sequential and coordinated fashion. In addition to these enzymes, three transcriptional regulators DnrO, DnrN and DnrI regulate this multi-step process by forming a coherent feed forward loop regulatory circuit, consequently controlling the entire enzyme coding genes. Since daunorubicin is a DNA intercalating drug, maintaining an optimal intracellular drug concentration is pivotal to prevent self-toxicity. Commencement of daunorubicin biosynthesis also activates the feedback mechanisms mediated by the metabolite. At exceeding intracellular concentrations, daunorubicin intercalates into DNA sequences and impedes the binding of these transcription factors. This feedback repression is relieved by a group of self-resistance genes, which concurrently efflux the excess intracellular daunorubicin. This review will discuss the mechanistic role of each transcription factor and their interplay in initiating and maintaining the biosynthesis of daunorubicin in S. peucetius.