Carnaby Street undressed

Carnaby Street Undressed is a story of fashion, music and eye opening insights into London's Carnaby Street in its 1960s heyday, told by the owners of the fashion shops that defined the iconic Street, and the popular musicians who were part of the “the scene”. This includes The Who lead sing Roger Daltrey, Donovan, Frank Allen from the Searchers, Gary Leeds from The Walker Brothers, and Peter Noone from Herman’s Hermits. The film is the story of a generation that rebelled against the grey conformity of the 1950s with a cultural revolution emanating from Carnaby Street from where it spread across the globe changing fashion and music forever. This a story about a street of firsts: the first time music was played in a shop, the first time men and women's clothes were sold in the same shop, the first time there was fashion for children, the first time the national flag was used as a fashion item, and the first time clothes had colour - lots of bright colours. The film reveals the cultural, philosophical and practical background and responses to these innovations.

Converting Mrs Crouch: women, wonders and the formation of English methodism, 1738-1741

This article examines the development of English Methodism during the formative period between 1738 and 1741, focusing upon the experiences of women, who made up the majority of Methodists both at this time and through much of the movement’s history. In particular, the role that women and questions of gender played in the conflict between the Wesley brothers and the Moravian leadership in London is considered. Using accounts written by the male leaders of both groups and the women who supported them, it is argued that women’s choices determined the outcome of this early battle, shaping the nascent movement in crucial ways.

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research.

Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways. Secondly, although mild inflammatory responses are present in depression, other immune-related pathways cannot be disregarded as new drug targets, e.g., activation of cell-mediated immunity, oxidative and nitrosative stress (O&NS) pathways, autoimmune responses, bacterial translocation, and activation of the toll-like receptor and neuroprogressive pathways. Thirdly, anti-inflammatory treatments are sometimes used without full understanding of their effects on the broader pathways underpinning depression. Since many of the activated immune-inflammatory pathways in depression actually confer protection against an overzealous inflammatory response, targeting these pathways may result in unpredictable and unwanted results. Furthermore, this paper discusses the required improvements in research strategy, i.e., path and drug discovery processes, omics-based techniques, and systems biomedicine methodologies. Firstly, novel methods should be employed to examine the intracellular networks that control and modulate the immune, O&NS and neuroprogressive pathways using omics-based assays, including genomics, transcriptomics, proteomics, metabolomics, epigenomics, immunoproteomics and metagenomics. Secondly, systems biomedicine analyses are essential to unravel the complex interactions between these cellular networks, pathways, and the multifactorial trigger factors and to delineate new drug targets in the cellular networks or pathways. Drug discovery processes should delineate new drugs targeting the intracellular networks and immune-related pathways.

The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases

Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

The putative role of viruses, bacteria, and chronic fungal biotoxin exposure in the genesis of intractable fatigue accompanied by cognitive and physical disability

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

Functionalism, co-operation, good faith, and the making of the "daily-preventive justice" in contract law theory and practice. A contribution to a rational understanding of good faith and to its future reseasonable developments. Evaluations from

The thoughts and observations contained in this paper were first presented in a preliminary form at the Staff Seminar that I gave at the University of Cape Town (UCT) - Department of Private Law, on Tuesday May 8 2012. The organizers generously offered me a free choice of subject. Such an offer always poses a problem to imaginative people like myself. I finally chose as my subject the role of good faith in contract law theory and practice and then entitled the Seminar “Good Faith & Contracts - Brothers in Arms”. The aim of the talk was to briefly describe what I see behind the doctrine of good faith (and, more broadly, behind the general course of the parties’ behavior before and after the conclusion of an agreement), to then explain the need of its protection and future reasonable developments by challenging the limitations of both traditional and current legal approaches to contract law theory and practice. By adopting a comparative modus investigandi, it emerged that especially in the area of contract law a new law-finding process is emerging in the European continent and it is leading to re-conceive the meta-national legislative interventions by challenging the limits of Hobbes’s Leviathan. As asserted, we ought to not take this process for granted because although there are many forms of social organization, contract is the most pervasive and the law of contract still is the most important vehicle to support and supplement private arrangements. However, the point of departure for theorizing about private law is based on experience. Consequently, despite the growing emphasis on the convergence of national legal systems in Europe, conducting research on private law theory and practice requires that imagination and creativity be matched with prudence. Proficiency has to be aligned with what we have learned from history.

Effect of lactoferrin protein on red blood cells and macrophages: mechanism of parasite-host interaction

BACKGROUND: Lactoferrin is a natural multifunctional protein known to have antitumor, antimicrobial, and anti-inflammatory activity. Apart from its antimicrobial effects, lactoferrin is known to boost the immune response by enhancing antioxidants. Lactoferrin exists in various forms depending on its iron saturation. The present study was done to observe the effect of lactoferrin, isolated from bovine and buffalo colostrum, on red blood cells (RBCs) and macrophages (human monocytic cell line-derived macrophages THP1 cells). METHODS: Lactoferrin obtained from both species and in different iron saturation forms were used in the present study, and treatment of host cells were given with different forms of lactoferrin at different concentrations. These treated host cells were used for various studies, including morphometric analysis, viability by MTT assay, survivin gene expression, production of reactive oxygen species, phagocytic properties, invasion assay, and Toll-like receptor-4, Toll-like receptor-9, and MDR1 expression, to investigate the interaction between lactoferrin and host cells and the possible mechanism of action with regard to parasitic infections. RESULTS: The mechanism of interaction between host cells and lactoferrin have shown various aspects of gene expression and cellular activity depending on the degree of iron saturation of lactoferrin. A significant increase (P<0.05) in production of reactive oxygen species, phagocytic activity, and Toll-like receptor expression was observed in host cells incubated with iron-saturated lactoferrin when compared with an untreated control group. However, there was no significant (P>0.05) change in percentage viability in the different groups of host cells treated, and no downregulation of survivin gene expression was found at 48 hours post-incubation. Upregulation of the Toll-like receptor and downregulation of the P-gp gene confirmed the immunomodulatory potential of lactoferrin protein. CONCLUSION: The present study details the interaction between lactoferrin and parasite host cells, ie, RBCs and macrophages, using various cellular processes and expression studies. The study reveals the possible mechanism of action against various intracellular pathogens such as Toxoplasma, Plasmodium, Leishmania, Trypanosoma, and Mycobacterium. The presence of iron in lactoferrin plays an important role in enhancing the various activities taking place inside these cells. This work provides a lot of information about targeting lactoferrin against many parasitic infections which can rule out the exact pathways for inhibition of diseases caused by intracellular microbes mainly targeting RBCs and macrophages for their survival. Therefore, this initial study can serve as a baseline for further evaluation of the mechanism of action of lactoferrin against parasitic diseases, which is not fully understood to date.

Suicidal ideation reported by adults with type 1 or type 2 diabetes: results from Diabetes MILES-Australia

AIMS: To examine the prevalence and correlates of suicidal ideation in a community-based sample of adults with Type 1 or Type 2 diabetes.

METHODS: Participants were 3338 adults aged 18-70 years with Type 1 diabetes (n=1376) or Type 2 diabetes (non-insulin: n=1238; insulin: n=724) from a national survey administered to a random sample registered with the National Diabetes Services Scheme. Depression and suicidal ideation were assessed using the Patient Health Questionnaire, and diabetes-specific distress with the Problem Areas In Diabetes scale. Separate logistic regression analyses by diabetes type/treatment were used to determine relative contribution to suicidal ideation.

RESULTS: Overall, we observed a suicidal ideation rate of 14% in our sample. Participants with Type 2 diabetes using insulin reported more frequent depressive symptoms, and were more likely to report recent suicidal ideation (19%) compared with those with either Type 1 diabetes or Type 2 diabetes not using insulin (14 and 12%, respectively). After controlling for depression, there was little difference in the prevalence of suicidal ideation between diabetes types/treatments, but higher diabetes-specific distress significantly increased the odds of suicidal ideation.

CONCLUSIONS: As suicidal ideation is a significant risk factor for a suicide attempt, the findings have implications for healthcare professionals, pointing to the importance of adequate screening and action plans for appropriate follow-up of those reporting depression. Our findings are also indicative of the psychological toll of diabetes more generally, and the need to integrate physical and mental healthcare for people with diabetes. This article is protected by copyright. All rights reserved.