Use of complementary and alternative medicine by those with a chronic disease and the general population - results of a national population based survey

<p>Abstract</p> <p>Background</p> <p>The use of complementary and alternative medicine (CAM) is becoming more common, but population-based descriptions of its patterns of use are lacking. This study aimed to determine the prevalence of CAM use in the general population and for those with asthma, diabetes, epilepsy and migraine.</p> <p>Methods</p> <p>Data from cycles 1.1, 2.1 and 3.1 of the Canadian Community Health Survey (CCHS) were used for the study. The CCHS is a national cross-sectional survey administered to 400,055 Canadians aged ≥12 between 2001-2005. Self-reported information about professionally diagnosed health conditions was elicited. CCHS surveys use a multistage stratified cluster design to randomly select a representative sample of Canadian household residents. Descriptive data on the utilization of CAM services was calculated and logistic regression was used to determine what sociodemographic factors predict CAM use.</p> <p>Results</p> <p>Weighted estimates show that 12.4% (95% Confidence Interval (CI): 12.2-12.5) of Canadians visited a CAM practitioner in the year they were surveyed; this rate was significantly higher for those with asthma 15.1% (95% CI: 14.5-15.7) and migraine 19.0% (95% CI: 18.4-19.6), and significantly lower for those with diabetes 8.0% (95% CI: 7.4-8.6) while the rate in those with epilepsy (10.3%, 95% CI: 8.4-12.2) was not significantly different from the general population.</p> <p>Conclusion</p> <p>A large proportion of Canadians use CAM services. Physicians should be aware that their patients may be accessing other services and should be prepared to ask and answer questions about the risks and benefits of CAM services in conjunction with standard medical care.</p

Improving early childhood care and development, HIV testing, treatment and support, and nutrition in Mokhotlong, Lesotho: study protocol for a cluster randomized controlled trial

Background Since 1990, the lives of 48 million children under the age of 5 have been saved because of increased investments in reducing child mortality. However, despite these unprecedented gains, more than 200 million children in low and middle income countries (LMIC) cannot meet their developmental potential due to poverty, poor health and nutrition, and lack of necessary stimulation and care. Lesotho has high levels of poverty, HIV and malnutrition, all of which affect child development outcomes. There is a unique opportunity to address these complex issues through the widespread network of informal preschools in rural villages in the country, which provide a setting for inclusive, integrated Early Childhood Care and Development (ECCD), HIV and nutrition interventions. Methods We are conducting a cluster randomised controlled trial in Mokhotlong district, Lesotho, to evaluate a newly developed community-based intervention programme to integrate HIV testing and treatment services, ECCD, and nutrition education for caregivers with children aged 1-5 years living in rural villages. Caregivers and their children are randomly assigned by village to intervention or control condition. We select, train, and supervise community health workers recruited to implement the intervention, which consists of nine group-based sessions with caregivers and children over 12 weeks (eight weekly sessions, and a ninth top up session one month later), followed by a locally hosted community health outreach day event. Group-based sessions focus on using early dialogic booksharing to promote cognitive development and caregiver-child interaction, health-related messages, including motivation for HIV-testing and treatment uptake for young children, and locally appropriate nutrition education. All children aged 1-5 years and their primary caregivers living in study villages are eligible for participation. Caregivers and their children will be interviewed and assessed at baseline, immediately after completion of the intervention, and 12 months post intervention. Discussion This study provides a unique opportunity to assess the potential of an integrated early childhood development intervention to prevent or mitigate developmental delays in children living in a context of extreme poverty and high HIV rates in rural Lesotho. This paper presents the intervention content and research protocol for the study

Generation of human vascular smooth muscle subtypes provides insight into embryological origin-dependent disease susceptibility.

Heterogeneity of embryological origins is a hallmark of vascular smooth muscle cells (SMCs) and may influence the development of vascular disease. Differentiation of human pluripotent stem cells (hPSCs) into developmental origin-specific SMC subtypes remains elusive. Here we describe a chemically defined protocol in which hPSCs were initially induced to form neuroectoderm, lateral plate mesoderm or paraxial mesoderm. These intermediate populations were further differentiated toward SMCs (>80% MYH11(+) and ACTA2(+)), which displayed contractile ability in response to vasoconstrictors and invested perivascular regions in vivo. Derived SMC subtypes recapitulated the unique proliferative and secretory responses to cytokines previously documented in studies using aortic SMCs of distinct origins. Notably, this system predicted increased extracellular matrix degradation by SMCs derived from lateral plate mesoderm, which was confirmed using rat aortic SMCs from corresponding origins. This differentiation approach will have broad applications in modeling origin-dependent disease susceptibility and in developing bioengineered vascular grafts for regenerative medicine

Role of Sphingomyelin Synthase in Controlling the Antimicrobial Activity of Neutrophils against Cryptococcus neoformans

The key host cellular pathway(s) necessary to control the infection caused by inhalation of the environmental fungal pathogen Cryptococcus neoformans are still largely unknown. Here we have identified that the sphingolipid pathway in neutrophils is required for them to exert their killing activity on the fungus. In particular, using both pharmacological and genetic approaches, we show that inhibition of sphingomyelin synthase (SMS) activity profoundly impairs the killing ability of neutrophils by preventing the extracellular release of an antifungal factor(s). We next found that inhibition of protein kinase D (PKD), which controls vesicular sorting and secretion and is regulated by diacylglycerol (DAG) produced by SMS, totally blocks the extracellular killing activity of neutrophils against C. neoformans. The expression of SMS genes, SMS activity and the levels of the lipids regulated by SMS (namely sphingomyelin (SM) and DAG) are up-regulated during neutrophil differentiation. Finally, tissue imaging of lungs infected with C. neoformans using matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS), revealed that specific SM species are associated with neutrophil infiltration at the site of the infection. This study establishes a key role for SMS in the regulation of the killing activity of neutrophils against C. neoformans through a DAG-PKD dependent mechanism, and provides, for the first time, new insights into the protective role of host sphingolipids against a fungal infection

Increased Membrane Cholesterol in Lymphocytes Diverts T-Cells toward an Inflammatory Response

Cell signaling for T-cell growth, differentiation, and apoptosis is initiated in the cholesterol-rich microdomains of the plasma membrane known as lipid rafts. Herein, we investigated whether enrichment of membrane cholesterol in lipid rafts affects antigen-specific CD4 T-helper cell functions. Enrichment of membrane cholesterol by 40–50% following squalene administration in mice was paralleled by an increased number of resting CD4 T helper cells in periphery. We also observed sensitization of the Th1 differentiation machinery through co-localization of IL-2Rα, IL-4Rα, and IL-12Rβ2 subunits with GM1 positive lipid rafts, and increased STAT-4 and STAT-5 phosphorylation following membrane cholesterol enrichment. Antigen stimulation or CD3/CD28 polyclonal stimulation of membrane cholesterol-enriched, resting CD4 T-cells followed a path of Th1 differentiation, which was more vigorous in the presence of increased IL-12 secretion by APCs enriched in membrane cholesterol. Enrichment of membrane cholesterol in antigen-specific, autoimmune Th1 cells fostered their organ-specific reactivity, as confirmed in an autoimmune mouse model for diabetes. However, membrane cholesterol enrichment in CD4+ Foxp3+ T-reg cells did not alter their suppressogenic function. These findings revealed a differential regulatory effect of membrane cholesterol on the function of CD4 T-cell subsets. This first suggests that membrane cholesterol could be a new therapeutic target to modulate the immune functions, and second that increased membrane cholesterol in various physiopathological conditions may bias the immune system toward an inflammatory Th1 type response

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior

Evolutionary Hypotheses and Moral Skepticism

Proponents of evolutionary debunking arguments aim to show that certain genealogical explanations of our moral faculties, if true, undermine our claim to moral knowledge. Criticisms of these arguments generally take the debunker’s genealogical explanation for granted. The task of the anti-debunker is thought to be that of reconciling the (supposed) truth of this hypothesis with moral knowledge. In this paper, I shift the critical focus instead to the debunker’s empirical hypothesis and argue that the skeptical strength of an evolutionary debunking argument is dependent upon the evidence for that hypothesis—evidence which, upon further inspection, proves far from compelling. Following that, however, I suggest that the same considerations which spell trouble for the empirical hypotheses of traditional debunking arguments can also be taken to give rise to an alternative—and better supported—style of debunking argument

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Increased expression of the Hutchinson–Gilford progeria syndrome truncated lamin A transcript during cell aging

Most cases of the segmental progeroid syndrome, Hutchinson–Gilford progeria syndrome (HGPS), are caused by a de novo dominant mutation within a single codon of the LMNA gene. This mutation leads to the increased usage of an internal splice site that generates an alternative lamin A transcript with an internal deletion of 150 nucleotides, called lamin AΔ150. The LMNA gene encodes two major proteins of the inner nuclear lamina, lamins A and C, but not much is known about their expression levels. Determination of the overall expression levels of the LMNA gene transcripts is an important step to further the understanding of the HGPS. In this study, we have performed absolute quantification of the lamins A, C and AΔ150 transcripts in primary dermal fibroblasts from HGPS patients and unaffected age-matched and parent controls. We show that the lamin AΔ150 transcript is present in unaffected controls but its expression is >160-fold lower than that in samples from HGPS patients. Analysis of transcript expression during in vitro aging shows that although the levels of lamin A and lamin C transcripts remain unchanged, the lamin AΔ150 transcript increases in late passage cells from HGPS patients and parental controls. This study provides a new method for LMNA transcript analysis and insights into the expression of the LMNA gene in HGPS and normal cells