Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

Can We Really Prevent Suicide?

Every year, suicide is among the top 20 leading causes of death globally for all ages. Unfortunately, suicide is difficult to prevent, in large part because the prevalence of risk factors is high among the general population. In this review, clinical and psychological risk factors are examined and methods for suicide prevention are discussed. Prevention strategies found to be effective in suicide prevention include means restriction, responsible media coverage, and general public education, as well identification methods such as screening, gatekeeper training, and primary care physician education. Although the treatment for preventing suicide is difficult, follow-up that includes pharmacotherapy, psychotherapy, or both may be useful. However, prevention methods cannot be restricted to the individual. Community, social, and policy interventions will also be essentia

Population Genetic Analysis Infers Migration Pathways of Phytophthora ramorum in US Nurseries

Recently introduced, exotic plant pathogens may exhibit low genetic diversity and be limited to clonal reproduction. However, rapidly mutating molecular markers such as microsatellites can reveal genetic variation within these populations and be used to model putative migration patterns. Phytophthora ramorum is the exotic pathogen, discovered in the late 1990s, that is responsible for sudden oak death in California forests and ramorum blight of common ornamentals. The nursery trade has moved this pathogen from source populations on the West Coast to locations across the United States, thus risking introduction to other native forests. We examined the genetic diversity of P. ramorum in United States nurseries by microsatellite genotyping 279 isolates collected from 19 states between 2004 and 2007. Of the three known P. ramorum clonal lineages, the most common and genetically diverse lineage in the sample was NA1. Two eastward migration pathways were revealed in the clustering of NA1 isolates into two groups, one containing isolates from Connecticut, Oregon, and Washington and the other isolates from California and the remaining states. This finding is consistent with trace forward analyses conducted by the US Department of Agriculture's Animal and Plant Health Inspection Service. At the same time, genetic diversities in several states equaled those observed in California, Oregon, and Washington and two-thirds of multilocus genotypes exhibited limited geographic distributions, indicating that mutation was common during or subsequent to migration. Together, these data suggest that migration, rapid mutation, and genetic drift all play a role in structuring the genetic diversity of P. ramorum in US nurseries. This work demonstrates that fast-evolving genetic markers can be used to examine the evolutionary processes acting on recently introduced pathogens and to infer their putative migration patterns, thus showing promise for the application of forensics to plant pathogens

A new accuracy measure based on bounded relative error for time series forecasting

Many accuracy measures have been proposed in the past for time series forecasting comparisons. However, many of these measures suffer from one or more issues such as poor resistance to outliers and scale dependence. In this paper, while summarising commonly used accuracy measures, a special review is made on the symmetric mean absolute percentage error. Moreover, a new accuracy measure called the Unscaled Mean Bounded Relative Absolute Error (UMBRAE), which combines the best features of various alternative measures, is proposed to address the common issues of existing measures. A comparative evaluation on the proposed and related measures has been made with both synthetic and real-world data. The results indicate that the proposed measure, with user selectable benchmark, performs as well as or better than other measures on selected criteria. Though it has been commonly accepted that there is no single best accuracy measure, we suggest that UMBRAE could be a good choice to evaluate forecasting methods, especially for cases where measures based on geometric mean of relative errors, such as the geometric mean relative absolute error, are preferred

Knowledge, Attitudes and Practices (KAP) related to the Pandemic (H1N1) 2009 among Chinese General Population: a Telephone Survey

<p>Abstract</p> <p>Background</p> <p>China is at greatest risk of the Pandemic (H1N1) 2009 due to its huge population and high residential density. The unclear comprehension and negative attitudes towards the emerging infectious disease among general population may lead to unnecessary worry and even panic. The objective of this study was to investigate the Chinese public response to H1N1 pandemic and provide baseline data to develop public education campaigns in response to future outbreaks.</p> <p>Methods</p> <p>A close-ended questionnaire developed by the Chinese Center for Disease Control and Prevention was applied to assess the knowledge, attitudes and practices (KAP) of pandemic (H1N1) 2009 among 10,669 responders recruited from seven urban and two rural areas of China sampled by using the probability proportional to size (PPS) method.</p> <p>Results</p> <p>30.0% respondents were not clear whether food spread H1N1 virusand. 65.7% reported that the pandemic had no impact on their life. The immunization rates of the seasonal flu and H1N1vaccine were 7.5% and 10.8%, respectively. Farmers and those with lower education level were less likely to know the main transmission route (cough or talk face to face). Female and those with college and above education had higher perception of risk and more compliance with preventive behaviors. Relationships between knowledge and risk perception (OR = 1.69; 95%CI 1.54-1.86), and knowledge and practices (OR = 1.57; 95%CI 1.42-1.73) were found among the study subjects. With regard to the behavior of taking up A/H1N1 vaccination, there are several related factors found in the current study population, including the perception of life disturbed (OR = 1.29; 95%CI 1.11-1.50), the safety of A/H1N1 vaccine (OR = 0.07; 95%CI 0.04-0.11), the knowledge of free vaccination policy (OR = 7.20; 95%CI 5.91-8.78), the state's priority vaccination strategy(OR = 1.33; 95%CI 1.08-1.64), and taking up seasonal influenza vaccine behavior (OR = 4.69; 95%CI 3.53-6.23).</p> <p>Conclusions</p> <p>This A/H1N1 epidemic has not caused public panic yet, but the knowledge of A/H1N1 in residents is not optimistic. Public education campaign may take the side effects of vaccine and the knowledge about the state's vaccination strategy into account.</p

Is Cancer survival associated with cancer symptom awareness and barriers to seeking medical help in England? An ecological study

Abstract BACKGROUND: Campaigns aimed at raising cancer awareness and encouraging early presentation have been implemented in England. However, little is known about whether people with low cancer awareness and increased barriers to seeking medical help have worse cancer survival, and whether there is a geographical variation in cancer awareness and barriers in England. METHODS: From population-based surveys (n=35?308), using the Cancer Research UK Cancer Awareness Measure, we calculated the age- and sex-standardised symptom awareness and barriers scores for 52 primary care trusts (PCTs). These measures were evaluated in relation to the sex-, age-, and type of cancer-standardised cancer survival index of the corresponding PCT, from the National Cancer Registry, using linear regression. Breast, lung, and bowel cancer survival were analysed separately. RESULTS: Cancer symptom awareness and barriers scores varied greatly between geographical regions in England, with the worst scores observed in socioeconomically deprived parts of East London. Low cancer awareness score was associated with poor cancer survival at PCT level (estimated slope=1.56, 95% CI: 0.56; 2.57). The barriers score was not associated with overall cancer survival, but it was associated with breast cancer survival (estimated slope=-0.66, 95% CI: -1.20; -0.11). Specific barriers, such as embarrassment and difficulties in arranging transport to the doctor's surgery, were associated with worse breast cancer survival. CONCLUSIONS: Cancer symptom awareness and cancer survival are associated. Campaigns should focus on improving awareness about cancer symptoms, especially in socioeconomically deprived areas. Efforts should be made to alleviate barriers to seeking medical help in women with symptoms of breast cancer.British Journal of Cancer advance online publication 18 August 2016; doi:10.1038/bjc.2016.246 www.bjcancer.com

Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

Aims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In the Lantus plus Metformin (LANMET) study, 110 poorly controlled insulin-naive type 2 diabetic patients were randomised to receive metformin with either insulin glargine (G+MET) or NPH insulin (NPH+MET). In the present study, IGF-I bioactivity was measured, retrospectively, in 104 out of the 110 initially included LANMET participants before and after 36 weeks of insulin therapy. IGF-I bioactivity was measured using an IGF-I kinase receptor activation assay. Results After 36 weeks of insulin therapy, insulin doses were comparable between the G+MET (68±5.7 U/day) and NPH+MET (71±6.2 U/day) groups (p=0.68). Before insulin therapy, circulating IGF-I bioactivity was similar between the G+MET (134±9 pmol/l) and NPH+MET (135 ±10 pmol/l) groups (p=0.83). After 36 weeks, IGF-I bioactivity had decreased significantly (p=0.001) and did not differ between the G+MET (116±9 pmol/l) and NPH+MET (117± 10 pmol/l) groups (p=0.91). At baseline and after insulin therapy, total IGF-I concentrations were comparable in both groups (baseline: G+MET 13.3±1.0 vs NPH+MET 13.3± 1.0 nmol/l, p=0.97; and 36 weeks: 13.4±1.0 vs 13.1± 0.9 nmol/l, p=0.71). Total IGF-I concentration did not change during insulin therapy (13.3±0.7 vs 13.3±0.7 nmol/l, baseline vs 36 weeks, p=0.86). Conclusions/interpretation Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases serum IGF-I bioactivity in a similar manner

Cancer incidence patterns by region and socioeconomic deprivation in teenagers and young adults in England

Data on 35 291 individuals with cancer, aged 13–24 years, in England from 1979 to 2001 were analysed by region and socio-economic deprivation of census ward of residence, as measured by the Townsend deprivation index. The incidence of leukaemia, lymphoma, central nervous system tumours, soft tissue sarcomas, gonadal germ cell tumours, melanoma and carcinomas varied by region (P<0.01, all groups) but bone tumour incidence did not. Lymphomas, central nervous system tumours and gonadal germ cell tumours all had higher incidence in less deprived census wards (P<0.01), while chronic myeloid leukaemia and carcinoma of the cervix had higher incidence in more deprived wards (P<0.01). In the least deprived wards, melanoma incidence was nearly twice that in the most deprived, but this trend varied between regions (P<0.001). These cancer incidence patterns differ from those seen in both children and older adults and have implications for aetiology and prevention

Predictors of colorectal cancer screening in diverse primary care practices

BACKGROUND: To explain why rates of colorectal cancer (CRC) screening including fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), colonoscopy (CS), and barium enema (BE), are low, this study assessed determinants of CRC screening from medical records. METHODS: Data were abstracted from patients aged ≥64 years selected from each clinician from 30 diverse primary care practices (n = 981). Measurements included the rates of annual FOBT, ever receiving FOBT, ever receiving FS/CS/BE under a combination variable, endoscopy/barium enema (EBE). RESULTS: Over five years, 8% had received annual FOBT, 53% had ever received FOBT and 22% had ever received EBE. Annual FOBT was negatively associated with female gender, odds ratio (OR) = .23; 95% confidence interval = .12–.44 and positively associated with routinely receiving influenza vaccine, OR = 2.55 (1.45–4.47); and more office visits: 3 to <5 visits/year, OR = 2.78 (1.41–5.51), and ≥5 visits/year, OR = 3.35 (1.52-7.42). Ever receiving EBE was negatively associated with age ≥75 years, OR = .66 (.46–.95); being widowed, OR = .59 (.38–.92); and positively associated with more office visits: 3 to <5 visits/year, OR = 1.83 (1.18–2.82) and ≥5 visits/year, OR = 2.01 (1.14–3.55). CONCLUSION: Overall CRC screening rates were low, but were related to the number of primary care office visits. FOBT was related to immunization status, suggesting the possible benefit of linking these preventive services