Are Risk Factors Associated with Outcomes in Pancreatic Cancer?

Background

The development of pancreatic cancer is a process in which genes interact with environmental factors. We performed this study to determine the effects of the ABO blood group, obesity, diabetes mellitus, metabolic syndrome (MetS), smoking, alcohol consumption and hepatitis B viral (HBV) infection on patient survival.

Methods

A total of 488 patients with pancreatic cancer were evaluated.

Result

Patients who presented as chronic carriers of HBV infection were younger at disease onset (p = 0.001) and more predominantly male (p = 0.020) than those never exposed to HBV. Patients with MetS had later disease staging (p = 0.000) and a lower degree of pathological differentiation (p = 0.008) than those without MetS. In a univariate analysis, the ABO blood group, smoking and alcohol consumption were not associated with overall survival. HBsAg–positivity and elevated fasting plasma glucose were significantly associated with unfavorable survival though not in the multivariate analysis. The presence of MetS (HR: 1.541, 95% CI: 1.095–2.169, p = 0.013), age ≥65, an elevated CA19–9 baseline level, TNM staging, the type of surgery, the degree of differentiation and chemotherapy were independently associated with overall survival.

Conclusion

We report, for the first time, that patients with chronic HBV infection may represent a special subtype of pancreatic cancer, who have a younger age of disease onset and male dominancy. Patients with MetS had later disease staging and a poorer histological grade. Patients with MetS demonstrated significantly poorer survival.     

Patients with Primary Immunodeficiencies: How Are They at Risk for Fungal Disease?

Purpose of Review

In this review, we focus on the inborn errors of immunity known to render the host susceptible to fungal infections, including candidias, aspergillosis, dermatophytosis, phaeohyphomycosis, pneumocystosis, fusariosis, cryptococcosis, and endemic mycoses.

Recent Findings

Classically, the burden of fungal disease in humans is believed to be carried by patients with a secondary immunodeficiency, either due to malignancy, to chemotherapy, to an immunocompromised state post hematopoietic stem cell transplantation, or to treatment with anti-cytokine therapies. However, in the last decade, the study of patients affected by fungal infections without any overt risk factors has led to the unraveling of several monogenic defects of human immunity to fungi. The study of these inborn errors of immunity has added vastly to our comprehension of antifungal immunity. For example, the role of IL-17 immunity in human defense against mucocutaneous candidiasis has been extensively characterized through the analysis of IL-17F, IL-17RA, IL-17Rc, ACT1, RORγT and, indirectly, CARD9 deficiency.

Summary

Many monogenic causes of susceptibility to superficial and/or invasive fungal infections have been recently unraveled. Most of these inborn errors of immunity associate with a specific type of fungal infection, and such a defect should always be suspected and sought in patients affected by fungal infection in the absence of predisposing factors.

     

Does the Fractionalization of Daily Physical Activity (Sporadic vs. Bouts) Impact Cardiometabolic Risk Factors in Children and Youth?

Objective

Children and youth accumulate their daily moderate-to-vigorous physical activity (MVPA) in bouts (i.e., ≥5 consecutive minutes) and in a sporadic manner (i.e., <5 consecutive minutes). The study objective was to determine, within children and youth, whether MVPA accumulated in bouts is more strongly associated with cardiometabolic risk factors than an equivalent volume of MVPA accumulated sporadically.

Methods

Participants consisted of 2754 children and youth aged 6–19 years from the 2003–2006 National Health and Nutrition Examination Survey, a representative cross-sectional study. Bouts and sporadic MVPA were measured objectively over 7 days using Actigraph accelerometers. Thresholds of 5 and 10 consecutive minutes were used to differentiate between bouts and sporadic MVPA. A high cardiometabolic risk factor score (CRS) was created based on measures of waist circumference, non-high-density lipoprotein cholesterol, C-reactive protein, and systolic blood pressure. Associations were examined using logistic regression and controlled for covariates (sex, age, ethnicity, socioeconomic status, dietary fat and sodium, smoking, and accelerometry wear time).

Results

The odds of a high CRS decreased in a dose-response for both the sporadic and bout MVPA measures. Relative to quartile 1, the odds ratio (95% confidence interval) for a high CRS in quartile 4 was 0.25 (0.10–0.60) for sporadic MVPA, 0.17 (0.09–0.34) for ≥5 minute bouts of MVPA, and 0.19 (0.11–0.34) for ≥10 minute bouts of MVPA. The sporadic and bout MVPA measures had a similar ability to distinguish between participants with high and normal CRS. Relative to 0 minutes of MVPA, an equivalent number of minutes of sporadic MVPA and bouts of MVPA had an almost identical odds ratio for a high CRS. The findings were consistent for 5 and 10 minute bout thresholds.

Conclusions

The relations between sporadic MVPA and bouts of MVPA with cardiometabolic risk factors were remarkably similar in children and youth.     

Are Current UK National Institute for Health and Clinical Excellence (NICE) Obesity Risk Guidelines Useful? Cross-Sectional Associations with Cardiovascular Disease Risk Factors in a Large,Representative English Population

The National Institute for Health and Clinical Excellence (NICE) has recently released obesity guidelines for health risk. For the first time in the UK, we estimate the utility of these guidelines by relating them to the established cardiovascular disease (CVD) risk factors. Health Survey for England (HSE) 2006, a population-based cross-sectional study in England was used with a sample size of 7225 men and women aged ≥35 years (age range: 35–97 years). The following CVD risk factor outcomes were used: hypertension, diabetes, total and high density lipoprotein cholesterol, glycated haemoglobin, fibrinogen, C-reactive protein and Framingham risk score. Four NICE categories of obesity were created based on body mass index (BMI) and waist circumference (WC): no risk (up to normal BMI and low/high WC); increased risk (normal BMI & very high WC, or obese & low WC); high risk (overweight & very high WC, or obese & high WC); and very high risk (obese I & very high WC or obese II/III with any levels of WC. Men and women in the very high risk category had the highest odds ratios (OR) of having unfavourable CVD risk factors compared to those in the no risk category. For example, the OR of having hypertension for those in the very high risk category of the NICE obesity groupings was 2.57 (95% confidence interval 2.06 to 3.21) in men, and 2.15 (1.75 to 2.64) in women. Moreover, a dose-response association between the adiposity groups and most of the CVD risk factors was observed except total cholesterol in men and low HDL in women. Similar results were apparent when the Framingham risk score was the outcome of interest. In conclusion, the current NICE definitions of obesity show utility for a range of CVD risk factors and CVD risk in both men and women.     

Fasting Glucose Levels Correlate with Disease Severity of Guillain-Barré Syndrome

Objective

A potential association between diabetes and Guillain-Barré syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS.

Methods

Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG.

Results

The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge.

Conclusions

Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS.     

How Can Inequalities in Mortality Be Reduced? A Quantitative Analysis of 6 Risk Factors in 21 European Populations

Background

Socioeconomic inequalities in mortality are one of the greatest challenges for health policy in all European countries, but the potential for reducing these inequalities is unclear. We therefore quantified the impact of equalizing the distribution of six risk factors for mortality: smoking, overweight, lack of physical exercise, lack of social participation, low income, and economic inactivity.

Methods

We collected and harmonized data on mortality and risk factors by educational level for 21 European populations in the early 2000s. The impact of the risk factors on mortality in each educational group was determined using Population Attributable Fractions. We estimated the impact on inequalities in mortality of two scenarios: a theoretical upward levelling scenario in which inequalities in the risk factor were completely eliminated, and a more realistic best practice scenario, in which inequalities in the risk factor were reduced to those seen in the country with the smallest inequalities for that risk factor.

Findings

In general, upward levelling of inequalities in smoking, low income and economic inactivity hold the greatest potential for reducing inequalities in mortality. While the importance of low income is similar across Europe, smoking is more important in the North and East, and overweight in the South. On the basis of best practice scenarios the potential for reducing inequalities in mortality is often smaller, but still substantial in many countries for smoking and physical inactivity.

Interpretation

Theoretically, there is a great potential for reducing inequalities in mortality in most European countries, for example by equity-oriented tobacco control policies, income redistribution and employment policies. Although it is necessary to achieve substantial degrees of upward levelling to make a notable difference for inequalities in mortality, the existence of best practice countries with more favourable distributions for some of these risk factors suggests that this is feasible.     

β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors

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How Are Physical Activity Behaviors and Cardiovascular Risk Factors Associated with Characteristics of the Built and Social Residential Environment?

Background

The aim of our study was to identify perceptions of built and social residential characteristics and their association with behaviors such as physical activity (PA), nutrition and smoking and with cardiovascular risk factors (elevated BMI and fasting blood glucose).

Methods

Among participants of a preventive medical checkup at an Austrian District Health Insurance Fund (n=904, response rate = 82.2%, 42% women, 18-91 years) self-reported and measured data were collected.

Results

Total PA was positively associated with the presence of trees along the streets and high levels of pro-physical activity social modeling (SM) and it was negatively related to perceived safety from crime. More leisure-time PA was associated with higher levels of cycling/walking infrastructure and high levels of SM. PA for transportation was positively related to high levels of connectivity and high levels of SM. Better behavioral cardiovascular risk factor profiles (smoking and nutrition) were associated with high levels of SM and high levels of total PA. Lower BMI values were associated with high levels of infrastructure and high levels of SM.

Conclusions

Both built and social residential characteristics are important correlates of PA as well as of major cardiovascular risk factors besides PA.     

Membrane traffic: How do GGAs fit in with the adaptors?

The AP-1 adaptor complex has been cast as the major player in clathrin coat formation for vesicular transport from the trans-Golgi to the endocytic pathway. But new results on 'GGA' proteins have raised doubts about this paradigm and suggest both a new sorting mechanism and an unexpected complexity in the roles of clathrin.     

Secular Trends in Prevalence and Risk Factors of Obesity in Infants and Preschool Children in 9 Chinese Cities, 1986–2006

Introduction

No prevalence/trends were reported in Chinese infants and preschool children at the national level in this historical period of 1980s–2000s. The objectives of this paper were to present the 20-year trends in prevalence and risk factors of obesity in children below 7 years.

Methods

Data obtained from a series of three sequential national surveys performed using the same design in the same 9 cities in 1986, 1996 and 2006. Weight and height (length <3 years) were measured using unified procedures at each period. Obesity was defined as a weight-for-height ≥120% of median of the NCHS/WHO international reference. A population-based paired matching case-control study was employed for screening risk factors.

Results

In 1986, there was no substantial obesity epidemic, but the overall obesity prevalence reached 3.4% (boys 4.1% and girls 2.7%) in 2006, rising by 2.8 times between 1986 and 2006. Reversed gender difference, relatively higher prevalence in preschool age and more rapid increase in the second 10-year were three very obvious characteristics in China, e.g. prevalence of boys 9.9% and girls 4.9% in 2006 and increasing rate of boys 0.45 percentage points per year (pp/y) and girls 0.21 pp/y at 6–7 years groups, 0.17 pp/y of the second 10-year higher 1-fold than previous.

Conclusions

China has been moving into the alarming epidemic of childhood obesity. Effort should be immediately made to prevent further deterioration. High birth weight, high parental BMI and several behavioral and family-related factors were identified and had important practical value for obesity intervention.     

Are Genetic Risk Factors for Psychosis Also Associated with Dimension-Specific Psychotic Experiences in Adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴) and rs9960767 (p-value = 6.23×10⁻⁴). Replication in an independent sample of 16-year-olds (N = 3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed.     

Calibration of Optical Tweezers for In?Vivo Force Measurements: How do Different Approaches Compare?

There is significant interest in quantifying force production inside cells, but since conditions in vivo are less well controlled than those in vitro, in vivo measurements are challenging. In particular, the in vivo environment may vary locally as far as its optical properties, and the organelles manipulated by the optical trap frequently vary in size and shape. Several methods have been proposed to overcome these difficulties. We evaluate the relative merits of these methods and directly compare two of them, a refractive index matching method, and a light-momentum-change method. Since in vivo forces are frequently relatively high (e.g., can exceed 15 pN for lipid droplets), a high-power laser is employed. We discover that this high-powered trap induces local temperature changes, and we develop an approach to compensate for uncertainties in the magnitude of applied force due to such temperature variations.     

Tramped Teats – Clinical Mastitis Disease Complex in Tied Cows. Environmental Risk Factors and Interrelationships with Other Diseases

The effects of stall length, manure system, type of bedding and calving disorders on incidence rates of tramped teats, udder injuries, and clinical mastitis in Swedish Red and White tied cows, as well as interrelationships between these 3 disorders were investigated. Data used consisted of 370 herds, for a total of 45,133 cow records. Cows in herds with liquid manure system were at hihger risk of udder injuries and mastitis than in herds with solid system. Lower risk of both udder injuries and mastitis was found for cows in herds with short stall size (< 180 cm) compared to herds with stalls of 205–219 cm length. It was suggested that other factors, such as slipperiness of the stall floor and presence and type of feeding barrier, must be considered when the effect of stall characteristics on tramped teats is investigated. In farms with solid manure system cut straw or sawdust bedding increased the risk of tramped teats and mastitis relative to uncut straw. Parity and calving disorders were important risk factors for udder health and their effect was greater in herds with liquid manure system. Tramped teats and udder injuries were the most serious risk factors for clinical mastitis.     

Emergence of Coxiella burnetii in Ruminants on Reunion Island? Prevalence and Risk Factors

Q fever is a widespread zoonosis that is caused by Coxiella burnetii (C. burnetii), and ruminants are identified as the main sources of human infections. Some human cases have been described, but very limited information was available about Q fever in ruminants on Reunion Island, a tropical island in the Indian Ocean. A cross-sectional study was undertaken from March 2011 to August 2012 to assess the Q fever prevalence and to identify the major risk factors of C. burnetii infection in ruminants. A total of 516 ruminants (245 cattle, 137 sheep and 134 goats) belonging to 71 farms and localized in different ecosystems of the island were randomly selected. Samples of blood, vaginal mucus and milk were concomitantly collected from females, and a questionnaire was submitted to the farmers. Ticks from positively detected farms were also collected. The overall seropositivity was 11.8% in cattle, 1.4% in sheep and 13.4% in goats. C. burnetii DNA was detected by PCR in 0.81%, 4.4% and 20.1% in cow, sheep and goat vaginal swabs, respectively. C. burnetii shedding in milk was observed in 1% of cows, 0% in sheep and 4.7% in goats. None of the ticks were detected to be positive for C. burnetii. C. burnetii infection increased when the farm was exposed to prevailing winds and when there were no specific precautions for a visitor before entering the farm, and they decreased when a proper quarantine was set up for any introduction of a new ruminant and when the animals returned to the farm at night. MLVA genotyping confirmed the role of these risk factors in infection.     

Early-Life Factors and Risk of Parkinson’s Disease: A Register-Based Cohort Study

Parkinson’s disease (PD) may take decades to develop and early life exposures such as infection may be important. However, few epidemiological studies have evaluated early life risk factors in relation to PD risk. We therefore examined such associations in a prospective analysis of 3 545 612 individuals born in Sweden between 1932 and 1970 without PD on January 1, 2002. Incident PD cases were identified using the Swedish Patient Register during 2002–2010. Information on sibship size, number of older and younger siblings, multiple births, parental age, birth month and season was obtained from the Swedish Multi-Generation Register. Monthly data on national burden of influenza-like illness during 1932–1970 were obtained from the Swedish Public Health Agency. Hazard ratios with 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. During the follow-up, 8779 incident PD cases were identified. As expected, older age, male sex, parental occupation as farmers, and family history of PD were associated with higher PD risk. Overall, early life factors, including flu burden in the year of birth, were not associated with PD risk, although we did find a lower PD risk among participants with older siblings than those without (HR = 0.93, 95%CI: 0.89, 0.98). Our study therefore provided little support for important etiological contributions of early life factors to the PD risk late in life. The finding of a lower PD risk among individuals with older siblings will need confirmation and further investigation.     

How do oomycete effectors interfere with plant life?

Oomycete genomes have yielded a large number of predicted effector proteins that collectively interfere with plant life in order to create a favourable environment for pathogen infection. Oomycetes secrete effectors that can be active in the host's extracellular environment, for example inhibiting host defence enzymes, or inside host cells where they can interfere with plant processes, in particular suppression of defence. Two classes of effectors are known to be host-translocated: the RXLRs and Crinklers. Many effectors show defence-suppressive activity that is important for pathogen virulence. A striking example is AVR3a of Phytophthora infestans that targets an ubiquitin ligase, the stabilisation of which may prevent host cell death. The quest for other effector targets and mechanisms is in full swing.     

How do predators cope with chemically defended foods?

Many prey species (including plants) deter predators with defensive chemicals. These defensive chemicals act by rendering the prey's tissues noxious, toxic, or both. Here, I explore how predators cope with the presence of these chemicals in their diet. First, I describe the chemosensory mechanisms by which predators (including herbivores) detect defensive chemicals. Second, I review the mechanisms by which predators either avoid or tolerate defensive chemicals in prey. Third, I examine how effectively free-ranging predators can overcome the chemical defenses of prey. The available evidence indicates that predators have mixed success overcoming these defenses. This conclusion is based on reports of free-ranging predators rejecting unpalatable but harmless prey, or voluntarily ingesting toxic prey.