Induction and suppression of antiviral RNA silencing by Tomato spotted wilt virus

RNA silencing is an essential antiviral defense system in plants. Triggered by doublestranded RNA, silencing results in degradation or translational repression of target RNA. Viruses are inducers and targets of RNA silencing. To condition susceptibility, most plant viruses encode silencing suppressor proteins that interfere with RNA silencing. Tomato spotted wilt virus (TSWV) NSs protein is an RNA silencing suppressor. The mechanism of RNA silencing suppression by NSs and its role in virus infection and movement remain to be determined. We cloned NSs from the Hawaii isolate of TSWV. Using two independent assays, we show that NSs restored pathogenicity and supported the formation of local infection foci by suppressor-deficient Turnip mosaic virus (TuMV) and Turnip crinkle virus (TCV). Suppression of silencing directed against heterologous viruses establishes the foundation to determine the mechanism of antiviral RNA silencing suppression by NSs

Evaluation of a training program for general ultrasound screening for developmental dysplasia of the hip in preventive child health care

Background: A research study in the Netherlands showed that general ultrasound (US) screening was cost-effective in the detection of developmental dysplasia of the hip (DDH). This study was followed by a pilot implementation study. Part of this pilot implementation study is to investigate whether professionals of the infant health care (IHC) system, with no previous US experience, would be able to perform US of the hip. Objective: This study looks at health care worker ability to classify US images into a modified Graf system. Materials and methods: After theoretical and practical training, seven nurses and physicians of the participating IHC centers reported their findings on sonographic images of 80 children. This was repeated five months later. From the two evaluation moments the intraobserver agreement and the interobserver agreement was determined. Results: The average estimated interobserver Cohen’s kappa for both sessions was for nurses 0.6 and for physicians 0.5. The second evaluation showed a decrease from an average of 4.3% missed cases per screener to 2.3% and an increase of an average of 5% false positives per screener to 9.1%. Conclusion: The inter- and intra-observer agreement is comparable to similar studies in which the participants had a professional background in US examination. The level of agreement of the trainees in the perspective of the screening process was considered sufficient for the pilot implementation project

Trade-offs between morphology and thermal niches mediate adaptation in response to competing selective pressures

The effects of climate change—such as increased temperature variability and novel predators—rarely happen in isolation, but it is unclear how organisms cope with mul- tiple stressors simultaneously. To explore this, we grew replicate Paramecium caudatum populations in either constant or variable temperatures and exposed half to predation. We then fit thermal performance curves (TPCs) of intrinsic growth rate (rmax) for each replicate population (N = 12) across seven temperatures (10°C–38°C). TPCs of P. caudatum exposed to both temperature variability and predation re- sponded only to one or the other (but not both), resulting in unpredictable outcomes. These changes in TPCs were accompanied by changes in cell morphology. Although cell volume was conserved across treatments, cells became narrower in response to temperature variability and rounder in response to predation. Our findings sug- gest that predation and temperature variability produce conflicting pressures on both thermal performance and cell morphology. Lastly, we found a strong correlation between changes in cell morphology and TPC parameters in response to predation, suggesting that responses to opposing selective pressures could be constrained by trade-offs. Our results shed new light on how environmental and ecological pressures interact to elicit changes in characteristics at both the individual and population levels. We further suggest that morphological responses to interactive environmen- tal forces may modulate population-level responses, making prediction of long-term responses to environmental change challenging

Trade-Offs Between Morphology and Thermal Niches Mediate Adaptation in Response to Competing Selective Pressures

Abstract The effects of climate change—such as increased temperature variability and novel predators—rarely happen in isolation, but it is unclear how organisms cope with multiple stressors simultaneously. To explore this, we grew replicate Paramecium caudatum populations in either constant or variable temperatures and exposed half to predation. We then fit thermal performance curves (TPCs) of intrinsic growth rate (rmax) for each replicate population (N = 12) across seven temperatures (10°C–38°C). TPCs of P. caudatum exposed to both temperature variability and predation responded only to one or the other (but not both), resulting in unpredictable outcomes. These changes in TPCs were accompanied by changes in cell morphology. Although cell volume was conserved across treatments, cells became narrower in response to temperature variability and rounder in response to predation. Our findings suggest that predation and temperature variability produce conflicting pressures on both thermal performance and cell morphology. Lastly, we found a strong correlation between changes in cell morphology and TPC parameters in response to predation, suggesting that responses to opposing selective pressures could be constrained by trade-offs. Our results shed new light on how environmental and ecological pressures interact to elicit changes in characteristics at both the individual and population levels. We further suggest that morphological responses to interactive environmental forces may modulate population-level responses, making prediction of long-term responses to environmental change challenging

Excess Early Postnatal Weight Gain Leads to Increased Abdominal Fat in Young Children

Background. Increased childhood weight gain has been associated with later adiposity. Whether excess early postnatal weight gain plays a role in childhood abdominal fat is unknown. Design. In the ongoing Wheezing Illnesses Study Leidsche Rijn (WHISTLER), birth cohort weight and length from birth to age 3 months were obtained. In the first 316 five-year-olds, intra-abdominal and subcutaneous fat were measured ultrasonographically. Individual weight and length gain rates were assessed in each child. Internal Z-scores of weight for length gain (WLG) were calculated. Multiple imputation was used to deal with missing covariates. Results. Per-1-unit increase in Z-score WLG from birth to 3 months, BMI, waist circumference, and subcutaneous fat were significantly higher; 0.51 kg/m2, 0.84 cm, and 0.50 mm, respectively. After multiple imputation, a trend towards significance was observed for intra-abdominal fat as well (0.51 mm/SD). In the associations with 5-year adiposity, no interaction between postnatal Z-score WLG and birth size was found. Conclusion. Excess early postnatal weight gain is associated with increased general and central adiposity, characterized by more subcutaneous and likely more intra-abdominal fat at 5 years of age

Antibiotic Treatment for First Episode of Acute Otitis Media Is Not Associated with Future Recurrences

OBJECTIVES: Antibiotic treatment of acute otitis media (AOM) has been suggested to increase the risk of future AOM episodes by causing unfavorable shifts in microbial flora. Because current evidence on this topic is inconclusive and long-term follow-up data are scarce, we wanted to estimate the effect of antibiotic treatment for a first AOM episode occurring during infancy on AOM recurrences and AOM-related health care utilization later in life. METHODS: We obtained demographic information and risk factors from data of the Wheezing Illnesses Study Leidsche Rijn, a prospective birth cohort study in which all healthy newborns born in Leidsche Rijn (between 2001 and 2012), The Netherlands, were enrolled. These data were linked to children’s primary care electronic health records up to the age of four. Children with at least one family physician-diagnosed AOM episode before the age of two were included in analyses. The exposure of interest was the prescription of oral antibiotics (yes vs no) for a child’s first AOM episode before the age of two years. RESULTS: 848 children were included in analyses and 512 (60%) children were prescribed antibiotics for their first AOM episode. Antibiotic treatment was not associated with an increased risk of total AOM recurrences (adjusted rate ratio: 0.94, 95% CI: 0.78–1.13), recurrent AOM (≥3 episodes in 6 months or ≥4 in one year; adjusted risk ratio: 0.79, 95% CI: 0.57–1.11), or with increased AOM-related health care utilization during children’s first four years of life. CONCLUSIONS: Oral antibiotic treatment of a first AOM episode occurring during infancy does not affect the number of AOM recurrences and AOM-related health care utilization later in life. This information can be used when weighing the pros and cons of various AOM treatment options

Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy

Background: The long-term longitudinal evidence for a relation between coffee intake and hypertension is relatively scarce. Objective: The objective was to assess whether coffee intake is associated with the incidence of hypertension. Design: This study was conducted on a cohort of 2985 men and 3383 women who had a baseline visit and follow-up visits after 6 and 11 y. Baseline coffee intake was ascertained with questionnaires and categorized into 0, > 0-3, > 3-6, and > 6 cups/d. Hypertension was defined as a mean systolic blood pressure (SBP) >= 140 mm Hg over both follow-up measurements, a mean diastolic blood pressure (DBP) >= 90 mm Hg over both follow-up measurements, or the use of antihypertensive medication at any follow-up measurement. Results: Coffee abstainers at baseline had a lower risk of hypertension than did those with a coffee intake of > 0-3 cups/d [odds ratio (OR): 0.54; 95% CI: 0.31, 0.92]. Women who drank > 6 cups/d had a lower risk than did women who drank > 0-3 cups/d (OR: 0.67; 95% CI: 0.46, 0.98). Subjects aged >= 39 y at baseline had 0.35 mm Hg (95% CI: -0.59, -0.11 mm Hg) lower SBP per cup intake/d and 0.11 mm Hg lower DBP (95% CI: -0.26, 0.03 mm Hg) than did those aged <39 y at baseline, although the difference in DBP was not statistically significant. Conclusions: Coffee abstinence is associated with a lower hypertension risk than is low coffee consumption. An inverse U-shaped relation between coffee intake and risk of hypertension was observed in the women

Postnatal Acute Famine and Risk of Overweight: The Dutch Hungerwinter Study

Objective. To examine the association between undernutrition during postnatal periods of development and the risk of overweight in adulthood. Methods. We studied 8,091 women from Prospect-EPIC, exposed to the Dutch famine at ages between 0 and 21 years, recruited at ages between 49 and 70 years. We used linear and logistic regression models to explore the effect of famine on BMI, waist circumference, and the risk of overweight. Results. Overall, postnatal famine exposure was associated with increased BMI and waist circumference in a dose-dependent manner (P  for trend < 0.01). Furthermore, risk of overweight was increased following famine exposure (P  for trend = 0.01), with those severely exposed at ages 0–9 years having 25% (95% CI 1.05 to 1.50) higher risk compared to unexposed women. Conclusions. This study is the first to directly show a positive association between short and transient undernutrition during postnatal development and BMI, waist circumference, and overweight in adulthood

Antiviral RNA silencing suppression activity of \u3ci\u3eTomato spotted wilt virus\u3c/i\u3e NSs protein

In addition to regulating gene expression, RNA silencing is an essential antiviral defense system in plants. Triggered by double-stranded RNA, silencing results in degradation or translational repression of target transcripts. Viruses are inducers and targets of RNA silencing. To condition susceptibility, most plant viruses encode silencing suppressors that interfere with this process, such as the Tomato spotted wilt virus (TSWV) NSs protein. The mechanism by which NSs suppresses RNA silencing and its role in viral infection and movement remain to be determined. We cloned NSs from the Hawaii isolate of TSWV and using two independent assays show for the first time that this protein restored pathogenicity and supported the formation of local infection foci by suppressor-deficient Turnip mosaic virus and Turnip crinkle virus. Demonstrating the suppression of RNA silencing directed against heterologous viruses establishes the foundation to determine the means used by NSs to block this antiviral process

Validity, practical utility, and reliability of the activPAL in preschool children

&lt;p&gt;Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g. sedentary time) contributing to positive energy balance in early childhood. For pre-school children, single unit monitors such as the activPALTM are promising. However, validation is required as activity patterns differ from adults.&lt;/p&gt; &lt;p&gt;Methods: Thirty pre-school children participated in a validation study. Children were videoed for one hour undertaking usual nursery activity while wearing an activPALTM. Video (criterion method) was analyzed on a second-by-second basis to categorise posture and activity. This was compared with the corresponding activPALTM output. In a subsequent sub-study investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24-hour periods.&lt;/p&gt; &lt;p&gt;Results: A total of 97,750 seconds of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), walk (16%); with 3% of time in nonsit/lie/upright postures (e.g. crawl/crouch/kneel-up). Sensitivity for the overall total time matched seconds detected as activPALTM ‘sit/lie’ was 86.7%, specificity 97.1%, and positive predictive value (PPV) 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1-97.4), specificity 97.3% (94.9-99.2), PPV 97.0% (91.5-99.1). The activPALTM underestimated total time spent sitting (mean difference -4.4%, p&#60;0.01), and overestimated time standing (mean difference 7.1%, p&#60;0.01). There was no difference in overall % time categorised as ‘walk’ (p=0.2). The monitors were well tolerated by children during a seven day period of free-living activity. In the reliability study, at least five days of monitoring were required to obtain an intraclass correlation coefficient of ≥0.8 for time spent sit/lie according to activPALTM output.&lt;/p&gt; &lt;p&gt;Conclusion: The activPAL had acceptable validity, practical utility, and reliability for the measurement of posture and activity during freeliving activities in pre-school children.&lt;/p&gt