Establishment of Intestinal Microbiota during Early Life: a Longitudinal,Explorative Study of a Large Cohort of Danish Infants

Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18, and 36 months after birth, enabling characterization of interbacterial relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA gene targets representing different phylogenetic levels. Nutritional parameters and measures of growth and body composition were determined and investigated in relation to the observed development in microbiota composition. We found that significant changes in the gut microbiota occurred, particularly from age 9 to 18 months, when cessation of breastfeeding and introduction of a complementary feeding induce replacement of a microbiota characterized by lactobacilli, bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium spp. and Bacteroides spp. Classification of samples by a proxy enterotype based on the relative levels of Bacteroides spp. and Prevotella spp. showed that enterotype establishment occurs between 9 and 36 months. Thirty percent of the individuals shifted enterotype between 18 and 36 months. The composition of the microbiota was most pronouncedly influenced by the time of cessation of breastfeeding. From 9 to 18 months, a positive correlation was observed between the increase in body mass index and the increase of the short-chain-fatty-acid-producing clostridia, the Clostridum leptum group, and Eubacterium hallii. Considering previously established positive associations between rapid infant weight gain, early breastfeeding discontinuation, and later-life obesity, the corresponding microbial findings seen here warrant attention.     

Incidence of Otitis Media in a Contemporary Danish National Birth Cohort

Objectives

In recent years welfare in Denmark has increased which might be expected to reduce otitis media (OM) incidence. We examined the age-specific incidence of OM in a nation-wide cohort of children aged 0–7 years born in 1996–2003 (Danish National Birth Cohort, DNBC). Only selection was ability to understand and speak Danish.

Methods

Information of OM and ventilation tubes (VT) was collected through three maternal interviews at 6-month, 18-month and 7-years of age and based on this age-specific and cumulative incidence of OM was calculated. As different numbers of the total population answered the different interviews, the calculations are done with different denominators. The information in DNBC was validated against two population based registries containing information of VT insertions.

Results

Cumulative incidence of OM at 7 years was 60.6% (31,982/52,755). For children with OM, 16.2% (7143/44194) had their first OM episodes between 0–6 months of age, 44.3% (19579/44194) between 7–18 months, and 39.5% (17472/44194) between 19 months and 7 years. Four or more OM episodes before 7 years were reported by 39.5% (12620/31982) and by 64.0% (2482/3881) of those who had their OM debut between 0–6 months; by 48.2% (4998/10378) with debut between 7–18 months; and by 28.7% (4996/17344) with debut between 19 months and 7 years. These figures are essentially unchanged from earlier figures from Denmark. VT insertion at least once was reported by 26,1% in the 7-year interview. Assuming recordings in the Danish National Patient Registry to be gold standard, maternal self-reportings in DNBC of insertion of VT showed high sensitivity (96.4%), specificity (98.2%), and positive (94.8%) and negative predictive values (98.8%).

Conclusion

OM affects nearly 2/3 of preschool children in Denmark despite reduction in known OM risk factors.     

Residential Radon Exposure and Skin Cancer Incidence in a Prospective Danish Cohort

Background

Although exposure to UV radiation is the major risk factor for skin cancer, theoretical models suggest that radon exposure can contribute to risk, and this is supported by ecological studies. We sought to confirm or refute an association between long-term exposure to residential radon and the risk for malignant melanoma (MM) and non-melanoma skin cancer (NMSC) using a prospective cohort design and long-term residential radon exposure.

Methods

During 1993–1997, we recruited 57,053 Danish persons and collected baseline information. We traced and geocoded all residential addresses of the cohort members and calculated radon concentrations at each address lived in from 1 January 1971 until censor date. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and confidence intervals (CI) for the risk associated with radon exposure for NMSC and MM, and effect modification was assessed.

Results

Over a mean follow-up of 13.6 years of 51,445 subjects, there were 3,243 cases of basal cell carcinoma (BCC), 317 cases of squamous cell carcinoma (SCC) and 329 cases of MM. The adjusted IRRs per 100 Bq/m³ increase in residential radon levels for BCC, SCC and MM were 1.14 (95% CI: 1.03, 1.27), 0.90 (95% CI: 0.70, 1.37) and 1.08 (95% CI: 0.77, 1.50), respectively. The association between radon exposure and BCC was stronger among those with higher socio-economic status and those living in apartments at enrollment.

Conclusion and Impact

Long-term residential radon exposure may contribute to development of basal cell carcinoma of the skin. We cannot exclude confounding from sunlight and cannot conclude on causality, as the relationship was stronger amongst persons living in apartments and non-existent amongst those living in single detached homes.     

Seasonal Variation of Virioplankton in a Eutrophic Shallow Lake

Lake Donghu is a typical eutrophic freshwater lake in which high abundance of planktonic viruses was recently revealed. In this study, seasonal variation of planktonic viruses were observed at three different trophic sites, hypertrophic, eutrophic, and mesotrophic regions, and the correlation between their abundances and other aquatic environmental components, such as bacterioplankton, chlorophyll a, burst size, pH, dissolved oxygen, and temperature, was analyzed for the period of an year. Virioplankton abundance detected by transmission electron microscope (TEM) ranged from 5.48 × 10⁸ to 2.04 × 10⁹ ml⁻¹ in all the sites throughout the study, and the high abundances and seasonal variations of planktonic viruses were related to the trophic status at the sampled sites in Lake Donghu. Their annual mean abundances were, the highest at the hypertrophic site (1.23×10⁹ ml⁻¹), medium at the eutrophic site (1.19×10⁹ ml⁻¹), and the lowest at the mesotrophic site (1.02×10⁹ ml⁻¹). The VBR (virus-to-bacteria ratio) values were high, ranging from 49 to 56 on average at the three sampled sites. The data suggested that the high viral abundance and high VBR values might be associated with high density of phytoplankton including algae and cyanobacteria in this eutrophic shallow lake, and that planktonic viruses are important members of freshwater ecosystems.     

Goblet Cell Carcinoids: Characteristics of a Danish Cohort of 83 Patients

BackgroundAppendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features.ResultsMedian age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25). According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2). Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75%) and higher in Tang group C (50%) compared to group A (30%; p<0.0001), and group B (30%; p<0.004). All patients had surgery. Sixty-three (76%) had radical resections including all patients with localized disease. Median OS was 83 months. The 1-, 5- and 10-year survival rates were 90%, 58%, and 38%, respectively. For localized disease OS was 164 months and 1-, 5- and 10-year survival rates were 100%, 80%, and 55%, respectively. For disseminated disease OS was 19 months and 1-, 5- and 10-year survival rates were 73%, 18% and 6%, respectively. The 1-, 5- and 10 year-survival rates for f/m were 87%/96%, 49%/76% and 31%/57%, respectively (p = 0.02). According to the Tang classification group A, B, and C OS was 118, 83 and 20 months, respectively (p = 0.0002).ConclusionThe Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.     

Seasonal Dynamics of Periphyton in a Large Tropical Lake

Tropical aquatic systems are generally assumed to have little seasonality in productivity patterns. However, this study indicated that there was substantial seasonal variation in epilithic productivity and biomass in tropical Lake Tanganyika, due primarily to seasonal patterns in lake hydrodynamics that influence nutrient availability. Although they support much of the lake’s biological diversity, epilithic algae made a minor contribution to the total energy budget in Lake Tanganyika. A comparison among large, oligotrophic lakes revealed no significant latitudinal trends in periphyton productivity or biomass. However, Lake Tanganyika has relatively low benthic algal biomass and is therefore more efficient at photosynthesis than the temperate lakes. The influence of wave action and consumer density and diversity may be important in moderating productivity of the epilithic community.     

Sedentary Behavior and Obesity in a Large Cohort of Children

The purpose of this study was to examine the association between sedentary behavior and obesity among 12‐year‐old children, while adjusting for moderate‐to‐vigorous physical activity (MVPA) and other potential confounding variables. Cross‐sectional analyses were carried out with data from 5,434 children who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC). Fat mass was derived using dual‐energy X‐ray emission absorptiometry, and height and weight measurements were used to calculate BMI (kg/m²). The children wore an accelerometer for 7 days. The cut points for sedentary behavior and MVPA were ≤199 and ≥3,600 counts per minute (cpm), respectively. Logistic regression analyses were performed to estimate odds ratios (ORs), adjusting for potential confounders of physical activity that included gender, social factors, early life factors, and maturation. The minimally adjusted association between sedentary behavior and obesity was positive, OR = 1.18 (1.08, 1.28). After adjusting for the series of potential confounders of physical activity the positive association remained, OR = 1.32 (1.14, 1.53). The crude association between 15 min of MVPA per day and obesity was negative, OR = 0.54 (0.48, 0.62). When 15 min of MVPA per day was additionally controlled for in the models, the positive associations between sedentary behavior and obesity were negated. Sedentary behavior was positively associated with obesity in the 12‐year‐old children, but this association was not independent of MVPA; low levels of MVPA among the sedentary children increased the odds of obesity. These findings support the importance of specifically engaging in MVPA during childhood to reduce the prevalence of obesity.     

Seasonal Variation of Suicide in Brazil

Most of what is known about the seasonal variation in suicide rate originates from studies conducted in the northern hemisphere; very few studies have been done in the southern hemisphere. The purpose of the present study was to explore the possibility that in Brazil, the seasonal variation of suicides is a function of photoperiod. This was accomplished by analyzing monthly suicide data for a 12 yr period (1979 to 1990), within latitudes ranging from 2°N to 33°S. Single cosinor analyses with periods of 12 or 6 months were applied to time series of monthly total and suicidal deaths, separated by gender and state. Significant spring or early summer peaks of suicide were found only in the south of Brazil for both men and women, except for the latter in one state. These peaks did not coincide with those found for total deaths, which occurred in the autumn or winter in all areas. No significant six‐month period was found. In the present study, the chance of a suicide was typically 10–17% higher during the peak period than during the other months of the year. Although this moderate seasonal effect might not be sufficient to justify planning large scale prophylactic interventions, those dealing with patients who have suicide ideation should be aware of this high risk time.     

Seasonal Variation of Ichthyoplankton in a Western Caribbean Bay System

The plankton of Bahia de la Ascension was sampled monthly, from August 1990 to July 1991, to ascertain ichthyoplankton composition, abundance, and seasonality. These data were used to assess the inferred function of the bay as spawning and nursery grounds. Fifty-one families, 66 genera, and 53 species of fish embryos and larvae were identified. Engraulidae, Clupeidae, Labrisomidae, Callionymidae, Gerreidae, and Gobiidae comprised 81.5% of the larvae captured: the remaining 18.5% included several coral reef fish families. Greatest mean fish egg densities were recorded between December and April, 341–246 per 100m³, suggesting a major spawning period. The monthly mean density of total fish embryos and larvae showed two peaks: one in late dry season (June), dominated by newly hatched engraulid, and a second (December) during the cold-front season with high densities of preflexion labrisomid and engraulid embryos. When labrisomid and engraulid embryos and larvae were excluded, densities peaked in the rainy season (July to October). Gerreidae and Callionymidae were significantly more abundant in the rainy season, while Labrisomidae and Gobiidae in the cold-front season. The highest embryos and larvae richness was observed in August during the rainy season with mean value significatively greater than those from cold-front and dry seasons. The occurrence of high egg densities and the wide range of embryos and larva stages are evidences that Bahia de la Ascension is a regionally important spawning and nursery ground for marine fish. Because this study covered partially the marine ecosystem of Bahia de la Ascension using convential gear, we suggest to conduct further research for have a full understanding of the importance of this bay for fish recruitment.     

Seasonal Variation in Pollen Catch in a Black Spruce Orchard

Pollen monitoring was conducted over three years (1987–1989) in a 12.4 ha Picea mariana (Mill.) B.S.P. (black spruce) seedling seed orchard established from 1979 to 1984. Pollen traps were installed around and within the orchard and collected daily. Pollen-cone production was highest in 1988 with an average of 0, 11, 20, and 38 cones per tree for 5-, 8-, 9-, and 10-year-old trees. Trees of the oldest section of the orchard bore about 60% of the total number of orchard pollen cones in 1987 and 1988 but only 26% in 1989. Pollen contamination during seed-cone receptivity was important in all three years assessed. The increase in pollen contamination from 1988 to 1989 resulted, in part, from 1) the roguing of 63% of trees in the oldest section of the orchard and 2) a 17-fold decrease in orchard pollen production from 1988 to 1989 compared to a 5-fold decrease from contamination sources.     

Seasonal Variation in Mortality,Medical Care Expenditure and Institutionalization in Older People: Evidence from a Dutch Cohort of Older Health Insurance Clients

Background

The mortality rates of older people changes with the seasons. However, it has not been properly investigated whether the seasons affect medical care expenditure (MCE) and institutionalization. Seasonal variation in MCE is plausible, as MCE rises exponentially before death. It is therefore important to investigate the impact of the seasons on MCE both mediated and unmediated by mortality.

Methods

Data on mortality, MCE and institutionalization from people aged 65 and older in a region in the Netherlands from July 2007 through 2010 were retrieved from a regional health care insurer and were linked with data from the Netherlands Institute for Social Research, and Statistics Netherlands (n = 61,495). The Seasonal and Trend decomposition using Loess (STL) method was used to divide mortality rates, MCE, and institutionalization rates into a long-term trend, seasonal variation, and remaining variation. For every season we calculated the 95% confidence interval compared to the long-term trend using Welch’s t-test.

Results

The mortality rates of older people differ significantly between the seasons, and are 21% higher in the winter compared to the summer. MCE rises with 13% from the summer to the winter; this seasonal difference is higher for the non-deceased than for the deceased group (14% vs. 6%). Seasonal variation in mortality is more pronounced in men and people in residential care. Seasonal variation in MCE is more pronounced in women. Institutionalization rates are significantly higher in the winter, but the other seasons show no significant impact.

Conclusions

Seasonal changes affect mortality and the level of MCE of older people; institutionalization rates peak in the winter. Seasonal variation in MCE exists independently from patterns in mortality. Seasonal variation in mortality is similar for both institutionalized and community-dwelling elderly. Policy-makers, epidemiologists and health economists are urged to acknowledge and include the impact of the seasons in future policy and research.     

Seasonal Variation in Pathogenicity of Phytophthora infestans

During a four year study it was shown that the mean lesion area (M.L.A.) developed on leaflets of different potato cultivars by isolates of P. infestans after artificial inoculation varied periodically during the year. Disease symptoms observed changed from pinpoint necroses to regular sporulating lesions depending on the season and the cultivar. Analysis of variance revealed that differences in lesion size between experiments performed in different seasons were significant. The largest M.L.A. was found in late spring or in autumn but autumnal increase of M.L.A. was usually significantly lower than that in spring. Periodicity of M.L.A. was accompanied by a similar phenomenon in sporulation density of P. infestans isolates cultured in vitro. However, the peaks of sporulation, in comparison with peaks of M.L.A. appeared in different seasons. The highest disease level coincided with a decline in sporulation density of P. infestans cultured in vitro and the decrease of M.L.A. corresponded with an increase in sporulation density per cm² of medium. Variation in M.L.A. found in this study seemed not to be related to variability in plant reaction. In this connection a hypothesis has been proposed that the changes of M.L.A. were due to variation in pathogenicity of the fungus.     

Seasonal Variation in Sporulation of Phytophthora infestans

Sporulation ability of two isolates of Phytophthora infestans maintained on potato tuber slices of a susceptible cv. ‘Bintje’ and on-rye agar medium was studied for four years (1981–1984). This feature of the fungus was shown to vary in particular seasons during the year. Significantly higher sporulation density per cm² of aerial mycelium on potato tuber slices was observed in winter and late autumn while significantly lower sporulation was found in spring. Similar tendencies were observed when one of the isolates was cultivated on rye agar medium under controlled conditions. Positive correlation was found between sporulation patterns of isolates of the fungus maintained on rye agar and on tuber slices. Hypothesis has been proposed that these changes are due, to a biorhythm in the fungus.     

Seasonal Variation in Estimates of Cereal-ear Photosynthesis

The potential contribution by ear photosynthesis to yield ofwheat grain was estimated to be greater in summer than winterin glasshouse conditions, and to be light-dependent in controlledenvironment. These results offer an explanation for variationsin published results.     

Seasonal Variation in the Structure of a Marine Benthic Microbial Community

Abstract The patterns of seasonal variation in the structure of a marine benthic microbial community were examined using phospholipid fatty acid analysis (PLFA). Principal component analysis of PLFA profiles indicated a strong seasonal pattern dominated the variance within the data set. Three functional groups of microorganisms (phototrophic microeukaryotes, and two groups of anaerobic bacteria) were disproportionately abundant in the communities that mapped to either extreme of the first principle component. Phototrophic microeukaryotes were most abundant and exhibited the greatest relative abundance during periods of cold water. In contrast, the two functional groups of anaerobic bacteria showed the greatest relative abundance during times of warm water. Differential responses by these groups, and macrofaunal deposit feeders, to light intensity and water temperature were offered as the proximal causes of the observed patterns. Received: 28 April 1997; Accepted: 10 September 1997     

Development and Validation of a Vitamin D Status Prediction Model in Danish Pregnant Women: A Study of the Danish National Birth Cohort

Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen''s weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence.     

Unraveling Seasonality in Population Averages: An Examination of Seasonal Variation in Glucose Levels in Diabetes Patients Using a Large Population-based Data Set

It has been shown that the population average blood glucose level of diabetes patients shows seasonal variation, with higher levels in the winter than summer. However, seasonality in the population averages could be due to a tendency in the individual to seasonal variation, or alternatively due to occasional high winter readings (spiking), with different individuals showing this increase in different winters. A method was developed to rule out spiking as the dominant pattern underlying the seasonal variation in the population averages. Three years of data from three community-serving laboratories in Israel were retrieved. Diabetes patients (N?=?3243) with a blood glucose result every winter and summer over the study period were selected. For each individual, the following were calculated: seasonal average glucose for all winters and summers over the period of study (2006–2009), winter-summer difference for each adjacent winter-summer pair, and average of these five differences, an index of the degree of spikiness in the pattern of the six seasonal levels, and number of times out of five that each winter-summer difference was positive. Seasonal population averages were examined. The distribution of the individual's differences between adjacent seasons (winter minus summer) was examined and compared between subgroups. Seasonal population averages were reexamined in groups divided according to the index of the degree of spikiness in the individual's glucose pattern over the series of seasons. Seasonal population averages showed higher winter than summer levels. The overall median winter-summer difference on the individual level was 8?mg/dL (0.4?mmol/L). In 16.9% (95% confidence interval [CI]: 15.6–18.2%) of the population, all five winter-summer differences were positive versus 3.6% (95% CI: 3.0–4.2%) where all five winter-summer differences were negative. Seasonal variation in the population averages was not attenuated in the group having the lowest spikiness index; comparison of the distributions of the winter-summer differences in the high-, medium-, and low-spikiness groups showed no significant difference (p?=?.213). Therefore, seasonality in the population average blood glucose in diabetes patients is not just the result of occasional high measurements in different individuals in different winters, but presumably reflects a general periodic tendency in individuals for winter glucose levels to be higher than summer levels. (Author correspondence: anneke@clalit.org.il)