Primary prevention of gestational diabetes mellitus and large-for-gestational-age newborns by lifestyle counseling: a cluster-randomized controlled trial

Background

Our objective was to examine whether gestational diabetes mellitus (GDM) or newborns'' high birthweight can be prevented by lifestyle counseling in pregnant women at high risk of GDM.

Method and Findings

We conducted a cluster-randomized trial, the NELLI study, in 14 municipalities in Finland, where 2,271 women were screened by oral glucose tolerance test (OGTT) at 8–12 wk gestation. Euglycemic (n = 399) women with at least one GDM risk factor (body mass index [BMI] ≥25 kg/m², glucose intolerance or newborn''s macrosomia (≥4,500 g) in any earlier pregnancy, family history of diabetes, age ≥40 y) were included. The intervention included individual intensified counseling on physical activity and diet and weight gain at five antenatal visits. Primary outcomes were incidence of GDM as assessed by OGTT (maternal outcome) and newborns'' birthweight adjusted for gestational age (neonatal outcome). Secondary outcomes were maternal weight gain and the need for insulin treatment during pregnancy. Adherence to the intervention was evaluated on the basis of changes in physical activity (weekly metabolic equivalent task (MET) minutes) and diet (intake of total fat, saturated and polyunsaturated fatty acids, saccharose, and fiber). Multilevel analyses took into account cluster, maternity clinic, and nurse level influences in addition to age, education, parity, and prepregnancy BMI. 15.8% (34/216) of women in the intervention group and 12.4% (22/179) in the usual care group developed GDM (absolute effect size 1.36, 95% confidence interval [CI] 0.71–2.62, p = 0.36). Neonatal birthweight was lower in the intervention than in the usual care group (absolute effect size −133 g, 95% CI −231 to −35, p = 0.008) as was proportion of large-for-gestational-age (LGA) newborns (26/216, 12.1% versus 34/179, 19.7%, p = 0.042). Women in the intervention group increased their intake of dietary fiber (adjusted coefficient 1.83, 95% CI 0.30–3.25, p = 0.023) and polyunsaturated fatty acids (adjusted coefficient 0.37, 95% CI 0.16–0.57, p<0.001), decreased their intake of saturated fatty acids (adjusted coefficient −0.63, 95% CI −1.12 to −0.15, p = 0.01) and intake of saccharose (adjusted coefficient −0.83, 95% CI −1.55 to −0.11, p  =  0.023), and had a tendency to a smaller decrease in MET minutes/week for at least moderate intensity activity (adjusted coefficient 91, 95% CI −37 to 219, p = 0.17) than women in the usual care group. In subgroup analysis, adherent women in the intervention group (n = 55/229) had decreased risk of GDM (27.3% versus 33.0%, p = 0.43) and LGA newborns (7.3% versus 19.5%, p = 0.03) compared to women in the usual care group.

Conclusions

The intervention was effective in controlling birthweight of the newborns, but failed to have an effect on maternal GDM.

Trial registration

Current Controlled Trials ISRCTN33885819 Please see later in the article for the Editors'' Summary     

Clone identification and clonal structure of the European aspen (Populus tremula)

The European aspen (Populus tremula) is thought to reproduce mostly asexually. Thus aspen forms clones, in which several ramets belong to one genetically defined genet. We compared the clonal structure of aspen in old-growth and managed forests in southern and northeastern Finland. Clones were identified using morphological characters and nine microsatellite loci originally developed for Populus tremuloides. There were more clones identified by microsatellites than morphotypes both in old-growth and managed forest. The average size of the clones was only 2.3 ramets and most clones (70%) consisted of just one ramet. The size of the clones showed no difference between managed and old-growth forests or between northeastern and southern Finland. The small size of the clones suggests that most of them are relatively young. Therefore, sexual reproduction may be more common than previously thought. There was an aggregated spatial genetic structure as measured by Moran's I (0-10 m) and by co-ancestry (rho(ij), 0-20 m). Low level of co-ancestry can be explained by relatively unrestricted gene flow, the important role of disturbance in reproduction, and/or local selection.     

Medroxyprogesterone improves nocturnal breathing in postmenopausal women with chronic obstructive pulmonary disease

Background

Progestins as respiratory stimulants in chronic obstructive pulmonary disease (COPD) have been investigated in males and during wakefulness. However, sleep and gender may influence therapeutic responses. We investigated the effects of a 2-week medroxyprogesterone acetate (MPA) therapy on sleep and nocturnal breathing in postmenopausal women.

Methods

A single-blind placebo-controlled trial was performed in 15 postmenopausal women with moderate to severe COPD. A 12-week trial included 2-week treatment periods with placebo and MPA (60 mg/d/14 days). All patients underwent a polysomnography with monitoring of SaO₂ and transcutaneous PCO₂ (tcCO₂) at baseline, with placebo, with medroxyprogesterone acetate (MPA 60 mg/d/14 days), and three and six weeks after cessation of MPA.

Results

Thirteen patients completed the trial. At baseline, the average ± SD of SaO₂ mean was 90.6 ± 3.2 % and the median of SaO₂ nadir 84.8 % (interquartile range, IQR 6.1). MPA improved them by 1.7 ± 1.6 %-units (95 % confidence interval (CI) 0.56, 2.8) and by 3.9 %-units (IQR 4.9; 95% CI 0.24, 10.2), respectively. The average of tcCO₂ median was 6.0 ± 0.9 kPa and decreased with MPA by 0.9 ± 0.5 kPa (95% CI -1.3, -0.54). MPA improved SaO₂ nadir and tcCO₂ median also during REM sleep. Three weeks after cessation of MPA, the SaO₂ mean remained 1.4 ± 1.8 %-units higher than at baseline, the difference being not significant (95% CI -0.03, 2.8). SaO₂ nadir was 2.7 %-units (IQR 4.9; 95% CI 0.06, 18.7) higher than at baseline. Increases in SaO₂ mean and SaO₂ nadir during sleep with MPA were inversely associated with baseline SaO₂ mean (r = -0.70, p = 0.032) and baseline SaO₂ nadir (r = -0.77, p = 0.008), respectively. Treatment response in SaO₂ mean, SaO₂ nadir and tcCO₂ levels did not associate with pack-years smoked, age, BMI, spirometric results or sleep variables.

Conclusion

MPA-induced respiratory improvement in postmenopausal women seems to be consistent and prolonged. The improvement was greater in patients with lower baseline SaO₂ values. Long-term studies in females are warranted.     

Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay

Background  

We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF).     

Are Anticapsular Antibodies the Primary Mechanism of Protection against Invasive Pneumococcal Disease?

Background

Antibody to capsular polysaccharide has been the basis of several vaccines that offer protection against invasive disease from Streptococcus pneumoniae. The success of such vaccines has led to the inference that natural protection against invasive pneumococcal disease is largely conferred by anticapsular antibody. If this is so, one would expect that the decline in disease from different serotypes would vary significantly, and that the appearance of substantial concentrations of anticapsular antibodies would coincide temporally with the decline in age-specific incidence.

Methods and Findings

Using incidence data from the United States, we show that, on the contrary, the decline in incidence with age is quite similar for the seven most important serogroups, despite large differences in exposure in the population. Moreover, only modest increases in antibody concentration occur over the second and third years of life, a period in which serotype-specific incidence declines to less than 25% of its peak. We also present detailed data on the distribution of antibody concentrations in Israeli toddlers, which are consistent with the United States findings. The same conclusion is supported by new data on age-specific incidence in Finland, which is compared with published data on antibody acquisition in Finnish toddlers.

Conclusion

We suggest some additional studies of the mechanisms of protection that could distinguish among potential alternative mechanisms, including acquired immunity to noncapsular antigens, maturation of nonspecific immune responses, or changes in anatomy or exposure.     

Using multilocus sequence data to define the pneumococcus

We investigated the genetic relationships between serotypeable pneumococci and nonserotypeable presumptive pneumococci using multilocus sequence typing (MLST) and partial sequencing of the pneumolysin gene (ply). Among 121 nonserotypeable presumptive pneumococci from Finland, we identified isolates of three classes: those with sequence types (STs) identical to those of serotypeable pneumococci, suggesting authentic pneumococci in which capsular expression had been downregulated or lost; isolates that clustered among serotypeable pneumococci on a tree based on the concatenated sequences of the MLST loci but which had STs that differed from those of serotypeable pneumococci in the MLST database; and a more diverse collection of isolates that did not cluster with serotypeable pneumococci. The latter isolates typically had sequences at all seven MLST loci that were 5 to 10% divergent from those of authentic pneumococci and also had distinct and divergent ply alleles. These isolates are proposed to be distinct from pneumococci but cannot be resolved from them by optochin susceptibility, bile solubility, or the presence of the ply gene. Complete resolution of pneumococci from the related but distinct population is problematic, as recombination between them was evident, and a few isolates of each population possessed alleles at one or occasionally more MLST loci from the other population. However, a tree based on the concatenated sequences of the MLST loci in most cases unambiguously distinguished whether a nonserotypeable isolate was or was not a pneumococcus, and the sequence of the ply gene fragment was found to be useful to resolve difficult cases.     

EARLY RESPONSIVE TO DEHYDRATION 15, a negative regulator of abscisic acid responses in Arabidopsis

EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15) is rapidly induced in response to various abiotic and biotic stress stimuli in Arabidopsis (Arabidopsis thaliana). Modulation of ERD15 levels by overexpression or RNAi silencing altered the responsiveness of the transgenic plants to the phytohormone abscisic acid (ABA). Overexpression of ERD15 reduced the ABA sensitivity of Arabidopsis manifested in decreased drought tolerance and in impaired ability of the plants to increase their freezing tolerance in response to this hormone. In contrast, RNAi silencing of ERD15 resulted in plants that were hypersensitive to ABA and showed improved tolerance to both drought and freezing, as well as impaired seed germination in the presence of ABA. The modulation of ERD15 levels not only affected abiotic stress tolerance but also disease resistance: ERD15 overexpression plants showed improved resistance to the bacterial necrotroph Erwinia carotovora subsp. carotovora accompanied with enhanced induction of marker genes for systemic acquired resistance. We propose that ERD15 is a novel mediator of stress-related ABA signaling in Arabidopsis.     

University students' knowledge of, and attitudes towards, hiv and AIDS, homosexuality and sexual risk behaviour: a questionnaire survey in two finnish universities

Summary This study describes Finnish university students' knowledge and attitudes towards HIV and AIDS, homosexuality and sexual risk behaviour. Finnish-speaking students were randomly selected from all registered students at two universities in Finland (N=9715, n=950). The data were collected by using a modified version of the State University of New York at Buffalo School of Nursing AIDS Study Questionnaire on sexual risk behaviour developed by Held and Chng. The total response rate was 35% (n=333). The data were analysed using quantitative statistical methods. Normally distributed data were analysed by t-test and one-way ANOVA, with Bonferroni corrections. Non-normally distributed data were analysed using the Mann-Whitney U-test and Kruskal-Wallis test, followed by a post-hoc test. The majority of students were familiar with HIV and AIDS, including its mode of transmission. However, there were still some misconceptions concerning HIV and AIDS. The oldest students and women had a more positive attitude towards people living with HIV and AIDS (PLWHA). Of patients with HIV or AIDS, intravenous drug users were perceived most negatively. Male students had more homophobic attitudes. Students who reported that religion had an important role in their lives had significantly stricter attitudes towards sexual risk behaviour. Students' knowledge correlated positively with general attitudes towards HIV and AIDS. Knowledge about HIV and AIDS will lead to more positive attitudes towards HIV and AIDS as a disease, towards those infected as well as homosexual people. There is a need to focus on preventive health care and sexual health promotion by educating young people and changing their attitudes towards sexual risk behaviour.     

Pathology of Puumala hantavirus infection in macaques

Hantaviruses are globally important human pathogens that cause hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Capillary leakage is central to hantaviral diseases, but how it develops, has remained unknown. It has been hypothesized that the pathogenesis of hantavirus infection would be a complex interplay between direct viral effects and immunopathological mechanisms. Both of these were studied in the so far best model of mild hemorrhagic fever with renal syndrome, i.e. cynomolgus macaques infected with wild-type Puumala hantavirus. Viral RNA detected by in situ hybridization and nucleocapsid protein detected by immunohistochemical staining were observed in kidney, spleen and liver tissues. Inflammatory cell infiltrations and tubular damage were found in the kidneys, and these infiltrations contained mainly CD8-type T-cells. Importantly, these results are consistent with those obtained from patients with hantaviral disease, thus showing that the macaque model of hantavirus infection mimics human infection also on the tissue level. Furthermore, both the markers of viral replication and the T-cells appeared to co-localize in the kidneys to the sites of tissue damage, suggesting that these two together might be responsible for the pathogenesis of hantavirus infection.     

Regulation, cycles and stability in northern carnivore-herbivore systems: back to first principles

In studies on dynamics of northern predator‐prey systems, two assumptions are often made. First, the bifurcation from stable to cyclic dynamics is seen as a consequence of changing generalist‐specialist ratio, ultimately due to reduced prey diversity at high latitudes and the negative impact of snow on the efficiency of generalists as predators of small, folivorous mammals. Supposedly, the primary mechanism is the qualitative difference between the functional response of specialist and generalist predators. Second, the interaction between large predators and ungulates is supposed to be prone to lead to two alternative equilibria, one where predation regulates ungulates at a relatively low equilibrium and another, where ungulate densities are close to carrying capacity. In the first‐mentioned issue, our analysis corroborates the general idea of snow favoring specialists and leading to cycles. However, differences in functional response appear to be of secondary importance only, and rather special conditions are required for generalists to have a stabilizing type III functional response. A destabilizing type II functional response or a slight modification of it should be common in generalists, too, as also indicated by the classical experiments. Stability of generalist dominated systems seems primarily to derive from their relative inefficiency, allowing prey's density‐dependent mechanisms to play a bigger role in the neighborhood of the equilibrium. Moreover, the main destabilizing impact of deep, long‐lasting snow cover appears to lie in the protection it offers to the efficient but vulnerable specialists, which are eliminated or marginalized by intraguild predation in areas with snow‐free winters, unless the habitat offers some other form of efficient protection. As for the conjecture of multiple equilibria in northern wolf‐ungulate systems, it seems to be derived from an erroneous operational definition of numerical response and has little if any empirical support. Available data suggest that predation limitation of folivorous mammals prevails along the entire gradient from relatively productive low arctic habitats to the humid parts of the temperate zone, provided that the numbers of predators are not controlled by man.