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Purpose Obesity is the most important risk factor for obstructive sleep apnea (OSA); however, the exact underlying mechanisms are still not fully understood. The aim of this study was to examine the morphology of upper airways in overweight habitual snorers and in mild OSA patients. Furthermore, the associations between weight loss, parapharyngeal fat pad area and OSA were assessed in a 1-year randomised, controlled follow-up study originally conducted to determine the effects of lifestyle changes with weight reduction as a treatment of OSA. Methods Thirty-six overweight adult patients with mild OSA [apnea–hypopnea index (AHI) 5–15 events/h] and 24 weight-matched habitual snorers (AHI < 5 events/h) were included in the study. All patients underwent nocturnal cardiorespiratory recordings and multislice computed tomography (CT) of parapharyngeal fat pad area, the smallest diameter and area in naso-, oro- and hypopharynx, the smallest diameter and area of the whole pharyngeal airway, the distance from the hyoid bone to the mandibular plane and to cervical tangent as well as the distance between mandibular symphysis and cervical spine. In addition, OSA patients were further randomised to receive either an active 1-year lifestyle intervention with an early weight loss programme or routine lifestyle counselling. After 1 year, the cardiorespiratory recordings and CT scans were repeated. Results The pharyngeal fat pad area was significantly larger, and the distance from the hyoid bone to cervical spine was longer in patients with OSA than in habitual snorers ( p  = 0.002 and p  = 0.018, respectively). The multiple regression analysis showed that besides a large pharyngeal fat pad area and a long distance from the cervical spine to hyoid bone, also a short distance from the mandibular symphysis to cervical tangent increased a risk to OSA. During the 1-year follow-up in OSA patients, the pharyngeal fat pad area and AHI decreased significantly in the intervention group ( p  = 0.003 and p  < 0.001, respectively). Conclusions In the early stages of OSA, the pharyngeal fat pad seems to play an important role in the development of disease in overweight patients. Furthermore, weight reduction by lifestyle intervention-based programme reduces both central obesity and pharyngeal fat pads, resulting in an improvement of OSA.

Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk 1 . Furthermore, LDL-C fluctuations are associated with ASCVD outcomes 2 – 4 . However, the precise mechanisms behind this increased ASCVD risk are not understood. Here we find that early intermittent feeding of mice on a high-cholesterol Western-type diet (WD) accelerates atherosclerosis compared with late continuous exposure to the WD, despite similar cumulative circulating LDL-C levels. We find that early intermittent hyperlipidaemia alters the number and homeostatic phenotype of resident-like arterial macrophages. Macrophage genes with altered expression are enriched for genes linked to human ASCVD in genome-wide association studies. We show that LYVE1 + resident macrophages are atheroprotective, and identify biological pathways related to actin filament organization, of which alteration accelerates atherosclerosis. Using the Young Finns Study, we show that exposure to cholesterol early in life is significantly associated with the incidence and size of carotid atherosclerotic plaques in mid-adulthood. In summary, our results identify early intermittent exposure to cholesterol as a strong determinant of accelerated atherosclerosis, highlighting the importance of optimal control of hyperlipidaemia early in life, and providing insights into the underlying biological mechanisms. This knowledge will be essential to designing effective therapeutic strategies to combat ASCVD. Early intermittent feeding of mice with a high-cholesterol Western-type diet accelerates atherosclerosis compared with late continuous exposure to the Western-type diet, despite similar cumulative circulating LDL-C levels.

PurposeTo find out if a moderate protrusion with a mandibular advancement device (MAD) can significantly increase the upper airway volume and, further, what signs and symptoms of obstructive sleep apnea (OSA) can be improved by this maneuver.MethodsThere were 58 adults diagnosed with OSA who were referred for MAD therapy. The mean apnea-hypopnea index (AHI) was 19.2 (SD 8.6). Five indicators of signs and symptoms of OSA (AHI, oxygen saturation, snoring, daytime sleepiness, and health-related quality of life) were evaluated at the baseline and after 6 months of MAD therapy. Nasal resistance and airway volume and cross-sectional areas with and without the MAD in situ were recorded. Based on AHI reduction, the treatment response was classified as complete, partial, or non-complete. Statistical analyses included the chi-square, t tests, Mann–Whitney U tests, and regression analyses (linear and logistic).ResultsTwenty-three patients attained a complete response (residual AHI < 5 events/h) to MAD therapy. In 13 subjects, the response was partial, and in 9 patients, it was non-complete. The complete responders were significantly younger, and they had a deeper overbite than partial/non-complete responders. A convex profile associated positively, but a vertically restricted throat and increased lower facial height associated negatively with the increase in airway volume.ConclusionsExcellent MAD therapy outcomes were achieved in most patients. Only age and deep bite had some influence on AHI reduction, indicating multifactorial nature in the response to MAD therapy.

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P  = 3.96 × 10 −14 ). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality. Gestational duration depends on both maternal and fetal genetic influences. Here, the authors perform a fetal genome-wide association meta-analysis and find that a locus on 2q13 is associated with pregnancy duration and further show that the lead SNP rs7594852 changes the binding properties of transcriptional repressor HIC1.

BackgroundMost obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children.MethodsWe constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist–hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3–18 years.ResultsThe genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = −0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = −0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01–1.13, P = 0.012, n = 536).ConclusionsGenetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.

Age-specific survival and breeding (ASSAB) models were developed with data from 146 common buzzards (Buteo buteo) radio-tagged in southern Britain during 1990-1998, in a 120- km2 study area that had on average 25 egg-laying pairs. Survival checks were aided by philopatric behaviour and a maximum annual tag failure rate of 7%: minimum survival rates, that were estimated by assuming death of buzzards with lost tags, were close to maximum rates that were estimated using only the recorded deaths. First-year survival rate estimates for 35 buzzards fitted in 1990-1991 with 25-30-g backpack radios were 69-74% (minimum-maximum), close to the 61-71% for 16 buzzards with 12-g tail-mount radios; the backpacks transmitted for 2-4 yr. Overall survival rates were 66-73% in the first year, 91-97% in the second and 88-91% thereafter. Survival estimates from 288 recent British ring recoveries were lower in the first and second years, at 55% and 75%, but similar (88%) thereafter. Most deaths were from natural causes (40%) or interaction with artefacts (36%). ASSAB models, from radio-tracking and the observed 1.71 young clutch-1, predicted breeding by 16-21% of all the buzzards present in spring, or up to 25% with the minimum likely productivity of 1.4 young clutch-1 or 12% net emigration. Ringing data predicted breeding rates of 33-38%. The models were tested with density data from nest surveys and new radio-corrected-transect and truncation-mark-resighting estimates of buzzard numbers. Surveys in autumn and late winter estimated breeding rates of 21-25%. The high non-breeder density in spring, of three other buzzards for each paired bird with eggs, has important implications for understanding evolutionary fitness, predation and population ecology.

We studied the morphology of the goshawk in northern Finland by measuring skin and skeletal characters of 258 museum specimens dated between 1961 and 1997. We predicted a decrease in the size of male goshawks from the 1960s because availability of their main prey, grouse, has decreased since then and grouse have been replaced in the diet by smaller prey during the breeding season. Based on the assumption that winter is the most critical period for females, we predicted that female size should have increased because their winter diet consisted of more and more mountain hare, which is a prey generally larger than grouse. Analyses revealed that male size has indeed decreased since the 1960s, while adult females have increased in size. Our data suggest that these morphological shifts were the result of selective pressures due to changes in diet. We also found changes in the (size-independent) shape of the hawks. Relative wing and tail lengths of adult hawks became longer between 1980 and 1990 compared with the 1960-1970 period, while relative juvenile wing and tail lengths tended to decrease. As a result of these morphological changes size dimorphism between the sexes increased from the 1960s to the 1990s.

Effects of different combinations of stressors (viz. temperature, food level) on growth, developmental and survival rates of Rana temporaria tadpoles from two geographically widely (∼ 1500 km) separated populations were studied in a common garden experiment. In both populations, low temperature and low food level lead to towered growth rates and delayed metamorphosis, whereas high temperature and high food level had the opposite effect. Tadpoles from north metamorphosed earlier and exhibited higher growth rates than tadpoles from south, suggesting local adaptation to shorter growth period and cooler ambient temperature in north. Size at metamorphosis did not differ between the two populations, but when the differences in metamorphic age were accounted for, then the tadpoles from north were larger than those from south. These results suggest considerable adaptive genetic differentiation in growth rates, size and timing of metamorphosis between northern and southern R. temporaria populations. In both populations, high food levels tended to reduce tadpole survival rates and there was a negative correlation between growth and survival rates across different treatments in both populations. In general, tadpoles from north experienced high mortality rates in high food level ‐ low temperature treatments, whereas southern tadpoles experienced high mortality in high food level‐high temperature treatments. This suggest that there may be genetic differences among different populations as how they would be influenced by high nutrient loads, such as brought along for example by fertilization of forest or agricultural soils.