To examine the independent and combined associations of obesity and muscle strength with mortality in adult men and women.
Follow-up study with 33 years of mortality follow-up.
A total of 3594 men ...and women aged 50-91 years at baseline with 3043 deaths during the follow-up.
Body mass index (BMI) and handgrip strength were measured at baseline.
Based on Cox models adjusted for age, sex, education, smoking, alcohol use, physical activity and chronic conditions, baseline obesity (BMI ≥30 kg m(-2)) was associated with mortality among participants aged 50-69 years (hazard ratio (HR) 1.14, 95% confidence interval (CI), 1.01-1.28). Among participants aged 70 years and older, overweight and obesity were protective (HR 0.77, 95% CI, 0.66-0.89 and HR 0.76, 95% CI, 0.62-0.92). High handgrip strength was inversely associated with mortality among participants aged 50-69 (HR 0.89, 95% CI, 0.80-1.00) and 70 years and older (HR 0.78, 95% CI, 0.66-0.93). Compared to normal-weight participants with high handgrip strength, the highest mortality risk was observed among obese participants with low handgrip strength (HR 1.23, 95% CI, 1.04-1.46) in the 50-69 age group and among normal-weight participants with low handgrip strength (HR 1.30, 95% CI, 1.09-1.54) among participants aged 70+ years. In addition, in the old age group, overweight and obese participants with high handgrip strength had significantly lower mortality than normal-weight participants with high handgrip strength (HR 0.79, 95% CI, 0.67-0.92 and HR 0.77, 95% CI, 0.63-0.94).
Both obesity and low handgrip strength, independent of each other, predict the risk of death in adult men and women with additive pattern. The predictive value of obesity varies by age, whereas low muscle strength predicts mortality in all age groups aged>50 years and across all BMI categories. When promoting health among older adults, more attention should be paid to physical fitness in addition to body weight and adiposity.
Determining the date of snowmelt clearance is an important issue for hydrological and climate research. Spaceborne radiometers are ideally suited for global snowmelt monitoring. In this paper, four ...different algorithms are used to determine the snowmelt date from Scanning Multichannel Microwave Radiometer and Special Sensor Microwave/Imager data for a nearly 30-year period. Algorithms are based on thresholding channel differences, on applying neural networks, and on time series analysis. The results are compared with ground-based observations of snow depth and snowmelt status available through the Russian INTAS-SSCONE observation database. Analysis based on Moderate Resolution Imaging Spectroradiometer data indicates that these pointwise observations are applicable as reference data. The obtained error estimates indicate that the algorithm based on time series analysis has the highest performance. Using this algorithm, a time series of the snowmelt from 1979 to 2007 is calculated for the whole Eurasia showing a trend of an earlier snow clearance. The trend is statistically significant. The results agree with earlier research. The novelty here is the demonstration and validation of estimates for a large continental scale (for areas dominated by boreal forests) using extensive reference data sets.
Purpose
To compare three health-related quality of life (HRQoL) instruments in detecting the effect of distance visual acuity (VA) on generic HRQoL in an adult population.
Methods
We used ...cross-sectional, population-based data from a nationwide health survey conducted in Finland in 2011–2012. It included three self-reported HRQoL instruments, EuroQol-5 Dimension (EQ-5D), 15D, and EUROHIS-QOL8, and a health examination in which habitual distance VA was measured binocularly. We assessed 3764 survey participants aged 30 years and older with information available on these parameters. The comparability and sensitivity of the instruments were evaluated using Pearson correlation coefficients and multivariable linear regression in different VA groups.
Results
EQ-5D and 15D index scores showed strong positive correlation (0.65–0.74) with each other regardless of distance VA, whereas EUROHIS-QOL8 index score showed moderate-to-strong correlation (0.46–0.79) with EQ-5D and 15D. All three instruments showed a negative trend with deteriorating VA, although EQ-5D and 15D showed better sensitivity than EUROHIS-QOL8. When adjusted for age, gender, and co-morbidities, adequate vision (VA 0.63–0.8), weak vision (VA 0.32–0.5), and impaired vision or worse (VA ≤ 0.25) were independently associated with declined EQ-5D and 15D, whereas declined EUROHIS-QOL8 was associated only with adequate and weak vision.
Conclusion
All three instruments can be viable tools in evaluating the relation between vision and HRQoL. While 15D is preferred due to its wide coverage of dimensions, EQ-5D can be an equal alternative, as it has less respondent burden. The feasibility of EUROHIS-QOL8 on detecting differences between lower VA levels may require further evidence.
Preeclampsia (PE) is a common vascular disease of pregnancy with genetic predisposition. Dysregulation of the complement system has been implicated, but molecular mechanisms are incompletely ...understood. In this study, we determined the potential linkage of severe PE to the most central complement gene,
. Three cohorts of Finnish patients and controls were recruited for a genetic case-control study. Participants were genotyped using Sequenom genotyping and Sanger sequencing. Initially, we studied 259 Finnish patients with severe PE and 426 controls from the Southern Finland PE and the Finnish population-based PE cohorts. We used a custom-made single nucleotide polymorphism (SNP) genotyping assay consisting of 98 SNPs in 18 genes that encode components of the complement system. Following the primary screening,
was selected as the candidate gene and consequently Sanger sequenced. Fourteen SNPs from
were also genotyped by a Sequenom panel in 960 patients with severe PE and 705 controls, including already sequenced individuals. Three of the 43 SNPs observed within
were associated with severe PE: rs2287845 (
= 0.038, OR = 1.158), rs366510 (
= 0.039, OR = 1.158), and rs2287848 (
= 0.041, OR = 1.155). We also discovered 16 SNP haplotypes with extreme linkage disequilibrium in the middle of the gene with a protective (
= 0.044, OR = 0.628) or a predisposing (
= 0.011, OR = 2.110) effect to severe PE depending on the allele combination. Genetic variants associated with PE are located in key domains of C3 and could thereby influence the function of C3. This is, as far as we are aware, the first candidate gene in the complement system with an association to a clinically relevant PE subphenotype, severe PE. The result highlights a potential role for the complement system in the pathogenesis of PE and may help in defining prognostic and therapeutic subgroups of preeclamptic women.
Transmission spectroscopy at UV wavelengths is a rich and largely unexplored source of information about the upper atmospheres of extrasolar planets. So far, UV transit observations have led to the ...detection of atomic hydrogen, oxygen, and ionized carbon in the upper atmosphere of HD209458b. The interpretation of these observations is controversial--it is not clear if the absorption arises from an escaping atmosphere interacting with the stellar radiation and stellar wind, or from the thermosphere inside the Roche lobe. In this paper, we introduce an empirical model that can be used to analyze UV transit depths of extrasolar planets. We use this model to interpret the transits of HD209458b in the H I 1216 and the O I 1304 triplet emission lines. The results indicate that the mean temperature of the thermosphere is T = 8000-11,000 K and that the H2/H dissociation front is located at pressures between p = 0.1 and 1 Delta *mbar, which correspond to a distance r 1.1 Rp from the center of the planet. The upper boundary of the model thermosphere is located at r = 2.7-3 Rp , above which the atmosphere is mostly ionized. We find that the H I transit depth in the wings of the H Ly Delta *a line reflects the optical depth of the thermosphere, but that the atmosphere also overflows the Roche lobe. By assuming a solar mixing ratio of oxygen, we obtain an O I transit depth that is statistically consistent with the observations. An O I transit depth comparable to the H I transit depth is possible if the atmosphere is undergoing fast hydrodynamic escape, the O/H ratio is supersolar, or if a significant quantity of neutral oxygen is found outside the Roche lobe. We find that the observations can be explained solely by absorption in the upper atmosphere and extended clouds of energetic neutral atoms or atoms strongly perturbed by radiation pressure are not required. Due to the large uncertainty in the data, repeated observations are necessary to better constrain the O I transit depths and thus the composition of the thermosphere.
Standard of care for cancer is commonly a combination of surgery with radiotherapy or chemoradiotherapy. However, in some advanced cancer patients this approach might still remaininefficient and may ...cause many side effects, including severe complications and even death. Oncolytic viruses exhibit different anti-cancer mechanisms compared with conventional therapies, allowing the possibility for improved effect in cancer therapy. Chemotherapeutics combined with oncolytic viruses exhibit stronger cytotoxic responses and oncolysis. Here, we have investigated the systemic delivery of the oncolytic adenovirus and paclitaxel encapsulated in extracellular vesicles (EV) formulation that, in vitro, significantly increased the transduction ratio and the infectious titer when compared with the virus and paclitaxel alone. We demonstrated that the obtained EV formulation reduced the in vivo tumor growth in animal xenograft model of human lung cancer. Indeed, we found that combined treatment of oncolytic adenovirus and paclitaxel encapsulated in EV has enhanced anticancer effects both in vitro and in vivo in lung cancer models. Transcriptomic comparison carried out on the explanted xenografts from the different treatment groups revealed that only 5.3% of the differentially expressed genes were overlapping indicating that a de novo genetic program is triggered by the presence of the encapsulated paclitaxel: this novel genetic program might be responsible of the observed enhanced antitumor effect. Our work provides a promising approach combining anticancer drugs and viral therapies by intravenous EV delivery as a strategy for the lung cancer treatment.
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To cite this article: Laatikainen T, von Hertzen L, Koskinen J‐P, Mäkelä MJ, Jousilahti P, Kosunen TU, Vlasoff T, Ahlström M, Vartiainen E, Haahtela T. Allergy gap between Finnish and Russian Karelia ...on increase. Allergy 2011; 66: 886–892.
Background: Multinational time‐trend analyses of atopic disease have shown that the East–West gradients in prevalence are shrinking. We set out to clarify whether the disparities in the occurrence of atopy and atopic diseases in Finnish and Russian Karelia during the past 10 years have diminished and how the prevalence of atopy has evolved with successive years of birth.
Methods: Two surveys with identical methodology were performed in 1997/1998 and 2007. The study population comprised randomly selected adults, aged 25–54 years, from Finnish and Russian Karelia. Serum samples were collected for total and specific IgE measurements. Clinical data were obtained by questionnaires.
Results: Sensitization rates to birch pollen increased from 7.8% to 14.8% (P < 0.001) and to cat from 6.1% to 10.8% (P < 0.001) in Finland. In Russia, no significant increase was found. Contrary to this, total IgE remained stable in Finland but decreased significantly (P < 0.001) in Russia. Analyses based on years of birth revealed that the prevalence of sensitization to allergens increased with successive birth years in Finland, but remained stable in Russia. Over the 10 years, self‐reported physician‐diagnosed asthma increased from 5.5% to 8.1% (P = 0.05) and hay fever from 8.1% to 13.2% (P < 0.001) in Finland.
Conclusions: Disparities in the prevalence of atopy and atopic disease between Finnish and Russian Karelia have further grown. The ‘allergy epidemic’ continues in Finland and is mainly attributable to the years of birth effect shown in atopy prevalence. In Russia, no signs of the epidemic are discernible, although the decrease in total IgE may indicate a change in environmental exposure.
Dysregulation of the developmentally important Notch signaling pathway is implicated in several types of cancer, including breast cancer. However, the specific roles and regulation of the four ...different Notch receptors have remained elusive. We have previously reported that the oncogenic PIM kinases phosphorylate Notch1 and Notch3. Phosphorylation of Notch1 within the second nuclear localization sequence of its intracellular domain (ICD) enhances its transcriptional activity and tumorigenicity. In this study, we analyzed Notch3 phosphorylation and its functional impact. Unexpectedly, we observed that the PIM target sites are not conserved between Notch1 and Notch3. Notch3 ICD (N3ICD) is phosphorylated within a domain, which is essential for formation of a transcriptionally active complex with the DNA-binding protein CSL. Through molecular modeling, X-ray crystallography, and isothermal titration calorimetry, we demonstrate that phosphorylation of N3ICD sterically hinders its interaction with CSL and thereby inhibits its CSL-dependent transcriptional activity. Surprisingly however, phosphorylated N3ICD still maintains tumorigenic potential in breast cancer cells under estrogenic conditions, which support PIM expression. Taken together, our data indicate that PIM kinases modulate the signaling output of different Notch paralogs by targeting distinct protein domains and thereby promote breast cancer tumorigenesis via both CSL-dependent and CSL-independent mechanisms.
Simultaneously transparent and flexible conductive materials are in demand to follow the current trend in flexible technology. The search for materials with compliant optoelectronic properties, while ...simultaneously retaining their electric conductivity at high strain deformation, comprises promising opportunities in modern nanotechnology. Copper iodide (CuI) is not only the most transparent and highly conductive p-type material, but its optimization has contributed to improved
ZT
values in planar thin-film thermoelectrics. In this work, the readiness of CuI thin films to transparent, flexible technology is evidenced. A maximum
ZT
value of 0.29 for single CuI thin films of
ca.
300 nm in thickness is reported. Values of open-circuit voltage
V
oc
, short circuit current
I
sc
and power output of p-n thermoelectric modules of Gallium-doped zinc oxide (GZO) and CuI thin films deposited on a transparent flexible Kapton® (type CS) substrate are reported, and a prototype of a flexible transparent thermoelectric generator based on 17 p-n modules was constructed. Bending analysis of CuI thin films reveals interesting, distinct results when submitted to compression and tension analysis - a behaviour not seen in conventional semiconducting thin films under equivalent strain conditions. A plausible account for such diversity is also included.
Simultaneously transparent and flexible conductive materials are in demand to follow the current trend in flexible technology. A highly transparent and flexible thermoelectric generator of 17 p-n modules was constructed based on copper iodide thin films.
We describe a detailed study on the properties of alkali atoms in extrasolar giant planets, and specifically focus on their role in generating the atmospheric free electron densities, as well as ...their impact on the transit depth observations. We focus our study on the case of HD209458b, and we show that photoionization produces a large electron density in the middle atmosphere that is about two orders of magnitude larger than the density anticipated from thermal ionization. Our purely photochemical calculations, though, result in a much larger transit depth for K than observed for this planet. This result does not change even if the roles of molecular chemistry and excited state chemistry are considered for the alkali atoms. In contrast, the model results for the case of exoplanet XO-2b are in good agreement with the available observations. Given these results we discuss other possible scenarios, such as changes in the elemental abundances, changes in the temperature profiles, and the possible presence of clouds, which could potentially explain the observed HD209458b alkali properties. We find that most of these scenarios cannot explain the observations, with the exception of a heterogeneous source (i.e., clouds or aerosols) under specific conditions, but we also note the discrepancies among the available observations.
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