Browsing by Subject "MAINTENANCE"

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  • Uusi-Rasi, Kirsti; Patil, Radhika; Karinkanta, Saija; Kannus, Pekka; Tokola, Kari; Lamberg-Allardt, Christel; Sievanen, Harri (2017)
    Background: Both exercise and vitamin D are recommended means to prevent falls among older adults, but their combined effects on fallinduced injuries are scarcely studied. Methods: A 2-year follow-up of a previous 2-year randomized controlled trial with vitamin D and exercise (Ex) of 409 older home-dwelling women using a factorial 2 x 2 design (D(-)Ex(-), D(+)Ex(-), D(-)Ex(+), D(+)Ex(+)). Besides monthly fall diaries, femoral neck bone mineral density (fn-BMD), and physical functioning were assessed at 1 and 2 years after the intervention. Results: After the intervention, S-25OHD concentrations declined to baseline levels in both supplement groups. The groups did not differ for change in fn-BMD or physical functioning, except for leg extensor muscle strength, which remained about 10% greater in the exercise groups compared with the reference group (D(-)Ex(-)). There were no between-group differences in the rate of all falls, but medically attended injurious falls reduced in D+ Ex-and D(-)Ex(+) groups compared with D(-)Ex(-). However, all former treatment groups had less medically attended injured fallers, HRs (95% CI) being 0.62 (0.39-1.00) for D+ Ex-, 0.46 (0.28-0.76) for D(-)Ex(+), and 0.55 (0.34-0.88) for D(+)Ex(+), compared with D(-)Ex(-). Conclusions: Exercise-induced benefits in physical functioning partly remained 2 years after cessation of supervised training. Although there was no difference in the rate of all falls, former exercise groups continued to have lower rate of medically attended injured fallers compared with referents even 2 years after the intervention. Vitamin D without exercise was associated with less injurious falls with no difference in physical functioning.
  • Lin, Hai; Li, Wei-ping; Carlson, Synnöve (2019)
    Top-down modulation is engaged during multiple stages of working memory (WM), including expectation, encoding, and maintenance. During WM maintenance period, an "incidental cue" can bring one of the two items into a privileged state and make the privileged item be recalled with higher precision, despite being irrelevant to which one to be probed as the target. With regard to the different representational states of WM, it's unclear whether there is top-down modulation on earth sensory cortical areas. Here, We used this behavioral paradigm of "incidental cue" and event-related fMRI to investigate whether there were a privileged WM state and top-down modulation for complex stimuli including faces and natural scenes. We found that faces, not scenes, could enter into the privileged state with improved accuracy and response time of WM task. Meanwhile, cue-driven baseline activity shifts in fusiform face area (FFA) were identified by univariate analysis in the recognition of privileged faces, compared to that of nonprivileged ones. In addition, the functional connectivity between FFA and right inferior frontal junction (IFJ), middle frontal gyrus (MFG), inferior frontal gyrus, right intraparietal sulcus (IPS), right precuneus and supplementary motor area was significantly enhanced, corresponding to the improved WM performance. Moreover, FFA connectivity with IFJ and IPS could predict WM improvements. These findings indicated that privileged WM state and potential top-down modulation existed for faces, but not scenes, during WM maintenance period.
  • Lewis, Samantha C.; Joers, Priit; Willcox, Smaranda; Griffith, Jack D.; Jacobs, Howard T.; Hyman, Bradley C. (2015)
    Mitochondrial DNA (mtDNA) encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s) of its synthesis remain hotly debated. Here we have developed Caenorhabditis elegans as a convenient animal model for the study of metazoan mtDNA synthesis. We demonstrate that C. elegans mtDNA replicates exclusively by a phage-like mechanism, in which multimeric molecules are synthesized from a circular template. In contrast to previous mammalian studies, we found that mtDNA synthesis in the C. elegans gonad produces branched-circular lariat structures with multimeric DNA tails; we were able to detect multimers up to four mtDNA genome unit lengths. Further, we did not detect elongation from a displacement-loop or analogue of 7S DNA, suggesting a clear difference from human mtDNA in regard to the site(s) of replication initiation. We also identified cruciform mtDNA species that are sensitive to cleavage by the resolvase RusA; we suggest these four-way junctions may have a role in concatemer-to-monomer resolution. Overall these results indicate that mtDNA synthesis in C. elegans does not conform to any previously documented metazoan mtDNA replication mechanism, but instead are strongly suggestive of rolling circle replication, as employed by bacteriophages. As several components of the metazoan mitochondrial DNA replisome are likely phage-derived, these findings raise the possibility that the rolling circle mtDNA replication mechanism may be ancestral among metazoans.
  • Mammola, Stefano; Pavlek, Martina; Huber, Bernhard A.; Isaia, Marco; Ballarin, Francesco; Tolve, Marco; Cupic, Iva; Hesselberg, Thomas; Lunghi, Enrico; Mouron, Samuel; Graco-Roza, Caio; Cardoso, Pedro (2022)
    Species traits are an essential currency in ecology, evolution, biogeography, and conservation biology. However, trait databases are unavailable for most organisms, especially those living in difficult-to-access habitats such as caves and other subterranean ecosystems. We compiled an expert-curated trait database for subterranean spiders in Europe using both literature data (including grey literature published in many different languages) and direct morphological measurements whenever specimens were available to us. We started by updating the checklist of European subterranean spiders, now including 512 species across 20 families, of which at least 192 have been found uniquely in subterranean habitats. For each of these species, we compiled 64 traits. The trait database encompasses morphological measures, including several traits related to subterranean adaptation, and ecological traits referring to habitat preference, dispersal, and feeding strategies. By making these data freely available, we open up opportunities for exploring different research questions, from the quantification of functional dimensions of subterranean adaptation to the study of spatial patterns in functional diversity across European caves.
  • Penttila, Tero; Makynen, Heikki; Hartikainen, Juha; Hyppola, Harri; Lauri, Timo; Lehto, Mika; Lund, Juha; Raatikainen, M. J. Pekka; FinFib2 Investigators (2017)
    Background: Atrial fibrillation (AF) is a common arrhythmia that causes numerous visits to emergency departments (ED). The aim of the FinFib2 study was to evaluate whether treatment of patients with AF in ED is consistent with the contemporary European Society of Cardiology (ESC) management guidelines. Here we report the results of antiarrhythmic drug therapy (AAD) in ED. Methods: All patients within the two-week study period whose primary reason for the ED visit was symptomatic AF were included into this prospective multicentre study. Comprehensive data on factors contributing to the treatment of AF were collected, including a data of previous use of ADDs, and changes made for them during a visit in ED. Results: The study population consisted of 1013 consecutive patients (mean age 70 +/- 13 years, 47.6% female). The mean European Heart Rhythm Association (EHRA) symptom score was 2.2 +/- 0.8. Rhythm control strategy was opt for 498 (63.8%) and 140 (64.5%) patients with previously and newly diagnosed AF, respectively. In patients with previously diagnosed AF the most frequently used AAD was a beta blocker (80.9%). Prior use of class I (11.4%) and III (9.1%) AADs as well as start or adjustment of their dosage (7.4%) were uncommon. Most of the patients with newly diagnosed AF were prescribed a beta blocker (71.0%) or a calcium channel antagonist (24.0%), and only two of them received class I or class III AADs. Conclusions: Our data demonstrated that in patients presenting to the ED with recurrent symptomatic AF and aimed for rhythm control strategy, the use of class I and class III AADs was rare despite ESC guideline recommendations. It is possible that early adaptation of a more aggressive rhythm control strategy might improve a quality of life for symptomatic patients and alleviate the ED burden associated with AF. Beta blockers were used by majority of patients as rate control therapy both in rate and rhythm control groups.
  • Coppock, Rachel L.; Lindeque, Penelope K.; Cole, Matthew; Galloway, Tamara S.; Nakki, Pinja; Birgani, Hannah; Richards, Saskiya; Queiros, Ana M. (2021)
    Microplastics are ubiquitous in the marine environment, however, the mechanisms governing their uptake by, and burial within, seabed habitats are poorly understood. In this study, microplastic burial and its impact on fauna-mediated sedimentary processes was quantified at three coastal sites, and the potential contribution of burrowing faunal communities to this process assessed via functional trait diversity analysis of field data. In addition, laboratory exposures were used to assess whether sediment-processing undertaken by the brittlestar Amphiura filiformis, a key species in the sampled area, could explain the burial of microplastic fibres. Field observations confirmed broad-scale burial of microplastics across the coastal seabed, consistent across sites and seasons, with microplastic sequestration linked to benthic-pelagic exchange pathways, driven by burrowing fauna. Brittlestars were observed to bury and line their burrow walls with microfibres during experiments, and their burial activity was also modified following exposure to nylon fibres, relative to controls. Collectively, these results indicate that biodiverse and functionally important seabed habitats act as microplastic sinks, with burrowing fauna contributing to this process via well-known benthic-pelagic pathways, the rates of which are modified by plastic exposure.
  • Miettinen, Reijo; Kerosuo, Hannele; Metsälä, Teemu; Paavola, Sami (2018)
    Purpose - The purpose of this paper is to study the conditions of the building information modelling (BIM) implementation in facility management (FM) specifically from the point of view of different groups of FM practitioners, and the FM infrastructures already in use. Design/methodology/approach - A literature review on the gap between the uses of BIM in design and FM has been done. The key professional groups of FM in the Premises Centre of the City of Helsinki were interviewed on the information tools they use, and the needs and impediments of the BIM implementation in the FM. Cultural-historical activity theory is used as a theoretical framework. Findings - The literature discussing the BIM implementation tends to omit the analysis of the existing FM information systems and software tools in use. The challenge in the BIM implementation is in which ways the relevant information included in the BIM models could be integrated with these systems. No well-articulated problems or developmental contradictions came up that would demand the investment in the BIM implementation. Practical implications - The results call for experimenting with incremental implementation of BIM in different FM activities and in the FM information infrastructures in use. Originality/value - This paper studies empirically different FM activities and information systems used by the professional groups. Such studies are needed for a realistic view of the potential integration of the BIM information to the FM information systems.
  • Buso, Marion E. C.; Seimon, Radhika V.; McClintock, Sally; Muirhead, Roslyn; Atkinson, Fiona S.; Brodie, Shannon; Dodds, Jarron; Zibellini, Jessica; Das, Arpita; Wild-Taylor, Anthony L.; Burk, Jessica; Fogelholm, Mikael; Raben, Anne; Brand-Miller, Jennie C.; Sainsbury, Amanda (2021)
    Background: Previous research showed that weight-reducing diets increase appetite sensations and/or circulating ghrelin concentrations for up to 36 months, with transient or enduring perturbations in circulating concentrations of the satiety hormone peptide YY. Objective: This study assessed whether a diet that is higher in protein and low in glycemic index (GI) may attenuate these changes. Methods: 136 adults with pre-diabetes and a body mass index of >= 25 kg/m(2) underwent a 2-month weight-reducing total meal replacement diet. Participants who lost >= 8% body weight were randomized to one of two 34-month weight-maintenance diets: a higher-protein and moderate-carbohydrate (CHO) diet with low GI, or a moderate-protein and higher-CHO diet with moderate GI. Both arms involved recommendations to increase physical activity. Fasting plasma concentrations of total ghrelin and total peptide YY, and appetite sensations, were measured at 0 months (pre-weight loss), at 2 months (immediately post-weight loss), and at 6, 12, 24, and 36 months. Results: There was a decrease in plasma peptide YY concentrations and an increase in ghrelin after the 2-month weight-reducing diet, and these values approached pre-weight-loss values by 6 and 24 months, respectively (P = 0.32 and P = 0.08, respectively, vs. 0 months). However, there were no differences between the two weight-maintenance diets. Subjective appetite sensations were not affected by the weight-reducing diet nor the weight-maintenance diets. While participants regained an average of similar to 50% of the weight they had lost by 36 months, the changes in ghrelin and peptide YY during the weight-reducing phase did not correlate with weight regain. Conclusion: A higher-protein, low-GI diet for weight maintenance does not attenuate changes in ghrelin or peptide YY compared with a moderate-protein, moderate-GI diet.
  • Chevance, Guillaume; Baretta, Dario; Heino, Matti; Perski, Olga; Olthof, Merlijn; Klasnja, Predrag; Hekler, Eric; Godino, Job (2021)
    Despite the positive health effect of physical activity, one third of the world's population is estimated to be insufficiently active. Prior research has mainly investigated physical activity on an aggregate level over short periods of time, e.g., during 3 to 7 days at baseline and a few months later, post-intervention. To develop effective interventions, we need a better understanding of the temporal dynamics of physical activity. We proposed here an approach to studying walking behavior at "high-resolution" and by capturing the idiographic and day-to-day changes in walking behavior. We analyzed daily step count among 151 young adults with overweight or obesity who had worn an accelerometer for an average of 226 days (similar to 25,000 observations). We then used a recursive partitioning algorithm to characterize patterns of change, here sudden behavioral gains and losses, over the course of the study. These behavioral gains or losses were defined as a 30% increase or reduction in steps relative to each participants' median level of steps lasting at least 7 days. After the identification of gains and losses, fluctuation intensity in steps from each participant's individual time series was computed with a dynamic complexity algorithm to identify potential early warning signals of sudden gains or losses. Results revealed that walking behavior change exhibits discontinuous changes that can be described as sudden gains and losses. On average, participants experienced six sudden gains or losses over the study. We also observed a significant and positive association between critical fluctuations in walking behavior, a form of early warning signals, and the subsequent occurrence of sudden behavioral losses in the next days. Altogether, this study suggests that walking behavior could be well understood under a dynamic paradigm. Results also provide support for the development of "just-in-time adaptive" behavioral interventions based on the detection of early warning signals for sudden behavioral losses.
  • Williams, Monique; Valayannopoulos, Vassili; Altassan, Ruqaiah; Chung, Wendy K.; Heijboer, Annemieke C.; Keng, Wei Teik; Lapatto, Risto; McClean, Patricia; Mulder, Margot F.; Tylki-Szymanska, Anna; Walenkamp, Marie-Jose E.; Alfadhel, Majid; Alakeel, Hajar; Salomons, Gajja S.; Eyaid, Wafaa; Wamelink, Mirjam M. C. (2019)
    BackgroundTransaldolase deficiency (TALDO-D) is a rare autosomal recessive inborn error of the pentose phosphate pathway. Since its first description in 2001, several case reports have been published, but there has been no comprehensive overview of phenotype, genotype, and phenotype-genotype correlation. MethodsWe performed a retrospective questionnaire and literature study of clinical, biochemical, and molecular data of 34 patients from 25 families with proven TALDO-D. In some patients, endocrine abnormalities have been found. To further evaluate these abnormalities, we performed biochemical investigations on blood of 14 patients. Results and conclusionsMost patients (n =22) had an early-onset presentation (prenatally or before 1 month of age); 12 patients had a late-onset presentation (3 months to 9 years). Main presenting symptoms were intrauterine growth restriction, dysmorphic facial features, congenital heart disease, anemia, thrombocytopenia, and hepato(spleno)megaly. An older sib of two affected patients was asymptomatic until the age of 9 years, and only after molecular diagnosis was hepatomegaly noted. In some patients, there was gonadal dysfunction with low levels of testosterone and secondary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) abnormalities later in life. This overview provides information that can be helpful for managing patients and counseling families regarding prognosis. Diagnostic guidelines, possible genotype-phenotype correlations, treatment options, and pathophysiological disease mechanisms are proposed.
  • Karsisto, Virve; Tijm, Sander; Nurmi, Pertti (2017)
    High-quality road condition forecasts are a prerequisite for road authorities to ensure wintertime road safety. Harsh winter conditions can cause problems for traffic not only in countries where snowy winters are common but also in regions where the temperature drops below the freezing point occasionally. This study reports on the evaluation of the Royal Netherlands Meteorological Institute's (KNMI) new road weather forecasting model by comparing it with the Finnish Meteorological Institute's (FMI) road weather model, both run for 321 Dutch road weather stations, four times daily (0300, 0900, 1500, and 2100 UTC) during the test period, 15 January-28 February 2015. Road surface temperature forecasts by both models were evaluated against observations. The KNMI model produced slightly more accurate forecasts than the FMI model. The main reason for the difference is probably due to the optimization of the physical properties of the KNMI model for the Netherlands, whereas the FMI model is designed for quite different Finnish wintertime meteorological conditions. However, in general the road surface temperature forecasts were of quite comparable quality.
  • Chmielarz, Piotr; Konovalova, Julia; Najam, Syeda Sadia; Alter, Heike; Piepponen, Timo Petteri; Erfle, Holger; Sonntag, Kai C.; Schutz, Gunther; Vinnikov, Ilya A.; Domanskyi, Andrii (2017)
    MicroRNAs (miRs) are important post-transcriptional regulators of gene expression implicated in neuronal development, differentiation, aging and neurodegenerative diseases, including Parkinson's disease (PD). Several miRs have been linked to PD-associated genes, apoptosis and stress response pathways, suggesting that deregulation of miRs may contribute to the development of the neurodegenerative phenotype. Here, we investigate the cell-autonomous role of miR processing RNAse Dicer in the functional maintenance of adult dopamine (DA) neurons. We demonstrate a reduction of Dicer in the ventral midbrain and altered miR expression profiles in laser-microdissected DA neurons of aged mice. Using a mouse line expressing tamoxifen-inducible CreERT2 recombinase under control of the DA transporter promoter, we show that a tissue-specific conditional ablation of Dicer in DA neurons of adult mice led to decreased levels of striatal DA and its metabolites without a reduction in neuronal body numbers in hemizygous mice (Dicer(HET)) and to progressive loss of DA neurons with severe locomotor deficits in nullizygous mice (Dicer(CKO)). Moreover, we show that pharmacological stimulation of miR biosynthesis promoted survival of cultured DA neurons and reduced their vulnerability to thapsigargin-induced endoplasmic reticulum stress. Our data demonstrate that Dicer is crucial for maintenance of adult DA neurons, whereas a stimulation of miR production can promote neuronal survival, which may have direct implications for PD treatment.
  • van der Kolk, Birgitta W.; Muniandy, Maheswary; Kaminska, Dorota; Alvarez, Marcus; Ko, Arthur; Miao, Zong; Valsesia, Armand; Langin, Dominique; Vaittinen, Maija; Paakkonen, Mirva; Jokinen, Riikka; Kaye, Sanna; Heinonen, Sini; Virtanen, Kirsi A.; Andersson, Daniel P.; Männistö, Ville; Saris, Wim H.; Astrup, Arne; Ryden, Mikael; Blaak, Ellen E.; Pajukanta, Paivi; Pihlajamaki, Jussi; Pietiläinen, Kirsi H. (2021)
    Context: Mitochondria are essential for cellular energy homeostasis, yet their role in subcutaneous adipose tissue (SAT) during different types of weight-loss interventions remains unknown. Objective: To investigate how SAT mitochondria change following diet-induced and bariatric surgery-induced weight-loss interventions in 4 independent weight-loss studies. Methods: The DiOGenes study is a European multicenter dietary intervention with an 8-week low caloric diet (LCD; 800 kcal/d; n = 261) and 6-month weight-maintenance (n = 121) period. The Kuopio Obesity Surgery study (KOBS) is a Roux-en-Y gastric bypass (RYGB) surgery study (n = 172) with a 1-year follow-up. We associated weight-loss percentage with global and 2210 mitochondria-related RNA transcripts in linear regression analysis adjusted for age and sex. We repeated these analyses in 2 studies. The Finnish CRYO study has a 6-week LCD (800-1000 kcal/d; n = 19) and a 10.5-month follow-up. The Swedish DEOSH study is a RYGB surgery study with a 2-year (n = 49) and 5-year (n = 37) follow-up. Results: Diet-induced weight loss led to a significant transcriptional downregulation of oxidative phosphorylation (DiOGenes; ingenuity pathway analysis [IPA] z-scores: -8.7 following LCD, -4.4 following weight maintenance; CRYO: IPA z-score: -5.6, all P < 0.001), while upregulation followed surgery-induced weight loss (KOBS: IPA z-score: 1.8, P < 0.001; in DEOSH: IPA z-scores: 4.0 following 2 years, 0.0 following 5 years). We confirmed an upregulated oxidative phosphorylation at the proteomics level following surgery (IPA z-score: 3.2, P < 0.001). Conclusions: Differentially regulated SAT mitochondria-related gene expressions suggest qualitative alterations between weight-loss interventions, providing insights into the potential molecular mechanistic targets for weight-loss success.
  • European Soc Blood Marrow Transpla; HOVON-SAKK (2018)
    Background. Disease recurrence remains the major cause of death in adults with acute myeloid leukaemia (AML) treated using either intensive chemotherapy (IC) or allogenic stem cell transplantation (allo-SCT). Aims. The timely delivery of maintenance drug or cellular therapies represent emerging strategies with the potential to reduce relapse after both treatment modalities, but whilst the determinants of overall relapse risk have been extensively characterized the factors determining the timing of disease recurrence have not been characterized. Materials and Methods. We have therefore examined, using a series of sequential landmark analyses, relapse kinetics in a cohort of 2028 patients who received an allo-SCT for AML in CR1 and separately 570 patients treated with IC alone. Results. In the first 3 months after allo-SCT, the factors associated with an increased risk of relapse included the presence of the FLT3-ITD (P <0.001), patient age (P = 0.012), time interval from CR1 to transplant (P <0.001) and donor type (P = 0.03). Relapse from 3 to 6 months was associated with a higher white cell count at diagnosis (P = 0.001), adverse-risk cytogenetics (P <0.001), presence of FLT3-ITD mutation (P <0.001) and time interval to achieve first complete remission (P = 0.013). Later relapse was associated with adverse cytogenetics, mutated NPM1, absence of chronic graft-versus-host disease (GVHD) and the use of in vivo T-cell depletion. In patients treated with IC alone, the factors associated with relapse in the first 3 months were adverse-risk cytogenetics (P <0.001) and FLT3-ITD status (P = 0.001). The factors predicting later relapse were the time interval from diagnosis to CR1 (P = 0.22) and time interval from CR1 to IC (P = 0.012). Discussion and Conclusion. Taken together, these data provide novel insights into the biology of disease recurrence after both allo-SCT and IC and have the potential to inform the design of novel maintenance strategies in both clinical settings.
  • Toomey, E.; Hardeman, W.; Hankonen, N.; Byrne, M.; McSharry, J.; Matvienko-Sikar, K.; Lorencatto, F. (2020)
    Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.
  • Livingstone, Katherine M.; Celis-Morales, Carlos; Papandonatos, George D.; Erar, Bahar; Florez, Jose C.; Jablonski, Kathleen A.; Razquin, Cristina; Marti, Amelia; Heianza, Yoriko; Huang, Tao; Sacks, Frank M.; Svendstrup, Mathilde; Sui, Xuemei; Church, Timothy S.; Jääskeläinen, Tiina; Lindstrom, Jaana; Tuomilehto, Jaakko; Uusitupa, Matti; Rankinen, Tuomo; Saris, Wim H. M.; Hansen, Torben; Pedersen, Oluf; Astrup, Arne; Sorensen, Thorkild I. A.; Qi, Lu; Bray, George A.; Martinez-Gonzalez, Miguel A.; Martinez, J. Alfredo; Franks, Paul W.; McCaffery, Jeanne M.; Lara, Jose; Mathers, John C. (2016)
    OBJECTIVE To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity. RESULTS We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category. CONCLUSIONS We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.
  • Binder, Martin; Chmielarz, Piotr; Mckinnon, Peter J.; Biggs, Leah C.; Thesleff, Irma; Balic, Anamaria (2019)
    Continuous growth of the mouse incisor teeth is due to the life-long maintenance of epithelial stem cells (SCs) in their niche called cervical loop (CL). Several signaling factors regulate SC maintenance and/or their differentiation to achieve organ homeostasis. Previous studies indicated that Hedgehog signaling is crucial for both the maintenance of the SCs in the niche, as well as for their differentiation. How Hedgehog signaling regulates these two opposing cellular behaviors within the confinement of the CL remains elusive. In this study, we used in vitro organ and cell cultures to pharmacologically attenuate Hedgehog signaling. We analyzed expression of various genes expressed in the SC niche to determine the effect of altered Hedgehog signaling on the cellular hierarchy within the niche. These genes include markers of SCs (Sox2 and Lgr5) and transit-amplifying cells (P-cadherin, Sonic Hedgehog, and Yap). Our results show that Hedgehog signaling is a critical survival factor for SCs in the niche, and that the architecture and the diversity of the SC niche are regulated by multiple Hedgehog ligands. We demonstrated the presence of an additional Hedgehog ligand, nerve-derived Desert Hedgehog, secreted in the proximity of the CL. In addition, we provide evidence that Hedgehog receptors Ptch1 and Ptch2 elicit independent responses, which enable multimodal Hedgehog signaling to simultaneously regulate SC maintenance and differentiation. Our study indicates that the cellular hierarchy in the continuously growing incisor is a result of complex interplay of two Hedgehog ligands with functionally distinct Ptch receptors. Stem Cells 2019;37:1238-1248
  • Koskenpato, Katja; Lehikoinen, Aleksi; Lindstedt, Carita; Karell, Patrik (2020)
    Camouflage may promote fitness of given phenotypes in different environments. The tawny owl (Strix aluco) is a color polymorphic species with a gray and brown morph resident in the Western Palearctic. A strong selection pressure against the brown morph during snowy and cold winters has been documented earlier, but the selection mechanisms remain unresolved. Here, we hypothesize that selection favors the gray morph because it is better camouflaged against predators and mobbers in snowy conditions compared to the brown one. We conducted an online citizen science experiment where volunteers were asked to locate a gray or a brown tawny owl specimen from pictures taken in snowy and snowless landscapes. Our results show that the gray morph in snowy landscapes is the hardest to detect whereas the brown morph in snowy landscapes is the easiest to detect. With an avian vision model, we show that, similar to human perceivers, the brown morph is more conspicuous than the gray against coniferous tree trunks for a mobbing passerine. We suggest that with better camouflage, the gray morph may avoid mobbers and predators more efficiently than the brown morph and thus survive better in snowy environments. As winters are getting milder and shorter in the species range, the selection periods against brown coloration may eventually disappear or shift poleward.
  • Møller, Grith; Rikardt Andersen, Jens; Ritz, Christian; P. Silvestre, Marta; Navas-Carretero, Santiago; Jalo, Elli; Christensen, Pia; Simpson, Elizabeth; Taylor, Moira; Martinez, J. Alfredo; Macdonald, Ian; Swindell, Nils; Mackintosh, Kelly A.; Stratton, Gareth; Fogelholm, Mikael; Larsen, Thomas M.; Poppitt, Sally D.; Dragsted, Lars O.; Raben, Anne (2018)
    Concerns about detrimental renal effects of a high-protein intake have been raised due to an induced glomerular hyperfiltration, since this may accelerate the progression of kidney disease. The aim of this sub-study was to assess the effect of a higher intake of protein on kidney function in pre-diabetic men and women, aged 55 years and older. Analyses were based on baseline and one-year data in a sub-group of 310 participants included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World). Protein intake was estimated from four-day dietary records and 24-hour urinary urea excretion. We used linear regression to assess the association between protein intake after one year of intervention and kidney function markers: creatinine clearance, estimated glomerular filtration rate (eGFR), urinary albumin/creatinine ratio (ACR), urinary urea/creatinine ratio (UCR), serum creatinine, and serum urea before and after adjustments for potential confounders. A higher protein intake was associated with a significant increase in UCR (p = 0.03) and serum urea (p = 0.05) after one year. There were no associations between increased protein intake and creatinine clearance, eGFR, ACR, or serum creatinine. We found no indication of impaired kidney function after one year with a higher protein intake in pre-diabetic older adults.