| 1. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 2. |
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| 3. |
- Justice, Anne E., et al.
(författare)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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| 4. |
- Do, Ron, et al.
(författare)
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Common variants associated with plasma triglycerides and risk for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
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Tidskriftsartikel (refereegranskat)abstract
- Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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| 5. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 6. |
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| 9. |
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| 11. |
- Bannuru, R. R., et al.
(författare)
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OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis
- 2019
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. Methods: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Results: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. Conclusion: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.
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| 12. |
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| 13. |
- Naukkarinen, J., et al.
(författare)
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Characterising metabolically healthy obesity in weight-discordant monozygotic twins
- 2014
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Ingår i: Diabetologia. - New York, USA : Springer. - 0012-186X .- 1432-0428. ; 57:1, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this ‘metabolically healthy obesity’ (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon.Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (∆) in BMI ≥3 kg/m2), aged 22.8–35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT.Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics.Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO.
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| 19. |
- Moilanen, A. M., et al.
(författare)
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WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Aims In a recent genome-wide association study, WD-repeat domain 12 (WDR12) was associated with early-onset myocardial infarction (MI). However, the function of WDR12 in the heart is unknown. We characterized cardiac expression of WDR12, used adenovirus-mediated WDR12 gene delivery to examine effects of WDR12 on left ventricular (LV) remodeling, and analyzed relationship between MI associated WDR12 allele and cardiac function in human subjects. LV WDR12 protein levels were increased in patients with dilated cardiomyopathy and rats post-infarction. In normal adult rat hearts, WDR12 gene delivery into the anterior wall of the LV decreased interventricular septum diastolic and systolic thickness and increased the diastolic and systolic diameters of the LV. Moreover, LV ejection fraction (9.1%, P<0.05) and fractional shortening (12.2%, P<0.05) were declined. The adverse effects of WDR12 gene delivery on cardiac function were associated with decreased cellular proliferation, activation of p38 mitogen-activated protein kinase (MAPK)/heat shock protein (HSP) 27 pathway, and increased protein levels of Block of proliferation 1 (BOP1), essential for ribosome biogenesis. Post-infarction WDR12 gene delivery decreased E/A ratio (32%, P<0.05) suggesting worsening of diastolic function. In human subjects, MI associated WDR12 allele was associated significantly with diastolic dysfunction and left atrial size. WDR12 triggers distinct deterioration of cardiac function in adult rat heart and the MI associated WDR12 variant is associated with diastolic dysfunction in human subjects.
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| 20. |
- Moilanen, Lauri J., et al.
(författare)
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TRPA1 Contributes to the Acute Inflammatory Response and Mediates Carrageenan-Induced Paw Edema in the Mouse
- 2012
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Transient receptor potential ankyrin 1 (TRPA1) is an ion channel involved in thermosensation and nociception. TRPA1 is activated by exogenous irritants and also by oxidants formed in inflammatory reactions. However, our understanding of its role in inflammation is limited. Here, we tested the hypothesis that TRPA1 is involved in acute inflammatory edema. The TRPA1 agonist allyl isothiocyanate (AITC) induced inflammatory edema when injected intraplantarly to mice, mimicking the classical response to carrageenan. Interestingly, the TRPA1 antagonist HC-030031 and the cyclo-oxygenase (COX) inhibitor ibuprofen inhibited not only AITC but also carrageenan-induced edema. TRPA1-deficient mice displayed attenuated responses to carrageenan and AITC. Furthermore, AITC enhanced COX-2 expression in HEK293 cells transfected with human TRPA1, a response that was reversed by HC-030031. This study demonstrates a hitherto unknown role of TRPA1 in carrageenan-induced inflammatory edema. The results also strongly suggest that TRPA1 contributes, in a COX-dependent manner, to the development of acute inflammation.
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| 21. |
- Rodriguez, Alina, et al.
(författare)
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Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts
- 2008
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 32:3, s. 550-557
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring. Design: Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD. Methods: Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as 'severe' and two as 'present' (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to children's ADHD core symptoms. Results: Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women. Conclusions: We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.
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| 22. |
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| 23. |
- Fergelot, Patricia, et al.
(författare)
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Phenotype and genotype in 52 patients with Rubinstein–Taybi syndrome caused by EP300 mutations
- 2016
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 170:12, s. 3069-3082
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Tidskriftsartikel (refereegranskat)abstract
- Rubinstein–Taybi syndrome (RSTS) is a developmental disorder characterized by a typical face and distal limbs abnormalities, intellectual disability, and a vast number of other features. Two genes are known to cause RSTS, CREBBP in 60% and EP300 in 8–10% of clinically diagnosed cases. Both paralogs act in chromatin remodeling and encode for transcriptional co-activators interacting with >400 proteins. Up to now 26 individuals with an EP300 mutation have been published. Here, we describe the phenotype and genotype of 42 unpublished RSTS patients carrying EP300 mutations and intragenic deletions and offer an update on another 10 patients. We compare the data to 308 individuals with CREBBP mutations. We demonstrate that EP300 mutations cause a phenotype that typically resembles the classical RSTS phenotype due to CREBBP mutations to a great extent, although most facial signs are less marked with the exception of a low-hanging columella. The limb anomalies are more similar to those in CREBBP mutated individuals except for angulation of thumbs and halluces which is very uncommon in EP300 mutated individuals. The intellectual disability is variable but typically less marked whereas the microcephaly is more common. All types of mutations occur but truncating mutations and small rearrangements are most common (86%). Missense mutations in the HAT domain are associated with a classical RSTS phenotype but otherwise no genotype–phenotype correlation is detected. Pre-eclampsia occurs in 12/52 mothers of EP300 mutated individuals versus in 2/59 mothers of CREBBP mutated individuals, making pregnancy with an EP300 mutated fetus the strongest known predictor for pre-eclampsia.
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| 24. |
- Högman, Marieann, et al.
(författare)
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Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects
- 2017
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Ingår i: Journal of Breath Research. - : IOP Publishing. - 1752-7155 .- 1752-7163. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.
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| 25. |
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| 26. |
- Jenniskens, Peter, et al.
(författare)
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The impact and recovery of asteroid 2018 LA
- 2021
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Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 56:4, s. 844-893
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Tidskriftsartikel (refereegranskat)abstract
- The June 2, 2018 impact of asteroid 2018 LA over Botswana is only the second asteroid detected in space prior to impacting over land. Here, we report on the successful recovery of meteorites. Additional astrometric data refine the approach orbit and define the spin period and shape of the asteroid. Video observations of the fireball constrain the asteroid's position in its orbit and were used to triangulate the location of the fireball's main flare over the Central Kalahari Game Reserve. Twenty‐three meteorites were recovered. A consortium study of eight of these classifies Motopi Pan as an HED polymict breccia derived from howardite, cumulate and basaltic eucrite, and diogenite lithologies. Before impact, 2018 LA was a solid rock of ~156 cm diameter with high bulk density ~2.85 g cm−3, a relatively low albedo pV ~ 0.25, no significant opposition effect on the asteroid brightness, and an impact kinetic energy of ~0.2 kt. The orbit of 2018 LA is consistent with an origin at Vesta (or its Vestoids) and delivery into an Earth‐impacting orbit via the ν6 resonance. The impact that ejected 2018 LA in an orbit toward Earth occurred 22.8 ± 3.8 Ma ago. Zircons record a concordant U‐Pb age of 4563 ± 11 Ma and a consistent 207Pb/206Pb age of 4563 ± 6 Ma. A much younger Pb‐Pb phosphate resetting age of 4234 ± 41 Ma was found. From this impact chronology, we discuss what is the possible source crater of Motopi Pan and the age of Vesta's Veneneia impact basin.
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| 28. |
- Linnet, K.M., Dalsgaard, S., Obel, C., Wisborg, K., Henriksen, T.B., Rodriguez, Alina, Kotimaa, A., Moilanen, I., Thomsen, P.H., Olsen, J., Järvelin, M.R.
(författare)
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Maternal lifestyle factors in pregnancy and risk of Attention-Deficit Hyperactivity Disorders: A review of current evidence.
- 2003
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Ingår i: American Journal of Psychiatry. ; 160:6, s. 1028-1040
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Tidskriftsartikel (refereegranskat)
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| 29. |
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| 30. |
- Moilanen, C., et al.
(författare)
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Modelling and simulation of radial spruce compression to optimize energy efficiency in mechanical pulping
- 2016
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Ingår i: International Mechanical Pulping Conference 2016, IMPC 2016. - : TAPPI Press. - 9781510830738 ; , s. 18-35
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Konferensbidrag (refereegranskat)abstract
- Energy efficiency of mechanical pulping is rather low. One possibility to facilitate design of more energy efficient defibration is to model and simulate wood compression. This paper presents an effort to model the behavior of Norwegian spruce in radial compression at defibration circumstances. To identify strain rate dependent properties, compression tests were conducted at both quasi-static conditions and at high strain rate. All tests were done at relevant moisture content and up to defibration zone temperatures and strain rates. Additionally the tests were performed both on native wood and on pre-fatigued wood to include behavior dependency of fatigue. The compression tests were monitored on fiber level to separately model behavior of early- and latewood. The chosen continuum model structure for earlywood and latewood was Voight-Kelvin to enable explicit viscous behavior conditioned by strain rate in parallel to the elastic behavior. The presented model is the first wood compression behavior model individually for earlywood and latewood that is based on wood experiments at industrial defibration circumstances. The influences of temperature and pre-fatigue rise are both softening as expected, The utilization of the compression model was demonstrated in an initial multilayered wood compression simulation.
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| 31. |
- Niemela, T., et al.
(författare)
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Relationship Between Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Disease Outcome in Adult-Onset Asthma
- 2022
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Ingår i: Journal of Asthma and Allergy. - 1178-6965. ; 15, s. 579-593
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Tidskriftsartikel (refereegranskat)abstract
- Background: Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a novel biomarker for various inflammatory conditions and has been proposed to associate with the severity of asthma. However, the relationship between suPAR and clinical asthma features is poorly understood. Objective: To examine associations of serum suPAR levels with clinical characteristics of asthma and to define the phenotype with high suPAR levels in patients with adult-onset asthma. Methods: Serum suPAR levels were measured with ELISA from patients with adult-onset asthma participating in the 12-year followup visit in the Seinajoki Adult Asthma Study. Results: In total, 201 patients were divided into quartiles according to suPAR values. High suPAR patients had more severe asthma symptoms and poorer asthma control. They also had higher levels of interleukin 8 (IL-8), interleukin 6 (IL-6), matrix metalloproteinase 9 (MMP-9), and blood neutrophil counts than those with low suPAR levels. The use of high-dose inhaled and oral corticosteroids was more common in patients with elevated suPAR. Such patients also had visited healthcare more frequently during the follow-up period, had more comorbidities, and were physically less active than those with low suPAR levels. The above-mentioned results remained similar after excluding the patients with co-existing COPD; only association to hospitalizations was lost. In multivariable binary regression analyses, the highest suPAR quartile was associated with higher cumulative dispensed oral corticosteroid use, more severe symptoms, and uncontrolled asthma. Conclusion: High suPAR levels occur in uncontrolled adult-onset asthma patients characterized by neutrophilic inflammation, high corticosteroid use, frequent healthcare visits, and multimorbidity with unhealthy lifestyle. This biomarker could be useful in determining asthma phenotypes and target new asthma treatments.
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| 32. |
- Nikinmaa, S, et al.
(författare)
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Indocyanine Green-Assisted and LED-Light-Activated Antibacterial Photodynamic Therapy Reduces Dental Plaque
- 2021
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Ingår i: Dentistry journal. - : MDPI AG. - 2304-6767. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This study aimed to determine the feasibility and first efficacy of indocyanine green (ICG)-assisted antimicrobial photodynamictherapy (aPDT) as activated using LED light to the dental plaque. Methods: Fifteen healthy adults were assigned to this four-day randomized study. After rinsing with ICG, 100 J/cm2 of 810 nm LED light was applied to the aPDT-treatment area. Plaque area and gingival crevicular fluid (GCF) matrix metalloproteinase-8 (MMP-8) were measured, and plaque bacteriomes before and after the study were analyzed using 16S rRNA sequencing. Results: aPDT administration was preformed successfully and plaque-specifically with the combination of ICG and the applicator. Total plaque area and endpoint MMP-8 levels were reduced on the aPDT-treatment side. aPDT reduced Streptococcus, Acinetobacteria, Capnocytophaga, and Rothia bacteria species in plaques. Conclusion: ICG-assisted aPDT reduces plaque forming bacteria and exerts anti-inflammatory and anti-proteolytic effects.
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| 41. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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