| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Cederholm, Tommy, et al.
(författare)
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ESPEN guidelines on definitions and terminology of clinical nutrition
- 2017
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Ingår i: Clinical Nutrition. - 0261-5614 .- 1532-1983. ; 36:1, s. 49-64
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundA lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research.ObjectiveThis initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures.MethodsThe European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round.ResultsFive key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery.ConclusionAn agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.
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| 4. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 5. |
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| 6. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 7. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 8. |
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| 9. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 10. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 11. |
- Ou, Anna H., et al.
(författare)
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Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study
- 2024
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Ingår i: TRANSLATIONAL PSYCHIATRY. - 2158-3188. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
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| 12. |
- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders
- 2024
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Ingår i: International Journal of Bipolar Disorders. - 2194-7511. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
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| 13. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 14. |
- Pironi, Loris, et al.
(författare)
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Characteristics of adult patients with chronic intestinal failure due to short bowel syndrome: An international multicenter survey
- 2021
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Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 45, s. 433-441
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The case-mix of patients with intestinal failure due to short bowel syndrome (SBS-IF) can differ among centres and may also be affected by the timeframe of data collection. Therefore, the ESPEN international multicenter cross-sectional survey was analyzed to compare the characteristics of SBS-IF cohorts collected within the same timeframe in different countries. Methods: The study included 1880 adult SBS-IF patients collected in 2015 by 65 centres from 22 countries. The demographic, nutritional, SBS type (end jejunostomy, SBS-J; jejuno-colic anastomosis, SBS-JC; jejunoileal anastomosis with an intact colon and ileocecal valve, SBS-JIC), underlying disease and intravenous supplementation (IVS) characteristics were analyzed. IVS was classified as fluid and electrolyte alone (FE) or parenteral nutrition admixture (PN). The mean daily IVS volume, calculated on a weekly basis, was categorized as <1, 1–2, 2–3 and >3 L/day. Results: In the entire group: 60.7% were females and SBS-J comprised 60% of cases, while mesenteric ischaemia (MI) and Crohn’ disease (CD) were the main underlying diseases. IVS dependency was longer than 3 years in around 50% of cases; IVS was infused ≥5 days/week in 75% and FE in 10% of cases. Within the SBS-IF cohort: CD was twice and thrice more frequent in SBS-J than SBS-JC and SBS-JIC, respectively, while MI was more frequent in SBS-JC and SBS-JIC. Within countries: SBS-J represented 75% or more of patients in UK and Denmark and 50-60% in the other countries, except Poland where SBS-JC prevailed. CD was the main underlying disease in UK, USA, Denmark and The Netherlands, while MI prevailed in France, Italy and Poland. Conclusions: SBS-IF type is primarily determined by the underlying disease, with significant variation between countries. These novel data will be useful for planning and managing both clinical activity and research studies on SBS.
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| 15. |
- Cederholm, Tommy E., et al.
(författare)
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Toward a Definition of Sarcopenia
- 2011
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Ingår i: Clinics in Geriatric Medicine. - : Elsevier BV. - 0749-0690 .- 1879-8853. ; 27:3, s. 341-353
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Tidskriftsartikel (refereegranskat)abstract
- The definition of sarcopenia has been thoroughly discussed by scientific stakeholders and industry representatives to increase the clinical applicability of the concept. The pooled consensus from 3 of 5 recent and parallel processes, of which 2 are pending, is that sarcopenia is mainly, but not only, an age-related condition defined by the combined presence of reduced muscle mass and muscle function. Contributing factors to sarcopenia are senescence, chronic disease, physical inactivity, and poor food intake. Cachexia may be considered as one etiologic pathway of an accelerated sarcopenia. The adjusted and extended definitions of sarcopenia promote the clinical use of the concept.
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| 16. |
- Cruz-Jentoft, Alfonso J., et al.
(författare)
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Sarcopenia : European consensus on definition and diagnosis
- 2010
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 39:4, s. 412-423
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Tidskriftsartikel (refereegranskat)abstract
- The group met and addressed the following questions, using the medical literature to build evidence-based answers: (i) What is sarcopenia? (ii) What parameters define sarcopenia? (iii) What variables reflect these parameters, and what measurement tools and cut-off points can be used? (iv) How does sarcopenia relate to cachexia, frailty and sarcopenic obesity? For the diagnosis of sarcopenia, EWGSOP recommends using the presence of both low muscle mass + low muscle function (strength or performance). EWGSOP variously applies these characteristics to further define conceptual stages as 'presarcopenia', 'sarcopenia' and 'severe sarcopenia'. EWGSOP reviewed a wide range of tools that can be used to measure the specific variables of muscle mass, muscle strength and physical performance. Our paper summarises currently available data defining sarcopenia cut-off points by age and gender; suggests an algorithm for sarcopenia case finding in older individuals based on measurements of gait speed, grip strength and muscle mass; and presents a list of suggested primary and secondary outcome domains for research. Once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to define the natural course of sarcopenia and to develop and define effective treatment.
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| 17. |
- Volkert, Dorothee, et al.
(författare)
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Development of a Model on Determinants of Malnutrition in Aged Persons : A MaNuEL Project
- 2019
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Ingår i: Gerontology and geriatric medicine. - : Sage Publications. - 2333-7214. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- In older persons, the origin of malnutrition is often multifactorial with a multitude of factors involved. Presently, a common understanding about potential causes and their mode of action is lacking, and a consensus on the theoretical framework on the etiology of malnutrition does not exist. Within the European Knowledge Hub "Malnutrition in the Elderly (MaNuEL)," a model of "Determinants of Malnutrition in Aged Persons" (DoMAP) was developed in a multistage consensus process with live meetings and written feedback (modified Delphi process) by a multiprofessional group of 33 experts in geriatric nutrition. DoMAP consists of three triangle-shaped levels with malnutrition in the center, surrounded by the three principal conditions through which malnutrition develops in the innermost level: low intake, high requirements, and impaired nutrient bioavailability. The middle level consists of factors directly causing one of these conditions, and the outermost level contains factors indirectly causing one of the three conditions through the direct factors. The DoMAP model may contribute to a common understanding about the multitude of factors involved in the etiology of malnutrition, and about potential causative mechanisms. It may serve as basis for future research and may also be helpful in clinical routine to identify persons at increased risk of malnutrition.
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| 18. |
- Alfoeldi, Jessica, et al.
(författare)
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The genome of the green anole lizard and a comparative analysis with birds and mammals
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 477:7366, s. 587-591
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Tidskriftsartikel (refereegranskat)abstract
- The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments(1). Among amniotes, genome sequences are available for mammals and birds(2-4), but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes(2). Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds(5). We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.
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| 19. |
- Bengmark, Stig, et al.
(författare)
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Roles of microbiota manipulations in the ICU
- 2009
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Ingår i: Nutrition Clinique et Metabolisme. - : Elsevier BV. - 0985-0562. ; 23:4, s. 235-244
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Forskningsöversikt (refereegranskat)abstract
- The intestinal microbiota displays dramatic changes in the ICU patient, with a loss of the entire beneficial lactic bacterial flora. In situations of hyperinflammation followed by immune paresis that are due to the acute disease but also to chronic diseases and drugs used, it is crucial to reestablish inflammatory and immune homeostasis, and microbiota manipulations with probiotics or synbiotics is an instrument of choice. It is not recommended to give any ICU patient any probiotic or synbiotic, for fear of inefficacy or even increased mortality. However, there is strong evidence in elective surgery, polytrauma and acute pancreatitis for well-defined formulations of bacterial strains and fibers. The inflammatory response is immediate and therefore administration of probiotics or synbiotics in these situations must also be immediate. (C) 2009 Elsevier Masson SAS. All rights reserved.
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| 20. |
- Cruz-Jentoft, Alfonso J, et al.
(författare)
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Prevalence of and interventions for sarcopenia in ageing adults : a systematic review : Report of the International Sarcopenia Initiative (EWGSOP and IWGS)
- 2014
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Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 43:6, s. 748-759
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.
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| 21. |
- Cruz-Jentoft, Alfonso J., et al.
(författare)
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Sarcopenia : revised European consensus on definition and diagnosis
- 2019
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Ingår i: Age and Ageing. - : OXFORD UNIV PRESS. - 0002-0729 .- 1468-2834. ; 48:1, s. 16-31
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings.Objectives: To increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia.Recommendations: Sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia.Conclusions; EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.
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| 22. |
- Gomes, Filomena, et al.
(författare)
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ESPEN guidelines on nutritional support for polymorbid internal medicine patients
- 2018
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Ingår i: Clinical Nutrition. - : CHURCHILL LIVINGSTONE. - 0261-5614 .- 1532-1983. ; 37:1, s. 336-353
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Polymorbidity (also known as multimorbidity)-defined as the co-occurrence of at least two chronic health conditions - is highly prevalent, particularly in the hospitalized population. Nonetheless, clinical guidelines largely address individual diseases and rarely account for polymorbidity. The aim of this project was to develop guidelines on nutritional support for polymorbid patients hospitalized in medical wards.Methods: The methodology used for the development of the current project follows the standard operating procedures for ESPEN guidelines. It started with an initial meeting of the Working Group in January 2015, where twelve key clinical questions were developed that encompassed different aspects of nutritional support: indication, route of feeding, energy and protein requirements, micronutrient requirements, disease-specific nutrients, timing, monitoring and procedure of intervention. Systematic literature searches were conducted in three different databases (Medline, Embase and the Cochrane Library), as well as in secondary sources (e.g. published guidelines), until April 2016. Retrieved abstracts were screened to identify relevant studies that were used to develop recommendations, which were followed by submission to Delphi voting rounds.Results: From a total of 4532 retrieved abstracts, 38 relevant studies were analyzed and used to generate a guideline draft that proposed 22 recommendations and four statements. The results of the first online voting showed a strong consensus (agreement of >90%) in 68% of recommendations and 75% of statements, and consensus (agreement of >75-90%) in 32% of recommendations and 25% of statements. At the final consensus conference, a consensus greater than 89% was reached for all of the recommendations.Conclusions: Despite the methodological difficulties in creating non-disease specific guidelines, the evidence behind several important aspects of nutritional support for polymorbid medical inpatients was reviewed and summarized into practical clinical recommendations. Use of these guidelines offer an evidence-based nutritional approach to the polymorbid medical inpatient and may improve their outcomes.
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| 23. |
- Muscaritoli, Maurizio, et al.
(författare)
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Effectiveness and efficacy of nutritional therapy : A cochrane systematic review
- 2017
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 36:4, s. 939-957
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Disease-related malnutrition has deleterious consequences on patients' outcome and healthcare costs. The demonstration of improved outcome by appropriate nutritional management is on occasion difficult. The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed the Nutrition Education Study Group (ESPEN-NESG) to increase recognition of nutritional knowledge and support in health services.METHODS: To obtain the best available evidence on the potential effects of malnutrition on morbidity, mortality and hospital stay; cost of malnutrition; effect of nutritional treatment on outcome parameters and pharmaco-economics of nutritional therapy, a Cochrane systematic review of the literature was performed by the Croatian Cochrane Branch to answer the following key questions: Q1) Is malnutrition an independent predictive factor for readmission within 30 days from hospital discharge? Q2) Does nutritional therapy reduce the risk of readmission within 30 days from hospital discharge? Q3) Is nutritional therapy cost-effective/does it reduce costs in hospitalized patients? and Q4) Is nutritional therapy cost effective/does it reduce costs in outpatients?RESULTS: For Q1 six of 15 identified observational studies indicated that malnutrition was predictive of re-admissions, whereas the remainder did not. For Q2 nine randomized controlled trials and two meta-analyses gave non-conclusive results whether re-admissions could be reduced by nutritional therapy. Economic benefit and cost-effectiveness of nutritional therapy was consistently reported in 16 identified studies for hospitalized patients (Q3), whereas the heterogeneous and limited corresponding data on out-patients (Q4) indicated cost-benefits in some selected sub-groups.CONCLUSIONS: This result of this review supports the use of nutritional therapy to reduce healthcare costs, most evident from large, homogeneous studies. In general, reports are too heterogeneous and overall of limited quality for conclusions on impact of malnutrition and its treatment on readmissions.
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| 24. |
- Ostaszewski, Marek, et al.
(författare)
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COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms
- 2021
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Ingår i: Molecular Systems Biology. - : John Wiley & Sons. - 1744-4292 .- 1744-4292. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.
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| 25. |
- Snyders, Rony, et al.
(författare)
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Influence of the chemical composition on the phase constitution and the elastic properties of RF sputtered hydrozyapatite coatings
- 2008
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Ingår i: Plasma Processes and Polymers. - : Wiley. - 1612-8850 .- 1612-8869. ; 5:2, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the influence of chemical composition on the constitution and elastic properties of dense radio-frequency (RF)-sputtered hydroxyapatite (HA) coatings. The chemical composition was modified by varying the RF sputtering power density (P-D). As the P-D was increased by 240%, the Ca/P ratio measured by X-ray photoelectron spectroscopy increased from approximate to 1.51 to approximate to 1.82. X-ray diffraction indicates phase pure hexagonal HA except for the sample prepared at the highest P-D where CaO and Ca-3(PO4)(2) also form. Deviations from the stoichiometric Ca/P ratio result in reduction of the elastic modulus. For Ca/P = 1.51 +/- 0.02, the elastic modulus decreases by approximate to 15%. This maybe due to incorporation of Ca vacancies in the lattice, while for Ca/P = 1.82 +/- 0.02, the average elastic modulus decreases by approximate to 10% due to formation of additional phases.
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