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2.
N Biotechnol ; 83: 1-15, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38871051

RESUMO

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations. In this work, we used three different and independent adaptive laboratory evolution (ALE) strategies to evolve the wild-type C. autoethanogenum to grow faster, without yeast extract and to be robust in operating continuous bioreactor cultures. Multiple evolved strains with improved phenotypes were isolated on minimal media with one strain, named "LAbrini", exhibiting superior performance regarding the maximum specific growth rate, product profile, and robustness in continuous cultures. Whole-genome sequencing of the evolved strains identified 25 mutations. Of particular interest are two genes that acquired seven different mutations across the three ALE strategies, potentially as a result of convergent evolution. Reverse genetic engineering of mutations in potentially sporulation-related genes CLAU_3129 (spo0A) and CLAU_1957 recovered all three superior features of our ALE strains through triggering significant proteomic rearrangements. This work provides a robust C. autoethanogenum strain "LAbrini" to accelerate phenotyping and genetic engineering and to better understand acetogen metabolism.

3.
ACR Open Rheumatol ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923834

RESUMO

OBJECTIVE: Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation. METHODS: We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response. RESULTS: Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs. CONCLUSION: Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use.

4.
Sci Data ; 11(1): 432, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693191

RESUMO

The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C. saccharobutylicum, 4 C. saccharoperbutylacetonicum, 5 C. butyricum, 7 C. acetobutylicum, and 3 C. tetanomorphum genomes. We report methods, analyses and characterization for phylogeny, key attributes, core biosynthetic genes, secondary metabolites, plasmids, prophage/CRISPR diversity, cellulosomes and quorum sensing for the 6 species. The expanded genomic data described here will facilitate engineering of solvent-producing clostridia as well as non-model microorganisms with innately desirable traits. Sequences could be applied in conventional platform biocatalysts such as yeast or Escherichia coli for enhanced chemical production. Recently, gene sequences from this collection were used to engineer Clostridium autoethanogenum, a gas-fermenting autotrophic acetogen, for continuous acetone or isopropanol production, as well as butanol, butanoic acid, hexanol and hexanoic acid production.


Assuntos
Clostridium , Genoma Bacteriano , Filogenia , Clostridium/genética , Solventes , Fermentação
5.
Artigo em Inglês | MEDLINE | ID: mdl-38749001

RESUMO

OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

6.
Data Brief ; 54: 110326, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590615

RESUMO

The operational building data presented in this paper has been collected from six office rooms located in an office building (research and educational purposes) located on the main campus of Aalborg University in Denmark. The dataset consists of measurements of occupancy, indoor environmental quality, room-level and system-level heating, ventilation and lighting operation at a 5 min resolution. The indoor environmental quality and building system data were collected from the building management system. The occupancy level in each monitored room is established from the computer vision-based analysis of wall-mounted camera footage of each office. The number of people present in the room is estimated using the YOLOv5s image recognition algorithm. The present dataset can be used for occupancy analysis, indoor environmental quality investigations, machine learning, and model predictive control.

7.
J Struct Biol ; 216(2): 108067, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38367824

RESUMO

Cellular cryo-electron tomography (cryo-ET) has emerged as a key method to unravel the spatial and structural complexity of cells in their near-native state at unprecedented molecular resolution. To enable quantitative analysis of the complex shapes and morphologies of lipid membranes, the noisy three-dimensional (3D) volumes must be segmented. Despite recent advances, this task often requires considerable user intervention to curate the resulting segmentations. Here, we present ColabSeg, a Python-based tool for processing, visualizing, editing, and fitting membrane segmentations from cryo-ET data for downstream analysis. ColabSeg makes many well-established algorithms for point-cloud processing easily available to the broad community of structural biologists for applications in cryo-ET through its graphical user interface (GUI). We demonstrate the usefulness of the tool with a range of use cases and biological examples. Finally, for a large Mycoplasma pneumoniae dataset of 50 tomograms, we show how ColabSeg enables high-throughput membrane segmentation, which can be used as valuable training data for fully automated convolutional neural network (CNN)-based segmentation.


Assuntos
Algoritmos , Microscopia Crioeletrônica , Tomografia com Microscopia Eletrônica , Software , Microscopia Crioeletrônica/métodos , Tomografia com Microscopia Eletrônica/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Membrana Celular/ultraestrutura , Mycoplasma pneumoniae/ultraestrutura , Interface Usuário-Computador , Imageamento Tridimensional/métodos
8.
Joint Bone Spine ; 91(4): 105699, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38309517

RESUMO

OBJECTIVE: To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. METHODS: HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. RESULTS: Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. CONCLUSION: HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.


Assuntos
Acro-Osteólise , Calcinose , Escleroderma Sistêmico , Tomografia Computadorizada por Raios X , Humanos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico por imagem , Calcinose/diagnóstico por imagem , Acro-Osteólise/diagnóstico por imagem , Acro-Osteólise/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto , Sensibilidade e Especificidade , Índice de Gravidade de Doença
9.
bioRxiv ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38328068

RESUMO

Plasmodium falciparum pathology is driven by the accumulation of parasite-infected erythrocytes in microvessels. This process is mediated by the parasite's polymorphic erythrocyte membrane protein 1 (PfEMP1) adhesion proteins. A subset of PfEMP1 variants that bind human endothelial protein C receptor (EPCR) through their CIDRα1 domains is responsible for severe malaria pathogenesis. A longstanding question is whether individual antibodies can recognize the large repertoire of circulating PfEMP1 variants. Here, we describe two broadly reactive and binding-inhibitory human monoclonal antibodies against CIDRα1. The antibodies isolated from two different individuals exhibited a similar and consistent EPCR-binding inhibition of 34 CIDRα1 domains, representing five of the six subclasses of CIDRα1. Both antibodies inhibited EPCR binding of both recombinant full-length and native PfEMP1 proteins as well as parasite sequestration in bioengineered 3D brain microvessels under physiologically relevant flow conditions. Structural analyses of the two antibodies in complex with two different CIDRα1 antigen variants reveal similar binding mechanisms that depend on interactions with three highly conserved amino acid residues of the EPCR-binding site in CIDRα1. These broadly reactive antibodies likely represent a common mechanism of acquired immunity to severe malaria and offer novel insights for the design of a vaccine or treatment targeting severe malaria.

10.
Int J Rheum Dis ; 27(2): e15068, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38334245

RESUMO

PURPOSE: Osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) can all lead to the formation of bony proliferations (BP). This systematic review aimed to examine the characteristics of BPs in patients with RA, PsA, OA, and healthy controls (HC) using high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondarily, we examined any treatment-related effect on BP number and size. METHODS: A systematic literature search was conducted in PubMed and Embase, and a total of 15 studies were included. RESULTS: Seven studies demonstrated a disease-specific variation in BP location. One study showed no difference in the number of BPs between patients with PsA and OA. The number of BPs was greater in patients with PsA compared to RA in one study, and to HC in another study, while one study documented no difference in the number of BPs between patients with RA and HC. Five studies showed larger BPs in patients with PsA compared to HC, and one study larger BPs in patients with PsA compared to RA. One study showed no difference in BP size between patients with PsA and OA. Secukinumab may have a potential effect on arresting BP progression. Otherwise, no other treatment was reported to influence BP size and progression. No standard definitions or measurement techniques for BPs using HR-pQCT have been identified. CONCLUSION: BPs showed disease-specific variations in location, size, and number. Results regarding treatment-related effects are sparse. An agreement on the definition and measurement technique for BPs using HR-pQCT is warranted for diagnostic accuracy, disease comparability, and monitoring potential.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Osteoartrite , Humanos , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Osteoartrite/diagnóstico por imagem , Tomografia
11.
Scand J Med Sci Sports ; 34(2): e14571, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38389143

RESUMO

During submaximal exercise, there is a heterogeneous recruitment of skeletal muscle fibers, with an ensuing heterogeneous depletion of muscle glycogen both within and between fiber types. Here, we show that the mean (95% CI) mitochondrial volume as a percentage of fiber volume of non-glycogen-depleted fibers was 2 (-10:6), 5 (-21:11), and 12 (-21:-2)% lower than all the sampled fibers after continuing exercise for 1, 2 h, and until task failure, respectively. Therefore, a glycogen-dependent fatigue of individual fibers during submaximal exercise may reduce the muscular oxidative power. These findings suggest a relationship between glycogen and mitochondrial content in individual muscle fibers, which is important for understanding fatigue during prolonged exercise.


Assuntos
Glicogênio , Fibras Musculares Esqueléticas , Humanos , Glicogênio/metabolismo , Tamanho Mitocondrial , Fibras Musculares Esqueléticas/metabolismo , Fadiga/metabolismo , Estresse Oxidativo , Músculo Esquelético/fisiologia
12.
Sci Rep ; 13(1): 20039, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973887

RESUMO

The inflammatory activity in cirrhosis is often pronounced and related to episodes of decompensation. Systemic markers of inflammation may contain prognostic information, and we investigated their possible correlation with admissions and mortality among patients with newly diagnosed liver cirrhosis. We collected plasma samples from 149 patients with newly diagnosed (within the past 6 months) cirrhosis, and registered deaths and hospital admissions within 180 days. Ninety-two inflammatory markers were quantified and correlated with clinical variables, mortality, and admissions. Prediction models were calculated by logistic regression. We compared the disease courses of our cohort with a validation cohort of 86 patients with cirrhosis. Twenty of 92 markers of inflammation correlated significantly with mortality within 180 days (q-values of 0.00-0.044), whereas we found no significant correlations with liver-related admissions. The logistic regression models yielded AUROCs of 0.73 to 0.79 for mortality and 0.61 to 0.73 for liver-related admissions, based on a variety of modalities (clinical variables, inflammatory markers, clinical scores, or combinations thereof). The models performed moderately well in the validation cohort and were better able to predict mortality than liver-related admissions. In conclusion, markers of inflammation can be used to predict 180-day mortality in patients with newly diagnosed cirrhosis. Prediction models for newly diagnosed cirrhotic patients need further validation before implementation in clinical practice.Trial registration: NCT04422223 (and NCT03443934 for the validation cohort), and Scientific Ethics Committee No.: H-19024348.


Assuntos
Hospitalização , Cirrose Hepática , Humanos , Cirrose Hepática/diagnóstico , Estudos Prospectivos , Prognóstico , Inflamação , Índice de Gravidade de Doença
13.
Animals (Basel) ; 13(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37684959

RESUMO

Four formulations of concentrate feeds, three contrasting qualities of grass silages, and mixtures of the silages (55%) and concentrates (45%, dry weight) were tested for in vitro fermentation kinetics, in vitro dry matter degradation (IVDMD), utilizable crude protein (uCP), and metabolizable energy (ME) values. The concentrates were pelleted control concentrate for dairy cows (CONT-P); pelleted alkaline concentrate with ammoniated cereal grains (ALKA-P); mash form concentrate with ALKA-P main ingredients but with feed-grade urea and barley replacing ammoniated cereal grain (UREA-M); and mash form of ALKA-P ingredients prior to alkalization (ALKA-M). The grass silages were early cut, late cut, and a mixture (1:1) of early and late cut. The objectives were to test if the feeds differed in the tested parameters within each feed category and assess the modulatory effect of concentrate feeds on the grass silage fermentation characteristics in the mixed diets. No interaction effects of the concentrate feeds by silage quality were observed for the tested parameters in the mixed diets. For concentrates, the pelleted diets were higher (p < 0.05) in IVDMD and molar proportion of propionate but lower in butyrate. The ALKA-P produced the highest estimated uCP (p < 0.01). For silages, uCP, ME, total short-chain fatty acids (VFAs), and molar proportions of propionate and branched-chain VFAs decreased (p < 0.05) with increasing stage of maturity. In conclusion, the ALKA-P could match the CONT-P in uCP and ME values and fermentation characteristics. Results for silages and their mixtures with concentrates highlight the importance of silage quality in dietary energy and protein supply for ruminants.

14.
Sci Data ; 10(1): 661, 2023 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770445

RESUMO

Bank transactions are highly confidential. As a result, there are no real public data sets that can be used to investigate and compare anti-money laundering (AML) methods in banks. This severely limits research on important AML problems such as efficiency, effectiveness, class imbalance, concept drift, and interpretability. To address the issue, we present SynthAML: a synthetic data set to benchmark statistical and machine learning methods for AML. The data set builds on real data from Spar Nord, a systemically important Danish bank, and contains 20,000 AML alerts and over 16 million transactions. Experimental results indicate that performance on SynthAML can be transferred to the real world. As use cases, we present and discuss open problems in the AML literature.

15.
Structure ; 31(10): 1174-1183.e4, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37582356

RESUMO

Severe Plasmodium falciparum malaria infections are caused by microvascular sequestration of parasites binding to the human endothelial protein C receptor (EPCR) via the multi-domain P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands. Using cryogenic electron microscopy (Cryo-EM) and PfEMP1 sequence diversity analysis, we found that group A PfEMP1 CIDRα1 domains interact with the adjacent DBLα1 domain through central, conserved residues of the EPCR-binding site to adopt a compact conformation. Upon EPCR binding, the DBLα1 domain is displaced, and the EPCR-binding helix of CIDRα1 is turned, kinked, and twisted to reach a rearranged, stable EPCR-bound conformation. The unbound conformation and the required transition to the EPCR-bound conformation may represent a conformational masking mechanism of immune evasion for the PfEMP1 family.

16.
Chem Sci ; 14(28): 7733-7742, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37476724

RESUMO

One of the primary challenges prohibiting demonstrations of practical quantum advantages for near-term devices amounts to excessive measurement overheads for estimating relevant physical quantities such as ground state energies. However, with major differences between the electronic and vibrational structures of molecules, the question of how the resource requirements of computing anharmonic, vibrational states can be reduced remains relatively unexplored compared to its electronic counterpart. Importantly, bosonic commutation relations, distinguishable Hilbert spaces and vibrational coordinates allow manipulations of the vibrational system that can be exploited to minimize resource requirements. In this work, we investigate the impact of different coordinate systems and measurement schemes on the number of measurements needed to estimate anharmonic, vibrational states for a variety of three-mode (six-mode) molecules. We demonstrate an average of 3-fold (1.5-fold), with up to 7-fold (2.5-fold), reduction in the number of measurements required by employing appropriate coordinate transformations, based on an automized construction of qubit Hamiltonians from a conventional vibrational structure program.

17.
Diabetologia ; 66(9): 1680-1692, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37303007

RESUMO

AIMS/HYPOTHESIS: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. METHODS: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000-3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. RESULTS: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. CONCLUSION/INTERPRETATION: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Peso ao Nascer/genética , Estudos Transversais , Fatores de Risco , Predisposição Genética para Doença , Glucose
18.
Diabetologia ; 66(9): 1669-1679, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37303008

RESUMO

AIMS/HYPOTHESIS: Low birthweight is a risk factor for type 2 diabetes. Most previous studies are based on cross-sectional prevalence data, not designed to study the timing of onset of type 2 diabetes in relation to birthweight. We aimed to examine associations of birthweight with age-specific incidence rate of type 2 diabetes in middle-aged to older adults over two decades. METHODS: Adults aged 30-60 years enrolled in the Danish Inter99 cohort in 1999-2001 (baseline examination), with information on birthweight from original birth records from 1939-1971 and without diabetes at baseline, were eligible. Birth records were linked with individual-level data on age at diabetes diagnosis and key covariates. Incidence rates of type 2 diabetes as a function of age, sex and birthweight were modelled using Poisson regression, adjusting for prematurity status at birth, parity, polygenic scores for birthweight and type 2 diabetes, maternal and paternal diabetes history, socioeconomic status and adult BMI. RESULTS: In 4590 participants there were 492 incident type 2 diabetes cases during a mean follow-up of 19 years. Type 2 diabetes incidence rate increased with age, was higher in male participants, and decreased with increasing birthweight (incidence rate ratio [95% CI per 1 kg increase in birthweight] 0.60 [0.48, 0.75]). The inverse association of birthweight with type 2 diabetes incidence was statistically significant across all models and in sensitivity analysis. CONCLUSIONS/INTERPRETATION: A lower birthweight was associated with increased risk of developing type 2 diabetes independent of adult BMI and genetic risk of type 2 diabetes and birthweight.


Assuntos
Diabetes Mellitus Tipo 2 , Recém-Nascido , Gravidez , Feminino , Pessoa de Meia-Idade , Masculino , Humanos , Idoso , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Peso ao Nascer/genética , Incidência , Predisposição Genética para Doença , Índice de Massa Corporal , Estudos Transversais
19.
Int J Rheum Dis ; 26(8): 1512-1520, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37337629

RESUMO

OBJECTIVES: To compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR-pQCT. METHODS: This single-center cross-sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR-pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method. RESULTS: Among 42 participants, 30 patients were classified with erosive RA and 12 with non-erosive RA by CR. HR-pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p = .03). The optimal cut-off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR-pQCT was 7.5 erosions and 11.7 mm3 , respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR-pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head. CONCLUSION: The superiority of HR-pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR-pQCT could be used for diagnosing erosive RA in the future.


Assuntos
Artrite Reumatoide , Articulação Metatarsofalângica , Humanos , Estudos Transversais , Artrite Reumatoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Radiografia , Articulação Metatarsofalângica/diagnóstico por imagem
20.
J Anim Physiol Anim Nutr (Berl) ; 107(5): 1251-1261, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37144326

RESUMO

Supplementation with marine-derived n-3 long-chain polyunsaturated fatty acids (LC PUFAs), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) is linked to beneficial health effects in both humans and horses. Krill oil (KO), which is extracted from the Antarctic krill (Euphausia superba), is well documented as a safe and biologically available dietary supplement in humans and several animal species, but there is a lack of documentation regarding its effect as a dietary ingredient for horses. The objective of this study was to test whether KO as a dietary supplement had the ability to raise horse red blood cell (RBC) membrane EPA and DHA, expressed as the n-3 index. Five nonworking Norwegian cold-blooded trotter horse geldings (body weight [BW]: 567 ± 38 kg) were supplemented with KO (10 mL/100 kg BW) for 35 days in a longitudinal study. Blood samples were analysed for RBC membrane fatty acid (FA) profile, haematology and serum biochemistry every 7th day. KO was well accepted by all horses, and no adverse health effects were observed during the 35-day trial period. KO supplementation affected the RBC membrane FA profile by increasing the n-3 index from Day 0 to 35 (Day 0: 0.53% vs. Day 35: 4.05% of total RBC FAs). The observed increase in the sum of EPA and DHA (p < 0.001), total n-3 FAs (p < 0.001) and the reduction of n-6 FAs (p < 0.044) resulted in a lower n-6:n-3 ratio (p < 0.001) by Day 35 of KO supplementation. In conclusion, the RBC n-3 index was increased and the general n-6:n-3 ratio was decreased in horses receiving 35-day dietary KO supplementation.


Assuntos
Euphausiacea , Ácidos Graxos Ômega-3 , Animais , Masculino , Membrana Celular , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico , Euphausiacea/química , Euphausiacea/metabolismo , Ácidos Graxos , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Óleos de Peixe , Cavalos , Estudos Longitudinais
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