scholarly journals Detection of a polymorphic site of the porcine <i>C8G</i> gene and evaluation of association with haemolytic complement activity

2012 ◽  
Vol 55 (3) ◽  
pp. 255-262
Author(s):  
V. A. K. Do ◽  
S. Ponsuksili ◽  
E. Muráni ◽  
H. T. P. Loan ◽  
R. M. Brunner ◽  
...  

Abstract. C8 is a component of the membrane attack complex (MAC) of the complement system, which causes lysis of the target cells. C8 consists of three subunits C8A, C8B, and C8G. This study focus on the porcine C8G gene aiming to identify its cDNA sequence, to detect single nucleotide polymorphism (SNP), and to analyse its association with haemolytic complement activity in the classical (CH50) and the alternative (AH50) pathway. The C8G is 840 bp in length encoding 202 amino acids. The C8G is similar (≥65 %) among mammalian species (pig, human, cattle, dog, and mouse) at both the cDNA and the protein level. One SNP was detected at nucleotide 423C→T (SNP c.423C>T; codon 124GAC→GAT). The SNP does not segregate among the European commercial breeds German Landrace and Pietrain but in the Vietnamese autochthonous breed Muong Khuong (Vietnamese potbelly pig) and an experimental F2 crossbreed population based on Duroc and Berlin Miniature Pig (DUMI). Haemolytic complement activity of animals of the DUMI populations obtained at about 6, 14 and 16 weeks of age before and after vaccinations showed short-termed increments due to the immune stimulation and long-term increase due to aging. Family based association tests indicate effects of C8G on AH50 and CH50 at 16 weeks of age immediately before PRRS vaccination (AH50_PRRS0, P=0.087; CH50_PRRS0, P=0.027). However, the results did not indicate a consistent effect of the respective alleles on haemolytic complement activity in the alternative and the classical pathway. The study provides weak evidence for the candidacy of the porcine C8G for innate immune response and disease resistance in pigs.

2021 ◽  
pp. jnnp-2021-326043
Author(s):  
Alis Heshmatollah ◽  
Lisanne J. Dommershuijsen ◽  
Lana Fani ◽  
Peter J. Koudstaal ◽  
M. Arfan Ikram ◽  
...  

ObjectiveAlthough knowledge on poststroke cognitive and functional decline is increasing, little is known about the possible decline of these functions before stroke. We determined the long-term trajectories of cognition and daily functioning before and after stroke.MethodsBetween 1990 and 2016, we repeatedly assessed cognition (Mini-Mental State Examination (MMSE), 15-Word Learning, Letter–Digit Substitution, Stroop, Verbal Fluency, Purdue Pegboard) and basic and instrumental activities of daily living (BADL and IADL) in 14 712 participants within the population-based Rotterdam Study. Incident stroke was assessed through continuous monitoring of medical records until 2018. We matched participants with incident stroke to stroke-free participants (1:3) based on sex and birth year. Trajectories of cognition and daily functioning of patients who had a stroke 10 years before and 10 years after stroke and the corresponding trajectories of stroke-free individuals were constructed using adjusted linear mixed effects models.ResultsDuring a mean follow-up of 12.5±6.8 years, a total of 1662 participants suffered a first-ever stroke. Patients who had a stroke deviated from stroke-free controls up to 10 years before stroke diagnosis in cognition and daily functioning. Significant deviations before stroke were seen in scores of MMSE (6.4 years), Stroop (5.7 years), Purdue Pegboard (3.8 years) and BADL and IADL (2.2 and 3.0 years, respectively).ConclusionPatients who had a stroke have steeper declines in cognition and daily functioning up to 10 years before their first-ever stroke compared with stroke-free individuals. Our findings suggest that accumulating intracerebral pathology already has a clinical impact before stroke.


2021 ◽  
Vol 11 ◽  
Author(s):  
Phoebe Yam ◽  
Jody Albright ◽  
Melissa VerHague ◽  
Erik R. Gertz ◽  
Fernando Pardo-Manuel de Villena ◽  
...  

Defined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics, and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.


2021 ◽  
Vol 64 (2) ◽  
Author(s):  
C. Michael Goplen ◽  
Sung Hyun Kang ◽  
Jason R. Randell ◽  
Allyson Jones ◽  
Donald C. Voaklander ◽  
...  

Background: Up to 40% of patients are receiving opioids at the time of total knee arthroplasty (TKA) in the United States despite evidence suggesting opioids are ineffective for pain associated with arthritis and have substantial risks. Our primary objective was to determine whether preoperative opioid users had worse knee pain and physical function outcomes 12 months after TKA than patients who were opioidnaive preoperatively; our secondary objective was to determine the prevalence of opioid use before and after TKA in Alberta, Canada. Methods: In this retrospective analysis of population-based data, we identified adult patients who underwent TKA between 2013 and 2015 in Alberta. We used multivariable linear regression to examine the association between preoperative opioid use and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores 12 months after TKA, adjusting for potentially confounding variables. Results: Of the 1907 patients, 592 (31.0%) had at least 1 opioid dispensed before TKA, and 124 (6.5%) were classified as long-term opioid users. Long-term opioid users had worse adjusted WOMAC pain and physical function scores 12 months after TKA than patients who were opioid-naive preoperatively (pain score β = 7.7, 95% confidence interval [CI] 4.0 to 11.6; physical function score β = 7.8, 95% CI 4.0 to 11.6; p < 0.001 for both). The majority (89 ([71.8%]) of patients who were long-term opioid users preoperatively were dispensed opioids 180–360 days after TKA, compared to 158 (12.0%) patients who were opioid-naive preoperatively. Conclusion: A substantial number of patients were dispensed opioids before and after TKA, and patients who received opioids preoperatively had worse adjusted pain and functional outcome scores 12 months after TKA than patients who were opioidnaive preoperatively. These results suggest that patients prescribed opioids preoperatively should be counselled judiciously regarding expected outcomes after TKA.


2019 ◽  
Author(s):  
Tamsyn M. Uren Webster ◽  
Deiene Rodriguez-Barreto ◽  
Giovanni Castaldo ◽  
John Taylor ◽  
Peter Gough ◽  
...  

AbstractMicrobial communities associated with the gut and the skin are strongly influenced by environmental factors, and can rapidly adapt to change. Historical processes may also affect the microbiome. In particular, variation in microbial colonisation in early life has the potential to induce lasting effects on microbial assemblages. However, little is known about the relative extent of microbiome plasticity or the importance of historical colonisation effects following environmental change, especially for non-mammalian species. To investigate this we performed a reciprocal translocation of Atlantic salmon between captive and semi-natural conditions. Wild and hatchery-reared fry were transferred to three common garden experimental environments for six weeks: standard hatchery conditions, hatchery conditions with an enriched diet, and simulated wild conditions. We characterised the faecal and skin microbiome of individual fish before and after the environmental translocation, using a BACI (before-after-control-impact) design. We found evidence of extensive plasticity in both gut and skin microbiota, with the greatest changes in alpha and beta diversity associated with the largest changes in environment and diet. Microbiome richness and diversity were entirely determined by environment, with no detectable historical effects of fish origin. Microbiome structure was also strongly influenced by current environmental conditions but, for the first time in fish, we also found evidence of colonisation history, including a number of OTUs characteristic of captive rearing. These results may have important implications for host adaptation to local selective pressures, and also highlight how conditions during early life can have a long-term influence on the microbiome and, potentially, host health.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mandip Dhamoon ◽  
Yeseon P Moon ◽  
Myunghee C Paik ◽  
Consuelo McLaughlin-Mora ◽  
Ralph L Sacco ◽  
...  

Background: Previous research in our population showed a steeper long-term decline in functional status after first ischemic stroke among those with Medicaid or no insurance compared to those with Medicare or private insurance. With only post-stroke data, it was unknown whether these findings were caused by the stroke. We sought to compare the long-term trajectory of functional status before and after ischemic stroke. Methods: The Northern Manhattan Study contains a prospective, population-based study of stroke-free individuals >40 years of age, followed for a median of 10 years. The Barthel index (BI) was assessed annually. Generalized estimating equations were used to assess functional decline over time before and after stroke. The 6 months after stroke were ignored, since the course of recovery during this period is well documented, and our interest was the long-term course of functional status. Follow-up was censored at the time of recurrent stroke. Sociodemographic and medical risk factors were included and results were stratified by insurance status. Linearity of the curves was evaluated by plotting residuals against time and with a lowess curve. Results: Among 3298 participants, 261 had an ischemic stroke during follow-up, of which 51 died within 6 months of stroke. Among the remaining 210 participants, mean age at stroke (standard deviation) was 77+9 years, 38% were male, 52% were Hispanic, 37% had diabetes, and 31% had coronary artery disease. There was no difference in functional decline over time before and after stroke (p= 0.51), with a decline of 0.96 BI points per year before stroke (p<.0001) and 1.24 after stroke (p=0.001). However, when stratified by insurance status, among those with Medicaid or no insurance, in a fully adjusted model, there was a difference in slope before and after stroke (p=0.04), with a decline of 0.58 BI points per year before stroke (p=0.02) and 1.94 after stroke (p=0.001). Other predictors of worse functional status were increasing age, female sex, diabetes, and being married. Conclusion: In this large, prospective, population-based study with long-term follow-up, there was a significantly steeper decline in functional status after ischemic stroke compared to before stroke among those with Medicaid or no insurance, after adjusting for confounders. The cause of this differential decline is not known but may be related to poor control of risk factors, silent strokes, or an effect of socioeconomic status.


2007 ◽  
Vol 156 (4) ◽  
pp. 455-462 ◽  
Author(s):  
Agatha A van der Klaauw ◽  
Nienke R Biermasz ◽  
Edith J M Feskens ◽  
Marieke B Bos ◽  
Johannes W A Smit ◽  
...  

Objectives: Many reports demonstrate improvements in cardiovascular risk factors during GH replacement (rhGH) in adult GH deficiency (GHD). However, it remains to be determined to what extent these changes translate into a reduction of increased cardiovascular morbidity and mortality. The aim of this study was to evaluate the effects of long-term rhGH replacement on the prevalence of the metabolic syndrome (MS). Design, settings, main outcome measures: The MS was scored by the National Cholesterol Education Program-Adult Treatment Panel III definition in 50 consecutive GHD patients (45 ± 9 years of age), before and after 2 and 5 years of rhGH replacement, and the data of untreated patients were compared with the general population using data from a Dutch population-based study (n = 1062, 44 ± 8 years of age). Results: Hypertriglyceridaemia (46.0 vs 18.5%, P < 0.0001), hypertension (66.0 vs 35.5%, P < 0.0001) and abdominal obesity (38.0 vs 23.4%, P = 0.0178) were more prevalent in untreated patients when compared with controls, resulting in a higher prevalence of the MS in patients (38.0 vs 15.7%, P < 0.0001). During rhGH replacement at a mean dose of 0.5 ± 0.2 mg/day resulting in IGF-I concentrations in the normal age-adjusted reference range, mean high-density lipoprotein cholesterol level increased compared with baseline (P < 0.001). However, the prevalence of (components of) the MS did not change after 2 or 5 years of treatment with rhGH. Conclusion: In this study, the prevalence of the MS in patients with GHD is increased compared with healthy controls, irrespective of rhGH replacement.


2019 ◽  
Vol 54 (6) ◽  
pp. 1900826 ◽  
Author(s):  
Wan C. Tan ◽  
Jean Bourbeau ◽  
Shawn D. Aaron ◽  
James C. Hogg ◽  
François Maltais ◽  
...  

BackgroundPrevious studies have associated marijuana exposure with increased respiratory symptoms and chronic bronchitis among long-term cannabis smokers. The long-term effects of smoked marijuana on lung function remain unclear.MethodsWe determined the association of marijuana smoking with the risk of spirometrically defined chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio <0.7) in 5291 population-based individuals and the rate of decline in FEV1 in a subset of 1285 males and females, aged ≥40 years, who self-reported use (or non-use) of marijuana and tobacco cigarettes and performed spirometry before and after inhaled bronchodilator on multiple occasions. Analysis for the decline in FEV1 was performed using random mixed effects regression models adjusted for age, sex and body mass index. Heavy tobacco smoking and marijunana smoking was defined as >20 pack-years and >20 joint-years, respectively.Results∼20% of participants had been or were current marijuana smokers with most having smoked tobacco cigarettes in addition (83%). Among heavy marijuana users, the risk of COPD was significantly increased (adjusted OR 2.45, 95% CI 1.55–3.88). Compared to never-smokers of marijuana and tobacco, heavy marijuana smokers and heavy tobacco smokers experienced a faster decline in FEV1 by 29.5 mL·year−1 (p=0.0007) and 21.1 mL·year−1 (p<0.0001), respectively. Those who smoked both substances experienced a decline of 32.31 mL·year−1 (p<0.0001).InterpretationHeavy marijuana smoking increases the risk of COPD and accelerates FEV1 decline in concomitant tobacco smokers beyond that observed with tobacco alone.


2018 ◽  
Vol 128 (4) ◽  
pp. 840-853 ◽  
Author(s):  
Andrew J. Davidson ◽  
Lena S. Sun

Abstract A recent U.S. Food and Drug Administration warning advised that prolonged or repeated exposure to general anesthetics may affect neurodevelopment in children. This warning is based on a wealth of preclinical animal studies and relatively few human studies. The human studies include a variety of different populations with several different outcome measures. Interpreting the results requires consideration of the outcome used, the power of the study, the length of exposure and the efforts to reduce the confounding effects of comorbidity and surgery. Most, but not all, of the large population-based studies find evidence for associations between surgery in early childhood and slightly worse subsequent academic achievement or increased risk for later diagnosis of a behavioral disability. In several studies, the amount of added risk is very small; however, there is some evidence for a greater association with multiple exposures. These results may be consistent with the preclinical data, but the possibility of confounding means the positive associations can only be regarded as weak evidence for causation. Finally, there is strong evidence that brief exposure is not associated with any long term risk in humans.


2009 ◽  
Vol 52 (11) ◽  
pp. 1815-1823 ◽  
Author(s):  
Stefan D. Holubar ◽  
Kirsten Hall Long ◽  
Edward V. Loftus ◽  
Bruce G. Wolff ◽  
John H. Pemberton ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. M. Schott ◽  
A. Termoz ◽  
M. Viprey ◽  
K. Tazarourte ◽  
C. Della Vecchia ◽  
...  

Abstract Background Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County. Methods The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006–7 and 2015–16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term. Results Between 2015–16 and 2006–7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p < 0.0001), calls to emergency call-center from 40 to 68% (p < 0.0001), first admission in stroke unit from 8 to 30% (p < 0.0001), and MRI within 24 h from 18 to 42% (p < 0.0001). Onset-to-reperfusion time significantly decreased from 3h16mn [2 h54-4 h05] to 2h35mn [2 h05-3 h19] (p < 0.0001), mainly related to a decrease in delay from admission to imaging. A significant decrease of disability was observed, as patients with mild disability (mRS [0–2]) at 12 months increased from 48 to 61% (p < 0.0001). Pre-hospital times, however, did not change significantly. Conclusions We observed significant improvement in access to reperfusion therapy, mainly through a strong decrease of in-hospital management times, and in 12-month disability after the implementation of four sets of actions between 2006 and 2016 in the Rhône County. Reducing pre-hospital times remains a challenge.


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