Intravital imaging reveals inflammation as a dominant pathophysiology of age-related hepatovascular changes

Author(s):  
Ravi Vats ◽  
Zimming Li ◽  
Eun-Mi Ju ◽  
Rikesh K Dubey ◽  
Tomasz W Kaminski ◽  
...  

Aging is the most significant risk factor for the majority of chronic diseases, including liver disease. The cellular, molecular, and pathophysiological mechanisms that promote age-induced hepatovascular changes are unknown due to our inability to visualize changes in liver pathophysiology in live mice over time. We performed quantitative liver intravital microscopy (qLIM) in live C57BL/6J mice to investigate the impact of aging on the hepatovascular system over a 24-month period. qLIM revealed that age-related hepatic alterations include reduced liver sinusoidal blood flow, increased sinusoidal vessel diameter and loss of small hepatic vessels. The ductular cell structure deteriorates with age, resulting in altered expression of hepatic junctional proteins. Furthermore, qLIM imaging revealed increased inflammation in the aged liver, which was linked to increased expression of proinflammatory macrophages, hepatic neutrophils, liver sinusoidal endothelial cells, and procoagulants. Finally, we detected elevated NF-κB pathway activity in aged livers. Overall, these findings emphasize the importance of inflammation in age-related hepatic vasculo-epithelial alterations and highlight the utility of qLIM in studying age-related effects in organ pathophysiology.

2020 ◽  
Author(s):  
Raquel R. Martins ◽  
Mazen Zamzam ◽  
Mariya Moosajee ◽  
Ryan Thummel ◽  
Catarina M. Henriques ◽  
...  

ABSTRACTAgeing is a significant risk factor for degeneration of the retina. Harnessing the regenerative potential of Müller glia cells (MG) in the retina offers great promise for the treatment of blinding conditions. Yet, the impact of ageing on MG regenerative capacity has not yet been considered. Here we show that the zebrafish retina undergoes telomerase-independent age-related neurodegeneration. Yet, this progressive neuronal loss in the ageing retina is insufficient to stimulate the MG regenerative response. Instead, age-related neurodegeneration leads to MG gliosis and loss of vision, similarly to humans. Nevertheless, gliotic MG cells retain Yap expression and the ability to regenerate neurons after acute light damage. Therefore, we identify key differences in the MG response to acute versus chronic damage in the zebrafish retina and show that aged gliotic MG can be stimulated to repair damaged neurons in old age.SUMMARYOur data suggest there are key differences between mechanisms driving regeneration in response to acute damage versus age-related chronic damage. It may be that either the number of cells dying in natural ageing is not enough to stimulate MG to proliferate, or the low number of microglia and respective signals released are not sufficient to trigger MG proliferation. Importantly, we show that gliotic MG cells can be stimulated to repair damaged neurons in old zebrafish retina.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S745-S746
Author(s):  
Casey S Zelus ◽  
Michael Blaha ◽  
Kaeli Samsom ◽  
Jasmine R Marcelin ◽  
Trevor C Van Schooneveld ◽  
...  

Abstract Background Pneumonia is a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of co-infection. However, the impact of methodology to obtain lower respiratory samples along with the utility of various microbiological diagnostic testing remains unclear. Methods A single-center retrospective analysis was performed on bronchoalveolar lavage (BAL) samples obtained from mechanically ventilated adults treated in critical care units from August 2012 to December 2017. BAL methodology (bronchoscopic vs blinded), microbiological diagnostic testing, and outcomes measures were obtained. Associations between categorical variables were assessed using Chi-Square or Fisher’s exact tests. Kruskal Wallace tests analyzed differences in distributions of measures between categories based on number of organism types detected. SAS software version 9.4 (SAS Institute Inc., Cary, NC). Results Analysis of the 803 samples that met inclusion criteria found a significant linear association between mortality and number of organism types detected by BAL, with 30 day mortality rates of 43.0%, 47.8%, and 58.3% among those with zero, one, and two or more organisms respectively (p = 0.003). Comparing BALs with at least one organism isolated, the detection of viruses specifically was associated with increased mortality, with the presence and absence of viral organisms corresponding to 56.3% and 46.5% mortality at thirty days (p = 0.03). No association was found between mortality and isolation of acid-fast bacilli, bacteria, or fungi. Co-infection was detected more frequently among bronchoscopic BALs than blinded BALs (26.3% vs 8.6%, p < 0.0001), with more viruses detected bronchoscopic BALs (41.9% vs 13.1%, p < 0.0001), and more bacteria in blinded BALs (41.8% vs 33.0%, p = 0.01). 30 Day Mortality vs Isolation of Specific Organism Types from BAL Number of Organism Types Isolated from BAL Compared to BAL Methodology BAL Methodology vs Isolation of Specific Organism Types Conclusion Co-infection in mechanically ventilated adult patients with pneumonia appears to be a significant risk factor for mortality, with the detection of viral organisms potentially playing an independent role. Within this population, bronchoscopic BALs may have a valuable diagnostic and prognostic methodology. Disclosures All Authors: No reported disclosures


2021 ◽  
pp. 1753495X2110641
Author(s):  
Diana Oprea ◽  
Nadine Sauvé ◽  
Jean-Charles Pasquier

Background Hypothyroidism affects 3% of pregnant women, and to date, no studies have addressed the impact levothyroxine-treated hypothyroidism on delivery outcome. Methods This retrospective cohort study was conducted among 750 women with a singleton pregnancy who gave birth between 2015 and 2019. Delivery modes were compared between 250 hypothyroid women exposed to levothyroxine and 500 euthyroid control women. The aim of this study was to determine the impact of levothyroxine exposure on delivery outcome. Results Multiple logistic regression showed no significant association between exposure to levothyroxine and the overall rate of caesarean delivery (aOR 1.1; 95% CI 0.8 to 1.6). Mean TSH concentrations were significantly higher throughout the pregnancy in hypothyroid women despite levothyroxine treatment. Maternal and neonatal outcomes in both groups were not different. Conclusion Hypothyroidism treated with levothyroxine during pregnancy according to local guidelines is not a significant risk factor for caesarean delivery.


2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Paula Ferrada ◽  
Rahul J. Anand ◽  
Ajai Malhotra ◽  
Michel Aboutanos

Objective.The aim of this study is to evaluate the impact of obesity on patient outcomes after emergency surgery.Methods.A list of all patients undergoing emergent general surgical procedures during the 12 months ending in July 2012 was obtained from the operating room log. A chart review was performed to obtain the following data: patient characteristics (age, gender, BMI, and preexisting comorbidities), indication for surgery, and outcomes (pulmonary embolus (PE), deep venous thrombosis (DVT), respiratory failure, ICU admission, wound infection, pneumonia, and mortality). Obesity was defined as a BMI over 25. Comparisons of outcomes between obese and nonobese patients were evaluated using Fischer’s exact test. Predictors of mortality were evaluated using logistic regression.Results.341 patients were identified during the study period. 202 (59%) were obese. Both groups were similar in age (48 for obese versus 47 for nonobese,P=0.42). Obese patients had an increased incidence of diabetes, (27% versus 7%,P<0.05), hypertension (52% versus 34%,P<0.05), and sleep apnea (0% versus 5%,P<0.05). There was a statistically significant increased incidence of postoperative wound infection (obese 9.9% versus nonobese 4.3%,P<0.05) and ICU admission (obese 58% versus nonobese 42%,P=0.01) among the obese patients. Obesity alone was not shown to be a significant risk factor for mortality.Conclusions.A higher BMI is not an independent predictor of mortality after emergency surgery. Obese patients are at a higher risk of developing wound infections and requiring ICU admission after emergent general surgical procedure.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Shelby M. Kleweis ◽  
Alison G. Cahill ◽  
Anthony O. Odibo ◽  
Methodius G. Tuuli

Objective. To test the hypothesis that maternal obesity is an independent risk factor for rectovaginal group B streptococcus (GBS) colonization at term.Study Design. Retrospective cohort study of consecutive women with singleton term pregnancies admitted in labor at Barnes-Jewish Hospital (2004–2008). Maternal BMI ≥ 30 Kg/m2(obese) or <30 Kg/m2(nonobese) defined the two comparison groups. The outcome of interest was GBS colonization from a positive culture. Baseline characteristics were compared using Student’st-test and Chi-squared or Fisher’s exact test. The association between obesity and GBS colonization was assessed using univariable and multivariable analyses.Results. Of the 10,564 women eligible, 7,711 met inclusion criteria. The prevalence of GBS colonization in the entire cohort was relatively high (25.8%). Obese gravidas were significantly more likely to be colonized by GBS when compared with nonobese gravidas (28.4% versus 22.2%,P<0.001). Obese gravidas were still 35% more likely than nonobese women to test positive for GBS after adjusting for race, parity, smoking, and diabetes (adjusted OR 1.35 [95% CI 1.21–1.50]).Conclusion. Maternal obesity is a significant risk factor for GBS colonization at term. Further research is needed to evaluate the impact of this finding on risk-based management strategies.


Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 547
Author(s):  
Mi Sook Jung ◽  
Eunyoung Chung

This study examined the association between television (TV) viewing and cognitive dysfunction in elderly Koreans. Among participants of the 2014 National Survey of Older Koreans, 9644 were considered in this study. To better identify the association between two factors, propensity score (PS) matching with exact method was used. Finally, 168 viewers and non-viewers each were selected based on estimated PS on key variables and eliminating double matches. Multivariate logistic regression analysis was performed when controlling for possible covariates. Viewers were more likely to have cognitive dysfunction than non-viewers, with significant differences in most covariates. After correcting confounding effects of these covariates with PS matching, TV viewing was found to be a significant risk factor of cognitive dysfunction, along with absence of diagnosed hypertension and non-participation in physical leisure activities. TV viewing might be associated with increased risk of cognitive dysfunction in later life. Appropriate education and strategies to minimize TV viewing among older adults should be established to contribute to attenuating cognitive aging. More interventional studies can help older adults, caregivers, and healthcare professionals explore the cognitively beneficial alternatives to TV use considering the impact of socioeconomic factors of selecting TV viewing as a preferred leisure activity.


2017 ◽  
Vol 45 (2) ◽  
Author(s):  
Cenk Gezer ◽  
Atalay Ekin ◽  
Gokhan Goynumer ◽  
Kaan Pakay ◽  
Hicran Acar ◽  
...  

AbstractObjective:To determine the impact of the chorion villus sampling (CVS) technique on adverse perinatal outcomes.Methods:In this case-control study, 412 women who underwent CVS at 11–14 weeks of gestation and 231 women who did not undergo any invasive procedure were retrospectively evaluated. The women in the CVS group were further divided into two groups according to the use of single-needle technique (n=148) vs. double-needle technique (n=264). The adverse outcomes were compared between controls and the two CVS groups, and regression analysis was used to determine the significance of independent contribution.Results:The rate of preeclampsia for the control group was 2.2%, for the double-needle group was 3% and for the single-needle group was 8.1%. CVS with single-needle technique was found to be an independent and statistically significant risk factor for preeclampsia [odds ratio (OR)=2.1, 95% confidence interval (CI); 1.4–2.7, P=0.008].Conclusion:The risk of preeclampsia after CVS appears to be increased with single-needle technique compared with double-needle technique.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gina E. C. Charnley ◽  
Ilan Kelman ◽  
Nathan Green ◽  
Wes Hinsley ◽  
Katy A. M. Gaythorpe ◽  
...  

Abstract Background Temperature and precipitation are known to affect Vibrio cholerae outbreaks. Despite this, the impact of drought on outbreaks has been largely understudied. Africa is both drought and cholera prone and more research is needed in Africa to understand cholera dynamics in relation to drought. Methods Here, we analyse a range of environmental and socioeconomic covariates and fit generalised linear models to publicly available national data, to test for associations with several indices of drought and make cholera outbreak projections to 2070 under three scenarios of global change, reflecting varying trajectories of CO2 emissions, socio-economic development, and population growth. Results The best-fit model implies that drought is a significant risk factor for African cholera outbreaks, alongside positive effects of population, temperature and poverty and a negative effect of freshwater withdrawal. The projections show that following stringent emissions pathways and expanding sustainable development may reduce cholera outbreak occurrence in Africa, although these changes were spatially heterogeneous. Conclusions Despite an effect of drought in explaining recent cholera outbreaks, future projections highlighted the potential for sustainable development gains to offset drought-related impacts on cholera risk. Future work should build on this research investigating the impacts of drought on cholera on a finer spatial scale and potential non-linear relationships, especially in high-burden countries which saw little cholera change in the scenario analysis.


2020 ◽  
Author(s):  
Nan Hu ◽  
Chunyi Wang ◽  
Yan Liao ◽  
Qichen Dai ◽  
Shiyi Cao

Abstract Background: Both smoking and insomnia are worldwide problems and this study aims to investigate the impact of smoking on the incidence of insomnia. Methods: PubMed, EMBASE and OVID were searched through March, 2020. Cohort studies reporting the effect of smoking on the incidence of insomnia were included. We quantitatively analyzed the basic framework and study characteristics, and then pooled estimate effects with 95% confidence intervals (CIs) of outcomes of each included studies using fixed-effects meta-analyses. Results: This systematic review included six cohort studies involving 12445 participants. Quantitatively summarized results suggested smoking could significantly increase the incidence of insomnia (OR: 1.07, 95%CI: 1.02,1.13). Regular smoking was significantly associated with incidence of insomnia (OR=1.07, 95% CI:1.01,1.13). As for occasional smokers and ex-smokers, the pooled analysis didn’t indicate a significant association (occasional smoker: OR=2.09, 95% CI:0.44,9.95; ex-smoker; OR=1.02, 95% CI:0.67,1.54). Subgroup analysis by age, gender ratio and region showed statistically significant relationship between smoking and incidence of insomnia in specific groups. Conclusions: Integrated longitudinal observational evidence identified smoking as a significant risk factor of insomnia. Considering the limited amount of available studies, more high-quality and prospective cohort studies of large sample sizes are needed to explore details of this association.


2020 ◽  
Vol 32 (S1) ◽  
pp. 173-173
Author(s):  
Catarina Pedro ◽  
Mariana Duarte ◽  
Beatriz Jorge ◽  
Daniela Freitas

Introduction:Personality and emotions have not been studied as thoroughly as cognition in old age. Recent research suggests personality changes across the entire life span, through middle age and even into old age. Thus, the previous assumption of stability in personality traits from early adulthood has been challenged and novel approaches to the study of personality development have emerged.Objectives:The aim of this presentation is to describe the effects of the ageing process in personality and emotions.Methods:A non-systematic review of the literature was performed on PubMed, PsycINFO and Web of science using selected keywords.Results:When older adults compare their current and past selves, they usually perceive a subjective growth in personality. Descriptive research suggests that the big five personality characteristics (neuroticism, extraversion, openness, agreeableness and conscientiousness) remain generally stable over the lifespan, despite variations in life experiences. Some studies revealed age-related linear decrease in extraversion. One of the studies found that hearing impairment, already identified as a significant risk factor for social isolation, was related to this decline in extraversion. Although levels of neuroticism tends to go down over the course of adulthood, the increased vulnerabilities that accompany old age may amplify neurotic traits, increasing worries about physical health and memory, common features of depression in the elderly. Emotions, relative to more neutral knowledge and skills, increase in later years. Elderly have better control over emotions than do younger adults, they reason more flexibly about emotion-laden dilemmas and remember emotionally charged information better than neutral facts. Older people also rely more often on emotion-focused forms of coping, as opposed to active, problem-solving approaches.Conclusions:Core features of personality seem to remain relatively stable throughout adulthood and any marked change in mood or social behavior may indicate a disorder. However, more subtle reordering of personal priorities and shifts in coping styles are common with normal ageing. The richness of emotional processing in older persons runs counter to the generally declining patterns seen in many cognitive and physical skills.


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