Aging changes in bladder HCN are associated with increasing heterogeneity of adrenergic/mucosal influence on detrusor control in the mouse

2021 ◽  
Author(s):  
Cara C Hardy ◽  
Iman M Al-Naggar ◽  
Chia-Ling Kuo ◽  
George A Kuchel ◽  
Phillip P Smith
Keyword(s):  
Bladder Wall ◽  
Bladder Volume ◽  
Clinical Model ◽  
Mean Values ◽  
Bladder Control ◽  
Increased Risk ◽  
Neural Information ◽  
Sensory Neural ◽  
Aging Bladder ◽  
The Impact

Abstract A geroscience-informed approach to the increasing prevalence of bladder control problems in older adults requires understanding the impact of aging on dynamic mechanisms that ensure resilience in response to stressors challenging asymptomatic voluntary control over urine storage and voiding. Bladder control is predicated on sensory neural information about bladder volume. Modulation of volume-induced bladder wall tensions by autonomic and mucosal factors controls neural sensitivity to bladder volume. We hypothesized that HCN (hyperpolarization-activated cyclic nucleotide-gated) channels integrate these factors and thereby mediate adrenergic detrusor tension control. Furthermore, loss of HCN expression compromises that integration, and could result in loss of precision of detrusor control. Using a lifespan mouse model, RT-qPCR and pharmacologic studies in pre-tensioned intact and mucosa-denuded bladder strips were made. The dominant hcn1 expression declines with maturation and aging, however aging is also associated with increased variance around mean values. In strips from mature animals, isoproterenol had less effect in denuded muscle strips than in intact strips, and HCN blockade diminished isoproterenol responsiveness. With aging, variances about mean response values significantly increased, paralleling hcn1 expression. Our findings support a role for HCN in providing neuroendocrine/paracrine integration and suggest an association of increased heterogeneity of HCN expression in aging with reductions in response precision to neuroendocrine control. The functional implication is an increased risk of dysfunction of brainstem/bladder regulation of neuronal sensitivity to bladder volume. This supports the clinical model of the aging bladder phenotype as an expression of loss of resilience, and not as emerging bladder pathology with aging.

Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease

2017 ◽  
Vol 87 (1-2) ◽  
pp. 10-16 ◽  
Author(s):  
Salah Gariballa ◽  
Awad Alessa
Keyword(s):  
Nutritional Status ◽  
Inductively Coupled Plasma ◽  
Older Patients ◽  
Controlled Trial ◽  
Prognostic Indicators ◽  
Hospitalised Patients ◽  
Increased Risk ◽  
Co Morbidity ◽  
The Impact ◽  
Poor Nutrition

Abstract. Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. Methods: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. Results: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 μmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. Conclusions: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Lea Weingarz ◽  
Marc Schindewolf ◽  
Jan Schwonberg ◽  
Carola Hecking ◽  
Zsuzsanna Wolf ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Younger Patients ◽  
Risk Of Recurrence ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

Percutaneous Coronary Intervention in Patients with Diabetes and Multivessel or Left Main Disease – a Review

2012 ◽  
Vol 7 (1) ◽  
pp. 37
Author(s):  
Donald E Cutlip ◽  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Coronary Artery ◽  
Statistical Significance ◽  
Bare Metal Stents ◽  
Coronary Intervention ◽  
Metal Stents ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Patients With Diabetes ◽  
The Impact

Coronary artery disease in patients with diabetes is frequently a diffuse process with multivessel involvement and is associated with increased risk for myocardial infarction and death. The role of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with diabetes and multivessel disease who require revascularisation has been debated and remains uncertain. The debate has been continued mainly because of the question to what degree an increased risk for in-stent restenosis among patients with diabetes contributes to other late adverse outcomes. This article reviews outcomes from early trials of balloon angioplasty versus CABG through later trials of bare-metal stents versus CABG and more recent data with drug-eluting stents as the comparator. Although not all studies have been powered to show statistical significance, the results have been generally consistent with a mortality benefit for CABG versus PCI, despite differential risks for restenosis with the various PCI approaches. The review also considers the impact of mammary artery grafting of the left anterior descending artery and individual case selection on these results, and proposes an algorithm for selection of patients in whom PCI remains a reasonable strategy.

Working conditions and occupational pathology of coal miners in the Arctic

2019 ◽  
pp. 452-457 ◽  
Author(s):  
S. A. Gorbanev ◽  
S. A. Syurin ◽  
N. M. Frolova
Keyword(s):  
Coal Mining ◽  
Working Conditions ◽  
Occupational Diseases ◽  
Climatic Factors ◽  
Coal Mines ◽  
The Arctic ◽  
Morbidity Rate ◽  
Coal Miners ◽  
Increased Risk ◽  
The Impact

Introduction. Due to the impact of adverse working conditions and climate, workers in coal-mining enterprises in the Arctic are at increased risk of occupational diseases (OD).The aim of the study was to study the working conditions, causes, structure and prevalence of occupational diseases in miners of coal mines in the Arctic.Materials and methods. Th e data of social and hygienic monitoring “Working conditions and occupational morbidity” of the population of Vorkuta and Chukotka Autonomous District in 2007–2017 are studied.Results. It was established that in 2007–2017 years, 2,296 ODs were diagnosed for the first time in 1851 coal mines, mainly in the drifters, clearing face miners, repairmen and machinists of mining excavating machines. Most often, the ODs occurred when exposed to the severity of labor, fibrogenic aerosols and hand-arm vibration. The development of professional pathology in 98% of cases was due to design flaws of machines and mechanisms, as well as imperfections of workplaces and technological processes. Diseases of the musculoskeletal system (36.2%), respiratory organs (28.9%) and nervous system (22.5%) prevailed in the structure of professional pathology of miners of coal mines. Among the three most common nosological forms of OD were radiculopathy (32.1%), chronic bronchitis (27.7%) and mono-polyneuropathy (15.4%). In 2017, coal miners in the Arctic had a professional morbidity rate of 2.82 times higher than the national rates for coal mining.Conclusions. To preserve the health of miners of coal mining enterprises, technical measures to improve working conditions and medical interventions aimed at increasing the body’s resistance to the effects of harmful production and climatic factors are necessary.

Study of Biochemical and Clinical Markers in Steatohepatitis Related to Obesity

2018 ◽  
Vol 69 (6) ◽  
pp. 1501-1505
Author(s):  
Roxana Maria Livadariu ◽  
Radu Danila ◽  
Lidia Ionescu ◽  
Delia Ciobanu ◽  
Daniel Timofte
Keyword(s):  
Liver Disease ◽  
Liver Biopsy ◽  
Large Scale ◽  
Biological Data ◽  
Obese Patients ◽  
Clinical Markers ◽  
Mean Values ◽  
Nonalcoholic Fatty Liver ◽  
Obstructive Sleep ◽  
Increased Risk

Nonalcoholic fatty liver disease (NAFLD) is highly associated to obesity and comprises several liver diseases, from simple steatosis to steatohepatitis (NASH) with increased risk of developing progressive liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver biopsy is the gold standard in diagnosing the disease, but it cannot be used in a large scale. The aim of the study was the assessment of some non-invasive clinical and biological markers in relation to the progressive forms of NAFLD. We performed a prospective study on 64 obese patients successively hospitalised for bariatric surgery in our Surgical Unit. Patients with history of alcohol consumption, chronic hepatitis B or C, other chronic liver disease or patients undergoing hepatotoxic drug use were excluded. All patients underwent liver biopsy during sleeve gastrectomy. NAFLD was present in 100% of the patients: hepatic steatosis (38%), NASH with the two forms: with fibrosis (31%) and without fibrosis (20%), cumulating 51%; 7 patients had NASH with vanished steatosis. NASH with fibrosis statistically correlated with metabolic syndrome (p = 0.036), DM II (p = 0.01) and obstructive sleep apnea (p = 0.02). Waist circumference was significantly higher in the steatohepatitis groups (both with and without fibrosis), each 10 cm increase increasing the risk of steatohepatitis (p = 0.007). The mean values of serum fibrinogen and CRP were significantly higher in patients having the progressive forms of NAFLD. Simple clinical and biological data available to the practitioner in medicine can be used to identify obese patients at high risk of NASH, aiming to direct them to specialized medical centers.

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

scholarly journals Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery

2011 ◽  
Vol 114 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Laurent G. Glance ◽  
Andrew W. Dick ◽  
Dana B. Mukamel ◽  
Fergal J. Fleming ◽  
Raymond A. Zollo ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Noncardiac Surgery ◽  
Pulmonary Complications ◽  
Wound Complications ◽  
Severe Anemia ◽  
Thromboembolic Complications ◽  
Mortality And Morbidity ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Background The impact of intraoperative erythrocyte transfusion on outcomes of anemic patients undergoing noncardiac surgery has not been well characterized. The objective of this study was to examine the association between blood transfusion and mortality and morbidity in patients with severe anemia (hematocrit less than 30%) who are exposed to one or two units of erythrocytes intraoperatively. Methods This was a retrospective analysis of the association of blood transfusion and 30-day mortality and 30-day morbidity in 10,100 patients undergoing general, vascular, or orthopedic surgery. We estimated separate multivariate logistic regression models for 30-day mortality and for 30-day complications. Results Intraoperative blood transfusion was associated with an increased risk of death (odds ratio [OR], 1.29; 95% CI, 1.03-1.62). Patients receiving an intraoperative transfusion were more likely to have pulmonary, septic, wound, or thromboembolic complications, compared with patients not receiving an intraoperative transfusion. Compared with patients who were not transfused, patients receiving one or two units of erythrocytes were more likely to have pulmonary complications (OR, 1.76; 95% CI, 1.48-2.09), sepsis (OR, 1.43; 95% CI, 1.21-1.68), thromboembolic complications (OR, 1.77; 95% CI, 1.32-2.38), and wound complications (OR, 1.87; 95% CI, 1.47-2.37). Conclusions Intraoperative blood transfusion is associated with a higher risk of mortality and morbidity in surgical patients with severe anemia. It is unknown whether this association is due to the adverse effects of blood transfusion or is, instead, the result of increased blood loss in the patients receiving blood.

Pre-Existing Psychiatric Illness Is Associated With an Increased Risk of Delirium in Patients With Acute Respiratory Distress Syndrome

2021 ◽  
pp. 088506662110190
Author(s):  
Saminder Singh Kalra ◽  
Johnny Jaber ◽  
Bashar N. Alzghoul ◽  
Ryan Hyde ◽  
Sarina Parikh ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Psychiatric Illness ◽  
Distress Syndrome ◽  
Multivariable Logistic Regression Analysis ◽  
Psychiatric Illnesses ◽  
Increased Risk ◽  
Icu Delirium ◽  
The Impact

Background: Patients with acute respiratory distress syndrome (ARDS) are highly susceptible to developing delirium for a multitude of reasons. Previous studies have linked pre-existing depression with an increased risk of postoperative delirium in patients undergoing cardiac and non-cardiac surgery. However, the evidence regarding the association between pre-existing psychiatric illnesses and delirium in ARDS patients is unknown. In this study, we aim to determine the relationship between pre-existing psychiatric illness and the risk of development of delirium amongst ARDS patients. Study Design and Methods: We performed a retrospective study of a mixed group of patients admitted to the intensive care unit (ICU) between January 2016 and December 2019 with a diagnosis of ARDS per the Berlin definition. The study group was divided into 2 cohorts: subjects with delirium and subjects without delirium. Comparison between the 2 groups was conducted to examine the impact of pre-existing psychiatric illnesses including major depressive disorder (MDD), generalized anxiety disorder (GAD), bipolar disorder, schizophrenia, or post-traumatic stress disorder. Multivariable logistic regression analysis was performed adjusting for benzodiazepine use, sedatives, analgesics, sequential organ failure assessment score, and corticosteroid use to determine the association between pre-existing psychiatric disorders and delirium. Results: 286 patients with ARDS were identified; 124 (43%) of whom were diagnosed with ICU delirium. In patients diagnosed with ICU delirium, 49.2% were found to have preexisting psychiatric illnesses, compared to 34.0% without any preexisting psychiatric illness (OR = 1.94, P = 0.01). In a subgroup analysis of individual psychiatric illnesses, GAD and MDD were associated with the development of delirium (OR = 1.88, P = 0.04 and OR = 1.76, P = 0.05 respectively). Interpretation: ARDS patients with preexisting psychiatric illnesses, particularly GAD and MDD are associated with an increased risk of developing ICU delirium. Clinicians should be aware of the effect of psychiatric co-morbidities on developing delirium in critically ill patients.

Body mass index and risk of all-cause mortality in normotensive and hypertensive adults: The Rural Chinese Cohort Study

2021 ◽  
pp. 1-25
Author(s):  
Qionggui Zhou ◽  
Xuejiao Liu ◽  
Yang Zhao ◽  
Pei Qin ◽  
Yongcheng Ren ◽  
...  
Keyword(s):  
Cohort Study ◽  
Population Based ◽  
Normal Weight ◽  
Sensitivity Analyses ◽  
Hypertension Status ◽  
Moderation Effect ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Chinese Cohort ◽  
The Impact

Abstract Objective: The impact of baseline hypertension status on the BMI–mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI–mortality association using a rural Chinese cohort. Design: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. Setting: Longitudinal population-based cohort Participants: 17,262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. Results: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the HRs (95% CI) for mortality in normotensive participants were 1.92 (1.23-3.00), 1.44 (1.01-2.05), 1.14 (0.82-1.58), 0.96 (0.70-1.31), 0.96 (0.65-1.43), 1.32 (0.81-2.14), and 1.32 (0.74-2.35) respectively, and in hypertensive participants were 1.85 (1.08-3.17), 1.67 (1.17-2.39), 1.29 (0.95-1.75), 1.20 (0.91-1.58), 1.10 (0.83-1.46), 1.10 (0.80-1.52), and 0.61 (0.40-0.94) respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity versus normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. Conclusions: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

scholarly journals Exploring the impact of COVID-19 and restrictions to daily living as a result of social distancing within veterans with pre-existing mental health difficulties

2020 ◽  
pp. bmjmilitary-2020-001622 ◽  
Author(s):  
Dominic Murphy ◽  
C Williamson ◽  
J Baumann ◽  
W Busuttil ◽  
N T Fear
Keyword(s):  
Mental Health ◽  
Social Support ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Post Traumatic Stress ◽  
Increased Risk ◽  
Mental Health Difficulties ◽  
Post Traumatic ◽  
The Impact

IntroductionData are emerging showing the adverse consequences on mental health of the general public due to the COVID-19 pandemic. Little is known about the needs of veterans with pre-existing mental health difficulties during the COVID-19 pandemic.MethodsData were collected through a cross-sectional online survey from a randomly selected sample (n=1092) of military veterans who have sought help for mental health difficulties from a veteran-specific UK-based charity. The response rate was 25.2% (n=275). Participants were asked to complete a range of standardised mental health outcomes (post-traumatic stress disorder (PTSD): Post-traumatic Stress Disorder Checklist, common mental health difficulties (CMDs): 12-Item General Health Questionnaire, difficulties with anger: 5-Item Dimensions of Anger Reactions—Revised and alcohol misuse: Alcohol Use Disorders Identification Test) and endorse a list of potential stressors related to changes to daily life resulting from COVID-19. Regression analyses were fitted to explore predictors of mental health severity.ResultsIt was observed that symptoms of common mental disorder and PTSD (69.3% and 65.0%, respectively) were the most commonly reported to have been exacerbated by the pandemic. Lack of social support and reporting increasing numbers of stressors related to COVID-19 were consistently associated with increasing severity of a range of mental health difficulties.ConclusionsOur findings suggest veterans who had pre-existing mental health difficulties prior to the outbreak of COVID-19 may be at increased risk of experiencing CMDs as a result of the pandemic. Intervening to improve levels of social support and offering practical guidance to better manage any additional stressors relating to the pandemic may provide strategies to help reduce the burden of mental health symptoms.

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