scholarly journals Estrogen and neuroprotection: from clinical observations to molecular mechanisms

2002 ◽  
Vol 4 (2) ◽  
pp. 149-161 ◽  
Keyword(s):  
Molecular Mechanisms ◽  
Science Studies ◽  
Adult Brain ◽  
Health Concern ◽  
Past Century ◽  
Clinical Observations ◽  
Protective Actions ◽  
Increased Risk ◽  
The Impact

We now appreciate that estrogen is a pleiotropic gonadal steroid that exerts profound effects on the plasticity and cell survival of the adult brain. Over the past century, the life span of women has increased, but the age of the menopause remains constant. This means that women may now live over one third of their lives in a hypoestrogenic, postmenopausal state. The impact of prolonged hypoestrogenicity on the brain is now a critical health concern as we realize that these women may suffer an increased risk of cognitive dysfunction and neurodegeneration due to a variety of diseases. Accumulating evidence from both clinical and basic science studies indicates that estrogen exerts critical protective actions against neurodegenerative conditions such as Alzheimer's disease and stroke. Here, we review the discoveries that comprise our current understanding of estrogen action against neurodegeneration. These findings carry far-reaching possibilities for improving the quality of life in our aging population.

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.

Management of Oral Anti-Coagulation in Patients with Heart Failure—Insights from the ThrombEVAL Study

2018 ◽  
Vol 118 (11) ◽  
pp. 1930-1939
Author(s):  
Sebastian Göbel ◽  
Jürgen Prochaska ◽  
Lisa Eggebrecht ◽  
Ronja Schmitz ◽  
Claus Jünger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Vitamin K Antagonists ◽  
Plasma Concentrations ◽  
Regular Care ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
Specialized Care ◽  
The Impact

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outcome, results were compared with data from individuals receiving specialized care for anti-coagulation (n = 760). Overall, the sample comprised of 813 individuals with HF and 1,160 subjects without HF in the regular care cohort. Quality of OAC assessed by time in therapeutic range (TTR) was 66.1% (47.8%/82.8%) for patients with HF and 70.6% (52.1%/85.9%) for those without HF (p = 0.0046). Stratification for New York Heart Classification (NYHA)-class demonstrated a lower TTR with higher NYHA classes: TTRNYHA-I 69.6% (49.4%/85.6%), TTRNYHA-II 66.5% (50.1%/82.9%) and TTRNYHA-≥III 61.8% (43.1%/79.9%). This translated into a worse net clinical benefit outcome for HF (hazard ratio [HR] 1.63 [1.31/2.02]; p < 0.0001) and an increased risk of bleeding (HR 1.40 [1.04/1.89]; p = 0.028). Management in a specialized coagulation service resulted in an improvement of all, TTR (∆+12.5% points), anti-coagulation-specific and non-specific outcome of HF individuals. In conclusion, HF is an independent risk factor for low quality of OAC therapy translating into an increased risk for adverse events, which can be mitigated by specialized care.

The Impact of Hurricane Maria on Individuals Living with Non-Communicable Disease in Puerto Rico: The experience of 10 communities

2021 ◽  
Author(s):  
Elizabeth L. Andrade ◽  
Amalis Cordova Mustafa ◽  
Courtney Riggle-vanSchagen ◽  
Megan Jula ◽  
Carlos E. Rodriguez-Diaz ◽  
...  
Keyword(s):  
Puerto Rico ◽  
Natural Hazards ◽  
Structural Damage ◽  
Communicable Disease ◽  
Community Level ◽  
Morbidity And Mortality ◽  
Health Concern ◽  
Increased Risk ◽  
The Impact ◽  
Non Communicable Disease

Abstract Background Coinciding with the rising non-communicable disease (NCD) prevalence worldwide is the increasing frequency and severity of natural hazards. Protecting populations with NCDs against natural hazards is ever more pressing given their increased risk of morbidity and mortality in disaster contexts. Methods This investigation examined Hurricane Maria’s impact across 10 communities in Puerto Rico to determine whether and how disaster impact and community attributes affected NCD management. We conducted 40 qualitative interviews with mayors, first responders, faith leaders, community leaders, and municipal employees, with 4 interviews per selected municipality. Using QSR NVivo software, we coded interview transcripts and created categorical community-level impact variables based on participant responses. We undertook thematic analysis to characterize community-level impact and consequences for NCD management, and to identify convergent and divergent themes. Using a matrix coding query, we compared NCD management experiences across communities by impact variables and community attributes. Results The delivery of healthcare, pharmacy, and dialysis services was compromised due to facility structural damage and ineffective contingencies for electrical power and water supply. The challenges resulting from power outages were immediate, and individuals who were reliant on life-sustaining medical equipment, dialysis, or the refrigeration of medications were most vulnerable. Inaccessible roadways and the need to travel greater distances to locate operational health services were major impediments to transporting patients in need of NCD care, with those requiring dialysis and living in remote, mountainous communities at highest risk due to landslides and lengthy roadway obstruction. These barriers were compounded by limited communication to locate services and coordinate care. Two weeks post-hurricane, emerging challenges to NCD management included widespread diesel fuel shortages for generators, and shortages in medications, oxygen, and medical supplies. In the weeks to months post-hurricane, the emergence or exacerbation of mental health disorders was characterized as a pressing health concern. Conclusions Study findings identify contributors to morbidity and mortality among individuals with NCDs following Hurricane Maria. The degree to which these impacts were experienced across communities with different characteristics is discussed, offering important lessons regarding the impact of catastrophic disasters on NCD management for improve community disaster resilience.

scholarly journals Impact of a Smoking Cessation Quitline in Vietnam: Evidence Base and Future Directions

2019 ◽  
Vol 16 (14) ◽  
pp. 2538
Author(s):  
Chau Quy Ngo ◽  
Phuong Thu Phan ◽  
Giap Van Vu ◽  
Quyen Thi Le Pham ◽  
Hanh Thi Chu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Tobacco Consumption ◽  
Evidence Base ◽  
Health Concern ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Quit Attempt ◽  
Early Action ◽  
The Impact

Smoking is considered the most critical modifiable factor with regard to lung cancer and remains a public health concern in many countries, including Vietnam, which is among those countries with the highest tobacco consumption rates in the world. This study has examined the impact of national telephone counselling for smoking cessation and has identified the factors associated with the impact of the quitline among male callers in Vietnam. A randomized cross-sectional survey of 469 smokers who sought smoking cessation services via the national quitline was performed from September 2015 to May 2016. The primary outcomes were measured by a self-reported quit rate at the time of assessment, 7 day point prevalence abstinence (PA), 6 month prolonged PA, service satisfaction, and level of motivation. Among the participants, 31.6% were abstinent, and 5.1% of participants successfully stopped smoking and did not need to seek quitline support. Most of the clients were satisfied with the quality of service (88.5%), felt more confident about quitting (74.3%), and took early action via their first quit attempt (81.7%); 18.3% reported a more than 7 day abstinence period at the time of survey. The primary reasons for smoking relapse were surrounding smoking environments (51.6%) and craving symptoms (44.1%). Future smoking cessation efforts should focus on improving the quality of quitline services, client satisfaction, and developing a tailored program and counseling targeting smokers with specific characteristics, especially ones experiencing chronic diseases.

scholarly journals O26 Non-serious infections in patients with RA: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Katie Bechman ◽  
Kapil Halai ◽  
Sam Norton ◽  
Andrew P Cope ◽  
Kimme L Hyrich ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
British Society ◽  
Tnf Inhibitor ◽  
Drug Survival ◽  
Increased Risk ◽  
Serious Infections ◽  
The Impact ◽  
Biologics Register

Abstract Background Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number. Results There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1). Conclusion These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life. Disclosures K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.

scholarly journals Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic

Gut ◽  
2020 ◽  
Vol 69 (9) ◽  
pp. 1555-1563 ◽  
Author(s):  
Gianluca Ianiro ◽  
Benjamin H Mullish ◽  
Colleen R Kelly ◽  
Zain Kassam ◽  
Ed J Kuijper ◽  
...  
Keyword(s):  
Healthcare Professionals ◽  
Faecal Microbiota ◽  
Clostridioides Difficile ◽  
Research Activities ◽  
Increased Risk ◽  
Recruitment And Selection ◽  
Spread Of Infection ◽  
The Impact

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

scholarly journals Lack of application of the European Work Time Directive: effects on workload, work satisfaction and burnout among Italian physicians

2017 ◽  
Vol 11 (2) ◽  
pp. 159
Author(s):  
Paola Gnerre ◽  
Domenico Montemurro ◽  
Andrea P. Rossi ◽  
Costantino Troise ◽  
Carlo Palermo ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Work Conditions ◽  
Public Hospitals ◽  
Burnout Syndrome ◽  
Negative Consequences ◽  
Work Time ◽  
Increased Risk ◽  
Wide Range ◽  
The Impact

The Italian Parliament has excluded hospital physicians from the application of the European Work Time Directive (EWTD), which imposes a maximum workweek of 48 h and compulsory resting periods. This resulted in extended and excessive work time for the category. This paper is aimed at evaluating the impact of this legislation gap, by assessing the presence of excessive work-related stress and risk for burnout syndrome among Italian physicians working in public hospitals. This observational study is based on an on-line survey conducted on a sample of 1925 Italian doctors (covering a wide range of age, work experience and contractual positions) from October 2014 to February 2015. The questionnaire included 30 questions concerning their personal and professional life (<em>e.g</em>., assessment of workloads, number of uncomfortable or extra shifts, unused days-off, <em>etc</em>.). On the basis of the results, it can be inferred that the average Italian doctor working in public hospitals is under considerable stress at work with negative consequences on his health. He is exposed to high risk of suffering from sleep disorders and cardiovascular diseases (due to the lack of time for private practice and eating regular meals). Overall, his perception is that his job worsens his quality of life. This study shows the relevance of the risk of burnout among Italian physicians employed in public hospitals due to severe workload and work conditions. The resulting impact on the quality of care and the significant cost involved - both in human and economic terms - calls for significant emergency measures by the Italian health work organization. An important increase and prolonged working time is associated with a worsening of the objective cognitive performance and an increase of clinical risk, but also to an increased risk of diseases for operators and of the burnout syndrome. Our survey shows that lack of application of the EWTD has adverse effects on the quality of life and performance of Italian doctors. Failure to respond by all Italian doctors is the greatest limitation of our survey.

scholarly journals Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001726
Author(s):  
Anthony P Carnicelli ◽  
Ruth Owen ◽  
Stuart J Pocock ◽  
David B Brieger ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Increased Risk ◽  
History Of ◽  
The Impact

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

scholarly journals Urinary Dysfunction in Women Following Total Mesorectal Excision Vs. Partial Mesorectal Excision for Treatment of Rectal Cancer

2021 ◽  
Author(s):  
Henry H. Chill ◽  
Shani Parnasa ◽  
Noam Shussman ◽  
Roie Alter ◽  
Briggite Helou ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Rectal Cancer ◽  
Total Mesorectal Excision ◽  
Urinary Dysfunction ◽  
University Hospital ◽  
Mesorectal Excision ◽  
Increased Risk ◽  
The Impact ◽  
Substantial Morbidity

Abstract Background: Colorectal cancer is a condition which is associated with substantial morbidity and mortality. The aim of this study was to assess urinary dysfunction and its effect on quality of life in women who underwent total mesorectal excision compared to women treated by partial mesorectal excision for treatment of rectal cancer. Methods: We performed a retrospective cohort study at a tertiary university hospital between January 2014 and December 2019. A comparison was performed between women who underwent total mesorectal excision as opposed to partial mesorectal excision for treatment of rectal cancer. Pre-operative, intra-operative and post-operative data were compared between groups. Urinary dysfunction and its impact on quality of life were assessed using UDI-6 and USIQ questionnaires. Further univariate and multivariate analyses were performed in the attempt of assessing risk factors for urinary dysfunction. Results: A total of 107 women were included in the study, 73 women underwent partial mesorectal excision as opposed to 34 women who were treated by total mesorectal excision. Urinary dysfunction following surgery as assessed using the UDI-6 questionnaire did not differ between groups. Similar findings were recorded with regard to the impact of urinary dysfunction on quality of life as assessed using the USIQ questionnaire. Following multivariate analysis longer hospital stay was associated with increased risk of some degree of urinary dysfunction. Conclusions: Women undergoing total mesorectal excision have comparable results to partial mesorectal excision with regard to urinary dysfunction.

scholarly journals Convergent and distributed effects of the schizophrenia-associated 3q29 deletion on the human neural transcriptome

2020 ◽  
Author(s):  
Esra Sefik ◽  
Ryan H. Purcell ◽  
Elaine F. Walker ◽  
Gary J. Bassell ◽  
Jennifer G. Mulle ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Single Gene ◽  
Normal Function ◽  
Cellular Functions ◽  
Protein Coding ◽  
Post Translational Modifications ◽  
Increased Risk ◽  
Disease Associations ◽  
Guilt By Association ◽  
The Impact

AbstractThe 3q29 deletion (3q29Del) confers >40-fold increased risk for schizophrenia. However, no single gene in this interval is definitively associated with disease, prompting the hypothesis that neuropsychiatric sequelae emerge upon loss of multiple functionally-connected genes. 3q29 genes are unevenly annotated and the impact of 3q29Del on the human neural transcriptome is unknown. To systematically formulate unbiased hypotheses about molecular mechanisms linking 3q29Del to neuropsychiatric illness, we conducted a systems-level network analysis of the non-pathological adult human cortical transcriptome and generated evidence-based predictions that relate 3q29 genes to novel functions and disease associations. The 21 protein-coding genes located in the interval segregated into seven clusters of highly co-expressed genes, demonstrating both convergent and distributed effects of 3q29Del across the interrogated transcriptomic landscape. Pathway analysis of these clusters indicated involvement in nervous-system functions, including synaptic signaling and organization, as well as core cellular functions, including transcriptional regulation, post-translational modifications, chromatin remodeling and mitochondrial metabolism. Top network-neighbors of 3q29 genes showed significant overlap with known schizophrenia, autism and intellectual disability-risk genes, suggesting that 3q29Del biology is relevant to idiopathic disease. Leveraging “guilt by association”, we propose nine 3q29 genes, including one hub gene, as prioritized drivers of neuropsychiatric risk. These results provide testable hypotheses for experimental analysis on causal drivers and mechanisms of the largest known genetic risk factor for schizophrenia and highlight the study of normal function in non-pathological post-mortem tissue to further our understanding of psychiatric genetics, especially for rare syndromes like 3q29Del, where access to neural tissue from carriers is unavailable or limited.

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