scholarly journals Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 933 ◽  
Author(s):  
Rajeshwary Ghosh ◽  
Vishaka Vinod ◽  
J. David Symons ◽  
Sihem Boudina
Keyword(s):  
Quality Control ◽  
Myocardial Dysfunction ◽  
Indirect Costs ◽  
The United States ◽  
Cardiovascular Complications ◽  
Control Mechanisms ◽  
Cardiac Aging ◽  
The Us ◽  
Ubiquitin Proteasome ◽  
Primary Risk Factor

Cardiovascular disease (CVD) is the number one cause of death in the United States. Advancing age is a primary risk factor for developing CVD. Estimates indicate that 20% of the US population will be ≥65 years old by 2030. Direct expenditures for treating CVD in the older population combined with indirect costs, secondary to lost wages, are predicted to reach $1.1 trillion by 2035. Therefore, there is an eminent need to discover novel therapeutic targets and identify new interventions to delay, lessen the severity, or prevent cardiovascular complications associated with advanced age. Protein and organelle quality control pathways including autophagy/lysosomal and the ubiquitin-proteasome systems, are emerging contributors of age-associated myocardial dysfunction. In general, two findings have sparked this interest. First, strong evidence indicates that cardiac protein degradation pathways are altered in the heart with aging. Second, it is well accepted that damaged and misfolded protein aggregates and dysfunctional mitochondria accumulate in the heart with age. In this review, we will: (i) define the different protein and mitochondria quality control mechanisms in the heart; (ii) provide evidence that each quality control pathway becomes dysfunctional during cardiac aging; and (iii) discuss current advances in targeting these pathways to maintain cardiac function with age.

scholarly journals Indirect costs associated with out-of-country referral for proton therapy: a survey of adult and pediatric patients in Alberta, Canada

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jacqueline Middleton ◽  
Karina Black ◽  
Sunita Ghosh ◽  
David D. Eisenstat ◽  
Samir Patel
Keyword(s):  
United States ◽  
Proton Therapy ◽  
Financial Support ◽  
Family Members ◽  
Indirect Costs ◽  
The United States ◽  
For Profit ◽  
The Us ◽  
Proton Treatment ◽  
Time Away

Abstract Background Patients in Alberta, Canada are referred to the United States (US) for proton treatment. The Alberta Ministry of Health pays for the proton treatment and the cost of flights to and from the United States. This study aimed to determine the out-of-pocket expenses incurred by patients or patients’ families. Methods An electronic survey was sent to 59 patients treated with proton therapy between January 2008 and September 2019. Survey questions asked about expenses related to travel to the US and those incurred while staying in the US, reimbursement of expenses, and whether any time away from work was paid or unpaid leave. Results Seventeen respondents (response rate, 29%) reported expenses of flights for family members (mean, CAD 1886; range CAD 0–5627), passports/visas and other travel costs (mean, CAD 124; range CAD 0–546), accommodation during travel to the US (mean, CAD 50; range CAD 0–563), food during travel to the US (mean, CAD 89; range CAD 0–338), accommodation in the US (rented home/apartment mean, CAD 7394; range CAD 3075-13,305; hotel mean, CAD 4730; range CAD 3564-5895; other accommodation mean CAD 2660; range CAD 0–13,842), transportation in the US (car mean, CAD 2760; range CAD 0–7649; bus/subway mean, CAD 413; range CAD 246–580), and food in the US (mean, CAD 2443; range 0–6921). Expenses were partially reimbursed or covered by not-for-profit organizations or government agencies for some patients (35%). Patients missed a mean of 59 days of work; accompanying family members missed an average of 34 days. For 29% this time away from work was paid, but unpaid for 71% of respondents. Conclusions Multiple factors contributed to the expenses incurred including age of the patient, number of accompanying individuals, available accommodation, mode of transportation within the US, and whether the patient qualified for financial support. Added to this burden is the potential loss of wages for time away from work. The study showed a large variation in indirect costs for each family and supports actively seeking more opportunities for financial support for families with children with cancer.

US Control over Technology Transfer International Channels: Challenges, Mechanisms, Trends

2021 ◽  
Vol 65 (7) ◽  
pp. 89-97
Author(s):  
E. Kirichenko
Keyword(s):  
United States ◽  
World War Ii ◽  
Technology Transfer ◽  
Control Policy ◽  
The United States ◽  
Control Mechanisms ◽  
International Technology Transfer ◽  
Technological Leadership ◽  
The Us ◽  
Transfer Channels

With the end of World War II, the United States is constantly fighting for global technological leadership, claiming a dominant position in this area. Control over international technology transfer channels is seen by the United States as an essential mechanism for maintaining this leadership. The article identifies three “waves” of tightening control over technology transfer in the context of maintaining national security: the cold war period, the 80s in response to the unfolding competition with Japan, and the modern stage. Within each stage, the author examines the main challenges to American technological dominance, control mechanisms, and trends in control policy. The development of technology transfer controls in the United States is currently undergoing another cycle of tightening. In the US export control regime, the role of embargoes and sanctions has again increased. The extraterritorial use of the punitive apparatus has expanded, and the language of ultimatums has become more common. Control over investment transactions is tightening. Mechanisms for controlling technology transfer within the United States are being improved. The US is looking for an enemy. In the National Strategy for Critical and Emerging Technologies, China and Russia are considered as the main strategic competitors. It is argued that both states have a vital interest in American technology and use all possible means to obtain it. Nevertheless, China has become the No. 1 enemy for the Trump administration. The technological war between the United States and China most clearly reflects the methods of struggle for global leadership. Perhaps the actions of the new American administration will become less impulsive, it will change the focus in this struggle, but will not abandon it. Control over international technology transfer channels will continue to be in demand and will be improved.

scholarly journals Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates

2020 ◽  
Vol 21 (9) ◽  
pp. 3369 ◽  
Author(s):  
Hyungsun Park ◽  
Ju-Hee Kang ◽  
Seongju Lee
Keyword(s):  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Inclusion Bodies ◽  
Amyloid Β ◽  
Control Mechanisms ◽  
Autophagy Induction ◽  
Ubiquitin Proteasome ◽  
Autophagy Pathway ◽  
The Relationship ◽  
Intracellular Inclusion

Cells have developed elaborate quality-control mechanisms for proteins and organelles to maintain cellular homeostasis. Such quality-control mechanisms are maintained by conformational folding via molecular chaperones and by degradation through the ubiquitin-proteasome or autophagy-lysosome system. Accumulating evidence suggests that impaired autophagy contributes to the accumulation of intracellular inclusion bodies consisting of misfolded proteins, which is a hallmark of most neurodegenerative diseases. In addition, genetic mutations in core autophagy-related genes have been reported to be linked to neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Conversely, the pathogenic proteins, such as amyloid β and α-synuclein, are detrimental to the autophagy pathway. Here, we review the recent advances in understanding the relationship between autophagic defects and the pathogenesis of neurodegenerative diseases and suggest autophagy induction as a promising strategy for the treatment of these conditions.

scholarly journals Heat Shock Proteins: Cell Protection through Protein Triage

2010 ◽  
Vol 10 ◽  
pp. 1543-1552 ◽  
Author(s):  
David Lanneau ◽  
Guillaume Wettstein ◽  
Philippe Bonniaud ◽  
Carmen Garrido
Keyword(s):  
Quality Control ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Quality ◽  
Ubiquitin Proteasome System ◽  
Control Mechanisms ◽  
Cell Protection ◽  
Ubiquitin Proteasome ◽  
Folded Proteins ◽  
Shock Proteins

Heat shock proteins (HSPs) are chaperones that catalyze the proper folding of nascent proteins and the refolding of denatured proteins. The ubiquitin-proteasome system is an error-checking system that directs improperly folded proteins for destruction. A coordinated interaction between the HSPs (renaturation) and the proteasome (degradation) must exist to assure protein quality control mechanisms. Although it still remains unknown how the decision of folding vs. degradation is taken, many pieces of evidence demonstrate that HSPs interact directly or indirectly with the proteasome, assuring quite selectively the proteasomal degradation of certain proteins under stress conditions. In this review, we will describe the different data that demonstrate a role for HSP90, HSP70, HSP27, and alpha-B-crystallin in the partitioning of proteins to either one of these pathways, referred as protein triage.

scholarly journals Clinical, humanistic, and economic burden of severe hemophilia B in the United States: Results from the CHESS US and CHESS US+ population surveys

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tom Burke ◽  
Sohaib Asghar ◽  
Jamie O’Hara ◽  
Eileen K. Sawyer ◽  
Nanxin Li
Keyword(s):  
United States ◽  
Economic Burden ◽  
Indirect Costs ◽  
The United States ◽  
Factor Ix ◽  
Hemophilia B ◽  
Patient Records ◽  
Severe Hemophilia ◽  
The Us ◽  
The Mean

Abstract Background Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients’ functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The ‘Cost of Severe Hemophilia across the US: a Socioeconomic Survey’ (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US. Results We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931. Conclusions This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies.

Relation of Statistically Significant, Abnormal, and Typical WAIS-R VIQ-PIQ Discrepancies to Full Scale IQs

2000 ◽  
Vol 16 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Louis M. Hsu ◽  
Judy Hayman ◽  
Judith Koch ◽  
Debbie Mandell
Keyword(s):  
Graphical Method ◽  
The United States ◽  
Full Scale ◽  
True Score ◽  
Absolute Value ◽  
Normative Population ◽  
The Us ◽  
The Mean ◽  
And Performance ◽  
Quadratic Models

Summary: In the United States' normative population for the WAIS-R, differences (Ds) between persons' verbal and performance IQs (VIQs and PIQs) tend to increase with an increase in full scale IQs (FSIQs). This suggests that norm-referenced interpretations of Ds should take FSIQs into account. Two new graphs are presented to facilitate this type of interpretation. One of these graphs estimates the mean of absolute values of D (called typical D) at each FSIQ level of the US normative population. The other graph estimates the absolute value of D that is exceeded only 5% of the time (called abnormal D) at each FSIQ level of this population. A graph for the identification of conventional “statistically significant Ds” (also called “reliable Ds”) is also presented. A reliable D is defined in the context of classical true score theory as an absolute D that is unlikely (p < .05) to be exceeded by a person whose true VIQ and PIQ are equal. As conventionally defined reliable Ds do not depend on the FSIQ. The graphs of typical and abnormal Ds are based on quadratic models of the relation of sizes of Ds to FSIQs. These models are generalizations of models described in Hsu (1996) . The new graphical method of identifying Abnormal Ds is compared to the conventional Payne-Jones method of identifying these Ds. Implications of the three juxtaposed graphs for the interpretation of VIQ-PIQ differences are discussed.

Quality Control of Data in a Large-Scale Cancer Register Program

1966 ◽  
Vol 05 (02) ◽  
pp. 67-74 ◽  
Author(s):  
W. I. Lourie ◽  
W. Haenszeland
Keyword(s):  
United States ◽  
Quality Control ◽  
Cancer Patients ◽  
Large Scale ◽  
The United States ◽  
Newly Diagnosed ◽  
Related Data ◽  
Cancer Register ◽  
Independent Review ◽  
End Results

Quality control of data collected in the United States by the Cancer End Results Program utilizing punchcards prepared by participating registries in accordance with a Uniform Punchcard Code is discussed. Existing arrangements decentralize responsibility for editing and related data processing to the local registries with centralization of tabulating and statistical services in the End Results Section, National Cancer Institute. The most recent deck of punchcards represented over 600,000 cancer patients; approximately 50,000 newly diagnosed cases are added annually.Mechanical editing and inspection of punchcards and field audits are the principal tools for quality control. Mechanical editing of the punchcards includes testing for blank entries and detection of in-admissable or inconsistent codes. Highly improbable codes are subjected to special scrutiny. Field audits include the drawing of a 1-10 percent random sample of punchcards submitted by a registry; the charts are .then reabstracted and recoded by a NCI staff member and differences between the punchcard and the results of independent review are noted.

The Politics of Prophecy: The US Culture Wars and the Battle Over Public Education in the Left Behind Series for Kids

2009 ◽  
Vol 2 (1) ◽  
pp. 1-27
Author(s):  
Ann Abate Michelle
Keyword(s):  
Public Education ◽  
The United States ◽  
Culture Wars ◽  
Church History ◽  
Good News ◽  
Cultural Issues ◽  
School Prayer ◽  
Left Behind ◽  
Religious Books ◽  
The Us

This essay argues that in spite of their obvious Biblically-based subject matter, clear Christian content, and undeniable evangelical perspective, the Left Behind novels for kids are not simply religious books; they are also political ones. Co-authors Tim LaHaye and Jerry B. Jenkins may claim that their narratives are interested in sharing the good news about Jesus for the sake of the future, but they are equally concerned with offering commentary on contentious US cultural issues in the present. Given the books’ adolescent readership, they are especially preoccupied with the ongoing conservative crusade concerning school prayer. As advocates for this issue, LaHaye and Jenkins make use of a potent blend of current socio-political arguments and of past events in evangelical church history: namely, the American Sunday School Movement (ASSM). These free, open-access Sabbath schools became the model for the public education system in the United States. In drawing on this history, the Left Behind series suggests that the ASSM provides an important precedent for the presence not simply of Christianity in the nation's public school system, but of evangelical faith in particular.

The United States and the Iranian Nuclear Programme

2018 ◽  
Author(s):  
Steven Hurst
Keyword(s):  
United States ◽  
Decision Making ◽  
Domestic Politics ◽  
The United States ◽  
Nixon Administration ◽  
Comprehensive Plan ◽  
The Us ◽  
Nuclear Issue ◽  
The Relationship

The United States, Iran and the Bomb provides the first comprehensive analysis of the US-Iranian nuclear relationship from its origins through to the signing of the Joint Comprehensive Plan of Action (JCPOA) in 2015. Starting with the Nixon administration in the 1970s, it analyses the policies of successive US administrations toward the Iranian nuclear programme. Emphasizing the centrality of domestic politics to decision-making on both sides, it offers both an explanation of the evolution of the relationship and a critique of successive US administrations' efforts to halt the Iranian nuclear programme, with neither coercive measures nor inducements effectively applied. The book further argues that factional politics inside Iran played a crucial role in Iranian nuclear decision-making and that American policy tended to reinforce the position of Iranian hardliners and undermine that of those who were prepared to compromise on the nuclear issue. In the final chapter it demonstrates how President Obama's alterations to American strategy, accompanied by shifts in Iranian domestic politics, finally brought about the signing of the JCPOA in 2015.

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