Network medicine might lead to new treatments for dyslipidemia. It will be a challenging method to implement in a clinical context

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Decision Making ◽  
Single Cell Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Clinical Decision ◽  
The Other ◽  
Molecular Networks ◽  
Network Medicine ◽  
Other Hand ◽  
New Treatments

With statin-based therapies to prevent or delay atherosclerotic progression, the reductionist approach of strict guidelines for treating dyslipidemias resulted in remarkable low-density lipoprotein transported cholesterol reduction. The precise estimation of residual cardiovascular diseases risk, on the other hand, remains a significant challenge that necessitates the development of new integrated approaches. The application of a network medicine approach could lead to the development of novel strategies. This is unquestionably a multidisciplinary strategy that will be difficult to put into practice in a clinical setting. We must dissect a patient with dyslipidemia to the level of single cell analysis and then reconstruct the puzzle to get a complete picture of nodes and disease modules. These efforts are critical for fully comprehending the molecular networks that underpin dyslipidemia and atherosclerosis. Furthermore, computer-aided decision-making is becoming more common in the clinical evaluation of subjects with suspected coronary heart disease. Physicians, on the other hand, should keep in mind that machines lack a "sense of reasoning" and should therefore question the reliability of a clinical decision made solely by robots. As a result, AI should be referred to as "augmented intelligence," which can aid physicians in decision-making but should leave the final strategy in their hands.

The use of a network medicine approach might result in innovative strategies for lowering coronary heart disease and CV risks

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Single Cell Analysis ◽  
Clinical Decision ◽  
Clinical Situation ◽  
Molecular Networks ◽  
Network Medicine ◽  
Innovative Strategies ◽  
Comprehensive Picture ◽  
Correct Estimation

The reductionist approach of stringent guidelines for treating dyslipidemia led to significant lipoprotein transported cholesterol (LDLC) reduction with statin-based treatment to prevent or postpone development of atherosclerosis. Correct estimation of residual CV risk, however, remains a critical problem requiring the development of new integrated approaches Using a network-medicine approach might lead to creative methods. This is clearly a multidisciplinary technique that will be difficult in a clinical situation. To get a comprehensive picture of nodes and disease modules, we need to dissect a dyslipidemic patient to the level of single-cell analysis and then reconstruct the picture. These efforts are crucial to understanding the molecular networks that drive dyslipidemia and atherosclerosis. Moreover, in clinical assessment of persons with suspected coronary heart disease (CHD), computer-aided decision-making is more widespread. On the other hand, doctors should remember that robots lack a "sense of thinking" and should thus distrust the reliability of a purely robotic clinical decision. As a consequence, AI should be called "increased intelligence," which can help physicians make judgments but should keep the ultimate strategy in the physician's hands.

Abstract 123: Reciprocal Regulation of Plasma PCSK9 and Cell-surface Low-density Lipoprotein Receptor

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Hagai Tavori ◽  
Daping Fan ◽  
MacRae F Linton ◽  
Sergio Fazio
Keyword(s):  
Transgenic Mice ◽  
Serum Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
The Other ◽  
Low Density ◽  
Reciprocal Regulation ◽  
Cholesterol Levels ◽  
Other Hand

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates low-density lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. On the other hand, LDLR binds to and clears PCSK9 from the circulation, thus modulating its serum levels. To study the global and reciprocal effects of PCSK9 and LDLR on serum cholesterol, we developed transgenic mice expressing human (h) PCSK9 and characterized its activity, serum levels, and tissue distribution. Serum hPCSK9 concentration in transgenic mice was 2181±423 ng/ml, about 10 times higher than normal level in human serum. Although hPCSK9 was expressed mainly in the kidney, LDLR degradation activity was most evident in the liver and small intestine. In contrast, LDLR levels were not affected by hPCSK9 expression in the adrenals and large intestine. On a chow diet, hPCSK9 transgenic mice on either C57BL/6 (wild-type, WT) or LDLR -/- background had higher cholesterol levels than their non-transgenic counterparts. Human PCSK9 transgenic mice had over a 4-fold increase in murine (m) PCSK9 serum levels compared to WT controls. However, transgenic expression of hPCSK9 in LDLR -/- mice did not affect the already elevated levels of mPCSK9. On the other hand, induction of hLDLR expression in transgenic mice caused a dramatic decrease in mPCSK9 levels. In addition hPCSK9 levels were increased by 2 fold in transgenic mice under LDLR -/- compare to WT background. Turnover studies with native PCSK9 showed rapid serum clearance in WT mice (half-life 5.2 min), whereas clearance was much slower in LDLR -/- recipient mice (50.5 min), and faster in hLDLR transgenic mice (2.9 min). In WT mice the injected PCSK9 accumulated in the liver and kidney but not in the adrenal gland. Ultracentrifugation and FLPC analysis showed that approximately one quarter of circulating hPCSK9 is associated with LDL, and that the LDL-associated PCSK9 is mainly in monomeric form. Our results show a reciprocal regulation between LDLR and PCSK9, which determines serum PCSK9 levels, hepatic LDLR expression, and serum LDL levels. Understanding these interactions will increase our knowledge of serum cholesterol homeostasis and should provide the basis for an intelligent design of anti-PCSK9 therapies.

Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis

2019 ◽  
Vol 20 (10) ◽  
pp. 1029-1040 ◽  
Author(s):  
Xinjie Lu
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Proprotein Convertase ◽  
Novel Target ◽  
New Treatments ◽  
And Function

Background:One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.Methods:We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.Results:New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.Conclusion:PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.

scholarly journals Machine Learning in Medical Emergencies: a Systematic Review and Analysis

2021 ◽  
Vol 45 (10) ◽  
Author(s):  
Inés Robles Mendo ◽  
Gonçalo Marques ◽  
Isabel de la Torre Díez ◽  
Miguel López-Coronado ◽  
Francisco Martín-Rodríguez
Keyword(s):  
Machine Learning ◽  
Systematic Review ◽  
Language Processing ◽  
Emergency Services ◽  
Clinical Decision ◽  
Quality Of Healthcare ◽  
The Other ◽  
Other Hand ◽  
Increasing Demand ◽  
Commercial Applications

AbstractDespite the increasing demand for artificial intelligence research in medicine, the functionalities of his methods in health emergency remain unclear. Therefore, the authors have conducted this systematic review and a global overview study which aims to identify, analyse, and evaluate the research available on different platforms, and its implementations in healthcare emergencies. The methodology applied for the identification and selection of the scientific studies and the different applications consist of two methods. On the one hand, the PRISMA methodology was carried out in Google Scholar, IEEE Xplore, PubMed ScienceDirect, and Scopus. On the other hand, a review of commercial applications found in the best-known commercial platforms (Android and iOS). A total of 20 studies were included in this review. Most of the included studies were of clinical decisions (n = 4, 20%) or medical services or emergency services (n = 4, 20%). Only 2 were focused on m-health (n = 2, 10%). On the other hand, 12 apps were chosen for full testing on different devices. These apps dealt with pre-hospital medical care (n = 3, 25%) or clinical decision support (n = 3, 25%). In total, half of these apps are based on machine learning based on natural language processing. Machine learning is increasingly applicable to healthcare and offers solutions to improve the efficiency and quality of healthcare. With the emergence of mobile health devices and applications that can use data and assess a patient's real-time health, machine learning is a growing trend in the healthcare industry.

scholarly journals Probability and loss: two sides of the risk assessment coin

2011 ◽  
Vol 35 (11) ◽  
pp. 413-418 ◽  
Author(s):  
Matthew M. Large ◽  
Olav B. Nielssen
Keyword(s):  
Mental Health ◽  
Risk Assessment ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The Other ◽  
Current Form ◽  
Mental Health Settings ◽  
Future Harm ◽  
Two Sides

SummaryRisk assessment has been widely adopted in mental health settings in the hope of preventing harms such as violence to others and suicide. However, risk assessment in its current form is mainly concerned with the probability of adverse events, and does not address the other component of risk – the extent of the resulting loss. Although assessments of the probability of future harm based on actuarial instruments are generally more accurate than the categorisations made by clinicians, actuarial instruments are of little assistance in clinical decision-making because there is no instrument that can estimate the probability of all the harms associated with mental illness, or estimate the extent of the resulting losses. The inability of instruments to distinguish between the risk of common but less serious harms and comparatively rare catastrophic events is a particular limitation of the value of risk categorisations. We should admit that our ability to assess risk is severely limited, and make clinical decisions in a similar way to those in other areas of medicine – by informed consideration of the potential consequences of treatment and non-treatment.

scholarly journals Applicability of Artificial Intelligence in Decision-Making for Land Forces

2021 ◽  
Vol 30 (2) ◽  
pp. 039-054
Author(s):  
Paul Tudorache
Keyword(s):  
Artificial Intelligence ◽  
Decision Making ◽  
Research Methodology ◽  
Research Paper ◽  
The Other ◽  
Military Operations ◽  
Other Hand ◽  
The Military

Similar to other fields, also in the military one, the Artificial Intelligence has become recently an evident solution for optimizing specific processes and activities. Therefore, this research paper aims to highlight the potential uses of Artificial Intelligence in the military operations carried out by the Land Forces. In this regard, analysing the framework of the operations process and applying suitable research methodology, the main findings are related to AI’s contributions in optimizing commander’s decisions during the progress of planning and execution. On the other hand, picturing the AI upgrated combat power of the Land Forces is another significant result of this study.

Rationality and Consensus in Kwasi Wiredu’s Traditional African Polities

Theoria ◽  
2016 ◽  
Vol 63 (146) ◽  
pp. 36-55
Author(s):  
Bernard Matolino
Keyword(s):  
Decision Making ◽  
Crucial Role ◽  
Modern Society ◽  
The Other ◽  
Rational Persuasion ◽  
Other Hand

Abstract The disagreement over what was responsible for arriving at consensual positions, in traditional African polities, is best captured in the classic debate between Kwasi Wiredu and Emmanuel Eze. The former holds that rational persuasion was the sole informant of decision-making while the latter argues that non-rational factors played a crucial role in securing a consensual decision. If Wiredu is correct then consensus could work in modern society as it can be argued that it does not rely on traditionalistic scaffoldings. If, on the other hand, Eze is correct, then consensus cannot work in modern largely urbanised Africa as its traditional underpinnings have largely disappeared. While Emmanuel Ani’s intervention in this debate is welcome for its earnest search for a system that could work, his support for Eze is not bold enough to undermine Wiredu’s rationalistic orientation in consensus.

scholarly journals Effect of Spirulina platensis on Lipid Profile of Long Evans Rats

1970 ◽  
Vol 45 (3) ◽  
pp. 249-254 ◽  
Author(s):  
M Omar Faruq Mridha ◽  
Parvin Noor ◽  
Rahima Khaton ◽  
Dipa Islam ◽  
Motaher Hossain
Keyword(s):  
Lipid Profile ◽  
Spirulina Platensis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Other ◽  
High Fat ◽  
High Sugar ◽  
Group B ◽  
Group D ◽  
Effective Result

To study the Effect of Spirulina platensis on lipid profile of Long Evan rats, an experiment was conducted by feeding the rats with diets supplemented with Spirulina platensis dry powder. Five different types of diets were included in the feeding. Group A containing high fat and high sugar considered as control-01. Group B with high fat, high sugar and 0.5% Spirulina. Group C with high fat, high sugar and 2.5% Spirulina. These three groups were included in Diet-1. Group D with laboratory diets considered as control-02 and Group E i.e., laboratory diet with Spirulina 150mg/kg/body weight. These two groups were included in Diet-2. This study describes the useful effect of Spirulina powder after administration in high fat and high sugar diet and in normal laboratory diet. Spirulina platensis powder showed an effective result in the lipid profile of Long Evan rats. Total cholesterol (TC) serum lipid significantly reduced in Group B than that of 2.5% of Spirulina powder in Group C rats. 0.5% and 2.5% Spirulina powder had the same effect in dropping low density lipoprotein (LDL) in both B and C Groups of rats. Conversely 2.5% Spirulina powder was found more effective in increasing high density lipoprotein (HDL) in Group C (50.54%) rats than the group B (24.18%) rats. On the other hand, the dose 150mg/kg b.w Spirulina powder mixed in laboratory diet showed an effective result in decreasing total cholesterol (TC) and low density lipoprotein (LDL) 19.21% and 46.06%, respectively. The findings clearly indicated that 150mg/kg b.w Spirulina powder had positive effect to increase the value of high density lipoprotein (HDL) in Group E (24.98%) rats compare to control group D rats. There were no significant differences in diet-1 groups' TC, TG and LDL-C of the groups of A (control- 01), B and C (p<0.05), although they varies statistically for HDL among these groups (p>0.05). On the other hand in diet-2 groups' TG, LDL and HDL of E groups of rats were significantly varies than control-2 groups of rats D ( p>0.05), although TC was not significant statistically (p<0.05). Keywords: High fat diet; Body weight (b.w); Hypercholesterolemia; Hypolipidaemic; Spirulina platensis. DOI: 10.3329/bjsir.v45i3.6533Bangladesh J. Sci. Ind. Res. 45(3), 249-254, 2010

Selective aggregation of zinc phthalocyanines in the skin

2000 ◽  
Vol 04 (03) ◽  
pp. 278-284 ◽  
Author(s):  
KENJI TABATA ◽  
KAORU FUKUSHIMA ◽  
KAZUO ODA ◽  
ICHIRO OKURA
Keyword(s):  
Photodynamic Therapy ◽  
Side Effects ◽  
Bovine Serum Albumin ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
The Other ◽  
Low Density ◽  
Monomeric Form ◽  
Zinc Phthalocyanines ◽  
Selective Aggregation

In photodynamic therapy it is important to avoid undesirable side effects caused by photodynamic reactions with accumulated photosensitizers, especially in the skin. Although phthalocyanine monomers can serve as photosensitizers, aggregated phthalocyanines are inactive. In this study the aggregations of five zinc phthalocyanines (MSPc, TSPc, TX-101A, TX-105A and TX-106A) in the skin and in the tumor are compared. Every phthalocyanine was more dissociated in the tumor than in the skin. In particular, TX-101A and TX-106A remained in monomeric form in the tumor but were aggregated in the skin. The aggregation effects of phthalocyanines in organic solvents and biological materials were also investigated. These phthalocyanines were aggregated in water and ethanol and also by the addition of bovine serum albumin and ghosts of red cells. On the other hand, they were dissociated in propanol and also by the addition of low-density lipoprotein. It was found that the dissociation of these phthalocyanines depended strongly on the polarity of the solvents and on the biological microenvironment.

scholarly journals The Number of Parties and Decision-Making in Legislatures

Games ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 76
Author(s):  
Marina Bannikova ◽  
Artyom Jelnov ◽  
Pavel Jelnov
Keyword(s):  
Decision Making ◽  
Political System ◽  
The Other ◽  
Optimal Threshold ◽  
Parliamentary Democracies ◽  
Vote Outcome ◽  
Other Hand ◽  
Number Of Parties

This paper proposes a model of a legislature, formed by several parties, which has to vote for or against a certain bill in the presence of a lobbyist interested in a certain vote outcome. We show that the ease with which the lobbyist can manipulate a legislature decision increases with the number of elected parties, and, consequently, decreases with an electoral threshold. On the other hand, a lower electoral threshold increases the representativeness of a legislature. We combine these two effects in a notion of fairness. We show the existence of an electoral threshold that optimizes the fairness of a political system, which is close to 1–5%. Namely, the optimal threshold (in our sense) is close to thresholds that exist in most parliamentary democracies.

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