Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

Psoriasis is a chronic inflammatory skin pathology of autoimmune origin and unknown etiology. There are various therapies for treating it, including a wide range of biopharmaceuticals indicated in moderate-to-severe psoriasis. Depending on their therapeutic target, they are classified as tumor necrosis factor inhibitors (anti-TNF) or cytokine inhibitors (interleukin-12, 23, and 17 antagonists). Although they have proved effective and safe, in clinical practice, many patients show a short- and long-term suboptimal response and even varying degrees of toxicity. This variability in response may be influenced by genetic factors, such as polymorphisms in the genes involved in the pathological environment, metabolism or mechanism of action of the drug that could affect the effectiveness and toxicity of biological therapies. This review assesses pharmacogenetic studies of the impact of genetic factors on response to biopharmaceuticals and toxicity in patients diagnosed with moderate-to-severe psoriasis. The results suggest that polymorphisms detected in the HLA genes, in genes that encode cytokines (TNF, IL genes, TNFAIP3), transporters (PDE3A-SLCO1C1, SLC12A8), receptors (TNFRSF1B, CD84, FCGR2A and FCGR3A, IL17RA, IL23R, TLR genes, PGLYRP4) and associated proteins (TNFAIP3, LY96, TIRAP, FBXL19), as well as other genes implicated in the pathogenesis of psoriasis (CDKAL1, CARD14, PTTG1, MAP3K1, ZNF816A, GBP6, CTNNA2, HTR2A, CTLA4, TAP1) can be used in the future as predictive markers of treatment response and/or toxicity with biological therapies in patients diagnosed with moderate-to-severe psoriasis, tailoring treatment to the individual patient.

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Earth-based observations of impact phenomena

International Astronomical Union Colloquium ◽

10.1017/s0252921100115465 ◽

1996 ◽

Vol 156 ◽

pp. 81-109

Author(s):

Philip D. Nicholson

Keyword(s):

Hubble Space Telescope ◽

Common Pattern ◽

Mid Infrared ◽

Wide Range ◽

Impact Phenomena ◽

Infrared Wavelengths ◽

Positive Correlations ◽

The Individual ◽

The Impact ◽

Size Estimates

Earth-based observations at near- and mid-infrared wavelengths were obtained for at least 15 of the SL9 impacts, ranging from the spectacular G, K and L events to the barely-detected N and V impacts. Although there were a few exceptions, most of the IR lightcurves fit a common pattern of one or two relatively faint precursor flashes, followed several minutes later by the main infrared event as the explosively-ejected plume crashed down onto the jovian atmosphere. Correlations with the impact times recorded by the Galileo spacecraft and plumes imaged by the Hubble Space Telescope lead to an interpretation of the twin precursors in terms of (i) the entry of the bolide into the upper atmosphere, and (ii) the re-appearance of the rising fireball above Jupiter's limb. Positive correlations are observed between the peak IR flux observed during the splashback phase and both pre-impact size estimates for the individual SL9 fragments and the scale of the resulting ejecta deposits. None of the fragments observed to have moved off the main train of the comet by May 1994 produced a significant impact signature. Earth-based fireball temperature estimates are on the order of 750 K, 30-60 sec after impact. For the larger impacts, the unexpectedly protracted fireball emission at 2.3 μm remains unexplained. A wide range of temperatures has been inferred for the splashback phase, where shocks are expected to have heated the re-entering plume material at least briefly to several thousand K, and further modelling is required to reconcile these data.

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On Compressor Station Layout

Volume 4: Turbo Expo 2003 ◽

10.1115/gt2003-38019 ◽

2003 ◽

Cited By ~ 3

Author(s):

Rainer Kurz ◽

Sebouh Ohanian ◽

Matt Lubomirsky

Keyword(s):

Gas Turbine ◽

Electric Motor ◽

Operating Conditions ◽

Performance Characteristics ◽

General Context ◽

Operational Flexibility ◽

Gas Engine ◽

Wide Range ◽

The Individual ◽

The Impact

This paper discusses issues that influence the decision on the arrangement of compressors and the type of equipment in gas pipeline compressor stations. Different concepts such as multiple small units versus single large units are considered, both regarding their impact on the individual station and the overall pipeline. The necessity of standby units is discussed. Various concepts for drivers (gas turbine, gas motor and electric motor) and compressors (centrifugal and reciprocating) are analyzed. The importance of considering all possible operating conditions is stressed. With the wide range of possible operating conditions for the pipeline in mind, the discussion will be brought into the general context of operational flexibility, availability, reliability, installation issues, remote control, and operability of gas turbine driven centrifugal compressors compared to other solutions such as electric motor driven compressors or gas engine driven reciprocating compressors. The impact of different concepts on emissions and fuel cost is discussed. Among the assumptions in this paper are the performance characteristics of the compressor. It will be outlined how these performance characteristics influence the conclusions.

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PLAYBACK-THEATRE IN THE SYSTEM OF SOCIALIZATION AND RE-SOCIALIZATION OF PERSONALITY

Bulletin of Taras Shevchenko National University of Kyiv. Series “Psychology” ◽

10.17721/bsp.2018.2(9).4 ◽

2018 ◽

pp. 17-20

Author(s):

M. Dergach

Keyword(s):

Psychological Adaptation ◽

Psychological Support ◽

Psychological Climate ◽

Psychological State ◽

Wide Range ◽

Important Means ◽

The Common ◽

Main Thing ◽

The Individual ◽

The Impact

The article reveals the peculiarities of playback theater as a psychodramatic technique, analyzes the current practice of using playback theater in the system of socialization and re-socialization. The author found that socialization, as a necessary process for interaction with the outside world, is manifested in the assimilation and appropriation of social experience for the purpose of productive functioning in it and to construct an image of the common and own world (as a part of the common), which allows a person to live a life while preserving individuality. and creatively influence the world. Within this provision, playback theater should be regarded as a technology of the paratheater system of dramatherapy, which is relevant at any stage of the socialization of the individual or as a means in the mechanisms of socialization. Playback theater contributes to the development of tolerance for social differences, the acceptance of another with all its features, values. Thanks to him, we learn to listen to understand others, because in the performance the main thing is the story of the viewer, the realization of which is impossible in reality without careful perception. The author has found that playback theater as a paratheater system of drama is a rather interesting and important means of socialization and re-socialization of the personality, it can be used in any group of people to solve problems of a wide range. The article describes in detail the content of the playback theater application, namely: social integration of individual subgroups into society; social and psychological adaptation of personality; social-psychological and therapeutic support for people who are in emotional and psychological state; creation of a more favorable social and psychological climate for the team; social and psychological support in complex events; development of personal qualities of children in educational institutions; social and psychological support of people in recreational activities; playback theater as a means of creating space for social networking. Prospects for further research on the topic of the article are to study the attitude of the audience to the performances of the playback theater, the search for the means of expression of the actors, the impact of playback on the children's audience.

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Factors Contributing to the Occurrence of Leptospirosis, and the Impact on Public Health in Saint Lucia 2008-2019

TEXILA INTERNATIONAL JOURNAL OF PUBLIC HEALTH ◽

10.21522/tijph.2013.08.04.art008 ◽

2020 ◽

Vol 8 (4) ◽

pp. 69-78

Author(s):

Edward L. Emmanuel

Keyword(s):

Public Health ◽

Secondary Data ◽

Educational Programme ◽

Easy Access ◽

Bacterial Disease ◽

Mortality And Morbidity ◽

Wide Range ◽

Saint Lucia ◽

The Individual ◽

The Impact

Leptospirosis is a bacterial disease that affects humans and animals. The causative agent is a spirochete of the genus Leptospira. In humans, it causes a wide range of symptoms, however, asymptomatic presentation is not uncommon. Without proper treatment, leptospirosis can lead to kidney damage, meningitis, liver failure, and respiratory distress. Death may occur in some patients. The aim of the study is to identify the factors contributing to the occurrence of leptospirosis, and the impact on public health in Saint Lucia 2008-2019. The study design is a mixed – method, comprising quantitative and qualitative data. A stratified sampling design using probability proportionate to size sampling at the settlement level was used. Secondary data on the incidence of leptospirosis were obtained from the Ministry of Health, and rainfall data were obtained from the Meteorology Office. Analysis of the data reveals several factors contributing to the occurrence of leptospirosis in Saint Lucia: poor garbage disposal; a large rodent population with easy access to garbage; and a lack of knowledge of leptospirosis. The impact on public health is manifested in the mortality and morbidity of individuals primarily men, and the health, social, and economic impact on the country. Reducing the impact of leptospirosis on the individual and country necessitates an island wide multi - sectoral control and prevention educational programme; an evaluation of the collection, storage, and disposal of household garbage; and the enforcement of legislation governing the proper collection, storage and disposal of garbage.

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The impact of the manager's emotional intelligence on organisational performance

Management Theory and Studies for Rural Business and Infrastructure Development ◽

10.15544/mts.2016.6 ◽

2016 ◽

Vol 38 (1) ◽

pp. 58-69 ◽

Cited By ~ 1

Author(s):

Karolis Karolis

Keyword(s):

Sustainable Development ◽

Emotional Intelligence ◽

Balanced Scorecard ◽

Economic Indicators ◽

Organisational Performance ◽

Development Methodology ◽

Wide Range ◽

The Individual ◽

The Impact

The problem dealt with in the paper is the impact of manager's emotional intelligence (EI) on the economic, social, and ecological sides of the organisational activity and the qualitative criteria of the evaluation of the organisational performance from the viewpoint of sustainable development (SD) of the organisation. The aim of the paper is to justify the interrelationship of the EI of the manager of an organization and the performance of the organization in terms of its sustainable development. Methodology: to evaluate EI, the methodology proposed by J. N. Hall (2005) was adopted as a basis, by means of which the EI of the respondents – the heads of eight organisations that provided a wide range of services (logistics, ICT, etc.) – has been measured. To evaluate the effectiveness of the organisational performance, the indicators of effectiveness proposed by R. S. Kaplan and D. P. Norton (1992, 2001) and supplemented by the author – a balanced scorecard (BS) – has been applied. It was established that, in the evaluation of any organisation, the existing BS of economic indicators should be supplemented by social-cultural and environmental instruments. The EI of managers was found to be closely related both to the individual indicators of the organisational performance and with the integrated BS.

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Lipoprotein(a) levels are not independently associated with endogenous steroid hormone levels, in contrast to other non-genetic and genetic factors: the population-based SKIPOGH study

European Heart Journal ◽

10.1093/eurheartj/ehab724.2578 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

E Tessitore ◽

K Dobretz ◽

N A Dhayat ◽

S Estoppey ◽

I Kern ◽

...

Keyword(s):

Genetic Factors ◽

Steroid Hormone ◽

Population Based ◽

Endogenous Hormone ◽

Genetic Origin ◽

Lipoprotein A ◽

Hormone Levels ◽

Wide Range ◽

The Impact ◽

Endogenous Steroid

Abstract Introduction Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causally related to cardiovascular events. Lp(a) levels are highly variable, by more two orders of magnitude, and most of this variability appears to be of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of the variation of endogenous hormone levels on Lp(a) is unknown. Purpose To investigate the association between Lp(a) levels and non-genetic factors, as endogenous steroid hormone levels, in contrast to genetic factors. Methods We investigated the association of 28 endogenous steroids with Lp(a) levels and compared the association to other non-genetic and genetic variables in a prospective, population-based sample (N=1,021). Results The average age of the participants was 51 years and 53% were female. Median Lp(a) levels were 62 (±204) mg/l and the 90th and 99th percentile of Lp(a) was 616mg/l and 1035 mg/l respectively. The prevalence of a Lp(a) elevation ≥700mg/l was 3.2% and Lp(a) varied greatly from undetectable to 1,690mg/l. Age explained 2.0% of Lp(a) variability (p<0.001), 1% was explained by LDL levels (p=0.001), and 40% by two single nucleotide polymorphisms near the Lp(a) gene that have been previously described. Lp(a) levels were on average almost two times more elevated in secondary prevention and in individuals with very elevated LDL levels (≥4.9 mmol/l). Of the 28 endogenous steroid hormones assessed, 5-androstene-3b,16α,17β-triol, androsterone, 16α-hydroxy DHEA, and estriol were nominatively associated with serum Lp(a) levels and explained 0.4–1% of Lp(a) variability in univariate analyses, but they did not reach significance in multi-variate models. Conclusion Our results confirm previous findings demonstrating that the majority of the Lp(a) variation in the general population is of genetic origin. Age and LDL-levels explain a further small part of Lp(a) variability. Endogenous hormone levels do not contribute significantly to the wide range of variability. FUNDunding Acknowledgement Type of funding sources: None. Coefficient plot Lp(a) and variables

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Introduction: the comprehensive approach

10.1093/med/9780199668847.003.0020 ◽

2016 ◽

Author(s):

Michael Doherty ◽

Johannes Bijlsma ◽

Nigel Arden ◽

David J. Hunter ◽

Nicola Dalbeth

Keyword(s):

Illness Perceptions ◽

Response To Treatment ◽

Predictors Of Response ◽

Wide Range ◽

Mechanical Factors ◽

Inflammatory Drugs ◽

The Individual ◽

The Impact

This introductory chapter to the section on management of osteoarthritis (OA) emphasizes the need for a full assessment of the patient, not just in terms of joint symptoms and examination findings but a full holistic assessment of the person, including the impact of OA on their life, their illness perceptions of OA, and the presence of comorbidities. An individualized package of care can then be developed. Patients should be fully informed about OA and fully involved in all management decisions. Apart from education, which is an ongoing not one-off process, other core treatments to be considered in every person with OA are exercise (both strengthening and aerobic) and strategies to reduce adverse mechanical factors, including weight loss if overweight or obese. Topical non-steroidal anti-inflammatory drugs are the safest analgesic drug to try first for peripheral joint OA. Other treatments can be selected as required from a wide range of drug and non-pharmacological options, to address the needs of the individual. The patient requires regular follow-up for reassessment and re-adjustment of management as required. Currently there are sparse data on predictors of response to treatment, limiting a stratified medicine approach. Caveats to the research evidence for OA and its transition to clinical practice are discussed, and one way of improving this (reporting overall treatment effect and the proportion attributable to placebo in clinical trials) is presented. Optimizing contextual effects, which are an integral part of any treatment and which may explain the majority of improvement that a patient experiences for their OA, is emphasized as a key aspect of care.

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Optimized Piston Motion for an Alpha-Type Stirling Engine

Entropy ◽

10.3390/e22060700 ◽

2020 ◽

Vol 22 (6) ◽

pp. 700 ◽

Cited By ~ 7

Author(s):

Robin Masser ◽

Abdellah Khodja ◽

Mathias Scheunert ◽

Karsten Schwalbe ◽

Andreas Fischer ◽

...

Keyword(s):

Waste Heat ◽

Stirling Engine ◽

Piston Motion ◽

Performance Improvements ◽

Engine Model ◽

Wide Range ◽

The Individual ◽

Parameter Values ◽

The Impact ◽

Alpha Type

The Stirling engine is one of the most promising devices for the recovery of waste heat. Its power output can be optimized by several means, in particular by an optimized piston motion. Here, we investigate its potential performance improvements in the presence of dissipative processes. In order to ensure the possibility of a technical implementation and the simplicity of the optimization, we restrict the possible piston movements to a parametrized class of smooth piston motions. In this theoretical study the engine model is based on endoreversible thermodynamics, which allows us to incorporate non-equilibrium heat and mass transfer as well as the friction of the piston motion. The regenerator of the Stirling engine is modeled as ideal. An investigation of the impact of the individual loss mechanisms on the resulting optimized motion is carried out for a wide range of parameter values. We find that an optimization within our restricted piston motion class leads to a power gain of about 50% on average.

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Non-steroidal anti-inflammatory drugs and arterial hypertension: drug interaction-adjusted management of patients

Medical Council ◽

10.21518/2079-701x-2021-4-258-264 ◽

2021 ◽

pp. 258-264

Author(s):

K. M. Muratov ◽

E. V. Shikh ◽

N. I. Lapidus ◽

Zh. I. Sizova

Keyword(s):

Gene Polymorphism ◽

Arterial Hypertension ◽

Antihypertensive Therapy ◽

Genetic Factors ◽

Antihypertensive Drugs ◽

Individual Characteristics ◽

Wide Range ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

The Individual

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common drugs in clinical practice and account for 5–10% of all drugs prescribed each year. However, the use of this group of drugs is associated with the risk of a wide range of side effects, most of which are cardiovascular complications. In addition, NSAIDs interact with other drugs, for example, their effect on antihypertensive therapy has recently been recognized as particularly important. Improvement of not only efficacy, but also safety is another important principle of rational pharmacotherapy. Adverse drug reactions (ADR) can very often result from underlying genetic factors of the human body. In this regard, a personalized approach suggesting the prescription of drugs according to the individual characteristics of patients is especially important. In such cases, pharmacogenetic testing is the most promising method that identifies the genetic factors of patients and allows to predict patients’ responses to specific drugs. This applies especially to a large range of drugs metabolised via the cytochrome P450 system in the liver. Results from numerous studies show that the effect of P450 family gene polymorphism determines the individual sensitivity to antihypertensive drugs, as it is these isozymes that are involved in the metabolism of drugs used to treat arterial hypertension (AH). In particular, the cytochrome (CYP) 450 isoenzyme is one of the basic enzymes involved in the biotransformation of losartan, an angiotensin receptor antagonist. Therefore, the CYP2C9 gene polymorphism largely determines the pharmacological response to NSAIDs and affects the effectiveness of antihypertensive therapy due to the change in the drug metabolism, as well as the structure and function of the receptors, on which they have an effect.

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What Regional Living Conditions Affect Individual Smoking of Adults in Russia

International Journal of Public Health ◽

10.3389/ijph.2021.599570 ◽

2021 ◽

Vol 66 ◽

Author(s):

Sergey A. Maksimov ◽

Svetlana A. Shalnova ◽

Yulia A. Balanova ◽

Vladimir A. Kutsenko ◽

Svetlana E. Evstifeeva ◽

...

Keyword(s):

Mutual Influence ◽

Adult Population ◽

Principal Component ◽

Estimating Equation ◽

Individual Level ◽

Composite Indices ◽

Individual Probability ◽

Wide Range ◽

The Individual ◽

The Impact

Objectives: Our study evaluated the impact of a wide range of characteristics of large administrative regions on the individual level of cigarette smoking in the Russian adult population.Methods: The pool of participants included 20,303 individuals aged 25–64 years. We applied 64 characteristics of the 12 Russian regions under study for 2010–2014. Using principal component analysis, we deduced five evidence-based composite indices of the regions. We applied the generalized estimating equation to determine associations between the regional indices and the individual level of smoking.Results: The increased Industrial index in the region is associated with the probability of smoking (odds ratio = 1.15; 95% confidence interval = 1.06–1.24). The other indices show associations with smoking only in separate gender and educational groups. Surprisingly, it was found that the Economic index has no associations with the probability of smoking.Conclusion: We evaluated the key associations of the territorial indices with the individual probability of smoking, as well as the mutual influence between the territorial indices and individual factors.

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