When too much of a novel thing may be what's "bad": commentary on Fisher, Godwin, and Seltman (2014).
Ontology highlight
ABSTRACT:
SUBMITTER: Imuta K
PROVIDER: S-EPMC4274873 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundInsulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also too high systemic insulin levels are detrimental for body functions.Main bodyThe physiological function and clinical relevance of insulin are usually seen in association with its role in maintaining glucose homeostasis. However, insulin is an anabolic hormone which stimulates a large number of cellular responses. Not only too low, but also excess insulin concentrations are detrimental to the physiological balance. Although the glucoregulatory activity of insulin is mitigated during hyperinsulinemia by dampening the efficiency of insulin signaling ("insulin resistance"), this is not the case for most other hormonal actions of insulin, including the promotion of protein synthesis, de novo lipogenesis, and cell proliferation; the inhibition of lipolysis, of autophagy-dependent cellular turnover, and of nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; and other defense mechanisms. Hence, there is no general insulin resistance but selective impairment of insulin signaling which causes less glucose uptake from the blood and reduced activation of endothelial NO synthase (eNOS). Because of the largely unrestricted insulin signaling, hyperinsulinemia increases the risk of obesity, type 2 diabetes, and cardiovascular disease and decreases health span and life expectancy. In epidemiological studies, high-dose insulin therapy is associated with an increased risk of cardiovascular disease. Randomized controlled trials of insulin treatment did not observe any effect on disease risk, but these trials only studied low insulin doses up to 40 IU/day. Proof for a causal link between elevated insulin levels and cardiovascular disease risk comes from Mendelian randomization studies comparing individuals with genetically controlled low or high insulin production.ConclusionsThe detrimental actions of prolonged high insulin concentrations, seen also in cell culture, argue in favor of a lifestyle that limits circadian insulin levels. The health risks associated with hyperinsulinemia may have implications for treatment regimens used in type 2 diabetes.
| S-EPMC7441661 | biostudies-literature
Project description:Acquired resistance to targeted inhibitors remains a major, and inevitable, obstacle in the treatment of oncogene-addicted cancers. Newer-generation inhibitors may help overcome resistance mutations, and inhibitor combinations can target parallel pathways, but durable benefit to patients remains elusive in most clinical scenarios. Now, recent studies suggest a third approach may be available in some cases-exploitation of oncogene overexpression that may arise to promote resistance. Here, we discuss the importance of maintaining oncogenic signaling at "just-right" levels in cells, with too much signaling, or oncogene overdose, being potentially as detrimental as too little. This is highlighted in particular by recent studies of mutant-BRAF in melanoma and the fusion kinase nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) in anaplastic large cell lymphoma. Oncogene overdose may be exploitable to prolong tumor control through intermittent dosing in some cases, and studies of acute lymphoid leukemias suggest that it may be specifically pharmacologically inducible.
| S-EPMC4681422 | biostudies-literature
Project description:There is growing evidence of risks associated with excessive technology use, especially among teens and young adults. However, little is known about the characteristics of those who are at elevated risk of being problematic users. Using data from the 2012 Current Population Survey Internet Use Supplement and Educational Supplement for teens and young adults, this study developed a conceptual framework for modeling technology use. A three-part categorization of use was posited for utilitarian, social and entertainment purposes, which fit observed data well in confirmatory factor analysis. Seemingly unrelated regression was used to examine the demographic characteristics associated with each of the three categories of use. Exploratory factor analysis uncovered five distinct types of users, including one user type that was hypothesized to likely be at elevated risk of problematic use. Regression results indicated that females in their twenties who are in school and have greater access to technology were most likely to fall into this higher-risk category. Young people who live with both parents were less likely to belong to this category. This study highlighted the importance of constructing models that facilitate identification of patterns of use that may characterize a subset of users at high risk of problematic use. The findings can be applied to other contexts to inform policies related to technology and society as well.Supplementary informationThe online version of this article (10.1007/s11293-020-09683-1) contains supplementary material, which is available to authorized users.
| S-EPMC7610009 | biostudies-literature
Project description: Not available
| S-EPMC11307708 | biostudies-literature
Project description:The opportunity to receive individual research results (IRRs) in accordance with personal preferences may incentivize biobank participation and maximize perceived benefit. This trial investigated the relationship between parents' preferences and intent to participate (ITP) in biobank research utilizing their child's genetic information. We randomized parents of pediatric patients to four hypothetical biobanks, one of which employed a preference-setting model for return of results regarding their child. ITP was highest among those desiring all types of IRRs (93.3%) and decreased as participants became increasingly selective with their preferences ( p < .0001). We demonstrated that most parents would participate in a biobank that allows for preference setting; however, those who set preferences to receive a narrower set of IRRs are less likely to participate.
| S-EPMC8793343 | biostudies-literature
Project description:Traditionally the management of any chronic condition starts with its diagnosis. The labelling of disease can be beneficial in terms of defining appropriate treatment such as in coronary artery disease. However, sometimes it may be detrimental such as when x-rays are used to diagnose lumbar spondylosis leading to patients inappropriately limiting their activity. Chronic knee pain in the elderly is another example where applying labels is problematical. A common diagnosis in this situation is osteoarthritis, but this label can be applied in two ways: as a radiological diagnosis, or as a clinical one. The x-ray diagnosis, however, does not equate with the clinical syndrome, and vice versa. In addition, diagnosing knee pain as osteoarthritis does not necessarily help in management, since a patient's debility is more dependent upon their clinical signs and symptoms than the presence of radiographic osteoarthritis, and by the same token its clinical counterpart. GPs are consistent in their management of knee pain, but in attempting to diagnose the pain as osteoarthritis, these plans can alter and become more dependent on the actual diagnosis than the clinical picture. As a result management may well diverge from what the current best evidence supports. Diagnosis for diagnosis sake, should therefore be discouraged, and chronic knee pain gives us one example of why this is the case. GPs would be better placed to manage this condition if it was considered more as a regional pain syndrome, perhaps defining it simply as 'chronic knee pain in older people'. This example suggests that there is a pressing need in primary care to carefully consider in chronic disease when it is appropriate to be definitive in diagnosis such that when using disease specific labels, there is definite benefit for the patient and doctor.
| S-EPMC1326113 | biostudies-literature
Project description:OBJECTIVES:Prior studies investigating hospital mechanical ventilation volume-outcome associations have had conflicting findings. Volume-outcome relationships within contemporary mechanical ventilation practices are unclear. We sought to determine associations between hospital mechanical ventilation volume and patient outcomes. DESIGN:Retrospective cohort study. SETTING:The California Patient Discharge Database 2016. PATIENTS:Adult nonsurgical patients receiving mechanical ventilation. INTERVENTIONS:The primary outcome was hospital death with secondary outcomes of tracheostomy and 30-day readmission. We used multivariable generalized estimating equations to determine the association between patient outcomes and hospital mechanical ventilation volume quartile. MEASUREMENTS AND MAIN RESULTS:We identified 51,689 patients across 274 hospitals who required mechanical ventilation in California in 2016. 38.2% of patients died in the hospital with 4.4% receiving a tracheostomy. Among survivors, 29.5% required readmission within 30 days of discharge. Patients admitted to high versus low volume hospitals had higher odds of death (quartile 4 vs quartile 1 adjusted odds ratio, 1.40; 95% CI, 1.17-1.68) and tracheostomy (quartile 4 vs quartile 1 adjusted odds ratio, 1.58; 95% CI, 1.21-2.06). However, odds of 30-day readmission among survivors was lower at high versus low volume hospitals (quartile 4 vs quartile 1 adjusted odds ratio, 0.77; 95% CI, 0.67-0.89). Higher hospital mechanical ventilation volume was weakly correlated with higher hospital risk-adjusted mortality rates (? = 0.16; p = 0.008). These moderately strong observations were supported by multiple sensitivity analyses. CONCLUSIONS:Contrary to previous studies, we observed worse patient outcomes at higher mechanical ventilation volume hospitals. In the setting of increasing use of mechanical ventilation and changes in mechanical ventilation practices, multiple mechanisms of worse outcomes including resource strain are possible. Future studies investigating differences in processes of care between high and low volume hospitals are necessary.
| S-EPMC7245578 | biostudies-literature
Project description:Microbial sequencing revealed progressive reduction of gut microbiota that showed some differences in the two ABX groups compared to untreated controls. Interestingly, duration of ABX was associated with a gradual disappearance of the CD4+ and CD4+CD8+ subset of gut intraepithelial lymphocytes (IELs). This IEL subset is microbiota-dependent and is absent in germ-free mice. Relative abundance of Lactobacillus reuteri correlated with frequencies of CD4+CD8+ IELs and reduced EAU. Notably, IELs in culture suppressed antigen-specific activation of autoreactive T cells.
2023-11-17 | GSE236922 | GEO
Project description:Provisioning of abundant food resources in human-altered landscapes can have profound effects on wildlife ecology, with important implications for pathogen transmission. While empirical studies have quantified the effects of provisioning on host behaviour and immunology, the net interactive effect of these components on host-pathogen dynamics is unknown. We use simple compartmental models to investigate how provisioning-induced changes to host demography, contact behaviour and immune defence influence pathogen invasion and persistence. We show that pathogen invasion success and equilibrium prevalence depend critically on how provisioning affects host immune defence and that moderate levels of provisioning can lead to drastically different outcomes of pathogen extinction or maximizing prevalence. These results highlight the need for further empirical studies to fully understand how provisioning affects pathogen transmission in urbanized environments.
| S-EPMC4126624 | biostudies-literature
Project description: Not available
| S-EPMC10643586 | biostudies-literature