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At least 595 records · Page 33Linked to original sources
PubMed2004

Ethyl acrylate risk assessment with a hybrid computational fluid dynamics and physiologically based nasal dosimetry model.

Cytotoxicity in the nasal epithelium is frequently observed in rodents exposed to volatile organic acids and esters by inhalation. An interspecies, hybrid computational fluid dynamics and physiologically based pharmacokinetic (CFD-PBPK) dosimetry model for inhaled ethyl acrylate (EA) is available for estimating internal dose measures for EA, its metabolite acrylic acid (AA), and EA-mediated reductions in tissue glutathione (GSH). Nasal tissue concentrations of AA were previously used as the dose metric for a chronic Reference Concentration (RfC) calculation with this compound. However, EA was more toxic than expected, based on calculated tissue AA concentrations. Unlike AA, EA causes depletion of tissue GSH. We have developed an RfC for EA using tissue GSH depletion in the olfactory epithelium as the primary measure of nasal tissue dose. The hybrid CFD-PBPK model was refined to improve the accuracy of simulations for GSH in rat olfactory tissues. This refined model was used to determine the concentration for continuous human exposures to EA predicted to reduce nasal GSH levels to the same extent as seen in rats exposed to EA at the no-observed-effect level (NOEL). Importantly, AA concentrations in the human nasal olfactory epithelium at the proposed chronic RfC were predicted to be lower than the AA concentrations estimated in the rat at the NOEL. Thus, a chronic RfC based on maintaining GSH in the human nasal olfactory epithelium at levels equivalent to the rat NOEL would also provide an adequate margin of safety with respect to AA concentrations in nasal tissues.

Acrylates↗
PubMed2004

Dynamic prognostication in non-ST-elevation acute coronary syndromes: insights from GUSTO-IIb and PURSUIT.

BACKGROUND: Risk assessment in patients with non-ST-elevation acute coronary syndromes (NSTE-ACS) traditionally focuses on and is limited to admission findings. The objective of the current study was to develop an approach to predicting outcome in NSTE-ACS that could account for the changing nature of risk. METHODS: In 7294 of 8010 patients with NSTE-ACS and complete electrocardiographic data in the GUSTO-IIb trial, we predicted the mortality probability at days 0-2, 0-30, 3-30, 5-30, and 7-30 using multiple logistic regression. Resulting risk estimates were incorporated into a composite, dynamic model to estimate the effects of changing probabilities over time. These models were validated against an independent sample of 9461 patients from the PURSUIT trial. RESULTS: As time passed after admission, the risk of 30-day death declined in stable patients. This risk, which was 3.72% at baseline, declined to 1.92% in 6-day survivors, and the risk reduction was greatest for those with the highest baseline risk. Importantly, however, the development of inhospital complications modified these trends. The use of dynamic models not only allowed us to estimate early (<48 h) mortality with a high degree of accuracy (C-index of 0.87), but also to continuously update the longer-term prognosis with increasing accuracy: the C-index increased from 0.75 for the day 0-30 model to 0.81 and 0.82 for the composite and day 7-30 models, respectively. CONCLUSIONS: Dynamic risk assessment is feasible and reliable. This approach can improve risk assessment and provide valuable guidance for management of patients with NSTE-ACS.

Age Factors↗
PubMed1991

[The results of the dynamic observation of bronchial hyperreactivity in risk-group subjects and in bronchial asthma patients. Some corrective procedures].

The following bronchial provocation tests were carried out: 310 with acetylcholine, 216 with submaximal physical exercise, 246 with cold air inhalation, and 103 with aspirin in healthy subjects, relatives of bronchial asthma patients, in patients with preasthma and asthma in a stage of exacerbation abatement or remission. Based on the data obtained the authors show nonspecific hyperreactivity of the bronchi in healthy relatives of bronchial asthma patients, heterogeneity and a high incidence of responses to acetylcholine, cold air and physical exercise, augmentation of the reaction intensity to different stimuli in all asthma patients. The follow-up of bronchial hyperreactivity discovered its progression in the absence of the treatment and the lowering of its intensity as a result of the treatment with calcium antagonists, magnesium sulfate, punctate massage, sublaminal physical exercise, ultraviolet radiation of autologous blood, specific desensitization with aspirin.

Acetylcholine↗
PubMed1995

[The dynamics of the prevalence of the basic risk factors for IHD in men engaged in the expedition--duty-watch form of work at an oil-producing complex in western Siberia].

Monitoring of the main risk factors of ischemic heart disease was conducted in an ordered population of males aged 20-59. The examinees worked in expeditions engaged in oil production at the West Siberia oil fields. The prospective epidemiological survey lasted 3 years for the study population and 2 years for two representative comparison groups. The examination program involved filling WHO risk factor questionnaire, two measurements of arterial pressure, anthropometric examination, total blood cholesterol assay. Systolic pressure was found to increase upon service duration 2.9 and 4.3 years, diastolic pressure rose after 2.9 years of service, body mass index after 4.3 and 5.6 years. It is evident that preventive measures should be taken within 3 years of service in conditions of expedition work schedule.

Adult↗
PubMed1993

An ergonomic approach for the evaluation of health risk in drug research and production.

Scientists and workers engaged in the study and production of drugs may be exposed to harmful events not yet adequately evaluated. An ergonomic approach to this problem with a view to defining projects of primary prevention, based on the respect for organizational congruences and on the knowledge of risk sources and dynamics, can represent an important measure of security and also a way to promote scientific advancement.

Drug Industry↗
PubMed1997

[The dynamics of ischemic heart disease and the risk factors among the male population of Moscow in the 1985 to 1995 period].

The trends in prevalence of ischemic heart disease (IHD) and risk factors for 1985-1995 have been studied on random representative samples of male population from Moscow. For the decade studied IHD incidence increased, especially in younger males. Changes in IHD risk factors were the following: systolic and diastolic pressures were on the increase. HDLP cholesterol and total cholesterol in the blood lowered, total triglycerides were unchanged, incidence of smoking remained high.

Adult↗
PubMed2001

Hop tests as predictors of dynamic knee stability.

Single leg hop tests are commonly used as physical performance measures of function and are also commonly used to evaluate progress in knee rehabilitation programs, particularly for individuals recovering from anterior cruciate ligament injury or reconstructive surgery. While there is some evidence that hop tests may show promise as a predictive measure for identifying individuals who are at risk for recurrent dynamic instability, further work is needed to clearly define the role of hop test measurements for this purpose. The purposes of this clinical commentary are to review the research that has been done to establish hop tests as a physical performance measure of function, to discuss neuromuscular and biomechanical considerations related to hop performance and dynamic knee stability, to discuss existing evidence that supports the potential for hop tests as a predictor of dynamic knee stability, and to discuss considerations for future studies that are designed to more clearly define the role of hop tests in predicting dynamic knee stability.

Anterior Cruciate Ligament Injuries↗
PubMed2026

Temporal mismatch in allogeneic iPSC therapies: biological risks and implications for clinical translation.

INTRODUCTION: The clinical translation of pluripotent stem cell-derived therapies has entered a new phase following conditional approval of first-in-class allogeneic induced pluripotent stem cell (iPSC)-derived products in Japan. These approvals highlight both the therapeutic promise of iPSC technologies and regulatory challenges associated with evaluating complex cell-based interventions. AREAS COVERED: This report examines the evidentiary basis supporting recent approvals and reviews key biological characteristics of allogeneic iPSC-derived therapies, including pluripotency-associated instability, immunological constraints, and manufacturing-related genomic variability. Drawing on recent clinical studies and relevant experimental literature, we analyze how these multilayered risks evolve over extended time horizons and assess their implications for the interpretation of early-phase clinical data and current regulatory frameworks. EXPERT OPINION: We argue that the central challenge extends beyond limited clinical evidence to a fundamental mismatch between the temporal dynamics of biological risk and the duration of conventional clinical evaluation. As a result, early clinical observations may systematically underestimate long-term risks. Conditional approval pathways should therefore incorporate safeguards aligned with this temporal uncertainty, including long-term follow-up, rigorous post-approval evaluation, and enhanced transparency in biological and manufacturing data. Aligning regulatory design with intrinsic properties of pluripotent stem cell-derived therapies will be essential for ensuring safe and responsible clinical translation.

Humans↗
PubMed2026

Beyond data and technology: the need for new thinking to enable the era of precision prevention.

BACKGROUND: Global flagship initiatives increasingly advocate for proactive health maintenance to alleviate the growing burden on reactive, disease-focused healthcare systems. Precision prevention is conceived as the targeted modulation of causal pathways across the disease continuum, from latent risk and pre-disease states to clinical manifestation, surpassing conventional public health prevention strategies that prioritise managing population-level risk factors. Traditional discovery and implementation models, however, remain poorly aligned with the pace and breadth of scientific and technological advances. This review outlines key barriers to scaling precision prevention and argues for the integration of conceptual, methodological, and policy perspectives into a single implementation&#x2011;oriented framework. MAIN: Individualised risk stratification lies at the core of precision prevention. Genomics serves as a stable substrate for lifetime susceptibility assessment, while meaningful prediction in multifactorial chronic disease requires additional risk monitoring using dynamic intermediate molecular markers and high-resolution exposomic data. Machine learning and other artificial intelligence (AI) methods are increasingly helpful tools for integrating large, heterogeneous and temporally structured real-world data to generate personalised predictions of health trajectories. Trustworthy AI-enabled risk prediction or decision-support systems are expected to provide transparency about model logic, assumptions and performance. In discovery, existing diagnostic classifications and conventional case-control designs can obscure mechanistic heterogeneity. Shifting toward precision phenotyping and biologically grounded disease redefinition could reveal a new layer of molecular understanding. Evidence generation strategies that reflect the temporal change of disease, including high&#x2011;risk enrichment, surrogate endpoints, and adaptive, trajectory-based monitoring, are particularly important for common conditions with prolonged latency periods (e.g., cancer, cardiovascular disease). Features often dismissed as "noise", such as stochastic molecular variation and minimal exposures, may in fact encode meaningful individual-level signals and thus merit investigation. CONCLUSION: To shift healthcare from reactive treatment toward proactive health maintenance requires coordinated action from stakeholders to reshape the pillars of discovery, reform outcome assessments and modernise implementation strategies.

Humans↗
PubMed2002

Risk assessment in offenders with intellectual disability: the evidence base.

A review of the current literature on risk assessment and management in offenders with intellectual disability (ID) revealed little direct evidence for the specific population. Theoretical models and non-ID populations have been abstracted and adapted, but not validated, for those with ID. The varying conceptual frameworks of risk, and its assessment and management, must be considered in context. Difficulties remain with the consideration of offences versus offence-like behaviour, offender versus those with similar needs, and indeed, what is regarded as 'intellectual disability'. Mainstream forensic assessment has moved towards a more dynamic appreciation of risk and risk management, as opposed to risk elimination. This development is more in line with the normalization principles of 'risk-taking' in ID. Consideration is given to future research and development priorities.

Comorbidity↗
PubMed2006

A population-based and longitudinal study of sexual behavior and multidrug-resistant HIV among patients in clinical care.

BACKGROUND: Population-based and longitudinal information regarding sexual risk behavior among patients with multidrug resistant (MDR) HIV and their sexual partners is of great public health and clinical importance. OBJECTIVE: To characterize the HIV sexual risk behaviors of patients with and without drug-resistant HIV in the clinical care setting over time. MEASUREMENTS: 393 HIV-positive patients completed questionnaires of self-reported sexual risk behaviors at approximate 6-month intervals extending over 24 months. HIV viral load and genotypic drug resistance obtained during the same time points were matched to the behavioral data. Multidrug resistance was defined as having resistance to 2 or 3 antiretroviral (ARV) drug classes. RESULTS: In serial cross-sectional analyses, 393 patients (44% female and 79% heterosexual) contributed 919 matched behavioral and virologic results over the 24 months of data collection. Of these, 250 patients (64%) reported having sex during at least 1 survey period resulting in greater than 10,000 sexual events with more than 1000 partners. Unprotected sexual behavior was reported by 45% of sexually active patients, resulting in 34% of all sex events that exposed 29% of all partners. Of these patients with unprotected sexual events, 31% had HIV drug resistance--11.6% with resistance to 2 classes of ARVs (2-class), and 1.8% with 3-class ARV resistance at the time of a sexual risk event. Close to 1000 or 28% of all unprotected sexual events involved resistant strains (11% of these with resistance to 2 classes and 0.2% with 3-class resistance, exposing 20% of unprotected sexual partners to resistant HIV (8% to 2-class and 0.6% to 3-class resistance). In longitudinal analysis among the 78 patients who reported a cumulative total of 12 months of sexual history and had resistance testing, 38% reported engaging in unprotected sexual behavior. There was substantial and complex variation in the distribution of unprotected sexual events and in the detection of resistance over time. CONCLUSION: In this study of HIV sexual risk and resistance over time among HIV-infected patients in clinical care, a substantial proportion engaged in unprotected sex and had drug-resistant HIV, frequently exposing partners to 1- or 2-class resistant HIV strains. However, relatively few exposures involved 3-class resistance. The dynamics of sexual risk behavior and HIV drug resistance are complex and vary over time and urgently require both general and targeted interventions to reduce transmission of resistant HIV.

Adult↗
PubMedDate not supplied

[Frequency dynamics of foxes as a factor of epizootic risk of rabies].

During the period preceding the year 1998 when the peak values of the rabies incidence were registered in the Moscow region, a noticeable increase in fox frequency and the density of their population occurred, especially in 3 endemic areas of the north-western zone. Considering the fact that this zone was endemic for rabies, an increased density of the fox population was, most probably, the critical factor of the epizootological risk and the main cause of the emergency situation in rabies in 1998. The data obtained in this investigation may serve as a real basis for the prediction of the epizootic situation.

Animals↗
PubMed2004

Relationship of plasma HIV-1 RNA dynamics to baseline factors and virological responses to highly active antiretroviral therapy in adolescents (aged 12-22 years) infected through high-risk behavior.

We characterized the viral dynamics of human immunodeficiency virus (HIV) type 1-infected adolescents receiving highly active antiretroviral therapy regimens (lamivudine [3TC]/zidovudine [ZDV]/efavirenz [EFV], 3TC/ZDV/nelfinavir [NFV], or other regimens) and studied the relationship of viral dynamics with baseline factors and virological responses. Viral decay rates for 115 evaluable subjects were estimated from a viral dynamic model. Viral dynamics in HIV-1-infected individuals aged 12-22 years were similar to those of HIV-1-infected adults and infants. Individuals who received 3TC/ZDV/EFV had a more rapid phase 1 viral decay rate than those who received 3TC/ZDV/NFV or other regimens. Phase 1 viral decay rates were positively correlated with baseline RNA levels and week 1 virus load reductions. Our findings indicate that the 3TC/ZDV/EFV regimen may be more potent than 3TC/ZDV/NFV or other regimens and that early viral dynamics or week 1 virus load reduction measurements may be useful in evaluating the potency of antiretroviral regimens.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[The psycho-relational aspects of the psychopathological dynamics and profile in postpartum mental disorders in the county of Iaşi in 1988-1993].

642 cases of mental disorder occurring or aggravating during the evolution of a pregnancy or postpartum assisted at the "Socola" University Hospital of Psychiatry in the interval 1988-1993 were analyzed. In 91 (38.39%) of these cases the postpartum mental disorders occurred in the absence of a psychotic psychiatric history. Based on a computerized record, the psycho-social factors with a potential pathologic risk were analyzed dynamically. The influence of social dynamics on the incidence and psychopathologic profile of mental disturbances with onset in the postpartum was evidenced, a somewhat paradoxical correlation of the frequency of these disorders with the dynamics of abortions and not with that of deliveries being underlined. Characteristic to these patients would be a lower education level, a more labile biological and psychological structure, the absence of obstetrical history and marital relational problems. An increased incidence of some postnatal complications in the evolution of these women' newborns was also found.

Adult↗
PubMed1997

The influence of exercise on albumin excretion rate in borderline hypertensives and in offspring of hypertensive parents.

We investigated exercise induced urinary albumin excretion rate (UAE)(ex-UAE) in patients with borderline hypertension (BH) compared to normotensives with positive-PFH and negative-NFH family history of hypertension. The study population consisted of 20 young, non-obese males with BH defined according to WHO criteria and confirmed by 24 h ambulatory blood pressure (ABP) and 40 healthy matched normotensives (PFH = 20 and NFH = 20). Twenty-four hour UAE was assessed by day and night time urine collection. BH and normotensive subjects performed a 20 min ergometric graded exercise test. The relationship between 24 h UAE, 24 h ABP and 2-D-echocardiographic left ventricular mass index (LVMI) were examined. The three groups did not differ in 24 h UAE. Exercise induced a significant increase in UAE only in BH. Exercise induced UAE was greater in BH compared to normotensives: BH = 54.3(21-125), PFH = 37.6(13-62), NFH = 9.7(0-35)micrograms/min, data expressed as median (I quartile-III quartile). Pooled data from all three groups showed a positive correlation between ex-UAE and systolic BP (SBP) during night time (by multiple regression analysis). In conclusion, BH without other known cardiovascular risk factors, moderate dynamic exercise induced an excessive increase in UAE.

Albuminuria↗
PubMed2003

The coagulation system.

Congenital and acquired hypercoagulable states arise from an imbalance between procoagulant and anticoagulant activity. Although these imbalances are present throughout the entire vascular tree, thrombotic lesions are usually localized in discrete segments of the veins or arteries and in certain organ systems. Thus, hypercoagulable states are likely to be associated with focal defects in the vascular wall to produce thrombosis. Many recently described factors are associated with hypercoagulability. Because thrombosis is a disease in which genetic and acquired risk factors interact dynamically, a thorough history, family history, and physical examination should be performed before ordering an extensive and costly coagulation panel.

Antiphospholipid Syndrome↗
PubMed1996

A sociobehavioural perspective on genetic testing and counselling for heritable breast, ovarian and colon cancer.

Testing for susceptibility to heritable breast, ovarian and colon cancer has unique psychosocial costs. Negative test results may not be sufficient to relieve anxiety, and positive results can cause sufficient distress to compromise patient compliance with surveillance and risk reduction measures. More needs to be learned about how sociocultural factors affect the understanding of risk, how decisions to undergo testing are made and how information about increased risk affects family dynamics. As the demand for testing and counselling grows, health care providers will be faced with new challenges and dilemmas. A better understanding of genetics by the public is needed to mitigate deterministic attitudes that can lead to the neglect of health promotion. Also of concern are the socioeconomic implications of being identified as having a high risk for heritable cancer and the dangers inherent in using genetics to explain sociological phenomena. Health care providers must take the lead in ensuring that developments in genetics are used to the benefit of all.

Attitude↗