Extrapolating brain development from experimental species to humans

To better understand the neurotoxic effects of diverse hazards on the developing human nervous system, researchers and clinicians rely on data collected from a number of model species that develop and mature at varying rates. We review the methods commonly used to extrapolate the timing of brain development from experimental mammalian species to humans, including morphological comparisons, "rules of thumb" and "event-based" analyses. Most are unavoidably limited in range or detail, many are necessarily restricted to rat/human comparisons, and few can identify brain regions that develop at different rates. We suggest this issue is best addressed using "neuroinformatics", an analysis that combines neuroscience, evolutionary science, statistical modeling and computer science. A current use of this approach relates numeric values assigned to 10 mammalian species and hundreds of empirically derived developing neural events, including specific evolutionary advances in primates. The result is an accessible, online resource (http://www.translatingtime.net/) that can be used to equate dates in the neurodevelopmental literature across laboratory species to humans, predict neurodevelopmental events for which data are lacking in humans, and help to develop clinically relevant experimental models.     

The limbic system in Mammalian brain evolution

Previous accounts of mammalian brain allometry have relied largely on data from primates, insectivores and bats. Here we examine scaling of brain structures in carnivores, ungulates, xenarthrans and sirenians, taxa chosen to maximize potential olfactory and limbic system variability. The data were compared to known scaling of the same structures in bats, insectivores and primates. Fundamental patterns in brain scaling were similar across all taxa. Marine mammals with reduced olfactory bulbs also had reduced limbic systems overall, particularly in those structures receiving direct olfactory input. In all species, a limbic factor with olfactory and non-olfactory components was observed. Primates, insectivores, ungulate and marine mammals collectively demonstrate an inverse relationship between isocortex and limbic volumes, but terrestrial carnivores have high relative volumes of both, and bats low relative volumes of both. We discuss developmental processes that may provide the mechanistic bases for understanding these findings.     

Prostate cancer risk and diet, recreational physical activity and cigarette smoking

Associations between prostate cancer and dietary factors, physical activity and smoking were assessed based on data from a population-based case-control study. The study was conducted among residents of northeastern Ontario. Cases were identified from the Ontario Cancer Registry and diagnosed between 1995 and 1998 at ages 50 to 84 years (N=752). Male controls were identified from telephone listings and were frequency matched to cases on age (N=1,613). Logistic regression analyses investigated history of diet, physical activity and smoking as potential risk factors. Tomato intake had a significant positive association with prostate cancer risk for highest versus lowest quartiles (OR=1.6; 95 percent CI: 1.2-2.0). Associations were observed for tomato or vegetable juices and ketchup (OR=1.5; 95 percent CI: 1.2-1.9; OR=1.2; 95 percent CI: 1.0-1.5, respectively). Neither other dietary variables nor smoking were associated with prostate cancer risk. Strenuous physical activity by men in their early 50s was associated with reduced risk (OR=0.8; 95 percent CI: 0.6-0.9). While the recreational physical activity association was consistent with results from previous studies, the tomato products association was not.     

Overview of research on health-related quality of life in patients with chronic liver disease

Health-related quality of life (HRQoL) has become an important outcome measure in patients with chronic liver disease (CLD). In this article, an overview is given of the most common measurement instruments of HRQoL, determinants of HRQoL in patients with CLD, and current developments in the implementation of routine measurement of HRQoL in daily clinical practice. Well-developed generic instruments of HRQoL are the Short Form-36 (SF-36), the Nottingham Health Profile (NHP) and the Sickness Impact Profile (SIP). Well-developed liver disease-specific HRQoL instruments are the Hepatitis Quality of Life Questionnaire (HQLQ), the Chronic Liver Disease Questionnaire (CLDQ), the Liver Disease Quality Of Life Questionnaire (LDQOL ), and the Liver Disease Symptom Index 2.0 (LDSI 2.0). Commonly used HRQoL measures in cost-effectiveness studies are the Health Utilities Index (HUI), Short Form-6D (SF-6D) and the EuroQol-5D (EQ-5D). HRQoL of patients with chronic liver disease has been shown to be impaired, with patients with hepatitis C showing the worst HRQoL. Disease severity, pruritis, joint pain, abdominal pain, muscle cramps, fatigue, depression and anxiety have been associated with HRQoL in patients with CLD. Recently, studies assessing the feasibility and effectiveness of measuring HRQoL in daily clinical practice have been performed, generally showing positive results regarding the discussion of HRQoL-related topics, but mixed results regarding the added value of actual improvement in HRQoL. Furthermore, logistic and attitudinal barriers seem to impede successful implementation. Nevertheless, given the importance of HRQoL in liver patients, we should persist in measuring and subsequently improving HRQoL in clinical practice.     

Coping strategies as determinants of quality of life in stroke patients: a longitudinal study

BACKGROUND: Quality of life (QoL) is reduced for stroke patients and coping strategies have been suggested as determinants of QoL. Thus far the relationship between coping and QoL has only been examined in small-scale cross-sectional designs. Therefore, the current study set out to examine this relationship in a longitudinal setting. METHODS: Stroke patients who were discharged home were interviewed at 4 different time points; just before discharge (T1), and 2 months (T2), 5 months (T3) and 9-12 months after discharge (T4). QoL was measured by the EQ-5D index score and the SF-36 utility score and coping expressed in terms of tenacious goal pursuit and flexible goal adjustment. Modified Rankin scale was assessed as a measure of general functioning. RESULTS: Eighty stroke patients were included. Coping was not predictive of QoL at T1 and T2 but rather at T3 and T4. At T4 both coping strategies determined the levels of QoL as measured with the EQ-5D index score; higher levels of tenacious goal pursuit as well as flexible goal adjustment were associated with higher levels of QoL. This regression model explained 44% of the variance. CONCLUSIONS: Coping is a powerful determinant of QoL, but only more than 5 months after discharge; before this time QoL is mainly determined by general functioning. Both coping strategies were important determinants of QoL.     

Web-based method for translating neurodevelopment from laboratory species to humans

Biomedical researchers and medical professionals are regularly required to compare a vast quantity of neurodevelopmental literature obtained from an assortment of mammals whose brains grow at diverse rates, including fast developing experimental rodent species and slower developing humans. In this article, we introduce a database-driven website, which was created to address this problem using statistical-based algorithms to integrate hundreds of empirically derived developing neural events in 10 mammalian species (http://translatingtime.net/). The site, based on a statistical model that has evolved over the past decade, currently incorporates 102 different neurodevelopmental events obtained from 10 species: hamsters, mice, rats, rabbits, spiny mice, guinea pigs, ferrets, cats, rhesus monkeys, and humans. Data are arranged in a Structured Query Language database, which allows comparative brain development measured in postconception days to be converted and accessed in real time, using Hypertext Preprocessor language. Algorithms applied to the database also allow predictions for dates of specific neurodevelopmental events where empirical data are not available, including for the human embryo and fetus. By designing a web-based portal, we seek to make these comparative data readily available to all those who need to efficiently estimate the timing of neurodevelopmental events in the human fetus, laboratory species, or across several different species. In an effort to further refine and expand the applicability of this database, we include a mechanism to submit additional data.     

Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications

Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. However, numerous patients will experience a recurrent atherothrombotic vascular event despite adequate antiplatelet therapy. Individual differences in the rate of platelet activation and reactivity markedly influence normal hemostasis and the pathological outcome of thrombosis. Such an individual variability is largely determined by environmental and genetic factors. These are known to either hamper platelets' response to agonists, and thereby mimic the pharmacological modulation of platelet function or mask therapy effect and sensitize platelets. In this article, we reviewed the antiplatelet mechanisms of aspirin and clopidogrel and the possible role of different polymorphisms, which may affect the efficacy of antiplatelet therapy. Heterogeneity in the way patients respond to aspirin and clopidogrel may in part reflect variation in cyclooxygenase (COX)-1, COX-2, glycoprotein (GP) Ib alpha, GP Ia/IIa, GP IIb/IIIa, UGT1A6*2, P2Y₁, P2Y₁₂, CYP2C9, CYP3A4 and CYP3A5 genotypes.     

Quality of life in a heterogeneous sample of caregivers of cancer patients: an in‐depth interview study

MANCINI J., BAUMSTARCK‐BARRAU K., SIMEONI M.‐C., GROB J.‐J., MICHEL G., TARPIN C., LOUNDOU A.‐D., LAMBERT A., CLÉMENT A. & AUQUIER P. (2010) European Journal of Cancer Care
Quality of life in a heterogeneous sample of caregivers of cancer patients: an in‐depth interview study To establish the best approach to develop a quality of life (QoL) questionnaire for cancer‐patient caregivers, this study attempts to identify primary domains of QoL in terms of their impact on a purposive sample of caregivers. Seventy‐seven informal adult caregivers of cancer patients (breast cancer, paediatric haematological malignancies or melanoma) with different relationships with the patients (parents, children, spouses, siblings, and friends) were recruited at three specialised French centres and extensively interviewed. Caregivers' lives were altered in several domains: psychological well‐being, leisure and everyday activities, relationships with institutional caregivers, occupation and finances, relationships with family and friends, physical well‐being, and relationship with the patient. The relative importance of these domains varied mainly in association with the caregiver‐patient relationship. Multiple correspondence analysis identified two isolated clusters: children, and, most significantly, friends and siblings. The latter groups emphasised the repercussions on their psychological well‐being and their relationship with the patient, but were less willing to discuss the impact on their relationship with caregivers and on occupation, finances, leisure, and everyday activities. This study focuses on the caregiver's perspective and advocates the development of a short QoL core questionnaire. Additional modules should be cancer‐specific or dedicated to specifics of the caregiver‐patient relationship.