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Biological Plausibility (biological + plausibility)
Selected AbstractsAre antidepressants safe in the treatment of bipolar depression?ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008A critical evaluation of their potential risk to induce switch into mania or cycle acceleration Objective:, To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself. Method:, A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford,Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose,response relation, temporal relation with exposure to agent preceding effect and biological plausibility. Results:, There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone. Conclusion:, When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied. [source] Disease-specific Helicobacter pylori Virulence Factors: The Unfulfilled PromiseHELICOBACTER, Issue S1 2000David Y. Graham A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA +H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA,H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori -related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori -related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency. [source] Effect of forklift operation on lower back pain: An evidence-based approachHUMAN FACTORS AND ERGONOMICS IN MANUFACTURING & SERVICE INDUSTRIES, Issue 2 2008Heriberto Barriera Viruet Most studies on the occupational hazards associated with forklift operation have examined risks of fatalities and traumatic injuries. Few studies have examined the magnitude of risk of lower back pain. This research deals with an evidence-based approach designed to examine if there is a relationship between whole-body vibration and driver postures with lower back pain among forklift operators and to offer some recommendations to minimize the risk of lower back pain. To accomplish the study goal, an evidence-based approach was adopted from evidence-based medicine. The basic steps of this evidence-based approach were: (1) formulation of a clear research question from a worker-occupational problem; (2) search of the literature for the best evidence with which to answer the question; (3) critically appraise the evidence; and (4) implement useful findings in occupational health and safety practices. In addition, the metarelative risk was calculated and the biological plausibility between whole body vibration (WBV) and operator posture with lower back pain was investigated. Six observational articles satisfied the inclusion criteria adopted in this research. The methodological qualities of the published studies ranged from marginal to average. The metarelative risk was 2.1, indicating that operators exposed to driving forklifts are greater than twice the risk of those not exposed to driving forklifts to experience lower back pain. There are biological mechanisms by which WBV and operator postures could develop lower back pain. Some aspects of the work environment that influenced vibration are seat, speed, track, and tires. Awkward postures and static postures are affected by cab design, seat, time spent seated, and the task performed. It appears that there is a causal relationship between forklift operation and lower back pain. The evidence examined shows a strong association and consistency between all studies and this relationship is biologically plausible. It is recommended that intervention studies be conducted to determine the effectiveness of ergonomic controls. © 2008 Wiley Periodicals, Inc. [source] Carbaryl exposure and incident cancer in the Agricultural Health StudyINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Rajeev Mahajan Abstract Carbaryl is a carbamate insecticide with a broad spectrum of uses in agricultural, commercial and household settings. It has previously been linked with non-Hodgkin lymphoma (NHL) but studies of cancer risk in humans are limited. We examined occupational carbaryl use and risk of all cancers in the Agricultural Health Study, a prospective study of a cohort of pesticide applicators in North Carolina and Iowa. This analysis included 21,416 subjects (1,291 cases) enrolled from 1993,1997 and followed for cancer incidence through 2003. Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. Carbaryl was not associated with cancer risk overall. Relative to subjects who never used carbaryl, melanoma risk was elevated with >175 lifetime exposure-days (RR = 4.11; 95%CI, 1.33,12.75; p -trend = 0.07), >10 years of use (RR = 3.19; 95%CI, 1.28,7.92; p -trend = 0.04), or ,10 days of use per year (RR = 5.50; 95%CI, 2.19,13.84; p -trend < 0.001). Risk remained after adjusting for sunlight exposure. Although not significant, there appeared to be a trend of decreasing prostate cancer risk with increasing level of exposure. A small increase in NHL risk was observed using some, but not all, exposure measures. No associations were observed with other examined cancer sites. Because the observed results were not hypothesized a priori and because of limited study of their biological plausibility, they should be interpreted with caution. © 2007 Wiley-Liss, Inc. [source] Association between pacifier use and breast-feeding, sudden infant death syndrome, infection and dental malocclusionINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 6 2005Ann Callaghan RN RM BNurs(Hons) Executive summary Objective, To critically review all literature related to pacifier use for full-term healthy infants and young children. The specific review questions addressed are: What is the evidence of adverse and/or positive outcomes of pacifier use in infancy and childhood in relation to each of the following subtopics: ,breast-feeding; ,sudden infant death syndrome; ,infection; ,dental malocclusion. Inclusion criteria, Specific criteria were used to determine which studies would be included in the review: (i) the types of participants; (ii) the types of research design; and (iii) the types of outcome measures. To be included a study has to meet all criteria. Types of participants,The participants included in the review were healthy term infants and healthy children up to the age of 16 years. Studies that focused on preterm infants, and infants and young children with serious illness or congenital malformations were excluded. However, some total population studies did include these children. Types of research design, It became evident early in the review process that very few randomised controlled trials had been conducted. A decision was made to include observational epidemiological designs, specifically prospective cohort studies and, in the case of sudden infant death syndrome research, case,control studies. Purely descriptive and cross-sectional studies were excluded, as were qualitative studies and all other forms of evidence. A number of criteria have been proposed to establish causation in the scientific and medical literature. These key criteria were applied in the review process and are described as follows: (i) consistency and unbiasedness of findings; (ii) strength of association; (iii) temporal sequence; (iv) dose,response relationship; (v) specificity; (vi) coherence with biological background and previous knowledge; (vii) biological plausibility; and (viii) experimental evidence. Studies that did not meet the requirement of appropriate temporal sequencing of events and studies that did not present an estimate of the strength of association were not included in the final review. Types of outcome measures,Our specific interest was pacifier use related to: ,breast-feeding; ,sudden infant death syndrome; ,infection; ,dental malocclusion. Studies that examined pacifier use related to procedural pain relief were excluded. Studies that examined the relationship between pacifier use and gastro-oesophageal reflux were also excluded as this information has been recently presented as a systematic review. Search strategy, The review comprised published and unpublished research literature. The search was restricted to reports published in English, Spanish and German. The time period covered research published from January 1960 to October 2003. A protocol developed by New Zealand Health Technology Assessment was used to guide the search process. The search comprised bibliographic databases, citation searching, other evidence-based and guidelines sites, government documents, books and reports, professional websites, national associations, hand search, contacting national/international experts and general internet searching. Assessment of quality, All studies identified during the database search were assessed for relevance to the review based on the information provided in the title, abstract and descriptor/MeSH terms, and a full report was retrieved for all studies that met the inclusion criteria. Studies identified from reference list searches were assessed for relevance based on the study title. Keywords included: dummy, dummies, pacifier(s), soother(s), comforter(s), non-nutritive sucking, infant, child, infant care. Initially, studies were reviewed for inclusion by pairs of principal investigators. Authorship of articles was not concealed from the reviewers. Next, the methodological quality of included articles was assessed independently by groups of three or more principal investigators and clinicians using a checklist. All 20 studies that were accepted met minimum set criteria, but few passed without some methodological concern. Data extraction, To meet the requirements of the Joanna Briggs Institute, reasons for acceptance and non-acceptance at each phase were clearly documented. An assessment protocol and report form was developed for each of the three phases of review. The first form was created to record investigators' evaluations of studies included in the initial review. Those studies that failed to meet strict inclusion criteria were excluded at this point. A second form was designed to facilitate an in-depth critique of epidemiological study methodology. The checklist was pilot tested and adjustments were made before reviewers were trained in its use. When reviewers could not agree on an assessment, it was passed to additional reviewers and discussed until a consensus was reached. At this stage, studies other than cohort, case,control and randomised controlled trials were excluded. Issues of clarification were also addressed at this point. The final phase was that of integration. This phase, undertaken by the principal investigators, was assisted by the production of data extraction tables. Through a process of trial and error, a framework was formulated that adequately summarised the key elements of the studies. This information was tabulated under the following headings: authors/setting, design, exposure/outcome, confounders controlled, analysis and main findings. Results, With regard to the breast-feeding outcome, 10 studies met the inclusion criteria, comprising two randomised controlled trials and eight cohort studies. The research was conducted between 1995 and 2003 in a wide variety of settings involving research participants from diverse socioeconomic and cultural backgrounds. Information regarding exposure and outcome status, and potential confounding factors was obtained from: antenatal and postnatal records; interviews before discharge from obstetric/midwifery care; post-discharge interviews; and post-discharge postal and telephone surveys. Both the level of contact and the frequency of contact with the informant, the child's mother, differed widely. Pacifier use was defined and measured inconsistently, possibly because few studies were initiated expressly to investigate its relationship with breast-feeding. Completeness of follow-up was addressed, but missing data were not uniformly identified and explained. When comparisons were made between participants and non-participants there was some evidence of differential loss and a bias towards families in higher socioeconomic groups. Multivariate analysis was undertaken in the majority of studies, with some including a large number of sociodemographic, obstetric and infant covariates and others including just maternal age and education. As might be expected given the inconsistency of definition and measurement, the relationship between pacifier use and breast-feeding was expressed in many different ways and a meta-analysis was not appropriate. In summary, only one study did not report a negative association between pacifier use and breast-feeding duration or exclusivity. Results indicate an increase in risk for a reduced overall duration of breast-feeding from 20% to almost threefold. The data suggest that very infrequent use may not have any overall negative impact on breast-feeding outcomes. Six sudden infant death syndrome case,control studies met the criteria for inclusion. The research was conducted with information gathered between 1984 and 1999 in Norway, UK, New Zealand, the Netherlands and USA. Exposure information was obtained from a variety of sources including: hospital and antenatal records, death scene investigation, and interview and questionnaire. Information for cases was sought within 2 days after death, within 2,4 weeks after death and in one study between 3 and 11 years after death. Information for controls was sought from as early as 4 days of a nominated sudden infant death syndrome case, to between 1 and 7 weeks from the case date, and again in one study some 3,11 years later. In the majority of the studies case ascertainment was determined by post-mortem. Pacifier use was again defined and measured somewhat inconsistently. All studies controlled for confounding factors by matching and/or using multivariate analysis. Generally, antenatal and postnatal factors, as well as infant care practices, and maternal, family and socioeconomic issues were considered. All five studies reporting multivariate results found significantly fewer sudden infant death syndrome cases used a pacifier compared with controls. That is, pacifier use was associated with a reduced incidence of sudden infant death syndrome. These results indicate that the risk of sudden infant death syndrome for infants who did not use a pacifier in the last or reference sleep was at least twice, and possibly five times, that of infants who did use a pacifier. Three studies reported a moderately sized positive association between pacifier use and a variety of infections. Conversely, one study found no positive association between pacifier use at 15 months of age and a range of infections experienced between the ages of 6 and 18 months. Given the limited number of studies available and the variability of results, no meaningful conclusions could be drawn. Five cohort studies and one case,control study focused on the relationship between pacifier use and dental malocclusion. Not one of these studies reported a measure of association, such as an estimate of relative risk. It was therefore not possible to include these studies in the final review. Implications for practice, It is intended that this review be used as the basis of a ,best practice guideline', to make health professionals aware of the research evidence concerning these health and developmental consequences of pacifier use, because parents need clear information on which they can base child care decisions. With regard to the association between pacifier use and infection and dental malocclusion it was found that, due to the paucity of epidemiological studies, no meaningful conclusion can be drawn. There is clearly a need for more epidemiological research with regard to these two outcomes. The evidence for a relationship between pacifier use and sudden infant death syndrome is consistent, while the exact mechanism of the effect is not well understood. As to breast-feeding, research evidence shows that pacifier use in infancy is associated with a shorter duration and non-exclusivity. It is plausible that pacifier use causes babies to breast-feed less, but a causal relationship has not been irrefutably proven. Because breast-feeding confers an important advantage on all children and the incidence of sudden infant death syndrome is very low, it is recommended that health professionals generally advise parents against pacifier use, while taking into account individual circumstances. [source] Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental modelsIUBMB LIFE, Issue 11 2008Peter Møller Abstract The objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid peroxidation products depend on both the duration and severity of the exposure to hypoxia. Largest effects are observed with exposure to hypoxia at high altitude, but other factors, including ultraviolet light, exercise, exertion, and low intake of antioxidants, might contribute to the effect observed in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity. © 2008 IUBMB IUBMB Life, 60(11): 707,723, 2008 [source] Evaluation of physiologically based pharmacokinetic models for use in risk assessment,JOURNAL OF APPLIED TOXICOLOGY, Issue 3 2007Weihsueh A. Chiu Abstract Physiologically based pharmacokinetic (PBPK) models are sophisticated dosimetry models that offer great flexibility in modeling exposure scenarios for which there are limited data. This is particularly of relevance to assessing human exposure to environmental toxicants, which often requires a number of extrapolations across species, route, or dose levels. The continued development of PBPK models ensures that regulatory agencies will increasingly experience the need to evaluate available models for their application in risk assessment. To date, there are few published criteria or well-defined standards for evaluating these models. Herein, important considerations for evaluating such models are described. The evaluation of PBPK models intended for risk assessment applications should include a consideration of: model purpose, model structure, mathematical representation, parameter estimation, computer implementation, predictive capacity and statistical analyses. Model purpose and structure require qualitative checks on the biological plausibility of a model. Mathematical representation, parameter estimation, computer implementation involve an assessment of the coding of the model, as well as the selection and justification of the physical, physicochemical and biochemical parameters chosen to represent a biological organism. Finally, the predictive capacity and sensitivity, variability and uncertainty of the model are analysed so that the applicability of a model for risk assessment can be determined. Published in 2007 by John Wiley & Sons, Ltd. [source] Biological foundation for periodontitis as a potential risk factor for atherosclerosisJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2005Yong-Hee P. Chun Objectives:, Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:, The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:,In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:, An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis. [source] Extracts of various species of Epilobium inhibit proliferation of human prostate cellsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2003Annabella Vitalone This study examined whether various species of Epilobium, a phytotherapeutic agent used in folk medicine as a treatment for benign prostatic hyperplasia, may have an antiproliferative effect in PZ-HPV-7 human prostatic epithelial cells in-vitro. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) test, [methyl- 3H]thymidine incorporation into DNA and flow cytometry analysis were used to evaluate cell proliferation. Ethanolic extracts of E. spicatum, E. rosmarinifolium and E. tetragonum inhibited DNA synthesis in PZ-HPV-7 cells. While at high concentrations all extracts were cytotoxic, DNA synthesis was also decreased at levels that caused no or little cytotoxicity. Treatment of cells with Epilobium extracts did not result in a formation of DNA fragments (evaluated by the TUNEL assay) or chromatin condensation (assessed by Hoechst staining). Flow cytometry analysis indicated that Epilobium extracts inhibit the progression of the cell cycle from the G0/G1 phase. These results suggest that extracts of Epilobium inhibit proliferation of human PZ-HPV-7 cells in-vitro by affecting progression of the cell cycle. This study provides some initial biological plausibility for the use of Epilobium extracts in benign prostatic hyperplasia. [source] Behavioral genetics in antisocial spectrum disorders and psychopathy: A review of the recent literatureBEHAVIORAL SCIENCES & THE LAW, Issue 2 2010Tracy D. Gunter M.D. Behavioral geneticists are increasingly using the tools of molecular genetics to extend upon discoveries from twin, family, and adoption studies concerning the heritability of antisocial spectrum disorders and psychopathy. While there is a substantial body of research concerning antisocial spectrum disorders in the behavioral genetics literature, only a few studies could be located using the phenotype of psychopathy. In this report we summarize some of the recent molecular genetics work concerning antisocial spectrum disorders and psychopathy, with a focus on genes involved in the serotonergic and dopaminergic pathways, while also mentioning some of the novel genetic factors being considered. Monoamine oxidase (MAOA) and the serotonin transporter (5HTT) are reviewed at length, as these genes have received significant scientific attention in recent years and are sites of high biological plausibility in antisocial spectrum disorders and psychopathy. Copyright © 2010 John Wiley & Sons, Ltd. [source] The role of paracetamol in the pathogenesis of asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2010H. Farquhar Summary Paracetamol use represents a putative risk factor for the development of asthma. There is convincing epidemiological evidence that the risk of asthma may be increased with exposure to paracetamol in the intrauterine environment, infancy, later childhood and adult life. A dose-dependent association has also been observed in these different age groups in different populations world-wide. An association has also been shown between paracetamol use in both rhinoconjunctivitis and eczema. There is biological plausibility with paracetamol use leading to decreased glutathione levels resulting in increased oxidant-induced inflammation and potentially enhanced T-helper type 2 responses. At the population level, patterns of paracetamol use might explain, to some extent, the world-wide variation in the prevalence of asthma and related disorders, particularly the high rates in English-speaking countries, which have high per capita prescription and over-the-counter use of paracetamol. A temporal association also exists between the international trends of increasing paracetamol use and increasing prevalence of asthma over recent decades. Further research is urgently required, in particular randomized-controlled trials (RCTs) into the long-term effects of frequent paracetamol use in childhood, to determine the magnitude and characteristics of any such risk. Importantly, RCTs will also enable evidence-based guidelines for the recommended use of paracetamol to be developed. Cite this as: H. Farquhar, A. Stewart, E. Mitchell, J. Crane, S. Eyers, M. Weatherall and R. Beasley, Clinical & Experimental Allergy, 2010 (40) 32,41. [source] A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2CLINICAL & EXPERIMENTAL ALLERGY, Issue 12 2009J. Genuneit Summary Background Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case,control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. Methods We compared 1105 wheezing and 3137 non-wheezing children aged 8,12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. Results Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. Conclusions Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema. [source] Activational effects of sex hormones on cognition in menCLINICAL ENDOCRINOLOGY, Issue 5 2009A. Ulubaev Summary Background, Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer's. In normally ageing men, these age-related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre- and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility. Methods, This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross-sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined. Conclusions, Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis including receptors, enzymes and other hormones. [source] | ||||||||||