Age- and sex-specific response to population density and sex ratio

Both population density and sex ratio shape competition for mates, resources and mating costs. Thus they may critically affect the intensity of sexual selection in the populations. Susceptibility to inter- and intrasexual competition, which changes with age in a large number of species, may additionally influence population response to these demographic factors. In this study, we monitored 16 seminatural populations of common lizards (Lacerta vivipara) to determine whether the reproductive output varied with male and female densities as a function of the individual sex and age. Our results suggest that the intensity of sexual selection was weaker in male-biased populations, supporting new theoretical models. In populations with a male-biased sex ratio, reproductive success was more equally distributed between males and, unlike female-biased populations, the choosiest females (middle-aged) did not obtain sires of higher quality than low-performance females. Our results also suggest that age may influence the intensity of sexual conflict. Middle-aged females (the class with the best performance) produced offspring with a lower body condition in male-biased populations, suggesting that they may be the preferred target of male harassment. By contrast, a male-biased sex ratio appeared to be beneficial for low-quality females, allowing these females to obtain higher quality sires and to produce offspring with a better body condition. These age- and sex-dependent responses to population density and sex ratio have important implications for population ecology and sexual selectio

Reappraisal of Temporary Levodopa Withdrawal ("Drug Holiday") in Parkinson's Disease

Transient withdrawal of therapy has been advocated as a method of dealing with the complications of long-term use of levodopa in the treatment of Parkinson's disease. We retrospectively examined the effect of a 10-day period of levodopa withdrawal, or "drug holiday," in 28 patients. We then compared the subsequent clinical course of these patients over one year with that of 30 other randomly selected, similar patients with Parkinson's disease. In both groups the disease progressed; there was no difference in disease severity, capacity for daily living activities, or total amounts of dopamine agonists eventually used. For some patients, it was possible to reduce dopamine agonists used immediately after the drug holiday without causing deterioration, but a pulmonary embolus and other complications occurred. Subsequent complications related to long-term dopamine-agonist therapy during the follow-up period were similar in the two groups. This investigation indicates that a drug holiday carries some risk and does not improve the efficacy of levodopa therapy or prevent the problems that occur with long-term administration

Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

Smoking and Parkinson's Disease

Smoking was examined in relation to Parkinson's disease (PD) in a population-based study in northern Manhattan (New York City) because of its putative “protective effect.” Using a case-control design, information on smoking and associated behaviors was obtained in structured interviews after standard diagnostic evaluations in both cases and controls. The overall prevalence of smoking in the population was 43.7%, decreasing to 37% after age 85. Smoking was most frequent in men, Blacks, and in both cases and controls using alcohol once per week or more. Cases had quit smoking more often than controls (87 vs. 64%), and had smoked for significantly fewer years (31 vs. 41 yrs; p < 0.05 for both). The age-at-onset for smokers with PD was similar to age-at-onset for nonsmokers with PD. The odds ratio (OR) for a history of smoking associated with PD was 1.1 (95% CI 0.7–1.8). No protective gradient was associated with heavier smoking patterns. However, the odds that patients with PD were still smoking at the time of the interview were significantly less than those for controls (OR = 0.2; 95% CI 0.1–0.5). These results do not support the hypothesis that smoking protects against PD; rather they strongly imply the converse, that PD reduces smoking

The Frequency and Associated Risk Factors for Dementia in Patients with Parkinson's Disease

Objectives: To estimate the frequency and determine the risk factors for incident dementia in community-dwelling patients with Parkinson's disease (PD) and in control subjects. Design: Prospective cohort study. During a 3.5-year period, 140 patients with idiopathic PD without evidence of dementia and 572 nondemented control subjects were identified in the community of Washington Heights—Inwood in New York, NY. All subjects underwent neurological and neuropsychological evaluations and follow-up examinations. Results: Twenty-seven patients with PD (19.2%) became demented throughout 2 years, as compared with 87 (15.2%) of the control subjects. The relative risk (RR) for the development of dementia with PD was 1.7 (95% confidence interval [CI], 1.1 to 2.7) after adjusting for age, education, and gender. Predictive features of incident dementia were an extrapyramidal score greater than 25 (RR, 3.56; 95% CI, 1.4 to 8.9) and a Hamilton Depression Rating Scale score greater than 10 (RR, 3.55; 95% CI, 1.6 to 7.9). Conclusion: Patients with PD, especially those with severe extrapyramidal signs, have almost twice the risk for the development of dementia than do community-dwelling control subjects

Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

Extrinsic and intrinsic preanalytical variables affecting liquid biopsy in cancer

Liquid biopsy, through isolation and analysis of disease-specific analytes, has evolved as a promising tool for safe and minimally invasive diagnosis and monitoring of tumors. It also has tremendous utility as a companion diagnostic allowing detection of biomarkers in a range of cancers (lung, breast, colon, ovarian, brain). However, clinical implementation and validation remains a challenge. Among other stages of development, preanalytical variables are critical in influencing the downstream cellular and molecular analysis of different analytes. Although considerable progress has been made to address these challenges, a comprehensive assessment of the impact on diagnostic parameters and consensus on standardized and optimized protocols is still lacking. Here, we summarize and critically evaluate key variables in the preanalytical stage, including study population selection, choice of biofluid, sample handling and collection, processing, and storage. There is an unmet need to develop and implement comprehensive preanalytical guidelines on the optimal practices and methodologies

The Liquid Biopsy Consortium: Challenges and opportunities for early cancer detection and monitoring

The emerging field of liquid biopsy stands at the forefront of novel diagnostic strategies for cancer and other diseases. Liquid biopsy allows minimally invasive molecular characterization of cancers for diagnosis, patient stratification to therapy, and longitudinal monitoring. Liquid biopsy strategies include detection and monitoring of circulating tumor cells, cell-free DNA, and extracellular vesicles. In this review, we address the current understanding and the role of existing liquid-biopsy-based modalities in cancer diagnostics and monitoring. We specifically focus on the technical and clinical challenges associated with liquid biopsy and biomarker development being addressed by the Liquid Biopsy Consortium, established through the National Cancer Institute. The Liquid Biopsy Consortium has developed new methods/assays and validated existing methods/technologies to capture and characterize tumor-derived circulating cargo, as well as addressed existing challenges and provided recommendations for advancing biomarker assays

The Relationship of Serotonin to Depression in Parkinson's Disease

We have previously reported a correlation between depression in patients with idiopathic Parkinson's disease and decreased concentrations of the cerebrospinal fluid content of the serotonin metabolite, 5-HIAA. To further examine this relationship, we repeated the study in a new cohort of patients while they remained on dopaminergic medications, conducted follow-up interviews and examinations in our original cohort, and conducted an open trial of the serotonin precursor, 5-hydroxytryptophan in a group of new patients with depression. We were again able to demonstrate a significant reduction in cerebrospinal 5-HIAA in depressed patients in comparison to controls and patients without depression. Demented patients with Parkinson's disease, particularly those with concurrent depression, had the lowest values of 5-HIAA. No new cases of depression occurred in our orignial cohort after 21/2 years of follow-up, and depression remitted following conventional or experimental treatment in four patients. Depression improved in six of the seven new patients following oral 5-hydroxytryptophan. Three of these patients allowed a repeat lumbar puncture, and the concentration of 5-HIAA increased following 5-hydroxytryptophan. These three studies support our hypothesis that depression in idiopathic Parkinson's disease is associated with a reduction in brain serotonin. However, it also suggests that other factors, biological or environmental, may be causal factors

Neuropsychological Characteristics of Preclinical Dementia in Parkinson's Disease

The goal of this study was to characterize the changes in cognition associated with the earliest, or preclinical, stages of dementia in Parkinson's disease (PD). We administered a comprehensive neuropsychological test battery to a group of initially nondemented PD patients participating in a longitudinal community-based epidemiologic study. We used Cox proportional hazards models to assess the relative risk of incident dementia associated with baseline scores on the neuropsychological tests. Baseline performance on two verbal fluency tasks (letter fluency and category fluency) was significantly and independently associated with incident dementia. Tests of memory, orientation, abstract reasoning, naming, and constructional skill were less sensitive predictors of subsequent dementia. The neuropsychological pattern characterizing the preclinical stages of dementia in PD differed from that described previously in preclinical Alzheimer's disease. Results suggest that poor performance on tests of verbal fluency may represent a distinct characteristic of the preclinical phase of dementia in PD