Clinical relevance of genetic instability in prostatic cells obtained by prostatic massage in early prostate cancer

We investigated whether genetic lesions such as loss of heterozygosity (LOH) are detected in prostatic cells obtained by prostatic massage during early diagnosis of prostate cancer (CaP) and discussed their clinical relevance. Blood and first urine voided after prostatic massage were collected in 99 patients with total prostate-specific antigen (PSA) between 4 and 10 ng ml−1, prior to prostate biopsies. Presence of prostatic cells was confirmed by quantitative RT–PCR analysis of PSA mRNA. Genomic DNA was analysed for LOH on six chromosomal regions. One or more allelic deletions were found in prostatic fluid from 57 patients analysed, of whom 33 (58%) had CaP. Sensitivity and specificity of LOH detection and PSA free to total ratio <15% for positive biopsy were respectively 86.7 and 44% (P=0.002) for LOH, and 55 and 74% (P=0.006) for PSA ratio <15%. Analysis of LOH obtained from prostatic tumours revealed similar patterns compared to prostatic fluid cells in 86% of cases, confirming its accuracy. The presence of LOH of urinary prostatic cells obtained after prostatic massage is significantly associated with CaP on biopsy and may potentially help to identify a set of patients who are candidates for further prostate biopsies

Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for Chronic Daily Headache: Protocol for a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.</p> <p>Methods</p> <p>Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.</p> <p>Results</p> <p>Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/(NCT01157208)">(NCT01157208)</a></p

Injury rates and injury risk factors among federal bureau of investigation new agent trainees

<p>Abstract</p> <p>Background</p> <p>A one-year prospective examination of injury rates and injury risk factors was conducted in Federal Bureau of Investigation (FBI) new agent training.</p> <p>Methods</p> <p>Injury incidents were obtained from medical records and injury compensation forms. Potential injury risk factors were acquired from a lifestyle questionnaire and existing data at the FBI Academy.</p> <p>Results</p> <p>A total of 426 men and 105 women participated in the project. Thirty-five percent of men and 42% of women experienced one or more injuries during training. The injury incidence rate was 2.5 and 3.2 injuries/1,000 person-days for men and women, respectively (risk ratio (women/men) = 1.3, 95% confidence interval = 0.9-1.7). The activities most commonly associated with injuries (% of total) were defensive tactics training (58%), physical fitness training (20%), physical fitness testing (5%), and firearms training (3%). Among the men, higher injury risk was associated with older age, slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the physical fitness test (PFT), lower self-rated physical activity, lower frequency of aerobic exercise, a prior upper or lower limb injury, and prior foot or knee pain that limited activity. Among the women higher injury risk was associated with slower 300-meter sprint time, slower 1.5-mile run time, lower total points on the PFT, and prior back pain that limited activity.</p> <p>Conclusion</p> <p>The results of this investigation supported those of a previous retrospective investigation emphasizing that lower fitness and self-reported pain limiting activity were associated with higher injury risk among FBI new agents.</p

Aggressive dominance can decrease behavioral complexity on subordinates through synchronization of locomotor activities

Social environments are known to influence behavior. Moreover, within small social groups, dominant/subordinate relationships frequently emerge. Dominants can display aggressive behaviors towards subordinates and sustain priority access to resources. Herein, Japanese quail (Coturnix japonica) were used, given that they establish hierarchies through frequent aggressive interactions. We apply a combination of different mathematical tools to provide a precise quantification of the effect of social environments and the consequence of dominance at an individual level on the temporal dynamics of behavior. Main results show that subordinates performed locomotion dynamics with stronger long-range positive correlations in comparison to birds that receive few or no aggressions from conspecifics (more random dynamics). Dominant birds and their subordinates also showed a high level of synchronization in the locomotor pattern, likely emerging from the lack of environmental opportunities to engage in independent behavior. Findings suggest that dominance can potentially modulate behavioral dynamics through synchronization of locomotor activities.publishedVersionAlcala, Rocio. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Caliva, Jorge Martín. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Caliva, Jorge Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Flesia, Ana Georgina. Facultad de Matemática, Astronomía, Física y Computación; Argentina.Flesia, Ana Georgina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Estudios de Matemática; Argentina.Marin, Raúl Hector. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Marin, Raúl Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina.Kembro, Jackelyn Melissa. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Kembro, Jackelyn Melissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics from 10 to 100 au

We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M $>$ 1.5 $M_\odot$ more likely to host planets with masses between 2-13 M$_{\rm Jup}$ and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M $>$ 1.5M$_\odot$) of the form $\frac{d^2 N}{dm da} \propto m^\alpha a^\beta$, finding $\alpha$ = -2.4 $\pm$ 0.8 and $\beta$ = -2.0 $\pm$ 0.5, and an integrated occurrence rate of $9^{+5}_{-4}$% between 5-13 M$_{\rm Jup}$ and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8$^{+0.8}_{-0.5}$% of stars hosting a brown dwarf companion between 13-80 M$_{\rm Jup}$ and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability

The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics from 10 to 100 au

We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M $>$ 1.5 $M_\odot$ more likely to host planets with masses between 2-13 M$_{\rm Jup}$ and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M $>$ 1.5M$_\odot$) of the form $\frac{d^2 N}{dm da} \propto m^\alpha a^\beta$, finding $\alpha$ = -2.4 $\pm$ 0.8 and $\beta$ = -2.0 $\pm$ 0.5, and an integrated occurrence rate of $9^{+5}_{-4}$% between 5-13 M$_{\rm Jup}$ and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.8$^{+0.8}_{-0.5}$% of stars hosting a brown dwarf companion between 13-80 M$_{\rm Jup}$ and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability