The present study was performed to determine the effects of central administration of leptin on food intake and sympathetic nervous system activity in a nonrodent species, the rhesus monkey. Peripheral administration of leptin at doses (1 and 3 microg/kg, s.c.) that produced increments of circulating leptin concentrations within a physiological range did not inhibit food intake over the subsequent 3 days. In contrast, leptin (1 microg/kg, intracerebroventricularly) had no acute effect on food intake, but caused a significant and sustained suppression (40-50%) of food intake during the entire following day (P < 0.01). In addition, circulating norepinephrine levels increased by 55 +/- 16% (P < 0.02) 1 h after intracerebroventricular leptin administration, but did not increase after artificial cerebrospinal fluid administration. These results indicate that leptin can provide a signal to the central nervous system that decreases food intake in primates and in addition acutely activates the sympathetic nervous system. However, the results showing an acute increase in circulating leptin concentrations after peripheral administration of human leptin suggest that in primates, increases in circulating leptin within the physiological range do not acutely regulate food intake. Leptin may be more important in regulating food intake when there are sustained changes in circulating concentrations of leptin (e.g. with obesity, prolonged energy restriction, or diabetes).

Objective/hypothesis

To investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.

Study design

Systematic review.

Methods

A systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates. After study screening and full-text assessment, two authors independently extracted all data using a pre-established abstraction form.

Results

Forty cases were included from 38 studies. The average age (standard deviation [SD]) of the sample at presentation was 28.5 (23.3) and was equally distributed across genders. The average time (SD) between initial diagnosis to local recurrence was 40.1 (60.3) months. The average time (SD) from primary tumor detection to the diagnosis of metastatic disease was 55.2 (49.0) months. The most common subsite for metastatic spread were the lungs (32.5%). Of the 33 patients with data on outcomes, 48.5% were found to have expired by the time of publication. The median overall survival was estimated to be 84 months (95% confidence interval [CI] 62.3-105.7).

Conclusions

The most common subsites for metastatic spread of skull base chordoma were the lungs and bone. Overall survival for patients in the current cohort was a median of 84 months, with no significant differences noted when stratifying by the extent of surgery or the site of metastases.

Level of evidence

3a.

Mental health problems are common for persons with neurological disorders (PWNDs) and their caregivers (CGs) but often are not adequately treated. Despite this growing need, the training of clinical psychologists typically does not include coursework or practicum experience working with these populations. To address this, a team of faculty, supervisors, and doctoral students in UC Berkeley's Clinical Science program undertook a year-long process that consisted of building a training curriculum that integrated coursework and consultation with visiting experts; providing supervised practicum training with PWNDs and CGs and evaluating training and clinical outcomes. We hoped to prepare students to train other mental health professionals to work with these populations in the future. In this article, we describe the Specialty Clinic with special attention given to the training provided, challenges faced and solutions found, clinic operations and logistics, and lessons learned. We also review key clinical issues and report key indicators of client outcomes. Finally, we evaluate the success of the Specialty Clinic and offer recommendations for others interested in providing these kinds of much needed training and clinical services in this important area.

Many developmental traits that are critical to the survival of the organism are also robust. These robust traits are resistant to phenotypic change in the face of variation. This presents a challenge to evolution. In this article, we asked whether and how a well-established robust trait, Drosophila segment patterning, changed over the evolutionary history of the genus. We compared segment position scaled to body length at the first-instar larval stage among 12 Drosophila species. We found that relative segment position has changed many times across the phylogeny. Changes were frequent, but primarily small in magnitude. Phylogenetic analysis demonstrated that rates of change in segment position are variable along the Drosophila phylogenetic tree, and that these changes can occur in short evolutionary timescales. Correlation between position shifts of segments decreased as the distance between two segments increased, suggesting local control of segment position. The posterior-most abdominal segment showed the highest magnitude of change on average, had the highest rate of evolution between species, and appeared to be evolving more independently as compared to the rest of the segments. This segment was exceptionally elongated in the cactophilic species in our dataset, raising questions as to whether this change may be adaptive.

Background

Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART.

Methods

A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models.

Results

Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation.

Conclusions

ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening.

Stable, hydrogen-burning, M dwarf stars make up about 75% of all stars in the Galaxy. They are extremely long-lived, and because they are much smaller in mass than the Sun (between 0.5 and 0.08 M(Sun)), their temperature and stellar luminosity are low and peaked in the red. We have re-examined what is known at present about the potential for a terrestrial planet forming within, or migrating into, the classic liquid-surface-water habitable zone close to an M dwarf star. Observations of protoplanetary disks suggest that planet-building materials are common around M dwarfs, but N-body simulations differ in their estimations of the likelihood of potentially habitable, wet planets that reside within their habitable zones, which are only about one-fifth to 1/50th of the width of that for a G star. Particularly in light of the claimed detection of the planets with masses as small as 5.5 and 7.5 M(Earth) orbiting M stars, there seems no reason to exclude the possibility of terrestrial planets. Tidally locked synchronous rotation within the narrow habitable zone does not necessarily lead to atmospheric collapse, and active stellar flaring may not be as much of an evolutionarily disadvantageous factor as has previously been supposed. We conclude that M dwarf stars may indeed be viable hosts for planets on which the origin and evolution of life can occur. A number of planetary processes such as cessation of geothermal activity or thermal and nonthermal atmospheric loss processes may limit the duration of planetary habitability to periods far shorter than the extreme lifetime of the M dwarf star. Nevertheless, it makes sense to include M dwarf stars in programs that seek to find habitable worlds and evidence of life. This paper presents the summary conclusions of an interdisciplinary workshop (http://mstars.seti.org) sponsored by the NASA Astrobiology Institute and convened at the SETI Institute.