Phylogeny and historical biogeography of neotropical catfishes Trichomycterus (Siluriformes: Trichomycteridae) from eastern Brazil.

The catfish subfamily Trichomycterinae is widely distributed in South America inhabiting several habitats, but specially mountain streams. Trichomycterus is the most speciose trichomycterid genus and recently due to his paraphyletic condition has been restricted to a clade from eastern Brazil called Trichomycterus sensu stricto comprising around 80 valid species distributed in seven areas of endemism of eastern Brazil. This paper aims to analyse the biogeographical events responsible for the distribution of Trichomycterus s.s., by reconstructing the ancestral data based on a time-calibrated multigene phylogeny. A multi-gene phylogeny was generated using 61 species of Trichomycterus s.s. and 30 outgroups, with divergence events calculated based on the estimated origin of Trichomycteridae. Two event-based analyses were applied to investigate the biogeographical events responsible the present distribution of Trichomycterus s.s. and suggest that the modern distribution of the group is a result of different vicariance and dispersal events. The diversification of Trichomycterus s.s. subgenera occurred in the Miocene, except for Megacambeva, with different biogeographical events shaping its distribution in eastern Brazil. An initial vicariant event split up the Fluminense ecoregion from the Northeastern Mata Atlantica + Paraíba do Sul + Fluminense + Ribeira do Iguape + Upper Paraná ecoregions. Dispersal events occurred mainly between Paraíba do Sul and neighboring river basins, with additional dispersal events from Northeastern Mata Atlantica to Paraíba do Sul, from São Francisco to Northeastern Mata Atlântica, and from Upper Paraná to São Francisco.

Absence of deficits in social behaviors and ultrasonic vocalizations in later generations of mice lacking neuroligin4.

Mutations in NLGN4X have been identified in individuals with autism spectrum disorders and other neurodevelopmental disorders. A previous study reported that adult male mice lacking neuroligin4 (Nlgn4) displayed social approach deficits in the three-chambered test, altered aggressive behaviors and reduced ultrasonic vocalizations. To replicate and extend these findings, independent comprehensive analyses of autism-relevant behavioral phenotypes were conducted in later generations of the same line of Nlgn4 mutant mice at the National Institute of Mental Health in Bethesda, MD, USA and at the Institut Pasteur in Paris, France. Adult social approach was normal in all three genotypes of Nlgn4 mice tested at both sites. Reciprocal social interactions in juveniles were similarly normal across genotypes. No genotype differences were detected in ultrasonic vocalizations in pups separated from the nest or in adults during reciprocal social interactions. Anxiety-like behaviors, self-grooming, rotarod and open field exploration did not differ across genotypes, and measures of developmental milestones and general health were normal. Our findings indicate an absence of autism-relevant behavioral phenotypes in subsequent generations of Nlgn4 mice tested at two locations. Testing environment and methods differed from the original study in some aspects, although the presence of normal sociability was seen in all genotypes when methods taken from Jamain et al. (2008) were used. The divergent results obtained from this study indicate that phenotypes may not be replicable across breeding generations, and highlight the significant roles of environmental, generational and/or procedural factors on behavioral phenotypes.

Low stress reactivity and neuroendocrine factors in the BTBR T+tf/J mouse model of autism.

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that displays robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including low social interactions, reduced vocalizations in social settings, and high levels of repetitive self-grooming. Autism-relevant phenotypes in BTBR offer translational tools to discover neurochemical mechanisms underlying unusual mouse behaviors relevant to symptoms of autism. Because repetitive self-grooming in mice may be a displacement behavior elevated by stressors, we investigated neuroendocrine markers of stress and behavioral reactivity to stressors in BTBR mice, as compared to C57BL/6J (B6), a standard inbred strain with high sociability. Radioimmunoassays replicated previous findings that circulating corticosterone is higher in BTBR than in B6. Higher basal glucocorticoid receptor mRNA and higher oxytocin peptide levels were detected in the brains of BTBR as compared to B6. No significant differences were detected in corticotrophin releasing factor (CRF) peptide or CRF mRNA. In response to behavioral stressors, BTBR and B6 were generally similar on behavioral tasks including stress-induced hyperthermia, elevated plus-maze, light ↔ dark exploration, tail flick, acoustic startle and prepulse inhibition. BTBR displayed less reactivity than B6 to a noxious thermal stimulus in the hot plate, and less immobility than B6 in both the forced swim and tail suspension depression-related tasks. BTBR, therefore, exhibited lower depression-like scores than B6 on two standard tests sensitive to antidepressants, did not differ from B6 on two well-validated anxiety-like behaviors, and did not exhibit unusual stress reactivity to sensory stimuli. Our findings support the interpretation that autism-relevant social deficits, vocalizations, and repetitive behaviors are not the result of abnormal stress reactivity in the BTBR mouse model of autism.

Mortality and cancer morbidity in a cohort of Canadian petroleum workers.

AIMS: To assess mortality and cancer morbidity in Canadian petroleum workers and explore exposure-response relations for specific petroleum agents. METHODS: A total of 25 292 employees hired between 1964 and 1994 were linked to the Canadian tumour registry and national mortality database. Exposure-response trends were assessed for hydrocarbon solvents/fuels, hydrocarbon lubricants, petroleum coke/spent catalyst, and hydrogen sulphide (H2S). RESULTS: External comparison analyses (mortality and incidence) showed deficits for all causes and all malignant neoplasms combined and were consistent with expectation for most malignant and non-malignant sites analysed. Gall bladder cancer mortality was increased among males based on four deaths, but cases had no common job assignments and the increase was focused in workers employed <10 years. Mesothelioma incidence was increased. Most exposure-specific analyses were compromised by small numbers. Statistically significant increases were observed for H2S exposure and a subgroup of accidental deaths as well as for petroleum coke/spent catalyst exposure and lung cancer. While both findings have a degree of biologic plausibility, the H2S association, which exhibited a clearer exposure-response pattern, could be subject to unmeasured confounders. Additionally, interpretation was complicated by the high correlation between hydrocarbon and H2S exposures. With regard to lung cancer, the analysis could not adequately control for smoking, was based on small numbers, and exhibited a tenuous exposure-response pattern. CONCLUSION: The findings for mesothelioma suggest the need for continued attention to asbestos in the petroleum industry. The relation between accidental deaths and H2S exposure deserves closer scrutiny in similarly exposed populations. Further analyses of lung cancer are underway and will be reported separately.

Heart failure: a hemodynamic disorder complicated by maladaptive proliferative responses.

Heart failure has traditionally been viewed as a hemodynamic syndrome characterized by fluid retention, high venous pressure, and low cardiac output. Over the past decade, however, it has become clear that because of deterioration and progressive dilatation (remodeling) of the diseased heart, this is also a rapidly fatal syndrome. The importance of prognosis came to be appreciated when clinical trials showed that therapy which initially improves such functional abnormalities, as high venous pressure and low cardiac output, often fail to improve survival, and that some drugs which improve hemodynamics worsen long-term prognosis. The latter is true for most vasodilators which, in spite of alleviating the adverse short-term consequences of high afterload, shorten survival. Notable exceptions are ACE inhibitors, whose vasodilator effects do not explain their ability to prolong survival; instead, these drugs slow both deterioration and remodeling of the failing heart. Inotropic agents, while providing immediate relief of symptoms, generally shorten long-term survival, whereas beta-blockers slow deterioration and remodeling, and reduce mortality. Aldosterone antagonists exert beneficial effects on prognosis that are not easily explained by their diuretic effects, but instead can be explained by their ability to inhibit signaling pathways that stimulate maladaptive hypertrophy, remodeling, apoptosis and other deleterious responses that cause deterioration of the failing heart. These and other findings demonstrate that heart failure is more than a hemodynamic disorder; these patients suffer from maladaptive proliferative responses that cause cardiac cell death and progressive dilatation that play a key role in determining the poor prognosis in this syndrome.

Circulation Research: origin and early years.

Circulation Research, first published in 1953, was created by the American Heart Association as "the authoritative new journal for investigators of the basic sciences as they apply to the heart and circulation." This review of the early years of the journal highlights the contributions of the first four Editors: Carl J. Wiggers, Carl F. Schmidt, Eugene M. Landis, and Julius H. Comroe, Jr. The success of Circulation Research is seen not only in the high quality of the articles published in its pages but also in the remarkable improvements in prevention and treatment of cardiovascular disease that have occurred over the past half century.

Updated mortality among diverse operating segments of a petroleum company.

OBJECTIVES: To update mortality for 34 560 employees from diverse operating segments of a Canadian petroleum company; and to investigate potential relations with occupational factors. METHODS: Employees from 1964-83 were linked to the Canadian mortality data base to provide 11 years additional follow up. There were 6760 deaths and 750 683 person-years of follow up compared with 3909 and 428 190, respectively, in the earlier study. Analyses used standardised mortality ratios (SMRs) to compare worker cause specific mortality with the Canadian general population. Duration of employment and latency analyses were performed for causes previously found to be increased in this and other petroleum cohorts, as well as any findings of interest. RESULTS: For the period 1964-94, employees experienced significantly low overall mortality (SMR=0.86 men, SMR=0.80 women). Kidney cancer, which has been increased in some studies of petroleum workers, was not increased. Acute non-lymphocytic leukaemia in exposed operating segments was consistent with the expected or only slightly, non-significantly increased. The most notable finding was increased deaths from mesothelioma among refinery and petrochemical workers (SMR 8.68; 95% confidence interval (95% CI) 5.51 to 13.03), most of whom were long term employees in jobs with presumed exposure to asbestos (mechanical and pipefitters). Deaths from multiple myeloma among marketing and distribution workers, which were previously increased, remained increased (SMR 2.08; 95% CI 0.95 to 3.95) in the update period 1984-94; however, there was no clear pattern by duration of employment or latency. Aortic aneurysms, which also were previously significantly increased among marketing and distribution workers approached the expected in the update period (SMR 1.18; 95% CI 0. 65-1.98). Analyses by duration of employment showed suggestive trends for aortic aneurysms, but earlier studies of this cohort have not found a relation between aortic aneurysms and exposure to hydrocarbons. CONCLUSION: The additional 2851 deaths and 322 493 person-years of follow up strengthened the assessment of mortality patterns relative to occupational factors. With the exception of mesothelioma, no clear work related increases in disease were identified.

A council of elders: creating a multi-voiced dialogue in a community of care.

In an era of 'medical care delivery systems', there is an increasing need for the patient's voice to be heard, for it to be invited, listened to, and taken seriously. This challenge is particularly evident in geriatrics education, a domain of clinical training in which educators and clinicians alike must struggle to overcome adverse attitudes towards the elderly ('ageism'). In this paper we introduce a 'Council of Elders' as an educational innovation in which we invited community elders to function as our 'Senior Faculty', to whom medical residents present their challenging and heartfelt dilemmas in caring for elder patients. In the conversations that ensue, the elders come to function not simply as teachers, but collaborators in a process in which doctors, researchers, and elders together create a community of resources, capable of identifying novel ways to overcome health-related difficulties which might not have been apparent to either group separately. Using the first meeting of the Council as an exemplar, we describe and discuss the special nature of such meetings and also the special preparations required to build a dialogic relationship between participants from very different worlds--different generations, different cultures (including the professional culture and the world of lived experience). Meetings with the council have become a required part of the primary care residency program--a very different kind of 'challenging case conference' in which moral dilemmas can be presented, discussed and reflected upon. It is not so much that elders give good advice in their responses--although they often do--as that they provide life world and value orientation as young residents gain a better sense of the elder's experience and what matters most to them. This project has been particularly worthwhile in addressing the problem of ageism--a way to render visible stereotypes and adverse physician values, with implications for decision-making with the patient, not for the patient.

Lyme disease: summary notes.

The intention of the Summary Notes section is to provide the practitioner and trainee with a current, concise reference source to dermatologic diseases and to serve as a form of Continuing Medical Education. Each installment will deal with a specific disease. When included, the pretest questions indicate some of the areas to be covered and will challenge your present knowledge of the material before reading further. The self-assessment post-test questions appear on page 308; the answers are on page 316.

Interval-force relation is unaffected by the presence of cardiomyopathy or coronary artery disease in patients with atrial fibrillation.

BACKGROUND: We tested the hypothesis that cycle length-dependent cardiac contractility in atrial fibrillation is primarily governed by the negative interval-force relation in patients with normal and depressed systolic function. METHODS AND RESULTS: We performed two-dimensional guided M-mode echocardiography in 41 patients (mean age, 69 +/- 4 years; range, 48 to 92 years; 19 men, 11 women). Twelve patients had objective evidence of left ventricular systolic dysfunction (CMP; mean ejection fraction, 37% +/- 7%) in the absence of coronary artery disease (CAD), 13 patients had documented CAD (mean ejection fraction, 43% +/- 6%), and 16 patients had normal resting left ventricular systolic function (mean ejection fraction, 58% +/- 7%). Simultaneous beat-to-beat blood pressure, end-systolic and end-diastolic dimension, circumferential velocity of fiber shortening (Vcf), and end-systolic wall stress (ESWS) were calculated for all patients. All three groups showed a significant linear relation between beat-to-beat Vcf and Vcf corrected for afterload (represented as the Vcf/ESWS ratio) and preceding cycle length. There was, however, no significant difference in the relation between either of these variables and cycle length among the three groups. There was also no difference in the rate of change in either Vcf or Vcf corrected for afterload (Vcf/ESWS ratio) from beat-to-beat among the three groups. Control patients with normal systolic function showed greater Vcf at any given cycle length compared with patients with CMP or CAD. CONCLUSION: Our data show that, for each beat in atrial fibrillation, Vcf and Vcf/ESWS ratio are decreased after shorter cycle lengths and increased after long cycles, but there is no significant attenuation of this effect in patients with systolic dysfunction with or without coronary disease compared with controls. Thus, the negative interval-force relation, the predominant determinant of beat-to-beat variation in contractility in atrial fibrillation, is preserved in patients with CAD or reduced left ventricular systolic function.