Pectoral Dimorphism Is a Pervasive Feature of Skate Diversity and Offers Insight into their Evolution.

Mature skates (Batoidea: Rajoidei) display a unique form of sexual dimorphism in which males develop a concave anterior pectoral fin, giving them a bell-shaped appearance. Recent work has linked the male-specific transformation to differential skeletal development that is coincident with the rapid elongation of claspers, cartilage-supported intromittent organs. Still, little is known about the prevalence of pectoral dimorphism across skates or of interspecific variation in its expression. Here, we use various morphological approaches to broadly explore pectoral dimorphism in skates, with the goal of understanding its significance in their evolutionary history. We find that pectoral fin sexual dimorphism exists across skate diversity, positively identifying its presence in at least 131 species spanning 33 genera, approximately 40% of valid species. Further, we show that the nature of male-female shape change is largely consistent across species, but that it differs in its magnitude at a biologically meaningful scale. Finally, we use the pygmy skate Fenestraja plutonia as a case study to illustrate ontogenetic patterns in the development of pectoral fin dimorphism, additionally identifying sex-based differences in the pelvic girdle and jaw. Our work suggests that the diversity of pectoral dimorphism in skates is linked to comparative growth and maturation, and potentially to processes underlying reproductive and life history diversification within the group.

El Dimorfismo Pectoral es una Característica Generalizada de la Diversidad de Patines y Ofrece una Perspectiva de su Evolución Los patines (Batoidea: Rajoidei) muestran una forma única de dimorfismo sexual en el que los machos desarrollan una aleta pectoral anterior cóncava que les da una apariencia de campana. Estudios recientes han relacionado este dimorfismo en los machos con el desarrollo esquelético diferencial que coincide con la rápida elongación de los gonopterigios, órganos intromitentes soportados por cartílago. Sin embargo, poco se sabe acerca de la prevalencia del dimorfismo pectoral en patines o de la variación interespecífica en su expresión. En este estudio abordamos varios enfoques morfológicos para explorar ampliamente el dimorfismo pectoral en patines, con el objetivo de comprender su importancia en su historia evolutiva. Identificamos dimorfismo sexual en al menos 131 especies que abarcan 33 géneros, aproximadamente el 40% de las especies válidas. Además, mostramos que la naturaleza del cambio de forma masculino­femenino es en gran medida consistente en todas las especies, pero que difiere en su magnitud en una escala biológicamente significativa. Por último, utilizamos el patín pigmeo Fenestraja plutonia como estudio de caso para ilustrar los patrones ontogenéticos en el desarrollo del dimorfismo de la aleta pectoral, además de identificar dimorfismo sexual a nivel de cintura pélvica y mandíbula. Nuestro trabajo sugiere que la diversidad del dimorfismo pectoral en los patines está relacionada con el crecimiento y la maduración comparativos y, potencialmente, con los procesos subyacentes a la diversificación de la reproducción e historias de la vida dentro del grupo. Translated to Spanish by S. Hinojosa (hinojosa.silvia@gmail.com).

O Dimorfismo Peitoral é uma Característica Difusa da Diversidade do Skate e Oferece Informações sobre sua Evolução Rajídeos maduros (Batoidea: Rajoidei) exibem uma forma única de dimorfismo sexual em que os machos desenvolvem uma nadadeira peitoral anterior côncava, dando-lhes uma aparência em forma de sino. Trabalhos recentes correlacionam a forma específíca dos machos ao desenvolvimento diferencial do esqueleto, que coincide com o rápido alongamento dos clásperes, órgãos intromitantes cartilaginosos. Entretanto, pouco se sabe sobre a prevalência do dimorfismo peitoral em rajideos, ou sobre a variação interespecífica dessa expressão. Nesse trabalho utilizamos diversas abordagens morfológicas para explorar de forma ampla o dimorfismo peitoral dessas raias, com o objetivo de compreender sua significancia em relação à história evolutiva desse grupo. Descobrimos que o dimorfismo sexual da nadadeira peitoral existe entre de toda a diversidade dos rajídeos, observando sua presença em ao menos 131 espécies espalhadas por 33 gêneros, compreendendo aproximadamente 40% das espécies válidas. Além disso, mostramos que a natureza da mudança da forma entre machos e fêmeas é consistente entre as espécies, mas que diferem em sua magnitude em uma escala biologicamente significativa. Finalmente, usamos o rajideo pigmeu Fenestraja plutonia como um estudo de caso para ilustrar padrões ontogenéticos no desenvolvimento do dimorfismo da nadadeira peitoral, além de identificar diferenças baseadas no sexo na cintura pélvica e na mandíbula. Nosso trabalho sugere que a diversidade do dimorfismo peitoral em rajídeos está ligada ao crescimento e maturação comparativos e, potencialmente, aos processos subjacentes à diversificação reprodutiva e de história de vida dentro do grupo. Translated to Portuguese by J.P. Fontenelle (jp.fontenelle@mail.utoronto.ca).

The experiences of Latino siblings of children with developmental disabilities.

OBJECTIVE: This qualitative study explored the experiences of Latino siblings of children with developmental disabilities. METHODS: Parents and typically developing siblings from 15 Latino families with a child with a developmental disability participated in separate interviews. RESULTS: Using consensual qualitative research methodology, domains reflecting siblings' relationships, emotional experiences and communication about the disability were identified. The child's need for caregiving was a prominent topic in the sibling and parent narratives. Parents reported concerns about siblings' experience of differential treatment, whereas siblings reported concerns about restricted social activities because of their brother/sister. CONCLUSIONS: Including multiple informants revealed commonalities and differences in parents' and siblings' perspectives on the impact of a child's disability. The importance of considering sibling adaptation in sociocultural context is discussed.

The use of the Impact on Sibling scale with families of children with chronic illness and developmental disability.

OBJECTIVE: This study evaluated the Impact on Sibling scale, a six-item measure of parents' perception of the effects of a child's illness on healthy siblings. METHODS: Participants were 122 parents of a child with chronic illness, developmental disability, or autism spectrum disorder, and a well sibling aged 4-13 years. Parents completed the Impact on Sibling scale and the Child Behavior Checklist about the sibling, and completed the revised Impact on Family scale and the Brief Symptom Inventory about themselves. RESULTS: The Impact on Sibling score was correlated with measures of sibling, parent and family functioning. The internal consistency of the Impact on Sibling scale was higher for families with children with chronic illness compared with the other two diagnostic groups. CONCLUSION: The Impact on Sibling scale is a brief set of items that can help identify siblings who are negatively affected by a brother/sister's illness. Findings support further research on the Impact on Sibling scale, particularly with families of children with chronic illnesses.

Inhaled epinephrine for the treatment of transient tachypnea of the newborn.

OBJECTIVE: Infants with transient tachypnea of the newborn (TTN) have relatively low levels of epinephrine, which is known to mediate fetal lung fluid absorption. Providing exogenous epinephrine could be a valuable diagnostic and therapeutic intervention for this common condition. Our primary objective was to determine if inhaled racemic epinephrine is safe for the treatment of TTN. Our secondary objective was to determine its efficacy. STUDY DESIGN: We conducted a randomized, blinded, placebo-controlled pilot trial. Inhaled racemic epinephrine or placebo was administered to 20 newborns with TTN. Physiologic variables of cardiopulmonary function were measured during and after treatment. RESULT: No infant in either the treatment or control arm experienced an adverse event, including tachycardia or hypertension. We did not detect a difference between the two groups regarding rate of resolution of tachypnea. CONCLUSION: We did not observe any adverse effects of inhaled racemic epinephrine when administered for the treatment of TTN. Larger studies are necessary to determine efficacy.

Endogenous production and elevated levels of long-chain n-3 fatty acids in the milk of transgenic mice.

N-3 Polyunsaturated fatty acids (n-3 PUFA) are important for the normal development and functioning of all organisms. Mammals lack the n-3 fatty acid desaturase required for the synthesis of alpha-linolenic acid (18:3n-3), and are therefore dependent on dietary sources to obtain this essential fatty acid. Currently, the richest source of dietary long-chain n-3 PUFA, eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), are triacylglycerides extracted from rapidly declining marine resources. The nematode Caenorhabditis elegans synthesizes a wide range of PUFA and possesses the only known example of an n-3 fatty acid desaturase enzyme in the animal kingdom. Transgenic mice expressing the C. elegans n-3 desaturase under the control of the lactation-induced goat beta-casein mammary gland promoter were generated via pronuclear microinjection. Significant increases in n-3 PUFA, decreases in n-6 PUFA, and an overall decrease in the n-6:n-3 PUFA ratio were observed in the milk produced by transgenic mice. Neonate mice consuming milk from transgenic females accumulated increased levels of docosahexaenoic acid in their brains. This transgenic model may provide useful information to address some basic questions of neonatal nutrition, and demonstrates one of the steps that would be required to increase the n-3 PUFA content of milk and dairy products endogenously. Increasing the proportion of n-3 PUFA in milk fat would help to improve the nutritional composition of an important component of the North American diet.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation.

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart-lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.

Isolation and characterization of posteriorly restricted genes in the zebrafish gastrula.

In order to understand anteroposterior axis formation in vertebrates, we have used subtractive hybridization to clone genes expressed posteriorly in the zebrafish gastrula-stage embryo. Here we report the initial characterization of eight clones isolated from this screen. We find that all eight genes are expressed in posteriorly restricted domains, suggesting that they are involved in regulating posterior development during zebrafish embryogenesis.

Brain expression of presenilins in sporadic and early-onset, familial Alzheimer's disease.

BACKGROUND: Mutations in the presenilin proteins cause early-onset, familial Alzheimer's disease (FAD). MATERIALS AND METHODS: We characterized the cellular localization and endoproteolysis of presenilin 2 (PS2) and presenilin 1 (PS1) in brains from 25 individuals with presenilin-mutations causing FAD, as well as neurologically normal individuals and individuals with sporadic Alzheimer's disease (AD). RESULTS: Amino-terminal antibodies to both presenilins predominantly decorated large neurons. Regional differences between the broad distributions of the two presenilins were greatest in the cerebellum, where most Purkinje cells showed high levels of only PS2 immunoreactivity. PS2 endoproteolysis in brain yielded multiple amino-terminal fragments similar in size to the PS1 amino-terminal fragments detected in brain. In addition, two different PS2 amino-terminal antibodies also detected a prominent 42 kDa band that may represent a novel PS2 form in human brain. Similar to PS1 findings, neither amino-terminal nor antiloop PS2 antibodies revealed substantial full-length PS2 in brain. Immunocytochemical examination of brains from individuals with the N141I PS2 mutation or eight different PS1 mutations, spanning the molecule from the second transmembrane domain to the large cytoplasmic loop domain, revealed immunodecoration of no senile plaques and only neurofibrillary tangles in the M139I PS1 mutation stained with PS1 antibodies. CONCLUSIONS: Overall presenilin expression and the relative abundance of full-length and amino-terminal fragments in presenilin FAD cases were similar to control cases and sporadic AD cases. Thus, accumulation of full-length protein or other gross mismetabolism of neither PS2 nor PS1 is a consequence of the FAD mutations examined.

Modeling splice sites with Bayes networks.

MOTIVATION: The main goal in this paper is to develop accurate probabilistic models for important functional regions in DNA sequences (e.g. splice junctions that signal the beginning and end of transcription in human DNA). These methods can subsequently be utilized to improve the performance of gene-finding systems. The models built here attempt to model long-distance dependencies between non-adjacent bases. RESULTS: An efficient modeling method is described which models biological data more accurately than a first-order Markov model without increasing the number of parameters. Intuitively, a small number of parameters helps a learning system to avoid overfitting. Several experiments with the model are presented, which show a small improvement in the average accuracy as compared with a simple Markov model. These experiments suggest that single long distance dependencies do not help the recognition problem, thus confirming several previous studies which have used more heuristic modeling techniques. AVAILABILITY: This software is available for downloaded and as a web resource at http://www.ai.uic.edu/software CONTACT: kasif@eecs.uic.edu

[Intrathoracic coelomic cysts]. / Kystes coelomiques intrathoraciques.

Intrathoracic coelomic cysts are benign embryonic tumors with a mesothelial lining. The aim of this work was to review possible localizations (pleuropericardic and other), the remaining surgical indications, and the current situation of minimally invasive techniques. We reviewed retrospectively, 28 cases of intrathoracic coelomic cysts in 12 men and 16 women, mean age 44 years. We recorded the cyst localization, clinical signs, indication for surgery, access routes used, and outcome. Twenty-one cysts were pleuropericardial cysts and 7 were ectopic mediastinal cysts. In all 7 of the ectopic mediastinal cysts and 4 of the pleuropericardial cysts surgery was indicated for diagnosis; for the other pleuropericardial cysts the indication was based on clinical signs (n = 4), large volume (n = 4), progressing volume (n = 7), no apparent reason (n = 1) and association with surgery for pneumothorax (n = 1). Assess was by mediastinoscopy (n = 1), mediastinotomy (n = 1), sub-xyphoid route (n = 1), thoracotomy (n = 18), and videothoracoscopy (n = 7). Long-term outcomes (mean follow-up 4 years 4 months) were good with no recurrences. Postoperative sequelae were observed in 6 cases after thoracotomy and in 1 case after videothoracoscopy. In summary, pleuropericardial cysts warrant surveillance without surgery unless their volume increases or clinical signs develop. Ectopic mediastinal cysts usually require surgery for diagnosis. It would appear advisable to prefer videothoracoscopy which allows diagnosis and excision of pleuropericardial cysts. Minimal thoracotomy may be helpful for ectopic mediastinal cysts.

Chronic naltrexone differentially affects supraspinal delta-opioid receptor-mediated antinociception.

The effects of chronic treatment with naltrexone, an opioid receptor antagonist, on delta1- and delta2-opioid receptor agonist-induced antinociception and ligand binding were investigated in mice. Antinociception by intracerebroventricular (i.c.v.) [D-Pen2,5]enkephalin (DPDPE) and [D-Ala2]deltorphin II, agonists selective for delta1- and delta2-opioid receptors, respectively, was blocked following subcutaneous (s.c.) implantation of a naltrexone pellet (7.5 mg) for 7 days. Removal of the naltrexone pellet was followed 24 h later by a decrease of 7.5-fold in the ED50 value of [D-Ala2]deltorphin II, but not that of DPDPE. In a whole brain homogenate the binding of [3H][D-Ala2]deltorphin II was increased twice as much as that of [3H]DPDPE. Chronic naltrexone treatment also produced an 8.6-fold decrease in the ED50 value of i.c.v. administered morphine. The increase in morphine potency was reversed to a control (placebo-treated mice) value by the selective delta2-opioid receptor antagonist, naltriben (25 pmol, i.c.v.). Thus, chronic naltrexone selectively increases delta2-opioid receptor-mediated antinociception, supporting the existence of delta opioid receptor subtypes with distinct adaptive characteristics. The data also indicate that delta2-opioid receptors are critically involved in the expression of morphine supersensitivity.

Recurrent ventricular tachyarrhythmias associated with QT prolongation following hydrofluoric acid burns.

BACKGROUND: Some hydrofluoric acid burns appear initially as only a slight wound, but patients may show dramatic changes within several hours. The extent of such burns are directly related to the concentration, amount, and duration of exposure. CASE REPORT: A 64-year-old man sustained 44% total body surface burns after exposure to 30% hydrofluoric acid. Approximately 5 h after injury, he developed recurrent ventricular tachycardia and ventricular fibrillation which occurred in conjunction with long QT syndrome. In this case, the occurrence of hypocalcemia and especially hypomagnesemia played an important role in the development of long QT syndrome.

The competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist LY293558 attenuates and reverses analgesic tolerance to morphine but not to delta or kappa opioids.

Antagonists of the NMDA type of excitatory amino acid (EAA) receptor attenuate or reverse the development of tolerance to the analgesic effects of the mu opioid agonist morphine, the delta-1 opioid agonist DPDPE but not the kappa-1 agonist U50,488H or the kappa-3 agonist naloxone benzoylhydrazone. The role of the AMPA subtype of EAA receptor in analgesic tolerance was examined using LY293558, a selective competitive antagonist that is active after systemic administration. Administration of morphine, DPDPE, or U50,488H three times daily for 3 days according to an escalating dosing schedule resulted in analgesic tolerance as indicated by an increase in analgesic ED50 values using the tail-flick test in mice. Analgesic tolerance was attenuated when mice received a continuous subcutaneous infusion of LY293558 at doses of 30, 45 or 60 mg/kg/24 hr via an osmotic pump concurrent with the morphine treatment. Continuous subcutaneous infusion of LY293558 (45 mg/kg/24 hr) also reversed established morphine tolerance. In contrast, continuous subcutaneous infusion of the highest dose of LY293558 (60 mg/kg/24 hr) was ineffective in preventing the development of analgesic tolerance to DPDPE or U50,488H. Continuous subcutaneous infusion of LY293558 (60 mg/kg/24 hr) for 3 days protected mice from generalized convulsions produced by the selective AMPA agonist ATPA, indicating that the dosage of LY293558 that attenuated morphine tolerance was effective as an antagonist at AMPA receptors. These results demonstrate that AMPA receptors may play a role in the development and maintenance of morphine, but not DPDPE or U50,488H, analgesic tolerance.

Do estimates of emergency physician workforce underestimate current needs?

STUDY OBJECTIVE: Two widely used formulas for calculating the number of practicing emergency physicians (EPs) are based on the total number of US emergency departments and patient visits. In this study we hypothesized that the number of physicians now working in EDs is significantly greater than the estimates yielded by these formulas. Therefore we attempted to determine the accuracy of these methods for predicting the true number of practicing EPs. We also examined the training, board certification, and distribution of EPs. METHODS: The EDs of all hospitals listed by the Missouri Hospital Association (MHA), excluding children's and psychiatric hospitals, were surveyed over a 9-month period in 1994 with regard to the number and board status of all physicians practicing in their EDs and the numbers of full-time equivalents (FTEs) required for adequate staffing. These numbers were compared with 1994 estimates for Missouri based on two common methods of calculation. RESULTS: Of 134 hospitals with EDs, 118 (88%) completed our survey. These EDs employed 458 full-time EPs and 690 part-time EPs, with 41% and 7% board-certified in emergency medicine, respectively. Board-certified emergency physicians were concentrated in large cities and at university hospitals and were sparsely represented in rural areas. Adequate staffing of these EDs required 677 FTEs, compared with estimates of 358 (formula A) and 555 (formula B). Previously published formulas underestimate the need for EPs in our state by 47% (formula A) or 18% (formula B). CONCLUSION: Current staffing estimates regarding EPs working in Missouri greatly underestimate actual staffing needs. Board-certified EPs are in severe shortage and are unequally distributed in Missouri. Extrapolated nationally, these estimates may negatively affect funding and available residency positions for emergency medicine.

N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development.

This laboratory perspective reviews the pharmagologic approaches that have been used in preclinical animal models to demonstrate the ability of competitive (LY274614) and noncompetitive (MK801 and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists to attenuate or reverse the development of morphine tolerance. We provide additional data to support previous observations that these NMDA antagonists modulate morphine (mu) opioid tolerance but do not affect U50488H (kappa 1) opioid tolerance. A strategy, which utilizes efficacy as an NMDA receptor antagonist and clinical safety, provides the basis for a discussion of the clinical potential of dextromethorphan, ketamine, and felbamate as modulators of opioid tolerance in pain patients or opioid addicts. The potential use of NMDA receptor antagonists and nitric oxide synthase (NOS) inhibitors in neuropathic pain is also discussed.

Morphine fails to produce tolerance when administered in the presence of formalin pain in rats.

The present study examined the development of tolerance to morphine analgesia under conditions in which morphine was administered in the presence or absence of pain induced by subcutaneous injection of 50 microliters of 2.5% formalin into the hind paw of rats. Animals were injected with morphine (25 mg/kg, i.p.) or saline for 3 consecutive days either in the presence of pain (10 min after formalin injection) or in the absence of pain (6 h prior to formalin injection). On the 4th day, tolerance to the analgesic effect of test doses of morphine (6 or 10 mg/kg) was assessed in the formalin and tail-flick tests, respectively. Significant tolerance in both tests was observed in animals receiving morphine in the absence of pain during the tolerance induction period, but not in animals receiving morphine in the presence of pain.

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.

[The destroyed lung. Apropos of 46 surgical patients]. / Les poumons détruits. A propos de 46 malades opérés.

The authors report the results of a retrospective study of 46 patients operated upon for lung destruction of various origins. The main points that emerged were: (1) this type of pathology is regressing in France but persists in North Africa and Black Africa; (2) tuberculosis is the predominant cause of lung destruction; (3) superinfection with aspergillosis is frequent and must always be looked for; (4) surgery is difficult, especially pleuropneumonectomy for tuberculosis or its sequelae which has numerous complications (e.g. haemorrhage and pyothorax) responsible for a high mortality rate in this and other published series. However, in all patients operated upon for complications of lung destruction, when cure was obtained it was complete and permanent.

Monoclonal antibody based immunoassay for human aminoacylase-1.

Aminoacylase-1 is expressed in a wide variety of cell types. Although the exact role of this enzyme in cellular physiology remains unclear, it has been postulated to function in the salvage of acylated aminoacids. The enzyme is also of interest due to its gene map location on chromosome 3p21, a region deleted in several neoplasms. We have produced mouse monoclonal antibodies and rabbit antisera which recognize human aminoacylase-1. A sandwich ELISA has been developed which allows the measurement of human aminoacylase-1.