Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.

Skeletal Microstructural Abnormalities in Postmenopausal Women With Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and mu CT and compared with age-matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (+/-SD) cancellous bone volume (15.20 +/- 5.91 versus 21.34 +/- 5.53%, p = .01), trabecular number (1.31 +/- 0.26 versus 1.77 +/- 0.51/mm, p = .003), and trabecular thickness (141 +/- 23 versus 174 +/- 36 mu m, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 +/- 2.78 versus 7.94 +/- 3.08 mu m, p = .04), and correlated negatively with smoking (r = -0.67; p = .0005). Trabecular separation (785 +/- 183 versus 614 +/- 136 mu m, p = .01) and cortical porosity (4.11 +/- 1.02 versus 2.32 +/- 0.94 voids/mm(2); p < .0001) were higher in COPD while cortical width (458 +/- 214 versus 762 +/- 240 mu m; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 +/- 0.16 versus 0.66 +/- 0.12 mu m/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLDI and II (0.028 +/- 0.009 versus 0.016 +/- 0.011 mu m(3)/mu m(2)/day;p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease. (C) 2010 American Society for Bone and Mineral Research.

Biomechanical failure properties and microstructural content of ruptured and unruptured abdominal aortic aneurysms

Purpose: To test the hypothesis that ruptured abdominal aortic aneurysms (AAA) are globally weaker than unruptured ones. Methods: Four ruptured and seven unruptured AAA specimens were harvested whole from fresh cadavers during autopsies performed over an 18-month period. Multiple regionally distributed longitudinally oriented rectangular strips were cut from each AAA specimen for a total of 77 specimen strips. Strips were subjected to uniaxial extension until failure. Sections from approximately the strongest and weakest specimen strips were studied histologically and histochemically. From the load-extension data, failure tension, failure stress and failure strain were calculated. Rupture site characteristics such as location, arc length of rupture and orientation of rupture were also documented. Results: The failure tension, a measure of the tissue mechanical caliber was remarkably similar between ruptured and unruptured AAA (group mean +/- standard deviation of within-subject means: 11.2 +/- 2.3 versus 11.6 +/- 3.6 N/cin; p=0.866 by mixed model ANOVA). In post-hoc analysis, there was little difference between the groups in other measures of tissue mechanical caliber as well such as failure stress (95 +/- 28 versus 98 +/- 23 N/cm(2); p=0.870), failure strain (0.39 +/- 0.09 versus 0.36 +/- 0.09; p=0.705), wall thickness (1.7 +/- 0.4 versus 1.5 +/- 0.4 mm; p=0.470), and % coverage of collagen within tissue cross section (49.6 +/- 12.9% versus 60.8 +/- 9.6%; p=0.133). In the four ruptured AAA, primary rupture sites were on the lateral quadrants (two on left; one on left-posterior; one on right). Remarkably, all rupture lines had a longitudinal orientation and ranged from 1 to 6 cm in length. Conclusion: The findings are not consistent with the hypothesis that ruptured aortic aneurysms are globally weaker than unruptured ones. (C) 2011 Elsevier Ltd. All rights reserved.

Tessier No. 4 Facial Cleft: Evolution of Surgical Treatment in a Large Series of Patients

Background: Tessier no. 4 facial cleft is a rare, complex, and challenging craniofacial malformation. The present article aims to describe different clinical features evidenced in 21 cases of this malformation, discussing a 20-year experience with and evolution of its surgical treatment. Methods: Some demographic data, clinical features, and reconstructive results were evaluated retrospectively. These patients have been evaluated and treated in three specialized Brazilian craniofacial centers. Nineteen were already operated on, with a mean follow-up of 3.5 years (range, 1 to 20 years). Results: Sex distribution showed a male prevalence (2: 1). The average age of initial treatment was 5.4 years. Four cases were affected on the right side of the face, seven on the left, and 10 bilaterally. Six patients had other rare associated facial clefts, including nos. 5 (three patients), 7, 9, and 10. Cleft upper lip was evidenced in all patients, and maxillary hypoplasia was present in five and maxilla cleft in eight. Lower eyelid coloboma was seen in almost every case (19 patients); 10 of these had medial canthus dystopia. Four patients had amniotic bands in the limbs. Surgical repair was individualized to each patient. Surgical experience gained with these patients allowed the authors to develop some technical modifications, which have improved aesthetic results, camouflaging scars into natural folds and anatomical units, without compromising functional outcomes. Conclusions: The great majority of Tessier no. 4 facial clefts can be appropriately treated using local flaps. Classic techniques are extremely useful, but long-term results could be improved if the technical modifications described were adopted. (Plast. Reconstr. Surg. 122: 1505, 2008.)

Increased Immunoglobulin G Anti-Paracoccidioides brasiliensis Serum Antibody Avidity as a Predictor of Favorable Posttherapeutic Evolution in Paracoccidioidomycosis

Paracoccidioidomycosis is endemic in Latin America, and ca. 80% of all cases occur in Brazil. Little is known about antibody avidity or the evolution of such avidity in the posttherapeutic period for the different clinical presentations of the disease. In the present study, we evaluated 53 patients with paracoccidioidomycosis and calculated the avidity index. Medium-and high-avidity antibodies were found in 79.5% of patients with chronic presentation (n = 39). Among patients with the acute form (n = 14), 57.1% of the antibodies presented low avidity. In the posttherapeutic period, there was a significant increase in antibody avidity in patients presenting with the chronic multifocal form. In our preliminary study, which needs to be confirmed using a larger number of samples, the optimized method for studying antibody avidity detected differences among the clinical presentations of the mycosis and indicated the value of the avidity index as a marker of posttherapeutic evolution of patients with a multifocal chronic form of the disease.

Chronic hepatitis C: Hepatic fibrosis evolution after ineffective specific treatment

Background/Aims: Specific treatment of chronic hepatitis C is effective in 50% of patients, improving the]liver`s fibrosis, necroinflammatory changes and steatosis. However, in patients still viremic after treatment the extension of these benefits remains doubtful. The evolution of the disease in this group and its relationship to demographic data, biometric indices and time lapse between biopsies was evaluated. Methodology: In 141 patients, paired biopsies were classified and compared according to fibrosis grading. Necroinflammation, steatosis, demographic data (age and gender), body mass index (BMI) and time lapse between biopsies were compared with fibrosis grading. Results: The grade of fibrosis of the patients, after approximately 3.5 years time lapse between biopsies, could be classified into 4 groups; Improved: 29(20.0%), Unaltered: 64(45.0%), Worsened: 48(34%) and Cirrhotic: 14(9.93%). For necroinflammation, the Improved/Unaltered groups were statistically similar but different from the Worsened and Cirrhotic. The mean age, BMI and time lapse between biopsies were statistically similar in all groups. Steatosis occurred in 35 (24.82%) between biopsies and its incidence was reduced in the Worsened and Cirrhotic groups. Conclusions: Fibrosis turned into cirrhosis in a significant number of patients, after a short time lapse. The reverse correlation of steatosis to fibrosis and its occurrence during the time lapse between biopsies suggests it might induce hepatic necrosis and contribute to fibrogenesis.

THE TEMPO AND MODE OF EVOLUTION OF TRANSPOSABLE ELEMENTS AS REVEALED BY MOLECULAR PHYLOGENIES RECONSTRUCTED FROM MOSQUITO GENOMES

Although many mathematical models exist predicting the dynamics of transposable elements (TEs), there is a lack of available empirical data to validate these models and inherent assumptions. Genomes can provide a snapshot of several TE families in a single organism, and these could have their demographics inferred by coalescent analysis, allowing for the testing of theories on TE amplification dynamics. Using the available genomes of the mosquitoes Aedes aegypti and Anopheles gambiae, we indicate that such an approach is feasible. Our analysis follows four steps: (1) mining the two mosquito genomes currently available in search of TE families; (2) fitting, to selected families found in (1), a phylogeny tree under the general time-reversible (GTR) nucleotide substitution model with an uncorrelated lognormal (UCLN) relaxed clock and a nonparametric demographic model; (3) fitting a nonparametric coalescent model to the tree generated in (2); and (4) fitting parametric models motivated by ecological theories to the curve generated in (3).

The efficacy of functional endoscopic sinus surgery in the evolution of fever of unknown origin in ICU patients

Conclusion: Functional endoscopic sinus surgery (FESS) was found to be effective in treating fever of unknown origin (FUO) in intensive care unit (ICU) patients with rhinosinusitis, with 62% of patients showing improvement within 5 days of the procedure. Objective: To correlate improvement in FUO with FESS drainage of the paranasal sinuses. Methods: Fifty patients that developed FUO during ICU stay, with CT findings suggestive of rhinosinusitis, and showed no improvement in fever after clinical treatment underwent FESS for drainage of the paranasal sinuses and were evaluated for postoperative improvement of fever. Results: The study sample consisted of 50 patients (74% of whom were male, mean age 48.1 years). The most frequent diagnoses at ICU admission were tetanus, pulmonary disease, and cardiovascular disease. In all, 68% of patients underwent nasogastric or enteral intubation. CT scanning most commonly showed involvement of the sphenoid sinus. In 54% of cases, sinusitis was bilateral and extended throughout the maxillary, ethmoidal, and sphenoidal sinuses. Sinusectomy was performed in all patients, and pathological secretion in the paranasal sinuses was seen in 52% of patients during surgery. Gram-negative bacteria were the most commonly isolated organisms, followed by Gram-positive bacteria and fungi. Improvement of fever was found in 82% of patients after FESS; 38% of these improved within the first 48 h post-procedure, and the remaining 62% within the first 5 postoperative days.

State-dependent microstructural white matter changes in bipolar I depression

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.

A prospective study on the dynamics of the clinical and immunological evolution of human Leishmania (L.) infantum chagasi infection in the Brazilian Amazon region

This prospective study was carried out from October 2003 to December 2005 and involved a cohort of 946 individuals of both genders, aged 1-89 years, from an endemic area for American visceral leishmaniasis (AVL), in Para State, Brazil. The aim of the study was to analyze the dynamics of the clinical and immunological evolution of human Leishmania ( L.) infantum chagasi infection represented by the following clinical-immunological profiles: asymptomatic infection (AI); symptomatic infection (SI = AVL); subclinical oligosymptomatic infection (SOI); subclinical resistant infection (SRI); and indeterminate initial infection (III). Infection diagnosis was determined by the indirect fluorescent antibody test and leishmanin skin test. In total, 231 cases of infection were diagnosed: the AI profile was the most frequent (73.2%), followed by SRI (12.1%), III (9.9%), SI (2.6%) and SOI (2.2%). The major conclusion regarding evolution dynamics was that the III profile plays a pivotal role from which the cases evolve to either the resistant, SRI and AI, or susceptible, SOI and SI, profiles; only one of the 23 III cases evolved to SI, while most evolved to either SRI (nine cases) or SOI (five cases) and eight cases remained as III. (C) 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction-an experimental study in growing animals

Background: Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai`s portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals. Methods: In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses. Results: The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group. Conclusions: Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces. (C) 2009 Elsevier Inc. All rights reserved.

Effects of Salivary Gland Homogenate from Wild-Caught and Laboratory-Reared Lutzomyia longipalpis on the Evolution and Immunomodulation of Leishmania (Leishmania) amazonensis Infection

We investigated the effects of Lutzomyia longipalpis salivary glands homogenate of wild-caught and laboratory-reared vectors on the lesion evolution and immunomodulation of the infection caused by Leishmania (Leishmania) amazonensis. To compare the effect of both salivary glands homogenate (SGH), C57BL/6 mice were inoculated Subcutaneously into the hind footpads or into the ear dermis with 10(6) promastigotes in the presence or not of SGH from wild-caught and laboratory-colonized sand flies. Comparing SGH groups, the lesion size was lower in mice co-inoculated with wild-caught SGH, as the parasitism and the infiltration of macrophages at the inoculation site. Wild-caught SGH also determined lower production of IL-4 and IL-10 but higher IL-12 levels compared with laboratory-reared SGH. Our findings address a probable bias by using SGH from laboratory-colonized sand flies instead of wild-caught vector SGH in studies concerning saliva effects. A possible mild influence of sand fly saliva in natural infections caused by Leishmania is also speculated, as infection is transmitted by wild and not by laboratory-reared vectors.

Evolution of Laparoscopic Colorectal Surgery in Brazil Results of 4744 Patients From the National Registry

Background: Since its introduction, laparoscopic colorectal surgery has raised intense debate and controversies regarding its safety and effectiveness. Methods: This multicentric registry reports the experience of 28 Brazilian surgical teams specializing in laparoscopic colorectal surgery. Results: Between 1992 and 2007, 4744 patients (1994 men-42% and 2750 women-58%) were operated upon, with ages ranging from 13 to 94 years (average 57.5y). Benign diseases were diagnosed in 2356 patients (49.6%). Most diseases were located in 50.7% of the left and sigmoid colon, 28.2% in the rectum and anal canal. 8.0% in the right colon, and diffuse 7.0%. There were 181 (3.8%) intraoperative complications (from 0% to 14%). There were 261 (5.5%) reported conversions to laparotomy (from 0% to 16.5%), mainly during the early experience (n = 119 - 59.8%). Postoperative complications were registered in 683 (14.5%) patients (from 5.0% to 50%). Mortality occurred in 43 patients (0.8%). Surgeons who performed less than 50 cases reported similar rates of intraoperative (4.2% vs. 3.8%,- P = 0.7), postoperative complications (20.8% vs. 14.3%; P = 0.07), and mortality (1.0% vs. 0.9%; P = 0.5) but the conversion rate was higher (10.4% vs. 5.4%; P = 0.04). Two thousand three hundred and eighty-nine (50.4%) malignant tumors were operated upon, and histologic classification showed 2347 (98%) adenocarcinomas, 30 (0.6%) spinocelular carcinomas, and 12 (0.2%) other histologic types. Tumor recurrence rate was 16.3% among patients followed more than I year. After an average follow-Lip of 52 months, 19 (0.8%) parietal recurrences were reported, 18 of which were in port sites and I in a patient with disseminated disease. There was no incisional recurrence in the ports used to withdraw the pathologic specimen. Compared with other registries, there was a 75% increase in the number of groups pet-forming laparoscopic colorectal surgery and a decrease in conversions (from 10.5%. to 5.5%) and mortality (from 1.5% to 0.9%) rates. Conclusions: (1) The number of patients operated upon increased expressively during the last years; (2) operative indications for benign and malignant diseases were similar, and diverticular disease of the colon comprised 40% of the benign ones; (3) conversion and mortality rates decreased over time; (4) Surgeon`s experience did not influence the complication rates, but was associated with a lower conversion; and (5) oncologic outcome expressed by recurrence rates showed results similar to those reported in conventional surgery.

High rates of molecular evolution in hantaviruses

Hantaviruses are rodent-borne Bunyaviruses that infect the Arvicolinae, Murinae, and Sigmodontinae subfamilies of Muridae. The rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. If substantiated, this would make the hantaviruses among the slowest evolving of all RNA viruses. However, as hantaviruses replicate with an RNA-dependent RNA polymerase, with error rates in the region of one mutation per genome replication, this low rate of nucleotide substitution is anomalous. Here, we use a Bayesian coalescent approach to estimate the rate of nucleotide substitution from serially sampled gene sequence data for hantaviruses known to infect each of the 3 rodent subfamilies: Araraquara virus ( Sigmodontinae), Dobrava virus ( Murinae), Puumala virus ( Arvicolinae), and Tula virus ( Arvicolinae). Our results reveal that hantaviruses exhibit shortterm substitution rates of 10(-2) to 10(-4) substitutions/site/year and so are within the range exhibited by other RNA viruses. The disparity between this substitution rate and that estimated assuming rodent-hantavirus codivergence suggests that the codivergence hypothesis may need to be reevaluated.

Glomerular Nucleus of the Weakly Electric Fish, Gymnotus sp.: Cytoarchitecture, Histochemistry, and Fiber Connections-Insights from Neuroanatomy to Evolution and Behavior

The present study provides a detailed description of morphological and hodological aspects of the glomerular nucleus in the weakly electric fish Gymnotus sp., and explores the evolutionary and functional implications flowing from this analysis. The glomerular nucleus of Gymnotus shows numerous morphological similarities with the glomerular nucleus of percomorph fish, although cytoarchitectonically simpler. In addition, congruence of the histochemical acetylcholinesterase (AChE) distribution with cytoarchitectonic data suggests that the glomerular nucleus, together with the ventromedial cell group of the medial subdivision of the preglomerular complex (PGm-vmc) rostrally, and the subglomerular nucleus (as identified by Maler et al. [1991] J Chem Neuroanat 4:1-38) caudally, may form a distinct longitudinally organized glomerular complex. Our results show that an important source of sensory afferents to the glomerular nucleus originates in the pretectal and electrosensorius nuclei. The glomerular nucleus in turn projects to the hypothalamus (inferior lobe and anterior hypothalamus), to the anterior tuberal nucleus, and to the medial region of the preglomerular nucleus (PGm). These data suggest that visual and electrosensory information reach the glomerular nucleus and are relayed to the hypothalamus and, via PGm, to the pallium. Such connections are similar to those of the glomerular nucleus in percomorphs and the posterior pretectal nucleus in osteoglossomorph, esocids, and salmonids, where they comprise one component of a visual processing pathway. In Gymnotiform fish, however, the pretectal region that projects to the glomerular nucleus is dominated by electrosensory input (visual input is minor), which is consistent with the dominant role of electroreception in these fish. J. Comp. Neurol. 519:1658-1676, 2011. (c) 2011 Wiley-Liss, Inc.