WITHDRAWN: Recommendations for evaluation and management of pain in patients with mucopolysaccharidosis in Latin America.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.jpainsymman.2018.03.023. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

HPV load and anal cytological abnormalities.

OBJECTIVES: The objective of this study was to evaluate the association between estimated human papillomavirus (HPV) viral load and abnormal cytology on anal samples. METHODS: Anal cytological samples of 42 HIV-positive patients were analysed by conventional cytology and Hybrid Capture II. RESULTS: On cytology, 30.95% (13 of 42) anal samples were positive for cytological abnormalities, 47.61% (20 of 42) were negative and 21.42% (nine of 42) were unsatisfactory. High-risk HPV infection was more frequent in anal samples with cytological abnormalities than in negative samples (P = 0.0002, Fisher's exact test), it was detected in all samples with cytological abnormalities and in 35% (seven of 20) of the negative samples. On samples with cytological abnormalities, the median of the relative light unit/cutoff (RLU/CO) value (viral load estimate) was 10.39 (1.02-572.6) and in negative samples it was 0.51 (0.26-51.70). The median of the RLU/CO value was higher in samples with cytological abnormalities when compared with the median in negative samples (P = 0.0001, Mann-Whitney U-test) and only samples with cytological abnormalities showed RLU/CO values > 100. CONCLUSIONS: The estimated high-risk HPV viral load is significantly higher in samples with cytological abnormalities than in negative anal samples and may be useful as an adjunct to anal cytology for triage of patients to high-resolution anoscopy and biopsy.

Morphological changes in eosinophils are reliable markers of the severity of an acute asthma exacerbation in children.

BACKGROUND: Early identification of the severity of asthma exacerbation would be helpful for the management of patients. We aimed to evaluate the correlation of morphological change in activated eosinophils and the severity of an asthma exacerbation. METHODS: Blood was collected from 55 asthmatic children: 40 of whom were having an exacerbation, 15 symptom-free, and 15 healthy controls. The percentage of eosinophils with morphological changes (emission of single or multiple pseudopods, presence of cytoplasmic vacuoles, releasing a small, moderate, or large quantity of granules, spreading, eosinophil death, and presence of cluster of free eosinophil granules) was quantified after the adherence to a slide and compared using the Mann-Whitney test. The correlation between the severity of the asthma exacerbation and the percentage changed eosinophils was tested with Spearman's correlation. RESULTS: The proportion of activated eosinophils was higher in asthmatic symptom-free children than in the control group, and acute asthma exacerbation produced an additional increase in eosinophil activation (P < 0.01). More significantly increased morphological changes were emissions of multiple pseudopods, presence of cytoplasmic vacuoles, spreading, and presence of a cluster of free eosinophil granules (P < 0.001). The following were correlated with the severity of an asthma exacerbation: ≥14% of eosinophils emitting single pseudopod, 8% emitting multiple pseudopods, 17% with vacuoles, 28% eosinophils releasing a large quantity of granules, and 66% of spread eosinophils. CONCLUSIONS: Quantifying the morphological changes in eosinophils is a feasible, easy, and reliable manner to identify the severity of an asthma exacerbation and therefore might improve the clinical management of asthmatic children.

Initial experiences with a multidisciplinary approach to decreasing the length of hospital stay for patients undergoing unilateral mastectomy.

BACKGROUND: We hypothesized that the introduction of a short-stay pathway would result in a significant reduction in length of stay for patients undergoing unilateral mastectomy, without a negative impact on patient safety. MATERIALS AND METHODS: As part of a quality improvement project, a multidisciplinary committee designed a 1-day stay program for unilateral mastectomy patients. The study period was the first year after the 1-day pathway had routinely been implemented. We report on consecutive patients undergoing unilateral mastectomy ± tissue expander at Memorial Sloan-Kettering Cancer Center from July 1, 2009 to June 30, 2010. The primary endpoint was the percentage of patients discharged on postoperative day 1. Secondary endpoints included the incidence of postoperative complications within 30 days of surgery, reoperations, readmissions, and urgent-care visits within 7 days. RESULTS: Over a 12-month period, 537 patients underwent unilateral mastectomy. Of those, 82.7% (444/537) were performed on a 1-day hospitalization basis, compared with 9.6% in 2008, before implementation of the 1-day plan. The 30-day complication rate was 6.1% (33/537). Overall, 2.6% of all patients had reoperation for hematoma (14/537), 0.9% had to be readmitted (5/537), and 1.5% (8/537) attended the urgent-care department. If all patients had stayed in the hospital for more than 1 day, none of the readmissions and only 2 urgent-care visits would have been prevented. CONCLUSIONS: This study shows that a 1-day stay following mastectomy is easy to implement and safe for patients if a multidisciplinary team is involved in planning and implementation.

Subchronic effects of nasally instilled diesel exhaust particulates on the nasal and airway epithelia in mice.

Diesel exhaust is the major source of ultrafine particles released during traffic-related pollution. Subjects with chronic respiratory diseases are at greater risk for exacerbations during exposure to air pollution. This study evaluated the effects of subchronic exposure to a low-dose of diesel exhaust particles (DEP). Sixty male BALB/c mice were divided into two groups: (a) Saline: nasal instillation of saline (n = 30); and (b) DEP: nasal instillation of 30 microg of DEP/10 microl of saline (n = 30). Nasal instillations were performed 5 days a week, over 30 and 60 days. Animals were anesthetized with pentobarbital sodium (50 mg/kg intraperitoneal [i.p.]) and sacrificed by exsanguination. Bronchoalveolar lavage (BAL) fluid was performed to evaluate the inflammatory cell count and the concentrations of the interleukin (IL)-4, IL-10, and IL-13 by enzyme-linked immunosorbent assay (ELISA). The gene expression of oligomeric mucus/gel-forming (Muc5ac) was evaluated by real-time polymerase chain reaction (PCR). Histological analysis in the nasal septum and bronchioles was used to evaluate the bronchial and nasal epithelium thickness as well as the acidic and neutral nasal mucus content. The saline group (30 and 60 days) did not show any changes in any of the parameters. However, the instillation of DEP over 60 days increased the expression of Muc5ac in the lungs and the acid mucus content in the nose compared with the 30-day treatment, and it increased the total leukocytes in the BAL and the nasal epithelium thickness compared with saline for 60 days. Cytokines concentrations in the BAL were detectable, with no differences among the groups. Our data suggest that a low-dose of DEP over 60 days induces respiratory tract inflammation.

Celulite: artigo de revisão / Cellulite: a review

Apesar de o termo celulite ser inadequado, já que não se trata de inflamação ou infecção do tecido celular subcutâneo, está consagrado pelo uso para definir condição feminina caracterizada pelo aspecto ondulado da pele de algumas áreas corporais. Constitui queixa frequente e problema importante para a maioria das mulheres e, por ter etiopatogenia complexa, multifatorial e incompletamente conhecida, não há tratamento eficaz e definitivo. Sendo assim, proporciona uma gama de propostas terapêuticas sem evidências científicas suficientes e outras baseadas em publicações de qualidade questionável. Sabe-se que tratamentos tópicos são ineficazes, embora alguns possam ser coadjuvantes.Até o momento, não há tecnologia disponível que possa corrigir as alterações estruturais do tecido adiposo feminino e da derme profunda.A perspectiva, sem dúvida, dependerá de tecnologia baseada no princípio da fototermólise seletiva para a gordura superficial da hipoderme e para a derme profunda. Este artigo apresenta uma revisão da epidemiologia, etiopatogenia, histologia, classificação clínica, métodos para diagnóstico e avaliação e tratamento da celulite.

Foxp3 expression in lesions of the different clinical forms of American tegumentary leishmaniasis.

As the diversity in clinical presentation of American tegumentary leishmaniasis (ATL) is determined mainly by the immune response of host, our aim was to evaluate the in situ expression of Foxp3 [marker of regulatory T (Treg) cell] in lesions of the different clinical forms of ATL. Foxp3(+) cells were observed in 39.5% (32/81) of the samples and the number of positive cells was low in all the clinical forms. Even presenting a significantly lower number of CD4(+) T cells, diffuse cutaneous leishmaniasis (DCL) showed a higher expression of Foxp3 when compared with localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL). In LCL and MCL, the number of Foxp3(+) cells correlated positively with the number of apoptotic cells (active caspase-3(+) cells). A positive correlation was also observed between the expression of active caspase-3 and FasL in these clinical forms. Our data suggest that increased number of Treg cells may be associated to the hyporesponsiveness observed in DCL and also indicate that the apoptosis may be a possible mechanism of action of Foxp3(+) Treg cell in LCL and MCL. However, further studies are required to better understand the mechanism of action of Treg cell.

Bothrops insularis venomics: a proteomic analysis supported by transcriptomic-generated sequence data

A joint transcriptomic and proteomic approach employing two-dimensional electrophoresis, liquid chromatography and mass spectrometry was carried out to identify peptides and proteins expressed by the venom gland of the snake Bothrops insularis, an endemic species of Queimada Grande Island, Brazil. Four protein families were mainly represented in processed spots, namely metalloproteinase, serine proteinase, phospholipase A2 and lectin. Other represented families were growth factors, the developmental protein G10, a disintegrin and putative novel bradykinin-potentiating peptides. The enzymes were present in several isoforms. Most of the experimental data agreed with predicted values for isoelectric point and Mr of proteins found in the transcriptome of the venom gland. The results also support the existence of posttranslational modifications and of proteolytic processing of precursor molecules which could lead to diverse multifunctional proteins. This study provides a preliminary reference map for proteins and peptides present in Bothrops insularis whole venom establishing the basis for comparative studies of other venom proteomes which could help the search for new drugs and the improvement of venom therapeutics. Altogether, our data point to the influence of transcriptional and post-translational events on the final venom composition and stress the need for a multivariate approach to snake venomics studies.

Ultra-sonografia bidimensional convencional, de alta resolução e tridimensional no acompanhamento da gestação em cadela / Two-dimensional conventional, high resolution two-dimensional and three-dimensional ultrasonography in the evaluation of pregnant bitch

Gestational period in a bitch, after natural mating with a normal dog, was evaluated by two-dimensional conventional, high-resolution two-dimensional and three-dimensional ultrasonography. High-resolution two-dimensional ultrasonography show better image and provides early diagnosis of pregnancy (15 days) in comparison to conventional one (20 days). Three-dimensional ultrasonography was use to evaluate fetal morphology during late gestation period, however its application is still limited

Progesterone receptor (PROGINS) polymorphism and the risk of endometrial cancer development.

The progesterone receptor gene (PROGINS) has been identified as a risk modifier for benign and malignant gynecological diseases. The present case-control study is to evaluate the role of the PROGINS polymorphisms, as risk factor, for endometrial cancer development and to investigate the association between these genetics variants and clinical/pathologic variables of endometrial cancer. PROGINS polymorphism was examined in a total of 121 patients with endometrial cancer and 282 population-based control subjects, all located at the same area in São Paulo, SP, Brazil. The genotyping of PROGINS polymorphism was determined by polymerase chain reaction. The frequencies of PROGINS polymorphism T1/T1, T1/T2, and T2/T2 were 82.6%, 14.9%, and 2.5% in the endometrial cancer patients and 78.4%, 21.6%, and 0% in the controls, respectively. The chi(2) test showed a higher incidence of the T2/T2 genotype in the endometrial cancer group subjects, these results were statistically different (P= 0.012). However, due to the fact that there were no women in the control group showing homozygosis for the allele T2, the correct evaluation of odds ratio could not be properly calculated. Regarding the clinical and pathologic findings observed within the group of patients with endometrial cancer, there was significant correlation between T1/T2 genotype and the presence of myoma (P= 0.048). No correlations were observed among the other variables. These data suggest that the PROGINS polymorphism T2/T2 genotype might be associated with an increased risk of endometrial cancer.

A hypothesis: autonomic rhythms are reflected in growth lines of teeth in humans and extinct archosaurs.

A major determinant of tooth architecture is the arrangement of lines in dentin and in the enamel following the contour of the surface. Since the original description of these lines in the 19th century, they have been attributed to recurring events during tooth development. They have also attracted the attention of dental scientists and anthropologists; however, to date, studies of these structures have been largely theoretical and microscopic. We show here that the statistical properties of the spacing between the lines are similar in teeth from both ancient and modern humans and from extinct archosaurs, reptiles that lived tens or hundreds of millions of years ago-they also resemble heart rate variability of living humans. We propose that the deposition of these recurring structures is controlled by the autonomic nervous system. This control accounts for their regularity and recurrent nature and implies that the lines are an expression of a biologic rhythm which has been conserved throughout evolution. Details of the rhythms give clues to life styles in ancient civilizations and to the physiology of extinct archosaurs.

Control of the rat angiotensin I converting enzyme gene by CRE-like sequences

We characterized the role of potential cAMP-responsive elements (CRE) in basal and in induced angiotensin converting enzyme (ACE) gene promoter activity in order to shed light on the regulation of somatic ACE expression. We identified stimulators and repressors of basal expression between 122 and 288 bp and between 415 and 1303 bp upstream from the transcription start site, respectively, using a rabbit endothelial cell (REC) line. These regions also contained elements associated with the response to 8BrcAMP. When screening for CRE motifs we found pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two CRE-like sequences conserved between rats, mice and humans, was detected between 834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated that pCRE and dCRE bind to the same protein complexes as bound by a canonical CRE. Mutation of pCRE and dCRE in REC established the former as a positive element and the latter as a negative element. In 293 cells, a renal cell line, pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c-Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled by cellular stress. Although mapping of cAMP responsiveness was consistent with roles for pCRE and dCRE, mutation analysis indicated that they were not required for cAMP responsiveness. We conclude that the basal activity of the somatic ACE promoter is controlled by proximal and distal CREs that can act as enhancers or repressors depending on the cell context.

Control of the rat angiotensin I converting enzyme gene by CRE-like sequences.

We characterized the role of potential cAMP-responsive elements (CRE) in basal and in induced angiotensin converting enzyme (ACE) gene promoter activity in order to shed light on the regulation of somatic ACE expression. We identified stimulators and repressors of basal expression between 122 and 288 bp and between 415 and 1303 bp upstream from the transcription start site, respectively, using a rabbit endothelial cell (REC) line. These regions also contained elements associated with the response to 8BrcAMP. When screening for CRE motifs we found pCRE, a proximal sequence between 209 and 222 bp. dCRE, a distal tandem of two CRE-like sequences conserved between rats, mice and humans, was detected between 834 and 846 bp. Gel retardation analysis of nuclear extracts of REC indicated that pCRE and dCRE bind to the same protein complexes as bound by a canonical CRE. Mutation of pCRE and dCRE in REC established the former as a positive element and the latter as a negative element. In 293 cells, a renal cell line, pCRE and dCRE are negative regulators. Co-transfection of ATF-2 or ATF-2 plus c-Jun repressed ACE promoter activity, suggesting that the ACE gene is controlled by cellular stress. Although mapping of cAMP responsiveness was consistent with roles for pCRE and dCRE, mutation analysis indicated that they were not required for cAMP responsiveness. We conclude that the basal activity of the somatic ACE promoter is controlled by proximal and distal CREs that can act as enhancers or repressors depending on the cell context.

Influence of tumor necrosis factor-alpha on the ability of monocytes and lymphocytes to destroy intraerythrocytic Plasmodium falciparum in vitro.

It has been shown that administration of TNF-alpha causes an increase of survival of plasmodium-infected mice. However, this anti-parasitic effect cannot be reproduced in vitro upon direct incubation of the cytokine with the parasite. This suggests that TNF-alpha may act through modulation of some plasmodicidal mechanism not yet clarified. We evaluated the effect of exogenous TNF-alpha on the phagocytosis of Plasmodium falciparum-infected erythrocytes by monocytes and its influence on the ability of monocytes and lymphocytes to inhibit parasite growth. The capacity of endogenous TNF-alpha to influence the ability of monocytes to inhibit the parasite was also verified. We found that addition of 33 ng TNF-alpha/mL to cultures of human monocytes and P. falciparum-infected erythrocytes increased the phagocytic index from 3.8 to 7.8 in the presence of serum containing P. falciparum antibody. TNF-alpha increased the capacity of monocyte plus lymphocyte to inhibit parasite growth by about 3 times at 0.5 and 5 ng/mL. Sera from severely ill P. falciparum-infected individuals inhibited the parasite growth, but addition of anti-TNF-alpha antibody was unable to modify this inhibition. These data show that TNF-alpha can increase the phagocytic capacity. This was probably due to an increased expression of Fc receptors on monocytes or to the modulation of Fc receptor signaling pathways by signals originating from the binding of TNF-alpha to its receptors. TNF-alpha also acted on lymphocytes plus monocytes by increasing the inhibition of P. falciparum by a mechanism not related to phagocytosis. These findings suggest that TNF-alpha has a pleiotropic anti-malaria effect and that this protective effect depends on the interplay of different factors, such as monocytes/macrophages, lymphocytes, and antibodies, in addition to other cells and molecules.

The Agamma-195 (C-->G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro.

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C-->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C-->G) mutation. Furthermore, this is the first time that the -195 (C-->G) mutation of the Agamma-globin gene has been evaluated by in vitro gene expression.

The Agamma-195 (C->G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C->G) mutation. Furthermore, this is the first time that the -195 (C->G) mutation of the Agamma-globin gene has been evaluated by in vitro gene expression

Vascular oxidant stress early after balloon injury: evidence for increased NAD(P)H oxidoreductase activity.

Available evidence for oxidative stress after angioplasty is indirect or ambiguous. We sought to characterize the pattern, time course, and possible sources of free radical generation early after arterial balloon injury. Ex vivo injury performed in arterial rings in buffer with lucigenin yielded a massive oxygen-dependent peak of luminescence that decayed exponentially and was proportional to the degree of injury. Signals for injured vs. control arteries were 207. 1 +/- 17.9 (n = 13) vs 4.1 +/- 0.7 (n = 22) cpm x 10(3)/mg/min (p <. 001). Data obtained with 0.25 mmol/l lucigenin were validated with 0. 005-0.05 mmol/l lucigenin or the novel superoxide-sensitive probe coelenterazine (5 micromol/l). Gentle removal of endothelium prior to injury scarcely affected the amount of luminescence. Lucigenin signals were amplified 5- to 20-fold by exogenous NAD(P)H, and were >85% inhibited by diphenyliodonium (DPI, a flavoenzyme inhibitor). Antagonists of several other potential free radical sources, including xanthine oxidase, nitric oxide synthase, and mitochondrial electron transport, were without effect. Overdistension of intact rabbit iliac arteries in vivo (n = 7) induced 72% fall in intracellular reduced glutathione and 68% increase in oxidized glutathione, so that GSH/GSSG ratio changed from 7.93 +/- 2.14 to 0. 81 +/- 0.16 (p <.005). There was also 28.7% loss of the glutathione pool. Further studies were performed with electron paramagnetic resonance spectroscopy. Rabbit aortas submitted to ex vivo overdistension in the presence of the spin trap DEPMPO (5-diethoxy-phosphoryl-5-methyl-1-pyrroline-N-oxide, 100 mmol/l, n = 5) showed formation of radical adduct spectra, abolished by DPI or superoxide dismutase. Computer simulation indicated a mixture of hydroxyl and carbon-centered radical adducts, likely due to decay of superoxide adduct. Electrical mobility shift assays for NF-kappaB activation were performed in nuclear protein extracts from intact or previously injured rabbit aortas. Balloon injury induced early NF-kappaB activation, which was decreased by DPI. In conclusion, our data show unambiguously that arterial injury induces an immediate profound vascular oxidative stress. Such redox imbalance is likely accounted for by activation of vessel wall NAD(P)H oxidoreductase(s), generating radical species potentially involved in tissue repair.