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Background and Aims Radiotherapy may cause hemorrhagic radiation proctopathy (HRP). For conservative treatment of refractory HRP, argon plasma coagulation (APC) is the first-choice therapy. Endorectal formalin instillation (EFI), in turn, is an attractive treatment option because of its satisfactory results, great availability, and low cost. Nevertheless, comparative studies between these procedures are rather scarce. This study aims to make a prospective and randomized comparison of the outcomes in 2 HRP patient groups treated with either APC or EFI. Methods Twenty-seven patients (11 women), with a mean age of 67 years (range, 36-83), were randomized to receive either APC (n = 14) or EFI (n = 13). On completion of the treatment, comparisons were made in relation to the baseline for each patient and between groups for endoscopic findings according to the Vienna score and the telangiectasia distribution pattern score (TDP); the impact of radiation proctitis on patients’ lives was made according to the modified radiation toxicity score (MRTS) and hemoglobin levels. Number of sessions, duration of therapy, and adverse events were also compared between groups. The endoscopic therapeutic success (ETS) was defined by the absence or only few residual telangiectasias (TDP ≤1) on conclusion. Results An ETS of 92.8% was achieved in patients treated with APC and 92.3% for those treated with EFI (P > .05); there was an MRTS improvement of 85.7% in APC patients and 69.2% in EFI patients (P > .05). Mild adverse events occurred, respectively, in 23% and 28.5% in the EFI and APC groups (P > .05). Conclusions The study showed that APC and EFI have similar efficacy and a high safety profile for HRP treatment. (Clinical trial registration number: 3.120.353.)

Changes in sleep behavior are considered a public health problem, since they interfere with the health of the individual, especially in early childhood, and can impair growth and development. The objective of this study was to evaluate the knowledge about children's sleep in parents of children aged 0 to 24 months. Quasi-experimental study, of the type before and after, with a single group, developed in a pediatric outpatient clinic in northeastern Brazil. Convenience sample of 60 parents of children discharged from the neonatal unit, who represent preliminary data from a larger study. Data collected between November / 2019 and January / 2020, using the CAP survey (Knowledge, Attitude and Practice). A child sleep instrument was used in the pre-test (first time with the parents) and post-test (15 days after the first application). After the pre-test, the parents read an educational booklet containing the information to which they were asked. The knowledge about sleep was assessed including, time, place and sleeping clothes, position in the crib, prevention of sudden infant death syndrome and total sleep time. Scores ≤ 3 represented inadequate knowledge; 4-7 adequate knowledge. Only 5 parents had inadequate knowledge in the pre-test. In the post-test, everyone demonstrated adequate knowledge. The average of points in the pre-test was 4.3, median of 4. In the post-test, the average of points (6.15), median (6). In the pre-test, less correct questions were total sleep time, adequate sleeping position, with 12 and 20 errors, respectively. After the application of the booklet, the question regarding the total sleep time remained with an equal number of errors, however only 7 parents were wrong about the position of the child at the time of sleep. It is concluded that there is a need for guidance to parents on sleep, and it is pertinent to evaluate their previous knowledge, contributing to the strengthening of public policies aimed at children's sleep. Key messages Parents should receive guidance on infant sleep hygiene. Strengthening the promotion of children's sleep by health professionals.

Currently, authorities and specialists in child development and public health have been concerned with the growth and nutritional status of children, especially due to the uncontrollable increase in overweight / obesity that has occurred in recent years. Obesity causes organic-functional complications, such as chronic-degenerative diseases (diabetes, high blood pressure, coronary heart disease), and psychosocial complications, such as withdrawal from social relationships, shame, exclusion and disturbances in body awareness. The objective was to identify in the literature the parents' knowledge about complementary feeding for infants. Integrative literature review based on the guidelines recommended by PRISMA. The search was carried out between the months of May and June 2017 by two researchers independently in the Scopus, PubMed, Scielo, LILACS and CINAHL databases. The following descriptors were used: “infant”, “complementary feeding”, “parents” and “knowledge” and “infant”, “complementary feeding”, “relatives” and “knowledge” in the DECs and MESH respectively. 1,012 studies were identified and a sample of 06 articles was obtained after applying the eligibility criteria. The knowledge evidenced was: use of appropriate utensils for feeding the child, not using cow's milk, caution with processed foods, issues related to breastfeeding and age of introduction of food and other liquids. Even so, there were still mistakes by parents regarding the recommendations of the main bodies dealing with food, such as the use of processed foods from the fourth month of life of the child and the relationship of the “fat” baby being the health model. It was concluded that the knowledge of parents / caregivers about complementary feeding is still permeated by mistakes. Thus, the nursing consultation should focus on health education and search for strategies that facilitate the process of introducing complementary feeding and help parents in this period. Key messages Targeting health strategies on complementary feeding in a timely manner. Guidance for the prevention of obesity in early childhood and the development of non-infectious diseases.

Laparoscopic liver resections (LLR) have been increasingly performed in recent years. Most of the available evidence, however, comes from specialized centers in Asia, Europe and USA. Data from South America are limited and based on single-center experiences. To date, no multicenter studies evaluated the results of LLR in South America. The aim of this study was to evaluate the experience and results with LLR in South American centers. From February to November 2019, a survey about LLR was conducted in 61 hepatobiliary centers in South America, composed by 20 questions concerning demographic characteristics, surgical data, and perioperative results. Fifty-one (83.6%) centers from seven different countries answered the survey. A total of 2887 LLR were performed, as follows: Argentina (928), Brazil (1326), Chile (322), Colombia (210), Paraguay (9), Peru (75), and Uruguay (8). The first program began in 1997; however, the majority (60.7%) started after 2010. The percentage of LLR over open resections was 28.4% (4.4–84%). Of the total, 76.5% were minor hepatectomies and 23.5% major, including 266 right hepatectomies and 343 left hepatectomies. The conversion rate was 9.7%, overall morbidity 13%, and mortality 0.7%. This is the largest study assessing the dissemination and results of LLR in South America. It showed an increasing number of centers performing LLR with the promising perioperative results, aligned with other worldwide excellence centers.

Facial nerve schwannoma (FNS) is an uncommon benign tumor that arises from the Schwann cells of the facial nerve (FN). Although rare, this is the most frequent type of FN tumor, potentially affecting any segment of the nerve. Nevertheless, a higher incidence of intracranial lesions and a predilection for the geniculate ganglion has been reported. Hearing loss, facial paresis and tinnitus are the most frequent symptoms. Conversely, pain, is not among the most prominent complaints and when present, it can be misdiagnosed as an orofacial pain of other source, including pain due to a temporomandibular disorder (TMD). In this paper, we describe a rare case of a patient presenting a FNS located in the intratemporal part and geniculate ganglion of the FN, which was initially masked by the symptoms of a coexistent TMD. It highlights the importance of considering intracranial tumors in the differential diagnosis of orofacial pains. Keywords: Facial nerve schwannoma, Intracranial tumors, Facial paralysis, Orofacial pain, Temporomandibular disorder

Objective To perform a systematic review of the viscosupplementation effectiveness with hyaluronic acid (HA) in the articular Temporomandibular Dysfunctions (TMDs) clinical management. Method Electronic searches were performed in the following databases: MEDLINE (via PubMed), Scopus, Web of Science, Cochrane Library, EMBASE, LILACS, BBO, SIGLE (System for Information on Grey Literature in Europe), ClinicalTrials.gov, and the Brazilian Clinical Trials Registry (ReBec). Only randomized clinical trials that evaluated the intra-articular administration of HA or its derivatives in osteoarthritis and/or anterior displacement of the temporomandibular joint (TMJ) disc were included. The primary outcomes evaluated were patients' self-report of pain and/or discomfort in the TMJ. Each study was assessed for the risk of bias, using the Cochrane collaboration's risk of bias tool. Results A total of 640 studies were obtained in the electronic search. After the application of the eligibility criteria, manual search, and duplicate removal, 21 articles were included. Five articles classified their volunteers with internal derangements of the TMJ, in 4 articles the treatment was directed to participants with disc displacement with reduction and the other articles evaluated HA therapy in osteoarthritis. The protocols presented heterogeneity, varying in the form of application, associated or not with arthrocentesis, number of applications, molecular weight, dose and concentration. Nine studies presented high risk of bias. Conclusion Due to the heterogeneity and methodological inconsistencies of the studies evaluated, it was not possible to establish the efficacy of HA in articular TMDs.

Background Neurological and other systemic complications occur in adults with severe COVID-19. Here we describe SARS-CoV-2 infection complicated by neuroinvasion in the post-mortem tissues of a child. Methods We performed a complete autopsy of a 14-month-old child who died of COVID-19 pneumonitis. Histological sections of multiple organs were stained with haematoxylin and eosin. Luxol fast blue staining for myelin and immunohistochemistry were performed in selected areas of the brain. The presence of SARS-CoV-2 was investigated by immunostaining with anti-spike protein antibody and by RT-qPCR. Findings Lesions included microthrombosis, pulmonary congestion, interstitial oedema, lymphocytic infiltrates, bronchiolar injury, collapsed alveolar spaces, cortical atrophy, and severe neuronal loss. SARS-CoV-2 staining was observed along the apical region of the choroid plexus (ChP) epithelium and in ependymal cells of the lateral ventricle, but was restricted to ChP capillaries and vessels in some regions. SARS-CoV-2 infection of brain tissue was confirmed by RT-qPCR in fragments of the ChP, lateral ventricle, and cortex. Interpretation Our results show multisystemic histopathological alterations caused by SARS-CoV-2 infection and contribute to knowledge regarding the course of fatal COVID-19 in children. Furthermore, our findings of ChP infection and viral neurotropism suggest that SARS-CoV-2 may invade the central nervous system by blood-cerebrospinal fluid barrier disruption. Funding Carlos Chagas Filho Foundation for Supporting Research in the State of Rio de Janeiro (FAPERJ); the National Council for Scientific and Technological Development (CNPq) and Coordination for the Improvement of Higher Education Personnel (CAPES), in addition to intramural grants from D'Or Institute for Research and Education. Editor's Note This translation in Portuguese was submitted by the authors and we reproduce it as supplied. It has not been peer reviewed. Our editorial processes have only been applied to the original abstract in English, which should serve as reference for this manuscript. Resumo Complicacoes sistemicas e neurologicas foram descritas em adultos com COVID-19 grave. Neste trabalho, descrevemos a infeccao por SARS-CoV-2, incluindo sua neuroinvasao, nos tecidos post-mortem de uma crianca. Metodos Realizamos a autopsia completa de uma crianca de 14 meses que morreu de pneumonite por COVID-19. Cortes histologicos de multiplos orgaos foram corados com Hematoxilina e Eosina. A coloracao de Luxol Fast Blue para mielina e imuno-histoquimica foram realizadas em areas selecionadas do cerebro. A presenca de SARS-CoV-2 foi investigada por imunomarcacao com anticorpo anti-proteina spike e por RT-qPCR. Achados As lesoes incluiram microtrombose, congestao pulmonar, edema intersticial, infiltrados linfociticos, lesao bronquiolar, colapso dos espacos alveolares, atrofia cortical e perda neuronal grave. A presenca de SARS-CoV-2 foi observada ao longo da regiao apical do epitelio do plexo coroide (PC) e nas celulas ependimarias do ventriculo lateral, mas ficou restrita aos capilares e vasos do PC em outras regioes. A infeccao do tecido cerebral por SARS-CoV-2 foi confirmada por RT-qPCR em fragmentos do PC, ventriculo lateral e cortex cerebral. Interpretacao Nossos resultados mostram alteracoes histopatologicas multissistemicas causadas pela infeccao por SARS-CoV-2 e contribuem para ampliar o conhecimento sobre a evolucao da COVID-19 fatal em criancas. Alem disso, nossos achados sobre a infeccao no PC e neurotropismo viral sugerem que o SARS-CoV-2 pode invadir o sistema nervoso central pela ruptura da barreira sangue-liquido cefalorraquidiano. Financiamento Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) e Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), alem de financiamento intramural do Instituto D'Or de Pesquisa e Educacao.

Background and Aims The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil. Methods Seven hundred and three de novo pediatric AML cases (2000–2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3 , NRAS , KRAS , PTPN11 , and c- KIT genes were analyzed as well as fusion genes ( RUNX1 - RUNX1T1 , MLL / KMT2A -r, CBFβ - MYH11 , and PML - RARα ) associated with AML. Patients were treated out of the clinical trial although following the BFM-AML2004 protocol. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded. Results There were significant differences in gene mutations among age ranges (≤2 years-old; >2–10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50 × 10 9 /L) was associated with RUNX1 - RUNX1T1 , whereas higher WBC with CBFβ-MYH11 ( p p = 0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year pOS, whereas the Midwest region presented the poorest pOS (23.7 ± 4.9%). PTPN11 mutations conferred an adverse prognosis as an independent prognostic factor. Conclusions Identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil.

Osteoclastogenesis is the major cellular event responsible for bone loss and is triggered by inflammation. Acai-berry has proven anti-inflammatory effects. However, there is a lack of evidence for its effects on osteoclastogenesis. Thus, the aim of this study was to determine whether acai-berry extract (ABE) could inhibit osteoclastogenesis and osteoclast activity in vitro. The secretion of cytokines by osteoclasts has been also evaluated. RAW 264.7 cells were stimulated with RANKL (50ng/mL) and treated with various concentrations of ABE (25-100μg/mL) to verify: cell viability (MTT), total protein concentration (BCA), osteoclast differentiation and activity, and cytokine secretion. Cell viability and protein assays showed no toxicity to RAW cells for the tested ABE concentrations (p>0.05). ABE also showed a dose-dependent inhibition of osteoclastogenesis and osteoclast activity evaluated by tartrate-resistant acid phosphatase (TRAP) and hydroxylapatite resorption assay, respectively (p

Ankle joint sprains are a common medical condition estimated to be responsible for 15–25% of all musculoskeletal injuries worldwide. The pathophysiology of the lesion can represent considerable time lost to injury, as well as long-term disability in up to 60% of patients. A percentage between 10% and 20% may complicate with chronic instability of the ankle joint and disability in walking, contributing to morbidity and poor life quality. Ankle sprains can be classified as grade I, II, or III, based on the extent of damage and number of ligaments affected. The diagnostic grading is important for setting further treatment and rehabilitation, since more severe injuries carries risk of recurrence, added morbidity and decrease in life quality. The aim of this work was to evaluate the adequacy of infrared thermography as a potential complimentary diagnostic tool of the distinct lesions grades. Evaluation of different thermographic values of the ankle region (in both affected and non-affected foot) was conducted for this purpose. The principal results to be highlighted are that some of the regions, namely anterior view for non defined time after injury analysis, and anterior, frontal, posterior and anterior talofibular ligament regions and proximal calcaneofibular ligament regions in acute lesions (herein defined as less than 6 h post-traumatic event) presented consistent profiles of variation. The analyses were performed considering affected and non-affected ankles results on plotted graphics representing termographic evaluation and grading of these lesions performed using ultrasound by experimented medical radiologists. An increase in temperature values was observed when progressing from mild to severe ankle sprain injuries, with these regions presenting lower values for the affected ankle when compared to the non-affected ankle in all the analysis performed. The remaining analysed regions did not present the same variations. Statistical analysis using Kruskal–Wallis tests for non-parametric samples, however, did not confer statistical significance to the differences encountered in the graphics analysis ( p > 0.05). The major conclusions were that thermographic analysis of ankle sprain injuries might have some potential to be used clinically, especially in acute settings such as those that occur in hospital emergency areas and in sports practice. There is currently no practical technology to be used for grading ankle sprain lesions, with the gold standard being magnetic resonance imaging. Thermography provides results rapidly and without the need for extensive equipment operating expertise. Based on scientific data present in the literature, this is the first description of the use of this technology with such an objective regarding ankle sprain lesions. Further work is needed, nonetheless, to amplify the sample number with the herein chosen parameters and possibly use dynamic thermography.

Physical exercise is known to activate the sympathetic nervous system, which influences the production of saliva from salivary glands. Our examination of saliva collected from highly trained athletes before and after a number of physical competititions showed an increase in the secretion of S-type cystatins and cystatin C as a subacute response to aerobic and anaerobic exercise. The elevation in salivary cystatins was transient and the recovery time course differed from that of amylase and other salivary proteins. An in vitro assay was developed based on a cell line from a human submandibular gland (HSG) that differentiated into acinus-like structures. Treatments with the β-adrenergic agonist isoproterenol caused a shift in the intracellular distribution of S-type cystatins and cystatin C, promoting their accumulation at the outer regions of the acinus prior to release and suggesting the activation of a directional transport involving co-migration of both molecules. In another treatment using non-differentiated HSG cells, it was evident that both expression and secretion of cystatin C increased upon addition of the β-adrenergic agonist, and these effects were essentially eliminated by the antagonist propranolol. The HSG cell line appears to have potential as a model for exploring the mechanism of cystatin secretion, particularly the S-type cystatins that originate primarily in the submandibular glands.

GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G>A) in the GH releasing hormone receptor gene, and shown that adult GH-naïve individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi-detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis.

O presente estudo tem como objetivo avaliar o efeito da administração do Zolazepam/Tiletamina nas funções cardiorrespiratórias e eletrocardiográficas em lobos-guará (Chrysocyon brachyurus) mantidos em cativeiro. Foram utilizados dez lobos-guará clinicamente saudáveis (seis machos e quatro fêmeas), com média de peso 23,5±3,5kg, e idade de 6,5±2,8 anos. Os lobos eram mantidos em cativeiro e foram capturados pelos tratadores, proporcionando o mínimo de estresse possível para avaliação dos parâmetros pré-anestésicos. Foram avaliadas frequência cardíaca e respiratória, temperatura retal, pressão arterial média e eletrocardiografia. Após coleta dos parâmetros fisiológicos e eletrocardiográficos pré-anestesia, foi administrada a dose de 5,1±0,7mg/kg de Zolazepam/Tiletamina intramuscular. Depois da anestesia, colocaram-se os eletrodos do eletrocardiograma nos membros torácicos e pélvicos. Os animais eram monitorados durante uma hora, sendo que, a cada 10 minutos, era realizado o registro dos valores eletrocardiográficos, assim como os valores dos parâmetros fisiológicos e cardiorrespiratórios. Os resultados mostraram alteração significativa na amplitude da onda P entre 10 a 50 minutos pós-anestesia. Frequência cardíaca (153±20bmp), frequência respiratória (29±6mpm), temperatura corporal (38,4±1oC), pressão arterial média (114±20mmHg) e as outras variáveis eletrocardiográficas não apresentaram alterações. O aumento da amplitude da onda P nos animais deste trabalho sugeriu um aumento atrial, oriundo de doenças cardíacas ou simplesmente pelo aumento da frequência cardíaca durante a contenção. ABSTRACT The aim of this study was to assess the effects of the anesthetic combination of Tiletamine/Zolazepam on the cardiorespiratory function and electrocardiographic profile in captive maned wolves (Chrysocyon brachyurus). Ten maned wolves were used in this study (6 males and 4 females). All animals were healthy, with an average body weight of 23.5±3.5kg, and age of 6.5±2.8years. The wolves were conditioned to be physically restrained by their keepers in order to minimize stress during assessment of pre-anesthetic parameters. Data on heart and respiratory rates, rectal temperature, mean arterial blood pressure and electrocardiography were collected. Pre-anesthetic physiological an eletrocardiographic parameters were collected before the administration of 5.1±0.73mg/kg Tiletamine/Zolazepam intramuscularly. Under anesthesia, electrocardiogram electrodes were placed on thoracic and pelvic limbs and eletrocardiographic data was recorded every 10 minutes for approximately one hour, totaling 6 electrocardiograms. Heart rate 153±20bmp, respiratory rate 29±6mpm, rectal temperature 38,4±1oC, mean arterial blood pressure 114±20mmHg, and the other electrocardiographic parameters did not change; however, the P wave amplitude changed from 10 to 50 minutes after anesthesia. The increase in the P wave on the animals in this study suggested an atrial increase, probably due to cardiac disease or just by increasing the heart rate during the capture.

Growth hormone (GH)-releasing hormone (GHRH) is the most important stimulus for GH secretion by the pituitary gland. Subjects homozygous for GHRH receptor (GHRHR) gene (GHRHR) inactivating mutations have severe GH deficiency, resulting in severe short stature if not treated. We previously reported that young adults heterozygous for the c.57+1GA null GHRHR mutation (MUT/N) have reduced weight and body mass index (BMI) but normal stature. Here we have studied whether older MUT/N have an additional phenotype. In a cross-sectional study, we measured height, weight and blood pressure, and calculated BMI in two groups (young, 20-40 years of age) and old (60-80 years) of individuals heterozygous for the same GHRHR mutation, and compared with a large number of individuals of normal genotype residing in the same geographical area. Standard deviation score (SDS) of weight was lower, and BMI had a trend toward reduction in young heterozygous compared with young normals, without significant difference in stature. Conversely, SDS of height was lower in older heterozygous individuals than in controls, corresponding to a reduction of 4.2 cm. These data show a reduced stature in older subjects heterozygous for the c.57+1GA GHRHR mutation, indicating different effects of heterozygosis through lifespan.

Cryptococcosis is a fungal infection caused by Cryptococcus neoformans , generally associated with immunodefi y and immunosuppressive agents, and it is rarely reported in systemic lupus erythematosus (SLE), particularly in juvenile SLE (JSLE). From January 1983 to June 2011, 5,604 patients were followed at our University Hospital and 283 (5%) of them met the American College of Rheumatology (ACR) classification criteria for SLE. Only one (0.35%) of our JSLE patients had cryptococcal meningitis and is described in this report. A 10-year old girl was diagnosed with JSLE. By the age of 15 years, she presented persistent headaches, nausea and vomiting for a 5 day period without fever, after a cave-exploring trip. At that moment, she was under 10 mg/day of prednisone, azathioprine and hydroxychloroquine. A lumbar puncture was performed and India ink preparation was positive for cryptococcosis, cerebrospinal fl culture yielded Cryptococcus neoformans and serum cryptococcal antigen titer was 1:128. Azathioprine was suspended, and liposomal amphotericin B was introduced. Despite of treatment, after four days she developed amaurosis and fell into a coma. A computer tomography of the brain showed diffuse ischemic areas and nodules suggesting fungal infection. Four days later, she developed severe sepsis and vancomycin and meropenem were prescribed, nevertheless she died due to septic shock. In conclusion, cryptococcal meningitis is a rare and severe opportunistic infection in juvenile lupus population. This study reinforces the importance of an early diagnosis and prompt introduction of antifungal agents, especially in patients with history of contact with bird droppings.

Melanoma is a serious and deadly form of skin cancer. However, patients’ chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at Sao Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.

ObjectivesGH-releasing hormone (GHRH) exerts hypnotic actions increasing the non-rapid eye movement (NREM) sleep. Conversely, GH stimulates the REM sleep. GH deficiency (GHD) often leads to sleep problems, daytime fatigue and reduced quality of life (QoL). GHD may be due to lack of hypothalamic GHRH or destruction of somatotroph cells. We have described a cohort with isolated GHD (IGHD) due to GHRH resistance caused by a homozygousnullmutation (c.57 + 1G > A) in the GHRH receptor gene. They have normal QoL and no obvious complaints of chronic tiredness. The aim of this study was to determine the sleep quality in these subjects.MethodsA cross-sectional study was carried out in 21 adult IGHD subjects, and 21 age- and gender-matched controls. Objective sleep assessment included polygraphic records of the awake, stages NREM [N1 (drowsiness), N2 and N3 (already sleeping)] and REM (R). Subjective evaluation included the Pittsburgh Sleep Quality Index, the Insomnia Severity Index and the Epworth Sleepiness Scale.ResultsIGHD subjects showed a reduction in sleep efficiency (P = 0.007), total sleep time (P = 0.028), duration of N2 and R in minutes (P = 0.026 andP = 0.046 respectively), but had increased duration and percentage of N1 stage (P = 0.029 andP = 0.022 respectively), wake (P = 0.007) and wake-time after sleep onset (P = 0.017). There was no difference in N3 or in sleep quality questionnaire scores.ConclusionPatients with IGHD due to GHRH resistance exhibit objective reduction in the sleep quality, with changes in NREM and REM sleep, with no detectable subjective consequences. GHRH resistance seems to have a preponderant role over GHD in the sleep quality of these subjects.

Case series Patients: Female, 19 • Female, 18 Final Diagnosis: Solid pseudopapillary tumor of pancreas Symptoms: Abdominal discomfort Medication: — Clinical Procedure: Surgery Specialty: Oncology Objective: Unusual setting of medical care Background: Solid pseudopapillary tumor of the pancreas (Frantz tumor) is a rare, low-grade malignant neoplasm. Laparoscopic pancreatoduodenectomy is a good approach for tumors located in the pancreatic head. We present two successful cases in young women. Case Report: A 19-year-old woman was admitted to Department of Digestive Surgery due to epigastric pain, nausea, and vomiting. Computed tomography scan of the abdomen was performed, and a 3.0×2.2 cm solid tumor localized in the head of the pancreas was observed. After the diagnosis of Frantz tumor of the pancreas, the patient underwent laparoscopic pancreatoduodenectomy. Histopathology confirmed solid and cystic pseudopapillary tumor. The postoperative course was uneventful, and after 8 months the patient remained disease-free. An 18-year-old woman was admitted at the emergency room with abdominal pain, vomiting, and diarrhea. Computed tomography scans revealed a mass of 4.1×3.3 cm in size in the head of the pancreas consistent with a solid pseudopapillary tumor. Laparoscopic pancreatoduodenectomy was performed by two expert surgeons who divided the work: one did resection and the other did reconstruction. The patient was discharged at postoperative day 6 without complications, and during five months of follow-up the patient has been well and without disease. Conclusions: Laparoscopic pancreatoduodenectomy can be performed safely in patients with Frantz tumor by surgeons with expertise in laparoscopic surgery, technical skill, and adequate equipment.

Objective Ocular function is fundamental for environmental adaptation and survival capacity. Growth factors are necessary for a mature eyeball, needed for adequate vision. However, the consequences of the deficiency of circulating growth hormone (GH) and its effector insulin-like growth factor I (IGF-I) on the physical aspects of the human eye are still debated. A model of untreated isolated GH deficiency (IGHD), with low but measurable serum GH, may clarify this issue. The aim of this study was to assess the ocular aspects of adult IGHD individuals who have never received GH therapy. Design Cross sectional study. Methods Setting : University Hospital, Federal University of Sergipe, Brazil. Patients : Twenty-five adult (13 males, mean age 50.1years, range 26 to 70years old) IGHD subjects homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene, and 28 (15 males, mean age 51.1years, range 26 to 67years old) controls were submitted to an endocrine and ophthalmological assessment. Forty-six IGHD and 50 control eyes were studied. Main outcome measures : Visual acuity, intraocular pressure, refraction (spherical equivalent), ocular axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous depth (VD), mean corneal curvature (CC) and central corneal thickness (CCT). Results IGHD subjects exhibited unmeasurable serum IGF-I levels, similar visual acuity, intraocular pressure and LT, higher values of spherical equivalent and CC, and lower measures of AL, ACD, VD and CCT in comparison to controls, but within their respective normal ranges. While mean stature in IGHD group was 78% of the control group, mean head circumference was 92% and axial AL was 96%. Conclusions These observations suggest mild ocular effects in adult subjects with severe IGF-I deficiency due to non-treated IGHD.

The purpose of this study was to establish baseline data on lacrimal quantity (STT-1) and intraocular pressure (IOP) in captive maned wolves. Ten healthy adult maned wolves were contained with a snare pole and muzzle and kept in decubitus of the left side. STT-1 measurement was performed on the lateral third of the lower conjunctival sac for one minute. The cornea was desensitized and intraocular pressure was measured with an tonopen. Average STT-1 in both eyes was 11±5mm.min-1, with no statistical difference between the left and right eye (p=0.960). Average IOP in both eyes was 20±6mmHg, with no statistical difference between the left and right eye (p=0.836). Average STT-1 was lower than, and IOP was the same as normal levels found in dogs. There was no statistical difference in the age of the animals, and STT-1 and IOP values. In the present paper, average maned wolf STT-1 levels were lower compared with those found in dogs, while the IOP was the same in maned wolves as in dogs. Due to the increased incidence in providing emergency care for maned wolf victims of road kill and fires, determination reference values of ocular parameters may improve the correct diagnosis and treatment of the disease. Resumo: O objetivo deste estudo foi estabelecer dados de referência sobre a produção lacrimal (STT-1) e pressão intraocular (PIO) em lobos-guará em cativeiro. Foram utilizados 10 lobos-guará, saudáveis e adultos. Os animais foram contidos com cambão e mordaça e mantidos em decúbito lateral esquerdo. O TLS foi realizado no terço médio da pálpebra inferior, durante um minuto. A córnea foi dessensibilizada e a PIO mensurada com tonopen. A média do TLS-1 dos olhos direitos e esquerdo foi 11±5mm/min, não havendo diferença significativa entre os olhos (p=0,960). A média da PIO dos olhos direitos e esquerdo foi 20±6mmHg, não observando diferença entre os olhos direitos e esquerdos (p=0,836). Média STT-1 foi menor do que, e PIO foi o mesmo que os níveis normais em cães. Não houve diferença estatística na idade dos animais e valores STT-1 e da PIO. No presente trabalho, os níveis médios de guará STT-1 foram mais baixos em comparação com as observadas nos cães, enquanto que a pressão intraocular foi a mesma nos lobos guará como em cães. Devido ao aumento da incidência na prestação de cuidados de emergência para vítimas de lobos-guará atropelamentos e incêndios, determinar os valores de referência dos parâmetros oculares podem melhorar o diagnóstico correto e tratamento de doenças.

The objectives were to evaluate clinical and histopathological aspects of topical application of sunflower-seed oil ( Helianthus annuus ) on the healing process of experimentally induced wounds in lumbar and metacarpal areas of healthy horses. Six adult horses were used. Eight wounds were surgically produced on each horse: two 6.25-cm 2 wounds cranial to the sacrum on each side of the lumbar region and two 2.89-cm 2 wounds close to the proximal epiphysis of the metacarpus on the lateral aspect of each forelimb. Left side was used for macroscopic observations and right side for histopathological analysis. The experimental lesions were treated daily with sunflower-seed oil, whereas saline solution was used in control lesions. Macroscopic and histopathological analyses were performed on tissue harvested at 3, 7, 14, and 21 days. Complete healing time for all wounds was recorded. For lumbar region’s wounds, a contraction of 90.78% was recorded for those treated with oil and of 79.27% for control wounds after 21 days of treatment. For metacarpal region’s wounds, a contraction of 47.63% was recorded for wounds treated with oil and of 30.21% for control wounds. Wounds in the sunflower-seed oil treatment group had an elevation of polymorphonuclear cells, a newly formed vascular bed during the inflammatory phase, and a better alignment of collagen fibers during the remodeling phase. In conclusion, topical application of sunflower-seed oil was beneficial in the healing process of experimentally induced skin wounds in horses, with best results for treatment of lumbar wounds, making it a therapeutic option in equine wound healing.

Summary Objective To analyse the data reported by the national surveillance system of Brazil, including data on diarrhoea mortality and hospital admissions before and after rotavirus vaccine introduction, and evaluate the impact of its widespread use under operational conditions. Method Retrospective analysis of routinely collected data was reported by several surveillance systems of Brazil, comprising an 8-year period of all diarrhoea-related hospitalisations and deaths in children

Introduction: Bronchoalveolar lavage (BAL) with quantitative cultures has been used in order to increase ventilator associated pneumonia (VAP) diagnosis specificity, although the accurate technique for this entity diagnosis remains controversial. Objectives: To evaluate the influence of using positive BAL and quantitative cultures results in microbiologic diagnosis and treatment of patients with suspected late VAP and prior antibiotherapy. Material and methods: Retrospective analysis of intensive care unit (UCI) patients, during a one year period, with clinical suspicion of late VAP and prior use of antibiotics that presented a growth in BAL cultures. Results: Of 243 BAL performed, there were 71 (29.2 %) positive cultures (60 patients, 76.7 % male, 54 ± 19 years). BAL was done after 13 days (median) of invasive mechanical ventilation, 11 days of ICU antibiotherapy and in the day in which a new antibiotic for VAP suspicion was started. Colony forming units (CFU)/ml count was performed in 71.8 % and endotracheal aspirate (ETA) simultaneously collected for qualitative analysis in 85.9 %. Therapeutic approach was changed in 38.0 %: correction (16.9 %), de-escalation (12.7 %) and directed antibiotherapy start (8.4 %). Therapeutic changes were made in the presence of CFU > 104 in 84.2 % and in agreement with ETA in 70.8 %. In cases in which antibiotherapy was maintained (62.0 %), quantitative cultures would have allowed de-escalation in 9.1 %. Changes in prescription were more frequent when CFU was > 104 (48.5 %), comparing with situations in which counts were lower and BAL analysis was only qualitative (28.9 %), p = 0.091. There were no significant differences between patients submitted to different therapeutic approaches concerning to ICU mortality or length of stay. Conclusion: In late onset VAP, positive BAL and quantitative cultures allowed therapeutic changes, leading to antibiotic adequacy and consumption reduction, which can however be maximised. Resumo: Introdução: O lavado broncoalveolar (LBA) com culturas quantitativas tem sido utilizado no sentido de permitir um aumento da especificidade diagnóstica da pneumonia associada ao ventilador (PAV), embora a técnica padrão para o diagnóstico definitivo desta entidade permaneça controversa. Objectivos: Avaliar a influência dos resultados positivos do LBA e das culturas quantitativas no diagnóstico microbiológico e no tratamento de doentes com suspeita de PAV tardia e antibioterapia prévia. Material e Métodos: Análise retrospectiva de doentes em unidade de cuidados intensivos (UCI) polivalentes, com suspeita de PAV tardia e antibioterapia prévia, que apresentaram crescimento cultural nos LBA efectuados durante o período de um ano. Resultados: Dos 243 LBA realizados, obtiveram-se 71 (29,2 %) resultados positivos (60 doentes, 76,7 % do sexo masculino, 54 ± 19 anos). O LBA foi realizado após em mediana 13 dias de ventilação invasiva, 11 dias de antibioterapia na UCI e no dia em que se instituiu um novo antibiótico perante a suspeita de PAV. Foi efectuada contagem de unidades formadoras de colónias (UFC)/ml em 71,8 % e simultaneamente obtido aspirado endotraqueal (AET) para análise qualitativa em 85,9 %. Verificou-se mudança terapêutica em 38,0 %: correcção terapêutica (16,9 %), descalação (12,7 %) e início de antibioterapia dirigida (8,4 %). As alterações terapêuticas foram efectuadas na presença de > 104 UFC em 84,2 % e em concordância com o AET em 70,8 %. Nos casos em que se verificou manutenção da antibioterapia (62,0 %) as culturas quantitativas teriam permitido descalação em 9,1 %. A alteração na prescrição foi mais frequente na presença de > 104 UFC (48,5 %), do que nas situações em que as contagens de UFC foram inferiores ou a análise do LBA qualitativa (28,9 %), p = 0,091. Não se verificaram diferenças significativas entre os doentes submetidos às diferentes atitudes terapêuticas no que diz respeito à mortalidade na UCI ou duração do internamento. Conclusão: Na PAV tardia, o resultado positivo do LBA e das culturas quantitativas condicionou mudanças terapêuticas, no sentido da adequação da antibioterapia e da redução do consumo de antibióticos, que podem contudo ser maximizadas. Keywords: Ventilator associated pneumonia, Bronchoalveolar lavage, Quantitative cultures, Palavras-chave: Pneumonia associada ao ventilador, Lavado broncoalveolar, Culturas quantitativas

Prenatal malnutrition is responsible for the onset of alterations in renal Na(+) transport in the adult offspring. Here we investigated the molecular mechanisms by which increased formation of reactive oxygen species during prenatal malnutrition affects the pathways that couple angiotensin II (Ang II) receptors (AT(1)R and AT(2)R) to kidney Na(+)-ATPase in adulthood, and how maternal treatment with α-tocopherol can prevent alterations in the main regulatory cascade of the pump. The experiments were carried out on the adult progeny of control and malnourished dams during pregnancy that did or did not receive α-tocopherol during lactation. Malnutrition during pregnancy increased maternal hepatic and adult offspring renal malondialdehyde levels, which returned to control after supplementation with α-tocopherol. In the adult offspring, placental malnutrition programmed: decrease in Na(+)-ATPase activity, loss of the physiological stimulation of this pump by Ang II, up-regulation of AT(1)R and AT(2)R, decrease in membrane PKC activity, selective decrease of the PKCε isoform expression, and increase in PKA activity with no change in PKA α-catalytic subunit expression. These alterations were reprogrammed to normal levels by α-tocopherol during lactation. The influence of α-tocopherol on the signaling machinery in adult offspring indicates selective non-antioxidant effects at the gene transcription and protein synthesis levels.

Recent evidence has shown that the serotonergic mechanism of the lateral parabrachial nucleus (LPBN) participates in the regulation of renal and hormonal responses to isotonic blood volume expansion (BVE). We investigated the BVE-induced Fos activation along forebrain and hindbrain nuclei and particularly within the serotonergic clusters of the raphé system that directly project to the LPBN. We also examined whether there are changes in the concentration of serotonin (5HT) within the raphé nucleus in response to the same stimulus. With this purpose, we analyzed the cells doubly labeled for Fos and Fluorogold (FG) following BVE (NaCl 0.15 M, 2 ml/100 g b.w., 1 min) 7 days after FG injection into the LPBN. Compared with the control group, blood volume-expanded rats showed a significant greater number of Fos-FG double-labeled cells along the nucleus of the solitary tract, locus coeruleus, hypothalamic paraventricular nucleus, central extended amygdala complex, and dorsal raphé nucleus (DRN) cells. Our study also showed an increase in the number of serotonergic DRN neurons activated in response to isotonic BVE. We also observed decreased levels of 5HT and its metabolite 5-hydroxyindoleacetic acid (measured by high-pressure liquid chromatography) within the raphé nucleus 15 min after BVE. Given our previous evidence on the role of the serotonergic system in the LPBN after BVE, the present morphofunctional findings suggest the existence of a key pathway (DRN-LPBN) that may control BVE response through the modulation of 5HT release.

Chemotherapy-induced oral mucositis is a frequent therapeutic challenge in cancer patients. The purpose of this retrospective study was to estimate the prevalence and risk factors of oral mucositis in 169 acute lymphoblastic leukaemia (ALL) patients treated according to different chemotherapeutic trials at the Darcy Vargas Children's Hospital from 1994 to 2005. Demographic data, clinical history, chemotherapeutic treatment and patients' follow-up were recorded. The association of oral mucositis with age, gender, leucocyte counts at diagnosis and treatment was assessed by the chi-squared test and multivariate regression analysis. Seventy-seven ALL patients (46%) developed oral mucositis during the treatment. Patient age (P = 0.33), gender (P = 0.08) and leucocyte counts at diagnosis (P = 0.34) showed no correlation with the occurrence of oral mucositis. Multivariate regression analysis showed a significant risk for oral mucositis (P = 0.009) for ALL patients treated according to the ALL-BFM-95 protocol. These results strongly suggest the greater stomatotoxic effect of the ALL-BFM-95 trial when compared with Brazilian trials. We concluded that chemotherapy-induced oral mucositis should be systematically analysed prospectively in specialized centres for ALL treatment to establish the degree of toxicity of chemotherapeutic drugs and to improve the quality of life of patients based on more effective therapeutic and prophylactic approaches for prevention of its occurrence.

GH deficiency (GHD) in adults is associated with increased abdominal adiposity and systolic blood pressure, total and low-density lipoprotein cholesterol, and C-reactive protein.We have studied the effects of 6-month GH replacement therapy in 20 adult members of a large Brazilian kindred with lifelong severe and isolated GHD due to a homozygous mutation in GHRH receptor gene (46 +/- 14.5 yr; 122 +/- 7.7 cm; 36.7 +/- 5.4 kg; 10 men). Subjects were studied at baseline, after 6-month bimonthly depot GH injections (Nutropin Depot; Genentech, Inc., South San Francisco, CA) [post GH (pGH)], and after 6- and 12-month washout.Despite modest trough serum IGF-I increase, GH replacement therapy caused a decrease in skinfolds and in waist-hip ratio, with a rebound increase at 12 months. Total and low-density lipoprotein cholesterol were reduced pGH and returned to baseline at 6 months. High-density lipoprotein cholesterol increased pGH, but at 12 months was lower than baseline. A progressive increase in left ventricular mass index, posterior wall, and septum thickness occurred from pGH to 12 months, and of carotid intima-media thickness, from 6 to 12 months. Individuals were 6, 16, and 52 times more likely to have an atherosclerotic carotid plaque at pGH, 6 and 12 months, respectively, when compared with baseline.In patients with lifetime isolated GHD, 6-month treatment with GH has reversible beneficial effects on body composition and metabolic profile, but it causes a progressive increase in intima-media thickness and in the number of atherosclerotic carotid plaques.

Context: Biallelic mutations in the GHRH receptor (GHRHR) gene (GHRHR) are a frequent cause of isolated GH deficiency (IGHD). Although heterozygous carriers of these mutations appear normal, we hypothesized that heterozygosity for a GHRHR mutation might be associated with a subclinical phenotype. Methods: We studied members of a large Brazilian kindred with IGHD (Itabaianinha cohort) caused by a homozygous null GHRHR mutation. We compared 76 adult subjects (age, 25–75 yr) heterozygous for the mutation (WT/MT) with 77 sex-matched controls from the same population who are homozygous for the wild-type GHRHR allele (WT/WT). Results: We found no difference in adult height and sd score for serum IGF-I between the two groups. Body weight, body mass index, skin folds, waist and hip circumferences, and lean mass were all reduced in WT/MT subjects. Percentage fat mass and waist/hip ratio were similar in the two groups. Fasting insulin and homeostasis model assessment of insulin resistance were lower in WT/MT. The other biochemical parameters [total and fractionated cholesterol, triglycerides, lipoprotein (a), and C-reactive protein] were not different between the two groups. Conclusions: Heterozygosity for a null GHRHR mutation is not associated with reduction in adult stature or in serum IGF-I but is associated with changes in body composition and possibly an increase in insulin sensitivity. These effects do not seem to be modulated by changes in circulating IGF-I.

The progressive increase in lif€ expectancy within the last century has led to the appearance of novel health related problems, some of those within the musculoskeletal Íield. Among the latter, one can find diseases such as osteoporosis, rheumatoid arthritis and bone cancer, just to mention some of the most relevant. Other related problems are those that arise from serious injuries, often leading to non-recoverable critical size defects. The therapies currently used to treat this type of diseases/injuries are based on the use of pharmaceutical agents, auto/allotransplant and synthetic materials. However, such solutions present a number of inconveniences and therefore, there is â constant search for novel therapeutic solutions. The appearance of a novel field of science called Tissue engileering brought some hope for the solution of the above mentioned problems. In this field, it is believed that by combining a 3D porous template - scaffold - with an adequate cell population, with osteo or chondrogenic potential, it will be possible to develop bone and cartilage tissue €quivalents that when implanted lr? vivo, could lead to the total regeneration of the affected area. This ideal cell population should have a series of properties, namely a high osteo and chondrogenic potential and at the same time, should be easily expandable and maintained in cuÌtures for long periods of time. Due to its natural and intrinsic properties, stem cells are on€ ofthe best available cell types. However, after this sen(ence, the readers may ask, "Whiçh Stem Cells?". During the last l0/15 yeaÍs, the scientific community witnessed and reported the appearanceo f several sourceso f stem cells with both osteo and chondrogenicp otential.T herefbre,t he present review intends to make an overview of data reported on different sources of adult stem cells (bone marfow, periosteum. adipose tissue, skeletal muscle and umbilical cord) for bone and cartilage regenerative medicine, namely those focusing on the differentiation potential of the latter as well as h y,vo proof of concept of their applicability. Simultaneously novel aspects of adult stem cells biotechnology such as their immunogenicc haraçteristicsa nd cell expansionm ethodologiesr vill also be put forward. The presentr eview also points out on issues such as the bone and caÍtiìage regenerativ€ market, and gives a brief description on bone and cartilage bone biology, so the readers can have a true idea of the cunent statc of the an, and how adult stem cells can be an added value to this field., (undefined)

The aim of this research was to verify the incidence of endocrine dysfunction associated with mercury intoxication in the hypothalamus-pituitary reproductive system of normally cycling or castrated female rats and the possible protective action of estrogen replacement therapy. We found no differences in the frequency of estrus cycle stages (diestrus I, diestrus II, proestrus, and estrus) in normally cycling female rats during 54 days of daily oral administration of 0.004, 0.02, and 1 mg/kg MeHgCl. Conversely, the higher dose (1 mg/kg) induced a significant decrease in content of luteinizing hormone releasing hormone (LHRH) into the medial hypothalamus when administered daily during 3 days in ovariectomized rats. This effect was associated with increased levels of mercury found in the anterior pituitary gland and medial hypothalamus, rather than the anterior and posterior hypothalamus, striatum or cerebellum. A decrease in plasma levels of luteinizing hormone (LH) was also detected after administration of 7.5 mg/kg MeHgCl. These disturbances in LHRH and LH secretion induced by mercury were abolished or superimposed (respectively) by estrogenic replacement therapy (0.025 mg/kg 17beta estradiol cypionate, intramuscular). These effects were associated with a significant reduction in mercury content of the anterior pituitary gland and medial hypothalamus, suggesting a protective estrogenic effect.

Aging represents a major risk factor for numerous illnesses that are of increasing importance to society, including two of the most prevalent: diabetes and Alzheimer׳s disease. Studies have shown that diabetes is a risk factor for spontaneous Alzheimer׳s disease. While these studies suggest that diabetes can contribute to Alzheimer׳s disease, the implications of AD on diabetes are practically unexplored. The major mediator of the pathophysiological effects, the Aβ42 peptide, has been shown to enter neurons and lead to an alteration of the intracellular distribution of the molecular motor myosin Vb. Myosin Vb functions in memory and learning by participating in the strengthening of the long-term potentiation (LTP) of synaptic transmissions. It has also been implicated in the translocation of the glucose transporter, GLUT4, to the plasma membrane in response to insulin, a process that is defective in diabetes. Here, the effect on GLUT4 upon entry of the Aβ42 peptide into cultured chick retinal neurons was explored. The results suggest an alteration in distribution and a reduced level at the cell surface, as well as an increased colocalization with myosin Vb, which can partially explain the changes in glucose metabolism associated with AD. It is also shown that the presence of the Aβ40 peptide inhibits the internalization of the Aβ42 peptide in cultured cells. Together, the results provide additional targets for the development of therapeutics against the progression and effects of Alzheimer׳s disease.

We assessed the effects of anoxia exposure and recovery on glycogen synthesis and mobilization, glucose uptake, and on the enzymes that control carbohydrate metabolism in the hepatopancreas of Chasmagnathusgranulata crabs receiving either a carbohydrate-rich (HC) or a high-protein diet (HP). In both dietary groups, anoxia led to a reduction in glucose uptake and in glycogen synthesis, and to an increase in hepatopancreas glycogen mobilization and in hemolymph glucose concentration. During the first 4 h of exposure to anoxia, total glycogen phosphorylase (GPT) and a form activity increased in HP and HC crabs, leading to a decrease in hepatopancreas glycogen concentration. During recovery, HP and HC crabs rapidly restored the hemolymph glucose levels to pre-anoxia concentrations. In HC crabs, incorporation of 14C from glucose into glycogen increased gradually after 12 h in normoxia, leading to restoration of glycogen concentration. Also during recovery, the ratio of glycogen synthase I (GSI) to glycogen phosphorylase a (GPa) increased in the HC group. In turn, recovering HP crabs had two peaks of glycogen synthesis, related with two peaks in the ratio of GSI to GPa. Consequently, no mobilization of 14C-glycogen occurred in recovering HP animals. Anoxia in C.granulata induces a marked decrease in the synthesis of carbohydrate reserves that is accompanied by an increase in glycogen mobilization and in circulating glucose levels. During the recovery period, there is an activation of endergonic processes which cause a decrease in hemolymph glucose levels. In C.granulata, glycogen metabolism seems to be controlled by the ratio of the GSI form to the GPa form. In field conditions, theses changes in the metabolic pattern may result from environmental PO2 availability. In the winter, C.granulata stays in its holes, where environmental PO2 falls to zero. The carbohydrate or protein content of the diets administrated to the crabs seem to induce different metabolic adjustments during anoxia and recovery.

Summary: Gymnastics and tbe practice of martial arts are very frequent nowadays. These activities involve a great risk of infections in shower rooms, gymnasium grounds, using training tatami judo mattress, etc. The problem of fungus contamination in these places is a serious one. In a study of samples collected in the Sport Club of the Escola Paulista de Medicina, Sao Pado Brasil by using the technique of the sterile square of carpet according to Mariat & Tapia 1966 we isolated dermatophytes from 37.2% of the samples. Epidermophyton floccosum was recovered from tatami and dressing rooms and Trichophyton mentagrophytes was fonnd in bathrooms, tatami and male dressing rooms. Based on present results we propose some prophylactic measures. Zusammenfassung. Gymnastik und andere Leibesubungen werden heute von weiten Bevolke-rungskreiisen betrieben. Bei diesen Aktivitaten besteht ein Infektionsrisiko insbesondere bei der Benutzung von Duschraumen, Turnhallen, Sportmatratzen etc. Das Problem der Pilzkontamination dieser Bereiche ist durchaus ernstzunehmen. In einer Untersuchung, die im Sportklub der Escola Paulista de Medicina, Sao Paulo Brasilien mit Hilfe der 1966 von Mariat & Tapia angegebenea Methode durchgefuhrt wurde, konnten in 37,2% der Proben Dermatophyten isoliert werden. Epidermophyton floccosum fand sich auf Ubungsmatratzen und in Umkleideraumen. Trichophyton mentagrophytes wurde ebenfalls von Matratzen, aus Baderaumen und aus Umkleideraumen von Mannern isoliert. Aufgrund dieser Ergebnisse werden prophy-laktische Masnahmen vorgeschlagen.

Objetivo: analisar as alterações histopatológicas provocadas pela ação da quimioterapia neoadjuvante (fluoracil, epirrubicina e ciclofosfamida; FEC -- 4 ciclos) na área tumoral, no tecido mamário adjacente e nos linfonodos homolaterais, em peças cirúrgicas obtidas de pacientes portadoras de carcinomas primários da mama. Método: estudo histológico detalhado de 30 peças cirúrgicas obtidas por mastectomia radical (Patey) de pacientes portadoras de carcinomas primários da mama, previamente submetidas a esse tipo de terapêutica sistêmica. Resultados: observamos regressão tumoral, de grau variável, em todas as peças analisadas. Esta regressão ocorreu de forma irregular, restando inúmeros focos refratários na área ocupada pelo tumor primário. Observamos focos celulares resistentes independentes do tumor primário no tecido mamário. Detalhamos outros achados histopatológicos decorrentes da ação quimioterápica nos tecidos tumoral e mamário, como calcificações e fibrose, e nos linfonodos axilares homolaterais. Conclusão: concluímos que a ação da quimioterapia neoadjuvante não é uniforme, restando focos tumorais refratários, tanto na área do tumor inicial, quanto à distância. A regressão do tumor independe da resposta de regressão dos linfonodos axilares metastáticos. A utilização da cirurgia conservadora pós-quimioterapia neoadjuvante (FEC) deve ser evitada. Purpose: analysis of histopathologic alterations caused by neoadjuvant chemotherapy (fluorouracil, epirubicine, cyclophosphamide; FEC - 4 cycles) at the tumor site, adjacent mammary tissue and homolateral lymph nodes, as observed in sections of patients with primary breast carcinomas. Method: histological studies performed on 30 surgical sections obtained from radical mastectomy (Patey) of patients with primary breast carcinomas, who underwent prior neoadjuvant systemic therapy. Results: all sections showed tumor regression with variable intensity. This regression occurred irregularly, several refractory tumor cells remaining at the primary tumor site. Resistant tumor cells, independent of the primary tumor, were found in mammary tissue. Other histopathological findings, resulting from chemotherapy in tumoral and mammary tissues, such as calcifications and fibrosis, and in axillary homolateral lymph nodes were obtained. Conclusion: the effect of neoadjuvant chemotherapy is not uniform, refratory tumor cells remaining not only at primary tumor site, but also in distant regions. Furthermore, we found no correlation between the regression of the tumor and the axillary metastatic lymph nodes. Thus, a conservative surgery after neoadjuvant chemotherapy (FEC) should be avoided.

The capacity for glucose synthesis in Chasmagnathus granulata hepatopancreas, associated with phosphoenolpyruvate carboxykinase activity, argues in favor of this tissue as a site for gluconeogenesis. In order to obtain more information on the gluconeogenic capacity in crabs, we investigated the effects of different diets on the incorporation of 14C-alanine or 14C-lactic acid into glucose in Chasmagnathus granulata hepatopancreas, as well as on the phosphoenolpyruvate carboxykinase activity in this organ. In contrast to what occurs in vertebrates, in Chasmagnathus granulata, the intrinsic capacity of the hepatopancreas to synthetize glucose from alanine or lactic acid, and its phosphoenolpyruvate carboxykinase activity, was not influenced by high-protein or carbohydrate diets. The amount of labelled glucose recovered from 14C-alanine was significantly higher than that recovered from 14C-lactic acid, and 40 mM of alanine is not a saturated concentration for the gluconeogenic pathway. Phosphoenolpyruvate carboxykinase activity was detected into the mitochondrial (10,000 × g) and cytosol (100,000 × g) fractions. The data suggest that gluconeogenesis from 14C-alanine in the hepatopancreas from Chasmagnathus granulata fed a high-protein or carbohydrate-rich diet is equally subject to end-point inhibition by glucose, as has been found in vertebrates.

Patients with lung cancer commonly require the ICU for a variety of acute illnesses related to the underlying malignancy, treatment, or comorbid conditions. ICU admission of patients with nonresectable lung cancer has been criticized based on the high mortality rate in this population. However, recent advances in critical care may have changed this scenario. The aim of this study was to identify factors associated with hospital mortality in this group of patients.

The aim of this study was to compare the ratio of activation of the vastus lateralis (VL) and biceps femoris (BF) muscles between healthy (CG) and anterior cruciate ligament reconstructed (ACL-R) subjects during gait. Nineteen subjects, ten from GC and nine from ACL-R, participated in the study. VL and BF activity was captured and the VL/BF ratio was obtained by dividing each point on the curve of the vastus lateralis and biceps femoris. This ratio was compared between the two groups using an unpaired t test (a = 0.05). Differences between the two groups were found (p

It has been demonstrated that reabsorption of Na⁺ in the thick ascending limb is reduced and the ability to concentrate urine can be compromised in undernourished individuals. Alterations in phospholipid and cholesterol content in renal membranes, leading to Na⁺ loss and the inability to concentrate urine, were investigated in undernourished rats.Sixty-day-old male Wistar rats were utilized to evaluate (1) phospholipid and cholesterol content in the membrane fraction of whole kidneys, (2) cholesterol content and the levels of active Na⁺ transporters, (Na⁺ + K⁺)ATPase and Na⁺-ATPase, in basolateral membranes of kidney proximal tubules, and (3) functional indicators of medullary urine concentration.Body weight in the undernourished group was 73 % lower than in control. Undernourishment did not affect the levels of cholesterol in serum or in renal homogenates. However, membranes of whole kidneys revealed 56 and 66 % reduction in the levels of total phospholipids and cholesterol, respectively. Furthermore, cholesterol and (Na⁺ + K⁺)ATPase activity in proximal tubule membranes were reduced by 55 and 68 %, respectively. Oxidative stress remained unaltered in the kidneys of undernourished rats. In contrast, Na⁺-ATPase activity, an enzyme with all regulatory components in membrane, was increased in the proximal tubules of undernourished rats. Free water clearance and fractional Na⁺ excretion were increased by 86 and 24 %, respectively, and urinary osmolal concentration was 21 % lower in undernourished rats than controls.Life-long undernutrition reduces the levels of total phospholipids and cholesterol in membranes of renal tubular cells. This alteration in membrane integrity could diminish (Na⁺ + K⁺)ATPase activity resulting in reduced Na⁺ reabsorption and urinary concentrating ability.

To the best of our knowledge, no cases of ulcerative colitis (UC) mimicking Henoch–Schonlein purpura (HSP) have been reported so far. During a 28-year period 5635 patients were followed up at our Pediatric Rheumatology Unit and 357 had HSP according to the European League Against Rheumatism, the Paediatric Rheumatology International Trials Organisation and the Paediatric Rheumatology European Society validated classification criteria. At the same period, 148 patients with IBD according to the European Society for Paediatric Gastroenterology, Hepatology and Nutrition criteria were followed up at the Pediatric Gastroenterology Unit in our University Hospital. Only two of them had vasculitis, as an extra intestinal manifestation of UC mimicking HSP, and fulfilled both disease criteria. A 2-year old girl had bloody diarrhoea, severe abdominal pain, arthritis in ankles, petechiae and palpable purpura not related to thrombocytopenia in lower limbs. A 5-year old boy had bloody diarrhoea, palpable purpura in buttocks, lower limbs, penis and scrotum associated with arthritis in knees, orchitis in right testicle and periarticular swelling in hands and feet. Their ileocolonoscopy showed diffuse mucosal erythema, oedema, friability and multiple irregular ulcers, and histopathological examination of colonic specimen revealed diffuse chronic mucosal inflammation, crypt distortion and crypt abscesses suggesting ulcerative colitis. There were no signs of intestinal vasculitis in both cases. In conclusion, this is the first study in a paediatric population that evidenced palpable purpura associated with UC mimicking HSP.

The consolidation of intensive care fundamentals was accompanied by growth of ICUs and increased utilization of intensive care services. Unfortunately it was not followed by national health planning. The demographic changing profile with a higher number of elderly patients and a changing case mix with less trauma patient admissions, associated with the high prevalence of cardiovascular diseases and the early approach to septic patients, will have implications on intensive care organization. A regulatory policy system for public ICUs was started in Rio de Janeiro to ensure appropriate selection and allocation of patients who need intensive care. The aim of this study is to report the profile of patients admitted to the ICU since the beginning of this new policy.

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation of β-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.Key words: Endothelial dysfunction; Hypertension; Sympathetic hyperactivity; Diabetes; Obesity

In breast cancer patients submitted to neoadjuvant chemotherapy (4 cycles of doxorubicin and cyclophosphamide, AC), expression of groups of three genes (gene trio signatures) could distinguish responsive from non-responsive tumors, as demonstrated by cDNA microarray profiling in a previous study by our group. In the current study, we determined if the expression of the same genes would retain the predictive strength, when analyzed by a more accessible technique (real-time RT-PCR). We evaluated 28 samples already analyzed by cDNA microarray, as a technical validation procedure, and 14 tumors, as an independent biological validation set. All patients received neoadjuvant chemotherapy (4 AC). Among five trio combinations previously identified, defined by nine genes individually investigated (BZRP, CLPTM1, MTSS1, NOTCH1, NUP210, PRSS11, RPL37A, SMYD2, and XLHSRF-1), the most accurate were established by RPL37A, XLHSRF-1 based trios, with NOTCH1 or NUP210. Both trios correctly separated 86% of tumors (87% sensitivity and 80% specificity for predicting response), according to their response to chemotherapy (82% in a leave-one-out cross-validation method). Using the pre-established features obtained by linear discriminant analysis, 71% samples from the biological validation set were also correctly classified by both trios (72% sensitivity; 66% specificity). Furthermore, we explored other gene combinations to achieve a higher accuracy in the technical validation group (as a training set). A new trio, MTSS1, RPL37 and SMYD2, correctly classified 93% of samples from the technical validation group (95% sensitivity and 80% specificity; 86% accuracy by the cross-validation method) and 79% from the biological validation group (72% sensitivity and 100% specificity). Therefore, the combined expression of MTSS1, RPL37 and SMYD2, as evaluated by real-time RT-PCR, is a potential candidate to predict response to neoadjuvant doxorubicin and cyclophosphamide in breast cancer patients.