ADAM10 as a biomarker for Alzheimer's disease: A systematic review.

BACKGROUND: Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-ß peptide (Aß), one of the pathological hallmarks of Alzheimer's disease (AD). OBJECTIVE: To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD. METHODS: A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239). RESULTS: Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection. CONCLUSION: Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.

Lack of evidence for longitudinal dissociation of the atrioventricular conduction axis.

Longitudinal dissociation of the aggregated specialized cardiomyocytes within the non-branching portion of atrioventricular conduction axis has proved a controversial topic for both morphologists and electrophysiologists. We have now used morphological methods, including three-dimensional assessment, to revisit, in human, canine, and bovine hearts, the presence or absence of interconnections between the aggregated cardiomyocytes making up the non-branching bundle. We analyzed three datasets from human and canine hearts, and two from bovine hearts, using longitudinal and orthogonal serial histological sections. In addition, we assessed three hearts using translucent India ink injected specimens, permitting assessment of the three-dimensional arrangement of the cardiomyocytes. Using the longitudinal sections, we found numerous oblique interconnections between the groups of specialized cardiomyocytes. When assessing orthogonal sections, we noted marked variation in the grouping of the cardiomyocytes. We interpreted this finding as evidence of bifurcation and convergence of the groups seen in the longitudinal sections. The three-dimensional assessment of the bovine material confirmed the presence of the numerous interconnections. The presence of multiple connections between the cardiomyocytes in the non-branching bundle rules out the potential for longitudinal dissociation.

American visceral leishmaniasis in a state of northeastern Brazil: clinical, epidemiological and laboratory aspects

Abstract In Brazil, American visceral leishmaniasis (AVL) has become a public health concern due to its high incidence and lethality. This study aimed to analyze the clinical, epidemiological, and laboratory aspects of AVL in a state of Brazil. This descriptive, cross-sectional, retrospective, and quantitative study of notified cases of AVL was carried out in Alagoas between 2008 and 2017 from data obtained from DATASUS/SINAN. Sociodemographic, clinical, and laboratory variables were analyzed. A descriptive analysis was performed using absolute values and valid percentages, using tables and/or graphs. Data processing was performed using Stata 12.0®. Results with P 0.05 were considered statistically significant. During the study period, 352 cases of AVL were reported, of which 6.82% died and 38.92% had met a cure criterion. Male patients were predominant (66.76%). Of the total infected patients, 16.76% had attended only the 1st to the 4th grades, with those most affected aged 1 to 4 years (28.69%). Laboratory diagnostic criteria were most commonly used to confirm the notified cases (76.42%), whereas 51.70% and 8.52% of the cases had positive parasitological and immunofluorescence diagnoses, respectively. Finally, the study showed a higher prevalence of the disease in children, men and in rural residents. Although with low lethality, the expressive frequency of AVL in the State of Alagoas was still verified, since there was an increase in the number of cases during the years of the study.

Resumo No Brasil, a leishmaniose visceral americana (LVA) tornou-se uma preocupação de saúde pública devido à sua alta incidência e letalidade. Este estudo teve como objetivo analisar os aspectos clínicos, epidemiológicos e laboratoriais da AVL em um estado brasileiro. Este estudo descritivo, transversal, retrospectivo e quantitativo dos casos notificados de AVL foi realizado em Alagoas entre 2008 e 2017 a partir de dados obtidos do DATASUS/SINAN. Foram analisadas variáveis sociodemográficas, clínicas e laboratoriais. Foi realizada uma análise descritiva utilizando-se valores absolutos e percentuais válidos, utilizando tabelas e/ou gráficos. O processamento dos dados foi realizado por meio do Stata 12.0®. Os resultados com P 0,05 foram considerados estatisticamente significativos. Durante o período de estudo, foram notificados 352 casos de LVA, dos quais 6,82% morreram e 38,92% atenderam a um critério de cura. Os pacientes do sexo masculino foram predominantes (66,76%). Do total de pacientes infectados, 16,76% tinham sido atendidos apenas do 1º ao 4º ano, com os mais afetados entre 1 e 4 anos (28,69%). Os critérios de diagnóstico laboratorial foram mais utilizados para confirmar os casos notificados (76,42%), enquanto 51,70% e 8,52% dos casos apresentaram diagnósticos positivos parasitológicos e imunofluorescência, respectivamente. Por fim, o estudo demonstrou maior prevalência da doença em crianças, homens e nos residentes em zona rural. Embora com letalidade baixa, constatou-se ainda a expressiva frequência da LVA no Estado de Alagoas, uma vez que houve aumento do número de casos durante os anos do estudo.

American visceral leishmaniasis in a state of northeastern Brazil: clinical, epidemiological and laboratory aspects / Leishmaniose visceral americana em estado do nordeste brasileiro: aspectos clínicos, epidemiológicos e laboratoriais

In Brazil, American visceral leishmaniasis (AVL) has become a public health concern due to its high incidence and lethality. This study aimed to analyze the clinical, epidemiological, and laboratory aspects of AVL in a state of Brazil. This descriptive, cross-sectional, retrospective, and quantitative study of notified cases of AVL was carried out in Alagoas between 2008 and 2017 from data obtained from DATASUS/SINAN. Sociodemographic, clinical, and laboratory variables were analyzed. A descriptive analysis was performed using absolute values and valid percentages, using tables and/or graphs. Data processing was performed using Stata 12.0®. Results with P <0.05 were considered statistically significant. During the study period, 352 cases of AVL were reported, of which 6.82% died and 38.92% had met a cure criterion. Male patients were predominant (66.76%). Of the total infected patients, 16.76% had attended only the 1st to the 4th grades, with those most affected aged 1 to 4 years (28.69%). Laboratory diagnostic criteria were most commonly used to confirm the notified cases (76.42%), whereas 51.70% and 8.52% of the cases had positive parasitological and immunofluorescence diagnoses, respectively. Finally, the study showed a higher prevalence of the disease in children, men and in rural residents. Although with low lethality, the expressive frequency of AVL in the State of Alagoas was still verified, since there was an increase in the number of cases during the years of the study.

No Brasil, a leishmaniose visceral americana (LVA) tornou-se uma preocupação de saúde pública devido à sua alta incidência e letalidade. Este estudo teve como objetivo analisar os aspectos clínicos, epidemiológicos e laboratoriais da AVL em um estado brasileiro. Este estudo descritivo, transversal, retrospectivo e quantitativo dos casos notificados de AVL foi realizado em Alagoas entre 2008 e 2017 a partir de dados obtidos do DATASUS/SINAN. Foram analisadas variáveis sociodemográficas, clínicas e laboratoriais. Foi realizada uma análise descritiva utilizando-se valores absolutos e percentuais válidos, utilizando tabelas e/ou gráficos. O processamento dos dados foi realizado por meio do Stata 12.0®. Os resultados com P<0,05 foram considerados estatisticamente significativos. Durante o período de estudo, foram notificados 352 casos de LVA, dos quais 6,82% morreram e 38,92% atenderam a um critério de cura. Os pacientes do sexo masculino foram predominantes (66,76%). Do total de pacientes infectados, 16,76% tinham sido atendidos apenas do 1º ao 4º ano, com os mais afetados entre 1 e 4 anos (28,69%). Os critérios de diagnóstico laboratorial foram mais utilizados para confirmar os casos notificados (76,42%), enquanto 51,70% e 8,52% dos casos apresentaram diagnósticos positivos parasitológicos e imunofluorescência, respectivamente. Por fim, o estudo demonstrou maior prevalência da doença em crianças, homens e nos residentes em zona rural. Embora com letalidade baixa, constatou-se ainda a expressiva frequência da LVA no Estado de Alagoas, uma vez que houve aumento do número de casos durante os anos do estudo.

American visceral leishmaniasis in a state of northeastern Brazil: clinical, epidemiological and laboratory aspects.

In Brazil, American visceral leishmaniasis (AVL) has become a public health concern due to its high incidence and lethality. This study aimed to analyze the clinical, epidemiological, and laboratory aspects of AVL in a state of Brazil. This descriptive, cross-sectional, retrospective, and quantitative study of notified cases of AVL was carried out in Alagoas between 2008 and 2017 from data obtained from DATASUS/SINAN. Sociodemographic, clinical, and laboratory variables were analyzed. A descriptive analysis was performed using absolute values ​​and valid percentages, using tables and/or graphs. Data processing was performed using Stata 12.0®. Results with P <0.05 were considered statistically significant. During the study period, 352 cases of AVL were reported, of which 6.82% died and 38.92% had met a cure criterion. Male patients were predominant (66.76%). Of the total infected patients, 16.76% had attended only the 1st to the 4th grades, with those most affected aged 1 to 4 years (28.69%). Laboratory diagnostic criteria were most commonly used to confirm the notified cases (76.42%), whereas 51.70% and 8.52% of the cases had positive parasitological and immunofluorescence diagnoses, respectively. Finally, the study showed a higher prevalence of the disease in children, men and in rural residents. Although with low lethality, the expressive frequency of AVL in the State of Alagoas was still verified, since there was an increase in the number of cases during the years of the study.

Chronic alcohol consumption increases inflammation and osteoclastogenesis in apical periodontitis.

AIM: To investigate the effect of chronic alcohol consumption on apical periodontitis in rats. METHODOLOGY: Thirty-two male Wistar rats were arranged into four groups: Control (C): without apical periodontitis and nonalcoholic diet; (AL): without apical periodontitis and alcoholic diet; (AP): with apical periodontitis and nonalcoholic diet; and (AP + AL): with apical periodontitis and alcoholic diet. The alcoholic solution at 20% was given to the AL and AP + AL groups as the sole source of hydration throughout the experiment. AP was induced in the mandibular left first molars at the end of the 4th week. Weight changes and the amount of solid and liquid foods were recorded for 8 weeks. At the end, the animals were euthanized and the jaws removed followed by histological processing for histopathological and RANKL, OPG, TRAP and HIF-1α analyses. The Mann-Whitney test was used for nonparametric data, and anova followed by the Tukey test was performed for parametric data, with P < 0.05. RESULTS: Animals that received the alcoholic diet had a lower weight gain than the other groups (P < 0.05). Control and AL groups did not have an inflammatory response in the periapical tissues. The median score of inflammatory infiltrate was significantly higher in the AP + AL group (2.5) compared to the AP group (1.5; P < 0.05). In the same comparison, AP + AL was associated with score 3 for RANKL and HIF-1α versus score 2 for AP group (P < 0.05). Moreover, the values for TRAP were 3.88 ± 0.70 cells mm-1 for the AP + AL group and 2.43 ± 0.94 cells mm-1 for the AP group (P < 0.05). CONCLUSION: In rats, an alcoholic diet had a significant effect on the severity of apical periodontitis, exacerbating the inflammatory response and osteoclastogenesis.

Three-Dimensional Volume Imaging to Increase the Accuracy of Surgical Management in a Case of Recurrent Chordoma of the Clivus.

BACKGROUND The clivus is a depression in the anterior occipital bone of the skull base, posterior to the dorsum sellae, at the junction with the sphenoid bone. Chordoma is a rare tumor arising from embryonic remnants of the notochord and can be locally aggressive with a tendency to recur. The optimal management of this rare tumor remains controversial. A report of a case of recurrent chordoma of the clivus is presented to illustrate the value of volumetric three-dimensional (3-D) reconstruction with computed tomography (CT) and magnetic resonance imaging (MRI) to determine optimal surgical management. CASE REPORT A 53-year-old man presented with pain in the right orbital cavity, right proptosis, swelling of the right cheek, and bilateral loss of vision. He also had adrenal insufficiency. CT and contrast-enhanced (gadolinium) T1-weighted MRI with multiplanar acquisition were performed with volumetric 3-D reconstruction of the tumor, to increase the chances of treatment success. Surgical resection was performed to remove the tumor and reduce the risk of recurrence. Histology of the tumor was consistent with chordoma, supported by positive immunohistochemical staining for S-100 and epithelial membrane antigen (EMA). CONCLUSIONS This report highlighted the value of 3-D volume imaging in the diagnosis and treatment planning in a rare case of recurrent chordoma of the clivus. Analysis of tumor volume may be an indicator of the efficacy of surgery, complementing the Response Evaluation Criteria In Solid Tumors (RECIST) system and as a valuable tool to predict treatment outcome.

Stability of anterior open bite treatment with bonded spurs associated with high-pull chincup.

OBJECTIVE: To evaluate the stability of anterior open bite (AOB) treatment with bonded spurs associated with high-pull chincup (BS/HPCC). METHODS: The experimental group consisted of 25 Class I AOB patients (15 female, 10 male) treated with BS/HPCC for 1 year. Cephalograms were analysed at pre-treatment (T1), post-treatment (T2) and at the 3-year post-treatment (T3) stage with the patients mean ages of 8.10, 9.14 and 12.18 years, respectively. The control group consisted of 23 subjects (13 female, 10 male) with normal occlusion, with comparable ages at the 3 stages (8.45, 9.45 and 12.50 years at T1, T2 and T3, respectively). T tests were used for intergroup comparisons at T1 and to compare the changes during the 3-year post-treatment period (T2-T3). Intragroup comparison in the treated group was evaluated with dependent t tests between T1 and T2. Correlations between the overbite changes in the T2-T3 period, the pre-treatment AOB severity and the amount of correction achieved during treatment were evaluated with Pearson's correlation coefficient. RESULTS: No statistically significant relapse of the AOB was found at T3. Only 1 patient had a clinically significant AOB relapse. Neither the pre-treatment AOB severity nor the amount of correction was related to overbite changes during the 3-year post-treatment period. CONCLUSIONS: There was no statistically significant relapse of the AOB, and the clinical stability of AOB correction 3-year post-treatment was of 96%.

Comparative study between fasciocutaneous and myocutaneous flaps in the surgical treatment of pressure ulcers of the sacral region.

INTRODUCTION: Decubitus ulcers of the sacral region are common conditions in bedridden patients. Deep lesions (Stages III and IV) often require surgical treatment for closure. Flaps of the region are the first choice for treatment. We present our experience in the treatment of these lesions and compare two different approaches: local fasciocutaneous flap and gluteus maximus myocutaneous flap with V-Y advancement. METHOD: From March 2009 to May 2014, 32 patients underwent closure of sacral pressure ulcers by flaps, 17 of them with rotational local fasciocutaneous flaps and 15 with myocutaneous flaps of the gluteus maximus muscle with V-Y advancement. Evolution regarding complications and rate of success after two months was compared between the groups. RESULTS: Out of the 32 operated patients we obtained resolution of lesions after two months in 23 (71.8%), 10 patients in the fasciocutaneous flap group (58.8%) and 13 cases in the myocutaneous flap group (86.6%). The most common complication was partial dehiscence of sutures in 12 patients (37.5%), 8 patients in the fasciocutaneous flap group (47%) and 4 patients in the myocutaneous flap group (26.6%). The group of patients reconstructed with local fasciocutaneous flaps presented 3 cases with seroma, one with hematoma and 6 with partial cutaneous necrosis; these patients also required more drainage time. CONCLUSIONS: Both the local rotational fasciocutaneous flap and the myocutaneous flap of the gluteus maximus muscle in V-Y flap can be used in the surgical treatment of sacral ulcers. In our experience, a reduced success rate and more complications were found in the local fasciocutaneous reconstructive method.

Microbiological analysis of conjunctival secretion in anophthalmic cavity, contralateral eye and ocular prosthesis of patients with maxillofacial abnormalities.

The purpose of this study was to identify and analyse the micro-organisms present in the conjunctival secretion in anophthalmic cavities of wearers of ocular prostheses, as well as on the prostheses used by them, correlating them with the microbiota of the contralateral eye. Nine patients with maxillofacial abnormalities, wearers of an acrylic resin ocular prosthesis participated in the study. Collections of conjunctival secretions and biofilm were performed on the prosthesis, anophthalmic cavity and contralateral eye for the mycological and bacterial analyses. The data were submitted to statistical analysis, performing a Kendall correlation test to identify the correlation between the collection site and the identified micro-organism (P < 0·05). It was verified that the most prevalent micro-organisms were the Staphylococcus aureus and Staphylococcus epidermidis, independent of the collection site, and that negative cultures for fungi were encountered in 85·2% of collections, independent of the region. It was not possible to establish a correlation among the types of micro-organisms and the collection sites. SIGNIFICANCE AND IMPACT OF THE STUDY: Some evidence suggests that the surface roughness of ocular prostheses can influence interactions with micro-organisms, with greater prejudicial consequences, such as the establishment of biofilms, which could lead to infections. Thus, it becomes extremely important to identify the micro-organisms present on the acrylic surfaces of ocular prostheses, as well as the microbiota of the anophthalmic cavity and contralateral eye of wearers of the same, so that subsequent control measures promote the homeostatic maintenance of the ocular region.

Assessment of Interexaminer Agreement in the Detection of Condyle Morphology and positioning with Two Methods: Radiographic and Tomographic.

AIM: This study aims at evaluating the interexaminer agreement between radiographic and tomographic methods to determine condyle morphological variations and positioning. MATERIALS AND METHODS: The sample comprised 100 individuals aged 13 to 30 years, from the patient files of University of North Paraná. The assessment of condyles morphology and positioning was performed in images of digital panoramic radiography (DPR) and reconstructed panoramic images from the cone beam computed tomography (CBCT) scans, by using the Dolphin three-dimensional (3D) program. The condyle morphology was categorized as flat, convex, and angular as well as its positioning classified into anterior, posterior, and concentric. Three calibrated examiners performed this subjective evaluation. After that, another examiner performed an objective assessment of the condyles positioning using tomographic sagittal scans of the condyles, applying the same 3D program. This objective evaluation of the condyle position, considered the gold standard (GS), was achieved by using a formula based on the measurement values of the joint spaces, anterior and posterior. The kappa test was used to assess the interexaminer agreement in determining the condyles morphology and positioning, as well as between the condyle positioning results determined by the examiners and the GS. RESULTS: The results showed poor agreement among examiners and between the subjective and objective condyle positioning evaluation. CONCLUSION: It was concluded that the panoramic radiography (PR), either digitalized or reconstructed from CBCT scans, is not suitable for determining variations in condyle morphology and position. CLINICAL SIGNIFICANCE: Whenever it is necessary to evaluate the mandibular condyle during the orthodontic screening, the orthodontist should consider another image modality better than the PR.

Absolute standardization of the impurity (121)Te associated to the production of the radiopharmaceutical (123)I.

(123)I is widely used for radiodiagnostic procedures. It is produced by reaction of (124)Xe (p,2n) (123)Cs →(123)Xe →(123)I in cyclotrons. (121)Te and (125)I appear in a photon energy spectrum as impurities. An activity of (121)Te was calibrated absolutely by sum-peak method and its photon emitting probability was estimated, whose results were consistent with published results.

Determination of impurities in (124)I samples by high resolution gamma spectrometry.

(124)I is a radionuclide used in the diagnosis of tumors. The National Health Agency requires identification and activity measurement of impurities. Using gamma spectrometry with an efficiency calibrated high-purity germanium detector, impurities (125)I and (126)I in an (1)(24)I production sample were identified. Activity ratios of (125)I and (126)I to (124)I were approximately 0.5% and 98%, respectively.

Early neonatal deaths with perinatal asphyxia in very low birth weight Brazilian infants.

OBJECTIVE: The objective of this study was to assess the frequency of early deaths associated with birth asphyxia of very low birth weight infants between 2005 and 2010, in Brazil. STUDY DESIGN: This population study enrolled all live births with birth weight from 400 to 1499 g, gestational age ⩾ 22 weeks, without malformations that died up to 6 days after birth with perinatal asphyxia. Asphyxia was defined if intrauterine hypoxia, asphyxia at birth or meconium aspiration syndrome were written in any line of the death certificate. Active search was carried out in 27 Brazilian federative units. RESULT: For every 1000 live births of very low birth weight infants without congenital malformations, 40.25 and 32.38 died with birth asphyxia in the first week after birth, respectively, in 2005 and 2010 (P<0.001). The contribution of birth asphyxia to early neonatal death of these infants was approximately 10 to 12% all study years. CONCLUSION: Reduction of birth asphyxia in very low birth weight infants is essential to reducing neonatal mortality in Brazil.

Chromosomal organization of repetitive DNA in Sorubim lima (Teleostei; Pimelodidae).

Interspaced repetitive DNA elements and segmental duplications have been extensively analyzed in fishes through physical chromosome mapping methods, providing a better comprehension of the structure and organization of the genome of this group. In order to contribute to this scenario, a sequence integration study of different classes of repetitive DNA with high resolution physical chromosome mapping was performed in Sorubim lima. Fluorescence in situ hybridization (FISH) and fiber-FISH with probes for 18S and 5S rRNA genes, TTAGGGn sequence and non-LTR retrotransposon family members Rex1, Rex3 and Rex6 showed that non-LTR elements may be dispersed in the chromosome set with relative concentration in heterochromatic regions, as shown by Rex1, or may even intercalate in 45S rDNA and the telomeric sequence, as found for Rex3 and Rex6. These results reinforce the presence of preferential regions of retroelement accumulation and contribute to a better understanding of the genomic organization of some repetitive DNA classes in fishes.

La píldora anticonceptiva a debate / The contraceptive pill submitted for debate

El propósito de este trabajo es hacer una revisión sobre los riesgos y beneficios de la píldora anticonceptiva y la necesidad de informar desde las consultas de enfermeras/os y de matronas con base en la evidencia científica. Desde su comercialización en los años 60, se ha publicado una gran cantidad de información sobre los riesgos de la píldora , tanto en el ámbito científico como en los medios de comunicación social y sin embargo, los beneficios han sido poco difundidos. La píldora combinada es uno de los métodos anticonceptivos reversibles con mayor eficacia para evitar el embarazo. Se asocia a un aumento de riesgo de tromboembolismo venoso y presenta efectos beneficiosos no anticonceptivos relacionados con la menstruación, la fertilidad, la masa ósea, el acné, y reduce el riesgo de cáncer de ovario y de endometrio. Los profesionales de enfermería, al igual que el resto de profesionales del equipo de salud, deben abordar el derecho a la información de la población basada en datos científicos y deben implicarse en funciones de orientación en planificación familiar para mejorar la salud materno-infantil, promoviendo los embarazos deseados y que el derecho a tener el número de hijos e intervalo entre ellos sea respetado.

The objective of this research is to reflect on the risks and benefits of the contraceptive pill and the need for women to be informed by qualified health care providers including nurse midwives and nurse practitioners based on scientific evidence. Since its commercialization in the 60's, a lot of information has been published about the risks of the pill by both scientists and the social media and yet the benefits have been little known. The combined pill is one of the most effective reversible methods of preventing pregnancy. It is associated with increased risk factors for venous thromboembolism and it has non-contraceptive benefits not related to menstruation, fertility, bone mass, acne, and it reduces the risk of ovarian and endometrial cancer. Nursing professionals, like all other health care team professionals should address the right to inform the population based on scientific data as well as get involved in family planning counseling to improve maternal and child health, promoting unintended pregnancies and the right to decide the number of children and the time interval be respected.

Swim training restores glucagon-like peptide-1 insulinotropic action in pancreatic islets from monosodium glutamate-obese rats.

AIMS: Glucagon-like peptide-1 (GLP-1) is an important modulator of insulin secretion by endocrine pancreas. In the present study, we investigated the effect of swim training on GLP-1 insulinotropic action in pancreatic islets from monosodium glutamate (MSG)-obese rats. METHODS: Obesity was induced by neonatal MSG administration. MSG-obese and control (CON) exercised rats swam for 30 min (3 times week(-1) ) for 10 weeks. Pancreatic islets were isolated by colagenase technique and incubated with low (5.6 mM) or high (16.7 mM) glucose concentrations in the presence or absence of GLP-1 (10 nM). In addition, GLP-1 gene expression in ileum was quantified in fasting and glucose conditions. RESULTS: Exercise reduced obesity and hyperinsulinemia in MSG-obese rats. Swim training also inhibited glucose-induced insulin secretion in islets from both groups. Islets from MSG-obese rats maintained GLP-1 insulinotropic response in low glucose concentration. In contrast, in the presence of high glucose concentration, GLP-1 insulinotropic action was absent in islets from MSG-obese rats. Islets from MSG-exercised rats showed reduced GLP-1 insulinotropic action in the presence of low glucose. However, in high glucose concentration swim training restored GLP-1 insulinotropic response in islets from MSG-obese rats. In all groups, glucose intake increased GLP-1 immunoreactivity and gene expression in ileum cells in relation to fasting conditions. Swim training reduced these parameters only in ileum cells from CON-exercised rats. Neither MSG treatment nor exercise affected GLP-1 expression in the ileum. CONCLUSIONS: Exercise avoids insulin hypersecretion restoring GLP-1's insulinotropic action in pancreatic islets from MSG-obese rats.

Synthesis and HIV-1 inhibitory activities of dicaffeoyl and digalloyl esters of quinic acid derivatives.

Twenty analogues of the anti-HIV-1 integrase (IN) inhibitors dicaffeoylquinic acids (DCQAs) were prepared. Their IC(50) values for 3'-end processing and strand transfer against recombinant HIV-1IN were determined in vitro, and their cell toxicities and EC(50) against HIV-1 were measured in cells (ex vivo). Acetylated or benzylated and/or with cyclohexylidene group compounds exhibited no inhibition of integration in biochemical assays or viral replication in HIV-infected cells, with the exception of 16 and 36. Removal of these groups, however, correlated with potent inhibition. Compounds 19, 31, and 38, all digalloyls, exhibited the most robust inhibitory performance in biochemical assays as well as in cell culture and less toxicity than other molecules in the current study.

Proactive management of extreme prematurity: disagreement between obstetricians and neonatologists.

OBJECTIVE: To verify, in extremely preterm infants, if disagreement between obstetricians and neonatologists regarding proactive management is associated with early death. STUDY DESIGN: Prospective cohort of 484 infants with 23(0/7) to 26(6/7) weeks, without malformations, born from January 2006 to December 2009 in eight Brazilian hospitals. Pro-active management was defined as indication of ≥1 dose of antenatal steroid or cesarean section (obstetrician) and resuscitation at birth according to the international guidelines (neonatologist). Main outcome was neonatal death in the first 24 h of life. RESULT: Obstetricians and neonatologists disagreed in 115 (24%) patients: only neonatologists were proactive in 107 of them. Disagreement between professionals increased 2.39 times the chance of death in the first day (95% confidence interval 1.40 to 4.09), adjusted for center and maternal/neonatal clinical conditions. CONCLUSION: In infants with 23 to 26 weeks of gestation, disagreement between obstetricians and neonatologists, translated as lack of antenatal steroids and/or vaginal delivery, despite resuscitation procedures, increases the odds of death in the first day.