Mismatch novelty exploration training enhances hippocampal synaptic plasticity: A tool for cognitive stimulation?

Memory formation relies on experience-dependent changes in synaptic strength such as long-term potentiation (LTP) or long-term depression (LTD) of synaptic activity, that in turn depend on previous learning experiences through metaplasticity. Novelty detection is a particularly important cognitive stimulus in this respect, and mismatch novelty has been associated with the activation of the hippocampal CA1 area in human studies. A single exposure to a new location of known objects in a familiar environment, a behavioural mismatch novelty paradigm, is known to favour the expression of LTD in hippocampal CA3 to CA1 synaptic transmission in vivo, through short-term metaplasticity. Aiming to shape hippocampal responsiveness to synaptic plasticity phenomena we developed a training program based on exploration of a known environment containing familiar objects, everyday presented in a new location. Repeated exposure to this new location of objects for two weeks caused a mild long-lasting decrease in synaptic efficacy. Furthermore, it enhanced both LTP evoked by theta-burst stimulation and depotentiation evoked by low-frequency stimulation of CA3 to CA1hippocampal synaptic transmission in juvenile rats. This suggests that training programs using these behavioural tasks involving mismatch novelty can be used to reshape brain circuits and promote cognitive recovery in pathologies where LTP/LTD imbalance occurs, such as epilepsy, aging or Down's syndrome, an approach that requires further investigation at the behavioural level.

Bacterial degradation of moxifloxacin in the presence of acetate as a bulk substrate.

Fluoroquinolones constitute a group of emerging pollutants and their occurrence in different environmental compartments is becoming object of increasing public concern due to their ecotoxicological effects and the potential to develop resistant bacteria. This study aimed to investigate the biodegradation of moxifloxacin (MOX), for which studies in the literature are very scarce. An activated sludge (AS) consortium and three bacterial strains able to degrade fluoroaromatic compounds - strains F11, FP1 and S2 - were tested. Biodegradation studies were conducted using acetate as a bulk carbon source. Strain F11 showed the highest biodegradation capacity, being able to completely consume and dehalogenate 7.5 µM of the target antibiotic when daily co-supplemented with acetate present as a readily degradable organic substrate in wastewaters. MOX could be used by strain F11 as a sole nitrogen source but the presence of an external nitrogen source in the culture medium was essential for complete biodegradation. Strain F11 was capable of completely consuming MOX in a range between 2 and 11 µM, although stoichiometric fluoride release was not obtained for the highest tested concentration. The antibacterial activity of residual MOX and of the metabolic products potentially resultant from the biodegradation process was investigated by agar diffusion tests, demonstrating that MOX biodegradation is associated with the elimination of the antibacterial properties of the target antibiotic and of the produced metabolites, which is an important result, as the activity of antibiotics and/or their metabolites in the environment, even at low levels, may lead to the development of resistant bacterial strains. Overall, the results obtained in this study suggest that strain F11 is a promising microorganism for the treatment of waters contaminated with MOX, where it could be used for bioaugmentation/bioremediation purposes. To the best of our knowledge, this is the first study reporting complete removal and dehalogenation of MOX by a single microorganism.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.

Efficacy of Er,Cr:YSGG laser with endodontical radial firing tips on the outcome of endodontic treatment: blind randomized controlled clinical trial with six-month evaluation.

Clinical reports stating the efficacy of novel root canal disinfection protocols are an important focus in endodontic research. This blind randomized clinical trial assessed the clinical efficacy of the erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser radial firing tips (RFT) versus the concomitant use of 3 % sodium hypochlorite and interim calcium hydroxide paste in necrotic teeth with chronic apical periodontitis. We hypothesized to find similar or improved bone healing in the laser-assisted endodontic treatment. Thirty-six anterior and premolar teeth were randomly assigned. In group 1, teeth were prepared with 3 % sodium hypochlorite for irrigation and calcium hydroxide as inter-appointment dressing; in group 2, teeth were prepared with saline solution and irradiated with Er,Cr:YSGG laser using RFT2 (140 µs, 37.5 mJ, 20 Hz) and RFT3 (140 µs, 62.5 mJ, 20 Hz) in the first and second appointment, respectively, four times each, moving at 2 mm s(-1) from apical to coronal. The primary outcome measure was changed in apical bone density at 6 months, using the periapical index (PAI) for blind radiographic evaluation. Twenty-nine patients were examined and subjected to statistical analysis, 12 in group 1 and 17 in group 2. There was one treatment failure in group 1. Both groups gave similar outcomes exhibiting statistically significant decreases in PAI scores.

Validity of computed tomography in diagnosing midfacial fractures.

The aim of this study was to evaluate the sensitivity, accuracy, and reliability of two-dimensional computed tomography (2D-CT) scans (axial, coronal, sagittal planes) and three-dimensional computed tomography (3D-CT) reconstructions in diagnosing midfacial fractures in relation to actual fractures identified clinically and during surgery (gold standard). The imaging diagnosis was performed by a radiologist and an oral and maxillofacial surgeon. Sixty-two patients with a total of 429 midfacial fractures were included. Frontal sinus and nose fractures were easily diagnosed. For the three CT planes, there was a statistically significant difference between the CT examination and the gold standard for five to seven of the nine bones evaluated, while for 3D-CT, a difference was observed only for fractures of the orbital floor. The inter-observer agreement between the oral and maxillofacial surgeon and the radiologist was 75.5%. In conclusion, in this study 3D-CT reconstructions showed significantly the best sensitivity, accuracy, and reliability for the diagnosis of midfacial fractures. The sagittal reconstructions were the least diagnostic of the 2D-CT images. For areas where the parameters studied showed less agreement and hence a more difficult diagnosis, we recommend a combination of 3D and 2D-CT images to improve diagnostic accuracy.

Tomographic analysis of nasomaxillary and zygomaticomaxillary buttress bone thickness for the fixation of miniplates.

The purpose of this study was to evaluate the bone thickness of the nasomaxillary and zygomaticomaxillary buttresses to identify the most favourable region for the installation of miniplates. Bilateral tomographic images of 103 individuals were evaluated, for a total of 206 nasomaxillary and zygomaticomaxillary buttresses. Measurements of bone thickness were performed in the parasagittal reconstructions along three vertical lines on the nasomaxillary buttress (21 measurement points) and four vertical lines on the zygomaticomaxillary buttress (28 measurement points). The vertical line measurements for each buttress were compared using the Kruskal-Wallis test. Spearman's correlation coefficient was used to determine the correlation between the thicknesses obtained and patient sex and side (right/left). The level of significance adopted was 5%. The nasomaxillary and zygomaticomaxillary buttresses presented statistical differences in thickness at their respective points (P=0.001). The analysis of the nasomaxillary buttress showed that the thicker bone for the installation of miniplates follows the long axis of the upper canine at a distance of 3mm from the root apex. For the zygomaticomaxillary buttress, thicker bone to install miniplates was found distal to the distobuccal root of the first molar, at a distance of 3.5mm from the limit of the infraorbital foramen.

Diagnosis at different stages of paracoccidioidomycosis with oral manifestation: Report of two cases.

Paracocciodiomycosis (PCDM) is a chronic systemic fungal infection, mainly affecting residents and rural workers, being characterized by a long incubation period, which it can take months or years without clinical manifestations, making diagnosis late and difficult. Depending on the stage of the disease, it can cause sequelae and low quality of life, so its correct diagnosis is of great importance for the accurate treatment. Therefore, the aim of this report is to present two cases of diagnosis of patients with PCDM at different stages, who developed chronic manifestations, pain, clinical involvement of the oral cavity and in one case also presented lung injury with fibrosis, as well as to weight loss, dysphagia and cachexia. Both of patients were treated with antifungal therapy and it was observed total remission of the lesions and no recurrences were detected.

Adsorption of fluorobenzene onto granular activated carbon: isotherm and bioavailability studies.

The adsorption of a recalcitrant fluoroaromatic compound, fluorobenzene (FB), onto granular activated carbon (GAC) was evaluated. The respective isotherm was obtained and the Langmuir, Freundlich and Redlich-Peterson models were fitted to the experimental data, with the Redlich-Peterson model giving the best fitting. Freundlich model also provided a good fit but the Langmuir model could not adequately fit the experimental data, especially at high FB concentrations. Maximal adsorption capacity of FB onto GAC was found to be 388mg of FB per gram of GAC. The reversibility of the adsorption of FB onto GAC was investigated, both in the absence and presence of microorganisms. Abiotic desorption of FB occurred to a small extent (between 3% and 22%, for amounts of FB initially adsorbed to the GAC between 37 and 388mgg(-1)), and bioregeneration of GAC was shown to occur when the matrix was exposed to a FB degrading culture, with 58-80% of the adsorbed FB being biodegraded. A residual amount of FB showed not to be bioavailable, suggesting that part of the adsorbed FB may be irreversibly bound. The fraction of the non-bioavailable FB increased at higher amounts of adsorbed FB, from 19% to 33%. The results indicate that the GAC employed in this study has a good capacity to adsorb FB and that bioregeneration of this matrix is a feasible process.

Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies.

OBJECTIVES: The scientific literature presents conflicting data on a possible causal relationship between marijuana users and the development of head and neck cancer. DESIGN: This study performed a systematic review with meta-analysis. Articles were selected from various electronic databases using keywords obtained from the Medical Subject Headings (MeSH). After reading by three reviewers and scoring of methodological quality, six articles (totaling nine case-control studies) were assessed with Comprehensive Meta-Analysis(®) software. The value of effect (odds ratio) was calculated, which represented the chance of developing head and neck cancer between individuals who had smoked marijuana in their lifetime in models controlled for age, gender, race, and tobacco consumption. RESULTS: Approximately 12.6% of cases and 14.3% of controls were marijuana users. The meta-analysis found no association between exposure and disease (OR=1.021; IC 95%=0.912-1.14; p=0.718). CONCLUSION: No association between lifetime marijuana use and the development of head and neck cancer was found. The different methods of collection/presentation of results in the selected articles prevented other analyzes from being conducted. Additional studies are needed to assess for long-term effects.

Effects of the K+ channel blockers paspalitrem-C and paxilline on mammalian smooth muscle.

The tremorgenic alkaloids, paxilline and paspalitrem-C (0.1-10 microM), increased the spontaneous contractility of guinea-pig and rat urinary bladder, and rat duodenum, and induced tension in guinea-pig trachea. These effects are ascribed to blockade of high-conductance, Ca(2+)-activated K+ (BKCa) channels. Paxilline potentiated the charybdotoxin-induced stimulation of guinea-pig detrusor muscle; this is consistent with the alkaloid's ability to allosterically enhance the binding of charybdotoxin to smooth muscle membranes (Knaus et al., 1994). Paspalitrem-C and paxilline did not affect the myogenic activity of isolated portal vein from guinea-pig, which is insensitive to charybdotoxin, or of that from rat which is stimulated by charybdotoxin. Paxilline and paspalitrem-C also differed from charybdotoxin in that the alkaloids did not consistently elicit tension in guinea-pig aortic rings. These discrepancies are attributed to differences in relative potency, sites and/or mechanisms of action of the indole alkaloids vs. peptidyl blockers of the BKCa channel.

Effects of protein deficiency and natural intestinal infection with Giardia lamblia on jejunal intraepithelial lymphocytes in rats of different ages.

1. The interaction between experimental protein deprivation and natural intestinal infection by Giardia lamblia was studied in terms of its effects on the intraepithelial lymphocyte (IEL) population and morphology of the jejunal mucosa of rats of different ages. 2. Young, adult and old male Wistar rats received a protein-deficient diet (2% casein) or a control diet (20% casein) for 42 days. Mucosal height and the number of lymphocytes located among 500 consecutive epithelial cells (EC) along the villi or crossing the basement membrane were determined in PAS-stained jejunal fragments. 3. The number of IEL increased progressively with animal age, from 14 to 25 per 100 epithelial cells, with significant differences between age ranges. However, the number of IEL did not differ between control and protein-deficient rats in any of the age groups. The proportion of lymphocytes crossing the basement membrane was approximately two-fold greater in young (2.8/100 EC) and adult (5.8/100 EC) protein-deficient animals than in their respective controls (1.6 and 2.8/100 EC). The intensity of parasite colonization was moderate, from 3 to 5/100 EC and did not differ between groups. The pattern of morphologic changes of jejunal mucosa in protozoal infection did not differ between control and protein-deficient animals in any of the three age groups. 4. We conclude that intestinal infection with Giardia lamblia probably stimulated the local immune response, masking the reduction of the IEL population induced by protein deficiency. The increase in lymphocyte numbers with age may be related to prolonged antigenic stimulation promoted by infection.

Reactive sulfides relationship with metals in sediments from an eutrophicated estuary in Southeast Brazil.

The potential association of acid-volatile sulfides (AVS) and reactive (HCl soluble) Fe with the distribution of reactive trace metals (Cu, Cd, Ni, Pb and Zn) was investigated in sediment cores collected in the Iguaçu river estuarine system (Guanabara bay, Brazil), within the river (core R) and the bay (core B) areas. Moderate to extremely high AVS concentrations (33-314 micromol g(-1)) were found in the rapidly-accumulated sediments of this eutrophicated estuary. AVS showed significant correlations with Fe, Ni and Pb in core B, whereas no correlation between AVS and metals was observed in core R. Results suggest that the AVS:Fe molar ratio may often reflect the diagenetic conditions controlling the distribution of Cd and Cu in core B better than AVS and Fe levels themselves. A shift in the biogeochemical controls of metal distribution from the river to the open bay sediments is suggested, with a greater association of most metals with AVS and Fe in bay sediments.

Amastigotes forms of Trypanosoma cruzi detected in a renal allograft.

Trypanosoma cruzi, the causative agent of Chagas' disease assumes two distinct forms in vertebrate hosts: circulating trypomastigote and tissular amastigote. This latter form infects predominantly the myocardium, smooth and skeletal muscle, and central nervous system. The present work describes for the first time the detection of amastigote forms of T. cruzi in the renal parenchyma of a kidney graft recipient one month after transplantation. The patient was serologically negative for Chagas' disease and received no blood transfusion prior to transplant. The cadaver donor was from an endemic area for Chagas' disease. The recipient developed the acute form of the disease with detection of amastigote forms of T. cruzi in the renal allograft biopsy and circulating trypomastigote forms. The present report demonstrates that T. cruzi can infect the renal parenchyma. This mode of transmission warrants in endemic areas of Chagas' disease.

[Systemic lupus erythematous and myasthenia gravis: case report]. / Lupus eritematoso sistêmico associado a miastenia gravis. Relato de caso.

We report the case of a 24-year-old white woman admitted with a four year diagnosis of systemic lupus erythematosus and the recent onset of myasthenia gravis discussing the main differential diagnosis of weakness and fatigue in this patient. A review of literature approaching the association of myasthenia gravis and systemic lupus erythematosus is also done with emphasis on the clinical characteristics of these patients and the role of thymoma and thymectomy in the development of systemic lupus erythematosus in myasthenic patients.

Onychomycosis in João Pessoa City, Brazil.

Onychomycosis epidemiology is a combination of various factors which include, among others, clinical presentation, etiologic agents of the infection and the patient's history background. Out of a total of 672 nail samples examined, 460 (68.4%) were microscopy positive for fungi and 306 (66.5%) of these were culture positive, including Candida (82%), dermatophytes (13.4%), Trichosporon spp (3.6%) and nondermatophyte molds (1%). Onychomycosis was more frequent in females (79.7%) than in males (20.3%). These were more common in fingernails (96.1%) than in toenails (60%) and yeasts were the most isolated etiologic agents. Among the clinical presentations, paronychia (CP) (57.2%) and onycholysis (CO) (24.8%) were the most common, caused frequently by C. albicans in 52.6% and 60.5% of the cases, respectively. T. rubrum (44.4%) and Trichosporon spp (22.2%) were the most frequent species in the case of distal lateral subungual onychomycosis (DLSO). Fusarium spp was the agent responsible for 33.3% of the cases of proximal subungual onychomycosis (PSO) and for 14.3% of white superficial onychomycosis (WSO), whereas Acremonium spp was responsible for 14.3% of the cases of WSO.

[Lupus glomerulonephritis: a long-term follow-up]. / Glomerulonefrite lúpica: estudo da evolução a longo prazo.

PURPOSE: To evaluate and the long term course of patients with lupus nephritis, METHOD: Thirty seven patients with lupus nephritis followed in a referral, tertiary care center of a developing country (Brazil) were studied. The length of follow up was 52.4 + 13.3 months and mean age was 26.05 + 11.12 years. 84% of the patients were females and class IV nephritis was found to be the most frequent (80%). RESULTS: At the time of renal biopsy mean serum creatinine was 1.74 + 1.15 mg/dl, and 24 h-proteinuria was 2.62 + 2.89 g. Fifty one per cent of the patients with elevated serum creatinine showed a decrease in these values. Of the variables studied (age, sex, proteinuria, presence of hypertension and serum creatinine at biopsy), serum creatinine elevation was the only one to be associated with poorer prognosis. Remission of the nephrotic syndrome occurred in 65% of the patients. Actuarial survival rate was 96% at 1 year, 82% at 5 years, 70% at 10 years and 70% at 12 years. Five patients developed end stage renal failure and 7 died. Infection was the most frequent(57%) cause of death. CONCLUSION: Among several factors studied the only which has been associated with chronic renal failure was elevated serum creatinine at the time of biopsy. Infections were the main cause of death.

[Lupus band test: diagnostic value in disseminated lupus erythematosus]. / Lupus band test: valor diagnóstico no lupus eritematoso disseminado.

By direct immunoflurescence, deposits of immunoglubins and complement were investigated at the dermal epidermal junction in skin specimens from 210 patients divided into three groups: A--134 patients without lupus; B--54 patients with Systemic Lupus Erythematosus (SLE); C--22 patients with Discoid Lupus Erythematosus. Twenty two patients from group B were submitted to renal biopsy: 20 of these demonstrated a positive lupus band test and data suggested a positive correlation between the intensity of immunoglobulin and complement deposition at the dermal epidermal junction with more severe renal involvement. The other 32 patients were not submitted to renal biopsy; in sediment and band test, may be of value in the prevision of patients with higher probability of developing more serious renal lesions. Our results revealed a high specificity (85.5%) and sensitivity (87%). Test positivity was uninfluenced by steroid and immunosuppressive therapy. The test appears to be of great interest for use on all patients who fail to meet the criteria for the diagnosis of SLE but whose condition suggest such a diagnosis.

Methods of analysis for peritubular capillaritis and glomerulitis in acute renal rejection: capillaritis in management of routine diagnosis.

Glomerulitis and peritubular capillaritis have been recognized as important lesions in acute renal rejection (AR). We studied glomerulitis and peritubular capillaritis in AR by 2 methods and investigated associations with C4d, type/grade of AR, and allograft survival time. Glomerulitis was measured according to Banff scores (glomerulitis by Banff Method [gBM]) and by counting the number of intraglomerular inflammatory cells (glomerulitis by Quantitative Method [gQM]). Capillaritis was classified by the Banff scoring system (peritubular capillaritis by Banff Method [ptcBM]) and by counting the number of cells in peritubular capillaries in 10 high-power fields (hpf; peritubular capillaritis by Quantitative Method [ptcQM]). These quantitative analyses were performed in an attempt to improve our understanding of the role played by glomerulitis and capillaritis in AR. The g0 + g1 group (gBM) associated with negative C4d (P = .02). In peritubular capillaritis, a larger number of cells per 10 hpf in peritubular capillaries (ptcQM) were observed in positive C4d cases (P = .03). The group g2 + g3 (gBM) correlated with graft loss (P = .01). Peritubular capillaritis was not significantly related to graft survival time. Our study showed that the Banff scoring system is the best method to study glomerulitis and observed that the evaluation of capillaritis in routine biopsies is difficult and additional studies are required for a better understanding of its meaning in AR biopsy specimens of renal allografts.

Safety of kidney transplantation using anti-HBc-positive donors.

BACKGROUND: Prospective studies evaluating the risk of hepatitis B virus (HBV) transmission in transplants of kidneys from hepatitis B core antibody (anti-HBc)-positive/hepatitis B surface antibody (anti-HBs)-negative donors are still lacking. The objective of this study was to assess the safety of kidney transplantation with the use of anti-HBc-positive donors. METHODS: This prospective case series study included 50 kidney transplant recipients from anti-HBc-positive donors with or without anti-HBs positivity. Recipients were required to test positive for anti-HBs (titers >10 mUI/mL), regardless of anti-HBc status, and negative for hepatitis B surface antigen (HBsAg). Recipient and donor data were retrieved from medical records, databases, and organ procurement organization sheets. Liver function tests were performed at progressively increasing post-transplantation intervals. Complete serologic tests for HBV were performed before transplantation, 3 and 6 months after transplantation, and annually thereafter. RESULTS: Six months after transplantation, all recipients were negative for HBsAg, HBeAg, anti-HBe, and anti-HBcIgM. No seroconversion was observed among the 20 patients who received kidneys from anti-HBc-positive/anti-HBs-negative donors. No patient showed elevated liver enzymes during follow-up. CONCLUSIONS: Kidney transplantation using organs from anti-HBcIgG-positive donors (even when they are concurrently anti-HBs negative) in anti-HBs-positive recipients is a safe procedure and may be considered as a way to expand the donor pool.

Acute antibody-mediated rejection of renal transplant associated with cellular crescents: first case report.

Acute antibody-mediated rejection is characterized by histological abnormalities such as glomerulitis, capillaritis, or thrombosis associated with presence of C4d and specific anti-donor antibodies. Reports on the association of glomerular injuries with cellular crescents in antibody-mediated rejection are not found in the literature. We report a unique case of antibody-mediated rejection associated with cellular crescents and suggest that such histological abnormality should be considered in the differential diagnosis of acute antibody-mediated rejection.