Comparison of the Effect of Agitation on Whitening and Tooth Sensitivity of In-Office Bleaching: A Randomized Clinical Trial.

OBJECTIVE: This single-blind, split-mouth, randomized trial was aimed at evaluating the bleaching efficacy (BE) and tooth sensitivity (TS) of a 20% hydrogen peroxide (HP) bleaching agent used under active or passive application. METHODS AND MATERIALS: Twenty-two patients with canines darker than C2 were selected. Teeth were bleached in two sessions, with a one-week interval between treatments. The bleaching agent was applied using active (HPactive) or passive (HPpassive) application. Each tooth in the HPactive-allocated hemiarch received bleaching gel with sonic activation after 10 and 30 minutes from the start of treatment, with rounded movements all over the buccal surface. The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (VITA Easyshade Spectrophotometer) methods at baseline and 30 days after the second session. TS was recorded up to 48 hours after treatment using a 0-10 visual analog scale. Color change in shade guide units (SGUs) and ΔE was analyzed using a Wilcoxon test (α=0.05). The absolute risk and intensity of TS were evaluated using McNemar test and a Wilcoxon test, respectively (α=0.05). RESULTS: Significant whitening was observed in both groups after 30 days of clinical evaluation. The activation did not significantly influence BE (ΔSGU HPpassive=5.6 and HPActive=5.8; p=0.98; and ΔE HPpassive=10.6 and HPactive=10.3; p=0.83). Absolute risk of TS (HPactive=36.4% and HPpassive=31.8%; p=0.94) was similar for both groups (Fisher exact test). TS intensity (visual analogue scale) was higher during the bleaching sessions and up to 24 hours thereafter for both groups, with no differences between groups (two-way analysis of variance and Tukey). CONCLUSION: The active application of a 20% HP gel did not improve BE and TS.

Sonic Activation of a Desensitizing Gel Prior to In-Office Bleaching.

This double-blind, randomized, and controlled clinical trial evaluated the effect of sonic activation during the application of a desensitizing agent (DA) containing 5% potassium nitrate and 2% sodium fluoride on the occurrence of tooth sensitivity (TS) associated with in-office dental bleaching. Treatment with or without sonic activation of the DA was randomly assigned to one-half of the maxillary teeth of 34 patients in a split-mouth design. On the side without sonic activation (noSA), the DA was applied and maintained in contact with the teeth for 10 minutes. On the sonic activation side (SA), the DA was activated 30 seconds per tooth. The DA application was followed by application of 35% hydrogen peroxide in two bleaching sessions separated by a one-week interval. The primary outcome was the absolute risk of TS, recorded using a numeric rating scale and a visual analog scale. Color was evaluated with a digital spectrophotometer and a value-oriented shade guide. No significant difference between treatments was observed in the absolute risk of TS, which occurred in 93% (p=1.00) of both noSA and SA groups. The TS intensity was higher in the 24-hour interval after sessions, for both treatments, without differences between them. There was no difference in the color change for the treatments, with the average change in number of shade guide units of the Vita Classical scale of 6.35 for both (p=0.87). Sonic activation of DA containing 5% potassium nitrate and 2% sodium fluoride did not reduce the absolute risk and intensity of TS associated with in-office bleaching.

Comparison of the Effect of Agitation on Whitening and Tooth Sensitivity of In-Office Bleaching: A Randomized Clinical Trial.

OBJECTIVE: This single-blind, split-mouth, randomized trial was aimed at evaluating the bleaching efficacy (BE) and tooth sensitivity (TS) of a 20% hydrogen peroxide (HP) bleaching agent used under active or passive application. METHODS AND MATERIALS: Twenty-two patients with canines darker than C2 were selected. Teeth were bleached in two sessions, with a one-week interval between treatments. The bleaching agent was applied using active (HPactive) or passive (HPpassive) application. Each tooth in the HPactive-allocated hemiarch received bleaching gel with sonic activation after 10 and 30 minutes from the start of treatment, with rounded movements all over the buccal surface. The color changes were evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (VITA Easyshade Spectrophotometer) methods at baseline and 30 days after the second session. TS was recorded up to 48 hours after treatment using a 0-10 visual analog scale. Color change in shade guide units (SGUs) and ΔE was analyzed using a Wilcoxon test (α=0.05). The absolute risk and intensity of TS were evaluated using McNemar test and a Wilcoxon test, respectively (α=0.05). RESULTS: Significant whitening was observed in both groups after 30 days of clinical evaluation. The activation did not significantly influence BE (ΔSGU HPpassive=5.6 and HPActive=5.8; p=0.98; and ΔE HPpassive=10.6 and HPactive=10.3; p=0.83). Absolute risk of TS (HPactive=36.4% and HPpassive=31.8%; p=0.94) was similar for both groups (Fisher exact test). TS intensity (visual analogue scale) was higher during the bleaching sessions and up to 24 hours thereafter for both groups, with no differences between groups (two-way analysis of variance and Tukey). CONCLUSION: The active application of a 20% HP gel did not improve BE and TS.

Aspergillus section Flavi and aflatoxins in Brazilian cassava (Manihot esculenta Crantz) and products.

Aflatoxins are carcinogenic compounds produced by some species of Aspergillus, especially those belonging to Aspergillus section Flavi. Their occurrence in food may start in the field, in the post-harvest, or during storage due to inadequate handling and storage. Because cassava is a staple food for a high percentage of the Brazilian population, we evaluated the presence of aflatoxin-producing species in cassava tubers, cassava products (cassava flour, cassava starch, sour starch, and tapioca flour), and in soil samples collected from cassava fields. In addition, the levels of aflatoxin contamination in cassava products were quantified. A total of 101 samples were analyzed, and 45 strains of Aspergillus section Flavi were isolated. Among the identified species, Aspergillus flavus, Aspergillus arachidicola, Aspergillus novoparasiticus, and Aspergillus parasiticus were found. The majority of strains (73.3%) tested for their aflatoxin-producing ability in synthetic media was positive. Despite that, cassava and cassava products were essentially free of aflatoxins, and only one sample of cassava flour contained traces of AFB1 (0.35 µg/kg).

A new radon prediction approach for an assessment of radiological potential in drinking water.

Inhaled radon from groundwater used for domestic purposes is one of the sources of natural radioactivity into indoor air. Due to uranium-bearing minerals occurrences, hydrogeochemical conditions, tectonic structures, and hydraulic circuits, the radon pathway from rocks to groundwater is quite unpredictable. High radon potential from bedrocks is not always associated with high radon levels in groundwater. Besides, inhaled radon from domestic use may also increase the exposure toindoor radon levels. This innovative methodology using hydrogeochemical conditions and groundwater flow transport was used for radon predictions in the underground to ensure safe drinking water ingestion and inhalation. This innovative radon prediction methodology is based on classic hydrogeochemical analyses (Eh-pH, Piper, Schöeller and Gibb's diagrams) and multivariate statistical analyses (Principal Component Analysis and Pearson's correlation). High dissolution of major ions does not imply high radon mobilization from rocks to groundwater. The travel time was estimated to developed a flow transport of contaminated groundwater. Radiological results show that of the 25 sampled springs, five of them contained radon concentrations above the Portuguese imposed limit (222Rn = 500 Bq·L-1), and 16 of them with values above the WHO recommended limit (222Rn = 100 Bq·L-1). Overall, this new approach of radon prediction showed that uranium enrichment in rocks at ideal hydrochemical conditions and emanation coefficient, and shallow circuits, are responsible for radon increasing in drinking water. The proposed approach allow to predict the areas with high radon potential groundwaters, being a tool to be used by water planners and policy makers for corrective and preventive measures in shallow groundwater flows. To safeguard clean water within the predefined deadline of Sustainable Development Goals (2030) and to ensure human health in compliance with WHO guidelines for safe drinking water, should be established priority water protection policies to reduced radon in this contaminated springs (n = 16).

Clinical Effects of Desensitizing Prefilled Disposable Trays in In-office Bleaching: A Randomized Single-blind Clinical Trial.

OBJECTIVES: This study aimed to evaluate the desensitizing effect of a prefilled disposable tray containing potassium nitrate and fluoride on the self-reported tooth sensitivity (TS) and the bleaching efficacy of 40% hydrogen peroxide bleaching agent used for in-office bleaching in comparison with potassium nitrate and fluoride gel applied in a conventional-delivered tray system in an equivalence clinical trial. METHODS AND MATERIALS: Seventy-eight patients, with a right maxillary canine darker than A3, were selected for this single-blind (evaluators), randomized clinical trial. Teeth were bleached in two sessions with a one-week interval in between. Before in-office bleaching, the prefilled disposable tray or conventional tray containing potassium nitrate and fluoride was used for 15 minutes. Subsequently, the bleaching agent was applied in two 20-minute applications (per the manufacturer's directions) in each session. The color change was evaluated by subjective (Vita Classical and Vita Bleachedguide) and objective (Easyshade Advance Spectrophotometer) methods at baseline and 30 days after the first bleaching session. TS was recorded for up to 48 hours using a 0-10 visual analog scale. The absolute risk was evaluated by chi-square test, while the intensity of TS was evaluated by McNemar test (α=0.05). Color change in shade guide units and ΔE was analyzed by Student t-test for independent samples (α=0.05). RESULTS: Significant whitening was observed in both groups after 30 days of clinical evaluation. The use of different methods of desensitizer in a tray did not influence the absolute risk and intensity of TS (p>0.05), although a tendency of lower risk of TS with the prefilled disposable tray containing potassium nitrate and fluoride was observed. CONCLUSION: The use of a prefilled disposable tray containing potassium nitrate and fluoride before the application of the in-office bleaching product did not affect the whitening degree and decreased self-reported TS when compared with a conventional-delivered tray system.

Targeting Cancer Resistance via Multifunctional Gold Nanoparticles.

Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR). Selective delivery of the ZnD nanosystem to cancer cells was achieved by active targeting via cetuximab, NanoZnD, which significantly inhibited cell proliferation and triggered the death of resistant tumor cells, thus improving efficacy. In vivo studies in a colorectal DOX-resistant model corroborated the capability of NanoZnD for the selective targeting of cancer cells, leading to a reduction of tumor growth without systemic toxicity. This approach highlights the potential of gold nanoformulations for the targeting of drug-resistant cancer cells.

An approach to validate groundwater contamination risk in rural mountainous catchments: the role of lateral groundwater flows.

Computer models dedicated to the validation of groundwater contamination risk in the rural environment, namely the risk of contamination by nitrate leachates from agriculture fertilizers, are frequently based on direct comparison of risky areas (e.g., cropland, pastures used for livestock production) and spatial distributions of contaminant (nitrate) plumes. These methods are fated to fail where lateral flows dominate in the landscape (mountainous catchments) displacing the nitrate plumes downhill and from the risky spots. In these cases, there is no connection between the spatial location of risky areas and nitrate plumes, unless the two locations can be linked by a contaminant transport model. The main purpose of this paper is therefore to introduce a method whereby spatio-temporal links can be demonstrated between risky areas (contaminant sources), actual nitrate plumes (contaminant sinks) and modeled nitrate distributions at specific groundwater travel times, thereby validating the risk assessment. The method assembles a couple of well known algorithms, namely the DRASTIC model [1,2] and the Processing Modflow software (https://www.simcore.com), but their combination as risk validation method is original and proved efficient in its initial application, the companion paper of Pacheco et al. [3].

Diversity of Anopheles mosquitoes from four landscapes in the highest endemic region of malaria transmission in Brazil.

Malaria transmission in South America is overwhelmingly located in the Amazon region with limited cases outside that biome. A key factor in the mitigation of malaria transmission is the determination of vector diversity and bionomics in endemic areas. Anopheles mosquitoes were collected in four different landscapes of Cruzeiro do Sul-Acre, the current area with highest malaria transmission in Brazil. We performed adult mosquito collections every three months over two years and associated vector occurrence with local abiotic factors. A total of 1,754 Anopheles belonging to nine species were collected, but only four of them (An. albitarsis s.l. Lynch-Arribalzaga, An. braziliensis Chagas, An. peryassui Dyar and Knab, and An. triannulatus Neiva and Pinto) represented 77.1% of the total. Vector density and diversity was uneven across field sites and collection periods. Higher Anopheles abundance (54.8%) and richness were observed in a deforested palm tree area (IFC), with An. braziliensis the most frequent mosquito (40.5%). Only 7.3% of mosquitoes were collected in the SAB village, but 66.4% of them were An. darlingi and An. oswaldoi, species often regarded as primary and secondary vectors of malaria in the Amazon region. A distinct biting preference was observed between 18:00-19:40. The distance from the nearest breeding site and minimum temperature explained 41.6% of the Anopheles community composition. Our data show that the Anopheles species composition may present great variation on a microgeographic scale.

Effectiveness of In-office Hydrogen Peroxide With Two Different Protocols: A Two-center Randomized Clinical Trial.

OBJECTIVES: The aim of this study was to compare the bleaching efficacy and tooth sensitivity (TS) of a 38% hydrogen peroxide bleaching agent used for in-office bleaching, applied under different time protocols: a 40-minute application or two 20-minute applications. METHODS AND MATERIALS: Forty-four patients from Brazil and Colombia, with right superior canines darker than C2, were selected for this multicenter, single-blind, randomized trial. The teeth were bleached in two sessions, with a one-week interval between them, in a split-mouth design. The bleaching agent was applied in two 20-minute (2×20) applications or one 40-minute (1×40) application in each session according to the manufacturer's instructions. The color changes were evaluated by using subjective (Vita Classical and Vita Bleachedguide) and objective (Easyshade Spectrophotometer) methods at baseline and 30 days after the second session. Tooth sensitivity was recorded up to 48 hours with a 0-10 visual analog scale. Also, the pH values during the application of bleaching were recorded. Color change in shade guide units and ΔE were analyzed by using the Student t-test (α=0.05). The absolute risk and intensity of TS were evaluated with the McNemar test, the Wilcoxon signed-rank test, and the Friedman test, respectively (α= 0.05). RESULTS: Significant whitening was observed in both groups after 30 days of clinical evaluation. The use of a 40-minute application did not significantly influence the absolute risk of TS (68%, 95% confidence interval [CI] = 53-80) as well as the intensity of TS compared with the acid bleaching gel (absolute risk of 82%, 95% CI = 68-91). The pH values did not differ significantly between groups and at the different assessment periods ( p=0.42). CONCLUSION: The use of a 40-minute in-office bleaching agent gel application produced the same whitening degree and TS that the two 20-minute bleaching agent applications did. The former preferably should be applied because one 40-minute application does not require gel refreshing.

Targeting canine mammary tumours via gold nanoparticles functionalized with promising Co(II) and Zn(II) compounds.

BACKGROUND: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). AIMS: Evaluate the efficiency of two metal compounds [Zn(DION)2 ]Cl (TS262, DION = 1,10-phenanthroline-5,6-dione) and [CoCl(H2 O)(DION)2 ][BF4 ] (TS265) and novel nanovectorizations designed to improve the anti-cancer efficacy of these compounds in a new CMT derived cell line (FR37-CMT). MATERIALS AND METHODS: FR37-CMT cells were exposed to different concentrations of TS262 and TS265 and two new nanoparticle systems and cellular viability was determined. These nanosystems are composed of polyethylene-glycol, bovine-serum-albumin and TS262 or TS265 (NanoTS262 or NanoTS265, respectively). RESULTS: In FR37-CMT, TS262 and TS265 displayed IC50 values well below those displayed by doxorubicin and cisplatin. The nanovectorizations further decreased the IC50 values. DISCUSSION: TS262 and TS265 proved to be effective against FR37-CMT cells and more effective than of doxorubicin and cisplatin. The Nanosystems efficiently delivered the cytotoxic cargo inducing a significant reduction of cell viability in FR37-CMT cell line when compared to the free compounds. CONCLUSIONS: TS262 and TS265 are compounds with potential in the treatment of CMTs. NanoTS262 and NanoTS265 demonstrate that such simple nanovectorization via gold nanoparticles shows tremendous potential as anti-cancer formulations, which may easily be expanded to suit other cargo.

The characterization of Bordetella pertussis strains isolated in the Central-Western region of Brazil suggests the selection of a specific genetic profile during 2012-2014 outbreaks.

Pertussis is a worldwide acute respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, the bacterium continues to circulate in populations and is still one of the most common vaccine-preventable diseases. In Brazil, pertussis incidence has presented a significant decrease since 1990 but since 2011 a sudden increase in incidence has been observed. Thus, the aim of this study was to perform a molecular epidemiological characterization of B. pertussis strains isolated in the Central-Western region (specifically in Distrito Federal) of Brazil from August 2012 to August 2014. During this period, 92 B. pertussis strains were isolated from the outbreaks. All strains were characterized by serotyping and XbaI pulsed-field gel electrophoresis profiles. From August to December 2012, the most prevalent serotype observed was 1,3 (13/17). During 2013 the prevalence of serotype 1,3 decreased (13/30) and from January 2014 to August 2014 the most prevalent serotype was 1,2 (33/45). Fourteen PFGE profiles were identified. Of these, BP-XbaI0039 prevalence increased from 3/17 in 2012 to 10/30 in 2013, and 35/45 in 2014. These results evidence the selection of a specific genetic profile during this period, suggesting the occurrence of a bacterial genomic profile with high circulation potential.

Treatment of periodontal disease with guided tissue regeneration technique using a hydroxyapatite and polycaprolactone membrane / Tratamento da doença periodontal pela técnica da regeneração tecidual guiada utilizando uma membrana de hidroxiapatita e policaprolactona

The aim of this study was to evaluate the use of a malleable membrane composed of hydroxyapatite (60%) and polycaprolactone (40%) as treatment of periodontal disease experimentally induced in dogs. A bone defect of standardized dimensions was created between the roots of the third and fourth premolar of 12 dogs for periodontal disease induction. Six dogs had the defect covered by the membrane and six dogs received only standard treatment for periodontal disease, also applied to dogs in the treated group. The animals were clinically monitored during the experiment. Radiographs were taken after surgery and at 60 days after treatment initiation. Clinical attachment level was also assessed in those moments. On the 60th day, dental sample of all animals, containing tooth, defect and periodontal tissues, were harvested, fixed in formalin and analyzed by microtomography and histology. During the experimental period, the animals showed no pain and purulent discharge, however, there was dehiscence in 50% of animals and membrane exposure in five out of six animals in the treated group. Clinical attachment level showed no difference between groups. Radiographs showed radiopacity equal to the alveolar bone in both groups. The microtomography revealed that the control group had higher bone volume in the defect compared to the treated group; however, the furcation was not filled by new alveolar bone in any animal. Histological analysis revealed that junctional epithelium invasion was lighter in the control group. New bone was only observed in the apical edge of the defect in both groups. Although the composite is biocompatible and able to keep the space of the defect, it did not promote periodontal tissue regeneration within 60 days of observation.(AU)

O objetivo do presente trabalho foi avaliar a utilização de membrana moldável constituída por hidroxiapatita (60%) e policaprolactona (40%) como tratamento da doença periodontal, induzida experimentalmente em cães. Um defeito ósseo de dimensões padronizadas foi realizado entre as raízes do terceiro e do quarto pré-molares de 12 cães para indução da doença periodontal. Todos os cães receberam tratamento padrão para doença periodontal, e seis desses animais foram tratados também com a aplicação da membrana sobre o defeito. Os animais foram acompanhados clinicamente durante o experimento. Radiografias foram realizadas no pós-operatório e aos 60 dias após o início do tratamento. O nível clínico de inserção também foi avaliado nesses momentos. Aos 60 dias, a amostra dental de todos os animais contendo o dente, o defeito e os tecidos periodontais foi coletada, fixada em formol e analisada por microtomografia e histologia. Durante o período experimental, os animais não apresentaram dor e secreção purulenta, entretanto houve deiscência em 50% dos animais e exposição de membrana em cinco dos seis animais do grupo tratado. Nível clínico de inserção não apresentou diferença entre os grupos. As imagens radiográficas mostraram radiopacidade igual ao osso alveolar em ambos os grupos. A microtomografia revelou que o grupo controle apresentou maior volume ósseo no defeito em relação ao grupo tratado, no entanto, em todos os animais, a região de furca não foi preenchida por novo osso alveolar. A análise histológica revelou que a invasão por epitélio juncional foi mais discreta no grupo controle. Osso novo foi apenas observado na borda apical do defeito em ambos os grupos. Embora o compósito seja biocompatível e tenha sido capaz de manter o espaço do defeito, ele não promoveu a regeneração dos tecidos periodontais no período de 60 dias de observação.(AU)

Indoor radon risk associated to post-tectonic biotite granites from Vila Pouca de Aguiar pluton, northern Portugal.

At Vila Pouca de Aguiar area, northern Portugal, crops out a post-tectonic Variscan granite pluton, related with the Régua-Vila Real-Verín fault zone, comprising three types of biotite granites. Among these granites, PSG granite yield the highest average contents of U, probably due to its enrichment in accessory U-bearing minerals such as zircon. In the proximity of faults and joints, these granites are often affected by different degrees of hydrothermal alteration, forming reddish altered rocks, commonly known as "episyenites". These altered rocks are probably associated to the occurrence of hydrothermal processes, which led to uranium enrichment in the most advanced stages of episyenitization. In these granites, both average gamma absorbed dose rates in outdoor and indoor air are higher than those of the world average. Furthermore, even in the worst usage scenario, all these granites can be used as a building material, since their annual effective doses are similar to the limit defined by the European Commission. The geometric mean of radon activity of 91 dwellings located at the Vila Pouca de Aguiar pluton is 568Bqm(-3), exceeding that of other northern Portuguese granites. Measurements carried out during a winter season, indicate that 62.6% of the analysed dwellings yield higher indoor radon average values than the Portuguese legislation limit (400Bqm(-3)), and annual effective doses due higher than the world's average value (1.2mSvy(-1)). The interaction of geogenic, architectural and anthropogenic features is crucial to explain the variance in the geometric mean of radon activity of dwellings from Vila Pouca de Aguiar pluton, but the role of geologic faults is probably the most important decisive factor to increase the indoor radon concentration in dwellings. Hence, the development of awareness campaigns in order to inform population about the incurred radiological risks to radon exposure are highly recommended for this specific area.

Mitofusin-mediated ER stress triggers neurodegeneration in pink1/parkin models of Parkinson's disease.

Mutations in PINK1 and PARKIN cause early-onset Parkinson's disease (PD), thought to be due to mitochondrial toxicity. Here, we show that in Drosophila pink1 and parkin mutants, defective mitochondria also give rise to endoplasmic reticulum (ER) stress signalling, specifically to the activation of the protein kinase R-like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response (UPR). We show that enhanced ER stress signalling in pink1 and parkin mutants is mediated by mitofusin bridges, which occur between defective mitochondria and the ER. Reducing mitofusin contacts with the ER is neuroprotective, through suppression of PERK signalling, while mitochondrial dysfunction remains unchanged. Further, both genetic inhibition of dPerk-dependent ER stress signalling and pharmacological inhibition using the PERK inhibitor GSK2606414 were neuroprotective in both pink1 and parkin mutants. We conclude that activation of ER stress by defective mitochondria is neurotoxic in pink1 and parkin flies and that the reduction of this signalling is neuroprotective, independently of defective mitochondria. A video abstract for this article is available online in the supplementary information.

Parp mutations protect against mitochondrial dysfunction and neurodegeneration in a PARKIN model of Parkinson's disease.

The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is an essential co-factor for cellular energy generation in mitochondria as well as for DNA repair mechanisms in the cell nucleus involving NAD(+)-consuming poly (ADP-ribose) polymerases (PARPs). Mitochondrial function is compromised in animal models of Parkinson's disease (PD) associated with PARKIN mutations. Here, we uncovered alterations in NAD(+) salvage metabolism in Drosophila parkin mutants. We show that a dietary supplementation with the NAD(+) precursor nicotinamide rescues mitochondrial function and is neuroprotective. Further, by mutating Parp in parkin mutants, we show that this increases levels of NAD(+) and its salvage metabolites. This also rescues mitochondrial function and suppresses dopaminergic neurodegeneration. We conclude that strategies to enhance NAD(+) levels by administration of dietary precursors or the inhibition of NAD(+)-dependent enzymes, such as PARP, that compete with mitochondria for NAD(+) could be used to delay neuronal death associated with mitochondrial dysfunction.

Highly efficient and reusable CNT supported iron(ii) catalyst for microwave assisted alcohol oxidation.

The highly efficient eco-friendly synthesis of ketones (yields over 99%) from secondary alcohols is achieved by combination of [FeCl2{η(3)-HC(pz)3}] (pz = pyrazol-1-yl) supported on functionalized multi-walled carbon nanotubes and microwave irradiation, in a solvent-free medium. The carbon homoscorpionate iron(ii) complex is the first one of this class to be used as catalyst for the oxidation of alcohols.

Isolation and molecular identification of lactic acid bacteria and Bifidobacterium spp. from faeces of the blue-fronted Amazon parrot in Brazil.

In Brazil, the blue-fronted Amazon parrot (Amazona aestiva) is a common pet. The faecal microbiota of these birds include a wide variety of bacterial species, the majority of which belong to the Gram-positive lactic acid bacteria (LAB) clade. The aim of this study was to investigate differences in the diversity and abundance of LAB and Bifidobacterium spp. in the cloacae between wild and captive birds and to select, identify and characterise LAB for consideration as a parrot probiotic. Cloacal swabs were collected from 26 wild and 26 captive birds. Bacterial DNA was extracted, and the 16S rRNA genes were amplified. The numbers of PCR-positive Enterococcus, Pediococcus, and Lactobacillus species isolated from wild and captive birds were significantly different (P<0.05). Enterococcus was the most frequently isolated genus, followed by Pediococcus, Lactobacillus, Lactococcus and Bifidobacterium. Enterococcus faecium, Pediococcus pentosaceus, Lactococcus lactis, Lactobacillus coryniformis, Lactobacillus sanfranciscensis and Bifidobacterium bifidum were the most frequently isolated species from all birds. This study increases our understanding of the faecal microbiota, and may help to improve the nutrition and habitat management of captive and wild parrots. The bacterial population identified in the faecal microbiota of clinically healthy wild and captive parrots can serve as a database to analyse variations in the gut microbiota of pathogen-infected parrots and to develop probiotics specific to these genera.

Mitochondrial proteolytic stress induced by loss of mortalin function is rescued by Parkin and PINK1.

The mitochondrial chaperone mortalin was implicated in Parkinson's disease (PD) because of its reduced levels in the brains of PD patients and disease-associated rare genetic variants that failed to rescue impaired mitochondrial integrity in cellular knockdown models. To uncover the molecular mechanisms underlying mortalin-related neurodegeneration, we dissected the cellular surveillance mechanisms related to mitochondrial quality control, defined the effects of reduced mortalin function at the molecular and cellular levels and investigated the functional interaction of mortalin with Parkin and PINK1, two PD-related proteins involved in mitochondrial homeostasis. We found that reduced mortalin function leads to: (1) activation of the mitochondrial unfolded protein response (UPR(mt)), (2) increased susceptibility towards intramitochondrial proteolytic stress, (3) increased autophagic degradation of fragmented mitochondria and (4) reduced mitochondrial mass in human cells in vitro and ex vivo. These alterations caused increased vulnerability toward apoptotic cell death. Proteotoxic perturbations induced by either partial loss of mortalin or chemical induction were rescued by complementation with native mortalin, but not disease-associated mortalin variants, and were independent of the integrity of autophagic pathways. However, Parkin and PINK1 rescued loss of mortalin phenotypes via increased lysosomal-mediated mitochondrial clearance and required intact autophagic machinery. Our results on loss of mortalin function reveal a direct link between impaired mitochondrial proteostasis, UPR(mt) and PD and show that effective removal of dysfunctional mitochondria via either genetic (PINK1 and Parkin overexpression) or pharmacological intervention (rapamycin) may compensate mitochondrial phenotypes.

Unravelling mitochondrial pathways to Parkinson's disease.

Mitochondria are essential for cellular function due to their role in ATP production, calcium homeostasis and apoptotic signalling. Neurons are heavily reliant on mitochondrial integrity for their complex signalling, plasticity and excitability properties, and to ensure cell survival over decades. The maintenance of a pool of healthy mitochondria that can meet the bioenergetic demands of a neuron, is therefore of critical importance; this is achieved by maintaining a careful balance between mitochondrial biogenesis, mitochondrial trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that underlie these processes are gradually being elucidated. It is widely recognized that mitochondrial dysfunction occurs in many neurodegenerative diseases, including Parkinson's disease. Mitochondrial dysfunction in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress, is observed in several Parkinson's disease models. However, identification of the recessive genes implicated in Parkinson's disease has revealed a common pathway involving mitochondrial dynamics, transport, turnover and mitophagy. This body of work has led to the hypothesis that the homeostatic mechanisms that ensure a healthy mitochondrial pool are key to neuronal function and integrity. In this paradigm, impaired mitochondrial dynamics and clearance result in the accumulation of damaged and dysfunctional mitochondria, which may directly induce neuronal dysfunction and death. In this review, we consider the mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In particular, we focus on the mechanisms that underlie mitochondrial homeostasis, and discuss their importance in neuronal integrity and neurodegeneration in Parkinson's disease.