Assessing cognitive decline in the aging brain: lessons from rodent and human studies.

As life expectancy continues to increase worldwide, age-related dysfunction will largely impact our societies in the future. Aging is well established to promote the deterioration of cognitive function and is the primary risk factor for the development of prevalent neurological disorders. Even in the absence of dementia, age-related cognitive decline impacts specific types of memories and brain structures in humans and animal models. Despite this, preclinical and clinical studies that investigate age-related changes in brain physiology often use largely different methods, which hinders the translational potential of findings. This review seeks to integrate what is known about age-related changes in the brain with analogue cognitive tests used in humans and rodent studies, ranging from "pen and paper" tests to virtual-reality-based paradigms. Finally, we draw parallels between the behavior paradigms used in research compared to the enrollment into clinical trials that aim to study age-related cognitive decline.

Achieving waste recovery goals in the medium/long term: Eco-efficiency analysis in a Brazilian city by using the LCA approach.

The aim of this study was to analyse how to ensure that medium- and long-term waste recovery goals can be achieved in Brazilian cities, based on the incorporation of viable and accessible technology. The identification of the strengths of the Brazilian cities with better (dry and wet) waste recovery rates allowed different strategies to be proposed for João Pessoa (the city selected as a case study). Those strategies were based on the improvement of (1) the selective collection of the recyclable dry waste fraction, (2) the material recovery facility to increase the recovery of recyclable dry waste fraction to be recycled and/or wet waste fraction to be composted, and finally (3) the working conditions of waste workers. A combination of these improvement strategies at two different levels of implementation (partial and total) allowed the definition of 14 alternative scenarios, which were analysed from an eco-efficiency perspective (environmental vs. economic). After analysing the evolution over time of the alternative scenarios proposed, the proposal that was finally selected was based on the initial implementation of a mechanical biological and composting facility capable of handling up to 50% of the mixed municipal solid waste collected by 2023 with a material recovery efficiency of 30%. From there, the efficiency of the mechanical biological and composting facility should increase up to 60% to achieve the waste recovery goals by 2034 (management of 60% of the mixed waste collected). This rate has not yet been reached in any of the Brazilian mechanical biological and composting facilities analysed, so the reduction in the amount of waste generated and the increase in the selective separation of waste at source are identified as key elements to be able to fulfil the long-term goals. The approach used in the case study provides guidelines for application in other geographical contexts.

Performance assessment of 11 commercial serological tests for SARS-CoV-2 on hospitalised COVID-19 patients.

BACKGROUND: Commercial availability of serological tests to evaluate immunoglobulins (Ig) targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has grown exponentially since the start of the coronavirus disease 2019 (COVID-19) outbreak. Thorough validation of these tests is important before use as epidemiological tools to infer seroprevalence in specific populations and as diagnostic tools to complement molecular approaches (e.g., quantitative reverse transcription-polymerase chain reaction). METHODS: Commercial serological tests from 11 suppliers were assayed side-by-side using 126 samples from SARS-CoV-2-infected inpatients and 36 from healthy and HIV-infected individuals. RESULTS: The majority of the tests assayed have >95% specificity. For the sensitivity calculation, samples were stratified by days since symptoms onset; sensitivity peaks at 16-21 days for IgM and IgA (maximum 91.2%, Euroimmun) and, dependant on the test, at 16-21 or >21 days for IgG (maximum 94.1%, Snibe). Data from semiquantitative tests show that patients with a severe clinical presentation have lower levels of Ig targeting SARS-CoV-2 at <10 days since symptoms onset and higher levels at >21 days, compared to patients with a non-severe presentation. CONCLUSIONS: This study highlights the heterogeneity of sensitivity and generally high specificity of the serological tests and establishes a basis for their usefulness to complement diagnostic techniques and population seroprevalence studies.

Serologic evidence for Schmallenberg virus circulation at high altitude, Central Portugal, 2015-2016.

A few years after the initial 2011 large scale Schmallenberg virus (SBV) epidemic that affected Europe, a subsequent decrease in new SBV infections was observed presumably associated with natural substitution of previously exposed animals. In the present work, a 2-year prospective serosurvey was performed to evaluate SBV circulation in a population of sheep living at high altitude in the central region of Portugal and with restricted movement. Blood from a representative sample of 168 autochthonous sheep was collected in 2015 and again in 2016, and tested for the presence of anti-SBV IgG by ELISA. Of the 2015 sample collection, seven animals tested positive for anti-SBV IgG, corresponding to a seroprevalence of 4.2% while of the 2016 sample collection, 10 presented SBV antibodies, showing a seroprevalence of 6.0% (p = 0.619). Results show that SBV is endemic in sheep of central Portugal, even in herds at high altitude locations. When comparing anti-SBV seroprevalences of 2015/2016 found in this study, to one detected in 2014 in the same region, a steep decrease could be observed (p < 0.001). This is in accordance with what has been documented in Western European countries, where a decrease in the number of SBV-infected sheep has been found, a fact which may pose a new threat for SBV re-emergence.

Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery.

INTRODUCTION: Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation. AREAS COVERED: This paper provides critical information on existing in vitro and in vivo models to screen the efficacy and toxicity of innovative UBC therapies and point out the challenges for new and improved models. EXPERT OPINION: In our opinion, results obtained with in vitro and in vivo models should be interpreted together, as a set of delicate biological tools that can be used at different stages in the drug discovery process, to address specific questions. With the development of new technologies, new assays and biomarkers are going to play an important role in the study of UBC. The molecular diagnostics and genomic revolution will not only help to develop new drug therapies, but also to achieve tailored therapies.

Factors that determine the quality of bigeye tuna, caught in the western tropical Atlantic Ocean / Fatores que determinam a qualidade da albacora-bandolim, capturada no Oceano Atlântico oeste tropical

Tuna are highly prized in Oriental cuisine, and the bigeye tuna (Thunnus obesus) is of great commercial importance. Quality is assessed by the tuna meat quality, freshness, texture and fat, which can be altered by factors inherent to capture, such as days of onboard storage, months of the year, whether the catch was living or dead, fish weight and year. These factors were correlated to identify those that affect quality. We obtained data from nine vessels, from January 2007 to April 2010, creating an information bank of 21,908 bigeye tuna. Fish quality and parameters were related using multiple linear regression analysis, in which the variables were included in the model by a stepwise procedure (F>4). We found that live catch, heavier fish and fewer days of storage positively affected the quality, and that there is a seasonality of quality related to biological factors, which are not amenable to control...

Os atuns são peixes muito apreciados na culinária oriental, e a albacora-bandolim (Thunnus obesus) é de grande importância comercial. A qualidade do atum é avaliada pela qualidade da carne, frescor, textura e gordura, a qual pode ser alterada por fatores inerentes à captura, tais como: dias de armazenamento a bordo, meses do ano, capturado vivo ou morto, peso e ano. Esses fatores foram correlacionados para se identificarem aqueles que afetam a qualidade da carne. Foram obtidos dados de nove embarcações, de janeiro de 2007 a abril de 2010, e criou-se um banco de informações de 21.908 atuns. A qualidade do pescado e os parâmetros foram relacionados utilizando-se análise de regressão linear múltipla, em que as variáveis foram incluídas no modelo de stepwise (F> 4). Descobriu-se que captura do animal vivo, peixe mais pesado e menos dias de armazenamento afetaram positivamente a qualidade da carne e que há uma sazonalidade da qualidade relacionada a fatores biológicos que não são passíveis de controle...

A bacteriophage detection tool for viability assessment of Salmonella cells.

Salmonellosis, one of the most common food and water-borne diseases, has a major global health and economic impact. Salmonella cells present high infection rates, persistence over inauspicious conditions and the potential to preserve virulence in dormant states when cells are viable but non-culturable (VBNC). These facts are challenging for current detection methods. Culture methods lack the capacity to detect VBNC cells, while biomolecular methods (e.g. DNA- or protein-based) hardly distinguish between dead innocuous cells and their viable lethal counterparts. This work presents and validates a novel bacteriophage (phage)-based microbial detection tool to detect and assess Salmonella viability. Salmonella Enteritidis cells in a VBNC physiological state were evaluated by cell culture, flow-cytometry and epifluorescence microscopy, and further assayed with a biosensor platform. Free PVP-SE1 phages in solution showed the ability to recognize VBNC cells, with no lysis induction, in contrast to the minor recognition of heat-killed cells. This ability was confirmed for immobilized phages on gold surfaces, where the phage detection signal follows the same trend of the concentration of viable plus VBNC cells in the sample. The phage probe was then tested in a magnetoresistive biosensor platform allowing the quantitative detection and discrimination of viable and VBNC cells from dead cells, with high sensitivity. Signals arising from 3 to 4 cells per sensor were recorded. In comparison to a polyclonal antibody that does not distinguish viable from dead cells, the phage selectivity in cell recognition minimizes false-negative and false-positive results often associated with most detection methods.

E-cadherin and ß-catenin expression during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in mice.

BACKGROUND: E-cadherin and ß-catenin are adhesion molecules that promote integrity and stability of the urothelium. A decrease in their expression is associated with more aggressive tumour phenotypes with the ability to invade and metastasize. MATERIAL AND METHODS: 45 ICR male mice were used, of which 25 received N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05%) in drinking water for a period of 12 weeks. Immunohistochemical expression was evaluated in all urinary bladder preparations for E-cadherin and for ß-catenin. RESULTS: Preneoplastic lesions showed staining patterns similar to normal urothelium. In simple and nodular hyperplasia, membrane staining was dominant (66.7-78.6 and 50-100%, respectively). In dysplasia a cytoplasmic pattern was prevalent (86.7-100%). Neoplastic lesions exhibit an abnormal staining pattern (100%) with heterogeneous staining (cytoplasmic, nuclear and membrane staining). A strong correlation was observed between both adhesion molecule staining patterns (r = 0.83; p = 0.039). CONCLUSIONS: In mice, as in humans, E-cadherin and ß-catenin are valuable tools to investigate cellular adhesion status of urothelium and can be considered as indicators of tumour aggressiveness and evolution.

Review: BBN as an urothelial carcinogen.

Experimental urinary bladder tumours have been proposed as a useful model for the study of urinary bladder carcinogenesis, as well as for evaluating new therapeutic strategies. Consequently, the administration of chemical carcinogens is one of the most commonly used methods for inducing urinary bladder tumours. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is, undoubtedly, the most-used urothelial chemical carcinogen. BBN belongs to the nitrosamine family, a wide group of alkylating agents that are able to induce bladder tumours in laboratory animals. Depending on the animal species, the spectrum of urothelial lesions induced by BBN varies, but is similar to those observed in humans. BBN has a high propensity to induce mutations affecting the expression of genes such as p53, RAS and H19 among others. The aim of this study was to review BBN as a urothelial tumour inducer, taking into consideration its chemical characteristics, properties and spectrum of lesions induced, as well as its possible applications.

An analysis of the heat and mass transfer roles in air dehumidification by solid desiccants.

Although Passive and active solid desiccant dehumidification have been increasingly investigated and applied in modern air-conditioning design, some discrepancies regarding the effectiveness and the psychrometric representation of the two processes can be found in the literature. Passive desiccant wheels are usually applied as an energy saving technique for vapor-compression cooling systems, unburdening the cooling coil from handling the humidity of outside ventilation air stream. In contrast, active desiccant wheels are designed to promote a thorough dehumidification of outside ventilation air, many times allowing for the use of an evaporative cooler and achieving an appreciable cooling effect, using only water as the refrigerant. The present work is comprised of a comparative study of the roles played by heat and mass transfer in passive and active adsorptive air dehumidification. The adequate definition of effectiveness for desiccant wheels is also discussed.

Experimental study of the anticancer effect of gemcitabine combined with sirolimus on chemically induced urothelial lesions.

BACKGROUND: The purpose of this study was to determine the efficacy of a combination of gemcitabine and sirolimus in a mouse model of invasive bladder cancer. MATERIALS AND METHODS: Gemcitabine (50 mg/kg) and sirolimus (1.5 mg/kg) were administered to animals previously exposed to N-butyl-N-4(hydroxybutyl)nitrosamine in drinking water. Tumour development was determined by histopathological evaluation. RESULTS: Both drugs were well tolerated by animals. The incidence of lesions in mice treated with gemcitabine was lower in comparison to those not treated, however this result was not statistically significant. The incidence of invasive bladder cancer in animals treated with sirolimus was statistically lower (20%) than in animals not treated (54%) (p=0.008). The results indicate that this drug combination has no statistical significance on the development of pre-neoplastic urothelial lesions and had only a minor impact on invasive bladder cancer incidence in mice. CONCLUSION: The combination of gemcitabine and sirolimus had only a marginal impact on invasive bladder cancer in a mouse model.

Studies of the species barrier between Drosophila subobscura and D. madeirensis V: the importance of sex-linked inversion in preserving species identity.

The X chromosome is known to exert a disproportionately large effect on characters related to post-zygotic reproductive isolation. There is also growing evidence about the important role of the chromosomal regions with reduced recombination (such as inversions) in maintaining the identity of closely related species. Using molecular markers, we examine the effect of different regions of the X chromosome on determination of hybrid traits (viability, testes size, sperm motility and morphological anomalies) in hybrid males between Drosophila madeirensis and Drosophila subobscura. The preponderant effect of a region localized inside the A2 inversion in the X chromosome in all hybrid traits is identified. Other marked regions exert a weaker influence or only influence some of the hybrid trait. Our results confirm the crucial role of sex-linked chromosomal inversion in preserving the identity of species with incomplete reproductive isolation. The specific genomic make-up of parental lines used to perform crosses has a great effect on hybrid fitness.

Environmental enrichment does not compromise the immune response in mice chronically infected with Mycobacterium avium.

Research on infectious diseases using animal models has been a successful example of translational research. However, because chronic infections are still one of the main causes of death and disability in the world, it is expected that a great number of mice will continue to be used to address this subject. Although increasing awareness regarding animal welfare has led to novel recommendations for animal housing enrichment, studies evaluating the impact of these modifications on the immune response to infection are lacking. The present study shows that validated and recommended simple environmental enrichment does not interfere with the immune response to chronic infection with Mycobacterium avium for up to 20 weeks, as assessed by the bacterial load in the spleen and lung, by the number and activation status of the main cell populations of the immune system and the serum concentration of interferon-gamma. Therefore, enrichment can be encouraged without concern regarding comparability of results among laboratories studying this type of chronic infections.

Retrosternal gastric bypass for inoperable esophageal cancer: a report of 71 patients.

Palliative substernal gastric bypass was performed in 71 patients with unresectable cancer of the intrathoracic esophagus. Fifty-six patients (78.9%) left the hospital, 53 eating normally and 3 on a soft diet. There were 15 hospital deaths (21%), 8 due to respiratory failure and pulmonary sepsis with tracheoesophageal fistulization. The remaining 7 deaths were due to aspiration and respiratory failure in 2 patients, anastomotic leakage with sepsis in 2, subphrenic abscess and septicemia in 1, mediastinitis in 1, and intestinal obstruction in 1. Anastomotic leakage occurred in 17 patients (23.9%), 5 of whom died. Wound infections developed in 28 patients (39.4%), 3 with mediastinal esophagocutaneous fistulas. Reestablishment of unimpeded swallowing, relief of respiratory aspiration, isolation of cancerous tracheobronchial infiltration, and freedom from incident-prone endoesophageal tubes were achieved in all patients leaving the hospital. Information is presented on 25 patients who were available for follow-up.