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Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture and aspiration. The stress that is induced by this procedure can also lead to confounding results. In several animal models, drug vehicles must be sugar-free, deliver drugs in a specific formulation, and sometimes supply water. Gelatin has all of these properties. The current study aimed to evaluate the use of gelatin vehicles with different sensory features as an alternative to oral gavage. We investigated the time taken by 2 different inbred mouse strains, FVB/N and C57BL/6J, to ingest sugar-free gelatin pellets of varying flavors. Results showed that FVB/N mice took more time to eat the unflavored, strawberry and diet-flavored gelatin pellets than did C57BL/6J mice. Both strains showed low preference for lemon flavor, with the same ingestion times after the second day. This study showed that the C57BL/6J mice are more likely to eat gelatin than are FVB/N mice, and that the 2 strains of mice show a lower preference for lemon flavoring as compared with other flavors. This method of voluntarily oral administration offers an alternative to gavage for studies that use oral dosing studies.

The rise of antimicrobial resistance (AMR) in animals is being fuelled by the widespread use of veterinary antimicrobials. China is the largest global consumer of veterinary antimicrobials, and improving AMR surveillance strategies in this region could help prioritize intervention and preserve antimicrobial efficacy. Here we mapped AMR rates in pigs, chickens and cattle in China using 446 surveys of event-based surveillance between 2000 and 2019 for foodborne bacteria, in combination with geospatial models to identify locations where conducting new surveys could have the highest benefits. Using maps of uncertainty, we show that eastern China currently has the highest AMR rates, and southwestern and northeastern China would benefit the most from additional surveillance efforts. Instead of distributing new surveys evenly across administrative divisions, using geographically targeted surveillance could reduce AMR prediction uncertainty by two-fold. In a context of competing disease control priorities, our findings present a feasible option for optimizing surveillance efforts—and slowing the spread of AMR., Nature Food, 2 (8), ISSN:2662-1355

Aim: This work intended to improve the knowledge of the rat model of prostate cancer (PCa) by ultrasonographic monitoring. Materials and Methods: Male Wistar rats were divided into control (n=8) and PCa (n=14) groups. PCa development was induced in the PCa group through the sequential administration of the anti-androgenic drug flutamide, testosterone propionate and the carcinogenic N-methyl-N-nitrosourea. The prostate was evaluated by ultrasonography at five timepoints along 49 weeks of the experimental protocol. Ventral prostate lobes were observed in all ultrasonographic examinations. Results: The ventral prostate area of the control group increased gradually between the first and the last ultrasonographic examination. The ventral prostate area of PCa groups decreased due to flutamide administration and increased after androgen and carcinogen administration. The area of the dorsal prostate lobe increased between the fourth and the fifth ultrasonographic examination. In the last ultrasonographic examination, hypoechoic and anechoic lesions were observed in the PCa group. Conclusion: To our knowledge, this is the first study presenting a follow-up of rat prostatic dimensions by ultrasonography. Ultrasonography is a feasible approach for prostate cancer monitoring in experimental models. published

Resilience is currently an increasing concern in supply chain (SC), caused by their globalization, which is subject to diverse types of disturbances. Such disturbances need to be handled in the right way, compelling the use of tools that can support resilient supply chain decisions. To comprehend how the academic community has been treating such concern we developed a systematic literature review on SC resilience, focusing on the analysis of the development of quantitative methods to support such decisions. A content analysis was performed, in an identified sample of 39 papers, exploiting a solid methodology in the preparation; collection; and analysis of the information obtained. Additionally, published SC resilience definitions were examined and, as result, it was found that there is no consensus in the literature. A sound definition is then proposed, which is supported by a comprehensive framework that includes the four main identified SCR elements: focus event; adaptive framing or adaptive response; speed; performance level. Moreover, it was concluded that the use of quantitative models, although recognised with high relevance in SC resilience, should be further researched as most of the published work explores the conceptualization of only a limited number of resilience elements, lacking the development of integrated holistic approaches. These should simultaneously address the main supply chain characteristics and SC resilience elements. Future directions for the academic community are presented, aiming to guide future research work in the area.

Objectives This study aimed to evaluate the impact of long-term exercise training on the vascularization of rat mammary tumors. Methods Female rats were divided into 4 groups: N-methyl-N-nitrosourea (MNU) treated sedentary, MNU treated exercised, control sedentary, and control exercised. Tumor development was induced in the MNU groups by MNU administration. Exercised groups were trained for 35 weeks. Tumor vascularization was evaluated by pulsed Doppler and contrast-enhanced ultrasonography. Results The pulsatility and resistive indices were slightly higher in the MNU sedentary group (P > .05). Mammary tumors mainly had centripetal and heterogeneous enhancement of the contrast, clear margins, and the presence of penetrating vessels. The MNU exercised group had a lower arrival time and time to peak and higher peak intensity, wash-in, and wash-out (P > .05). The area under the curve was similar between groups (P > .05). Conclusions The contrast-enhanced ultrasonographic study did not detect differences in mammary tumor vascularization between MNU sedentary and MNU exercised groups previously detected by power Doppler imaging, B-flow imaging, and immunohistochemistry.

Records management systems support organization in reaching business benefits when properly aligned with business processes. This paper frames records management in business process management by identifying the role records management plays in business. This research proposes Business Layer a solution that replaces a records management system workflow module by an open source solution, composed of an enterprise service bus and two workflow engines, whose capabilities are accessed through a single API. The business layer acts as the back end for the workflow module and allows it to communicate to several workflow engines through a single REST API. The API is develop in the WSO2 Enterprise Integrator ESB profile, where for each identified functionality, message transformation and forwarding integration flows are produced. The results show that the business layer is a flexible and scalable solution to the workflow modules. This paper supports that Records Management enables the automation of the document management, along with the management, monitoring and preservation of documents, increasing the efficiency of business activities.

This paper overviews the key architectures and network design and operation solutions to efficiently exploit low margin provisioning in optical transport networks.

The global scale-up in demand for animal protein is the most notable dietary trend of our time. Antimicrobial consumption in animals is threefold that of humans and has enabled large-scale animal protein production. The consequences for the development of antimicrobial resistance in animals have received comparatively less attention than in humans. We analyzed 901 point prevalence surveys of pathogens in developing countries to map resistance in animals. China and India represented the largest hotspots of resistance, with new hotspots emerging in Brazil and Kenya. From 2000 to 2018, the proportion of antimicrobials showing resistance above 50% increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs. Escalating resistance in animals is anticipated to have important consequences for animal health and, eventually, for human health., SCOPUS: ar.j, info:eu-repo/semantics/published

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).

BackgroundRising antimicrobial resistance (AMR) is a threat to modern medicine, and increasing international mobility facilitates the spread of AMR. Infections with resistant organisms have higher morbidity and mortality, are costlier to treat, result in longer hospital stays and place a greater burden on health systems than infections caused by susceptible organisms. Here we review the role of travel in the international dissemination of AMR and consider actions at the levels of travelers, travel medicine practitioners and policymakers that would mitigate this threat.ResultsResistant pathogens do not recognize international borders; travelers to areas with high AMR prevalence are likely to be exposed to resistant bacteria and return to their home countries colonized. Medical tourists go between health facilities with drastically different rates of AMR, potentially transmitting highly resistant strains.Drug-resistant bacteria have been found in every continent; however, differences between countries in the prevalence of AMR depend on multiple factors. These include levels of antibiotic consumption (including inappropriate use), access to clean water, adequate sanitation, vaccination coverage, the availability of quality healthcare and access to high-quality medical products.ConclusionsTravelers to areas with high levels of AMR should have vaccines up to date, be aware of ways of treating and preventing travelers’ diarrhea (other than antibiotic use) and be informed on safe sexual practices. The healthcare systems of low- and middle-income countries require investment to reduce the transmission of resistant strains by improving access to clean water, sanitation facilities and vaccines. Efforts are needed to curb inappropriate antibiotic use worldwide. In addition, more surveillance is needed to understand the role of the movement of humans, livestock and food products in resistance transmission. The travel medicine community has a key role to play in advocating for the recognition of AMR as a priority on the international health agenda.Key policy recommendationsAMR is a threat to modern medicine, and international travel plays a key role in the spread of highly resistant strains. It is essential that this is addressed at multiple levels. Individual travelers can reduce antibiotic consumption and the likelihood of infection. Travelers should have up-to-date vaccines and be informed on methods of preventing and treating travelers’ diarrhea, other than use of antibiotics and on safe sexual practices, such as condom use. Healthcare facilities need to be aware of the travel history of patients to provide appropriate treatment to those who are at high risk of exposure and to prevent further spread. Internationally, in countries without reliable and universal access to clean water, sanitation and hygiene, investment is needed to reduce the emergence and spread of resistance and ensure the antimicrobials available are of assured quality. High-income countries must ensure their use of antimicrobials is appropriate to reduce selection for AMR. Surveillance across all countries is needed to monitor and respond to this emerging threat.

In long-term emergency operations such as refugee camps, humanitarian aid faces logistical and budgetary limitations. Thus far, the energy systems that supply these operations are designed with little insight on demand needs, leading to the deployment of standardized fossil-dependent solutions which, albeit presenting low investment costs, are pollutant and often inefficient. This work applies a multi-disciplinary methodology to develop an energy demand modelling framework for Tier 0 refugee camps, and assesses the implementation of alternative power supply systems. It does so by not only focusing on its techno-economic feasibility, but equally through investigating the challenges on adoption in the specific context of refugee camps, by undertaking interviews with relevant stakeholders in the humanitarian sector. The modelling application has been performed for the Mantapala refugee camp, in Zambia, enabling the comparison of different combinations of power supply systems against current diesel-based solutions, using HOMER software. Results show that the implementation of hybrid renewable energy systems is viable, both technically and economically, with energy costs being reduced up to 50%, with paybacks lower than five years. However, from the interviews performed, some non-technical constraints that may hinder the adoption of these systems in refugee camps were identified, such as uncertainty, lack of funding and difficulties on risk-sharing collaborations. As such, a discussion focused on possible strategies that may help overcome these barriers is presented.

To characterize the kidney alterations associated with renal mass reduction by two-dimensional ultrasound and assess the correlation of the ultrasonographic parameters with the histological and biochemical findings. Materials and Methods: Rats were divided into two groups: sham-operated animals (n=13), and animals which underwent renal mass reduction (RMR) through 5/6 nephrectomy (n=14). Renal length, renal thickness, cortical thickness, medullary length and echogenicity of the kidneys were evaluated by ultrasonography at 3 and 6 months after the RMR. Results: Except for the renal length, the renal dimensions at 3 and 6 months were significantly higher in the RMR group when compared to the sham-operated group (p < 0.05). Furthermore, the cortical and medullary echogenicity was significantly higher in the RMR group when compared to the sham-operated group (p < 0.05). A significant correlation was observed between the plasma creatinine level and the renal length 3 months after RMR (r=-0.612, p=0.045). Conclusion: These data support future application of ultrasonography for monitoring the progression of renal damage in chronic studies with the 5/6 nephrectomy model. This work was supported by : European Investment Funds by FEDER/COMPETE/POCI Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT – the Portuguese Foundation for Science and Technology, under project UID/AGR/04033/2013; and by European Investment Funds by FEDER/COMPETE/POCI Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT – the Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/2014. info:eu-repo/semantics/publishedVersion

Cape Verde is an African country where consumers pay one of the highest tariffs for water supply services in the world. However, the current levels of service coverage and quality still fall short from adequate, as acknowledged by local authorities and international agencies. Thus, an assessment of how much Cape Verdean households are willing to pay (WTP) for service improvements becomes a fundamental ingredient informing sector policy formulation going forward. This has been the focus of this present study. For that purpose, valuation functions were estimated using suitable estimation methods. The results show that, taking into consideration their current levels of expenditure with this service, households would in general not be WTP more for significant improvements in their current water supply services, and that household income and the age of the head of the household both have significant effects on their WTP.

For an organization to achieve benefits from records management, it needs to include several practices such as the implementation of a records management system in alignment with the organization's reality and business processes. The focus of this work is on framing records management in business process management by identifying the role that records management plays in business. This research is applied in the replacement of a records management system workflow module. This research proposes the replacement of the workflow module by a flexible and open source solution, composed by an enterprise service bus and two workflow engines, accessed through a single API. The solution proves to be a flexible and scalable solution to the workflow module and that can even be used by more systems than records management systems. The implementation of records management in organizations is analysed, including the alignment between business processes, records management and workflows. This research shows that records management acts as an essential component to business that supports business processes and all the phases of their management, allowing for improvement regarding the storage, management and monitoring of records while also optimizing the execution of business activities.

This paper proposes a novel framework tailored for provisioning unprotected and protected services in a DWDM network where current- and next-generation line interfaces will co-exist. Simulation results highlight that it enables to carry more capacity without increasing line interface count.

Cancers induced by human papillomavirus (HPV) infection remain a significant public health threat, fueling the study of new therapies. Laurel (Laurus nobilis) compounds and extracts recently showed in vitro activity against HPV-transformed cell lines. This work aims to evaluate the in vivo efficacy and hepatic toxicity of a laurel extract in a transgenic mouse model of HPV16-induced cancer. The extract was administered in drinking water (20 mg per animal per day) for three consecutive weeks, using four experimental groups (n = 10) (group I: HPV16−/− without treatment, group II: treated HPV16−/−, group III: HPV16+/− without treatment and group IV: treated HPV16+/−). Following the treatment period, animals were sacrificed and skin samples were used to classify skin lesions histologically. Toxicological parameters included hematological and biochemical blood markers, splenic and hepatic histology and hepatic oxidative stress. The extract did not prevent the progression of HPV16-induced cutaneous lesions in this model. The treated wildtype animals showed mild hepatitis, while transgenic animals suffered weight loss. However, there were no changes concerning hematological, biochemical and hepatic oxidative stress markers. This work was supported by: Integrative Research in Environment, Agro-Chains and Technology no. NORTE-01- 0145-FEDER-000017, in its line of research entitled ISAC, cofinanced by the European Regional Development Fund (ERDF) through NORTE 2020 (North Regional Operational Program 2014/2020). European Investment Funds by FEDER/COMPETE/ POCI– Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. This study was also funded by Liga Portuguesa Contra o Cancro, by the Research Center of the Portuguese Institute of Oncology of Porto (CI-IPOP 37-2016), by project POCI-01-0145- FEDER-006939 (Laboratory for Process Engineering, Environment, Biotechnology and Energy – LEPABE), project POCI-01-0145-FEDER-006958 and UID/AGR/04033/2013, funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT – Fundação para a Ciência e a Tecnologia; Rui M. Gil da Costa was funded by grant number SFRH/BPD/85462/2012 from FCT, funded by the Portuguese Government and the Social European Fund. The authors are also grateful to FCT, Portugal and FEDER under Programme PT2020 for financial support to CIMO (UID/AGR/ 00690/2013), and to the Interreg España-Portugal for financial support through the project 0377_Iberphenol_6_E. info:eu-repo/semantics/publishedVersion

The search for renewable alternatives to petroleum products for industrial applications is increasing. Each year, many tons of inedible plant material is produced, much of which is landfilled. Cellulose, the most abundant biopolymer in nature, present in lignocellulosic biomass wastes can be extracted and converted to nanometric scale. Nanocellulose (NC) has unique characteristics for the development of new materials: abundance, renewability and biodegradability, mechanical properties and its nanometric dimensions open a wide range of possible properties and applications to be discovered. One of the most promising uses of NC is as reinforcement of mechanical properties in polymeric bionanocomposites. This review aims to give a recent view on this emerging nanomaterial, focusing on lignocellulosic biomass wastes extraction procedures, and its application in new technological developments. The challenges and future opportunities of bionanocomposites reinforced with NC will be discussed, as well as the remaining obstacles to its valorization and use.

Obesity is linked to the onset of many diseases such as diabetes mellitus, cardiovascular diseases and cancer, among others. The prevalence of obesity nearly doubled worldwide between 1980 and 2014. Simultaneously, in the last decade, the effects of sulforaphane as a potential treatment for obesity have been investigated, with promising results. Fruits and vegetables and their processed agri-food co-products are good sources of natural health-promoting compounds. Brassica crops are among the most produced crops in the world and are a good source of glucoraphanin, which, following hydrolysis, releases sulforaphane. The Brassicaceae family generates large amounts of co-products with no intended use, causing negative economic and environmental impact. Valorization of these co-products could be achieved through their exploitation for the extraction of bioactive compounds such as sulforaphane. However, the extraction process still needs further improvement for its economic feasibility. This article reviews the potential effects of sulforaphane in the treatment of obesity, linked to the relevance of giving Brassica co-products added value, which is of key importance for the competitiveness of farmers and the agri-food industry. © 2018 Society of Chemical Industry.

Currently, there is a growing demand for cleaner and sustainable technologies due to environmental issues. In this sense, there is a necessity to manage the assessment of production processes and the rationalization of energy consumption. In this study, an Energy Life-Cycle Assessment (ELCA) was carried out through energy efficiency indicators, directed to the characterization and renewability of the peach production system life-cycle in the Portuguese region of Beira Interior. The study intends to investigate the non-renewable energy inputs from fossil fuels, as well as the emissions resulting from machinery. In addition, warehouse energy inputs are analyzed, mainly cooling systems of refrigerated chambers where fruits are preserved. This analysis aims to find opportunities for technological, environmental and best practices improvements. Test scenarios were analyzed and revealing soil groundcover maintenance is the operation with the largest impact in the energy consumption of the production process (3176 MJ&middot, ha&minus, 1). In the post-harvest processes, the energy consumption largest impact is given by the warehouse&rsquo, s operations (35,700 MJ&middot, 1), followed by transportation (6180 MJ&middot, 1). Concerning the emissions resulting from the fuels consumption, the largest impact is due to the plantation machinery and the transportation from warehouse to retailers.

Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers.HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O-3/O-2 (80 mL/kg, at O-3 50 mu g/mL), once a day, for 5 consecutive days. The animals were sacrificed at 25 weeks-old, and skin samples were analyzed histologically to study tumour progression. Blood and internal organ samples were used to study toxicological parameters.85.7% of untreated transgenic mice showed dysplastic skin lesions, compared with 28.6% of O-3-treated mice.This was associated with a marked reduction of dermal inflammation associated with those lesions. No significant changes were observed in any toxicological parameters.These preliminary results support the hypothesis that O-3 therapy is effective against papillomavirus-induced lesions, particularly against those induced by the most common high-risk virus, HPV16. Further studies are needed to confirm the mechanisms underlying these effects.

The presence of Methicillin-Resistant Staphylococcus aureus (MRSA) in pig farms has been widely reported, and the emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) has been documented in several countries. However, data for Switzerland are very scarce. This study aimed to compare changes in the prevalence of MRSA in Swiss pig farms between 2008 and 2015 and make the first ever estimates of the presence of ESBL-E and carbapenemase producers in pigs and pig farm workers. Results showed that ESBL-E was present in both pigs and farm workers and that the proportion of farms with MRSA had increased fourfold in seven years (from 7% to 31%). Associations between antibiotic use and resistant bacteria carriage were shown.

Limiting cancer-induced cardiac damage has become an increasingly important issue to improve survival rates and quality of life. Exercise training has been shown to reduce cardiovascular complications in several diseases; however, its therapeutic role against cardiovascular consequences of cancer is in its infancy. In order to add new insights on the potential therapeutic effect of exercise training on cancer-related cardiac dysfunction, we used an animal model of urothelial carcinoma submitted to 13 weeks of treadmill exercise after 20 weeks of exposure to the carcinogenic N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). Data showed that 13 weeks of treadmill exercise reverted cancer-induced cardiomyocytes atrophy and fibrosis, improved cardiac oxidative capacity given by citrate synthase activity and MnSOD content, and increased the levels of the mitochondrial biogenesis markers PGC-1α and mtTFA. Moreover, exercise training reverted cancer-induced decrease of cardiac c-kit levels suggesting enhanced regenerative ability of heart. These cardiac adaptations to exercise were related to a lower incidence of malignant urothelial lesions and less signs of inflammation. Taken together, data from the present study support the beneficial effect of exercise training when started after cancer diagnosis, envisioning the improvement of the cardiovascular function.

Microspherical activated carbons were successfully prepared via a novel synthetic route that involves hydrothermal carbonization of a renewable material, sucrose, and activation with K2CO3. The use of K2CO3 resulted in better yields (similar to 50%) and the retention of the spherical shape of the hydrochar, while with the less environmentally desirable and commonly used activating agent, KOH, the process occurs at the expense of the spherical morphology. The superior performance of the K2CO3 activated samples for methane storage and upgrade of landfill gas or biogas results from the combination of several key properties including high packing densities (similar to 0.9 g cm(-3)), high surface areas (up to 1400 m(2) g(-1)) and micropore sizes suitable for methane storage and selective CO2-CH4 separation. In fact, the micropore size distributions assessed from CO2 adsorption data through a methodology not imposing a Gaussian distribution gave meaningful values to explain both the selectivity and storage capacity of samples. Sample activated with K2CO3 at 800 degrees C presenting micropore sizes similar to 0.8 nm and high packing density has high volumetric methane uptake (90 (V/V) at 1000 kPa), close to the best activated carbons reported in the literature. Sample activated with K2CO3 at 700 degrees C has narrower micropores (similar to 0.5 nm) and presents a remarkable selectivity (4-7) in CO2-CH4 mixtures for the upgrade of methane based fuels, like natural gas, landfill gas, and biogas. Although a superactivated carbon (similar to 2400 m(2) g(-1)) was obtained with KOH activation, the low packing density and wider micropores rendered it less effective for both methane storage and upgrade.

Purpose.This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction.Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment(n=14); RMR + CAA: RMR rats treated with CAA(n=13); SO: SO rats without treatment(n=13); and SO + CAA: SO rats treated with CAA(n=13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months.Results.RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity(p<0.05)and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity(p<0.05)and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function.Conclusions.These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n = 13); SO + CAA: SO rats treated with CAA (n = 13); RMR:RMR rats without treatment (n = 14); and RMR + CAA:RMR rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p < 0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p < 0.001) in the RMR + CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR + CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease. This work is supported by : European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013; and by European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/2014. info:eu-repo/semantics/publishedVersion

The inhibition of mast cells' degranulation may be an approach to prevent the formation of new vessels during the mammary carcinogenesis.Female Sprague-Dawley rats were randomly divided into five experimental groups. Mammary tumors were induced by intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Animals from group II were treated with ketotifen for 18weeks immediately after the MNU administration, while animals from group III only received the ketotifen after the development of the first mammary tumor. Mammary tumors vascularization was assessed by ultrasonography (Doppler, B Flow and contrast-enhanced ultrasound) and immunohistochemistry (vascular endothelial growth factor-A).Similar to what occurs in women with breast cancer, the majority of MNU-induced mammary tumors exhibited a centripetal enhancement order of the contrast agent, clear margin and heterogeneous enhancement. Ultrasonographic and immunohistochemical data suggest that the inhibition of mast cells' degranulation did not change the mammary tumors vascularization.

Cancer patients often show a wasting syndrome for which there are little therapeutic options. Dietary polyphenols have been proposed for treating this syndrome, but their usefulness in cases associated with human papillomavirus (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a model of cancer cachexia and tested the efficacy of long-term oral supplementation with polyphenols curcumin and rutin. Both compounds were orally administered to six weeks-old HPV16-transgenic mice showing characteristic multi-step skin carcinogenesis, for 24 weeks. Skin lesions and blood, liver and spleen inflammatory changes were characterized histologically and hematologically. Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro-inflammatory transcription factor NF-kappa B were also assessed. Skin carcinogenesis was associated with progressive, severe, systemic inflammation (leukocytosis, hepatitis, splenitis), significant mortality and cachexia. Curcumin and rutin totally suppressed mortality while reducing white blood cells and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more effectively than curcumin. Preservation of muscle mass and reduced hepatic inflammation were associated with down-regulation of the NF-kappa B canonical pathway and with reduced oxidative stress, respectively. These results point out HPV16-transgenic mice as a useful model for studying the wasting syndrome associated with HPV-induced cancers. Dietary NF-kappa B inhibitors may be useful resources for treating this syndrome.

Zika virus infection in humans is usually mild or asymptomatic. However, some babies born to women infected with Zika virus have severe neurological sequelae. An unusual cluster of cases of congenital microcephaly and other neurological disorders in the WHO Region of the Americas, led to the declaration of a public health emergency of international concern by the World Health Organization (WHO) on 1 February 2016. By 5 May 2016, reports of newborns or fetuses with microcephaly or other malformations – presumably associated with Zika virus infection – have been described in the following countries and territories: Brazil (1271 cases); Cabo Verde (3 cases); Colombia (7 cases); French Polynesia (8 cases); Martinique (2 cases) and Panama (4 cases). Additional cases were also reported in Slovenia and the United States of America, in which the mothers had histories of travel to Brazil during their pregnancies.1 Zika virus is an intensely neurotropic virus that particularly targets neural progenitor cells but also – to a lesser extent – neuronal cells in all stages of maturity. Viral cerebritis can disrupt cerebral embryogenesis and result in microcephaly and other neurological abnormalities.2 Zika virus has been isolated from the brains and cerebrospinal fluid of neonates born with congenital microcephaly and identified in the placental tissue of mothers who had had clinical symptoms consistent with Zika virus infection during their pregnancies.3–5 The spatiotemporal association of cases of microcephaly with the Zika virus outbreak and the evidence emerging from case reports and epidemiologic studies, has led to a strong scientific consensus that Zika virus is implicated in congenital abnormalities.6,7 Existing evidence and unpublished data shared with WHO highlight the wider range of congenital abnormalities probably associated with the acquisition of Zika virus infection in utero. In addition to microcephaly, other manifestations include craniofacial disproportion, spasticity, seizures, irritability and brainstem dysfunction including feeding difficulties, ocular abnormalities and findings on neuroimaging such as calcifications, cortical disorders and ventriculomegaly.3–6,8–10 Similar to other infections acquired in utero, cases range in severity; some babies have been reported to have neurological abnormalities with a normal head circumference. Preliminary data from Colombia and Panama also suggest that the genitourinary, cardiac and digestive systems can be affected (Pilar Ramon-Pardo, unpublished data). The range of abnormalities seen and the likely causal relationship with Zika virus infection suggest the presence of a new congenital syndrome. WHO has set in place a process for defining the spectrum of this syndrome. The process focuses on mapping and analysing the clinical manifestations encompassing the neurological, hearing, visual and other abnormalities, and neuroimaging findings. WHO will need good antenatal and postnatal histories and follow-up data, sound laboratory results, exclusion of other etiologies and analysis of imaging findings to properly delineate this syndrome. The scope of the syndrome will expand as further information and longer follow-up of affected children become available. The surveillance system that was established as part of the epidemic response to the outbreak initially called only for the reporting of microcephaly cases. This surveillance guidance has been expanded to include a spectrum of congenital malformations that could be associated with intrauterine Zika virus infection.11 Effective sharing of data is needed to define this syndrome. A few reports have described a wide range of abnormalities,3–6,8–10 but most data related to congenital manifestations of Zika infection remain unpublished. Global health organizations and research funders have committed to sharing data and results relevant to the Zika epidemic as openly as possible.12 Further analysis of data from cohorts of pregnant women with Zika virus infection are needed to understand all outcomes of Zika virus infection in pregnancy. Thirty-seven countries and territories in the Region of the Americas now report mosquito-borne transmission of Zika virus and risk of sexual transmission. With such spread, it is possible that many thousands of infants will incur moderate to severe neurological disabilities. Therefore, routine surveillance systems and research protocols need to include a larger population than simply children with microcephaly. The health system response, including psychosocial services for women, babies and affected families will need to be fully resourced. The Zika virus public health emergency is distinct because of its long-term health consequences and social impact. A coordinated approach to data sharing, surveillance and research is needed. WHO has thus started coordinating efforts to define the congenital Zika virus syndrome and issues an open invitation to all partners to join in this effort.

New technologies are emerging to make optical transport networks increasingly flexible and cost-effective. Transponder modules capable of rate adaptation and sliceability promise a scalable way to support the upcoming traffic growth. The deployment of these flexible modules on the line-side can be enhanced with a pay-as-you-grow approach also on the client-side, where capacity is provisioned on demand for maximum cost-efficiency. Bridging these two elements together with flexible client-to-line interconnection switch fabrics ties together the concept of a fully-flexible next-generation optical transport network. Such a high degree of configurability greatly expands the ability to automatically reuse equipment modules in multiple situations over the course of the network lifecycle. On the other hand, manual re-provisioning of available equipment is an alternative to improve resource reuse in otherwise rigid network designs based on fixed transponders and client-to-line interconnections. The policy each operator chooses regarding the level of manual reconfigurations it allows in its network to reuse idle hardware can have a lasting impact on the overall cost of deploying a transport infrastructure. This paper addresses, through a multi-period planning simulation, the effect of idle part handling on network deployment cost and resource efficiency. The analysis is conducted for multiple transport architectures, ranging from traditional transponders and muxponders to more flexible designs on both the client- and line-sides.

Resumo: Em Janeiro 2008, foi implementada, em Portugal, uma nova medida legislativa que condiciona o consumo de tabaco em espaços colectivos fechados. Como a exposição passiva ao fumo do tabaco provoca a exacerbação dos sintomas de asma, tornou-se pertinente conhecer a percepção dos doentes asmáticos sobre as repercussões desta nova lei no seu bem-estar.Foi realizado um estudo descritivo transversal, numa amostra de conveniência, constituída por 96 doentes asmáticos da consulta de Pneumologia do Hospital Pulido Valente e do Hospital de Santa Marta, de Lisboa. Os dados foram recolhidos a partir de um questionário padronizado com respostas voluntárias, anónimas e confidenciais. Para tratamento estatístico recorreu-se ao programa Epi InfoTM e foi aplicado o teste qui-quadrado para análise dos resultados (α=5%).Dos doentes inquiridos, a percentagem dos que estiveram expostos a fumo de tabaco até Dezembro 2007 foi de 67,7%, com maior prevalência no grupo de indivíduos activos. Apesar de a maioria dos inquiridos não referir alterações no seu bem-estar, 39,6% referiu alterações positivas (melhoria na realização de actividades diárias, diminuição dos sintomas ou menor necessidade de recorrer a medicação SOS). Destes indivíduos, que indicaram alterações positivas, 81,6% deixaram de estar expostos após entrada da nova lei e 65,8% indicaram-na como factor responsável.Os resultados deste estudo, apenas dois meses após a implementação legal, reforçam a importância da aplicação de medidas legais eficazes que evitem a exposição ao fumo de tabaco, como forma de redução da exacerbação dos sintomas e de melhoria do bem-estar dos doentes asmáticos.Rev Port Pneumol 2009; XV (1): 27-42 Abstract: January 2008 saw new legislation implanted in Portugal restricting smoking in closed public spaces. As second-hand smoke worsens asthma symptoms, it is important to understand how asthma patients feel this new legislation impacts on their well-being.A descriptive cross-sectional study was conducted in a convenience sample formed of 96 asthma patients who had Pulmonology appointments at the Pulido Valente and Santa Marta Hospitals. All data was collected from a standardised questionnaire with volunteer, anonymous and confidential answers. Epi InfoTM software was used for statistical processing purposes, and the results analysed using the chi-squared test (α=5%).67.7% of the patients polled were exposed to second-hand smoke until December 2007, with a higher percentage in those currently in work. A considerable percentage (39.6%) described positive changes (measured by improved performance of daily life activities, decrease in symptoms or lesser recourse to SOS medication), even though the majority did not recognise any improvement. 81.6% of those who noted positive changes said they were no longer exposed to second-hand smoke with the passing of the new legislation, and 65.8% stated that the smoking ban was the factor responsible for those changes.These results, only two months after the implementation of the legislative ban on smoking in public spaces, underline the importance of approving effective measures to create and enforce smoke-free environments, reducing worsening of symptoms and improving asthma patientsâ well-being.Rev Port Pneumol 2009; XV (1): 27-42 Palavras-chave: Asma, tabaco, exposição, fumo, fumo passivo, lei, Key-words: Asthma, tobacco, exposure, smoke, second-hand smoke, legislation

Separation of the major components of landfill and natural gas by four adsorbent materials was investigated, and a high selectivity was obtained in some materials. The adsorbents, prepared from a natural clay, were two porous clay heterostructures (PCH) obtained by use of tetraethoxysilane (TEOS) and phenyltriethoxysilane (PhOS), and two other PCH prepared by use of 3-aminopropyltriethoxysilane (APTES) and TEOS. A pillared clay, with aluminum oxide pillars, was used also. CH4, C2H6, and CO2 high-pressure adsorption isotherms (measured up to 1000 kPa) were used to estimate the selectivity and phase diagrams for separation of binary mixtures of these gases. The significant differences found between the materials were related to the surface chemistry. The material modified with APTES presents the highest CO2 affinity, suggesting a strong interaction between this gas and the amine group. The new materials presented interesting properties regarding CO2/CH4 separation. The porosity and apparent specific surface...

It is increasingly important that chemistry reaches people who have not studied directly this field of science but that, daily, have practices where chemistry is involved in various extents. This is what happens, for instance, in the activities related with the study and the preservation of cultural heritage. In this sense, the present work is a short review of the particular case of techniques based on the thermal analysis and calorimetry applied within the context of the characterization of art and archeological objects, exemplified by various case studies, as the characterization of mortars, preparatory grounds, ancient painting materials and drying oils.

Porous materials were obtained from clays by gallery templated synthesis. The equivalent surface areas of the samples were in the range 600–700 m 2 g −1 and the corresponding microporous volumes were near 0.3 cm 3 g −1 . HRTEM confirmed the lack of long-range order of the prepared samples. Low temperature nitrogen adsorption showed textural differences in the samples, namely those arising from the neutral amines of different chain length used in synthesis. The possibility of using such materials as adsorbents of volatile organic compounds, due to their textural and hydrophobic characteristics, was studied by the adsorption of ethanol and methyl ethyl ketone and water for comparison. Their potential use as adsorbents for the purification of methane, e.g., for upgrading natural or landfill gas, was also studied by the determination of the room temperature adsorption isotherms of carbon dioxide, ethane, methane and nitrogen, where high initial selectivity values were obtained for the methane/carbon dioxide separation.

The main research goal in patients with chronic kidney disease (CKD) is the development of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. The aim of this work was to evaluate the effects of long-term administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on chronic kidney lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Materials and Methods: Sixty male Wistar rats were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery, surviving animals were distributed into four groups: SO–SO rats receiving no treatment (n = 13); SO+CAA–SO rats receiving CAA treatment (n = 13); RMR–RMR rats receiving no treatment (n = 14); RMR+CAA–RMR rats receiving CAA treatment (n = 13). CAA was administered intraperitoneally three times a week for 6 months. Renal fibrosis was evaluated by ultrasonography and histopathological analysis. All experimental procedures followed the European (European Directive 2010/63/EU) and National (Decree-Law 113/2013) legislation on the protection of the animals used for scientific purposes. Results: The kidneys of the RMR animals treated with CAA showed a significant decrease in medullary echogenicity (P

The data-center interconnection (DCI) market has been rising sharply for some time, leading to the development of networking solutions tailored specifically for it. On the side of the transport network, DCI devices are characterized by simple, footprint-efficient designs focused on scalability, but still leverage the benefits of flexible-rate transponders on the line-side, to extract the most from costly optical transport infrastructures. Accompanying this evolution arose the need for a technology that could provide a flexible client layer where aggregation was done outside the transport device, but flows could still be efficiently mapped to flexible-rate transponder modules. In this context, the appearance of Flex Ethernet (FlexE) is targeted at decoupling the rates of interfaces connecting routers to transport boxes, from the actual flows traversing them. Through the introduction of an additional mapping/de-mapping layer, the capacity of multiple Ethernet interfaces can be virtualized in a resource pool for different flows. This paper addresses the application of FlexE to dense wavelength division multiplexing (DWDM) transport scenarios. Specifically, it evaluates how agnostic to FlexE a transport box should be, considering the potential trade-off between its complexity and the ability to efficiently fill lightpaths. Through a network simulation handling the provisioning of Ethernet flows in a DCI scenario, we evaluate the various FlexE use cases envisioned for transport networks, and how they affect the efficiency of router port usage and transport box provisioning, as well as their effect on the capacity of the DWDM layer.

To assess the efficacy of meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on three human urinary bladder-cancer cell lines (HT1376, T24 and 5637) and on mice urinary bladder cancer chemically induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). The in vitro effects of meloxicam were assessed by optical microscopy, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and comet assay. In vivo, Hsd:ICR male mice were exposed to BBN in drinking water, over the course of 12 weeks. Subsequently, animals were treated with meloxicam by intraperitoneal route, for 6 consecutively weeks. Tumour development was evaluated by haematoxylin and eosin staining. Renal and hepatic functions, interleucin-6 (IL-6), C-reactive protein (CRP) and tumour necrosis factor (TNFα) were also evaluated. In vitro, meloxicam induced a significant (P

Mammary tumors similar to those observed in women can be induced in rats by intraperitoneal administration of N-methyl-N-nitrosourea. Determining tumor volume is a useful and quantitative way to monitor tumor progression. In this study, the authors measured dimensions of rat mammary tumors using a caliper and using real-time compound B-mode ultrasonography. They then used different formulas to calculate tumor volume from these tumor measurements and compared the calculated tumor volumes with the real tumor volume to identify the formulas that gave the most accurate volume calculations. They found that caliper and ultrasonography measurements were significantly correlated but that tumor volumes calculated using different formulas varied substantially. Mammary tumors seemed to take on an oblate spheroid geometry. The most accurate volume calculations were obtained using the formula V = (W-2 x L)/2 for caliper measurements and the formula V = (4/3) x pi x (L/2) x (L/2) x (D/2) for ultrasonography measurements, where V is tumor volume, W is tumor width, L is tumor length and D is tumor depth.

We employ a cost-optimization procedure for the static planning of flexible-grid networks with heterogeneous interfaces spanning 40, 100 and 400 Gb/s channels. The optimization results show that the extra capacity enabled by this setup can reach 37% in a long-haul network, and more than double in a metro network. Furthermore, we evaluate different scenarios in terms of the traffic profile and the cost ratio between 100G and 400G technology. It is shown that 400G channels already have a strong case for cost-efficient deployment in the range of 2.5 to 3 times the cost of 100G, and for demands exceeding 200 Gb/s, more so in metro scenarios.

In order for transport networks to cost-effectively provide higher capacity, it is expected that channel bit-rates beyond 100 Gb/s will be accomplished by resorting to a flexible WDM grid with variable channel spacing. Among the implications of this concept is the need for planning tools that fully exploit the additional degrees of freedom enabled by a flexible grid to further optimize network cost and spectral efficiency. This paper proposes an optimization framework to minimize the transponder and regenerator deployment cost in a translucent WDM network featuring channel bit-rates of 40, 100 and 400 Gb/s and multiple transmission formats per bit-rate, each characterized by its own spectral width, optical reach and cost properties. Firstly, we formulate the problem via a novel Integer Linear Programming (ILP) model, whose resolution finds the optimal (cheapest) feasible network configuration. Secondly, we propose an efficient heuristic called Narrowest First-Iterative Cost Reduction (NF-ICR) to handle network scenarios for which solving the ILP entails an unreasonable computational burden. The NF-ICR heuristic is shown to provide tight optimality bounds where the benchmark given by the ILP solution is attainable. For larger networks, we show that the use of a flexible grid and multiple format options for each bit-rate results in around 10% less cost in transponders and regenerators for metro networks, and a substantial increase in the total traffic load supported by the network. We also conclude that a distinction emerges between metro/regional scenarios and long-haul networks with long paths, wherein the shorter transparent reach of 400 Gb/s channels drives up the cost due to extra regeneration, favoring the use of parallelized solutions of lower bit-rate channels.

Continuous traffic growth and crunched profit margins are leading network operators to deploying high-capacity backbone infrastructures with minimal capital investment. However, the cost-effective design of optical transport networks (OTNs) remains a complex challenge subjected to multiple constraints, e.g., maximum bit rate per channel, electrical multiplexing capabilities, wavelength count per fiber, optical interface cost, maximum transparent reach, etc. To efficiently solve this multi-constrained dimensioning problem in presence of heterogeneous client demands and optical channel rates of 40 Gb/s and 100 Gb/s, this paper presents a novel hybrid optimization framework. The proposed approach is based on an iterative combination of linear programming and rounding algorithms for the demand routing, with graph coloring heuristics for the wavelength assignment. The performance of this framework is assessed and compared with a similar approach that resorts to an integer linear programming (ILP) model to route the demands. The results obtained show that our proposal is able to reach the same low network expenditures as the ILP while requesting less computation time. We also confirm that the most cost-effective network solutions are attained when optical line rate heterogeneity is jointly applied with diverse multiplexing capabilities at the OTN electrical layer, such as grooming and inverse-multiplexing.

Hepatocellular carcinoma (HCC) is responsible for more then 600 000 deaths worldwide. HCC accounts for 85 to 90% of primary liver cancers [1]. Laboratory mouse is one of the best animal models to study cancer in vivo due to various features like the similarities to humans. Animal models that mimic human diseases are quite important to understand biopathology mechanisms underlying those diseases [2]. N-diethylnitrosamine (DEN) is a genotoxic carcinogen activated by a P450-dependent mono-oxigenase into a highly reactive molecule that will affect liver tissue [3]. The aim of this study was to evaluate the effect of DEN on 5 weeks old male ICR mice physiologic parameters. Mice were euthanized 7 and 14 weeks after last DEN injections. A thorough necropsy was performed and registered the weight and macroscopic evaluation of organs. Blood for hematocrit analysis was collected by cardiac puncture. Some animals of the experimental group developed visible alterations in the liver. Significant values in biochemistry parameters between control/experimental groups were determined to alanine aminotransferase (p = 0.044) and total bilirrubin (p = 0.026). Mean weight values were also significant between groups in the first euthanized mice (p = 0.048).