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INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response.Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS.Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%.There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.

Data on glycemic control and its determinants among Brazilian patients with type-2 diabetes (DM2) are scarce. The BrazIliaN Type 12 DiabetEs Disease Registry (BINDER) is a multicenter, longitudinal study, designed to investigate the glycemic control in a real-word scenario.1142 patients participated in the five visits of the BINDER study between April/2017 and October/2019. For each visit, glycemic control was assessed using the last measure available for HbA1c. Sociodemographic and anthropometric characteristics were also analyzed.At baseline, the median HbA1c level was 7.1% (4.1-15.0%); 259 (31.4%) participants had HbA1c ≤ 6.5% and 396 (48.2%) had HbA1c ≤ 7.0%. Younger age (p = 0.014), low educational level (p = 0.025) and the type of healthcare service (public sector; p = 0.0058) were independently associated with the elevated HbA1c. After 2 years, there were no statistically significant differences in HbA1c median values in relation to baseline.In this sample of DM2 patients, younger age, low educational level and being treated at the public service were associated with worse glycemic control. Over a 2-year follow-up, there was no significant change in the median HbA1c. These findings suggest that strategies are needed to improve glycemic control, especially in those treated in the public service.

The historical concept that obesity protects against bone fractures has been questioned. Weight loss appears to reduce bone mineral density (BMD); however, the results in young adults are inconsistent, and data on the effects of weight loss on bone microstructure are limited. This study aimed to evaluate the impact of weight loss using an intragastric balloon (IGB) on bone density and microstructure. Forty obese patients with metabolic syndrome (mean age 35.1 ± 7.3 yr) used an IGB continuously for 6 mo. Laboratory tests, areal BMD, and body composition measurements via dual-energy X-ray absorptiometry, and volumetric BMD and bone microstructure measurements via high-resolution peripheral quantitative computed tomography were conducted before IGB placement and after IGB removal. The mean weight loss was 11.5%. After 6 mo, there were significant increases in vitamin D and carboxyterminal telopeptide of type 1 collagen levels. After IGB use, areal BMD increased in the spine but decreased in the total femur and the 33% radius. Cortical BMD increased in the distal radius but tended to decrease in the distal tibia. The observed trabecular bone loss in the distal tibia contributed to the decline in the total volumetric BMD at this site. There was a negative correlation between the changes in leptin levels and the measures of trabecular quality in the tibia on high-resolution peripheral quantitative computed tomography. Weight loss may negatively impact bone microstructure in young patients, especially for weight-bearing bones, in which obesity has a more prominent effect.

Here, we report a flow chemistry approach for kinetic resolution of (±)-1,2-propanediol protected by trityl group using the packed-bed reactor filled with different immobilized enzymes. It was investigated the performance of 16 immobilized lipases, including commercial Lipozyme TL, Novozym 51032, Novozym 435 (N435) and lipases immobilized by our group. Based on the values of conversion and enantioseletivity, batch experiments were then translated to the continuous-flow environment. Continuous flow (CF) reactors allowed reaction time reduction, from 6 h in batch to 7 min, keeping the values of conversion (up to 50%) and selectivity (E value >200) during the reaction procedure using the commercial enzyme Novozym 435. In addition, continuous flow conditions increased the productivity of kinetic resolution 3 times when compared to conventional batch reactor, after its optimization.

The Pacific oyster Crassostrea gigas is among the most frequently cultured aquaculture species worldwide. In bivalve aquaculture, some environmental factors may induce the production of Reactive Species of Oxygen (ROS) that besides causing injuries to several vital cellular components, may lead to inflammatory processes. Usually, antioxidant enzymes of bivalves defense systems have an important role in the diminution of harmful effects of ROS. However sometimes it is not enough to restore the oxidative balance, being required an additional action of external antioxidant compounds. Knowing that biochemical composition of the diets may influence the physiology of bivalves, the aim of this study was to evaluate the effects of different ratios of microalgae and macroalgae on the oxidative stress responses during broodstock conditioning of C. gigas. Seven hundred and twenty oysters were divided in four dietary groups (3 tanks/diet; 60 oysters/tank). Each group was fed with one of the following diets: 100% macroalgae (Ulva rigida) (Diet 1); 50% macroalgae +50% live microalgae blend (Diet 2); 25% macroalgae +75% microalgae blend (Diet 3); or 100% microalgae blend (Diet 4). The microalgae blend comprised 33% Tisochrysis lutea and 66% diatoms (75% Skeletonema costatum + 25% Chaetoceros calcitrans). To assess diets effectiveness in the reduction of oysters oxidative stress, antioxidant capacity of the diets and the oxidative stress responses of the oysters were determined. The ABTS+ , DPPH , ORAC, O2 − and −NO assays were performed on diets to characterize their antioxidant capacity; Moreover, a possible anti-inflammatory effect of diets was assessed via human red blood cell (HRBC) membrane stabilization by heat induced assay. Catalase, lipid peroxidation, glutathione S-transferase and total and oxidized glutathione were quantified in the oysters to evaluate the dietary effects on the oxidative stress responses. Flesh weight of oysters fed Diet 3 and 4 was significantly higher than oysters fed with diets 1 and 2 (P ≤ .001). Results revealed that a 25% macroalgae and 75% microalgae blend (Diet 3) was the most effective dietary formulation in decreasing the oxidative stress, in terms of TG levels during the broodstock conditioning of the Pacific oysters, and in terms of NO and O2 −; also exhibiting a potential anti-inflammatory effect. An additional advantage in supplementing 25% of Ulva rigida is the reduction of microalgae production costs during the broodstock conditioning of Pacific oysters.

Summary Background Patients with relapsed or refractory high-risk chronic lymphocytic leukaemia or mantle cell lymphoma often do not derive durable benefit from ibrutinib monotherapy. We hypothesised that dual B-cell receptor pathway blockade would be tolerable and efficacious. We investigated a next-generation phosphoinositide-3-kinase-δ inhibitor (PI3K-δi), umbralisib, plus a Bruton tyrosine kinase inhibitor (BTKi), ibrutinib, in relapsed or refractory chronic lymphocytic leukaemia and mantle cell lymphoma. Methods We did an investigator-initiated, multicentre, phase 1–1b study of patients from five sites in the USA (academic and community sites). Patients were 18 years and older with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma, with an Eastern Cooperative Oncology Group performance status of 2 or less, and were given umbralisib orally once daily (400 mg, 600 mg, or 800 mg) and ibrutinib orally once daily (420 mg for chronic lymphocytic leukaemia or 560 mg for mantle cell lymphoma) until disease progression or unacceptable toxicity. The phase 1 dose-escalation cohorts for each histology escalated independently in a standard 3 × 3 design. The primary endpoints were intention-to-treat assessment of maximum-tolerated dose, safety, and dose-limiting toxicities. This trial is ongoing and is registered with ClinicalTrials.gov , number NCT02268851 . Findings Between Dec 5, 2014, and March 7, 2018, we enrolled 44 patients, of which 42 were given at least one dose of study drug (chronic lymphocytic leukaemia, n=21; mantle cell lymphoma, n=21). Patients had a median age of 68 years (range 48–85) and had a median of two (IQR 1–3) previous therapies. No dose-limiting toxicities were observed and the maximum-tolerated dose of umbralisib was not reached. The recommended phase 2 dose of umbralisib when given in combination with ibrutinib was 800 mg once daily. The most frequent adverse events included diarrhoea (22 [52%] patients, 10% of whom had grade 3), infection (21 [50%], 17% grade 3–4), and transaminitis (ten [24%], 2% grade 3). Serious adverse events occurred in 12 (29%) patients and included lipase elevation, atrial fibrillation, hypophosphataemia, adrenal insufficiency, transaminitis, and infections. Interpretation Umbralisib plus ibrutinib is well tolerated and active in relapsed or refractory chronic lymphocytic leukaemia and mantle cell lymphoma, with a recommended phase 2 dose of umbralisib 800 mg once daily. To the best of our knowledge, these are the first clinical data on a BTKi and PI3K-δi doublet in B-cell malignancies, and the results suggest that this approach is feasible and worthy of further study. Funding TG Therapeutics, Leukemia and Lymphoma Society Therapy Accelerator Program.

The current standard of care for the treatment of locally advanced rectal cancer includes neoadjuvant chemoradiation (nCRT) followed by total mesorrectal excision (TME). The observation of significant primary tumor response to radiation and chemotherapy led to the idea of organ-preserving strategies in selected patients who achieved clinical, endoscopic and radiological evidence of complete tumor regression. One of these strategies includes no immediate surgery with close surveillance, known as the Watch and Wait strategy (WW). The potential benefits of this approach with the avoidance of radical TME have to be weighed against the potential risk of local tumor regrowth. Exploration of these advantages and disadvantages will attempt to answer why WW may be an attractive alternative to rectal cancer patients and their treating physicians. In order to safely implement this strategy, some key issues related to baseline staging, neoadjuvant treatment regimens, timing for tumor response assessment, must be carefully considered. The combination of these features will attempt to clarify "how" and "to whom" the WW strategy may be considered. Ultimately, in the setting of contemporary neoadjuvant treatment regimens including total neoadjuvant therapy strategies (TNT), the achievement of a clinical complete response is likely to affect a significant proportion of patients. As endoscopic and radiological imaging modalities have evolved and improved, WW is expected to become an integral part during multidisciplinary management decision. Finally, understanding the clinical consequences of local tumor regrowth both in terms of local and distant relapse may allow for optimal and safe selection of patients fully aware of advantages or disadvantages of this strategy.

Layer-by-layer thin films of arylenediimides were grown on phosphonate-primed silicon and quartz substrates by the zirconium phosphonate method. The method consists in depositing alternated organic/inorganic layers, where the organic layer was a phosphonate-substituted arylenediimide and the inorganic layer was Zr4+. Heterogeneous films with up to 50 layers, containing different imides, were produced. The building blocks were N,N′-bis(2-phosphonoethyl)pyromellitimide (PPMI), N,N′-bis(2-phosphonoethyl)-1,4,5,8-naphthalenediimide (PNDI) and N,N′-bis(2-phosphonoethyl)-3,4,9,10-perylenediimide (PPDI). Thin films with the sequence PPDI/PNDI, PPDI/PPMI, PNDI/PPMI and PPDI/PNDI/PPMI were produced. Organized film growth was observed by UV–visible–NIR spectroscopy (quartz substrates) and ellipsometry (silicon substrates). AFM images showed that the surface of the films was smooth and uniform. The imides in the films were reduced using sodium dithionite as a reducing agent, generating stable radical anions and dianions of the imides. The following species were detected in the absorption spectra of the reduced films: PPDI−∙, PPDI2−, PNDI−∙, and PNDI2−. Reduction of the imides in the films was rather slow, as compared to homogeneous solutions. When the reduced films were exposed to atmospheric oxygen, reoxidation took place, which was also much slower than in homogeneous solutions. In conclusion, a mix of aromatic imide reduced species, absorbing through the whole visible range, was produced and stabilized in thin films.

The technical debt (TD) metaphor describes actions made during various stages of software development that lead to a more costly future regarding system maintenance and evolution. According to recent studies, on average 25% of development effort is spent, i.e. wasted, on TD caused issues in software development organizations. However, further research is needed to investigate the relations between various software development activities and TD. The objective of this study is twofold. First, to get empirical insight on the understanding and the use of the TD concept in the IT industry. Second, to contribute towards precise conceptualization of the TD concept through analysis of causes and effects. In order to address the research objective a family of surveys was designed as a part of an international initiative that congregates researchers from 12 countries -- InsighTD. At country level, national teams ran survey replications with industry practitioners from the respective countries. In total 653 valid responses were collected from 6 countries. Regarding the prevalence of the TD concept 22% of practitioners have only theoretical knowledge about it, and 47% have some practical experiences with TD identification or management. Further analysis indicated that senior practitioners who work in larger organizations, larger teams, and on larger systems are more likely to be experienced with TD management. Time pressure or deadline was the single most cited cause of TD. Regarding the effects of TD: delivery delay, low maintainability, and rework were the most cited. InsighTD is the first family of surveys on technical debt in software engineering. It provided a methodological framework that allowed multiple replication teams to conduct research activities and to contribute to a single dataset. Future work will focus on more specific aspects of TD management., Comment: Journal of Systems and Software

This study aimed to evaluate the protective effects of four autochthonous bacteria isolated from juvenile sole (Solea senegalensis) intestine as dietary probiotic supplement against bacterial pathogen infection and handling/transport stressors. Growth performance and immune responses were evaluated after 85 days of feeding trial. Sole (IBW = 16.07 ± 0.11 g) were fed six experimental diets, a control diet (CTRL, without the dietary probiotic supplementation), and five diets supplemented with probiotic bacteria: PB1 (Shewanella hafniensis), PB2 (Enterococcus raffinosus), PB3 (Shewanella hafniensis + Arthrobacter soli), PB4 (Pseudomonas protegens + Arthrobacter soli) and PB5 (Shewanella hafniensis + Arthrobacter soli + Enterococcus raffinosus). All bacteria were selected based on their in vitro antimicrobial activity. After the growth trial, fish were submitted to a stress factor (transport) and then each dietary group was divided in two additional groups: non-infected (placebo) and infected with Photobacterium damselae subsp. piscicida. Immune and antioxidant responses were evaluated at day 10 post-infection. In infection trial A, fish were infected on the same day of transport, whereas in trial B fish were infected after a 7-day recovery from the transport stress. At the end of the feeding trial, fish fed with PB2 and PB4 showed lower final body weight when compared with the other dietary groups. Respiratory burst activity and nitric oxide production were not affected by probiotic supplementation. Fish fed with PB5 presented lower peroxidase activity compared to CTRL. Lysozyme and alternative complement pathway activity (ACH50) showed no significant differences between treatments. The innate immune responses were significantly affected after handling stress and bacterial infection. In trial A, the ACH50 levels of infected fish were significantly lower than the placebo groups. On the other hand, in trial B fish infected with Pdp demonstrated higher ACH50 levels when compared to placebos. Peroxidase levels were strongly modulated by bacterial infection and handling stress. In trials A and B, infection had a clear downgrade effect in peroxidase levels. Lipid peroxidation, catalase, glutathione S-transferase and glutathione reductase were altered by both bacterial infection and transport. Overall, dietary probiotic supplementation did not influence growth performance of sole. The immune and oxidative defenses of sole responded differently to infection depending on the probiotic and the synergy between pathogen infection and transport. © 2018 The current study was partially supported by the project PROBIOSOLEA (reference 13551), co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN) , through the European Regional Development Fund . The current study was also supported by the Research Line INSEAFOOD of the project INNOVMAR-Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035 ), funded by the Northern Regional Operational Programme (NORTE 2020) through the ERDF. B. Costas was supported by FCT, Portugal ( IF/00197/2015 ).

Enantiomerically pure alcohols and amines are important building blocks for the pharmaceutical and agrochemical industries. Among the different approaches to reach these compounds, enzyme-catalyzed kinetic resolution (EKR) of racemates is one of the most widely studied and employed methodologies. In this kind of reaction, the acyl donor plays an important role, making the search for new acylating agents an attractive field. Herein, we report our results over the use of PEG600 carboxylates as acylating agent for separation of amines and alcohols enantiomers in continuous flow. For the EKR of 1-phenylethylamine, PEG600-diester show the best results, and (S)-1-phenylethylamine was obtained with high yield and enantiomeric purity (49% yield and >99% (S)) with a productivity of 211 mg h−1 genzyme−1. (R)-1-phenylethylamine was recovered after chemical hydrolysis of the amide formed with high yield and ee (35% yield and 95% ee). In addition, the immobilized enzyme remains active for at least 20 h operation. On the other hand, (R)- and (S)-1-phenylethanol was obtained after continuous lipase-catalyzed hydrolysis of the ester (formed after reaction with PEG) in good conversions to both enantiomers, with a productivity of 68 mg h−1 g enzyme−1 for the (S)- enantiomer and 64 mg h−1 genzyme−1 for the (R) enantiomer.

Context The concept of technical debt (TD) contextualizes problems faced during software evolution considering the tasks that are not carried out adequately during its development. Currently, it is common to associate any impediment related to the software product and its development process to the definition of TD. This can bring confusion and ambiguity in the use of the term. Besides, due to the increasing amount of work in the area, it is difficult to have a comprehensive view of the plethora of proposals on TD management. Objective This paper intends to investigate the current state of research on TD by identifying what research topics have been considered, organizing research directions and practical knowledge that has already been defined, identifying the known types of TD, and organizing what activities, strategies and tools have been proposed to support the management of TD. Method A tertiary study was performed based on a set of five research questions. In total, 13 secondary studies, dated from 2012 to March 2018, were evaluated. Results The results of this tertiary study are beneficial for both practitioners and researchers. We evolved a taxonomy of TD types, identified a list of situations in which debt items can be found in software projects, and organized a map representing the state of the art of activities, strategies and tools to support TD management. Besides, we also summarized some research directions and practical knowledge, and identified the research topics that have been more considered in secondary studies. Conclusion This tertiary study revisited the TD landscape. Its results can help to identify points that still require further investigation in TD research.

Made available in DSpace on 2018-11-26T16:01:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-09-01 Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Embrapa Cafe Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Cafestol and kahweol (C&K), two coffee diterpene alcohols with structural similarity which exhibit anticarcinogenic effects, were isolated from green coffee Arabica beans, followed by their lipase-catalysed esterification and purification by preparative high-performance liquid chromatography (HPLC). The isolation and enzymatic synthesis parameters of C&K esters were studied, with the latter optimised by a Central Composite Design; both procedures were monitored by gas chromatography. Scale up and improved isolation conditions resulted in 1.29 g of C&K, with 98% purity from 300 g of green Arabica beans. The highest C&K ester yields were observed using an alcohol: fatty acid molar ratio of 1:5, 73.3 mg mL(-1) of CAL-B enzyme, 70 degrees C and 240 rpm for 3 days in toluene, leading to 85-88% conversion among a variety of tested C&K esters, including n-C-14:0-C-20:0, C-18:1, C-18:2 and C-18:3. Univ Fed Rio de Janeiro, Inst Quim, Lab Anal Aromas, Ave Athos da Silveira Ramos 149,Bloco A,Sala 626, BR-21941895 Rio De Janeiro, RJ, Brazil Univ Fed Rio de Janeiro, Inst Quim, LADETEC, Ave Horacio Macedo 1281, BR-21941598 Rio De Janeiro, RJ, Brazil Univ Fed Rio de Janeiro, Escola Quim, Dept Engn Bioquim, Ave Athos da Silveira Ramos,Bloco E,Sala E203, BR-21941909 Rio De Janeiro, RJ, Brazil Univ Estadual Paulista, Dept Engn Bioproc & Biotecnol, Campus Botucatu,Rua Jose Barbosa de Barros 1780, BR-18610307 Lageado, SP, Brazil Monash Univ, Sch Chem, Australian Ctr Res Separat Sci, Wellington Rd, Clayton, Vic 3800, Australia Embrapa Agroind Alimentos, Ave Amer 29501, BR-23020470 Rio De Janeiro, RJ, Brazil Univ Fed Rio de Janeiro, Inst Quim, Lab Biocatalise & Sintese Organ, Ave Athos da Silveira Ramos 149, BR-21941895 Rio De Janeiro, RJ, Brazil Univ Estadual Paulista, Dept Engn Bioproc & Biotecnol, Campus Botucatu,Rua Jose Barbosa de Barros 1780, BR-18610307 Lageado, SP, Brazil

AIM: The present study determined the role of renin-angiotensin system (RAS), endothelin system, and eicosanoid system in the blood pressure (BP) regulation in male and female Zucker rats, and whether the pressor response change similarly in lean and obese animals. MATERIAL AND METHODS: In female (f) and male (m), lean (L) and obese (O) Zucker rats (ZR) at 22 weeks old, we evaluated the role of the 3 mentioned systems using the following treatments: 1) enalapril (angiotensin I converting enzyme inhibitor), 2) the ABT-627 (endothelin receptor A (ET(A)) antagonist), and 3) the 1-aminobenzotriazol (1-ABT: eicosanoid synthesis inhibitor). KEY FINDINGS: MAP by radiotelemetry was similar and significantly higher in mOZR (120 ± 2 mm Hg) and fOZR (116 ± 4 mm Hg) (p < 0.05 vs. m-, fLZR), than mLZR (105 ± 3 mm Hg) and fLZR (106 ± 1 mm Hg), that were also similar. Enalapril reduced MAP more in mOZR (23%) and mLZR (26%), than fLZR (20%, p < 0.905 vs. mLZR) or fOZR (9%; p < 0.05 vs. other groups). After 10 days of drug-free and recovery period, ABT-627 reduced MAP in fLZR and mLZR by similar amounts (102 ± 4 to 92 ± 3 mm Hg, n = 6; p < 0.05 and 105 ± 2 vs. 92 ± 3 mm Hg, n = 6; p < 0.05, respectively), but did not affect either fOZR or mOZR. After another 10 days of drug-free and recovery period, 1-ABT reduced MAP in fOZR (116 ± 4 to 95 ± 2, n = 6; p < 0.05), and did not affect all other groups. SIGNIFICANCE: We show that the mechanisms responsible for elevated BP in male and female OZR and LZR are different, and suggest that obesity may cause an increase in BP via different mechanisms in men and women as well.

The decarboxylation of amino acids in presence of a carboxylic anhydride leading to the corresponding ketones, known as Dakin-West reaction, is about to complete almost one century of discovery. In this review, we firstly present the chronological progress in the mechanistic study of the reaction, with an overview about types of substrates, anhydrides and bases already used in the Dakin-West reaction. And ultimately, the application of the reaction in the synthesis of compounds of pharmaceutical or industrial interest is also discussed.

Crizotinib is an anti-cancer agent approved for treatment of non-small cell lung carcinoma. Retrosynthetic analysis revels 1-(2,6-dichloro-3-fluorophenyl)ethanol as an important intermediate, which can be made available by different biocatalytic approaches. Herein we report our results on the kinetic and dynamic resolution towards the desired chiral intermediate for Crizotinib synthesis. The results obtained show that very good conversions and high selectivity could be obtained for the kinetic resolution (45% conv. and E > 200) while dynamic kinetic resolution under continuous-flow conditions afforded the desired product in 57% conversion and 98% e.e.

The requirement of NMDA receptor (NMDAR) activity for memory formation is well described. However, the plasticity mechanisms for memory can be modified by experience, such that a future similar learning becomes independent of NMDARs. This effect has often been reported in learning events conducted with a few days interval. In this work, we asked whether the NMDAR-independency is permanent or the brain regions and plasticity mechanisms of experience-dependent learning may change over time. Considering that contextual memories undergo a gradual reorganization over time, becoming progressively independent from the hippocampus and dependent upon cortical regions, we investigated the brain regions mediating a new related learning conducted at a remote time-point, when the first memory was already cortically established. First, we demonstrated that anterior cingulate cortex was not able to support a learning subsequent to a previous systems-level consolidated memory; it did require at least one functional subregion of the hippocampus (ventral or dorsal). Moreover, after replicating findings showing that a few days interval between trainings induces a NMDAR-independent learning, we managed to show that a learning following a longer interval once again becomes dependent on NMDARs in the hippocampus. These findings suggest that while the previous memory grows independent from the hippocampus over time, an experience-dependent learning following a systems-consolidated memory once again engages the hippocampus and a NMDAR-dependent plasticity mechanism.

Cultured fish can be induced to swim, although the suitability and benefits remain to be tested. Sustained swimming exercise (SSE) training and detraining (DET) were applied in juvenile gilthead sea bream (Sparus aurata) and the metabolic rates were investigated. Fish with a total body mass of 80.5 ± 1.5 g and total length 17.2 ± 0.1 cm were maintained untrained (spontaneously swimming activity, UNT), swim-trained (induced sustained swimming activity, SSE) at 1 BL s−1 for 28 days, or detrained (28 days of swimming followed by 10 days of untraining, DET). Standard metabolic rate (SMR), maximum metabolic rate (MMR), and excess post-exercise oxygen consumption (EPOC) were assessed (n = 10). In addition, the effects of SSE training (51 days) on blood and plasma parameters were investigated before and immediately after applying a high-intensity swimming (HIS) protocol. SMR, MMR, and EPOC values were not different between SSE, UNT, or DET fish (143.2, 465.5 mg O2 kg−1 h−1, and 459.1 mg O2 kg−1, respectively). Spite the lack of differences between treatments, the dispersion in the residuals for SMR, MMR, and absolute aerobic scope (AAS) values followed the order UNT > DET > SSE, indicating that swim training decreases the individual variation of these metabolic parameters. Haematological parameters, plasma glucose, lactate, and cortisol levels were similar between SSE and UNT groups before HIS. Plasma glucose and lactate levels increased in both groups after HIS, being higher in the SSE group. Plasma cortisol levels were similar between both groups after HIS. Results suggest that SSE training improves energy use and reduces individual variation in SMR and MMR, an effect that declines with detraining.

Context: Architectural decisions are considered one of the most common sources of technical debt (TD). Thus, it is necessary to understand how TD is perceived by software architects, particularly, the practices supporting the elimination of debt items from projects, and the practices used to reduce the chances of TD occurrence. Objective: This paper investigates the most commonly used practices to pay off TD and to prevent debt occurrence in software projects from the architect’s point of view. Method: We used the available data from InsighTD, which is a globally distributed family of industrial surveys on the causes, effects, and management of TD. We analyze responses from a corpus of 72 software architects from Brazil, Chile, Colombia, and the United States. Results: Results showed that refactoring (30.2%) was the main practice related to TD payment, followed by design improvements (14.0%). Refactoring, design improvements, and test improvements are the most cited payment practices among cases of code, design and test debt. Concerning the TD preventive practices, we find that having a well-defined architecture and design is the most cited practice (13.6%), followed by having a well-defined scope and requirements. This last practice is the most cited one for expert software architects. Finally, when comparing preventive practices among the three major roles derived from the survey (software architects, engineer roles, and management roles), we found that none of the roles shared the most cited practice, meaning that each role had its worries and focus on different strategies to reduce TD’s presence in the software. Conclusion: The lists of TD payment and prevention practices can guide software teams by having a catalog of practices to keep debt controlled or reduced.

The stressful conditions of intensive aquaculture systems, combined with excessive antibiotic use, may have dysbiotic effects on aquaculture microbiomes and promote the spread of opportunistic pathogens. Here, we hypothesized that humic substances (HS), when added to the rearing water of a marine recirculating aquaculture system (RAS), will act as a chemical modulator of fish-associated bacterial communities and suppress potential pathogens. To test this, a 28-day RAS trial for juvenile European sea bass (Dicentrarchus labrax) was conducted with and without HS modulation. High-throughput sequencing of the 16S rRNA gene was used to evaluate role of HS in modulating fish bacterial assemblages (gut and skin mucus). In addition to this, biometric, digestive and oxidative stress parameters were measured to assess the impact of HS on fish performance. HS modulation was associated with an increased bacterial diversity and a distinct bacterial community composition in the fish skin mucus. HS modulation significantly increased the relative abundance of amplicon sequence variants (ASVs) related to the potentially beneficial Roseobacter clade and lowered the abundances of ASVs related to potential fish pathogens (e.g., Acinetobacter jonhsonii and Vibrio harveyi). In line with compositional differences, there was an enrichment of predictive KEGG categories related to antagonism and significantly lower abundances of KEGG categories related to pathogenesis and invasibility. In the fish gut, HS modulation was associated with a lower abundance of the orders Enterobacteriales and Bacillales. HS modulation also was associated with significant reductions in fish oxidative stress parameters and a significant increase in the activity of the digestive enzyme chymotrypsin. For the first time, our results demonstrate the potential of dissolved HS as a modulator of fish microbial communities.

This study evaluated the use of Gracilaria by-products in gilthead seabream diet to modulate intestinal bacterial community, physiological responses as well as skin and fillet attributes during cold storage. Fish were fed for 52 days with six experimental diets: i) a diet containing a commercial antioxidant (CTR), ii) a diet without antioxidant (NO-AOX), iii) a NO-AOX with 0.5% ethanolic extract (0.5% EE), iv) a NO-AOX with 5% ethanolic waste (5% EEW), v) a NO-AOX with 5% agar waste (5% AW), vi) a NO-AOX with 2.5% agar waste (2.5% AW). Fish growth performance was not affected by the experimental diets. Proteobacteria (63–83%), Firmicutes (4–19%) and Actinobacteria (2–4%) were the predominant phyla in the intestine of fish fed all diets. The diet with 5% AW increased the relative abundance of Firmicutes phyla as compared to the other diets. Fish fed NO-AOX, 5% EEW, 5% AW and 2.5% AW showed a lower abundance of Oxalobacteraceae than those fed CTR diet. The Clostridium genera increased in the 5% AW compared to 5% EEW. Nevertheless, no major differences were detected in the richness and diversity of the intestinal bacterial communities of gilthead seabream fed the experimental diets. Fish fed 5% AW showed higher intestinal trypsin activity than those fed 0.5% EE. The skin yellowness was higher in the skin of fish fed 2.5% AW diet compared to those fed 0.5% EE diet. The results presented provided evidences of the potential application of AW and EEW as a novel and eco-friendly dietary supplement to be included in future aquaculture feed formulations.

In this work lipase CaLB was immobilized on functionalized Pd-SiO 2 nanoparticles in order to simplify the DKR of α-methylbenzylamine. Hybrid biocatalysts showed immobilization efficiencies of 82%, 80% and 76% when containing 1, 5 and 10% of Pd respectively. On DKR reaction values of ee > 99% and conversion of 82% were found with only 1% of Pd, generating a productivity of 2.21 mg of product h −1 mg of support −1 against 0.76 found by N435®. Compared to commercial N435®, the novel biocatalysts showed protein loads about 15-fold lower and higher activity, demonstrating competitive performances and high industrial applications.

The asymmetric synthesis of serinol-derivatives was investigated employing different amine transaminases as biocatalysts. Under the optimized conditions conversions up to 92% and excellent enantiomeric excesses up to 99% ee were obtained providing access to both, the ( R )- and ( S )-configurations of the serinol-monoester (2-amino-3-hydroxypropyl hexanoate).

The concentrations of ten metals (As, Cd, Cu, Fe, Hg, K, Na, Pb, Sn and Zn) were monitored in coastal seawater and biomass of the seaweed Alaria esculenta from Aughinish Bay on the West coast of Ireland during March–June 2014 in order to study their temporal variations and assimilation efficiencies and to assess the ecological quality of these ecosystems. Seawater and A. esculenta showed significant temporal variations in their metal concentrations during March–June 2014 and A. esculenta accumulated more efficiently Fe and Zn, but showed low sensitivity to Na and K. On the other hand, A. esculenta showed no active detoxication mechanisms for Cd and Pb, but no saturation point was observed during this work to any metal. Considering metal concentrations bioaccumulated by A. esculenta, the Irish coast of Aughinish Bay was always ecologically classified as “Class I – Unpolluted” during March–June 2014. The significant correlations between seawater and A. esculenta obtained to all metals proved that this seaweed species: (i) is a suitable biomonitor of metal contamination in Irish coasts; (ii) it can be included in the European Environmental Specimen Banks and (iii) it can be used in European Real-Time Environmental Monitoring Networks.

Objective: To investigate the relationship between serum thyrotropin (TSH), insulin resistance (IR), and cardiovascular risk factors (CRF) in a sample of overweight and obese Brazilian adolescents. Methods: A retrospective, longitudinal analysis of 199 overweight and obese pubescent adolescents was performed. The TSH and free T4 (fT4) levels, anthropometric measurements, and laboratory test results of these patients were analyzed. Results: 27 individuals (13.56%) presented with TSH levels above the normal level (subclinical hypothyroidism [SCH]). Their waist circumference (WC) was significantly higher than those of euthyroid individuals. Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Using TSH and BMI as independent variables, TSH levels were shown to be independently related to HOMA-IR (p = 0.001) and TG (p = 0.007). Among euthyroid subjects, individuals with TSH values