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Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest of this work., (Copyright © 2022 Infante, Salmanton-García, Fernández-Cruz, Marchesi, Jaksic, Weinbergerová, Besson, Duarte, Itri, Valković, Szotkovski, Busca, Guidetti, Glenthøj, Collins, Bonuomo, Sili, Seval, Machado, Cordoba, Blennow, Abu-Zeinah, Lamure, Kulasekararaj, Falces-Romero, Cattaneo, Van Doesum, Piukovics, Omrani, Magliano, Ledoux, de Ramon, Cabirta, Verga, López-García, Da Silva, Stojanoski, Meers, Lahmer, Martín-Pérez, Dávila-Vals, Van Praet, Samarkos, Bilgin, Karlsson, Batinić, Nordlander, Schönlein, Hoenigl, Ráčil, Mladenović, Hanakova, Zambrotta, De Jonge, Adžić-Vukičević, Nunes-Rodrigues, Prezioso, Navrátil, Marchetti, Cuccaro, Calbacho, Giordano, Cornely, Hernández-Rivas and Pagano.)

Background: Interplay between vaginal microbiome and human papillomavirus (HPV) remains unclear, partly due to heterogeneity of microbiota., Methods: We used data from 546 women enrolled in a cross-sectional study in 5 Brazil. We genotyped vaginal samples for HPV and sequenced V3-V4 region of 16S rRNA gene for vaginal microbiome analysis. We used stepwise logistic regression to construct 2 linear scores to predict high-risk HPV (hrHPV) positivity: one based exclusively on presence of individual bacterial taxa (microbiome-based [MB] score) and the other exclusively on participants' sociodemographic, behavioral, and clinical (SBC) characteristics. MB score combined coefficients of 30 (of 116) species. SBC score retained 6 of 25 candidate variables. We constructed receiver operating characteristic curves for scores as hrHPV correlates and compared areas under the curve (AUC) and 95% confidence intervals (CI)., Results: Overall, prevalence of hrHPV was 15.8%, and 26.2% had a Lactobacillus-depleted microbiome. AUCs were 0.8022 (95% CI, .7517-.8527) for MB score and 0.7027 (95% CI, .6419-.7636) for SBC score (P = .0163)., Conclusions: The proposed MB score is strongly correlated with hrHPV positivity-exceeding the predictive value of behavioral variables-suggesting its potential as an indicator of infection and possible value for clinical risk stratification., Competing Interests: Potential conflicts of interest. L. L. V. was an occasional speaker and consultant on Merck, Sharp & Dohme for HPV prophylactic vaccines. E. L. F.’s institution has received grants from Merck in support of investigator-initiated research outside the present work. E. L. F. has received consultancy fees from Merck and Roche outside the present work. E. L. F. and M. Z. hold a patent related to the discovery “DNA methylation markers for early detection of cervical cancer,” registered at the Office of Innovation and Partnerships, McGill University. All other authors declare no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Alkaloids play an important role in the chemical composition of tobacco, due to their effects that have led to the global consumption of this commodity. The β-carboline alkaloids present inhibitory action against the enzyme monoamine oxidase (MAO), which enhances the susceptibility to chemical dependence in smokers. There is a need for scientific studies to ensure the correct identification and quantification of these compounds in tobacco matrices. In this work, we present the development and validation of a microextraction analytical method for determination and quantification of the alkaloids harmaline, harmalol, harmane, harmine, norharmane, and tetrahydroharmine in natural and processed samples of tobacco, employing micro-matrix solid-phase dispersion (μMSPD), ultra-performance liquid chromatography (UPLC), and mass spectrometry (MS). The optimized μMSPD procedure employed of 0.01 g of sample, 0.1 g of Discovery® DPA-6S adsorbent, and elution with 2 mL of aqueous 1 % formic acid solution, resulting in a fast, practical, economical, and environmentally friendly technique. Validation of the methodology showed that it presented good linearity (R 2 > 0.9945), satisfactory accuracy and precision (in the range from 72 ± 16 % to 109 ± 9 %), and limits of quantification (LOQ) and detection (LOD) in the ranges 0.02-1.0 µg g -1 and 0.01-0.2 µg g -1 , respectively. The developed method was applied to tobacco samples, proving to be efficient for determination of β-carboline alkaloids. The compounds harmane and norharmane were quantified in samples of fresh tobacco leaves, cured tobacco leaves, twisted tobacco, and cigarettes. Harmine was only not quantified in the cigarettes., (Copyright © 2022. Published by Elsevier B.V.)

An expert panel convened by the European Alliance for Personalized Medicine (EAPM) reflected on achievements and outstanding challenges in Europe in mantle cell lymphoma (MCL). Through the prism of member state experience, the panel noted advances in outcomes over the last decade, but highlighted issues constituting barriers to better care. The list notably included availability of newer treatments, infrastructure and funding for related testing, and shortages of relevant skills and of research support. The prospect of improvements was held to reside in closer coordination and cooperation within and between individual countries, and in changes in policy and scale of investment at both national and EU levels.

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19., Methods: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting., Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR = 1.022, 95%CI 1.007‒1.038 and OR = 1.025, 95%CI 1.001‒1.051, respectively), while thromboprophylaxis use was protective (OR = 0.199, 95%CI 0.061‒0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR = 1.062, 95%CI 1.017-1.109 and OR = 2.438, 95%CI 1.023-5.813, respectively)., Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration., (© 2022. The Author(s).)

Mitochondria are the major organelles of energy production; however, active mitochondria can decline their energetic role and show a dysfunctional status. Mitochondrial dysfunction was induced by high non-physiological level of L-galactone-1,4-lactone (L-GalL), the precursor of ascorbate (AsA), in plant mitochondria. The dysfunction induced by L-GalL was associated with the fault in the mitochondrial electron partition and reactive oxygen species (ROS) over-production. Using mitochondria from RNAi-plant lines harbouring silenced L-galactone-1,4-lactone dehydrogenase (L-GalLDH) activity, it was demonstrated that such dysfunction is dependent on this enzyme activity. The capacity of alternative respiration was strongly decreased by L-GalL, probably mediated by redox-inactivation of the alternative oxidase (AOX) enzyme. Although, alternative respiration was shown to be the key factor that helps support AsA synthesis in dysfunctional mitochondria. Experiments with respiratory inhibitors showed that ROS formation and mitochondrial dysfunction were more associated with the decline in the activities of COX (cytochrome oxidase) and particularly AOX than with the lower activities of respiratory complexes I and III. The application of high L-GalL concentrations induced proteomic changes that indicated alterations in proteins related to oxidative stress and energetic status. However, supra-optimal L-GalL concentration was not deleterious for plants. Instead, the L-GalLDH activity could be positive. Indeed, it was found that wild type plants performed better growth than L-GalLDH-RNAi plants in response to high non-physiological L-GalL concentrations., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria.

Background: Systemic arterial hypertension is one of the most common cardiovascular risks, corresponding to 45% of deaths involving CVDs. The use of natural products, such as medicinal plants, belongs to a millennial part of human therapeutics history and has been employed as an alternative anti-hypertensive treatment., Objective: The present review aims to prospect some natural products already experimentally assayed against arterial hypertension through scientific virtual libraries and patent documents over the past 20 years. Search strategy . This is a systematic review of the adoption of the PRISMA protocol and a survey of the scientific literature that synthesizes the results from published articles between 2001 and 2020 concerning the use of medicinal plants in the management of hypertension, including which parts of the plant or organism are used, as well as the mechanisms of action underlying the anti-hypertensive effect. Furthermore, a technological prospection was also carried out in patent offices from different countries in order to check technologies based on natural products claimed for the treatment or prevention of hypertension. Inclusion criteria . Scientific articles where a natural product had been experimentally assayed for anti-hypertensive activity (part of plants, plant extracts, and products derived from other organisms) were included. Data extraction and analysis . The selected abstracts of the articles and patent documents were submitted to a rigorous reading process. Those articles and patents that were not related to anti-hypertensive effects and claimed potential applications were excluded from the search., Results: Eighty specimens of biological species that showed anti-hypertensive activity were recovered, with 01 representative from the kingdom Fungi and 02 from the kingdom Protista, with emphasis on the families Asteraceae and Lamiaceae, with 6 representatives each. Leaves and aerial parts were the most used parts of the plants for the extraction of anti-hypertensive products, with maceration being the most used extraction method. Regarding phytochemical analyses, the most described classes of biomolecules in the reviewed works were alkaloids, terpenes, coumarins, flavonoids, and peptides, with the reduction of oxidative stress and the release of NO among the mechanisms of action most involved in this process. Regarding the number of patent filings, China was the country that stood out as the main one, with 813 registrations., Conclusion: The anti-hypertensive activity of natural products is still little explored in Western countries. Besides, China and India have shown more results in this area than other countries, confirming the strong influence of traditional medicine in these countries., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Maisa Gomes da Silva et al.)

Background: Due to social and geographical isolation, indigenous people are more vulnerable to adverse conditions; however, there is a lack of data on the epidemics' impact on these populations. Thus, this article's objective was to describe the epidemiological situation of COVID-19 in indigenous communities in Brazil., Methods: This descriptive observational study was carried out in indigenous communities in the municipality of Amaturá (Amazonas, Brazil). Individuals from the Alto Rio Solimões Special Indigenous Sanitary District (DSEI) who met the Sars-Cov-2 infection case definitions during the period between January and August 2020 were included. For case notification, the definitions adopted by the Ministry of Health of Brazil and by the Special Secretariat for Indigenous Health were considered., Results: Out of the entire population served by the Alto Rio Solimões DSEI (n = 2890), 109 indigenous people were suspected of having been infected with Sars-Cov-R during the study period; a total of 89 cases were actually confirmed (rate: 3.08 cases/100,000 inhabitants). Most patients diagnosed with COVID-19 were female (56.2%), with a mean age of 32.4 (± 23.6) years. Predominant symptoms were fever (76.4%), dry cough (64%), and headache (60.7%). Complications occurred in 7.9% of the patients; no deaths were reported., Conclusion: These results enhance the observation that indigenous populations, even if relatively isolated, are exposed to COVID-19. The disease cases assessed showed a favorable evolution, which does not mean reducing the need for caring of this population., (© 2021. W. Montague Cobb-NMA Health Institute.)

Ammonia (NH[Formula: see text]) from manure is a concern in raising broiler due to possible damages to production and the environment. Brazil is the main exporter of chicken meat in the world and is also responsible for large waste of poultry litter. The country, likewise, figures as top 5 producers of green coconut, which results in considerable volumes of waste, since 80%-85% of the fruit is unusable. This work analyzes the ammonia concentration profile of two bedding substrates for raising broiler, to know, coir-husk fiber and a commonly used pine wood shavings in a Brazilian climate. A differential home-made photoacoustic cell combined with a diode laser was employed for sensing ammonia at trace levels. Such combination confers selectivity as well as lower limits of detection to the system. The chemical compositions pH, N, C, Ca, Mg, P[Formula: see text]O[Formula: see text] and K[Formula: see text]O were also determined, in addition to the moisture, dry matter and mineral content of substrates and litters. NH[Formula: see text] concentrations varied from (0.9 ± 0.3) ppmv to (19 ± 3) ppmv and from (2.1 ± 0.5) ppmv to (21 ± 3) ppmv for the coir-husk fiber and wood shavings substrates, respectively. Results showed the feasibility of using coconut fiber as poultry litter in regions where this material is a common waste. Moreover, as NH[Formula: see text] concentrations were lower for coconut fiber bedding compared to shavings, this coir-husk fiber is a potential residue to guarantee the environmental sustainability by Brazilian poultry farming. Coir-husk fibers presented significantly higher amounts of P and K in comparison to pine wood. NH[Formula: see text] profiles revealed that coir-husk fiber emitted lower quantities than wood shavings. Besides, a delay on the NH[Formula: see text] emission pattern was clearly seen when the coconut waste was the bedding material. Such a tendency was confirmed by the logistic model. Our findings, in turn, make the coir-husk an environmentally friendly alternative low-cost product for poultry litter as well as its potential use as natural fertilizer. The later deserves attention since there is a need to accurately assess the emissions of methane, nitrous oxide, and carbon dioxide during the composting process. In Brazil, the waste generated by the high production of green coconut is an environmental liability. The cost of poultry production has been high, reducing the profit of producers, who seek to make production cheaper. Measuring NH[Formula: see text] from poultry activity in Brazil, a tropical country, aims to control management and reduce production losses, since NH[Formula: see text] is a harmful gas to birds. The measurement of NH[Formula: see text] concentrations at trace levels from raising broilers by photoacoustic diode laser spectroscopy, to the best of our knowledge, has been reported for the very first time., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The main objectives of our work were to produce new nanostructured lipid carriers (NLCs) from interesterified and simple lipid phases and to study the influence of lipid composition on the physical characteristics and stability of NLCs. We used conventional oils and fats already used in lipid-based foods, in addition to soy lecithin as a natural emulsifier. The NLCs were formulated using as lipid phase, simple and interesterified blends composed of soybean oil as liquid lipid and fully hydrogenated oils from palm, soybean, microalgae, and crambe as solid lipids. NLCs were produced using high-pressure homogenization. NLCs were influenced by chemical interesterification and by the composition of the solid lipid used, mainly in relation to the fatty acid chain size. NLC formulations developed with a simple lipid phase were 256-323 nm (d 32 ) in size, with zeta potential values ranging from -36.93 to -42.87 mV after 60 days of storage. NLCs developed with the interesterified lipid phase were 250-288 nm (d 32 ) in size, with zeta potential values ranging from -40.17 to -44.20 mV after 60 days of storage. NLCs produced with saturated fatty acids with larger chain sizes showed larger particle sizes but showed less variation in this parameter over storage. Interesterification reduced the melting temperature of NLCs, indicating decreased crystallinity and a less organized structure. Moreover, interesterification favored crystals in the β' form, which is a positive characteristic for incorporating bioactive compounds. Thus, the systems developed in this study are innovative, mainly in terms of the composition of the NLCs, and have good potential for food applications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction. Two high-oncogenic-risk human papilomavirus (hrHPV) genotypes - HPV16 and HPV18 - cause most of the cases of cervical cancer worldwide. Bacterial vaginosis is associated with increased hrHPV persistence, although the mechanism underlying this association remains unclear. Gardnerella spp. are detected in nearly all cases of bacterial vaginosis and are the major source of cervicovaginal sialidases. The NanH1 gene is present in virtually all Gardnerella sialidase-producing strains and has been proposed as a potential marker for persistent hrHPV infection. Hypothesis. Gardnerella spp. load and the NanH1 gene are associated with hrHPV persistence. Aim. To compare the cervicovaginal load of Gardnerella spp. and the frequency of the NanH1 gene between women with persistent HPV16 and/or HPV18 infection and those who cleared the infection after 11 months. Methodology. Among a population of 1638 HPV screened, we detected 104 with positive HPV16 and/or HPV18 results. Samples were obtained at two time points (baseline and at a median of 11 months at follow-up) and tested using the Linear Array HPV Genotyping kit (Roche Molecular Systems, Pleasanton, CA, USA). Based on their HPV16/HPV18 status at enrolment and follow-up, participants were assigned to 'persistence' or 'clearance' groups. We used cervicovaginal fluid samples obtained upon enrolment to determine the load of the 23 s rRNA gene of Gardnerella spp. and the presence of the NanH1 gene using real-time polymerase chain reaction (PCR). We compared Gardnerella spp. loads and NanH1 frequency between the groups by, respectively, Mann-Whitney and chi-squared tests, with a P -value <0.05 considered to be significant. Results. Of the 104 participants who were positive for HPV16/HPV18, 73 (70.2 %) persisted with at least 1 of the baseline genotypes at follow-up, while 31 (29.8 %) cleared the infection in this time frame. Participants in the persistence group had significantly higher loads of Gardnerella spp. [5.8E+02 (0-3.0E+05) copies µl -1 ] than those in the clearance group [9.9E+01 (0-7.7E+04) copies µl -1 ] ( P =0.03). The baseline frequency of NanH1 was higher in the persistence' ( n =46, 63.0 %) than in the clearance ( n =14, 45.2 %) group, although this was not statistically significant ( P =0.09). Conclusion. These findings reinforce the negative effect of vaginal microbiota for the clearance of hrHPV and indicate a possible association between sialidase-producing species with hrHPV persistence.

Objective: The present study aims to describe the clinical protocols used for administration of colostrum therapy in newborns. Methods: An integrative review was carried out in the following databases: Medline, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Embase, Scientific Electronic Library Online (SciELO), Scopus, Latin American and Caribbean Health Sciences Literature (LILACS), and LIVIVO, using a combination of controlled terms in English, such as "Infant, Newborn," "Colostrum," and "Administration, Oral" associated with the entry terms and keywords. The selection of studies was carried out by reading titles and abstracts, through the Rayyan program to apply inclusion and exclusion criteria, and then reading them in full. Results: Five thousand eight hundred eighty-four studies were found in the databases; 15 studies were included in this review based on the inclusion and exclusion criteria. The selected articles presented variations in terms of cutoff criteria regarding gestational age and weight classification, in addition to the diversification between the beginning and the end of the application of colostrum therapy. In contrast, there was a predominance of the site of administration, type of colostrum used, and time to offer maternal colostrum. Conclusions: The studies present differences in terms of clinical parameters for standardizing the procedure. Therefore, this study can contribute to the generalized implementation of colostrum therapy in neonatal units through creation of a standard operating procedure based on systematization of the analyzed studies.

Background: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group., Methods: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance., Results and Conclusion: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic., Competing Interests: DIsclosure CB reports honoraria from Roche/Genentech, Janssen, BeiGene, Novartis, Pfizer, Incyte, AbbVie, Gilead Sciences, Celltrion, MorphoSys, Regeneron; he reports consulting or advisory role: Gilead Sciences, Janssen, Roche, Pfizer, BeiGene, Celltrion, AbbVie, Incyte, Regeneron, MorphoSys, Novartis; he reports speaker’s engagement: Roche, Janssen, BeiGene, Celltrion, AbbVie, Pfizer, Gilead Sciences; he reports research funding: Roche/Genentech, Janssen, Celltrion, Merck Sharp & Dohme (MSD), Pfizer, Amgen. MD reports honoraria as Advisory Board Member of AstraZeneca, Bayer, BeiGene, Celgene, Genmab, Gilead, Incyte, Janssen, Lilly, MorphoSys, Novartis, Roche; he reports honoraria for speaker’s engagement from Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Novartis, Roche; he reports institutional research grants from AbbVie, Bayer, Gilead, Celgene, Janssen, Roche. AA-L has declared no conflicts of interest. JA reports personal financial interests as advisory board and invited speaker from Incyte, advisory board from Mallinckrodt, advisory board and invited speaker from Novartis, advisory board and invited speaker from Pfizer; she reports non-financial interests as principal investigator from Incyte, principal investigator from Novartis. LA received advisory honoraria from Roche, Celgene, Janssen-Cilag, Verastem, Eusa Pharma, Incyte, ADC Therapeutics and Gilead; research support from Gilead, and travel expenses from Roche, Celgene, Janssen-Cilag, and Eusa Pharma; speakers bureau from Novartis. CB has declared no conflicts of interest. LB reports Advisory Committee activities for AbbVie, Amgen, Astellas, Bristol Myers Squibb (BMS), Celgene, Daiichi Sankyo, Gilead, Hexal, Janssen, Jazz Pharmaceuticals, Menarini, Novartis, Pfizer, Sanofi, Seattle Genetics and has research support from Bayer and Jazz Pharmaceuticals. PC has declared no conflicts of interest. MGDP has declared no conflicts of interest. MD reports personal fees from Amgen, personal fees from Takeda, personal fees from Janssen, personal fees from BeiGene, personal fees from BMS, outside the submitted work. SD reports personal financial interests as advisory board, invited speaker, fellow funding, and coordinating PI from BeiGene, writing engagement from Karger, advisory board and coordinating PI from Sanofi, funding, and other from Janssen; she reports non-financial interests as advisory role at British Society for Haematology Lymphoma Special Interest Group, advisory role at Lymphoma Action, member of board of directors at WMUK Charity. HTE has declared no conflicts of interest. RF reports honoraria for advisory boards and/or speaker bureau from Janssen, Gilead, AbbVie, Amgen, Novartis, Roche, Incyte, Pfizer, all outside the submitted work. PG reports grants and personal fees from AbbVie, grants and personal fees from Acerta/AstraZeneca, personal fees from BeiGene, personal fees from Celgene/Juno/BMS, grants and personal fees from Janssen, personal fees from Lilly/Loxo, personal fees from MEI, personal fees from Roche, personal fees from Sanofi, personal fees from ArQule/MSD, outside the submitted work; MGdS reports grants, personal fees, non-financial support and other from Gilead Sciences, grants from AstraZeneca, personal fees, non-financial support, and other from Janssen Cilag, personal fees and non-financial support from Roche, non-financial support from AbbVie, personal fees and non-financial support from BMS, personal fees and non-financial support from MSD, personal fees and non-financial support from Takeda, personal fees from Novartis, personal fees from ADC Therapeutics, outside the submitted work. JG reports personal fees from AbbVie, grants and personal fees from AstraZeneca, grants and personal fees from BMS/Celgene, grants and personal fees from Janssen, personal fees from Kite/Gilead, personal fees from MorphoSys, personal fees from Novartis, personal fees from TG Therapeutics, outside the submitted work. RH has had a consultant or advisory relationship with Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; has received honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; has received research funding from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda. CH reports grants and personal fees from Novartis, grants and personal fees from BMS, personal fees from Sierra Oncology, personal fees from CTI pharmaceuticals, personal fees from Jannsen, personal fees from Geron, grants and personal fees from AOP Orphan Pharma, personal fees from Galecto, grants, personal fees and other from Constellation, outside the submitted work. MH reports personal fees from Novartis, personal fees from Pfizer, personal fees from Roche, personal fees from AbbVie, personal fees from Daiichi Sankyo, personal fees from Bayer Pharma AG, personal fees from Jazz Pharmaceuticals, personal fees from BMS, personal fees from Tolremo, outside the submitted work. BK has received honoraria for lectures from Ipsen, Novartis and MSD (all outside of the submitted work). J-JK reports consulting fees and honoraria from Novartis, consulting fees from AbbVie, honoraria from AOP Orphan Pharma, participation on a monitoring board or advisory board from BMS/Celgene, participation on a monitoring board or advisory board from Incyte. NK reports grants and honoraria from Neovii, honoraria from Sanofi, grants and honoraria from Jazz, grants and honoraria from Celgene, grants and honoraria from Riemser, honoraria from Gilead/Kite, honorarium from AOP Oprhan Pharma, grants and honorarium from Novartis, honorarium from Amgen. PM reports personal fees from Celgene, Amgen, Janssen, AbbVie, Sanofi, outside the submitted work. JP has declared no conflicts of interest. FP has declared no conflicts of interest. DR received honoraria from Incyte, Novartis Pharma, Pfizer; clinical trial steering committee membership: Novartis; membership on advisory boards: Incyte, Novartis Pharma, Pfizer. J-MR reports grants and honoraria from Novartis, Amgen, Pfizer, Takeda, Incyte, and Servier. TR has declared no conflicts of interest. JF-M reports consulting and advisory boards honoraria (received by CUN ) from AbbVie, Amgen, BMS, Celgene, Janssen, GlaxoSmithKline, Karyopharm, MSD, Novartis, Takeda, Sanofi, SecuraBio, Regeneron, Roche, outside the submitted work. VS has declared no conflicts of interest. GFS reports personal fees and other from AbbVie, other from Amgen, other from Astellas, other from Boehringer-Ingelheim, grants, personal fees and other from Celgene, other from Helsinn Healthcare, grants, personal fees, and other from Janssen-Cilag, grants and other from Novartis, other from Onconova, grants, personal fees and other from Roche, and other from Takeda, outside the submitted work. PS reports honoraria from Amgen, Celgene, Janssen, Karyopharm, SkylineDx, Takeda, and research support from Celgene, Janssen, Amgen, Takeda, BMS, SkylineDx, Karyopharm, all outside the submitted work. MvL-T has received travel grants and honoraria from Celgene, Gilead, Chugai, Janssen, Novartis, Amgen, Takeda, BMS, Medac, Oncopeptides, Merck, CDDF, Pfizer, Medac, Thermo Fisher, AstraZeneca; is a consultant for Celgene, Gilead, Oncopeptides, MSD, 4D Pharma, Janssen, Shionogi and received research funding from BMBF, Deutsche Jose Carreras Leukämie-Stiftung, IZKF Jena, Novartis, Gilead, Deutsche Krebshilfe, Celgene, Oncopeptides, Deutsche Forschungsgemeinschaft (DFG). CW has declared no conflicts of interest. GP reports grants from Amgen, grants, personal fees and non-financial support from Merck, grants and non-financial support from AstraZeneca, grants and personal fees from Roche, grants and personal fees from BMS, grants from Lilly, grants and personal fees from MSD, grants and personal fees from Novartis, outside the submitted work. FP reports grants from Novartis, Celgene, BMS, Abbvie, Karyopharma, Janssen., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ammonia (NH 3 ) has been reported as a breath biomarker for chronic kidney disease (CKD) usually detected at concentrations greater than 0.25 parts per million by volume (ppmV). NH 3 was detected in breath of individuals with CKD through gaseous photoacoustic spectroscopy (PAS). The efficiency of hemodialysis (HD) was demonstrated. Eight volunteers aged between 20 and 60 years and without previous respiratory disease were eligible, among which six were control volunteers (CV) and two volunteers with advanced CKD, named CKDV1 and CKDV2. The presence of CKD was confirmed by the calculation of creatinine clearance (CC) according to the Cockcroft-Gault equation. Before HD, the mean NH 3 concentration exhaled by CKDV1 was 0.9 ± 0.1 ppmV and after HD was 0.20 ± 0.03 ppmV, which demonstrated an efficiency of 76% NH 3 reduction in breath. The CKDV2 exhaled 1.27 ± 0.03 ppmV of NH 3 pre-HD and 0.42 ± 0.08 ppmV post-HD, which resulted in efficiency of about 67%. It was not possible to quantify NH 3 from CV, what led us to infer that all of them exhaled amounts below the detection limit, i.e., 0.20 ppmV. This assumption is underpinned by CC, whose values hovered at 90 ≤ CC ≤ 120 mL/ min, confirming normal renal function., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The pathogenesis and treatment of lateral elbow epicondylitis (LEE) are still controversial. The purpose of the current study was to evaluate the production of inflammatory cytokines by LEE-derived cells and to compare the anti-inflammatory effect of triamcinolone acetonide with platelet-rich plasma (PRP) on cytokines production in primary culture of these cells., Methods: Third passage cells from primary cultures of LEE were assessed for the production of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by immune-enzymatic assay (ELISA), after the treatment with 1, 10 and 100 μM triamcinolone compared to no treated controls at the time points 6, 12, 18, 24, 48, 72 and 96 h, and to PRP at 48, 72 and 96 h., Results: The cytokines IL-6 and IL-8 were produced in high concentrations by LEE cells. One, 10 and 100 μM triamcinolone induced significant decrease in the production of IL-6 and IL-8 at 48, 72 and 96 h, adding the time point 12 h for IL-8. Compared to controls, PRP caused a significant increase in the production of IL-6 and IL-8 and there was a significant increase in IL-10 production with the use of 100 μM triamcinolone at 48 h. The production of IL1-β and TNF-α was very low and did not change when the cultures were treated with triamcinolone or PRP., Conclusion: LEE-derived cells produce IL-6 and IL-8, confirming the inflammatory nature of this condition. While triamcinolone inhibited the production of IL-6 and IL-8 by LEE cells, PRP induced an increase in these cytokines compared with controls., (© 2022. The Author(s).)

Introduction: Sialidase activity in the cervicovaginal fluid (CVF) is associated with microscopic findings of bacterial vaginosis (BV). Sequencing of bacterial 16S rRNA gene in vaginal samples has revealed that the majority of microscopic BV cases fit into vaginal community-state type IV (CST IV), which was recently named "molecular-BV." Bacterial vaginosis-associated bacterial species, such as Gardnerella spp., may act as sources of CVF sialidases. These hydrolases lead to impairment of local immunity and enable bacterial adhesion to epithelial and biofilm formation. However, the impact of CVL sialidase on microbiota components and diversity remains unknown., Objective: To assess if CVF sialidase activity is associated with changes in bacterial components of CST IV., Methods: One hundred forty women were cross-sectionally enrolled. The presence of molecular-BV (CST IV) was assessed by V3-V4 16S rRNA sequencing (Illumina). Fluorometric assays were performed using 2-(4-methylumbelliferyl)-α-D-N-acetylneuraminic acid (MUAN) for measuring sialidase activity in CVF samples. Linear discriminant analysis effect size (LEfSe) was performed to identify the differently enriched bacterial taxa in molecular-BV according to the status of CVF sialidase activity., Results: Forty-four participants (31.4%) had molecular-BV, of which 30 (68.2%) had sialidase activity at detectable levels. A total of 24 bacterial taxa were enriched in the presence of sialidase activity, while just two taxa were enriched in sialidase-negative samples., Conclusion: Sialidase activity in molecular-BV is associated with changes in bacterial components of the local microbiome. This association should be further investigated, since it may result in diminished local defenses against pathogens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ferreira, Marconi, Parada, Ravel and Silva.)

Bioactive compounds, synthesized by photosynthetic microorganisms, have drawn the attention of the pharmaceutical field. This study aimed at evaluating synthesis and in vitro antioxidant capacity of phenolic compounds produced by a microalgae species P. boryanum , which was grown in six different culture media (standard BG11, modified BG11/MBG11, standard WC, modified WC, WC*2 and basal). The highest concentrations of biomass (1.75 ± 0.01 g.L -1 ) and phenolic content (3.18 ± 0.00 mg.g -1 ) were obtained when P. boryanum was grown in MBG11 and phenolic acids were identified: gallic, protocatechuic, chlorogenic, hydroxybenzoic and vanillic ones. All extracts exhibited scavenger activity in the ABTS assay and inhibited peroxidase. However, phenolic compounds from P. boryanum grown in BG11 and MBG11 had the most potent scavenger activity in the DPPH assay. In sum, P. boryanum can be a new source of free phenolic compounds with potential antioxidant activity when grown in MBG11, since it yields high amounts of biomass and phenolic compounds.

Objective: A homeostatic balance between reactive oxygen species production and the antioxidant redox system is an important component of normal pregnancy. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) preserves cellular homeostasis by enhancing the cell's innate antioxidant status to reduce oxidative stress and inflammatory damage to the cell during pregnancy. Active Nrf2, in the nucleus of the cell, transactivates various antioxidant genes. The objective of this systematic review was to synthesize evidence on the role of Nrf2 in various adverse pregnancy outcomes (APOs)., Methods: We conducted a systematic review of the role of Nrf2 in pregnancy. Articles written in English, Portuguese, and Spanish were obtained from three different databases from inception until January 2021. The titles, abstracts and full text were reviewed independently by six reviewers. The quality of the included studies was assessed using a quality assessment tool developed to assess basic science and clinical studies. Nrf2 expression (gene and protein), functional contributions, and association with APOs were assessed., Results: A total of 747 citations were identified; 80 were retained for full review. Most studies on Nrf2 have been carried out using placental tissues and placenta-derived cells. Limited studies have been conducted using fetal membranes, uterus, and cervix. Nuclear translocation of Nrf2 results in transactivation of antioxidant enzymes, including glutathione peroxidase, hemeoxygenase-1, and superoxide dismutase in gestational cells during pregnancy. This antioxidant response maintains cellular homeostasis during pregnancy. This promotes trophoblast cell survival and prevents cell death and abnormal angiogenesis in the placenta. Excessive and insufficient Nrf2 response may promote oxidative and reductive stress, respectively. This Nrf2 dysregulation has been associated with APOs including gestational diabetes mellitus, intrauterine growth restriction, reproductive toxicity, preeclampsia, and preterm birth., Conclusion: Several studies have localized and reported an association between Nrf2's differential expression in reproductive tissues and the pathogenesis of APOs. However, a comprehensive functional understanding of Nrf2 in reproductive tissues is still lacking. Nrf2's activation and functions are complex, and therefore, current in vitro and in vivo studies are limited in their experimental approaches. We have identified key areas for future Nrf2 research that is needed to fill knowledge gaps., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome., Objectives: Describe the clinical characteristics, treatment, outcomes and incidence of HT., Methods: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT)., Results: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor., Conclusion: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance., Competing Interests: Declaration The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions., (Copyright © 2021. Published by Elsevier Inc.)

Phenolic compounds in crude extracts were obtained from defatted sunflower seed flour using sodium bisulfite and ethanol solutions as extracting agents. The antioxidant, antimicrobial, anti-proliferative, and DNA protective activities of the phenolic compounds in crude extract were analyzed. The phenolic compound contents were determined as chlorogenic acid (CGA) equivalent, presenting 11.57 and 15.44 g CGA eq/100g regarding the sodium bisulfite extract and ethanolic extract, respectively. The ORAC, DPPH, and ABTS methods were used to evaluate antioxidant activity. Both extracts presented antioxidant properties, considering that the ethanolic extract demonstrated higher values (EC 50 0.36 g extract/g DPPH•). The antimicrobial action was analyzed as to the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC) of 4 kinds of bacteria ( Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and Bacillus subtilis ). The ethanolic extract was effective against all of these microorganisms, out of which E. coli was the most sensitive, with a MIC of 11.6 mg CGA/mL. The ethanolic extract presented DNA protective activity without cytotoxic activity concerning in vitro anti-proliferative assay. These findings can be considered as initial evidence of the potential use of phenolic compounds obtained from sunflower seed flour as natural additives in the food industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V.)

In this work, a gas-diffusion microextraction (GDME) methodology was optimized and validated for the analysis of selected staling aldehydes (furfural (FURF), 2-methylpropanal (2-MP), 2-methylbutanal (2-MB), 3-methylbutanal (3-MB), and acetaldehyde (ACET)) during natural and forced aging of beer. The methodology was optimized considering time, temperature of extraction, and derivatizing agent. Using 4-hydrazinobenzoic acid (HBA) as a derivatizing agent, the performance of the method was evaluated by assessing several parameters such as detection limits (ranging from 1.2 to 1857.7 µg/L for 2-MB and ACET, respectively), quantification limits (ranging from 3.9 to 6192.4 µg/L for 2-MB and ACET, respectively), recoveries (higher than 96%), intraday and interday precisions (lower than 3.4 and 9.2%, respectively), and linearity (r 2 ≥ 0.995). During beer aging, higher content of Strecker aldehydes and FURF were found, while no significant variations in ACET levels were observed. In general, the aldehydes content assessed for beers stored at 37 ± 1 °C for 7 and 14 days mimics that observed for beers stored at 20 ± 2 °C for 3 and 6 months, respectively. Lower temperatures of storage (4 ± 1 °C) delayed the development of staling aldehydes. Based on PCA analysis, the content of staling aldehydes and beer color were responsible for 91.39% of the variance among the analyzed samples, and it was demonstrated that these are key parameters to discriminate fresh from aged beers. The results herein presented showed that the proposed analytic methodology is a valuable strategy for the characterization and quantification of important staling aldehydes in beer with a potential application in the quality control of beer during storage.

The importance of yeasts in aroma production during wine fermentation is a significant concern for obtaining a wine that appraises a broad number of consumers. For wine producers, wine aroma modulation is an essential issue where the yeasts used during the winemaking process represents a feasible way to improve the complexity and enhance wines specific characteristics. During the fermentation process of wines, yeasts convert grapes sugars into alcohol, carbon dioxide and a large number of secondary metabolites, depending on yeast metabolism, affecting the wine composition, namely its aroma and amino acids (AAs) composition. So, the present work aims to study the effect of different Saccharomyces-type yeasts on the AAs composition and volatile profile of Arinto white wines. To pursue this goal, four white wines from Arinto grapes were fermented with three different commercial yeasts (Saccharomyces bayanus EC1118, Saccharomyces cerevisiae CY3079, Saccharomyces bayanus QA23) and one Native yeast. Arinto wines AAs composition was quantified by HPLC-DAD, after a derivatization step to obtain the aminoenone derivatives. The volatile content of Arinto wines was determined by GC/MS, after an HS-SPME extraction. Results showed significant differences among the AAs content and volatile profile in the Arinto wines. The higher AAs content was found in the Arinto wines fermented with the CY3079 yeast (470.74 mg•L -1 ), and the lowest content of AAs in the Arinto wines fermented with EC1118 yeast (343.06 mg•L -1 ). Native yeast results in wines with a volatile profile richer in esters compared to the other sample wines. Principal component analysis (PCA) obtained with combined data of AAs and volatile compounds, after normalization, for each Arinto wine samples, shows a clear separation of wines fermented with Native and CY3079 yeasts in relation to QA23 and EC1118 fermented wines . The first and second principal components are responsible for 44.40% and 32.20%, respectively, of the system's variance, which clearly showed a differentiation among wines., Competing Interests: Declaration of Competing Interest All authors have participated in this research, either by conception and design, or analysis and interpretation of the data; drafting the article or revising it critically for important intellectual content; and approval of the final version. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome All of the sources of funding for the work described in this publication are acknowledged Therefore, there is none Declarations of interest, (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Identified in December 2019 in the city of Wuhan, China, the outbreak of COVID-19 spread throughout the world and its impacts affect different populations differently, where countries with high levels of social and economic inequality such as Brazil gain prominence, for understanding of the vulnerability factors associated with the disease. Given this scenario, in the absence of a vaccine or safe and effective antiviral treatment for COVID-19, nonpharmacological measures are essential for prevention and control of the disease. However, many of these measures are not feasible for millions of individuals who live in territories with increased social vulnerability. The study aims to analyze the spatial distribution of COVID-19 incidence in Brazil's municipalities (counties) and investigate its association with sociodemographic determinants to better understand the social context and the epidemic's spread in the country., Methods: This is an analytical ecological study using data from various sources. The study period was February 25 to September 26, 2020. Data analysis used global regression models: ordinary least squares (OLS), spatial autoregressive model (SAR), and conditional autoregressive model (CAR) and the local regression model called multiscale geographically weighted regression (MGWR)., Findings: The higher the GINI index, the higher the incidence of the disease at the municipal level. Likewise, the higher the nurse ratio per 1,000 inhabitants in the municipalities, the higher the COVID-19 incidence. Meanwhile, the proportional mortality ratio was inversely associated with incidence of the disease., Discussion: Social inequality increased the risk of COVID-19 in the municipalities. Better social development of the municipalities was associated with lower risk of the disease. Greater access to health services improved the diagnosis and notification of the disease and was associated with more cases in the municipalities. Despite universal susceptibility to COVID-19, populations with increased social vulnerability were more exposed to risk of the illness., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of the study was to conduct a systematic review of the literature to investigate the time of onset and duration of symptoms of loss of smell and taste in patients diagnosed with COVID-19., Methods: Two independent authors performed a systematic review of the Medline/PubMed, SCOPUS, COCHRANE, Lilacs and Web of Science electronic databases. The time of onset and duration of symptoms were considered primary outcomes. The sex and age of individuals, the geographical location of the study, the prevalence of symptoms, other associated symptoms, associated comorbidities, and the impact on quality of life and eating habits were considered secondary outcomes., Results: Our search generated 17 articles. Many of the studies reported that the onset of anosmia and ageusia occurred 4 to 5 days after the manifestation of other symptoms of the infection and that these symptoms started to disappear after one week, with more significant improvements in the first two weeks., Conclusion: The present study concludes that the onset of symptoms of loss of smell and taste, associated with COVID-19, occurs 4 to 5 days after other symptoms, and that these symptoms last from 7 to 14 days. Findings, however, varied and there is therefore a need for further studies to clarify the occurrence of these symptoms. This would help to provide early diagnosis and reduce contagion by the virus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ayahuasca is a decoction with psychoactive properties, used for millennia for therapeutic and religious purposes by indigenous groups and the population of amazonian countries. As described in this narrative review, it is essentially constituted by β-carbolines and tryptamines, and it has therapeutic effects on behavioral disorders due to the inhibition of the monoamine oxidase enzyme and the activation of 5-hydroxytryptamine receptors, demonstrated through preclinical and clinical studies. It was recently observed that the pharmacological response presented by ayahuasca is linked to its anti-inflammatory action, attributed mainly to dimethyltryptamines (N, N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine), which act as endogenous systemic regulators of inflammation and immune homeostasis, also through sigma-1 receptors. Therefore, since neuroinflammation is among the main pathophysiological mechanisms related to the development of neurological and psychiatric diseases, we suggest, based on the available evidence, that ayahuasca is a promising and very safe therapeutic strategy since extremely high doses are required to reach toxicity. However, even so, additional studies are needed to confirm such evidence, as well as the complete elucidation of the mechanisms involved., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Autologous stem cell transplantation (ASCT) is a well-established approach to treatment of patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) recommended by both the European Society for Medical Oncology and the National Comprehensive Cancer Network based on the results from randomized controlled studies. However, a considerable number of patients who receive ASCT will progress/relapse and display suboptimal post-transplant outcomes. Over recent years, a number of different strategies have been assessed to improve post-ASCT outcomes and augment HL cure rates. These include use of pre- and post-ASCT salvage therapies and post-ASCT consolidative therapy, with the greatest benefits demonstrated by targeted therapies, such as brentuximab vedotin. However, adoption of these new approaches has been inconsistent across different centers and regions. In this article, we provide a European perspective on the available treatment options and likely future developments in the salvage and consolidation settings, with the aim to improve management of patients with HL who have a high risk of post-ASCT failure. CONCLUSIONS: We conclude that early intervention with post-ASCT consolidation improves outcomes in patients with R/R HL who require ASCT. Future approvals of targeted agents are expected to further improve outcomes and provide additional treatment options in the coming age of personalized medicine.

Human tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC), including Mycobacterium tuberculosis var. tuberculosis (MTB) and Mycobacterium tuberculosis var. africanum (MAF). While MTB is isolated worldwide, MAF is almost completely restricted to the African continent, and despite the historical proximity between Brazil and Africa during the slave trade, no case of TB being caused by MAF has been reported in Brazil to date. We hereby describe the first case of TB caused by MAF in Brazil comparing its genome against the published ones. A female patient who had never visited Africa presented with clinical symptoms typical of pulmonary TB. Based on 16S rRNA gene sequencing, the cultured isolate was identified as belonging to MTBC and partial sequence of the hsp65 gene was identical to that of MAF. This was confirmed by genotyping based on detection of Single Nucleotide Polymorphism (SNP), Region of Difference (RD) and spoligotyping. The isolate presented the Shared International Typing (SIT) 181. In the whole-genome comparison against MAF genomes available on published EMBL-EBI European Nucleotide Archive (ENA), the Brazilian genome (MAFBRA00707) was identified as belonging to Lineage 6 and clustered with isolates from The Gambia. This is the first report of the isolation of MAF from a patient from Brazil, without evidence of having any contact with an African index case., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Preterm labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) impose substantial morbimortality on mothers and newborns. Exosomes act in intercellular communication carrying molecules involved in physiopathological processes. Little is known about exosomal proteins in prematurity. Our aim was to evaluate the protein expression of hemopexin, C1 inhibitor (C1INH) and alpha-2-macroglobulin (A2M) from circulating exosomes of women with PTL and PPROM. Plasma was obtained from PTL, PPROM, Term in labor and Term out of labor (T) patients, exosomes were isolated by ultracentrifugation, then lysed and the proteins quantified. Western Blot (WB) and Nanoparticle Tracking Analysis (NTA) were performed. Data were compared by Kruskal-Wallis, unpaired T-test and one-way ANOVA. WB and NTA confirmed exosome isolation (concentration: 4.3 × 10 10  particles/ml ± 1.9 × 10 10 ). There was no difference regarding hemopexin or C1INH expression between the groups. For A2M, the fold change was significantly higher on preterm groups when compared to term groups (1.07 ± 0.30 vs. 0.42 ± 0.17, p < 0.0001). Higher levels of A2M in circulating exosomes are linked to preterm pregnancies. sEV are strong candidates to intermediate maternal-fetal communication, carrying preterm labor-related immunomodulatory proteins.

Telomere disorders have been associated with aging-related diseases, including diabetes, vascular, and neurodegenerative diseases. The main consequence of altered telomere is the induction of the state of irreversible cell cycle arrest. Though several mechanisms responsible for the activation of senescence have been identified, it is still unclear how a cell is indeed induced to become irreversibly arrested. Most tissues in the body will experience senescence throughout its lifespan, but intrinsic and extrinsic stressors, such as chemicals, pollution, oxidative stress (OS), and inflammation accelerate the process. Pregnancy is a state of OS, as the higher metabolic demand of the growing fetus results in increased reactive oxygen species production. As a temporary organ in the mother, senescence in fetal membranes and placenta is expected and linked to term parturition (>37 weeks of gestation). However, a persistent, overwhelming, or premature OS affects placental antioxidant capacity, with consequent accumulation of OS causing damage to lipids, proteins, and DNA in the placental tissues. Therefore, senescence and its main inducer, telomere length (TL) reduction, have been associated with pregnancy complications, including stillbirth, preeclampsia, intrauterine growth restriction, and prematurity. Fetal membranes have a notable role in preterm births, which continue to be a major health issue associated with increased risk of neo and perinatal adverse outcomes and/or predisposition to disease in later life; however, the ability to mediate a delay in parturition during such cases is limited, because the pathophysiology of preterm births and physiological mechanisms of term births are not yet fully elucidated. Here, we review the current knowledge regarding the regulation of telomere-related senescence mechanisms in fetal membranes, highlighting the role of inflammation, methylation, and telomerase activity. Moreover, we present the evidences of TL reduction and senescence in gestational tissues by the time of term parturition. In conclusion, we verified that telomere regulation in fetal membranes requires a more complete understanding, in order to support the development of successful effective interventions of the molecular mechanisms that triggers parturition, including telomere signals, which may vary throughout placental tissues., (Copyright © 2020 Polettini and da Silva.)

A non-reversible state of epithelial to mesenchymal transition (EMT) at term accumulates proinflammatory mesenchymal cells and predisposes fetal membrane to weakening prior to delivery at term. We investigated the induction of EMT in amnion epithelial cells (AEC) in response to inflammation and infection associated with spontaneous preterm birth (SPTB). For this, membranes from SPTB were screened for EMT markers. Primary AEC in culture were treated with TNF-α (10 and 50 ng/mL) and LPS (50 and 100 ng/mL) for 72 h. Cell shape index (SI) was determined based on morphological shift (microscopy followed by ImageJ software analysis). Immunocytochemistry and Western blot assessed changes in epithelial markers (cytokeratin-18 and E-cadherin) and mesenchymal markers (vimentin and N-cadherin). Involvement of transforming growth factor beta (TGF-β) in EMT induction and EMT associated inflammation was tested using specific markers (Western blot) and by measuring MMP9 (ELISA), respectively. We report that PTB is associated with fetal membrane EMT. TNF-α produced dose- and time-dependent induction of EMT; within 24 h by 50 ng/mL and after 72 h by 10 ng/mL. AEC showed mesenchymal morphology, lower E-cadherin, higher vimentin and N-cadherin and higher MMP9 compared to control. TNF-α-induced EMT was not associated with canonical TGF-β pathway. LPS, regardless of dose or time, did not induce EMT in AEC. We conclude that PTB with intact membranes is associated with EMT. Our data suggest that inflammation, but not infection, is associated with non-canonical activation of EMT and inflammation that can predispose membrane to undergo weakening.

Gestations at the extremes of reproductive age are characterized as high-risk pregnancies, conditions that might influence colostrum composition. This first milk secretion contains nutrients necessary for the development and immunity of the newborn; therefore, this study aims to compare adolescent and advanced maternal age mothers regarding sociodemographic, gestational, and perinatal characteristics and the colostrum levels of pro-inflammatory cytokines in these groups of study. This cross-sectional study has compared sociodemographic, gestational and perinatal data from adolescent mothers (between 10 and 24 years old) (n = 117), advanced maternal age mothers (over 35 years of age) (n = 39) and mothers considered a control group (25 to 34 years old) (n = 58). Additionally, colostrum samples were obtained from the studied and control group subjects by manual milking, between 48 and 72 hours postpartum, and the samples were analyzed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). The majority of the studied mothers reported living a stable union, and 81.2% of the adolescent mothers did not carry out any paid activity. Mothers with advanced maternal age mainly delivered by cesarean section and presented a higher body mass index (BMI). Neonatal weight and Apgar score were not different between the groups. The concentrations of interleukin (IL)-1β and IL-6 were higher in the colostrum of mothers with advanced age compared to adolescent mothers, but did not differ from the control group. The concentrations of IL-8 and tumor necrosis factor alpha did not differ between the three groups. Therefore, our data demonstrated that maternal age influenced the sociodemographic and gestational characteristics as well as the composition of colostrum cytokines., Competing Interests: The authors have declared that no competing interests exist.

MOVE.TE is a non-profit participatory physiotherapy platform that aims at translating knowledge in the field of physiotherapy and developing freely available evidence-based physiotherapy programmes targeting the primary care services of the Portuguese National Health service. A group of volunteer academics and clinicians collaborated at different stages and time points to create the first ever falls prevention and management programme and guidance for Physiotherapy in primary care, in Portugal. This report describes this seven-step process. In spite of many challenges, this project constitutes an example of advocacy in physiotherapy for the promotion of better healthcare for older adults., Competing Interests: The authors have no conflict of interest., (Copyright: © 2020 Hylonome Publications.)

In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase 3 trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. ( Trial registered at clinicaltrials.gov identifier: NCT02354313 )., (Copyright© 2020 Ferrata Storti Foundation.)

The benefits of the regular exercise on quality of life of individuals living with a headache are well known. However, whether the benefits of the exercise training on headache parameters (i.e., intensity, frequency, and pain duration) occur in an intensity-dependent fashion remains unknown., Objective: The aim of the study was to investigate the effects of different exercise intensities on headache parameters., Design: A systematic review of clinical trials that analyzed the effect of physical exercise on headache, without time or language restriction. The TESTEX scale was used to evaluate the methodological quality of the articles., Results: Sixteen (16) articles were included with interventions with aerobic training and resistance training. Primary results are positive effects of exercise on migraine symptoms, tension-type headache among others, and a decrease in the use of headache-related medications. On the other hand, the studies did not provide information on exercise intensity, especially studies with aerobic exercises. The intensities used for aerobic training was mostly controlled subjectively and the resistance training ranged from 10% to 80% of maximum repetition., Conclusions: Exercise had a positive influence on the frequency and severity of headache crises, although the studies presented inconclusive data regarding the exercise parameters.

Lenalidomide maintenance therapy prolonged progression-free survival (PFS) versus placebo in elderly patients with diffuse large B-cell lymphoma (DLBCL) responding to induction chemotherapy in the phase 3 REMARC study. This subpopulation analysis assessed the impact of lenalidomide maintenance and treatment-emergent adverse events (TEAEs) on health-related quality of life (HRQOL). Global health status (GHS), and physical functioning and fatigue subscales were evaluated in patients who completed the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 v3.0. The impact of TEAEs classified post hoc as subjective (patients can feel) or observable (only measurable by physicians) on dose reductions and discontinuations was assessed. Among 457 patients (lenalidomide, n = 229; placebo, n = 228), mean (standard deviation) GHS was similar between treatment arms [68·2 (20·7) Versus 72·0 (17·8)] at randomisation and remained similar during maintenance. Patients receiving lenalidomide experienced no meaningful changes in GHS, physical functioning, or fatigue. Observable TEAEs were more common (81·1% Versus 66·3%) and more likely to lead to dose reductions, than subjective TEAEs in both arms. PFS was superior in the lenalidomide arm regardless of dose reduction. Lenalidomide maintenance prolonged PFS and did not negatively impact HRQOL in patients with DLBCL despite TEAEs being more common, when compared with placebo., (© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Infections related to non-tuberculous mycobacteria (NTM) have recently increased worldwide. The transmission of these microorganisms from the environment has been suggested as the main source for human infections. To elucidate the epidemiological aspects and distribution of these pathogens, many studies have evaluated several decontamination methods and protocols to properly isolate NTM from environmental samples, mainly from water. However, no satisfactory strategy has been found for isolation of most of the NTM species harboring different phenotypic characteristics. Here, we evaluated the susceptibility of 23 NTM strains presenting variable growth rate and pigmentation patterns to eight different methods: oxalic acid (2.5% and 5%), cetylpyridinium chloride (CPC) (0.0025% and 0.005%), sodium hydroxide (NaOH) (2% and 4%), and sodium dodecyl sulfate (SDS) plus NaOH (SDS 1.5%-NaOH 0.5% and SDS 3%-NaOH 1%). It was found that the viability of NTM exposed to different decontamination methods varies according to their phenotypic characteristics and two methods (SDS 1.5% plus NaOH 0.5% and CPC 0.0025%) were necessary for effective isolation of all of the species tested. These findings supply important insights for future studies on the environmental occurrence of mycobacteria and improving the sensibility of traditional strategies.

The reduction of telomere length, the protective cap structures of chromosomes, is one of the biomarkers of senescence (a mechanism of ageing), and ageing of foetal gestational tissues is associated with both term and preterm parturition. A mechanism regulating telomere length is the activity of telomerase, an enzyme that adds telomere fragments during DNA replication and cell division; however, its role in regulating telomere length is not well studied in gestational tissues. The objective of this study is to correlate telomere length and telomerase activity in foetal membranes from term and spontaneous preterm births. Foetal membrane samples were collected from pregnant women experiencing term labour (TL), term not in labour (TNL), preterm premature rupture of membranes (pPROM) and spontaneous preterm labour (PTL) with intact membranes (n = 20/group). Telomere length and telomerase activity were analyzed by relative quantification (T/S), real-time PCR and PCR-based fluorometric detection, respectively. Data were analyzed by ANOVA or the Kruskal-Wallis test. Demographic variables were not statistically different among the groups. Foetal membranes from the TL group showed telomere length reduction compared with those from the others (p < 0.0002). Telomerase activity did not change in foetal membranes irrespective of pregnancy outcome. Telomere shortening in foetal membranes is suggestive of senescence associated with triggering of labour at term; however, this is likely independent of telomerase activity, while prematurity may be associated with senescence, but due to other mechanisms than telomere length reduction in foetal membranes.

Mycobacterium bovis is the main causative agent of bovine tuberculosis (bTB) being among the animal-adapted Mycobacterium tuberculosis complex. Herds can also be infected with non-tuberculous mycobacteria (NTM) causing a negative effect on the economy and on animal and human health through zoonotic infections. Molecular tools are required for mycobacteria identification; thus, it is laborious to determine the epidemiological information of mycobacteria among herds. We aimed to describe the mycobacterial pathogens associated with cases of suspected bTB lesions in cattle/buffaloes slaughtered for consumption and to investigate bTB transmission. We evaluated 74 lesion samples from 48 animals (27 bovine/21 buffaloes) from 16 mapped farms. Positives samples from nested-PCR were cultured in Lowenstein-Jensen (LJ), 2% pyruvate (LJ + P), and 2% glycerol (LJ + G) media, followed by Ziehl-Neelsen (ZN) staining technique and partial gene sequencing (hsp65, rpoB, and 16S-rRNA). Spoligotyping and 24-MIRU-VNTR were performed. The LJ + P increased the chance of obtaining bacilli. The respiratory tract and the oral cavity were the most important infection route. In addition, the calcified part of the lesions suggested chronic bTB. Spoligotypes of M. bovis (SIT986/SB0885) differed from others found in South America, and the MIRU-VNTR 24 loci suggested that bTB was associated to highly related strains. The NTM species found are of clinical importance in humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pharmaceutical nanotechnology represents an efficient alternative for the delivery of pharmacologically active plant-derived compounds, considering their protective capacity, oral bioavailability and drug vectorization capacity. In this context, butters obtained from plant seeds have emerged as promising products for the development of pharmacologically active nanostructures. They possess a complex lipid composition, allowing the formation of different emulsion systems with solid cores, since this mixture of different triglycerides is solid at room temperature and body temperature. Therefore, the systematic mapping around the technological development of nanostructures produced from plant-derived butters is potentially valuable for researchers interested in novel alternative formulations for pharmacological therapy, with potential industrial, economic, health and societal impacts., Methods: Systematic review was carried out by the search of scientific papers and patents deposited in official databases concerning the development of nanostructured pharmaceutical products using plantderived butters as starting material. The publications obtained were subjected to sorting and analysis by applying the following inclusion/exclusion criteria., Results: The Solid Lipid Nanoparticle (SLN) was the type of nanostructure produced in all the analyzed scientific papers, due to the physicochemical characteristics of the lipid constituents of plantderived butters. In this sense, 54% of the articles have reported the use of Cocoa Butter for the production of nanostructures; 28% for Shea Butter; 6% for Cupuacu Butter, 6% for Murumuru Butter and 6% for Bacuri Butter., Discussion: In the technological prospection, only two patents exhibited SLN as an invention based on cocoa butter and on shea butter, respectively. The production methods employed have included: phase inversion temperature, microemulsion, hot high pressure homogenization, high shear homogenization and ultrasonication., Conclusion: In light of this prospective review, the encouragement of novel studies in lipids-based nanotechnology is evident, considering the small number of findings so far, in order to stimulate new research involving plant-derived butters from easily cultivated fruits in tropical regions, then stimulating the pharmaceutical development of new therapeutic alternatives using biocompatible and sustainable raw materials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The replacement of fossil-based fuels by renewable fuels (biofuels) was proposed in the IPCC report, as an alternative to reduce greenhouse gas emission and reach out to a low-carbon economy. On this perspective, the Brazilian government had implemented a renewable energy program based on the use of ethanol in the transport sector. This work evaluates the scenario of pollutant gas emissions and particulate material that comes from the biomass burning process involved in ethanol production cycle, in the city of Campos dos Goytacazes, Brazil. The gases and particulate material emitted by sugarcane and bagasse burning processes-the last one in energy co-generation mills-were analyzed. A laboratory-controlled burning of both samples was realized in an oven with temperature ramp from 250 to 400 °C, at a regular rate of 50 °C. The gas samples were collected directly from the oven's exhaust pipe. The particulates obtained were the residual material taken out of the burned samples: a powder with the aspect of soot. A photoacoustic spectroscopy system coupled with quantum cascade laser and electrochemical analyzers was used to measure the emission of polluting gases such as N 2 O, CO 2 , CO, NO x (NO, NO 2 ), and SO 2 in ppmv range. Fluorescent X-ray spectrometry was applied to evaluate the chemical composition of particulate material, enabling the identification of elements such as Si, Al, Ca, K, Fe, S, P, Ti, Mn, Cu, Zn, Sc, V, Cu, and Sr.

Chemotherapy-resistant cancer recurrence is a major cause of mortality. In acute myeloid leukemia (AML), chemorefractory relapses result from the complex interplay between altered genetic, epigenetic and transcriptional states in leukemic cells. Here, we develop an experimental model system using in vitro lineage tracing coupled with exome, transcriptome and in vivo functional readouts to assess the AML population dynamics and associated molecular determinants underpinning chemoresistance development. We find that combining standard chemotherapeutic regimens with low doses of DNA methyltransferase inhibitors (DNMTi, hypomethylating drugs) prevents chemoresistant relapses. Mechanistically, DNMTi suppresses the outgrowth of a pre-determined set of chemoresistant AML clones with stemness properties, instead favoring the expansion of rarer and unfit chemosensitive clones. Importantly, we confirm the capacity of DNMTi combination to suppress stemness-dependent chemoresistance development in xenotransplantation models and primary AML patient samples. Together, these results support the potential of DNMTi combination treatment to circumvent the development of chemorefractory AML relapses.

Purpose: The PRIMA study (ClinicalTrials.gov identifier: NCT00140582) established that 2 years of rituximab maintenance after first-line immunochemotherapy significantly improved progression-free survival (PFS) in patients with follicular lymphoma compared with observation. Here, we report the final PFS and overall survival (OS) results from the PRIMA study after 9 years of follow-up and provide a final overview of safety., Methods: Patients (> 18 years of age) with previously untreated high-tumor-burden follicular lymphoma were nonrandomly assigned to receive one of three immunochemotherapy induction regimens. Responding patients were randomly assigned (stratified by induction regimen, response to induction treatment, treatment center, and geographic region) 1:1 to receive 2 years of rituximab maintenance (375 mg/m 2 , once every 8 weeks), starting 8 weeks after the last induction treatment, or observation (no additional treatment). All patients in the extended follow-up provided their written informed consent (data cutoff: December 31, 2016)., Results: In total, 1,018 patients completed induction treatment and were randomly assigned to rituximab maintenance (n = 505) or observation (n = 513). Consent for the extended follow-up was provided by 607 patients (59.6%) of 1,018 (rituximab maintenance, n = 309; observation, n = 298). After data cutoff, median PFS was 10.5 years in the rituximab maintenance arm compared with 4.1 years in the observation arm (hazard ratio, 0.61; 95% CI, 0.52 to 0.73; P < .001). No OS difference was seen in patients randomly assigned to rituximab maintenance or observation (hazard ratio, 1.04; 95% CI, 0.77 to 1.40; P = .7948); 10-year OS estimates were approximately 80% in both study arms. No new safety signals were observed., Conclusion: Rituximab maintenance after induction immunochemotherapy provides a significant long-term PFS, but not OS, benefit over observation.

The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to‑lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC 50 values of 1.55 and 14.7 μM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC 50 . Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV-vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The aim of this work was to evaluate simultaneously the effect of produced ethanolic biodiesel from several feedstocks (soybean, crambe, macaw, sunflower, and waste cooking oil) and engine operational conditions (low and high engine speed) during combustion of biodiesel/diesel blends on the N 2 O, NO x , NO, CO 2 , and CO emission levels in the atmosphere. The biodiesel samples were prepared in one and/or two reaction steps, according to the acid index of each raw material, by esterification using H 2 SO 4 and/or chemical transesterification using sodium ethoxide, both, through ethanolic route. The quality of the produced biodiesels was confirmed by ASTM/EN specifications. Then, biodiesel/diesel blends were prepared according to the following proportions: 10% (B10), 15% (B15), 25% (B25), and 50% (B50). In general way, all raw materials under combustion at low and high engine speed contributed to the formation of NO x and this effect was more drastically increased as the biodiesel concentration in the blends increases. N 2 O presented a similar behavior except for blends containing crambe and macaw biodiesel whose emissions were slightly reduced as a function of biodiesel content in these blends. Then, Principal component analysis (PCA) was applied to discriminate the effect of engine operating conditions, biodiesel kind, and biodiesel content in the blends during their combustion on the exhaust emissions. The attained results point to crambe and macaw as more environmentally sustainable feedstocks for biodiesel production because they generate less greenhouse gas emissions. These results are particularly attractive considering that, both, crambe and macaw are non-edible feedstocks with great potential for biodiesel production.

Keratoconjunctivitis sicca (KCS) is of predominantly immune-mediated origin. Dogs are an excellent model for understanding this disease, as the origin of KCS in dogs is like that in humans. The objective of this study was to localize and quantify immunological markers, such as CD4 lymphocytes, interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα), before and after topical treatment with mesenchymal stem cells (MSCs). Twenty-two dogs positive for KCS were topically treated with 50 μL (1 × 10 6 MSCs) in the conjunctival sac and were evaluated for 6 months. The levels of the markers CD4, IL-6, IL-1 and TNFα were analyzed in conjunctival biopsy and cytology of the third eyelid gland by immunohistochemistry and immunocytochemistry. The results showed that before treatment, there was marked expression of all the markers (CD4, IL-6, IL-1 and TNFα), and after 6 months, there were significant (p < .05) reductions in the expression levels of all the markers. These results demonstrated that topical MSC treatment promotes a significant decrease in the expression levels of these inflammatory markers and could be used as adjuvant therapy in the treatment of KCS in dogs and humans. In addition, these markers can be excellent tools for diagnosing and analyzing the progression of KCS., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Dexamethasone (Dex), a corticosteroid hormone, is used during the perinatal period to help fetal lung and other organ development. Conversely, Dex-induced cell proliferation has been associated with accelerated aging. Using primary amnion epithelial cells (AECs) from term, not in labor, fetal membranes, we tested the effects of Dex on cell proliferation, senescence, and inflammation. Primary AECs treated with Dex (100 and 200 nM) for 48 h were tested for cell viability (crystal violet dye exclusion), cell cycle progression and/or type of cell death (flow cytometry), expression patterns of steroid receptors (glucocorticoid receptor, progesterone receptor membrane component 1&2), inflammatory mediators (IL-6 and IL-8), and telomere length (quantitative RT-PCR). Mechanistic mediators of senescence (p38MAPK and p21) were determined by western blot analysis. Dex treatment did not induce AEC proliferation, cell cycle, influence viability, or morphology. However, Dex caused dependent telomere length reduction and p38MAPK-independent but p21-dependent (confirmed by treatment with p21 inhibitor UC2288). Senescence was not associated with an increase in inflammatory mediators, which is often associated with senescence. Co-treatment with RU486 produced DNA damage, cell cycle arrest, and cellular necrosis with an increase in inflammatory mediators. The effect of Dex was devoid of changes to steroid receptors, whereas RU486 increased GR expression. Dex treatment of AECs produced nonreplicative and noninflammatory senescence. Extensive use of Dex during the perinatal period may lead to cellular senescence, contributing to cellular aging associated pathologies during the perinatal and neonatal periods., (© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

A comprehensive characterization of muscle's FA composition of sea lamprey ammocoetes and adults was performed to test the hypothesis that larvae, and early spawning migrants have a similar FA profile prior to metamorphosis and to spawning migration. Subsequently, the role played by FA signature in these two highly demanding stages of life cycle was inferred. The results confirm that muscle represents an important fat reservoir, and the FA trophic markers revealed the importance of bacteria as sources of iso and anteiso FA and the strong trophic representation of benthic phytoplankton (diatoms) to larvae muscle FA profile. In early spawning migrants, the significance of marine food web to FA muscle profile is highlighted by the presence of FA signatures characteristics of herbivorous calanoid copepods. Although both life cycle phases studied do not share the same muscle FA signature, there is a part of the profile that is common, which is characterized by FA used in β-oxidation, such as C18:1ω9 but also by medium chain FA and PUFA which points that PUFA are spared as fuel to β-oxidation process and probably used to the development of tissues membranes (ammocoetes) and gonadal development and eicosanoid production among others (early spawning migrants). Further studies on FA profile are necessary to elucidate the FA role either during different life stages (ontogeny) or in the distinct habitats frequented (freshwater versus marine) by this diadromous species.

In this paper, we further extend the recently proposed Poisson-Tweedie regression models to include a linear predictor for the dispersion as well as for the expectation of the count response variable. The family of the considered models is specified using only second-moments assumptions, where the variance of the count response has the form μ+ϕμp $\mu + \phi \mu^p$, where µ is the expectation, ϕ and p are the dispersion and power parameters, respectively. Parameter estimations are carried out using an estimating function approach obtained by combining the quasi-score and Pearson estimating functions. The performance of the fitting algorithm is investigated through simulation studies. The results showed that our estimating function approach provides consistent estimators for both mean and dispersion parameters. The class of models is motivated by a data set concerning CD4 counting in HIV-positive pregnant women assisted in a public hospital in Curitiba, Paraná, Brazil. Specifically, we investigate the effects of a set of covariates in both expectation and dispersion structures. Our results showed that women living out of the capital Curitiba, with viral load equal or larger than 1000 copies and with previous diagnostic of HIV infection, present lower levels of CD4 cell count. Furthermore, we detected that the time to initiate the antiretroviral therapy decreases the data dispersion. The data set and R code are available as supplementary materials.