NK cell defects: implication in acute myeloid leukemia.

Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, the focus has been on developing newer therapies for AML; however, relapse remains a significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity is often restricted by cellular defects caused by disease-associated mechanisms, which can lead to disease progression. A stark feature of AML is the low/no expression of the cognate HLA ligands for the activating KIR receptors, due to which these tumor cells evade NK-mediated lysis. Recently, different Natural Killer cell therapies have been implicated in treating AML, such as the adoptive NK cell transfer, Chimeric antigen receptor-modified NK (CAR-NK) cell therapy, antibodies, cytokine, and drug treatment. However, the data available is scarce, and the outcomes vary between different transplant settings and different types of leukemia. Moreover, remission achieved by some of these therapies is only for a short time. In this mini-review, we will discuss the role of NK cell defects in AML progression, particularly the expression of different cell surface markers, the available NK cell therapies, and the results from various preclinical and clinical trials.

Falsificações por troca de espécies de peixes: uma revisão sistemática das espécies mais comumente substituídas / Fish mislabeling: a systematic review of the most commonly mislabeled species

O objetivo deste artigo é determinar quais são as espécies de peixes mais comumente substituídas, relatadas em revisões sobre falsificações por troca de espécies, em artigos científicos publicados entre 2002 e 2022, assim como expor quais são os fatores que levam à ocorrência de casos de falsificação, quais os danos sociais que tal prática ilegal pode gerar e em que tipo de estabelecimentos as falsificações normalmente são detectadas. Assim, por meio de uma revisão sistemática de literatura, foi verificado que as espécies de peixes mais comumente falsificadas foram Anoplopoma fimbria, Gadus morhua, Solea solea, Thunnus albacares, Scomberomorus commerson, Lates calcarifer e Rastrelliger brachysoma. As motivações por trás das falsificações intencionais foram predominantemente econômicas, tendo sido observados impactos negativos das falsificações na economia, na saúde pública e no meio ambiente. A maioria das falsificações foi encontrada no final da cadeia produtiva, em locais como varejos, restaurantes e peixarias. Dessa forma, ao saber como as falsificações acontecem e suas razões, torna-se possível saber como minimizar a sua ocorrência.

The aim of this article is to identify the most frequently mislabeled fish species, based on reports and reviews of species mislabeling-related falsifications, in scientific articles published between 2002 and 2022. It also aims to explore the factors contributing these counterfeiting incidents, the social harms associated with this illegal practice and the types of establishments where counterfeits are typically detected. Through a systematic literature review, it was verified that the most commonly mislabeled fish species were Anoplopoma fimbria, Gadus morhua, Solea solea, Thunnus albacares, Scomberomorus commerson, Lates calcarifer and Rastrelliger brachysoma. The primary motivations behind intentional counterfeiting were economic in nature, and negative impacts of counterfeiting on the economy, public health and the environment were widely recognized. Most counterfeits were found at the end of the production chain, in places such as retail stores, restaurants and fishmongers' businesses. By understanding the mechanisms and motivations behind counterfeiting, we can effectively minimize its prevalence.

Investigation of the Effects of Monomeric and Dimeric Stilbenoids on Bacteria-Induced Cytokines and LPS-Induced ROS Formation in Bone Marrow-Derived Dendritic Cells.

Stilbenoids are anti-inflammatory and antioxidant compounds, with resveratrol being the most investigated molecule in this class. However, the actions of most other stilbenoids are much less studied. This study compares five monomeric (resveratrol, piceatannol, pterostilbene, pinostilbene, and trimethoxy-resveratrol) and two dimeric (dehydro-δ-viniferin and trans-δ-viniferin) stilbenoids for their capability to modulate the production of bacteria-induced cytokines (IL-12, IL-10, and TNF-α), as well as lipopolysaccharide (LPS)-induced reactive oxygen species (ROS), in murine bone marrow-derived dendritic cells. All monomeric species showed dose-dependent inhibition of E. coli-induced IL-12 and TNF-α, whereas only resveratrol and piceatannol inhibited IL-10 production. All monomers, except trimethoxy-resveratrol, inhibited L. acidophilus-induced IL-12, IL-10, and TNF-α production. The dimer dehydro-δ-viniferin remarkably enhanced L. acidophilus-induced IL-12 production. The contrasting effect of resveratrol and dehydro-δ-viniferin on IL-12 production was due, at least in part, to a divergent inactivation of the mitogen-activated protein kinases by the two stilbenoids. Despite having moderate to high total antioxidant activity, dehydro-δ-viniferin was a weak inhibitor of LPS-induced ROS formation. Conversely, resveratrol and piceatannol potently inhibited LPS-induced ROS formation. Methylated monomers showed a decreased antioxidant capacity compared to resveratrol, also depending on the methylation site. In summary, the immune-modulating effect of the stilbenoids depends on both specific structural features of tested compounds and the stimulating bacteria.

Sensibilidad y especificidad de las escalas diagnósticas en la apendicitis aguda. Estudio prospectivo / Sensitivity and specificity of the diagnostic scales in acute appendicitis. Prospective study

La Apendicitis Aguda se manifiesta cuando existe inflamación del apéndice cecal, representando una de las más notables causas de abdomen agudo con pronóstico quirúrgico en el mundo. Existen sistemas de puntuaciones que se han generado para su comprobación, mediante técnicas no invasivas, de fácil aplicación y reproducción; destacando entre ellas las escalas de ALVARADO, RIPASA, AIR, entre otras. Objetivo: Comparar la sensibilidad y especificidad de las escalas AIR Vs. RIPASA para el diagnóstico de la Apendicitis Aguda en el Hospital General Nacional "Dr. Ángel Larralde", período enero 2020 ­ diciembre 2022. Materiales: Estudio observacional, descriptivo y evaluativo, prospectivo y de corte transversal. Muestra fue intencional no probabilística, cumpliendo con los criterios de inclusión. Para la recolección de datos, se empleó la observación directa como técnica y como instrumentos las escalas AIR y RIPASA. Resultados: Muestra conformada por 192 pacientes, sin predisposición de géneros. Sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y exactitud diagnóstica AIR: 70%; 58,33%; 73,68%; 53,84%; 65,62%; RIPASA: 88,88%; 42,85%; 66,66%; 75%; 68,75%. Conclusiones: La exactitud diagnóstica para la escala de RIPASA fue ligeramente mayor que para AIR (68,75% vs. 65,62%), permitiendo afirmar que, en el grupo de estudio, resultó más conveniente la aplicación de la escala de RIPASA en pacientes sanos para el diagnóstico correcto de Apendicitis Aguda(AU)

Acute Appendicitis manifests when there is inflammation of the cecal appendix, representing one of the most notable causes of acute abdomen with surgical prognosis in the world. There are scoring systems that have been generated for verification, using non-invasive techniques that are easy to apply and reproduce; highlighting among them the scales of ALVARADO, RIPASA, AIR, among others.Objective : To compare the sensitivity and specificity of the AIR Vs. RIPASA scales for the diagnosis of Acute Appendicitis at the National General Hospital "Dr. Ángel Larralde", period January 2020 ­ December 2022. Materials: Observational, descriptive and evaluative, prospective and cross-sectional study. Sample was intentional, non-probabilistic, meeting the inclusion criteria. For data collection, direct observation was used as a technique and the AIR and RIPASA scales as instruments.Results : Sample made up of 192 patients, with no gender predisposition. Sensitivity, specificity, positive predictive value, negative predictive value, and AIR diagnostic accuracy: 70%; 58.33%; 73.68%; 53.84%; 65.62%; RIPASE: 88.88%; 42.85%; 66.66%; 75%; 68.75%.Conclusions : The diagnostic accuracy for the RIPASA scale was slightly higher than for AIR (68.75% vs. 65.62%), allowing us to affirm that, in the study group, the application of the RIPASA scale was more convenient in healthy patients for the correct diagnosis of Acute Appendicitis(AU)

Odontopediatría en el contexto de la COVID-19: publicaciones científicas y práctica clínica / Odontopediatria no contexto da COVID-19: publicações científicas e prática clínica / Pediatric dentistry in the context of COVID-19: scientific publications and clinical practice

El propósito es analizar las características de los estudios y las tendencias en las publicaciones científicas y las recomendaciones clínicas relacionadas con el COVID-19 en odontopediatría. La búsqueda electrónica se realizó en las bases de datos MEDLINE, Scopus, Web of Science Core Collection y LILACS/BVS, sin restricciones. Se incluyeron estudios que usaron términos referentes a COVID-19, odontología pediátrica y niños en el título, resumen o palabras clave. Se extrajeron datos bibliométricos y características de los estudios. Cada estudio se categorizó de acuerdo con su diseño, muestra y tema principal. Se incluyeron 49 estudios, la mayoría revisiones (n=25; 51,00%), estudios observacionales (n=23; 47,00%) y estudio clínico (n=1; 2%). Los principales temas fueron urgencias odontológicas (n=9; 18,30%), bioseguridad (n= 8; 16,30%) y teleodontología (n=6; 12,20%). Las urgencias odontológicas más reportadas fueron trauma (n=12; 63,10%), edema (n=9; 47,30%) y dolor (n=9; 47,30%). Se concluyó que se realizaron pocos estudios sobre COVID-19 y odontología pediátrica, y la mayoría de las revisiones y estudios observacionales sobre emergencias dentales se publicaron en Asia.

O objetivo é analisar as características dos estudos e tendências nas publicações científicas e recomendações clínicas relacionadas ao COVID-19 em odontopediatria. A busca eletrônica foi realizada nas bases de dados MEDLINE, Scopus, Web of Science Core Collection e LILACS/BVS, sem restrições. Foram incluídos estudos que usaram termos referentes a COVID-19, odontopediatria e crianças no título, resumo ou palavras-chave. Os dados bibliométricos e as características do estudo foram extraídos. Cada estudo foi categorizado de acordo com seu desenho, amostra e tema principal. Quarenta e nove estudos foram incluídos, sendo a maioria revisões (n=25; 51,00%), estudos observacionais (n=23; 47,00%) e estudo clínico (n=1; 2%). Os principais temas foram emergências odontológicas (n=9; 18,30%), biossegurança (n= 8; 16,30%) e teleodontologia (n=6; 12,20%). As emergências odontológicas mais relatadas foram trauma (n=12; 63,10%), edema (n=9; 47,30%) e dor (n=9; 47,30%). Concluiu-se que poucos estudos sobre COVID-19 e odontopediatria foram realizados, com a maioria das revisões e estudos observacionais sobre emergências odontológicas publicados na Ásia

The purpose is to analyze the characteristics of the studies and trends in scientific publications and the clinical recommendations related to COVID-19 in pediatric dentistry. Electronic search was performed on MEDLINE, Scopus, Web of Science Core Collection, and LILACS/VHL databases, without restrictions. Studies that used terms referring to COVID-19, pediatric dentistry, and children in the title, abstract, or keywords were included. Bibliometric data and studies' characteristics were extracted. Each study was categorized according to its design, sample, and main subject. Forty-nine studies were included, most of them reviews (n=25; 51.00%), observational studies (n=23; 47.00%), and clinical study (n=1; 2%). The main topics were dental emergencies (n=9; 18.30%), biosafety (n= 8; 16.30%) and teledentistry (n=6; 12.20%). The most reported dental emergencies were trauma (n=12; 63.10%), edema (n=9; 47.30%), and pain (n=9; 47.30%). It was concluded that few studies on COVID-19 and pediatric dentistry were conducted, and most reviews and observational studies regarding dental emergencies were published in Asia.

Effect of endodontic sealers on push-out bond strength of CAD-CAM or prefabricated fiber glass posts

Abstract This study aimed to evaluate the effect of endodontic sealer (ES) on bond strength (BS) of prefabricated or milled-CAD-CAM (computer-aided design and computer-aided manufacturing) glass-fiber-posts (GFP). Canals of 90 single-rooted teeth were prepared for filling by the single-cone technique with gutta-percha and one of the following ES: AH Plus (epoxy resin), Endofill (zinc-oxide and eugenol), and Bio-C Sealer (calcium-silicate). After post-space preparation, tooth-specimens were equally divided in half according to type of GFP to be used. In the half to receive milled-CAD-CAM posts, tooth specimens were molded with acrylic resin to obtain replicas. These were scanned to enable the laboratory to produce the milled-CAD-CAM GFPs (Fiber CAD Lab, Angelus) by the subtractive technique. The other half of samples received prefabricated GFPs (Exacto, Angelus) (n=15). The GFPs were cemented with dual-cure resin cement (Panavia F2.0, Kuraray). Each root was sectioned into two slices per root region (cervical, middle, apical) that were subjected to the push-out BS test, in a universal testing machine. Failure mode (FM) was classified by scores. The BS data were submitted to generalized linear model analyses, while FM was analyzed using the chi-square test (a=0.05). BS showed no significant difference among the three ES (p > 0.05). BS was significantly higher for prefabricated (mean 10.84 MPa) versus milled-CAD-CAM GFPs (mean 6.94 MPa) (p <0.0001), irrespective of ES. The majority showed mixed failures. It could be concluded that type of ES did not affect BS of GFPs to dentin, and prefabricated-GFPs had higher bond-strength than customized-milled-CAD-CAM GFPs.

Correlation between Perturbation of Redox Homeostasis and Antibiofilm Capacity of Phytochemicals at Non-Lethal Concentrations.

Biofilms are the multicellular lifestyle of microorganisms and are present on potentially every type of biotic or abiotic surface. Detrimental biofilms are generally targeted with antimicrobial compounds. Phytochemicals at sub-lethal concentrations seem to be an exciting alternative strategy to control biofilms, as they are less likely to impose selective pressure leading to resistance. This overview gathers the literature on individual phytocompounds rather than on extracts of which the use is difficult to reproduce. To the best of our knowledge, this is the first review to target only individual phytochemicals below inhibitory concentrations against biofilm formation. We explored whether there is an overall mechanism that can explain the effects of individual phytochemicals at sub-lethal concentrations. Interestingly, in all experiments reported here in which oxidative stress was investigated, a modest increase in intracellular reactive oxygen species was reported in treated cells compared to untreated specimens. At sub-lethal concentrations, polyphenolic substances likely act as pro-oxidants by disturbing the healthy redox cycle and causing an accumulation of reactive oxygen species.

Stormfires in La Palma, Chile: Shared Meanings Emerging from a Post-disaster Community Intervention / Tormenta de fuego en la palma (chile): significados compartidos surgidos de una intervención comunitaria postdesastre

RESUMEN Los desastres socioambientales afectan desigualmente a las zonas rurales en comparación con las urbanas. Esta realidad hace que la movilización de recursos comunitarios sea esencial para afrontar estos eventos. El objetivo de este trabajo fue analizar la construcción de significados derivados del proceso de intervención comunitaria posterior a un desastre (incendio forestal) entre la comunidad La Palma y el equipo de la Fundación Tierra de Esperanza, planteando como pregunta de investigación ¿Qué significados compartidos surgen del proceso de intervención vivenciado por la comunidad de La Palma y el equipo interventor? El estudio tuvo un diseño fenomenológico, utilizando análisis interpretativo del discurso. Los resultados muestran la emergencia de categorías vinculadas a procesos identitarios, ruralidad, y el despliegue de procesos psicosociales durante la experiencia de intervención vinculados con el afrontamiento comunitario, apoyo social, rol clave de liderazgos femeninos y aprendizajes de la comunidad. Se discute cómo la toma de conciencia de esta comunidad rural incrementó su capacidad de agencia ante eventos en los que cuentan con escaso apoyo gubernamental.

ABSTRACT Socio-environmental disasters affect rural areas unequally, compared to urban areas. This reality makes the mobilization of community resources essential when facing these events. The objective of this study was to analyze the construction of meanings derived from the process of community intervention after a disaster (forest fires) between the La Palma community and the Tierra de Esperanza Foundation team, posing as a research question: What shared meanings emerge from the intervention process experienced by the La Palma community and the intervention team? The study had a phenomenological design, using interpretative discourse analysis. The results show the emergence of categories linked to identity processes, rurality, and the unfolding of psychosocial processes during the intervention experience, linked to community coping, social support, the key role of female leadership, and community learning. It is discussed how the awareness of this rural community increased its capacity for agency in the face of events with little government support.

From Batch to Continuous Flow Bioprocessing: Use of an Immobilized γ-Glutamyl Transferase from B. subtilis for the Synthesis of Biologically Active Peptide Derivatives.

γ-Glutamyl-peptides are frequently endowed with biological activities. In this work, "kokumi peptides" such as γ-glutamyl-methionine (1) and γ-glutamyl-(S)-allyl-cysteine (2), as well as the neuroprotective γ-glutamyl-taurine (3) and the antioxidant ophthalmic acid (4), were synthesized through an enzymatic transpeptidation reaction catalyzed by the γ-glutamyl transferase from Bacillus subtilis (BsGGT) using glutamine as the γ-glutamyl donor. BsGGT was covalently immobilized on glyoxyl-agarose resulting in high protein immobilization yield and activity recovery (>95%). Compounds 1-4 were obtained in moderate yields (19-40%, 5-10 g/L) with a variable purity depending on the presence of the main byproduct (γ-glutamyl-glutamine, 0-16%). To achieve process intensification and better control of side reactions, the synthesis of 2 was moved from batch to continuous flow. The specific productivity was 1.5 times higher than that in batch synthesis (13.7 µmol/min*g), but it was not accompanied by a paralleled improvement of the impurity profile.

3-Bromo-Isoxazoline Derivatives Inhibit GAPDH Enzyme in PDAC Cells Triggering Autophagy and Apoptotic Cell Death.

A growing interest in the study of aerobic glycolysis as a key pathway for cancer-cell energetic metabolism, favouring tumour progression and invasion, has led to consider GAPDH as an effective drug target to specifically hit cancer cells. In this study, we have investigated a panel of 3-bromo-isoxazoline derivatives based on previously identified inhibitors of Plasmodium falciparum GAPDH (PfGAPDH). The compounds are active, to a different extent, as inhibitors of human-recombinant GAPDH. They showed an antiproliferative effect on pancreatic ductal-adenocarcinoma cells (PDAC) and pancreatic-cancer stem cells (CSCs), and among them two promising compounds were selected to be tested in vivo. Interestingly, these compounds were not effective in fibroblasts. The AXP-3019 derivative was able to block PDAC-cell growth in mice xenograft without apparent toxicity. The overall results support the assumption that selective inhibition of the glycolytic pathway, by targeting GAPDH, is an effective therapy for pancreatic cancer and that 3-bromo-isoxazoline derivatives represent a new class of anti-cancer compounds targeting glycolysis.

Biophysical Characterization of the Oligomeric States of Recombinant Immunoglobulins Type-M and Their C1q-Binding Kinetics by Biolayer Interferometry.

Immunoglobulins type-M (IgMs) are one of the first antibody classes mobilized during immune responses against pathogens and tumor cells. Binding to specific target antigens enables the interaction with the C1 complex which strongly activates the classical complement pathway. This biological function is the basis for the huge therapeutic potential of IgMs. But, due to their high oligomeric complexity, in vitro production, biochemical characterization, and biophysical characterization are challenging. In this study, we present recombinant production of two IgM models (IgM617 and IgM012) in pentameric and hexameric states and the evaluation of their polymer distribution using different biophysical methods (analytical ultracentrifugation, size exclusion chromatography coupled to multi-angle laser light scattering, mass photometry, and transmission electron microscopy). Each IgM construct is defined by a specific expression and purification pattern with different sample quality. Nevertheless, both purified IgMs were able to activate complement in a C1q-dependent manner. More importantly, BioLayer Interferometry (BLI) was used for characterizing the kinetics of C1q binding to recombinant IgMs. We show that recombinant IgMs possess similar C1q-binding properties as IgMs purified from human plasma.

Efficient 2-Step Enzymatic Cascade for the Bioconversion of Oleuropein into Hydroxytyrosol.

Among the plant bioactive components, oleuropein (OLE) is the most abundant phenolic compound in all parts of olive trees (Olea europaea L.), particularly concentrated in olive leaves. It has been shown to present various remarkable biological actions, such as antimicrobial, antioxidant, anticancer and anti-inflammatory ones. On the other hand, hydroxytyrosol (HT), the main degradation product of OLE, is considered one of the most powerful antioxidant agents, with higher beneficial properties than the OLE parent compound. In this work, oleuropein was efficiently transformed into hydroxytyrosol using a 2-step biotransformation involving a thermo-halophilic ß-glucosidase from Alicyclobacillus herbarius (Ahe), which gave the corresponding aglycone with complete conversion (>99%) and rapid reaction times (30 min), and an acyltransferase from Mycobacterium smegmatis (MsAcT), here employed for the first time for its hydrolytic activity. After cascade completion, hydroxytyrosol was obtained in excellent yield (>99% m.c., 96% isolated yield) in 24 h. Starting from a natural substrate and employing enzymatic approaches, the final hydroxytyrosol can be claimed and commercialized as natural too, thus increasing its market value.

Biocatalytic Approaches for an Efficient and Sustainable Preparation of Polyphenols and Their Derivatives.

Many sectors of industry, such as food, cosmetics, nutraceuticals, and pharmaceuticals, have increased their interest in polyphenols due to their beneficial properties. These molecules are widely found in Nature (plants) and can be obtained through direct extraction from vegetable matrices. Polyphenols introduced through the diet may be metabolized in the human body via different biotransformations leading to compounds having different bioactivities. In this context, enzyme-catalyzed reactions are the most suitable approach to produce modified polyphenols that not only can be studied for their bioactivity but also can be labeled as green, natural products. This review aims to give an overview of the potential of biocatalysis as a powerful tool for the modification of polyphenols to enhance their bioaccessibility, bioavailability, biological activity or modification of their physicochemical properties. The main polyphenol transformations occurring during their metabolism in the human body have been also presented.

Grapevine stilbenoids as natural food preservatives: calorimetric and spectroscopic insights into the interaction with model cell membranes.

Food contamination with pathogenic microorganisms, such as Listeria monocytogenes, Salmonella enterica, Staphylococcus aureus and Bacillus cereus, is a common health concern. Natural products, which have been the main source of antimicrobials for centuries, may represent a turning point in alleviating the antibiotic crisis, and plant polyphenolic compounds are considered a promising source for new antibacterial agents. Resveratrol and resveratrol-derived monomers and oligomers (stilbenoids) have been shown to exert a variegated pattern of efficacy as antimicrobials depending on both the polyphenols' structure and the nature of the microorganisms, and the bacterial cell membrane seems to be one of their primary targets.In this scenario and based on the thermodynamic information reported in the literature about cell membranes, this study aimed at the investigation of the direct interaction of selected stilbenoids with a simple but informative model cell membrane. Three complete stilbenoid "monomer/dimer/dehydro-dimer" sets were chosen according to different geometries and substitution patterns. Micro-DSC was performed on 2 : 3 DPPC : DSPC small unilamellar vesicles with incorporated polyphenols at physiological pH and the results were integrated using complementary NMR data. The study highlighted the molecular determinants and mechanisms involved in the stilbenoid-membrane interaction, and the results were well correlated with the microbiological evidence previously assessed.

Plant-Derived Stilbenoids as DNA-Binding Agents: From Monomers to Dimers.

Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)-trans-δ-viniferin, deriving from trans-resveratrol dimerization, was investigated in its ability to target DNA duplex and G-quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)-trans-δ-Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3'- and 5'-ends of a G-quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)-trans-δ-viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)-trans-δ-viniferin and trans-resveratrol, i. e. (±)-pterostilbene-trans-dihydrodimer and trans-pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at µM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G-quadruplex structures.

Mycobacterium bovis detection in slaughtered pigs in the state of Rio Grande do Sul, Brazil

The infection by the Mycobacterium genus is important in pig farming due to the economic losses caused by total or partial carcass condemnation in slaughterhouses. The present study investigated the occurrence of a tuberculosis outbreak in pigs, based on the identification of lesions at the slaughter line of a slaughterhouse. At the inspection line of the slaughterhouse, carcasses were identified with viscera containing macroscopic lesions that indicated tuberculosis (granulomatous lymphadenitis). Tracheobronchial, mesenteric, and submandibular lymph nodes were collected, as well as liver samples and their corresponding lymph nodes. The samples were sent to the Federal Agricultural Defense Laboratory (LFDA/RS) and processed for the diagnosis of tuberculosis and the molecular characterization of Mycobacterium bovis. Based on the results of post-mortem and laboratory inspections, the occurrence was characterized as a tuberculosis outbreak in pigs, which originated from a farm in the state of Rio Grande do Sul, Brazil. Over three months, three batches, adding up to 2884 animals, were sent to slaughter, of which 102 (3.5%) had tuberculosis-like lesions at the inspection line. Based on these results, the productive process was investigated, assessing the feeding, water supply, and milk whey offered in the diet of pigs. It was concluded that the outbreak was caused by feeding unpasteurized or inadequately pasteurized (insufficient time x temperature relation) whey to the pigs. The use of whey from cheese production is a frequent practice in the state of Rio Grande do Sul and one of the risk factors for granulomatous lymphadenitis in pigs.

Slaughter condemnation in bovine due to parasitic lesions and their economic impact in Federal Inspection System establishments in Brazil and in State inspection System in Rio Grande do Sul State / Condenação ao abate em bovinos devido a lesões parasitárias e seu impacto econômico em estabelecimentos do Sistema Federal de Inspeção no Brasil e no Sistema Estadual de Inspeção no Rio Grande do Sul

Abstract Slaughter condemnations are important sources of information on cattle health. The incidence of bovine parasitic diseases is still very high in Brazil. These diseases, in addition to causing harm to the animals health, are neglected zoonotic diseases in several parts of world. The study analysed not only the Carcass losses, but also the economic damage resulting from slaughter condemnations due to parasitic causes. Cattle slaughter data from the Brazilian Ministry of Agriculture, Livestock and Supply (MAPA), over the period of 2012 to 2015 and data from the Secretary of Livestock and Irrigation of the state of Rio Grande do Sul (SEAPI-RS) were analyzed between 2014 and 2018.The number of organs and carcasses condemned was multiplied by the respective values (in Brazilian Real) obtained from slaughterhouses and subsequently converted into dollars. Brazilian analysis in SIF (Federal Inspection System) establishments showed that more than 1.2 million organs (3,884,505 kg) and 20,000 carcasses (4,547,718 kg) were condemned only due to parasitic causes during post-mortem inspection. In Rio Grande do Sul, in state inspection establishments, more than 1.7 million organs (8,210,559 kg) and 5,000 carcasses (1,243,200 kg) were condemned. These data are alarming and support the need for public policies to control these parasitic diseases.

Resumo Condenações durante o abate são importantes fontes de informação sobre a sanidade dos rebanhos. Ainda são altas as incidências de doenças parasitárias, as quais trazem consequências à saúde dos animais, são zoonoses e têm sua importância negligenciada em diversos países. O estudo objetivou quantificar não apenas as perdas encontradas, mas o prejuízo econômico resultante das condenações ao abate por causas parasitárias. Para isso foram analisados dados de abate de bovinos do Ministério da Agricultura Pecuária e Abastecimento, no período de 2012 a 2015, e dados da Secretaria da Agricultura Pecuária e Irrigação, do estado do Rio Grande do Sul, no período de 2014 a 2018. A quantidade de órgãos e carcaças condenados foi multiplicada pelos respectivos valores (em Reais), obtidos da indústria frigorífica e, posteriormente, convertidos para dólar. A análise brasileira de estabelecimentos com SIF (Serviço de Inspeção Federal) mostrou que mais de 1,2 milhão de órgãos (3.884.505 kg) e 20 mil carcaças (4.547.718 kg) foram condenados devido a causas parasitárias durante a inspeção. No estado do Rio Grande do Sul, nos estabelecimentos de inspeção estadual, foram condenados mais de 1,7 milhão de órgãos (8.210.559 kg) e 5 mil carcaças (1.243.200 kg). Os dados são alarmantes e ressaltam a necessidade de políticas públicas para controlar estas parasitoses.

Tripodal gold(i) polypyridyl complexes and their Cu+ and Zn2+ heterometallic derivatives. Effects on luminescence.

Three gold(i) tripodal complexes containing the tris(2-pyridylmethyl)amine (TPA) ligand coordinated to Au-PR3 moieties (PR3 = 1,3,5-triaza-7-phosphatricyclo[3.3.1.13.7]decane, PTA (1), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane, DAPTA (2) and triphenylphosphane (3)) were prepared together with a cage-like structure containing triphosphane 1,1,1-tris(diphenylphosphinomethyl)ethane (4). The luminescence of these complexes has been studied and they show a red shift upon the formation of heterometallic complexes by reaction with Zn(NO3)2, CuCl and [Cu(CH3CN)4]BF4. The different coordination motifs of the Zn2+ and Cu+ heterometallic species and the resulting changes in the recorded absorption, emission and NMR spectra were analysed and supported by TD-DFT calculations.

Flattening filter for Gaussian-shaped monochromatic X-ray beams: an application to breast computed tomography.

The vertical intensity distribution of synchrotron-based X-ray beams usually has a Gaussian profile encompassing large intensity variations. For biomedical imaging applications this may entail sub-optimal dose distributions and large fluctuations in terms of image noise. Commonly, planar metallic filters coupled with absorbing slits systems are applied to adjust the delivered flux and to limit intensity variations, respectively. The latter results in a reduction of the effective beam size. A flattening filter that counterbalances the transverse inhomogeneity, while retaining a sufficient flux, has been developed in the context of a monochromatic phase-contrast breast computed tomography application, ongoing at the Elettra synchrotron facility. The implementation of the new filtration system results in homogeneous intensity (hence dose) distribution and signal-to-noise ratio across the imaged volume. Finally, and most importantly, it allows a wider portion of the beam to be used, directly translating into a major (∼40%) reduction of the overall scan time for samples requiring a field of view larger than the beam size (i.e. multiple translation steps).

Identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign.

The LIBRA compound library is a collection of 522 non-commercial molecules contributed by various Italian academic laboratories. These compounds have been designed and synthesized during different medicinal chemistry programs and are hosted by the Italian Institute of Technology. We report the screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase 1, TbPTR1 and LmPTR1. Nine compounds were active against parasitic PTR1 and were selected for cell-based parasite screening, as single agents and in combination with methotrexate (MTX). The most interesting TbPTR1 inhibitor identified was 4-(benzyloxy)pyrimidine-2,6-diamine (LIB_66). Subsequently, six new LIB_66 derivatives were synthesized to explore its Structure-Activity-Relationship (SAR) and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties. The results indicate that PTR1 has a preference to bind inhibitors, which resemble its biopterin/folic acid substrates, such as the 2,4-diaminopyrimidine derivatives.