Progress on Phage Display Technology: Tailoring Antibodies for Cancer Immunotherapy.

The search for innovative anti-cancer drugs remains a challenge. Over the past three decades, antibodies have emerged as an essential asset in successful cancer therapy. The major obstacle in developing anti-cancer antibodies is the need for non-immunogenic antibodies against human antigens. This unique requirement highlights a disadvantage to using traditional hybridoma technology and thus demands alternative approaches, such as humanizing murine monoclonal antibodies. To overcome these hurdles, human monoclonal antibodies can be obtained directly from Phage Display libraries, a groundbreaking tool for antibody selection. These libraries consist of genetically engineered viruses, or phages, which can exhibit antibody fragments, such as scFv or Fab on their capsid. This innovation allows the in vitro selection of novel molecules directed towards cancer antigens. As foreseen when Phage Display was first described, nowadays, several Phage Display-derived antibodies have entered clinical settings or are undergoing clinical evaluation. This comprehensive review unveils the remarkable progress in this field and the possibilities of using clever strategies for phage selection and tailoring the refinement of antibodies aimed at increasingly specific targets. Moreover, the use of selected antibodies in cutting-edge formats is discussed, such as CAR (chimeric antigen receptor) in CAR T-cell therapy or ADC (antibody drug conjugate), amplifying the spectrum of potential therapeutic avenues.

Autologous blood transfusion reduces the requirement for perioperative allogenic blood transfusion in patients undergoing major hepatopancreatobiliary surgery: a retrospective cohort study.

INTRODUCTION: Major hepatopancreatobiliary surgery is associated with a risk of major blood loss. The authors aimed to assess whether autologous transfusion of blood salvaged intraoperatively reduces the requirement for postoperative allogenic transfusion in this patient cohort. MATERIALS AND METHODS: In this single centre study, information from a prospective database of 501 patients undergoing major hepatopancreatobiliary resection (2015-2022) was analysed. Patients who received cell salvage ( n =264) were compared with those who did not ( n =237). Nonautologous (allogenic) transfusion was assessed from the time of surgery to 5 days postsurgery, and blood loss tolerance was calculated using the Lemmens-Bernstein-Brodosky formula. Multivariate analysis was used to identify factors associated with allogenic blood transfusion avoidance. RESULTS: 32% of the lost blood volume was replaced through autologous transfusion in patients receiving cell salvage. Although the cell salvage group experienced significantly higher intraoperative blood loss compared with the noncell salvage group (1360 ml vs. 971 ml, P =0.0005), they received significantly less allogenic red blood cell units (1.5 vs. 0.92 units/patient, P =0.03). Correction of blood loss tolerance in patients who underwent cell salvage was independently associated with avoidance of allogenic transfusion (Odds ratio 0.05 (0.006-0.38) P =0.005). In a subgroup analysis, cell salvage use was associated with a significant reduction in 30-day mortality in patients undergoing major hepatectomy (6 vs. 1%, P =0.04). CONCLUSION: Cell salvage use was associated with a reduction in allogenic blood transfusion and a reduction in 30-day mortality in patients undergoing major hepatectomy. Prospective trials are warranted to understand whether the use of cell salvage should be routinely utilised for major hepatectomy.

Intraoperative cell salvage using swab wash and serial thromboelastography in elective abdominal aortic aneurysm surgery involving massive blood loss.

The loss of 50% blood volume is one accepted definition of massive haemorrhage, which ordinarily would trigger the massive transfusion protocol, involving the administration of high ratios of fresh frozen plasma and platelets to allogeneic red cells. We investigated 53 patients who experienced >50% blood loss during open elective abdominal aortic aneurysm surgery to assess allogeneic blood component usage and coagulopathy. Specialist patient blood management practitioners used a tailored cell salvage technique including swab wash to maximise blood return. We assessed the proportion of patients who did not require allogeneic blood components and develop evidence of coagulopathy by thromboelastography (TEG) parameters. Blood loss was 50%-174% (mean [SD] 68% [27%]) of blood volume. The mean (SD) intraoperative decrease in haemoglobin concentration, assessed by arterial blood gas analysis, was 5 (13) g/l. No patient received allogeneic red cells intraoperatively. Four of the 53 (8%) patients received blood components in the first 24 h postoperatively at the anaesthetists' discretion. No patient had intraoperative TEG changes indicative of fibrinolysis or coagulopathy. The 30-day mortality was 2% (one of 53). Reduction of allogeneic transfusion is one aim of patient blood management techniques. We have demonstrated virtual avoidance of allogeneic blood product transfusion despite massive blood loss. These data show possible alternatives to the current massive transfusion protocols to the management of elective vascular surgical patients.

Dynamics of Thermolysis and Skin Microstructure in Water Buffaloes Reared in Humid Tropical Climate-A Microscopic and Thermographic Study.

The thermolytic capacity test is used to assess the adaptability of animals to existing environmental conditions. However, there is insufficient information on the relationship between histomorphometry and adaptability of buffaloes. Thus, this study aimed to assess the use of thermolysis pathways by buffaloes reared in a hot and humid environment so as to understand the relationships between environment, skin morphological characteristics, and heat storage, as well as the intensity and proportionality of use of its ways of dissipating heat to maintain homeothermy. The heat tolerance test, associated with the evaluations via infrared thermography, was applied to 10 female Murrah buffaloes and tegument histomorphometry was carried out. The animals exhibited very high heat tolerance with an average of 9.66 ± 0.21 and used thermal polypnea as the main heat dissipation pathway. Their mean skin thickness was 6.03 ± 1.16 mm and the active sweat and sebaceous gland tissue were 1.57 ± 0.38% and 1.08 ± 0.39%, respectively. The buffaloes exhibited a positive correlation between eyeball temperature and internal body temperature (r = 0.84523, p < 0.0001) and a negative correlation between respiratory rate and skin thickness (r = -0.73371, p = 0.0157). The high thermolytic capacity in shade conditions confirms the importance of access to shade in buffalo rearing systems in tropical regions.

Family caregiver grief and post-loss adjustment: A longitudinal cohort study.

OBJECTIVE: In order to better understand the different grieving trajectories of the family caregivers (FCs), this study aims to examine the evolution of prolonged grief disorder (PGD) symptoms and the predictive role of the caregiving-related factors in the FCs' grieving trajectory from pre- to post-death. METHOD: A prospective cohort study was carried out with advanced cancer FCs evaluated before death (T1) and 6-12 months post-loss (T2). RESULTS: Participants in T1 (n = 156) were mostly female, adult child, or spouse of the care recipient, with a mean age of 51.78 (SD = 13.29). At T2, 87 FCs participated in the survey. PGD prevalence was higher pre-death (38.6%) than in bereavement (33.7%). Of those who met the PGD criteria before death, most also met these criteria after death (n = 26, 61.9%). Psychological distress and caregiver burden were highly correlated with pre-death grief, which in turn played a critical role in mediating the link between psychological distress and bereavement outcome. Great emotional closeness in the relationship was predictive of PGD symptoms persistence. In contrast, the long-term consequences of caregiver burden were not confirmed. SIGNIFICANCE OF RESULTS: This study provides evidence for the diversity of individual FC responses and the complex pattern of interactions between caregiving-related factors, relationship quality, and PGD symptoms evolution from pre- to post-death.

Centro de referência de álcool, tabaco e outras drogas: seis anos de uma intervenção / Reference center for alcohol, tobacco and other drugs: six years of intervention / Centro de referencia en el tratamiento de alcohol, tabaco y otras drogas: seis años de intervención

OBJETIVO: descrever a evolução dos modelos de intervenção e tratamento do Centro de Referência de Álcool, Tabaco e Outras Drogas do Estado de São Paulo, apresentando dados de produção dos últimos 6 anos. MÉTODO: estudo transversal, retrospectivo, com dados e registros dos atendimentos realizados entre 2013 e 2018 em diversos setores do CRATOD. RESULTADOS: o serviço contabilizou nos últimos seis anos 204.933 registros de atendimentos sendo 31.807 de casos novos, 12.318 testes rápidos para HIV, Sífilis, Hepatite B e C e atendeu 69 pacientes na Moradia Monitorada. CONCLUSÃO: a linha de cuidados do serviço engloba três premissas: acolhimento com escuta qualificada, tratamento ambulatorial/hospitalar e reinserção social, nesse contexto, o profissional de enfermagem aparece como peça fundamental durante todas as fases do tratamento. A consistência desse trabalho em conjunto com a equipe multiprofissional resultou na consolidação e estruturação de um fluxo de atendimento que visa a constante motivação e cuidado do dependente químico.

OBJECTIVE: to describe the evolution of the intervention and treatment models of the Reference Center for Alcohol, Tobacco and Other Drugs in the State of São Paulo, submitting production data for the last 6 years. METHOD: a cross-sectional and retrospective study, with data and records of the consultations carried out between 2013 and 2018 in different CRATOD sectors. RESULTS: the service counted 204,933 service records in the last six years, 31,807 of which were new cases, 12,318 rapid tests for HIV, Syphilis, and Hepatitis B and C. and served 69 patients in the Monitored Housing. CONCLUSION: the service's line of care encompasses three premises: reception with qualified listening, outpatient/hospital treatment and social reintegration, in this context, the nursing professional appears as a fundamental part during all treatment phases. The consistency of this work in conjunction with the multi-professional team resulted in the consolidation and structuring of a service flow aimed at the constant motivation and care of the drug addict.

OBJETIVO: describir la evolución de los modelos de intervención y tratamiento del Centro de Referencia en el tratamiento de Alcohol, Tabaco y Otras Drogas en el Estado de São Paulo, presentando datos registrados en los últimos 6 años. MÉTODO: estudio transversal, retrospectivo, con datos y registros de las consultas realizadas entre 2013 y 2018 en diferentes sectores de CRATOD. RESULTADOS: se computaron 204,933 registros de servicio en los últimos seis años, 31,807 de los cuales referían a casos nuevos, 12,318 pruebas rápidas para VIH, Sífilis, Hepatitis B y C y fueron atendidos 69 pacientes en la Vivienda Monitoreada. CONCLUSIÓN: la línea de atención del servicio abarca tres premisas: admisión con escucha calificada, tratamiento ambulatorio/hospitalario y reintegración social, en este contexto, el profesional de enfermería surge como parte fundamental en todas las fases del tratamiento. La coherencia de este trabajo junto con el equipo multiprofesional dio como resultado la consolidación y estructuración de un flujo de servicio dirigido a la motivación y el cuidado constante del adicto.

Network Substrates of Centromedian Nucleus Deep Brain Stimulation in Generalized Pharmacoresistant Epilepsy.

Deep brain stimulation (DBS), specifically thalamic DBS, has achieved promising results to reduce seizure severity and frequency in pharmacoresistant epilepsies, thereby establishing it for clinical use. The mechanisms of action are, however, still unknown. We evidenced the brain networks directly modulated by centromedian (CM) nucleus-DBS and responsible for clinical outcomes in a cohort of patients uniquely diagnosed with generalized pharmacoresistant epilepsy. Preoperative imaging and long-term (2-11 years) clinical data from ten generalized pharmacoresistant epilepsy patients (mean age at surgery = 30.8 ± 5.9 years, 4 female) were evaluated. Volume of tissue activated (VTA) was included as seeds to reconstruct the targeted network to thalamic DBS from diffusion and functional imaging data. CM-DBS clinical outcome improvement (> 50%) appeared in 80% of patients and was tightly related to VTAs interconnected with a reticular system network encompassing sensorimotor and supplementary motor cortices, together with cerebellum/brainstem. Despite methodological differences, both structural and functional connectomes revealed the same targeted network. Our results demonstrate that CM-DBS outcome in generalized pharmacoresistant epilepsy is highly dependent on the individual connectivity profile, involving the cerebello-thalamo-cortical circuits. The proposed framework could be implemented in future studies to refine stereotactic implantation or the parameters for individualized neuromodulation.

Use of Saccharomyces cerevisiae-based products and effects on rumen environment and performance of sheep subjected to dietary changes / Utilização de produtos à base de Saccharomyces cerevisiae e seus efeitos sobre o ambiente ruminal e desempenho de ovinos submetidos a mudanças de dieta

ABSTRACT: Natural additives in ruminant diet optimizes animal performance by controlling or modifying the rumen fermentation pattern. The aim of this study was to evaluate the effects of using Saccharomyces cerevisiae products during abrupt changes in dietary starch concentration on ruminal pH maintenance, performance and metabolism of confined sheep. Twenty adult ewes, crossbred Texel x Corriedale(44.7±6.97 Kg BW) were divided into three groups: Control (n=6), Cultron X (yeast culture; n=7) and Cultron Pro (hydrolyzed yeast; n=7), administered at a dose of 5 g/sheep/day (10x1010CFU/g DM). The experiment lasted 20 days divided into four periods, alternating between 40 and 60% concentrate. Blood and ruminal fluid were collected at the end of each period, and daily dry matter intake was measured to determine the average daily gain (ADG). Blood tests included blood count and biochemical parameters such as glucose, urea, total plasma proteins (TPP), liver enzymes, acute phase proteins and minerals. There was an upward trend in ADG in group Cultron X compared to control in period 3. Although, ruminal pH did not differ between groups, protozoan motility was higher in animals supplemented with hydrolyzed yeast. The Cultron Pro group showed an increase in TPP in periods 3 and 4, and AST in periods 2 and 3 compared to the control group. There was no difference in other metabolites. Yeast supplementation is a potential tool in times of feeding challenge, in which yeast culture is the most effective for improving performance of confined sheep being in improving performance of confined sheep.

RESUMO: A utilização de aditivos naturais na dieta de ruminantes é uma prática que otimiza o desempenho, controlando ou modificando o padrão de fermentação ruminal. O objetivo do estudo buscou avaliar os efeitos da utilização de produtos à base de Saccharomyces cerevisiae durante mudanças na concentração de amido da dieta sobre a manutenção do pH ruminal, desempenho e metabolismo de ovinos confinados. Dessa forma, 20 fêmeas ovinas adultas mestiças das raças Texel e Corriedale (44,7±6,97 PV) foram divididas em três grupos: Controle (n=6), Cultron X (cultura de levedura; n=7) e Cultron Pro (levedura hidrolisada; n=7), administrados na dose de 5 g/ovelha/dia (10x1010ufc/g de MS). O experimento teve duração de 20 dias divididos em quatro períodos, alternando entre 40 e 60% de concentrado. Foram realizadas coletas de sangue e líquido ruminal ao final de cada período e mensuração da ingestão de matéria seca diariamente, a fim de determinar o ganho médio diário (GMD). As análises sanguíneas incluíram hemograma e parâmetros bioquímicos como glicose, ureia, proteínas plasmáticas totais (PPT), enzimas hepáticas, proteínas de fase aguda e minerais. Houve tendência de aumento no GMD no grupo Cultron X em relação ao controle no período 3. Apesar do pH ruminal não diferir entre grupos, a motilidade de protozoários foi melhor nos animais suplementados com levedura hidrolisada. O grupo Cultron Pro apresentou aumento de PPT nos períodos 3 e 4 e aumento nos níveis da enzima hepática AST nos períodos 2 e 3 em comparação ao grupo controle. Não houve diferença nos demais metabólitos. A suplementação com levedura apresentou-se como potencial ferramenta em momentos de desafio alimentar, sendo a cultura de levedura mais eficaz na melhora da performance de ovinos confinados.

Sweet Potato Flour as a Replacement for Ground Corn as an Energetic Concentrate / Utilização de farinha de batata-doce como substituto ao milho moído como concentrado energético

ABSTRACT: This study evaluated the effects of different levels of substitution of ground corn by sweet potato flour on intake, digestibility, microbial protein synthesis and total Nitrogen (N) retention in sheep fed mixed diets based on corn silage. Eight castrated male sheep were used, kept in metabolic cages. The animals received fixed proportions of oat hay, corn silage and soybean meal. The control group (0%) received only ground corn, while the other groups received different levels of inclusion of sweet potato flour (SPF) to replace ground corn, in the proportions of 33%, 66%, and 100%. The 0% and 33% groups had lower neutral detergent fiber (NDF) intake than the 66% and 100% groups. There was a trend (P = 0.07) of effect of treatments on crude protein (CP) intake with a significant positive linear effect (P = 0.03). There was a trend (P = 0.07) for treatment effects in N intake with a significant positive linear effect (P = 0.03). The other parameters as urine N excretion (P = 0.91) and feces N excretion (P = 0.16) were not affected by the replacement of ground corn by SPF. Moreover, there was no effect on N retention (P = 0.43) and on efficiency of N use (P = 0.69). Adding SPF to a diet instead of corn did not alter the microbial protein parameters. The inclusion of sweet potato flour did not cause changes in the protein metabolism of animals, suggesting it can be used instead of corn.

RESUMO: O objetivo desse estudo foi avaliar os efeitos dos diferentes níveis de substituição de milho moído por farinha de batata-doce na ingestão, digestibilidade, síntese de proteína microbiana e a retenção de Nitrogênio (N) em ovinos alimentados por dietas com base em silagem de milho. Foram utilizados oito ovinos machos castrados, mantidos em gaiolas metabólicas, divididos em quatro grupos no quadrado latino 4 x 4, totalizando quatro períodos de 15 dias cada. Os animais receberam proporções fixas de feno de aveia, silagem de milho e farelo de soja. O grupo controle (0%) recebeu apenas milho moído, enquanto os outros grupos receberam diferentes níveis de inclusão de farinha de batata doce (FBD) em substituição ao milho moído, nas proporções de 33%, 66% e 100%. Amostras de alimentos e sobras foram coletadas para avaliação do consumo e análise bromatológica. A urina foi coletada para avaliação da síntese proteica microbiana através dos derivados da purina (DP). As fezes foram coletadas para análise e estimativa da digestibilidade. Os grupos de 0% e 33% apresentaram menor consumo de fibra em detergente neutro (FDN) do que os grupos de 66% e 100%. Houve uma tendência (P = 0,07) de efeito dos tratamentos na ingestão de proteína bruta (PB) com efeito linear positivo significativo (P = 0,03). Houve uma tendência (P = 0,07) para os efeitos do tratamento na ingestão de N com um efeito linear positivo significativo (P = 0,03). Os demais parâmetros como excreção de N na urina (P = 0,91) e excreção de N nas fezes (P = 0,16) não foram afetados pela substituição do milho moído pela FBD. Além disso, não houve efeito na retenção de N (P = 0,43) e na eficiência do uso de N (P = 0,69). A adição de FBD a uma dieta em vez de milho não alterou os parâmetros das proteínas microbianas. A inclusão de farinha de batata-doce não causou alterações no metabolismo proteico dos animais, sugerindo que pode ser utilizada no lugar do milho.

Use of sulfonamides for the treatment of bovine neonatal diarrhea: clinical and performance parameters / Utilização de sulfonamidas para o tratamento de diarreia neonatal bovina: parâmetros clínicos e zootécnicos

This study was developed to evaluate the clinical, hematological, and performance parameters of calves affected by diarrhea caused by the bacterial enteric pathogen Escherichia coli, treated with three different protocols containing sulfonamides. Fourteen Holstein calves were monitored from birth to 60 days of age, and divided into 3 groups. Group 1 (n=5) animals were treated with 80 g of Kaopek®, Ibasa, Brazil, administered orally (BM), dissolved in 160 ml of water every 24 h; Group 2 (n=4) received IM sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil), and Group 3 (n=5) animals were treated with 80 g of Kaopek®, Ibasa, Brazil, which is made up of 16 g of phthalylsulfathiazole, associated with 2.28 g neomycin sulfate, 1.6 g of pectin, and 80 g of kaolin, dissolved in 160 ml of water and administered every 24 h by mouth, in addition to sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil), at a daily dose of 16 mg/kg live weight, through IM injection. During the study, the animals were clinically evaluated, and once they were diagnosed with diarrhea, feces samples were collected to identify the bacterial enteric pathogen, antibiogram, polymerase chain reaction (PCR), and coproparasitological exams. Blood samples were collected to evaluate the hematological profile, and the performance profile was monitored weekly. In the clinical examination, all calves presented a reduction in body temperature (<39.2°C) and some improvement in hydration after treatment (p=0,31). However, group 2 had a better concentration of lymphocytes and TP concerning the other animals, as well as better performance. Besides, E.coli was detected in 100% of feces samples. Thus, the therapeutic protocols with sulfonamides used to treat bovine neonatal diarrhea were effective in the clinical improvement of the animals. Nonetheless, the protocol with systemic therapy using sulfadiazine and trimethoprim (Ibatrim®, Ibasa, Brazil) intramuscularly, provided better performance, with better weight gain, and body development of the animals.(AU)

Este estudo foi desenvolvido com o objetivo de avaliar parâmetros clínicos, hematológicos e zootécnicos de bezerras acometidas por diarreia provocada pelo agente bacteriano Escherichia coli, tratadas com três diferentes protocolos contendo sulfonamidas. Quatorze bezerras da raça Holandês foram monitoradas do nascimento até os 60 dias de vida e divididas em 3 grupos: Grupo 1 (n=5), animais tratados com a dose de 80g de Kaopek®, Ibasa, Brasil, por via oral (VO), dissolvido em 160ml de água a cada 24 horas; Grupo 2 (n=4) receberam sulfadiazina e trimetropim (Ibatrim®, Ibasa, Brasil), na dose de 16mg/Kg de peso vivo, por dia, por via intramuscular (IM); Grupo 3 (n=5) 80g de Kaopek®, Ibasa, Brasil, por VO dissolvido em 160ml de água, a cada 24 horas e com 16mg/Kg de peso vivo, por dia, de sulfadiazina e trimetoprim (Ibatrim®, Ibasa, Brasil), por via IM. Durante o estudo, os animais foram avaliados clinicamente e a partir do diagnóstico de diarreia foram coletadas amostras de fezes para a identificação do agente bacteriano, antibiograma, reação em cadeia da polimerase (PCR) e exames coproparasitológicos. Amostras de sangue foram coletadas para avaliação do perfil hematológico e o perfil zootécnico foi acompanhado semanalmente. No exame clínico, todas as bezerras apresentaram redução na temperatura corporal (<39,2°C) e melhora na hidratação após o período de tratamento (p=0,31), porém o grupo 2 obteve maior concentração de linfócitos e PPT em relação aos demais, assim como melhor desempenho zootécnico, além disso em 100% das amostras de fezes foi detectado E. coli. Sendo assim, os protocolos terapêuticos com sulfonamidas utilizados para o tratamento da diarreia neonatal bovina foram eficazes na melhora clínica dos animais. Porém, o protocolo com terapia sistêmica com sulfadiazina e trimetoprim (Ibatrim®, Ibasa, Brasil) por via intramuscular proporcionou um melhor desempenho zootécnico, com melhor ganho de peso e desenvolvimento corporal dos animais.(AU)

Heterotopic Heart Transplantation as a Left Ventricular Biological Assistance: a New Two-Stage Method Proposal.

Since Barnard's first heterotopic heart transplant in 1974, Copeland's method has been the greatest contribution to heterotopic transplants but has the drawback of donor's right ventricular atrophy. This new method proposes a modification in the anastomosis of the superior vena cava aiming to pre-serve donor's right ventricular function by decompressing the pulmonary territory and reducing the pulmonary arterial pressure, as a biological ventricular assist device. Finally, a second intervention is proposed, where a "twist" is performed to place the donor's heart in an orthotopic position after re-moval of the native heart. A pioneering research on this method received approval from the ethics committee of the Heart Institute of São Paulo. We believe that this method has the potential to im-prove quality of life in a selected group of patients.

A prion-like domain in ELF3 functions as a thermosensor in Arabidopsis.

Temperature controls plant growth and development, and climate change has already altered the phenology of wild plants and crops1. However, the mechanisms by which plants sense temperature are not well understood. The evening complex is a major signalling hub and a core component of the plant circadian clock2,3. The evening complex acts as a temperature-responsive transcriptional repressor, providing rhythmicity and temperature responsiveness to growth through unknown mechanisms2,4-6. The evening complex consists of EARLY FLOWERING 3 (ELF3)4,7, a large scaffold protein and key component of temperature sensing; ELF4, a small α-helical protein; and LUX ARRYTHMO (LUX), a DNA-binding protein required to recruit the evening complex to transcriptional targets. ELF3 contains a polyglutamine (polyQ) repeat8-10, embedded within a predicted prion domain (PrD). Here we find that the length of the polyQ repeat correlates with thermal responsiveness. We show that ELF3 proteins in plants from hotter climates, with no detectable PrD, are active at high temperatures, and lack thermal responsiveness. The temperature sensitivity of ELF3 is also modulated by the levels of ELF4, indicating that ELF4 can stabilize the function of ELF3. In both Arabidopsis and a heterologous system, ELF3 fused with green fluorescent protein forms speckles within minutes in response to higher temperatures, in a PrD-dependent manner. A purified fragment encompassing the ELF3 PrD reversibly forms liquid droplets in response to increasing temperatures in vitro, indicating that these properties reflect a direct biophysical response conferred by the PrD. The ability of temperature to rapidly shift ELF3 between active and inactive states via phase transition represents a previously unknown thermosensory mechanism.

Utilização de taninos como aditivo nutricional na dieta de ruminantes / Use of tannins as a nutritional additive for ruminants / Uso de taninos como aditivo nutricional en dieta de rumiantes

Os taninos são compostos fenólicos presentes em plantas, classificados quanto à estrutura química em compostos hidrolisáveis e condensados. Os condensados são adicionados à dieta de ruminantes devido a sua capacidade de formar complexos com proteínas tornando-as não degradáveis no ambiente ruminal. Dessa forma, aumenta o aporte proteico no intestino delgado onde ocorrerá a maior absorção na porção cranial do órgão, o duodeno. A vantagem desse mecanismo é aumentar o aproveitamento da proteína da dieta pelos animais o que influenciará na produtividade e sistema imunológico, entre outros. Os efeitos positivos com a utilização desse composto como aditivo nutricional ainda precisam ser estudados, portanto, o objetivo dessa revisão consiste em demonstrar os resultados, até então conhecidos, da utilização de taninos condensados na dieta de ruminantes.(AU)

Tannins are phenolic compounds present in plants. According to their chemical structure, they can be classified into hydrolysable and condensed compounds. Condensed compounds are added to the ruminant nutrition due to their ability to form complexes with proteins, rendering them as non-degradable in the rumen environment. Thus, it increases the protein supply in the small intestine, where the highest absorption will occur in the duodenum, the cranial portion of the organ. The advantage of this mechanism is the increase of the use of dietary protein by the animals, which will thus influence productivity and the immune system, among others. The positive effects of the use of this compound as a nutritional additive still need to be further investigated, therefore, the purpose of this review is to demonstrate the known results of the use of condensed tannins in the diet of ruminants.(AU)

Los taninos son compuestos fenólicos presentes en plantas, clasificados según la estructura química en compuestos hidrolizables y condensados. Los condensados se agregan a la dieta de rumiantes debido a su capacidad de formar complejos con proteínas, haciéndolas no degradables en el entorno del rumen. Así, aumenta el aporte proteico en el intestino delgado donde habrá mayor absorción en la porción craneal del órgano, el duodeno. La ventaja de ese mecanismo es aumentar el aprovechamiento de la proteína de la dieta por los animales, lo que influirá en la productividad y sistema inmunológico, entre otros. Los efectos positivos con la utilización de ese compuesto, como aditivo nutricional, todavía necesita ser estudiado, el objetivo de esa revisión consiste en demostrar los resultados, hasta ahora conocidos, del uso de taninos condensados en la dieta de rumiantes.(AU)

Episodic Cancer Pain: Patient Reporting, Prevalence, and Clinicodemographic Associations at Initial Cancer Pain Clinic Assessment.

Background: Better understanding of the episodic cancer pain (CP) spectrum, including pains that occur in addition to its conventionally defined breakthrough CP (BTcP) and incident CP (IcP) components, may inform CP assessment and management. This study aimed to determine the prevalence of episodic patient-reported CP and the prevalence and associations of study-defined BTcP (S-BTcP) and IcP (S-IcP) in patients with CP. Methods: In a cross-sectional study at their first CP clinic attendance, participants with CP had the following assessments: Brief Pain Inventory (BPI); Pain Management Index (PMI), with PMI-negative status indicating undertreatment; standardized neuropathic pain component (NPC) status; S-BTcP (no trigger identified) and S-IcP (trigger identified) status, based on a preceding 7-day history of transitory pain flares distinct from background pain, and BPI-Worst or BPI-Now pain intensity ≥ 4. Clinicodemographic variables' association with S-BTcP and S-IcP was examined in logistic regression analyses. Results: Of 371 participants, 308 (83%) had episodic CP by history alone; 140 (37.7%) and 181 (48.8%) had S-BTcP and S-IcP, respectively. Multivariable analyses demonstrated significant (p < 0.05) associations (odds ratios: 95% CIs) for 6 variables with S-BTcP: head and neck pain location (2.53; 1.20-5.37), NPC (2.39; 1.34-4.26), BPI average pain (1.64; 1.36-1.99), abdominal pain (0.324; 0.120-0.873), S-IcP (0.207; 0.116-0.369), and PMI-negative status (0.443; 0.213-0.918). Similar independent associations (p < 0.05) occurred for S-IcP with NPC, BPI average pain, and PMI-negative status, in addition to radiotherapy, S-BTcP, soft tissue pain, and sleep interference. Conclusions: Episodic or transient patient-reported CP flares often do not meet the more conventional criteria that define BTcP and IcP, the principal episodic CP types. Both BTcP and IcP occur frequently and both are associated with a NPC, higher pain intensity, and less opioid underuse in the management of CP. Further studies are warranted to both better understand the complex presentations of episodic CP and inform its classification.

Caregiving and bereavement in palliative care: A cross-cultural study between Brazil and Portugal.

Caregiving and bereavement outcomes are strongly influenced by socio-cultural context. Past research has found higher levels of caregiver burden and psychological morbidity in Portuguese compared to Brazilian caregivers. This study compared Brazilian and Portuguese family caregivers in palliative care to identify differences in psychological morbidity and caregiver burden and their relationship with psychosocial factors such as sociodemographic variables, circumstances of end-of-life care and dying, social support, family functioning, and perception of quality of care. Prospective data were collected from convenience samples of family caregivers in Brazil (T0 n = 60; T1 n = 35) and Portugal (T0 n = 75; T1 n = 29) at two separate time points-during caregiving (T0), and during the first two months of bereavement (T1). The study samples consisted mostly of women, offspring, and spouses. In both countries, family caregivers devoted most of their day to taking care of their sick relatives and reported a lack of practical support. Portuguese caregivers had higher levels of burden than Brazilian caregivers, and in both populations a greater burden was associated with more psychopathological symptoms. Higher caregiver burden among Portuguese caregivers was associated with the circumstances of death and the perceived lack of emotional support. Among Portuguese caregivers, symptomatology persisted during bereavement, reaching significantly higher levels of anxiety, somatization, and peritraumatic symptoms compared to the Brazilian sample. These results show differences between family caregiver samples in Portugal and Brazil during the bereavement process. Understanding the underlying cultural patterns and mechanisms requires future research.

Family Caregivers' Anticipatory Grief: A Conceptual Framework for Understanding Its Multiple Challenges.

The end-of-life trajectory of cancer patients in palliative care (PC) elicits an anticipatory grief (AG) process in family caregivers (FCs). Although widely recognized, AG lacks conceptual clarification. This study aims to qualitatively explore the experience of FCs of patients with terminal cancer to identify the core characteristics and the specific adaptive challenges related to AG in the context of end-of-life caregiving. Data were collected through in-depth semi-structured interviews conducted in a clinical sample of 26 FCs of cancer patients in PC. Findings from thematic analysis suggest that the AG experience is characterized by traumatic distress from being exposed to life-threatening conditions and the separation distress induced by loss anticipation and current relational losses, challenging the FCs to long-term emotional regulation effort demands. These results contribute to the conceptualization of AG and may inform intervention programs for the main challenges the FCs face when adjusting to loss during end-of-life caregiving.

Prepartum lameness on subsequent lactation in Holstein dairy cows / Impactos da claudicação pré-parto na lactação subsequente de vacas leiteiras da raça Holandês

ABSTRACT: The aim of this study was to confirm the possible consequences of prepartum lameness on subsequent lactation among Holstein cows. In this research, 27 multiparous cows, were monitored from the 30th to 63rd day, relative to calving. Thirty days prior to parturition, the animals were segregated into two groups based on the locomotion score (LS), where LS 1 is attributed to animals without claudication, LS 2 to those with suspected lameness and LS 3, 4 and 5 to those with mild, moderate and severe lameness, respectively; in the lame cows group (LC) (n=15), the animals displayed LS ≥ 3, whereas in the non-lame cows group (NLC) (n=12) they showed LS 1. Milk production, body condition score (BCS) and blood concentration levels of β-hydroxybutyrate (BHB), urea, phosphorus, calcium aspartate aminotransferase (AST), gamma glutamyl transferase (GGT) and total plasma proteins (PPT) were evaluated. Milk production (17.675 ± 0.31 L of milk/day) and blood calcium concentration (7.42 ± 0.12 mg/dL) were lower in the lame cows in comparison to those without lameness (22.27 ± 0.42 L of milk/day and 9.63 ± 0.13 mg/dL). Besides, the lame cows showed higher BCS loss during the early postpartum period. The metabolites AST, GGT, PPT, urea, BHB and phosphorus revealed no difference between the groups during the period evaluated. The lameness evident in cows during prepartum exerted major negative effects on the milk production and calcemia, making the LS evaluation during these period an important tool in the early diagnosis of losses for future lactation.

RESUMO: O objetivo deste estudo foi verificar as consequências da claudicação no período pré-parto no início da lactação subsequente de vacas da raça Holandês. Vinte e sete vacas multíparas foram monitoradas do dia -30 até o dia 63 em relação ao parto. Trinta dias antes do parto os animais foram divididos em dois grupos de acordo com classificação de escore de locomoção (EL) em que EL é atribuído ao animal sem claudicação, EL 2 suspeito de claudicar e EL 3, 4 e 5 representam claudicação leve, moderada e severa, respectivamente. No grupo de vacas claudicantes (n=15) os animais apresentavam EL ≥3 e no grupo controle (n=12) apresentavam EL de 1. Foi mensurada a produção de leite, escore de condição corporal (ECC) e as concentrações sanguíneas de β-hidroxibutirato (BHB), ureia, fósforo, cálcio, aspartato aminotransferase (AST), gama glutamil transferase (GGT) e proteínas plastmáticas totais (PPT). A produção média de leite das vacas claudicantes (17,675 ± 0,31 L/dia) e concentração de cálcio sanguíneo (7,42 ± 0,12 mg/dL) foram menores quando comparadas com as não-claudicantes (22,27 ± 0,42 L/dia e 9,63 17,675 ± 0,13 mg/dL). Além disso, vacas claudicantes perderam mais ECC no pós-parto recente. Os metabólitos AST, GGT, PPT, ureia, BHB e fósforo não diferiram entre grupos durante o período avaliado. A claudicação evidente em vacas no pré-parto apresenta grandes reflexos negativos na produção de leite e calcemia desses animais, tornando o EL pré-parto uma ferramenta importante no diagnóstico precoce de prejuízos na futura lactação.

Clinical, hematological and histopathological aspects of experimental induction of laminitis in cattle through lipopolysaccharide infusion / Aspectos clínicos, hematológicos e histopatológicos da indução experimental por lipopolissacarídeos de laminite em bovinos

ABSTRACT: The purpose of this research was to confirm the changes occurring in the foot system of the heifers challenged with lipopolysaccharides (LPS), at the clinical, serum and histological levels. We studied 16 clinically healthy heifers, 14 months of age, placed in a confinement system. All the animals were provided with an accelerometer collar to establish their activity. They were categorized into two groups: the LPS group (n=8), or those which were administered two intravenous applications of 2 mL containing 0.5 μg/kg of body weight of LPS, with a 24-hour interval and the Control group (n=8) which were given two infusions of 2 mL of saline solution in the same time interval. General clinical examination and blood collection were done at 0, 4 and 8 hours post the LPS challenges and analyses of the hemograms and paroxonese-1 were performed. The animals were then slaughtered on day 4 and the laminar tissue was collected for histological analysis. The LPS group revealed a lower total leukocyte count with heart rate and greater activity. None of the animals revealed any abnormal signs symptomatic of foot pathology after histological analysis. Hence, the challenge with LPS failed to induce any clinical and histological changes in the foot tissue compatible with laminitis.

RESUMO: O objetivo deste trabalho foi verificar alterações do sistema podal á nível clínico, hematológico e histológico de animais desafiados com lipopolissacarídeo (LPS). Foram utilizadas 16 novilhas de corte com 14 meses de idade, clinicamente saudáveis, em sistema de confinamento. Todos os animais continham uma coleira com acelerômetro para verificar atividade, sendo divididos em 2 grupos: LPS (n= 8), que recebeu duas aplicações de 2 mL contendo 0,5 μg/kg de peso corporal de LPS via intravenosa, com intervalo de 24 horas e Controle (n= 8) que recebeu duas aplicações de 2 mL de solução salina com o mesmo intervalo de tempo. Foram realizados exame clinico geral e coletas de sangue às 0, 4 e 8 horas após os desafios com LPS para análise de hemogramas e paroxonase-1. Os animais foram abatidos aos 5 dias sendo executada a coleta de tecido laminar para análise histológica. A análise estatística foi executada com a utilização do programa NCSS(2004) através de ANOVA-medidas repetidas, considerando o efeito do tratamento do período e sua interação (tratamento*horas), sendo considerados significativos valores de P<0,05. O grupo LPS apresentou superior contagem total de leucócitos com maior frequência cardíaca e atividade. Nenhum animal apresentou sinal de anormalidade compatível com laminite através da análise histológica. Entretanto, o desafio com LPS foi capaz de gerar alterações a nível clínico, constatado pelas alterações nos parâmetros de frequência cardíaca, respiratória e temperatura corporal, além de mudanças no leucograma.

Impact of high-energy diets on the rumen environment and digital cushion in confined cattle / O impacto de dietas de alto valor energético sobre o ambiente ruminal e o tecido digital em bovinos confinados

This study aimed to identify gross and microscopic changes, caused by high-energy diets, in the rumen environment and hoof of confined beef cattle. The study sample comprised 40 confined heifers (Bos taurus) with no disease history divided into four experimental groups using different diets: Group 1 (D1, control), 48:52 forage:concentrate ratio; Group 2 (D2), 30:70 forage:concentrate ratio; Group 3 (D3), 30:70 forage:concentrate ratio + sucrose; Group 4 (D4), 100% concentrate. All animals underwent clinical examination, assessment of ruminal fluid pH and lameness, and sample collection after slaughter for histopathology of the hoof laminae and digital cushion and ruminal tissue. All dependent variables of the study were compared using the SPSS 20.0 statistical software. The variables that did not show normality (HR, RM, ST, and CRT) were compared with application of the Kruskal-Wallis test followed by the Dunnet's multiple comparison test. All other variables were submitted to analysis of variance (ANOVA) followed by Tukey's test. The different diets had an impact on the rumen environment (p<0.05) of the heifers assessed, with momentary general depression in the first 12 h after sucrose induction (D3), as well as mild clinical signs in D4. The animals in D3 and D4 presented lower motility (p<0.05) and ruminal pH (p<0.01) than those in D1. Of the 40 heifers, 27.5% (n=11) showed gross lesions in the epithelium of ruminal pillars, whereas 22.5% (n=9) of those in D3 and D4 presented these lesions. Sole corium thickness varied between heifers in D3 compared with those in D1 and D2 (p<0.05). Therefore, high-energy diets, as used in this study, alter some clinical parameters and the rumen environment, causing lesions in the rumen mucosa, and of lesser intensity, in the hoof corium and laminae, suggestive of laminitis.(AU)

O objetivo deste trabalho foi identificar alterações macroscópicas e microscópicas provocadas por dietas de alto valor energético no ambiente ruminal e casco de bovinos de corte (Bos taurus) em confinamento. Foram utilizadas 40 novilhas mantidas em confinamento, sendo divididas em 4 grupos experimentais: Grupo D1(controle) - 48% de volumoso e 52% de concentrado; Grupo D2 - 30% de volumoso e 70% de concentrado; Grupo D3 - 30% de volumoso e 70% de concentrado + sacarose; Grupo D4 - 100% de concentrado. Foi realizado exame clínico dos animais, avaliação do pH ruminal, da claudicação, além de coletas de amostras post-mortem para análises histopatológicas da região laminar do casco, coxim digital e do rúmen. Todas as variáveis dependentes do estudo foram comparadas por meio do software estatístico SPSS 20.0. As variáveis sem normalidade (FC, MR, Tc e TPC) foram comparadas pelo teste de Kruskal Wallis, seguido pelo teste de comparação múltipla de Dunnet. Todas demais foram submetidas a análise de variância (ANOVA), seguida pelo teste de Tukey. Foi observado impacto das distintas dietas ao ambiente ruminal (p<0,05). Os grupos D3 e D4 exibiram menor motilidade (p<0,05) e pH ruminal (p<0,01). 27,5% (n=11) dos animais tiveram registros macroscópicos de lesões no epitélio dos pilares ruminais enquanto que os submetidos às dietas 3 e 4 foi observada ocorrência de 22,5% (n=9) de lesões macroscópicas no rúmen. As espessuras do córium solear variaram entre os grupos que receberam a indução de sacarose em relação ao grupo controle e novilhas alimentadas com a dieta 2 (p<0,05). Sendo assim dietas com elevada densidade energética, na condição em que foi empregada, alteraram alguns parâmetros clínicos e o ambiente ruminal, provocando lesões na mucosa do rúmen e de pouca intensidade no córium e tecido laminar, sugestiva de laminite.(AU)

Cancer-Related Pain: A Longitudinal Study of Time to Stable Pain Control and Its Clinicodemographic Predictors.

CONTEXT: Multidimensional assessment is pivotal in managing cancer-related pain. OBJECTIVES: The objectives of this study were to determine time to stable pain control (SPC) and identify its baseline clinicodemographic predictors in patients with cancer pain. METHODS: This is a prospective longitudinal study of patients attending a cancer pain clinic. Scheduled clinic attendances and weekly investigator-led phone calls enabled monitoring of patients' daily pain diary, opioid use, and other analgesic interventions. Baseline clinicodemographic variables were examined in survival analyses, which included the construction of accelerated failure time models with time ratios [TRs, (95% CIs)], based on time to SPC (pain intensity ≤3 and <3 breakthrough opioid doses over three consecutive days) for variable categories. RESULTS: Of 319 participants, 22 died before achieving SPC and were censored in the survival analysis. The median survival time (95% CI) to SPC was 22 (19-25) days. In multivariable analysis, compared to their respective reference categories, female sex (P = 0.001), substance abuse (P < 0.001), a neuropathic pain component (P < 0.001), and use of ≥1 adjuvant analgesic (P = 0.022) each had TRs > 1 (1.03-2.54), whereas soft tissue pain (P < 0.001) had a TR = 0.71 (0.62-0.82), reflecting longer and shorter time to SPC, respectively. CONCLUSION: SPC is achievable for most patients with cancer pain. Recognition of strong predictors of time to SPC, such as substance abuse, a neuropathic pain component, soft tissue pain, and current use of adjuvant analgesia, may help to triage care services based on therapeutic need and guide analgesic interventions.