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Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells has shown promising results in early-phase clinical studies. However, advancing CAR-NK cell therapeutic efficacy is imperative. In this study, we investigated the impact of a fourth-generation CD19-targeted CAR (CAR.19) coexpressing IL-27 on NK-92 cells. We observed a significant improvement in NK-92 cell proliferation and cytotoxicity activity against B-cell cancer cell lines, both in vitro and in a xenograft mouse B-cell lymphoma model. Our systematic transcriptome analysis of the activated NK-92 CAR variants further supports the potential of IL-27 in fourth-generation CARs to overcome limitations of NK cell-based targeted tumor therapies by providing essential growth and activation signals. Integrating IL-27 into CAR-NK cells emerges as a promising strategy to enhance their therapeutic potential and elicit robust responses against cancer cells. These findings contribute substantially to the mounting evidence supporting the potential of fourth-generation CAR engineering in advancing NK cell-based immunotherapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Leprosy is an infectious disease characterized by slow and chronic evolution, caused by Mycobacterium leprae and or Mycobacterium lepromatosis, an intracellular alcohol-acid-resistant (BAAR) bacillus. The objective of this study was to provide an epidemiological, clinical, and geographic characterization of leprosy in the city of Santarém-Pará during the period 2011–2020. A cross-sectional, descriptive, and quantitative approach was used, employing maps and tables to illustrate clinical and epidemiological variables, including: sex, age, race, area of residence, operational classification, clinical form, number of skin lesions, number of affected nerves, and health units. During the analyzed period, 581 cases of leprosy were diagnosed, resulting in the following cumulative incidence rates: male (60%); age over 15 years (94%); urban area (73%); multibacillary (74%); borderline form (46%); skin lesions greater than 5 (34%); and no nerves affected (68%). In the urban perimeter, a higher cumulative incidence of cases was observed in the central area with 133 cases. However, the health unit reporting the largest number of cases belonged to the southern area, specifically the Basic Health Unit of Nova República, with 48 cases. This study highlights the need to characterize the nuances of leprosy and its variability within the urban environment, according to different areas. Further research is essential to inform the implementation of public policies aimed at addressing the population with the highest vulnerability index, thereby reducing leprosy rates in Santarém. Author summary: This article addresses the incidence of leprosy in Santarém, Brazil, during the COVID-19 pandemic. In 2020, there was a 41% reduction in cases compared to the average between 2015 and 2019, possibly due to the cancellation and rescheduling of appointments, affecting diagnoses and follow-up. Men constituted 60% of the cases, with their hesitation to seek care associated with late diagnoses. Alarmingly, 6% of patients were under 14 years old, indicating possible intrafamilial transmission. Socioeconomic and ethnic inequalities were evident, with 74% of cases in individuals of mixed race. The article emphasizes the importance of addressing leprosy not only as a public health challenge but also as a reflection of social and economic inequalities in Brazil. It proposes comprehensive health policies, expansion of medical services in remote regions, and educational initiatives for awareness and early diagnosis, especially in vulnerable communities. The association between age and clinical form of the disease, as well as spatial distribution analyses, provides crucial insights for developing targeted prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Por meio da formalização lacaniana da teoria dos discursos e do discurso do capitalista, objetivamos localizar os modos de operação presentes na racionalidade neoliberal. Partimos da introdução de uma nova modalidade de laço social, que parece travar as possibilidades de funcionamento do quarto de giro e opera sob o psiquismo aos moldes de uma produção ilimitada, reduzindo o desejo à dimensão da demanda. Esse movimento realiza uma manobra de captura da subjetividade por meio do supereu e passa a se orientar por horizontes forjados pelo neoliberalismo. A empreitada do discurso do capitalista se assemelha a um "crime perfeito", a qual tem como meta o apagamento de qualquer rastro que sirva como uma orientação desejante. Apostamos na inscrição do desejo por meio do ato de escuta como estratégia de localização de representações possíveis. Assim evita-se a consumação de um crime perfeito e trata-se de uma operação com um resto inassimilável pela economia de mercado. É na medida em que esse resto pode ser acolhido por meio de uma escuta que se inscreve a possibilidade de produção não apenas de uma coordenada pautada no desejo bem como de uma estratégia política frente ao ilimitado dos mercados contemporâneos.

Simple Summary: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the presence of BCR::ABL1 fusion in p190 isoform is a marker for worse prognosis, associated with treatment resistance and reduced overall survival. We aim to determine the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL using a small molecule inhibitor, AZD2461, and we hope that our findings may help improve molecular stratification and prognosis of ALL patients. Detection of t(9;22), and consequent BCR::ABL1 fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets. Overall, we demonstrate the effectiveness of PARPi in the treatment of BCR::ABL1 p190+ ALL cell models and that PARP1 is differentially expressed in patient samples. We hope our findings help expand the characterization of molecular profiles in ALL settings and guide future investigations into novel biomarker detection and pharmacological choices in clinical practice. [ABSTRACT FROM AUTHOR]

Background : Cardiorespiratory depression caused by anesthesia decreases the quality and increases the time of postoperative recovery. The acupoint Governor Vessel 26 (GV26) is a resuscitation point that can reverse this depression and can be safely used without side effects. Objectives: The objective of this study was to evaluate the stimulation and anesthetic recovery time of GV26 in bitches submitted to ovariohysterectomy (OH) under dissociative anesthesia. Methods : As pre-anesthetic protocol, acepromazine 0.2% (0.1 mg/kg) and tramadol hydrochloride (2 mg/kg) was used, and induction was performed using midazolam (0.5 mg/kg) and ketamine (10 mg/kg). For the control group, standard procedure was performed for OH, with anesthetic recovery and post-surgical procedures. For the acupuncture group (AP), the stimulation of acupoint GV26 was performed 20 minutes after the anesthetic induction and maintained for 5 minutes. Respiratory rate, amplitude (superficial, normal or deep), type of respiratory movement (abdominal, abdominocostal or thoracoabdominal), heart rate, capillary filling time, temperature, presence or absence of laryngotracheal reflex, presence or absence of interdigital reflexes were assessed immediately before PAM application, and 2 (T1), 5 (T2), 10 (T3), 15 (T4), 20 (T5), 25 (T6) and 30 (T7) minutes after treatment. The results were tabulated and statistically analyzed. Results : When comparing the AP group with the control group, an improvement in amplitude of the chest cage was observed at all times, where the animals remained in normal or deep respiratory amplitude. The heart rate was significantly higher for the AP group (155.5 ± 34.4 bpm) than the control group at T1 (105.1 ± 15.4 bpm), while recovery time was lower for the AP group (54.1 ± 14.9 min) when compared to control group (79.9 ± 17.9 min). Conclusion : The present paper demonstrated the efficacy of GV26 in maintaining adequate respiratory amplitude and decreasing the anesthetic recovery time.

O presente texto faz parte de uma pesquisa de dissertação de mestrado realizada no ano de 2019 e defendida no ano de 2021, no Programa de Pós-Graduação em Geografia (PPGG/UFGD). A pesquisa teve como um dos objetivos, compreender como é o dia a dia de ensino em sala de aula de professores de geografia que possuem alunos com Deficiência Intelectual em suas turmas. A pertinência deste trabalho se dá pelo fato de o direito à educação para o aluno com DI nas escolas regulares ter se iniciado a partir da Política Nacional de Educação Especial/2008 e Lei Brasileira de Inclusão/2015, que juntas trouxeram visibilidade e dignidade para aqueles que anteriormente viviam segregados em instituições filantrópicas ou classes especiais. Dessa maneira, destacamos nesse artigo aspectos sobre o ensino de geografia e a opinião de professores das escolas municipais de Dourados-MS que relatam suas experiências acerca da inclusão dos estudantes que têm Deficiência Intelectual e das práticas que desenvolvem nos processos de ensino-aprendizagem envolvendo os estudantes com DI e demais alunos sem deficiência.

The suppression of natural spaces due to urban sprawl and increases in built and agricultural environments has affected water resource quality, especially in areas with high population densities. Considering the advances in the Brazilian environmental legal framework, the present study aimed to verify whether land use has still affected water quality through a case study of a peri-urban watershed in a Brazilian metropolitan region. Analyses of physical–chemical indicators, collected at several sample points with various land-use parameters at different seasons of the year, were carried out based on an approach combining variance analysis and genetic programming. As a result, some statistically significant spatiotemporal effects on water quality associated with the land use, such as urban areas and thermotolerant coliform (R = −0.82, p < 0.01), mixed vegetation and dissolved oxygen (R = 0.80, p < 0.001), agriculture/pasture and biochemical oxygen demand (R = 0.40, p < 0.001), and sugarcane and turbidity (R = 0.65, p < 0.001), were verified. In turn, gene expression programming allowed for the computing of the importance of land-use typologies based on their capability to explain the variances of the water quality parameter. In conclusion, in spite of the advances in the Brazilian law, land use has still significantly affected water quality. Public policies and decisions are required to ensure effective compliance with legal guidelines.

Este trabalho objetivou investigar em que medida práticas de professores da Educação Infantil influenciam no desenvolvimento emocional e afetivo das crianças, na percepção de professoras de escolas autointituladas inovadoras. Foram feitas cinco entrevistas semiestruturadas com professoras de Educação Infantil. Após a análise de conteúdo, chegou-se às seguintes categorias temáticas: concepções de desenvolvimento emocional e afetivo na perspectiva das professoras; promovendo o desenvolvimento emocional e afetivo saudável no ambiente escolar; influência do docente na relação professor-aluno. Espera-se, com este estudo, fomentar reflexões sobre as práticas docentes, de modo que elas colaborem para o desenvolvimento emocional e afetivo de crianças, de maneira intencional

This study aimed to identify the possible advantages of administering butorphanol (BUT), associated with ketamine/xylazine (KX) sedation or not, for semen collection using electroejaculation (EE) in rams. Fifteen rams received four treatments in a cross-over design using a 2 × 2 factorial arrangement. The treatments were 1) control; 2) received KX; 3) received BUT; and 4) received both treatments. The responses to the procedures regarding heart rate, respiratory frequency, and rectal temperature were recorded, glucose and creatine kinase were measured, and semen quality was determined. More pulses were required when BUT was administered (P = 0.0067), but rams vocalized fewer times (P = 0.046). The administration of KX also tended to reduce the respiratory frequency (P = 0.068) and rectal temperature (P = 0.089), with no other effects. The administration of BUT reduced the heart rate (P < 0.0001), and there was an interactive effect between the administration of BUT and time on the heart rate (P < 0.0001), respiratory frequency (P = 0.01), and rectal temperature (P = 0.047). The administration of BUT reduced the heart rate increase immediately after EE (P < 0.0001). The respiratory frequency following EE was greater when BUT was administered (P < 0.0001), but the administration of BUT reduced the rectal temperature at the same time (P = 0.002). Glucose concentration was greater when BUT was administered (P < 0.0001). The only significant effect on the ejaculate characteristics was from the interaction between KX and BUT on sperm concentration (P = 0.004). The administration of KX alone increased sperm concentration (P = 0.035), but when BUT was added to KX, sperm concentration decreased (P = 0.002). Moreover, sperm concentration was greater when only BUT was administered than when KX and BUT were administered simultaneously (P = 0.037). The addition of BUT markedly decreased most negative responses more effectively than sedation with KX alone. In conclusion, BUT appears to be an interesting alternative to reduce the welfare concerns raised by the use of EE in rams; however, its possible effects on the ejaculate characteristics when associated with other anesthesia/sedation drugs require further study. • Semen collection took longer after administering butorphanol, but rams vocalized less times. • Administration of butorphanol reduced the heart rate. • Administration of butorphanol reduced temporarily the rectal temperature. • The administration of ketamine/xylazine alone increased sperm concentration, but association of butorphanol decreased it. [ABSTRACT FROM AUTHOR]

The use of mammalian hair as a nest-building material by Amazonian birds is poorly documented. Here, we describe the use of the hair of a domestic dog as nest-building material by the Spotted Tody-Flycatcher, Todirostrum maculatum. The nesting pair collected the dog hair from the ground to construct their nest. The use of this material appeared to be highly opportunistic.

Existe pouco consenso sobre o que constitui um bom reconto de uma história e como avaliar essa importante habilidade linguística. Este estudo revisou artigos publicados entre 2010 e 2018 que avaliaram narrativas orais de histórias por crianças, a fim de mapear e sistematizar as medidas qualitativas e quantitativas empregadas. Inicialmente os estudos analisados foram classificados de acordo com o uso de uma de quatro metodologias amplas: avaliações padronizadas, gramática narrativa, unidades-C e protocolos de pontuação de narrativa. No entanto, um exame mais detalhado mostrou que essa classificação geral obscureceu o fato de que as medidas específicas podiam não ser equivalentes entre estudos. Para melhorar esse esquema conceitual, as medidas específicas foram organizadas em novas categorias, baseadas em dimensões diferentes do desempenho da narrativa oral de histórias, como fluência, coesão e inclusão de elementos psicológicos. A aplicação desse novo esquema classificatório aos estudos publicados entre 2010 e 2018 revelou que as medidas específicas da qualidade narrativa variam ampla e ortogonalmente aos métodos mais gerais empregados, o que explica parte da confusão conceitual e metodológica presente na literatura sobre avaliação de habilidades narrativas orais. Espera-se que esse novo esquema de classificação possa ajudar a dissipar parte dessa confusão e melhorar a comparabilidade e a replicabilidade dos estudos.

Background: The objective was to compare the use of micronized vaginal progesterone 800 mg daily and oral dydrogesterone 40 mg daily in the endometrial preparation for frozen-thawed embryo transfer (FET). Methods: Prospective randomized study with women undergoing FET along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally received 40 mg/day dydrogesterone (DYD group, n = 36) or 800 mg/day micronized vaginal progesterone (MVP group, n = 37) after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation. Biochemical pregnancy, clinical pregnancy and live birth rates were the secondary outcome. Results: The reproductive outcomes in FET cycles were similar, with pregnancy and Live birth rates in the didrogesterone and MVP treatment groups being respectively: Biochemistry (38.9%/37.8%; p = 0.189 [95% confidence interval (CI) = –23.4–21.2]), Clinical (33.3%/35.1%; p = 0.192 [95% CI = –20.0–23.6]); 12 Weeks Pregnancy (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]); Live birth (33.3%/32.4%; p = 0.196 [95% CI = –22.4–20.6]). Conclusions: 40 mg/day dydrogesterone and 800 mg/day MVP revealed similar reproductive results in FET cycles. The use of oral dydrogesterone is a reasonable option, may be more accepted by patients in terms of ease of use and lower cost. Clinical Trial Registration: U1111-1247-1845.

Micromachining allows the production of parts and components on a micro scale with high precision and has become a key process to meet the growing demand for micro parts and micro components. To meet the quality requirements of the generated surfaces and reduce the cutting forces, strategies have been analysed, such as the use of the cutting fluid. Therefore, this research aimed to verify the effect of the frequency of the use of cutting fluid during the micro-milling of the Inconel 718 alloy. For this purpose, an ultra-refined cemented carbide micro end mill coated with (Al, Ti) N and 400 µm in diameter was used. A spindle speed of 20,000 rpm, a cutting speed of 13.8 m/min, a feed per tooth of 5 µm/tooth and an axial depth of cut of 40 µm were used as cutting parameters. Two frequencies of application of the cutting fluid were evaluated, corresponding to the flow rate of 40.7 and 270.0 ml/ h, in addition to the dry test. To measure the cutting forces, a Kistler dynamometer with operating range of -5 kN to +10 kN was used. In addition, the process simulation was performed using the AdvantEdge software by ThirdWave Systems. The results showed that the higher flow of the cutting fluid provided lower cutting forces and that, in dry machining, the cutting force increased significantly during the machining of a slot.

The objective of this study was to evaluate the partial replacement effect on body measurements (body mass, muscle thickness, and fat thickness) of the concentrated fraction of foals’ diet with a protein supplement containing whey protein, glutamine, and lysine during the post-weaning period. Eighteen Mangalarga Marchador foals were randomly divided into two groups in the post-weaning phase, with nine animals each in the control group (CG) and the group receiving protein supplementation (WG). Based on 4% of their body weight (BW), the CG animals received a diet with roughage to concentrate in a ratio of 50:50, which composed of Cynodon sp. hay and a 15% crude protein (CP) commercial horse ration. The WG diet consisted of the same amount of hay used for the CG diet, half the amount of concentrate used in the CG diet, and 102 g of a protein supplement containing whey protein, glutamine, and lysine. During the experiment, five evaluations were performed, starting on the day of weaning (day 0), followed by evaluations conducted at 7, 14, 28, and 42 days after weaning. Body measurements, body mass, and thickness of the fat and muscle layers were assessed at each time point. The substitution of a portion of the commercial diet with protein supplement containing whey protein, glutamine, and lysine did not cause changes in the weight gain or linear measurements of Mangalarga Marchador foals during the post-weaning period; however, the change in diet increased muscle thickness and decreased fat thickness when compared to animals in the control group.

Resumen El análisis conceptual es un eje metodológico de la investigación científica. Aunque un concepto a menudo sufre cambios como parte de una teoría, el análisis de su operación lógica original es condición previa para comprender estos cambios y evaluar su utilidad. Se analizó el funcionamiento lógico del concepto de comprensión, con fundamento en técnicas de la Filosofía del Lenguaje Ordinario. Son características lógicas importantes del concepto: (1) comprender es un verbo de logro (2) puede haber diferentes grados de logro (3) es un concepto polimórfico y (4) es un concepto disposicional. Son discutidas implicaciones metodológicas y teóricas de este análisis, ejemplificadas con una propuesta para el análisis de la comprensión de textos narrativos.

O mercado cada vez mais competitivo exige desafios para o aumento da produtividade das empresas, que necessitam de equipamentos com alta disponibilidade e confiabilidade. Isso torna fundamental a implantação do gerenciamento estratégico da manutenção. Os objetivos desse trabalho consistem em analisar a manutenção executada em um moinho de bolas de uma metalúrgica, por meio de indicadores de manutenção: MTBF, MTTR, Disponibilidade, Confiabilidade e Mantenabilidade; identificar, na curva da banheira, o ciclo de vida do moinho, e verificar se a estratégia de manutenção utilizada é a mais indicada. O método de pesquisa utilizado consistiu no estudo de caso. Para a realização das análises, foram colhidos os tempos entre falhas e para reparo do moinho, nos sistemas de informação da empresa, e avaliados por meio do software ProConf 2000. Os resultados mostraram que a implantação da manutenção preditiva não aumentou a disponibilidade operacional. Na curva da banheira tem-se que o ciclo de vida do moinho consiste no envelhecimento, indicando a utilização da manutenção preventiva.

A qualidade de um curso hídrico está diretamente relacionada às alterações verificadas na bacia hidrográfica. O uso e ocupação do solo exercem fundamental influência no escoamento superficial para estes cursos, podendo alterar sua qualidade e quantidade. O distrito de Barão Geraldo (Campinas/SP) faz parte parcialmente da bacia do Ribeirão das Pedras, que nasce entre o Alto Taquaral e o Jardim Primavera, e que, após passar pela sede do distrito, desemboca na margem esquerda do rio Anhumas. Este, por sua vez, desemboca na margem esquerda do rio Atibaia, importante rio do estado de São Paulo. Este trabalho visou avaliar os impactos ambientais nas nascentes da bacia do Ribeirão das Pedras, a fim de se verificar a qualidade das mesmas por meio da Matriz de Leopold e Índice de Qualidade de Águas (IQA). Por meio de imagens de satélite, carta topográfica e visitas a campo localizaram-se treze nascentes distribuidas ao longo da bacia, sendo aplicado o IQA em seis nascentes principais. A análise do IQA permitiu a classificação de 5 das 6 nascentes como “BOA”, ainda que as mesmas apresentassem irregularidades para alguns parâmetros. Verificou-se pela matriz, que o parâmetro mais impactante nas nascentes era o não cumprimento do raio de mata ciliar, indicando que as medidas a serem tomadas preferencialmente neste momento dizem respeito à sua recuperação.

Objetivo: Avaliar o estado nutricional de pacientes portadores de doenças cardiovasculares internados em um hospital. Método: Trata-se de um estudo analítico, prospectivo, transversal, com abordagem quantitativa, realizado em uma instituição hospitalar na qual a amostra foi composta por 54 pacientes de uma cardiologia. Foi utilizado um formulário semiestruturado, uma balança antropométrica e uma fita métrica. Resultados: Em relação ao índice de massa corpórea, prevaleceu a eutrofia e a pré-obesidade (40,7%). Observa-se ausência de risco cardiometabólico. Quanto aos hábitos de vida, 33,3% têm ou já tiveram hábitos tabagistas, 53,7% têm hábitos etilistas e 83,3% não praticam atividade física. A hipertensão arterial foi encontrada em 51,8% da população. O diagnóstico prevalente foi a insuficiência cardíaca (29,7%). Os exames laboratoriais não tiveram alterações significativas. Conclusão: O perfil nutricional de pacientes com doenças cardiovasculares não se caracteriza por alterações antropométricas e laboratoriais, mas sim pelo histórico clínico e hábitos de vida dos pacientes.

Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJETIVO: Identificar os fatores obstétricos e perinatais associados à morbimortalidade perinatal em gestações que cursaram com amniorrexe prematura.MÉTODOS: Estudo transversal de base hospitalar, com dados secundários de prontuários de pacientes (n=87) que evoluíram com quadro de amniorrexe prematura com idade gestacional entre 24 e 42 semanas, definida pela ultrassonografia, e internadas no período de janeiro a abril de 2013 em uma maternidade pública no estado do Acre, região Norte do Brasil. Os dados foram submetidos à análise bivariada para seleção de variáveis que compuseram o modelo múltiplo utilizando a técnica de regressão logística de Poisson. RESULTADOS: A prevalência de morbimortalidade perinatal foi de 51,4%. Nesse total estão computados 2,3% de óbitos fetais (2 casos) e 9,2% de óbitos neonatais (8 casos). As variáveis que apresentaram associação no modelo múltiplo final com morbimortalidade foram: número de consultas de pré-natal ≥6, com razão de prevalência (RP) 0,5 e intervalo de confiança de 95% (IC95%) 0,3-0,9, idade gestacional ≥30 semanas (RP=0,6; IC95% 0,4-0,8), baixo peso ao nascer (RP=2,9; IC95% 1,5-5,4) e necessidade de ventilação mecânica (RP=3,8; IC95% 2,0-7,2).CONCLUSÃO: Observou-se elevada morbimortalidade perinatal entre casos que cursaram com amniorrexe prematura. A morbimortalidade esteve associada a fatores como menor número de consultas de pré-natal, extrema prematuridade e o baixo peso.

This study aimed to compare the effect of the administration of either medroxyprogesterone acetate (MPA) or progesterone (P4) in superovulation (SOV) treatments applied during the first follicular wave on follicular development, embryo yield, and the expression of genes related to pluripotency maintenance, differentiation of the trophectoderm, cell growth and differentiation, apoptosis and energy metabolism in sheep embryos. The estrous cycle of 36 multiparous ewes was synchronized with a short protocol, and the animals were randomly allocated to three groups. At the beginning of SOV, 12 ewes per treatment received an intravaginal sponge impregnated with 60 mg of MPA (TMPA), or an intravaginal device containing 0.33 g of P4 (TP4), or received no progestogen treatment (CON). The device was kept until the fifth dose of FSH. Ewes were mated with five fertile rams. Gene expression was performed by RT-qPCR using grade I and II blastocysts. The numbers of corpora lutea, total structures and viable embryos recovered per ewe were similar (P > 0.05) among groups. However, the viability rate was higher in TP4 (71.9 ± 16.3%) compared to CON (24.4 ± 16.8%; P = 0.01) and similar to TMPA (49.9 ± 16.3%; P = 0.2). Similarly, when compared with CON, treatment with P4 or MPA positively regulated the TGFB1 transcript involved in cell proliferation and differentiation (P = 0.01 and P = 0.03, respectively). In conclusion, supplementation with P4 during the first follicular wave of the estrous cycle improves embryo viability and alters the expression of the TGFB1 gene. • Progestogens during superovulation (SOV) did not influence follicular growth. • Exogenous progesterone during superovulation increased the viability rate embryos. • Progestogens during SOV increased the expression of TGFB1 gene in embryos. [ABSTRACT FROM AUTHOR]

Abstract Parasitic diseases reflect the health and balance of ecosystems, affecting not only individuals but also entire populations or communities. The aim of this study was to report on the diversity of parasitic helminths detected in the feces of a wild feline in southern Brazil. Parasites were obtained from fecal samples, and four techniques were used for parasitological examination: direct examination, centrifugal flotation with zinc sulfate (Faust technique), simple sedimentation (Hoffman technique) and Baermann-Moraes. The parasites were identified through micrometry and morphology, as follows: Ancylostoma sp., Toxocara sp., Trichuridae, Aelurostrongylus abstrusus, Alaria sp., and Spirometra sp. We recorded the genus Ancylostoma parasitizing L. colocolo for the first time.

ABSTRACT: Liquid pig manure (LPM) is widely used as a compost fertilizer for vegetable crops destined for human consumption. However, these wastes may contain parasites eggs, such as the nematode Ascaris suum, that pose serious health risks to humans. We attempted to determine the most appropriate technique for recovering A. suum eggs from LPM compost. Samples were collected from two waste sources during composting, including 23 samples containing LPM, sawdust, and wood shavings, and 14 samples of LPM alone-both in triplicate. Samples were analyzed using several different recovery methods. Recovery of eggs by the modified Bailenger method with adaptations was significantly more effective and recovered 57% more eggs than by the modified Bailenger method alone. Willis-Mollay method, modified Faust method, and the simple sedimentation technique only recovered 4.4%, 13.9%, and 26% of eggs, respectively, compared with the modified Bailenger method with adaptations, indicating that the adjustments made to the Bailenger method were key to improving the recovery of A. suum eggs from compost and LPM.

Introduction: Ileal obstruction caused by thick meconium associated with functional immaturity (IOMFI) is an uncommon disease associated with prematurity. IOMFI is not well known, and late or wrong diagnosis is a problem. In this research, we review the clinical characteristics and therapeutic methods of IOMFI., Methods: Critical descriptive literature review., Results: Most patients eliminate meconium previously to IOMFI. More premature babies tend to become symptomatic in their second week of life, with progressive abdominal distension. The most frequent complication is perforation. Radiologically there is diffuse intestinal distention without air-fluid levels. In contrast enema a caliber transition zone is observed in the distal ileum with multiple filling defects in the ileum and colon. Neural ganglia are present in biopsies from the rectum, colon, and stoma, mostly with characteristics of immature ganglia. Most patients respond to treatment with water soluble contrast enemas. Surgery is needed for patients who do not respond to enemas and those presenting perforations., Discussion: IOMFI literature is limited to retrospective mainly small and heterogeneous cohorts. Patients usually respond promptly to water soluble enemas, but a favorable response is highly dependent in contrast reflux through the ileocecal valve and success is related to early treatment. Contrast inflow may be controlled by intermittent radiographies or real time ultrasound., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The impact of closed-loop control systems to titrate oxygen flow in critically ill patients, including their effectiveness, efficacy, workload and safety, remains unclear. This systematic review investigated the utilization of closed-loop oxygen systems for critically ill patients in comparison to manual oxygen titration systems focusing on these topics., Methods and Findings: A search was conducted across several databases including MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, LOVE, ClinicalTrials.gov, and the World Health Organization on March 3, 2022, with subsequent updates made on June 27, 2023. Evidence databases were searched for randomized clinical parallel or crossover studies investigating closed-loop oxygen control systems for critically ill patients. This systematic review and meta-analysis was performed following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. The analysis was conducted using Review Manager software, adopting the mean difference or standardized mean difference with a 95% confidence interval (95% CI) for continuous variables or risk ratio with 95% CI for dichotomous outcomes. The main outcome of interest was the percentage of time spent in the peripheral arterial oxygen saturation target. Secondary outcomes included time for supplemental oxygen weaning, length of stay, mortality, costs, adverse events, and workload of healthcare professional. A total of 37 records from 21 studies were included in this review with a total of 1,577 participants. Compared with manual oxygen titration, closed-loop oxygen control systems increased the percentage of time in the prescribed SpO2 target, mean difference (MD) 25.47; 95% CI 19.7, 30.0], with moderate certainty of evidence. Current evidence also shows that closed-loop oxygen control systems have the potential to reduce the percentage of time with hypoxemia (MD -0.98; 95% CI -1.68, -0.27) and healthcare workload (MD -4.94; 95% CI -7.28, -2.61) with low certainty of evidence., Conclusion: Closed-loop oxygen control systems increase the percentage of time in the preferred SpO2 targets and may reduce healthcare workload., Trial Registration: PROSPERO: CRD42022306033., Competing Interests: MJS was the team leader of Research and New Technologies at Hamilton Medical AG, Bonaduz, Switzerland, from January 2022 until January 2023. The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Mól et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Leishmaniasis encompasses a cluster of neglected tropical diseases triggered by kinetoplastid phatogens belonging to the genus Leishmania. Current therapeutic approaches are toxic, expensive, and require long-term treatment. Nanoparticles are emerging as a new alternative for the treatment of neglected tropical diseases. Silk Fibroin is a biocompatible and amphiphilic protein that can be used for formulating nanoemulsions, while kojic acid is a secondary metabolite with antileishmanial actions. Thus, this study evaluated the efficacy of a nanoemulsion, formulated with silk fibroin as the surfactant and containing kojic acid (NanoFKA), against promastigote and amastigote forms of Leishmania ( Leishmania ) amazonensis . The NanoFKA had an average particle size of 176 nm, Polydispersity Index (PDI) of 0.370, and a Zeta Potential of -32.3 mV. It presented inhibitory concentration (IC 50 ) values of >56 μg/mL and >7 μg/mL for the promastigote and amastigote forms, respectively. Ultrastructural analysis, cell cycle distribution and phosphatidylserine exposure showed that NanoFKA treatment induces apoptosis-like cell death and cell cycle arrest in L. ( L. ) amazonensis . In addition, NanoFKA exhibited no cytotoxicity against macrophages. Given these results, NanoFKA present leishmanicidal activity against L. ( L. ) amazonensis ., 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 © 2024 Queiroz-Souza, Galue-Parra, Silveira Moraes, Macedo, Rodrigues, H. S. Marinho, H. Holanda, M. Ferreira and Oliveira da Silva.)

(1) Background: Leishmaniasis refers to a group of anthropozoonotic diseases caused by Leishmania. The major chemotherapeutic agent used for its treatment is Glucantime ®® , but the search continues for new compounds that are economically viable and act on the protozoan without causing damage to the host cell. As an alternative approach, this study used a combination of copaiba oil (CO) and kojic acid (KA) to determine their in vitro action on host cells, on the Leishmania (Leishmania) amazonensis protozoan and its interaction with macrophages. (2) Methods: In vitro culture, analysis of cytokine release and microscopy assays were performed. Statistical analysis was performed with ANOVA (GraphPad Prism). (3) Results: The combination did not induce cytotoxic effects on macrophages after treatment but promoted morphological changes in the protozoan, such as nuclear alterations (apoptotic characteristics), alterations in the cellular body and an increase in the number of electrodense structures and acidocalcisomes, observed mainly at the concentrations of CO20KA50 and CO30KA50 μg/mL. We observed reductions in the intracellular amastigote number and in the production of proinflammatory cytokines, such as IL-6 and TNF-α, after treatment with CO30KA at 50 µg/mL. (4) Conclusions: We report here, for the first time, that the combination of CO and KA may be a promising approach against Leishmania (Leishmania) amazonensis .

Background: Cardiorespiratory depression caused by anesthesia decreases the quality and increases the time of postoperative recovery. The acupoint Governor Vessel 26 (GV26) is a resuscitation point that can reverse this depression and can be safely used without side effects., Objectives: The objective of this study was to evaluate the stimulation and anesthetic recovery time of GV26 in bitches submitted to ovariohysterectomy (OH) under dissociative anesthesia., Methods: As pre-anesthetic protocol, acepromazine 0.2% (0.1 mg/kg) and tramadol hydrochloride (2 mg/kg) was used, and induction was performed using midazolam (0.5 mg/kg) and ketamine (10 mg/kg). For the control group, standard procedure was performed for OH, with anesthetic recovery and post-surgical procedures. For the acupuncture group (AP), the stimulation of acupoint GV26 was performed 20 minutes after the anesthetic induction and maintained for 5 minutes. Respiratory rate, amplitude (superficial, normal or deep), type of respiratory movement (abdominal, abdominocostal or thoracoabdominal), heart rate, capillary filling time, temperature, presence or absence of laryngotracheal reflex, presence or absence of interdigital reflexes were assessed immediately before PAM application, and 2 (T1), 5 (T2), 10 (T3), 15 (T4), 20 (T5), 25 (T6) and 30 (T7) minutes after treatment. The results were tabulated and statistically analyzed., Results: When comparing the AP group with the control group, an improvement in amplitude of the chest cage was observed at all times, where the animals remained in normal or deep respiratory amplitude. The heart rate was significantly higher for the AP group (155.5 ± 34.4 bpm) than the control group at T1 (105.1 ± 15.4 bpm), while recovery time was lower for the AP group (54.1 ± 14.9 min) when compared to control group (79.9 ± 17.9 min)., Conclusion: The present paper demonstrated the efficacy of GV26 in maintaining adequate respiratory amplitude and decreasing the anesthetic recovery time.

Objective: This study aimed to evaluate the prevalence of ovarian hyperstimulation syndrome (OHSS) and associated risk factors in patients undergoing fertilization cycles at risk of OHSS (≥15 antral follicles or ≥15 oocytes aspirated) and submitted to cryopreservation of all embryos in the Human Reproduction Service of the Pérola Byington Hospital (Referral Center for Women's Health) in São Paulo, SP, Brazil., Methods: This cross-sectional, institutional, descriptive study of secondary data from patients' charts enrolled in the Assisted Reproduction Service of the Pérola Byington Hospital at risk of OHSS after controlled ovarian stimulation and submitted to cryopreservation of all embryos was conducted between January 2015 and September 2017., Results: OHSS occurred in 47.5% of cycles, all with mild severity, and there were no moderate or severe cases of OHSS., Conclusion: The cryopreservation of all embryos is associated with a reduction in moderate and severe forms of OHSS. Risk factors for OHSS should be evaluated prior to initiation of treatment, with less intense stimulation protocols accordingly.

Our current genetic engineering capacity through synthetic biology and genome editing is the foundation of a revolution in biomedical science: the use of genetically programmed cells as therapeutics. The prime example of this paradigm is the adoptive transfer of genetically engineered T cells to express tumor-specific receptors, such as chimeric antigen receptors (CARs) or engineered T-cell receptors (TCR). This approach has led to unprecedented complete remission rates in patients with otherwise incurable hematological malignancies. However, this approach is still largely ineffective against solid tumors, which comprise the vast majority of neoplasms. Also, limitations associated with the autologous nature of this therapy and shared markers between cancer cells and T cells further restrict the access to these therapies. Here, we described how cutting-edge genome editing approaches have been applied to unlock the full potential of these revolutionary therapies, thereby increasing therapeutic efficacy and patient accessibility., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Oxygen is the most common drug used in critical care patients to correct episodes of hypoxaemia. The adoption of new technologies in clinical practice, such as closed-loop systems for an automatic oxygen titration, may improve outcomes and reduce the healthcare professionals' workload at the bedside; however, certainty of the evidence regarding the safety and benefits still remains low. We aim to evaluate the effectiveness, efficacy and safety of the closed-loop oxygen control for patients with hypoxaemia during the hospitalisation period by conducting a systematic review and meta-analysis., Methods and Analysis: MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL and LOVE evidence databases will be searched. Randomised controlled trials and cross-over studies investigating the PICO (Population, Intervention, Comparator and Outcome) framework will be included. The primary outcomes will be the time in the peripheral oxygen saturation target. Secondary outcomes will include time for oxygen weaning time; length of stay; costs; adverse events; mortality; healthcare professionals' workload, and percentage of time with hypoxia and hyperoxia. Two reviewers will independently screen and extract data and perform quality assessment of included studies. The Cochrane risk of bias tool will be used to assess risk of bias. The RevMan V.5.4 software will be used for statistical analysis. Heterogeneity will be analysed using I 2 statistics. Mean difference or standardised mean difference with 95% CI and p value will be used to calculate treatment effect for outcome variables., Ethics and Dissemination: Ethical approval is not required because this systematic review and meta-analysis is based on previously published data. Final results will be published in peer-reviewed journals and presented at relevant conferences and events., Prospero Registration Number: CRD42022306033., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune checkpoint (IC) blockade using monoclonal antibodies is currently one of the most successful immunotherapeutic interventions to treat cancer. By reinvigorating antitumor exhausted T cells, this approach can lead to durable clinical responses. However, the majority of patients either do not respond or present a short-lived response to IC blockade, in part due to a scarcity of tumor-specific T cells within the tumor microenvironment. Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CARs) or engineered T-cell receptors (TCRs) provide the necessary tumor-specific immune cell population to target cancer cells. However, this therapy has been considerably ineffective against solid tumors in part due to IC-mediated immunosuppressive effects within the tumor microenvironment. These limitations could be overcome by associating adoptive cell transfer of genetically engineered T cells and IC blockade. In this comprehensive review, we highlight the strategies and outcomes of preclinical and clinical attempts to disrupt IC signaling in adoptive T-cell transfer against cancer. These strategies include combined administration of genetically engineered T cells and IC inhibitors, engineered T cells with intrinsic modifications to disrupt IC signaling, and the design of CARs against IC molecules. The current landscape indicates that the synergy of the fast-paced refinements of gene-editing technologies and synthetic biology and the increased comprehension of IC signaling will certainly translate into a novel and more effective immunotherapeutic approaches to treat patients with cancer., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.)

Objective: The aim of this study was to compare the use of micronized vaginal progesterone and oral dydrogesterone in the endometrial preparation for frozen-thawed embryo transfer., Methods: This was a randomized, controlled, open, two-armed clinical trial, with women undergoing frozen-thawed embryo transfer along with hormone replacement therapy for endometrial preparation, between September 2019 and February 2021. A total of 73 patients were randomly selected and orally administered 40 mg/day dydrogesterone (dydrogesterone group, n=36) or 800 mg/day micronized vaginal progesterone (micronized vaginal progesterone group, n=37), after endometrial preparation with transdermal estradiol. The main outcome was a viable ongoing pregnancy with 12 weeks of gestation as evaluated by ultrasound., Results: The reproductive outcomes in frozen-thawed embryo transfer cycles were similar, with pregnancy rates in the dydrogesterone and micronized vaginal progesterone treatment groups being, respectively, 33.3 and 32.4% at 12 weeks pregnancy (confidence interval= -22.4-20.6, p=0.196)., Conclusions: The use of oral dydrogesterone may be a more patient-friendly approach to endometrial preparation in frozen-thawed embryo transfer cycles, avoiding undesirable side effects and discomfort resulting from vaginal administration, while also providing similar reproductive results.

Background: To evaluate the impact of oral health on the quality of life (QOL) of individuals undergoing cancer treatment at the time of diagnosis of medication-related osteonecrosis of the jaw (MRONJ)., Material and Methods: The present cross-sectional study analyzed patients with MRONJ from 2013 to 2019. The collected data included demographic data, base disease, medications associated with MRONJ, route of administration and time of use, signs, symptoms, and tomographic features of acute MRONJ, staging according to American Association of Oral and maxillofacial Surgeons position paper 2014 (AAOMS), type of dental treatment performed, outcome, and the responses to the Oral Health Impact Profile questionnaire (OHIP-14). Statistical analysis was performed using the Tukey test to study the association between oral condition and the QOL. A p-value of less than 0.05 was considered statistically significant., Results: The sample consisted of 16 medical records of patients with MRONJ. Psychological discomfort showed alarmingly significant results ( p < 0.001) with strong negative impact on the QOL of the patients. Functional limitation was the least affected dimension ( p = 0.747). The other dimensions did not show statistically significant results., Conclusions: MRONJ compromises oral health and negatively impacts the QOL, especially with respect to the psychological discomfort (worry and stress). The OHIP-14 questionnaire proved to be an effective tool in the assessment of this impact. Key words: Medication-related osteonecrosis of the jaw, quality of life, oral health, OHIP-14., Competing Interests: Conflicts of interest No competing financial interests exist., (Copyright: © 2020 Medicina Oral S.L.)

Purpose: To identify obstetric and perinatal factors associated with perinatal morbidity and mortality in pregnancies that progressed with ruptured membranes., Methods: A cross-sectional hospital-based study with secondary data from records of patients (n=87) that evolved with the premature rupture of membranes between 24 and 42 weeks of gestation, admitted from January to April 2013 to a public hospital in Acre State, North of Brazil. Data were subjected to bivariate analysis for selection of variables to be used in a multiple regression model according to Poisson logistic regression with robust error., Results: The prevalence of perinatal morbidity-mortality was 51.4%, including a 2.3% death rate (2 cases) and a 9.2% fetal neonatal death rate (8 cases). The variables associated with mortality in the final multiple model were: number of prenatal consultations ≥6, with a prevalence ratio (PR) of 0.5 and a 95% confidence interval (95%CI) of 0.3-0.9, gestational age ≥30 weeks (PR=0.6; 95%CI 0.4-0.8), low birth weight (PR=2.9; 95%CI 1.5-5.4), and mechanical ventilation (PR=3.8; 95%CI 2.0-7.2)., Conclusion: Perinatal morbidity and mortality were high among cases of ruptured membranes. Morbidity and mortality were associated with factors such as fewer prenatal visits, extreme prematurity and low birth weight in this group.

Purpose: To describe the maternal and perinatal outcomes after the use of 12.5 µg of sublingual misoprostol for labor induction in women with term pregnancy and a live fetus., Methods: We conducted a multicenter, open and non-randomized clinical trial during the period from July to December 2009. We included 30 pregnant women with an indication for labor induction at term, carrying a live fetus, with a Bishop score of six or less, cephalic presentation, estimated fetal weight of less than 4,000 g and an amniotic fluid index greater than five. We excluded women with a previous uterine scar, non-reassuring fetal status, congenital anomalies, multiple pregnancy, intrauterine growth restriction, genital bleeding, and contraindications of vaginal delivery. A tablet of 12.5 µg sublingual misoprostol was administered every six hours, until the beginning of labor, with the maximum of eight doses., Results: Labor was successfully induced in 90% of pregnant women. The mean interval between the first dose and the onset of uterine contractions and delivery was 14.3±11.7 hours and 25.4±13 hours, respectively. The frequency of vaginal delivery was 60%. Uterine tachysystole occurred in two pregnant women, being reversed in both cases without the need for cesarean section. Meconium-stained amniotic fluid was observed in four patients, and an Apgar score of less than 7 at five minutes in only one newborn., Conclusion: Maternal and perinatal outcomes were favorable after induction of labor with sublingual misoprostol at a dose of 12.5 µg every six hours. However, controlled trials are needed to compare this regimen with other doses and routes of administration.