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In the southern Indian Ocean, the position of the subtropical front – the boundary between colder, fresher waters to the south and warmer, saltier waters to the north – has a strong influence on the upper ocean hydrodynamics and biogeochemistry. Here we analyse a sedimentary record from the Agulhas Plateau, located close to the modern position of the subtropical front and use alkenones and coccolith assemblages to reconstruct oceanographic conditions over the past 300,000 years. We identify a strong glacial-interglacial variability in sea surface temperature and productivity associated with subtropical front migration over the Agulhas Plateau, as well as shorter-term high frequency variability aligned with variations in high latitude insolation. Alkenone and coccolith abundances, in combination with diatom and organic carbon records indicate high glacial export productivity. We conclude that the biological pump was more efficient and strengthened during glacial periods, which could partly account for the reported reduction in atmospheric carbon dioxide concentrations.

The dominant feature of large-scale mass transfer in the modern ocean is the Atlantic meridional overturning circulation (AMOC). The geometry and vigour of this circulation influences global climate on various timescales. Palaeoceanographic evidence suggests that during glacial periods of the past 1.5 million years the AMOC had markedly different features from today 1 ; in the Atlantic basin, deep waters of Southern Ocean origin increased in volume while above them the core of the North Atlantic Deep Water (NADW) shoaled 2 . An absence of evidence on the origin of this phenomenon means that the sequence of events leading to global glacial conditions remains unclear. Here we present multi-proxy evidence showing that northward shifts in Antarctic iceberg melt in the Indian–Atlantic Southern Ocean (0–50° E) systematically preceded deep-water mass reorganizations by one to two thousand years during Pleistocene-era glaciations. With the aid of iceberg-trajectory model experiments, we demonstrate that such a shift in iceberg trajectories during glacial periods can result in a considerable redistribution of freshwater in the Southern Ocean. We suggest that this, in concert with increased sea-ice cover, enabled positive buoyancy anomalies to ‘escape’ into the upper limb of the AMOC, providing a teleconnection between surface Southern Ocean conditions and the formation of NADW. The magnitude and pacing of this mechanism evolved substantially across the mid-Pleistocene transition, and the coeval increase in magnitude of the ‘southern escape’ and deep circulation perturbations implicate this mechanism as a key feedback in the transition to the ‘100-kyr world’, in which glacial–interglacial cycles occur at roughly 100,000-year periods. Iceberg-trajectory models along with multi-proxy evidence from sediment cores from the Indian Ocean show that northward shifts in Antarctic iceberg melt redistributed freshwater in the Southern Ocean during the Pleistocene.

Intensification of the Agulhas Leakage (AL) during glacial terminations has long been proposed as a necessary mechanism for reverting the Atlantic Meridional Overturning Circulation (AMOC) to its interglacial mode. However, lack of records showing the downstream evolution of AL signal and substantial temporal differences between AL intensification and resumption of deep‐water convection have cast doubt on the importance of this mechanism to the AMOC. Here, we analyze a combination of new and previously published data relating to Mg/Ca‐derived temperatures and ice volume‐corrected seawater δ18O records (δ18OIVC‐SW, as a proxy for relative changes in ocean salinity), which demonstrate propagation of AL signal via surface and thermocline waters to the western South Atlantic (Santos Basin) during Termination II and the early Last Interglacial. The saline AL waters were temporally stored in the upper subtropical South Atlantic until they were abruptly released in two stages into the North Atlantic via surface and thermocline waters at ca. 129 and 123 ka BP, respectively. Accounting for age model uncertainties, these two stages are coeval with the resumption of convection in the Labrador and Nordic seas during the Last Interglacial. We propose a mechanism whereby both active AL and a favorable ocean‐atmosphere configuration in the tropical Atlantic were required to allow flux of AL waters into the North Atlantic, where they then contributed to enhancing the AMOC during the Last Interglacial period. Our results provide a framework that connects AL strengthening to the AMOC intensifications that followed glaciations.

Inflammatory mammary carcinoma (IMC), a neoplasia affecting women and female dogs, is considered an aggressive cancer with high metastatic potential and a low survival rate. Studies focused on the tumour microenvironment indicate that the aggressive behaviour of this tumour is primarily correlated with immunological factors as well as inflammation. The objective of this study was to analyse the possible strategies used by the tumour cells to suppress the immune response in female dogs with IMC. Forty-six female dogs were divided into three groups: control (C, n = 10), IMC (n = 14) and mammary carcinoma (MC, n = 22). Clinical-pathological evaluations, survival at follow-up, immunophenotyping of leukocytes in peripheral blood and tumours, and immunohistochemical evaluation of CD4 + , granzyme B, perforin and FAS-L were performed. Clinical and pathological results showed a higher frequency of the primary form of neoplasia, solid arrays of tumor cells and a lower survival rate in the IMC group (30 days). Morphometric analysis of inflammatory infiltrate revealed more lymphocytes and macrophages in the IMC group. Immunophenotyping analysis of peripheral blood revealed a higher frequency of CD8 + T-cells (p = 0.0017), a lower frequency of CD4 + T-cells (p <0.0001), and significantly higher mean MHCI and MHCII CD14 + fluorescence intensity in the IMC group (p = 0.038 and p = 0.0117, respectively). The immunohistochemical evaluation of tumour sections showed fewer FAS-L-positive inflammatory cells in the IMC group. These results suggest the important contribution of CD8 + T-cells, macrophages and FAS-L in the aggressiveness of IMC.

This study aimed to evaluate the effects of different nutritional strategies on the intensification of beef cattle farming on pastures during the rainy season. Eighty male cattle (testers) were randomly allocated to 16 paddocks formed with Mombaça grass ( Megathyrsus maximus ), totaling five animals (testers) per paddock. The strategies consisted of two levels of concentrates (LC) [7 and 10 g.kg -1 of body weight (BW)], i.e., low and high LC, and two protein sources (PS) with dried distillers’ grain with solubles (DDGS) and soybean meal (SBM) in a completely randomized design with a 2 × 2 factorial arrangement. The forage’s chemical, structural, and productive characteristics and the supplemented animals’ performance, productivity, and serum parameters were evaluated. The forage had the greatest height (P = 0.038) at the lowest LC; however, a greater leaf proportion (P = 0.049) and leaf: stem ratio (L:S) (P = 0.042) were observed when the highest LC was used. The animals receiving the highest LC had the highest supplement intake (P < 0.001) and a lower pasture intake (P = 0.001). The average daily gain (ADG) did not differ between the LC (P = 0.135) and PS (P = 0.190) groups (0.97 kg.day -1 ). The LC used in the nutritional strategies did not affect the stocking rate (P = 0.272) or productivity (P = 0.986). Supplementation of 7 g.kg -1 BW is recommended for intensive rearing of beef cattle during the rainy season, as it results in high gains at a relatively low cost. In addition, as there were no negative responses to the use of DDGS as a protein source in the supplement, it represents an alternative for replacing soybean meal in the formulations.

This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards. The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer.

O objetivo deste trabalho foi quantificar o carbono orgânico e as frações húmicas de horizontes superficiais de perfis de solo em três topolitossequências no ambiente de Mar de Morros, no município de Pinheiral, RJ. Foram selecionadas as topolitossequências: T1 (basalto), T2 (muscovita-biotita-gnaisse) e T3 (gabro). Os horizontes superficiais de 14 perfis de solo, sob cobertura de pastagem (T1 e T3) e pastagem mista não manejada e leguminosa (pasto sujo/capoeira) (T2), foram descritos e coletados para análises químicas, físicas e do teor de carbono nas frações húmicas. Os teores de carbono orgânico variaram de acordo com o material de origem e decrescem na seguinte ordem: T3 > T1 > T2. Os teores de carbono orgânico aumentam do topo para a várzea na T1, ocorrendo o inverso na T3 e sem um padrão definido na T2. A fração humina predominou em todos os perfis de solo das topolitossequências e foi seguida pela fração ácidos fúlvicos na T1 e de forma equitativa entre as frações ácidos fúlvicos e ácidos húmicos na T2 e T3. Considerando o ambiente similar em termos da vegetação original e o uso agrícola, as mudanças no carbono do solo e nas frações húmicas podem refletir as interações com os componentes minerais e processos pedogenéticos, influenciados pelo material de origem e o relevo.

Background During aging, changes occur in the proportions of muscle, fat, and bone. Body composition (BC) alterations have a great impact on health, quality of life, and functional capacity. Several equations to predict BC using anthropometric measurements have been developed from a bi-compartmental (2-C) approach that determines only fat mass (FM) and fat-free mass (FFM). However, these models have several limitations, when considering constant density, progressive bone demineralization, and changes in the hydration of the FFM, as typical changes during senescence. Thus, the main purpose of this study was to propose and validate a new multi-compartmental anthropometric model to predict fat, bone, and musculature components in older adults of both sexes. Methods This cross-sectional study included 100 older adults of both sexes. To determine the dependent variables (fat mass [FM], bone mineral content [BMC], and appendicular lean soft tissue [ALST]) whole total and regional dual-energy X-ray absorptiometry (DXA) body scans were performed. Twenty-nine anthropometric measures and sex were appointed as independent variables. Models were developed through multivariate linear regression. Finally, the predicted residual error sum of squares (PRESS) statistic was used to measure the effectiveness of the predicted value for each dependent variable. Results An equation was developed to simultaneously predict FM, BMC, and ALST from only four variables: weight, half-arm span (HAS), triceps skinfold (TriSK), and sex. This model showed high coefficients of determination and low estimation errors (FM: R 2 adj : 0.83 and SEE: 3.16; BMC: R 2 adj : 0.61 and SEE: 0.30; ALST: R 2 adj : 0.85 and SEE: 1.65). Conclusion The equations provide a reliable, practical, and low-cost instrument to monitor changes in body components during the aging process. The internal cross-validation method PRESS presented sufficient reliability in the model as an inexpensive alternative for clinical field use.

Undue exposure to antimicrobials has led to the acquisition and development of sophisticated bacterial resistance mechanisms, such as efflux pumps, which are able to expel or reduce the intracellular concentration of various antibiotics, making them ineffective. Therefore, inhibiting this mechanism is a promising way to minimize the phenomenon of resistance in bacteria. In this sense, the present study sought to evaluate the activity of the Carvacrol (CAR) and Thymol (THY) terpenes as possible Efflux Pump Inhibitors (EPIs), by determining the Minimum Inhibitory Concentration (MIC) and the association of these compounds in subinhibitory concentrations with the antibiotic Norfloxacin and with Ethidium Bromide (EtBr) against strains SA-1199 (wild-type) and SA-1199B (overexpresses NorA) of Staphylococcus aureus. In order to verify the interaction of the terpenes with the NorA efflux protein, an in silico molecular modeling study was carried out. The assays used to obtain the MIC of CAR and THY were performed by broth microdilution, while the Efflux Pump inhibitory test was performed by the MIC modification method of the antibiotic Norfloxacin and EtBr. docking was performed using the Molegro Virtual Docker (MVD) program. The results of the study revealed that CAR and THY have moderate bacterial activity and are capable of reducing the MIC of Norfloxacin antibiotic and EtBr in strains of S. aureus carrying the NorA efflux pump. The docking results showed that these terpenes act as possible competitive NorA inhibitors and can be investigated as adjuvants in combined therapies aimed at reducing antibiotic resistance.

Bryophyllum pinnatum (Lam.) Oken (BP) is a plant that is used worldwide to treat inflammation, infections, anxiety, restlessness, and sleep disorders. While it is known that BP leaves are rich in flavonoids, the extent of the beneficial and toxic effects of its crude extracts remains unclear. Although some neurobehavioral studies using leaf extracts have been conducted, none has examined the effects of water-extracted leaf samples. The zebrafish is a powerful animal model used to gain insights into the efficacy and toxicity profiles of this plant due to its high fecundity, external development, and ease of performing behavioral assays. In this study, we performed behavioral testing after acute exposure to different concentrations of aqueous extract from leaves of B . pinnatum (LABP) on larval zebrafish, investigating light/dark preference, thigmotaxis, and locomotor activity parameters under both normal and stressed conditions. LABP demonstrated dose-and time-dependent biphasic effects on larval behavior. Acute exposure (25 min) to 500 mg/L LABP resulted in decreased locomotor activity. Exposure to 300 mg/L LABP during the sleep cycle decreased dark avoidance and thigmotaxis while increasing swimming velocity. After sleep deprivation, the group treated with 100 mg/L LABP showed decreased dark avoidance and increased velocity. After a heating stressor, the 30 mg/L and 300 mg/L LABP-treated groups showed decreased dark avoidance. These results suggest both anxiolytic and psychoactive effects of LABP in a dose-dependent manner in a larval zebrafish model. These findings provide a better understanding of the mechanisms underlying relevant behavioral effects, consequently supporting the safe and effective use of LABP for the treatment of mood disorders.