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Background and objectiveGestational diabetes mellitus (GDM) is a comorbidity which may cause acute and lifelong disorders to mother and child. Alterations in muscular and connective tissues have been associated with GDM in translation studies, characterizing gestational diabetic myopathy. Pregnancy-specific urinary incontinence and sexual disabilities, disorders that depend on the pelvic floor muscle (PFM) integrity, are also associated with GDM both during and after pregnancy. The aim was to compare PFM activation patterns between GDM and non-GDM women from 24–30 gestational weeks to 18–24 months postpartum during a standard clinical test during gestation and postpartum.MethodsWe conducted a prospective three-time-point cohort study from gestation (24–30 weeks—T1, and 36–38 weeks—T2) to 18–24 months postpartum (T3). PFM electromyography was recorded in primigravida or primiparous women with one previous elective c-section with or without the diagnosis of GDM according to the American Diabetes Association criteria. A careful explanation of the muscle anatomy and functionality of the PFM was given to participants before EMG assessment. The outcome measures were PFM activation patterns assessed during pregnancy and postpartum, comparing intra and between groups. PFM activation patterns were assessed by normalized electromyography signal at rest and during 1-second (sec) phasic, 10-sec hold, and 60-sec sustained contractions.ResultsDemographic and obstetric data showed homogeneity between groups. The GDM group achieved peak PFM EMG amplitudes similarly to the non-GDM group, but they took longer to return to baseline levels during the ~1-sec contraction (flicks). During 10-sec hold contractions, the GDM group sustained lower levels of PFM activation than the non-GDM group at both 36–38 weeks of gestation and 18–24 months postpartum when compared to the non-GDM group.ConclusionThe results suggest that GDM impaired PFM control mainly on 1-sec flicks and 10-sec hold contraction, which appears to develop during late pregnancy and extends long-term postpartum. This motor behavior may play a role on pelvic floor dysfunctions.

Abstract Background Pelvic floor muscles (PFM) and rectus abdominis muscles (RAM) of pregnant diabetic rats exhibit atrophy, co-localization of fast and slow fibers and an increased collagen type I/III ratio. However, the role of similar PFM or RAM hyperglycemic-related myopathy in women with gestational diabetes mellitus (GDM) remains poorly investigated. This study aims to assess the frequency of pelvic floor muscle disorders and pregnancy-specific urinary incontinence (PS-UI) 12 months after the Cesarean (C) section in women with GDM. Specifically, differences in PFM/RAM hyperglycemic myopathy will be evaluated. Methods The Diamater is an ongoing cohort study of four groups of 59 pregnant women each from the Perinatal Diabetes Research Centre (PDRC), Botucatu Medical School (FMB)-UNESP (São Paulo State University), Brazil. Diagnosis of GDM and PS-UI will be made at 24–26 weeks, with a follow-up at 34–38 weeks of gestation. Inclusion in the study will occur at the time of C-section, and patients will be followed at 24–48 h, 6 weeks and 6 and 12 months postpartum. Study groups will be classified as (1) GDM plus PS-UI; (2) GDM without PS-UI; (3) Non-GDM plus PS-UI; and (4) Non-GDM without PS-UI. We will analyze relationships between GDM, PS-UI and hyperglycemic myopathy at 12 months after C-section. The mediator variables to be evaluated include digital palpation, vaginal squeeze pressure, 3D pelvic floor ultrasound, and 3D RAM ultrasound. RAM samples obtained during C-section will be analyzed for ex-vivo contractility, morphological, molecular and OMICS profiles to further characterize the hyperglycemic myopathy. Additional variables to be evaluated include maternal age, socioeconomic status, educational level, ethnicity, body mass index, weight gain during pregnancy, quality of glycemic control and insulin therapy. Discussion To our knowledge, this will be the first study to provide data on the prevalence of PS-UI and RAM and PFM physical and biomolecular muscle profiles after C-section in mothers with GDM. The longitudinal design allows for the assessment of cause-effect relationships between GDM, PS-UI, and PFMs and RAMs myopathy. The findings may reveal previously undetermined consequences of GDM.

A realidade virtual pode ser definida como uma experiência imersiva, interativa etridimensional que ocorre em tempo real. Com este trabalho pretendemos responder à questão“Como é que as medidas de autorrelato da experiência de jogo e as medidas fisiológicasde excitação estão correlacionadas?”. A amostra foi constituída por 24 indivíduos do sexomasculino, com idades compreendidas entre os 18 e 44 anos. Utilizamos dois questionários,HTC Vive, QuietComfort 15, o jogo Endless Night e o Nexus 10 MKII. Como principal resultadoverificámos que os valores da frequência cardíaca e da atividade eletrodérmica variam emfunção dos níveis de dificuldade do jogo. Foi possível apurar que não existe uma relação entreo grau de satisfação e a excitação fisiológica nos diferentes níveis de dificuldade.

Abstract Background Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment. Results The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro. Conclusions Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.

Abstract Antibiotic resistance is a global healthcare crisis. Bacteria are highly adaptable and can rapidly acquire mechanisms of resistance towards conventional antibiotics. The permeability barrier conferred by the Gram-negative bacteria cell envelope constitutes a first line of defence against the action of antibiotics. Exposure to extracytoplasmic stresses can negatively affect cell envelope homoeostasis and this causes localised protein misfolding, compromised envelope integrity and impairs barrier function. The CpxA-CpxR two-component regulatory system has evolved to sense extracytoplasmic stresses and to regulate processes that restore homoeostasis of the cell envelope. Hence, controlled Cpx-signalling assists bacteria in adapting, surviving and proliferating in harsh environments, including exposure to antibiotics. Herein, we determined that an intact Cpx-signalling is key to maintaining the Yersinia pseudotuberculosis resistance to colistin and polymyxin B. The susceptibility displayed by Cpx-signalling defective mutants, correlated with cell-envelope deformity and specific modifications of Lipid-A. In vivo transcriptional analysis and in vitro protein-DNA binding studies demonstrated that these modifications were dependent on the direct regulation of Lipid-A biogenesis and modifications of operons by the active phosphorylated CpxR~P isoform. Altogether, our work defines the regulatory mechanism that enables Cpx-signalling to actively control cell envelope remodelling and the permeability of antibiotics in the clinically relevant enteropathogen Y. pseudotuberculosis.

Our study sought to investigate the impact of incorporating guava agroindustrial waste (GAW) at varying concentrations on nutrient utilization, lamb performance and economic viability. Forty non-castrated, 4-month-old Santa Inês lambs with an initial mean weight of 21.3 ± 2.18 kg were utilized in a confined setting. These lambs were allocated randomly to five treatment groups, each consisting of eight replicates, and were subjected to diets containing increasing levels of GAW (0 %, 7.5 %, 15 %, 22.5 % and 30 % based on dry matter). The feed formulation also included Tifton hay, corn, soybean and mineral salt. Throughout the trial period, parameters such as dry matter intake (DMI), nutrient digestibility and economic metrics were meticulously evaluated. Notably, the performance metrics among the different GAW treatments did not exhibit statistically significant differences (p > 0.05), with an average daily gain of 328 g d−1 observed across all the groups. However, there was a discernible positive effect on the intake of ether extract (p > 0.05). Regarding nutrient digestibility, only the crude protein digestibility demonstrated no significant variance (p > 0.001) among the treatments. Consequently, our findings suggest that GAW can be effectively integrated into sheep diets at levels of up to 30 % without compromising lamb performance. Moreover, from an economic standpoint, this incorporation proves to be the most financially viable and cost-effective option among the evaluated treatments.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

Abstract: Glaucoma is the leading cause of irreversible blindness worldwide, with many individuals unaware of their condition until advanced stages, resulting in significant visual field impairment. Despite effective treatments, over 110 million people are projected to have glaucoma by 2040. Early detection and reliable monitoring are crucial to prevent vision loss. With the rapid development of computational technologies, artificial intelligence (AI) and deep learning (DL) algorithms are emerging as potential tools for screening, diagnosing, and monitoring glaucoma progression. Leveraging vast data sources, these technologies promise to enhance clinical practice and public health outcomes by enabling earlier disease detection, progression forecasting, and deeper understanding of underlying mechanisms. This review evaluates the use of Big Data and AI in glaucoma research, providing an overview of most relevant topics and discussing various models for screening, diagnosis, monitoring disease progression, correlating structural and functional changes, assessing image quality, and exploring innovative technologies such as generative AI.

Abstract Many bacterial immune systems recognize phage structural components to activate antiviral responses, without inhibiting the function of the phage component. These systems can be encoded in specific chromosomal loci, known as defense islands, and in mobile genetic elements such as prophages and phage-inducible chromosomal islands (PICIs). Here, we identify a family of bacterial immune systems, named Tai (for ‘tail assembly inhibition’), that is prevalent in PICIs, prophages and P4-like phage satellites. Tai systems protect their bacterial host population from other phages by blocking the tail assembly step, leading to the release of tailless phages incapable of infecting new hosts. To prevent autoimmunity, some Tai-positive phages have an associated counter-defense mechanism that is expressed during the phage lytic cycle and allows for tail formation. Interestingly, the Tai defense and counter-defense genes are organized in a non-contiguous operon, enabling their coordinated expression.

Abstract The genome of Pseudomonas aeruginosa encodes three type VI secretion systems, each comprising a dozen distinct proteins, which deliver toxins upon T6SS sheath contraction. The least conserved T6SS component, TssA, has variations in size which influence domain organisation and structure. Here we show that the TssA Nt1 domain interacts directly with the sheath in a specific manner, while the C-terminus is essential for oligomerisation. We built chimeric TssA proteins by swapping C-termini and showed that these can be functional even when made of domains from different TssA sub-groups. Functional specificity requires the Nt1 domain, while the origin of the C-terminal domain is more permissive for T6SS function. We identify two regions in short TssA proteins, loop and hairpin, that contribute to sheath binding. We propose a docking mechanism of TssA proteins with the sheath, and a model for how sheath assembly is coordinated by TssA proteins from this position.

Abstract Salinity limits the growth and productivity of crops, to reverse these effects, natural pigments with antioxidant bioactivity can be studied, such as turmeric (Curcuma longa L.) and paprika (Capsicum annum L.). Therefore, it aimed to evaluate turmeric and paprika as possible saline stress attenuators and biostimulants during germination and initial development of smooth lettuce seedlings. In the laboratory, the seeds were treated for 1 hour with a solution of paprika and turmeric at doses 0 (negative control), 1, 2, 3 and 4 g L-1, and placed on a substrate with saline solution of sodium chloride 4 g L-1 (-0,4 Mpa), and a positive control, composed of dry seeds arranged in a substrate moistened with distilled water. Physiological quality analysis were carried out, and for the dose that showed the best result (4 g L-1), the treated seeds were grown in a greenhouse, and received weekly applications via foliar with a 4 g L-1 solution for turmeric and paprika. After the crop cycle, morphometric analyzes were performed. The turmeric and paprika solutions were analyzed by High-Performance Liquid Chromatography (HPLC) to identify the presence of bioactive substances. The turmeric doses were not efficient in overcoming the effects of salinity on seeds and seedlings, which was attributed to the low solubility of turmeric in water. Paprika, although it did not provide the biostimulant effect, was efficient in attenuating the effects of excess salt, at a concentration of 4 g L-1, promoting increases in physiological quality. In HPLC, a very low signal response was noted in relation to samples composed of turmeric and paprika solutions, indicating a low percentage of soluble compounds, which compromises bioactivity, and leads to the need for further analyses using surfactants and/or other solvents with which there is greater affinity.

The antifouling booster biocides are frequently studied for toxic effects on the aquatic ecosystems. The present investigation proposes passive silicone rubber samplers as a collection method for biocides, once these methods can concentrate substances in aqueous matrices at very low levels. Through the passive sampler-water partition coefficient (Ksw) and the analyte chemical nature, we can optimize their extraction from the membrane to apply in the sample medium. We used the co-solvent method to determine the Ksw of three third-generation antifouling biocides, chlorothalonil, dichlofluanid, and dichlorooctylisothiazolinone (DCOIT), with log Ksw = 2.24, 4.01, and 2.38, respectively. Improving extraction also led to a recovery range higher than 70%, determinations were carried out by gas chromatography with an electron capture detector. Biocides concentration in seawater samples from Itaqui port (São Marcos Bay, northern Brazil) ranged from 0.058 to 0.72 µg L-1 for chlorothalonil, 0.001 to 0.008 µg L-1 for dichlofluanid, and 0.018 to 0.64 µg L-1 for DCOIT.

This paper explores the theoretical economic outcome of management changes that result in different levels of antimicrobial use (AMU) in two types of UK pig farm. A static farm economic pig production model (FEPM) was used on a representative ‘Top-third’ most profitable farm and a representative ‘Mid-range’ profitable farm. Three AMU theoretical management scenarios were investigated; (a) management changes leading to a reduction of AMU by 35% (AMU35); (b) more extensive management changes leading to a reduction of AMU by 95% (AMU95); and (c) implementing depopulation of the herd (AMU Depop). A sensitivity analysis was conducted to determine the effect of increases or decreases in pig revenue and feed price on farm gross margin under these scenarios. Over a single year, the AMU35 scenario was estimated to have a small positive impact (+3%) on both farm types. The other two AMU reduction scenarios had higher AMU reduction on farms but required higher variable cost and hence they resulted in lower farm profitability. There was a substantial reduction (up to −50%) in farm gross margin under these two AMU reduction scenarios in the modeled short-term time-period. The impact of the alternative AMU scenarios was slightly higher on a farm representing the ‘Top-third’ farm type, reducing farm gross margin further by 7% compared to the ‘Mid-range’ farm. Nevertheless, both farm types stay profitable under all three AMU scenarios. The results showed that in the modeled short-term implementing management changes that result in a reduction of on-farm AMU by 35% had a good economic outcome. In practice, the other two scenarios would be considered as longer-term strategies. Although both require higher initial costs to implement, the improved biosecurity and hygiene will benefit from lower disease occurrence for a longer term. Farm gross margins were, however, found to be highly sensitive to changes on market prices especially increasing feed prices. An increase of more than 15% in feed price moved a profitable farm into a loss-making farm. It will be economically challenging for uptakes of these, or similar, AMU reduction scenarios on farms if the market prices become un-favorable to pig farmers.

Abstract Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution.

Abstract The valorisation of waste or by-products in Portland clinker production is a promising alternative for developing sustainable cements. The complexity of the chemical reactions during clinkering demands an adequate dosing method that considers the effect of feedstock impurities to maximise the potential substitution of natural resources by waste or by-products, while guaranteeing the clinker reactivity requirements. This study proposes a raw meal proportioning methodology for optimising co-processing of natural feedstocks with alternative raw materials in clinker production, intending to reduce the content of natural raw materials needed, while promoting an optimal clinker reactivity. A thermodynamic modelling sequence was developed considering the variability of raw materials composition and heating temperatures. The model was then validated by comparing simulation outcomes with results reported in previous studies. An experimental case study was conducted for validation of the proposed method using a spent fluid catalytic cracking catalyst (SFCC), a by-product from the oil industry as an alternative alumina source during clinkering. The modelling simulations indicated that substitution of natural feedstocks by 15 wt% SFCC promotes the formation of reactive clinkers with more than 54% tricalcium silicate (C3S). Mixes with the potential to form the highest C3S were then produced, and heating microscopy fusibility testing was applied for evaluating the clinkers’ stability. The main factors governing the reactivity and stability of the clinker phases were the melt phase content, alumina modulus, and formation of C3S and dicalcium silicate (C2S). The self-pulverisation of clinker during cooling was observed in selected mixes, and it is potentially associated with high viscosity and low Fe content in the melt phase. The proposed framework enables optimisation of the dosing of raw meals containing alternative alumina-rich feedstocks for clinker production and allows a deeper interpretation of limited sets of empirical data.

The (R,R)-Teth-TsDPEN-Ru(II) complex promoted the one-pot double C=O reduction of α-alkyl-β-ketoaldehydes through asymmetric transfer hydrogenation/dynamic kinetic resolution (ATH-DKR) under mild conditions. In this process, ten anti-2-benzyl-1-phenylpropane-1,3-diols (85:15 to 92:8 dr) were obtained in good yields (41–87%) and excellent enantioselectivities (>99% ee for all compounds). Notably, the preferential reduction of the aldehyde moiety led to the in situ formation of 2-benzyl-3-hydroxy-1-phenylpropan-1-one intermediates. These intermediates played a crucial role in enhancing both reactivity and stereoselectivity through hydrogen bonding.

One of the critical challenges facing the mining sector is related to the prevention and mitigation of catastrophic incidents associated with its tailing dams. As mining tailings are very heterogeneous and field characterization is expensive and complex, geotechnical properties of these materials are largely unknown. The seismic cone penetration test (SCPTu) provides a field approach to estimate a large array of geotechnical information, including the liquefaction potential of tailing dams. Yet, the exploration of strain softening behaviors in geomaterials under undrained loading, utilizing the state parameter (ψ) inferred from SCPTu tests initially applied to soft soils, has been often used for mining tailings. This study is concerned with the implementation of a tailing classification system which uses the ratio between the small strain shear modulus and the cone tip resistance (G0/qt). A series of laboratory tests was executed, and three different methodologies were adopted to assess the effects of (partial) drainage conditions based on 531.26 m of SCPTu measurements conducted at three different upstream iron ore tailing dams in Brazil. Furthermore, the G0/qt ratio is integrated with ψ to assess the liquefaction tendencies of the investigated materials. The findings reveal the heterogeneous nature of the tailings, wherein indications of partial drainage are discernible across numerous records. Liquefaction analyses demonstrate that the tailings exhibit a contractive behavior in over 94% of the SCPTu data, confirming their susceptibility to flow liquefaction. Our findings are relevant for site characterization within iron ore tailing dams and other mining sites with similar geotechnical attributes.

Abstract Antibiotics have shown less efficiency against resistance of pathogenic microorganisms. As a result, research centers have sought therapeutic alternatives against multidrug resistance of bacteria to antibiotics, one of which is using plant extracts. Bamboo extracts are used for several medicinal purposes. This study aimed to evaluate the antibacterial potential of hydroalcoholic extracts of culms and leaves of the species Guadua aff. lynnclarkiae on strains of Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae. We evaluated the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC). Only the leaves of G. aff. lynnclarkiae showed a bactericidal effect for all tested strains with MBC ranging from 1.55 mg ml-1 to 25 mg ml-1. The culms had bacteriostatic action with MIC ranging from 1.55 mg ml-1 to 6.25 mg ml-1, and bactericidal action at the concentration of 6.25 mg ml-1 only for S. aureus. This study provides bases for the use of this Amazonian native bamboo in bioprospecting.

Background: Obesity poses a major risk for cardiovascular diseases, while it is almost a consensus that intra-abdominal adiposity has a more deleterious effect for metabolic syndrome. In this sense, it is speculated that lipectomy or liposuction would be metabolically harmful, as it changes the abdominal-superficial adipose tissue ratio. However, the literature has shown conflicting evidence. Methods: In order to evaluate the possibility of metabolism alteration resulting from body coutouring surgery, a prospective cohort was implemented with 35 patients who underwent abdominoplasty, including some with a history of massive weight loss. Fasting blood glucose, fasting plasma insulin, triglycerides, total cholesterol and fractions were requested preoperatively and in the third postoperative month. The groups were also compared with each other. Results: No statistically significant variation between the exams collected in the preoperative period and those collected after abdominoplasty was found. There was a statistically significant difference in LDL (low-density lipoprotein; p = 0.033) and non-HDL (non-high-density lipoprotein) cholesterol (p = 0.020) between the two control tests of the groups surveyed. There were also differences in comorbidities (p = 0.006) and complications (p

Objective: To assess how inadequate reporting of cointerventions influences estimated treatment effects in recent cardiovascular trials. Methods: Medline/Embase were systematically searched from January 1, 2011 to July 1, 2021 for trials evaluating pharmacologic interventions on clinical cardiovascular outcomes published in 5 high-impact journals. Information on adequate vs inadequate reporting of cointerventions, blinding, risk of bias due to deviations of intended interventions (low vs high/some concerns), funding (nonindustry vs industry), design (superiority vs noninferiority), and results were assessed by 2 reviewers. The association with effect sizes was assessed using meta-regression random-effect analysis, expressed as ratios of odds ratios (ROR). RORs of >1.0 indicated that trials with the methodological factor pointing to lower quality report larger treatment estimates. Results: In total, 164 trials were included. Of the 164 trials, 124 (74%) did not adequately report cointerventions; 89 of the 164 trials (54%) provided no information regarding cointerventions, and 70 of the 164 (43%) were at risk of bias due to inadequate blinding. Moreover, 86 of the 164 (53%) were at risk of bias due to deviation of intended interventions. Of the 164 trials, 144 (88%) were funded by the industries. Trials with inadequate reporting of cointerventions had larger treatment estimates for the primary end point (ROR, 1.08; 95% CI, 1.01-1.15; I2=0%). No significant association with results for blinding (ROR, 0.97; 95% CI, 0.91-1.03; I2=66%), deviation of intended interventions (ROR, 0.98; 95% CI, 0.92-1.04; I2=0%), or funding (ROR, 1.01; 95% CI, 0.93-1.09; I2=0%) was found. Conclusion: We conclude that trials with inadequate reporting of cointerventions showed larger treatment effect estimates, potentially indicating overestimation of therapeutic benefit. Trial Registration: Prospero Identifier: CRD42017072522

ABSTRACT: Enterococcal spondylitis affects poultry and causes progressive lameness. This study reports what seems to be the first case of vertebral osteomyelitis caused by Enterococcus in broiler chickens in southern Brazil. We also conducted an experimental infection to evaluate microorganismal characteristics and pathogenicity in broiler chickens. We performed bacterial isolation, identification, and histopathology. The isolates were tested for their growth and survival capacity at different temperatures, pH values, and antimicrobial resistance profiles. The experiment infection was conducted with broiler breeders (n=9). Group 1 = negative control, Group 2 = challenged orally, Group 3 = challenged via air sac. The autopsy was performed on the 50th day of life (DOL). The report showed spondylitis and fusion of thoracic vertebra, accompanied by spinal cord compression, and femoral head necrosis. We used the isolates (n=17) to test their growth at 10°C and 45°C, survival capacity for up to 60° for 30 min, and growth under pH levels from four to 12. Higher resistance was observed against macrolides and quinolones. On experimental infections, all animals expressed signs of lameness and “sitting on the hocks”. Enterococcus faecalis is the causal agent of enterococcal spondylitis in broilers in southern Brazil, which is an underreported and emerging pathological condition that requires attention.

Abstract The Cerrado in Central Brazil is composed of unique vegetation types with a large source of bioactive compounds. The 1970s and 1980s were marked by the intensive incorporation of these forested areas into pastures and cropland, which increased the consumption of pesticides like glyphosate and atrazine. Today there continues to be a constant loss of native vegetation in this biome, and the pressure from land use is causing significant losses of native vegetation, driven mainly by agricultural expansion. This article offers a mapping of the estimated average consumption of pesticide per crop as well as an understanding of the risks associated with glyphosate and atrazine contamination in the state of Goiás. Both of these areas serve as a basis for understanding the challenges and opportunities for sustainability associated with agriculture in the Brazilian Cerrado.

ABSTRACTBacterial conjugation, a process of horizontal gene transfer, plays a key role in promoting the spread of antimicrobial resistance among human pathogens. The mechanism of conjugation involves the development of a conjugative pilus that forms a physical bridge between two bacterial cells and the subsequent unidirectional transfer of single-stranded DNA (ssDNA) complexed with a protein from the donor to the recipient cell. Atomic structures exist for many of the components of the type IV secretion system (T4SS), responsible for the nucleoprotein secretion, but little is known about the events preceding gene transfer, specifically what is the extent of the participation of the conjugative pilus in ssDNA transfer? There has been a longstanding debate about whether its main role is to bring a donor and a recipient cell into physical juxtaposition and form a mating junction that allows for ssDNA transfer via the T4SS machinery complex or whether ssDNA is actually transferred through the lumen of the pilus. Here, through a combination of maleimide labeling of the conjugative pilus and SeqA-YFP labeling of the transferred ssDNA, we visualize the process of bacterial conjugation in real time. We discover that the conjugative pilus is capable of transferring the ssDNA at a distance, between physically separated cells, and thus conclude that a physical mating junction is not essential for conjugative gene transfer.IMPORTANCEBacteria are constantly exchanging DNA, which constitutes horizontal gene transfer. While some of these occurs by a non-specific process called natural transformation, some occurs by a specific mating between a donor and a recipient cell. In specific conjugation, the mating pilus is extended from the donor cell to make contact with the recipient cell, but whether DNA is actually transferred through this pilus or by another mechanism involving the type IV secretion system complex without the pilus has been an open question. Using Escherichia coli, we show that DNA can be transferred through this pilus between a donor and a recipient cell that has not established a tight mating junction, providing a new picture for the role of this pilus.

We performed a retrospective analysis of the patients assessed at our memory unit for whom Alzheimer disease (AD) cerebrospinal fluid biomarker results were available. We selected patients diagnosed with mild cognitive impairment due to AD (National Institute on Aging-Alzheimer’s Association clinical criteria), confirmed neuropsychological deficit, a Global Deterioration Scale score of 3, and an abnormal profile of cerebrospinal fluid biomarkers. Of the 588 cases reviewed, 110 met the inclusion criteria. During follow-up, 50 cases (45.45%) progressed to dementia due to AD. Baseline levels of total and phosphorylated tau were higher in the group of patients that progressed to dementia than in those remaining with mild cognitive impairment. After adjusting for age, sex, history of hypertension, diabetes, and educational level, a 10% increase in total tau protein values was associated with a 7.60% increase in the risk of progression to dementia (hazard ratio: 2.22; 95% confidence interval, 1.28–3.84]; P = .004). Among patients with mild cognitive impairment due to AD and abnormal cerebrospinal fluid biomarker profiles, progressively higher concentrations of total or phosphorylated tau were associated with increased risk of progression to dementia. Resumen: Realizamos un análisis retrospectivo de los pacientes evaluados en nuestra unidad de memoria en los que se realizó determinación de biomarcadores licuorales de enfermedad de Alzheimer (EA). Se seleccionaron aquellos casos con diagnóstico de deterioro cognitivo leve debido a EA según criterios clínicos (criterios NIA-AA), déficit neuropsicológico comprobado, una puntuación igual a 3 en la escala GDS y un perfil alterado de biomarcadores en líquido cefalorraquídeo. De los 588 casos revisados, 110 cumplieron los criterios de inclusión. Durante el seguimiento, 50 de estos 110 casos (45,45%) progresaron a demencia por EA. Se observaron diferencias significativas en los niveles basales de tau total y tau fosforilada entre los casos que evolucionaron a demencia y los que permanecieron estables como deterioro cognitivo leve, siendo los niveles más altos en el grupo que progresó a demencia. Después del ajuste por edad, sexo, antecedentes de hipertensión, diabetes y nivel educativo, un aumento del 10% en los valores de proteína tau total se asoció con un aumento del 7,60% en el riesgo de progresión a demencia (HR = 2,22, IC 95% [1,28, 3.84], P = .004). En pacientes con deterioro cognitivo leve debido a EA un perfil alterado de biomarcadores licuorales, concentraciones progresivamente mayores de tau-t y tau-p se asocian a un mayor riesgo de conversión a demencia.

Enteropathogenic bacteria use extracellular appendages, known as F-pili, to share plasmids carrying antibiotic resistance genes. Here, the authors show that F-pili are highly flexible but robust at the same time, and this is important for plasmid transfer and formation of biofilms that protect against the action of antibiotics.

The chemical stability of azithromycin (AZM) may be compromised depending on the imposed thermo-oxidative conditions. This report addresses evidence of this process under varying conditions of temperature (20–80 °C), exposure time to UV radiation (1–3 h irradiation at 257 nm), and air saturation (1–3 h saturation with atmospheric air at 1.2 L min−1 and 15 kPa) through electrochemical measurements performed with a thermoactivated cerium molybdate (Ce2(MoO4)3)/multi-walled carbon nanotubes (MWCNT)-based composite electrode. Thermal treatment at 120 °C led to coordinated water elimination in Ce2(MoO4)3, improving its electrocatalytic effect on antibiotic oxidation, while MWCNT were essential to reduce the charge-transfer resistance and promote signal amplification. Theoretical–experimental data revealed remarkable reactivity for the irreversible oxidation of AZM on the working sensor using phosphate buffer (pH = 8) prepared in CH3OH/H2O (10:90%, v/v). Highly sensitive (230 nM detection limit) and precise (RSD < 4.0%) measurements were recorded under these conditions. The results also showed that AZM reduces its half-life as the temperature, exposure time to UV radiation, and air saturation increase. This fact reinforces the need for continuous quality control of AZM-based pharmaceuticals, using conditions closer to those observed during their transport and storage, reducing impacts on consumers’ health.

Abstract The maize yield, nutritional status, and grain fumonisins concentration were evaluated in different genotypes, doses, and nitrogen sources (N) in two years and three locations. Two experiments were carried out in each area and year in an experimental design of a subdivided plot with four replications. One experiment involved a 4x2 factorial treatment: four nitrogen (N) doses (0, 80, 160, and 240 kg ha-1) in coverage and having urea as a source of N and two genotypes. Another experiment involved a 4x2 factorial treatment: four N sources: urea, urea covered with polymer, ammonium nitrate, and ammonium nitrate + urea (UAN), at a dose of 160 kg ha-1, in two genotypes. The genotype generally influenced maize yield more than N doses and sources, mainly due to the bushy stunt/corn stunt tolerance of AG7098 PRO2 and AG8677 PRO2. The N doses linearly increased the N leaf content. However, the N sources did not affect the N leaf content. The N doses and sources had no significant effect on the content of fumonisins, which was affected only by the genotypes in Sete Lagoas in 2016 (N doses experiment) and 2017 (N sources experiment). The hybrids, P3630H and AG8677PRO2 (Sete Lagoas, 2016, N doses experiment and 2017, N sources experiment, respectively) exceeded the Brazilian legislation for Maximum Tolerance Limit for fumonisins in corn grains, which is 5,000 µg kg-1. The best result was obtained with AG7098 PRO2, with yields (above 10,000 kg ha-1) and fumonisins consistently below 5,000 µg kg-1. Therefore, the selection of corn hybrids is a strategy to reduce the occurrence of fumonisins in the grains.

Anemia falciforme (AF) é uma doença causada por mutação em homozigose no gene da β-globina, levando à formação de uma hemoglobina anormal (HbS), que leva à falcização das hemácias em condição de desoxigenação, reduzindo sua meia-vida. É caracterizada por anemia hemolítica crônica e recorrentes crises de vaso-oclusão. Além disso, ocorrem alterações na diferenciação terminal dos eritrócitos - uma potencial causa de piora da anemia. A apoptose das células que não se desenvolvem ocorre nas Ilhas Eritroblásticas (IEs), fazendo com que os macrófagos centrais desses nichos aumentem sua capacidade de fagocitose para retirada dessas células, podendo alterar o metabolismo do ferro nos macrófagos, evitando assim o estresse oxidativo. Anteriormente observamos que monócitos (MC) circulantes de pacientes com AF expressam moléculas relacionadas aos macrófagos de IEs (CD206, CD169, CD163 e VCAM-1) e têm participação na fagocitose de hemácias. O objetivo do trabalho foi investigar se essa atividade fagocítica está relacionada aos MCs ou às hemácias dos pacientes AF e qual a consequência para o metabolismo do ferro. Para isso, MCs foram isolados de sangue periférico e incubados por 2 horas com hemácias previamente marcadas com um corante de membrana para realização da fagocitose. As hemácias não fagocitadas foram lisadas e as marcações com os anticorpos anti-ferroportina (FPN) e anti-heme-oxigenase-1 intracelular (HO-1) foram feitas. A avaliação das expressões foi feita por citometria de fluxo e as análises estatísticas, através do teste t-Student pareado (p < 0,05). Quando expostos à hemácias AF, os MCs de ambos os grupos fagocitam mais do que na presença de hemácias CTRL (MCCTRL 22.9 ± 8 vs 9.4 ± 1.1, **p = 0,0099; MCAF 33.6 ± 11.4 vs 16.4 ± 11, **p = 0,0054; respectivamente). Por outro lado, não foi observada diferença estatística entre as fagocitoses encontradas nos MC CTRL e MC AF na presença de hemácias de pacientes (p = 0.0699). Quanto ao metabolismo do ferro, em todos os casos houve aumento de expressão de HO-1 e de FPN após a fagocitose (HO-1: MCCTRL 68.4 ± 3.5 vs 88.2 ± 7.6, ***p = 0.0003; MCAF 65.9 ± 16.8 vs 91.9 ± ,4 **p = 0.0098; FPN: MCCTRL 68.9 ± 5 vs 77.5 ± 5.2, **p = 0.0017; MCAF 66.5 ± 15.7 vs 81.8 ± 13.7, ***p = 0.0003; antes e depois da fagocitose, respectivamente), indicando maior capacidade de quebra do heme liberado pelas hemácias e de exportação do ferro ali presente. Os resultados sugerem que hemácias de pacientes com AF são responsáveis por induzir maior fagocitose e que essa não é uma função intrínseca dos MCs de pacientes com AF, apesar de participarem desse processo na circulação e apresentarem um fenótipo similar ao dos macrofágos das IEs. O aumento de expressão de moléculas do metabolismo de ferro foi relacionado apenas com a fagocitose e não a um grupo específico de indivíduos. Em conclusão, os MCs de pacientes com AF podem assumir uma função que não é completamente inata à eles quando expostos à hemácias falcizadas, contribuindo para a sua retirada da circulação e os aumentos de expressão de moléculas do metabolismo de ferro após a fagocitose, sugerindo influência importante dos MCs na disponibilidade do metal para suprir a demanda na produção de células eritróides e mostrando importante contribuição dessas células nos mecanismos da doença.

Anemia Falciforme é uma hemoglobinopatia genética e hereditária caracterizada por uma mutação que ocorre na cadeia beta da globina, a qual ocasiona a substituição de um ácido glutâmico por uma valina, formando a hemoglobina S. Essa é irreversivelmente polimerizada durante o processo de desoxigenação, causando a falcização das hemácias. Os glóbulos vermelhos falcizados possuem função anormal e iniciam uma série de manifestações clínicas agudas e crônicas em pacientes homozigotos (HbSS), devido à intensa hemólise, vaso-oclusão e inflamação crônica induzida por liberação de DAMPs. Estudos recentes mostram que pacientes falciformes possuem uma importante assinatura de genes induzidos por IFN-I em células mononucleares de sangue periférico, porém essas células não são as responsáveis pela produção da citocina. O objetivo do presente trabalho foi investigar se as células dendríticas plasmocitóides (pDCs) podem ser fontes de produção de IFN-I na patologia, já que elas são produtoras profissionais dessa citocina. Para isso coletamos sangue de 41 pacientes falciformes atendidos no ambulatório de Hematologia do Hemocentro-UNICAMP e de 35 doadores de sangue saudáveis para quantificar citocinas no soro por citometria de fluxo. Além disso, analisamos as células de camundongos transgênicos, os quais expressam HbS humana (Townes), e comparamos com as dos camundongos WT, os quais expressam a hemoglobina normal (HbA) também humana. Nossos dados confirmam a produção sistêmica de IFN-I na nossa coorte de pacientes falciformes, a qual foi significativamente maior que a dos indivíduos controles (***p = 0,0002). Além disso, nós observamos uma correlação positiva forte entre as concentrações de IFN- e as de citocinas pro- e anti-inflamatórias, como IL-18, IL-23, IL12p70, IL-6, IL-10, TNF-, IL-33 e IL-1β em pacientes falciformes (*** p = 0,0001 e *** p = 0,0002; 1< R xy

Objetivos: A Anemia Falciforme (AF) é uma hemoglobinopatia que causa deformação das hemácias devido à polimerização da hemoglobina S, tornando-as mais suscetíveis a rupturas. Moléculas liberadas na hemólise, como heme e hemoglobina, podem ativar células dendríticas (DCs), desencadeando resposta inflamatória e estresse oxidativo. Neste estudo, caracterizamos as subpopulações de DCs durante a doença falciforme quanto a sua ativação, distribuição e desenvolvimento durante a AF. Materiais e métodos: Foram utilizados camundongos transgênicos fêmeas homozigotos Townes (SS) (modelo de AF) e seus controles, camundongos selvagens Townes (AA), para a fenotipagem de DCs e seus progenitores nos linfonodos periféricos, baço e medula óssea por citometria de fluxo. A diferenciação in vitro de DCs foi realizada incubando células da medula óssea com flt3l por 9 dias. Resultados: Os animais com AF (SS) mostraram uma diminuição na porcentagem de DCs totais no baço e na medula óssea e um aumento na porcentagem dessas células nos linfonodos em comparação com o grupo controle (AA), enquanto o número absoluto de DCs aumentou nos três órgãos de camundongos SS. Em relação à proporção de subpopulações de DCs, houve um aumento significativo na porcentagem de células dendríticas convencionais do tipo 1 (cDC1s) em todos os órgãos dos animais com AF, enquanto a porcentagem relativa de células dendríticas plasmocitoides (pDCs) foi significativamente menor na medula óssea e maior nos linfonodos. Além disso, as pDCs dos camundongos SS mostraram um fenótipo mais maduro nos três órgãos analisados, como observado por um aumento significativo na expressão de Sca-1. Por outro lado, tanto cDC1 quanto cDC2 dos camundongos SS mostraram um perfil mais imaturo, como observado pela menor expressão de MHC-II e CD86. A análise dos progenitores de monócitos e DCs (MDP), os quais são Lin-CD135+CD117+CD115+, e os progenitores de DCs (CDP), que são Lin-CD135+CD117-CD115+ na medula óssea, mostraram que há um acúmulo na proporção de MDPs e uma diminuição de CDPs na medula óssea de camundongos SS. A diferenciação in vitro de DCs revelou que células da medula óssea de animais SS se diferenciaram nos três subtipos de DCs de maneira semelhante aos controles em condições controladas. Discussão: A menor proporção de DCs na medula e o aumento no baço e nos linfonodos sugere uma maior migração dessas células após uma ativação. Aliado a isso, o perfil mais imaturo das células pode refletir uma alteração na ativação de células T, afetando assim o sistema imune adaptativo. Ainda, a diferença observada na porcentagem das diferentes subpopulações de DCs e em seus progenitores indica uma mudança no desenvolvimento ou morte das subpopulações de DCs durante a AF que pode ocorrer desde o estágio de desenvolvimento. Por fim, uma vez que a diferenciação in vitro não reproduziu as proporções das subpopulações de DCs vista em ex vivo, podemos concluir que a alteração no desenvolvimento de DCs em camundongos SS se deve ao ambiente inflamatório, em vez de um defeito intrínseco de DCs ou dos progenitores. Conclusão: Esses dados podem nos ajudar a entender o comportamento das células dendríticas durante a AF, tanto em termos da proporção/distribuição de seus subtipos quanto de sua influência no quadro inflamatório da doença.

Abstract In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Bacteria can exchange DNA through extracellular appendages (‘mating pili’) in a process known as conjugation. Here, Beltran et al. determine atomic structures by cryo-electron microscopy of a bacterial conjugative pilus and two archaeal pili, showing that the archaeal pili are homologous to bacterial mating pili.