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Phloroglucinol (PL) or 1,3,5-trihydroxybenzene is a phenolic compound used therapeutically for its antispasmodic properties. However, an overdose or prolonged exposure to PL can have harmful effects on human health. This work describes for the first time the development of a photoelectrochemical (PEC) sensor to determine PL. The proposed sensor is based on a fluorine-doped tin oxide (FTO) substrate modified with bismuth calcium tantalate (CaBi2Ta2O9), a ceramic perovskite powder, and bismuth vanadate (BiVO4). Both materials were characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The morphology of the BiVO4/CaBi2Ta2O9/FTO platform was evaluated using scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The photoelectrochemical response of the platform was evaluated by exploiting with light from a 36 W LED lamp confined in a low-cost homemade box. The BiVO4/CaBi2Ta2O9/FTO sensor showed superior photocurrent response compared to the FTO modified by the individual components (BiVO4/FTO and CaBi2Ta2O9/FTO). Under optimized experimental conditions, the photoelectrochemical sensor showed two linear ranges for PL concentrations ranging from 1 up to 900 µmol L-1 and from 900 up to 2000 µmol L-1, respectively.  The BiVO4/CaBi2Ta2O9/FTO sensor exhibited excellent results regarding precision, accuracy, and selectivity for PL detection. PL determination was successfully performed in water and artificial urine samples, with recovery values between 100.1 and 102.2%.

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BACKGROUND: Intraosseous myofibroma of the jaw is a rare neoplasm of mesenchymal origin with limited comprehensive understanding. It typically affects patients in the first two decades of life with a male predilection. CASE PRESENTATION: This study presents a rare case of myofibroma mimicking an odontogenic lesion in a 2-year-old boy. The patient presented with an incidental finding of a painless swelling of the right mandibular ramus of unknown etiology. Imaging analysis revealed a solid, expansile lesion adjacent to the germinal zone of the right mandibular first molar. Histopathologic analysis and immunohistochemistry after incisional biopsy suggested a possible central odontogenic fibroma, and the patient underwent total enucleation, leading to the final diagnosis of intraosseous myofibroma. Follow-up examinations showed no evidence of recurrence. CONCLUSIONS: This report contributes to the understanding of myofibroma in pediatric patients and underscores the critical role of meticulous histopathologic examination for effective surgical planning and optimal patient outcomes.

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Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

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Spain is worldwide leader in deceased donation rates per million habitants and count on a strong network of twenty-five liver transplant institutions. Although the access to liver transplantation is higher than in other countries, approximately 10% of patients qualifying for liver transplantation in Spain will die in the waiting list or would be excluded due to clinical deterioration. A robust waiting list prioritization system is paramount to grant the sickest patients with the first positions in the waiting list for an earlier access to transplant. In addition, the allocation policy may not create or perpetuate inequities, particularly in a public and universal healthcare system. Hitherto, Spain lacks a unique national allocation system for elective liver transplantation. Most institutions establish their own rules for liver allocation and only two autonomous regions, namely Andalucía and Cataluña, share part of their waiting list within their territory to provide regional priority to patients requiring more urgent transplantation. This heterogeneity is further aggravated by the recently described sex-based disparities for accessing liver transplantation in Spain, and by the expansion of liver transplant indications, mainly for oncological indications, in absence of clear guidance on the optimal prioritization policy. The present document contains the recommendations from the first consensus of waiting list prioritization for liver transplantation issued by the Spanish Society of Liver Transplantation (SETH). The document was supported by all liver transplant institutions in Spain and by the Organización Nacional de Trasplantes (ONT). Its implementation will allow to homogenize practices and to improve equity and outcomes among patients with end-stage liver disease.

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To restore invaded areas, planting fast-growing native species such as Senegalia polyphylla (DC.) Britton & Rose (Fabaceae) is widely used. However, invasive grasses reduce light availability, alter fire regimes, and compete for water and nutrients, hindering the growth of native trees. Fertilization practices influence the competition dynamics between natives and invasives by altering soil fertility. Therefore, this study investigated the effects of mineral and organic fertilization on the nutritional status and growth of S. polyphylla cultivated during the first 120 days after transplanting. The experiment was conducted in a completely randomized design comprising five treatments and four replications, along with the unfertilized control (0-0%) as an additional treatment. Dystrophic red latosol and different proportions of mineral and organic fertilizers were used. The variables evaluated included dry mass of aboveground parts and roots, nutrient content in leaves, and nutrient use efficiency. The results showed that fertilizations with high nutrient concentrations (100-0% and 75-25%) resulted in greater accumulation of N, P, and K in the leaves, while balanced fertilization (50-50% and 25-75%) led to greater root dry mass. These results emphasize the importance of strategically choosing fertilizer formulations to promote the healthy development of seedlings in areas subject to interference from invasive grasses.

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An extensive number of publications have examined cross-education effects with adults, primarily investigating contralateral homologous (same) muscles. There are far fewer investigations on cross-education effects on contralateral heterologous (different) muscles and age (youth vs adult) and no studies investigating sex differences. Hence, the objective was to compare cross-education in female and male youth and young adults to contralateral homologous (chest press [CP], elbow flexors and extensors, handgrip isometric strength, and shot put) and heterologous (leg press, knee extension isometric strength, and countermovement jump) muscles. Twenty-eight female adults, 28 female youth, 28 male adults, and 28 male youth (total: 112) were examined before and after an 8-week (3 sessions/wk) unilateral, dominant arm, CP training program. Unilateral testing assessed dominant and nondominant leg press and CP 1-repetition maximum, knee extensors, elbow extensors, elbow flexors, and handgrip maximum voluntary isometric contraction (MVIC) strength, as well as shot put distance and countermovement jump height. Unilateral CP training induced training specific (CP 1-repetition maximum) and nonspecific (elbow extensors, elbow flexors, handgrip MVIC force, and shot put distance) improvements (P < .04, η2: .45-.85) but no significant lower body improvements. There was evidence for testing limb specificity as the dominant arm provided significantly (P < .021, η2: .17-.75) greater training gains than the nondominant arm. Youth's training adaptations exceeded with unilateral CP 1-repetition maximum, elbow extensors MVIC force, and shot put distance (P < .049, η2: .14-.49). No sex main effect differences were apparent. In conclusion, cross-education was training specific (greatest gains with upper body and dominant limbs) with greater benefits for youth and generally no sex differences with the exception of elbow extensors MVIC.

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INTRODUCTION: Non-specific chronic low back pain (CLBP) predominantly affects women aged 40-80 years. Physical exercise is a primary treatment form, with functional training (FT) and dual-task training (DT) emerging as potential modalities due to their distinct characteristics. However, limited information exists regarding the effects of these exercise modalities on CLBP. OBJECTIVE: To compare the FT and DT effects on trunk function and functional fitness in CLBP older women. METHODOLOGY: This was a randomized clinical trial with two training groups (FT and DT) and CLBP and non-CLBP individuals. We assessed the trunk stability, maximum isometric strength, endurance of trunk muscles, and functional fitness before and after 16 weeks of training RESULTS: We found only time effects for circular stability and instability (p <.001), flexors (p =.006), and extensors endurance (p <.001). For the lateral flexors, there was an average reduction of 17.3 units in lateral flexor endurance in the FT compared to the DT in CLBP individuals. For the strength of the flexor, CLBP individuals exhibited an increase of 69.3 units compared to non-CLBP. For the strength of extensors, CLBP individuals showed a decrease of 75.1 units compared to non-CLBP individuals. We identified a time effect for all functional fitness measures (p <.050) CONCLUSION: FT and DT increase trunk stability, maximum isometric strength, and endurance of trunk muscles, besides the functional fitness of CLBP older women SIGNIFICANCE: Professionals can choose either training type, as there are no differences in the initial 16 weeks of intervention.

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Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling delivery strategy, offering enhanced tumor targeting and reduced toxicity. Herein, we report a novel IDEPT strategy by employing a His-tagged Leishmania mexicana type I 2'-deoxyribosyltransferase (His-LmPDT) covalently attached to glutaraldehyde-activated magnetic iron oxide nanoparticles (MIONPs). Among the resulting derivatives, PDT-MIONP3 displayed the most favorable catalyst load/retained activity ratio, prompting its selection for further investigation. Substrate specificity studies demonstrated that PDT-MIONP3 effectively hydrolyzed a diverse array of 6-oxo and/or 6-amino purine 2'-deoxynucleosides, including 2-fluoro-2'-deoxyadenosine (dFAdo) and 6-methylpurine-2'-deoxyribose (d6MetPRib), both well-known prodrugs commonly used in DEPT. The biophysical characterization of both MIONPs and PDT-MIONPs was conducted by TEM, DLS, and single particle ICPMS techniques, showing an ideal nanosized range and a zeta potential value of -47.9 mV and -78.2 mV for MIONPs and PDT-MIONPs, respectively. The intracellular uptake of MIONPs and PDT-MIONPs was also determined by TEM and single particle ICPMS on HeLa cancer cell lines and NIH3T3 normal cell lines, showing a higher intracellular uptake in tumor cells. Finally, the selectivity of the PDT-MIONP/dFAdo IDEPT system was tested on HeLa cells (24 h, 10 µM dFAdo), resulting in a significant reduction in tumoral cell survival (11% of viability). Based on the experimental results, PDT-MIONP/dFAdo presents a novel and alternative IDEPT strategy, providing a promising avenue for cancer treatment.

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Roux-en-Y gastric bypass (RYGB) involves creating a small stomach pouch, bypassing part of the small intestine, and rerouting the digestive tract. These alterations can potentially change the drug exposure and response. Our primary aim was to assess the impact of RYGB on the pharmacokinetics of simvastatin lactone (SV) and its active metabolite, simvastatin hydroxy acid (SVA). Ultimately, we aimed to optimize dosing for this understudied population by employing a population pharmacokinetic-pharmacodynamic link approach. The study comprised patients who had undergone RYGB surgery and individuals without a previous history of RYGB. All participants received a single oral dose of simvastatin. Plasma concentration data were analyzed with a nonlinear mixed-effect modeling approach. A parent-metabolite model with first-order absorption, 2-compartments for SV and 1-compartment for SVA, linear elimination, and enterohepatic circulation best described the data. The model was linked to the turnover pharmacodynamic model to describe the SVA inhibition on LDL-cholesterol production. Our simulations indicated that following RYGB surgery, the exposure to SV and SVA decreased by 40%. Consequently, for low-intensity statin patients, we recommend increasing the dose from 10 to 20 mg in post-RYGB patients to maintain a comparable response to that of non-operated subjects. Moderate-intensity statin patients should require increasing doses to 40 or 60 mg or the addition of a non-statin medication to achieve similar therapeutic outcomes. In conclusion, individuals post-RYGB exhibit diminished exposure to SV and may benefit from increasing the dose or adjunctive therapy with non-statin drugs to attain equivalent responses and mitigate potential adverse events.

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The design of novel low-dimensional carbon materials is at the forefront of modern chemistry. Recently, on-surface covalent synthesis has emerged as a powerful strategy to synthesize previously precluded compounds and polymers. Here, we report a scanning probe microscopy study, complemented by theoretical calculations, about the sequential skeletal rearrangement of sumanene-based precursors into a coronene-based organometallic network by stepwise intra- and inter-molecular reactions on Au(111). Interestingly, upon higher annealing, the formed organometallic networks evolve into two-dimensional coronene-based covalently-linked patches through intermolecular homocoupling reactions. A new reaction mechanism is proposed based on the role of C-Au-C motifs to promote two stepwise carbon-carbon couplings to form cyclobutadiene bridges. Our results pave avenues for the conversion of molecular precursors on surfaces, affording the design of unexplored two-dimensional organometallic and covalent materials.

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This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, a significant efficacy of 54.5 and 36.4% was observed in the dissipation of the herbicide, especially at higher doses. Although metolachlor application reduced soil microbial biodiversity, phytoremediating plants, especially M. sativa, promoted greater richness and distribution of microbial species, mitigating the negative effects of the herbicide. Principal component analysis revealed the influence of these plants and metolachlor on the composition of the microbial community. These results highlight the importance of phytoremediation in promoting soil biodiversity and reducing herbicide contamination, providing crucial insights for remediation strategies in contaminated areas.

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Genioplasty is a widely used surgical approach to address chin deformities by performing an osteotomy on the inferior border of the mandible to allow for comprehensive repositioning of the chin. This study aimed to compare the accuracy of freehand chin repositioning with a guided technique that employed specialised surgical guides. For this retrospective study, data from 30 adult patients who underwent orthognathic surgery to correct dentofacial deformities were analysed. All patients underwent virtual planning before surgery, with half of them treated using freehand chin repositioning and the other half using the guided technique. The surgical outcomes were measured and compared with the virtual plan to assess the positional and rotational accuracy of the techniques. In terms of translational assessment, noteworthy values that exceeded clinically acceptable limits were observed only in sagittal movement in the freehand group (0.97 mm, interquartile range (IQR) 0.73-2.29 mm). Regarding rotational accuracy, both groups exhibited an IQR that surpassed acceptable limits for pitch (3.26°, IQR 2.06-5.20 for the guided group and 2.57°, IQR 1.63-4.24° for the freehand group). The Mann-Whitney test indicated no statistical differences between the groups in any translational or rotational assessment. In conclusion, although there was no statistical difference, the guided technique proved effective in achieving clinically acceptable accuracy in all positions and almost all rotations, displaying superior results in sagittal positioning compared with the freehand technique. To fully harness the advantages of guides and to guarantee accuracy in all rotations, we recommend further research involving guides made of more rigid materials, and customised implants.

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The prevalence of obesity is increasingly widespread, resembling a global epidemic. Lifestyle changes, such as consumption of high-energy-dense diets and physical inactivity, are major contributors to obesity. Common features of this metabolic pathology involve an imbalance in lipid and glucose homeostasis including dyslipidemia, insulin resistance and adipose tissue dysfunction. Moreover, the importance of the gut microbiota in the development and susceptibility to obesity has recently been highlighted. In recent years, new strategies based on the use of functional foods, in particular bioactive peptides, have been proposed to counteract obesity outcomes. In this context, the present study examines the effects of a lupin protein hydrolysate (LPH) on obesity, dyslipidemia and gut dysbiosis in mice fed a high-fat diet (HFD). After 12 weeks of LPH treatment, mice gained less weight and showed decreased adipose dysfunction compared to the HFD-fed group. HFD-induced dyslipidemia (increased triglycerides, cholesterol and LDL concentration) and insulin resistance were both counteracted by LPH consumption. Discriminant analysis differentially distributed LPH-treated mice compared to non-treated mice. HFD reduced gut ecological parameters, promoted the blooming of deleterious taxa and reduced the abundance of commensal members. Some of these changes were corrected in the LPH group. Finally, correlation analysis suggested that changes in this microbial population could be responsible for the improvement in obesity outcomes. In conclusion, this is the first study to show the effect of LPH on improving weight gain, adiposopathy and gut dysbiosis in the context of diet-induced obesity, pointing to the therapeutic potential of bioactive peptides in metabolic diseases.

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Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

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Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers among all solid tumors. First-line treatment relies on gemcitabine (Gem) and despite treatment improvements, refractoriness remains a universal challenge. Attempts to decipher how feedback-loops control signaling pathways towards drug resistance have gained attention in recent years, particularly focused on the role of phosphatases. In this study, a CRISPR/Cas9-based phenotypic screen was performed to identify members from the dual-specificity phosphatases (DUSP) family potentially acting on Gem response in PDAC cells. The approach revealed the atypical RNA phosphatase DUSP11 as a potential target, whose inhibition creates vulnerability of PDAC cells to Gem. DUSP11 genetic inhibition impaired cell survival and promoted apoptosis, synergistically enhancing Gem cytotoxicity. In silico transcriptome analysis of RNA-seq data from PDAC human samples identified NF-ĸB signaling pathway highly correlated with DUSP11 upregulation. Consistently, Gem-induced NF-ĸB phosphorylation was blocked upon DUSP11 inhibition in vitro. Mechanistically, we found that DUSP11 directly impacts nc886 expression and modulates PKR-NF-ĸB signaling cascade after Gem exposure in PDAC cells resulting in resistance to Gem-induced cell death. In conclusion, this study provides new insights on DUSP11 role in RNA biology and Gem response in PDAC cells.

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OBJECTIVE: To assess the quality of care transition from hospital to home for COVID-19 patients. METHOD: A cross-sectional study conducted at a University Hospital in Southern Brazil, involving 78 patients discharged after COVID-19 hospitalization. Data collection was performed via telephone using the Brazilian version of the Care Transitions Measure (CTM-15). Data were analyzed using descriptive and analytical statistics. RESULTS: The mean quality of care transition was 70.8 on a scale ranging from zero to 100, indicating moderate quality of care transition. The highest score was attributed to factor 1, "Preparation for self-management," and the lowest to factor 4, "Care Plan." CONCLUSIONS: It is important to enhance communication and support provided to patients during the transition process, especially regarding understanding prescribed medications and the development of clear care plans.

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BACKGROUND: Suicide is a complex public health issue. Surveillance systems play a vital role in identifying trends and epidemiologic needs, informing public health strategies, and tailoring effective context-based suicide prevention interventions. AIM: To identify and summarise the characteristics of specific surveillance systems and general health behaviour that include data onsuicide and self-harm. METHOD: A scoping review following the JBI recommendations and PRISMA-ScR guidelines identified 29 relevant studies on suicide and self-harm surveillance systems. A systematic search was performed on Cinahl, Embase, Lilacs-Latin American and Caribbean Health Sciences Literature, PubMed-US National Library of Medicine, Scopus, and Google Scholar. The eligibility criteria include papers that use qualitative, quantitative or mixed methods with no restrictions on time or language. The following papers were excluded regarding euthanasia and assisted suicide, as well as papers that did not explicitly describe suicide, self-harm, and surveillance systems. Two researchers independently screened the materials for eligibility and extracted data from the included studies. Data analysis was conducted using content analysis. RESULTS: Twenty-nine references were included, and 30 surveillance systems were identified and classified into general health behaviour surveillance (n = 15) and specific systems for suicide and self-harm (n = 15). General health behaviour systems often operate at national data collection level, collecting non-fatal data in healthcare settings, mainly emergency departments. The specific systems exhibited greater variability in terms of context, involved actors, data collection level, data collection procedures, and case classification. Limitations found by the studies pointed mostly to case definitions and data quality. Co-production, intersectoral collaboration, clear case definition criteria and data standardisation are essential to improve surveillance systems for suicide and self-harm. CONCLUSIONS: This review identified the characteristics of surveillance systems for suicide and self-harm. Monitoring and evaluation are crucial for ongoing relevance and impact on prevention efforts.

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Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden.

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OBJECTIVE: To compare the effect of a fully undisturbed culture strategy over a sequential one on embryo in vitro development and clinical outcomes in intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Retrospective cohort study. SETTING: University-affiliated private IVF center. PATIENT(S): This study included 4,564 ICSI cycles performed over 5 years, including autologous and oocyte donation treatments with extended embryo culture until blastocyst in one of the two defined culture strategies. INTERVENTION(S): Embryo cohorts were cultured in one of two culture systems: a fully undisturbed culture, including an incubator with integrated time-lapse technology, a one-step culture medium and embryo selection assisted by semi-automatic tools on the basis of embryo morphokinetics, or a sequential culture, using a conventional benchtop incubator, sequential media and traditional morphological evaluation under optical microscope. The effect of the culture strategies on embryo development and clinical outcomes was quantified by generalized estimated equations, controlling for possible confounders through the inverse probability of the treatment weighting method. MAIN OUTCOME MEASURE(S): Weighted odds ratios (ORs) and 95% confidence intervals (CIs) for live birth rate after fresh single embryo transfer and the cumulative live birth rate. In addition, blastocyst development and morphology and other intermediate outcomes were also assessed. RESULT(S): A significant positive association was found between the employment of undisturbed embryo culture and higher live birth rate in the first embryo transfer in both autologous (OR, 1.617; 95% CI, 1.074-2.435) and oocyte donation cycles (OR, 1.316; 95% CI, 1.036-1.672). Cumulative live birth rate after 1-year follow-up was also positively associated with the undisturbed culture strategy in oocyte donation cycles (OR, 1.5; 95% CI, 1.179-1.909), but not in autologous cycles (OR, 1.051; 95% CI, 0.777-1.423). Similarly, blastocyst rate, good morphology blastocyst rate, and utilization rate were positively associated with the employment of undisturbed culture in oocyte donation cycles, but not in autologous cycles. CONCLUSION(S): These findings imply that a culture system combining integrated time-lapse incubators with a one-step culture medium may enhance the success rates of patients undergoing ICSI treatment by increasing the production of higher quality blastocysts and improving embryo selection while streamlining laboratory procedures and workflow.

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BACKGROUND: Paracoccidioidomycosis (PCM) may involve the hepatic pedicle and peripancreatic lymph nodes, cause damage to the bile duct and manifest, exceptionally, in combination with extrahepatic cholestasis (EHC), making investigation and treatment challenging. AIM: To investigate the management of patients with visceral PCM admitted with EHC. METHODS: All patients diagnosed with PCM treated in a public, tertiary teaching hospital between 1982 and 2020 were retrospectively evaluated. Those also identified with EHC were allocated to two groups according to the treatment approach for the purpose of comparing clinical, laboratory, and imaging findings, resources used for etiological diagnosis, treatment results, and prognosis. Statistical analyses were performed using the linear mixed-effects model (random and fixed effects), which was adjusted using the PROC MIXED procedure of the SAS® 9.0 software, and Fisher's exact test. RESULTS: Of 1645 patients diagnosed with PCM, 40 (2.4%) had EHC. Of these, 20 (50.0%) lived in the rural area and 29 (72.5%) were men, with a mean age of 27.1 years (3-65 years). Jaundice as first symptom and weight loss of at least 10 kg were observed in 16 patients (40.0%), and a mass in the head of the pancreas was observed in 8 (20.0%). The etiological diagnosis was made by tissue collection during surgery in 4 cases (10.0%) and by endoscopic methods in 3 cases (7.5%). Twenty-seven patients (67.5%) received drug treatment alone (Group 1), whereas 13 (32.5%) underwent endoscopic and/or surgical procedures in combination with drug treatment (Group 2). EHC was significantly reduced in both groups (40.7% in Group 1, with a mean time of 3 months; and 38.4% in Group 2, with a mean time of 7.5 months), with no statistically significant difference between them. EHC recurrence rates, associated mainly with treatment nonadherence, were similar in both groups: 37% in Group 1 and 15.4% in Group 2. The mortality rate was 18.5% in Group 1 and 23% in Group 2, with survival estimates of 71.3% and 72.5%, respectively, with no statistically significant difference. CONCLUSION: Although PCM-related EHC is rare, it needs to be included in the differential diagnosis of malignancies, as timely treatment can prevent hepatic and extrahepatic sequelae.