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The objective of this study was to compare, in normal women, metabolic and cardiorespiratory variables at rest with those obtained during horseback riding at a walking gait. Metabolic and cardiorespiratory parameters were measured employing a portable VO2000 Medgraphics gas analyzer. The results demonstrated a significant increase in oxygen uptake, caloric expenditure, METs and heart rate at the beginning of the exercise. Maintenance of the activity was followed by a decrease in these values which became stable until the end of the riding. The results indicate that the postural adjustments induced by horseback riding are sufficient to produce metabolic and cardiorespiratory responses in the rider. [ABSTRACT FROM AUTHOR]

Background: To measure patient satisfaction with synchronous telehealth care, we administered the Telemedicine Satisfaction Questionnaire (TSQ) to assess the quality of care provided, its similarity to face-to-face meetings, and patients' perception of the interaction., Methods: The Portuguese version of the TSQ was administered during 2022 to patients who received postoperative synchronous telehealth care after strabismus surgery in Curitiba, Brazil, from 2020 to 2022. The interval between the questionnaire application and teleconsultation ranged from 2 to 22 months after the telehealth encounter. All patients received synchronous telehealth care from the same surgeon (LMH) between postoperative days 7 and 10 and attended an in-person consultation on postoperative day 30 6 months after surgery, and yearly thereafter., Results: We analyzed the data for 53 patients, of whom 26 (49%) were male and 28 (53%) were <18 years of age. Synchronous telehealth care was considered an excellent experience, with an overall average TSQ rating of 4.3 on a scale of 1-5. The mean score for quality of care provided was 4.1; for similarity of care to face-to-face meetings, 4.5; and for patients' perception of the interaction, 4.5., Conclusions: Ratings of the synchronous telehealth care were strongly associated with the 30-day postoperative evaluation, and patient perceptions of the quality of care in the telehealth encounter were positive., (Copyright © 2024. Published by Elsevier Inc.)

Fungal endocarditis following transcatheter aortic valve implantation (TAVI) is a rare and serious complication of this procedure. We describe a case of a 75-year-old patient who developed fungal endocarditis caused by Candida albicans, complicated by an aortic pseudoaneurysm., (© 2024. The Author(s).)

Citriculture is facing challenges due to the spread of various diseases, among which the most threatening, with worldwide occurrence, is Huanglongbing (HLB), caused by the bacteria Candidatus Liberibacter spp., vectored by psyllids. In orchards, HLB-infected plants are identified by visual observation of symptoms. For laboratory diagnosis, the gold standard is the polymerase chain reaction (PCR), requiring expertise and specific equipment, and with high financial cost. In this work, a selective impedimetric immunosensor was developed for the detection and determination of Ca. L. asiaticus (CLas) in citrus samples. An anti-HLB antibody against the outer membrane protein (OMP) sequence of CLas was obtained and immobilized on previously synthesized and characterized magnetic nanoparticles. The immobilized antibody was presented to various citrus leaf sample extracts. After the affinity reaction with the antigen, a washing step was performed to minimize matrix effects. The affinity reaction was monitored by electrochemical impedance spectroscopy, using a glassy carbon working electrode containing a neodymium magnet. The developed device was able to distinguish HLB-positive samples from HLB-negative samples and those with other infections. The results obtained with the proposed methodology were in good agreement with quantitative PCR (qPCR)., Competing Interests: Declaration of competing interest The authors declared than not exist conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

With the advent of advanced sequencing technologies, new insights into the genomes of pathogens, including those in the genus Curtobacterium, have emerged. This research investigates a newly isolated C. flaccumfaciens strain 208 (Cf208) from Arthrocereus glaziovii, and endemic plant from Iron Quadrangle. Previous results show that Cf208 exhibits the potential to remediate soils, facilitating the growth of tomato plants. Furthermore, Cf208 showed no virulence towards bean plants, thus, confounding its phytopathogenic origins. Using a comprehensive comparative genomics approach, we analyzed the Cf208 genome against 34 other Curtobacterium strains, aiming to discern the genomic landmarks associated with its adaptation as an endophyte and its avirulence in bean crops. This revealed a predominant core genome comprising about 2426 genes (68%). Notably, Cf208 possesses a unique plasmid, pCF208-73, which contains 84 unique genes (2.5%). However, unlike the plasmids previously described for pathogenic strains, pCF208-73 does not feature genes associated with virulence induction. In contrast, while several genes traditionally linked to virulence, like pectate lyases and proteases were identified, but the T4P apparatus emerged as new crucial factor for understanding virulence in the Curtobacterium genus. The presence or absence of this apparatus, especially in strains from different clades, may determine their virulence towards leguminous plants. In conclusion, this work highlights the significance of comparative genomics in unraveling the complexities of pathogenicity within the Curtobacterium genus. Our findings suggest that, although the limited genetic variations, specific genes, particularly those linked to the T4P apparatus, play a fundamental role in their interactions with host plants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase., Objective: To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group., Methods: This was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6)., Results: MB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group., Conclusion: Early administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock., Clinical Trial Registration: https://clinicaltrials.gov/, identifier RBR-96584w4., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luis-Silva, Menegueti, Peres, Sepeda, Jordani, Mestriner, Petroski-Moraes, Brito-de-Sousa, Costa-Rocha, Cruz, Donadel, de Souza, Reis, Bellissimo-Rodrigues, Basile-Filho, Becari, Evora, Martins-Filho and Auxiliadora-Martins.)

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg -1 ) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx., (© 2024. The Author(s).)

Introduction: Hidradenitis Suppurativa (HS) is a chronic inflammatory disorder that affects the pilosebaceous unit. Squamous Cell Carcinoma (SCC) can emerge as a complication., Presentation of Case: A 58-year-old male patient with a history of smoking, obesity, and type 2 diabetes was initially managed by a dermatology team for Follicular Occlusion Syndrome manifesting as HS. Despite clinical treatment, the patient was referred to the Coloproctology Unit because of the development of a lesion in the perianal region near the HS lesions. Physical examination revealed an ulcerated, vegetative, painful, and friable lesion in the right perianal region consistent with SCC of the HS scar. The patient underwent chemotherapy and radiotherapy, but the lesions recurred, necessitating abdominoperineal amputation of the rectum., Discussion: Although rare, patients with chronic HS are at an increased risk of developing SCC, particularly in the perineal and gluteal regions. The standard treatment protocol for SCC in HS involves chemoradiotherapy with the aim of preserving the anal sphincter and avoiding surgery. Surgical intervention is reserved for patients that are unresponsive to chemoradiotherapy or for advanced cases in which local resection is insufficient., Conclusion: This disease course aligns with the epidemiology of HS, which predominantly affects male individuals with chronic lesions in the perianal, gluteal, and perineal regions. Such lesions can progress severely, often resisting non-invasive treatments and requiring more aggressive surgical interventions., Competing Interests: Conflict of interest statement The authors declare no competing interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ramon syndrome (OMIM #266270) was first described in a patient with cherubism, gingival fibromatosis, epilepsy, intellectual disability, hypertrichosis, and stunted growth. In 2018, Mehawej et al. described a patient with Ramon syndrome in whom a homozygous variant in ELMO2 was identified, suggesting that this gene may be the causative for this syndrome. ELMO2 biallelic pathogenic variants were also described in patients with a primary intraosseous vascular malformation (PIVM; OMIM #606893). These patients presented gingival bleeding and cherubism phenotype. Herein, a patient with gingival hypertrophy, neurodevelopmental delay, and cherubism phenotype with a novel homozygous predicted loss-of-function (LOF) variant in the ELMO2 gene and family recurrence was reported. A surgical approach to treat gingival bleeding and mandible vascular malformation was also described. Furthermore, this study includes a comprehensive literature review of molecular data regarding the ELMO2 gene. All the variants, except one described in the ELMO2, were predicted as LOF, including our patient's variant. There is an overlapping between PIVM, also caused by LOF biallelic variants in the ELMO2 gene, and Ramon syndrome, which can suggest that they are not different entities. However, due to a limited number of cases described with molecular evaluation, it is hard to establish a genotype-phenotype correlation. Our study supports that LOF pathogenic biallelic variants in the ELMO2 gene cause a phenotype that has cherubism and gingival hypertrophy as main characteristics., (© 2024 Wiley Periodicals LLC.)

Introduction: High-dose cytarabine is considered standard of care as consolidation chemotherapy in adults with acute myeloid leukemia (AML) who are not eligible for allogeneic hematopoietic cell transplantation, but may be associated with significant toxicity. We evaluated the toxicity associated with high-dose cytarabine given as consolidation in AML patients treated at a Brazilian public hospital., Methods: We retrospectively reviewed the charts of all patients with AML treated between 2008 and 2020 who obtained complete remission (CR) after one cycle of induction chemotherapy and received consolidation with at least one cycle of high-dose cytarabine (defined as 3 g/m 2 every 12 h days 1, 3 and 5)., Results: Among 61 patients who received induction remission, 32 obtained CR and 28 received at least one cycle of high-dose cytarabine, for a total of 67 cycles (median 2 cycles per patient, range 1 - 4). In 45 cycles (67.2%) the patient was discharged after the end of chemotherapy, with a median of 6 days at home (range 3 - 8). Readmission occurred in 31 of the 45 cycles (68.9%). The most frequent toxicities were febrile neutropenia (56.7%), nausea and vomiting (23.9%), oral mucositis (14.9%) and diarrhea (11.9%). Bacteremia was documented in 13 cycles (34.2%). There were three cases of typhlitis and two of invasive fungal disease (aspergillosis and candidemia). Four patients died (14.3%), with two deaths considered treatment-related (candidemia and typhlitis)., Conclusion: In the setting of a Brazilian public hospital, high-dose cytarabine as consolidation therapy is feasible, with manageable toxicity profile., Competing Interests: Conflicts of interest None., (Copyright © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To develop and validate a predictive model utilizing machine-learning techniques for estimating the length of hospital stay among patients who underwent coronary artery bypass grafting., Methods: Three machine learning models (random forest, extreme gradient boosting and neural networks) and three traditional regression models (Poisson regression, linear regression, negative binomial regression) were trained in a dataset of 9,584 patients who underwent coronary artery bypass grafting between January 2017 and December 2021. The data were collected from hospital discharges from 133 centers in Brazil. Algorithms were ranked by calculating the root mean squared logarithmic error (RMSLE). The top performing algorithm was validated in a never-before-seen database of 2,627 patients. We also developed a model with the top ten variables to improve usability., Results: The random forest technique produced the model with the lowest error. The RMLSE was 0.412 (95%CI 0.405-0.419) on the training dataset and 0.454 (95%CI 0.441-0.468) on the validation dataset. Non-elective surgery, admission to a public hospital, heart failure, and age had the greatest impact on length of hospital stay., Conclusions: The predictive model can be used to generate length of hospital stay indices that could be used as markers of efficiency and identify patients with the potential for prolonged hospitalization, helping the institution in managing beds, scheduling surgeries, and allocating resources.

Aims: Cardiogenic shock (CS) and cardiac arrest (CA) are serious complications in ST-elevation myocardial infarction (STEMI) patients, with lack of long-term data according to their timing of occurrence. This study sought to determine the incidence and relationship between the timing of occurrence and prognostic impact of CS and CA complicating STEMI in the long-term follow-up., Methods and Results: We conducted a retrospective analysis of consecutive STEMI patients treated between 2004 and 2017. Patients were divided into four groups based on the occurrence of neither CA nor CS, CA only, CS only, and both CA and CS (CA-CS-, CA+, CS+, and CA+CS+, respectively). Adjusted Cox regression analysis was used to assess the independent association between the CS and CA categories and mortality. A total of 1603 STEMI patients were followed for a median of 3.6 years. CA and CS occurred in the 12.2% and 15.9% of patients, and both impacted long-term mortality [adjusted hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.53-4.41, P < 0.001; HR = 3.16, 95% CI: 2.21-4.53, P < 0.001, respectively). CA+CS+ occurred in 7.3%, with the strongest association with higher mortality (adjusted HR = 5.36; 95% CI: 3.80-7.55, P < 0.001). Using flexible parametric models with B-splines, the increased mortality was restricted to the first ∼10 months. In addition, overall mortality rates were higher at all timings (all with P < 0.001), except for CA during initial cardiac catheterization ( P < 0.183)., Conclusion: CS and CA complicating patients presenting with STEMI were associated with higher long-term mortality rate, especially in the first 10 months. Both CS+ and CA+ at any timeframe impacted outcomes, except for CA+ during the initial cardiac catheterization, although this will have to be confirmed in larger future studies, given the relatively small number of patients., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Gantenerumab is a monoclonal antibody targeting amyloid β protein (Aβ) in early Alzheimer's disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients., Methods: MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel-Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis., Results: A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD -0.11; 95% CI -0.19- -0.03; p  = 0.008569; I 2  = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55-16.11; p = <0.000001; I 2  = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50-2.13; p = <0.000001; I 2  = 0%), respectively., Discussion: In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.

Coronary heart disease (CHD) is a prevalent cardiac disease that causes over 370,000 deaths annually in the USA. In CHD, occlusion of a coronary artery causes ischemia of the cardiac muscle, which results in myocardial infarction (MI). Junctophilin-2 (JPH2) is a membrane protein that ensures efficient calcium handling and proper excitation-contraction coupling. Studies have identified loss of JPH2 due to calpain-mediated proteolysis as a key pathogenic event in ischemia-induced heart failure (HF). Our findings show that calpain-2-mediated JPH2 cleavage yields increased levels of a C-terminal cleaved peptide (JPH2-CTP) in patients with ischemic cardiomyopathy and mice with experimental MI. We created a novel knock-in mouse model by removing residues 479-SPAGTPPQ-486 to prevent calpain-2-mediated cleavage at this site. Functional and molecular assessment of cardiac function post-MI in cleavage site deletion (CSD) mice showed preserved cardiac contractility and reduced dilation, reduced JPH2-CTP levels, attenuated adverse remodeling, improved T-tubular structure, and normalized SR Ca 2+ -handling. Adenovirus mediated calpain-2 knockdown in mice exhibited similar findings. Pulldown of CTP followed by proteomic analysis revealed valosin-containing protein (VCP) and BAG family molecular chaperone regulator 3 (BAG3) as novel binding partners of JPH2. Together, our findings suggest that blocking calpain-2-mediated JPH2 cleavage may be a promising new strategy for delaying the development of HF following MI., Competing Interests: Declaration of competing interest XHTW is a consultant for Pfizer and Rocket Pharmaceuticals, and a founding partner and board member of Elex Biotech Inc., a start-up company that developed drug molecules that target ryanodine receptors to treat cardiac arrhythmia disorders. LZ is the co-founder and consultant for Pelagos Pharma Inc., a start-up company that develop drug molecules that target nuclear receptors to treat heart failure and neurodegenerative disorders. Other authors have no potential conflicts to disclose. AI-assisted technology is not used in the preparation of this work (except checking grammar and spelling)., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We report the genomic analysis from early equine cases of the Western equine encephalitis virus outbreak during 2023-2024 in Uruguay. Sequences are related to a viral isolate from an outbreak in 1958 in Argentina. A viral origin from South America or continuous enzootic circulation with infrequent spillover is possible.

Summarising hair cortisol concentration (HCC) methodology may provide much-needed data toward protocol standardisation to maximise future comparability of findings across studies. We searched five electronic databases, reviewing 11,716 publications focused on protocols previously used to measure hair cortisol. Our aim was to determine the frequency with which each procedure was reported in the literature. We then conducted a meta-analysis of the HCC results and proposed a checklist for reporting methodological procedures related to HCC. Using pre-selected key terms, we searched for population-based, non-experimental studies reporting HCC outcomes published up to November 2023. Eighty-seven analytical samples were included in the qualitative analysis and 28 in the quantitative analysis. The analyzed studies predominantly included children (≤10 years; 45.4 %) and mainly involved participants from European populations (72.6 %). There was significant variation in hair sample collection procedures across the studies. Most used hair samples up to 3 cm in length (92 %), with around one-third employing either milled (33.3 %) or minced (29.9 %) as grinding methods. For quantification, LC-MS was the most common method (47.1 %), followed by ELISA (24.1 %). Meta-analysis showed significant variability in the mean HCC observed. Meta-regression showed no association between differences in methodology and HCC. In conclusion, the absence of a standardized protocol in HCC research may result in procedural variability, making it difficult to compare findings across studies. Many published studies lacked sufficient detail in describing their methods. To address this, we propose a checklist of reporting guidelines for measurement procedures related to HCC., Competing Interests: Declaration of Competing Interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Endodontic microsurgery guided by navigation systems represents a precise and minimally invasive approach for retreatment of apical periodontitis following failed conventional endodontic therapy. Accurate localization and minimal access to the root apex are paramount for successful outcomes and preservation of anatomical structures. Workflow considerations, such as three-dimensional (3D) virtual planning and endodontic guidance represent new crucial aspects for addressing complex cases. This clinical case report presents the successful reintervention of a complex case using a Zekrya bur, operative microscopy, cone beam computed tomography and biocompatible materials. After a 48-month follow-up, complete healing of the treated area was observed. This minimally invasive technique, employing a simple instrument widely available globally, underscores the potential for efficient and predictable outcomes in complex endodontic microsurgical retreatment., (© 2024 Australian Society of Endodontology Inc.)

This document on myopia control is derived from a compilation of medical literature and the collective clinical expertise of an expert committee comprising members from the Brazilian Society of Pediatric Ophthalmology and the Brazilian Society of Contact Lenses and Cornea. To manage myopia in children, the committee recommends corneal topography and biannual visits with cycloplegic refraction, along with annual optical biometry. For fast-progressing myopia, biannual biometry should be considered. Myopic progression is defined as an annual increase in spherical equivalent greater than 0.50 D/year or in axial length greater than 0.3 mm (until 10 years old) or 0.2 mm (above 11 years). The proposed treatments for myopia progression include environmental control, low concentration atropine, defocus glasses, contact lenses, or Ortho-K lenses, and combinations of these methods may be necessary for uncontrolled cases. Treatment should be sustained for at least 2 years. This document serves as a comprehensive guideline for diagnosing, treating, and monitoring pre-myopic and myopic children in Brazil.

This study assessed the effects of increased pre-start diet density on the metabolism, crop filling, and overall performance of broilers under cold stress during their initial 14 days of life. Using 576 one-day-old Cobb500 male chicks from 27-week-old breeders, the experiment employed a 2 × 2 arrangement, varying thermal conditions (thermoneutrality or cold stress at 18 °C for 8 h) and pre-start diet composition (21.5% crude protein, 2970 kcal/kg or 22.5%, 3050 kcal/kg). The cold stress group exhibited lower cloacal temperature and decreased crop filling rate during the first two days (P < 0.05). Chick behavior was significantly affected at 1 and 5 days (P < 0.05), and corticosterone levels in serum were higher for the cold stress group at 7 days (P < 0.05). Feed intake at 7 days was lower in the high-density feed group (P < 0.05). No significant interactions were observed for feed intake, body weight gain, or feed conversion ratio at 7 and 35 days (P > 0.05). Cold stress resulted in performance losses, impacting feed conversion and the Productive Efficiency Index. The dense diet influenced performance only within the first week, with subsequent diets showing no effect, suggesting dietary manipulation alone was insufficient to mitigate cold stress-induced losses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Increased attention is being focused on the biological control of agricultural pests using microorganisms, owing to their potential as a viable substitute for chemical control methods. Insect cadavers constitute a potential source of entomopathogenic microorganisms. We tested whether bacteria and fungi isolated from Spodoptera frugiperda (JE Smith) cadavers could affect its survival, development, egg-laying pattern, and hatchability, as well as induce mortality in Anthonomus grandis Boheman adults. We isolated the bacteria Enterobacter hormaechei and Serratia marcescens and the fungi Scopulariopsis sp. and Aspergillus nomiae from fall armyworm cadavers and the pest insects were subjected to an artificial diet enriched with bacteria cells or fungal spores to be tested, in the case of S. frugiperda, and only fungal spores in the case of A. grandis. Enterobacter hormaechei and A. nomiae were pathogenic to S. frugiperda, affecting the survival of adults and pupae. The fungus Scopulariopsis sp. does not affect the survival of S. frugiperda caterpillars and pupae; however, due to late action, moths and eggs may be affected. Aspergillus nomiae also increased mortality of A. grandis adults, as well as the development of S. frugiperda in the early stages of exposure to the diet, as indicated by the vertical spore transfer to offspring and low hatchability. Enterobacter hormaechei and A. nomiae are potential biocontrol agents for these pests, and warrant further investigation from a toxicological point of view and subsequently in field tests involving formulations that could improve agricultural sustainability practices., (© 2024. The Author(s).)

Background: Accessory pathways are a common cause of supraventricular tachycardia (SVT) and can lead to sudden cardiac death in otherwise healthy children and adults when associated with Wolff-Parkinson-White syndrome. The goal of this study was to identify genetic variants within a large family with structurally normal hearts affected by SVT and Wolff-Parkinson-White syndrome and determine causality of the gene deficit in a corresponding mouse model., Methods: Whole exome sequencing performed on 2 distant members of a 3-generation family in which multiple members were affected by SVT or Wolff-Parkinson-White pattern (preexcitation) on ECG identified MRC2 as a candidate gene. Serial electrocardiograms, intracardiac electrophysiology studies, echocardiography, optical mapping studies, and histology were performed on both Mrc2 mutant and WT (wild-type) mice., Results: A rare HET (heterozygous) missense variant c.2969A>G;p.Glu990Gly (E990G) in MRC2 was identified as the leading candidate gene variant segregating with the cardiac phenotype following an autosomal-dominant Mendelian trait segregation pattern with variable expressivity. In vivo electrophysiology studies revealed reentrant SVT in E990G mice. Optical mapping studies in E990G mice demonstrated abnormal retrograde conduction, suggesting the presence of an accessory pathway. Histological analysis of E990G mouse hearts showed a disordered ECM (extracellular matrix) in the annulus fibrosus. Finally, Mrc2 knockdown in human cardiac fibroblasts enhanced accelerated cell migration., Conclusions: This study identified a rare nonsynonymous variant in the MRC2 gene in individuals with familial reentrant SVT, Wolff-Parkinson-White ECG pattern, and structurally normal hearts. Furthermore, Mrc2 knock-in mice revealed an increased incidence of reentrant SVT and bypass tract formation in the setting of preserved cardiac structure and function., Competing Interests: Dr Lupski has stock ownership in 23andMe (Sunnyvale, CA), is a paid consultant for the Regeneron Genetics Center (Tarrytown, NY), and is a coinventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing conducted at Baylor Genetics (BG) Laboratories (Houston, TX). Dr Lupski serves on the Scientific Advisory Board of BG. Dr Wehrens is a cofounder and board member of Elex Biotech LLC, a start-up company developing RyR2 (ryanodine receptor type-2) modifying drugs for heart disease. Dr Wehrens is also a consultant at Pfizer and Rocket Pharmaceuticals. The other authors report no conflicts.

Objective: To investigate excess mortality during the COVID-19 pandemic and its spatial distribution in Pernambuco, Brazil., Methods: This was an ecological, descriptive and analytical study of deaths, by municipality, recorded on the Mortality Information System, in 2020 and 2021. Excess mortality was measured by comparing observed and expected deaths, the latter estimated by calculating standardized mortality ratio (SMR). SMR and respective confidence intervals (95%CI) were calculated. Spatial analysis was performed by calculating the Global and Local Moran Index., Results: Excess mortality was 20.6% and 27.5%, respectively, in 2020 and 2021, with positive spatial correlation (p-value < 0.05). More populous municipalities (2020: SMR = 1.26; 95%CI 1.24;1.27 and 2021: SMR = 1.34; 95%CI 1.32;1.34), more developed municipalities (2020: SMR = 1.43; 95%CI 1.41;1.44 and 2021: SMR = 1.51;95%CI 1.50;1.53) and municipalities in the Sertão region (2020:SMR = 1.31;95%CI 1.30;1.33 and 2021: SMR = 1.44; 95%CI 1.42;1.46) showed greater excess deaths., Conclusion: Excess mortality coincided with peak periods of COVID-19 transmission.

Exploring the intricate relationships between plants and their resident microorganisms is crucial not only for developing new methods to improve disease resistance and crop yields but also for understanding their co-evolutionary dynamics. Our research delves into the role of the phyllosphere-associated microbiome, especially Actinomycetota species, in enhancing pathogen resistance in Theobroma grandiflorum, or cupuassu, an agriculturally valuable Amazonian fruit tree vulnerable to witches' broom disease caused by Moniliophthora perniciosa. While breeding resistant cupuassu genotypes is a possible solution, the capacity of the Actinomycetota phylum to produce beneficial metabolites offers an alternative approach yet to be explored in this context. Utilizing advanced long-read sequencing and metagenomic analysis, we examined Actinomycetota from the phyllosphere of a disease-resistant cupuassu genotype, identifying 11 Metagenome-Assembled Genomes across eight genera. Our comparative genomic analysis uncovered 54 Biosynthetic Gene Clusters related to antitumor, antimicrobial, and plant growth-promoting activities, alongside cutinases and type VII secretion system-associated genes. These results indicate the potential of phyllosphere-associated Actinomycetota in cupuassu for inducing resistance or antagonism against pathogens. By integrating our genomic discoveries with the existing knowledge of cupuassu's defense mechanisms, we developed a model hypothesizing the synergistic or antagonistic interactions between plant and identified Actinomycetota during plant-pathogen interactions. This model offers a framework for understanding the intricate dynamics of microbial influence on plant health. In conclusion, this study underscores the significance of the phyllosphere microbiome, particularly Actinomycetota, in the broader context of harnessing microbial interactions for plant health. These findings offer valuable insights for enhancing agricultural productivity and sustainability., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prcis: Selective laser trabeculoplasty (SLT) and medical therapy groups displayed comparable intraocular pressure (IOP) at most follow-ups. SLT was associated with significantly decreased rates of glaucoma surgeries, antiglaucomatous medications, and ocular adverse effects., Purpose: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) compared to medical therapy in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT)., Methods: A systematic search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Randomized controlled trials (RCTs) comparing SLT with medical therapy were included. We computed mean differences (MDs) or standardized mean differences (STDs) for continuous endpoints and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 statistics. Software R, version 4.2.1, was used for statistical analyses. Subgroup analyses were performed on treatment-naive patients and on the class of drugs in the medical therapy group., Results: Fourteen RCTs comprising 1,706 patients were included, of whom 936 were submitted to SLT. Medical therapy was associated with a significantly improved IOP at 1 month and a higher proportion of patients achieving ≥20% IOP reduction. There were no significant differences between groups in IOP at 2, 3, 6, and 12 months, IOP fluctuation, rate of eyes at target IOP, visual field, and quality of life. The SLT group exhibited significantly decreased rates of glaucoma surgeries, antiglaucoma medications, and ocular adverse effects., Conclusion: SLT demonstrated comparable efficacy to medical therapy in IOP control at most follow-ups, along with favorable impacts on critical treatment-related factors. Our findings support SLT as a safe and effective treatment for OAG or OHT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cancer is a disease caused by uncontrolled cell growth that is responsible for several deaths worldwide. Breast cancer is the most common type of cancer among women and is the leading cause of death. Chemotherapy is the most commonly used treatment for cancer; however, it often causes various side effects in patients. In this study, we evaluate the antineoplastic activity of a parent compound based on a combretastatin A4 analogue. We test the compound at 0.01 mg mL - 1 , 0.1 mg mL - 1 , 1.0 mg mL - 1 , 10.0 mg mL - 1 , 100.0 mg mL - 1 , and 1,000.0 mg mL - 1 . To assess molecular antineoplastic activity, we conduct in vitro tests to determine the viability of Ehrlich cells and the blood mononuclear fraction. We also analyze the cytotoxic behavior of the compound in the blood and blood smear. The results show that the molecule has a promising antineoplastic effect and crucial anticarcinogenic action. The toxicity of blood cells does not show statistically significant changes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD., Methods: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD., Results: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05)., Conclusions: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of β 2 -adrenergic receptors/AC/cAMP pathway., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes' high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits., (© 2024. The Author(s).)

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As 3+ ), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic., (© 2024. The Author(s).)

The need to find alternative materials to replace aqueous amine solutions for the capture of CO 2 in post-combustion technologies is pressing. This study assesses the CO 2 sorption capacity and CO 2 /N 2 selectivity of three dicationic ionic liquids with distinct anions immobilized in commercial mesoporous silica support (SBA- 15). The samples were characterized by UART-FTIR, NMR, Raman, FESEM, TEM, TGA, Magnetometry (VSM), BET and BJH. The highest CO 2 sorption capacity and CO 2 /N 2 selectivity were obtained for sample SBA@DIL&#95;2FeCl 4 [at 1 bar and 25 °C; 57.31 (±0.02) mg CO 2 /g; 12.27 (±0.72) mg CO 2 /g]. The results were compared to pristine SBA-15 and revealed a similar sorption capacity, indicating that the IL has no impact on the CO 2 sorption capacity of silica. On the other hand, selectivity was improved by approximately 3.8 times, demonstrating the affinity of the ionic liquid for the CO 2 molecule. The material underwent multiple sorption/desorption cycles and proved to be stable and a promising option for use in industrial CO 2 capture processes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978-2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes., (© 2024. The Author(s).)

Biosecurity refers to a set of practices that prevents and/or controls the introduction, spread, and elimination of harmful biological agents in a production system. In this study, we aimed to survey the biosecurity practices and determine their correlation with the size of production systems. A biosecurity assessment form was provided to 69 farms in the Campos Gerais region of Paraná, Brazil. The questionnaire was divided into two sections: general and bovine viral diarrhea virus- and bovine herpesvirus type-1-specific sections. The general section covered topics on traffic control, quarantine and animal isolation, hygiene practices, carcass disposal, and disease monitoring/control. The specific section consisted of questions on the reproductive and respiratory factors, use of antimicrobials, and vaccination schedule. The 69 farms were also classified into small (≤ 61), medium (62-201), and large (≥ 202) size farms based on the number of lactating cows. Moreover, multiple correspondence analysis (MCA) was performed between the biosecurity measures and farm size. The main risk factors and variability were related to the traffic control of people, animals, and vehicles/equipment, animal quarantine/isolation, and hygiene practices. MCA revealed that the small farms exhibited a lack of biosecurity measures, including those related to traffic control, animal quarantine, and hygiene. In medium-size farms, contact between bovine animals of different ages and difficulty in animal isolation in the quarantine system were among the main risk factors. In contrast, isolation of sick animals was easy, but the need to frequently purchase cattle was an important risk factor in large farms. These results highlight the relationship between biosecurity measures and farm size, providing valuable insights for the development of better biosecurity plans for production systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ferreira, Baccili, Nemoto, Vieira, Sviercoski, Ienk, Pagno and Gomes.)

Inappropriate expression of histone deacetylase (HDAC-6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signalling pathway are common aberrations observed in cancers. LASSBio-2208, has been previously described as a dual inhibitor in the nanomolar range of HDAC-6 and PI3Kα and is three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its drug metabolism and pharmacokinetics (DMPK) in vitro profile. Our studies have demonstrated that LASSBio-2208 has moderate cytotoxic potency on breast cancer cell line MCF-7 (IC 50 = 23 µM), human leukaemia cell line CCRF-CEM (IC 50 = 8.54 µM) and T lymphoblast cell line MOLT-4 (IC 50 = 7.15 µM), with no cytotoxic effect on human peripheral blood mononuclear cells (hPBMC). In addition, it has a good antiproliferative effect on MCF-7 cells (IC 50 = 5.44 µM), low absorption by parallel artificial membrane permeability-gastrointestinal tract (PAMPA-GIT) and low permeation by parallel artificial membrane permeability-blood-brain barrier (BBB) (PAMPA-BBB), exhibiting high metabolic stability in rat plasma. Moreover, LASSBio-2208 exhibited synergism when combined with getadolisib and tubastatin A, using the concentrations corresponding to their CC 50 values on MOLT-4 and CCRF-CEM cells.

Objectives: to compare the parameters of pain, oedema, temperature, and soft tissue closure in dental sockets that received two different photobiomodulation (PBM) protocols following extractions., Materials and Methods: Thirty-one participants had their teeth 38 and 48 extracted. Subsequently, one of the dental sockets received PBM at a wavelength (WL) of 808 nanometers (808 group- nm) and the other dental socket received the PBM at WLs of 808 nm and 660 nm, simultaneously (808 + 660 group). The PBM was applied immediately after the surgical procedure and on the 3rd and 7th days., Results: The mean of Visual Analogue Scale (VAS) values for pain were 1.45 for the 3rd day and 0.52 for the 7th day in the 808 + 660 and 808 group, respectively. The mean the pogonion-tragus measurement, used to assess facial oedema on the 3rd day, was 15.38 cm (range 13.5-17.5) in the 808 + 660 group and 15.48 cm (range 14.0-17.5) in the 808 group. The mean facial temperatures in the 808 + 660 group were 34.9 degrees Celsius (ºC) (range 33.5-36.4) on the 3rd day and 35 ºC (range 33.4-36.4) on the 7th day. In the 808 group, the mean temperatures were 34.9 ºC (range 33.9-36.2) on the 3rd day and 34.9 ºC (33.7-36.2) on the 7th day. Regarding the dimensions of the dental socket, the mean were similar for both groups. Significant differences between the groups were only observed in the pain parameter and only on the 7th day, being greater for the 808 + 660 group (p = 0.031)., Conclusions: The association of the 660 nm with 808 nm, and the increase in energy did not showed more benefits in pain reduction oedema, or acceleration of the closure of the soft tissues of the dental sockets of lower third molars, in the protocols used here., Clinical Relevance: There is no need to combine lasers at wavelengths of 660 and 808 nm to reduce oedema, pain and repair of soft tissues after extraction of lower third molars., Clinical Trial Registration: This trial was registered in the Brazilian Registry of Clinical Trials (ReBEC) with the following code: RBR-66pyrh8, on 29th December, 2022., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Dipeptidyl peptidase IV (DPP-4) is a key enzyme that regulates several important biological processes and it is better known to be targeted by gliptins as a modern validated approach for the management of type 2 diabetes mellitus (T2DM). However, new generations of DPP-4 inhibitors capable of controlling inflammatory processes associated with chronic complications of T2DM are still needed. In this scenario, we report here the design by molecular modelling of new β-amino- N -acylhydrazones, their racemic synthesis, chiral resolution, determination of physicochemical properties and their DPP4 inhibitory potency. Theoretical and experimental approaches allowed us to propose a preliminary SAR, as well as to identify LASSBio-2124 (6) as a new lead for DPP-4 inhibition, with good physicochemical properties, favourable eudismic ratio, scalable synthesis and anti-diabetes effect in a proof-of-concept model. These findings represent an interesting starting point for the development of a new generation of DPP-4 inhibitors, useful in the treatment of T2DM and comorbidities., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Burkholderia cepacia complex bacteria have emerged as opportunistic pathogens in patients with cystic fibrosis and immunocompromised individuals, causing life-threatening infections. Because of the relevance of these microorganisms, genetic manipulation is crucial for explaining the genetic mechanisms leading to pathogenesis. Despite the availability of allelic exchange tools to obtain unmarked gene deletions in Burkholderia , these require a step of merodiploid formation and another of merodiploid resolution through two independent homologous recombination events, making the procedure long-lasting. The CRISPR/Cas9-based system could ease this constraint, as only one step is needed for allelic exchange. Here, we report the modification of a two-plasmid system (pCasPA and pACRISPR) for genome editing in Burkholderia multivorans . Several modifications were implemented, including selection marker replacement, the optimization of araB promoter induction for the expression of Cas9 and λ-Red system encoding genes, and the establishment of plasmid curing procedures based on the sacB gene or growth at a sub-optimal temperature of 18°C-20°C with serial passages. We have shown the efficiency of this CRISPR/Cas9 method in the precise and unmarked deletion of different genes ( rpfR , bceF , cepR , and bcsB ) from two strains of B. multivorans , as well as its usefulness in the targeted insertion of the gfp gene encoding the green fluorescence protein into a precise genome location. As pCasPA was successfully introduced in other Burkholderia cepacia complex species, this study opens up the possibility of using CRISPR/Cas9-based systems as efficient tools for genome editing in these species, allowing faster and more cost-effective genetic manipulation.IMPORTANCE Burkholderia encompasses different species of bacteria, some of them pathogenic to animals and plants, but others are beneficial by promoting plant growth through symbiosis or as biocontrol agents. Among these species, Burkholderia multivorans , a member of the Burkholderia cepacia complex, is one of the predominant species infecting the lungs of cystic fibrosis patients, often causing respiratory chronic infections that are very difficult to eradicate. Since the B. multivorans species is understudied, we have developed a genetic tool based on the CRISPR/Cas9 system to delete genes efficiently from the genomes of these strains. We could also insert foreign genes that can be precisely placed in a chosen genomic region. This method, faster than other conventional strategies based on allelic exchange, will have a major contribution to understanding the virulence mechanisms in B. multivorans , but it can likely be extended to other Burkholderia species., Competing Interests: The authors declare no conflict of interest.

Despite advances in therapies, bacterial chronic respiratory infections persist as life-threatening to patients suffering from cystic fibrosis (CF). Pseudomonas aeruginosa and bacteria of the Burkholderia cepacia complex are among the most difficult of these infections to treat, due to factors like their resistance to multiple antibiotics and ability to form biofilms. The lack of effective antimicrobial strategies prompted our search for alternative immunotherapies that can effectively control and reduce those infections among CF patients. Previous work from our group showed that the anti-BCAL2645 goat polyclonal antibody strongly inhibited Burkholderia cenocepacia to adhere and invade cultured epithelial cells. In this work, we showed that the polyclonal antibody anti-BCAL2645 also strongly inhibited the ability of P. aeruginosa to form biofilms, and to adhere and invade the human bronchial epithelial cell line CFBE41o-. The polyclonal antibody also inhibited, to a lesser extent, the ability of B. multivorans to adhere and invade the human bronchial epithelial cell line CFBE41o. We also show that the ability of B. cenocepacia , P. aeruginosa and B. multivorans to kill larvae of the Galleria mellonella model of infection was impaired when bacteria were incubated with the anti-BCAL2645 antibody prior to the infection. Our findings show that an antibody against BCAL2645 possesses a significant potential for the development of new immunotherapies against these three important bacterial species capable of causing devastating and often lethal infections among CF patients.

Whey protein concentrate (WPC) and maltodextrin were used to microencapsulate polyphenols extract from organic coffee husks by spray drying. The microparticles were characterized and evaluated for their influence on the release, bioaccessibility, and antioxidant capacity of polyphenols in the simulated gastrointestinal tract. WPC as a single encapsulating agent promoted better yield (54.8%) of microparticles. The microparticles showed solubility above 92%, and lower hygroscopicity when encapsulated with maltodextrin alone (7.4%). Smaller diameter (6.78 µm), better encapsulation efficiency (89.1%) and retention of compounds (74.4%) were observed in microparticles with WPC in the composition. Polyphenols were completely released from the microparticles during simulated gastric digestion. The microparticles influenced the bioaccessibility of over 70% of the polyphenols in the intestinal phase. The microparticles showed rapid gastrointestinal release effect but favored the increase of bioaccessibility and preservation of the antioxidant capacity of polyphenols, especially those from the microparticles with WPC compared to the free extract., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The university is considered an environment that favors the initiation and use of substances, especially those that are legal, such as alcohol. This consumption can be differentiated in university students, which makes it necessary to better understand this behavior. Taking into account these aspects, we analyzed the abusive consumption of alcoholic beverages in university students and its association with socioeconomic and behavioral factors. We conducted a cross-sectional study with regularly enrolled students. We assessed the abusive consumption of alcoholic beverages using the binge drinking pattern. We collected socioeconomic and behavioral data using a questionnaire. The association between the variables was verified using logistic regression. Abusive consumption of alcoholic beverages was high, with a high weekly frequency. The association with sociodemographic and behavioral factors can increase the health risk. Education campaigns within institutions with students in the classroom and with all those who can influence these students are important. As there are few studies that consider other health risk factors that have not been analyzed yet, such as those treated in our study, with the abusive consumption of alcoholic beverages, this study seeks to contribute to the knowledge of the relationships between these variables and in the elaboration of actions aimed at improving the lifestyle and health of university students., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Aim: Among critical patients, there is an early onset of changes in both the quantity and quality of muscle mass. It is essential to find tools that promptly identify this muscle mass loss. The aim of this study was to compare the ultrasonography of the quadriceps femoris to the gold standard, thigh computed tomography (CT) for assessing the musculature of critically ill patients with different body mass index who have suffered traumatic brain injury., Methods: This is a prospective validation study in an Intensive Care Unit (ICU) specialized in trauma care, located at a tertiary teaching hospital. Our study involved a convenience sample of patients. Sequential ultrasound and CT scans were performed at three distinct time intervals: upon admission, between 24 and 96 h' post-admission, and finally, between 96 and 168 h' post-admission. For all ultrasound measurements, we conducted simultaneous quadriceps CT measurements. The correlation between measurements obtained by ultrasound and computed tomography at three different times and in three BMI ranges was analyzed, in individuals with normal weight, overweight and obese., Results: Results: We analyzed 252 images in 49 patients in time 1, 40 patients in time 2, and 37 in time 3 to compare the thickness quadriceps muscle using US and CT. Of these, 18 patients had a BMI ≤ 24.9 kg/m 2 (normal weight), 18 patients from 25 to 29.9 kg/m 2 (overweight), and 8 patients had a BMI ≥ 30 kg/m 2 (obese). The mean age was 37 years, the majority (94%) were male and the main comorbidities were: hypertension 12%, diabetes 4% and 14% smoking. The results revealed minor discrepancies between measurements obtained through the two methods, these changes were not influenced by the body mass index, with these variations being practically insignificant in the context of clinical application. Thus, the correlation and concordance between the values obtained found a strong positive correlation with good limits of agreement. The Spearman's correlation coefficients obtained were r = 0.89, 0.91 and 0.88, p < 0.01 at T1, T2 and T3 respectively for normal weight, r = 0.91, 0.80 and 0.81, p < 0.01 at T1, T2 and T3 respectively for overweight and r = 0.89, 0.94 and 0.84, p < 0.01 at T1, T2 and T3 respectively for obesity. In addition to a positive correlation, we observed a high agreement between the methods. The Bland & Altman analysis at time 1 showed, respectively, the bias of 1.46, 2.03 and 0.76. At time 2, the bias was 0.42, 3.11 and 2.12. At time 3, the bias was 2.26, 3.38 and 2.11 mm., Conclusion: Our findings suggest that measure femoral quadriceps muscle thickness ultrasound-based exhibits a comparable performance to thigh CT. This conclusion stems from the excellent correlation and good agreement observed between ultrasound and CT, which is considered the gold standard for muscle assessment in critically ill patients., Trial Registration: This clinical trial is registered at REBEC https://ensaiosclinicos.gov.br/ identifier: RBR-2bzspnz. The protocol was approved, on July 30, 2019, by the Research Ethics Committee of the Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto - Trial Registration Number: 3,475,851., Competing Interests: Declaration of competing interest The authors have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study was to evaluate the filling ability of 2 obturation techniques in 3-dimensional (3D) printed teeth with perforating internal resorption (PIR)., Methods: A maxillary central incisor was instrumented and scanned by micro-computed tomographic (micro-CT) imaging. The 3D model was exported in the stereolithographic format and, with the aid of OrtogOnBlender software (Cícero Moraes, Sinop, SP, Brazil), a PIR in the middle third of the root canal was designed. Thirty-two replicas were printed in surgical resin and distributed into 4 groups (n = 8) according to the obturation technique and the material used: 2 groups used the hybrid technique, 1 with Bio-C Sealer (BCS; Angelus, Londrina, PR, Brazil)/gutta-percha (GP; VDW GmbH, Munich, Germany) + Bio-C Repair (BCR; Angelus, Londrina, PR, Brazil) and the other with BioRoot (BR; Septodont, Saint Maur des Fosses, France)/gutta-percha (GP) + Biodentine (BD; Septodont, Saint Maur des Fosses, France), and 2 groups used the incremental technique, 1 with BCR and the other with BD. Postobturation micro-CT imaging was performed to measure the percentage volume of voids and laser confocal microscopy to measure the surface roughness (μm) of the repair cements. Data were compared using analysis of variance and Kruskal-Wallis tests., Results: Regarding the filling volume in the apical third, the BCS/GP + BCR (89.70 ± 5.15), BR/GP + BD (87.70 ± 8.43), and BCR (84.20 ± 9.00) groups showed the highest percentages compared with the BD group (69.70 ± 6.88) (P < .05). In the area of internal resorption, the BCS/GP + BCR (96.00 ± 2.64) and BCR (95.30 ± 2.93) groups showed the highest percentages compared with the BR/GP + BD group (91.50 ± 1.35) (P < .05). The BD group showed intermediate values that were sometimes similar to the BCS/GP + BCR and BCR groups and similar to the BR/GP + BD group (P > .05). Regarding the quality of the filling in the perforation area, the BCR group showed better results compared with the BD group (P < .001). Regarding roughness, the BCR group (1.66 ± 0.65) showed lower surface roughness compared with the BD group (2.51 ± 0.89) (P < .05)., Conclusions: The capacity and quality of the filling in teeth with PIR were superior with the incremental technique with BCR and the hybrid technique with BCS/GP + BCR., (Copyright © 2023 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: The large quantities of by-products generated in the coffee industry are a problem. Studies related to the biological potential of organic coffee husks are still limited. The aim of this work was to investigate the occurrence of phenolic compounds in organic coffee husks and to evaluate their potential as a source of bioactive dietary components., Results: To achieve this objective, three extracts were prepared, namely extractable polyphenols (EPs), hydrolyzable non-extractable polyphenols (H-NEPs), and non-extractable polyphenols (NEPs). These extracts were characterized and evaluated for their bioactive properties after simulated gastrointestinal digestion. The results show that the extraction process affected the occurrence of phenols from coffee peels, especially for caffeic acid, gallic acid, and chlorogenic acid. The free and bound polyphenols found in the extracts and digests not only showed antioxidant properties against 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals but were also strongly bioavailable and had good anticoagulant potential., Conclusion: These results highlight the potential health benefits of phytochemicals from coffee husks and open new perspectives for the use of such compounds in dietary supplements. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 "outbreak" (2015-16); and P2 "endemic" (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.

Xanthomonas is an important genus of plant-associated bacteria that causes significant yield losses of economically important crops worldwide. Different approaches have assessed genetic diversity and evolutionary interrelationships among the Xanthomonas species. However, information from clustered regularly interspaced short palindromic repeats (CRISPRs) has yet to be explored. In this work, we analyzed the architecture of CRISPR-Cas loci and presented a sequence similarity-based clustering of conserved Cas proteins in different species of Xanthomonas. Although absent in many investigated genomes, Xanthomonas harbors subtype I-C and I-F CRISPR-Cas systems. The most represented species, Xanthomonas citri, presents a great diversity of genome sequences with an uneven distribution of the CRISPR-Cas systems among the subspecies/pathovars. Only X. citri subsp. citri and X. citri pv. punicae have these systems, exclusively of subtype I-C system. Moreover, the most likely targets of the X. citri CRISPR spacers are viruses (phages). At the same time, few are plasmids, indicating that CRISPR/Cas system is possibly a mechanism to control the invasion of foreign DNA. We also showed in X. citri susbp. citri that the cas genes are regulated by the diffusible signal factor, the quorum sensing (QS) signal molecule, according to cell density increases, and under environmental stress like starvation. These results suggest that the regulation of CRISPR-Cas by QS occurs to activate the gene expression only during phage infection or due to environmental stresses, avoiding a possible reduction in fitness. Although more studies are needed, CRISPR-Cas systems may have been selected in the Xanthomonas genus throughout evolution, according to the cost-benefit of protecting against biological threats and fitness maintenance in challenging conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

This study aimed to investigate the effects of 8 h of cold stress (18 °C) every day in broiler chicks during the first 7 days of rearing on crop filling analysis, yolk sac consumption, digestive and immune organs weights, and physiological metabolism at seven days and performance between 1 and 35 days. Cobb500 male broiler chickens (n = 274) were randomly assigned to two treatments. The treatments consisted of varying environmental temperatures during the first week post-housing. Chicks were reared at a thermoneutral temperature (32 °C) or under cold stress (18 °C) for 8 h/day during the first week, and both groups were subsequently reared at a thermoneutral temperature for 8-35 days. The thermoneutral group reached 90% full crop after 48 h of housing (P < 0.05), while the cold-stressed group had more empty crops at 2 h and 48 h after housing (P < 0.05). The chick cloacal temperature was not affected by the treatments (P > 0.05). Additionally, the treatment did not affect serum amylase and corticosterone levels, feed intake, body weight gain, or feed conversion ratio (P > 0.05, while the cold-stressed group had elevated heterophil/lymphocyte count at day 7 (P < 0.05). The thermoneutral group showed higher viability (%) at 7 and 35 days and a higher production factor at 35 days (P < 0.05). Broiler chickens under cyclic cold stress experienced decreased yolk sac absorption during the first week and increased feed intake and feed conversion ratio after 35 days of rearing. Viability was also lower in the cold-stressed group. An appropriate strategy to minimize these adverse effects is to rear the chicks in a thermoneutral environment during the first week., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Schistosomiasis is a neglected tropical parasitic disease caused by trematode worms of the genus schistosoma, which affects approximately 240 million people worldwide. the diagnosis of the disease can be performed by parasitological, molecular, and/or immunological methods, however, the development of new diagnostic methods still essential to guide policy decisions, monitor disease trends and assess the effectiveness of interventions., Objective: in this sense, the current work summarizes the findings of a systematic review regarding antigens applied in the enzyme-linked immunosorbent assay test, which were patented and published over the last ten years., Methods: the literature search strategy used medical subject heading (mesh) terms to define as descriptors. "schistosoma mansoni" was used in arrangement with the descriptors "immunoassay", "enzyme-linked immunosorbent assay", "elisa", and "antigens", using the "and" connector. the patent search was done using keywords, including diagnosis and schistosoma or schistosomiasis or schistosome. several databases were employed for the patent search, such as intellectual property national institute; european patent office; the united states patent and trademark office; patent scope, and google patents., Results: forty-one articles were retrieved, of which only five met the eligibility criteria. seventeen patents were taken from the databases, and a brief description of the most relevant inventions is given here., Conclusion: schistosomiasis is considered the most important helminthic disease in worldwide. therefore, it is important to of searching for and develops diagnostic methods based on serology to reduce morbidity and mortality caused by the disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)