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1.
Chembiochem ; 25(16): e202400295, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-38830838

ABSTRACT

Only 0.016 % of all known natural products contain an aziridine ring, but this unique structural feature imparts high reactivity and cytotoxicity to the compounds in which it is found. Until 2021, no naturally occurring aziridine-forming enzymes had been identified. Since 2021, the biosynthetic enzymes for ~10 % of known aziridine containing natural products have been identified and characterized. This article describes the recent advances in our understanding of enzyme-catalyzed aziridine formation in the context of historical methods for aziridine formation through synthetic chemistry.


Subject(s)
Aziridines , Aziridines/chemistry , Aziridines/metabolism , Biological Products/chemistry , Biological Products/metabolism , Biocatalysis , Molecular Structure
2.
Neurosurg Rev ; 47(1): 523, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39223420

ABSTRACT

Stereotactic needle biopsy stands as a crucial method for diagnosing intracranial lesions unsuitable for surgical intervention. Nonetheless, the potential for sampling errors lead to innovative approaches to enhance diagnostic precision. This study contrasts the outcomes of patients undergoing fluorescein-assisted frameless stereotactic needle biopsy with those receiving traditional biopsies to evaluate the impact on diagnostic accuracy and safety. This study included patients with contrast-enhancing intracranial lesions, comprising a prospective group undergoing fluorescein-assisted biopsies and a retrospective group undergoing conventional biopsies at the same institution. We've collected data on demographics, procedural specifics, diagnostic outcomes, and postoperative events. A comparative analysis involved 43 patients who received fluorescein-assisted biopsies against 77 patients who underwent conventional biopsies. The average age was 60.5 years. The fluorescein group exhibited a 93% success rate in diagnosis, markedly higher than the 70.1% in the non-fluorescein group (OR = 5.67; 95%IC: 1.59-20.24; p < 0.01). The rate of complications was statistically similar across both cohorts. Despite its established value, stereotactic needle biopsy is susceptible to inaccuracies and complications. The application of fluorescence-based adjuncts like 5-ALA and fluorescein has been investigated to improve diagnostic fidelity and reduce risks. These technologies potentially minimize the necessity for multiple biopsies, decrease surgical duration, and provide immediate verification of tumor presence. Fluorescein-assisted stereotactic biopsy emerges as an effective, secure alternative to conventional methods.


Subject(s)
Brain Neoplasms , Fluorescein , Humans , Middle Aged , Female , Male , Aged , Brain Neoplasms/pathology , Brain Neoplasms/surgery , Brain Neoplasms/diagnosis , Biopsy, Needle/methods , Biopsy, Needle/adverse effects , Adult , Retrospective Studies , Stereotaxic Techniques , Aged, 80 and over , Prospective Studies
3.
Proc Natl Acad Sci U S A ; 117(28): 16616-16625, 2020 07 14.
Article in English | MEDLINE | ID: mdl-32601203

ABSTRACT

Enhanced inflammation is believed to contribute to overnutrition-induced metabolic disturbance. Nutrient flux has also been shown to be essential for immune cell activation. Here, we report an unexpected role of nutrient-sensing O-linked ß-N-acetylglucosamine (O-GlcNAc) signaling in suppressing macrophage proinflammatory activation and preventing diet-induced metabolic dysfunction. Overnutrition stimulates an increase in O-GlcNAc signaling in macrophages. O-GlcNAc signaling is down-regulated during macrophage proinflammatory activation. Suppressing O-GlcNAc signaling by O-GlcNAc transferase (OGT) knockout enhances macrophage proinflammatory polarization, promotes adipose tissue inflammation and lipolysis, increases lipid accumulation in peripheral tissues, and exacerbates tissue-specific and whole-body insulin resistance in high-fat-diet-induced obese mice. OGT inhibits macrophage proinflammatory activation by catalyzing ribosomal protein S6 kinase beta-1 (S6K1) O-GlcNAcylation and suppressing S6K1 phosphorylation and mTORC1 signaling. These findings thus identify macrophage O-GlcNAc signaling as a homeostatic mechanism maintaining whole-body metabolism under overnutrition.


Subject(s)
Macrophages/immunology , N-Acetylglucosaminyltransferases/immunology , Obesity/immunology , Ribosomal Protein S6 Kinases, 90-kDa/immunology , Acetylglucosamine/immunology , Adipose Tissue/immunology , Animals , Humans , Macrophage Activation , Macrophages/enzymology , Mice , Mice, Knockout , N-Acetylglucosaminyltransferases/genetics , Obesity/enzymology , Obesity/genetics , Obesity/metabolism , Phosphorylation , Ribosomal Protein S6 Kinases, 90-kDa/genetics , Signal Transduction
4.
Front Neuroendocrinol ; 63: 100944, 2021 10.
Article in English | MEDLINE | ID: mdl-34425188

ABSTRACT

Energy balance is the fine regulation of energy expenditure and energy intake. Negative energy balance causes body weight loss, while positive energy balance promotes weight gain. Modern societies offer a maladapted way of life, where easy access to palatable foods and the lack of opportunities to perform physical activity are considered the roots of the obesity pandemic. Physical exercise increases energy expenditure and, consequently, is supposed to promote weight loss. Paradoxically, physical exercise acutely drives anorexigenic-like effects, but the mechanisms are still poorly understood. Using an evolutionary background, this review aims to highlight the potential involvement of the melanocortin system and other hypothalamic neural circuitries regulating energy balance during and after physical exercise. The physiological significance of these changes will be explored, and possible signalling agents will be addressed. The knowledge discussed here might be important for clarifying obesity aetiology as well as new therapeutic approaches for body weight loss.


Subject(s)
Exercise , Hypothalamus , Energy Metabolism , Homeostasis , Humans , Obesity
5.
Neurochem Res ; 47(2): 470-480, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34623563

ABSTRACT

Glucose and oxygen (O2) are vital to the brain. Glucose metabolism and mitochondria play a pivotal role in this process, culminating in the increase of reactive O2 species. Hexokinase (HK) is a key enzyme on glucose metabolism and is coupled to the brain mitochondrial redox modulation by recycling ADP for oxidative phosphorylation (OXPHOS). GABA shunt is an alternative pathway to GABA metabolism that increases succinate levels, a Krebs cycle intermediate. Although glucose and GABA metabolisms are intrinsically connected, their interplay coordinating mitochondrial function is poorly understood. Here, we hypothesize that the HK and the GABA shunt interact to control mitochondrial metabolism differently in the cortex and the hypothalamus. The GABA shunt stimulated mitochondrial O2 consumption and H2O2 production higher in hypothalamic synaptosomes (HSy) than cortical synaptosomes (CSy). The GABA shunt increased the HK coupled to OXPHOS activity in both population of synaptosomes, but the rate of activation was higher in HSy than CSy. Significantly, malonate and vigabatrin blocked the effects of the GABA shunt in the HK activity coupled to OXPHOS. It indicates that the glucose phosphorylation is linked to GABA and Krebs cycle reactions. Together, these data shed light on the HK and SDH role on the metabolism of each region fed by GABA turnover, which depends on the neurons' metabolic route.


Subject(s)
Glucose , Hydrogen Peroxide , Glucose/metabolism , Hydrogen Peroxide/pharmacology , Mitochondria/metabolism , Phosphorylation , gamma-Aminobutyric Acid/metabolism
6.
Molecules ; 26(14)2021 Jul 09.
Article in English | MEDLINE | ID: mdl-34299448

ABSTRACT

Robust and selective quantification methods are required to better analyze feed supplementation effectiveness with specific amino acids. In this work, a reversed-phase high-performance liquid chromatography method with fluorescence detection is proposed and validated for lysine quantification, one of the most limiting amino acids in ruminant nutrition and essential towards milk production. To assess and widen method applicability, different matrices were considered: namely Li2CO3 buffer (the chosen standard reaction buffer), phosphate buffer solution (to mimic media in cellular studies), and rumen inoculum. The method was validated for all three matrices and found to be selective, accurate (92% ± 2%), and precise at both the inter- and intra-day levels in concentrations up to 225 µM, with detection and quantification limits lower than 1.24 and 4.14 µM, respectively. Sample stability was evaluated when stored at room temperature, 4 °C, and -20 °C, showing consistency for up to 48 h regardless of the matrix. Finally, the developed method was applied in the quantification of lysine on real samples. The results presented indicate that the proposed method can be applied towards free lysine quantification in ruminant feeding studies and potentially be of great benefit to dairy cow nutrition supplementation and optimization.


Subject(s)
Animal Feed/analysis , Lysine/analysis , Lysine/chemistry , Amino Acids/chemistry , Animals , Cattle , Chromatography, High Pressure Liquid/methods , Chromatography, Reverse-Phase/methods , Dietary Supplements/analysis , Reproducibility of Results , Ruminants/metabolism
7.
Exp Physiol ; 103(8): 1076-1086, 2018 08.
Article in English | MEDLINE | ID: mdl-29893447

ABSTRACT

NEW FINDINGS: What is the central question of this study? How does an acute session of exercise affect food intake of male Wistar rats? What is the main finding and its importance? Food intake in male Wistar rats is decreased in the first hour after physical exercise independent of the intensity. Moreover, high-intensity exercise potentiates the anorexic effect of peripheral glucose administration. This work raises new feeding-related targets that would explain how exercise drives body weight loss. ABSTRACT: Obesity has emerged as a critical metabolic disorder in modern society. An adequate lifestyle with a well-oriented programme of diet and physical exercise (PE) can prevent or potentially even cure obesity. Additionally, PE might lead to weight loss by increasing energy expenditure and decreasing hunger perception. In this article, we hypothesize that an acute exercise session would potentiate the glucose inhibitory effects on food intake in male Wistar rats. Our data show that moderate- or high-intensity PE significantly decreased food intake, although no changes in the expression of feeding-related neuropeptide in the arcuate nucleus of the hypothalamus were found. Exercised animals demonstrated a reduced glucose tolerance and increased blood insulin concentration. Intraperitoneal administration of glucose decreased food intake in control animals. In the animals submitted to moderate-intensity PE, the decrease in food intake promoted by glucose was similar to controls; however, an interaction was observed when glucose was injected in the high-intensity PE group, in which food intake was significantly lower than the effect produced by glucose alone. A different pattern of expression was observed for the monocarboxylate transporter isoforms (MCT1, 2 and 4) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFBP3) in the hypothalamus, which was dependent on the exercise intensity. In conclusion, PE decreases food intake independently of the intensity. However, an interaction between PE and the anorexic effect of glucose is only observed when a high-intensity exercise is performed. These data show an essential role of exercise intensity in the modulation of the glucose inhibitory effect on food intake.


Subject(s)
Eating/physiology , Glucose/pharmacology , Physical Conditioning, Animal/physiology , Animals , Arcuate Nucleus of Hypothalamus/metabolism , Eating/drug effects , Energy Intake/physiology , Energy Metabolism/drug effects , Energy Metabolism/physiology , Male , Monocarboxylic Acid Transporters/metabolism , Phosphofructokinase-2/metabolism , Rats , Rats, Wistar
8.
Zygote ; 26(4): 314-318, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30207264

ABSTRACT

SummaryThis study aimed to compare the efficiency of different incubation systems for in vitro embryo production in bovine. Oocytes/embryos were cultured in three incubators: conventional - CONV, mini bench - MINI and portable - PORT. After in vitro maturation (IVM), oocytes were verified for maturation rate. The remaining structures were submitted to in vitro fertilization and culture to verify cleavage (day 2) and blastocyst (day 7) rates. Reactive oxygen species (ROS) were evaluated in post-IVM oocytes and embryos (days 2 and 7) using arbitrary fluorescence units (AFUs). No significant difference (P>0.05) was observed for maturation rate. The CONV system (74.0%) produced the highest cleavage rate (P0.05) to MINI (65.0%). The same pattern and differences were observed for blastocyst rate: CONV (33.3%), MINI (32.3%) and PORT (21.9%). ROS levels were not different (P>0.05) in post-IVM oocytes: CONV (35.6±4.5), MINI (29.4±4.0) and PORT (35.6±4.5). For day-2 embryos, ROS levels were higher (P0.05) was observed in blastocysts. In conclusion, although it produced high ROS levels at day 2 of culture, the MINI system was as efficient as the CONV system for blastocyst production. This option may be an interesting and economical for the in vitro embryo industry.


Subject(s)
Embryonic Development , Fertilization in Vitro/veterinary , In Vitro Oocyte Maturation Techniques , Incubators/veterinary , Oocytes/physiology , Animals , Cattle , Female , Fertilization in Vitro/instrumentation , Fertilization in Vitro/methods , Oocytes/cytology
9.
Sensors (Basel) ; 18(6)2018 May 24.
Article in English | MEDLINE | ID: mdl-29794979

ABSTRACT

The increasing number of sensors used in diverse applications has provided a massive number of continuous, unbounded, rapid data and requires the management of distinct protocols, interfaces and intermittent connections. As traditional sensor networks are error-prone and difficult to maintain, the study highlights the emerging role of "citizens as sensors" as a complementary data source to increase public awareness. To this end, an interoperable, reusable middleware for managing spatial, temporal, and thematic data using Sensor Web Enablement initiative services and a processing engine was designed, implemented, and deployed. The study found that its approach provided effective sensor data-stream access, publication, and filtering in dynamic scenarios such as disaster management, as well as it enables batch and stream management integration. Also, an interoperability analytics testing of a flood citizen observatory highlighted even variable data such as those provided by the crowd can be integrated with sensor data stream. Our approach, thus, offers a mean to improve near-real-time applications.

10.
Molecules ; 20(6): 11103-18, 2015 Jun 16.
Article in English | MEDLINE | ID: mdl-26087258

ABSTRACT

Rheumatoid arthritis (RA) is the most common joint-related autoimmune disease and one of the most severe. Despite intensive investigation, the RA inflammatory process remains largely unknown and finding effective and long lasting therapies that specifically target RA is a challenging task. This study proposes a different approach for RA therapy, taking advantage of the new emerging field of nanomedicine to develop a targeted theranostic system for intravenous administration, using solid lipid nanoparticles (SLN), a biocompatible and biodegradable colloidal delivery system, surface-functionalized with an anti-CD64 antibody that specifically targets macrophages in RA. Methotrexate (MTX) and superparamagnetic iron oxide nanoparticles (SPIONs) were co-encapsulated inside the SLNs to be used as therapeutic and imaging agents, respectively. All the formulations presented sizes under 250 nm and zeta potential values lower than -16 mV, suitable characteristics for intravenous administration. Transmission electron microscopy (TEM) photographs indicated that the SPIONs were encapsulated inside the SLN matrix and MTX association efficiency values were higher than 98%. In vitro studies, using THP-1 cells, demonstrated that all formulations presented low cytotoxicity at concentrations lower than 500 µg/mL. It was proven that the proposed NPs were not cytotoxic, that both a therapeutic and imaging agent could be co-encapsulated and that the SLN could be functionalized for a potential future application such as anti-body specific targeting. The proposed formulations are, therefore, promising candidates for future theranostic applications.


Subject(s)
Lipids/chemistry , Nanoparticles/chemistry , Theranostic Nanomedicine , Antibodies, Monoclonal/administration & dosage , Arthritis, Rheumatoid/drug therapy , Cell Line , Chemistry, Pharmaceutical , Drug Carriers , Humans , Nanoparticles/ultrastructure , Particle Size , Spectroscopy, Fourier Transform Infrared
11.
Genet Mol Biol ; 38(3): 278-83, 2015.
Article in English | MEDLINE | ID: mdl-26500431

ABSTRACT

Genes that contain small open reading frames (smORFs) constitute a new group of eukaryotic genes and are expected to represent 5% of the Drosophila melanogaster transcribed genes. In this review we provide a historical perspective of their recent discovery, describe their general mechanism and discuss the importance of smORFs for future genomic and transcriptomic studies. Finally, we discuss the biological role of the most studied smORF so far, the Mlpt/Pri/Tal gene in arthropods. The pleiotropic action of Mlpt/Pri/Tal in D. melanogaster suggests a complex evolutionary scenario that can be used to understand the origins, evolution and integration of smORFs into complex gene regulatory networks.

12.
Am J Physiol Endocrinol Metab ; 307(11): E1020-9, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25294216

ABSTRACT

During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1α genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation.


Subject(s)
Cold Temperature , Iodide Peroxidase/biosynthesis , Muscle Fibers, Fast-Twitch/metabolism , Muscle Fibers, Slow-Twitch/metabolism , Adipose Tissue, Brown/metabolism , Animals , Body Temperature/physiology , Citrate (si)-Synthase/metabolism , Male , Oxygen Consumption/physiology , Rats , Rats, Wistar , Thyroxine/metabolism , Triiodothyronine/metabolism , Up-Regulation/physiology , Iodothyronine Deiodinase Type II
13.
J Knee Surg ; 37(3): 183-192, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36507661

ABSTRACT

Surgical reconstruction is recommended for symptomatic posterior cruciate ligament (PCL) deficiency. While anatomic double-bundle PCL reconstruction (PCLR) has been reported to be associated with biomechanical and clinical advantages over other methods, there is still debate regarding the optimal technique for tibial positioning and fixation. Based on reported advantages and disadvantages, we employed two tibial fixation techniques, transtibial (TT) and tibial inlay (TI) for anatomic double-bundle PCLR with technique selection based on body mass index, comorbidities, and primary versus revision surgery. This study aimed to compare clinical outcomes following PCLR utilizing either TT or TI techniques to validate relative advantages, disadvantages, and indications for each based on the review of prospectively collected registry data. For 37 patients meeting inclusion criteria, 26 underwent arthroscopic TT PCLR using all-soft- tissue allograft with suspensory fixation in the tibia and 11 patients underwent open TI PCLR using an allograft with calcaneal bone block and screw fixation in the tibia. There were no significant preoperative differences between cohorts. Success rates were 96% for TT and 91% for TI with all successful cases documented to be associated with good-to-excellent posterior stability and range of motion in the knee at the final follow-up. In addition, patient-reported outcome scores were within clinically meaningful ranges for pain, function, and mental health after PCLR in both cohorts, suggesting similarly favorable functional, social, and psychological outcomes. Patient-reported pain scores at 6 months postoperatively were significantly (p = 0.042) lower in the TT cohort, which was the only statistically significant difference in outcomes noted. The results of this study support the use of TT and TI techniques for double-bundle anatomic PCLR in restoring knee stability and patient function when used for the treatment of isolated and multiligamentous PCL injuries. The choice between tibial fixation methods for PCLR can be appropriately based on patient and injury characteristics that optimize respective advantages for each technique.


Subject(s)
Posterior Cruciate Ligament Reconstruction , Posterior Cruciate Ligament , Humans , Posterior Cruciate Ligament Reconstruction/methods , Tibia/surgery , Knee Joint/surgery , Posterior Cruciate Ligament/injuries , Pain , Treatment Outcome , Arthroscopy/methods
14.
Arthrosc Sports Med Rehabil ; 6(3): 100917, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006781

ABSTRACT

Purpose: To assess the risk of socket-tunnel overlap for posterior medial or lateral meniscal root repair combined with anterior cruciate ligament reconstruction (ACLR) using artificial tibias and computed tomography scans for 3-dimensional modeling. Methods: Artificial tibias (n = 27; n = 3/subgroup) were allocated to groups based on inclination of socket-tunnels (55°, 60°, 65°) created for posterior root of the medial meniscus (MMPR) and lateral meniscus posterior root (LMPR) repair, and ACLR. Three standardized socket-tunnels were created: one for the ACL and one for each posterior meniscal root insertion. Computed tomography scans were performed and sequentially processed using computer software to produce 3-dimensional models for assessment of socket-tunnel overlap. Statistical analysis was performed with Kruskal-Wallis and Mann-Whitney U tests. Significance was set at P < .05. Results: The present study found no significant risk of tunnel overlap when drilling for combined ACLR and MMPR repair, whereas 7 cases of tunnel overlap occurred between ACL tunnels and LMPR (25.9% of cases). No subgroup or specific pattern of angulation consistently presented significantly safer distances than other subgroups for all distances measured. Conclusions: This study demonstrated 25.9% rate of overlap for combined LMPR repair and ACLR, compared with 0% for MMPR repair with ACLR. Lower ACL drilling angle (55 or 60°) combined with greater lateral meniscus drilling angle (65°) produced no socket-tunnel overlap. Clinical Relevance: Socket-tunnel overlap during meniscal root repair combined with ACLR may compromise graft integrity and lead to impaired fixation and treatment failure of either the ACL, the meniscus, or both. Despite this, risk for socket-tunnel overlap has not been well characterized.

15.
Orthop J Sports Med ; 12(6): 23259671241246277, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38845611

ABSTRACT

Background: Socket-tunnel overlap during meniscal allograft transplantation (MAT) combined with anterior cruciate ligament reconstruction (ACLR) may compromise graft integrity and lead to impaired fixation and treatment failure. Purpose/Hypothesis: The purpose of this study was to determine optimal socket-tunnel drilling parameters for medial and lateral MAT with concurrent ACLR using artificial tibias and computed tomography (CT) scans for 3-dimensional (3D) modeling. It was hypothesized that clinically relevant socket tunnels could be created to allow for concurrent medial or lateral MAT and ACLR without significant risk for overlap at varying tunnel guide angles. Study Design: Descriptive laboratory study. Methods: A total of 27 artificial right tibias (3 per subgroup) were allocated to 9 experimental groups based on the inclination of the socket tunnels (55°, 60°, and 65°) created for simulating medial and lateral MAT and ACLR. Five standardized socket tunnels were created for each tibia using arthroscopic guides: one for the ACL tibial insertion and one for each meniscus root insertion. CT scans were performed for all specimens and sequentially processed using computer software to produce 3D models for quantitative assessment of socket-tunnel overlap risk. Statistical analysis was performed with Kruskal-Wallis and Mann-Whitney U tests. Results: No subgroup consistently presented significantly safer distances than other subgroups for all distances measured. Three cases (11%) and 24 cases (~90%) of tunnel overlap occurred between the ACL tunnel and tunnels for medial and lateral MAT, respectively. Most socket-tunnel overlap (25 of 27; 92.6%) occurred between sockets at depths ranging between 6.3 and 10 mm from the articular surface. For ACLR and posterior root of the lateral meniscus setting, the guide set at 65° increased socket-tunnel distances. Conclusion: When combined ACLR and MAT using socket tunnels for graft fixation is performed, the highest risk for tibial socket-tunnel overlap involves the ACLR tibial socket and the lateral meniscus anterior root socket at a depth of 6 to 10 mm from the tibial articular surface. Clinical Relevance: Setting tibial guides at 65° to the tibial articular surface with the tunnel entry point anteromedial and socket aperture location within the designated anatomic "footprint" will minimize the risk for socket-tunnel overlap.

16.
Toxics ; 12(10)2024 Sep 30.
Article in English | MEDLINE | ID: mdl-39453132

ABSTRACT

The effects of methylmercury (MeHg) on exposed populations are a public health problem. In contrast to widely studied neurological damage, few cardiovascular changes have been described. Our group evaluated the cardiotoxicity of a cumulative dose of 70 mg.kg-1 fractioned over a 14-day exposure period in mice (MeHg70 group). The effects of MeHg on proteins relevant to cardiac mitochondrial function were also investigated. The results obtained showed a reduction in oxygen consumption in the two settings. In cardiac tissue samples in oxygraphy studies, this reduction was related to a lower efficiency of complexes II and V, which belong to the oxidative phosphorylation system. In vivo, mice in the MeHg70 group presented lower oxygen consumption and running tolerance, as shown by ergometric analyses. Cardiac stress was evident in the MeHg70 group, as indicated by a marked increase in the level of the mRNA encoding atrial natriuretic peptide. Electrocardiogram studies revealed a lower heart rate at rest in the animals from the MeHg70 group, as well as prolonged left ventricular depolarisation and repolarisation. Through echocardiographic analysis, reductions in the left ventricular ejection fraction and left ventricular wall thickness of approximately 10% and 20%, respectively, were detected. These results indicate that the oral intake of MeHg can decrease cardiac function and oxidative metabolism. This finding highlights the importance of monitoring MeHg levels in humans and animals in contaminated areas, as well as periodically carrying out cardiac function tests.

17.
Epidemiol Serv Saude ; 33: e2023568, 2024.
Article in English, Portuguese | MEDLINE | ID: mdl-38232241

ABSTRACT

OBJECTIVE: To describe accidents involving brown spider (genus Loxosceles) bites notified by the Pernambuco Poison Information and Care Center (CIATox-PE), Brazil, from January 2018 to December 2022. METHODS: This was a case series study of brown spider bites notified by the CIATox-PE. RESULTS: The study included 22 cases with median age of 35 years, the majority being female (13); the cases occurred in rural and urban areas (12 versus 10), at night (10); Petrolina was the municipality with the highest number of notifications (6); spider bites occurred mainly in the lower (11) and upper (9) limbs, almost exclusively inside households (21); specific serum therapy was not indicated for 8 cases because the time for its effectiveness had already elapsed. CONCLUSION: Loxoscelism cases occurred more frequently in females, in both rural and urban areas and mainly at home, with delays in seeking medical care. MAIN RESULTS: The 22 cases described represent an alert for the presence of a venomous species not reported in previous studies in Pernambuco. The severity of cases may be associated with delays in seeking medical care, especially due to the population's lack of information. IMPLICATIONS FOR SERVICES: Identify the presence of brown spiders in households in the region and the potential severity of poisonings. Alert health professionals to recognize the clinical picture with a view to appropriate early treatment. PERSPECTIVES: Develop research on poisoning by venomous animals and educational actions alerting the population to prevent these accidents and updating health professionals on care.


Subject(s)
Spider Bites , Spiders , Animals , Humans , Female , Adult , Male , Spider Bites/epidemiology , Spider Bites/therapy , Brazil/epidemiology
18.
Nat Commun ; 14(1): 3985, 2023 Jul 06.
Article in English | MEDLINE | ID: mdl-37414776

ABSTRACT

OpenStreetMap (OSM) has evolved as a popular dataset for global urban analyses, such as assessing progress towards the Sustainable Development Goals. However, many analyses do not account for the uneven spatial coverage of existing data. We employ a machine-learning model to infer the completeness of OSM building stock data for 13,189 urban agglomerations worldwide. For 1,848 urban centres (16% of the urban population), OSM building footprint data exceeds 80% completeness, but completeness remains lower than 20% for 9,163 cities (48% of the urban population). Although OSM data inequalities have recently receded, partially as a result of humanitarian mapping efforts, a complex unequal pattern of spatial biases remains, which vary across various human development index groups, population sizes and geographic regions. Based on these results, we provide recommendations for data producers and urban analysts to manage the uneven coverage of OSM data, as well as a framework to support the assessment of completeness biases.


Subject(s)
Machine Learning , Sustainable Development , Humans , Cities , Urban Population , Spatio-Temporal Analysis , China
19.
Pharmaceutics ; 15(5)2023 May 07.
Article in English | MEDLINE | ID: mdl-37242672

ABSTRACT

Pilot bioavailability/bioequivalence (BA/BE) studies are usually conducted and analysed similarly to pivotal studies. Their analysis and interpretation of results usually rely on the application of the average bioequivalence approach. However, due to the small study size, pilot studies are inarguably more sensitive to variability. The aim of this work is to propose alternative approaches to the average bioequivalence methodology, in a way to overcome and reduce the uncertainty on the conclusions of these studies and on the potential of test formulations. Several scenarios of pilot BA/BE crossover studies were simulated through population pharmacokinetic modelling. Each simulated BA/BE trial was analysed using the average bioequivalence approach. As alternative analyses, the centrality of the test-to-reference geometric least square means ratio (GMR), bootstrap bioequivalence analysis, and arithmetic (Amean) and geometric (Gmean) mean ƒ2 factor approaches were investigated. Methods performance was measured with a confusion matrix. The Gmean ƒ2 factor using a cut-off of 35 was the most appropriate method in the simulation conditions frame, enabling to more accurately conclude the potential of test formulations, with a reduced sample size. For simplification, a decision tree is also proposed for appropriate planning of the sample size and subsequent analysis approach to be followed in pilot BA/BE trials.

20.
Rev Bras Med Trab ; 21(1): e2023809, 2023.
Article in English | MEDLINE | ID: mdl-37197340

ABSTRACT

Introduction: The strict demands of the military environment, associated with the increase in violence, as well as the frequent use of body armor, can further aggravate health problems. Objectives: To investigate the perception of police officers of the Countryside Specialized Police Battalion in relation to comfort, fatigue, and lower back pain, resulting from the use of body armor. Methods: This was a cross-sectional study conducted with 260 male military police officers (34.62 ± 5.83 years old) belonging to the ostensive rural police battalion in the state of Ceará, Brazil. The questionnaire related to comfort, fatigue, and lower back pain was used to identify the perception of pain from the use of body armor, with staggered responses, and the results were analyzed using the SPSS 21.0 software. Results: Regarding the use of body armor, 41.5% of participants perceived it to be little comfortable in general; furthermore, 45 and 47.5% of military police officers considered it little comfortable in relation to weight and use during operational activities, respectively. With regard to body measurements, 48.5% reported being little comfortable, and 70% perceived that the body armor is adjustable to the body. At the end of the work shift, 37.3% complained of lower back pain, and 45.8% felt moderate fatigue. Moreover, 70.1% felt pain in the lower back after the work shift. Conclusions: Military police officers reported lower back pain at the end and after the work shift due to use of body armor, as well as little comfort of the protective equipment and moderate fatigue at the end of the work shift.


Introdução: As rigorosas exigências do ambiente militar associadas ao aumento da violência, bem como ao uso frequente do colete balístico, podem agravar ainda mais os problemas de saúde. Objetivos: Investigar a associação do uso de colete balístico em relação ao conforto, à fadiga e à queixa de lombalgia em policiais do batalhão especializado do Ceará. Métodos: Tratou-se de um estudo transversal realizado com 260 policiais militares do sexo masculino (34,62 ± 5,83 anos) pertencentes ao batalhão de policiamento ostensivo rural do estado do Ceará. O questionário relacionado a conforto, fadiga e dores na região lombar foi utilizado para identificar a percepção de dor pelo uso do colete balístico, com respostas escalonadas, e seus resultados foram analisados no software SPSS 21.0. Resultados: Quanto ao uso do colete, 41,5% perceberam ser pouco confortável no geral; e 45 e 47,5% dos policiais militares consideraram ser pouco confortável em relação ao peso e em relação ao uso durante as atividades operacionais, respectivamente. No que se refere às medidas corporais, 48,5% reportaram ser confortável, e 70% percebem o colete como ajustável ao corpo. No momento da finalização do turno de trabalho, 37,3% apresentam dores na região lombar e 45,8% sentem fadiga moderada. Após o encerramento do turno de trabalho, 70,1% sentem dores na região lombar. Conclusões: Os policiais militares perceberam dores na região lombar ao final e depois do turno de trabalho pelo uso do colete balistico, além de relatarem sobre o pouco conforto do equipamento de proteção e sobre a fadiga moderada ao fim do turno de trabalho.

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