New Surgical Model for Bone–Muscle Injury Reveals Age and Gender-Related Healing Patterns in the 5 Lipoxygenase (5LO) Knockout Mouse

Signaling lipid mediators released from 5 lipoxygenase (5LO) pathways influence both bone and muscle cells, interfering in their proliferation and differentiation capacities. A major limitation to studying inflammatory signaling pathways in bone and muscle healing is the inadequacy of available animal models. We developed a surgical injury model in the vastus lateralis (VL) muscle and femur in 129/SvEv littermates mice to study simultaneous musculoskeletal (MSK) healing in male and female, young (3 months) and aged (18 months) WT mice compared to mice lacking 5LO (5LOKO). MSK defects were surgically created using a 1-mm punch device in the VA muscle followed by a 0.5-mm round defect in the femur. After days 7 and 14 post-surgery, the specimens were removed for microtomography (microCT), histopathology, and immunohistochemistry analyses. In addition, non-injured control skeletal muscles along with femur and L5 vertebrae were analyzed. Bones were microCT phenotyped, revealing that aged female WT mice presented reduced BV/TV and trabecular parameters compared to aged males and aged female 5LOKO mice. Skeletal muscles underwent a customized targeted lipidomics investigation for profiling and quantification of lipid signaling mediators (LMs), evidencing age, and gender related-differences in aged female 5LOKO mice compared to matched WT. Histological analysis revealed a suitable bone-healing process with osteoid deposition at day 7 post-surgery, followed by woven bone at day 14 post-surgery, observed in all young mice. Aged WT females displayed increased inflammatory response at day 7 post-surgery, delayed bone matrix maturation, and increased TRAP immunolabeling at day 14 post-surgery compared to 5LOKO females. Skeletal muscles of aged animals showed higher levels of inflammation in comparison to young controls at day 14 post-surgery; however, inflammatory process was attenuated in aged 5LOKO mice compared to aged WT. In conclusion, this new model shows that MSK healing is influenced by age, gender, and the 5LO pathway, which might serve as a potential target to investigate therapeutic interventions and age-related MSK diseases. Our new model is suitable for bone–muscle crosstalk studies

A ocorrência de eventos adversos com uso de Ceftriaxona

Cada vez mais as substâncias sintéticas têm ganhado espaço como antimicrobiano e consequentemente tem sido lançado na indústria farmacêutica, o que inclui a ceftriaxona. A alta utilização desses medicamentos tem constituído um problema de saúde pública global, visto que, também são considerados substâncias químicas que mais causam eventos adversos. O principal objetivo do presente estudo é abordar através da presente revisão sistematizada os principais eventos adversos decorrentes do uso de ceftriaxona na prática clínica. Trata-se de uma revisão sistemática, dos quais, foram realizadas buscas na PubMed, Periódico Capes e na Biblioteca Virtual em Saúde (BVS), com os principais Descritores e palavras-chave: “Ceftriaxone” AND “Drug-Related Side Effects and Adverse” AND Reactions, contanto com uma totalidade de 8 estudos para análise. Logo, os estudos abordam que os eventos adversos relacionados a utilização da ceftriaxona em sua maioria das vezes, foram ocasionados pelo uso não apropriado do medicamento pelos profissionais de saúde, além de condições médicas não apropriadas, tendo como menores abordagens a baixa qualidade do medicamento. Assim, é fundamental o compreendimento que mesmo a ceftriaxona apresentando eventos adversos, desde leves até mesmo raros, os riscos podem ser de alguma forma evitados, sobretudo, no que diz respeito a um protocolo e administração do medicamento adequadamente

Assessing the reclamation of a contaminated site affected by the Fundão dam tailings trough phytoremediation and bioremediation

The rupture of the Fundão dam (Brazil) spread tailings contaminated with sodium and ether-amine into the Doce River Basin. Aiming at rehabilitating a contaminated riparian site, phytoremediation with native species of the Atlantic Forest was performed under four treatments: ES-1: physical remediation (sediment scraping) + chemical remediation (organic matter) + bioremediation (double inoculation with the arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis and the plant growth-promoting bacteria Bacillus subtilis); ES-2: chemical remediation + bioremediation; ES-3: physical remediation + chemical remediation; ES-4: chemical remediation. Ether-amine and sodium contents, plant growth and, soil quality parameters were compared among treatments and relative to preserved and degraded sites. Two years after planting, the outstanding plant growth was attributed to the phytoremediation of ether-amine and ammonium, followed by a significant increase in soil microbial biomass (Phospholipid fatty acids-PLFAs), particularly the Gram+ bacteria and total fungi but not AMF, whose response was independent of the inoculation. While sodium and ether-amine declined, soil K, P, NO3− contents, dehydrogenase and acid phosphatase activities, cation exchange capacity (CEC) and soil aggregation increased, especially in ES-1. Thus, such remediation procedures are recommended for the restoration of riparian areas affected by the Fundão tailings, ultimately improving sediment fertility, aggregation and stabilization. To the best of our knowledge, this is the only successful example of fragment of riparian Atlantic Forest successfully rehabilitated using native trees from the Atlantic Forest in the riparian zone affected by the contaminated Fundão dam tailings. For that, phytoremediation and bioremediation procedures were adopted to alleviate etheramine and sodium toxicity, resulting in the amelioration of soil fertility and particularly the stabilization of such highly disaggregated sediments, ultimately protecting the Doce river basin against these contaminants.</p

Ponderal development and growth traits of Anglonubian goats raised under semi-intensive system Desenvolvimento ponderal e características de crescimento de caprinos da raça Anglonubiana criados em sistema semi-intensivo

The goal of this study was to characterize, by mathematic models, the growth pattern of Anglonubian goats raised under semi-intensive system. Data from 43 males and 33 females were used to estimate the growth of animals based on non-linear models. The effects from sex, birth month and birth type on living weight and on average daily weight gain (DWG) at different ages were analyzed. The logistic model has proved to be the most adequate one to estimate the growth curves of males and females. The birth type influenced the living weight up to 60 days of age (P&lt;0.05) and the birth month presented no effects. The sex affected the GPD until 150 days of age and affected the living weight at all ages, with males heavier than females (P&lt;0.05). The DWG was higher at younger ages, being equal to 194 ± 42 g from birth to 30 days and 91 ± 60 g from 210 to 240 days, with about 150 g/day from birth to 150 days of age. Anglonubian goats raised under semi-intensive system show satisfactory performance for meat production and the logistic model is adequate to estimate the growth pattern of the kids from this breed.<br>Objetivou-se avaliar o padrão de crescimento de caprinos da raça Anglonubiana criados sob sistema semi-intensivo. Os dados oriundos de 43 machos e 33 fêmeas foram utilizados para estimar o crescimento dos animais com base em modelos não-lineares, tendo sido analisados os efeitos de sexo, mês e tipo de nascimento, sobre o peso vivo e o ganho de peso diário (GPD) em diferentes idades. O modelo Logístico mostrou-se o mais adequado para estimar a curva de crescimento de machos e fêmeas. O tipo de nascimento influenciou o peso vivo até os 60 dias (P&lt;0,05), enquanto que o mês de nascimento não apresentou efeito significativo. O sexo afetou o GPD até 150 dias de idade assim como afetou o peso vivo em todas as idades, sendo os machos mais pesados que as fêmeas (P&lt;0,05). O GPD foi maior em idades mais jovens, sendo igual a 194 ± 42 g do nascimento aos 30 dias e 91 ± 60 g dos 210 aos 240 dias, sendo cerca de 150 g/dia do nascimento aos 150 dias de idade. Os caprinos da raça Anglonubiana criados sob sistema semi-intensivo apresentam desempenho ponderal satisfatório para produção de carne, sendo que o modelo Logístico é adequado para estimar o padrão de crescimento dos cabritos dessa raça

Support vector machine-based classification of neuroimages in Alzheimer’s disease: direct comparison of FDG-PET, rCBF-SPECT and MRI data acquired from the same individuals

Objective: To conduct the first support vector machine (SVM)-based study comparing the diagnostic accuracy of T1-weighted magnetic resonance imaging (T1-MRI), F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and regional cerebral blood flow single-photon emission computed tomography (rCBF-SPECT) in Alzheimer’s disease (AD). Method: Brain T1-MRI, FDG-PET and rCBF-SPECT scans were acquired from a sample of mild AD patients (n=20) and healthy elderly controls (n=18). SVM-based diagnostic accuracy indices were calculated using whole-brain information and leave-one-out cross-validation. Results: The accuracy obtained using PET and SPECT data were similar. PET accuracy was 68∼71% and area under curve (AUC) 0.77∼0.81; SPECT accuracy was 68∼74% and AUC 0.75∼0.79, and both had better performance than analysis with T1-MRI data (accuracy of 58%, AUC 0.67). The addition of PET or SPECT to MRI produced higher accuracy indices (68∼74%; AUC: 0.74∼0.82) than T1-MRI alone, but these were not clearly superior to the isolated neurofunctional modalities. Conclusion: In line with previous evidence, FDG-PET and rCBF-SPECT more accurately identified patients with AD than T1-MRI, and the addition of either PET or SPECT to T1-MRI data yielded increased accuracy. The comparable SPECT and PET performances, directly demonstrated for the first time in the present study, support the view that rCBF-SPECT still has a role to play in AD diagnosis

Selecting the most relevant brain regions to discriminate Alzheimer's disease patients from healthy controls using multiple kernel learning: A comparison across functional and structural imaging modalities and atlases

Background: Machine learning techniques such as support vector machine (SVM) have been applied recently in order to accurately classify individuals with neuropsychiatric disorders such as Alzheimer's disease (AD) based on neuroimaging data. However, the multivariate nature of the SVM approach often precludes the identification of the brain regions that contribute most to classification accuracy. Multiple kernel learning (MKL) is a sparse machine learning method that allows the identification of the most relevant sources for the classification. By parcelating the brain into regions of interest (ROI) it is possible to use each ROI as a source to MKL (ROI-MKL). Methods: We applied MKL to multimodal neuroimaging data in order to: 1) compare the diagnostic performance of ROI-MKL and whole-brain SVM in discriminating patients with AD from demographically matched healthy controls and 2) identify the most relevant brain regions to the classification. We used two atlases (AAL and Brodmann's) to parcelate the brain into ROIs and applied ROI-MKL to structural (T1) MRI, 18F-FDG-PET and regional cerebral blood flow SPECT (rCBF-SPECT) data acquired from the same subjects (20 patients with early AD and 18 controls). In ROI-MKL, each ROI received a weight (ROI-weight) that indicated the region's relevance to the classification. For each ROI, we also calculated whether there was a predominance of voxels indicating decreased or increased regional activity (for 18F-FDG-PET and rCBF-SPECT) or volume (for T1-MRI) in AD patients. Results: Compared to whole-brain SVM, the ROI-MKL approach resulted in better accuracies (with either atlas) for classification using 18F-FDG-PET (92.5% accuracy for ROI-MKL versus 84% for whole-brain), but not when using rCBF-SPECT or T1-MRI. Although several cortical and subcortical regions contributed to discrimination, high ROI-weights and predominance of hypometabolism and atrophy were identified specially in medial parietal and temporo-limbic cortical regions. Also, the weight of discrimination due to a pattern of increased voxel-weight values in AD individuals was surprisingly high (ranging from approximately 20% to 40% depending on the imaging modality), located mainly in primary sensorimotor and visual cortices and subcortical nuclei. Conclusion: The MKL-ROI approach highlights the high discriminative weight of a subset of brain regions of known relevance to AD, the selection of which contributes to increased classification accuracy when applied to 18F-FDG-PET data. Moreover, the MKL-ROI approach demonstrates that brain regions typically spared in mild stages of AD also contribute substantially in the individual discrimination of AD patients from controls. Keywords: Alzheimer's Disease, MRI, PET, SPECT, Multiple kernel learning, Brain atla