Automated creation and tuning of personalised muscle paths for OpenSim musculoskeletal models of the knee joint.

Computational modelling is an invaluable tool for investigating features of human locomotion and motor control which cannot be measured except through invasive techniques. Recent research has focussed on creating personalised musculoskeletal models using population-based morphing or directly from medical imaging. Although progress has been made, robust definition of two critical model parameters remains challenging: (1) complete tibiofemoral (TF) and patellofemoral (PF) joint motions, and (2) muscle tendon unit (MTU) pathways and kinematics (i.e. lengths and moment arms). The aim of this study was to develop an automated framework, using population-based morphing approaches to create personalised musculoskeletal models, consisting of personalised bone geometries, TF and PF joint mechanisms, and MTU pathways and kinematics. Informed from medical imaging, personalised rigid body TF and PF joint mechanisms were created. Using atlas- and optimisation-based methods, personalised MTU pathways and kinematics were created with the aim of preventing MTU penetration into bones and achieving smooth MTU kinematics that follow patterns from existing literature. This framework was integrated into the Musculoskeletal Atlas Project Client software package to create and optimise models for 6 participants with incrementally increasing levels of personalisation with the aim of improving MTU kinematics and pathways. Three comparisons were made: (1) non-optimised (Model 1) and optimised models (Model 3) with generic joint mechanisms; (2) non-optimised (Model 2) and optimised models (Model 4) with personalised joint mechanisms; and (3) both optimised models (Model 3 and 4). Following optimisation, improvements were consistently shown in pattern similarity to cadaveric data in comparison (1) and (2). For comparison (3), a number of comparisons showed no significant difference between the two compared models. Importantly, optimisation did not produce statistically significantly worse results in any case.

Machine learning methods to support personalized neuromusculoskeletal modelling.

Many biomedical, orthopaedic, and industrial applications are emerging that will benefit from personalized neuromusculoskeletal models. Applications include refined diagnostics, prediction of treatment trajectories for neuromusculoskeletal diseases, in silico design, development, and testing of medical implants, and human-machine interfaces to support assistive technologies. This review proposes how physics-based simulation, combined with machine learning approaches from big data, can be used to develop high-fidelity personalized representations of the human neuromusculoskeletal system. The core neuromusculoskeletal model features requiring personalization are identified, and big data/machine learning approaches for implementation are presented together with recommendations for further research.

Adverse effects of chronic treatment with the Main subclasses of highly active antiretroviral therapy: a systematic review.

OBJECTIVES: The aim of the review was to elucidate the adverse effects of chronic treatment with the main subclasses of highly active antiretroviral therapy (HAART). METHODS: A systematic review was carried out using the methods recommended in the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). Searches of articles in MEDLINE, SCIELO, Web of Science and LILACS were conducted from January to October 2018 based on the following descriptors and keywords: 'HIV' [AND]; 'AIDS' [OR]; 'HAART' [AND]; 'Highly Active Antiretroviral Therapy' [OR]; 'Adverse Effects' [AND]. All articles selected described the biochemical changes produced by, and the main adverse effects of, using one or more of the following HAART subclasses: nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and other new drugs. The selected articles included patients living with HIV (PLWH) initiating or continuing any type of HAART. The results are presented qualitatively and discussed. RESULTS: Twenty-one articles found in the searches were selected for the review, and they included a total of 5626 participants. Seven of the studies investigated mainly NRTIs, three studies mainly NNRTIs, eight studies predominantly PIs, and three studies other antiretroviral drugs as the main treatment. The most common adverse effects on biochemical parameters were the emergence of anaemia for NRTIs as well as NNRTIs and PIs, and plasma lipid alterations caused by their prolonged use. In general, it was found that biological differences among individuals can cause differences in adverse effects, such as virological and treatment failure. CONCLUSIONS: One or more occurrences of adverse effects of the chronic utilization of drugs were found for all subclasses of HAART, and certain combinations of drugs from different subclasses were also found to be associated with adverse events.

Heart rate variability and phantom pain in male amputees: application of linear and nonlinear methods.

Phantom-limb pain (PLP) is a phenomenon that may appear among people with amputation. Some studies reveal that 70% of people with amputation experience PLP years postamputation. There is a lack of scientific evidence about the cause of PLP. It has been hypothesized that the autonomic nervous system (ANS) could be involved in the mechanism that triggers PLP, but this hypothesis remains unclear. The aim of this study was to correlate ANS function, through heart rate variability (HRV) analysis, with PLP in adult males with amputation. The study population comprised 35 subjects, with 27 reporting PLP often or always. The rest of the subjects did not report any PLP. In order to calculate linear and nonlinear parameters of HRV, all subjects underwent 10 min of resting heart rate monitoring. The study did not find correlations between HRV parameters and PLP. Most of the subjects showed decreased values in linear parameters of HRV while nonlinear values were normal. HRV is not implicated in PLP. Linear and nonlinear methods for HRV analysis might reflect different physiological phenomena; while linear values place people with amputation at cardiovascular risk, nonlinear values indicate normality.

Hypoxic-ischemic brain injury stimulates inflammatory response and enzymatic activities in the hippocampus of neonatal rats.

Brain damage from neonatal hypoxia-ischemia (HI) plays a major role in neonatal mortality and morbidity. Using the Rice-Vannucci model of HI in rats, we verified that 8 days after HI injury, adenosine deaminase (ADA), N-acetyl-glucosaminidase (NAG) and myeloperoxidase (MPO) activities increased in the left hemisphere hippocampus (HI group); however, the activity of 5'-nucleotidase (5'NT) remained unchanged. In the hematoxylin-eosin analysis (HE), we detected selective and delayed degeneration of hippocampal pyramidal neurons and astroglial reaction accompanied by glial fibrillary acidic protein (GFAP)-positive and vimentin-positive in the immunohistochemistry analysis in the HI group compared with the control group. We observed the selective necrosis of neurons, vascular endothelial proliferation and inflammatory response accompanied by the increase of the key enzyme of adenosine metabolism in the HI group. The increase of ADA activity, despite the 5'NT activity was not altered, indicates the predominance of ADA activity in the postischemic homeostasis of extra cellular adenosine. The presence of leukocytes into the ischemic areas displays the possible importance of the neutrophil-macrophages associated with the increase of MPO and NAG activities 8 days after HI. These findings may contribute to the evaluation of some consequences of the damage caused by neonatal HI.

Adenosine deaminase activity, lipid peroxidation and astrocyte responses in the cerebral cortex of rats after neonatal hypoxia ischemia.

Hypoxia ischemia (HI) is a common cause of damage in the fetal and neonatal brain. Lifelong disabilities such as cerebral palsy, epilepsy, behavioral and learning disorders are some of the consequences of brain injury acquired in the perinatal periods. Inflammation and formation of free radicals appear to play key roles in neonatal HI. The aim of this study was to describe the chronological sequence of adenosine deaminase (ADA) activity, the oxidative damage changes and astrocyte response using the classic model of neonatal HI. We observed an increase in the activity of ADA and lipid peroxidation in the cerebral cortex 8 days after neonatal HI. This was accompanied by a GFAP-positive, and the degree of brain damage was determined histochemically by hematoxylin-eosin (HE). Taking into account the important anti-inflammatory role of adenosine, ADA may provide an efficient means for scavenging cell-surrounding adenosine and play an important part in subsequent events of neonatal HI in association with GFAP reactive gliosis. The present investigation showed that neonatal HI causes the increase of free radicals and significant damage in the cerebral cortex. The increase in ADA activity may reflect the activation of the immune system caused by HI because the morphological analysis exhibited a lymphocytic infiltration.

Activity of ectonucleotidases and adenosine deaminase in rats exposed to cigarette smoke.

Cigarette smoke is a complex mixture of various toxic substances that are capable of initiating oxidative damage and promoting blood platelet alterations. In this study, we investigated the activities of the ectoenzymes NTPDase (ectonucleoside triphosphate diphosphohydrolase, CD39) and 5'-nucleotidase (CD73) in platelets as well as adenosine deaminase (ADA) in the plasma of rats exposed to aged and diluted sidestream smoke during 4 weeks. The rats were divided into two groups: I (control) and II (exposed to smoke). After the exposure period, blood was collected and the platelets and plasma were separated for enzymatic assay. The results demonstrated that NTPDase (with ATP as substrate) and 5'-nucleotidase (AMP as substrate) activities were significantly higher in group II (p < 0.05) as compared to group I, while no significant difference was observed for NTPDase with ADP as substrate. The ADA activity was significantly reduced in group II (p < 0.05) as compared with group I. Platelet aggregation was significantly increased in group II (p < 0.05) as compared with group I. We suggest that these alterations in the activity of enzymes from the purinergic system are associated with an increase in platelet aggregation. However, our study has demonstrated that the organism tries to compensate for this enhanced aggregation by increasing hydrolysis of AMP and reducing hydrolysis of adenosine, a potent inhibitor of aggregation and an important modulator of vascular tone.

[Reactivity of a purified antigen of Paracoccidioides brasiliensis with paracoccidioidomycosis and histoplasmosis sera]. / Evaluación de la reactividad de un antígeno purificado de Paracoccidioides brasiliensis frente a sueros de paracoccidioidomicosis e histoplasmosis

The immunoelectrophoretic reactivity of a "crude" and a "purified" antigens of Paracoccidiodes brasiliensis against the sera of confirmed cases of paracoccidioidomycosis and histoplasmosis was evaluated. The "crude" antigen revealed precipitating antibodies in both the homologous and the heterologous human sera; the number of precipitating systems being higher with the former. The "purified" antigen reacted only with the homologous sera. It is postulated that the use of such "purified" antigen may significantly reduce the non specificity of the serologic tests in the immunodiagnosis of paracoccidioidomycosis.