Maximal static mouth respiratory pressure in spinal cord injured patients: correlation with motor level

STUDY DESIGN: Transversal. OBJECTIVES: The few studies concerning maximal static mouth respiratory pressures in patients with spinal cord lesions suggest a marked reduction. We studied the correlation of these parameters with the motor level of injury. SETTING: Rehabilitation Center, Brasília/DF, Brazil. METHODS: One hundred and thirty-one patients with traumatic spinal cord injury (C4-L3) were recruited. The participants were assessed by standard spirometry and maximal static mouth respiratory pressure. RESULTS: Forced vital capacity was most reduced in tetraplegics (subgroup C4-C5, 49%+/-25 predicted) and increase successively for each descending subgroup (C6-C8, 61%+/-22 predicted; T1-T6, 70%+/-15 predicted), becoming normal in low paraplegia (T7-L3, 84%+/-15 predicted). There is no evidence of an obstructive disturbance throughout all groups. The lowest average percent predicted of maximal static inspiratory pressure (MIP) was in the subgroup C4-C5 (50%+/-23). The average percent predicted of maximal static expiratory pressure (MEP) improved from 19%+/-14 in the C4-C5 subgroup to 51%+/-19 for T7-L3 subgroup. The average percent predicted of all participants for MIP was 74%+/-30 and for MEP was 37%+/-21. In patients with complete motor lesion, the correlation with the level of injury was stronger for MEP (r=0.81, P<0.0001; r (2)=0.65) than for MIP (r=0.62, P=0.004; r (2)=0.38). No correlation was found among incomplete motor lesion patients. CONCLUSIONS: The linear regression equations for the relationship of percent predicted MIP or MEP to level of injury are applicable only to complete motor lesions and may be useful to establish normative association between them.     

Multivessel percutaneous treatment of Takayasu arteritis

We report the case of a female patient with obstructive lesions in the right and left carotid, right renal, left subclavian and left common iliac arteries which were percutaneously treated.     

A new CHO (Chinese hamster ovary)-derived cell line expressing anti-TNFα monoclonal antibody with biosimilar potential

Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that mediates the homeostasis of immune responses; its exacerbated production is associated with the pathogenesis of autoimmune and chronic inflammatory diseases. Anti-TNFα drugs have revolutionized the treatment of inflammatory conditions such as rheumatoid arthritis and Crohn’s disease. Currently, a worldwide race is on stage for the production of biosimilars moved by patent expiration of monoclonal antibodies (mAbs), such as anti-TNFα adalimumab. Our goal was to develop the first stage of an adalimumab biosimilar candidate with potential for national production, through the generation of a productive and stable cell line and assess its functionality. The robotic system ClonePix was used for screening and isolation of colonies from transfected CHO-S stable pools plated in semisolid medium. Selected clones were expanded based on growth and productivity. Purified mAbs from different clones were tested for binding and functional activity. The binding affinity of the denominated adabut clones to TNFα and FcRγ did not differ statistically when compared to reference adalimumab. One functional activity assay demonstrated the antibody neutralization capacity of the cytotoxicity induced by TNFα in L929 murine fibroblasts. A second assay confirmed adabut as an antagonist of the TNFα activity by the inhibition of the cell adhesion molecule expression in HUVEC cultures. The binding and functional activity analyses performed with selected adabut clones in comparison to reference adalimumab represent an important status of “non-inferiority,” part of the process required for a biosimilar development. We generated and selected high-quality adabut clones which mAbs may be further developed as the first in-house made Brazilian biosimilar, demonstrating a success case for our incipient biotechnology industry, or also modified as biobetters, thus representing an innovative strategy for the patients’ welfare.     

Disruption of brain redox homeostasis in glutaryl-CoA dehydrogenase deficient mice treated with high dietary lysine supplementation

Deficiency of glutaryl-CoA dehydrogenase (GCDH) activity or glutaric aciduria type I (GA I) is an inherited neurometabolic disorder biochemically characterized by predominant accumulation of glutaric acid and 3-hydroxyglutaric acid in the brain and other tissues. Affected patients usually present acute striatum necrosis during encephalopathic crises triggered by metabolic stress situations, as well as chronic leukodystrophy and delayed myelination. Considering that the mechanisms underlying the brain injury in this disease are not yet fully established, in the present study we investigated important parameters of oxidative stress in the brain (cerebral cortex, striatum and hippocampus), liver and heart of 30-day-old GCDH deficient knockout (Gcdh^?/?) and wild type (WT) mice submitted to a normal lysine (Lys) (0.9% Lys), or high Lys diets (2.8% or 4.7% Lys) for 60 h. It was observed that the dietary supplementation of 2.8% and 4.7% Lys elicited noticeable oxidative stress, as verified by an increase of malondialdehyde concentrations (lipid oxidative damage) and 2-7-dihydrodichlorofluorescein (DCFH) oxidation (free radical production), as well as a decrease of reduced glutathione levels and alteration of various antioxidant enzyme activities (antioxidant defenses) in the cerebral cortex and the striatum, but not in the hippocampus, the liver and the heart of Gcdh^?/? mice, as compared to WT mice receiving the same diets. Furthermore, alterations of oxidative stress parameters in the cerebral cortex and striatum were more accentuated in symptomatic, as compared to asymptomatic Gcdh^?/? mice exposed to 4.7% Lys overload. Histopathological studies performed in the cerebral cortex and striatum of these animals exposed to high dietary Lys revealed increased expression of oxidative stress markers despite the absence of significant structural damage. The results indicate that a disruption of redox homeostasis in the cerebral cortex and striatum of young Gcdh^?/? mice exposed to increased Lys diet may possibly represent an important pathomechanism of brain injury in GA I patients under metabolic stress.     

A weighted blanket increases pre-sleep salivary concentrations of melatonin in young,healthy adults

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.     

Survival analysis of cancer patients in Portugal following the reference centre model implementation

The European Journal of Health Economics - Cancer has affected around eighteen million people all over the world in 2018. In Portugal, cancer was diagnosed in sixty thousand individuals during...