Factors associated with mortality of patients with COVID-19 on invasive mechanical ventilation: A retrospective cohort study in a university hospital in Northeastern Brazil.

The aim of this study is to identify the factors associated with mortality in patients with COVID-19 undergoing invasive mechanical ventilation at a university hospital in Northeastern Brazil. This is a retrospective cohort from April to August 2020 through an analysis of medical records, considering the demographic profile, comorbidities, complications, supports, respiratory and laboratory parameters. A total of 65 patients required invasive mechanical ventilation, of which 64.6% died in the ICU. They were older, had more comorbidities, shorter length of stay in the intensive care unit, received more support such as palliative care and two vasopressors simultaneously, showed lower levels of pH, hemoglobin and calcium, and higher levels of bicarbonate, lactate, prothrombin time, international normalized ratio, troponin and ferritin at the start of invasive mechanical ventilation. Furthermore, the time course of pH, arterial oxygen partial pressure to fractional inspired oxygen ratio, arterial carbon dioxide partial pressure, lactate, hemoglobin, platelets, lymphocytes, neutrophil-to-lymphocyte ratio, coagulation parameters, calcium, urea, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, ferritin, static compliance, airway resistance, tidal volume, and noradrenaline doses showed association with mortality. There was a high mortality rate in invasively mechanically ventilated COVID-19 patients, with some associated factors identified at the start of invasive mechanical ventilation and others identified over time.

Effectiveness of exercise and pramipexole in the treatment of restless leg syndrome: Implications on the dopaminergic system and PTPRD.

OBJECTIVE: Dopaminergic dysfunction, iron reduction and variations in the PTPRD gene (protein tyrosine phosphatase receptor type delta) may be associated with restless leg syndrome (RLS). Here, we evaluate the effect of pramipexole (PPX) and exercise on genes and proteins associated with RLS and on sleep patterns in spontaneously hypertensive rats (SHR). METHODS: Animals were distributed into 4 groups: 1) Control (CTRL); 2) Exercise (EX); 3) Exercise and pramipexole (EX + PPX); and 4) Pramipexole (PPX). PPX treatment was performed daily (0.125 mg/kg), while exercise was conducted over 5 sessions per week, both for 4 weeks. RESULTS: EX + PPX increased the protein levels of PTPRD, reduced the protein levels of the enzyme tyrosine hydroxylase (TH) and improved sleep parameters in both cycles; on the other hand, the use of PPX reduced mRNA and protein levels of PTPRD and TH but improved the sleep pattern in the light cycle. However, in the dark cycle, pramipexole caused the worsening of symptoms. CONCLUSIONS: We suggest that the improvement in sleep pattern by EX + PPX may be associated with the increased protein levels of PTPRD and that EX + PPX can reverse the negative effects of PPX.

PTPRD as a candidate druggable target for therapies for restless legs syndrome?

The gene that encodes the protein tyrosine phosphatase D (PTPRD) may be related to brain circuits associated with sleep, and has been seen as an interesting molecule, a "druggable" drug target. This gene is a potential candidate for increasing therapeutic advances in restless legs syndrome, a sleep-related movement disorder, that manifests as an uncontrollable desire to move limbs (legs) to relieve uncomfortable sensations. Changes in the PTPRD gene expression may increase the chance of developing this syndrome. Treatment with pramipexole is used in restless legs syndrome. This study aims to verify the effect of treatment with pramipexole on the PTPRD expression, as well as on the sleep pattern in an animal model for restless legs syndrome. For this, an animal model of sleep-related movement disorders (spontaneously hypertensive rats) was distributed in groups: (a) spontaneously hypertensive rats-control; (b) spontaneously hypertensive rats-pramipexole (0.125 mg kg-1 for 4 weeks). The analyses of PTPRD gene and protein expression were performed in the striatum and spinal cord by quantitative real-time polymerase chain reaction and indirect enzyme-linked immunosorbent assay, respectively. Electrocorticographic and electromyographic analyses were performed. There was no difference in the PTPRD mRNA levels, as well as in the protein levels, although a tendency has been observed for decreased gene expression in the striatum and increased protein expression in the spinal cord in the spontaneously hypertensive rats-pramipexole group. Pramipexole improved the animals' sleep pattern. Thus, the treatment with pramipexole in the evaluated dose and time tended to alter the expression of the PTPRD protein in the spinal cord, in addition to significantly improving the sleep pattern.