Distinct or shared actions of peptide family isoforms: I. Peptidespecific actions of pyrokinins in the lobster cardiac neuromuscular system

Although the crustacean heart is modulated by a large number of peptides and amines, few of these molecules have been localized to the cardiac ganglion itself; most appear to reach the cardiac ganglion only by hormonal routes. Immunohistochemistry in the American lobster Homarus americanus indicates that pyrokinins are present not only in neuroendocrine organs ( pericardial organ and sinus gland), but also in the cardiac ganglion itself, where pyrokinin-positive terminals were found in the pacemaker cell region, as well as surrounding the motor neurons. Surprisingly, the single pyrokinin peptide identified from H. americanus, FSPRLamide, which consists solely of the conserved FXPRLamide residues that characterize pyrokinins, did not alter the activity of the cardiac neuromuscular system. However, a pyrokinin from the shrimp Litopenaeus vannamei [ADFAFNPRLamide, also known as Penaeus vannamei pyrokinin 2 (PevPK2)] increased both the frequency and amplitude of heart contractions when perfused through the isolated whole heart. None of the other crustacean pyrokinins tested (another from L. vannamei and two from the crab Cancer borealis) had any effect on the lobster heart. Similarly, altering the PevPK2 sequence either by truncation or by the substitution of single amino acids resulted in much lower or no activity in all cases; only the conservative substitution of serine for alanine at position 1 resulted in any activity on the heart. Thus, in contrast to other systems (cockroach and crab) in which all tested pyrokinins elicit similar bioactivities, activation of the pyrokinin receptor in the lobster heart appears to be highly isoform specific

Distinct or shared actions of peptide family isoforms: II. Multiple pyrokinins exert similar effects in the lobster stomatogastric nervous system

Many neuropeptides are members of peptide families, with multiple structurally similar isoforms frequently found even within a single species. This raises the question of whether the individual peptides serve common or distinct functions. In the accompanying paper, we found high isoform specificity in the responses of the lobster (Homarus americanus) cardiac neuromuscular system to members of the pyrokinin peptide family: only one of five crustacean isoforms showed any bioactivity in the cardiac system. Because previous studies in other species had found little isoform specificity in pyrokinin actions, we examined the effects of the same five crustacean pyrokinins on the lobster stomatogastric nervous system (STNS). In contrast to our findings in the cardiac system, the effects of the five pyrokinin isoforms on the STNS were indistinguishable: they all activated or enhanced the gastric mill motor pattern, but did not alter the pyloric pattern. These results, in combination with those from the cardiac ganglion, suggest that members of a peptide family in the same species can be both isoform specific and highly promiscuous in their modulatory capacity. The mechanisms that underlie these differences in specificity have not yet been elucidated; one possible explanation, which has yet to be tested, is the presence and differential distribution of multiple receptors for members of this peptide family

Functional Recovery And Quality Of Life Of Intracerebral Hemorrhage (ich) Patients Over 12 Months

Intracerebral hemorrhage (ICH) is associated with high mortality (40-50%) among stroke subtypes, however survivors may exhibit robust functional recovery. Research regarding ICH recovery has focused almost exclusively on motor domains at short time-points, three to six months. This prospective observational study was initiated to follow ICH recovery up to 12 months post-injury across motor and non-motor domains. Patients were enrolled and evaluated at discharge as well as three, six, and 12 months post-injury utilizing the modified rankin scale (mRS), Barthel Index (BI), Montrael Cognitive Assessment (MoCA), European Qualtiy of Life 5 Dimensions (EQ-5D), European Qualtiy of Life Visual Analogue Scale (EQ-VAS), and the Stroke Specific Quality of Life (SS-QoL). As of October 2016, we have enrolled 173 ICH patients, with an average response rate (i.e. the ability to complete follow-up evaluations) of 85-89% across all follow-up time-points. Using either the mRS or BI, measures of motor disability, there was a significant improvement in scores (p values \u3c 0.001) between discharge and three, six, and 12 months. The mRS scores failed to show a significant difference between follow-up time-points (i.e. three to six months, six to 12 months, etc.). However the BI showed significant improvement in scores between three and 12 months (p = 0.013), as well as between six and 12 months (p = 0.025). A subsequent analysis, comparing BI scores between three to 12 months, showed a significant relationship of time by age (p = 0.047; i.e. differences in improvement depending on the age of the patient), time by admission GCS (p = 0.010; i.e. differences in improvement depending on the admission GCS of the patient), time by ICH volume (p = 0.004; i.e. differences in improvement depending on the initial ICH volume of the patient), and time by location (p = 0.005; i.e. differences in improvement depending on the initial ICH location of the patient). Follow-up plots suggest patients with characteristically more disabling injury as traditionally measured through metrics like the ICH score (i.e. older patients, lower admission GCS, larger ICH volume, deeper location) showed the most improvement between three and 12 months. These results would suggest that ICH motor recovery will improve up to at least 12 months post-injury and patients with more debilitating injury will show improved recovery at the late-stage. Across quality of life measures (i.e. EQ-5D, EQ-VAS, SS-QoL), patients showed the greatest recovery in motor domains (i.e. Mobility, Self-Care, Activities, Upper Extremities). Despite this improvement, patients self-reported health scores (EQ-VAS, a subjective 0 to 100 point score that patients use to describe their overall health) declined across time-points. There were additionally decreases in scores associated with the “Thinking” domain as well as increases in “Pain” symptoms. Since decreases in self-reported health score matched trends in the “Thinking” and “Pain” domains rather than the increases observed in motor-domains, patients may value non-motor domains when assessing their overall health compared to motor recovery. Finally, while there are improvements of cognitive impairment (measured via the MoCA, total score \u3c 18) across time-points (discharge: 72%, three months: 65%, six months: 53%, 12 months: 48%), these results are more profound for deep compared to lobar ICH. Preliminary analyses of the cohort enrolled thus far suggest ICH patients improve in motor recovery up to at least 12 months post-injury. However despite robust motor recovery, patients still exhibit high rates of cognitive impairment and impairment in quality of life. These results necessitate the need for long-term end-points in ICH interventional trials with further emphasis on non-motor domains. Continued enrollment and prospective evaluation of this cohort promises further insight into the recovery process

Clinical trial publication trends within neurology

Timely dissemination of results from clinical studies is crucial for the advancement of knowledge and clinical decision making. A large body of research has shown that up to half of clinical trials do not publish their findings. In this study, we sought to determine whether clinical trial publication rates within neurology have increased over time. Focusing on neurology clinical trials completed between 2008 to 2014, we found that while the overall percentage of published trials has not changed (remaining at approximately 50%), time to publication has significantly decreased. Our findings suggest that clinical trials within neurology are being published in a more timely manner

Elevated Hypoperfusion Intensity Ratio (HIR) observed in patients with a large vessel occlusion (LVO) presenting in the evening

International audienceBackground: Circadian variability has been implicated in timing of stroke onset, yet the full impact of underlying biological rhythms on acute stroke perfusion patterns is not known. We aimed to describe the relationship between time of stroke onset and perfusion profiles in patients with large vessel occlusion (LVO).Methods: A retrospective observational study was conducted using prospective registries of four stroke centers across North America and Europe with systematic use of perfusion imaging in clinical care. Included patients had stroke due to ICA, M1 or M2 occlusion and baseline perfusion imaging performed within 24h from last-seen-well (LSW). Stroke onset was divided into eight hour intervals: (1) Night: 23:00-6:59, (2) Day: 7:00-14:59, (3) Evening: 15:00-22:59. Core volume was estimated on CT perfusion (rCBF <30%) or DWI-MRI (ADC <620) and the collateral circulation was estimated with the Hypoperfusion Intensity Ratio (HIR = [Tmax>10s]/[Tmax>6s]). Non-parametric testing was conducted using SPSS to account for the non-normalized dependent variables.Results: A total of 1506 cases were included (median age 74.9 years, IQR 63.0-84.0). Median NIHSS, core volumes, and HIR were 14.0 (IQR 8.0-20.0), 13.0mL (IQR 0.0-42.0), and 0.4 (IQR 0.2-0.6) respectively. Most strokes occurred during the Day (n = 666, 44.2%), compared to Night (n = 360, 23.9%), and Evening (n = 480, 31.9%). HIR was highest, indicating worse collaterals, in the Evening compared to the other timepoints (p = 0.006). Controlling for age and time to imaging, Evening strokes had significantly higher HIR compared to Day (p = 0.013).Conclusion: Our retrospective analysis suggests that HIR is significantly higher in the evening, indicating poorer collateral activation which may lead to larger core volumes in these patients