Dependence of saccadic eye-movements on stimulus luminance, and an effect of task

Various aspects of saccadic eye-movements are related to stimulus luminance for a small lit stimulus that steps 10 degrees horizontally in complete darkness. The relations depend on whether the stimulus is the target for a foveating saccade, or is the cue for an "anti" saccade which peripheralizes the retinal image of the cue: (1) at scotopic luminances the differences between foveating and anti saccades are diminished, largely because foveation is the more severely affected. Latencies are long amplitudes are scattered, and direction errors are not infrequent in both tasks; (2) the latency-luminance relation for foveating saccades shows an abrupt discontinuity at the perceptual rod-cone transition. Above the cone threshold corrective secondary saccades appear in greater numbers; (3) the corresponding latency transition for anti saccades is anomalous and protracted. Latency remains constant for mesopic cue luminances up to 1.0 log unit brighter than the perceptual rod-cone threshold. Direction errors are especially common in this mesopic luminance range. Mechanisms are discussed.     

Involvement of MMPs in delayed neuronal death after global ischemia

Spatial and temporal relations between metalloproteinase (MMP-2 and MMP-9) activation and laminin degradation in gerbil hippocampus after transient cerebral ischemia has been studied. Activity of MMPs was determined by gelatin zymography in homogenates from dorsal (DP, an equivalent of CA1 sector) and abdominal (AbP, containing CA2-4 and gyrus dentatus) parts of hippocampus. A significant activation of both investigated metalloproteinases was found at 72 h of recovery. Whereas MMP-2 up-regulation did not show any spatial preferences, the increase of MMP-9 activity was observed exclusively in DP. Activation of MMP-9 at this time point correlated spatially with degradation of laminin-protein of extracellular matrix. These results show that MMP pathway may function as a component of delayed neuronal death cascade in the apoptogenic CA1 sector after transient global ischemia.     

Wczesna niehematologiczna toksyczność po chemioterapii w wysokich dawkach i autologicznym przeszczepieniu komórek krwiotwórczych u chorych na nowotwory limfoidalne powyżej 60. roku życia

Early non-haematological toxicity of high dose therapy (HDT) and autologous haematopoietic cell transplantation (autoHCT) can be more hazardous in older patients (pts) with comorbidities. The aim of the study was to analyze incidence and grade of the organ-related early complications up to 30 days post-transplant period in elderly lymphoma patients. Between January 2005 and November 2011, 44 consecutive lymphoma pts underwent HDT followed by autoHCT. Median age of pts was 62 years (range 60–67). Conditioning regimens were: BEAM(carmustine, etoposide, cytarabine, melphalan) in 16, melphalan 200 in 22, cytarabine, melphalan or cyclophosphamide – in 6 pts. 32% pts had comorbidities: in 71% cardiovascular. Early non-haematologic complications within 30 days after autoHCT were reported in 84% of pts. The most common events were gastrointestinal (77%): 55% pts had prolonged (more than 7 days) diarrhoea grade III—IV, nausea and vomiting occurred in 40% of pts, 50% of pts demonstrated mucositis (grade III—IV in 34% of pts). Neutropenic fever was reported in 59% of pts with sepsis in 1.9% of pts. Cardiac events occurred in 9% of pts. Median hospitalization was 21 days (range 16—45). One patient died from transplanted related toxicity. HDT resulted in high incidence of non-hematologic toxicity in elderly patients during early post-transplant period. The toxicity of this procedure is acceptable, with mortality rate of only 2% in the elderly transplanted patients. The most common toxicities were: neutropenic fever, gastrointestinal toxicity and cardiac complications     

Nicotine effects on exercise performance and physiological responses in nicotine‐naïve individuals: a systematic review

The purpose of this systematic review was to evaluate the effects of smokeless forms of nicotine on physiological responses and exercise performance. Methodology and reporting were based on the PRISMA statement. The intervention was defined as any product containing nicotine that did not require smoking. Searches were conducted across two electronic databases with supplementary approaches utilized. Studies were selected following set inclusion and exclusion criteria and checked by two independent authors. A modified PEDro scale was utilized to rate study quality with studies averaging 9·3/13. Six studies assessed exercise performance with endurance‐based parameters reported as significantly improved with nicotine in one study, while anaerobic parameters were unaffected or decreased compared to placebo except in one study which reported enhanced leg extensor torque but no effect on countermovement jump or Wingate anaerobic capacity. Sixteen of 28 studies investigating physiological responses reported that nicotine significantly increased heart rate compared to placebo or control. Blood pressure and blood flow were also reported as significantly increased in multiple studies. While there is strong evidence of nicotine‐induced changes in physiological function that would benefit physical performance, beneficial effects have only been reported on leg extensor torque and endurance performance by one study each. Subsequently, there is need for more research with strong methodological quality to definitively evaluate nicotine's potential as an ergogenic aid.     

Using Patient Feedback to Optimize the Design of a Certolizumab Pegol Electromechanical Self-Injection Device: Insights from Human Factors Studies

Introduction

We incorporated patient feedback from human factors studies (HFS) in the patient-centric design and validation of ava^®, an electromechanical device (e-Device) for self-injecting the anti-tumor necrosis factor certolizumab pegol (CZP).

Methods

Healthcare professionals, caregivers, healthy volunteers, and patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or Crohn’s disease participated in 11 formative HFS to optimize the e-Device design through intended user feedback; nine studies involved simulated injections. Formative participant questionnaire feedback was collected following e-Device prototype handling. Validation HFS (one EU study and one US study) assessed the safe and effective setup and use of the e-Device using 22 predefined critical tasks. Task outcomes were categorized as “failures” if participants did not succeed within three attempts.

Results

Two hundred eighty-three participants entered formative (163) and validation (120) HFS; 260 participants performed one or more simulated e-Device self-injections. Design changes following formative HFS included alterations to buttons and the graphical user interface screen. All validation HFS participants completed critical tasks necessary for CZP dose delivery, with minimal critical task failures (12 of 572 critical tasks, 2.1%, in the EU study, and 2 of 5310 critical tasks, less than 0.1%, in the US study).

Conclusion

CZP e-Device development was guided by intended user feedback through HFS, ensuring the final design addressed patients’ needs. In both validation studies, participants successfully performed all critical tasks, demonstrating safe and effective e-Device self-injections.

Funding

UCB Pharma.

Plain Language Summary

Plain language summary available on the journal website.

     

Enhanced thrombin generation in women with a history of oral contraception-related venous thrombosis

Introduction

In women who suffer venous thrombosis (VT) during oral contraceptive (OC) use, a transient risk factor (OC) is removed during the acute event, while most co-existing forms of thrombophilia persist and presumably continue to maintain hypercoagulability. The aim of this study was to establish if hypercoagulability persists long after OC-related VT and if it could be attributed to thrombophilia.

Materials and Methods

60 women (age 33.0 ± 8.5 years) were investigated 5 – 64 (median 33) months after OC-related VT (patients) and compared to 63 apparently healthy women (controls). All women were tested for thrombophilia, activated partial thromboplastin time (APTT), fibrinogen, D-dimer, P-selectin and C-reactive protein. Thrombin generation was measured by Technothrombin® TGA assay. Overall haemostasis potential (OHP) assay with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) as supplementary parameters were measured by repeated fibrin formation and degradation registration.

Results

In patients increased endogenous thrombin potential (4205 ± 440 nM x min vs 4015 ± 421 nM x min, p = 0.017), increased OCP (22.6 ± 4.6 Abs-sum vs 20.8 ± 4.1 Abs-sum, p = 0.025), shorter APTT (30.9 ± 3.8 s vs 33.4 ± 3.6 s, p < 0.001) and lower antithrombin activity (99, 93-105% vs 104, 100-109%, p < 0.05) were observed. Thrombophilia was observed in 22/60 (36%) patients and in 5/63 (7.9%, p < 0.001) controls. The only significant difference between thrombophilic and non-thrombophilic patients was higher soluble P-selectin in the former subgroup (22, 20-33 μg/L vs 17, 12-22 μg/L, p = 0.012).

Conclusions

In women with a history of OC-related VT persistent hypercoagulability was observed, which, however was not augmented by the presence of thrombophilia.     

Comparative usability study for a certolizumab pegol autoinjection device in patients with rheumatoid arthritis

Objectives: To compare the usability of a new certolizumab pegol (CZP) autoinjector with the adalimumab, etanercept, and golimumab devices in patients with rheumatoid arthritis.

Methods: Two identical studies were performed in 2013 and 2016; patients performed a simulated self-injection with the CZP autoinjector and the most up-to-date device versions at the time in a randomized, consecutive sequence. The primary end point was the ranking of the four autoinjectors in order of preference. Device usability and intuitiveness were assessed across a range of secondary and exploratory end points.

Results: The 2013 and 2016 study populations included 76 patients each; a significant majority (2013: 67%; 2016: 59%) ranked the CZP autoinjector as their most preferred device (p < 0.001). Most patients agreed that the CZP autoinjector was easier to use, start, and manipulate, and were more willing to use it than the comparator devices (p < 0.001 for all pairwise comparisons with CZP). Likert score differences also favored the CZP autoinjector regarding how easy it was to determine injection completion. The CZP autoinjector was associated with a low rate of use error.

Conclusions: In both studies, the CZP autoinjector was the preferred choice compared to the alternative devices and was associated with a high level of patient satisfaction.     

Impaired synthesis is not the reason for decreased activity of extracellular superoxide dismutase in patients with diabetes

BACKGROUND: The aim of the study was to find the cause of decreased activity of extracellular superoxide dismutase (EC SOD) in patients with diabetes-is it the decreased synthesis or increased glycation? METHODS: Total EC SOD activity, the activity of its fractions (A, B, and C) and its glycated form were determined in basal state and 30 min after intravenous (i.v.) administration of 50 mg of heparin. Patients were given i.v. heparin at a dose of 10,000 IU (100 mg) each 6 h for at least 3 days, and the activity of EC SOD was determined before the first heparin administration, just before each subsequent administration, and 30 min after heparin administration. RESULTS: Pre- and postheparinic activities of EC SOD and its fraction C in the group of patients with diabetes were significantly lower (p <0.001) than in control group. Preheparinic activities of EC SOD did not differ between the examined groups of patients. The postheparinic activities were different during the first 18 h of treatment. They were significantly lower in the group of patients with diabetes. During the following hours, after subsequently administered doses, there were no differences in the activity of EC SOD between the examined groups. Decline of EC SOD activity was observed after administration of repeated doses of heparin both in the examined and in the control groups. CONCLUSIONS: The decrease of extracellular superoxide dismutase activity in diabetes develops due to excessive glycation but not due to impaired synthesis. Therefore, appropriate glycemic control can lead to normalization of EC SOD activity.