Inhibition of return: Twenty years after

When responding to a suddenly appearing stimulus, we are slower and/or less accurate when the stimulus occurs at the same location of a previous event than when it appears in a new location. This phenomenon, often referred to as inhibition of return (IOR), has fostered a huge amount of research in the last 20 years. In this selective review, which introduces a Special Issue of Cognitive Neuropsychology dedicated to IOR, we discuss some of the methods used for eliciting IOR and its boundary conditions. We also address its debated relationships with orienting of attention, succinctly review findings of altered IOR in normal elderly and neuropsychiatric patients, and present results concerning its possible neural bases. We conclude with an outline of the papers collected in this issue, which offer a more in-depth treatment of behavioural, neural, and theoretical issues related to IOR.     

Obesity is associated with lower mortality risk in elderly diabetic subjects: the Casale Monferrato study

The relationship between obesity and mortality in people with type 2 diabetes has not been definitely assessed. We have examined this issue in a well-characterized population-based cohort of Mediterranean diabetic people. Standardized anthropometric data from the population-based Casale Monferrato Study have been prospectively analyzed. The cohort included 1,475 people (62.6% aged ≥65 years) who had been recruited in 1991 and followed-up to December 31, 2006. Cox proportional hazards modeling was employed to estimate the independent associations between all-cause and cardiovascular mortality and BMI. Out of 1,475 people, 972 deaths occurred during a 15-year follow-up. Cox regression analyses showed that with respect to BMI <24.2 kg/m², values of 30.0 kg/m² and over were associated with lower all-cause and cardiovascular mortality risk (HR = 0.68, 95% CI 0.56–0.85, P for trend = 0.001; HR = 0.59, 0.44–0.80, P for trend = 0.002), independently of classical and new risk factors. As interaction between age and BMI was significant, we performed a stratified analysis by age, providing evidence that our finding was entirely due to a significant protective effect of BMI of 30.0 kg/m² and over in the elderly (all-cause mortality HR = 0.75, 95% CI 0.58–0.96; cardiovascular mortality HR = 0.67, 95% CI 0.45–0.95). In contrast, obesity was not significantly associated with mortality risk in diabetic subjects aged <65 years. Results were confirmed even excluding from the analysis individuals who died within 2 years of follow-up, smokers and those with CHD. In Mediterranean diabetic people aged ≥65 years, obesity is significantly associated with lower 15-year mortality risk. In contrast, it was not significantly associated with mortality risk in diabetic subjects aged <65 years. As more than two-thirds of people with type 2 diabetes are elderly, our findings, if confirmed, could have clinical implications.     

“Polarizing” microplegia improves cardiac cycle efficiency after CABG for unstable angina

Background

Myocardial protection during coronary artery bypass grafting (CABG) for unstable angina (UA) still represents a major challenge, ought to the risk for further ischemia/reperfusion injury. Few studies investigate the biochemical, hemodynamic and echocardiographic results of microplegia (Mic) in UA.

Methods

Eighty UA-patients undergoing CABG were randomized to Mic (Mic-Group) or standard 4:1 blood Buckberg-cardioplegia (Buck-Group). Troponin-I and lactate were sampled from coronary sinus at reperfusion (T1), and from peripheral blood preoperatively (T0), at 6 (T2), 12 (T3) and 48 (T4) hours. Cardiac index (CI), indexed systemic vascular resistances (ISVR), Δp/Δt, cardiac cycle efficiency (CCE), and central venous pressure (CVP) were collected preoperatively (T0), and since Intensive Care Unit (ICU)-arrival (T1) to 24 h (T5). Echocardiographic E-wave (E), A-wave (A), E/A, peak early-diastolic TDI-mitral annular-velocity (Ea), and E/Ea investigated the diastolic function and Wall Motion Score Index (WMSI) the systolic function, preoperatively (T0) and at 96 h (T1).

Results

Mic-Group showed lower troponin-I and lactate from coronary sinus (p = .0001 for both) and during the postoperative course (between-groups p = .001 and .0001, respectively). WMSI improved only after Mic (time-p = .001). Higher CI Δp/Δt and CCE (between-groups p = .0001), with comparable CVP and ISVR (p = N.S.) were detected after Mic. Diastolic function improved in both groups, but better after Mic (between-groups p = .003, .001, and .013 for E, E/A, and Ea, respectively). Mic resulted in lower transfusions (p = .006) and hospitalization (p = .002), and a trend towards lower need/duration of inotropes (p = .04 and p = .041, respectively), and ICU-stay (p = .015).

Conclusion

Microplegia attenuates myocardial damage in UA, reduces transfusions, improves postoperative systo-diastolic function, and shortens hospitalization.     

Left visual neglect: is the disengage deficit space- or object-based?

Attention can be directed to spatial locations or to objects in space. Patients with left unilateral spatial neglect are slow to respond to a left-sided target when it is preceded by a right-sided “invalid” cue, particularly at short cue-target intervals, suggesting an impairment in disengaging attention from the right side in order to orient it leftward. We wondered whether this deficit is purely spatial, or it is influenced by the presence of a right-sided visual object. To answer this question, we tested 10 right brain-damaged patients with chronic left-neglect and 41 control participants on a cued response time (RT) detection task in which targets could appear in either of two lateral boxes. In different conditions, non-informative peripheral cues either consisted in the brightening of the contour of one lateral box (onset cue condition), or in the complete disappearance of one lateral box (offset cue condition). The target followed the cue at different stimulus-onset asynchronies (SOAs). If the disengagement deficit (DD) is purely space-based, then it should not vary across the two cueing conditions. With onset cues, patients showed a typical DD at short SOAs. With offset cues, however, the DD disappeared. Thus, patients did not show any DD when there was no object from which attention must be disengaged. These findings indicate that the attentional bias in left-neglect does not concern spatial locations per se, but visual objects in space.     

Ventral and dorsal visual streams in posterior cortical atrophy: A DT MRI study

Using diffusion tensor magnetic resonance imaging tractography, ventral (inferior longitudinal fasciculus) and fronto-occipital (inferior fronto-occipital fasciculus) and dorsal (fronto-parietal superior longitudinal fasciculus) visual pathways were assessed in 7 patients with posterior cortical atrophy (PCA), showing either predominantly ventral or additional dorsal cognitive deficits. Corpus callosum and corticospinal tracts were also studied. Gray and white matter atrophy was assessed using voxel-based morphometry. In all PCA patients, abnormal diffusivity indexes were found in bilateral inferior longitudinal fasciculus and inferior fronto-occipital fasciculus, with a left-side predominance. Patients also had mild microstructural damage to the corpus callosum. The 2 patients with more dorsal symptoms also showed right fronto-parietal superior longitudinal fasciculus abnormalities. Corticospinal tracts were normal, bilaterally. When studied separately, patients with ventral clinical impairment showed a pattern of atrophy mainly located in the ventral occipitotemporal regions, bilaterally; patients with both ventral and dorsal clinical deficits showed additional atrophy of the bilateral inferior parietal lobe. Magnetic resonance imaging patterns of abnormalities mirror closely the clinical phenotypes and could provide reliable ante mortem markers of tissue damage in PCA.     

Activity of tea tree oil and nerolidol alone or in combination against Pediculus capitis (head lice) and its eggs

Acanthamoeba castellanii causes amoebic keratitis which is a painful sight-threatening disease of the eyes. Its eradication is difficult because the amoebas encyst making it highly resistant to anti-amoebic drugs, but several medicinal plants have proven to be more effective than the usual therapy. This study aimed to evaluate the in vitro amoebicidal activity of ethanol extracts of Arachis hypogaea L. (peanut), Curcuma longa L. (turmeric), and Pancratium maritimum L. (sea daffodil) on A. castellanii cysts. Acanthamoeba were isolated from keratitic patients, cultivated on 1.5% non-nutrient agar, and then incubated with different concentrations of plant extracts which were further evaluated for their cysticidal activity. The results showed that all extracts had significant inhibitory effect on the multiplication of Acanthamoeba cysts as compared to the drug control (chlorhexidine) and non-treated control, and the inhibition was time and dose dependent. The ethanol extract of A. hypogaea had a remarkable cysticidal effect with minimal inhibitory concentration (MIC) of 100 mg/ml in all incubation periods, while the concentrations of 10 and 1 mg/ml were able to completely inhibit growth after 48 and 72 h, respectively. The concentrations 0.1 and 0.01 mg/ml failed to completely inhibit the cyst growth, but showed growth reduction by 64.4–82.6% in all incubation periods. C. longa had a MIC of 1 g and 100 mg/ml after 48 and 72 h, respectively, while the concentrations 10, 1, and 0.1 mg/ml caused growth reduction by 60–90.3% in all incubation periods. P. maritimum had a MIC of 200 mg/ml after 72 h, while the 20-, 2-, 0.2-, and 0.02-mg/ml concentrations showed growth reduction by 34–94.3% in all incubation periods. All extracts seemed to be more effective than chlorhexidine which caused only growth reduction by 55.3–80.2% in all incubation periods and failed to completely inhibit the cyst growth. In conclusion, ethanol extracts of A. hypogaea, C. longa, and P. maritimum could be considered a new natural agent against the Acanthamoeba cyst.     

Collecting core data in severely injured patients using a consensus trauma template: an international multicentre study

Introduction

No worldwide, standardised definitions exist for documenting, reporting and comparing data from severely injured trauma patients. This study evaluated the feasibility of collecting the data variables of the international consensus-derived Utstein Trauma Template.

Methods

Trauma centres from three different continents were invited to submit Utstein Trauma Template core data during a defined period, for up to 50 consecutive trauma patients. Directly admitted patients with a New Injury Severity Score (NISS) equal to or above 16 were included. Main outcome variables were data completeness, data differences and data collection difficulty.

Results

Centres from Europe (n = 20), North America (n = 3) and Australia (n = 1) submitted data on 965 patients, of whom 783 were included. Median age was 41 years (interquartile range (IQR) 24 to 60), and 73.1% were male. Median NISS was 27 (IQR 20 to 38), and blunt trauma predominated (91.1%). Of the 36 Utstein variables, 13 (36%) were collected by all participating centres. Eleven (46%) centres applied definitions of the survival outcome variable that were different from those of the template. Seventeen (71%) centres used the recommended version of the Abbreviated Injury Scale (AIS). Three variables (age, gender and AIS) were documented in all patients. Completeness > 80% was achieved for 28 variables, and 20 variables were > 90% complete.

Conclusions

The Utstein Template was feasible across international trauma centres for the majority of its data variables, with the exception of certain physiological and time variables. Major differences were found in the definition of survival and in AIS coding. The current results give a clear indication of the attainability of information and may serve as a stepping-stone towards creation of a European trauma registry.     

Attention networks and their interactions after right-hemisphere damage

Unilateral spatial neglect is a disabling condition, frequently observed after right-hemisphere damage (RHD), and associated with poor functional recovery. Clinical and experimental evidence indicates that attentional impairments are prominent in neglect. Recent brain imaging and behavioral studies in neglect patients and healthy individuals have provided insights into the mechanisms of attention and have revealed interactions between putative attentional networks. We recruited 16 RHD patients and 16 neurologically intact observers to perform a lateralized version of the Attention Network Test devised by Posner and co-workers (Fan et al., 2002). The results showed evidence of interaction between attentional networks during conflict resolution. Phasic alertness improved the orienting deficit to left-sided targets, reducing the interference of distracters in the neglected visual field, thus facilitating conflict resolution in the majority of patients. Modulating alertness may be an important way of improving basic deficits associated with neglect, such as those affecting spatial orienting.     

Ramucirumab as Second-Line Therapy in Metastatic Gastric Cancer: Real-World Data from the RAMoss Study

Background

Ramucirumab—alone or combined with paclitaxel—represents one of the main options for patients failing first-line treatment for advanced gastric cancer.

Objective

The RAMoss study aimed to evaluate the safety and efficacy profile of ramucirumab in the “real-life setting”.

Patients and Methods

Patients from 25 Italian hospitals started therapy consisting of ramucirumab 8 mg/kg i.v. d1,15q28 with or without paclitaxel 80 mg/m² i.v. d1,8,15q28. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).

Results

One hundred sixty-seven patients with disease progression on first-line therapy received ramucirumab as monotherapy (10%) or combined with paclitaxel (90%). Median treatment duration was 4 months (1–17 months). Global incidence of grade (G) 3–4 toxicity was 9.6%, and for neutropenia 5.4%; treatment was discontinued due to toxicity in 3% of patients. The most frequent adverse events (AE) were G1–2 fatigue (27.5%), G1–2 neuropathy (26.3%), and G1–2 neutropenia (14.9%). ORR was 20.2%. Stable disease was observed in 39.2% of patients, with a disease control rate of 59.4%. With a median follow-up of 11 months, median PFS was 4.3 months (95% confidence interval [CI] 4.1–4.7), whereas median OS was 8.0 months (95% CI: 7.09–8.9). In a multivariate analysis, ECOG performance status <1 or ≥1 (HR 1.13, 95% CI 1.0–1.27, p?=?0.04) and the presence versus absence of peritoneal metastases (HR 1.57, 95% CI 1.63–2.39, p?=?0.03) were independent poor prognostic factors.

Conclusions

These “real-life” efficacy data on ramucirumab treatment are in line with previous randomized trials. Ramucirumab is well tolerated in daily clinical practice.