Molecular docking of the pentapeptide derived from rice bran protein as anticancer agent inhibiting both receptor and non-receptor tyrosine kinases.

The cationic pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) belongs to the family of anti-cancer peptides with significant anti-cancer activity. However, the mechanism by which the peptide performs this activity is unknown. In this study, we explored the pharmaceutical profile of Glu-Gln-Arg-Pro-Arg pentapeptide and revealed its anticancer properties by in silico docking studies. Moreover, the effect of EQRPR behavior of the DPPC membrane was investigated by means of Langmuir monolayer technique and the results were discussed in terms of mutual interactions. To evaluate the binding mechanisms, the pentapeptide and its various D-amino acid substituted analogs were docked to both epidermal growth factor receptor (EGFR) tyrosine kinase and proto-oncogene tyrosine-protein kinase, Fyn. Simultaneous binding of the pentapeptides to both EGFR and Fyn proteins, which are receptor- and non-receptor-kinases, respectively, suggest that these peptides can be an effective agent for cancer treatment. Moreover, to show the potential of the investigated pentapeptides to overcome the generated mutation-related drug resistance to EGFR targeted therapies, molecular docking investigations of EQRPR and all its D-analogs were performed against the prospective targets: Wild type EGFRWT and mutant EGFRT790M. Erlotinib and TAK-285 were used as reference molecules. The strong interaction of the peptide with EGFRWT (from -9.24 to -9.75 kcal/mol) and the secondary mutant EGFRT790M (from -9.28 to -9.64 kcal/mol) observed in most cancer recurrence cases indicates its good potential to overcome drug resistance in cancer therapy. In addition, the pharmacological properties of the investigated pentapeptides were revealed by in silico ADME (Absorption, Distribution, Metabolism, Excretion) and toxicity analysis.Communicated by Ramaswamy H. Sarma.

Does musical interaction in a jazz duet modulate peripersonal space?

Researchers have widely studied peripersonal space (the space within reach) in the last 20 years with a focus on its plasticity following the use of tools and, more recently, social interactions. Ensemble music is a sophisticated joint action that is typically explored in its temporal rather than spatial dimensions, even within embodied approaches. We, therefore, devised a new paradigm in which two musicians could perform a jazz standard either in a cooperative (correct harmony) or uncooperative (incorrect harmony) condition, under the hypothesis that their peripersonal spaces are modulated by the interaction. We exploited a well-established audio-tactile integration task as a proxy for such a space. After the performances, we measured reaction times to tactile stimuli on the subjects' right hand and auditory stimuli delivered at two different distances, (next to the subject and next to the partner). Considering previous literature's evidence that integration of two different stimuli (e.g. a tactile and an auditory stimulus) is faster in near space compared to far space, we predicted that a cooperative interaction would have extended the peripersonal space of the musicians towards their partner, facilitating reaction times to bimodal stimuli in both spaces. Surprisingly, we obtained complementary results in terms of an increase of reaction times to tactile-auditory near stimuli, but only following the uncooperative condition. We interpret this finding as a suppression of the subject's peripersonal space or as a withdrawal from the uncooperative partner. Subjective reports and correlations between these reports and reaction times comply with that interpretation. Finally, we determined an overall better multisensory integration competence in musicians compared to non-musicians tested in the same task.

Association of the CC chemokine receptor 5 (CCR5) polymorphisms with preeclampsia in Turkish women.

AIM: Endothelial dysfunction and inflammation are involved in the pathogenesis of preeclampsia. The CC chemokine receptor 5 (CCR5) modulates inflammation secondary to endothelial dysfunction and related vascular disorders, by initiating chemotaxis. In this study, we examined the frequency of two polymorphisms, the CCR5D32 deletion and the CCR5-59029 A/G promoter point mutation in women with preeclampsia. METHODS: The CCR5 polymorphisms were genotyped in 74 preeclamptic and 128 controls who had been unaffected by preeclampsia in previous pregnancies. Genotyping was performed with the polymerase chain reaction and restriction fragment length polymorphism. Statistical evaluations were made using the chi-square test or Fisher's exact test when appropriate. RESULTS: The percentage of wild-type allele bearers (?/?plus ?/D32 genotypes) in the preeclamptic group was significantly higher than that of non-bearers (98.6 vs.91.4%, P = 0.03, by the Fisher's exact test). The number of the individuals with D32/D32 genotype was significantly high in the control group (P = 0.035). D32 allele revealed a 2.3-fold protective effect against the risk of preeclampsia.When the percentage of G allele bearers of CCR5 59029A/G polymorphism was compared between the groups, a significant increase was seen in preeclamptics (P = 0.002). CONCLUSION: CCR5 polymorphisms significantly influenced the susceptibility to preeclampsia in our study population consisted of Caucasians. The role of chemokines in this syndrome appears to be an important issue.

Influence of subjective visual vertical misperception on balance recovery after stroke.

BACKGROUND: Subjective visual vertical (SVV) perception can be perturbed after stroke, but its effect on balance recovery is not yet known. AIM: To evaluate the influence of SVV perturbations on balance recovery after stroke. METHODS: 28 patients (14 with a right hemisphere lesion (RHL) and 14 with a left hemisphere lesion (LHL)) were included, 5 were lost to follow-up. SVV perception was initially tested within 3 months after stroke, then at 6 months, using a luminous line, which the patients adjusted to the vertical position in a dark room. Mean deviation (V) and uncertainty (U), defined as the standard deviation of the SVV, were calculated for eight trials. Balance was initially assessed by the Postural Assessment Scale for Stroke (PASS), and at 6 months by the PASS (PASS6), a force platform (lateral and sagittal stability limits (LSL6 and SSL6)), the Rivermead Mobility Index (RMI6) and gait velocity (v6). Functional outcome was also assessed by the Functional Independence Measure at 6 months (FIM6). RESULTS: The scores for balance and for FIM6 were related to the initial V value: PASS6 (p = 0.01, tau = -0.38); RMI6 (p = 0.002, tau = -0.48), LSL6 (p = 0.06, tau = -0.29), SSL6 (p = 0.004, tau = -0.43), v6 (p = 0.01, tau = -0.36) and FIM6 (p = 0.001, tau = -0.49), as well as to the initial U value: PASS6 (p = 0.03, tau = -0.32), RMI6 (p = 0.02, tau = -0.35), SSL6 (p = 0.005, tau = -0.43) and FIM6 (p = 0.01, tau = -0.38). CONCLUSIONS: Initial misperception of verticality was related to a poor score for balance after stroke. This relationship seems to be independent of motricity and neglect. Rehabilitation programmes should take into account verticality misperceptions, which could be an important factors influencing balance recovery after stroke.

Evolution of subjective visual vertical perturbation after stroke.

OBJECTIVE: The perception of visual verticality is often perturbed after stroke and might be an underlying component of imbalance. The aim of this study was to describe the evolution of visual vertical (VV) perturbation and to investigate the factors affecting it. METHODS: Thirty patients with hemiplegia after a single hemispheric stroke (17 left lesioned [LL] and 13 right lesioned [RL]) were studied. Visual verticality was tested within 45 days of stroke, and then at 3 and 6 months. Subjects sat in a dark room and adjusted a luminous rod to the vertical position. The differences between patients' adjustments and vertical were calculated. The effects on VV evolution of the side, size, type, and location of the lesion were tested. RESULTS: Sixty percent of the recent stroke patients had an initial inaccurate perception of verticality, and 39% of these patients recovered during the 1st 3 months after stroke. The evolution of VV tilt depended on the side of the lesion (P = 0.01), with better recovery in LL patients. None of the other factors studied affected VV normalization. CONCLUSIONS: The poorer recovery of vertical perception after right-side stroke might be due to the predominant role of the right hemisphere in spatial cognition, and might be involved in the poorer recovery of balance after stroke in RL patients.

Fatigue after stroke.

OBJECTIVES: To examine the phenomenon of fatigue after stroke and to review the knowledge about frequency, consequences, associated factors, physiopathology and treatment. MATERIALS AND METHOD: Medline was systematically searched with the following keywords: stroke, fatigue, sleep disorders, exercise, and rehabilitation. All relevant articles found in the references were screened as well. RESULTS AND DISCUSSION: Fatigue is a common complaint after stroke and occurs in 39-72% of stroke survivors. Some studies show a severe functional impact of this symptom as well as a high mortality rate. Available evidence concerning associated factors is limited, but fatigue is clearly multifactorial. Some studies show that limited exercise capacity, increased gait energy cost, sleep-disordered breathing and sleep disorders can be related to physical fatigue. Other studies show a link between fatigue and depression. The existence of primary fatigue is still controversial. Treatment must follow a diagnostic approach. Treadmill training, among other treatments, improves fitness reserve and lowering of the energy cost of hemiparetic gait, which could be useful in relieving fatigue.

[Visual dependence after recent stroke]. / Dépendance visuelle après accident vasculaire cérébral récent.

INTRODUCTION: After chronic stroke, inability to use pertinent somatosensory or vestibular information have been described. The aim of the study was to determine whether visual dependence occurred early after stroke before rehabilitation. METHOD: Thirty patients with recent hemiplegia (16 right and 14 left hemispheric stroke) performed the rod and frame test (RFT). Patients were asked to adjust the rod to the vertical position under 3 conditions: basically, with a frame tilted 18 degrees to the right and then with the frame tilted to the left. Bias in each condition (mean, SD) was recorded and compared to adjustments of the rod by 23 controls. Motor control, sensibility, functional level (functional independence measure), age, neglect, and then balance by the postural assessment scale for stroke were assessed. RESULTS: Fifty-six per cent (17/30) of patients but only 26% of controls were influenced by the tilt of the frame on the 2 sides (visual dependence). No correlation was found between visual dependence and the characteristics of the patients. DISCUSSION: Many patients with recent hemiplegia seem to rely on visual input. The mechanisms of such visual dependence are discussed. Rehabilitation programs should take into account the possible impairment of sensory organisation and should include exercises to be performed under visual disturbances.

Postural visual dependence after recent stroke: assessment by optokinetic stimulation.

INTRODUCTION: This study was conducted to assess visual dependence of postural control early after stroke. DESIGN: Case control study. SETTING: A Physical Medicine and Rehabilitation Department. METHOD: Twenty-five patients impaired by severe hemiplegia due to a recent first stroke, were examined. Fourteen had a right and 11 a left hemispheric lesion. There were aged 52+/-13 years, time since stroke was 30+/-12 days. Patients' data were compared to data for 25 healthy subjects. Sitting posture was assessed on a dynamic balance, using two parameters: frontal plane displacement of the centre of pressure under optokinetic stimulation (OKS), and the total length of centre of pressure displacement for the stability reaction. On the basis of 90th percentile control data, patients' behaviour was classified as totally visuo independent (VI), totally visuo dependent (VD) or mixed. RESULTS: Body tilt under OKS was greater in patients than controls. No control subject was totally VD, 19 subjects were totally VI. Four patients were totally VD and only six were VI. The only clinical parameter linked to the effect of OKS was the sensitivity impairment. Overall patients with visuospatial neglect were the most perturbed, but two were totally visuo independent. DISCUSSION AND CONCLUSION: Assessment of postural variations in sitting under OKS is proposed for estimating visual dependence early after stroke. Individual reactions are more important than mean group reactions. Visual dependence is not solely due to neurological impairment, implying that previous physiological behaviour may be involved. Knowledge of these characteristics may affect rehabilitation programmes.

[Evaluation of the disabilities of hemiplegic patients]. / Evaluation des incapacités fonctionnelles chez le patient hémiplégique: mise au point.

OBJECTIVES: To identify and describe the most useful functional disability scales for assessing post-stroke hemiplegic patients and those used largely in clinical trials. METHODS: A literature review of Medline about the functional parameters for balance, gait and mobility, upper extremity functional abilities, and activities of daily living. The metrologic properties of the scales were specified as were their clinical use. RESULTS: Thirty-three scales were evaluated and classified into five categories: balance (6 scales), gait and mobility (4), upper limb function (11), global motricity scales (5) and independence in activities of daily living (7). DISCUSSION AND CONCLUSION: Many functional scales are useful for assessing post-stroke hemiplegic patients. To assess balance, the Postural Assessment Stroke Scale and Berg Balance Scale are the most interesting. The Functional Ambulation Classification and the Timed Up and Go Test are the most relevant to assess gait and mobility. The Action Research Arm Test is largely used to assess upper limb functional abilities. The Functional Independence Measure and the Barthel Index are largely used to assess independence in activities of daily living.

Microinvasive carcinoma of the cervix.

The clinical and pathologic features of 51 cases of microinvasive carcinoma of the cervix treated by radical hysterectomy and pelvic lymphadenectomy are presented. Microinvasion was defined as stromal penetration by carcinoma not exceeding a depth of 5 mm from the surface at the point of origin. Patients with confluent patterns and lymphatic invasion were not excluded. Lymphatic invasion was demonstrated in 24% of the patients, but none of the resected lymph nodes from the entire series contained metastatic tumor. Residual invasive disease was present in 9 of 47 patients who underwent conization including 1 in which the residual tumor invaded to 8 mm, although the depth of invasion in the cone biopsy was only 2.5 mm. Factors related to the presence of residual invasive disease included the pattern and extent of invasion and involvement of the cone margin. There were no surgery-related deaths or fistulae in this series; the actuarial survival rate at 5 years was 100%. Simple hysterectomy seems justified if the cone margin is free of tumor since none of these patients has residual disease. In contrast, radical hysterectomy may be indicated if the cone margins are involved in view of high frequency of residual tumor (39%) and the possibility of invasion in the cervix exceeding 5 mm.