Clinical efficacy of diazepam after whiplash: a randomized controlled study.

Aim To investigate the role of short-term diazepam therapy for improving long-term outcomes and reducing neck pain after whiplash injury. Methods A total of 89 patients suffering from whiplash injury were included. They were randomly assigned into 2 groups: group A (study group), and group B (control group). The test group was prescribed with diazepam 5 mg tablets one time per day for 7 days and the control group did not get the recommendation to use diazepam. Three previously validated scales, Visual Analogue Pain Scale (VAS), the Neck Disability Index (NDI), and the Whiplash Disability Questionnaire (WDQ), were used at different intervals (7 days, 6 weeks and 6 months after the injury). Results Among 89 patients, 50 (56.2%) were males, 39 (43.8%) females. The mean age of all participants was 34.80±12.531 years. According to the Mann Whitney U -Test, no significant difference was observed in VAS, NDI, and WDQ scores between the control group and study group at any time point (p>0.05). Conclusion Diazepam provides no substantial advantage in the treatment of whiplash, and accordingly, we do not recommend diazepam therapy in patients who suffered whiplash injury. The trial was registered in the database of the Federal National Library of Medicine (NLM) (https://clinicaltrials.gov) under clinical trials (unique protocol ID:1703016).

Comparison of early and delayed lumbar disc herniation surgery and the treatment outcome.

Aim To evaluate the influence of preoperative symptoms duration on surgical outcome of one-level lumbar disc herniation surgery. Methods In a prospective randomized study, 67 adult patients with one-level lumbar disc herniation were analysed. The patients whose duration of symptoms was <6 months were included in the case group, while those with the duration of symptoms ˃6 months formed the control group. The investigated preoperative variables were: pain intensity in the back and legs (Visual Analogue Scale - VAS), Sciatica Bothersomeness Index (SBI), index of disability (Oswestry Disability Index - ODI). Postoperative variables were: pain intensity in the back and legs (VAS), SBI, ODI, and outcome according to the Odom's criteria (excellent, good, satisfactory and poor). Significance level was set at p <0.05. Results A statistically significant difference was recorded between the groups, showing a better decrease of radicular pain intensity and sciatica bothersome, as well as patients disability in the case group (p<0.001). According to the Odom's criteria the outcome was better in the case group, since the difference between the groups was statistically significant too (p<0.05). Conclusion Early lumbar disc herniation surgery performed within the first 6 months from the start of symptoms is beneficial due to decreases of radicular pain intensity, sciatica bothersomeness, and patient's disability.

The PET and LIM1-2 domains of testin contribute to intramolecular and homodimeric interactions.

The focal adhesion protein testin is a modular scaffold and tumour suppressor that consists of an N-terminal cysteine rich (CR) domain, a PET domain of unknown function and three C-terminal LIM domains. Testin has been proposed to have an open and a closed conformation based on the observation that its N-terminal half and C-terminal half directly interact. Here we extend the testin conformational model by demonstrating that testin can also form an antiparallel homodimer. In support of this extended model we determined that the testin region (amino acids 52-233) harbouring the PET domain interacts with the C-terminal LIM1-2 domains in vitro and in cells, and assign a critical role to tyrosine 288 in this interaction.

Simple Tumor Localization Scale for Estimating Management Outcome of Intracranial Meningioma.

OBJECTIVE: Intracranial meningiomas are typically benign extracerebral tumors derived from dural arachnoid cells. Predominantly, these tumors are effectively managed surgically, but the prognosis is heavily dependent on a tumor's histologic heterogeneity and its location. It is known that reproductive and hormonal factors increase the risk for meningioma in adult females, but their prognostic value still remains controversial. This study's aim was to examine possible correlation between tumor location and outcome, as well as to evaluate the prognostic value of the proposed simple tumor localization scale in predicting the management outcome of intracranial meningioma. METHODS: In a retrospective, cross-section survey, a single-institution cohort of 243 patients operated on due to intracranial meningioma was analyzed. The investigated parameters were age and gender, tumor location, and extent of surgery (Simpson grading). The patients were divided into 2 groups allocating tumors to central and peripheral position within the cranial vault. The outcome was estimated by Karnofsky Performance Score (KPS) at discharge from hospital and Glasgow Outcome Scale at 1 year after surgery. RESULTS: A statistically significant correlation between tumor location and outcome, as well as negative correlation between age and outcome, were observed (P < 0.001). CONCLUSIONS: When estimating the management outcome of intracranial meningiomas, we propose a simple localization scale dividing the tumors into central and peripheral positions. Central tumor location might be prognostically unfavorable due to involvement of major neurovascular structures. Among the independent factors predicting favorable tumor response to surgery, more effective outcomes associated with peripheral tumor location and younger age were observed.

Delineating the Tes Interaction Site in Zyxin and Studying Cellular Effects of Its Disruption.

Focal adhesions are integrin-based structures that link the actin cytoskeleton and the extracellular matrix. They play an important role in various cellular functions such as cell signaling, cell motility and cell shape. To ensure and fine tune these different cellular functions, adhesions are regulated by a large number of proteins. The LIM domain protein zyxin localizes to focal adhesions where it participates in the regulation of the actin cytoskeleton. Because of its interactions with a variety of binding partners, zyxin has been proposed to act as a molecular scaffold. Here, we studied the interaction of zyxin with such a partner: Tes. Similar to zyxin, Tes harbors three highly conserved LIM domains of which the LIM1 domain directly interacts with zyxin. Using different zyxin variants in pull-down assays and ectopic recruitment experiments, we identified the Tes binding site in zyxin and showed that four highly conserved amino acids are crucial for its interaction with Tes. Based upon these findings, we used a zyxin mutant defective in Tes-binding to assess the functional consequences of abrogating the zyxin-Tes interaction in focal adhesions. Performing fluorescence recovery after photobleaching, we showed that zyxin recruits Tes to focal adhesions and modulates its turnover in these structures. However, we also provide evidence for zyxin-independent localization of Tes to focal adhesions. Zyxin increases focal adhesion numbers and reduces focal adhesion lifetimes, but does so independent of Tes. Quantitative analysis showed that the loss of interaction between zyxin and Tes affects the process of cell spreading. We conclude that zyxin influences focal adhesion dynamics, that it recruits Tes and that this interaction is functional in regulating cell spreading.

Low back and lumbar radicular syndrome: comparative study of the operative and non-operative treatment.

AIM: To compare the effectiveness of the discectomy and conservative treatment in patients with disc related low back and lumbar radicular syndrome. METHODS: We performed retrospective-prospective cohort study enrolling 100 patients. According to our extended criteria all of them had operative indications. We operated 50 patients, 50 patients refused operation and they were treated non-operatively. The following measures of outcome were used: Sciatica Bothersomeness Index, leg and back pain depending on the activity, Lasègue test, contralateral Lasègue test, neurological deficit. Data were assessed at the beginning of the treatment and after 2 months, 7 months, and 18 months. RESULTS: Treatment results were in favor of surgery for majority of outcome measures as well as for all periods of assessment. After 18 months there was significant difference between operated and non-operated patients related to Sciatica Bothersomeness Index (p less than 0,05), Lasègue test (p=0,002), neurological deficit (p less than 0,05) and leg and back pain depending on the activity (p=0,009). There was no significant difference between the groups related to contralateral Lasègue test (p=0,206). CONCLUSION: We expended formerly accepted operative indications. There were better treatment results in the operated group of patients. A fast reduction of symptoms is the main advantage of the operative treatment strategy. Patients whose pain is controlled in a manner that is acceptable for them may decide to postpone surgery. Patients preference for the type of treatment is crucial for an ultimate surgical decision in cases without widespread neurologic deficits.

Giant craniopharyngioma: 9-year follow up after stereotactic Yttrium -90 instillation and microsurgical resection.

The primary goal in craniopharyngioma treatment is a gross total neurosurgical resection. This paper presents a case with good outcome following a gross total removal of giant juvenile craniopharyngioma. There is a strong relationship between surgical experience in treating these lesions and the probability of total tumor resection without significant morbidity and mortality. The discussion on usefulness of stereotactic instillation of radioactive Yttrium-90 in the tumor cyst and bilateral fronto-orbital microsurgical approach utilized in 12-year-old male patient was conducted. A detailed description of the operative procedure was provided with comparison to other approaches commonly used for giant craniopharingioma. The long term (9 years) and intensive follow up showed good outcome without tumor recurrence. The patient has been receiving lifelong hormones substitution.

Quantitative kinetic study of the actin-bundling protein L-plastin and of its impact on actin turn-over.

BACKGROUND: Initially detected in leukocytes and cancer cells derived from solid tissues, L-plastin/fimbrin belongs to a large family of actin crosslinkers and is considered as a marker for many cancers. Phosphorylation of L-plastin on residue Ser5 increases its F-actin binding activity and is required for L-plastin-mediated cell invasion. METHODOLOGY/PRINCIPAL FINDINGS: To study the kinetics of L-plastin and the impact of L-plastin Ser5 phosphorylation on L-plastin dynamics and actin turn-over in live cells, simian Vero cells were transfected with GFP-coupled WT-L-plastin, Ser5 substitution variants (S5/A, S5/E) or actin and analyzed by fluorescence recovery after photobleaching (FRAP). FRAP data were explored by mathematical modeling to estimate steady-state reaction parameters. We demonstrate that in Vero cell focal adhesions L-plastin undergoes rapid cycles of association/dissociation following a two-binding-state model. Phosphorylation of L-plastin increased its association rates by two-fold, whereas dissociation rates were unaffected. Importantly, L-plastin affected actin turn-over by decreasing the actin dissociation rate by four-fold, increasing thereby the amount of F-actin in the focal adhesions, all these effects being promoted by Ser5 phosphorylation. In MCF-7 breast carcinoma cells, phorbol 12-myristate 13-acetate (PMA) treatment induced L-plastin translocation to de novo actin polymerization sites in ruffling membranes and spike-like structures and highly increased its Ser5 phosphorylation. Both inhibition studies and siRNA knock-down of PKC isozymes pointed to the involvement of the novel PKC-delta isozyme in the PMA-elicited signaling pathway leading to L-plastin Ser5 phosphorylation. Furthermore, the L-plastin contribution to actin dynamics regulation was substantiated by its association with a protein complex comprising cortactin, which is known to be involved in this process. CONCLUSIONS/SIGNIFICANCE: Altogether these findings quantitatively demonstrate for the first time that L-plastin contributes to the fine-tuning of actin turn-over, an activity which is regulated by Ser5 phosphorylation promoting its high affinity binding to the cytoskeleton. In carcinoma cells, PKC-delta signaling pathways appear to link L-plastin phosphorylation to actin polymerization and invasion.