Advancing glenohumeral dysplasia treatment in brachial plexus birth injury: the end-to-side spinal accessory to suprascapular nerve transfer technique.

PURPOSE: Brachial plexus birth injury (BPBI) is a common injury with the spectrum of disease prognosis ranging from spontaneous recovery to lifelong debilitating disability. A common sequela of BPBI is glenohumeral dysplasia (GHD) which, if not addressed early on, can lead to shoulder dysfunction as the child matures. However, there are no clear criteria for when to employ various surgical procedures for the correction of GHD. METHODS: We describe our approach to correcting GDH in infants with BPBIs using a reverse end-to-side (ETS) transfer from the spinal accessory to the suprascapular nerve. This technique is employed in infants that present with GHD with poor external rotation (ER) function who would not necessitate a complete end-to-end transfer and are still too young for a tendon transfer. In this study, we present our outcomes in seven patients. RESULTS: At presentation, all patients had persistent weakness of the upper trunk and functional limitations of the shoulder. Point-of-care ultrasounds confirmed GHD in each case. Five patients were male, and two patients were female, with a mean age of 3.3 months age (4 days-7 months) at presentation. Surgery was performed on average at 5.8 months of age (3-8.6 months). All seven patients treated with a reverse ETS approach had full recovery of ER according to active movement scores at the latest follow-up. Additionally, ultrasounds at the latest follow-up showed a complete resolution of GHD. CONCLUSION: In infants with BPBI and evidence of GHD with poor ER, end-to-end nerve transfers, which initially downgrade function, or tendon transfers, that are not age-appropriate for the patient, are not recommended. Instead, we report seven successful cases of infants who underwent ETS spinal accessory to suprascapular nerve transfer for the treatment of GHD following BPBI.

A Case Report of Infant-Type Hemispheric Glioma with a Novel GAB1-ABL2 Kinase Fusion Treated with Dasatinib.

INTRODUCTION: Infant-type hemispheric glioma (IHG) is a rare form of cancer that affects newborns and infants. It is classified as a pediatric-type high-grade glioma and typically harbors receptor tyrosine kinase (RTK) gene fusions. Here, we present the finding of a novel gene fusion IHG treated with a targeted therapy that has yet to be implemented for any other IHG case to date. CASE PRESENTATION: We report the case of a 12-month-old boy with IHG who presented with obstructive hydrocephalus due to a large mass in the right frontal lobe. The patient initially underwent mass resection, but subsequent imaging showed rapid interval progression of the residual tumor. Comprehensive molecular analysis of the tumor tissue revealed a novel GAB1-ABL2 gene fusion, and the patient was started on dasatinib, an ABL kinase inhibitor. Shortly after initiation of dasatinib treatment, there was a significant reduction in tumor size and enhancement, followed by stabilization of disease. DISCUSSION: The patient's robust response to treatment suggests that dasatinib is an effective targeted therapy for IHG harboring a GAB1-ABL2 gene fusion. This finding may inform future investigations into the disease processes of IHG and help guide the diagnosis and treatment of IHG in the absence of previously identified gene fusions, improving clinical management of this vulnerable patient population.

An adolescent case of sellar osteochondromyxoma in the setting of spondyloepiphyseal dysplasia.

PURPOSE: Osteochondromyxomas (OMX) are rare congenital bone tumors that have only been described in the context of Carney complex syndrome (CNC). Data on OMX as a separate entity and in association with other disorders remain limited, making both diagnosis and treatment difficult. METHODS: A case report of a 17-year-old female diagnosed with sellar OMX is presented in the setting of spondyloepiphyseal dysplasia (SED). We discuss the radiographic and histopathological interpretations in addition to reviewing the current literature on OMX. RESULTS: A successful gross total resection of the tumor was achieved via an endonasal endoscopic transsphenoidal approach. A diagnosis was established radiographically and pathologically. CONCLUSION: The diagnosis and treatment of OMX are best achieved via tissue biopsy. Following confirmed osteochondromyxoma cases long term for recurrence and outcomes will be essential in understanding its natural tumor history and in establishing standard treatments.

Ventriculopleural shunt outcomes for pediatric hydrocephalus: a single-institution experience.

PURPOSE: The aim of this study is to analyze rates of ventriculopleural (VPL) shunt failure and complications among patients with pediatric hydrocephalus, and to analyze which factors may predict early (< 1 year) or late (> 1 year) VPL shunt failure in this sample. METHODS: A retrospective chart review was conducted of all consecutive VPL shunt placements from 2000 to 2019 at our institution. Data was collected on patient characteristics, shunt history, and shunt type. Primary endpoints include rates of VPL shunt survival and rates of symptomatic pleural effusion. The Kaplan-Meier method was used to calculate shunt survival, and Fisher's exact test and t-test were used to compare differences between categorical variables and means, respectively (p < 0.05). RESULTS: Thirty-one patients with pediatric hydrocephalus underwent VPL shunt placement (mean age 14.2 years). Of the 27 patients with long-term follow-up (mean 46 months), VPL shunt revision was required in 19, seven of which were due to pleural effusion. Overall shunt survival rates at 1, 3, 5, and 7 years were 76%, 62%, 55%, and 46%, respectively. Mean duration of shunt survival was 26.74 months. Overall pleural effusion rate was 26%. No patient-specific factors, including shunt valve type, were significantly associated with shunt survival, risk of early revision, or risk of pleural effusion. CONCLUSIONS: Our results are comparable to those reported in the literature and represent one of the largest case series on the topic. VPL shunts are a viable second-line option when ventriculoperitoneal (VP) shunt placement is not possible or desirable, though there are high rates of shunt revision and pleural effusion.

Pediatric brain aneurysms: a review of 1458 brain MR angiograms.

PURPOSE: To evaluate clinical and imaging characteristics of pediatric brain aneurysms. MATERIALS AND METHODS: A retrospective review of 1458 MR angiograms of pediatric patients (≤18 years old) obtained between 2006 and 2021 was performed. A non-infundibular arterial luminal outpouching larger than 1mm in size was identified as an "Intracranial aneurysm." Patient demographics, clinical presentations, and predisposing risk factors, including family history and underlying medical conditions, were reviewed. MRA images were analyzed for aneurysm location, number, maximum diameter, and interval changes on follow-up. RESULTS: Forty-nine (3.3%) patients (30 females, 19 males) with 64 intracranial aneurysms were identified with an average age of 13.71 ± 3.67 years. Eleven (22.4%) patients had multiple aneurysms. An underlying systemic illness was observed in 81.6% (40/49) cases, with sickle cell disease as the most frequent (25/49, 51%) diagnosis. A first-degree family history of intracranial aneurysms was recognized in 36/1458 (2.5%) patients. However, no intracranial aneurysm was found in this group. While 02/49 (4%) patients presented with acute SAH, headache was the most common (16/49, 32.7%) symptom at presentation in unruptured cases. The majority (47/64, 73.4%) of the aneurysms were located in the anterior circulation, with the ICA ophthalmic segment being most frequently (24/47, 51%) involved. Most (54/64, 84.4%) aneurysms were smaller than 4mm in size at the time of diagnosis. At least one follow-up MRA was obtained in 72.3% (34/47) of the unruptured aneurysms cohort. There was no change in the aneurysm size and morphology in 31/34 (91.2 %) patients over an average imaging follow-up of 39.6 months. Three (6%) patients demonstrated an interval increase in the aneurysm size. SAH patients (n=2) and two unruptured aneurysm patients with an interval increase in size were successfully treated with endovascular techniques. CONCLUSION: Female predominance with a higher frequency of small and unruptured intracranial aneurysms was recognized in our cohort. A higher incidence of an underlying systemic illness, especially sickle cell disease, was also noted. Most intracranial aneurysms in children appear to remain stable. However, there seems to be the risk of an aneurysm size increase which warrants regular clinical and imaging follow-up.

Middle meningeal artery embolization in pediatric patient.

PURPOSE: There is paucity of data in management of recurrent and expanding subdural hematomas (SDH) within the pediatric population, who are otherwise not surgical candidates. Middle meningeal artery (MMA) embolization has been utilized minimally in this population and here, we explore the utility of this procedure in a 15-month-old-child, along with review of the literature. METHODS: A case report of a 15-month-old child who underwent MMA embolization for recurrent and expanding SDH in the setting of anticoagulation for cardiac condition. A literature review of MMA embolization in pediatric patients was conducted. RESULTS: Initially stabilization of SDH was noted on serial imaging; however, recurrent hemorrhages were noted with subsequent boluses of antiplatelet and anticoagulating agents. There are only 5 total reported cases, included ours, of MMA embolization in pediatrics with an overall success rate of 80%. CONCLUSION: Treatment of chronic or recurrent subdural hematoma by MMA embolization in the pediatric population is understudied. Our case notes limitation of this procedure and impact on long-term success, specifically in patients with systemic illness and ongoing anticoagulation.

Pediatric benign triton tumor of trigeminal nerve: a case report and literature review.

PURPOSE: Benign triton tumors (BTTs) in the pediatric population are extremely rare occurrences. Paucity of data on BTTs poses both diagnostic and therapeutic challenges, particularly when found intracranially. METHODS: A case report of a 10-year-old male diagnosed with incidental maxillary trigeminal (V2) BTT is presented. We discuss radiographic and histopathological interpretations. Furthermore, we provide a brief review of current literature and historical background on pediatric trigeminal BTT diagnosis, histopathology, and management. RESULTS: Successful gross total resection of the tumor was achieved via Dolenc approach to the cavernous sinus. Management options with consideration of outcomes from the few prior cases reported in the literature are presented. CONCLUSION: Treatment of trigeminal nerve tumors requires a broad differential diagnosis and understanding rare tumors is essential in the diagnosis and treatment algorithm.

Presentation, management and outcome of surgically managed pediatric thoracic outlet syndrome.

PURPOSE: Thoracic outlet syndrome (TOS) is a rare disorder involving compression of the brachial plexus, subclavian artery, and subclavian vein. There is a paucity of data for this pathology's surgical treatment within pediatrics. The objective of this study is to explore the presentation, management, and outcome of pediatric TOS. METHODS: A retrospective chart review was conducted for 44 patients at a single institution undergoing surgery for TOS. Data was collected on demographics, pre- and postoperative factors, and outcomes. RESULTS: Forty-four patients underwent 50 surgeries (8 bilaterally). The average age was 15.5 years with 72% female. The most common symptoms were numbness (72%) and pain (66%), with a normal exam in 58%. The average symptom duration prior to surgery was 35.2 months. A supraclavicular approach was performed in all patients, with anterior scalene section (90%), rib resection (72%), neurolysis (92%), and intraoperative EMG (84%) commonly used. Two patients had a lymphatic leak. All patients reported subjective improvement of preoperative symptoms of numbness (26%), pain (22%), and weakness (6%). Differences between vTOS (n = 9) and nTOS (n = 35) included higher preop swelling (p < 0.012), decreased symptom duration (p < 0.022), higher venogram usage (p < 0.0030), and higher preoperative thrombolytics/angioplasty (p < 0.001) in vTOS compared to nTOS. A comparison of soft tissue and soft tissue with bone decompression did not reveal any outcome differences. CONCLUSION: Pediatric TOS benefits from a multidisciplinary approach, showing good outcomes in postoperative symptom resolution. In our cohort, a supraclavicular approach provided an effective window for decompression with a low complication rate.

Pediatric primary high-grade spinal glioma: a National Cancer Database analysis of current patterns in treatment and outcomes.

PURPOSE: Pediatric primary high-grade spinal glioma (p-HGSG) is an extremely rare disease process, with little data within the current literature. Akin to primary high-grade gliomas, this cancer has been exemplified by dismal prognosis and poor response to modern treatment paradigms. This study seeks to investigate the current trends affecting overall survival using the National Cancer Database (NCDB). METHODS: The NCDB was queried for p-HGSG between 2004 and 2016, by utilizing the designated diagnosis codes. Kaplan-Meier curves were generated, and log-rank testing was performed to analyze factors affecting overall survival. In addition, a Cox proportional-hazards model was used to perform multivariate regression analysis of survival outcomes. RESULTS: A cohort of 97 patients was identified with a histologically confirmed p-HGSG. The overall incidence of p-HGSG in all pediatric spinal cord tumors is 7.5%, with a mean survival time of 25.3 months (SD, 21.0) and 5-year overall survival of 17.0%. The majority of patients underwent surgery (n = 87, 89.7%), radiotherapy (n = 73, 75.3%), and chemotherapy (n = 60, 61.9%). Univariate, multivariate, and Kaplan-Meier log-rank testing failed to demonstrate an association between performing surgery, extent of resection, radiotherapy, or chemotherapy with improved survival outcomes. CONCLUSIONS: The current study constitutes the largest retrospective analysis of p-HGSGs to date, finding that current treatment options of surgery, radiotherapy, and chemotherapy have unclear benefit. This disease process has a poor prognosis without a current modality of treatment that conclusively alters survival. The risks and side effects of these treatment modalities must be carefully considered in such a highly aggressive disease process, especially given potentially limited survival benefits.

A Comparative Analysis of Allergen Proteins between Plants and Animals Using Several Computational Tools and Chou's PseAAC Concept.

BACKGROUND: A large number of allergens are derived from plant and animal proteins. A major challenge for researchers is to study the possible allergenic properties of proteins. The aim of this study was in silico analysis and comparison of several physiochemical and structural features of plant- and animal-derived allergen proteins, as well as classifying these proteins based on Chou's pseudo-amino acid composition (PseAAC) concept combined with bioinformatics algorithms. METHODS: The physiochemical properties and secondary structure of plant and animal allergens were studied. The classification of the sequences was done using the PseAAC concept incorporated with the deep learning algorithm. Conserved motifs of plant and animal proteins were discovered using the MEME tool. B-cell and T-cell epitopes of the proteins were predicted in conserved motifs. Allergenicity and amino acid composition of epitopes were also analyzed via bioinformatics servers. RESULTS: In comparison of physiochemical features of animal and plant allergens, extinction coefficient was different significantly. Secondary structure prediction showed more random coiled structure in plant allergen proteins compared with animal proteins. Classification of proteins based on PseAAC achieved 88.24% accuracy. The amino acid composition study of predicted B- and T-cell epitopes revealed more aliphatic index in plant-derived epitopes. CONCLUSIONS: The results indicated that bioinformatics-based studies could be useful in comparing plant and animal allergens.

Global trends in the evaluation and management of cerebrospinal fluid shunt infection: a cooperative ISPN survey.

INTRODUCTION: Ventriculoperitoneal shunts (VPS) is commonly performed by pediatric neurosurgeons and there is no consensus in management of VPS infection as it relates to diagnosis and treatment. OBJECTIVE: We utilized an international practitioner-based survey to study the variability in VPS infection diagnostic and therapeutic measures. METHODS: A survey gauging practice patterns of pediatric neurosurgeons regarding VPS and its complication management was distributed. Survey endpoints were analyzed by VPS case volume and pediatric-focused case volume regarding diagnostic measures, use of cerebrospinal fluid (CSF) profile, microbiology, and treatment. RESULTS: A total of 439 surveys were distributed, with a response rate of 31%. Responders ranged from Americas (44.9%), European (31.4%), Asian (18.6%), African (2.5%), to Australian continents (2.5%). Practitioners were stratified based on number and percentage pediatric VPS performed. Institutions performing highest VPS and percentage pediatric case volumes had lower rate of VPS infection. Shunt tap was the most widely used diagnostic study. Overall CSF profile did not affect decision making towards VPS internalization, except for leukocyte count ≤ 20 × 109/L. Practitioners utilized 3 negative cultures prior to VPS internalization. Discrepancies in surgical management were noted amongst centers with high versus low VPS volume and proportion of pediatric-focused case volume. Practice patterns were not noted to be organism dependent. Antibiotic-impregnated shunts were utilized in the Americas and Europe over other regions but only in one third of all initial VPS or as a preventive strategy after a VPS infection has been resolved respectively. DISCUSSION: Survey results from 6 continents in VPS management revealed patterns of lower infection in high-volume centers, 3 negative cultures prior to internalization and aggressive surgical VPS infection management in high-volume institutions.

Treatment of pediatric extra-axial sinogenic infection: case series and literature review.

PURPOSE: Analyze the clinical presentation, microbiology, outcomes, and medical and surgical treatment strategies of intracranial extension of sinogenic infection in pediatric patients. METHODS: A retrospective, single-center study of patients < 18 years of age, presenting with intracranial extension of bacterial sinogenic infections requiring surgical intervention over a 5-year period, was conducted. Electronic medical records were reviewed for age, sex, primary symptoms, duration of symptoms, presence of sinusitis at initial presentation, microorganisms isolated, mode of surgery, timing of surgery, length of stay, and neurologic sequelae. RESULTS: Seventeen patients were identified; mean age was 10 years with 82.3% male predominance. Average duration of illness prior to presentation was 9.8 days, with 64.7% of patients displaying disease progression while on oral antibiotics prior to presentation. Sinusitis and intracranial extension were present in all patients upon admission. Simultaneous endoscopic endonasal drainage and craniotomy were performed on 70.5% of the patients, with the remaining 29.5% undergoing endonasal drainage only. Of the patients who underwent simultaneous endoscopic endonasal drainage and craniotomy, 17.6% required repeat craniotomy and 5.8% required repeat sinus surgery. The most commonly isolated organisms were S. intermedius (52.9%), S. anginosus (23.5%), and S. pyogenes (17.6%). All patients were treated postoperatively antibiotic on average 4-6 weeks. Frequently occurring long-lasting complications included seizures (29.4%) and focal motor deficits (17.6%); learning disability, anxiety disorders, impaired cognition, and sensory deficits occurred less frequently. CONCLUSION: In the case of intracranial extension of bacterial sinogenic infection, early identification and surgical treatment are crucial to avoid neurological sequelae.

Towards the first multi-epitope recombinant vaccine against Crimean-Congo hemorrhagic fever virus: A computer-aided vaccine design approach.

Crimean-Congo hemorrhagic fever (CCHF) is considered one of the major public health concerns with case fatality rates of up to 80%. Currently, there is no effective approved vaccine for CCHF. In this study, we used a computer-aided vaccine design approach to develop the first multi-epitope recombinant vaccine for CCHF. For this purpose, linear B-cell and T-cell binding epitopes from two structural glycoproteins of CCHF virus including Gc and Gn were predicted. The epitopes were further studied regarding their antigenicity, allergenicity, hydrophobicity, stability, toxicity and population coverage. A total number of seven epitopes including five T-cell and two B-cell epitopes were screened for the final vaccine construct. Final vaccine construct composed of 382 amino acid residues which were organized in four domains including linear B-cell, T-cell epitopes and cholera toxin B-subunit (CTxB) along with heat labile enterotoxin IIc B subunit (LT-IIc) as adjuvants. All the segments were joined using appropriate linkers. The physicochemical properties as well as the presence of IFN-γ inducing epitopes in the proposed vaccine, was also checked to determining the vaccine stability, solubility and its ability to induce cell-mediated immune responses. The 3D structure of proposed vaccine was subjected to the prediction of computational B-cell epitopes and molecular docking studies with MHC-I and II molecules. Furthermore, molecular dynamics stimulations were performed to study the vaccine-MHCs complexes stability during stimulation time. The results suggest that our proposed vaccine was stable, well soluble in water and potentially antigenic. Results also demonstrated that the vaccine can induce both humoral and cell-mediated immune responses and could serve as a promising anti-CCHF vaccine candidate.

Cortical gene expression: prognostic value for seizure outcome following temporal lobectomy and amygdalohippocampectomy.

Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between epilepsy patients rendered seizure-free versus non-seizure-free following anterior temporal lobectomy with amygdalohippocampectomy (ATL/AH). Twenty four patients underwent ATL/AH to treat medically intractable seizures of temporal lobe origin (mean age 35.5 years, mean follow-up 42.2 months); they were then dichotomized into seizure-free and non-seizure-free groups. Tissue RNA was isolated from the lateral temporal cortex and gene expression analysis was performed. Whole genome data were analyzed for prognostic value for seizure-free outcome following ATL/AH by logistic regression. Genes that could distinguish seizure outcome groups were identified based on providing an accuracy of >0.90 judging by area under the receiver operating characteristic curve, AUC, with a P value of the slope coefficient of <0.05. Four genes and seven RNA probes were with prognostic value for post-operative seizure-free outcome. Gene expression associated with seizure-free outcome included relative down-regulation of zinc finger protein 852 (ZNF852), CUB domain-containing protein 2 (CDCP2), proline-rich transmembrane protein 1 (PRRT1), hypothetical LOC440200 (FLJ41170), RNA probe 8047763, RNA probe 8126238, RNA probe 8113489, RNA probe 8092883, RNA probe 7935228, RNA probe 806293, and RNA probe 8104131. This study describes the predictive value of temporal cortical gene expression for seizure-free outcome after ATL/AH. Four genes and seven RNA probes were found to predict post-operative seizure-free outcome. Future prospective investigation of these genes and probes in human brain tissue and blood could establish new biomarkers predictive of seizure outcome following ATL/AH.

Analysis and comparison of lignin peroxidases between fungi and bacteria using three different modes of Chou's general pseudo amino acid composition.

Lignin peroxidases (LiPs) are important enzymes in the degradation process of lignin which are presented in different species of fungi and bacteria. In the present study, sequence and structure-based properties of LPs in fungi and bacteria are compared. These properties include pseudo amino acid composition (PseAAC), physicochemical properties and the secondary structure. Autodock 4 has been used for docking between LiPs and lignan. The motifs of LiP were predicted by MEME tool. Statistical analysis and Multinomial Naïve Bayes (MNB) algorithm were used for the classification of two LiP protein groups. The results demonstrated that molecular weight, isoelectric point, aliphatic, extinction coefficient and random coil percentage of LiPs in fungi and bacteria were significantly different between these two groups. The classification of these two groups based on the concept of PseAAC showed over 80% accuracy. The binding free energy between bacterial LiPs and lignan is significantly more than fungi LiP and ligand. The aliphatic and instability of most important motifs of bacteria and fungi were significantly different. In conclusion, the results indicated that computational techniques could provide useful information for comparing fungal and bacterial LiPs. These results can also explain that there is a relationship between efficacy and physicochemical properties of LiPs.

Thermal injury to corticospinal tracts and postoperative motor deficits after laser interstitial thermal therapy.

OBJECTIVE Laser interstitial thermal therapy (LITT) has been increasingly used to treat deep-seated tumors. Despite its being minimally invasive, there is a risk of LITT damaging adjacent critical structures, including corticospinal tracts (CSTs). In this study, the authors investigated the predictive value of overlap between the hyperthermic field and CSTs in determining postoperative motor deficit (PMDs). METHODS More than 140 patients underwent an LITT procedure in our institution between April 2011 and June 2015. Because of the tumor's proximity to critical structures, 80 of them underwent preoperative diffusion tensor imaging and were included in this study. Extent of the hyperthermic field was delineated by the software as thermal-damage-threshold (TDT) lines (yellow [43°C for 2 minutes], blue [43°C for 10 minutes], and white [43°C for 60 minutes]). The maximum volume and the surface area of overlaps between motor fibers and the TDT lines were calculated and compared with the PMDs. RESULTS High-grade glioma (n = 46) was the most common indication for LITT. Postoperative motor deficits (partial or complete) were seen in 14 patients (11 with permanent and 3 with temporary PMDs). The median overlap volumes between CSTs with yellow, blue, and white TDT lines in patients with any PMD (temporary or permanent) were 1.15, 0.68, and 0.41 cm3, respectively. The overlap volumes and surface areas revealed significant differences in those with PMDs and those with no deficits (p = 0.0019 and 0.003, 0.012 and 0.0012, and 0.001 and 0.005 for the yellow, blue, and white TDT lines, respectively). The receiver operating characteristic was used to select the optimal cutoff point of the overlapped volumes and areas. Cutoff points for overlap volumes and areas based on optimal sensitivity (92%-100%) and specificity (80%-90%) were 0.103, 0.068, and 0.046 cm3 and 0.15, 0.07, and 0.11 mm2 for the yellow, blue, and white TDT lines, respectively. CONCLUSIONS Even a minimal overlap between the TDT lines and CSTs can cause a PMD after LITT. Precise planning and avoidance of critical structures and important white matter fibers should be considered when treating deep-seated tumors.

Carotid bypass for carotid occlusion.

The 2-year risk of ipsilateral ischemic stroke following internal carotid artery occlusion (ICAO) in a patient undergoing maximal medical therapy is 5-8% per year. While medical therapy may reduce the risk of stroke, it does not completely eliminate it. Since the 1985 extracranial-intracranial (EC-IC) bypass study, additional trials have been conducted to further investigate the usefulness of EC-IC bypass surgery in more selected patients with cerebral ischemia and impaired hemodynamic reserve. These important studies will be briefly reviewed in this article, as well as a discussion regarding the utility of bypass surgery for ICAO in current clinical practice. In addition, a short discussion regarding the pathophysiology of carotid occlusion will be presented. We will also highlight our own institutional patient selection criteria based on the latest methods for hemodynamic assessment, as well as our intraoperative flow assisted surgical techniques (FAST), and post-operative patient follow-up.

Computational prediction of anti HIV-1 peptides and in vitro evaluation of anti HIV-1 activity of HIV-1 P24-derived peptides.

The world is entering the third decade of the acquired immunodeficiency syndrome (AIDS) pandemic. The primary cause of the disease has known to be human immunodeficiency virus type I (HIV-1). Recently, peptides are shown to have high potency as drugs in the treatment of AIDS. Therefore, in the present study, we have developed a method to predict anti-HIV-1 peptides using support vector machine (SVM) as a powerful machine learning algorithm. Peptide descriptors were represented based on the concept of Chou's pseudo-amino acid composition (PseAAC). HIV-1 P24-derived peptides were examined to predict anti-HIV-1 activity among them. The efficacy of the prediction was then validated in vitro. The mutagenic effect of validated anti-HIV-1 peptides was further investigated by the Ames test. Computational classification using SVM showed the accuracy and sensitivity of 96.76% and 98.1%, respectively. Based on SVM classification algorithm, 3 out of 22 P24-derived peptides were predicted to be anti-HIV-1, while the rest were estimated to be inactive. HIV-1 replication was inhibited by the three predicted anti-HIV-1 peptides as revealed in vitro, while the results of the same test on two of non-anti-HIV-1 peptides showed complete inactivity. The three anti-HIV-1 peptides were shown to be not mutagenic because of the Ames test results. These data suggest that the proposed computational method is highly efficient for predicting the anti-HIV-1 activity of any unknown peptide having only its amino acid sequence. Moreover, further experimental studies can be performed on the mentioned peptides, which may lead to new anti-HIV-1 peptide therapeutics candidates.

Predicting anticancer peptides with Chou's pseudo amino acid composition and investigating their mutagenicity via Ames test.

Cancer is an important reason of death worldwide. Traditional cytotoxic therapies, such as radiation and chemotherapy, are expensive and cause severe side effects. Currently, design of anticancer peptides is a more effective way for cancer treatment. So there is a need to develop a computational method for predicting the anticancer peptides. In the present study, two methods have been developed to predict these peptides using support vector machine (SVM) as a powerful machine learning algorithm. Classifiers have been applied based on the concept of Chou's pseudo-amino acid composition (PseAAC) and local alignment kernel. Since a number of HIV-1 proteins have cytotoxic effect, therefore we predicted the anticancer effect of HIV-1 p24 protein with these methods. After the prediction, mutagenicity of 2 anticancer peptides and 2 non-anticancer peptides was investigated by Ames test. Our results show that, the accuracy and the specificity of local alignment kernel based method are 89.7% and 92.68%, respectively. The accuracy and specificity of PseAAC-based method are 83.82% and 85.36%, respectively. By computational analysis, out of 22 peptides of p24 protein, 4 peptides are anticancer and 18 are non-anticancer. In the Ames test results, it is clear that anticancer peptides (ARP788.8 and ARP788.21) are not mutagenic. Therefore the results demonstrate that the described computation methods are useful to identify potential anticancer peptides, which are worthy of further experimental validation and 2 peptides (ARP788.8 and ARP788.21) of HIV-1 p24 protein can be used as new anticancer candidates without mutagenicity.

Antiviral and cytotoxic evaluation of coumarins from Prangos ferulacea.

CONTEXT: Prangos ferulacea (L.) Lindl. (Apiaceae) is a perennial plant found in the Middle-East, where it is commonly used as an antispasmodic and anti-inflammatory agent. It is a rich source of coumarins. OBJECTIVE: To purify several coumarins from P. ferulacea and to screen their cytotoxicity and anti-herpes activity. MATERIALS AND METHODS: Acetone extract of roots of P. ferulacea was subjected to several chromatographic separations to render pure coumarins (1-8). Anti-herpes virus effects of 1-7 were evaluated at concentration 2.5, 5, and 10 µgmL(-1), on a confluent monolayer of Vero cells infected with 25 PFU of HSV1. Cytotoxic effects of 1 and 2 were evaluated on an A2780S cell line using the MTT assay. The cells were exposed to a series of concentrations of coumarins (0.01-2.5 mM, 37°C, 72 h). RESULTS: Compounds 1-8 were identified as osthole, isoimperatorin, oxypeucedanin, psoralen, oxypeucedanin hydrate, gosferol, oxypeucedanin methnolate, and pranferol. This is the first report of occurrence of 4 and 7 in this plant. Compound 1 showed a viability of 9.41% ± 2.4 at 2.5 mM on A2780S cells (IC50 = 0.38 mM). The cell survival of 2 at 2.5 mM was 46.86% ± 5.5 with IC50 equal to 1.1 mM. DISCUSSION AND CONCLUSION: Compound 1 shows cytotoxic effects on the A2780S cell line. Compound 2 is a cyclooxygenase-2 inhibitor and the A2780S cell line does not express COX-2 which may interpret the non-toxic effect of the compound on this cell line. None of the tested compounds showed an anti-HSV effect at non-toxic concentrations.