Probing the mechanisms of two exonuclease domain mutators of DNA polymerase ϵ.

We report the properties of two mutations in the exonuclease domain of the Saccharomyces cerevisiae DNA polymerase ϵ. One, pol2-Y473F, increases the mutation rate by about 20-fold, similar to the catalytically dead pol2-D290A/E290A mutant. The other, pol2-N378K, is a stronger mutator.

Spontaneous Polyploids and Antimutators Compete During the Evolution of Mutator Cells.

Mutations affecting DNA polymerase exonuclease domains or mismatch repair (MMR) generate "mutator" phenotypes capable of driving tumorigenesis. Cancers with both defects exhibit an explosive increase in mutation burden that appears to reach a threshold, consistent with selection acting against further mutation accumulation. In haploid yeast, simultaneous defects in polymerase proofreading and MMR select for "antimutator" mutants that suppress the mutator phenotype.

Chinese translation and validation of the Sport Concussion Assessment Tool 3 (SCAT3).

Objective: The aim of this study was to translate, adapt and validate the Sport Concussion Assessment Tool 3rd edition (SCAT3), a test for assessing athletes for concussion, into the Chinese context.

Methods: Translation and adaptation were performed in several stages, which included forward translation by two independent teams, translation merging, backward translation, reviews by both native Cantonese-speaking and Mandarin-speaking multidisciplinary expert panels (n=49) for semantic and conceptual equivalence and reviews by pitch-side physiotherapists (n=18) as end-users of the SCAT3 and rugby players (n=11) for face validity. The Serial 3  s subtraction test was used as a substitute for the Months Backward Test (MBT) for measures of concentration in the Standardized Assessment of Concussion subscale.

Pre-optimization of spinal surgery patients: Development of a neurosurgical enhanced recovery after surgery (ERAS) protocol.

Objective: Despite surgical, technological, medical, and anesthetic improvements, patient outcomes following elective neurosurgical procedures can be associated with high morbidity. Enhanced recovery after surgery (ERAS) protocols are multimodal care pathways designed to optimize patient outcomes by addressing pre-, peri-, and post-operative factors. Despite significant data suggesting improved patient outcomes with the adoption of these pathways, development and implementation has been limited in the neurosurgical population.

A simplified pressure adjustment clinical pathway for programmable valves in NPH patients.

Objective: The goal of this study is to provide a clinical pathway for shunt valve adjustment in the treatment of normal pressure hydrocephalus (NPH) patients.

Patient And Methods: The authors conducted a single-center retrospective study of 102 patients (mean age 74 years, 66 men, 36 women) diagnosed with NPH. In all cases, a Medtronic Strata Adjustable Pressure valve set initially at 1.

Unique findings of subependymal giant cell astrocytoma within cortical tubers in patients with tuberous sclerosis complex: a histopathological evaluation.

Introduction: Tuberous sclerosis is associated with three central nervous system pathologies: cortical/subcortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Tubers are associated with epilepsy, which is often medication-resistant and often leads to resective surgery. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be effective reducing seizure burden in some patients with tuberous sclerosis complex (TSC)-related refractory epilepsy.

Open and endoscopic excision of calvarial dermoid and epidermoid cysts: a single center experience on 128 consecutive cases.

Objective: Dermoid and epidermoid cysts rank among the most common pediatric tumors. We analyzed the outcomes of surgical excision of dermal and epidermal inclusion cysts in a large consecutive series of children.

Methods: We retrospectively reviewed 128 consecutive children who underwent calvarial inclusion cyst resection between 2000 and 2010 at NYU Langone Medical Center.

Direct versus indirect revascularization procedures for moyamoya disease: a comparative effectiveness study.

OBJECTIVE Moyamoya disease (MMD) is a chronic cerebrovascular disease that can lead to devastating neurological outcomes. Surgical intervention is the definitive treatment, with direct, indirect, and combined revascularization procedures currently employed by surgeons. The optimal surgical approach, however, remains unclear.

Ultrasonographic Evaluation of Peripheral Nerves.

There are a variety of imaging modalities for evaluation of peripheral nerves. Of these, ultrasonography (US) is often underused. There are several advantages of this imaging modality, including its cost-effectiveness, time-efficient assessment of long segments of peripheral nerves, ability to perform dynamic maneuvers, lack of contraindications, portability, and noninvasiveness.

Resective Epilepsy Surgery for Tuberous Sclerosis in Children: Determining Predictors of Seizure Outcomes in a Multicenter Retrospective Cohort Study.

Background: There are no established variables that predict the success of curative resective epilepsy surgery in children with tuberous sclerosis complex (TSC).

Objective: We performed a multicenter observational study to identify preoperative factors associated with seizure outcome in children with TSC undergoing resective epilepsy surgery.

Methods: A retrospective chart review was performed in eligible children at New York Medical Center, Miami Children's Hospital, Cleveland Clinic Foundation, BC Children's Hospital, Hospital for Sick Children, and Sainte-Justine Hospital between January 2005 and December 2013.

PmPPAF is a pro-phenoloxidase activating factor involved in innate immunity response of the shrimp Penaeus monodon.

One of the major steps in the innate immune response of shrimp includes the activation of serine proteinases of the pro-phenoloxidase pathway by the prophenoloxidase activation enzyme (PPAF). In this study, the cDNA encoding a serine proteinase homologue (SPH) with prophenoloxidase activating activity of Penaeus monodon (PmPPAF) was cloned and characterized. PmPPAF cDNA consists of 1444 nucleotides encoding a protein with 394 amino acid residues.

Outcome comparison of atlantoaxial fusion with transarticular screws and screw-rod constructs: meta-analysis and review of literature.

Study Design: Literature review and meta-analysis.

Objective: To compare clinical and radiographic outcomes of patients treated with transarticular screws (TASs) and screw-rod constructs (SRCs) for posterior atlantoaxial fusion.

Background: Modern techniques for C1-C2 fusions include Magerl and Seeman's TAS and SRC using C1 lateral mass screws and C2 pars/pedicle screws as described by Goel and Laheri and later modified by Harms and Melcher.

Electrocorticographic evidence of perituberal cortex epileptogenicity in tuberous sclerosis complex.

Object: Tuberous sclerosis complex (TSC) is a multisystem autosomal dominant disorder resulting in hamartomas of several organs. Cortical tubers are the most prominent brain lesions in TSC. Treatment-resistant epilepsy often develops early in life in patients with TSC and is associated with severe intellectual and behavioral impairments.

Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo.

Special (lipid) delivery: The role of the ionizable lipid pK(a) in the in vivo delivery of siRNA by lipid nanoparticles has been studied with a large number of head group modifications to the lipids. A tight correlation between the lipid pK(a) value and silencing of the mouse FVII gene (FVII ED(50) ) was found, with an optimal pK(a) range of 6.2-6.

Comparison of screw malposition and vertebral artery injury of C2 pedicle and transarticular screws: meta-analysis and review of the literature.

Study Design: Literature review and meta-analysis.

Objectives: To compare the incidence of screw malposition and vertebral artery injury (VAI) with transarticular screws (TAS) and C2 pedicle screws (C2PS) using meta-analysis techniques.

Summary Of Background Data: Posterior instrumentation for atlantoaxial fusions can be challenging and risky.

Is external cervical orthotic bracing necessary after posterior atlantoaxial fusion with modern instrumentation: meta-analysis and review of literature.

Background: No guidelines exist regarding external cervical orthoses (ECO) after atlantoaxial fusion. We reviewed published series describing C1-2 posterior instrumented fusions with screw-rod constructs (SRC) or transarticular screws (TAS) and compared rates of fusion with and without postoperative ECO.

Methods: Online databases were searched for English-language articles between 1986 and April 2011 describing ECO use after posterior atlantoaxial instrumentation with SRC or TAS.

Atlantoaxial fusion with transarticular screws: meta-analysis and review of the literature.

Objective: To review published series describing C1-2 posterior instrumented fusions and summarize clinical and radiographic outcomes of patients treated with transarticular screw (TAS) fixation.

Methods: Online databases were searched for English-language articles published between 1986 and April 2011 describing posterior atlantoaxial instrumentation with C1-2 TAS fixation. There were 45 studies including 2073 patients treated with TAS that fulfilled inclusion criteria.

Atlantoaxial fusion with screw-rod constructs: meta-analysis and review of literature.

Objective: To review published series describing C1-2 posterior instrumented fusions and summarize clinical and radiographic outcomes of patients treated with screw-rod constructs (SRC).

Methods: Online databases were searched for English-language articles published between 1991 and April 2011 describing posterior atlantoaxial instrumentation with C1-2 SRC. There were 24 studies including 1073 patients treated with SRC that fulfilled inclusion criteria.

Epilepsy control following intracranial monitoring without resection in young children.

Purpose: Intracranial monitoring (IM) is a key diagnostic procedure for select patients with treatment-resistant epilepsy (TRE). Seizure focus resection may improve seizure control in both lesional and nonlesional TRE. IM itself is not considered to have therapeutic potential.

Personality traits and social behaviors predict the psychological adjustment of Chinese people with epilepsy.

Very little is known about the psychosocial correlates of psychological morbidity among Chinese people with epilepsy (PWE). No studies have investigated the association between social relationships and psychological morbidity, while most studies examined only the negative impact of maladaptive personalities on psychological adjustment in PWE. This study examined the association of psychological morbidity with a broad array of personality traits and social skills in a sample of 54 Chinese PWE.

Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms.

Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice.

Rational design of cationic lipids for siRNA delivery.

We adopted a rational approach to design cationic lipids for use in formulations to deliver small interfering RNA (siRNA). Starting with the ionizable cationic lipid 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA), a key lipid component of stable nucleic acid lipid particles (SNALP) as a benchmark, we used the proposed in vivo mechanism of action of ionizable cationic lipids to guide the design of DLinDMA-based lipids with superior delivery capacity. The best-performing lipid recovered after screening (DLin-KC2-DMA) was formulated and characterized in SNALP and demonstrated to have in vivo activity at siRNA doses as low as 0.

Improvement in quality of life after adenotonsillectomy in a child with Prader Willi syndrome.

We report a child with Prader Willi syndrome who developed obstructive sleep apnea (OSA). This patient underwent surgical treatment for OSA. There was improvement not only on her OSA but in her quality of life score as well.