Trans-sulcal parafascicular approach to subcortical lesions.

Historically, neoplasms which are located in the subcortical region of the brain are considered technically difficult to access. As such, tumours in these locations are usually avoided, due to the risks associated with traversing eloquent cortex, the disrupting of white matter tracts, or the need to use narrow corridors to approach the lesion. Tubular retractors are able to gently displace brain parenchyma and white matter in an atraumatic fashion to access these deep regions. We demonstrate a minimally invasive trans-sulcal parafascicular approach using the Brainpath system (NICO Corp, Indianapolis, Indiana) to a caudate head metastasis as a representative case.

Valgus Malalignment Due to Internally Malrotated Trochanteric Nail Placement, with Rotational Malalignment in Femoral Shaft Segmental Fracture Fixation, an Underestimated Avoidable Technical Error: A Case Report.

Coronal malalignment due to malrotated trochanteric nail placement in femoral fracture fixation has never been reported. We present a case of a femoral segmental fracture fixed with a trochanteric nail, with a malrotated placement resulting in a valgus malaligned nail and femur, associated with a rotational malalignment. Knowledge of the modern nail design with proper intra-operative precautions, would avoid this underestimated technical error.

Correlation between extent of sinus surgery, radiographic disease, and postoperative outcomes.

BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes. METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months. RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate. CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.

Nanomatrix Coated Stent Enhances Endothelialization but Reduces Platelet, Smooth Muscle Cell, and Monocyte Adhesion under Physiologic Conditions.

Cardiovascular disease is presently the number one cause of death worldwide. Current stents used to treat cardiovascular disease have a litany of unacceptable shortcomings: adverse clinical events including restenosis, neointimal hyperplasia, thrombosis, inflammation, and poor re-endothelialization. We have developed a biocompatible, multifunctional, peptide amphiphile-based nanomatrix coating for stents. In this study, we evaluated the ability of the nanomatrix coated stent to simultaneously address the issues facing current stents under physiological flow conditions in vitro. We found that the nanomatrix coated stent could increase endothelial cell migration, adhesion, and proliferation (potential for re-endothelialization), discourage smooth muscle cell migration and adhesion (potential to reduce neointimal hyperplasia and restenosis), and decrease both platelet activation and adhesion (potential to prevent thrombosis) as well as monocyte adhesion (potential to attenuate inflammatory responses) under physiological flow conditions in vitro. These promising results demonstrate the potential clinical utility of this nanomatrix stent coating, and highlight the importance of biocompatibility, multifunctionality, and bioactivity in cardiovascular device design.

Chronic Traumatic Sagittal Band Injury with Extensor Tendon Dislocation: Report of a Case and New Surgical Technique.

Chronic sagittal band injury with tendon dislocation of the extensor digitorum communis in the hand often requires operative stabilization. Various surgical techniques have been reported to repair and reconstruct the sagittal band. Nonetheless, most of the techniques are technically demanding and require donor graft. In this case report, we report a novel surgical technique to centralize and stabilize the tendon by reattaching the radial sagittal band with anchor sutures. The advantages of this new technique are simple, no donor morbidity and stable repair to restore the normal biomechanics of the tendon. The patient was able to return to work in three months and no recurrent dislocation was noted at review two years after surgery.

Efficacy of 12 or 18 weeks of elbasvir plus grazoprevir with ribavirin in treatment-naïve, noncirrhotic HCV genotype 3-infected patients.

Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed-dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development programme and supported by in vitro potency, the efficacy of EBR+GZR was assessed in HCV GT3-infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment-naïve, noncirrhotic HCV GT3-infected patients. Randomized patients received open-label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On-treatment virologic failure was observed in 41% (17 of 41) of patients. At virologic failure, resistance-associated substitutions (RASs) with a >five-fold shift in potency occurred in the NS3 region in six (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13 of 17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3-infected patients due to a high rate of on-treatment virologic failure and treatment-emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3-infected patients.clinicaltrials.gov: NCT01717326.

Efficacy and safety of grazoprevir + ribavirin for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1 infection.

Grazoprevir (GZR) is a second-generation hepatitis C virus NS3/4A protease inhibitor. The aim of this study was to evaluate GZR plus ribavirin (RBV) in patients with HCV GT1 infection. Noncirrhotic, IL28B CC patients with HCV genotype 1 infection were randomized to GZR 100 mg once daily and RBV for 12 or 24 weeks. Patients in the 12-week arm with detectable HCV RNA at treatment week 4 (TW4) had treatment extended to 24 weeks (response-guided therapy, RGT). The primary endpoint was sustained virologic response (SVR12) at follow-up week 12 (HCV RNA <25 IU/mL) in the per-protocol (PP) population (excluding patients with important protocol deviations). Twenty-six patients were randomized and 22 were included in the PP population. SVR12 was 58.3% (7 of 12) and 90% (9 of 10) in the RGT and 24-week arms, respectively. Seven PP patients had virologic failure, including one patient in the 24-week arm who relapsed after follow-up week 12. All three breakthrough patients had wild-type (WT) virus at baseline and developed breakthrough at TW6 or TW12 with Y56H, A156T and D168A/N mutations. Of the five relapse patients, four had WT at baseline (at relapse three had WT and one had V55A and D168A), and one had S122A/T at baseline and S122T at relapse. There were no serious adverse events (AEs), discontinuations due to AEs or grade 3/4 elevations in total and/or direct bilirubin. Grazoprevir plus RBV was associated with a rapid and sustained suppression of HCV RNA. These results support further evaluation of grazoprevir-based regimens (NCT01716156; protocol P039).

Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial.

UNLABELLED: Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100 mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25 mg, 50 mg or 100 mg plus PEG-IFN/RBV for 12 weeks. Patients with quantifiable HCV RNA (≥25 IU/mL) at week 4 received an additional 12 weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25 IU/mL 12 weeks after completing therapy [SVR12]). Eighty-seven patients were randomly assigned and received ≥1 dose of therapy. Median time to undetectable HCV RNA was 16 days in the 100-mg arm and 22 days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12 weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms). CONCLUSION: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100 mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038).

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells.

Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

Eckols reduce dental pulp inflammation through the ERK1/2 pathway independent of COX-2 inhibition.

OBJECTIVES: The aim of this study was to elucidate the role of 6-6 bieckol (EB1) and pholorofucofuroeckol-A (EB5) from brown seaweed marine algae (Eisenia bicyclis) on lipopolysaccharide (LPS)-induced inflammation in human dental pulp cells (HDPCs). METHODS: The cytotoxicity of EB1 and EB5 was examined by MTT assay on LPS-induced human dental pulp cells. Their role on expression of inflammatory, odontogenic, and osteogenic molecules was determined by Western blot analysis. The dentin mineralization was checked by alkaline phosphatase activity. RESULTS: The five compounds from E. bicyclis have different structure with non-cytotoxic in HDPCs. EB1 and EB5 showed anti-inflammatory properties and inhibited phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) and phosphorylated-c-jun N-terminal kinases (p-JNK) without any cytotoxicity. In particular, EB1 inhibited cyclooxygenase-2 (COX-2) and p-ERK1/2 signaling, and EB5 inhibited only p-ERK1/2 signaling but not COX-2. Both compounds inhibited nuclear factor kappa-B (NF-κB) translocation. Furthermore, EB1 and EB5 increased dentinogenic and osteogenic molecules, and dentin mineralized via alkaline phosphatase activity (ALP) in LPS-induced HDPCs. CONCLUSIONS: This study elucidates that EB1 and EB5 have different types of anti-inflammatory property and help in dentin formation. Therefore, these compounds derived from marine algae of E. bicyclis may be used as selective therapeutic strategies for pulpitis and oral diseases.

Anti-inflammatory effect of pachymic acid promotes odontoblastic differentiation via HO-1 in dental pulp cells.

OBJECTIVES: Heme oxygenase-1 (HO-1) is contributed to odontoblast differentiation in human dental pulp cells (HDPCs). In this study, pachymic acid from mushroom Formitopsis niagra is examined to determine whether it affects pulpal inflammation and promotes odontogenesis via HO-1 gene expression. MATERIALS AND METHODS: The HDPCs were given H2O2 for inflammation. The anti-inflammatory character and odontoblast differentiation by pachymic acid were analyzed by Western blotting, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of pachymic acid via HO-1 induction, the cells were treated with zinc protoporphyrin IX (ZnPP: HO-1 inhibitor). RESULTS: H2O2 induced pulp inflammation and disturbed odontoblast differentiation. However, the HDPCs treated with pachymic acid affected anti-inflammatory effect and induction of odontoblast differentiation through increasing HO-1 expression. In addition, pachymic acid has potent cytoprotection and mineralization under H2O2 treatment. Furthermore, pachymic acid significantly suppressed nuclear factor-kappa B (NF-κB) translocation into nucleus and induced NE-E2-related factor-2 (Nrf2) translocation into nucleus. Overall, NF-κB and Nrf2 translocation were regulated by the HO-1 pathway. CONCLUSIONS: The pachymic acid showed anti-inflammatory function and odontoblast differentiation via HO-1 pathway. These results suggested that pachymic acid may be applicable for prevention of oral inflammation or to improve dentin mineralization against several stresses.

Taiwanese nurses' cognition and attitudes towards the Magnet Hospitals Recognition Programme.

AIMS: To explore the relevance and feasibility of using the Magnet Recognition Programme (MRP) at a Taiwanese hospital. BACKGROUND: Since no hospitals in Taiwan have applied for American Nurses Credentialing Center Magnet Recognition, and the American medical system and customs are different from those in Taiwan, this study explores whether or not the MRP is appropriate for Taiwanese hospitals. METHOD: This study used a cross-sectional design with data collected from 905 nurses at a 1200-bed Taiwanese military hospital. The authors created the structured questionnaire from a framework based on the 14 Forces of Magnetism. The study used descriptive and inferential statistical analyses to explain the nurses' cognitions and attitudes towards the MRP and to discover if variations in these concepts occurred across nurses' demographics and their job classification. FINDINGS: The mean nurses' cognitive score on each item varies from 3.3 to 4.1, and the mean nurses' attitude score on each item varies from 3.0 to 4.0 (both with the highest possible score related to the 14 Forces of Magnetism being 5.0). Using regression analysis, overall cognitive score, working in the operating room, or the sub-critical Neonatal Care Unit, and part-time hours of work explained 42% of the variance in the total attitude score towards the MRP. CONCLUSION: The findings indicate that when nurses have a higher cognition towards MRP, the more positive are their attitudes towards seeking the MRP. Using these findings and information about the nurses, the authors suggest strategies that hospital executives and nursing supervisors can use to improve nurses' cognition and attitudes when preparing to seek recognition through the MRP.

Parents' descriptions and experiences of young children recently diagnosed with intellectual disability.

AIM: The aim of the present study was to explore the variation of parents' descriptions and experiences of their child that was recently identified to have an intellectual disability (ID). METHODS: The study applied interpretative phenomenological analysis and analysis of narrative style looking at content and form of parental narratives. Data was collected from nine fathers and eight mothers through semi-structured interviews within 6 months following diagnosis. RESULTS: Analysis revealed three factors indicating the parents' level of processing: (1) emotional expressions regarding the child - varying between limited (distanced or idealized) and balanced/affectionate; (2) experience of the disability - varying between preoccupation and acceptance; and (3) time orientation - varying in terms of flexibility and temporal focus. CONCLUSIONS: Although parents of children with ID describe negative emotions in relation to the child and the disability, most of these parents also describe positive emotions that seemed to balance the negative experiences.

Reduced amelogenin-MMP20 interactions in amelogenesis imperfecta.

Amelogenin with a proline 41 to threonine mutation (P41T) is hydrolyzed at a lower rate by matrix metalloproteinase 20 (MMP20), resulting in an inherited tooth enamel defect, amelogenesis imperfecta (AI). The aim of this study was to elucidate the effect of P41T on the interactions between amelogenin and MMP20, which may contribute to the formation of this type of AI. The interactions of a recombinant wild-type human amelogenin and its P41T mutant with recombinant human MMP20 were compared by substrate competition assay, pull-down assay, and surface plasmon resonance (SPR). The results showed that the binding of the P41T mutant amelogenin for MMP20 was significantly lower than that of wild-type amelogenin. Our study supports a model in which the P41T mutation reduces the interactions between amelogenin and MMP20, leading to decreased degradation of amelogenin by MMP20, and resulting in AI.

CBAP interacts with the un-liganded common beta-subunit of the GM-CSF/IL-3/IL-5 receptor and induces apoptosis via mitochondrial dysfunction.

The cytoplasmic domain of the common beta-chain (betac) of the granulocyte-macrophage-colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptor contains a membrane proximal region that is sufficient to mediate ligand-dependent mitogenic activity. Within this region two motifs, designated as box 1 and box 2, are highly conserved among members of the cytokine receptor superfamily. Whereas box 1 is required for the recruitment and phosphorylation of Janus kinase-2, the function of box 2 remains largely unknown. Here, we report the identification of a novel transmembrane protein (common beta-chain associated protein (CBAP)) which directly associated with betac via the box 2 motif. Interestingly, such an association only occurred in the absence of GM-CSF in vivo. Ectopic overexpression of CBAP triggered apoptosis of factor-dependent cells via mitochondrial dysfunction, which could be inhibited by Bcl-2 overexpression. Reduced expression of endogenous CBAP by small interfering RNA did not interfere GM-CSF-activated signaling molecules, but such treatment significantly inhibited apoptosis induced by GM-CSF deprivation, but not other death stimuli. Domain mapping studies indicated that one apoptogenic domain of CBAP correlated with its ability to interact with betac. Taken together, these results suggest that CBAP modulates GM-CSF-deprivation-induced apoptosis possibly via a novel mechanism involving interaction with an un-liganded betac molecule.

MR regional perfusion imaging: visualizing functional collateral circulation.

SUMMARY: We applied regional perfusion imaging (RPI), a new arterial spin-labeling MR imaging method that selectively studies regions of the brain perfused by individual carotid and basilar arteries. In a patient with cerebrovascular disease, RPI showed cerebral tissue perfused by pial collateral vessels, thereby demonstrating the relationship between anatomic and functional information, which was lacking in conventional x-ray angiography. RPI may be useful to study functional collateral circulation and hence guide therapy in ischemic disease.

Amphiphilic triblock copolymer poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol), enhancement of gene expression and inhibition of lung metastasis by aerosol delivery.

We describe the development of an aerosol system for topical gene delivery to the lungs of C57BL/6 mice. This system is based on the combination of the commercial cationic lipid Lipofectin with a novel amphiphilic triblock copolymer, poly(p-dioxanone-co-L-lactide)-block-poly(ethylene glycol) (PPDO/PLLA-b-PEG, and abbreviated in the text as polymeric micelles). After optimizing conditions for DNA delivery to the lungs of mice using the combination of polymeric micelles with Lipofectin and LacZ DNA, we used the Lipofectin/polymeric micelle system to deliver the tumor suppressor gene PTEN to the lungs of C57BL/6 mice bearing the B16-F10 melanoma. Lipofectin/PTEN/polymeric micelles significantly improved gene expression of PTEN in the lungs of mice with no evidence of cell toxicity or acute inflammation. Importantly, lung metastasis, as measured by lung weight, was significantly reduced (P<0.001), as were total tumor foci in the lungs (P<0.001) and size of individual tumor nodules in animals treated with Lipofectin/PTEN/polymeric micelles compared with control animals. Survival time was also extended. These results suggest that the Lipofectin/polymeric micelle system is appropriate for enhancing gene delivery in vivo and that it can be applied as a non-invasive gene therapy for lung cancer.

Endolymphatic sac tumour: a rare cause of recurrent vertigo.

Endolymphatic sac tumour occurring in a 32-year-old man presenting with Meniere's like symptoms of recurrent vertigo, hearing loss and tinnitus is described. Magnetic resonance imaging and computed tomography showed a vascular bone tumour centred over the retrolabyrinthine aspect of the temporal bone where the endolymphatic sac was located. Surgical excision via a translabyrinthine approach was performed. Endolymphatic sac tumours are rare papillary adenocarcinomas that arise from the endolympatic sac. It can be mistaken both on radiology and histology for other tumours such as paragangliomas, renal or papillary thyroid carcinoma metastases. Surgical excision is the treatment of choice but sacrifice of the auditory and facial nerve may be needed in advanced cases to achieve tumour clearance.