Establishment and characterization of in vivo orthotopic bioluminescent xenograft models from human osteosarcoma cell lines in Swiss nude and NSG mice

Abstract

Osteosarcoma is one of the most common primary bone tumors in childhood and adolescence. Metastases occurrence at diagnosis or during disease evolution is the main therapeutic challenge. New drug evaluation to improve patient survival requires the development of various preclinical models mimicking at best the complexity of the disease and its metastatic potential. We describe here the development and characteristics of two orthotopic bioluminescent (Luc/mKate2) cell-derived xenograft (CDX) models, Saos-2-B-Luc/mKate2-CDX and HOS-Luc/mKate2-CDX, in different immune (nude and NSG mouse strains) and bone (intratibial and paratibial with periosteum activation) contexts. IVIS SpectrumCT system allowed both longitudinal computed tomography (CT) and bioluminescence real-time follow-up of primary tumor growth and metastatic spread, which was confirmed by histology. The murine immune context influenced tumor engraftment, primary tumor growth, and metastatic spread to lungs, bone, and spleen (an unusual localization in humans). Engraftment in NSG mice was found superior to that found in nude mice and intratibial bone environment more favorable to engraftment compared to paratibial injection. The genetic background of the two CDX models also led to distinct primary tumor behavior observed on CT scan. Saos-2-B-Luc/mKate2-CDX showed osteocondensed, HOS-Luc/mKate2-CDX osteolytic morphology. Bioluminescence defined a faster growth of the primary tumor and metastases in Saos-2-B-Luc/mKate2-CDX than in HOS-Luc/mKate2-CDX. The early detection of primary tumor growth and metastatic spread by bioluminescence allows an improved exploration of osteosarcoma disease at tumor progression, and metastatic spread, as well as the evaluations of anticancer treatments. Our orthotopic models with metastatic spread bring complementary information to other types of existing osteosarcoma models.

New osteosarcoma preclinical models in an orthotropic bone setting with the possibility to follow in vivo both primary tumor growth and metastatic spread will further help testing and development of new drug in this disease which outcome has not improved since several decades.

http://ift.tt/2EJDqsN

LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer

Abstract

To study the regulatory effect of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT-PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull-down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR-20a-5p, as well as relationship of miR-20a-5p with high mobility group AT-hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR-20a-5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR-20a-5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR-20a-5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR-20a-5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer.

The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer.

http://ift.tt/2CED14O

Prognostic variables for temporal lobe injury after intensity modulated-radiotherapy of nasopharyngeal carcinoma

Abstract

To determine predictive factors for temporal lobe injury (TLI) in nasopharyngeal carcinoma patient (NPC) treated with intensity-modulated radiation therapy (IMRT). A total of 695 NPC cases treated with IMRT were retrospectively analyzed. TLI was diagnosed on MRI images. Volume-dose histograms for 870 evaluable temporal lobes were analyzed, and the predictive factors for the occurrence of TLI was evaluated. Receiver operating characteristic curve (ROC) and Logistic regression analysis was used to determine volume-dose parameters that predict temporal lobe injury (TLI). Univariate and multivariate analysis were used to analyze the predictive factors for TLI. The radiation dose-tolerance model of temporal lobe was calculated by logistic dose-response model. The median follow-up time was 73 months. A total of 8.5% patients were diagnosed with TLI. Among all the volume-dose parameters, logistic regression model showed D2cc (the dose Gray delivered to 2 cubic centimeter volume) was an only independent predictive factor. Multivariate analysis showed D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the independent predictive factors for TLI. Logistic dose-response model has indicated the TD_5/5 and TD_50/5 of D2cc are 60.3 Gy and 76.9 Gy, respectively. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD_5/5 and TD_50/5) of D2cc are considered to prevent TLI.

A total of 695 NPC cases treated with IMRT were retrospectively analyzed with the radiation-induced temporal lobe injury on MRI images. D2cc of temporal lobe, fraction size of prescription, T stage, and chemotherapy were the possible independent predictive factors for TLI after IMRT of NPC. Biologic effective doses (TD5/5 and TD50/5) of D2cc are considered to prevent TLI.

http://ift.tt/2EJDitj

CGB5 expression is independently associated with poor overall survival and recurrence-free survival in patients with advanced gastric cancer

Abstract

The human CGB5 gene encodes chorionic gonadotropin (hCG)β 5, which is aberrantly expressed in trophoblastic neoplasm and in some non-trophoblastic neoplasms. Fucntional studies observed that it involved tumor initiation, growth, and metastatic outgrowth. In this study, using data from the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD), we assessed the independent prognostic value of CGB5 expression in patients with primary gastric cancer (GC). Results showed that CGB5 expression was nearly not expressed in normal GC tissues. In comparison, its expression was detected in 214 of the 415 primary GC cases (51.6%) in TCGA-STAD and was associated with poor response to primary therapy and a higher risk of recurrence and death. In early stages, CGB5 expression was not a prognostic factor in terms of OS (HR: 1.448; 95% CI: 0.811–2.588, P = 0.211) or RFS (HR: 1.659; 95% CI: 0.778–3.540, P = 0.190). However, its expression was independently associated with unfavorable OS (HR: 1.719; 95% CI: 1.115–2.651, P = 0.014) and RFS (HR: 3.602; 95% CI: 1.708–7.598, P = 0.001) in advanced stages. Using deep sequencing data from TCGA-STAD, we found that CGB5 expression was not related to its genetic amplification or DNA methylation in GC. Based on these findings, we infer that CGB5 expression is common in GC patients and its expression might independently predict poor OS and RFS in advanced stages, but not in early stages of GC.

CGB5 expression is common in gastric cancer patients, and its expression might independently predict poor overall survival and recurrence-free survival in advanced stages, but not in early stages of gastric cancer.

http://ift.tt/2CCp7jP

Risk factors and survival outcomes in patients with breast cancer and lung metastasis: a population-based study

Abstract

The risk factors for morbidity and mortality in breast cancer lung metastases (BCLM) patients still remain poorly identified. The aim of this study was to assess the incidence and survival of BCLM and associated risk factors. Patients with BCLM were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate logistic regression analysis was used to determine the risk factors for BCLM. Predictors of factors associated with death were analyzed in Cox regression and Fine and Gray's test. Of the 11568 patients with stage IV breast cancer, 4213 (36.4%) had BCLM and 1214 (10.5%) had metastases confined to lungs. The median survival time for patients with BCLM was 21 months, and 15.5% of the patients were alive more than 3 years. The tumor subtype distribution was 45.3% HR⁻/HER2⁻, 12.2% HR⁺/HER2⁺, 7.8% HR⁻/HER2^+, and 15.0% triple-negative subtype. Compared with patients without BCLM, those with BCLM were more likely to be aged, female, black, higher tumor grade, HR⁻/HER2⁺, HR⁺/HER2^+, and triple-negative subtypes at diagnosis. Survival analysis showed that the aged, black race, HR⁻/HER2⁺, triple-negative subtype, higher grade were the independent risk factor for BCLM patients' survival, while HR⁺/HER2⁺ subtype, insured status, and married status suggested better prognosis. In conclusion, the incidence and prognosis of BCLM varied by tumor subtypes, age, and race. Elderly patients with HER2-positive or triple-negative tumors were more likely to have BCLM.

The aim of this study was to assess the incidence and survival in patients with breast cancer and lung metastases (BCLM) and associated risk factors on a population level. Of the 11,568 patients with stage IV breast cancer, 4213 (36.42%) had BCLM and 1214 (10.49%) had BCLM confined to lungs. Survival analysis showed that the aged, black race, HR⁻/HER2⁺, triple-negative subtype, higher grade were the independent risk factor for BCLM patients' survival, while HR⁺/HER2⁺ subtype, insured status, and married status suggested better prognosis.

http://ift.tt/2ELNvW3

Prediction of radiotherapy response with a 5-microRNA signature-based nomogram in head and neck squamous cell carcinoma

Abstract

Radiotherapy is unlikely to benefit all patients with head and neck squamous cell carcinoma (HNSCC). Therefore, novel method is warranted to predict the radiotherapy response. Our study aimed to construct a microRNA (miRNA)-based nomogram to predict clinical outcomes of patients with HNSCC receiving radiotherapy. We screened out 56 differential miRNAs by analyzing 44 paired tumor and adjacent normal samples miRNA expression profiles from The Cancer Genome Atlas (TCGA). A total of 307 patients with HNSCC receiving adjuvant radiotherapy were randomly divided into a training set (n = 154) and a validation set (n = 153). In the training set, we combined the differential miRNA profiles with clinical outcomes, and LASSO regression model was applied to establish a 5-miRNA signature. The prediction accuracy of the 5-miRNA signature was further validated. In addition, target genes of these miRNAs were predicted, and Gene Ontology (GO) analysis as well as KEGG pathway analysis was executed. A 5-miRNA signature including miR-99a, miR-31, miR-410, miR-424, and miR-495 was identified. With a cutoff value of 1.2201 from Youden's index, the training set was divided into high-risk and low-risk groups, and the 5-year overall survival was significantly different (30% vs. 73%, HR 3.65, CI 2.46–8.16; P < 0.0001). Furthermore, our 5-miRNA signature revealed that only low-risk group would benefit from radiotherapy. Then, a nomogram combining 5-miRNA signature with clinical variables to predict radiotherapy response was constructed. The analysis of 108 target genes of these miRNAs revealed some potential mechanisms in HNSCC radiotherapy response for future investigations. In conclusion, the 5-miRNA signature-based nomogram is useful in predicting radiotherapy response in HNSCC and might become a promising tool to optimize radiation strategies.

We used LASSO regression model to establish a 5-miRNA signature, which serve as a novel and reliable biomarker for prediction of clinical outcomes in patients with HNSCC receiving radiotherapy. What's more, we developed a nomogram integrating the 5-miRNA signature with clinical features of each patient with HNSCC, which could be further used in the evaluation of radiotherapy responses. In addition, target genes of these miRNAs were predicted, and Gene Ontology (GO) analysis as well as KEGG analysis was executed to reveal some potential mechanisms in HNSCC radiotherapy response for future investigations.

http://ift.tt/2CE9XKE

Chromosomal abnormality variation detected by G-banding is associated with prognosis of diffuse large B-cell lymphoma treated by R-CHOP-based therapy

Abstract

Diffuse large B-cell lymphoma (DLBCL), which is the most prevalent disease subtype of non-Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic and molecular features. This study retrospectively investigated the clinical impact of G-banding-defined chromosomal abnormality on treatment outcomes of DLBCL in the era of rituximab-containing immunochemotherapy. Of 181 patients who were diagnosed with DLBCL and treated with R-CHOP or an R-CHOP-like regimen between January 2006 and April 2014, metaphase spreads were evaluable for G-banding in 120. In these 120 patients, 40 were found to harbor a single chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs), which are defined by the presence of different types of chromosomal abnormalities in G-banding, including 19 with two CAVs and 44 with ≥3 CAVs; and 17 had normal karyotypes. No specific chromosomal break point or numerical abnormality was associated with overall survival (OS) or progression-free survival (PFS), but the presence of ≥3 CAVs was significantly associated with inferior OS rates (hazard ratio (HR): 2.222, 95% confidence interval (CI): 1.056–4.677, P = 0.031) and tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965–3.344, P = 0.061). In addition, ≥3 CAVs more frequently accumulated in high-risk patients, as defined by several conventional prognostic indices, such as the revised International Prognostic Index. In conclusion, our results suggest that the emergence of more CAVs, especially ≥3, based on chromosomal instability underlies the development of high-risk disease features and a poor prognosis in DLBCL.

The existence of more chromosomal abnormality variations associates with poor prognosis in diffuse large B-cell lymphoma, indicating the negative prognostic impact of karyotypic evolution.

http://ift.tt/2ELNv8v

Treatment-related mortality in newly diagnosed pediatric cancer: a population-based analysis

Abstract

Using a previously developed reliable and valid treatment-related mortality (TRM) definition, our objective was to describe the proportion of children newly diagnosed with cancer experiencing TRM and to identify risk factors for TRM in a population-based cohort. We included children with cancer <19 years diagnosed and treated in Ontario who were diagnosed between 2003 and 2012. Children with cancer were identified using data in a provincial registry. Cumulative incidence of TRM was calculated where progressive disease death was considered a competing event. Among the 5179 children included, 179 had TRM, 478 died of progressive disease, and 4522 were still alive. At 5 years, the cumulative incidence of TRM among the entire cohort was 3.9% (95% confidence interval (CI) 3.3–4.5%). When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM (hazard ratio (HR) 2.5, 95% CI: 1.6–4.0; P < 0.0001). Infants were at significantly higher risk of TRM across diagnostic groups. Other factors associated with higher risks of TRM were metastatic disease (P < 0.0001), diagnosis prior to 1 January 2008 (P = 0.001), hematopoietic stem cell transplantation (HSCT) (P < 0.0001), and relapse (P < 0.0001). The 5-year cumulative incidence of TRM was 3.9% among newly diagnosed children with cancer. Infants were at higher risk of TRM across diagnostic groups. Other risk factors for TRM were leukemia or lymphoma, metastatic disease, earlier diagnosis year, HSCT, and relapse. Future work should further refine prognostic factors by specific cancer diagnosis to best understand when and how to intervene to improve outcomes.

Objective was to describe the proportion of children newly diagnosed with cancer experiencing treatment-related mortality (TRM) and to identify risk factors for TRM in a population-based cohort. When compared to brain tumor patients, leukemia and lymphoma patients had a significantly higher risk of TRM. Infants were at significantly higher risk of TRM across diagnostic groups.

http://ift.tt/2CCIVDJ

Application of the red fluorescent protein mCherry in mycelial labeling and organelle tracing in the dermatophyte Trichophyton mentagrophytes

Abstract

Trichophyton mentagrophytes is a fungus that causes skin disease in humans and other animals worldwide. Studies on molecular biology and fluorescent labeling of the fungus are limited. Here, we applied mCherry for the first time in T. mentagrophytes to label the fungus and its organelles. We constructed four expression vectors of mCherry or mCherry fusions containing a variety of resistance markers and promoters, which were then integrated, together with two previous mCherry expression vectors, in T. mentagrophytes via Agrobacterium tumefaciens-mediated transformation (AtMT). The resulting transformants emitted bright red fluorescence. We used the histone protein H2B and the peroxisome targeting signal 1 (PTS1) peptide to target the nucleus and peroxisomes, respectively, in T. mentagrophytes. In the transformants expressing mCherry-fused H2B, the fluorescence was distinctly localized to the nuclei in hyphae, spores and the fungal cells in infected animal tissue. In the T. mentagrophytes transformants where the peroxisome was targeted, the mCherry was present as small dots (0.2–1 μm diameter) throughout the spores and the hyphae. We also constructed a T. mentagrophytes AtMT library containing more than 1,000 hygromycin-resistant transformants that were genetically stable. Our results provide useful tools for further investigations on molecular pathogenesis of T. mentagrophytes.

http://ift.tt/2ENDX90

Variations in the relative abundance of Wolbachia in the gut of Nasutitermes arborum across life stages and castes

Abstract

There are multiple forms of interactions between termites and bacteria. In addition to their gut microbiota, which has been intensively studied, termites host intracellular symbionts such as Wolbachia. These distinct symbioses have been so far approached independently and mostly in adult termites. We addressed the dynamics of Wolbachia and the microbiota of the eggs and gut for various life stages and castes of the wood-feeding termite, Nasutitermes arborum, using deep-sequencing of the 16S rRNA gene. Wolbachia was dominant in eggs as expected. Unexpectedly, it persisted in the gut of nearly all stages and castes, indicating a wide somatic distribution in termites. Wolbachia-related sequences clustered into few OTUs, but these were within the same genotype, acquired maternally. Wolbachia was largely dominant in DNA extracts from the guts of larvae and pre-soldiers (59.1% to 99.1% of reads) where gut-resident lineages were less represented and less diverse. The reverse was true for the adult castes. This is the first study reporting the age-dependency of the relative abundance of Wolbachia in the termite gut and its negative correlation with the diversity of the microbiota. The possible mechanisms underlying this negative interaction are discussed.

http://ift.tt/2FnYi5Q

The future of genomics in polar and alpine cyanobacteria

Abstract

In recent years, genomic analyses have arisen as an exciting way of investigating the functional capacity and environmental adaptations of numerous micro-organisms of global relevance, including cyanobacteria. In the extreme cold of Arctic, Antarctic and alpine environments, cyanobacteria are of fundamental ecological importance as primary producers and ecosystem engineers. While their role in biogeochemical cycles is well appreciated, little is known about the genomic makeup of polar and alpine cyanobacteria. In this article, we present ways that genomic techniques might be used to further our understanding of cyanobacteria in cold environments in terms of their evolution and ecology. Existing examples from other environments (e.g. marine/hot springs) are used to discuss how methods developed there might be used to investigate specific questions in the cryosphere. Phylogenomics, comparative genomics and population genomics are identified as methods for understanding the evolution and biogeography of polar and alpine cyanobacteria. Transcriptomics will allow us to investigate gene expression under extreme environmental conditions, and metagenomics can be used to complement tradition amplicon based methods of community profiling. Finally, new techniques such as single cell genomics and metagenome assembled genomes will also help to expand our understanding of polar and alpine cyanobacteria that cannot readily be cultured.

http://ift.tt/2EXjSAm

Arbuscular mycorrhizal fungal and soil microbial communities in African Dark Earths

Abstract

The socio-economic value of fertile and carbon-rich Dark Earth soils is well described from the Amazon region. Very recently, Dark Earths were also identified in tropical West Africa, with comparable beneficial soil properties and plant growth-promoting effects. The impact of this management technique on soil microbial communities, however, is less well understood, especially with respect to the ecologically relevant group of arbuscular mycorrhizal (AM) fungi. Thus, we tested the hypotheses that (1) improved soil quality in African Dark Earth (AfDE) will increase soil microbial biomass and shift community composition, and (2) concurrently increased nutrient availability will negatively affect AM fungal communities. Microbial communities were distinct in AfDE in comparison to adjacent sites, with an increased fungal:bacterial ratio of 71%, a pattern mainly related to shifts in pH. AM fungal abundance and diversity, however, did not differ despite clearly increased soil fertility in AfDE, with 3.7 and 1.7 times greater extractable P and total N content, respectively. The absence of detrimental effects on AM fungi, often seen following applications of inorganic fertilizers, and the enhanced role of saprobic fungi relevant for mineralization and C sequestration support previous assertions of this management type as a sustainable alternative agricultural practice.

http://ift.tt/2sNbK0z

Lyme borreliosis–from tick bite to diagnosis and treatment

Abstract

Lyme borreliosis is caused by certain genospecies of the Borrelia burgdorferi sensu lato complex, which are transmitted by hard ticks of the genus Ixodes. The most common clinical manifestation is erythema migrans, an expanding skin redness that usually develops at the site of a tick bite and eventually resolves even without antibiotic treatment. The infecting pathogens can spread to other tissues and organs, resulting in manifestations that can involve the nervous system, joints, heart and skin. Fatal outcome is extremely rare and is due to severe heart involvement; fetal involvement is not reliably ascertained. Laboratory support—mainly by serology—is essential for diagnosis, except in the case of typical erythema migrans. Treatment is usually with antibiotics for 2 to 4 weeks; most patients recover uneventfully. There is no convincing evidence for antibiotic treatment longer than 4 weeks and there is no reliable evidence for survival of borreliae in adequately treated patients. European Lyme borreliosis is a frequent disease with increasing incidence. However, numerous scientifically questionable ideas on its clinical presentation, diagnosis and treatment may confuse physicians and lay people. Since diagnosis of Lyme borreliosis should be based on appropriate clinical signs, solid knowledge of clinical manifestations is essential.

http://ift.tt/2GBYQVc

Epicrestal and subcrestal placement of platform-switched implants: 18 month-result of a randomized, controlled, split-mouth, prospective clinical trial

Abstract

Objectives

To evaluate the changes in marginal bone levels (MBL) and soft tissue dimension around platform-switched implants with the implant–abutment junction (IAJ) placed at the crest or 1.5–2 mm subcrestally.

Materials and methods

In all, 96 platform-switched implants were placed in either the posterior maxilla or mandible in 48 partially edentulous patients in a split-mouth study. All implants were provisionally restored after 4–5 months and definitively after 6 months (T6). Radiographic assessment of MBL was assessed at implant placement (T0), T6, 12 months (T12), and 18 months (T18) after placement. Mid-buccal soft tissue and papilla measurements were performed at T6, T12, and T18.

Results

In all, 43 patients with 86 implants completed the study. The T18 examination showed an implant survival rate of 100% in both groups. Analysis showed that MBL varied as a function of IAJ location, which indicated more coronal bone levels with subcrestal (2.39 ± 0.08 mm) than with epicrestal placements (0.88 ± 0.08 mm) (p < .05). Greater average marginal bone loss was found in the subcrestal group (0.40 ± 0.07 mm) compared to the epicrestal group (0.13 ± 0.08 mm) although no statistically significant difference was found at T18 (p > .05). Levels of mid-buccal soft tissue had no significant changes over time, regardless of group (p > .05). There was a significant difference in increase in papilla between T6 and T12 and T18 (p = .005 and .001), but not between T12 and T18 (p = .61). These papilla levels and changes were similar between groups (p > .05).

Conclusions

The MBL changes around platform-switched implants with same geometry were not affected by the epicrestal or subcrestal location of the IAJ. Furthermore, the location of the IAJ did not affect the implant survival and soft tissue dimensions. However, no bone loss was located apical to the IAJ when the implants were placed subcrestally.

http://ift.tt/2oiijUg

A sustainable tandem catalysis approach to plant oil based polyols via Schenck-Ene reaction and epoxidation

Abstract

Novel polyols were synthesized in a one-pot, tandem reaction approach. First, singlet oxygen was used as oxidant in the photochemical Schenck-Ene reaction to obtain allyl hydroperoxides of triglycerides, which were reacted in situ to the corresponding epoxy alcohols catalyzed by titanium(IV) isopropoxide. Subsequent acidic epoxide ring-opening with perchloric acid yielded a triglyceride-based polyol. Under basic conditions applying aqueous sodium hydroxide solution, cleavage of the ester bonds of the triglyceride and epoxide ring-opening occurred simultaneously resulting in a fatty acid-based polyol.

Practical applications: Polyols, especially also based on renewable fatty acids, are valuable monomers for the synthesis of polyurethanes, polyester- and alkyd-resins. With the here reported method, a maximum of three hydroxyl groups per double bond of the unsaturated triglyceride can be introduced, which cannot be realized with the methods reported to date.

http://ift.tt/2HD9wEe

Employment benefits and job retention: evidence among patients with colorectal cancer

Abstract

A "health shock," that is, a large, unanticipated adverse health event, can have long-term financial implications for patients and their families. Colorectal cancer is the third most commonly diagnosed cancer among men and women and is an example of a specific health shock. We examined whether specific benefits (employer-based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer. In 2011–14, we surveyed patients with Stage III colorectal cancer from two representative SEER registries. The final sample was 1301 patients (68% survey response rate). For this study, we excluded 735 respondents who were not employed and 20 with unknown employment status. The final analytic sample included 546 respondents. Job retention in the year following diagnosis was assessed, and multivariable logistic regression was used to evaluate associations between job retention and access to specific employment benefits. Employer-based health insurance (OR = 2.97; 95% CI = 1.56–6.01; P = 0.003) and paid sick leave (OR = 2.93; 95% CI = 1.23–6.98; P = 0.015) were significantly associated with job retention, after adjusting for sociodemographic, clinical, geographic, and job characteristics.

A "health shock," that is, a large, unanticipated adverse health event, can have long-term financial implications for patients and their families. We examined whether specific benefits (employer-based health insurance, paid sick leave, extended sick leave, unpaid time off, disability benefits) are associated with job retention after diagnosis and treatment of colorectal cancer, an example of a specific health shock. Employer-based health insurance and paid sick leave were associated with job retention.

http://ift.tt/2otu7C7

Central nervous system relapse in patients over 80 years with diffuse large B-cell lymphoma: an analysis of two LYSA studies

Abstract

CNS relapse is reported in 2–5% of diffuse large B-cell lymphoma (DLBCL) patients, dramatically decreasing overall survival (OS). Very few studies address incidence and risk factors of CNS relapse in very elderly patients, a challenging population to treat given their commonly associated comorbidities. A retrospective analysis was performed of 270 DLBCL patients >80 years treated between 2004 and 2013 in two multicentre phase II LYSA trials (LNH03-7B, LNH09-7B) evaluating the addition of rituximab or ofatumumab to mini-CHOP as front-line therapy. No patients received CNS prophylaxis. CNS relapse was evaluated according to cumulative incidence, patient characteristics, risk factors, and survival. Median age was 83 years (range: 79–95). After a median follow-up of 28.7 months, eight patients had CNS relapse (3.0%). Median time between inclusion and CNS relapse was 19.2 months (range: 3.2–32.6). Patients survived a median of 1.5 months after CNS relapse (range: 0.4–4.1). Median OS from relapse was significantly lower in CNS relapse patients (1.5 months, 95% CI: 0.4–3.5) compared to patients with non-CNS relapse (6.6 months; 95% CI: 4.6–11.9). No baseline characteristics were associated with CNS relapse. The proportion of patients with CNS disease did not differ significantly between patients with low-intermediate risk according to CNS-IPI and patients with high risk (3% vs. 2.8%, P = 1.00). CNS relapse cumulative incidence in very elderly treatment-naive patients is 1.8% at 2 years and is associated with poor survival. This population had a long median time to CNS relapse. Absence of prophylaxis did not strongly impact CNS relapse incidence.

Cumulative incidence of CNS relapse at 2 years in patients with diffuse large B-cell lymphoma aged over than 80 is 1.8% and is associated with a very poor survival. The absence of prophylaxis did not appear to have a strong impact on CNS relapse incidence. Consequently CNS prophylaxis can be avoided in this population given the potential for a negative impact of the associated toxicities.

http://ift.tt/2CeaOWK

Natural occurrence and production of tenuazonic acid in wine grapes in Argentina

Abstract

A survey was carried out to determine natural occurrence of tenuazonic acid (TA) in healthy and rotten wine grapes samples from different varieties (n = 37) collected during 2016 vintage in the region of DOC San Rafael (Argentina). In addition, inoculation experiments with three Alternaria alternata strains in wine grapes were done to elucidate TA production and its major influencing factors. The 16.2% (6/37) of total wine grape samples showed TA contamination with 4% (1/25) of incidence in healthy samples (77 μg·kg⁻¹) and 42% (5/12) in rotten samples (10–778 μg·kg⁻¹). Malbec, Cabernet Sauvignon, and Syrah varieties showed TA contamination, whereas Bonarda, Ancelota, Torrontés, Semillón, and Chenin did not. During inoculation experiments in wine grapes, two of three strains were able to produce TA among the evaluated conditions and the highest TA production was observed at 15°C and 25°C after 24 days of incubation. Nutritional composition of grapes results appropriate for A. alternata infection and TA production and, together with the adequate field conditions, favors TA natural occurrence in wine grapes.

The 16.2% of wine grape samples collected during 2016 vintage in the region of DOC San Rafael (Argentina) showed TA contamination, with 4% of incidence in healthy samples (77 µg·kg⁻¹) and 42% in rotten samples (10–778 µg·kg⁻¹). Two of three Alternaria alternata strains were able to produce TA during inoculation experiments in wine grapes; they showed an optimum of production at 15°C and 25°C after 24 days of incubation. Nutritional composition of grapes results appropriate for A. alternata infection and TA production and, together with the adequate field conditions, favors TA natural occurrence in wine grapes.

http://ift.tt/2CgiS9H

Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis – a case report and literature review

Abstract

Background

Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis.

Case presentation

A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response.

Conclusions

Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.

http://ift.tt/2EVHFAT

Prediction of suboptimal cytoreductive surgery in patients with advanced ovarian cancer based on preoperative and intraoperative determination of the peritoneal carcinomatosis index

Abstract

Background

The peritoneal carcinomatosis index (PCI) can be used to quantify the tumor burden in patients with advanced ovarian cancer. The aim of the present study was to establish a predictive model for suboptimal cytoreductive surgery (SCS) (residual tumor of > 1 cm) using preoperative and intraoperative determination of the PCI.

Methods

In total, 110 consecutive patients treated for advanced ovarian cancer during a 4-year period in our institution were assessed. Eighty of these patients were eligible for primary debulking surgery and thus included in the present study. All data were prospectively collected and retrospectively evaluated. We determined the PCI both preoperatively and intraoperatively and assessed postoperative complications.

Results

A PCI of > 20 was the best cut-off with which to predict a risk of SCS among all three diagnostic techniques assessed in this study (computed tomography, laparoscopy, and laparotomy). Intraoperative PCI determination was associated with the lowest risk of false negatives for SCS when detecting a PCI of < 20. The combination of preoperative computed tomography and laparoscopy, when both techniques predicted SCS, was associated with the lowest risk of false positives for SCS when detecting a PCI of > 20.

Conclusion

The combination of computed tomography and laparoscopy to obtain the PCI can help to determine which patients with advanced ovarian cancer are suitable for primary debulking surgery and which should undergo neoadjuvant chemotherapy.

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The extremity localized classic osteosarcomas have better survival than the axial non-classics

Abstract

Background

Osteosarcoma is one of the most malignant primary bone cancers, while is rarely reported in China. Of note, very few data of prognosis has been documented in this region. Thus, we carried a retrospective study to identify prognostic factors and to analyze outcomes in patients of both classic and non-classic high-grade osteosarcomas. Classic osteosarcoma is defined as of high-grade histology, age below 40 years, with extremity localized primary tumor, and without detectable metastasis at primary diagnosis.

Methods

A total of 98 patients (68 classic and 30 non-classic) aged from 4 to 64 years old were diagnosed as high-grade osteosarcoma from 2008 to 2015 in Nanfang Hospital, Guangzhou, China. Univariate and multivariate analyses were performed to identify the independent predictors for overall survival and event-free survival. Kaplan-Meier method was used for survival analysis.

Results

The median overall survival was 117 vs. 21 months, and the median event-free survival was 31 vs. 6 months in classic and non-classic osteosarcoma, respectively. The most frequently found tumor site was around the knee. The classic osteosarcoma had better overall survival and event-free survival than the non-classics. Tumor site and primary metastasis were found to be associated with overall survival and event-free survival in the univariate analysis. In the multivariate Cox regression analysis, tumor site and primary metastasis were each verified as independent prognostic factors. However, no similar result was found in elevated serum alkaline phosphatase or lactate dehydrogenase. Amputation or limb salvage surgery had no significant effect on overall survival and event-free survival in the extremity osteosarcomas. Classic osteosarcomas with extremity tumor site and free of primary metastasis exhibited better overall survival and event-free survival, while the axial and metastatic non-classics exhibited the worse.

Conclusions

The extremity classic osteosarcomas have better survivals than the axial non-classic cases. Amputation and limb salvage surgery make no significant change in overall survival and event-free survival in the extremity osteosarcomas.

Trial registration

Nanfang2013071; Date of registration: 7 September 2013 (retrospectively registered).

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Fast dictionary learning from incomplete data

This paper extends the recently proposed and theoretically justified iterative thresholding and K residual means (ITKrM) algorithm to learning dictionaries from incomplete/masked training data (ITKrMM). It furthe...

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Immunomodulation of mesenchymal stem cells in discogenic pain

Publication date: February 2018
Source:The Spine Journal, Volume 18, Issue 2
Author(s): Laura Miguélez-Rivera, Saúl Pérez-Castrillo, Maria Luisa González-Fernández, Julio Gabriel Prieto-Fernández, María Elisa López-González, José García-Cosamalón, Vega Villar-Suárez
Background ContextBack pain is a highly prevalent health problem in the world today and has a great economic impact on health-care budgets. Intervertebral disc (IVD) degeneration has been identified as a main cause of back pain. Inflammatory cytokines produced by macrophages or disc cells in an inflammatory environment play an important role in painful progressive degeneration of IVD. Mesenchymal stem cells (MSCs) have shown to have immunosuppressive and anti-inflammatory properties. Mesenchymal stem cells express a variety of chemokines and cytokines receptors having tropism to inflammation sites.PurposeThis study aimed to develop an in vitro controlled and standardized model of inflammation and degeneration of IVD with rat cells and to evaluate the protective and immunomodulatory effect of conditioned medium (CM) from the culture of MSCs to improve the conditions presented in herniated disc and discogenic pain processes.Study DesignThis is an experimental study.MethodsIn this study, an in vitro model of inflammation and degeneration of IVD has been developed, as well as the effectiveness of CM from the culture of MSCs.ResultsConditioned medium from MSCs downregulated the expression of various proinflammatory cytokines produced in the pathogenesis of discogenic pain such as interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor (TNF).ConclusionMesenchymal stem cells represent a promising alternative strategy in the treatment of IVD degeneration inasmuch as there is currently no treatment which leads to a complete remission of long-term pain in the absence of drugs.



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Prevalence and risk factors for neural axis anomalies in idiopathic scoliosis: a systematic review.

Publication date: Available online 14 February 2018
Source:The Spine Journal
Author(s): Johan L. Heemskerk, Moyo C. Kruyt, Dino Colo, René M. Castelein, Diederik H.R. Kempen
BackgroundThere is ongoing controversy about the routine use of magnetic resonance imaging (MRI) preoperatively in patients with presumed idiopathic scoliosis (IS). Routine MRI can help identify possible causes for the deformity and detect anomalies which could complicate deformity surgery. However, routine MRI increases health care costs significantly and may reveal mild variations from normal without clinical relevance, that can still lead to anxiety and influence decision making.PurposeGiven the necessity to make evidence based decisions both in the light of quality of care as well as cost control, the aim of this review is to report the prevalence of neural axis anomalies in idiopathic scoliosis and to identify risk factors associated with these anomalies.Study design: systematic reviewMethodsAn electronic search until May 2017 PubMed, Embase, Cochrane and Cinahl was performed. Studies were assessed by 2 reviewers independently according to predetermined inclusion (MRI in presumed IS) and exclusion criteria (other diagnosis than IS).ResultsFifty one studies were included consisting 8622 patients. In 981 patients, anomalies were found, resulting in an overall prevalence of 11.4%. The prevalencewas10.5%, 9.0% and 14.2% when screening was performed of all IS patients, pre-operative patients or patients with for presumed risk factors.. The prevalence of a syrinx (3.7%), an Arnold-Chiari malformation (3.0%) or a combination of both (2.5%) was highest. Less frequent diagnoses included tethered cord (0.6%), an incidental malignancy (0.3%) and split cord malformations (0.2%). Risk factors for intraspinal anomalies included early onset scoliosis, male gender, atypical curves, thoracic kyphosis and abnormal neurological findings such as reflexes and sensation.ConclusionsThis systematic review shows that a significant number of patients have intra-spinal anomalies on preoperative MRI in (presumed) IS. The prevalence of finding spinal axis abnormalities increases in pre-selected patients groups with specific risk factors.



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Short-term outcomes following posterior cervical fusion among octogenarians with cervical spondylotic myelopathy: a NSQIP database analysis

Publication date: Available online 14 February 2018
Source:The Spine Journal
Author(s): Caroline E. Vonck, Joseph E. Tanenbaum, Thomas T. Bomberger, Edward C. Benzel, Jason W. Savage, Iain H. Kalfas, Thomas E. Mroz, Michael P. Steinmetz
BackgroundContext: Degenerative changes in the cervical spine occur in an age-dependent manner. As the U.S. population continues to age, the incidence of age-dependent, multi-level, degenerative cervical pathologies is expected to increase. Similarly, the average age of patients with cervical spondylotic myelopathy (CSM) will likely trend upward. Posterior cervical fusion (PCF) is often the treatment modality of choice in the management of multi-level cervical spine disease. Although outcomes following anterior cervical fusion for degenerative disease have been studied among older patients (aged 80 years and older), it is unknown if these results extend to octogenarian patients undergoing PCF for the surgical management of CSM.PurposeThe present study aimed to quantify surgical outcomes following PCF for the treatment of CSM among the octogenarian patient population, as compared to patients younger than 80 years old.Study Design/SettingThis was a retrospective study that used the National Surgical Quality Improvement Program (NSQIP).Patient SampleThe sample included patients aged 60-89 who had CSM and who underwent PCF from 2012-2014.Outcome MeasuresThe outcome measures were multi-morbidity, prolonged length of stay (LOS), discharge disposition (to home or skilled nursing/rehabilitation facility), 30-day all-cause readmission, and 30-day reoperation.MethodsThe NSQIP database was queried for CSM patients (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] code 721.1) aged 60-89 who underwent PCF (Current Procedural Terminology [CPT] code 22600) from 2012-2014. Cohorts were defined by age group (60-69, 70-79, 80-89). Data were collected on gender, race, elective or emergent status, inpatient or outpatient status, where patients were admitted from (home versus skilled nursing facility), ASA class, comorbidities, and single- or multi-level fusion. After controlling for these variables, logistic regression analysis was used to compare outcome measures in the different age groups.Results819 patients with CSM who underwent PCF (416 aged 60-69, 320 aged 70-79, 83 aged 80-89) were identified from 2012-2014. 79.7% of PCF procedures were multi-level. There were no significant differences in the odds of multi-morbidity, prolonged LOS, readmission, or reoperation when comparing octogenarian patients with CSM to patients aged 60-69 or 70-79. Patients aged 60-69 and 70-79 were significantly more likely to be discharged to home than patients over 80 (OR 4.3, 95% CI 1.8-10.4, p<0.0001 and OR 2.7, 95% CI 1.1-6.4, p=0.0005, respectively).ConclusionsCompared to patients aged 60-69 and 70-79, octogenarian patients with CSM were significantly more likely to be discharged to a location other than home following PCF. After controlling for patient comorbidities and demographics, 80-89 year old CSM patients undergoing PCF did not differ in other outcomes when compared to the other age cohorts. These results can improve preoperative risk counseling and surgical decision-making.



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Back pain improves significantly following discectomy for lumbar disc herniation

Publication date: Available online 14 February 2018
Source:The Spine Journal
Author(s): R. Kirk Owens, Leah Y. Carreon, Erica F. Bisson, Mohamad Bydon, Eric A. Potts, Steven D. Glassman
Background ContextAlthough lumbar disc herniation (LDH) classically presents with lower extremity radiculopathy, there are patients who have substantial associated back painPurposeTo determine if patients with lumbar disc herniation (LDH) with substantial back pain improve with decompression alone.Study DesignLongitudinal observational cohortPatient samplePatients enrolled in the Quality and Outcomes Database (QOD) with LDH and a baseline back pain score ≥ 5 of 10 who underwent 1 or 2-level lumbar discectomy onlyOutcome measuresBack and leg pain scores (0-10), Oswestry Disability Index (ODI), and EuroQoL 5D (EQ-5D).Methods. Standard demographic and surgical variables were collected, as well as patient reported outcomes at baseline and at 3 and 12 months postoperatively.ResultsThe mean age of the cohort was 49.8 years and 1195 (52.8%) were male. Mean BMI was 30.1 kg/m². About half of the patients (1103, 48.8%) underwent single level discectomy and the other half (1159, 51.2%) had 2-level discectomy. Average blood loss was 44cc. Most of the patients (2217, 98%) were discharged home with routine postoperative care. The average length of stay was 0.53 days. At 3 months and 12 months postoperatively, there were statistically significant (p<0.000) improvements in back pain (7.7 to 2.9 to 3.2), leg pain (7.5 to 2.3 to 2.5) and ODI (26.2 to 11.6 to 11.2). Patients with a single-level discectomy, compared to patients with a two-level discectomy, had similar improvements in 3- and 12 month back pain, leg pain and ODI scores.ConclusionPatients with LDH who have substantial back pain can be counseled to expect improvement in their back pain scores 12 months after a discectomy.



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Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): Eric H. Ledet, Glenn P. Sanders, Darryl J. DiRisio, Joseph C. Glennon
BackgroundContext: Achieving a successful spinal fusion requires the proper biologic and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multi-level procedures where pseudarthrosis rates are significant.PurposeTo evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate.Study Design/SettingAn in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion.MethodsFourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed out to 18 weeks and were evaluated by plain x-ray, CT scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion.ResultsAnimals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks post-operatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant.ConclusionsLoad-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micromotion.



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Risk factors for perioperative morbidity in spine surgeries of different complexities: a multivariate analysis of 1009 consecutive patients

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): M. Farshad, D.E. Bauer, C. Wechsler, C. Gerber, A. Aichmair
Background ContextThere is a broad spectrum of complications during or after surgical procedures, with differing incidences reported in the published literature. Heterogeneity can be explained by the lack of an established evidence-based classification system for documentation and classification of complications in a standardized manner.PurposeTo identify predictive risk factors for peri- and early post-operative morbidities in spine surgeries of different complexities in a large cohort of consecutive patients.Study DesignRetrospective case series.Outcome MeasuresOccurrence of peri- and early post-operative morbidities.MethodsA classification of surgical complexity (grade I-III) was created and applied to 1009 patients who consecutively underwent spine surgery at a single university hospital. The incidence and type of peri- and early post-operative morbidities were documented. Multivariate binary logistic regression analyzed risk factors for (a) hospital stay≥10 days, (b) intermediate care unit (IMC) stay≥24 hours, (c) blood loss>500mL, and occurrence of a (d) surgical or (e) medical morbidity.ResultsA deviation from the regular postoperative course (defined as "morbidity") included surgical reasons such as relapse of symptoms of any kind (3.3%), wound healing problems (2.4%), implant-associated complications (1.6%), post-operative neurological deficits (1.5%), infection (1.5%), fracture (0.8%), and dural tear in need of revision (0.6%). Medical reasons included anemia (1.8%), symptomatic electrolyte derailment (1.0%), and cardiac complications (0.7%), among others. An independent risk factor associated with a surgical reason for an irregular post-operative course was male gender. For a medical reason high creatinine levels preoperatively, higher blood loss, and systemic steroid use were identified as risk factors. Independent risk factors for a prolonged hospitalization were preoperatively high CRP, prolonged postoperative IMC stay, and revision surgery. Spinal stabilization/fusion surgery, particularly if involving the lumbosacral spine, age, and length of surgery were associated with a blood loss>500mL. Higher surgical complexity, involvement of the pelvis in instrumentation, ASA class≥3, and higher creatinine levels preoperatively were associated with a postoperative IMC stay>24 hours.ConclusionThe present study confirms several modifiable and non-modifiable risk factors for peri- and early post-operative morbidities in spine surgery, among which surgical factors (complexity, revision surgery, instrumentation (including the pelvis etc.)) play a crucial role. A classification of surgical complexity is proposed and validated.



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Dental pulp stem cell-derived chondrogenic cells demonstrate differential cell motility in type I and type II collagen hydrogels

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): Li Yao, Nikol Flynn
Background ContextAdvances in the development of biomaterials and stem cell therapy provide a promising approach to regenerating degenerated discs. The normal nucleus pulposus (NP) cells exhibit the similar phenotype as chondrocytes. Because dental pulp stem cells (DPSCs) can be differentiated into chondrogenic cells, the DPSCs and DPSCs-derived chondrogenic cells encapsulated in type I and type II collagen hydrogels can potentially be transplanted into degenerated nucleus pulposus (NP) to repair damaged tissue. The motility of transplanted cells is critical because the cells need to migrate away from the hydrogels containing the cells of high density and disperse into the NP tissue after implantation.PurposeThe purpose of this study was to determine the motility of DPSC and DPSC-derived chondrogenic cells in type I and type II collagen hydrogels.Study Design/SettingThe time lapse imaging that recorded cell migration was analyzed to quantify the cell migration velocity and distance.MethodsThe cell viability of DPSCs in native or 4S-StarPEG – crosslinked type I and type II collagen hydrogels was determined using LIVE/DEAD^® cell viability assay and AlamarBlue® assay. DPSCs were differentiated into chondrogenic cells. The migration of DPSCs and DPSC-derived chondrogenic cells in these hydrogels was recorded using a time lapse imaging system. This study was funded by Regional Institute on Aging and Wichita Medical Research and Education Foundation and the authors declare no competing interest.ResultDPSCs showed high cell viability in non-crosslinked and crosslinked collagen hydrogels. DPSCs migrated in collagen hydrogels, and the cell migration speed was not significantly different in either type I collagen or type II collagen hydrogels. The migration speed of DPSC-derived chondrogenic cells was higher in type I collagen hydrogel than in type II collagen hydrogel. Crosslinking of type I collagen with 4S-StarPEG significantly reduced the cell migration speed of DPSC-derived chondrogenic cells.ConclusionsAfter implantation of collagen hydrogels encapsulating DPSCs or DPSC-derived chondrogenic cells, the cells can potentially migrate from the hydrogels and migrate into the NP tissue. This study also explored the differential cell motility of DPSCs and DPSC-derived chondrogenic cells in these collagen hydrogels.



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‘Micro endoscopic’ vs. ‘pure endoscopic’ surgery for spinal intra dural mass lesions: a comparative study and review

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): Sivashanmugam Dhandapani, Madhivanan Karthigeyan
BackgroundEndoscopy is increasingly being used for minimal invasiveness and panoramic visualization, with unclear efficacy and safety among spinal intradural lesions.ObjectiveTo compare micro-endoscopic and pure-endoscopic surgery for spinal intradural lesions.MethodsSpinal intradural lesions operated by us using endoscopic/access ports were categorized 'micro-endoscopic' (predominant microscope use), or 'pure-endoscopic' (standalone endoscopy) surgery, and studied with respect to clinico-radiological features, techniques, peri-operative course, histopathology, clinical and radiological outcome at minimum of 3 months.ResultsAmong 34 patients studied, the initial 15 had 'micro-endoscopic' surgery, 16 had 'pure-endoscopic' surgery, while 3 had 'mixed' use. There were 18 nerve sheath tumors, 6 meningiomas, 6 cysts, 2 ependymomas, 1 hemangioblastoma and 1 paraganglioma, from 1.5 to as large as 6.8cm (21%≥4cm). Intermuscular or paraspinous approach was utilized, followed by small bony fenestration/interlaminar corridor. Even larger schwannomas could be excised through smaller bony fenestration using 'sliding-delivery' technique. While visualization of sides and angles was better with endoscope, hemostasis and dural closure had steep learning curve, necessitating use of microscope in the initial cases. Clinical improvement and radiological resolution could be achieved in all. There was no significant difference between the groups. The change in Nurick grade had significant correlation with only the dimension of lesion (P=0.03) and pre-operative grade (P=0.05).ConclusionEndoscopy is effective and safe for even large intradural spinal tumors with better visualization of sides and angles, albeit with hemostasis and dural closure having initial learning curve. Wide heterogeneity of surgical terminologies in literature on these procedures warrants consensus for uniform reporting.



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Incidence and risk factors of post-operative neurological decline after complex adult spinal deformity surgery: results of the scoli-risk-1 study

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): Michael G. Fehlings, So Kato, Lawrence G. Lenke, Hiroaki Nakashima, Narihito Nagoshi, Christopher I. Shaffrey, Kenneth M.C. Cheung, Leah Carreon, Mark B. Dekutoski, Frank J. Schwab, Oheneba Boachie-Adjei, Khaled M. Kebaish, Christopher P. Ames, Yong Qiu, Yukihiro Matsuyama, Benny T. Dahl, Hossein Mehdian, Ferran Pellisé-Urquiza, Stephen J. Lewis, Sigurd H. Berven
Background ContextSignificant variability in neurologic outcomes following surgical correction for adult spinal deformity (ASD) has been reported. Risk factors for decline in neurologic motor outcomes are poorly understood.PurposeThe objective of the present investigation was to identify the risk factors for post-operative neurological motor decline in patients undergoing complex ASD surgery.Study Design/SettingA prospective international multicenter cohort study.Patient SampleFrom September 2011 to October 2012, 272 patients undergoing complex ASD surgery were prospectively enrolled in a multicenter, international cohort study in 15 sites.Outcome MeasuresNeurological decline was defined as any post-operative deterioration in American Spinal Injury Association Lower Extremity Motor Scores (LEMS) compared to pre-operative status.MethodsTo identify risk factors, 10 candidate variables were selected for univariable analysis from the dataset based on clinical relevance, and a multivariable logistic regression analysis was used with backward stepwise selection. Funds from The Scoliosis Research Society (SRS) and AOSpine International, both nonprofit organizations, and from Norton Healthcare, Louisville, KY, USA, were received in support of this work.ResultsComplete datasets on 265 patients were available for analysis and 61 (23%) patients showed a decline in LEMS at discharge. Univariable analysis showed that the key factors associated with post-operative neurological deterioration included older age, lumbar level osteotomy, three-column osteotomy, and larger blood loss. Multivariable analysis revealed that older age (odds ratio [OR] = 1.5 per 10 years, 95% confidence interval [CI]: 1.1 – 2.1, p = 0.005), larger coronal deformity angular ratio [DAR] (OR = 1.1 per 1 unit, 95% CI: 1.0 – 1.2, p = 0.037) and lumbar osteotomy (OR = 3.3, 95% CI: 1.2 – 9.2, p = 0.022) are the three major predictors of neurological decline.ConclusionsTwenty-three percent of patients undergoing complex ASD surgery experienced a post-operative neurological decline. Age, coronal DAR, and lumbar osteotomy were identified as the key contributing factors.



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Re: Are Modic changes associated with intervertebral disc cytokine profiles?

Publication date: February 2018
Source:The Spine Journal, Volume 18, Issue 2
Author(s): Francisco Kovacs, Estanislao Arana, Beatriz Asenjo-García, Ana Estremera-Rodrigo, Guillermo-José Amengual-Alemany, Helena Sarasíbar-Ezcurra, Ana Alonso, Luis Álvarez-Galovich




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Risk-factor analysis of adjacent segment disease requiring surgery after short lumbar fusion: the influence of rheumatoid arthritis

Publication date: Available online 13 February 2018
Source:The Spine Journal
Author(s): Jin-Sung Park, Kyu-Dong Shim, Young-Sik Song, Ye-Soo Park
BACKGROUND CONTEXTThe influence of rheumatoid arthritis (RA) on the lumbar spine has received relatively little attention compared with cervical spine, and few studies have been conducted for adjacent segment disease (ASD) after lumbar fusion in the patients with RA.PURPOSETo determine the incidence of ASD requiring surgery (ASDrS) after short lumbar fusion and to evaluate risk factors of ASDrS, including RA.STUDY DESIGNRetrospective cohort studyPATIENT SAMPLEThis study included 479 patients who underwent lumbar spinal fusion of 3 or fewer levels, with the mean follow-up period of 51.2 months (12 to 132).OUTCOME MEASRUESThe development of ASD and consequent revision surgery were reviewed using follow-up data.METHODSThe ASDrS-free survival rate of adjacent segments was calculated through Kaplan-Meier method. The log-rank test and Cox regression analysis were used to evaluate risk factors, comprising RA, age, sex, obesity, osteoporosis, diabetes, smoking, surgical method, and the number of fusion segments.RESULTSAfter short lumbar fusion, revision surgery for ASD was performed in 37 patients (7.7%). Kaplan-Meier analysis predicted that the ASDrS-free survival rate of adjacent segments was 97.8% at 3-years, 92.7% at 5-years, and 86.8% at 7-years. In risk factor analysis, patients with RA showed a 4.5 times higher risk for ASDrS than patients without RA (p < 0.001), and patients with 3-segment fusion showed a 2.7 times higher risk than 1- or 2-segment fusion (p = 0.005).CONCLUSIONASD requiring surgery was predicted in 13.2% of patients at 7-years after short lumbar fusion. RA and the number of fusion segments were confirmed as risk factors.



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Risk factors & associated complications for postoperative urinary retention after lumbar surgery for lumbar spinal stenosis

Publication date: Available online 12 February 2018
Source:The Spine Journal
Author(s): Joshua L. Golubovsky, Haariss Ilyas, Jinxiao Chen, Joseph E. Tanenbaum, Thomas E. Mroz, Michael P. Steinmetz
Background ContextPostoperative Urinary Retention (POUR) is a very common post-operative complication of all surgeries (5 – 70%) that may lead to complications such as urinary tract infection (UTI), bladder over-distention, autonomic dysregulation, and increased postoperative length of stay (LOS). Within the field of spine surgery, the reported incidence of POUR is highly variable (5.6 – 38%). Lack of clear stratification of surgical level, spinal pathology, and inadequate sample size is a major limitation of available studies concerning POUR following spine surgery that may lead to inconsistency in the incidence of POUR and the ability to model its occurrence and consequences.PurposeThis study examines the incidence, predictive factors, and complications of POUR in patients undergoing elective posterior lumbar decompression with or without fusion for lumbar stenosis in order to eliminate bias from studying procedures done in different anatomical regions and with different approaches. Additionally, this study intends to identify the consequences of POUR.Study Design/SettingA retrospective consecutive cohort analysis was performed to examine patients undergoing posterior lumbar decompression who did and did not develop POUR.Patient SampleAll patients undergoing posterior lumbar decompression with or without fusion for lumbar stenosis with claudication from January 2014 through December 2015 at our institution were evaluated. Patients under the age of 18 and patients with spinal malignancies or infections were excluded.Outcome MeasuresPhysiological measures included identification of POUR by evidence of re-insertion of a Foley catheter, use of straight catherization post-operatively, or by a clear medical diagnosis with pharmacological treatment. Other physiological measures included identification of development of UTI, sepsis, acute kidney injury (AKI), surgical site infection, or readmission within 90 days after surgery, as well as LOS and discharge disposition.MethodsThere were no external funding sources and no authors had any conflicts of interest. The electronic medical record was searched for all patients meeting inclusion and exclusion criteria. POUR was defined as re-insertion of a Foley catheter, use of straight catherization post-operatively, or by a clear medical diagnosis with pharmacological treatment. Statistical analysis was performed in R statistical software package version 3.3.2. Multiple variable selection techniques were used to determine appropriate variables for regression models, and logistic models were fit to the development of POUR and post-operative complications, while a linear regression model was used for LOS.ResultsData was collected on 1592 consecutive patients. Among the sample population, the mean age at surgery was 67 (SD 10.1) and 45% of patients were female. The incidence of POUR was 17.1% (273/1592). Increased age (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.02 - 1.06; p < 0.001), benign prostatic hyperplasia (BPH) (OR = 1.92; 95% CI, 1.32 - 2.78); p < 0.001), previous AKI (OR = 3.29; 95% CI, 1.11 - 9.29; p = 0.025), and previous UTI (OR = 1.69; 95% CI, 1.24 - 2.24; p < 0.001) significantly increased the probability of developing POUR. Factors including increased body mass index, coronary artery disease, congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, tobacco use, and fusion were found to be non-significant and were excluded from the model.With respect to complications, POUR was found to be associated with development of UTI (OR = 4.50; 95% CI, 3.14 - 6.45; p < 0.001), sepsis (OR = 4.05; 95% CI, 1.16 - 13.55; p = 0.022), increased LOS (p < 0.001), increased likelihood to be discharged to a skilled nursing facility (OR of discharge to home = 0.44; 95% CI, 0.32 – 0.62; p < 0.001), and increased risk for readmission within 90 days of the index surgery (OR = 1.60; 95% CI, 1.11 - 2.26), p = 0.009). Development of POUR did not increase the risk of developing AKI (OR = 2.45; 95% CI, 0.93 – 6.30; p = 0.063) or a surgical site infection (OR = 1.09; 95% CI, 0.56 – 2.02; p = 0.79).ConclusionsOverall, POUR was a significant risk factor for the development of UTI, sepsis, increased LOS, discharge to a skilled nursing facility, and readmission within 90 days. Surgeons and anesthesiologists should take preventative measures against POUR in individuals with increased age, BPH, and AKI and UTI within 90 days prior to surgery, as these factors were found to significantly increase the risk of POUR.



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Motor impairment in patients with chronic neck pain: does the traumatic event play a significant role? – a case control study

Publication date: Available online 31 January 2018
Source:The Spine Journal
Author(s): R. De Pauw, I. Coppieters, T. Palmans, L. Danneels, M. Meeus, B. Cagnie
Background contextMotor impairment is a key-sign in patients with traumatic (WAD) and non-traumatic (INP) neck pain.PurposeThis study aims at analyzing differences in motor impairment between both groups, and assesses the association with self-reported symptoms.Study DesignCase control.Patient Sample38 patients with chronic INP, 35 patients with chronic WAD, and 30 healthy pain-free controls were included.Outcome measuresMobility (°), Strength (N), Repositioning accuracy (°), endurance (s), sway velocity (cm/s), sway area (cm²) and neuromuscular control.MethodsGroup differences of motor impairment together with questionnaires to evaluate pain intensity, fear avoidance, pain catastrophizing, symptoms of central sensitization, and disability were analyzed with Analysis of Covariance, including age as a covariate.ResultsMotor impairment was observed in both patient groups with a higher degree in patients with chronic WAD. These impairments were moderately linked to self-reported disability and were in most cases associated with pain, fear-avoidance, and symptoms of central sensitization (|ρ| ranging from 0.28 to 0.59).ConclusionMotor impairment should be addressed when treating both groups of patients, keeping in mind the association with self-reported pain and disability, fear-avoidance and central sensitization.



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Impaction durability of porous PEEK and titanium-coated PEEK interbody fusion devices

Publication date: Available online 31 January 2018
Source:The Spine Journal
Author(s): F. Brennan Torstrick, Brett S. Klosterhoff, L. Erik Westerlund, Kevin T. Foley, Joanna Gochuico, Christopher S.D. Lee, Ken Gall, David L. Safranski
Background ContextVarious surface modifications, often incorporating roughened or porous surfaces, have recently been introduced to enhance osseointegration of interbody fusion devices. However, these topographical features can be vulnerable to damage during clinical impaction. Despite the potential negative impact of surface damage on clinical outcomes, current testing standards do not replicate clinically relevant impaction loading conditions.PurposeThe purpose of this study was to compare the impaction durability of conventional smooth PEEK cervical interbody fusion devices with two surface-modified PEEK devices that feature either a porous structure or plasma-sprayed titanium coating.Study Design/SettingA recently developed biomechanical test method was adapted to simulate clinically relevant impaction loading conditions during cervical interbody fusion procedures.MethodsThree cervical interbody fusion devices were used in this study: smooth PEEK, plasma-sprayed titanium-coated PEEK, and porous PEEK (n=6). Following Kienle et al., devices were impacted between two polyurethane blocks mimicking vertebral bodies under a constant 200 N pre-load. The posterior tip of the device was placed at the entrance between the polyurethane blocks and a guided 1 lb weight was impacted upon the anterior face with a maximum speed of 2.6 m/s to represent the strike force of a surgical mallet. Impacts were repeated until the device was fully impacted. Porous PEEK durability was assessed using micro-computed tomography (µCT) pre- and post- impaction. Titanium-coating coverage pre- and post-impaction was assessed using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDX). Changes to the surface roughness of smooth and titanium-coated devices were also evaluated.ResultsPorous PEEK and smooth PEEK devices showed minimal macroscopic signs of surface damage, while the titanium-coated devices exhibited substantial visible coating loss. Quantification of the porous PEEK deformation demonstrated that the porous structure maintained a high porosity (>65%) following impaction that would be available for bone ingrowth, and exhibited minimal changes to pore size and depth. SEM and EDX analysis of titanium-coated devices demonstrated substantial titanium coating loss after impaction that was corroborated with a decrease in surface roughness. Smooth PEEK showed minimal signs of damage using SEM, but demonstrated a decrease in surface roughness.ConclusionThough recent surface modifications to interbody fusion devices are beneficial for osseointegration, they may be susceptible to damage and wear during impaction. The current study found porous PEEK devices to show minimal damage during simulated cervical impaction, whereas titanium-coated PEEK devices lost substantial titanium coverage.



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Do findings identified on magnetic resonance imaging predict future neck pain? a systematic review

Publication date: Available online 2 February 2018
Source:The Spine Journal
Author(s): Laura Hill, David Aboud, James Elliott, John Magnussen, Michele Sterling, Daniel Steffens, Mark Hancock
Background ContextMagnetic resonance imaging (MRI) has the potential to identify pathology contributing to neck pain. However, the importance of findings on MRI remains unclear.PurposeTo investigate whether findings on cervical spine MRI predict future neck pain.Study DesignSystematic review.Patient SamplePeople with or without neck pain.Outcome measuresClinically important neck pain outcomes such as pain and disability. Methods: The review protocol was registered on PROSPERO [CRD42016049228]. MEDLINE, CINAHL and EMBASE databases were searched. Included were prospective cohort studies investigating the association between baseline MRI findings and clinical outcome. Cohorts with serious underlying diseases as the cause of their neck pain were excluded. Associations between MRI findings and neck pain outcomes were extracted from the included studies.ResultsA total of twelve studies met all inclusion criteria. Eight studies presented data on participants with current neck pain, two studies included a mixed sample, two studies included a sample of participants with no current neck pain. Due to the heterogeneity between the studies in terms of MRI findings, populations and clinical outcomes investigated, it was not possible to pool the results. No consistent associations between MRI findings and future outcomes were identified. Single studies of populations with neck pain reported significant associations for neck muscle fatty infiltrate (risk ratio (RR) 21.00, 95% CI 2.97 to 148.31) with persistent neck disability; disc protrusion (mean difference (MD) ranged from -1.83 to -2.88 on 10- point pain scale) and disc degeneration (RR: 0.59; 95% CI: 0.36 to 0.98) with neck pain. In a population without pain, the development of foraminal stenosis over a 10 year period was associated with development of neck pain (RR: 2.99; 95% CI: 1.23 to 7.23).ConclusionsThe limited number, heterogeneity and small sample size of the included studies, do not permit definitive conclusions on the association between MRI findings of the cervical spine with future neck pain.



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Ixazomib in the management of relapsed multiple myeloma

Future Oncology, Ahead of Print.


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Reporting guidelines for oncology research: helping to maximise the impact of your research

Reporting guidelines for oncology research: helping to maximise the impact of your research

Reporting guidelines for oncology research: helping to maximise the impact of your research, Published online: 22 February 2018; doi:10.1038/bjc.2017.407

Reporting guidelines for oncology research: helping to maximise the impact of your research

http://ift.tt/2CEiLAu

EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting, Published online: 22 February 2018; doi:10.1038/bjc.2017.427

EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

http://ift.tt/2EJ7g0x

Mass spectrometry-based proteomics reveals potential roles of NEK9 and MAP2K4 in resistance to PI3K inhibitors in triple negative breast cancers

Activation of phosphoinositide 3-kinase (PI3K) signaling is frequently observed in triple-negative breast cancer (TNBC), yet PI3K inhibitors have shown limited clinical activity. To investigate intrinsic and adaptive mechanisms of resistance, we analyzed a panel of patient-derived xenograft models of TNBC with varying responsiveness to buparlisib, a pan-PI3K inhibitor. In a subset of patient-derived xenografts, resistance was associated with incomplete inhibition of PI3K signaling and upregulated MAPK/MEK signaling in response to buparlisib. Outlier phosphoproteome and kinome analyses identified novel candidates functionally important to buparlisib resistance, including NEK9 and MAP2K4. Knockdown of NEK9 or MAP2K4 reduced both baseline and feedback MAPK/MEK signaling and showed synthetic lethality with buparlisib in vitro. A complex in/del frameshift in PIK3CA decreased sensitivity to buparlisib via NEK9/MAP2K4-dependent mechanisms. In summary, our study supports a role for NEK9 and MAP2K4 in mediating buparlisib resistance and demonstrates the value of unbiased omic analyses in uncovering resistance mechanisms to targeted therapy.

http://ift.tt/2GByz9n

Clinical Factors Predict Atezolizumab Response [News in Brief]

Six clinical factors predict survival of patients with bladder cancer after treatment with PD-L1 inhibitor.

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Polyunsaturated fatty acids and risk of melanoma: A Mendelian randomisation analysis

Abstract

Melanoma is the deadliest form of skin cancer, mainly affecting populations of European ancestry. Some observational studies suggest that particular diets reduce melanoma risk - putatively through an increase in polyunsaturated fatty acid (PUFA) consumption. However, interpretation of these observational findings is difficult due to residual confounding or reverse causality. To date, a randomised controlled trial has not been carried out to examine the relationship between PUFAs and melanoma. Hence, we performed a Mendelian randomisation (MR) study to evaluate the link between PUFAs and melanoma.

To perform MR we used summary results from the largest risk genome-wide association study (GWAS) meta-analysis of melanoma, consisting of 12,874 cases and 23,203 controls. As instrumental variables we selected SNPs associated with PUFA levels from a GWAS meta-analysis of PUFA levels, from the CHARGE consortium. We used the inverse variance weighted method to estimate a causal odds ratio. To aid interpretation, we established a benchmark "large" predicted change in PUFAs in which, for example, an increase in docosahexaenoic acid (DPA) of 0.17 units (equal to 1 standard deviation) moves a person from the 17^th percentile to the median.

Raising PUFA levels by a large amount (increasing DPA by 0.17 units) only negligibly changed melanoma risk - Odds Ratio [OR] = 1.03 (95% Confidence Interval [CI] = 0.96 - 1.10). Other PUFAs yielded similar results as DPA. Our MR analysis suggests that the effect of PUFA levels on melanoma risk is either zero or very small. This article is protected by copyright. All rights reserved.

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Tumor-associated auto-antibodies as early detection markers for ovarian cancer? A prospective evaluation

Abstract

Immuno-proteomic screening has identified several tumor-associated auto-antibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies.

We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53, and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited. This article is protected by copyright. All rights reserved.

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Systematic Complex Haploinsufficiency-Based Genetic Analysis of Candida albicans Transcription Factors: Tools and Applications to Virulence-Associated Phenotypes

Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen Candida albicans, genetic interaction analysis has been limited to a small number of large-scale screens and a handful for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain containing two heterozygous mutations at distinct loci shows a phenotype that is distinct from either of the corresponding single heterozygous mutants, is an expedient approach to genetic interactions analysis in diploid organisms. Here, we describe the construction of a barcoded-library of 133 heterozygous TF deletion mutants and deletion cassettes for designed to facilitate complex haploinsufficiency-based genetic interaction studies of the TF networks in C. albicans. We have characterized the phenotypes of these heterozygous mutants under a broad range of in vitro conditions using both agar-plate and pooled signature tag-based assays. Consistent with previous studies, haploinsufficiency is relative uncommon. In contrast, a set of 12 TFs enriched in mutants with a role in adhesion were found to have altered competitive fitness at early time points in a murine model of disseminated candidiasis. Finally, we characterized the genetic interactions of a set of biofilm related TFs in the first two steps of biofilm formation, adherence and filamentation of adherent cells. The genetic interaction networks at each stage of biofilm formation are significantly different indicating that the network is not static but dynamic.

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Photosensitive Alternative Splicing of the Circadian Clock Gene timeless Is Population Specific in a Cold-Adapted Fly, Drosophila montana

To function properly, organisms must adjust their physiology, behavior and metabolism in response to a suite of varying environmental conditions. One of the central regulators of these changes is organisms' internal circadian clock, and recent evidence has suggested that the clock genes are also important in the regulation of seasonal adjustments. In particular, thermosensitive splicing of the core clock gene timeless in a cosmopolitan fly, Drosophila melanogaster, has implicated this gene to be involved in thermal adaptation. To further investigate this link we examined the splicing of timeless in a northern malt fly species, Drosophila montana, which can withstand much colder climatic conditions than its southern relative. We studied northern and southern populations from two different continents (North America and Europe) to find out whether and how the splicing of this gene varies in response to different temperatures and day lengths. Interestingly, we found that the expression of timeless splice variants was sensitive to differences in light conditions, and while the flies of all study populations showed a change in the usage of splice variants in constant light compared to LD 22:2, the direction of the shift varied between populations. Overall, our findings suggest that the splicing of timeless in northern Drosophila montana flies is photosensitive, rather than thermosensitive and highlights the value of studying multiple species and populations in order to gain perspective on the generality of gene function changes in different kinds of environmental conditions.

http://ift.tt/2HGBA9N

A Genome-Wide Association Study for Host Resistance to Ostreid Herpesvirus in Pacific Oysters (Crassostrea gigas)

Ostreid herpesvirus (OsHV) can cause mass mortality events in Pacific oyster aquaculture. While various factors impact on the severity of outbreaks, it is clear that genetic resistance of the host is an important determinant of mortality levels. This raises the possibility of selective breeding strategies to improve the genetic resistance of farmed oyster stocks, thereby contributing to disease control. Traditional selective breeding can be augmented by use of genetic markers, either via marker-assisted or genomic selection. The aim of the current study was to investigate the genetic architecture of resistance to OsHV in Pacific oyster, to identify genomic regions containing putative resistance genes, and to inform the use of genomics to enhance efforts to breed for resistance. To achieve this, a population of ~1,000 juvenile oysters were experimentally challenged with a virulent form of OsHV, with samples taken from mortalities and survivors for genotyping and qPCR measurement of viral load. The samples were genotyped using a recently-developed SNP array, and the genotype data were used to reconstruct the pedigree. Using these pedigree and genotype data, the first high density linkage map was constructed for Pacific oyster, containing 20,353 SNPs mapped to the ten pairs of chromosomes. Genetic parameters for resistance to OsHV were estimated, indicating a significant but low heritability for the binary trait of survival and also for viral load measures (h2 0.12 - 0.25). A genome-wide association study highlighted a region of linkage group 6 containing a significant QTL affecting host resistance. These results are an important step towards identification of genes underlying resistance to OsHV in oyster, and a step towards applying genomic data to enhance selective breeding for disease resistance in oyster aquaculture.

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EQUATOR-Oncology: reducing the latitude of cancer trial design and reporting

http://ift.tt/2EN13wD

Reporting guidelines for oncology research: helping to maximise the impact of your research

http://ift.tt/2FpGbMI

Progression of corticospinal tract dysfunction in pre-ataxic spinocerebellar ataxia type 2: a two-years follow-up TMS study

Spinocerebellar ataxia type 2 (SCA2) is a severe and progressive autosomal dominant cerebellar ataxia caused by a dynamic mutation in the ATXN2 gene, consisting of an abnormal expansion of cytosine-adenine-guanine (CAG) triplets in the first codon of the gene, and leading to expression of long polyglutamine (PolyQ) stretches in the ataxin-2 protein (Auburger, 2012; Pulst et al., 1996). This protein seems to have global effects on mRNA metabolism, as well as on endocytosis, calcium signaling and control of metabolism and energy balance.

http://ift.tt/2GCFD5O

Value of ictal and interictal epileptiform discharges and high frequency oscillations for delineating the epileptogenic zone in patients with focal cortical dysplasia

Focal Cortical Dysplasia (FCD) is one of the most common etiology of medically intractable seizures in adults (Kabat and Król, 2012). Patients with this type of lesion often have drug-resistant epilepsy and become candidate for a surgical treatment. The area responsible to generate seizure, or the Epileptogenic Zone (EZ), however may be difficult to define, even in patients with identifiable lesions on MRI. Non-congruent semiology, scalp EEG and imaging findings often indicate poor localization of the EZ, and invasive EEG studies may help to define the EZ in patients with FCDs (Chassoux et al., 2000).

http://ift.tt/2HGnvZZ

Adherence to colorectal cancer screening measured as the proportion of time covered

Colorectal cancer (CRC) screening can reduce CRC incidence and mortality, but measuring screening adherence over time is challenging. We examined adherence using a novel measure characterizing the proportion of time covered (PTC) by screening tests.

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Identification of volumetric laser endomicroscopy features of colon polyps with histologic correlation

There is limited data on the use of volumetric laser endomicroscopy (VLE) in imaging for colon polyps. Our aim was to identify VLE features of colon polyps.

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Implementation of Medical Assistance in Dying (MAiD): A Scoping Review of Health Care Providers’ Perspectives

With the growing interest in Medical Assistance in Dying (MAiD), understanding health care professionals' roles and experiences in handling requests is necessary to evaluate the quality, consistency and efficacy of current practices. This scoping study sought to map the existing literature on health care providers' perspectives of their involvement in MAiD.

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Demonstration of safety and feasibility of hydrogel marking of the pancreas-duodenum interface for image-guided radiation therapy (IGRT) in a porcine model: Implications in IGRT for pancreatic cancer patients

This study presents the feasibility and safety of marking the pancreas and duodenum interface with a high-contrast hydrogel and demonstrates acceptable visibility of the marked location on cone beam computed tomography using a porcine model. Translation of this technique to the radiotherapy treatment of pancreatic cancer patients would enable on-board visualization of this important boundary between the radiation target and the dose-limiting duodenum, facilitating future efforts towards safe dose-escalation.

http://ift.tt/2CdWBcC

A Phase II Study of Stereotactic Body Radiotherapy and Stereotactic Body Proton Therapy for High-Risk Medically Inoperable Early-Stage Non-Small Cell Lung Cancer

A phase II randomized study to compare SBRT vs. SBPT was terminated early due to poor accrual; treatment outcomes after SBPT appeared no worse than those after SBRT numerically with low treatment related toxicity in both groups. Lack of volumetric imaging and insurance coverage for patients treated with SBPT were the major barriers to accrual. In addition to financial issues, similar maturity of treatment planning and imaged-guided delivery are essential for future comparison studies between proton and photon therapy.

http://ift.tt/2BL65en

Impact of Widespread Cervical Cancer Screening: Number of Cancers Prevented and Changes in Race-specific Incidence

Objectives: With recent approval of standalone HPV testing and increasing uptake of HPV vaccination, some have postulated that we are moving toward a "post-Pap" era of cervical cancer prevention. However, the total number cases that have been prevented by Pap smear screening as well as its impact on racial disparities are unknown. Methods: We estimated national cervical cancer incidence from 1976 to 2009 using the Surveillance, Epidemiology, and End Result database. Screening data were obtained from the literature and National Cancer Institute Progress Reports. We examined early, late, and race-specific trends in cancer incidence, and calculated the estimated number of cancers prevented over the past 3 decades. Results: From 1976 to 2009, there was a significant decrease in the incidence of early-stage cervical cancer, from 9.8 to 4.9 cases per 100,000 women (P

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Induction Therapies Plus Surgery Versus Exclusive Radiochemotherapy in Stage IIIA/N2 Non–Small Cell Lung Cancer (NSCLC)

In spite of the growing body of data from prospective randomized clinical trials (PRCTs) and meta-analyses, the optimal treatment approach in patients with stage IIIA non–small cell lung cancer remains unknown. This review focuses on the available data directly confronting induction chemotherapy or induction radiochemotherapy (RT-CHT) when followed by surgery with exclusive RT-CHT. Seven PRCTs and 4 meta-analyses investigated this issue. In addition, numerous retrospective studies attempted to identify potential predictors and/or prognosticators that may have influenced the decision to offer surgery in a particular patient subgroup. Several retrospective studies also evaluated exclusive RT-CHT in this setting. There is not a single piece of the highest level of evidence (PRCT or MA) showing any advantage of induction therapies followed by surgery over exclusive RT-CHT with the former treatment option leading to significantly more morbidity and mortality. Although several studies attempted to identify patient subgroups favoring induction therapies followed by surgery, they have invariably been retrospective in nature, and their results have never been reproduced even in other retrospective setting. Furthermore, no PRCT investigated potential pretreatment patient and/or tumor-related predictors of surgical multimodality success. Exclusive RT-CHT achieves similar results to induction therapies followed by surgery but with less morbidity and mortality. This is accompanied with the finding that no pretreatment predictor exists to enable identification of even a subgroup of stage IIIA/pN2 patients benefiting from any surgical approach.

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Early Results From the Implementation of a Lung Cancer Screening Program: The Beaumont Health System Experience

Purpose: In 2010, a new study published by the National Lung Screening Trial showed a 20% reduction in mortality for those patients screened with low-dose computed topography (CT) versus x-ray. Recently, the Centers of Medicare and Medicaid have agreed to cover this service for those patients who meet the screening criteria. We compare the outcomes and costs associated with developing and implementing a lung cancer screening program. Materials and Methods: One thousand sixty-five patients were screened from January 2014 to December 2014. These patients were screened on a low-dose CT screening protocol throughout Beaumont Health System. The American College of Radiology Lung Imaging Reporting and Data System (Lung-RADS) were used to assign the score for each patient. Screening eligibility criteria were based on the National Comprehensive Cancer Network guidelines. Downstream activity and revenue was determined after initial low-dose CT screening. Results: At 1 year, 20 patients (1.6%) were diagnosed with lung cancer and another 15 patients were diagnosed with another form of cancer after screening. The median age, packs per day, and pack years smoked for all patients was 63, 1.0, and 39.0 years, respectively. Lung-RADS scores for all patients was 18% (1), 24.1% (2), 6.3% (3), and 5.4% (4). The net revenue for all activity after screening was $3.2 million. Conclusions: The establishment of a low-dose CT lung cancer screening program improved the ability to screen patients as demonstrated by the number of patients screened and those diagnosed with a malignancy. These findings were also consistent with the findings from the National Lung Screening Trial study.

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