Self-Assembly of an Amphiphilic Janus Camptothecin–Floxuridine Conjugate into Liposome-Like Nanocapsules for More Efficacious Combination Chemotherapy in Cancer

The combination of camptothecin (CPT) and fluoropyrimidine derivatives acts synergistically at a 1:1 molar ratio. Practically, the greatest challenge is the development of a single liposomal formulation that can both encapsulate and maintain this drug combination at an exact 1:1 ratio to achieve coordinated pharmacokinetics. Consequently, a new type of liposome-like nanocapsule (NC) is developed from a highly symmetric Janus camptothecin–floxuridine conjugate (JCFC) amphiphile, which is synthesized by coupling two hydrophobic CPT molecules and two hydrophilic floxuridine (FUDR) molecules to multivalent pentaerythritol via a hydrolyzable ester linkage. JCFC NCs possess remarkably high drug-loading contents, and no premature release because of the highly stable co-delivery of the drug combination without the need for any carrier. It is shown that JCFC NCs consistently provide synergy and avoid antagonism in a broad panel of tumor cell lines. In vivo delivery of JCFC NCs leads to longer blood retention half-life, higher tumorous accumulation and cellular uptake of drugs, and greatly enhanced efficacy in murine tumor models compared to CPT, FUDR, and CPT + FUDR. This liposomal strategy can be extended to other hydrophilic and hydrophobic anticancer drugs that are coupled to pentaerythritol to self-assemble into nanocapsules for drug self-delivery, pointing to potential clinical translation in near future.

Novel liposome-like nanocapsules (NCs) are successfully developed from a highly symmetric Janus camptothecin–floxuridine conjugate (JCFC) amphiphile. JCFC NCs can deliver and preserve a fixed 1:1 molar ratio of the two drugs in a liposomal manner that can suppress premature burst release and coordinate the pharmacokinetics of different drugs after administration, thus resulting in higher apoptotic rate and synergetic anticancer activity.

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Stable Li Metal Anodes via Regulating Lithium Plating/Stripping in Vertically Aligned Microchannels

Li anodes have been rapidly developed in recent years owing to the rising demand for higher-energy-density batteries. However, the safety issues induced by dendrites hinder the practical applications of Li anodes. Here, Li metal anodes stabilized by regulating lithium plating/stripping in vertically aligned microchannels are reported. The current density distribution and morphology evolution of the Li deposits on porous Cu current collectors are systematically analyzed. Based on simulations in COMSOL Multiphysics, the tip effect leads to preferential deposition on the microchannel walls, thus taking full advantage of the lightening rod theory of classical electromagnetism for restraining growth of Li dendrites. The Li anode with a porous Cu current collector achieves an enhanced cycle stability and a higher average Coulombic efficiency of 98.5% within 200 cycles. In addition, the resultant LiFePO₄/Li full battery demonstrates excellent rate capability and stable cycling performance, thus demonstrating promise as a current collector for high-energy-density, safe rechargeable Li batteries.

A new strategy to restrain lithium dendrite growth is proposed and demonstrated using vertically aligned microchannel Cu current collectors for Li metal anodes. Most of the lithium is preferentially deposited into the microchannels. The current-density distribution, deposition behavior, and electrochemical performance are simulated and investigated experimentally to understand the effectiveness of the microchannel structure.

http://ift.tt/2xYJxT3

Tailoring Semiconductor Lateral Multijunctions for Giant Photoconductivity Enhancement

Semiconductor heterostructures have played a critical role as the enabler for new science and technology. The emergence of transition-metal dichalcogenides (TMDs) as atomically thin semiconductors has opened new frontiers in semiconductor heterostructures either by stacking different TMDs to form vertical heterojunctions or by stitching them laterally to form lateral heterojunctions via direct growth. In conventional semiconductor heterostructures, the design of multijunctions is critical to achieve carrier confinement. Analogously, successful synthesis of a monolayer WS₂/WS_2(1−x)Se_2x/WS₂ multijunction lateral heterostructure via direct growth by chemical vapor deposition is reported. The grown structures are characterized by Raman, photoluminescence, and annular dark-field scanning transmission electron microscopy to determine their lateral compositional profile. More importantly, using microwave impedance microscopy, it is demonstrated that the local photoconductivity in the alloy region can be tailored and enhanced by two orders of magnitude over pure WS₂. Finite element analysis confirms that this effect is due to the carrier diffusion and confinement into the alloy region. This work exemplifies the technological potential of atomically thin lateral heterostructures in optoelectronic applications.

The successful synthesis of a monolayer lateral heterostructure with multijunctions WS₂/WS_2(1−x)Se_2x/WS₂ (x ≈ 0.15) by chemical vapor deposition is reported. The grown structures are characterized by Raman and photoluminescence. Using light-assisted microwave impedance microscopy, the multijunctions demonstrate that the local photoconductivity in the alloy region can be tailored and enhanced by two orders of magnitude over pure WS₂.

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Gemcitabine and docetaxel in a patient with primary ovarian leiomyosarcoma: a case report and review of literature

Abstract

Primary ovarian leiomyosarcoma (POLMS) is extremely rare, and optimal therapy for this disease is unknown. A 40-year-old woman presented at a local hospital with abdominal pain. Tumor resection of the left ovary was performed. The pathological diagnosis was leiomyoma of the left ovary. Nine months after surgery, she developed of severe back pain and a subcutaneous tumor on her left shoulder. Magnetic resonance imaging and computed tomography revealed left ovarian tumor recurrence, pelvic bone metastasis, and multiple liver masses. Biopsy of the subcutaneous tumor on her left shoulder demonstrated metastatic leiomyosarcoma. The previously resected left ovarian tumor was re-examined, and the tumor was found to be a leiomyosarcoma. The patient received gemcitabine 800 mg/m² and docetaxel 60 mg/m² (GD therapy), administered at 3-week intervals. After three cycles of GD therapy, the patient experienced dyspnea and was diagnosed with mild interstitial pneumonia. Oral corticosteroid therapy resulted in complete symptom improvement. Thereafter, the dosage of GD was decreased, and after 13 cycles of GD therapy, radiofrequency ablation was performed twice for liver metastases. The tumors have shrunk by 65.5% after 23 cycles of GD. She remains alive after undergoing 24 cycles of GD. GD therapy may be effective for POLMS.

http://ift.tt/2wUi8Tw

On faculty development of STEM inclusive teaching practices

Abstract

Faculty development of inclusive teaching practices has become more common in response to significant differences in STEM student retention between underrepresented minorities in the USA and students from other ethnic groups. Approaches to solve this have shifted from focusing on student deficits to changing campus culture, including the mindsets of instructors who teach STEM courses. In this article, I argue that based on the literature informing the conceptual frameworks used for faculty development in inclusive teaching, faculty developers should reframe the message of their workshops to focus participants more on the scope of the journey, and shift the direction of overall efforts some to redevelop pedagogical training at the graduate and postdoc levels. Informed by historical as well as recent theories on the role of higher education to society, I highlight the areas of the literature that can effectively inform our current approaches to inclusion. I also briefly review the reasons why this approach is needed, and include suggestions for new faculty development approaches for long-term sustainable change in STEM inclusive education at the postsecondary level.

http://ift.tt/2xURN5t

Interactive problem-solving sessions in an introductory bioscience course engaged students and gave them feedback, but did not increase their exam scores

Abstract

Active learning, including the promotion of student interactivity in lectures, has been found to improve student engagement and performance in university science classes. This letter describes the use of Pearson's Learning Catalytics to run regular, formatively assessed problem-solving sessions as part of the semiflipped redesign of an introductory level university bioscience course. Students found the problem-solving sessions more engaging than a traditional lecture, and felt that they were receiving better feedback on their progress in the course. Their participation in the problem-solving sessions was strongly associated with their performance in the course's summative assessments, making it possible to identify and assist probable poor performers early in the course. Other measures of student engagement with the course were not improved, and neither were their average exam grades when compared with their grades in a course which had not been redesigned. Possible reasons for this are discussed.

http://ift.tt/2v2xn9M

Quantification of Agrobacterium tumefaciens C58 attachment to Arabidopsis thaliana roots

Abstract

Agrobacterium tumefaciens is the causal agent of crown gall disease and is a vector for DNA transfer in transgenic plants. The transformation process by A. tumefaciens has been widely studied, but the attachment stage has not been well characterized. Most measurements of attachment have used microscopy and colony counting, both of which are labor and time intensive. To reduce the time and effort required to analyze bacteria attaching to plant tissues, we developed a quantitative real-time PCR (qPCR) assay to quantify attached A. tumefaciens using the chvE gene as marker for the presence of the bacteria. The qPCR detection threshold of A. tumefaciens from pure culture was 10⁴ cell equivalents/ml. The A. tumefaciens minimum threshold concentration from root-bound populations was determined to be 10⁵ cell equivalents/ml inoculum to detect attachment above background. The qPCR assay can be used for measuring A. tumefaciens attachment in applications such as testing the effects of mutations on bacterial adhesion molecules or biofilm formation, comparing attachment across various plant species and ecotypes, and detecting mutations in putative attachment receptors expressed in plant roots.

http://ift.tt/2w3pHIv

First description of a new uncultured epsilon sulfur bacterium colonizing marine mangrove sediment in the Caribbean: Thiovulum sp. strain karukerense

Abstract

Here, the first description is reported of an epsilon sulfur-oxidizing bacterium from sulfide-rich sediments of marine mangrove in the Caribbean. By transition electron microscopy it was shown that this new strain contains intracytoplasmic large internal sulfur granules, which was confirmed by energy-dispersive X-ray spectroscopy analyses performed using an environmental scanning electron microscope. The sulfur distribution obtained for this sulfur-oxidizing bacterial strain allowed us to conclude that elemental sulfur is formed as an intermediate oxidation product and stored intracellularly. By conventional scanning electron microscopy it was shown that the bacterial cells are ovoid and extremely motile by lophotrichous flagella. Phylogenetic analyses based on partial sequence of the 16S rRNA gene confirmed that the bacterial strain belongs to the Thiovulum cluster and could be a representative of a new species in this poorly studied genus of sulfur-oxidizing free-living bacteria. Thus, reduced sediment of marine mangrove represents a sulfide-rich environment sustaining development of both gamma and epsilon sulfur-oxidizing Proteobacteria.

http://ift.tt/2uus9T9

Comparative genomics of a drug-resistant Pseudomonas aeruginosa panel and the challenges of antimicrobial resistance prediction from genomes

Abstract

Antimicrobial resistance (AMR) is now recognized as a global threat to human health. The accessibility of microbial whole-genome sequencing offers an invaluable opportunity for resistance surveillance via the resistome, i.e. the genes and mutations underlying AMR. Unfortunately, AMR prediction from genomic data remains extremely challenging, especially for species with a large pan-genome. One such organism, for which multidrug-resistant (MDR) isolates are frequently encountered in the clinic, is Pseudomonas aeruginosa. This study focuses on a commercially available panel of seven MDR P. aeruginosa strains. The main goals were to sequence and compare these strains' genomes, attempt to predict AMR from whole genomes using two different methods and determine whether this panel could be an informative complement to the international P. aeruginosa reference panel. As expected, the results highlight the complexity of associating genotype and AMR phenotype in P. aeruginosa, mainly due to the intricate regulation of resistance mechanisms. Our results also urge caution in the interpretation of predicted resistomes regarding the occurrence of gene identity discrepancies between strains. We envision that, in addition to accounting for the genomic diversity of P. aeruginosa, future development of predictive tools will need to incorporate a transcriptomic, proteomic and/or metabolomic component.

http://ift.tt/2tSiXfI

Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis

Abstract

Purpose

Though advanced and metastatic epidermal growth factor receptor 2 (HER2)-positive disease is not curable, a small proportion of patients with HER2-positive metastatic breast cancer remain in prolonged complete remission with anti-HER2 treatment. We hypothesized that some cases of HER2-positive metastatic breast cancer may be curable. In this large, multicenter retrospective study, we aimed to assess the long-term outcomes for patients with a durable response to trastuzumab.

Methods

We retrospectively evaluated the data of patients diagnosed with HER2-positive metastatic breast cancer who received trastuzumab for more than 2 years as the first-line treatment. Patients diagnosed between April 1, 2001 and December 31, 2014 at 19 institutions in Japan were included in the analysis. From 124 potential subjects, 16 were excluded and 108 were evaluated.

Results

The median follow-up length was 7.7 years. Disease progression occurred in 44/108 (40.7%) patients and 13/108 (12%) patients died. The median progression-free survival was 11.2 years, and as more than 80% of patients were alive 10 years after metastatic breast cancer diagnosis. Of the 108 patients, 57 achieved a clinical complete response. Trastuzumab therapy was interrupted for 27 (47.4%) of these patients (based on the doctor's recommendation for 19 patients, owing to adverse events for 4 patients, owing to unknown reasons for 3 patients, and at the request of 1 patient). Disease progression occurred in 4 of the 27 patients after the interruption of trastuzumab treatment. The median duration of trastuzumab therapy for all 27 patients was 5.1 years (0.9–9.3 years).

Conclusion

We found that some patients showed no evidence of disease after the interruption of trastuzumab therapy. Discontinuation of maintenance trastuzumab in this patient population after a limited time should be explored cautiously while awaiting a global collaborative effort for a randomized trial.

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Doctors should buckle up for health reforms: Barrette [News]

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The quadruple burden of sepsis [Commentary]

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Sepsis, one of CMAJs four new areas of focus [Editorial]

http://ift.tt/2vYF6KB

Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial [Research]

BACKGROUND:

Intravenous zoledronate 5 mg annually reduces fracture risk, and 5 mg every 2 years prevents bone loss, but the optimal dosing regimens for these indications are uncertain.

METHODS:

We conducted a 3-year open-label extension of a 2-year randomized, placebo-controlled, double-blind study. Late postmenopausal women with osteopenia were assigned to receive a single baseline dose of 1 mg, 2.5 mg or 5 mg of zoledronate or placebo. The primary outcome was change in spine bone mineral density (BMD). Secondary outcomes were changes in hip BMD and serum markers of bone turnover.

RESULTS:

The study involved 160 women. Zoledronate increased BMD and reduced markers of bone turnover in a dose-dependent manner. After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased spine BMD over placebo by 5.0% (95% confidence interval [CI] 3.0% to 7.0%), 5.7% (95% CI 3.7% to 7.7%) and 5.7% (95% CI 3.7% to 7.6%), respectively; after 5 years, the respective increases were 2.0% (95% CI –1.1% to 5.0%), 2.2% (95% CI –1.0% to 5.4%) and 5.1% (95% CI 2.2% to 8.1%). After 2 years, the 1-mg, 2.5-mg and 5-mg zoledronate doses increased total hip BMD over placebo by 2.6% (95% CI 1.3% to 3.9%), 4.1% (95% CI 2.9% to 5.4%) and 4.7% (95% CI 3.4% to 5.9%), respectively; after 5 years, the respective increases were 1.8% (95% CI –0.1% to 3.8%), 2.8% (95% CI 0.8% to 4.8%) and 5.4% (95% CI 3.5% to 7.3%). BMD remained above baseline values for 2–3 years in the 1-mg group, 3–4 years in the 2.5-mg group and at least 5 years in the 5-mg group.

INTERPRETATION:

The antiresorptive activity of single zoledronate doses of 1–5 mg persist for at least 3 years in postmenopausal women with osteopenia. Clinical trials would be justified to evaluate the effects on fracture risk of less frequent or lower doses of zoledronate than are currently recommended.

Trial registration:

www.anzctr.org.au, no. ACTRN12607000576426

http://ift.tt/2vZ0bnZ

Health leaders must share the reins of reform: outgoing CMA pres [News]

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Recommendations on screening for abdominal aortic aneurysm in primary care [Guideline]

http://ift.tt/2jgymBR

Physicians debate tax reforms at CMA annual meeting [News]

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Superimposed lateralized exanthem in a 30-year-old woman [Practice]

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Lively debate on disability insurance for medical students at CMA meeting [News]

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Physicians and regionalization in Canada: past, present and future [Humanities]

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Physicians support assisted death for mature minors, but not mental illness [News]

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Canadian hepatitis C virus screening guideline: a disconnect between evidence and recommendations [Letters]

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Doctors and health funding must focus on most vulnerable: Philpott [News]

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Extrapolation warning [Letters]

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Doctors dissect medicines bullying problem [News]

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How physicians can "flex their advocacy muscles" [News]

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Focus on patients, the rest will follow, says new CMA pres [News]

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CMA votes for review of medical liability system [News]

http://ift.tt/2jfezT8

Healthier doctors means healthier patients: CMA president-elect [News]

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Harm reduction is about providing safety for patients [News]

http://ift.tt/2vZ07Vh

Tuberculous cervicitis: A brief report with cytohistological correlation and differential diagnosis

http://ift.tt/2wTSWNd

IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity

Amino-acid catabolizing enzymes produced by mononuclear phagocytes play a central role in regulating the immune response. The mammalian phenylalanine-catabolizing enzyme IL4-induced gene 1 (IL4I1) inhibits effector T lymphocyte proliferation and facilitates regulatory T-cell development. IL4I1 expression by macrophages of various human tumors may affect patient prognosis as it facilitates tumor escape from the T-cell response in murine models. Its enzymatic activity appears to participate in its effects, but some actions of IL4I1 remain unclear. Here, we show that the presence of IL4I1 during T-cell activation decreases early signaling events downstream of TCR stimulation, resulting in global T-cell inhibition which is more pronounced when there is CD28 costimulation. Surprisingly, the enzymatic activity of IL4I1 is not involved. Focal secretion of IL4I1 into the immune synaptic cleft and its binding to CD3⁺ lymphocytes could be important in IL4I1 immunosuppressive mechanism of action.

This article is protected by copyright. All rights reserved

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Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

Ipilimumab (Yervoy, Bristol-Myers Squibb), a human IgG1 monoclonal antibody against cytotoxic T-lymphocyte antigen 4, and nivolumab (Opdivo, Bristol-Myers Squibb), a human IgG4 monoclonal antibody against programmed death 1 (PD-1), are approved for monotherapy and combination therapy in several…

http://ift.tt/2jgGFNV

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma

The incidence of cutaneous melanoma has continued to increase in recent years. For early-stage melanoma, surgical resection is the standard treatment and is associated with an excellent long-term prognosis, with 5-year survival rates of 98% for stage I disease and 90% for stage II disease. However,…

http://ift.tt/2eYhcY8

Genetic variation in the Vitamin D related pathway and breast cancer risk in women of African ancestry in the Root Consortium

Abstract

The vitamin D related pathway has been evaluated in carcinogenesis but its genetic contribution remains poorly understood. We examined single-nucleotide polymorphisms (SNPs) in the vitamin D related pathway genes using data from a genome-wide association study (GWAS) of breast cancer in the African Diaspora that included 3,686 participants (1,657 cases). Pathway- and gene-level analyses were conducted using the adaptive rank truncated product test. Odds ratios (OR) and 95% confidence intervals (CI) were estimated at SNP-level. After stringent Bonferroni corrections, we observed no significant association between variants in the vitamin D pathway and breast cancer risk at the pathway-, gene-, or SNP-level. In addition, no association was found for either the reported signals from GWASs of vitamin D related traits, or the SNPs within vitamin D receptor (VDR) binding regions. Furthermore, a decrease in genetically predicted 25(OH)D levels by Mendelian randomization was not associated with breast cancer (P = 0.23). However, an association for breast cancer with the pigment synthesis/metabolism pathway almost approached significance (pathway-level P = 0.08), driven primarily by a nonsense SNP rs41302073 in TYRP1, with an OR of 1.54 (95% CI = 1.24-1.91, P_adj = 0.007). In conclusion, we found no evidence to support an association between vitamin D status and breast cancer risk in women of African ancestry, suggesting that vitamin D is unlikely to have significant effect on breast carcinogenesis. Interestingly, TYRP1 might be related to breast cancer through a non-vitamin D relevant mechanism but further studies are needed. This article is protected by copyright. All rights reserved.

http://ift.tt/2xp8bPD

Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma

Abstract

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re-evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re-review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N=44); UPS(N=18); and Others (N=27; including undifferentiated spindle cell sarcoma (N=15) and dedifferentiated liposarcoma (N=6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N=88) showed a median age of 66 years (32-95), primarily with stage I-III disease (92%) and high grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations=36: solitary mutation(n=27); two mutations(n=3); three mutations(n=1)). The most commonly identified mutations were in TP53 (n=24), ATM (n=3) and PIK3CA (n=2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response, however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, this data does not support the routine use of targeted NGS panels outside of research protocols in UPS. This article is protected by copyright. All rights reserved.

http://ift.tt/2gW8HtL

Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer

Abstract

NF1 mutations predispose to neurofibromatosis type1 (NF1) and women with NF1 have a moderately elevated risk for breast cancer, especially under age 50. Germline genomic analysis may better define the risk so screening and prevention can be applied to the individuals who benefit the most. Survey conducted in several neurofibromatosis clinics in the United States has demonstrated a 17.2% lifetime risk of breast cancer in women affected with NF1. Cumulated risk to age 50 is estimated to be 9.27%. For genomic profiling, fourteen women with NF1 and a history of breast cancer were recruited and underwent whole exon sequencing (WES), targeted genomic DNA based and RNA based analysis of the NF1 gene. Deleterious NF1 pathogenic variants were identified in each woman. Frameshift mutations due to deletion/duplication/complex rearrangement were found in 50% (7/14) of the cases, nonsense mutations in 21% (3/14), in-frame splice mutations in 21% (3/14), and one case of missense mutation (7%, 1/14). No deleterious mutation was found in the following high/moderate penetrance breast cancer genes: ATM, BRCA1, BRCA2, BARD1, BRIP1, CDH1, CHEK2, FANCC, MRE11A, NBN, NF1, PALB2, PTEN, RAD50, RAD51C, TP53, and STK11. Twenty-five rare or common variants in cancer related genes were discovered and may have contributed to the breast cancers in these individuals. Breast cancer predisposition modifiers in women with NF1 may involve a great variety of molecular and cellular functions. This article is protected by copyright. All rights reserved.

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Issue Information

http://ift.tt/2vOEV08

Procedure and Key Optimization Strategies for an Automated Capillary Electrophoretic-based Immunoassay Method

A capillary-based immunoassay using a commercial platform to measure target proteins from total protein preparations is demonstrated. In addition, assay parameters of exposure time, protein concentration, and antibody dilution are optimized for a cell culture model system.

http://ift.tt/2gWnx77

Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs

The current protocol combines single cell paired human TCR alpha and beta chain sequencing with streamlined generation of retroviral vectors compatible with in vitro and in vivo TCR expression.

http://ift.tt/2vOyom6

Issue Information

http://ift.tt/2fbAFl4

Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections

The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

http://ift.tt/2eXQW01

Sodium-DNA for Bone Tissue Regeneration: An Experimental Study in Rat Calvaria

Surgical techniques in dental and maxillofacial surgery request fast bone tissue regeneration, so there is a significant need to improve therapy for bone regeneration. Several studies have recently underlined the importance of nucleotides and nucleosides to increase cell proliferation and activity; in particular, the ability of polydeoxyribonucleotide (PDRN) to induce growth and activity of human osteoblasts was demonstrated. Sodium-DNA is the deoxyribonucleic acid (DNA) extracted from the gonadic tissue of male sturgeon and then purified, depolymerized, and neutralized with sodium hydroxide. To date, there are no evidences about the use of Sodium-DNA for bone tissue regeneration. Consequently, our question is about the efficacy of Sodium-DNA in bone healing. For testing the role of Sodium-DNA in bone healing we used a rat calvarial defect model. Sodium-DNA at different concentrations used alone or in association with Fibrin and/or Bio-Oss was used for healing treatments and the bone healing process was evaluated by histomorphometric and immunohistochemical analyses. Our results suggested a positive effect of Sodium-DNA in bone regeneration, providing a useful protocol and a model for the future clinical evaluation of its osteogenic properties.

http://ift.tt/2vY36NV

Evaluation of Antioxidant Potentials and α-Amylase Inhibition of Different Fractions of Labiatae Plants Extracts: As a Model of Antidiabetic Compounds Properties

In an attempt to identify herbal drugs which may become useful in the prevention of diabetes, antioxidant potentials and α-amylase inhibition by the ethanol extracts of two plants belonging to Lamiaceae family, Otostegia persica and Zataria multiflora, and their different fractions were studied. Also, inhibition of α-amylase by Salvia mirzayanii and its fractions was evaluated. All of the samples exhibited antioxidant activities, among which ethyl acetate fraction of Zataria multiflora ( mg GAE/g) was found to contain the highest amounts of phenols and the ethyl acetate fraction of Zataria multiflora (218 ± 2.76 mg QUE/g) had the most values of flavonoids. Ethyl acetate fraction of Zataria multiflora (IC50 =  μg/ml) was shown to have the most reducing power and the ethyl acetate fraction of Zataria multiflora (IC50 =  μg/ml) exhibited the highest DPPH radical scavenging. The ethyl acetate fraction of Otostegia persica (%) showed the highest α-amylase inhibitory activity which was similar to acarbose used as a standard. Mode of α-amylase inhibition of the most samples was uncompetitive except for ZMC, OPP, OPC, and SMP which presented competitive inhibition. The present findings showed that studied samples may have some compounds with antioxidant and antidiabetic effects.

http://ift.tt/2xXJYNj

Phage-Displayed Peptides Selected to Bind Envelope Glycoprotein Show Antiviral Activity against Dengue Virus Serotype 2

Dengue virus is a growing public health threat that affects hundreds of million peoples every year and leave huge economic and social damage. The virus is transmitted by mosquitoes and the incidence of the disease is increasing, among other causes, due to the geographical expansion of the vector's range and the lack of effectiveness in public health interventions in most prevalent countries. So far, no highly effective vaccine or antiviral has been developed for this virus. Here we employed phage display technology to identify peptides able to block the DENV2. A random peptide library presented in M13 phages was screened with recombinant dengue envelope and its fragment domain III. After four rounds of panning, several binding peptides were identified, synthesized, and tested against the virus. Three peptides were able to block the infectivity of the virus while not being toxic to the target cells. Blind docking simulations were done to investigate the possible mode of binding, showing that all peptides appear to bind domain III of the protein and may be mostly stabilized by hydrophobic interactions. These results are relevant to the development of novel therapeutics against this important virus.

http://ift.tt/2vNS0XC

A review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is an age-related malignant lymphoma, characterized by immune system-dysregulated symptoms. Recent sequencing studies have clarified the recurrent mutations in ras homology family member A (RHOA) and in genes encoding epigenetic regulators, tet methyl cytosine dioxygenase 2 (TET2), DNA methyl transferase 3 alpha (DNMT3A), and isocitrate dehydrogenase 2, mitochondrial (IDH2), as well as those related to the T-cell receptor signaling pathway in AITL. In this review, we will focus on how this genetic information has changed the understanding of the developmental process of AITL and will in future lead to individualized therapies for AITL patients.

This article is protected by copyright. All rights reserved.

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Mucinous adenocarcinoma with lepidic pattern and with K-RAS mutation in a newborn with antenatal diagnosis of congenital pulmonary airway malformation

Abstract

Olivier Stephanov: substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; drafting the article and revising it critically for important intellectual content; final approval of the version to be published.

Yohan Robert : substantial contributions to acquisition of data and analysis and interpretation of data; final approval of the version to be published.

Florence De Fraipont substantial contributions to acquisition of data, and analysis and interpretation of data; revising it critically for important intellectual content; final approval of the version to be published.

This article is protected by copyright. All rights reserved.

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The epithelioid, BAP1-negative and p16-positive phenotype predicts prolonged survival in pleural mesothelioma

Abstract

Aims

Mesothelioma is a relatively uncommon but highly malignant neoplasm. Most patients die of disease within one year of diagnosis, but some have prolonged survival. Prospective identification of these longer-term survivors may help guide treatment. We therefore sought to investigate the role of p16 immunohistochemistry (IHC) both alone and in combination with other markers as a potential predictor of prolonged survival in mesothelioma.

Methods and Results

P16 IHC was performed on unselected pleural mesotheliomas biopsied from 1991 to 2014. 153 of 208 (74%) cases were p16-negative which significantly correlated with poor overall survival in both univariate (median survival 7.6 v 13.6 months; p = 0.001) and multivariate analysis (HR 1.632; 95% CI 1.103-2.415; p = 0.014). Other independent factors associated with prolonged survival included loss of expression of BAP1, and epithelioid morphology.

We therefore further stratified patients based on these three independent prognostic variables and demonstrated an unusually prolonged survival in mesotheliomas which were epithelioid, BAP1 IHC negative and p16 IHC positive (12% of cases, median survival 31.7 months, p<0.0001).

Conclusions

In conclusion, p16 IHC is an independent prognostic biomarker in pleural mesothelioma. When used in combination with BAP1 IHC and morphological subtyping, which are also readily available in routine clinical care, patients with exceptionally prolonged survival can potentially be identified.

This article is protected by copyright. All rights reserved.

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Treating pediatric neuromuscular disorders: The future is now

Pediatric neuromuscular diseases encompass all disorders with onset in childhood and where the primary area of pathology is in the peripheral nervous system. These conditions are largely genetic in etiology, and only those with a genetic underpinning will be presented in this review. This includes disorders of the anterior horn cell (e.g., spinal muscular atrophy), peripheral nerve (e.g., Charcot–Marie–Tooth disease), the neuromuscular junction (e.g., congenital myasthenic syndrome), and the muscle (myopathies and muscular dystrophies). Historically, pediatric neuromuscular disorders have uniformly been considered to be without treatment possibilities and to have dire prognoses. This perception has gradually changed, starting in part with the discovery and widespread application of corticosteroids for Duchenne muscular dystrophy. At present, several exciting therapeutic avenues are under investigation for a range of conditions, offering the potential for significant improvements in patient morbidities and mortality and, in some cases, curative intervention. In this review, we will present the current state of treatment for the most common pediatric neuromuscular conditions, and detail the treatment strategies with the greatest potential for helping with these devastating diseases.

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Intrafamilial variability of the triphalangeal thumb phenotype in a Dutch population: Evidence for phenotypic progression over generations?

Triphalangeal thumbs (TPTs) are regularly caused by mutations in the ZRS in LMBR1. Phenotypic variability can be present in TPT-families. However, recent observations suggest an increased occurrence of severe phenotypes in the Dutch TPT-population. Therefore, the aim of this study is to investigate the progression of the clinical severity of TPT-phenotype through generations. Index patients from a Dutch TPT-population were identified. A 105C>G mutation in the ZRS has previously been confirmed in this population. Questionnaires regarding family occurrence and phenotypes were distributed. Subsequently, families were visited to validate the phenotype. Both occurrence and inheritance patterns of the TPT-phenotype were analyzed through multiple generations. One hundred seventy patients with TPT were identified from 11 families. When considering all 132 segregations (parent-to-child transmission), 54% of the segregations produced a stable phenotype, 38% produced a more severe phenotype while only 8% of the phenotype was less severe when compared to the affected parents. Overall, 71% of the index patients had a more severe phenotype compared to their great-grandparent. Although all family members share an identical mutation in the ZRS (105C>G), it does not explain the wide phenotypic range of anomalies. Our observational study provides better estimations for counseling and provides new insights in the long-range regulation of SHH by the ZRS-enhancer. In the current study, we provide evidence that the assumed variability in TPT-phenotype is not random, but in fact it is more likely that the expression becomes more severe in the next generation. Therefore, we observe a pattern that resembles phenotypic anticipation in TPT-families.

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RHEB1 insufficiency in aged male mice is associated with stress-induced seizures

Abstract

The mechanistic target of rapamycin (mTOR), a protein kinase, is a central regulator of mammalian metabolism and physiology. Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP-binding protein. Increased activation of mTORC1 pathway has been associated with developmental abnormalities, certain form of epilepsy (tuberous sclerosis), and cancer. Clinically, those mTOR-related disorders are treated with the mTOR inhibitor rapamycin and its rapalogs. Because the effects of chronic interference with mTOR signaling in the aged brain are yet unknown, we used a genetic strategy to interfere with mTORC1 signaling selectively by introducing mutations of Rheb1 into the mouse. We created conventional knockout (Rheb1 ^+/− ) and gene trap (Rheb1 ^Δ/+ ) mutant mouse lines. Rheb1-insufficient mice with different combinations of mutant alleles were monitored over a time span of 2 years. The mice did not show any behavioral/neurological changes during the first 18 months of age. However, after aging (> 18 months of age), both the Rheb1 ^+/− and Rheb1 ^{Δ /−} hybrid males developed rare stress-induced seizures, whereas Rheb1 ^+/− and Rheb1 ^{Δ /−} females and Rheb1 ^Δ/+ and Rheb1 ^Δ/Δ mice of both genders did not show any abnormality. Our findings suggest that chronic intervention with mTORC1 signaling in the aged brain might be associated with major adverse events.

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Coliform Bacteria for Bioremediation of Waste Hydrocarbons

Raw, domestic sewage of Kuwait City contained about 106 ml−1 colony forming units of Enterobacter hormaechei subsp. oharae (56.6%), Klebsiella spp. (36%), and Escherichia coli (7.4%), as characterized by their 16S rRNA-gene sequences. The isolated coliforms grew successfully on a mineral medium with crude oil vapor as a sole source of carbon and energy. Those strains also grew, albeit to different degrees, on individual -alkanes with carbon chains between C9 and C36 and on the individual aromatic hydrocarbons, toluene, naphthalene, phenanthrene, and biphenyl as sole sources of carbon and energy. These results imply that coliforms, like other hydrocarbonoclastic microorganisms, oxidize hydrocarbons to the corresponding alcohols and then to aldehydes and fatty acids which are biodegraded by β-oxidation to acetyl CoA. The latter is a well-known key intermediate in cell material and energy production. E. coli cells grown in the presence of -hexadecane (but not in its absence) exhibited typical intracellular hydrocarbon inclusions, as revealed by transmission electron microscopy. Raw sewage samples amended with crude oil, -hexadecane, or phenanthrene lost these hydrocarbons gradually with time. Meanwhile, the numbers of total and individual coliforms, particularly Enterobacter, increased. It was concluded that coliform bacteria in domestic sewage, probably in other environmental materials too, are effective hydrocarbon-biodegrading microorganisms.

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Mammary and Extramammary Paget’s Disease Presented Different Expression Pattern of Steroid Hormone Receptors

Background and Objectives. Paget's disease (PD) is a rare intraepithelial adenocarcinoma, which is composed of mammary (MPD) and extramammary Paget's disease (EMPD). Currently, the published literature contains scant data on expression pattern of steroid hormone receptors in MPD and EMPD. Methods. Expression of estrogen receptor (ER) and androgen receptor (AR) was evaluated in 88 MPD and 72 EMPD by using immunohistochemical staining and H-score method. Results. Positive expression of AR was significantly higher in EMPD (61.11%, 44/72) than in MPD (32.95%, 29/88) (), while ER expression was positive 19.44% (14/72) in EMPD and only 9.09% (8/88) in MPD (). ER-AR expression pattern was significantly different between MPD (3.41%, 3/88) and EMPD (16.67%, 12/72) (). No difference of AR () or ER () expression was identified between invasive (48.57%, 51/105 of AR, and 11.43%, 12/105 of ER) and noninvasive PD. In MPD, no difference of AR expression between MPD alone (7/18, 38.89%) and MPD with underling ductal carcinoma of breast (22/70, 31.43%) was identified (). In EMPD, expression of AR was 63.33% (38/60) in penoscrotal EMPD. Conclusion. Our current results indicate that MPD and EMPD presented different expression pattern of AR and ER and would help to further identify the molecular subtype of MPD and EMPD for adjuvant hormonal therapy, especially for patients with penoscrotal EMPD.

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Automatic Segmentation of Ultrasound Tomography Image

Ultrasound tomography (UST) image segmentation is fundamental in breast density estimation, medicine response analysis, and anatomical change quantification. Existing methods are time consuming and require massive manual interaction. To address these issues, an automatic algorithm based on GrabCut (AUGC) is proposed in this paper. The presented method designs automated GrabCut initialization for incomplete labeling and is sped up with multicore parallel programming. To verify performance, AUGC is applied to segment thirty-two in vivo UST volumetric images. The performance of AUGC is validated with breast overlapping metrics (Dice coefficient (), Jaccard (), and False positive (FP)) and time cost (TC). Furthermore, AUGC is compared to other methods, including Confidence Connected Region Growing (CCRG), watershed, and Active Contour based Curve Delineation (ACCD). Experimental results indicate that AUGC achieves the highest accuracy ( and and ) and takes on average about 4 seconds to process a volumetric image. It was said that AUGC benefits large-scale studies by using UST images for breast cancer screening and pathological quantification.

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Curcumin Induces Autophagy, Apoptosis, and Cell Cycle Arrest in Human Pancreatic Cancer Cells

Objective. Curcumin is an active extract from turmeric. The aim of this study was to identify the underlying mechanism of curcumin on PCa cells and the role of autophagy in this process. Methods. The inhibitory effect of curcumin on the growth of PANC1 and BxPC3 cell lines was detected by CCK-8 assay. Cell cycle distribution and apoptosis were tested by flow cytometry. Autophagosomes were tested by cell immunofluorescence assay. The protein expression was detected by Western blot. The correlation between LC3II/Bax and cell viability was analyzed. Results. Curcumin inhibited the cell proliferation in a dose- and time-dependent manner. Curcumin could induce cell cycle arrest at G2/M phase and apoptosis of PCa cells. The autophagosomes were detected in the dosing groups. Protein expression of Bax and LC3II was upregulated, while Bcl2 was downregulated in the high dosing groups of curcumin. There was a significant negative correlation between LC3II/Bax and cell viability. Conclusions. Autophagy could be triggered by curcumin in the treatment of PCa. Apoptosis and cell cycle arrest also participated in this process. These findings imply that curcumin is a multitargeted agent for PCa cells. In addition, autophagic cell death may predominate in the high concentration groups of curcumin.

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Cancers, Vol. 9, Pages 121: The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL

Cancers, Vol. 9, Pages 121: The PI3Kδ Inhibitor Idelalisib Inhibits Homing in an in Vitro and in Vivo Model of B ALL

Cancers doi: 10.3390/cancers9090121

Authors: Etai Adam Hye Na Kim Eun Ji Gang Caitlin Schnair Solomon Lee Solah Lee Sajad Khazal Osanna Kosoyan Marina Konopleva Chintan Parekh Deepa Bhojwani Alan S. Wayne Hisham Abdel-Azim Nora Heisterkamp Yong-Mi Kim

The quest continues for targeted therapies to reduce the morbidity of chemotherapy and to improve the response of resistant leukemia. Adhesion of acute lymphoblastic leukemia (ALL) cells to bone marrow stromal cells triggers intracellular signals that promote cell-adhesion-mediated drug resistance (CAM-DR). Idelalisib, an U.S. Food and Drug Administration (FDA)-approved PI3Kδ-specific inhibitor has been shown to be effective in CLL in down-regulating p-Akt and prolonging survival in combination with Rituximab; herein we explore the possibility of its use in B ALL and probe the mechanism of action. Primary B ALL in contact with OP9 stromal cells showed increased p-Aktser473. Idelalisib decreased p-Akt in patient samples of ALL with diverse genetic lesions. Addition of idelalisib to vincristine inhibited proliferation when compared to vincristine monotherapy in a subset of samples tested. Idelalisib inhibited ALL migration to SDF-1α in vitro and blocked homing of ALL cells to the bone marrow in vivo. This report tests PI3Kδ inhibitors in a more diverse group of ALL than has been previously reported and is the first published report of idelalisib inhibiting homing of ALL cells to bone marrow. Our data support further pre-clinical evaluation of idelalisib for the therapy of B ALL.

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Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids Proliferation: Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix Metalloproteinases

The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2; ; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.

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Extrinsic Apoptosis Pathway Altered by Glycogen Synthase Kinase-3β Inhibitor Influences the Net Drug Effect on NSC-34 Motor Neuron-Like Cell Survival

Glycogen synthase kinase-3β (GSK-3β) inhibitors have been suggested as a core regulator of apoptosis and have been investigated as therapeutic agents for neurodegenerative diseases, including amyotrophic lateral sclerosis. However, GSK-3β has an interesting paradoxical effect of being proapoptotic during mitochondrial-mediated intrinsic apoptosis but antiapoptotic during death receptor-mediated extrinsic apoptosis. We assessed the effect of low to high doses of a GSK-3β inhibitor on survival and apoptosis of the NSC-34 motor neuron-like cell line after serum withdrawal. Then, we identified changes in extrinsic apoptosis markers, including Fas, Fas ligand, cleaved caspase-8, p38α, and the Fas-Daxx interaction. The GSK-3β inhibitor had an antiapoptotic effect at the low dose but was proapoptotic at the high dose. Proapoptotic effect at the high dose can be explained by increased signals in cleaved caspase-8 and the motor neuron-specific p38α and Fas-Daxx interaction. Our results suggest that GSK-3β inhibitor dose may determine the summation effect of the intrinsic and extrinsic apoptosis pathways. The extrinsic apoptosis pathway might be another therapeutic target for developing a potential GSK-3β inhibitor.

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Mycochemical Characterization of Agaricus subrufescens considering Their Morphological and Physiological Stage of Maturity on the Traceability Process

Agaricus subrufescens Peck is a basidiomycete with immunomodulatory compounds and antitumor activities. This research evaluated the mycochemical composition of A. subrufescens, considering their morphological and physiological stage of maturity, with a particular focus on the development of a traceability process for the formulation of new nutritional products based on fungal foods. The stipes contained a high amount of dry matter (10.33%), total carbohydrate (69.56%), available carbohydrate (63.89%), and energy value (363.97 kcal 100 g−1 DM). The pilei contained a high amount of moisture (90.66%), nitrogen (7.75%), protein (33.96%), ash (8.24), crude fat (2.44%), acid detergent fiber (16.75 g kg−1), neutral detergent fiber (41.82 g kg−1), hemicellulose (25.07 g kg−1), and lignin (9.77 g kg−1). Stipes with mature physiological stage had higher values of dry matter (10.50%), crude fiber (5.94%), total carbohydrate (72.82%), AC (66.88%), and energy value (364.91 kcal 100 g−1 DM). Pilei of the mushrooms in the immature physiological stage had higher values of P (36.83%), N (8.41%), and A (8.44%). Due to the differences between the mycochemical compositions of the morphological parts of mushrooms linked to their physiological stage of maturity, such characteristics have immense potential to be considered for a traceability process. This study can be used for the purpose of providing the consumer with more product diversity, optimizing bioactivities of composts, and allowing farmers an efficient and profitable use of the mushroom biomass.

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Biological and Phytochemical Investigations on Caesalpinia benthamiana, a Plant Traditionally Used as Antimalarial in Guinea

Caesalpinia benthamiana is widely used as antimalarial in Guinean traditional medicine. Leaf extracts of the plant were tested for their in vitro antiprotozoal activity against Trypanosoma brucei brucei and T. cruzi and the chloroquine-sensitive Ghana strain of Plasmodium falciparum along with their cytotoxicity on MRC-5 cells. The methanolic extract showed the strongest antiprotozoal activity against P. falciparum (IC50 4 μg/ml), a good activity against T. brucei (IC50 13 μg/ml), and a moderate activity against T. cruzi (IC50 31 μg/ml) along with an IC50 on human MRC-5 cells of 32 μg/ml. Bioassay-guided fractionation from the methanolic extract led to antiplasmodially active subfractions. A prospective, placebo-controlled ethnotherapeutic trial assessed the antimalarial effectiveness and tolerability of C. benthamiana syrup administered orally to children with uncomplicated malaria as compared with chloroquine syrup. Phytochemical screening of the leaf extracts indicated the presence of flavonoids, terpenoids, tannins, saponins, and iridoids.

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Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project.

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40-80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs. (C) 2017 International Anesthesia Research Society

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Postoperative Complications Affecting Survival After Cardiac Arrest in General Surgery Patients.

BACKGROUND: Postoperative cardiac arrest is uncommon but associated with a high mortality risk in general surgery patients and is often preceded by postoperative complications. The relationships between previous complications and mortality after cardiac arrest in general surgery patients have not been completely evaluated. METHODS: retrospective, observational cohort of general surgery in patients with cardiac arrest occurring after postoperative day (POD) #0 (and up to POD #30) was obtained from the 2012-2013 American College of Surgeons National Surgical Quality Improvement Program. Previous complication was defined as at least one of the following occurring before the POD of cardiac arrest: (1) acute kidney injury; (2) acute respiratory failure; (3) deep vein thrombosis/pulmonary embolus; (4) myocardial infarction; (5) sepsis/septic shock; (6) stroke; and/or (7) transfusion. The associations between previous complications and mortality after cardiac arrest were assessed using Cox proportional hazards models that adjusted for preoperative risk factors. RESULTS: Of 1352 patients with postoperative cardiac arrest, 746 patients (55%) developed at least 1 complication before cardiac arrest. Overall 30-day mortality was 71% (958/1352) and was similar among patients with and without a previous complication (71% [533/746] vs 70% [425/606]; P = .60). Patients with previous complications did not have an increased risk of mortality, compared to patients without previous complications, in adjusted Cox models (hazard ratio, 1.03; 95% confidence interval, 0.90-1.18; P = .70). In addition, no previous complication was associated with increased mortality risk in individual analyses. CONCLUSIONS: Among general surgery patients with cardiac arrest after POD #0, complications occurring before cardiac arrest are common but are not associated with increased mortality risk. (C) 2017 International Anesthesia Research Society

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The Assignment of American Society of Anesthesiologists Physical Status Classification for Adult Polytrauma Patients: Results From a Survey and Future Considerations.

BACKGROUND: The American Society of Anesthesiologists (ASA) physical status (PS) classification system assesses the preoperative health of patients. Previous studies demonstrated poor interrater reliability and variable ASA PS scores, especially in trauma scenarios. There are few studies that evaluated the assignment of ASA PS scores in trauma patients and no studies that evaluated ASA PS assignment in severely injured adult polytrauma patients. Our objective was to assess interrater reliability and identify sources of discrepancy among anesthesiologists and trauma surgeons in designating ASA PS scores to adult polytrauma patients. METHODS: A link to an online survey containing questions assessing attitudes regarding ASA PS classification, demographic information, and 8 fictional trauma cases was e-mailed to anesthesiologists and trauma surgeons. The participants were asked to assign an ASA PS score to each scenario and explain their choice. Rater-versus-reference and interrater reliability, beyond that expected by chance, among respondents was analyzed using the Fleiss kappa analysis. RESULTS: A total of 349 participants completed the survey. All 8 cases had inconsistent ASA PS scores; several cases had scores ranging from I to VI and variable emergency (E) designations. Using weighted kappa (Kw) analysis for a subset of 201 respondents (101 trauma surgeons [S] and 100 anesthesiologists [A]), we found moderate (Kw = 0.63; SE = 0.024; 95% confidence interval, 0.594-0.666; P

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Radiofrequency Treatments on the Spine, 1st ed.

No abstract available

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Descriptive Statistics: Reporting the Answers to the 5 Basic Questions of Who, What, Why, When, Where, and a Sixth, So What?.

Descriptive statistics are specific methods basically used to calculate, describe, and summarize collected research data in a logical, meaningful, and efficient way. Descriptive statistics are reported numerically in the manuscript text and/or in its tables, or graphically in its figures. This basic statistical tutorial discusses a series of fundamental concepts about descriptive statistics and their reporting. The mean, median, and mode are 3 measures of the center or central tendency of a set of data. In addition to a measure of its central tendency (mean, median, or mode), another important characteristic of a research data set is its variability or dispersion (ie, spread). In simplest terms, variability is how much the individual recorded scores or observed values differ from one another. The range, standard deviation, and interquartile range are 3 measures of variability or dispersion. The standard deviation is typically reported for a mean, and the interquartile range for a median. Testing for statistical significance, along with calculating the observed treatment effect (or the strength of the association between an exposure and an outcome), and generating a corresponding confidence interval are 3 tools commonly used by researchers (and their collaborating biostatistician or epidemiologist) to validly make inferences and more generalized conclusions from their collected data and descriptive statistics. A number of journals, including Anesthesia & Analgesia, strongly encourage or require the reporting of pertinent confidence intervals. A confidence interval can be calculated for virtually any variable or outcome measure in an experimental, quasi-experimental, or observational research study design. Generally speaking, in a clinical trial, the confidence interval is the range of values within which the true treatment effect in the population likely resides. In an observational study, the confidence interval is the range of values within which the true strength of the association between the exposure and the outcome (eg, the risk ratio or odds ratio) in the population likely resides. There are many possible ways to graphically display or illustrate different types of data. While there is often latitude as to the choice of format, ultimately, the simplest and most comprehensible format is preferred. Common examples include a histogram, bar chart, line chart or line graph, pie chart, scatterplot, and box-and-whisker plot. Valid and reliable descriptive statistics can answer basic yet important questions about a research data set, namely: "Who, What, Why, When, Where, How, How Much?" (C) 2017 International Anesthesia Research Society

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