High-resolution magic angle spinning magnetic resonance spectroscopy detects glycine as a biomarker in brain tumors

The non-essential amino acid neurotransmitter glycine (Gly) may serve as a biomarker for brain tumors. Using 36 biopsies from patients with brain tumors [12 glioblastoma multiforme (GBM); 10 low-grade (LG), including 7 schwannoma and 3 pylocytic astrocytoma; 7 meningioma (MN); 7 brain metastases (MT), including 3 adenocarcinoma and 4 breast cancer] and 9 control biopsies from patients undergoing surgery for epilepsy, we tested the hypothesis that the presence of glycine may distinguish among these brain tumor types. Using high-resolution magic angle spinning (HRMAS) 1H magnetic resonance spectroscopy (MRS), we determined a theoretically optimum echo time (TE) of 50 ms for distinguishing Gly signals from overlapping myo-inositol (Myo) signals and tested our methodology in phantom and biopsy specimens. Quantitative analysis revealed higher levels of Gly in tumor biopsies (all combined) relative to controls; Gly levels were significantly elevated in LG, MT and GBM biopsies (P≤0.05). Residual Myo levels were elevated in LG and MT and reduced in MN and GBM (P<0.05 vs. control levels). We observed higher levels of Gly in GBM as compared to LG tumors (P=0.05). Meanwhile, although Gly levels in GBM and MT did not differ significantly from each other, the Gly:Myo ratio did distinguish GBM from MT (P<0.003) and from all other groups, a distinction that has not been adequately made previously. We conclude from these findings that Gly can serve as a biomarker for brain tumors and that the Gly:Myo ratio may be a useful index for brain tumor classification

Desain Interior Insumo Palace Hotel and Resort Kediri Untuk Pengunjung Keluarga Bertema Modern Dengan Sentuhan Aplikasi Motif Batik Brantas Mulya Khas Kediri

Hotel merupakan suatu tempat umum yang menyediakan kamar untuk disewakan per harinya dengan ruangan tambahan seperti restoran, fasilitas olahraga, ruang rapat sebagai fasilitas penunjang. Semakin berkembangnya jaman, perkembangan pariwisata tidak hanya di kota-kota besar seperti Jakarta dan Surabaya namun juga di kota-kota kecil. Kota Kediri merupakan salah satu kota dengan pilihan pariwisata mulai dari wisata sejarah hingga wisata religi. Salah satu wisata yang terkenal di Kota Kediri adalah Kawasan Wisata Goa Selomangkleng. Saat ini kegiatan berwisata tidak hanya menjadi hiburan semata melainkan telah menjadi bagian dari kebutuhan bagi masyarakat di Indonesia. Hal ini terbukti dari meningkatnya jumlah wisatawan domestik pada tahun 2014 mencapai 251 juta orang (berdasarkan data dari Kementerian Pariwisata), dimana angka tersebut mengatakan bahwa jumlah masyarakat Indonesia yang melakukan kegiatan wisata jumlahnya hampir mendekati jumlah penduduk Indonesia. Namun dengan adanya peningkatan tersebut, tidak banyak hotel yang menyediakan fasilitas ataupun dekorasi yang variatif dan menarik bagi pengunjung khususnya untuk pengunjung keluarga. Metode pengambilan data yang digunakan untuk proses desain hotel ini meliputi pengumpulan data baik secara langsung ke lapangan maupun tidak langsung. Pengumpulan data mengenai Insumo Palace Hotel and Resort dilakukan dengan metode observasi lapangan guna mengetahui keadaan terkini desain hotel dan obervasi tidak langsung untuk mengumpulkan data-data tentang hotel melalui website hotel. Wawancara dengan beberapa narasumber yang pernah menginap di hotel tersebut untuk mengetahui bagaimana kesan dan Kenyamanan pengunjung terhadap desain dan fasilitas hotel. Sedangkan studi pustaka tentang standar hotel bintang tiga dan tema modern dilakukan dengan mengumpulkan beberapa informasi baik dari literatur buku, jurnal hingga blog internet. Pengumpulan data digunakan untuk mengetahui standar desain yang digunakan, pembanding dan referensi yang diperlukan berkaitan dengan objek desain. Sehingga dari hasil proses desain didapatkan bahwa tema modern yang menampilkan kesan kekinian pada ruangan merupakan tema yang cocok untuk desain ruangan dengan pengunjung keluarga dan dengan sentuhan aplikasi motif batik brantas mulya khas kediri akan memberikan nuansa berbeda sekaligus memberikan identitas Kota Kediri di dalam ruangan

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) (n = 1), Tuberous sclerosis complex (TSC) (n = 2), Focal cortical dysplasia (FCD) (n = 4), and Rasmussen encephalitis (RE) (n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45+ cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80-95 percent of the CD45+ cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up &gt;50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR+ CD11b+ CD4- cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA+ HLA-DR- CD11b+ CD16+ NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA- HLA-DR+ CD11b- CD16- cells comprised 86-96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αβ T cells and γδ T cells accounted for over 80% of the CD3+ T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40-66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO+ HLA-DR+ CD69+) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation

Size dependent magnetic properties and cation inversion in chemically synthesized MnFe2O4 nanoparticles

MnFe2O4nanoparticles with diameters ranging from about 4to50nm were synthesized using a modified coprecipitation method. X-ray diffractograms revealed a pure phase spinel ferrite structure for all samples. Transmission electron microscopy showed that the particles consist of a mixture of both spherical (smaller) and cubic (larger) particles dictated by the reaction kinetics. The Néel temperatures (TN) of MnFe2O4 for various particle sizes were determined by using high temperature magnetometry. The ∼4nm MnFe2O4 particles showed a TN of about 320°C whereas the ∼50nm particles had a TN of about 400°C. The high Néel temperature, compared with the bulk MnFe2O4 TN of 300°C, is due to a change in cation distribution between the tetrahedral and octahedral sites of the spinel lattice. Results of extended x-ray absorption fine structure measurements indicate a systematic change in the cation distribution dependent on processing conditions

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician’s considerations of disease features, phenotype, and response to previous therapy

The Dependence of the Superconducting Transition Temperature of Organic Molecular Crystals on Intrinsically Non-Magnetic Disorder: a Signature of either Unconventional Superconductivity or Novel Local Magnetic Moment Formation

We give a theoretical analysis of published experimental studies of the effects of impurities and disorder on the superconducting transition temperature, T_c, of the organic molecular crystals kappa-ET_2X and beta-ET_2X (where ET is bis(ethylenedithio)tetrathiafulvalene and X is an anion eg I_3). The Abrikosov-Gorkov (AG) formula describes the suppression of T_c both by magnetic impurities in singlet superconductors, including s-wave superconductors and by non-magnetic impurities in a non-s-wave superconductor. We show that various sources of disorder lead to the suppression of T_c as described by the AG formula. This is confirmed by the excellent fit to the data, the fact that these materials are in the clean limit and the excellent agreement between the value of the interlayer hopping integral, t_perp, calculated from this fit and the value of t_perp found from angular-dependant magnetoresistance and quantum oscillation experiments. If the disorder is, as seems most likely, non-magnetic then the pairing state cannot be s-wave. We show that the cooling rate dependence of the magnetisation is inconsistent with paramagnetic impurities. Triplet pairing is ruled out by several experiments. If the disorder is non-magnetic then this implies that l>=2, in which case Occam's razor suggests that d-wave pairing is realised. Given the proximity of these materials to an antiferromagnetic Mott transition, it is possible that the disorder leads to the formation of local magnetic moments via some novel mechanism. Thus we conclude that either kappa-ET_2X and beta-ET_2X are d-wave superconductors or else they display a novel mechanism for the formation of localised moments. We suggest systematic experiments to differentiate between these scenarios.Comment: 18 pages, 5 figure

Metformin Decreases Glucose Oxidation and Increases the Dependency of Prostate Cancer Cells on Reductive Glutamine Metabolism

Metformin inhibits cancer cell proliferation, and epidemiology studies suggest an association with increased survival in patients with cancer taking metformin; however, the mechanism by which metformin improves cancer outcomes remains controversial. To explore how metformin might directly affect cancer cells, we analyzed how metformin altered the metabolism of prostate cancer cells and tumors. We found that metformin decreased glucose oxidation and increased dependency on reductive glutamine metabolism in both cancer cell lines and in a mouse model of prostate cancer. Inhibition of glutamine anaplerosis in the presence of metformin further attenuated proliferation, whereas increasing glutamine metabolism rescued the proliferative defect induced by metformin. These data suggest that interfering with glutamine may synergize with metformin to improve outcomes in patients with prostate cancer.German Science Foundation (Grant FE1185)National Institutes of Health (U.S.)Glenn Foundation for Medical ResearchNational Institutes of Health (U.S.) (Grant 5-P50-090381-09)National Institutes of Health (U.S.) (Grant 5-P30-CA14051-39)Burroughs Wellcome FundSmith Family FoundationDamon Runyon Cancer Research FoundationNational Institutes of Health (U.S.) (Grant 1R01DK075850-01)National Institutes of Health (U.S.) (Grant 1R01CA160458-01A1

RNA-Peptide nanoplexes drug DNA damage pathways in high-grade serous ovarian tumors

DNA damaging chemotherapy is a cornerstone of current front‐line treatments for advanced ovarian cancer (OC). Despite the fact that a majority of these patients initially respond to therapy, most will relapse with chemo‐resistant disease; therefore, adjuvant treatments that synergize with DNA‐damaging chemotherapy could improve treatment outcomes and survival in patients with this deadly disease. Here, we report the development of a nanoscale peptide‐nucleic acid complex that facilitates tumor‐specific RNA interference therapy to chemosensitize advanced ovarian tumors to frontline platinum/taxane therapy. We found that the nanoplex‐mediated silencing of the protein kinase, MK2, profoundly sensitized mouse models of high‐grade serous OC to cytotoxic chemotherapy by blocking p38/MK2‐dependent cell cycle checkpoint maintenance. Combined RNAi therapy improved overall survival by 37% compared with platinum/taxane chemotherapy alone and decreased metastatic spread to the lungs without observable toxic side effects. These findings suggest (a) that peptide nanoplexes can serve as safe and effective delivery vectors for siRNA and (b) that combined inhibition of MK2 could improve treatment outcomes in patients currently receiving frontline chemotherapy for advanced OC.National Institutes of Health (U.S.) (Grant R01-ES015339)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant 1F32EB017614)National Science Foundation (U.S.) (Grant GFRP 1122374)National Cancer Institute (U.S.) (Grant P30-CA14051)National Science Foundation (U.S.) (Grant DMR-0819762

IoT in healthcare: A scientometric analysis

This paper reviews scientific articles and patents about Internet of Things (IoT) in healthcare. The aim is to explore both the domain of research and the one of practice simultaneously. We compare the annual growth, the country production, and the trend topics of publications and patents, by focusing on the most relevant themes concerning the IoT in the healthcare industry. The analysis started with the selection of the publications and patents for the period 2015–2020. Since this comparative analysis between scientometric data in healthcare is new, the findings of this study can represent the basis for future studies to determine novel research opportunities on IoT. The study provides scholars with a better understanding of IoT research in healthcare and simultaneously extends knowledge of entrepreneurship in this field. Practitioners may benefit from this review to understand new and underexplored opportunities