Distant metastases of differentiated thyroid cancer: diagnosis, treatment and outcome

The remarkably good prognosis and long-term survival in differentiated thyroid cancer (DTC) are significantly reduced in patients with distant metastasis (DM). Multi-site metastases are associated with a high mortality rate reaching 92% at 5 years necessitating early diagnosis and treatment. The most common site of metastases are the lungs, followed by the bone, with the former having better prognosis than the latter due to late detection. A number of factors contribute to the development of DM including large and multifocal primary tumour, extrathyroidal extension, aggressive histology and advanced age. In patients with good 131I uptake, 131I therapy appears highly effective and should be offered up to a cumulative activity of 22 GBq. Other measures such as surgery, radiotherapy, arterial embolisation and cementoplasty may be required. If there is low or no 131I uptake, FDG-PET should be obtained due to its prognostic impact. It may help in selecting patients for other modalities such as cytotoxic chemotherapy and redifferentiation therapy by 13-cis retinoic acid. The development of tyrosine kinase inhibitors has raised hopes in providing alternative therapy for bone metastasis, especially in older age groups with poorly differentiated tumours with no 131I uptake but good uptake of FDG

UPAYA KEPOLISIAN DAERAH SUMATER BARAT DALAM PENANGGULANGAN TINDAK PIDANA UJARAN KEBENCIAN (HATE SPEECH) DI MEDIA SOSIAL

ABSTRAK Demokrasi dan negara hukum adalah dua konsepsi mekanisme kekuasaan dalam menjalankan roda pemerintahan yang saling berkaitan dan tidak dapat dipisahkan. Demokrasi memberikan landasan serta mekanisme kekuasaan untuk prinsip persamaan kemanusian dalam negara hukum. Perkembangan teknologi internet yang sangat pesat.di Indonesia dalam pemanfaatan media sosial menimbulkan fenomena baru yaitu setiap orang bisa dengan bebasnya mengungkapkan apa saja melalui media sosial mereka. Ujaran Kebencian (Hate Speech merupakan tindakan menyebar rasa kebencian dan permusuhan yang bersifat SARA (Suku, Agama, Ras, dan Antar golongan). Hate speech sendiri diumumkan sebagai tindak pidana oleh Kepolisian Indonesia melalui Surat Edaran (SE) tentang ujaran kebencian pada tanggal 8 Oktober 2015 bernomor SE/06/X/2015. Bentuk ujaran kebencian yang masuk dalam tindak pidana KUHP adalah penghinaan, pencemaran nama baik, penistaan, perbuatan tidak menyenangkan, provokasi, penghasutan, dan penyebaran berita bohong (hoax). Kepolisian Republik Indonesia sebagai salah satu instrumen negara dalam mengawal situasi kamtibmas agar tetap kondusif, memiliki peranan strategis dan sangat penting dalam penanganan ujaran kebencian (hate speech). Penelitian ini bertujuan untuk mengetahui dan menjelaskan apa saja upaya yang dilakukan Kepolisian Daerah Sumatera Barat dalam menanggulangi tindak pidana Ujaran Kebencian (Hate Speech) di media sosial serta kendala-kendala apa saja yang dihadapi. Penelitian ini dilakukan dengan menggunakan pendekatan yuridis-sosiologis. Pengumpulan data diperoleh melalui wawancara dengan pihak Polda Sumbar dan studi dokumen atau bahan Pustaka yang berhubungan dengan penelitian penulis. Hasil penelitian menunjukan bahwa upaya yang dilakukan Kepolisian Daerah Sumatera Barat secara garis besar dibagi menjadi dua yaitu, melalui jalur penal yang menitikberatkan pada sifat represif dan jalur nonpenal yang menitikberatkan pada sifat preventif. Kendala yang dihadapi Kepolisian Daerah Sumatera Barat terletak pada beberapa faktor, yaitu dari faktor batasan hukumnya sendiri, faktor anonimitas dan pengguna palsu, faktor keterbatasan sumber daya dan kemampuan, dan faktor ketidaktahuan masyarakat. Kata kunci: Upaya Kepolisian, Penanggulangan, Ujaran Kebencian (Hate Speech), Media Sosia

Ion Microscopy: A New Approach for Subcellular Localization of Labelled Molecules

Secondary ion mass spectroscopy (SIMS) was used to obtain images representing the intracellular distribution of molecules labelled with carbon 14. Deoxyadenosine labelled with carbon 14 was added to a cultured human fibroblast cell medium, and the intracellular distribution of this molecule was studied using three different SIMS instruments: the CAMECA IMS 3F and SMI 300 ion microscopes and the UC-HRL scanning ion microprobe. Carbon 14 distribution images obtained by this method show that deoxyadenosine U-C14 is present in the cytoplasm as well as the nucleus, with a higher concentration in\u27 the nucleoli. Our study clearly demonstrates that ion microscopy is well suited for carbon 14 detection and localization at the subcellular level, permitting a wide variety of microanalytical tracer experiments

Contact guidance enhances the quality of a tissue engineered corneal stroma

Corneal stroma is a very complex structure, composed of 200 lamellae of oriented collagen fibers. This highly complex nature of cornea is known to be important for its transparency and mechanical integrity. Thus, an artificial cornea design has to take into account this complex structure. In this study, behavior of human corneal keratocytes on collagen films patterned with parallel channels was investigated. Keratocytes proliferated well on films and reached confluency after 7 days in the incubation medium. Nearly all of the cells responded to the patterns and were aligned in contrast to the cells on unpatterned surfaces. Collagen type I and keratan sulfate secreted by keratocytes on patterned films appeared to be aligned in the direction of the patterns. The films showed an intermediate degradation over the course of a month. On the whole, transparency of the films increased with degradation and decreased by the presence of the cells. The decrease was, however, low and transparency level was maintained on the patterned films while on the unpatterned films a sharp decrease in transparency was followed by an improvement. This was due to the more organized distribution of cells and the oriented secretion of extracellular matrix molecules on patterned collagen films. Thus, these results suggest that application of contact guidance in cornea tissue engineering may facilitate the remodeling process, hence decrease the rehabilitation period. © 2007 Wiley Periodicals, Inc

HENA, heterogeneous network-based data set for Alzheimer's disease.

Alzheimer's disease and other types of dementia are the top cause for disabilities in later life and various types of experiments have been performed to understand the underlying mechanisms of the disease with the aim of coming up with potential drug targets. These experiments have been carried out by scientists working in different domains such as proteomics, molecular biology, clinical diagnostics and genomics. The results of such experiments are stored in the databases designed for collecting data of similar types. However, in order to get a systematic view of the disease from these independent but complementary data sets, it is necessary to combine them. In this study we describe a heterogeneous network-based data set for Alzheimer's disease (HENA). Additionally, we demonstrate the application of state-of-the-art graph convolutional networks, i.e. deep learning methods for the analysis of such large heterogeneous biological data sets. We expect HENA to allow scientists to explore and analyze their own results in the broader context of Alzheimer's disease research

68Ga-Radiolabeling and Pharmacological Characterization of a Kit-Based Formulation of the Gastrin-Releasing Peptide Receptor (GRP-R) Antagonist RM2 for Convenient Preparation of [68Ga]Ga-RM2

Background: [68Ga]Ga-RM2 is a potent Gastrin-Releasing Peptide-receptor (GRP-R) antagonist for imaging prostate cancer and breast cancer, currently under clinical evaluation in several specialized centers around the world. Targeted radionuclide therapy of GRP-R-expressing tumors is also being investigated. We here report the characteristics of a kit-based formulation of RM2 that should ease the development of GRP-R imaging and make it available to more institutions and patients. Methods: Stability of the investigated kits over one year was determined using LC/MS/MS and UV-HPLC. Direct 68Ga-radiolabeling was optimized with respect to buffer (pH), temperature, reaction time and shaking time. Conventionally prepared [68Ga]Ga-RM2 using an automated synthesizer was used as a comparator. Finally, the [68Ga]Ga-RM2 product was assessed with regards to hydrophilicity, affinity, internalization, membrane bound fraction, calcium mobilization assay and efflux, which is a valuable addition to the in vivo literature. Results: The kit-based formulation, kept between 2 °C and 8 °C, was stable for over one year. Using acetate buffer pH 3.0 in 2.5–5.1 mL total volume, heating at 100 °C during 10 min and cooling down for 5 min, the [68Ga]Ga-RM2 produced by kit complies with the requirements of the European Pharmacopoeia. Compared with the module production route, the [68Ga]Ga-RM2 produced by kit was faster, displayed higher yields, higher volumetric activity and was devoid of ethanol. In in vitro evaluations, the [68Ga]Ga-RM2 displayed sub-nanomolar affinity (Kd = 0.25 ± 0.19 nM), receptor specific and time dependent membrane-bound fraction of 42.0 ± 5.1% at 60 min and GRP-R mediated internalization of 24.4 ± 4.3% at 30 min. The [natGa]Ga-RM2 was ineffective in stimulating intracellular calcium mobilization. Finally, the efflux of the internalized activity was 64.3 ± 6.5% at 5 min. Conclusion: The kit-based formulation of RM2 is suitable to disseminate GRP-R imaging and therapy to distant hospitals without complex radiochemistry equipment

ACS Omega

Neurotensin receptor 2 (NTS) is a well-known mediator of central opioid-independent analgesia. Seminal studies have highlighted NTS overexpression in a variety of tumors including prostate cancer, pancreas adenocarcinoma, and breast cancer. Herein, we describe the first radiometalated neurotensin analogue targeting NTS. JMV 7488 (DOTA-(βAla)-Lys-Lys-Pro-(D)Trp-Ile-TMSAla-OH) was prepared using solid-phase peptide synthesis, then purified, radiolabeled with Ga and In, and investigated on HT-29 cells and MCF-7 cells, respectively, and on HT-29 xenografts. [Ga]Ga-JMV 7488 and [In]In-JMV 7488 were quite hydrophilic (logD = -3.1 ± 0.2 and -2.7 ± 0.2, respectively, < 0.0001). Saturation binding studies showed good affinity toward NTS ( = 38 ± 17 nM for [Ga]Ga-JMV 7488 on HT-29 and 36 ± 10 nM on MCF-7 cells; = 36 ± 4 nM for [In]In-JMV 7488 on HT-29 and 46 ± 1 nM on MCF-7 cells) and good selectivity (no NTS binding up to 500 nM). On cell-based evaluation, [Ga]Ga-JMV 7488 and [In]In-JMV 7488 showed high and fast NTS-mediated internalization of 24 ± 5 and 25 ± 11% at 1 h for [In]In-JMV 7488, respectively, along with low NTS-membrane binding (<8%). Efflux was as high as 66 ± 9% at 45 min for [Ga]Ga-JMV 7488 on HT-29 and increased for [In]In-JMV 7488 up to 73 ± 16% on HT-29 and 78 ± 9% on MCF-7 cells at 2 h. Maximum intracellular calcium mobilization of JMV 7488 was 91 ± 11% to that of levocabastine, a known NTS agonist on HT-29 cells demonstrating the agonist behavior of JMV 7488. In nude mice bearing HT-29 xenograft, [Ga]Ga-JMV 7488 showed a moderate but promising significant tumor uptake in biodistribution studies that competes well with other nonmetalated radiotracers targeting NTS. Significant uptake was also depicted in lungs. Interestingly, mice prostate also demonstrated [Ga]Ga-JMV 7488 uptake although the mechanism was not NTS-mediated