Targeted delivery of anti-inflammatory therapy to rheumatoid tissue by fusion proteins containing an IL-4-linked synovial targeting peptide

We provide first-time evidence that the synovial endothelium-targeting peptide (SyETP) CKSTHDRLC successfully delivers conjugated IL-4 to human rheumatoid synovium transplanted into SCID mice. SyETP, previously isolated by in vivo phage display and shown to preferentially localize to synovial xenografts, was linked by recombinant technology to hIL-4 via an MMP-cleavable sequence. Both IL-4 and the MMP-cleavable sequence were shown to be functional. IL-4-SyETP augmented production of IL-1ra by synoviocytes stimulated with IL-1[beta] in a dose-dependent manner. In vivo imaging confirmed increased retention of SyETP-linked-IL-4 in synovial grafts which was enhanced by increasing number of copies (one to three) in the constructs. Strikingly, SyETP delivered bioactive IL-4 in vivo as demonstrated by increased pSTAT6 in synovial grafts. Thus, this study provides proof of concept for peptide-tissue-specific targeted immunotherapy in rheumatoid arthritis. This technology is potentially applicable to other biological therapies providing enhanced potency to inflammatory sites and reducing systemic toxicity

Illness perceptions of Libyans with T2DM and their influence on medication adherence: a study in a diabetes center in Tripoli.

BackgroundThe surrounding environment influences the constitution of illness perceptions. Therefore, local research is needed to examine how Libyan diabetes patients perceive diabetes and how their perceptions influence their medication adherence.MethodsA cross-sectional study was conducted at the National Centre for Diabetes and Endocrinology in Tripoli, Libya, between October and December 2013. A total of 523 patients with type 2 diabetes participated in this study. A self-administered questionnaire was used for data collection; this included the Revised Illness Perception Questionnaire and the eight-item Morisky Medication Adherence Scale.ResultsThe respondents showed moderately high personal control and treatment control perceptions and a moderate consequences perception. They reported a high perception of diabetes timeline as chronic and a moderate perception of the diabetes course as unstable. The most commonly perceived cause of diabetes was Allah's will. The prevalence of low medication adherence was 36.1%. The identified significant predictors of low medication adherence were the low treatment control perception (p=0.044), high diabetes identity perception (p=0.008), being male (p=0.026), and employed (p=0.008).ConclusionDiabetes illness perceptions of type 2 diabetic Libyans play a role in guiding the medication adherence and could be considered in the development of medication adherence promotion plans

Internal mimics hernias and their mimics: How would radiologists help?

AbstractPurposeTrying to define the most valuable radiological sign(s) for the diagnosis of internal hernias and their mimics; mainly cocoon syndrome and adhesions.ReviewNowadays with the increasing number of bariatric surgeries, the number of diagnosed internal hernias has increased significantly. Adhesions and cocoon syndrome are among the differential diagnosis. Although many signs were suggested for the diagnosis of such conditions, yet no single sign is enough to diagnose each of the above.Method and subjectsThis is a retrospective study. In a period of 32 consecutive months, from June 2010 to February 2013 a total of 240 patients were admitted with abdominal pain with signs of remittent or persistent intestinal obstruction. All cases are subjected to multislice CT examination. Several criteria are used to diagnose internal hernia. Informed consents were taken from all patients and organizational ethics committee were informed.ResultsThe age of the patients varies between 22 and 63years with average age of 36±2.3years. Most of the patients were females with ratio of 2:1. Commonest presentation was abdominal pain present in all cases. The study diagnosed 13 cases/internal hernias, 14/adhesions, two cases/cocoon syndrome, two cases/intussusceptions and one case/malrotation. The most important signs used are Swirl’s sign, localized bowel gathering and segmental bowel dilatation.ConclusionA single sign is not enough for the diagnosis of internal hernia, rather the use of more than one sign is essential to narrow the differential diagnosis.Clinical relevance/applicationThe prevalence of internal hernia is increasing due to increased rate of operative abdominal intervention. Prompt radiological diagnosis is crucial to avoid unwanted surgery in a non-virgin abdomen

Analisis Input-Output Atas Dampak Sektor Pariwisata terhadap Perekonomian Maluku

Sebagai provinsi bahari, Maluku memiliki potensi pariwisata yang beragam. Potensi ini dapat diberdayakan bagi pengembangan perekonomian Provinsi Maluku yang selama ini masih masuk dalam kategori daerah tertinggal. Menggunakan analisis input-output, studi ini bertujuan untuk meneliti seberapa besar pengaruh investasi pada industri pariwisata dan sektor pendukungnya terhadap perekonomian Provinsi Maluku. Analisis dilakukan untuk melihat efek pengganda, dampak terhadap output dan upah secara keseluruhan, dan sentralitas sektor pariwisata dalam perekonomian Provinsi Maluku. Hasil studi menunjukkan bahwa investasi pada sektor-sektor ini memiliki dampak yang dapat diperhitungkan bagi perekonomian Provinsi Maluku

In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome

Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict species specificity. Hence, in vivo examination of all aspects of CMV biology employs animal models using host-specific CMVs. Infection of rhesus macaques (RM) with rhesus CMV (RhCMV) has been established as a representative model for infection of humans with HCMV due to the close evolutionary relationships of both host and virus. However, the only available RhCMV clone that permits genetic modifications is based on the 68-1 strain which has been passaged in fibroblasts for decades resulting in multiple genomic changes due to tissue culture adaptations. As a result, 68-1 displays reduced viremia in RhCMV-naive animals and limited shedding compared to non-clonal, low passage isolates. To overcome this limitation, we used sequence information from primary RhCMV isolates to construct a full-length (FL) RhCMV by repairing all mutations affecting open reading frames (ORFs) in the 68-1 bacterial artificial chromosome (BAC). Inoculation of adult, immunocompetent, RhCMV-naive RM with the reconstituted virus resulted in significant viremia in the blood similar to primary isolates of RhCMV and furthermore led to high viral genome copy numbers in many tissues at day 14 post infection. In contrast, viral dissemination was greatly reduced upon deletion of genes also lacking in 68-1. Transcriptome analysis of infected tissues further revealed that chemokine-like genes deleted in 68-1 are among the most highly expressed viral transcripts both in vitro and in vivo consistent with an important immunomodulatory function of the respective proteins. We conclude that FL-RhCMV displays in vitro and in vivo characteristics of a wildtype virus while being amenable to genetic modifications through BAC recombineering techniques

Peningkatan Motivasi Belajar Siswa dalam Pembelajaran IPA Menggunakan Pendekatan Saintifik Kelas V SD

The research problem is how is the increasing of students motivation in learning natural sciences material in the fifth grade of SDN 31 West Pontianak by using Scientific Approaching?. The research purpose is to describe the increasing of students motivation by using Scientific Approaching. Method of this research is descriptive, by using classroom action research, collaborative. This research is alone three circles. Research result is students motivation of the first is 62,12%, the second circle is 73,99% got increased 11,87% and the three circles is 82, 07% got increased 8,08%. The concluding, by using Scientific Approaching it seems that students motivation increased

Molluscicidal and Mosquitocidal Activities of the Essential oils of Thymus capitatus Hoff. et Link. and Marrubium vulgare L.

A destilação por arraste a vapor dos óleos essenciais de partes aéreas de Thymus capitatus Hoff. et Link. e de Marrubium vulgare L. coletadas na costa norte do Egito resultaram em rendimento de 0,5% e 0,2%, respectivamente. Resultados de análises por cromatografia gasosa acoplada à espectrometria de massas de ambas as amostras possibilitaram a identificação de 96,27% e 90,19% dos constituintes químicos respectivamente de T. capitatus e M. vulgare. Verificou-se predomínio de constituintes oxigenados (88,22% para T. capitatus e 57,50% para M. vulgare, principalmente fenóis, como carvacrol (32,98%) e timol (32,82%) no óleo essencial de T. capitatus, e timol (34,55%) no óleo essencial de M. vulgare. Avaliou-se a atividade dos óleos essenciais obtidos contra adultos e ovos de Biomphalaria alexandrina, bem como em larvas e pupas de Culex pipiens. A CL50 e CL90 do óleo essencial de T. capitatus em moluscos adultos foi respectivamente 200 e 400 ppm/3hrs, enquanto para o óles essencial de M. vulgare verificou-se CL50 e CL90 de 50 e 100 ppm/3hrs, respectivamente. Além disso, M. vulgare apresentou atividade ovicida, com CL 100 de 200 ppm/24 horas, enquanto o óleo essencial de T. capitatus não demonstrou atividade ovicida. Verificou-se ainda atividade mosquitocida, com CL50 e CL90 de 100 e 200 ppm/12hrs respectivamente para larvas, e 200 e 400 ppm/12hrs contra pupas de C. pipiens.Steam distillation of essential oils of aerial parts of Thymus capitatus and Marrubium vulgare L. collected at North cost of Egypt yielded 0.5% and 0.2%, respectively. Results of Gas chromatography-mass spectrometry analyses of the two samples identified 96.27% and 90.19% of the total oil composition for T. capitatus and M. vulgare, respectively. The two oil samples appeared dominated by the oxygenated constituents (88.22% for T. capitatus and 57.50% for M. vulgare), composed of phenols, mainly carvacrol (32.98%) and thymol (32.82%) in essential oil of T. capitatus, and thymol (34.55%) in essential oil of M. vulgare. It was evaluated the molluscicidal activity of T. capitatus and M. vulgare essential oils on adult and eggs of Biomphalaria alexandrina as well as their mosquitocidal activity on Culex pipiens. The LC50 and LC90 of T. capitatus essential oil against adult snails was 200 and 400 ppm/3hrs, respectively, while for M. vulgare it was 50 and 100 ppm/3hrs, respectively. Moreover, M. vulgare showed LC100 ovicidal activity at 200 ppm/24 hrs while T. capitatus oil showed no ovicidal activity. It was verified mosquitocidal activity, with LC50 and LC90 of 100 and 200 ppm/12hrs respectively for larvae, and 200 and 400 ppm/12hrs respectively for pupae of C. pipiens