Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratio's

<p>Abstract</p> <p>Background</p> <p>Sirolimus (SRL, Rapamycin) has been used successfully to inhibit restenosis both in drug eluting stents (DES) and after systemic application. The current study reports on the effects of SRL in various human in vitro/ex vivo models and evaluates the theoretical clinical relevance of the data by SI/MPL- and SI/DES-ratio's.</p> <p>Methods</p> <p>Definition of the SI/MPL-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the <b>m</b>aximal <b>p</b>lasma <b>l</b>evel after systemic administration in vivo (6.4 ng/ml for SRL). Definition of the SI/DES-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the drug concentration in <b>DES </b>(7.5 mg/ml in the ISAR drug-eluting stent platform). Part I of the study investigated in cytoflow studies the effect of SRL (0.01–1000 ng/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of SRL (0.01–1000 ng/ml) on cell migration of HCMSMC. In part III, IV, and V of the study ex vivo angioplasty (9 bar) was carried out in a human organ culture model (HOC-model). SRL (50 ng/ml) was added for a period of 21 days, after 21 and 56 days cell proliferation, apoptosis, and neointimal hyperplasia was studied.</p> <p>Results</p> <p>Expression of ICAM-1 was significantly inhibited both in HCAEC (SRL ≥ 0.01 ng/ml) and HCMSMC (SRL ≥ 10 ng/ml). SRL in concentrations ≥ 0.1 ng/ml significantly inhibited migration of HCMSMC. Cell proliferation and neointimal hyperplasia was inhibited at day 21 and day 56, significance (p < 0.01) was achieved for the inhibitory effect on cell proliferation in the media at day 21. The number of apoptotic cells was always below 1%.</p> <p>Conclusion</p> <p>SI/MPL-ratio's ≤ 1 (ICAM-1 expression, cell migration) characterize inhibitory effects of SRL that can be theoretically expected both after systemic and local high dose administration, a SI/MPL-ratio of 7.81 (cell proliferation) represents an effect that was achieved with drug concentrations 7.81-times the MPL. SI/DES-ratio's between 10^-6and 10^-8indicate that the described inhibitory effects of SRL have been detected with micro to nano parts of the SRL concentration in the ISAR drug-eluting stent platform. Drug concentrations in DES will be a central issue in the future.</p

IMPLEMENTASI PRINSIP BAGI HASIL DI BANK MUAMALAH CABANG MAROS

ABSTRAKIQBAL S. Implementasi Prinsip Bagi Hasil di Bank Muamalat Cabang Maros (dibimbing oleh Minhajuddin dan Saleh Suratmin)Indonesia merupakan Negara dengan jumlah penduduk muslim terbesar di dunia, akan tetapi penerapan nilai nilai Islam secara Kaffah dan utuh dalam kehidupan sehari hari belum dilaksanakan seutuhnya. Misalnya dalam lembaga keuangan perbankan, perbankan syariah di Indonesia baru muncul pada tahun 1992 ketika di sahkannya Undang undang No 7 Tahun 1992 tentang Perbankan dalam Undang undang ini mulai mengakomodir perbankan syariah dengan nama perbankan bagi hasil, selanjutnya diganti dengan Undang undang No. 10 Tahun 1998 yang kemudian disempurnakan dalam Undang undang No. 21 Tahun 2008 .Permasalahan yang dihadapi adalah bagaimana implementasi prinsip bagi hasil dan risiko dalam kegiatan penghimpunan dana, implementasi prinsip bagi hasil dalam kegiatan pembiayaan di Bank Muamalah cabang Maros dan apa yang menjadi kendala operasional yang dihadapi dalam implementasi prinsip bagi hasil hasil tersebut.Penelitian ini menggunakan metode pendekatan doktrinal dan non doktrinal atau socio legal yakni memandang hukum bukan saja teks dalam Undang undang akan tetapi juga melihat hukum berinteraksi dengan masyarakat.Salah satu prinsip usaha Perbankan Syariah adalah akad Bagi Hasil dan resiko dimana bank dan nasabah membagi keuntungan berdasarkan rasio Bagi Hasil yang ditentukan sebelumnya. Fungsi perbankan adalah sebagai lembaga perantara (intermediary institution) antara pemilik dana dan orang yang membutuhkan dana, untuk itu kegiatan utama Perbankan Syariah adalah menghimpun dana dari masyarakat dan menyalurkan kembali dalam bentuk pembiayaan. Kegiatan penghimpunan dana di Bank Muamalah Cabang Maros dilakukan dengan prinsip wadiah dan mudharabah, beberapa produknya seperti giro wadiah bank Muamalat dalam mata uang Rupiah maupun Valas, pribadi maupun perusahaan, tabungan umat junior, tabungan simpatik. Sedangkan mudharabah seperti: Tabungan Haji, Tabungan Investa Cendekia, Tabungan Qurban dan Tabungan dengan Kartu SharE dan Deposito Mudharabah. Sedangkan penyaluran dana dalam bentuk pembiayaan Bagi Hasil adalah dengan akad mudharabah dan musyarakah. Prinsip Bagi Hasil ini merupakan karakteristik utama dalam Perbankan Syariah, akan tetapi dalam kegiatan pembiayaan di Perbankan Syariah masih rendah di bandingkan dengan pembiayaan lainnya seperti Murabahah (jual beli), hal ini disebabkan antara lain karena tingginya resiko yang harus di tanggung oleh bank apabila terjadi kerugian yang di akibatkan bukan dari kesengajaan atau kelalaian dari nasabah sehingga bank akan sangat berhati hati dalam memberikan pembiayaan kepada nasabah. Kendala lainnya adalah Sumber daya Manusia yang kurang memadai, manajemen perbankan syariah, system informasi dan teknologi, sikap masyarakat yang masih memandang Bank Syariah sama dengan bank Konvensional dan tidak adanya standar moral yang diterapkan dalam kegiatan pembiayaan

Leveraging the microbiome to understand clinical heterogeneity in depression: findings from the T-RAD study

Abstract Alterations in the gut microbiome have been linked to a variety of mental illnesses including anxiety and depression. This study utilized advanced bioinformatics tools that integrated both the compositional and community nature of gut microbiota to investigate how gut microbiota influence clinical symptoms in a sample of participants with depression. Gut microbiota of 179 participants with major depressive disorder (MDD) in the Texas Resilience Against Depression (T-RAD) study were analyzed by 16S rRNA gene sequencing of stool samples. Severity of anxiety, depression, and anhedonia symptoms were assessed with General Anxiety Disorder – 7 item scale, Patient Health 9-item Questionnaire, and Dimensional Anhedonia Rating Scale, respectively. Using weighted correlation network analysis, a data-driven approach, three co-occurrence networks of bacterial taxa were identified. One of these co-occurrence networks was significantly associated with clinical features including depression and anxiety. The hub taxa associated with this co-occurrence module –one Ruminococcaceae family taxon, one Clostridiales vadinBB60 group family taxon, and one Christencenellaceae family taxon– were connected to several additional butyrate-producing bacteria suggesting that deficits in butyrate production may contribute to clinical symptoms. Therefore, by considering the community nature of the gut microbiome in a real world clinical sample, this study identified a gut microbial co-occurrence network that was significantly associated with clinical anxiety in a cohort of depressed individuals

Early Improvement in Psychosocial Function Predicts Longer-Term Symptomatic Remission in Depressed Patients

<div><p>The goal of this study was to evaluate the relationship between early change in psychosocial function independent of depression severity and longer-term symptomatic remission. Participants of Combining Medications to Enhance Depression Outcomes trial were randomly selected for model selection (n = 334) and validation (n = 331). Changes in psychosocial function (Work and Social Adjustment Scale, WSAS) from baseline to week 6 were assessed and two data-driven sub-groups of WSAS change were identified in the randomly selected model selection half. Results of analyses to predict symptomatic remission at 3 and 7 months were validated for these sub-groups in the second half (validation sample). From baseline to week 6, psychosocial function improved significantly even after adjusting for depression severity at each visit and select baseline variables (age, gender, race, ethnicity, education, income, employment, depression onset before age 18, anxious features, and suicidal ideation), treatment-arm, and WSAS score. The WSAS change patterns identified two (early improvement and gradual change) subgroups. After adjusting for baseline variables and remission status at week 6, participants with early improvement in the second half (validation sample) had greater remission rates than those with gradual change at both 3 (3.3 times) and 7 months (2.3 times) following acute treatment initiation. In conclusion, early improvement in psychosocial function provides a clinically meaningful prediction of longer-term symptomatic remission, independent of depression symptom severity.</p></div

Zaitun: kajian Islam dan kemasyarakatan

Kondisi kehidupan yang kian mendunia seperti itu juga bakal melahirkan perubahan-perubahan baru dalam etika kehidupan dalam kerangka etika global (the global ethics) yang boleh jadi sepenuhnya bersifat situasional.1-146 hlm .; 23 c