Potential effects of the COVID-19 pandemic on future birth rate

Here, we examine the potential effect of the COVID-19 pandemic on future birth rates. This highly contagious disease originated in China, and rapidly spread worldwide, leading to extensive lockdown policies being implemented globally with the aim of containing the infection rates and its serious attendant consequences. Based on previous extant literature, this paper overviews the potential demographic consequences of the current progressively widespread epidemic on conception and fertility as driven by the data obtained during similar prior incidents. In general, epidemics manifest a common pattern as far as their impact on population, which is remarkably similar to natural disasters, i.e., a steep decline in birth rates followed by gradual increases and then followed by a baby boom. Additionally, we have also depicted how economic conditions, mental health, fear, and mortality may also influence future birth rates

Evaluasi Pelaksanaan RANHAM 2004-2009 dan Rencana Ratifikasi Optional Protocol To The Convention Against Torture (CAT) dalam RANHAM 2004-2009 dan Perencanaan RANHAM 2010-2014

Dalam rangka mengevaluasi kepatuhan (comply) Pemerintah Indonesia dalam menjalankan United Nations Convention Against Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment (UNCAT) yang telah dirati kasi dengan UU No 5 1998, Kemitraan merasa perlu mengadakan kajian ini karena alasan-alasan berikut: (i) Secara hukum Indonesia wajib menjalankan UNCAT karena telah mengikatkan diri pada Konvensi tersebut sejak tahun 1998, sehingga semua pasal-pasal UNCAT (kecuali pasal 20 karena Indonesia mengecualikan diri) bersifat wajib atau legally binding untuk melaksanakannya. (ii) Indonesia belum sepenuhnya mengintegrasikan UNCAT dalam sejumlah peraturan Perundang-undangan nasional sehingga perlu dicermati secara khusus. (iii) Rencana Aksi Nasional Hak Asasi Manusia (RANHAM) 1998-2003 dan RANHAM 2004-2009 dirasa masih memiliki kekosongan substansi dan pelaksanaannya belum konsisten dengan apa yang dituangkan dalam ke dua RANHAM tersebut. Berdasarkan alan-alasan di atas dan makin maraknya pelanggaran HAM yang terjadi di Indonesia, Kemitraan dengan bantuan dana dari Uni Eropa mencoba mengevaluasi secara komprehensive pelaksanaan RANHAM 2004-2009 dan melihat kemungkinan rencana rati kasi Optional Protocol UNCAT yang telah disepakati oleh Majelis Umum PBB pada tanggal 18 Desember 2002 dan telah enter into force pada tanggal 22 Juni 2006. Disamping itu, kajian ini juga memberikan masukan bagi Perencanaan RANHAM 2010-2014

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type Diffuse Large B Cell Lymphoma.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but falling short of providing a consistent relapse-specific genetic signature. In our study, we have focussed attention on the changes in gene expression profile accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo DLBCL patients. Cell of origin remained stable from diagnosis to relapse in 84% of patients, with only a single patient showing COO switching from ABC to GCB. Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC-DLBCLs derived from relapse-associated genes, that defined clinically distinct high and low risk subgroups in ABC-DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year-old patients with superior PFS and OS treated with Ibrutinib-R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials

Longitudinal expression profiling identifies a poor risk subset of patients with ABC-type diffuse large B-cell lymphoma

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell–like (ABC) to germinal center B-cell–like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC–DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC–DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of <60-year–old patients with superior PFS and OS treated with ibrutinib–R-CHOP as part of the PHOENIX trial. Altogether this new signature adds to the existing toolkit of putative genetic predictors now available in DLBCL that can be readily assessed as part of prospective clinical trials

Impact of infection on proteome-wide glycosylation revealed by distinct signatures for bacterial and viral pathogens

Mechanisms of infection and pathogenesis have predominantly been studied based on differential gene or protein expression. Less is known about posttranslational modifications, which are essential for protein functional diversity. We applied an innovative glycoproteomics method to study the systemic proteome-wide glycosylation in response to infection. The protein site-specific glycosylation was characterized in plasma derived from well-defined controls and patients. We found 3862 unique features, of which we identified 463 distinct intact glycopeptides, that could be mapped to more than 30 different proteins. Statistical analyses were used to derive a glycopeptide signature that enabled significant differentiation between patients with a bacterial or viral infection. Furthermore, supported by a machine learning algorithm, we demonstrated the ability to identify the causative pathogens based on the distinctive host blood plasma glycopeptide signatures. These results illustrate that glycoproteomics holds enormous potential as an innovative approach to improve the interpretation of relevant biological changes in response to infection

IGF-I induces vascular endothelial growth factor in human mesangial cells via a Src-dependent mechanism

IGF-I induces vascular endothelial growth factor in human mesangial cells via a Src-dependent mechanism.BackgroundBoth insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) have been implicated in the pathogenesis of early renal dysfunction in diabetes. We investigated whether IGF-I affects VEGF gene expression and protein secretion in human mesangial cells. Furthermore, we studied the intracellular signaling pathway involved and the interaction of IGF-I with mechanical stretch, a known VEGF inducer.MethodsHuman mesangial cells were exposed to IGF-I in the presence and in the absence of (1) anti-IGF-I type I receptor antibody (αIR3) (1 μg/mL), a monoclonal antibody blocking the IGF-I type I receptor; (2) wortmannin (600 nmol/L), a phosphatidylinositol 3-kinase (PI3K) inhibitor; (3) 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a specific Src inhibitor (10 μmol/L); and (4) cyclic stretch (∼10% elongation).ResultsIGF-I induced a dose-dependent increase in VEGF protein levels (10−11 mol/L, 5%; 10−10 mol/L, 14%; 10−9 mol/L, 46%; 10−8 mol/L, 66%; 10−7 mol/L, 68%; P < 0.001). IGF-I–induced VEGF production rose by 6 hours with a peak at 12 hours, and declined by 24 hours (52%, 72%, and 34%, respectively; P < 0.01 at 12 hours). A corresponding 50% increase in VEGF mRNA levels was seen at 6 hours (P < 0.01). IGF-I–induced VEGF protein secretion was not affected by the addition of wortmannin (IGF-I, 76% vs. IGF-I + wortmannin, 79% increase over control; P = NS), but was abolished by αIR3 (IGF-I, 69% vs. IGF-I +αIR3, 0%; P < 0.001) and significantly reduced by PP2 (IGF-I, 50% vs. IGF-I + PP2, 14%; P < 0.01). Simultaneous exposure of human mesangial cells to both IGF-I and stretch failed to further increase VEGF production (IGF-I, 1.49 ± 0.05; stretch, 1.76 ± 0.05; and IGF-I + stretch, 1.83 ± 0.11).ConclusionIGF-I induces VEGF gene expression and protein secretion in human mesangial cells via a Src-dependent mechanism