Comparison of ferric carboxymaltose and iron sucrose for treatment of iron deficiency anemia in pregnancy at tertiary care centre, Western India

Background: Iron deficiency anemia is the most common haematological health problem among pregnant women but can be prevented by effective measure. The study aimed to evaluate the efficacy and safety of intravenous ferric carboxymaltose (FCM) in comparison with intravenous Iron sucrose (IS) for treatment of iron deficiency anemia in pregnancy. Methods: A prospective interventional comparative study was conducted from (June 2021-June 2022) at a tertiary care hospital. Pregnant women diagnosed with moderate to severe iron deficiency anaemia were screened for the study. One hundred patients were randomized to receive either intravenous FCM or IS. Treatment effectiveness was assessed by repeat Haemoglobin (Hb) and RBC indices measurement after 4 weeks of completion of therapy. Safety was assessed by analysis of adverse drug reactions during infusion and 2 hours after infusion. Results: Mean rise in Hb at 4 weeks was significantly higher in FCM group (1.67±0.47 Vs 1.07±0.25; p<0.0001) as compared to IS group.  There was also rise in other biochemical parameters like MCV and MCHC in both groups. Numbers of visits were significantly less in FCM group. No serious adverse events were noted in either group. Conclusions: Intravenous ferric carboxymaltose is more effective and safer as compared to intravenous iron sucrose in the management of anemia during pregnancy. It has advantage to administer large dose in single sitting which reduce overall cost of therapy and hence will lead to better compliance in community setting

Myc-binding Protein Orthologue Interacts with AKAP240 In the Central Pair Apparatus of the \u3cem\u3eChlamydomonas\u3c/em\u3e Flagella

Background Flagella and cilia are fine thread-like organelles protruding from cells that harbour them. The typical ‘9 + 2’ cilia confer motility on these cells. Although the mechanistic details of motility remain elusive, the dynein-driven motility is regulated by various kinases and phosphatases. A-kinase anchoring proteins (AKAPs) are scaffolds that bind to a variety of such proteins. Usually, they are known to possess a dedicated domain that in vitro interacts with the regulatory subunits (RI and RII) present in the cAMP-dependent protein kinase (PKA) holoenzyme. These subunits conventionally harbour contiguous stretches of a.a. residues that reveal the presence of the Dimerization Docking (D/D) domain, Catalytic interface domain and cAMP-Binding domain. The Chlamydomonas reinhardtii flagella harbour two AKAPs; viz., the radial spoke AKAP97 or RSP3 and the central pair AKAP240. Both these were identified on the basis of their RII-binding property. Interestingly, AKAP97 binds in vivo to two RII-like proteins (RSP7 and RSP11) that contain only the D/D domain. Results We found a Chlamydomonas Flagellar Associated Protein (FAP174) orthologous to MYCBP-1, a protein that binds to organellar AKAPs and Myc onco-protein. An in silico analysis shows that the N-terminus of FAP174 is similar to those RII domain-containing proteins that have binding affinities to AKAPs. Binding of FAP174 was tested with the AKAP97/RSP3 using in vitro pull down assays; however, this binding was rather poor with AKAP97/RSP3. Antibodies were generated against FAP174 and the cellular localization was studied using Western blotting and immunoflourescence in wild type and various flagella mutants. We show that FAP174 localises to the central pair of the axoneme. Using overlay assays we show that FAP174 binds AKAP240 previously identified in the C2 portion of the central pair apparatus. Conclusion It appears that the flagella of Chlamydomonas reinhardtii contain proteins that bind to AKAPs and except for the D/D domain, lack the conventional a.a. stretches of PKA regulatory subunits (RSP7 and RSP11). We add FAP174 to this growing list

Crustal structure and rift tectonics across the Cauvery-Palar basin, Eastern Continental Margin of India based on seismic and potential field modelling

The Cauvery-Palar basin is a major peri-cratonic rift basin located along the Eastern Continental Margin of India (ECMI) that had formed during the rift-drift events associated with the breakup of eastern Gondwanaland (mainly India-Sri Lanka-East Antarctica). In the present study, we carry out an integrated analysis of the potential field data across the basin to understand the crustal structure and the associated rift tectonics. The composite-magnetic anomaly map of the basin clearly shows the onshore-to-offshore structural continuity, and presence of several high-low trends related to either intrusive rocks or the faults. The Curie depth estimated from the spectral analysis of offshore magnetic anomaly data gave rise to 23 km in the offshore Cauvery-Palar basin. The 2D gravity and magnetic crustal models indicate several crustal blocks separated by major structures or faults, and the rift-related volcanic intrusive rocks that characterize the basin. The crustal models further reveal that the crust below southeast Indian shield margin is similar to 36 km thick and thins down to as much as 13-16 km in the Ocean Continent Transition (OCT) region and increases to around 19-21 km towards deep oceanic areas of the basin. The faulted Moho geometry with maximum stretching in the Cauvery basin indicates shearing or low angle rifting at the time of breakup between India-Sri Lanka and the East Antarctica. However, the additional stretching observed in the Cauvery basin region could be ascribed to the subsequent rifting of Sri Lanka from India. The abnormal thinning of crust at the OCT is interpreted as the probable zone of emplaced Proto-Oceanic Crust (POC) rocks during the breakup. The derived crustal structure along with other geophysical data further reiterates sheared nature of the southern part of the ECMI

Crustal structure and rift architecture across the Krishna-Godavari basin in the central Eastern Continental Margin of India based on analysis of gravity and seismic data

The Krishna-Godavari basin is a rifted passive margin basin that developed orthogonally to the NW-SE trending Pranhita-Godavari graben along the central Eastern Continental Margin of India in response to the continental rifting process and the subsequent seafloor spreading between India and eastern Antarctica during the early Cretaceous period. The 3-D gravity interpretation of both the onshore and offshore sections of the basin integrated with detailed seismic reflection and refraction data provided significant new information about the crustal architecture and the early breakup history of the basin. The gravity-derived crustal models indicate that the crust at the eastern Indian shield margin is 39-41 km thick and thins to as much as 20-23 km at the Ocean Continent Transition (OCT) in the offshore. There is a significant variation in the nature of crust and the configuration along the margin between the three crustal domains encompassing the basin: the Cuddapah basin, Pranhita-Godavari Graben, and the Eastern Ghat Mobile Belt that indicates the lateral segmentation of the margin. A zone of high density (3.0 g/cm(3)) crustal material at the OCT separates the pure continental and oceanic crusts on either side. The Moho is shallowest along this zone and brought the upper mantle notably close to the surface, which indicates that it could be comprised of Proto-Oceanic Crustal rocks. Furthermore, the present study highlights a major basement structural high in the deep offshore area of the margin. The geophysical signatures over this structure suggest that it is a crustal scale feature that is characterized by intrusive volcanic rocks, comprised of low density crust, and lies close to the OCT towards offshore. Based on the inferred tectonic reconstruction, we believe that this structural high could be a continental fragment that was left behind during the process of breakup between India and the Elan Bank. (c) 2012 Elsevier Ltd. All rights reserved

Measurement of Signal‐to‐Noise Ratio In Graphene‐Based Passive Microelectrode Arrays

This work aims to investigate the influence of various electrode materials on the signal‐to‐noise ratio (SNR) of passive microelectrode arrays (MEAs) intended for use in neural interfaces. Noise reduction substantially improves the performance of systems which electrically interface with extracellular solutions. The MEAs are fabricated using gold, indium tin oxide (ITO), inkjet printed (IJP) graphene, and chemical vapor deposited (CVD) graphene. 3D‐printed Nylon reservoirs are adhered to glass substrates with identical MEA patterns and filled with neuronal cell culture media. To precisely control the electrode area and minimize the parasitic coupling of metal interconnects and solution, SU‐8 photoresist is patterned to expose only the area of the electrode to solution and cap the remainder of the sample. Voltage signals with varying amplitude and frequencies are applied to the solution using glass micropipettes, and the response is measured on an oscilloscope from a microprobe placed on the contact pad external to the reservoir. The time domain response signal is transformed into a frequency spectrum, and SNR is calculated. As the magnitude or the frequency of the input signal gets larger, a significantly increased signal‐to‐noise ratio was observed in CVD graphene MEAs compared to others. This result indicates that 2‐dimensional nanomaterials such as graphene can provide better signal integrity and potentially lead to improved performance in hybrid neural interface systems

Chronic Obstructive Pulmonary Diseased Human Lung Fibroblasts Secrete Increased Matrix Metalloproteases -12 and -8

INTRODUCTION: According to the American Lung Association, 16.5 million people have Chronic Obstructive Pulmonary Disease (COPD), the third leading cause of death in the United States. COPD is a condition in which the airways of the lung are inflamed, and the alveoli thicken leading to decreased oxygen exchange and the ability to breathe. The thickening of the airway is in part due to abnormal remodeling of the extracellular matrix. Dysregulation of Matrix Metalloprotease (MMP) activity leads to the breakdown of collagen type I, a necessary component of the extracellular matrix in the lung tissue. In this study, we measure MMP-8 and MMP-12 production by Human Lung Fibroblasts (HLFB) reared in serum-free media (normal (NHLFB) and COPD Diseased (DHLFB)). METHODS: Commercially available early passage HLFB established from lung tissue, obtained during a biopsy, were cultured and passaged in our laboratory through passage 4. Both normal (NHLFB) and diseased (DHLFB) cells were viable when cultured at subconfluence for 24 hours in a serum-free medium. We collected conditioned media (secreted fraction) and cell-associated matrix (incorporated fraction) from the cultures following 24 hours in serum-free medium or treatment with 5ug Extracellular Matrix Protection Factor-2 (ECPF-2). ECPF-2 is a novel inhibitor of MMP-8 and -12 activity. Utilizing commercially available ELISA kits, we measured intact collagen type I (Chondrex), degraded collagen type I (CUSABIO), MMP-8 (Quantikine, Abcam), MMP-12 (Abcam), and MMP-9 (Abcam). RESULTS: There were detectable levels of MMP-12 (ng/culture) and MMP-8 (pg/culture) in both the secreted (conditioned media) and incorporated (extracellular matrix) fractions. Overall, DHLFB produced 3-fold more secreted MMP-12 [150ng/culture versus 50ng/culture] and 14-fold less incorporated MMP-12 [20ng/culture versus 300ng/culture] than the NHLFB. In the case of MMP-8, DHLFB produced 2-fold less secreted MMP-8 [30pg/culture versus 80pg/culture], while the incorporated fractions of MMP-8 were relatively similar in both normal and diseased cultures. In line with these findings, the diseased lung fibroblasts secreted approximately 10-fold higher levels of degraded collagen type I, confirming the diseased nature of the cells. DISCUSSION: Our findings suggest that MMP-8 has a role in the increased degradation of the extracellular matrix in COPD since collagen type I is a preferred substrate for MMP-8. But the role of MMP-12 in the disease process may be more indirect and involve elastolysis that could disrupt the interactions with collagen type I and facilitate collagen degradation by allowing access to the fibril by MMP-8. Future studies will measure elastin turnover in these cultures to get a clearer picture of the dysregulation of the extracellular matrix associated with COPD

GDF15 Suppresses Lymphoproliferation and Humoral Autoimmunity in a Murine Model of Systemic Lupus Erythematosus

Growth and differentiation factor 15 (GDF15), a divergent member of the transforming growth factor-beta superfamily, has been associated with acute and chronic inflammatory conditions including autoimmune disease, i.e., type I diabetes and rheumatoid arthritis. Still, its role in systemic autoimmune disease remains elusive. Thus, we studied GDF15-deficient animals in Fas-receptor intact (C57BL/6) or deficient (C57BL/6(lpr/lpr)) backgrounds. Further, lupus nephritis (LN) microdissected kidney biopsy specimens were analyzed to assess the involvement of GDF15 in human disease. GDF15-deficiency in lupus-prone mice promoted lymphoproliferation, T-, B- and plasma cell-expansion, a type I interferon signature, and increased serum levels of anti-DNA autoantibodies. Accelerated systemic inflammation was found in association with a relatively mild renal phenotype. Splenocytes of phenotypically overall-normal Gdf15-/- C57BL/6 and lupus-prone C57BL/6(lpr/lpr) mice displayed increased in vitro lymphoproliferative responses or interferon-dependent transcription factor induction in response to the toll-like-receptor (TLR)-9 ligand CpG, or the TLR-7 ligand Imiquimod, respectively. In human LN, GDF15 expression was downregulated whereas type I interferon expression was upregulated in glomerular- and tubular-compartments versus living donor controls. These findings demonstrate that GDF15 regulates lupus-like autoimmunity by suppressing lymphocyte-proliferation and -activation. Further, the data indicate a negative regulatory role for GDF15 on TLR-7 and -9 driven type I interferon signaling in effector cells of the innate immune system