Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus

Modified oligodeoxynucleotides complementary to RNA of human immunodeficiency virus 1 (HIV-1) were tested for their ability to inhibit virally induced syncytium formation and expression of viral p24 protein. The modifications of oligomers include replacement of backbone phosphodiester groups with phosphorothioates and various phosphoramidates. All oligomers were found to be active. Oligomers with complete replacement of phosphodiesters with phosphoramidate or phosphorothioate groups were more active at the micromolar range than were unmodified oligomers of the same sequence. In addition, modified and unmodified homooligonucleotides also showed inhibition of HIV-1 replication. It is suggested that different classes of oligonucleotides may inhibit HIV replication by different mechanisms.     

Immune and Inflammatory Determinants Underlying Alzheimer’s Disease Pathology

Journal of Neuroimmune Pharmacology - This study examines the link between peripheral immune changes in perpetuation of the Alzheimer’s disease (AD) neuropathology and cognitive deficits. Our...     

Assistive Framework for Automatic Detection of All the Zones in Retinopathy of Prematurity Using Deep Learning

Journal of Digital Imaging - Retinopathy of prematurity (ROP) is a potentially blinding disorder seen in low birth weight preterm infants. In India, the burden of ROP is high, with nearly 200,000...     

Human pregnancy levels of estrogen and progesterone contribute to humoral immunity by activating TFH/B cell axis

Circulating T_FH (cT_FH) cells express CXCR5, PD-1, and, when activated, ICOS, and release IL-21. According to the production of IFN-γ, IL-4, and IL-17 and expression of FoxP3, these cells are also classified as cT_FH1, cT_FH2, cT_FH17, and cT_FR cells, respectively. This CD4⁺T-cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti-HBsAg IgG in HBV immunized women, but the frequency of cT_FH cells was directly correlated with estradiol levels. In vitro, pregnancy-related dose of 17-β-estradiol (E2) directly increased the percentage of different cT_FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T_FH cells derived from naïve CD4⁺T-cells, only E2 amplified the release of IL-21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB-activated B/T_FH cell co-cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL-10⁺T_FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT_FH and B cell subsets.     

Blood plasma separation in elevated dimension T-shaped microchannel

In recent years, microfluidic chips have proven ideal tools for biochemical analysis, which, however, demands a unique and compatible plasma separation scheme. Various research groups have established continuous flow separation methods in microfluidic devices; however, they have worked with relatively small dimension microchannels (similar to the blood cell diameter). The present work demonstrates separation of plasma by utilizing the hydrodynamic separation techniques in microchannels with size of the order of mm. The separation process exploits the phenomenon, which is very similar to that of plasma skimming explained under Zweifach-Fung bifurcation law. The present experiments demonstrates for, the first time, that applicability of the Zweifach-Fung bifurcation law can be extended to dimensions much higher than the suspended particle size. The T-microchannel device (comprising perpendicularly connected blood and plasma channels) were micro-fabricated using conventional PDMS micro-molding techniques. Three variables (feed hematocrit, main channel width, and flow rate distributions) were identified as the important parameters which define the device’s efficiency for the blood plasma separation. A plasma separation efficiency of 99.7 % was achieved at a high flow ratio. Novel concepts of 2-stage or multiple plasma channel designs are also proposed to yield high separation efficiency with undiluted blood. The possible underlying principle causing plasma separation (viz. aggregation and shear thinning) are investigated in detail as part of this work. The results are significant because they show nearly 100 % separations in microchannels which are much easier to fabricate than previously designed devices.     

Convalescent plasma therapy for severe Covid-19 in patients with hematological malignancies

BackgroundData on convalescent plasma therapy (CPT) in patients of hematological malignancies with severe Covid-19 is scarce.ObjectiveTo study 14-day mortality in patients who received CPT.Patients & methodsRetrospective multicentre observational study conducted in 4 centres treating haematological malignancies across Delhi-national capital region. Total 33 haematological malignancies patients with severe Covid-19 who received CPT were analysed.ResultsThe median age of the study cohort was 62 years (18–80 years). Twenty one percent patients had 1 comorbidity, 18 % had 2 comorbidities and 6% patients had 3 and 5 comorbidities each. Twenty four patients were on active therapy. Sixty nine percent of patients required ICU stay. Twenty five patients received plasma therapy within 7 days (early) of diagnosis of Covid-19 infection. Median day of plasma infusion from date of diagnosis of Covid-19 infection was 4 days (range: 2–25 days). Patient who had early initiation of plasma therapy had shorter duration of hospitalisation (12.7 vs 24.3 days, p = 0.000). Overall mortality in the cohort was 45.5%. There was no effect of disease status, active therapy, presence of comorbidity on mortality. There was no difference in the mortality in patients receiving early vs late initiation of plasma therapy or in patients receiving one versus two plasma therapy.ConclusionsWe provide a large series of patients with hematological malignancies and role of CPT in this group.     

Portal vein variations in 1000 patients: surgical and radiological importance

Objective:

The purpose of the study was to evaluate the spectrum and incidence of intrahepatic portal vein (PV) variations on triphasic abdomen multidetector CT (MDCT) and to discuss the surgical and radiological implications.

Methods:

A retrospective review of 1000 triphasic MDCT abdomen scans was performed in patients sent for various liver and other abdominal pathologies between January 2014 and August 2014. A total of 967 patients (N = 967) were included in the study. The variations in branching pattern of PV were classified according to classification used by Covey et al (Covey AM, Brody LA, Getrajdman GI, Sofocleous CT, Brown KT. Incidence, patterns, and clinical relevance of variant portal vein anatomy. AJR Am J Roentgenol 2004; 183: 1055–64) and Koç et al (Koç Z, Oğuzkurt L, Ulusan S. Portal vein variations: clinical implications and frequencies in routine abdominal CT. Diagn Interv Radiol 2007; 13: 75–80).

Results:

Normal anatomy (Type I) was seen in 773 patients (79.94%) out of 967 patients in our study. Trifurcation (Type II) anomaly was seen in 66 (6.83%) of cases. Right posterior vein as first branch of main PV (Type III) anomaly was seen in 48 (4.96%) of cases. Type IV anomaly and Type V anomaly was seen in 26 (2.69%) and 13 (1.34%) cases, respectively. 19 cases showed other types of variations.

Conclusion:

Variations in the hepatic PV branching patterns are commonly seen that are similar to variations in hepatic artery and biliary anatomy. Knowledge of these variations is extremely important for transplant surgeons and intervention radiologists.

Advances in knowledge:

Awareness of the variations in PV branching patterns is essential for intervention radiologists and vascular surgeons and avoids major catastrophic events.     

“Ride-on” technique and other simple and logical solutions to counter most common complications of silicone implants in augmentation rhinoplasty

Augmentation rhinoplasty can be carried out using a wide range of materials including autologous bone and/or cartilage as well as alloplasts. Use of biologic bone and cartilage grafts results in lower infection rates, but they are associated with long-term resorption and donor-site morbidity. Alloplastic materials, in particular silicone, have been associated in literature with extrusion, necrosis of the tip, mobility and deviation or displacement of the implant, immobile nasal tip and infection. However, they have the advantages of being readily available and easy to reshape with no requirement for harvesting autografts.

Aim:

To overcome these problems associated with silicone implants for which the authors have devised a novel technique, the “rideon technique”.

Materials and Methods:

The present study was carried out on 11 patients over a period of 4 years. The authors have devised a simple technique to fix the silicone implant and retain it in place. Restricting the implant to only dorsum avoided common complications related to the silicone implant.

Results:

The authors have used this technique in 11 patients with encouraging results. Follow-up ranged from 12 months to 36 months during which patients were assessed for implant mobility, implant extrusion and tip necrosis. There was no incidence of above mentioned complications in these patients.

Conclusion:

The “rideon technique” provides excellent stability to silicone implants and restricting the implant only to dorsum not only eliminates chances of tip necrosis and thus implant extrusion but also maintains natural shape, feel and mobility of the tip.KEY WORDS: Alloplasts, autografts, rhinoplasty, silicone implants