Anesthetic management of premature conjoined twins posted for nonseparation emergency surgery

Craniopagus conjoined twins are rare, and the chance that an anesthesiologist might face the challenge of providing anesthesia for this condition is very rare. The incidence of conjoined twins ranges from 1 : 50 000 to 1 : 200 000 births. We describe the anesthetic management of a pair of premature craniopagus conjoined twins posted for emergency surgery prior to their separation.     

Increasing the interaction of Borrelia burgdorferi with decorin significantly reduces the 50 percent infectious dose and severely impairs dissemination

Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of decorin-binding protein A (DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID(50)), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing DbpA expression dramatically increased the interaction of B. burgdorferi with decorin and sensitivity to growth inhibition/killing by anti-DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of decorin. Increasing DbpA expression significantly reduced ID(50) values and severely impaired dissemination in severe combined immunodeficiency (SCID) and immunocompetent mice. During infection of SCID mice, B. burgdorferi with increased DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating arthritis virulence. Although increasing DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian infection.     

Knowledge about HIV-AIDS among first-time and regular voluntary non-remunerated blood donors

Acquired Immune Deficiency Syndrome (AIDS) is one of the serious public health problems in India. AIDS education has been considered as one of the main intervention for control. Sexual route is the major route of transmission of Human Immunodeficiency Virus (HIV); however, approximately 2.5% is transmitted through blood and blood products. The present study was carried out to know the level of awareness about HIV infection and blood donation among first time (190) and repeat (310) voluntary donors of all age groups. One pre-structured questionnaire was circulated among altruistic blood donors. About 96.6% donors want to become repeat donors. Majority of the donors had good knowledge about routes of HIV transmission. According to 97.4% donors, it is transmitted by sexual route, according to 87.4% of donors by sharing needle, according to 85% of donors by blood transfusion and 82.4% of donors believe through vertical transmission. However, 32.4% of the donors, still believe that HIV infection could be transmitted through blood donation. Intense motivational program among donors is needed to remove this myth. Regular donors were convinced the importance of regular and repeat blood donation. They came forward to donate blood for the cause of humanity (80.6%) and the sense of pride (27.79%). First time donors were less motivated by the cause of humanity (56.21%) and volunteered because of peer pressure (26.03%) and motivated by relative or friend. Donors were very alert about precaution to be taken for protecting themselves from danger of HIV infection and priority wise use of safe sexual practice (90%), disposable needles (61.43%) and receive tested blood (45.71%) whenever required. When in need of blood for relatives the donors will give priority to the quality (64.65%) and properly tested blood from voluntary blood donors (86.7%).     

Development and evaluation of an in vitro isolation of street rabies virus in mouse neuroblastoma cells as compared to conventional tests used for diagnosis of rabies

In vitro isolation of rabies virus using mouse neuroblastoma cells (MNA) was evaluated. The sensitivity and reliability of in vitro procedure was performed in comparison with mouse inoculation test (MIT), the in vivo method of virus isolation, direct fluorescent antibody test (FAT) and Sellers staining. Of the 33 animal brain samples tested, 24 (72.72%) were positive by MIT. Sensitivity of Sellers stain, FAT and rapid tissue culture infection test (RTCIT) was found to be 54.16, 100 and 91.6% respectively. Concordance of Sellers stain, FAT, RTCIT with MIT was found to be 66.6, 100 and 93.93% respectively. Two samples which were positive by FAT and MIT showed gross contamination in cell lines, which is one of the drawbacks of RTCIT. However, rabies virus could be isolated in MNA cells from two of the eight human cerebrospinal fluid (CSF) samples from clinico-epidemiologically suspected cases of rabies. Both MIT and FAT showed negative results in the two CSF samples. RTCIT appears to be a fast and reliable alternative to MIT and holds promise in antemortem diagnosis of rabies, which is otherwise, a challenging task for a reference laboratory.     

Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion

The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9.     

Kinetics and Characterization of Non-enzymatic Fragmentation of Monoclonal Antibody Therapeutics

Purpose

To understand non-enzymatic hydrolytic fragmentation of a monoclonal antibody therapeutic under temperature stressed conditions and investigating possible mechanism for the same.

Methods

The mAb therapeutic was incubated at 50°C in phosphate buffer at pH 6.5 and fragmentation was monitored at different ionic strengths under stressed conditions. The incubated mAb was sampled at regular time intervals by analytical Size Exclusion Chromatography (SEC).

Results

It was observed that 57% of the mAb product fragmented over 4 days into two fragment species – Fc-Fab and Fab with molecular weights of 97 KDa and 47 KDa, respectively, as measured by mass spectrometry (MS) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The fragmentation rate was slow initially and then accelerated with time. No change in % aggregate level was observed in this duration, implying that degradation was primarily via fragmentation at high temperature. Kinetics of hydrolytic fragmentation was hypothesized and SEC data was fitted to estimate the kinetic rate constants. While degradation of the monomer into fragment species was non-Arrhenius with a negative activation energy, further degradation of Fab-Fc fragments into Fab or Fc fragments followed Arrhenius Law with an activation energy of 2.1 and 15.38 kcal/mol, respectively.

Conclusion

High temperature (50°C) causes mAb to cleave at the hinge region to form Fab-Fc and Fab/Fc, as confirmed by dynamic light scattering, SDS-PAGE, SEC, and MS. A kinetic model for hydrolytic fragmentation has been proposed. The results are expected to assist end users in formulation development as well as in monitoring stability of biotherapeutic products.

     

Pearl Millet Mapping Population Parents: Performance and Selection Under Salt Stress Across Environments Varying in Evaporative Demand

It is vital to screen the germplasm of crop plants for salt stress tolerance so as to utilize them in breeding programs. Accordingly, in the present study, twenty diverse inbred lines, parents of mapping populations of pearl millet were chosen to determine the phenotypic contrasts for seed yield, which can open the way for developing salt tolerance QTLs. Parents were grown in two summer seasons (late and early) with VPD ≥ 2 kPa, and one rainy season with VPD < 2 kPa, during flowering and grain filling under saline (150 and 200 mM) and non-saline (0 mM) conditions. Salinity delayed flowering time by a fortnight in the summer seasons but only 5–6 days in the low VPD rainy season. Salinity decreased grain yield by 86% in late-summer and 80% in early-summer, but less than 70% in rainy season. GY penalty was higher than vegetative biomass under saline conditions especially in summer season when the evaporative demand was very high. It appears that reproduction and grain filling are sensitive to high temperature that can compound the effect of salinity and high VPD. GY of inbreds under salinity was not better in comparison with non-saline conditions. DOF and grain density (thousand grain weight) were found as important correlated traits under salinity. Also, GY was affected significantly if VPD increased during flowering time.