Pattern of antibiotic use in neonatal intensive care unit in tertiary care hospital in Southern India

Background: Repeated and prolonged courses of antibiotics exposure have resulted in an increase in the prevalence of hospital acquired infections and antibiotic resistant profile. The objective of this study was to quantify the use of antibiotics in a neonatal intensive care unit (NICU) from rural tertiary health care centre.Methods: A hospital based cross-sectional study was conducted in the NICU of tertiary care hospital located in western Maharashtra, India during the year 2011-12. A total of 237 neonates admitted to NICU from October 2011 to March 2012 were enrolled in the study according to inclusion criteria of the study. Demographic details, data on antibiotic prescriptions (name, dose, frequency, route of administration) were recorded by utilizing pre-tested structured proforma.Results: A total of 3822 prescriptions were received by the neonates and commonly prescribed antibiotics were amikacin (75.53%), cefotaxime (43.34%) and ampicillin (31.33%) respectively. It was also noted that 50% of the drugs prescribed were in compliance with the national list of essential medicines 2011. The max, 68.75% of antibiotics prescribed were in generics forms however, 12.5% were prescribed in the form of fixed dose combinations.Conclusions: The revealed that 3rd generation cephalosporins and amikacin are most commonly used antibiotics in NICU

Nanocrystalline Pentaerythritoltetranitrate using Sol-Gel Process

The secondary explosives developed with reduced particle size tend to be more insensitive for mechanical stimuli and may release energy with faster rate and gaining more importance nowadays. Therefore, aiming to reduce the particle size of one of the popular explosives, viz., pentaerythritoltetranitrate (PETN) to the nanometer range, a method for preparation of nanocrystalline PETN in the silica (SiO2) gel matrix using sol-gel process has been demonstrated. The PETN-SiO2 xerogels were prepared containing PETN content ranging from 50 per cent to 90 per cent (w/w) and the xerogels were characterised using different techniques. An exothermic peak at around 185 oC preceded by an endotherm in thermal analysis accompanied with weight loss in the temperature range from 150 oC to 200 oC   for the xerogel confirmed the presence of PETN in xerogel. Infrared spectra of xerogels showed peaks at around 1285 cm-1 and 1700 cm-1 assigned to O-NO2 and C-O bond representing PETN. Small angle x-ray scattering measurements on xerogels indicated that PETN entered in the pores of silica matrix. Transmission electron microscopy revealed that cystalline PETN    with particle size of around 15 nm dispersed in silica xerogel. The specific surface area for the PETN-SiO2 (90:10) xerogels was found to be 75 m2/g.Defence Science Journal, 2011, 61(6), pp.534-539, DOI:http://dx.doi.org/10.14429/dsj.61.59

Using enhanced number and brightness to measure protein oligomerization dynamics in live cells

Protein dimerization and oligomerization are essential to most cellular functions, yet measurement of the size of these oligomers in live cells, especially when their size changes over time and space, remains a challenge. A commonly used approach for studying protein aggregates in cells is number and brightness (N&B), a fluorescence microscopy method that is capable of measuring the apparent average number of molecules and their oligomerization (brightness) in each pixel from a series of fluorescence microscopy images. We have recently expanded this approach in order to allow resampling of the raw data to resolve the statistical weighting of coexisting species within each pixel. This feature makes enhanced N&B (eN&B) optimal for capturing the temporal aspects of protein oligomerization when a distribution of oligomers shifts toward a larger central size over time. In this protocol, we demonstrate the application of eN&B by quantifying receptor clustering dynamics using electron-multiplying charge-coupled device (EMCCD)-based total internal reflection microscopy (TIRF) imaging. TIRF provides a superior signal-to-noise ratio, but we also provide guidelines for implementing eN&B in confocal microscopes. For each time point, eN&B requires the acquisition of 200 frames, and it takes a few seconds up to 2 min to complete a single time point. We provide an eN&B (and standard N&B) MATLAB software package amenable to any standard confocal or TIRF microscope. The software requires a high-RAM computer (64 Gb) to run and includes a photobleaching detrending algorithm, which allows extension of the live imaging for more than an hour

Persistent mullerian duct syndrome with testicular seminoma in transverse testicular ectopia

Persistent Mullerian Duct Syndrome (PMDS) is a disorder of male pseudohermaphroditism characterized by the persistence of Mullerian duct derivatives (uterus, fallopian tubes, and upper two-third of vagina) in a phenotypically and genotypically male. Transverse testicular ectopia (TTE) is a rare congenital anomaly in which both gonads migrate toward same hemiscrotum. About 150 cases of PMDS and 100 cases of TTE have been reported in previous studies. Testicular tumor in patients with PMDS with TTE is very rare. We report a case of testicular seminoma in a 35-year-old male patient with PMDS and TTE. Preoperative diagnosis was not possible in most of the reported cases

Emerging CAR T Cell Strategies for the Treatment of AML

Engineered T cells expressing chimeric antigen receptors (CARs) on their cell surface can redirect antigen specificity. This ability makes CARs one of the most promising cancer therapeutic agents. CAR-T cells for treating patients with B cell hematological malignancies have shown impressive results. Clinical manifestation has yielded several trials, so far five CAR-T cell therapies have received US Food and Drug Administration (FDA) approval. However, emerging clinical data and recent findings have identified some immune-related toxicities due to CAR-T cell therapy. Given the outcome and utilization of the same proof of concept, further investigation in other hematological malignancies, such as leukemias, is warranted. This review discusses the previous findings from the pre-clinical and human experience with CAR-T cell therapy. Additionally, we describe recent developments of novel targets for adoptive immunotherapy. Here we present some of the early findings from the pre-clinical studies of CAR-T cell modification through advances in genetic engineering, gene editing, cellular programming, and formats of synthetic biology, along with the ongoing efforts to restore the function of exhausted CAR-T cells through epigenetic remodeling. We aim to shed light on the new targets focusing on acute myeloid leukemia (AML)

Bispecific CD33/CD123 targeted chimeric antigen receptor T cells for the treatment of acute myeloid leukemia

CD33 and CD123 are expressed on the surface of human acute myeloid leukemia blasts and other noncancerous tissues such as hematopoietic stem cells. On-target off-tumor toxicities may limit chimeric antigen receptor T cell therapies that target both CD33 and CD123. To overcome this limitation, we developed bispecific human CD33/CD123 chimeric antigen receptor (CAR) T cells with an “AND” logic gate. We produced novel CD33 and CD123 scFvs from monoclonal antibodies that bound CD33 and CD123 and activated T cells. Screening of CD33 and CD123 CAR T cells for cytotoxicity, cytokine production, and proliferation was performed, and we selected scFvs for CD33/CD123 bispecific CARs. The bispecific CARs split 4-1BB co-stimulation on one scFv and CD3ζ on the other. In vitro testing of cytokine secretion and cytotoxicity resulted in selecting bispecific CAR 1 construct for in vivo analysis. The CD33/CD123 bispecific CAR T cells were able to control acute myeloid leukemia (AML) in a xenograft AML mouse model similar to monospecific CD33 and CD123 CAR T cells while showing no on-target off-tumor effects. Based on our findings, human CD33/CD123 bispecific CAR T cells are a promising cell-based approach to prevent AML and support clinical investigation