Effect of Formulation Variables on the Stability of a Live,Rotavirus (RV3-BB) Vaccine Candidate using in vitro Gastric Digestion Models to Mimic Oral Delivery

In this work, two different in vitro gastric digestion models were used to evaluate the stability of a live attenuated rotavirus vaccine candidate (RV3-BB) under conditions designed to mimic oral delivery in infants. First, a forced-degradation model was established at low pH to assess the buffering capacity of formulation excipients and to screen for RV3-BB stabilizers. Second, a sequential-addition model was implemented to examine RV3-BB stability under conditions more representative of oral administration to infants. RV3-BB rapidly inactivated at < pH 5.0 (37 °C, 1 h) as measured by an infectivity RT-qPCR assay. Pre-neutralization with varying volumes of infant formula (Enfamil®) or antacid (Mylanta®) conferred partial to full protection of RV3-BB. Excipients with sufficient buffering capacity to minimize acidic pH inactivation of RV3-BB were identified (e.g., succinate, acetate, adipate), however, they concomitantly destabilized RV3-BB in accelerated storage stability studies. Both effects were concentration dependent, thus excipient optimization was required to design candidate RV3-BB formulations which minimize acid-induced viral inactivation during oral delivery while not destabilizing the vaccine during long-term 2–8 °C storage. Finally, a statistical Design -of-Experiments (DOE) study examining RV3-BB stability in the in vitro sequential-addition model identified key formulation parameters likely affecting RV3-BB stability during in vivo oral delivery.     

Innocuous cardiac gunshot that proved fatal: A bitter lesson learned

The management of hemodynamically normal patients with retained intra-pericardial foreign body remains a matter of conjecture. The available literature supports non-operative management of such innocuous foreign bodies. We report our experience of a hemodynamically normal patient with a retained intra-pericardial pellet from a firearm injury. He initially received successful non-operative management but developed fatal hemopericardium 21 days after injury. In this paper, we discussed the pitfalls in the management of such injuries in light of the available literature and summarized the clinical experience.     

iNICU – Integrated Neonatal Care Unit: Capturing Neonatal Journey in an Intelligent Data Way

Neonatal period represents first 28 days of life, which is the most vulnerable time for a child’s survival especially for the preterm babies. High neonatal mortality is a prominent and persistent problem across the globe. Non-availability of trained staff and infrastructure are the major recognized hurdles in the quality care of these neonates. Hourly progress growth charts and reports are still maintained manually by nurses along with continuous calculation of drug dosage and nutrition as per the changing weight of the baby. iNICU (integrated Neonatology Intensive Care Unit) leverages Beaglebone and Intel Edison based IoT integration with biomedical devices in NICU i.e. monitor, ventilator and blood gas machine. iNICU is hosted on IBM Softlayer based cloud computing infrastructure and map NICU workflow in Java based responsive web application to provide translational research informatics support to the clinicians. iNICU captures real time vital parameters i.e. respiration rate, heart rate, lab data and PACS amounting for millions of data points per day per child. Stream of data is sent to Apache Kafka layer which stores the same in Apache Cassandra NoSQL. iNICU also captures clinical data like feed intake, urine output, and daily assessment of child in PostgreSQL database. It acts as first Big Data hub (of both structured and unstructured data) of neonates across India offering temporal (longitudinal) data of their stay in NICU and allow clinicians in evaluating efficacy of their interventions. iNICU leverages drools based clinical rule based engine and deep learning based big data analytical model coded in R and PMML. iNICU solution aims to improve care time, fills skill gap, enable remote monitoring of neonates in rural regions, assists in identifying the early onset of disease, and reduction in neonatal mortality.     

A Quality Improvement Initiative: Improving Exclusive Breastfeeding Rates of Preterm Neonates

This study is a single center quality improvement (QI) initiative in a tertiary care neonatal intensive care unit which was done with an objective to increase the proportion of neonates receiving mother’s own milk (at postnatal age of 7 d) from the current rate of 12.5% to 30% over a period of six weeks. Additional objectives were to evaluate the proportion of mothers’ expressing breast milk within 3 h of birth, on day one and three and the amount of expressed breast milk (EBM) on day one and day seven. A team was formulated to evaluate the reasons for inadequate breast milk expression and to plan the steps for promoting the same. Comprehensive postnatal breast feeding counseling (CPNC) to promote early breast milk expression was initiated soon after the birth of a preterm neonate. CPNC was done for next fifteen mothers and their breast feeding support was streamlined. The effect of CPNC and teamwork was discussed amongst the team members every day and adjustments incorporated (Plan-Do-Study-Act cycle). The proportion of neonates receiving mother’s only milk (MOM) on day 7 increased to 80% (12/15) after 4 wk of QI. Thus, a simple and feasible CPNC package lead to improved breast milk output in mothers.     

Design,synthesis and pharmacological analysis of 5-[4′-(substituted-methyl)[1,1′-biphenyl]-2-yl]-1<Emphasis Type="Italic">H</Emphasis>-tetrazoles

In the present paper 5-[4′-({4-[(4-aryloxy)methyl]-1H-1,2,3-triazol-1-yl}methyl)[1,1′-biphenyl]-2-yl]-1H-tetrazoles (5a–g) and [2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl-substituted-1-carbodithioates (11h–q) have been designed and synthesized. These compounds were subjected to docking (against AT₁ receptor protein enzyme in complex with Lisinopril), in vitro angiotensin converting enzyme inhibition, anti-proliferative, anti-inflammatory screening (through egg albumin denaturation inhibition and red blood cell membrane stabilization assay) and finally anti-fungal activity analyses. Some of the compounds have shown significant pharmacological properties.     

Unusual mode of firearm injury from the recoiled rear end of a gun barrel

Atypical gunshot wounds are caused by a diverse set of parameters relating to weapons and ammunition. We report a previously-unreported and atypical mode of gunshot wound produced by a detached rear end of the barrel of a gun following accidental gun fire, and discuss the difficulties in the management. A 36-year-old man presented to the emergency department with an alleged history of injury on the forehead with the rear end of a gun barrel following accidental gunfire while cleaning the nozzle. Since the time of injury, the patient was in an altered sensorium and had weakness on the right side of the body. There was minimal but continuous bleeding from the wound, with extrusion of brain matter. Skull radiograph showed that the rear end of the barrel had entered the left frontal bone, with associated depressed fracture of the frontal bone. The patient underwent a bicoronal, bifrontal craniotomy with a T-shaped extension towards the barrel to facilitate the reflection of the scalp flap and to avoid any movement of the barrel as it might further injure the brain. Necrotic brain, dura and bone pieces were removed. The patient was doing well at follow-up except for mild residual motor deficits. This case illustrates that while working with limited facilities, particularly in underdeveloped countries, a careful clinical assessment, interpretation of available images and a judicious operative approach can help to save the patient.     

Interrelationship between angiogenesis,inflammation and oxidative stress in Indian patients with multiple myeloma

Background

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal population of plasma cells in the bone marrow (BM). A variety of angiogenic factors, proteases, reactive oxygen species and inflammatory cytokines induce the formation of an extensive and suitable BM microenvironment. Previous studies have established the importance of angiogenic factors, inflammatory molecules and oxidative stress in MM but their interplay and effect on each other are not being taken together.

Methods

Circulatory levels of VEGF, angiopoietin-2 (Ang-2), IL-6 and TNF-α along with the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were investigated in 112 subjects including 62 MM patients and 50 healthy controls. Inter-stage analysis was done to evaluate the association of these molecules with the severity of disease. Pearson correlation was determined to find interrelationship, if any, between these molecules.

Results

We have observed elevated levels of VEGF, Ang-2, IL-6, TNF-α and decreased activity of SOD, GPx in MM patients in comparison to controls. All these molecules also showed a trend with the severity of disease. We have found strong association between these factors upon their correlation and regression analysis.

Conclusion

This study is a step toward understanding the indepth contribution of angiogenesis, inflammation and oxidative stress together in making BM microenvironment suitable for growth, survival and proliferation of malignant plasma cells in MM.