Search

Background and objectives The Score for Neonatal Acute Physiology II with Perinatal Extension (SNAPPE-II) is a vital tool for prognostication in newborns. The study was conducted with the hypothesis that the performance of the SNAPPE-II score might be affected by the presence of sepsis in newborns admitted with possible early onset septicemia and whether score performance varies between culture positive and culture negative sepsis. Methods The prospective observational study was conducted over a period of 1 year (January 2014 to January 2015) in neonates presenting with clinical suspicion of sepsis to the Sick Newborn Care Unit (SNCU) of a tertiary care hospital in Eastern India. Results SNAPPE-II score cut-off of ≥20 offered the highest sensitivity of 74.5% with specificity 48.3%, PPV 27.6% and NPV 87.7%. Comparison of mortality proportions between the two subgroups defined by this cut-off returned p= 0.005 with OR 3.47 (95% 1.40 to 8.64). No significant association was found between SNAPPE-II score and blood culture results; mean scores for culture positive (25.16 ± 15.6) and negative groups (24.49 ± 15.6) were comparable (p= 0.920). Conclusions At a cut-off value of ≥20 in presence of sepsis, SNAPPE-II score offers acceptable indices to predict mortality outcome. Prediction of outcome by SNAPPE-II score is not affected by positive or negative blood culture sepsis.

In cerebral tissues, due to continuous and high metabolic demand, energy is produced exclusively by mitochondrial oxidative phosphorylation (OXPHOS). Obstruction of blood flow leads to cerebral ischemia, hypoxia and decreased cellular ATP production. The reactive oxygen species (ROS) generated as by-product of OXPHOS alter many intracellular signaling pathways and result in damaged cellular components. Under such hypoxic conditions, a key factor known as hypoxia inducible factor 1 (HIF1) is stabilized and activated and such activation induces expression of a defined set of target genes which are required for cell survival and angiogenesis. Reperfusion that follows such ischemia alters signaling pathways which are involved in cellular fate. Here, we will review the role of ROS, HIF-1 alpha and other signaling network in mitochondrial dysfunction and cell fate determination in ischemia-reperfusion models in the brain. We will also address both current and future therapeutic strategies for clinical significance that are being developed for treatment of cerebral ischemia.

// Arijit Bhowmik 1 , Sayak Chakravarti 1, * , Aparajita Ghosh 2, * , Rajni Shaw 1, * , Suman Bhandary 2 , Satyaranjan Bhattacharyya 3 , Parimal C. Sen 2 and Mrinal K. Ghosh 1 1 Signal Transduction in Cancer and Stem Cells Laboratory, Translational Research Unit of Excellence (TRUE), Division of Cancer Biology and Inflammatory Disorder, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata 700091, India 2 Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata 700054, India 3 Division of Surface Physics, Saha Institute of Nuclear Physics, Kolkata 700064, India * These authors have contributed equally to this work Correspondence to: Mrinal K. Ghosh, email: mrinal.res@gmail.com Keywords: glioma, blood brain barrier, 3,3’-diindolylmethane encapsulated nanoparticle, somatostatin receptor 2 peptide, epidermal growth factor receptor Received: November 22, 2016 Accepted: May 22, 2017 Published: June 27, 2017 ABSTRACT Current therapy for Glioblastoma is insufficient because of the presence of blood brain barrier. It limits the transport of essential drugs to the tumor sites. To overcome this limitation we strategized the delivery of an anticancer compound 3,3’-diindolylmethane by encapsulation in poly (lactic-co-glycolic acid) nanoparticles. These nanoparticles were tagged with a novel peptide against somatostatin receptor 2 (SSTR2), a potential target in glioma. The nanoformulation (27-87nm) had loading and encapsulation efficiency of 7.2% and 70% respectively. It was successfully internalized inside the glioma cells resulting in apoptosis. Furthermore, an in vivo bio-distribution study revealed the selective accumulation of the nanoformulation into rat brain tumor sites by crossing the blood brain barrier. This resulted in abrogation of epidermal growth factor receptor pathway activation in glioma cells. Our novel nanopreparation therefore shows great promise to serve as a template for targeted delivery of other therapeutics in treating GBM.

To generate data of electrocardiogram (ECG) parameters according to gestational age in Indian newborns. An observational study was carried out over 7 months in neonatology unit of a tertiary care teaching hospital. Following auscultation, ECG parameters were recorded simultaneously in 12 leads, on third day of life, in hemodynamically stable neonates. Data from 364 babies were analyzed, keeping at least 30 records for each gestational age between 30 to 42 weeks. There was no difference in mean heart rate recorded through auscultation and ECG traces. The mean (SD) values recorded were: P wave duration 0.04 (0.01) s, P wave amplitude 1.3 (0.4) mm, T wave duration 0.07 (0.02) s, T wave amplitude 1.1 (0.6) mm, PR interval 0.09 (0.02) s, QRS duration 0.04 (0.01) s, QT interval 0.26 (0.02) s, QTc 0.4 (0.03) s and QRS axis 127 (22) degree. Gestation age-wise percentile charts of different ECG parameters were generated. These gestational age-wise percentile charts of different ECG parameters for Indian newborns can be used as reference for neonatal ECG.

Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences, ~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.

Triple negative breast cancer (TNBC) is one of the most common invasive malignancies among women, associated with poor prognosis. Standard chemotherapy targets all dividing cells, resulting in dose-limiting toxicities. In this study, we demonstrated a strategy of encapsulating a hydrophobic synthetic compound, nifetepimine, having anticancer properties, in poly (lactic-co-glycolic acid) nanoparticles to increase selectivity of drug to cancerous cells with minimum toxicity towards normal cells. Nanoencapsulated nifetepimine (30-100nm) having loading and encapsulation efficiency of 7.45% and 75% respectively, was successfully internalized inside TNBC cells upon sustained release resulting in apoptosis. An in vivo bio-distribution study indicated that nanonifetepimine selectively accumulated into breast tumor sites of mice, primarily due to prolonged blood circulation time and binding of nifetepimine to epidermal growth factor receptor that remains overexpressed in most of the TNBC tumors. Moreover, we observed significant reduction in breast tumor volume with improved survival implying high tumor targetability of nanonifetepimine.

Background: Perinatal asphyxia is a significant cause of neonatal mortality and morbidity. MRI is useful for assessing the severity and pattern of brain injuries. There is less data of MRI findings of perinatal asphyxia from India and the subcontinents. This prospective observational study was done to describe MRI brain findings in neonates with perinatal asphyxia with respect to various determinants.Methods: Initial MRI brain was done when babies were stable after fulfilling inclusion criteria. Immediate outcome was assessed at the end of hospital stay. They were followed up for presence of any sequel up to 1 year. Repeat MRI brain was done in few selected babies. Data was collected and statistically analyzed.Results: Total 55 babies were included in the study (term 27, preterm 28). There were 9 babies in stage 1, 17 babies in stage II and 22 babies in stage III. MRI brain findings were normal in 8 and abnormal in 47 patients. There were Deep gray matter injury (DG) in 22, Para Sagittal subcortical white matter injury (PS) in 6, Germinal matrix haemorrage (GMH), intraventricular haemorrage (IVH) and Periventricular leucomalacia (PVL) in 12 and Mixed pattern of injury in 7 babies. Findings among 9 expired babies were: 4 (44.4%) DG, 2 (22.2%) GMH+IVH and 3 (33.3%) mixed. There was neurological sequel in 13 babies (48.1%). Babies with normal MRI initially had no sequel.Conclusion: Brain injury due to perinatal asphyxia follows several patterns according to gestational age and severity. Early and accurate recognition of these patterns with the help of MRI brain helps in managing the baby and predicting the prognosis.

Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is involved in cell survival and proliferation and has been found to be persistently activated in most human cancers mainly through its phosphorylation at Tyr-705. However, the role and regulation of Stat3 Ser-727 phosphorylation in cancer cells have not been clearly evaluated. In our findings, correlation studies on the expression of CK2 and Stat3 Ser-727 phosphorylation levels in human glioma patient samples as well as rat orthotopic tumor model show a degree of negative correlation. Moreover, brain tumor cell lines were treated with various pharmacological inhibitors to inactivate the CK2 pathway. Here, increased Stat3 Ser-727 phosphorylation upon CK2 inhibition was observed. Overexpression of CK2 (α, α′ or β subunits) by transient transfection resulted in decreased Stat3 Ser-727 phosphorylation. Stat3 Tyr-705 residue was conversely phosphorylated in similar situations. Interestingly, we found PP2A, a protein phosphatase, to be a mediator in the negative regulation of Stat3 Ser-727 phosphorylation by CK2. In vitro assays prove that Ser-727 phosphorylation of Stat3 affects the transcriptional activity of its downstream targets like SOCS3, bcl-xl and Cyclin D1. Stable cell lines constitutively expressing Stat3 S727A mutant showed increased survival, proliferation and invasion which are characteristics of a cancer cell. Rat tumor models generated with the Stat3 S727A mutant cell line formed more aggressive tumors when compared to the Stat3 WT expressing stable cell line. Thus, in glioma, reduced Stat3 Ser-727 phosphorylation enhances tumorigenicity which may be regulated in part by CK2–PP2A pathway.

 A 9.5-year-old boy from Kolkata, presented to pediatric outpatient department with severe headache and mild fever of one month duration. Headache was bilateral, persistent and associated with neck pain. There were no visual disturbances or any ear discharge. Fever was continuous in nature and gradually increasing in intensity. There was no associated cough, respiratory distress, dysuria, abdominal pain, joint pain or joint swelling, myalgia, convulsion, altered sensorium. His sister was suffering from active pulmonary tuberculosis and she was on antituberculosis drugs for last 2 months. On examination, pulse was 88/min, blood pressure 116/84 mmHg. Temperature was mildly elevated (38.3oC). Patient had no hepatosplenomegaly, no sternal tenderness, and no lymphadenopathy. Sensorium was normal. Neck rigidity was absent. Neither sign of raised intracranial tension nor cranial nerve palsy were noted. Ophthalmoscopic examination was normal. Planter reflex bilaterally flexor. Power and tone in all four limbs were normal. On laboratory examination, hemoglobin 14.2 g/dL, total count 9400/mm 3 (neutrophil 62%, lymphocyte 24%, eosinophil 12%). Liver function tests, urea, creatinine were within normal range. Routine urine examination was normal. Blood and urine culture showed no growth. Malarial dual antigen

Urinoma (or perirenal uriniferous pseudo cyst) occurs due to extravasation of urine in the perirenal space. Common causes include traumatic renal injury or an obstruction in the outflow tract as in a posterior urethral valve. Though rare, such diagnosis should be considered in neonates presenting with expanding cystic masses in the abdomen. Here, we present a case of a four-day-old neonate, who presented to us with abdominal distension and bilious vomiting. The initial radiographic studies showed a cystic mass surrounding the right kidney. Urine was aspirated from the mass and Micturating Cysto-Urethrogram (MCU) showed the presence of a Posterior Urethral Valve (PUV). A diagnosis of urinoma secondary to PUV was confirmed. After relieving the obstruction by vesicostomy, symptoms of intestinal obstruction resolved. On later follow up, size of urinoma also gradually decreased. This proves that not every case of a distended abdomen and bilious vomiting in a neonate, necessarily points towards Necrotising Enterocolitis (NEC) or intestinal obstruction.

Genetic variations in cancer cells are the underpinning for the development of resistance and failure of the treatment by current anticancer drugs. Thus, an ideal drug must overcome failure of treatment and prevents development of drug resistance. There are a wide variety of emerging, easy to prepare and cost effective group of drugs that are collectively called peptoids or peptidomimetics. These new set of drugs exhibit distinct features including protease resistance, are non-immunogenic, do not hinder functionality and backbone polarity, and can adopt different conformations. These drugs have shown promise as diagnostic and therapeutic tools in a wide variety of diseases. Here, we discuss the recent advancement in the design and synthesis of peptoids and use of these drugs in the diganosis and treatment of a wide number of cancers of the lung, prostate, and breast.

Background: Kangaroo mother care (KMC) is an effective way to reduce mortality and morbidity of low-birth-weight babies. KMC feeding aims at the establishment of exclusive breastfeeding (EBF) for every baby. This study was conducted to analyze the actual feeding pattern and factors influencing it. Methods: Babies getting KMC were prospectively observed and the data related to feeding practice were collected. At discharge, the babies were divided into two groups: EBF and non-EBF. Different factors were compared between these groups. Results: Among 387 babies, 63.56% were on EBF. Postnatal counseling, early contact and initiation of feeding, early expression of breast milk, and first feeding with EBM played a pivotal role behind the establishment of EBF (P

Introduction Nuclear accumulation of β-catenin is important for cancer development and it is found to overlap with p68 (DDX5) immunoreactivity in most breast cancers, as indicated by both clinical investigations and studies in cell lines. In this study, we aim to investigate the regulation of p68 gene expression through β-catenin/transcription factor 4 (TCF4) signaling in breast cancer. Methods Formalin-fixed paraffin-embedded sections derived from normal human breast and breast cancer samples were used for immunohistochemical analysis. Protein and mRNA expressions were determined by immunoblotting and quantitative RT-PCR respectively. Promoter activity of p68 was checked using luciferase assay. Occupancy of several factors on the p68 promoter was evaluated using chromatin immunoprecipitation. Finally, a syngeneic mouse model of breast cancer was used to assess physiological significance. Results We demonstrated that β-catenin can directly induce transcription of p68 promoter or indirectly through regulation of c-Myc in both human and mouse breast cancer cells. Moreover, by chromatin immunoprecipitation assay, we have found that both β-catenin and TCF4 occupy the endogenous p68 promoter, which is further enhanced by Wnt signaling. Furthermore, we have also established a positive feedback regulation for the expression of TCF4 by p68. To the best of our knowledge, this is the first report on β-catenin/TCF4-mediated p68 gene regulation, which plays an important role in epithelial to mesenchymal transition, as shown in vitro in breast cancer cell lines and in vivo in an animal breast tumour model. Conclusions Our findings indicate that Wnt/β-catenin signaling plays an important role in breast cancer progression through p68 upregulation. Electronic supplementary material The online version of this article (doi:10.1186/s13058-014-0496-5) contains supplementary material, which is available to authorized users.

Brain tumors are one of the most formidable diseases of mankind. They have only a fair to poor prognosis and high relapse rate. One of the major causes of extreme difficulty in brain tumor treatment is the presence of blood brain barrier (BBB). BBB comprises different molecular components and transport systems, which in turn create efflux machinery or hindrance for the entry of several drugs in brain. Thus, along with the conventional techniques, successful modification of drug delivery and novel therapeutic strategies are needed to overcome this obstacle for treatment of brain tumors. In this review, we have elucidated some critical insights into the composition and function of BBB and along with it we have discussed the effective methods for delivery of drugs to the brain and therapeutic strategies overcoming the barrier.

To determine the common hematological abnormalities in HIV infected children and any association of these abnormalities with HIV disease severity.Cross-sectional study.Regional Pediatric ART centre, Medical College and Hospital, Kolkata, West Bengal, India, from November 2011 to November 2012.Children up to 12 years with confirmed diagnosis of HIV infection were clinically examined and tested for complete hemogram and CD4 count. Bone marrow study was done in selected patient depending on hemogram report. Children were divided in different stages according to WHO clinical staging. Each of the hematological parameters was assessed for any association with progression of disease. Fisher's Exact Test was used for determining the association between WHO clinical staging and abnormal blood parameters. P-value0.05 was taken as significant.Sixty nine percent of the study population was anemic; 47.37% (18/38), 66.67% (8/12), 71.43% (15/21) and 93.10% (27/29) of stage 1, 2, 3 and 4 respectively were anemic in the study population (p=0.001). Leucopenia was present in 34% (34/100) children. Neutropenia and lymphopenia was present in 19% (19/100) and 22% (22/100) children. Lymphopenia was present in 7.89% (3/38), 16.67% (2/12), 19.05% (4/21) and 44.83% (13/29) of patient with stage 1, 2, 3 and 4 respectively (p=0.020). Eosinophilia was present in 17% (17/100) and thrombocytopenia in 11% (11/100) children. 2 patients with stage 4 disease were with hypoplastic bone marrow.Anemia was the most common hematological abnormality in HIV infected children. Anemia and lymphopenia had a significant association with the stage of the disease.

Despite recent advances in medicine, 30-40% of patients with breast cancer show recurrence underscoring the need for improved effective therapy. In this study, by in vitro screening we have selected a novel synthetic indole derivative 2,2'-diphenyl-3,3'-diindolylmethane (DPDIM) as a potential anti- breast cancer agent. DPDIM induces apoptosis both in vitro in breast cancer cells MCF7, MDA-MB 231 and MDA-MB 468 and in vivo in 7,12-dimethylbenz[α]anthracene (DMBA) induced Sprague-Dawley (SD) rat mammary tumor. Our in vitro studies show that DPDIM exerts apoptotic effect by negatively regulating the activity of EGFR and its downstream molecules like STAT3, AKT and ERK1/2 which are involved in the proliferation and survival of these cancer cells. In silico predictions also suggest that DPDIM may bind to EGFR at its ATP binding site. DPDIM furthermore inhibits EGF induced increased cell viability. We have also shown decreased expression of pro-survival factor Bcl-XL as well as increase in the level of pro-apoptotic proteins like Bax, Bad, Bim in DPDIM treated cells in vitro and in vivo. Our results further indicate that the DPDIM induced apoptosis is mediated through mitochondrial apoptotic pathway involving the caspase-cascade. To the best of our knowledge this is the first report of DPDIM for its anticancer activity. Altogether this report suggests that DPDIM could be an effective therapeutic agent for breast cancer.

c-Myc is a proto-oncogenic transcription factor and its rapid turnover mediated by the ubiquitin-proteasome system is critical for maintaining normal cellular homeostasis. Multiple ubiquitin ligases have been assigned for c-Myc regulation till date. However, the available data suggest for the possible existence of additional E3 ligase(s). Here, we report a new E3 ligase for c-Myc, the carboxyl terminus of Hsc70-interacting protein or CHIP, which is a chaperone-associated Ubox-containing E3 ligase. In this report, we show that CHIP interacts and ubiquitinates c-Myc, thus targeting it for proteasome-mediated degradation. Overexpression of CHIP could accelerate the turnover rate of c-Myc protein. Conversely, knockdown of CHIP by RNAi stabilizes endogenous c-Myc. The interaction between CHIP and c-Myc depends on the N-terminally located tetratricopeptide repeats of CHIP, which has been implicated as a chaperone-binding motif. Inhibition of Hsp90 chaperone activity by 17-N-allylamino-17-demethoxygeldanamycin reduces c-Myc protein level. We found that the association between CHIP and c-Myc is dependent on the chaperones; particularly Hsp70. CHIP antagonizes the transcriptional activity of c-Myc and decreases the abundance of the transcripts of its target genes. Overall, CHIP-knockdown increases malignant behavior of C6 glioma cells. To the best of our knowledge, this is the first report of c-Myc being regulated by a bona-fide chaperone-associated E3 ligase in HEK293 as well as glioma cells. Because CHIP has been reported earlier to be negatively regulating Akt1, BCR-ABL and hTERT, and now c-Myc, the present study may strengthen the view that CHIP acts as a tumor suppressor.

Radiolabeled somatostatin analogs have become powerful tools in the diagnosis and staging of neuroendocrine tumors, which express somatostatin receptors. The aim of this study was to evaluate a new somatostatin analog, 6-hydrazinopyridine-3-carboxylic acid-Ser3-octreotate (HYNIC-SATE) radiolabeled with 99mTc, using ethylenediamine-N,N'-diacetic acid and tricine as coligands, to be used as a radiopharmaceutical for the in vivo imaging of somatostatin receptor subtype 2 (SSTR2)-positive tumor. Synthesis of the peptide was carried out on a solid phase using a standard Fmoc strategy. Peptide conjugate affinities for SSTR2 were determined by receptor binding affinity on rat brain cortex and C6 cell membranes. Internalization rate of 99mTc-HYNIC-SATE was studied in SSTR2-expressing C6 cells that were used for intracranial tumor studies in rat brain. A reproducible in vivo C6 glioma model was developed in Sprague-Dawley rat and confirmed by histopathology and immunohistochemical analysis. Biodistribution and imaging properties of this new radiopeptide were also studied in C6 tumor-bearing rats. Radiolabeling was performed at high specific activities, with a radiochemical purity of96%. Peptide conjugate showed high affinity binding for SSTR2 (HYNIC-SATE IC50=1.60±0.05 n m) and specific internalization into rat C6 cells. After administration of 99mTc-HYNIC-SATE in C6 glioma-bearing rats, a receptor specific uptake of radioactivity was observed in SSTR-positive organs and in the implanted intracranial tumor and rapid excretion from nontarget tissues via kidneys. 99mTc-HYNIC-SATE is a new receptor-specific radiopeptide for targeting SSTR2-positive brain tumor and might be of great promise in the scintigraphy of SSTR2-positive tumors.

Prolonged neonatal jaundice has been previously reported in neonates with congenital hypothyroidism. Isolated central hypothyroidism is a rare disease which may be missed by newborn screening programs. Here, we report a case of isolated central hypothyroidism presenting with neonatal hyperbilirubinemia, anemia, and hepatosplenomegaly, which showed marked improvement with levothyroxine supplementation.

Systemic Lupus Erythematosus (SLE) may have different neurological manifestations. Mononerits multiplex is the most common type of peripheral nervous system involvement in adult population, but case reports in pediatric population are sparse. We are reporting a case of pediatric SLE, presenting with polyarthritis and subsequently developing mononeuritis multiplex, identified by NCV.