Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is the commonest inflammatory gastrointestinal disorder of newborn infants, occurring primarily in premature neonates. Presenting as a medical and surgical emergency, it is associated with significant morbidity and mortality. NEC is characterized by acute intestinal inflammation and necrosis with intramural dissection of gas, pathognomically appearing as pneumatosis intestinalis on radiography. The incidence and mortality, with an inverse relationship to maturation, range between 3–11% and 17–20% respectively. Mortality may be up to 50% in extremely premature infants who require surgery for intestinal perforation or gangrene. The exact etiopathogenesis is unknown. Over 90% of infants are premature and more than 98% are enterally fed. NEC presents with feeding intolerance and abdominal distension, which may rapidly progress to cardiorespiratory decompensation and death in severe cases. Intestinal dysbiosis and its functional and immunological immaturity are proposed to play roles in the pathogenesis. While exact triggers are undetermined, the disease is marked by an anomalous immunological response of enterocytes to inflammation, invoking cytokines and chemokines. NEC is treated with bowel rest, antibiotics, cardiorespiratory support, parenteral nutrition, and blood products transfusion. Approximately 30% of cases require surgery and a significant number of survivors suffer from neurological deficits, intestinal dysfunction, and post surgical short bowel syndrome

Case control study of supervised and unsupervised medical abortion in first trimester of pregnancy

Background: The MTP act of India 1971 provides for the termination of pregnancy up to 20 weeks of gestation, by a registered medical practitioner, provided all the prerequisites are fulfilled. The objective of this study was to conduct case control study of supervised and unsupervised medical abortion in first trimester of pregnancy.Methods: A case control study was conducted with two groups of patients with period of gestation <9 weeks. Case group consist of 30 patients presenting to emergency department with unsupervised intake of medical abortion pill. Control group consist of 30 patients presenting to family planning outpatient department want medical abortion pill under supervision. The main outcome variables were comparison of success rate, failure rate, complications like pain, fever, heavy bleeding, shock, requirement of blood transfusion. Interventions required were compared in both the groups in terms of medical management, surgical evacuation and laparotomy.Results: In our study, the success rate achieved in terms of complete abortion was 66.7% in the supervised and 13.3% in the unsupervised group with (p value <0.001). The complication rate was 60% in the supervised group in contrast to 93.3% in the unsupervised group. 56.7% patients in unsupervised group required blood transfusion which was nil in supervised groups. 71.4% patients in the supervised group did not require intervention. In the unsupervised group, 13.8% required medical management, 65.5% required surgical evacuation and 6.7% had to undergo laparotomy for ectopic pregnancy.Conclusions: In present study we conclude that first trimester medical abortion under supervision is more effective, safe and convenient as compared to unsupervised medical abortion. We recommend that government must stop over the counter sell of medical abortion pills

Oligohydramnios and its perinatal outcome

Background: Oligohydramnios is one of the major causes of perinatal morbidity and mortality. The sonographic diagnosis of oligohydramnios is usually based on an AFI≤5 cm or on a single deepest pocket of amniotic fluid≤2 cm3. Our study was aimed to study the perinatal outcome in oligohydramnios. Aim and objective were to study obstetric risk factors associated with oligohydramnios and maternal outcome in the form of mode of delivery, and to assess neonatal complications in terms of APGAR score at birth, NICU admission rates, meconium stained liquor and still birth rates.Methods: It was an Observational, Prospective, clinical study of 100 pregnant patients diagnosed with oligohydramnios by ultrasound, carried out in Geetanjali medical college and hospital, Udaipur for period of from January 2020-August 2020. The study was conducted after ethical clearance and with informed consent. Detailed history on demographic profile, medical illness, obstetric history and antenatal complication if any in the present pregnancy; general examination, obstetric examination and bimanual examination were performed meticulously.Results: In our study 53% cases of oligohydramnios were associated with some of the risk factors like PIH (29%), IUGR (22%), fetal anomaly (1%), systemic maternal disease (1%) and 47% of the cases were Idiopathic. LSCS was done in 85.71% cases with AFI&lt;5 cm. Low birth weight was found in 51.43% cases with AFI&lt;5 cm. NICU admission was required for 28.57% cases with AFI&lt;5 cm.Conclusions: AFI is an important and convenient screening test for prediction of perinatal outcome. In presence of oligohydramnios, the risk of fetal distress, operative delivery, low Apgar score, low birth weight, perinatal morbidity and mortality are more. Hence early detection of oligohydramnios, associated antenatal risk factors and timely management can improve the maternal and fetal outcome

Preliminary study on diminution level of RNA/DNA ratio in tissue of Labeo rohita by exposure to some endocrine disrupting compounds (EDCs)

Effects of EDCs particularly on RNA/DNA ratio are yet to be investigated to manage the effluents in natural waters. We investigated exposure effects of endocrine disrupting compounds (EDCs) phthalic acid ester (PAE) and hexachlorocyclohexane (HCH) on the RNA/DNA ratio in tissue of an Indian major carp Labeo rohita. Fish were exposed to pre-determined sublethal concentrations of phthalic acid ester (Di-methyl phthalate (DMP), di-butyl phthalate (DBP), and di-(2- ethylhexyl) phthalate (DEHP) and also HCH for determining the tissue RNA/DNA ratio after 30, 60 and 90 days of exposure in the doses of 0.2 mg L-1, 0.3 mg L-1, and 0.5 mg L-1 respectively. All these tested chemicals significantly (P0.05) inhibited RNA/DNA ratio. The ratio gradually significantly (P0.05) decreased after DEHP where it was 1.9±0.51 F1, 18=15.8 P=0.014 n=19; in case of DBP it was 1.92±0.62 F1, 20=6.5 P=0.012 n=19 and for HCH it was 0.94±0.21 F1, 18=18.08 P=0.0012 n=19 at treatments concentrations of 0.3 mg L-1 and 0.5 mg L-1, compared to control (2.9±0.2) after 90 days. However, there was no statistical significance (P0.05) in RNA/DNA ratio after the DMP (F1, 20=2.4 P=0.15n=21) treatment

Relationship between anxiety, depression and quality of life in medical student with polycystic ovary syndrome

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 5-10% of women worldwide. It has clinical, hormonal and psychological manifestation like anxiety, depression and low self-esteem. Aim was to evaluate prevalence of anxiety, depression, and quality of life in medical students with PCOS. Objectives were to study the prevalence of anxiety, depression among medical students suffering from PCOS; and to evaluate quality of life (QoL) in students with PCOS and its association with anxiety, depression and quality of life.Methods: The cross sectional study was conducted among 70 medical students at Geetanjali Medical College and Hospital, Udaipur, Rajasthan, from February 2019 – June 2020. Students were screened and selected as per the Rotterdam’s 2003 criteria after informed consent. Mental health assessment done by using Hamilton depression rating scale for depression, Hamilton anxiety rating scale for anxiety, and using 36-item short form survey for QoL.Results: Twenty five (35.7%) students suffered from anxiety while 20 (28.5%) had depressive disorders. Forty five (64%) patient both anxiety and depression. These students had significant psychological morbidity and poor QoL.Conclusions: Psychological morbidity with PCOS is undertreated and need to be addressed and treated in time so as to turn these students into a responsible happy adult

Genetics of Sirenomelia, the Mermaid Syndrome

Sirenomelia (SML) is a rare, almost universally fatal congenital malformation presenting pathognomically with fused lower extremities and absent or malformed perineum. The classic Sirenomelia sequence includes a uniform spectrum of caudal malformations, spinal defects, and a single umbilical artery. SML is postulated to be due to a genetic predisposition, unmasked by biochemical or environmental triggers. Primary developmental defects in the formation of caudal mesoderm or embryonic caudal vessels with resultant local tissue hypoperfusion are proposed hypotheses for its pathogenesis. SML occurs sporadically in humans, presumably due to a spontaneous mutation, and is speculated to have an autosomal dominant inheritance pattern. In mutant mice, specific defects in Cyp26a1 and Bmp 7 genes are demonstrated to produce offsprings with SML. Bmp 7 is a signaling protein, which belongs to the transforming growth factor-β (TGF β) superfamily. Tsg 1, a Bmp and chordin-binding protein, functions as an activator-inhibitor of Bmp signaling in the embryonic caudal region (ECR). Loss of Bmp7 genes combined with a complete loss or half-dose of Tsg 1 is demonstrated to produce an invariable SML phenotype. SML is also demonstrated to occur with increased Retinoic acid (RA) signaling in the ECR. The Cyp26a1 gene is involved in coding for an enzyme, which expresses in ECR and degrades RA. A specific defect in this gene leads to excess local RA concentration and SML generation with a reported 20% penetrance in mutant mice. However, the mutational screening of Cyp26a1 and Bmp 7genes has failed to confirm their involvement in mankind and the molecular defect and genetic inheritability of SML in humans remain undefined

The Endosomal Sorting Complex Required for Transport Pathway Mediates Chemokine Receptor CXCR4 Akt Signaling by Promoting Lysosomal Degradation of mTOR Antagonist Deptor

The chemokine receptor CXCR4 is a member of the G protein-coupled receptor (GPCR) family. The cognate ligand for CXCR4 is the C-X-C chemokine known as CXCL12. The CXCL12/CXCR4 signaling axis is essential for a number of developmental processes including organogenesis, vascularization of the GI tract and hematopoiesis. Dysregulated CXCR4 signaling is also implicated in a variety of pathological conditions such as WHIM (Warts, Hypogammaglobunemia, Infections and myelokathexis) syndrome, cardiovascular disease and cancer. Despite its role in several pathologies, the molecular mechanisms mediating CXCR4 signaling are not completely understood. Upon CXCL12 binding to CXCR4, several signaling pathways are activated including the Akt/mTOR pathway, which mediates several cellular responses including survival, proliferation, invasion, and migration. In the current dissertation project, we aim to elucidate the molecular mechanisms regulating CXCR4 promoted Akt signaling. Akt is a serine/threonine kinase that is fully activated by a complex multistep process involving phosphorylation of two key amino acid residues. Akt is activated by phosphorylation at threonine residue 308 and serine residue 473 by phosphoinositide-dependent kinase (PDK1) and mechanistic/mammalian target of rapamycin complex 2 (mTORC2), respectively. The mechanisms by which GPCRs promote PDK1 mediated phosphorylation of Akt at T308 are well understood; however the mechanism by which mTORC2 phosphorylates Akt on S473 remain essentially unknown. mTORC2 is a multi-subunit kinase complex comprised of key units including rictor, Sin1 and mTOR, the catalytic subunit. An important subunit referred to as DEPTOR binds to mTOR and inhibits its catalytic activity. Aberrant expression of DEPTOR has been linked to altered mTORC2 kinase activity and Akt signaling in several cancers. However, the mechanisms that regulate DEPTOR expression remain poorly understood. We set out to understand the mechanisms that regulates DEPTOR levels in cells and how this impacts the mTORC2/Akt axis in response to CXCR4 activation. We show for the first time, that CXCL12 stimulation leads to rapid degradation of DEPTOR through lysosomes and that the ESCRT (Endosomal Sorting Complex Required for Transport) pathway that sorts ubiquitinated membrane receptors, mediates lysosomal degradation of DEPTOR. Pharmacological inhibition of heterotrimeric G protein G, PI3K signaling and siRNA targeting ESCRTs blocks CXCR4 promoted degradation of DEPTOR. We also show that by promoting DEPTOR degradation, the ESCRT pathway mediates Akt signaling promoted by CXCR4. Depletion of ESCRTs by siRNA leads to increased levels of DEPTOR and attenuates CXCR4 promoted, G protein and PI3K dependent Akt activation and signaling, consistent with decreased mTORC2 activity. In addition, ESCRTs likely have a broader role in Akt signaling because ESCRT depletion also attenuates receptor tyrosine kinase promoted Akt activation and signaling. Collectively, our data reveal a novel role for the ESCRT pathway in promoting intracellular signaling, which may begin to identify the signal transduction pathways that are important in the physiological roles of ESCRTs and Akt

Transposition of Great Arteries

TGA is the commonest complex congenital cyanotic cardiac anomaly occurring during the first week of life. It is characterized by the unusual anomaly of ventriculoarterial discordance, with the aorta (A) originating from the right ventricle (RV) and the pulmonary artery (PA) from the left ventricle (LV). In the common Dextro form (DTGA), A is abnormally located to the right, anterior, and inferior of PA. The anatomic configuration results in the lethal hemodynamic pattern of 2 independent and parallel running circulatory circuits, which mandates creating a conduit to ensure the mixing of oxygenated and deoxygenated blood for survival. In the rare Levo form (LTGA), the aorta is placed anterior and to the left of PA with ventricular inversion. TGA is well tolerated in the fetus and is challenging to diagnose by fetal echocardiography unless the outflow tracts are specifically visualized. Postnatally the typical findings of murmur and cyanosis vary according to the associated cardiac defects and the degree of intercirculatory mixing. The arterial switch operation (ASO), which involves establishing ventriculoarterial concordance, is the standard surgical repair of D-TGA and has replaced the atrial switch procedures due to its superior long-term outcomes. The Rastelli procedure is used for complex DTGA cases. DTGA has a 90% mortality rate in the first year of life if untreated, while over 95% survive for 5 to 25 years after surgery. Post-surgical course may be complicated and require surgical revisions. The long-term outcome is associated with normal or mild to moderate neurodevelopmental disabilities, depending upon the type, complexity, and course of the disease. Expert follow-up of the patients into adulthood is an integral part of the management of TGA for best outcomes

A COST AND PIPELINE TRADE-OFF IN A TRANSPORTATION PROBLEM

Abstract: The present paper deals with a trade off between cost and pipeline at a given time in a transportation problem. The time lag between commissioning a project and the time when the last consignment of goods reaches the project site is an important factor. This motivates the study of a bi-criteria transportation problem at a pivotal time T . An exhaustive set E of all independent cost-pipeline pairs (called efficient pairs) at time T is constructed in such a way that each pair corresponds to a basic feasible solution and in turn, gives an optimal transportation schedule. A convergent algorithm has been proposed to determine non-dominated cost pipeline pairs in a criteria space instead of scanning the decision space, where the number of such pairs is large as compared to those found in the criteria space. 197 198 Vikas Sharma, Rita Malhotra, Vanita Verma / A Cost And Pipelin