A homozygous mutation in TRIM36 causes autosomal recessive anencephaly in an Indian family.

Anencephaly (APH) is characterized by the absence of brain tissues and cranium. During primary neurulation stage of the embryo, the rostral part of the neural pore fails to close, leading to APH. APH shows a heterogeneous etiology, ranging from environmental to genetic causes. The autosomal recessive inheritance of APH has been reported in several populations. In this study, we employed whole-exome sequencing and identified a homozygous missense mutation c.1522C > A (p.Pro508Thr) in the TRIM36 gene as the cause of autosomal recessive APH in an Indian family. The TRIM36 gene is expressed in the developing brain, suggesting a role in neurogenesis. In silico analysis showed that proline at codon position 508 is highly conserved in 26 vertebrate species, and the mutation is predicted to affect the conformation of the B30.2/SPRY domain of TRIM36. Both in vitro and in vivo results showed that the mutation renders the TRIM36 protein less stable. TRIM36 is known to associate with microtubules. Transient expression of the mutant TRIM36 in HeLa and LN229 cells resulted in microtubule disruption, disorganized spindles, loosely arranged chromosomes, multiple spindles, abnormal cytokinesis, reduced cell proliferation and increased apoptosis as compared with cells transfected with its wild-type counterpart. The siRNA knock down of TRIM36 in HeLa and LN229 cells also led to reduced cell proliferation and increased apoptosis. We suggest that microtubule disruption and disorganized spindles mediated by mutant TRIM36 affect neural cell proliferation during neural tube formation, leading to APH.

Study of Obstetric Admissions to the Intensive Care Unit of a Tertiary Care Hospital.

PURPOSE: To analyze obstetric admissions to intensive care unit and to identify the risk factors responsible for intensive care admission. METHODS: This is a retrospective study of all obstetric cases admitted to the intensive care unit over a period of 3 years. Data were collected from case records. The risk factors responsible for ICU admission were analyzed. RESULTS: There were 765 obstetric admissions to ICU accounting for 1.24 % of all deliveries. 56.20 % were in the age group of 20-25 years. 38.43 % were in their first pregnancy. 36.48 % of cases were at 37-40 weeks of gestation. Postpartum admissions were 80.91 %. Major conditions responsible were obstetric hemorrhage in 44.05 %, hypertensive disorders of pregnancy in 28.88 %, severe anemia in 14.37 %, heart disease in 12.15 %, and sepsis in 7.97 % of ICU cases. 40.39 % cases required high dependency care. Maternal mortality was seen in 15.55 % of ICU cases. Commonest cause of mortality was hemorrhagic shock (26.89 %) and multiorgan dysfunction syndrome (26.05 %). CONCLUSION: Commonest risk factors for ICU admissions are obstetric hemorrhage and hypertensive disorders of pregnancy. Other major risk factors are severe anemia, heart disease, sepsis, more than one diagnosis on admission, and the need for cesarean delivery.

Partographic analysis of spontaneous labour at term in primigravida.

PURPOSE OF THE STUDY: To study the use of partogram in the analysis of spontaneous labour at term in primigravida with cephalic presentation. METHODOLOGY: Partographic analysis of labour was done in 200 primigravidae. Partographic variables are plotted, and the study population was divided into three groups. Group I: Cervix dilatation and descent curve falling to the left of alert line; Group II: Cervix dilatation and descent curve falling to the right of alert line; and Group III: Cervix dilatation and descent curve falling to the right of action line. Maternal and neonatal outcomes were studied in each of three groups. RESULTS: Amongst the 200 primigravid labours analysed, 133 (66.5 %) belonged to group I, 40 (20.0 %) belonged to group II and 27 (13.5 %) belonged to group III. Mean durations of active phases of labour were 4.1 h, 6.9 h and 9.6 h, in groups I, II and III, respectively. In group I, 130 women (97.7 %) delivered vaginally, 3 (2.3 %) underwent LSCS. In group II, 29 (72.5 %) delivered vaginally, 4 (10 %) delivered instrumentally and 7 (17.5 %) underwent LSCS, and in group III, 5 (18.5 %) delivered vaginally, 7 (25.9 %) delivered instrumentally and 15 (55.5 %) delivered by LSCS. CONCLUSION: Mean duration of active phase of labour increased as the partographic curve fell to the right of alert and action line. Increased rates of instrumental deliveries, LSCS, babies with lower APGAR score at 5 min, and NICU admissions were observed in group III compared with groups I and II.

Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents.

A series of arylthioureas (1), aromatic aldehyde thiosemicarbazones (2) and 5-aryl-2-furfuraldehyde thiosemicarbazones (3) were condensed with 2,4-dichloro-5-fluorophenacyl bromide to yield respective arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles (4). The newly synthesized compounds were characterized by IR, 1H-NMR and mass spectral studies. These compounds were also screened for their antibacterial and anti-inflammatory activities. Two of the newly synthesized compounds showed anti-inflammatory activity comparable with that of Ibuprofen.