In Parkinson's disease (PD), substantia nigra (SN) dopaminergic (DA) neurons degenerate, while related ventral tegmental area (VTA) DA neurons remain relatively unaffected. Here, we present a methodology that directs the differentiation of mouse and human pluripotent stem cells toward either SN-or VTA-like DA lineage and models their distinct vulnerabilities. We show that the level of WNT activity is critical for the induction of the SN-and VTA-lineage transcription factors Sox6 and Otx2, respectively. Both WNT signaling modulation and forced expression of these transcription factors can drive DA neurons toward the SN-or VTA-like fate. Importantly, the SN-like lineage enriched DA cultures recapitulate the selective sensitivity to mitochondrial toxins as observed in PD, while VTA-like neuron-enriched cultures are more resistant. Furthermore, a proteomics approach led to the identification of compounds that alter SN neuronal survival, demonstrating the utility of our strategy for disease modeling and drug discovery.

To evaluate the effects of epidural analgesia on the painrelief and maternal and fetal outcome. Study design: Comparative & analytical study. Place and Duration: In MilitaryHospital Rawalpindi fromOct 1998 to Oct 1999. Patients and Method: 100 full term healthy primigravida admitted forinduction of labour. Fifty patients were given epidural analgesia and 50 served as control to whom no analgesia wasgiven. Outcome measures observed were duration of labour, mode of delivery; Apgar score of the newborn; untowardreaction and intra-partum complications. Results: The data analysis revealed that epidural analgesia significantlyprolonged labour time and was associated with increased instrumental delivery rate. Significant reduction in intra-partumfetal complications was seen, while C-section rate was not effected by epidural analgesia. Apgar scores were higherin analgesia group as compared to control. Conclusion: Although accused of prolonging labour time, it’s benefits interms of great maternal satisfaction and reduced intra-partum complications still makes it an option for labouringpatients.

Objective: To find out fetal and maternal outcomes among obese pregnant females. Study Design: Cross-sectional study. Place and Duration of Study: Department of Gynaecology and Obstetrics, Combined Military Hospital Rawalpindi, from Jun 2020 to Jun 2021. Methodology: A total of 124 pregnant obese women (BMI more than 30kg/m2), gestational age between 13-24 months, having fasting blood glucose and blood pressure within normal limits were enrolled in the study and were subsequently followed throughout pregnancy upon antenatal visits scheduled as per guidelines. Participants with diabetes mellitus or hypertension,above 40 years of age, family or previous history of gestational diabetes, and pre-eclampsia were also excluded from the study. Fetal and maternal outcomes were noted. Results: One hundred and twenty-four (124) pregnant obese women were enrolled in the study with a mean age of 33.7±4.1 years (21 -38 years). Out of which, 86(69.4%) had cesarean section primarily due to pre-eclampsia, prolonged or dysfunctional labour causing fetal distress. There were 8 cases of miscarriage and 3 cases of stillbirth. 26(21.0%) women presented with gestational diabetes mellitus, 31(25.0%) with pre-eclampsia and 12(9.7%) developed both conditions. There were 7(5.6%) participants who delivered babies with macrosomia, 1(0.8%) anencephaly, 3(2.4%) congenital deafness and 1(0.8%) cleft lip. Conclusion: Obesity in pregnancy can lead to serious maternal and fetal outcomes ranging from abortions to neonatal anomalies and fetal death. A high index of suspicion is required to diagnose and manage these difficult conditions.

OBJECTIVE: To assess the relation of intra-operative hypotension with severity of pre-operative anxiety in patients undergoing caesarean section under spinal anesthesia. STUDY DESIGN: Prospective observational study. PLACE AND DURATION OF STUDY:  This study was carried out from June 2017 to May 2018 at anesthesia department of Combined Military Hospital Lahore. METHODOLOGY: One hundred and twenty patients belonging to America Society of Anesthesiology class I and II, undergoing caesarean section under spinal anesthesia were selected.  Verbal Analogue Scale for anxiety (VASA) and Straight Trait Anxiety Inventory (STAIs) questionnaire were used to measure pre-operative anxiety. Patients were divided into three groups as mild (VASA<3or STAIs<44), moderate (VASA 4-7 or STAIs 44-55) and severe (VASA 7-10 or STAIs>55) anxiety. Baseline mean arterial pressure was measured. Patients were placed in supine position immediately after induction of spinal anesthesia at L3-L4 or L4-L5 level with 12mg bupivacaine. Blood pressure was measured every two minutes until the delivery of baby. Hypotension was labeled when mean arterial pressure dropped by 20% below the baseline. The effect of level of anxiety on drop in MAP was assessed. RESULTS: Seventeen (14.17%) patients had mild pre-operative anxiety; out of which four (23.53%) developed hypotension. Seventy three (60.83%) patients had moderate anxiety; out of which twenty seven (36.99%) developed hypotension. Thirty (25%) patients had severe anxiety; out of which twenty two (73.33 %) developed hypotension. P-value (0.001) was quite significant. CONCLUSION:  It was concluded in our study that severity of pre-operative anxiety has significant effect on intra-operative spinal hypotension.