A Rare Case of Ectocervical Pregnancy and Its Successful Management: A Case Report and Review of the Literature.

Cervical pregnancy is a very rare form of ectopic pregnancy, which can be life-threatening due to the potential risk of massive haemorrhage. The most likely site of cervical implantation is within the endocervical canal. We report here an unusual and another possible site of cervical pregnancy on the surface of the ectocervix (portio). The patient presented with vaginal bleeding after a period of six weeks of amenorrhea and a positive urinary pregnancy test. Clinical examination was suggestive of a cervical mass on the surface of the portio, which was successfully managed by local excision and the application of haemostatic sutures. Histopathology of the mass was suggestive of trophoblasts amidst cervical epithelium and stroma, which was cytokeratin positive in immunohistochemical staining, confirming the diagnosis of cervical ectopic pregnancy on the portio. Postoperatively, the patient recovered well and beta-human chorionic gonadotropin (ßhCG) normalised within two weeks. Thus, the surface of the ectocervix is another possible site of cervical pregnancy, which can be successfully managed by total excision of the ectopic mass and local haemostatic measures.

Predictors of Successful Medical Management With Methotrexate in Unruptured Tubal Ectopic Pregnancy.

Introduction Medical treatment with methotrexate (MTX) is a safe and effective alternative to surgery in carefully selected cases of ectopic pregnancies diagnosed early prior to rupture. Aim To determine the optimal pre-treatment levels of beta human chorionic gonadotropin (𝛽-hCG) and its changing trends most likely to have a successful outcome with medical management. Material and methods A prospective observational study was conducted in a tertiary teaching hospital from December 2018 to May 2021. "Single-dose" MTX regime was used for medical management of ectopic pregnancy in patients fulfilling the selection criteria. The 𝛽-hCG levels were recorded at baseline and on day 4 and day 7 of MTX injection. Thereafter, at weekly intervals till complete resolution or surgical intervention due to failure of medical management. In addition, receiver operating characteristic (ROC) curve analysis for a pre-treatment 𝛽-hCG cut-off value and changing trends in post-treatment 𝛽- hCG levels most likely to have a successful outcome with MTX treatment were determined. Results Fifty patients fulfilling the inclusion criteria were included in the study, with successful medical management in 33 (66%). The mean pre-treatment 𝛽-hCG levels in women with successful medical management were 3270.97 (+/- 901) compared to 5249.17 (+/-808.02) for those with treatment failure (p=0.00001). The mean 𝛽-hCG level in the failed treatment group was significantly higher on day 4 than the pre-treatment levels (6742.56 +/- 572 vs. 5249.17+/- 808.02; p<0.05). Inadequate reduction of 𝛽-hCG level on day 7 (<15% of day 4 levels) requiring repeat dosage of MTX was more likely to have an unsuccessful outcome (p=0.00001). The area under curve (AUC) value of 0.905 (95% CI: 0.814-0.996) depicted that pre-treatment 𝛽-hCG level of 4000 mIU/ml taken as the cut-off value was able to predict levels ≤4000 mIU/ml had a greater likelihood of successful outcome with MTX, having a sensitivity of 84.5%, specificity of 83.3%, positive predictive value (PPV) of 90.3%, and negative predictive value (NPV) of 75% (p< 0.05). Demographic variables or previous clinical history, considered risk factors for ectopic pregnancy, did not affect the outcome of medical management in this study. Conclusion Medical management of ectopic pregnancy is a viable first-line treatment option in carefully selected patients. In this study, the most important predictors for the successful outcome of medical management were the pre-treatment ß-hCG levels and their fall on day 4 and day 7 after MTX therapy.

A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla.

Temporal patterning is an important mechanism for generating a great diversity of neuron subtypes from a seemingly homogenous progenitor pool in both vertebrates and invertebrates. Drosophila neuroblasts are temporally patterned by sequentially expressed Temporal Transcription Factors (TTFs). These TTFs are proposed to form a transcriptional cascade based on mutant phenotypes, although direct transcriptional regulation between TTFs has not been verified in most cases. Furthermore, it is not known how the temporal transitions are coupled with the generation of the appropriate number of neurons at each stage. We use neuroblasts of the Drosophila optic lobe medulla to address these questions and show that the expression of TTFs Sloppy-paired 1/2 (Slp1/2) is directly regulated at the transcriptional level by two other TTFs and the cell-cycle dependent Notch signaling through two cis-regulatory elements. We also show that supplying constitutively active Notch can rescue the delayed transition into the Slp stage in cell cycle arrested neuroblasts. Our findings reveal a novel Notch-pathway dependent mechanism through which the cell cycle progression regulates the timing of a temporal transition within a TTF transcriptional cascade.

Maternal and Neonatal Outcome of Pregnant Women With SARS-CoV-2 Infection During the First and Second Wave of COVID-19 in a Tertiary Care Institute in Eastern India.

Background The ongoing coronavirus 2019 (COVID-19) pandemic is the most devastating health care crisis of our times. Pregnant women with COVID-19 infection belong to a vulnerable group with concerns about the effect of the disease on maternal and neonatal health. As we are dealing with a new disease, we must study the changing trend of disease presentation, diagnosis, and treatment to successfully manage such pregnancies. Objective The purpose of the present study was to evaluate the differences in presenting features, comorbidities, the fetal and maternal outcomes in COVID-19 positive pregnant women in the first and second wave of the pandemic in a tertiary care institute in eastern India. Methodology This study was a retrospective observational cohort study conducted at Tata Main Hospital, Jamshedpur, a tertiary care hospital in eastern India. All COVID-19 positive by reverse transcription-polymerase chain reaction or rapid antigen (RTPCR) test pregnant women (249 women) admitted to the hospital from May 2020 to August 2021 were included in this study. Out of the total, 139 women were admitted during the first wave (May 2020 to February 2021), and 110 women were admitted during the second wave (March 2021 to August 2021) of the pandemic. Data like baseline characteristics, clinical presentation, associated co-morbidities, management modalities, the maternal and neonatal outcomes were analyzed and compared. Results The peak of the first wave of COVID-19 was found during the months of August-October 2020, while the second wave was in April-May 2021. The majority of women had the asymptomatic or mild disease during both waves, but 14 women had moderate to severe disease during the second wave as compared to two women during the first wave. There was a significant increase in maternal deaths in the second wave (3.64%) as compared to the first wave (0.00%). During the second wave, out of 85 women who delivered, 78.8% (n=67) women had a cesarean section which was significantly higher than the first wave (64.6%). Hypertensive disorders (pre-eclampsia, gestational hypertension, and chronic hypertension) were the most common associated comorbidity, followed by diabetes (gestational diabetes, diabetes mellitus type 2) and anemia during both waves of the pandemic. The rate of preterm delivery was 27.78% (n=35) and 24.71% (n=21) during the first and second waves, respectively. Two babies tested positive within 24 hours of delivery during the first wave and one during the second wave.  Conclusion A significantly higher number of moderate to severe disease and maternal deaths were reported during the second wave of the pandemic. A higher incidence of severe oligohydramnios and cesarean section was seen during the second wave. The frequency of preterm deliveries and low birth weight remained high during both waves. Neonatal COVID-19 infection was seen during both waves, but the incidence remained low.

Post-partum complete acute uterine inversion: A coordinated multi-disciplinary approach ameliorates an obstetric nightmare, a case report.

Acute uterine inversion is a rare life-threatening complication of third stage of labour. In majority of cases, exact aetiology is unknown. It should be strongly suspected when the triad of haemorrhage, shock and severe abdominal pain with bearing down sensation is present after delivery of placenta. It can occur even after active management of third stage of labour. Diagnosis is essentially clinical. Expeditious manual repositioning of uterus and simultaneous liberal use of uterotonics is the management of choice. This was successfully attempted in the present case where a 26-year-old multiparous woman, without any identifiable risk factors, developed acute puerperal uterine inversion after active management of labour. It was observed that quick and accurate clinical judgement and timely intervention can prevent maternal mortality. The role of a multidisciplinary team including primary health care provider, obstetrician, anaesthesiologist and critical care experts has significant effects on outcome especially in intractable cases.

A comprehensive temporal patterning gene network in Drosophila medulla neuroblasts revealed by single-cell RNA sequencing.

During development, neural progenitors are temporally patterned to sequentially generate a variety of neural types. In Drosophila neural progenitors called neuroblasts, temporal patterning is regulated by cascades of Temporal Transcription Factors (TTFs). However, known TTFs were mostly identified through candidate approaches and may not be complete. In addition, many fundamental questions remain concerning the TTF cascade initiation, progression, and termination. In this work, we use single-cell RNA sequencing of Drosophila medulla neuroblasts of all ages to identify a list of previously unknown TTFs, and experimentally characterize their roles in temporal patterning and neuronal specification. Our study reveals a comprehensive temporal gene network that patterns medulla neuroblasts from start to end. Furthermore, the speed of the cascade progression is regulated by Lola transcription factors expressed in all medulla neuroblasts. Our comprehensive study of the medulla neuroblast temporal cascade illustrates mechanisms that may be conserved in the temporal patterning of neural progenitors.

Transcriptional and epigenetic regulation of temporal patterning in neural progenitors.

During development, neural progenitors undergo temporal patterning as they age to sequentially generate differently fated progeny. Temporal patterning of neural progenitors is relatively well-studied in Drosophila. Temporal cascades of transcription factors or opposing temporal gradients of RNA-binding proteins are expressed in neural progenitors as they age to control the fates of the progeny. The temporal progression is mostly driven by intrinsic mechanisms including cross-regulations between temporal genes, but environmental cues also play important roles in certain transitions. Vertebrate neural progenitors demonstrate greater plasticity in response to extrinsic cues. Recent studies suggest that vertebrate neural progenitors are also temporally patterned by a combination of transcriptional and post-transcriptional mechanisms in response to extracellular signaling to regulate neural fate specification. In this review, we summarize recent advances in the study of temporal patterning of neural progenitors in Drosophila and vertebrates. We also discuss the involvement of epigenetic mechanisms, specifically the Polycomb group complexes and ATP-dependent chromatin remodeling complexes, in the temporal patterning of neural progenitors.

Maternal and Neonatal Outcomes of COVID-19 in Pregnancy: A Single-Centre Observational Study.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic is one of the most challenging healthcare crises faced globally. Adequate information and understanding of the clinical presentation and impact of the disease on maternal and neonatal outcomes is the key to successfully manage a pregnancy with COVID-19. OBJECTIVE: The purpose of the present study was to evaluate the clinical presentation of COVID-19 in pregnancy, its course during pregnancy and its effects on maternal and neonatal outcomes. STUDY DESIGN AND SETTING: This study was a retrospective observational study conducted at Tata Main Hospital, Jamshedpur, a tertiary care hospital in Eastern India. Population and study period: All COVID-19-positive (by reverse transcription polymerase chain reaction or rapid antigen test) pregnant women admitted to the hospital from 15th May 2020 to 15th November 2020.  Results: A total of 132 COVID-19-positive pregnant women were included in the study. Eighty-six women (65.15%) were asymptomatic, 45 women (34.09%) had mild symptoms and one woman had severe disease. Major co-morbidities seen were hypertensive disorders (pre-eclampsia, gestational hypertension and chronic hypertension) in 18 (13.64%) and diabetes (gestational diabetes, diabetes mellitus type 2) in 14women (10.60%). The rate of preterm delivery was 28.69% (n=35). Caesarean section was done for 78 women (63.93%) and 44 (36.07%) delivered vaginally. Average birth weight reported was 2.59 kilograms. Forty babies (33.06%) were admitted to the neonatal intensive care unit. Two babies (1.65%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 24 hours of delivery.  Conclusion: COVID-19 in pregnancy commonly presents as an asymptomatic or mild disease. It is associated with high rates of preterm births and neonatal admissions to the intensive care unit. Intrauterine and neonatal death rates remain low. Vertical transmission is possible; however, the incidence is low, and the majority of these neonates are asymptomatic.

Prolonged Oxygen Therapy Post COVID-19 Infection: Factors Leading to the Risk of Poor Outcome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a single-stranded ribonucleic acid (RNA) ß-coronavirus. Prolonged duration of symptoms, ill health, disability, and need for hospitalisation are all well-known features of severe COVID-19 disease. OBJECTIVE: To describe the epidemiological, clinical and imaging characteristics of hospitalised patients of COVID-19 who required prolonged oxygen therapy after testing negative for SARS-CoV-2 and attempt to determine the associated factors leading to delayed recovery, failure to wean, and mortality. MATERIAL AND METHOD: Prospective observational study from 9th September to 6th November 2020 in a tertiary care COVID hospital of Jharkhand. Included COVID-19-infected patients requiring oxygen to maintain a saturation of ≥95% after testing reverse transcription polymerase chain reaction (RT-PCR) negative. Patients were classified as Group I, those who could be weaned off oxygen, and Group II, those who could not be weaned off oxygen during their stay in the isolation ward. A detailed assessment for outcome in these two groups related to age, gender, presence or absence of co-morbidities, nature of co-morbidities and findings of high-resolution CT (HRCT) thorax was done to ascertain risk factors for failure to wean and adverse outcomes. RESULTS: During the study period, 93 patients suffering from moderate to severe COVID-19 infection, could not be discharged from the hospital and were admitted to the post-COVID isolation ward after testing RT-PCR negative, due to breathlessness and need for oxygen therapy, with a male predominance, M:F ratio of 2.2:1. Of these 93 patients, 51 could be weaned off oxygen in the isolation ward. The mean and median age of patients who could be successfully weaned was 58.5±14.3 years and 60 years respectively, compared to a mean age of 64±12.4 years and a median age of 67 years for patients who could not be weaned off oxygen during the isolation period. Patients aged ≥60 years were at risk for prolonged requirement of oxygen compared to those <50 years of age, relative risk (RR) 1.43 (95%CI 0.9-2, p=0.051). Failure to wean in <50 years was noted in presence of co-morbidities, RR 4 (95%CI 1.5-10.6, p=0.005). Multivariable logistic regression analysis calculated an odds ratio (OR) of 12.22 (95%CI 2.4-61.5, p<0.002) in patients of coronary artery disease (CAD), and 3.34 (95%CI 1.01-10.9, p<0.046) in patients of diabetes, for failure to wean with delayed recovery in patients aged 50 years and more, having multiple co-morbidities. Presence of ≥three co-morbid conditions was associated with increased risk of critical care unit (CCU) admissions (RR 2.1, p=0.02), failure to wean (RR 1.79, p<0.006), and death (p=0.02). Elderly male patients (mean age of 81.3±7.2years) with CAD and multiple comorbidities were at a high risk of mortality (p=0.01). CONCLUSION:  Patients ≥50 years of age having ≥three co-morbidities are at increased risk of prolonged hospitalisation and oxygen therapy in moderate to severe COVID-19 infection, precluding their discharge even after they test negative for SARS-CoV-2. Elderly male patients of COVID-19 with CAD and multiple comorbidities are at a high risk of mortality.

A Case Report of Twin Pregnancy with Hydatidiform Mole and Co-existing Live Fetus.

Complete hydatidiform mole with co-existing live fetus (CHMF) is a rare and high-risk pregnancy usually seen with ovulation induction protocols. These pregnancies are complicated with vaginal bleeding, pre-eclampsia, miscarriage, preterm delivery, fetal demise and the risk of gestational trophoblastic neoplasia (GTN). Here, we describe a case of CHMF and a second case of monozygotic twins: partial mole with live fetuses. The pregnancies were conceived after clomiphene citrate ovulation induction. Both cases presented with vaginal bleeding and hyperemesis in the early mid-trimester. The diagnosis was based on history, examination, ultrasound findings and high serum beta-human chorionic gonadotropin (ßHCG) levels. A CHMF can be differentiated from a singleton partial molar pregnancy with similar ultrasound appearance by amniocentesis and karyotyping of the live fetus, which is a normal diploid. After adequate counseling, both women refused prenatal karyotyping and underwent the termination of pregnancy. The method of termination needs to be carefully decided. Surgical evacuation maybe difficult due to the well-formed fetus in the second trimester, and uterotonic agents can be associated with the risk of trophoblastic embolization and GTN. Termination with misoprostol followed by ultrasound-guided suction evacuation was successfully done in both cases. Histopathology and karyotyping confirmed the diagnosis of CHMF in the first and partial mole in the second case. ßHCG normalized within 7 weeks postevacuation in both, with no increased risk of trophoblastic embolization or GTN. More studies are needed on the methods of termination in such pregnancies. Medical termination with misoprostol appears to be a viable option, though the optimal dosage is yet to be defined.

A Rare Case of Pregnancy Complicated by Uterine Prolapse and Cervical Fibroid.

Uterine prolapse and cervical fibroid are two common gynecological conditions but relatively uncommon in pregnant women. However, these conditions can complicate normal pregnancy by significantly altering its course and outcome. Obstetricians should, therefore, familiarize themselves with the presentations, challenges, and outcomes of these unique situations to effectively manage the patient in the perinatal period. We report a rare case, where both uterine prolapse and cervical fibroid coexisted in a single pregnancy.

Temporal progression of Drosophila medulla neuroblasts generates the transcription factor combination to control T1 neuron morphogenesis.

Proper neural function depends on the correct specification of individual neural fates, controlled by combinations of neuronal transcription factors. Different neural types are sequentially generated by neural progenitors in a defined order, and this temporal patterning process can be controlled by Temporal Transcription Factors (TTFs) that form temporal cascades in neural progenitors. The Drosophila medulla, part of the visual processing center of the brain, contains more than 70 neural types generated by medulla neuroblasts which sequentially express several TTFs, including Homothorax (Hth), eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D) and Tailless (Tll). However, it is not clear how such a small number of TTFs could give rise to diverse combinations of neuronal transcription factors that specify a large number of medulla neuron types. Here we report how temporal patterning specifies one neural type, the T1 neuron. We show that the T1 neuron is the only medulla neuron type that expresses the combination of three transcription factors Ocelliless (Oc or Otd), Sox102F and Ets65A. Using CRISPR-Cas9 system, we show that each transcription factor is required for the correct morphogenesis of T1 neurons. Interestingly, Oc, Sox102F and Ets65A initiate expression in neurons beginning at different temporal stages and last in a few subsequent temporal stages. Oc expressing neurons are generated in the Ey, Slp and D stages; Sox102F expressing neurons are produced in the Slp and D stages; while Ets65A is expressed in subsets of medulla neurons born in the D and later stages. The TTF Ey, Slp or D is required to initiate the expression of Oc, Sox102F or Ets65A in neurons, respectively. Thus, the neurons expressing all three transcription factors are born in the D stage and become T1 neurons. In neurons where the three transcription factors do not overlap, each of the three transcription factors can act in combination with other neuronal transcription factors to specify different neural fates. We show that this way of expression regulation of neuronal transcription factors by temporal patterning can generate more possible combinations of transcription factors in neural progeny to diversify neural fates.

Salt bridges gate α-catenin activation at intercellular junctions.

Cadherin complexes transduce force fluctuations at junctions to activate signals that reinforce stressed intercellular contacts. α-Catenin is an identified force transducer within cadherin complexes that is autoinhibited under low tension. Increased force triggers a conformational change that exposes a cryptic site for the actin-binding protein vinculin. This study tested predictions that salt bridges within the force-sensing core modulate α-catenin activation. Studies with a fluorescence resonance energy transfer (FRET)-based α-catenin conformation sensor demonstrated that each of the salt-bridge mutations R551A and D503N enhances α-catenin activation in live cells, but R551A has a greater impact. Under dynamic force loading at reannealing cell-cell junctions, the R551A mutant bound more vinculin than wild-type α-catenin. In vitro binding measurements quantified the impact of the R551A mutation on the free-energy difference between the active and autoinhibited α-catenin conformers. A 2-µs constant-force, steered molecular dynamics simulation of the core force-sensing region suggested how the salt-bridge mutants alter the α-catenin conformation, and identified a novel load-bearing salt bridge. These results reveal key structural features that determine the force-transduction mechanism and the force sensitivity of this crucial nanomachine.

Deciding the route for hysterectomy: Indian triage system.

OBJECTIVES: To review the limitations, major complications, and conversion rates associated with non-descent vaginal hysterectomy (NDVH); and develop a scoring system to predict the possibility of successful NDVH. METHODS: The risk analysis of conversion rates from vaginal to abdominal route while attempting NDVH was applied to formulate a scoring system for the assessment of successful NDVH. Parameters were selected based on Kovacs guidelines to determine the route of hysterectomy. RESULTS: From April 2005 to December 2008, NDVH was attempted in 364/1,378 women undergoing hysterectomy for benign conditions (Gp-I). Eight out of 364 cases (2.1 %) either had to be converted to the abdominal route or had major complication. Endometriosis and repeated sections had the highest risk. Scoring system was developed based on the risk analysis. Validity of this scoring system was tested in 1,177 women from January 2009 to September 2012 (Gp-II). 460 women with a score of 16 or less underwent NDVH successfully with a conversion rate of 0.2 %. CONCLUSION: Careful assessment by a simple scoring system can help in deciding the feasibility of performing NDVH.