Ambient Air Pollution: A New Intrauterine Environmental Toxin for Preterm Birth and Low Birth Weight.

Background: Urbanization and industrialization in developing and developed countries have led to rise of intrauterine environmental toxins-PM2.5, PM10, NO2 and Ozone. Aim: To determine association of ambient air pollution exposure with prematurity and low birth weight. Materials and Methods: It is a retrospective cohort study done from January 2021 till June 2022 in a tertiary care hospital, New Delhi. Purposive sampling was done, and for each patient, criteria pollutants exposure was recorded from the government recording stations nearest to her residence and pregnancy outcome correlated with same. Results: Total 1155 deliveries were recruited. Significant association was found between PM2.5 exposure and preterm birth during first trimester (p < 0.05). Significant association was found between ozone exposure and preterm birth during second trimester (p < 0.05). Significant association was also found between NO2 exposure and preterm birth during first and second trimester (p < 0.05). Maternal PM2.5 exposure during first trimester was significantly associated with low birth weight (p < 0.05). PM10 exposure during first trimester was significantly associated with low birth weight (p < 0.05). Conclusion: Current study reveals direct relationship between ambient air pollution exposure and pregnancy outcomes (preterm birth and low birth weight).

Huge Abdominopelvic Mass Arising from Cervical Fibroid around an Infected Cervical Diverticulum: A Very Rare Case and a Review of Literature.

Primary uterine diverticula are a very rare congenital anomaly of the uterus with only 21 reported cases. Even rarer is the occurrence of primary cervical diverticula with only six cases reported so far. This is a unique case of a huge abdominopelvic mass arising from cervical fibroid around an infected cervical diverticulum. A 44 year-old, P4L4 came to the OPD with a eighteen weeks size abdomino-pelvic mass. She had a failed surgery 6 months back, attempted to remove the mass. Magnetic resonance imaging revealed a cervical diverticulum which possibly had a pus collection. Relaparotomy was done. It revealed a huge cervical fibroid with dense adhesions all around the mass. A pan hysterectomy was done. In the postoperative period, she developed high-grade fever owing to the development of a pelvic collection, which had to be drained by dilating the vault sutures. Histopathology report confirmed a cervical fibroid with an infected diverticulum within. Primary uterine or cervical diverticula are a very rare anamoly which possibly arise because of a weakness in the area where the two mullerian ducts fuse. Women with this rare condition may suffer from infertility, fever and pain abdomen, acute abdomen owing to torsion or hemoperitoneum, pregnancy complications, and menorrhagia. Diverticulectomy and cervical/uterine reconstruction can be done on nulliparous women while hysterectomy can be offered to perimenopausal women. To conclude, unless known by the gynecologists, radiologists, and the pathologists, this diagnosis can be easily missed out, leading to multiple preventable complications.

Comparison of Feto-maternal Outcomes Among Various BMI Groups As Per Asia Pacific Standards: An Observational Retrospective Comparative Study in a Private Tertiary Care Center in Delhi.

Objective: To compare the feto-maternal outcomes among various BMI groups as per Asia Pacific Standards. Method: This is a retrospective non-interventional observational study on 1396 antenatal women with singleton pregnancy. Their BMI based on pre-pregnancy weight was calculated and the women were divided into various groups as per Asia Pacific standards for BMI classification. Details of associated morbidities and delivery outcomes were noted in a pre-structured proforma and a comparison was made among the various groups using Chi square test. A p value of < 0.05 was taken as significant. Results: Among the 1396 women under study, 10.6% were underweight, 36% had normal weight, 21% were overweight while 32% were obese or very obese. There was a significant association of low BMI with preterm labor (p value 0.03) and fetal growth restriction (p value < 0.01). Overweight and obese women were found to be more prone to hypertensive disorders of pregnancy (p value- 0.002), gestational diabetes (p value- 0.003) and overweight women were more prone to cholestasis of pregnancy (p value 0.03). The women with higher BMI had a significantly higher requirement of induction of labor (p value-0.0002). There was significant increased number of babies more than 90th percentile in overweight and obese women (p value 0.003). However, there was no change in Neonatal ICU admissions (p value 0.85) or neonatal mortality. Conclusion: Asia Pacific references should be used for studies related to all studies on BMI and pregnancy. All women having BMI outside the normal BMI spectrum are at increased risk of antenatal and postnatal complications. Early identification of such women will enable careful evaluation and counseling to improve the reproductive outcome and feto-maternal health.

Leadership Driven Persistent Reduction in Cesarean Trends: An Interventional Study for Quality Improvement.

Background: This is a quality improvement study in North India undertaken to observe the efficacy and safety of a proposed set of interventions along Quality Improvement guidelines to reduce cesarean rates. Materials and Methods: It was a retrospective cross-sectional study conducted in New Delhi. Measures were iteratively introduced from 2017 and improved using multiple PDSA (Plan, Do, Study, Act) cycles to note the overall reduction in cesarean rates. Chi square tests were done with subanalysis based on the Robsons classification. Results: There was a significant reduction of annual cesarean rates from 36.35 to 22.87% over four years (p < 0.01) and in neonatal nursery admissions (p < 0.01). Covid outbreak saw a comparatively increased cesarean rate in 2020, for which it was excluded from the detailed study. The relative risk of cesarean delivery in the postintervention period was 0.62. Maximum reductions were seen in Robsons II, VI &VII. Conclusion: Devising multipronged interventions and their implementation through PDSA cycles are essential. Such measures in moderate resources are replicable elsewhere as well.

Sequential use of drugs (prostaglandin e1 after failed trial of PGE2 gel) for induction of labour: Retrospective observational study.

With advancements in medicine, the scope of pregnancies have increased. This has subsequently increased the number of inductions and therefore more caesarean sections. We looked at the efficacy and safety of sequential induction with PGE2 gel followed by PGE1 tablets after a period of rest in a retrospective observational study. Women with failed induction of labour with 3 PGE2 gel were re-induced with 25ug vaginal PGE1 tablets, with a maximum of five doses (sequential regimen). Fetomaternal outcome and vaginal delivery rates were compared between the only-PGE2 gel group and the sequential group.There were 296 inductions of labour, of which 41 were included in the sequential group, amongst whom the vaginal delivery rate was 56%. Caesarean delivery rate with only PGE2 gel would have been 32%, but with the addition of PGE1 vaginal tablet (sequential induction), it reduced by >8% (p = 0.02). Fetomaternal outcomes were comparable in the two groups. We thus conclude that sequential induction with PGE1 tablets is an effective option.

Effect of low-dose exposure of aluminium oxide nanoparticles in Swiss albino mice: Histopathological changes and oxidative damage.

Rapid growth in the use of aluminium oxide nanoparticles (Al2O3 NPs) in various fields such as medicine, pharmacy, cosmetic industries, and engineering creates concerns since the literature is replete with data regarding their toxicity in living organisms. The objective of the present study was to demonstrate the potential toxicological manifestations of repeated exposure to Al2O3 NP at low doses in vivo. In the present study, Al2O3 NP was orally administered at 15, 30 or 60 mg kg-1 body weight for 5 days to Swiss albino male mice. A battery of well-defined assays was undertaken to evaluate aluminium (Al) bioaccumulation, haematological and histological changes, oxidative damage and genotoxicity. Physico-chemical characterisation demonstrated increases in hydrodynamic diameter along the concentration gradient of Al2O3 NP dispersed in MilliQ water. Brain, liver, spleen, kidney and testes showed high Al retention levels. Histopathological lesions were prominent in the brain and liver. Al2O3 NP treatment increased levels of lipid peroxidation and decreased glutathione content in the test organs at all dose levels. The enzyme activities of catalase and superoxide dismutase were also significantly altered. DNA damage quantified using the comet assay was markedly increased in all the soft organs studied. Anatomical abnormalities, redox imbalance and DNA damage were positively correlated with Al retention in the respective organs. Size, zeta potential and colloidal state might have contributed to the bio-physico-chemical interactions of the NPs in vivo and were responsible for the non-linear dose response. The overall data indicate that Al2O3 NP exposure may result in adverse health consequences, inclusive of but not limited to disturbed redox homeostasis, hepatocellular toxicity, neurodegeneration and DNA damage.

Complete Uterine Septum with Cervical Duplication and Longitudinal Vaginal Septum: An Anomaly Supporting Alternative Embryological Development.

The diagnosis and management of Mullerian abnormalities have revolutionized with the advent of magnetic resonance imaging, three-dimensional ultrasound, and endoscopic techniques. All the earlier unclassified abnormalities can now be classified as per the new European Society of Human Reproduction and Embryology 2013 nomenclature. The presence of complete uterine septum with cervical duplication and longitudinal vaginal septum reinforces the alternative theory of Mullerian development. The presence of this complex anomaly is discussed in the light of embryonic development along with management issues.

VBAC: Changes over Last 10 Years.

INTRODUCTION: Vaginal birth after caesarean section (VBAC) has been historically studied to be a standard and a safe procedure with good successful results. AIMS: This study was conducted to determine changes in pattern of VBAC by the same author over a period of 10 years. RESULTS: Data for 1 year between 2005-2006 and 2014-2015 were compared, and successful VBAC was found to be 74.46% in 2005-2006 period compared to only 34.42% in 2014-2015. Neonatal mortality and maternal morbidity were, however, much higher 10 years ago. CONCLUSIONS: It was concluded that better diagnostic techniques, awareness of patients and medico legal fear have led to safer health of mother and child and lesser incidence of VBAC over the last 10 years.

Inhibition of oncogenic cap-dependent translation by 4EGI-1 reduces growth, enhances chemosensitivity and alters genome-wide translation in non-small cell lung cancer.

Hyperactivation of eIF4F-mediated translation occurs in many if not all cancers. As a consequence, cancer cells aberrantly enhance expression of malignancy-related proteins that are involved in cell cycle progression, angiogenesis, growth, and proliferation. With this in mind eIF4F is a promising molecular target for therapeutics that counteract pathological eIF4F activity. Here we used 4EGI-1, a small-molecule inhibitor of cap-mediated translation that disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex to treat non-small cell lung cancer (NSCLC). Treatment of cells with 4EGI-1 reduced cell proliferation, decreased cap-dependent complex formation, induced apoptosis, enhanced sensitivity to gemcitabine, and altered global cellular translation. Suppression of cap-dependent translation by 4EGI-1 resulted in diminished expression of oncogenic proteins c-Myc, Bcl-2, cyclin D1, and survivin, whereas ß-actin expression was left unchanged. In light of these results, small-molecule inhibitors like 4EGI-1 alone or with chemotherapy should be further evaluated in the treatment of NSCLC.

Laparoscopic Management of Nonpuerperal Uterine Inversion.

Uterine inversions are a rare entity, and most occur in the postpartum period. Nonpuerperal inversion accounts for only 16% of cases and are mostly associated with a submucous myoma. A 38-year-old woman with a submucous myoma presented with severe lower abdominal pain, acute retention of urine, and hypotension. Because the clinical examination was inconclusive due to severe pain and the ultrasound was dubious, diagnosis was made with magnetic resonance imaging. Successful laparoscopic hysterectomy was contemplated after correcting uterine inversion. This case highlights the diagnostic dilemmas and the key points during laparoscopic management of uterine inversion.

Unilateral tubo-ovarian agenesis with contralateral adnexal torsion in a premenarchal girl.

Unilateral adnexal agenesis is a rare entity. Most of these cases are reported in reproductive age group. A case of a 10-year-old premenarchal girl is reported who presented with acute abdominal pain and vomiting. BothUltrasonography (USG) and MRI suggested right ovarian mass with torsion. Laparoscopic evaluation revealed an enlarged right ovary with torsion and contralateral agenesis of uterine tube and left ovary. Detortion of the ovary and an ovarian fixation to the ovarian pedicle was done. This is the first reported case of a premenarchal girl presenting with an acute abdomen due to adnexal torsion along with contralateral tubo-ovarian agenesis.

4EGI-1 represses cap-dependent translation and regulates genome-wide translation in malignant pleural mesothelioma.

Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells. This effect was associated with hypophosphorylation of 4E-binding protein 1 (4E-BP1) and decreased protein levels of the cancer-related genes, c-myc and osteopontin. 4EGI-1 showed enhanced cytotoxicity in combination with pemetrexed or gemcitabine. Translatome-wide polysome microarray analysis revealed a large cohort of genes that were translationally regulated upon treatment with 4EGI-1. The 4EGI-1-regulated translatome was negatively correlated to a previously published translatome regulated by eIF4E overexpression in human mammary epithelial cells, which is in agreement with the notion that 4EGI-1 inhibits the eIF4F complex. These data indicate that inhibition of the eIF4F complex by 4EGI-1 or similar translation inhibitors could be a strategy for treating mesothelioma. Genome wide translational profiling identified a large cohort of promising target genes that should be further evaluated for their potential significance in the treatment of MPM.

Comprehensive analysis of fly ash induced changes in physiological/growth parameters, DNA damage and oxidative stress over the life cycle of Brassica juncea and Brassica alba.

Fly ash (FA) being a heterogeneous mixture of heavy metal affects plant system in various ways. Previous studies have shown bioaccumulation of toxic metals in the plants and disturbance in cellular activities. Here, we have studied the impacts of FA treatment through the life cycle of economically important, annual crop plant mustard (Brassica juncea and Brassica alba). Result revealed that FA did not alter germination rate and photosynthetic pigment levels. Tolerance index of B. juncea was higher compared to B. alba. Seed setting was significantly affected by FA in B. alba. Significant increase in DNA damage was observed in both B. alba and B. juncea. Proline accumulation was significantly higher in B. alba. In B. juncea catalase activity and reduced glutathione content declined in initial days which were restored at the end of experimental period. Significant decrease in non-enzymatic antioxidants was noted in B. alba. Higher accumulation of Pb and As was noted in shoot of B. juncea and in B. alba Cu, Pb, Cr and As accumulated in shoots. As observed from these results, both plants could translocate certain toxic heavy metals from roots to the shoot which affected the physiological and biochemical balance and induced genotoxic response.

Surface capping and size-dependent toxicity of gold nanoparticles on different trophic levels.

In the present study, the toxicity of gold nanoparticles (Au NPs) was evaluated on various trophic organisms. Bacteria, algae, cell line, and mice were used as models representing different trophic levels. Two different sizes (CIT30 and CIT40) and surface-capped (CIT30-polyvinyl pyrrolidone (PVP)-capped) Au NPs were selected. CIT30 Au NP aggregated more rapidly than CIT40 Au NP, while an additional capping of PVP (CIT30-PVP capped Au NP) was found to enhance its stability in sterile lake water medium. Interestingly, all the forms of NPs evaluated were stable in the cell culture medium during the exposure period. Size- and dose-dependent cytotoxicities were observed in both bacteria and algae, with a strong dependence on reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. CIT30-PVP capped Au NP showed a significant decrease in toxicity compared to CIT30 Au NP in bacteria and algae. In the SiHa cell line, dose- and exposure-dependent decline in cell viability were noted for all three types of Au NPs. In mice, the induction of DNA damage was size and dose dependent, and surface functionalization with PVP reduced the toxic effects of CIT30 Au NP. The exposure to CIT30, CIT40, and CIT30-PVP capped Au NPs caused an alteration of the oxidative stress-related endpoints in mice hepatocytes. The toxic effects of the gold nanoparticles were found to vary in diverse test systems, accentuating the importance of size and surface functionalization at different trophic levels.

Rapid microfluidic solid-phase extraction system for hyper-methylated DNA enrichment and epigenetic analysis.

Genetic sequence and hyper-methylation profile information from the promoter regions of tumor suppressor genes are important for cancer disease investigation. Since hyper-methylated DNA (hm-DNA) is typically present in ultra-low concentrations in biological samples, such as stool, urine, and saliva, sample enrichment and amplification is typically required before detection. We present a rapid microfluidic solid phase extraction (µSPE) system for the capture and elution of low concentrations of hm-DNA (≤1 ng ml(-1)), based on a protein-DNA capture surface, into small volumes using a passive microfluidic lab-on-a-chip platform. All assay steps have been qualitatively characterized using a real-time surface plasmon resonance (SPR) biosensor, and quantitatively characterized using fluorescence spectroscopy. The hm-DNA capture/elution process requires less than 5 min with an efficiency of 71% using a 25 µl elution volume and 92% efficiency using a 100 µl elution volume.

Peptide nucleic acid (PNA)-DNA duplexes: comparison of hybridization affinity between vertically and horizontally tethered PNA probes.

We compare the PNA-DNA duplex hybridization characteristics of vertically tethered and new horizontally tethered PNA probes on solid surfaces. The horizontal 15-mer PNA probe has been synthesized with linker molecules attached at three locations (γ-points) positioned along the PNA backbone that provides covalent attachment of the probe with the backbone aligned parallel to the surface, which is important for DNA hybridization assays that use electric field effect sensors for detection. A radioactive labeled assay and real-time surface plasmon resonance (SPR) biosensor are used to assess the probe surface density, nonspecific binding, and DNA hybridization affinity, respectively, of the new PNA probe configuration. The estimated equilibrium dissociation constants of the horizontally tethered duplex and the vertically tethered duplex are of the same order of magnitude (KD ≈ 5 nM), which indicates a sufficient hybridization affinity for many electronic biosensors that benefit from the horizontal alignment, which minimizes the effects of counterion screening.

Integrated label-free silicon nanowire sensor arrays for (bio)chemical analysis.

We present a label-free (bio)chemical analysis platform that uses all-electrical silicon nanowire sensor arrays integrated with a small volume microfluidic flow-cell for real-time (bio)chemical analysis and detection. The integrated sensing platform contains an automated multi-sample injection system that eliminates erroneous sensor responses from sample switching due to flow rate fluctuations and provides precise sample volumes down to 10 nl. Biochemical sensing is demonstrated with real-time 15-mer DNA-PNA (peptide nucleic acid) duplex hybridization measurements from different sample concentrations in a low ionic strength, and the equilibrium dissociation constant KD ≈ 140 nM has been extracted from the experimental data using the first order Langmuir binding model. Chemical sensing is demonstrated with pH measurements from different injected samples in flow that have sensitivities consistent with the gate-oxide materials. A differential sensor measurement configuration results in a 30× reduction in sensor drift. The integrated label-free analysis platform is suitable for a wide range of small volume chemical and biochemical analyses.

Ras pathway activation in malignant mesothelioma.

INTRODUCTION: Mutations in Ras family genes are rare in malignant mesothelioma. The role of activation of the Ras signaling pathway in the pathogenesis of mesothelioma is not clear. METHODS: We studied the activation status of the Ras pathway and the status of other Ras-associated kinases in a panel of human mesothelioma cell lines. In addition, we tested the effect of inhibition of several kinase pathways on mesothelioma cell proliferation. The potential role of kinase signaling on the regulation of cap-dependent translation was also studied. RESULTS: In general, Ras-guanosine triphosphate (GTP) was higher in mesothelioma cell lines when compared with a nontransformed mesothelial cell line (LP9). Furthermore, known Ras effectors such as extracellular-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase were found to be active in most of the mesothelioma cell lines tested. Exposure to specific inhibitors of extracellular-regulated kinase 1/2 (U0126) and c-Jun N-terminal kinase (SP600125) significantly decreased the proliferation of H2596 and H2373 cells compared with mock-treated cells. SP600125-mediated c-Jun N-terminal kinase inhibition, but not extracellular-regulated kinase 1/2 inhibition, resulted in a decrease in phosphorylation of 4E-BP1, consequently decreasing cap-dependent activation. CONCLUSIONS: These experiments provide a rationale for targeting Ras and associated signaling pathways in mesothelioma and also suggest cap-dependent translation as one mechanism by which Ras induces proliferation in this disease.