Background: Programmed labor aims to minimize duration and inconvenience of labor both for patient and obstetrician. The present study attempts to provide labor analgesia by using infusion ...paracetamol in place of conventional ketamine and tramadol. Methods: This study was conducted in the labor room of department of obstetrics and gynecology, RIMS, Ranchi from March 2019 to February 2020. 50 primigravida and 50 multigravidas were studied, with singleton pregnancy, cephalic presentation presenting with spontaneous onset of labor with Gestational age of 37-41 week. Results: 30% of patients were greater than 40 weeks gestation.65% of primigravida experienced severe pain, but only 20% of multigravidas had severe pain.60%primigravidas and 60% multigravidas (of 20% who had severe pain) experienced adequate pain relief with labor analgesia. 60 % primigravida presented with <4 cm cervical dilatation, whereas 40% multigravidas had <4 cm dilatation. 60% primigravida had shortened active phase (3.5 hrs), 60% multigravidas (2.5 hrs) which is suggestive of benefit of obstetrical analgesia in programmed labor. 90% patients had third stage labor less than 3 minutes. Only one multigravida landed in postpartum hemorrhage. All neonates had Apgar score greater than 8. There was no perinatal mortality. Only one primigravida landed in caesarean section due to arrest in second stage. 2 multigravidas had instrumental delivery. Maternal side effects like tachycardia, nausea, cervical and vaginal tears were more in primigravida. Conclusions: Participants with good response to obstetrical analgesia fared better than rest. Response was more satisfactory in primigravida in terms of labor progress. Key Words: Labor, Analgesia, Pain, Singleton, Satisfaction, Paracetamol
Background: The present study undertaken is to identify the risk factors causing Preterm premature rupture of membranes (pPROM) and to study fetal and maternal outcome associated with pPROM, to ...diagnose and manage chorioamnionitis associated with pPROM and to evaluate levels of C reactive protein (CRP). Methods: This study was conducted in the department of obstetrics and gynaecology, Rajendra institute of medical sciences from March 2019 to February 2020.50 cases of confirmed preterm premature rupture of membrane before 35 weeks of pregnancy were taken as cases and 50 cases of normal pregnancy (28-40 weeks) were taken as controls. Results: Highest incidence of premature rupture of membrane was among 20-25-year (68%) age groups. Incidence of premature rupture of membrane was more in low socioeconomic status (72%). Maximum incidence of premature rupture of membrane in 31-33 weeks gestational age (52%). Most cases of premature rupture of membrane in 24-48-hour group (38%). Most of study group (90%) and control group (80%) delivered by vaginal route. 11 study cases with clinical chorioamnionitis had elevated CRP (43.5 mg/l). One presented with clinical chorioamnionitis. CRP was most sensitive (92%). Total maternal morbidity was due to puerperal pyrexia (22%). Four patients with neonatal sepsis had CRP>6 mg/l. CRP and presence of polymorphs in gastric aspirate have 100% association with septicemia in neonates. Conclusions: Preterm premature rupture of membrane can be associated with adverse foetal and maternal outcome if immediate measures are not taken. Keywords: Preterm, Chorioamnionitis, Septicemia, Neonate, Morbidity
Background: Pregnancy associated anxiety and depression is very well known for its prevalence. Pandemic like COVID-19 all the more is additive to the levels of anxiety and depression during ...pregnancy, especially for mothers who are concerned about feto-maternal wellbeing. This study makes an effort to analyze the health-related behavior changes and psychological impact of pregnant women after COVID-19 outbreak. Methods: Cross sectional, questionnaire-based study conducted on pregnant ladies visiting labor room and out-patients department RIMS, Ranchi from April 2020 to September 2020. Results: Most patients were primigravida and turned up only in third trimester. Pregnancy complications like heart disease, GDM, jaundice, PIH were present in 28% of participants. 48% participants had no family income during pandemic. The 92% women wore masks, 80% practiced social distancing, 72% practiced frequent handwashing, 72% practiced frequent handwashing during pandemic, 80% had no regular antenatal check-up. Almost 64% participants showed mild to moderate anxiety, 34% had moderate depression and 40% had moderate stress. Four percentages had severe anxiety, 2% had severe depression and 12% had severe stress. Usage of mask was inversely related to GAD7 scores, but had no correlation with EPDS scores. Rest parameters like frequent handwashing, social distancing, stressful behavior, not going out and frequent handwashing were directly related to GAD 7 and EPDS score. Conclusions: Mental health and preventive behavior of respondents could be attributed to socio demographic, social, situational, economic status, family conditions and perception of severity of Covid19. Keywords: Anxiety, Depression, Pandemic, Pregnancy, COVID-19
Gamma delta T cells (γδTc) have tremendous anti-tumoral activity, thus γδTc immunotherapy is currently under development for various malignancies. We targeted breast cancer stem-like cells (BCSC), a ...rare cell population responsible for patient mortality. BCSC were mostly susceptible to γδTc immunotherapy, yet some escaped. The BCSC secretome rendered γδTc hypo-responsive, and resistant BCSC expressed more PD-L1 and anti-apoptotic protein MCL-1 than non-stem-like cells (NSC). BCSC resistance was partially overcome by dMCL1-2, an MCL-1 degrader, or more fully by blocking PD-1 on γδTc. Increased MICA shedding was prevented by the ADAM inhibitor GW280264X, rendering BCSC as sensitive to γδTc cytotoxicity as NSC. Our data show promising potential for γδTc immunotherapy against BCSC while unraveling immune evasion mechanisms exploited by BCSC, which likely also enable their resistance to cytotoxic T and NK cells. Overcoming this resistance, as we have done here, will improve cancer immunotherapy, leading to better cancer patient outcomes.
•Breast cancer stem-like cells (BCSC) use multiple mechanisms to evade γδ T cells.•Blocking PD-1 partially reverses BCSC resistance to γδ T cell cytotoxicity.•Targeting the anti-apoptotic protein MCL-1 increases BCSC sensitivity.•BCSC express lower MICA on the cell surface and shed more MICA than non-BCSC .•ADAM inhibition prevents MICA shedding, overcoming BCSC resistance to γδTc.
There is a strong rationale for investigating nutritional interventions with docosahexaenoic acid (DHA) in cancer prevention and therapy; however, the effects of DHA on ovarian cancer (OC) have not ...been well studied. Here, we investigated if DHA alone and in combination with carboplatin reduces OC cell growth in vitro. In vivo, we used a high-grade serous OC patient-derived xenograft (PDX) mouse model to investigate if DHA affects OC growth and enhances the anticancer actions of carboplatin. We showed synergistic cell killing by DHA and carboplatin in DHA-resistant Kuramochi and SKOV3 OC cells, which corresponded with increased DHA incorporation into whole-cell membrane phospholipids (P < 0.05). In vivo, feeding mice a diet supplemented with 3.9% (w/w of fat) DHA resulted in a significant reduction in PDX growth with and without carboplatin (P < 0.05). This reduction in tumor growth was accompanied by an increased tumor necrotic region (P < 0.05) and improved survival. Plasma membranes in tumors and livers excised from mice fed a DHA diet had ∼ twofold increase in DHA incorporation as compared with mice fed a control diet. Our findings indicate that DHA supplementation reduces cancer cell growth and enhances the efficacy of carboplatin in preclinical models of OC through increased apoptosis and necrosis.
Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952453
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for ...neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability, and demonstrate that this technique is universal as it is applicable to multiple cell types and media.
Abstract
There is growing evidence that tumor-targeted cytotoxins can also enhance anti-tumor immunity by inducing immunogenic cell death (ICD) in tumor cells and promoting recruitment of immune ...effector cells. We sought to investigate the immune stimulating potential of STRO-003, an antibody drug conjugate (ADC) composed of an anti-Receptor Orphan Receptor Kinase 1 (ROR1) antibody conjugated to a topoisomerase I targeted exatecan warhead via a cleavable linker. ROR1 is an oncofetal transmembrane receptor with restricted expression in normal tissues. Its overexpression in several cancer indications has been described, including in ovarian, non-small cell lung carcinoma (NSCLC), triple negative breast cancer (TNBC), and hematological malignancies, thus making it an ideal ADC target. We have previously demonstrated potent in vivo activity of STRO-003 in a panel of ROR1-expressing lung cancer patient-derived xenograft (PDX) models. Here we show that the exatecan warhead, SC3386, and STRO-003 ADC induced ICD in vitro as evidenced by presentation of cell-surface calreticulin and release of HMGB1. Consistent with this finding, STRO-003-treated cells elicited monocyte activation in a PBMC co-culture assay. To determine if these immunogenic properties could improve therapeutic efficacy, we evaluated STRO-003 in combination with an immune checkpoint inhibitor in a mouse syngeneic model expressing ROR1. We have demonstrated that STRO-003 in combination with checkpoint inhibition significantly enhances efficacy in a syngeneic mouse model and supports durable anti-tumor immunity. Follow-up vaccination studies were performed to further explore the significance of STRO-003-induced ICD and protective immunity in vivo. These results demonstrate that tumor cells pre-treated with STRO-003 or SC3386 undergo potent immunogenic cell damage which can, in turn, mount protective immunity in vivo.
Citation Format: Alice Yam, Helena Kiefel, Andrew McGeehan, Robert Yuan, Sihong Zhou, Dayson Moreira, Indrani Dutta, Xiaofan Li, Cuong Tran, Gang Yin, Kristin Bedard, Trevor Hallam. The anti-ROR1 ADC STRO-003 demonstrates immune-modulating properties that may enhance checkpoint blockade. abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4894.
The Reelin signaling pathway is involved in the migration of neurons during brain development. Reelin binding to the receptors VLDLR (Very Low Density Lipoprotein Receptor) and ApoER2 (Apolipoprotein ...E Receptor 2) leads to Dab1 phosphorylation, thereby activating a cascade of downstream pathways. Here, we show that the neuronal splicing factor Nova1 is involved in the exclusion of Dab1 exons 9b and 9c. In particular, the expression of Nova1 isoform 2 (without its penultimate exon 4), coincides with exclusion of Dab1 exons 9b and 9c in a neuronal P19 cells. Nova1 knockdown in P19 cells results in increased inclusion of Dab1 exons 9b and 9c. We also show that Dab1 phosphorylation is regulated by the Shp-2 phosphatase. Intriguingly, in addition to its role as a phosphatase, Shp-2 can function as an adapter protein to recruit kinases that phosphorylate Dab1 in P19 cells but not HEK293T cells. These results suggest an additional level of complexity to the regulation of Dab1 phosphorylation during neuronal development.
The effect of boron deficiency was studied in tomato plants grown hydroponically. Morphological studies showed that boron deficiency in the root system caused a cessation of root elongation, browning ...and thickening of root tips, the formation of branch roots close to the apex and decrease in the overall size of the root. The pyrimidine biosynthetic pathway remained intact and functional under boron limitation. The sugar nucleotide, uridine diphosphate glucose, was diminished in boron deficient medium and its level was restored to that of born sufficiency when uracil, cytosine, uridine, cytidine or orotic acid was provided.
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