Rupture Of Membranes Research Articles

Preterm births and their associated clinical outcomes in a Tertiary Care Hospital in Lahore.

Objective: To assess the frequency of preterm births and their associated clinical outcomes in a tertiary care hospital in Lahore, Pakistan. Study Design: Prospective Observational study. Setting: Tertiary Care Hospital, Lahore. Period: Feb, 2024 to July 2024. Methods: The study included 219 preterm neonates delivered before 37 weeks of gestation. Data were collected on maternal complications, gestational age, birth weight, mode of delivery, APGAR scores, neonatal morbidities, and survival outcomes. Statistical analyses were performed to identify associations between maternal and neonatal factors and clinical outcomes. Significance was set at p < 0.05. Results: Of the 219 preterm neonates, 74.7% were delivered between 33–36 weeks, and 57.1% had a birth weight between 1.5–2.49 kg. The most common maternal complications were hypertension (41.7%) and premature rupture of membranes (34.8%). Neonatal jaundice (58.5%), respiratory distress syndrome (57.1%), and probable sepsis (55.3%) were the prevalent morbidities. Overall, 88% of neonates were discharged home. Survival outcomes were significantly associated with gestational age, birth weight, APGAR scores, feeding initiation, cesarean section, and hypothermia at presentation (p < 0.05). Conclusion: The prevalence of prematurity and associated morbidities was high. Early identification of maternal risk factors and adequate management of preterm neonates significantly improved survival. Enhancing maternal and neonatal care in resource-limited settings is essential to reducing neonatal mortality and morbidity.

CREG1 attenuates intervertebral disc degeneration by alleviating nucleus pulposus cell pyroptosis via the PINK1/Parkin-related mitophagy pathway.

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease with a complex pathophysiological mechanism. Increasing evidence suggests that the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated pyroptosis of nucleus pulposus cells (NPCs) plays a crucial role in the pathological progression of IVDD. Pyroptosis is a novel form of programmed cell death characterized by the formation of plasma membrane pores by gasdermin family proteins, leading to cell swelling, membrane rupture, and the release of inflammatory cytokines, which trigger an inflammatory response. The close relationship between pyroptosis and mitophagy has been previously described in various diseases, but the crosstalk between pyroptosis and mitophagy in IVDD remains unexplored. Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and homeostasis regulation and has been shown to promote lysosomal biogenesis and function. However, the potential role and underlying mechanisms of CREG1 in the progression of IVDD have not yet been reported. In this study, we first observed that CREG1 is downregulated following IVDD and that pyroptosis occurs. Furthermore, CREG1 knockdown inhibited NPC proliferation and exacerbated apoptosis and degeneration. Moreover, we confirmed that CREG1 knockdown induced NLRP3 activation while also leading to mitophagy inhibition and mitochondrial dysfunction in NPCs. CREG1 overexpression ameliorated LPS-induced mitophagy inhibition and mitochondrial dysfunction by promoting PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation. However, these protective effects were reversed by pretreatment with the mitophagy inhibitor cyclosporin A (CsA). In a rat model of IVDD, imaging and histological assessments revealed that CREG1 overexpression effectively alleviated the progression of IVDD. Additionally, CREG1 overexpression reduced the expression of NLRP3, caspase-1, and IL-1β while increasing the expression of collagen II, PINK1 and LC3, delaying the course of IVDD. Overall, this study highlights the importance of the interplay between CREG1-mediated regulation of mitophagy and pyroptosis in the pathogenesis of IVDD, identifying CREG1 as a promising therapeutic target for IVDD treatment.

Activity Evaluation and Mode of Action of ICA Against Toxoplasma gondii In Vitro

Toxoplasmosis is a significant zoonotic parasitic disease. Currently, there is no effective vaccine available to prevent human infection, and treatment primarily relies on chemotherapy. However, the lack of specific therapeutic agents and the limitations of existing drugs highlight the urgent need for novel, safe, and effective anti-Toxoplasma gondii (T. gondii) medications. In this study, we evaluated the toxicity of ICA (N-(pyridin-2-yl)-4-(pyridine-2-yl)thiazol-2-amine) to host cells and assessed its inhibitory and anti-proliferative effects on T. gondii tachyzoites. We further investigated the impact of ICA on the ultrastructure of T. gondii using transmission electron microscopy (TEM). Additionally, we measured alterations in mitochondrial membrane potential, superoxide levels, and ATP levels in T. gondii to assess the effect of ICA on mitochondrial function. Our findings demonstrated that ICA exhibits a safe and effective inhibitory effect on T. gondii, with a selectivity index (SI) of 258.25. Notably, ICA demonstrated a more potent anti-proliferative effect than pyrimethamine (PYR). Ultrastructural observations revealed that ICA induces mitochondrial swelling and membrane rupture in T. gondii. Further investigations confirmed that ICA leads to mitochondrial dysfunction in T. gondii. In conclusion, our results suggest that ICA possesses the potential to serve as a lead compound for the development of novel anti-T. gondii therapies.

Copper excess induces autophagy dysfunction and mitochondrial ROS-ferroptosis progression, inhibits cellular biosynthesis of milk protein and lipid in bovine mammary epithelial cells.

Excessive copper (Cu) has the potential risk to ecosystems and organism health, with its impact on dairy cow mammary glands being not well-defined. This study used a bovine mammary epithelial cell (MAC-T) model to explore how copper excess affects cellular oxidative stress, autophagy, ferroptosis, and protein and lipid biosynthesis in milk. Results showed the increased intracellular ROS, MDA, and CAT (P < 0.05), alongside decreased T-SOD and GSH in CuSO4-treated cells (P < 0.05). Transmission electron microscopy and Ad-mCherry-GFP-LC3B assays revealed significant autophagosome accumulation in CuSO4 exposed cells (P < 0.05). Additionally, CuSO4 exposure modulated autophagy markers, evidenced by upregulation of genes such as LC3, ATG5, JNK1, and Beclin1, and downregulation of genes such as ATG4B, and p62 (P < 0.05). CuSO4 also led to notable mitochondrial changes, including size reduction, membrane rupture, and cristae loss, and reduced expression of the ferroptosis inhibitor GPX4 (P < 0.05). The expression of mTOR, HIF-1α and β-catenin signaling pathway were inhibited in differentiated MAC-T cells by CuSO4 exposure (P < 0.05), activated autophagy through activation of the AMPK-mTOR pathway which in turn affected downstream levels of genes related to milk protein and lipid. In conclusion, excessive copper induces oxidative stress in MAC-T cells, promoting autophagy through JNK-Bcl2, Beclin1-Vps34 and AMPK-mTOR pathways, leading to cell ferroptosis, as well as inhibits the cellular biosynthesis of milk protein and lipid.

Insights into neuromyelitis optica spectrum disorder and pregnancy from a single-center study in Thailand

Our study focused on assessing disease and pregnancy outcomes in Thai patients with Neuromyelitis Optica Spectrum Disorder (NMOSD), a condition that disproportionately affects women of childbearing age and poses risks to both mother and fetus. We retrospectively analyzed eight NMOSD patients with a total of 10 pregnancies from our central nervous system inflammatory demyelinating diseases (CNS-IDDs) registry. Over a 12-months spanning from before pregnancy to 12 months postpartum, we observed 13 relapses, with a notable 76.92% occurring postpartum. The mean annualized relapse rate (ARR) peaked at 1.2 (SD ± 1.93) during specific postpartum intervals (0–3 and 6–9 months postpartum), significantly increasing from 0.20 (SD ± 0.42) in the 12 months before pregnancy (BP) to 1.00 (SD ± 1.49) during the 12 months postpartum (PP). Disability, assessed using the Expanded Disability Status Scale (EDSS) scores, worsened from 1.56 (SD ± 2.18) before pregnancy to 2.1 (SD ± 2.63) at six months postpartum. Maternal and fetal complications were prevalent, with six out of nine pregnancies experiencing adverse outcomes such as false labor, premature rupture of membranes, postpartum hemorrhage, intrauterine growth restriction, preterm birth, stillbirth, and low birth weight. Based on our findings, azathioprine and rituximab may be suitable treatment options for maintaining therapy throughout pregnancy, particularly in cases of high disease activity. Our study highlights the critical need for comprehensive management strategies for NMOSD patients of childbearing age. Preconception planning and counselling, along with early obstetrical consultation and closely monitored treatments during pregnancy and postpartum, are vital to mitigating pregnancy-related relapses and adverse fetal outcomes in this vulnerable patient population.

Factors associated with early onset hypocalcemia: A retrospective cohort study.

Early onset hypocalcemia, occurring within 3 days of birth, is prevalent among preterm infants. A central line is required to deliver calcium (Ca). The prediction of hypocalcemia is therefore clinically important when the requirement for initial intravascular calcium administration is anticipated. This retrospective study included preterm infants born between 2019 and 2023 with a birthweight <1500 g or a gestational age (GA) <32 weeks in a single tertiary center. Hypocalcemia was defined as serum Ca <7 mg/dL or ionized calcium (iCa) <0.8 mmol/L within 72 h after birth. Perinatal factors and laboratory test results associated with hypocalcemia were collected and analyzed. Of the 348 infants, 20 died within 7 postnatal days, 22 were transferred to other hospitals, and eight were transferred from other hospitals and were thus excluded. Of 298 enrolled infants, 20 were diagnosed with hypocalcemia. In multivariate analysis, male sex, elevated day 1 phosphorus (d1P), magnesium (d1Mg) levels, and maternal premature rupture of membranes (PROM) were significant risk factors for early onset hypocalcemia. These factors, along with birthweight, a widely recognized risk factor, were used to develop predictive models for early onset hypocalcemia. Among the six suggested models, logistic regression exhibited the highest accuracy. Conversely, the random forest model outperformed others in the Youden index and area under the receiver operating characteristic curve. In our cohort, early onset hypocalcemia was linked to male sex, lower GA, higher d1P and d1Mg, and maternal PROM. Notably, higher d1P has not been previously reported as a risk factor.

Detection and Quantification of Polymorphic MICA and MICB Molecules in Immunoassays: Initial Insights.

The MICA and MICB molecules, expressed on the cell membrane in response to cellular stress or cancer transformation, pose significant challenges for immunoassays. They exhibit high sequence and structural similarity, alongside considerable allelic polymorphism, with 291 and 53 known protein sequences, respectively. Some researchers treat MICA and MICB as a unified target because of their structural and functional similarities, while others distinguish between them. However, which approach is superior and under what circumstances remains unknown. Moreover, information about assays' reactivity with MICA and MICB allelic variants is often missing. In this study, we developed 10 monoclonal antibodies (mAbs) and two sandwich ELISAs for the detection and quantification of these molecules. We assembled a panel of recombinant proteins representing the diversity of MICA and MICB in the European population and profiled the reactivities of the mAbs and ELISAs. The performance of these sandwich ELISAs was evaluated using samples from prostate cancer patients and pregnant women experiencing premature rupture of membranes. Our study assessed the impact of MICA and MICB polymorphism on their detection and quantification by immunological methods, providing evidence to support differential or non-differential approaches for their detection.

The first Ranatuerin antimicrobial peptide with LPS-neutralizing and anti-inflammatory activities in vitro and in vivo.

Pelophylax nigromaculata, common traditional Chinese medicinal material used for several hundreds of years, is one of the most widely distributed amphibians in China. In this study, a novel Ranatuerin-2 family antimicrobial peptide, Rana-2PN, was identified and characterized from its skin, and its structural characteristics and functional activities were studied extensively. First, Rana-2PN exhibited a broad spectrum of antimicrobial activity, displaying minimum inhibitory concentration (MIC) values ranging from 12.5 to 100 μM against all strains tested. Mechanistically, Rana-2PN exerted its bacteriostatic effects by binding to bacterial cells and inducing bacterial membrane rupture and subsequent bacterial death. Secondly, Rana-2PN effectively inhibited the inflammatory response in RAW264.7 cells induced by lipopolysaccharide (LPS) and reduced inflammation induced by carrageenan in mouse toes. Thus, Rana-2PN with LPS-neutralizing, anti-inflammatory, and antimicrobial properties, represents the first member of the Ranatuerin antimicrobial peptide family, and its discovery offers a promising therapeutic candidate for addressing inflammatory disorders resulting from bacterial infections.

Assessing Second-Trimester Ferning in Diagnosing Preterm Prelabor Rupture of Membranes.

Preterm prelabor rupture of membranes (PPROM) diagnosis is made through visualization of amniotic fluid (pooling), nitrizine testing, sonographic low amniotic fluid, and microscopic detection of amniotic fluid arborization (ferning). Data exist on the specificity and sensitivity of ferning detection but have not focused on the second trimester. Our objective is to evaluate the presence of ferning in transvaginally collected amniotic fluid in pregnancies with known second-trimester PPROM to determine if there is a difference in ferning based on gestational age and sample drying time. This was a prospective study evaluating amniotic fluid in individuals undergoing termination of pregnancy between 15 and 24 weeks gestation. A control vaginal swab was collected prior to rupture of membranes and a sample vaginal swab was collected at the time of rupture of membranes at a termination procedure. A 10-mL sample of amniotic fluid was collected too and then centrifuged to separate blood. Slides were analyzed at five different drying time intervals after rupture of membranes, on both the vaginal and centrifuged samples, and examined by two blinded investigators to assess for ferning. Maternal demographics, obstetrical history, and termination information were collected. Statistical analysis was performed using descriptive statistics and regression analyses. A total of 99 individuals consented and 93 were included. The mean gestational age at the time of the termination was 19.5 ± 2.5 weeks. There was a significant effect of drying time with the odds of observing ferning increasing with longer drying time, up to 10 minutes (p < 0.001). Gestational age did not impact ferning detection (p = 0.09). Centrifuging increased ferning detection by 15% at 10 minutes compared to the vaginal swab. In cases of known second-trimester PPROM, ferning was detected more often after 10 minutes of sample drying, and centrifuging the amniotic fluid to remove blood. · The detection of ferning in the second trimester was improved with longer drying times.. · The highest detection rate was seen after at least 10 minutes of drying time.. · Gestational age did not impact the rates of ferning.. · Blood contamination impacts the ability to see ferning on microscopic examination..

The Association Between C-Reactive Protein and the Duration of the Latent Phase of Labor in Women with Term Premature Rupture of Membranes

The Association Between C-Reactive Protein and the Duration of the Latent Phase of Labor in Women with Term Premature Rupture of Membranes

Potential Mechanisms for Chorioamniotic Membrane Rupture after Subchorionic Hematoma.

Subchorionic hematoma is a risk factor for preterm prelabor rupture of membranes and preterm birth. A small proportion of persistent subchorionic hematoma leads to a chronic abruption-oligohydramnios sequence. To determine the mechanism by which subchorionic hematomas may damage chorioamniotic membranes. 1) The number and subtype of macrophages were determined by immunohistochemistry in chorioamniotic membranes from eight subchorionic hematoma patients who delivered preterm (25.5 (24-32) weeks of gestation (median and range)) and six gestational age-matched control patients (25.5 (25-28) weeks of gestation (median and range)). Further, the thickness and fibrosis of the membranes were quantified. 2) We also developed an intrauterine hematoma model in pregnant mice, and the effects of hematoma on the amnion were analyzed by histology and immunofluorescence. 3) In vitro, primary human amnion mesenchymal cells were cocultured with M2-differentiated macrophages, and changes in mesenchymal cells were analyzed. 1) Subchorionic hematoma increased the number of iron-laden macrophages in the human amnion. These macrophages were CD206+, a marker of macrophages required for the maintenance of homeostasis, tissue remodeling, and metabolic adaptations. The collagen layer of the amnion tended to be thickened in patients with subchorionic hematoma. Interestingly, α-smooth muscle actin+ myofibroblasts were increased in the amnion mesenchymal layer in patients with subchorionic hematoma. Vimentin, a mesenchymal marker, was expressed in the epithelial layer of the hematoma amnion. Together, these findings indicate epithelial-mesenchymal transition in amnion of membranes from pregnancies with subchorionic hematomas. 2) These findings in human amnion were confirmed in a mouse model of intrauterine hematoma. 3) Further, in vitro, coculture of human amnion mesenchymal cells with M2-differentiated human macrophages resulted in transformation of these cells into α-smooth muscle actin-expressing myofibroblasts via the TGF-β‒Smad3 pathway. Subchorionic hematoma induces migration of macrophages to chorioamniotic membranes which activate the transition of amnion mesenchymal cells to myofibroblasts. These myofibroblasts may contribute to fibrosis of the amnion and damage chorioamniotic membranes.

Maternal, fetal, and perinatal outcomes of COVID-19-infected pregnancies in Saudi Arabia: a meta-analysis and systematic review

The SARS-CoV-2 pandemic has been researched in various conditions to know the extent of its damage. During pregnancy, there is a placental exchange of blood between mother and fetus. This meta-analysis aimed to investigate the prevalence of maternal, fetal, and perinatal outcomes of COVID-19-positive pregnancy cases in Saudi Arabia. PubMed, Google Scholar, and Web of Science were searched for the period 2019-2024. Pregnancy cases only from Saudi Arabia and reverse transcription polymerase chain reaction confirmed COVID-19 positive were included. Women with any other diseases were excluded. Six studies were selected for meta-analysis with a total of 1065 COVID-19-infected pregnancies. Among the maternal conditions, preterm rupture of membrane (PROM) had the highest prevalence [odds ratio (OR)=4.21; 95% confidence interval (CI): 1.4-7]. Among fetal outcomes, the odds of postpartum anomalies were 4.8 (95% CI: 1.3-11). Intrapartum complications among perinatal outcomes were most likely to occur (OR=2.11; 95% CI: 120.9-125.1). No factual trend for a particular condition can be declared. PROM, postpartum, and intrapartum complications were more likely to occur in COVID-19-infected pregnancies.

P-1144. Low prevalence of neonatal sepsis due to Streptococcus agalactiae in two large Mexican NICUs: multicenter retrospective study from 2021-2023

Abstract Background Group B Streptococcus (GBS), or S. agalactiae, is reported as a leading cause of neonatal sepsis in several regions including the United States. Although in recent years its incidence has shown a steady decline, current treatment guidelines still consider it a predominant cause of neonatal sepsis. Its prevalence varies according to geographical and racial factors; however, information regarding the epidemiology and clinical presentation of neonatal GBS infection in Mexico is scarce. Methods Retrospective multicenter study conducted in the NICUs of the two pediatric reference hospitals in NL, Mexico. Data of all newborns ≤28 days (d) diagnosed with blood culture-proven GBS infection from 2021-2023 were collected. Maternal premature rupture of membranes (PROM) was defined as &amp;gt;12h. GBS infection was classified as early (&amp;lt; 7 d) and late-onset (≥7 d). LBWIs were defined as newborns &amp;lt; 2500 g and very LBWI (VLBWI) as &amp;lt; 1500 g at birth, respectively. Clinical scenarios were classified as sepsis, pneumonia and meningitis. Sepsis was classified as early (≤3 d) and late-onset ( &amp;gt;3 d). Descriptive statistical analyses were performed to determine frequencies. Results A total of 928 positive blood cultures were included. 28 blood cultures (3%) from 27 patients were positive for GBS. Maternal PROM was documented in 11.1%. Most patients were term infants (77%) and 92.6% of the cases were early-onset. The most common presentation was sepsis (92.6%). One patient (3.7%) had pneumonia and one (3.7%) had meningitis due to GBS. Low mortality was documented (3.7%). Table 1 shows clinical characteristics of patients with GBS infection. As expected, all isolates were susceptible to Ampicillin. Conclusion We report a low prevalence of culture-proven GBS infection (3%) in two large Mexican NICUs during the studied period. This is consistent with previous single-center reports from Mexico, which date back to more than two decades. Although the international epidemiology and treatment guidelines consider GBS a predominant cause of neonatal sepsis, its frequency in Mexico remains low. The vast majority of cases were early-onset infections, and the most common clinical presentation was sepsis, which is consistent with global epidemiology. Disclosures All Authors: No reported disclosures

Do routine antibiotics change the myelomeningocele infection rate? A case series.

Myelomeningocele (MMC) is the most common type of congenital spinal malformation, typically requiring surgical intervention. While prenatal repair is increasingly favored, postnatal repair remains the standard in many settings. This study aims to evaluate the antibiotics prescribed to neonates with MMC and their correlation with central nervous system (CNS) infection rates following postnatal surgical repair. A retrospective cohort study was conducted, including newborns who underwent postnatal MMC repair between August 2017 and June 2021 at the Children's Hospital of Goiânia. The study examined variables related to the pregnancy and birth periods, as well as anatomical and neurosurgical factors. Neonates were categorized into four groups based on the time interval between birth and surgical repair (within 24, 48, 72h, and beyond 72h) and were evaluated for CNS infection rates. A total of 38 neonates were included, with 24.32% diagnosed with CNS infections post-surgery. Notably, 22.86% of mothers did not receive prenatal care. Cesarean section was the predominant mode of delivery, accounting for 77.78% of cases. The average time from birth to surgery was 67h. At admission, 73.68% of MMC cases presented with a rupture of the MMC membrane, and 78.94% of newborns received intravenous antibiotics. The mean surgical time was 60min, with 78.94% of surgeries performed by experienced surgeons. Timely surgical intervention and the use of prophylactic antibiotics are critical in reducing CNS infection rates in neonates undergoing postnatal MMC repair. Delays in surgery and the lack of antibiotic prophylaxis were associated with higher infection rates, whereas factors such as delivery mode and surgeon experience had less impact on infection outcomes. These findings highlight the need for standardized care protocols and improved prenatal care to optimize neonatal outcomes.

The role of D-dimer changes in predicting delivery time in preterm premature rupture of membranes: a retrospective analysis.

Pregnancy induces a hypercoagulable state, characterized by increased coagulation factors and decreased anticoagulants, alongside ongoing fibrinolysis marked by elevated D-dimer (DD) levels. Reference values for DD in pregnancy often exceed the non-pregnant cutoff due to these changes. Elevated DD levels are common in late pregnancy and may correlate with complications such as gestational diabetes, hypertension, and preterm delivery, particularly in cases of preterm premature rupture of membranes (PPROM). This study investigates the association between DD levels, the duration from PPROM diagnosis to delivery, and neonatal outcomes. This retrospective study was conducted at the Department of Perinatology, Etlik City Hospital, Ankara, Turkey, from October 2022 to May 2023. Eighty patients with PPROM between 24 and 36weeks of gestation were included. Routine blood tests and coagulation parameters, including DD, were monitored every other day for 2weeks. Patients were classified into two subgroups based on whether labor occurred within 7days of PPROM diagnosis. Statistical analyses included the Mann-Whitney U test, Student's t test, Chi-square test, Friedman test, Durbin-Conover test, generalized estimating equations (GEE), and ROC analysis. Gestational age at admission was significantly lower in patients who delivered later than 7days post-PPROM. Significant differences were observed in ultrasonographic measurements, with larger fetal parameters in the early delivery group. Higher DD levels at the third follow-up correlated with shorter durations to delivery (p = 0.021). Longitudinal analysis showed significant fluctuations in DD levels over time, particularly near delivery. The GEE analysis demonstrated a strong inverse relationship between DD levels and time to delivery (p = 0.004), supported by ROC analysis (AUROC = 0.811). Elevated DD levels are associated with shorter durations from PPROM diagnosis to delivery, indicating their potential utility in predicting labor onset. Monitoring DD levels may help in clinical decision-making for managing PPROM, including planning neonatal care and timing of interventions.

Modulation of placental angiogenesis by metformin in a rat model of gestational diabetes.

Gestational diabetes mellitus (GDM) significantly disrupts placental structure and function, leading to complications such as intrauterine growth restriction (IUGR) and preeclampsia. This study aimed to investigate the effects of GDM on placental histology, angiogenesis, and oxidative stress, as well as evaluate metformin's protective role in mitigating these changes. A total of 60 pregnant Sprague-Dawley rats were divided into four groups: control, metformin-treated, GDM, and GDM with metformin. GDM was induced using streptozotocin (STZ) at 40mg/kg, and metformin was administered at 200mg/kg from gestational day (GD) 4 to GD17. Blood glucose and insulin levels were assessed, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated. Placentae were weighed and subjected to histological, immunohistochemical, and molecular analyses, focusing on key angiogenesis markers (VEGF, VEGFR, CD31, KLF2) and oxidative stress indicators (MDA, eNOS). GDM increased placental weight, angiogenesis (elevated VEGF, VEGFR, CD31), and oxidative stress (elevated MDA, eNOS). Histopathological changes included villous edema, membrane rupture, and hemosiderin deposition. Metformin treatment reduced placental weight; normalized VEGF, KLF2, and PlGF expression; and improved placental architecture. Additionally, oxidative stress was significantly reduced in metformin-treated GDM rats. In conclusion, GDM induces placental abnormalities, promoting excessive angiogenesis and oxidative stress, potentially leading to IUGR and other complications. Metformin showed protective effects by reducing placental overgrowth and restoring vascular and oxidative balance. These findings suggest that metformin may play a therapeutic role in improving placental health in GDM pregnancies, warranting further investigation into its long-term effects on fetal development and maternal health.

Effects of Enterocytozoon hepatopenaei infection on intestinal immune defense and physiological processes of Penaeus vannamei

As the main pathogen causing growth retardation, EHP is considered to be mainly parasitic in the hepatopancreas of shrimp. However, the intestines of shrimp infected with EHP frequently exhibit syndromes such as jejunum and white midgut. Therefore, the challenge experiment was carried out in this study to compare the differences in intestinal histology, digestion and absorption, immune defense and oxidative stress of P. vannamei between the control group and EHP infection group. Histological analysis showed that EHP infection significantly damaged the intestine of the shrimp, including intestinal villus rupture and outer membrane impairment. Concurrently, EHP infection can trigger intestinal immune response, and the expression of key immune genes like Toll, myeloid differentiation factor, anti-lipopolysaccharide factor, and Relish was significantly enhanced, while the expression of IMD and alkaline phosphatase was suppressed. Additionally, antioxidant genes manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, and nuclear factor E2-related factor 2 were up-regulated to varying extents in EHP infection group, and the contents of lipid peroxides and malondialdehyde were heavily accumulated. Moreover, the expression levels of key genes involved in nutrient absorption, transport and synthesis, such as glucose transporter 1, Na+-K+ATPase, fatty acid synthase, acetyl-CoA carboxylase, rapamycin kinase, mTOR regulation-related protein, eukaryotic translation initiation factor 4E binding protein, ribosomal protein S6 kinase, were significantly up-regulated. However, the activities of amylase, lipase, and trypsin were inhibited in EHP infection group throughout the experiment. In summary, EHP infection damaged the intestine of P. vannamei, accompanied by immune response and oxidative stress. At the same time, nutrient transport and synthesis pathways were activated, while digestive enzyme activities were inhibited, indicating that in order to maintain survival, shrimps must accelerate material transport. Unfortunately, it remains in a state of nutrient deficiency that ultimately affects growth.

Retained versus removed copper intrauterine device during pregnancy: An updated systematic review and meta-analysis.

Intrauterine devices (IUDs) are highly effective contraceptives. Despite their effectiveness, pregnancies can occur during IUD use, and the management of such cases, particularly when the pregnancy is desired, remains controversial. We conducted a systematic review and meta-analysis to evaluate outcomes in women who unintentionally conceived while using IUDs and chose to continue their pregnancies. We searched PubMed, Embase, and Cochrane databases to identify studies comparing women who removed their IUD after pregnancy discovery to those who retained it. The primary outcomes assessed were miscarriage, bleeding during pregnancy, and preterm delivery. Secondary outcomes included cesarean delivery, chorioamnionitis, congenital malformations, intrauterine growth restriction, preterm premature rupture of membranes, and stillbirth. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the binary outcomes using random-effects models to account for variability across studies. The certainty of evidence was measured using the Grading of Recommendations Assessment, Development, and Evaluation approach. From 3719 records, 4 cohorts were included. Among the 693 pregnant women analyzed, 402 had their IUD removed, while 291 retained the device. The analysis focused on copper IUDs, with most studies reporting removal during the first trimester and after ultrasound evaluation, although gaps in standardized reporting practices and removal methods were noted. Significant benefits were observed for the IUD-removed group, including reduced incidences of bleeding during gestation (OR 0.42; 95% CI 0.24 to 0.73; p < 0.01. Moderate certainty of evidence), and miscarriage (OR 0.29; 95% CI 0.17 to 0.48; p < 0.01. Moderate certainty of evidence). There was no significant difference in preterm delivery rates (OR 0.78; 95% CI 0.34 to 1.76; p = 0.55). This meta-analysis, based on data from cohort studies with moderate certainty of evidence, indicates that removing an IUD after pregnancy diagnosis may reduce the odds of miscarriage and bleeding during gestation. However, further high-quality research is needed to evaluate outcomes in pregnancies associated with hormonal IUDs, as well as critical factors such as gestational age at diagnosis, timing of IUD removal, and the position of the gestational sac relative to the device.

Time to recovery of neonatal sepsis and its predictors in public hospitals of North Shoa Zone, Central Ethiopia

BackgroundNeonatal sepsis remains one of the most common causes of morbidity and mortality among neonates in developing countries. It can cause severe morbidities and sequelae, even though patients survive. Prolonged recovery time of neonatal sepsis leads to hospitalization, increased cost of treatments, antimicrobial resistance, disseminated intravascular coagulation, respiratory failure, septic shock, brain lesions, renal failure, and cardiovascular dysfunction, and eventually death. Thus, this study aimed to identify the time-to-recovery of neonatal sepsis and its predictors among newborns admitted to public hospitals in the North Shoa Zone, Central Ethiopia.MethodsA retrospective cohort study was conducted among 508 septic neonates admitted to selected public hospitals in the North Shoa Zone between March 1, 2021, and March 1, 2023. A systematic random sampling method was used to select eligible medical records. The data were collected through the open data kit (ODK) Collect Android app and consequently exported to STATA version 17 for analysis. The data were analyzed using both univariable and multivariable Cox regression models. The adjusted hazard ratio (AHR) with its corresponding 95% confidence interval (CI) was employed.ResultsOf all septic neonates, 441 were recovered. The predictors of time-to-recovery of neonatal sepsis were premature rupture of membrane (PROM) (AHR = 0.37; 95% CI: 0.21, 0.63), intrapartum fever (AHR = 0.49; 95% CI: 0.32, 0.75), chest-indrawing (AHR = 0.50; 95% CI: 0.36, 0.68), fifth-minute appearance, pulse, grimace, activity, and respiration (Apgar) score less than seven (AHR = 0.54; 95% CI: 0.38, 0.77), gestational age between 37 and 42 weeks (AHR = 1.35; 95% CI: 1.06, 1.70), septic shock (AHR = 0.52; 95% CI: 0.31, 0.85).ConclusionThe median time to recovery from neonatal sepsis in this study was comparable to the previous studies. Premature rupture of membranes, intrapartum fever, term gestational age, low fifth minute Apgar score, chest indrawing, and septic shock were the predictors of time-to recovery of neonatal sepsis. Therefore, birth attendants are advised to closely adhere to the obstetrics management protocols when providing care for women who have intrapartum fever and premature rupture of membranes, as this will help to minimize neonatal sepsis and the subsequent delay in recovery.

Neonatal near miss and associated factors among neonates delivered at East Gojjam zone public health hospitals, Northwest Ethiopia

Neonatal mortality and morbidity is a significant public health issue globally, particularly in low-income countries including Ethiopia. This study aimed to determine the proportion and associated factors of neonatal near misses among newborns delivered at public hospitals in the East Gojjam zone of Northwest Ethiopia. A facility-based cross-sectional study was conducted from April 21 to June 20, 2023, among 560 newborns and their mothers in randomly selected five public hospitals. Data was collected using an interviewer-administered questionnaire, medical record review, and a standard checklist with a systematic random sampling technique in each proportionally allocated hospital. The data was entered using 4.6 Epi-data software and exported to SPSS version 25. Bivariable and multivariable logistic regression analyses were performed using a backward stepwise approach method, and statistical significance was declared at a 95% confidence interval with a p-value < 0.05. A total of 552 participants responded to the study, with a response rate of 98.6%. The prevalence of neonatal near miss was 41.3% with a 95% confidence interval of 37.1–45.3. Unplanned pregnancy (AOR = 4.91, 95% CI: 2.43–9.94), current obstetric complications at birth (AOR = 5.48, 95% CI: 2.92–10.27), pregnancy-induced hypertension (AOR = 2.75, 95% CI: 1.23–6.12), premature rupture of membrane (AOR = 3.40, 95% CI: 1.71–6.78), mother referred from other healthcare facilities (AOR = 7.12, 95% CI: 4.01–12.63), delivered on-duty time (AOR = 5.04, 95% CI: 2.94–8.65), less than three ultrasound scans (AOR = 3.71, 95% CI: 2.11–6.53), and no ultrasound scan (AOR = 9.44, 95% CI: 2.55–34.99) were significantly associated with neonatal near miss. The prevalence of neonatal near-misses was 41.3% (95% CI: 37.1%, 45.3%). Unplanned pregnancy, obstetric complications at birth, ultrasound scan, premature rupture of membrane, pregnancy-induced hypertension, and mothers referred from other healthcare facilities, and delivered on-duty time were significant factors associated with neonatal near misses.