Nevin Manimala

Am J Obstet Gynecol. 2023 Aug 18:S0002-9378(23)00547-1. doi: 10.1016/j.ajog.2023.08.013. Online ahead of print.

ABSTRACT

BACKGROUND: Having a Caesarean section at full dilatation (CSfd) has been associated with an increased subsequent risk of spontaneous preterm birth (sPTB). The Aberdeen Maternity and Neonatal Databank (AMND) provides a rare opportunity to study subsequent pregnancy outcomes after a previous CSfd over 40 years with an ability to include a detailed evaluation of potential confounding factors.

OBJECTIVE(S): To investigate if having an initial CSfd is associated with sPTB or other adverse pregnancy outcomes in the subsequent pregnancy.

STUDY DESIGN: A retrospective cohort study was conducted including women with a first and second pregnancy recorded within the AMND between 1976 and 2017, where previous CSfd at term in the first birth was the exposure. The primary outcome was spontaneous preterm birth (defined as spontaneous birth <37 weeks). Multivariate logistic regression was used to investigate any association between CSfd and the odds of spontaneous preterm birth (sPTB). Women with a prior CSfd were compared to (a) women with any other mode of birth (b) individual modes of birth including planned CS, CS in first stage of labour (<10cm dilated), vaginal birth (including spontaneous vaginal birth (SVB), non-rotational forceps, Kielland’s forceps, vacuum-assisted birth, breech vaginal birth). Other outcomes such as antepartum haemorrhage and mode of second birth were also compared.

RESULTS: Of the 30253 women included, 900 women had a prior CSfd in the first pregnancy. Women with prior CSfd had a three-fold increased risk of spontaneous preterm birth in a second pregnancy (unadjusted OR 2.63; 95%CI 1.82 – 3.81); adjusted OR 3.31; 95%CI 2.17 – 5.05) compared to all other modes of first birth adjusted for maternal age, diabetes, BMI, smoking, pre-eclampsia, antepartum haemorrhage, socioeconomic deprivation (SIMD 2016), year of birth and interpregnancy interval (in second pregnancy). When compared to women with vaginal births only, women with CSfd had five-fold increased odds of sPTB (aOR 5.37 (95%CI 3.40 – 8.48)). Compared to first spontaneous vaginal birth (SVB), first instrumental births (non-rotational forceps, Kielland’s forceps and vacuum births) were not associated with an increased risk of sPTB in the second birth. After an initial CSfd, 3.7% of women had a repeat CSfd and 48% had a planned CS in the second birth.

CONCLUSION: This study is a substantial addition to the body of evidence on the risk of subsequent sPTB after CSfd and demonstrates a strong association with spontaneous preterm birth following a CSfd in the first birth though the absolute risk remains small. This is a large retrospective cohort and includes a comprehensive assessment of potential confounding factors, including pre-eclampsia, antepartum haemorrhage (APH) as well as length of first and second stage of labour Future research must focus on understanding possible causality and to develop primary and secondary preventative measures.

PMID:37598995 | DOI:10.1016/j.ajog.2023.08.013

Biochem Pharmacol. 2023 Aug 18:115757. doi: 10.1016/j.bcp.2023.115757. Online ahead of print.

ABSTRACT

AIM: Previous evidence suggest that a sexual dimorphism in exercise fat oxidation and adipokines levels may explain a lower risk of cardio-metabolic disorders in women. Therefore, we investigated the role of sex in the relationship between adipokines levels, maximal fat oxidation (MFO) during exercise and insulin resistance.

METHODS: Fifty young adults with excess adiposity (31 women; body fat: 38.7 ± 5.3%) were included in this study. The fasting levels of leptin, adiponectin, glucose and insulin were determined from blood samples and the homeostatic model assessment of insulin resistance index (HOMA-IR) subsequently calculated. Body fat percentage and visceral adipose tissue (VAT) were assessed through dual-energy X-ray absorptiometry whereas MFO was estimated during an incremental-load exercise test after an overnight fasting through indirect calorimetry.

RESULTS: Men had lower levels of body fat (d = 1.80), adiponectin (d = 1.35), leptin (d = 0.43) and MFO (d = 1.25) than women. Conversely, men showed higher VAT (d = 0.85) and fasting glucose levels (d = 0.89). No sex differences were observed in HOMA-IR (d = 0.34). Adipokines levels were not associated with MFO in both sexes (r < 0.30), whereas adiponectin levels were inversely related with HOMA-IR in both men (r = -0.58) and women (r = -0.50). Leptin concentration was associated to HOMA-IR only in men (r = 0.41), while no statistically significant relationships were observed between MFO and HOMA-IR in both sexes (r < 0.44).

CONCLUSION: Insulin resistance was similar between sexes regardless of superior levels of adipokines and MFO during exercise in women. Therefore, adiponectin and leptin may regulate glucose homeostasis without altering whole body fat oxidation rate during exercise.

PMID:37598975 | DOI:10.1016/j.bcp.2023.115757

Sci Total Environ. 2023 Aug 18:166352. doi: 10.1016/j.scitotenv.2023.166352. Online ahead of print.

ABSTRACT

The occurrence of 25 multi-class pollutants comprising phthalate esters (PAEs), polycyclic aromatic hydrocarbons (PAHs), and synthetic musks (SMs) were studied in PM_2.5 samples collected at an industrial/commercial/residential/traffic mixed area in Shanghai during four seasons. During the whole period, a slight exceedance of the PM_2.5 annual limit was observed, with an average of 36.8 μg/m³, and PAEs were the most predominant, accounting for >70 % of the studied organic pollutants in PM_2.5, followed by PAHs and SMs. Statistically significant differences were observed for the concentrations of PM_2.5, PAEs, PAHs, and SMs in winter and summer. This seasonal variation could be derived from anthropogenic activities and atmospheric dynamics. Principal component analysis (PCA) and PAHs ratios suggested a mixed source mainly derived from vehicle emissions and industrial processes. Moreover, gaseous pollutants were also accounted for, indicating the emission of PAHs might accompany the NO₂ emission process. Finally, inhalation of PM_2.5-bound organic pollutants for carcinogenic and non-carcinogenic risks were estimated as average values for each season, showing outside the safe levels in autumn and winter in some cases, suggesting that new policies should be to developed to reduce their emissions and protect human health in this area.

PMID:37598962 | DOI:10.1016/j.scitotenv.2023.166352

J Neurosci Methods. 2023 Aug 18:109950. doi: 10.1016/j.jneumeth.2023.109950. Online ahead of print.

ABSTRACT

BACKGROUND: Consistent noise variance across data points (i.e. homoscedasticity) is required to ensure the validity of statistical analyses of MRI data conducted using linear regression methods. However, head motion leads to degradation of image quality, introducing noise heteroscedasticity into ordinary-least square analyses.

NEW METHOD: The recently introduced QUIQI method restores noise homoscedasticity by means of weighted least square analyses in which the weights, specific for each dataset of an analysis, are computed from an index of motion-induced image quality degradation. QUIQI was first demonstrated in the context of brain maps of the MRI parameter R2*, which were computed from a single set of images with variable echo time. Here, we extend this framework to quantitative maps of the MRI parameters R1, R2*, and MTsat, computed from multiple sets of images.

RESULTS: QUIQI restores homoscedasticity in analyses of quantitative MRI data computed from multiple scans. QUIQI allows for optimization of the noise model by using metrics quantifying heteroscedasticity and free energy.

COMPARISON WITH EXISTING METHODS: QUIQI restores homoscedasticity more effectively than insertion of an image quality index in the analysis design and yields higher sensitivity than simply removing the datasets most corrupted by head motion from the analysis.

CONCLUSION: QUIQI provides an optimal approach to group-wise analyses of a range of quantitative MRI parameter maps that is robust to inherent homoscedasticity.

PMID:37598941 | DOI:10.1016/j.jneumeth.2023.109950

Am J Med. 2023 Aug 18:S0002-9343(23)00489-8. doi: 10.1016/j.amjmed.2023.07.020. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary fibrosis is associated with significant morbidity. Data are scarce on the link between COVID-19 and pulmonary fibrosis. We aimed to assess the association between COVID-19 with pulmonary fibrosis.

METHODS: We conducted a nested case-control study in a cohort of 2,894,801 adults without a diagnosis of pulmonary fibrosis. The underlying cohort consisted of members of the largest healthcare provider in Israel aged 18 years or older as of May 1, 2020. Subjects were followed up from cohort entry until June 30, 2022 for the occurrence of pulmonary fibrosis. Ten randomly selected controls were matched to each case of pulmonary fibrosis on age, sex and calendar time. To account for surveillance bias a lag-time of 60 days was used for ascertainment of prior COVID-19 and COVID-severity.

RESULTS: During follow-up 1,284 patients were newly diagnosed with pulmonary fibrosis and matched with 12,840 controls. Multivariable conditional logistic-regression models showed that the OR for pulmonary fibrosis was 1.80 (95% CI, 1.47-2.19) in patients with COVID-19 compared to no COVID-19. The multivariable OR for pulmonary fibrosis was 1.33 (1.06-1.68), 2.98 (1.16-7.65), and 9.30 (5.77-14.98) for mild, moderate, and severe COVID-19, respectively, compared to no COVID-19. The magnitude of the association was attenuated but remained statistically significant for severe disease when the lag-time was extended to 180 days; 1.08 (0.78-1.49), 2.37 (0.75-7.46), and 5.34 (2.75-10.36) for mild, moderate, and severe COVID-19, respectively.

CONCLUSIONS: COVID-19 appears to be associated with an increased risk of pulmonary fibrosis and the magnitude of the association increases with COVID-19 severity.

PMID:37598922 | DOI:10.1016/j.amjmed.2023.07.020

Am J Obstet Gynecol MFM. 2023 Aug 18:101136. doi: 10.1016/j.ajogmf.2023.101136. Online ahead of print.

ABSTRACT

BACKGROUND: Placenta previa diagnosed on midtrimester ultrasound often resolves by the third trimester. Multiparity and prior cesarean delivery have been associated with persistence of placenta previa at delivery. Risk factors for persistent placenta previa in nulliparas are not well characterized.

OBJECTIVES: To identify risk factors for persistent placenta previa in the nulliparous population, as well as evaluate differences in outcomes between persistent and resolved placenta previa.

STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort study that followed 10,037 nulliparous individuals throughout pregnancy. Nulliparas diagnosed with placenta previa on midtrimester ultrasound were included in this analysis. Baseline characteristics and delivery outcomes of nulliparas with persistent placenta previa were compared to those with resolved placenta previa. Multivariate logistic regression with stepwise model selection was used for adjusted analyses.

RESULTS: A total of 171 nulliparas (1.7%) in the nuMoM2b study were diagnosed with placenta previa on midtrimester ultrasound, of whom 17% (n=29) had persistent placenta previa at delivery. When compared to those with resolved placenta previa, nulliparas with persistent placenta previa were more likely to be older (median 32 years (IQR 30-37) vs. 29 years (IQR 25-31), p<0.01), have a prior pregnancy <20 weeks (48.3% vs. 22.5%, p=0.01), have a prior dilation and curettage/evacuation procedure (27.6% vs. 10.6%, p=0.03), or have a pregnancy that resulted from assisted reproductive technology (31% vs. 4.9%, p=0.01). After adjusting for potential confounders, maternal age (aOR 1.11, 95% CI 1.02-1.21), in vitro fertilization (aOR 9.00, 95% CI 1.97-41.14), and prior pregnancy <20 weeks (aOR 2.77, 95% CI 1.10-6.95) remained statistically significant risk factors for persistent placenta previa. Persistent placenta previa also had a higher likelihood of antepartum admission (10.3% vs. 0%, p<0.01), preterm delivery (34.5% vs. 12%, p<0.01), lower neonatal birthweight (median 2847 grams, IQR 2655-3310, vs 3263 grams, IQR 2855-3560) and cesarean delivery (100% vs. 20.4%, p<0.001), but there were no differences in overall pregnancy or neonatal outcomes.

CONCLUSION: In nulliparous individuals diagnosed with placenta previa on midtrimester ultrasound, older maternal age, prior pregnancy <20 weeks, and in vitro fertilization are associated with persistent placenta previa at delivery.

PMID:37598887 | DOI:10.1016/j.ajogmf.2023.101136

Am J Obstet Gynecol MFM. 2023 Aug 18:101134. doi: 10.1016/j.ajogmf.2023.101134. Online ahead of print.

ABSTRACT

BACKGROUND: Umbilical cord gases are often use to assess the impact of labor and delivery on the fetus. However, no large series exists which reflects contemporary obstetric practice or analyses blood gas ranges by route of delivery. Baseline, pre-labor acid-base status in the human fetus is also poorly defined, rendering assessment of blood gas changes during labor difficult.

OBJECTIVE: To define normal umbilical cord gas and lactate values stratified by mode of delivery in a large contemporary series in which universal cord gas collection was dictated by protocol.

STUDY DESIGN: Retrospective cohort study. We analyzed umbilical cord gas and lactate data from an unselected population of infants born between March 2012 and April 2022 at a large teaching hospital. These values were then analyzed by mode of delivery and, for cesarean deliveries, by indication for cesarean and type of anesthesia. Cord gas values from infants delivered by elective cesarean under general anesthesia without labor were considered representative of baseline, pre-labor values.

RESULTS: Data was available for 45,475 infants. Median arterial pH values and interquartile ranges for vaginal births, elective cesarean births without labor and cesarean births performed for fetal heart rate concerns were 7.27 (0.09), 7.27 (0.06) and 7.25 (0.09), respectively. Arterial lactate values for these same 3 groups were 4.1 (2.5), 2.5 (1.2) and 4.0 (2.8) mmoles/l. Due to the very large sample size, most comparisons yielded differences which were statistically significant, but clinically irrelevant. Of all infants, 14% had an arterial pH < 7.20; a pH value of 7.1 represents 2 standard deviations from the mean.

CONCLUSION: This large, population-based study of cord gas/lactate levels in an unselected population stratified by delivery mode represents a previously unavailable benchmark for evaluation of umbilical cord gases. Arterial cord pH values for infants delivered by elective caesarean without labor (median pH 7.28) reflect a lower pre-labor fetal pH baseline than that previously assumed. This finding, coupled with our determination of a 2 standard deviation lower pH limit of 7.1 rather than the historic arbitrary pH 7.2 threshold of normal helps explain the poor positive predictive value of electronic fetal heart rate monitoring, a test designed to detect arterial pH levels which have fallen from an assumed baseline near pH 7.4 to an assumed potentially injurious pH level < 7.2. Uncomplicated labor, even when prolonged, does not generally result in a clinically significant cumulative hypoxic stress to the human fetus. These findings, along with our determination of no difference in acid-base status among infants delivered by cesarean for fetal heart rate concerns, help explain the failure of current approaches to labor and delivery management in reducing the rates of neonatal hypoxic-ischemic encephalopathy and cerebral palsy, condition which almost always reflect developmental events rather than the effects of labor on the fetus.

PMID:37598886 | DOI:10.1016/j.ajogmf.2023.101134

Biol Psychol. 2023 Aug 18:108661. doi: 10.1016/j.biopsycho.2023.108661. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effects of sustained mental activity on perceptions of mental fatigue, cognitive performance, and autonomic response in patients with clinical burnout as compared to a healthy control group.

METHODS: Patients with clinical burnout (n = 30) and healthy control participants (n = 30) completed a 3-hour test session, in which they were administered a set of cognitive tests before and after an effortful cognitive task with concurrent sound exposure. Perceptions of mental fatigue and task demands (mental effort and concentration difficulties) were assessed repeatedly over the course of the test session. Heart rate variability was recorded to index autonomic response.

RESULTS: In comparison with controls, perceived mental fatigue increased earlier in the session for the clinical burnout group and did not recover following a short rest period. Throughout the session, patients rated the tasks as more demanding and showed less improvement on measures of attention and processing speed, inhibition and working memory. While autonomic responses were initially comparable, there was a unique decrease in high-frequency heart rate variability in the clinical burnout group after extended testing and exposure.

CONCLUSION: Patients with clinical burnout are affected differently than healthy controls by sustained mental activity, as reflected by ratings of perceived mental fatigue, aspects of cognitive performance and autonomic response. Further investigation into the role of autonomic regulation in relation to cognitive symptoms in clinical burnout is warranted.

PMID:37598882 | DOI:10.1016/j.biopsycho.2023.108661

Biochim Biophys Acta Biomembr. 2023 Aug 18:184216. doi: 10.1016/j.bbamem.2023.184216. Online ahead of print.

ABSTRACT

Boosted by the indiscriminate use of antibiotics, multidrug-resistance (MDR) demands new strategies to combat bacterial infections, such as photothermal therapy (PTT) based on plasmonic nanostructures. PTT efficiency relies on photoinduced damage caused to the bacterial machinery, for which nanostructure incorporation into the cell envelope is key. Herein, we shall unveil the binding and photochemical mechanisms of gold shell-isolated nanorods (AuSHINRs) on bioinspired bacterial membranes assembled as Langmuir and LS monolayers of DOPE, Lysyl-PG, DOPG and CL. AuSHINRs incorporation expanded the isotherms, with stronger effect on the anionic DOPG and CL. Indeed, FTIR of LS films revealed more modifications for DOPG and CL owing to stronger attractive electrostatic interactions between anionic phosphates and the positively charged AuSHINRs, while electrostatic repulsions with the cationic ethanolamine (DOPE) and lysyl (Lysyl-PG) polar groups might have weakened their interactions with AuSHINRs. No statistical difference was observed in the surface area of irradiated DOPE and Lysyl-PG monolayers on AuSHINRs, which is evidence of the restricted nanostructures insertion. In contrast, irradiated DOPG monolayer on AuSHINRs decreased 4.0 % in surface area, while irradiated CL monolayer increased 3.7 %. Such results agree with oxidative reactions prompted by ROS generated by AuSHINRs photoactivation. The deepest AuSHINRs insertion into DOPG may have favored chain cleavage while hydroperoxidation is the mostly like outcome in CL, where AuSHINRs are surrounding the polar groups. Furthermore, preliminary experiments on Escherichia coli culture demonstrated that the electrostatic interactions with AuSHINRs do not inhibit bacterial growth, but the photoinduced effects are highly toxic, resulting in microbial inactivation.

PMID:37598878 | DOI:10.1016/j.bbamem.2023.184216

Kidney Int. 2023 Aug 18:S0085-2538(23)00563-X. doi: 10.1016/j.kint.2023.07.025. Online ahead of print.

ABSTRACT

Systematic screening for BKPyV-DNAemia has been advocated to aid prevention and treatment of polyomavirus associated nephropathy (PyVAN), an important cause of kidney graft failure. The added value of performing a biopsy at time of BKPyV-DNAemia, to distinguish presumptive PyVAN (negative SV40 immunohistochemistry) and proven PyVAN (positive SV40) has not been established. Therefore, we studied an unselected cohort of 950 transplantations, performed between 2008-2017. BKPyV-DNAemia was detected in 250 (26.3%) transplant recipients, and positive SV40 in 91 cases (9.6%). Among 209 patients with a concurrent biopsy at time of first BKPyV-DNAemia, 60 (28.7%) biopsies were SV40 positive. Plasma viral load showed high diagnostic value for concurrent SV40 positivity (ROC-AUC 0.950, 95% confidence interval 0.916-0.978) and the semiquantitatively scored percentage of tubules with evidence of polyomavirus replication (pvl score) (0.979, 0.968-0.988). SV40 positivity was highly unlikely when plasma viral load is below 4 log₁₀ copies/ml (negative predictive value 0.989, 0.979-0.994). In SV40 positive patients, higher plasma BKPyV-DNA load and higher pvl scores were associated with slower viral clearance from the blood (hazard ratio 0.712, 95% confidence interval 0.604-0.839, and 0.327, 0.161-0.668, respectively), whereas the dichotomy positivity/negativity of SV40 immunohistochemistry did not predict viral clearance. Although the pvl score offers some prognostic value for viral clearance on top of plasma viral load, the latter provided good guidance for when a biopsy was unnecessary to exclude PyVAN. Thus, the distinction between presumptive and proven PyVAN, based on SV40 immunohistochemistry, has limited clinical value. Hence, management of BKPyV-DNAemia and immunosuppression reduction should be weighed against the risk of occurrence of rejection, or exacerbation of rejection observed concomitantly.

PMID:37598855 | DOI:10.1016/j.kint.2023.07.025