Nevin Manimala

Placenta. 2021 Aug 18;114:42-49. doi: 10.1016/j.placenta.2021.08.054. Online ahead of print.

ABSTRACT

INTRODUCTION: Malaria infection in pregnancy has adverse consequences for both fetal and maternal health. There is insufficient data on the effect malaria in pregnancy has on the structure of the chorioamniotic membrane. Our objective was to determine the structure of the chorioamniotic membrane in patients with malaria in pregnancy.

METHODS: Specimens of the chorioamniotic membrane from 58 women with malaria in pregnancy and 58 women without malaria in pregnancy were used for this study. Biopsies of the fetal membranes were obtained immediately after delivery and processed for light microscopy. They were stained using H & E. Photomicrographs were taken for morphological analysis and statistical analyses were performed using Statistical Package for Social Sciences (SPSS, Version 23.0, Chicago, Illinois). The independent-sample t-test and odds ratios were used to compare the appropriate values between the two groups at a 95% confidence interval.

RESULTS: Photomicrographs of the chorioamniotic membrane showed histological alterations, including a change of amniotic epithelium to columnar and stratified types, epithelial delamination, extensive fibrin deposition, and leukocyte infiltration in women with malaria in pregnancy. Statistical analysis found significant differences in epithelial type (p-value 0.001, ×2 = 17.9), epithelial denudation (p-value <0.001, ×2 = 19.4) and extensive fibrin deposition (p-value of 0.02 and ×2 = 7.5) between the study groups.

DISCUSSION: This study has demonstrated histological alterations in the chorioamniotic membrane in association with malaria in pregnancy. Further studies may be conducted to characterize chorioamnionitis in malaria in pregnancy and associations with adverse pregnancy outcomes.

PMID:34425402 | DOI:10.1016/j.placenta.2021.08.054

Cancer Epidemiol. 2021 Aug 20;74:102003. doi: 10.1016/j.canep.2021.102003. Online ahead of print.

ABSTRACT

BACKGROUND: Time spent in hospital (length of stay) is an important component of patient experience and the financial cost of cancer care. This study documents the length of stay across English cancer diagnoses at a national level and reports on variation by patient demographics and tumour characteristics.

METHODS: Data on all diagnoses of malignant neoplasms from the English National Cancer Registration and Analysis Service for 252,202 patients first diagnosed in 2015 was linked with NHS Digital’s Admitted Patient Care and Outpatient Hospital Episode Statistics datasets to quantify length of stay within one year following diagnosis. Length of stay was modelled using linear regression adjusted for sex, age, tumour type, stage, time spent alive during the study period, vital status at end of study period, region, deprivation and ethnicity.

RESULTS: Patients spend a mean of 25 days (median = 17 days; IQR = 8-34 days) in hospital in their first year. Tumour type, stage, age and vital status corrections had the strongest effects in the model adjusting for other independent variables. Younger patients tended towards longer stays.

CONCLUSION: Length of stay varies among patients by tumour type, age and stage. Estimating future health service demands should account for changes in incident tumour characteristics.

PMID:34425383 | DOI:10.1016/j.canep.2021.102003

Environ Pollut. 2021 Jul 20;290:117816. doi: 10.1016/j.envpol.2021.117816. Online ahead of print.

ABSTRACT

Paraquat (PQ), a widely used herbicide and well-known oxidative stress inducer, has been linked to numerous neurodegenerative diseases, but the underlying mechanism(s) remains unknown. Circular RNAs (circRNAs) have recently been reported to be associated with oxidative stress in Parkinson’s disease. Herein, we performed methylated RNA immunoprecipitation and RNA sequencing assays for mouse neuroblastoma (Neuro-2a) cells and successfully established a positive link between the alteration of circRNAs driven by m⁶A modification and PQ-induced oxidative stress. We observed oxidative stress and antioxidative stress present distinct m⁶A modification pattern of circRNAs as well as biological effect. Gene ontology and pathway analysis predicted that differentially m⁶A-methylated and expressed circRNAs are highly clustered in pathways associated with function and development of nervous system, including axon cargo transport, nervous system development, long-term potentiation, and neurotrophic signaling pathways. Moreover, we demonstrated that the alteration of m⁶A-methylated circRNAs upon PQ exposure could be partially reversed by N-acetylcysteine pretreatment. The mechanistic analysis further demonstrated that N-acetylcysteine pretreatment attenuated the decreased expression of target genes (UBC and PPP2CA) induced by PQ. These findings revealed distinct patterns of differentially m⁶A-modified circRNAs, indicating that m⁶A could participate in a specific regulatory network of circRNAs to modulate the expression of downstream genes in response to PQ-induced oxidative stress. In conclusion, our work established a link between m⁶A modification of circRNAs and PQ-induced oxidative stress, and further studies are required to explore the underlying molecular mechanisms associated with PQ-induced neurotoxicity.

PMID:34425375 | DOI:10.1016/j.envpol.2021.117816

J Magn Reson Imaging. 2021 Aug 23. doi: 10.1002/jmri.27894. Online ahead of print.

ABSTRACT

BACKGROUND: Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis.

PURPOSE: The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM.

STUDY TYPE: Retrospective.

POPULATION: Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females).

FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*.

ASSESSMENT: For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison.

STATISTICAL TESTS: Continuous (categorical) variables were compared between patients and HCs using Student’s t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant.

RESULTS: Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P = 0.717 and 0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r = -0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r = 0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age.

DATA CONCLUSION: DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

PMID:34425037 | DOI:10.1002/jmri.27894

J Gastroenterol Hepatol. 2021 Aug 23. doi: 10.1111/jgh.15670. Online ahead of print.

ABSTRACT

The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study. Twenty-one patients were enrolled prospectively prior to LT. Postoperative complications were observed in 47.6 % (n=10). Seven patients (33.3%) had early allograft dysfunction (EAD) and six patients (28.5%) experienced acute cellular rejection within six months of LT. cmtDNA levels were significantly elevated in all recipients post-LT compared with healthy controls and pre-operative samples (1,361,937 copies/ml [IQR 586,781 – 3,399,687] post-LT; 545,531 copies/ml [IQR 238,562-1,381,015] pre-LT; 194,562 copies/ml [IQR 182,359-231,515] in healthy controls) and returned to normal levels by five days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early post-operative period (p < 0.001). In all patients there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (p <0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at post-operative day seven, which did not correlate with liver function tests. The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests.

PMID:34425021 | DOI:10.1111/jgh.15670

Artif Organs. 2021 Aug 23. doi: 10.1111/aor.14055. Online ahead of print.

ABSTRACT

BACKGROUND: We previously reported low rates of pump thrombosis and hemorrhagic stroke, but increased bleeding, under our original antithrombosis protocol (P1) in Heartware recipients. We designed and implemented a revised protocol (P2) to reduce complexity and bleeding.

METHODS: Thrombelastography and PFA-100 guide antiplatelet titration. Goals for P2 were altered to decrease antiplatelet use and anticoagulation intensity. We compared incidence and rates of gastrointestinal bleeding (GIB), embolic (eCVA) and hemorrhagic (hCVA) stroke, pump thrombosis (PT), and total bleeding (GIB+hCVA), total thrombosis (eCVA+PT), and total events between P1 and P2. Laboratory and medication data were assessed. Patients with and without hemocompatibility-related adverse events (HRAEs) were compared.

RESULTS: The study included 123 patients (P1: 65; P2: 58). GIB rate decreased (P1: 0.66; P2 0.30 EPPY, p = 0.003). CVA rates and incidence were statistically similar, although hCVA incidence increased (P1:3%; P2: 12%, p = 0.06). Incidence (P1: 3%; P2: 16%, p =0.02) and rate (P1: 0.03; P2: 0.12 EPPY, p = 0.08) of PT increased. Incidence and rate of overall HRAEs and thrombotic events were similar, while bleeding rate decrease (P1: 0.69; P2: 0.40 EPPY, p = 0.02). Twelve-month medication burden decreased. Compared to non-HRAE patients, patients with bleeding HRAEs had moreantiplatelet and pentoxifylline use, but less statin use; and lower PFAs. Patients with thrombotic HRAEs had less dual antiplatelet use, lower INRs, R-times, and PFA-ADP values.

CONCLUSIONS: A revised antithrombotic protocol decreased GIB and overall hemorrhagic HRAE rate and medication burden. Unfortunately, PT increased. Non-HRAE and HRAE patients differed in anticoagulation and antiplatelet intensity. These differences will guide revision of P2.

PMID:34425001 | DOI:10.1111/aor.14055

J Exp Biol. 2021 Apr 1;224(7):jeb233544. doi: 10.1242/jeb.233544. Epub 2021 Apr 15.

ABSTRACT

Dynamic body acceleration (DBA), measured through animal-attached tags, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. Following respirometry to calibrate oxygen consumption rate (ṀO2) with DBA under controlled conditions, predictive models can be applied to DBA data collected from free-ranging individuals. However, laboratory calibrations are generally performed on a relatively narrow size range of animals, which may introduce biases if predictive models are applied to differently sized individuals in the field. Here, we tested the mass dependence of the ṀO2-DBA relationship to develop an experimental framework for the estimation of field metabolic rates when organisms differ in size. We performed respirometry experiments with individuals spanning one order of magnitude in body mass (1.74-17.15 kg) and used a two-stage modelling process to assess the intraspecific scale dependence of the ṀO2-DBA relationship and incorporate such dependencies into the coefficients of ṀO2 predictive models. The final predictive model showed scale dependence; the slope of the ṀO2-DBA relationship was strongly allometric (M1.55), whereas the intercept term scaled closer to isometry (M1.08). Using bootstrapping and simulations, we evaluated the performance of this coefficient-corrected model against commonly used methods of accounting for mass effects on the ṀO2-DBA relationship and found the lowest error and bias in the coefficient-corrected approach. The strong scale dependence of the ṀO2-DBA relationship indicates that caution must be exercised when models developed using one size class are applied to individuals of different sizes.

PMID:34424983 | DOI:10.1242/jeb.233544

J Exp Biol. 2021 Apr 1;224(7):jeb240994. doi: 10.1242/jeb.240994. Epub 2021 Apr 6.

ABSTRACT

Heat tolerance plasticity is predicted to be an important buffer against global warming. Nonetheless, basal heat tolerance often correlates negatively with tolerance plasticity (‘trade-off hypothesis’), a constraint that could limit plasticity benefits. We tested the trade-off hypothesis at the individual level with respect to heat hardening in two lizard species, Anolis carolinensis and Anolis sagrei. Heat hardening is a rapid increase in heat tolerance after heat shock that is rarely measured in reptiles but is generally considered to be a first line of physiological defense against heat. We also employed a biophysical model of operative habitat temperatures to estimate the performance consequences of hardening under ecologically relevant conditions. Anolis carolinensis hardened by 2 h post-heat shock and maintained hardening for several hours. However, A. sagrei did not harden. Biophysical models showed that hardening in A. carolinensis reduces their overheating risk in the field. Therefore, while not all lizards heat harden, hardening has benefits for species that can. We initially found a negative relationship between basal tolerance and hardening within both species, consistent with the trade-off hypothesis. However, permutation analyses showed that the apparent trade-offs could not be differentiated from statistical artifact. We found the same result when we re-analyzed published data supporting the trade-off hypothesis in another lizard species. Our results show that false positives may be common when testing the trade-off hypothesis. Statistical approaches that account for this are critical to ensure that the hypothesis, which has broad implications for thermal adaptation and responses to warming, is assessed appropriately.

PMID:34424976 | DOI:10.1242/jeb.240994

J Exp Biol. 2021 Apr 1;224(7):jeb231712. doi: 10.1242/jeb.231712. Epub 2021 Apr 15.

ABSTRACT

Characterizing sex and species differences in muscle physiology can contribute to a better understanding of proximate mechanisms underlying behavioral evolution. In Xenopus, the laryngeal muscle’s ability to contract rapidly and its electromyogram potentiation allows males to produce calls that are more rapid and intensity-modulated than female calls. Prior comparative studies have shown that some species lacking typical male features of vocalizations sometimes show reduced sex differences in underlying laryngeal physiology. To further understand the evolution of sexually differentiated laryngeal muscle physiology and its role in generating behavior, we investigated sex differences in the laryngeal physiology of X. muelleri, a species in which male and female calls are similar in rapidity but different with respect to intensity modulation. We delivered ethologically relevant stimulus patterns to ex vivo X. muelleri larynges to investigate their ability to produce various call patterns, and we also delivered stimuli over a broader range of intervals to assess sex differences in muscle tension and electromyogram potentiation. We found a small but statistically significant sex difference in laryngeal electromyogram potentiation that varied depending on the number of stimuli. We also found a small interaction between sex and stimulus interval on muscle tension over an ethologically relevant range of stimulus intervals; male larynges were able to produce similar tensions to female larynges at slightly smaller (11-12 ms) inter-stimulus intervals. These findings are consistent with behavioral observations and present a previously undescribed intermediate sex difference in Xenopus laryngeal muscle physiology.

PMID:34424964 | DOI:10.1242/jeb.231712

Cereb Cortex. 2021 Aug 23:bhab284. doi: 10.1093/cercor/bhab284. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) is characterized by atypical connectivity lateralization of functional networks. However, previous studies have not directly investigated if differences in specialization between ASD and typically developing (TD) peers are present in infancy, leaving the timing of onset of these differences relatively unknown. We studied the hemispheric asymmetries of connectivity in children with ASD and infants later meeting the diagnostic criteria for ASD. Analyses were performed in 733 children with ASD and TD peers and in 71 infants at high risk (HR) or normal risk (NR) for ASD, with data collected at 1 month and 9 months of age. Comparing children with ASD (n = 301) to TDs (n = 432), four regions demonstrated group differences in connectivity: posterior cingulate cortex (PCC), posterior superior temporal gyrus, extrastriate cortex, and anterior prefrontal cortex. At 1 month, none of these regions exhibited group differences between ASD (n = 10), HR-nonASD (n = 15), or NR (n = 18) infants. However, by 9 months, the PCC and extrastriate exhibited atypical connectivity in ASD (n = 11) and HR-nonASD infants (n = 24) compared to NR infants (n = 22). Connectivity did not correlate with symptoms in either sample. Our results demonstrate that differences in network asymmetries associated with ASD risk are observable prior to the age of a reliable clinical diagnosis.

PMID:34424949 | DOI:10.1093/cercor/bhab284