Building a growing genomic data repository for maternal and fetal health through the PING Consortium.

Background: Prenatally transmitted viruses can cause severe damage to the developing brain. There is unexplained variability in prenatal brain injury and postnatal neurodevelopmental outcomes, suggesting disease modifiers. Discordant outcomes among dizygotic twins could be explained by genetic susceptibly or protection. Among several well-recognized threats to the developing brain, Zika is a mosquito-borne, positive-stranded RNA virus that was originally isolated in Uganda and spread to cause epidemics in Africa, Asia, and the Americas. In the Americas, the virus caused congenital Zika syndrome and a multitude of neurodevelopmental disorders. As of now, there is no preventative treatment or cure for the adverse outcomes caused by prenatal Zika infection. The Prenatal Infection and Neurodevelopmental Genetics (PING) Consortium was initiated in 2016 to identify factors modulating prenatal brain injury and postnatal neurodevelopmental outcomes for Zika and other prenatal viral infections. Methods: The Consortium has pooled information from eight multi-site studies conducted at 23 research centers in six countries to build a growing clinical and genomic data repository. This repository is being mined to search for modifiers of virally induced brain injury and developmental outcomes. Multilateral partnerships include commitments with Children's National Hospital (USA), Instituto Nacional de Salud (Colombia), the Natural History of Zika Virus Infection in Gestation program (Brazil), and Zika Instituto Fernandes Figueira (Brazil), in addition to the Centers for Disease Control and Prevention and the National Institutes of Health. Discussion: Our goal in bringing together these sets of patient data was to test the hypothesis that personal and populational genetic differences affect the severity of brain injury after a prenatal viral infection and modify neurodevelopmental outcomes. We have enrolled 4,102 mothers and 3,877 infants with 3,063 biological samples and clinical data covering over 80 phenotypic fields and 5,000 variables. There were several notable challenges in bringing together cohorts enrolled in different studies, including variability in the timepoints evaluated and the collected clinical data and biospecimens. Thus far, we have performed whole exome sequencing on 1,226 participants. Here, we present the Consortium's formation and the overarching study design. We began our investigation with prenatal Zika infection with the goal of applying this knowledge to other prenatal infections and exposures that can affect brain development.

Neuroprotective Role of Selenium Nanoparticles Against Behavioral, Neurobiochemical and Histological Alterations in Rats Subjected to Chronic Restraint Stress.

Chronic stress induces changes in the prefrontal cortex and hippocampus. Selenium nanoparticles (SeNPs) showed promising results in several neurological animal models. The implementation of SeNPs in chronic restraint stress (CRS) remains to be elucidated. This study was done to determine the possible protective effects of selenium nanoparticles on behavioral changes and brain oxidative stress markers in a rat model of CRS. 50 rats were divided into three groups; control group (n = 10), untreated CRS group (n = 10) and CRS-SeNPs treated group (n = 30). Restraint stress was performed 6 h./day for 21 days. Rats of CRS-SeNPs treated group received 1, 2.5 or 5 mg/kg SeNPs (10 rats each) by oral gavage for 21 days. Rats were subjected to behavioral assessments and then sacrificed for biochemical and histological analysis of the prefrontal cortex and hippocampus. Prefrontal cortical and hippocampal serotonin levels, oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx), tumor necrosis factor alpha (TNF-α) and caspase-3 were assessed. Accordingly, different doses of SeNPs showed variable effectiveness in ameliorating disease parameters, with 2.5 mg/kg dose of SeNPs showing the best improving results in all studied parameters. The present study exhibited the neuroprotective role of SeNPs in rats subjected to CRS and proposed their antioxidant, anti-inflammatory and anti-apoptotic effects as the possible mechanism for increased prefrontal cortical and hippocampal serotonin level, ameliorated anxiety-like and depressive-like behaviors and improved prefrontal cortical and hippocampal histological architecture.

Pediatric and Adolescent Traumatic Macular Hole: A Systematic Review.

PURPOSE: The optimal management of pediatric traumatic macular holes (TMH) is unclear from lack of prospective randomized trials. The literature is divided into early (≤1month post-trauma), delayed (>1 month) pars plana vitrectomy (PPV), and observation. Our aim is to find which group can achieve best-superior spectacle corrected visual acuity (VA), visual gain, and time for hole closure. DESIGN: Systematic review. METHODS: This systematic review was registered with PROSPERO (ID:CRD42022383134). The databases searched from inception until July 31, 2023, were MEDLINE OVID, Scopus, Web of Science, Embase, and Google Scholar. The articles were screened for title and abstract then for full text. Risk of bias was also assessed. Three outcome measures were analyzed: final VA, visual gain, and time to closure of macular hole (MH). MH size was divided into small (≤250 µm), medium (>250-500 µm), and large (>500 µm). RESULTS: Ninety eight (98) studies with 234 patients in the PPV group and 87 patients in the observation group were included in the review. Final VA (logarithm of the minimum angle of resolution) and visual gain were respectively in PPV vs observation groups: (1) small MH 0.37 ± 0.52 vs 0.42 ± 0.56 (P = .484) and -0.96 ± 0.83 vs -0.49 ± 0.40 (P = .005); (2) medium MH 0.58 ± 0.39 vs 0.34 ± 0.34 (P = .06) and -0.36 ± 0.42 vs -0.74 ± 0.44 (P < .001); (3) large MH 0.62 ± 0.42 vs 0.59 ± 0.35 (P = .337) and -0.31 ± 0.48 vs -0.62 ± 0.37 (P = .11). Small TMH had comparable closure time: 3.21 ± 2.52 months vs 3.49 ± 4.43 (P = .954) in the PPV and observation groups. Early and late PPV yielded comparable final VA 0.67 ± 0.66 vs 0.54 ± 0.35 (P = .576) and visual gain -0.58 ± 0.69 vs -0.49 ± 0.48 (P = .242) in the PPV and observation groups. CONCLUSIONS: PPV was very effective in closing TMH and VA gain in children throughout a wide range of hole size. Early and delayed PPV yielded similar anatomic and visual results. Observation and PPV yielded comparable final VA and closure time. Clinicians can choose either early PPV or delayed PPV when healing biomarkers are absent on periodic optical coherence tomography.

Retinal Pigment Epithelial Adenoma: Initial Treatment Outcomes following Episcleral Brachytherapy.

Introduction: We aim to explore the safety and efficacy of episcleral brachytherapy as a primary management option for eyes with retinal pigment epithelial (RPE) adenoma. Methods: Retrospective chart review of the demographic, clinical, ancillary, and postoperative outcome data of patients with RPE adenoma in 2 tertiary referral centers. Tumor regression, final visual acuity, and complications were assessed. Results: Five patients (3 females and 2 males) were included. Four of the 5 eyes had peripheral and mid-peripheral lesions, while one tumor was juxtapapillary. Three eyes were treated with ruthenium-106 (100 Gray), and 2 received iodine-125 episcleral plaques (85 Gray). All eyes showed clinical and imaging-based evidence of regression. Four eyes had stable or improved visual acuity, while 1 eye exhibited one line loss of visual acuity due to radiation retinopathy. Local recurrence was not observed in any eye over a median follow-up of 24 (range 6-112) months. Conclusions: Episcleral brachytherapy is an effective management option for select cases of RPE adenoma that is capable of achieving tumor regression while maintaining favorable visual acuity. The initial safety profile of brachytherapy is good without significant vision-compromising complications.

Exploring agro-morphological and fiber traits diversity in cotton (G. barbadense L.).

Cotton (Gossypium barbadense L.) is a leading fiber and oilseed crop globally, but genetic diversity among breeding materials is often limited. This study analyzed genetic variability in 14 cotton genotypes from Egypt and other countries, including both cultivated varieties and wild types, using agro-morphological traits and genomic SSR markers. Field experiments were conducted over two seasons to evaluate 12 key traits related to plant growth, yield components, and fiber quality. Molecular diversity analysis utilized 10 SSR primers to generate DNA profiles. The Molecular diversity analysis utilized 10 SSR primers to generate DNA profiles. Data showed wide variation for the morphological traits, with Egyptian genotypes generally exhibiting higher means for vegetative growth and yield parameters. The top-performing genotypes for yield were Giza 96, Giza 94, and Big Black Boll genotypes, while Giza 96, Giza 92, and Giza 70 ranked highest for fiber length, strength, and fineness. In contrast, molecular profiles were highly polymorphic across all genotypes, including 82.5% polymorphic bands out of 212. Polymorphism information content was high for the SSR markers, ranging from 0.76 to 0.86. Genetic similarity coefficients based on the SSR data varied extensively from 0.58 to 0.91, and cluster analysis separated genotypes into two major groups according to geographical origin. The cotton genotypes displayed high diversity in morphology and genetics, indicating sufficient variability in the germplasm. The combined use of physical traits and molecular markers gave a thorough understanding of the genetic diversity and relationships between Egyptian and global cotton varieties. The SSR markers effectively profiled the genotypes and can help select ideal parents for enhancing cotton through hybridization and marker-assisted breeding.

E-cadherin expression and gene expression profiles in corticotroph pituitary neuroendocrine tumor subtypes.

Corticotroph adenomas/pituitary neuroendocrine tumors (PitNETs) are associated with significant morbidity and mortality. Predictors of tumor behavior have not shown high prognostic accuracy. For somatotroph adenomas/PitNETs, E-cadherin expression correlates strongly with prognosis. E-cadherin expression has not been investigated in other PitNETs. A retrospective chart review of adults with corticotroph adenomas/PitNETs was conducted to assess correlation between E-cadherin expression and tumor characteristics. In addition, gene expression microarray was performed in subset of tumors (n = 16). Seventy-seven patients were identified; 71% were female, with median age of cohort 45.2 years. Seventy-five percent had macroadenomas, of which 22% were hormonally active. Ninety-five percent of microadenomas were hormonally active. Adrenocorticotropic hormone granulation pattern by IHC identified 63% as densely granulated (DG) and 34% as sparsely granulated (SG). All microadenomas were DG (p < .001); 50% of macroadenomas were DG associated with increased tumor invasion compared to SG. E-cadherin IHC was positive in 80%, diminished in 17%, and absent in 20% and did not correlate with corticotroph PitNETs subtype, size, or prognosis. In contrast to the distinct transcriptomes of corticotroph PitNETs and normal pituitaries, a comparison of clinically active and silent corticotroph PitNETs demonstrated similar molecular signatures indicating their common origin, but with unique differences related to their secretory status.

Refining the predictive value of preoperative apparent diffusion coefficient (ADC) by whole-tumor analysis for facial nerve outcomes in vestibular schwannomas.

BACKGROUND: Apparent diffusion coefficient (ADC) in MRI has been shown to correlate with postoperative House-Brackmann (HB) scores in patients with vestibular schwannoma despite limited methodology. To rectify limitations of single region of interest (ROI) sampling, we hypothesize that whole-tumor ADC histogram analysis will refine the predictive value of this preoperative biomarker related to postoperative facial nerve function. METHODS: Of 155 patients who underwent resection of vestibular schwannoma (2014-2020), 125 patients were included with requisite clinical and radiographic data. After volumetric analysis and whole-tumor ADC histogram, regression tree analysis identified ADC cutoff for significant differences in HB grade. Outcomes were extent of resection, facial nerve function, hospital length of stay (LOS), and complications. RESULTS: Regression tree analysis defined three quantitative ADC groups (× 10-6 mm2/s) as high (> 2248.77; HB 1.7), mid (1468.44-2248.77; HB 3.1), and low (< 1468.44; HB 2.3) range (p 0.04). The mid-range ADC group had significantly worse postoperative HB scores and longer hospital LOS. Large tumor volume was independently predictive of lower rates of gross total resection (p <0.0001), higher postoperative HB score (p 0.002), higher rate of complications (p 0.04), and longer LOS (p 0.003). CONCLUSIONS: Whole-tumor histogram yielded a robust regression tree analysis that defined three ADC groups with significantly different facial nerve outcomes. This likely reflects tumor heterogeneity better than solid-tumor ROI sampling. Whole-tumor ADC warrants further study as a useful radiographic biomarker in patients with vestibular schwannoma who are considering surgical resection.

Assessment of the therapeutic potential of a novel phosphoramidate acyclic nucleoside on induced hepatocellular carcinoma in rat model.

AIMS: Hepatocellular Carcinoma (HCC) is renowned as a deadly primary cancer of hepatic origin. Sorafenib is the drug-of-choice for targeted treatment of unresectable end-stage HCC. Unfortunately, great proportion of HCC patients showed intolerance or unresponsiveness to treatment. This study assesses potency of novel ProTide; SH-PAN-19 against N-Nitrosodiethylamine (DEN)-induced HCC in male Wistar rats, compared to Sorafenib. MAIN METHODS: Structural entity of the synthesized compound was substantiated via FT-IR, UV-Vis, 1H NMR and 13C NMR spectroscopic analysis. In vitro, SH-PAN-19 cytotoxicity was tested against 3 human cell lines; hepatocellular carcinoma; HepG-2, colorectal carcinoma; HCT-116 and normal fibroblasts; MRC-5. In vivo, therapeutic efficacy of SH-PAN-19 (300 mg/kg b.w./day) against HCC could be revealed and compared to that of Sorafenib (15 mg/kg b.w./day) by evaluating the morphometric, biochemical, histopathological, immunohistochemical and molecular key markers. KEY FINDINGS: SH-PAN-19 was relatively safe toward MRC-5 cells (IC50 = 307.6 µg/mL), highly cytotoxic to HepG-2 cells (IC50 = 24.9 µg/mL) and prominently hepato-selective (TSI = 12.35). Oral LD50 of SH-PAN-19 was >3000 mg/kg b.w. DEN-injected rats suffered hepatomegaly, oxidative stress, elevated liver enzymes, hypoalbuminemia, bilirubinemia and skyrocketed AFP plasma titre. SH-PAN-19 alleviated the DEN-induced alterations in apoptotic, angiogenic and inflammatory markers. SH-PAN-19 produced a 2.5-folds increase in Caspase-9 and downregulated VEGFR-2, IL-6, TNF-α, TGFß-1, MMP-9 and CcnD-1 to levels comparable to that elicited by Sorafenib. SH-PAN-19 resulted in near-complete pathological response versus partial response achieved by Sorafenib. SIGNIFICANCE: This research illustrated that SH-PAN-19 is a promising chemotherapeutic agent capable of restoring cellular plasticity and could stop HCC progression.

Age, Gender, and Liver Enzyme Impact Hospital Stay in COVID-19 Minority Patient with Cancer in the USA: Does Race Matters in the Pandemic?

Patients with cancer are known to have a poor prognosis when infected with SARS-CoV-2 infection. We aimed in this study to assess health outcomes in COVID-19 patients with different cancers in comparison to non-cancer COVID-19 patients from different centers in the United States (US). We evaluated medical records of 1,943 COVID-19 Cancer patients from 3 hospitals admitted between December 2019 to October 2021 and compared them with non-cancer COVID-19 patients. Among 1,943 hospitalized COVID-19 patients, 18.7% (n=364) have an active or previous history of cancer. Among these 364 cancer patients, 222 were African Americans (61.7%) and 121 were Caucasians (33.2%). Cancer patients had significantly longer hospitalization compared to controls (8.24 vs 6.7 days). Overall, Lung cancer is associated with high mortality. Patients with a previous history of cancer were more prone to death (p=0.04) than active cancer patients. In univariate and multivariate analyses, predictors of death among cancer patients were male sex, older age, presence of dyspnea, elevated troponin, elevated AST (0.001) and ALT (0.05), low albumin (p=0.04) and mechanical ventilation (p=0.001). Patients with a previous history of cancer were more prone to death when compared to active cancer COVID-19 patients. Early recognition of cancer COVID-19 patients' death-associated risk factors can help determine appropriate treatment and management plans for better prognosis and outcome.

Novel classification of foramen magnum meningiomas predicted by topographic position relative to neurovascular bundle.

PURPOSE: Proximity to critical neurovascular structures can create significant obstacles during surgical resection of foramen magnum meningiomas (FMMs) to the detriment of treatment outcomes. We propose a new classification that defines the tumor's relationship to neurovascular structures and assess correlation with postoperative outcomes. METHODS: In this retrospective review, 41 consecutive patients underwent primary resection of FMMs through a far lateral approach. Groups defined based on tumor-neurovascular bundle configuration included Type 1, bundle ventral to tumor; Type 2a-c, bundle superior, inferior, or splayed, respectively; Type 3, bundle dorsal; and Type 4, nerves and/or vertebral artery encased by tumor. RESULTS: The 41 patients (range 29-81 years old) had maximal tumor diameter averaging 30.1 mm (range 12.7-56 mm). Preoperatively, 17 (41%) patients had cranial nerve (CN) dysfunction, 12 (29%) had motor weakness and/or myelopathy, and 9 (22%) had sensory deficits. Tumor type was relevant to surgical outcomes: specifically, Type 4 demonstrated lower rates of gross total resection (65%) and worse immediate postoperative CN outcomes. Long-term findings showed Types 2, 3, and 4 demonstrated higher rates of permanent cranial neuropathy. Although patients with Type 4 tumors had overall higher ICU and hospital length of stay, there was no difference in tumor configuration and rates of postoperative complications or 30-day readmission. CONCLUSION: The four main types of FMMs in this proposed classification reflected a gradual increase in surgical difficulty and worse outcomes. Further studies are warranted in larger cohorts to confirm its reliability in predicting postoperative outcomes and possibly directing management decisions.

Antioxidant Status, Lipid Metabolism, Egg Fatty Acids, and Nutritional Index of White-Egg Laying Hens Fed Flaxseed Cake.

Flaxseed cake contains high levels of phenolic compounds, which have numerous biological activities, as well as a considerable amount of omega-3 fatty acids, such as α-linolenic acid, which remains after oil extraction. In this study, we examined the effects of flaxseed cake meal (FSCM) on the antioxidative status, lipid metabolism, egg fatty acid profile, and egg health index of white-egg laying hens. A total of 63 Hisex White laying hens were divided into three experimental treatment groups and fed diets containing 0, 5, or 10% FSCM from 48 to 58 weeks of age. Feeding with 5 and 10% FSCM did not significantly (p>0.05) influence total lipid, triglyceride, total cholesterol, very low-density lipoprotein-cholesterol, or low-density lipoprotein-cholesterol concentrations, or the high-/low-density lipoprotein ratio in the serum and egg yolk; however, 10% FSCM significantly (P<0.05) increased serum high-density lipoprotein. Dietary FSCM also did not affect (P>0.05) antioxidant markers in the eggs and blood plasma. Notably, dietary inclusion of FSCM significantly increased (P<0.05) total n-3 polyunsaturated fatty acids (PUFAs), α-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid levels in egg yolk, whereas the n-6:n-3 PUFAs ratio was markedly (P<0.05) decreased in a dose-dependent manner. Moreover, including 5-10% FSCM improved (P<0.05) egg health indices, with 10% being the most beneficial. Together, these findings indicated that the inclusion of up to 10% FSCM in laying hen diets improved egg yolk lipid and fatty acid profiles, as well as egg quality and nutritional and metabolic indices.

Effect of dietary electrolyte balance and arginine to lysine ratio on hematological, antioxidant and immunological traits in dual-purpose breeding hens under cyclic heat stress condition.

A total of 245 hens and 35 cocks (32 weeks age) were assigned to seven treatment groups (five replicates with seven hens and one cock) to investigate the effect of dietary electrolyte balance (DEB) and arginine to lysine ratio (Arg/Lys) on birds' physiological and biochemical traits under cyclic heat stress (CHS) condition. Birds were housed in an environmentally controlled facility having four sectors. The first group (positive control, PC) was kept under thermoneutral conditions and fed diet with DEB of 180 mEq and Arg/Lys of 1.25, whereas the other six treatments were kept in the second sector under CHS and fed diet with DEB and Arg/Lys equal to: 180 mEq and 1.25 (negative control, NC); 250 mEq and 1.25; 320 mEq and 1.25; 180 mEq and 1.37; 250 mEq and 1.37; 320 mEq and 1.37, respectively. Hens on NC group had significantly decreased red blood cells (RBCs), white blood cells (WBCs) and its fractions. The groups fed different DEB and Arg/Lys in diet significantly enhanced the blood parameters and plasma lipid profile compared NC group. Hens under CHS fed on 250 and 320 DEB with 1.37 Arg/Lys recorded the lowest concentration of low-density lipoprotein (LDL) compared with the other groups. Triiodothyronine (T3) activity was not differed among groups, while T4 activity in layer exposed to CHS (NC group) recorded the highest activity compared to PC. From findings, it can be concluded that laying hens fed a diet having DEB 250 mEq with 1.37 Arg/Lys could be successfully applied to counteract the adverse effect of CHS and to improve blood hematological and biochemical traits, antioxidants, and immunity response.

Correction: Menstrual cycle changes: A cross-sectional study of Saudi females following SARS-CoV-2 infection.

[This corrects the article DOI: 10.1371/journal.pone.0279408.].

Growth performance, plasma metabolites, meat quality, and meat and lipid health indices of New Zealand White rabbits as affected by dietary dried tomato pomace powder supplementation during the summer season.

One hundred and twenty New Zealand White rabbits (NZW) (5-week-old; 735.27 ± 27.23 g) were kept in an open-sided house during the summer season. The experiment aims to evaluate the impacts of dried tomato pomace powder (DTPP) supplementation on rabbits' performance, blood metabolites, carcass traits, meat quality, and lipid and health indices of NZW rabbits during 5-13 weeks of age. The four treatments were a standard rabbit feed (control) and the control diet supplemented with 0.5, 1.0, and 1.5% DTPP, respectively. Rabbits fed a diet containing 1.5% DTPP showed the highest growth rate through weeks 9-13 of age despite having the lowest feed intake spanning 5-13 weeks. The best feed conversion ratio (FCR) was recorded in rabbits fed with 1.5% DTPP-supplemented diet for 5-13 weeks. Diets supplemented with 0.5 or 1.0% DTPP enhanced markedly dressing %, total edible flesh, saturated (SFAs), monounsaturated (MUFAs), and polyunsaturated fatty acid (PUFAs) contents, as well as the ∑n - 6/∑n - 3 ratio and the total n - 6 of meat. Dietary supplementation with DTPP decreased kidney, abdominal, and back fat. Diets supplemented with DTTP decreased total cholesterol, triglycerides, and very low-density lipoprotein (vLDL) concentrations. The greatest levels of linoleic acid, arachidonic and water-holding capacity in meat were observed in rabbits fed 1.5% DTPP-supplemented diets. Diets containing 1 and 1.5% DTPP improved meats' atherogenic and thrombogenic indices, meat lipid quality desired fatty acids/undesired fatty acids ratio, and meat health index. Conclusively, DTPP up to 1.5% maintained the growth performance of rabbits, boosted meat quality through increasing vitamin E, reduced fat deposition, modified fatty acid composition, and improved atherogenic, thrombogenic, and hypocholesterolemic indices of rabbit meat.

Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative Stress, preventing inflammation and apoptosis: Ultrastructural and computational approaches.

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

Feasibility and reproducibility of new technique for measurement of transverse diameter of levator ani muscle hiatus using two-dimensional transperineal ultrasound in nulliparous women with term pregnancy.

OBJECTIVES: The aim of the present study was two-fold. Firstly, we aimed to develop and describe a technique for measurement of the transverse diameter (TD) of the levator ani muscle (LAM) hiatus in the coronal view using two-dimensional (2D) transperineal ultrasound (TPUS) in nulliparous women with a term pregnancy. Secondly, we aimed to evaluate the feasibility and reproducibility of 2D-TPUS assessment of LAM hiatal TD and assess intermethod agreement between 2D-TPUS and three-dimensional (3D) TPUS measurement of TD in the axial plane, which is considered the gold standard in nulliparous women with term pregnancy. METHODS: We recruited a group of nulliparous women with term pregnancy before the onset of labor. The study was conducted in two phases: Phase 1 involved developing and describing the 2D-TPUS technique for measuring LAM hiatal TD, and Phase 2 focused on assessing the technique's feasibility, reproducibility and intermethod agreement with 3D-TPUS measurement of LAM hiatal TD. In Phase 1, we enrolled 30 women. Each woman underwent acquisition of a 3D-TPUS volume, which was analyzed using multiplanar mode to identify and determine the appearance of the lateral borders of the LAM in the coronal plane, at the level of the plane of minimal hiatal dimensions. These borders were used as landmarks for TD measurement. Additionally, we measured the distance between the plane used for TD measurement and the center of the urethra in the axial view. In Phase 2, we recruited 100 women. Each woman underwent acquisition of three 2D-TPUS videoclips in the coronal plane, each encompassing a sweep of the entire LAM hiatus, and a 3D volume, all obtained during rest. On the 2D videoclips, TD was measured twice by one operator and once by another operator. In the 3D volume, TD was measured once, by one operator, in the axial plane; this measurement was considered the gold standard. Each operator was blinded to all other measurements during their assessments. We analyzed intraobserver and interobserver reproducibility and performed an intermethod (2D vs 3D) comparison. Bland-Altman analysis was conducted, and Levene's W0 test and Student's t-test were performed to explore clinical factors that might contribute to systematic differences. RESULTS: In Phase 1, we identified successfully the landmarks denoting the lateral borders of the LAM hiatal TD in the coronal view. These appeared as two symmetrical hypoechogenic indentations located at the inner border of the hyperechogenic structure of the LAM, at the point of maximum distance between the two sides of the LAM. The distance between the urethra and the plane where TD should be measured using 3D-TPUS in the axial plane had a median of 4 mm and varied from 0 to 9 mm. This enabled us to describe a method for assessing LAM hiatal TD in the coronal plane using 2D-TPUS. In Phase 2, LAM hiatal TD was measured successfully in all 2D and 3D acquisitions from the entire group of 100 women. The analyses for intraobserver and interobserver reproducibility and the intermethod comparison (2D vs 3D) revealed almost perfect agreement in TD measurements using 2D-TPUS, with intraclass correlation coefficients of 0.95 (95% CI, 0.92-0.96), 0.87 (95% CI, 0.78-0.92) and 0.85 (95% CI, 0.78-0.90), respectively. The average differences between measurements were 0.1 mm for intraobserver, 1.0 mm for interobserver and 0.2 mm for intermethod repeatability. No systematic differences were observed in any of the measurement sets, except in the interobserver analysis, although this difference was clinically not significant (38.2 vs 37.2 mm, P = 0.01). None of the examined clinical factors (maternal body mass index and maternal age) exhibited a statistically significant impact on intraobserver, interobserver or intermethod reliability. CONCLUSIONS: Utilizing our technique, described herein, to measure the LAM hiatal TD in the coronal view using 2D-TPUS is not only feasible but also highly reproducible and accurate in nulliparous women with term pregnancy. Moreover, it yields measurements that are comparable to those obtained in the reconstructed axial plane generated by 3D-TPUS. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Oncogenic Potential of Replication Factor C Subunit 4: Correlations with Tumor Progression and Assessment of Potential Inhibitors.

Replication Factor C Subunit 4 (RFC4), an oncogene implicated in many human cancers, has yet to be extensively studied in many cancer types to determine its expression patterns and tumor tissue function. Various bioinformatics tools were used to analyze RFC4 as a potential oncogene and therapeutic target across many cancers. We first examined RFC4 expression levels in several human tumor types to determine relationships with tumor grade, stage, metastasis, and patient survival. We also examined RFC4's genetic changes, epigenetic methylation, and effect on tumor microenvironment (TME) immune cell infiltration. We also analyzed RFC4's connections with immunological checkpoints to identify potential molecular pathways involved in carcinogenesis. Our findings show that RFC4 is upregulated in several tumor types and associated with poor prognoses in many human cancers. This study shows that RFC4 significantly affects the tumor immunological microenvironment, specifically immune cell populations. Finally, we screened for RFC4-inhibiting pharmacological compounds with anti-cancer potential. This study fully elucidates RFC4's carcinogenic activities, emphasizing its potential as a prognostic biomarker and a target for anti-cancer therapy.