Tag: pubmed

Sci Rep. 2022 Oct 25;12(1):17856. doi: 10.1038/s41598-022-22507-3.

ABSTRACT

Pre-eclampsia (PE) is a hypertensive condition that occurs during pregnancy and complicates up to 4% of pregnancies. PE exhibits several circadian-related characteristics, and the placenta possesses a functioning molecular clock. We examined the associations of 17 core circadian gene transcripts in placenta with PE vs. non-PE (a mixture of pregnant women with term, preterm, small-for-gestational-age, or chorioamnionitis) using two independent gene expression datasets: GSE75010-157 (80 PE vs. 77 non-PE) and GSE75010-173 (77 PE and 96 non-PE). We found a robust difference in circadian gene expression between PE and non-PE across the two datasets, where CRY1 mRNA increases and NR1D2 and PER3 transcripts decrease in PE placenta. Gene set variation analysis revealed an interplay between co-alterations of circadian clock genes and PE with altered hypoxia, cell migration/invasion, autophagy, and membrane trafficking pathways. Using human placental trophoblast HTR-8 cells, we show that CRY1/2 and NR1D1/2 regulate trophoblast migration. A subgroup study including only term samples demonstrated that CLOCK, NR1D2, and PER3 transcripts were simultaneously decreased in PE placenta, a finding supported by CLOCK protein downregulation in an independent cohort of human term PE placenta samples. These findings provide novel insights into the roles of the molecular clock in the pathogenesis of PE.

PMID:36284122 | DOI:10.1038/s41598-022-22507-3

Sci Rep. 2022 Oct 25;12(1):17854. doi: 10.1038/s41598-022-20412-3.

ABSTRACT

Hepatic encephalopathy (HE) is a deterioration of brain function in patients suffering from chronic liver disease, cirrhosis as a result of elevated blood ammonia and the production of pseudo-neurotransmitters. Herein, we investigated the chemical composition of hexane extract from Origanum vulgare (O. vulgare) leaves as well as its possible protective effects against thioacetamide (TAA)-induced HE in rats. GC-MS analysis of the extract revealed tentative identification of twenty-five compounds (82.93%), predominated by cholesten-3-one (27.30%), followed by γ-tocopherol (13.52%), α-tocopherol (5.01%), β-amyrin (5.24%) and α-amyrin (4.89%). Albino rats were distributed into seven groups (n = 7). G₁ served as negative control; G₂ and G₃ served as controls treated with O. vulgare (100 and 200 mg/kg/p.o b.w, respectively); G₄ served as TAA-positive control group (100 mg/kg/day/i.p., three alternative days per week for six weeks); G5, G6, and G7 served as TAA -induced HE rat model that received O. vulgare 100, O. vulgare 200, and silymarin (100 mg/kg of SILY, as standard drug), respectively. TAA showed depressive and anxiety-like behaviors in forced swimming test (FST) and reduction of cognitive score in elevated plus-maze test (EPMT) as well as impairment of locomotor and exploratory activities in open-field test (OFT). TAA caused a significant decline in body weight gain; however, the relative liver weight and brain water content were statistically increased. TAA-intoxicated rats showed significant increase of serum biomarker enzymes, proinflammatory cytokines, blood ammonia levels, brain serotonin, acetyl cholinesterase and cellular lipid peroxidation with significant decrease of brain dopamine, norepinephrine, antioxidant status. The hepatoprotective/neuro-protective activities of O. vulgare was found to be comparable with that of SILY in HE rats model. Where, treatment of TAA-intoxicated rats with O. vulgare attenuated anxiety, depressive-related behaviors, and reduced the biochemical changes in HE-induced by TAA. Therefore, O. vulgare could be an excellent hepato-/neuroprotective against hepatic injury and HE via improving the oxidative/inflammatory status through its antioxidant and neuro-modulatory properties and its effect is equal to that of SILY.

PMID:36284120 | DOI:10.1038/s41598-022-20412-3

Dermatol Ther (Heidelb). 2022 Oct 25. doi: 10.1007/s13555-022-00831-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Chlormethine (CL) gel is a skin-directed therapy approved for treatment of stage IA/IB mycosis fungoides-type cutaneous T-cell lymphoma (MF-CTCL) in the USA. MF-CTCL has a chronic clinical course, requiring long-term maintenance therapy with one or more therapies. This analysis describes real-world patterns of maintenance therapy and use of concomitant therapy with CL gel among patients with stage IA/IB MF-CTCL.

METHODS: In a US-based registry, MF-CTCL patients treated with CL gel were enrolled between 3/2015 and 10/2018 across 46 centers and followed for up to 2 years. Patient demographics, clinical characteristics, CL gel treatment patterns, concomitant treatments, clinical response, and adverse events (AEs) were collected from medical records. Descriptive statistics are reported.

RESULTS: Of the 206 patients with stage IA/IB MF-CTCL, 58.7% were male, and average age was 60.7 years with 4.6 years since diagnosis. Topical steroids, phototherapy, and topical retinoids were used concomitantly with CL gel in 62.6%, 26.2%, and 6.3% of patients, respectively. Most concomitant therapies (up to 85%) were started before CL gel initiation and, in about half of the cases (up to 57%), were used concurrently for ≥ 12 months. Overall, 158 (76.7%) patients experienced partial response (PR) and 144 continued with maintenance therapy. After achieving PR, most patients (74.3%) kept the same maintenance therapy schedule, most commonly once daily. Of patients who had any skin-related AE (31.6%) or skin-related AEs associated with CL gel (28.2%), nearly half experienced CL gel treatment interruption and ~40% had a dosing reduction. The observed real-world treatment patterns were concordant with National Comprehensive Cancer Network (NCCN) guidelines.

CONCLUSION: The study results suggest that continuing CL gel maintenance therapy and combining treatments with CL gel are common practice in the real-world setting, with most maintained on a stable dosing schedule. Careful management of AEs may help patients maintain long-term optimal dosing with less treatment interruptions and dosing reductions.

PMID:36284059 | DOI:10.1007/s13555-022-00831-w

Int J Behav Med. 2022 Oct 25. doi: 10.1007/s12529-022-10131-4. Online ahead of print.

ABSTRACT

BACKGROUND: People with advanced cancer experience psychological distress due to physical symptoms, functional decline, and a limited prognosis. Difficult thoughts, feelings, and emotions may exacerbate distress and lead to avoidance of these experiences which is sometimes referred to as experiential avoidance (EA). Advanced cancer patients may be more likely to engage in EA especially when no obvious solutions to their problems exist. This study aims to examine the terms used to describe EA, the processes that might indicate EA, associations between EA and psychological distress, and to understand why individuals might engage in EA.

METHODS: A mixed-methods review. Literature search of Medline, Embase, Psych INFO, and CINAHL 1980-October 2019.

INCLUSION: adults ≥ 18 years; advanced cancer not amenable to cure.

EXCLUSION: no measures of EA or psychological distress. Risk of bias and study quality assessed. Evidence of statistical techniques collected. Themes coded, grouped, and developed based on meaning.

RESULTS: Nineteen studies identified, 13 quantitative studies and 6 qualitative. The quantitative of which 6 compared early-stage cancers with advanced cancers and examined subscales of EA alongside mood, quality of life, and psychological distress. EA covers a range or terms of which ‘avoidant coping’ is the commonest. EA is manifest as cognitive, behavioural, and emotional avoidance. A thematic synthesis suggests the function of EA is to protect people from distress, and from confronting or expressing difficult emotions by avoiding communication about cancer, controlling negative information, and maintaining normality and hope and optimism.

CONCLUSIONS: EA may be beneficial in the short term to alleviate distress, but in the longer term, it can impair function and limit engagement in life. Greater clinical awareness of the complexity of EA behaviours is needed. Clinicians and researchers should define EA precisely and be aware of the function it may serve in the short and longer term. Future research studies may consider using specific measures of EA as a primary outcome, to assess the impact of psychological interventions such as ACT.

PMID:36284042 | DOI:10.1007/s12529-022-10131-4

Cancer Causes Control. 2022 Oct 25. doi: 10.1007/s10552-022-01646-y. Online ahead of print.

ABSTRACT

PURPOSE: Clinical trials advance the standard of care for patients. Patients enrolled in trials should represent the population who would benefit from the intervention in clinical practice. The aim of this study was to assess whether clinical trials enrolling patients with gynecologic cancers report racial and ethnic participant composition and to examine the level of diversity in clinical trials.

METHODS: Using ClinicalTrials.gov, we identified clinical trials enrolling patients with ovarian, uterine/endometrial, cervical, vaginal, and vulvar cancers from 1988 to 2019. Race and ethnicity data were extracted from participant demographics. Descriptive statistics on race, ethnicity, cancer type, location, study status, and sponsor type were calculated. Among trials which reported race and/or ethnicity, sub-analyses were performed on composition of race and ethnicity by funding source, location, and completed study status.

RESULTS: A total of 1,882 trials met inclusion criteria; only 179 trials (9.5%) reported race information. Of these, the racial distribution of enrollees was 66.9% White, 8.6% Asian, 8.5% Black/African American, 0.4% Indian/Alaskan Native, 0.1% Native Hawaiian/Pacific Islander, 1.0% more than one race, and 14.5% unknown. Only 100 (5.3%) trials reported ethnicity. Except for trials enrolling patients with cervical cancer which enrolled 65.2% White and 62.1% Non-Hispanic/Latino/a patients, enrollees in trials for other gynecologic cancers were over 80% White and 88% Non-Hispanic/Latino/a. Industry funded trials enrolled higher proportions of White (68.4%) participants than non-industry funded trials (57.5%). Domestic trials report race (11.5%) and ethnicity (7.6%) at higher rates than international trials (6.9% and 2.3%, respectively). Reporting of race (1.7% vs. 13.9%) and ethnicity (1.7% vs. 11.1%) has increased over time for patients enrolled in 2000 vs. 2018.

CONCLUSION: Less than 10% of trials enrolling patients with gynecologic malignancies report racial/ethnic participant composition on ClinicalTrials.gov. Accurate reporting of participant race/ethnicity is imperative to ensuring minority representation in clinical trials.

PMID:36284031 | DOI:10.1007/s10552-022-01646-y

Res Synth Methods. 2022 Oct 25. doi: 10.1002/jrsm.1608. Online ahead of print.

ABSTRACT

OBJECTIVE: Effect modification (EM) may cause bias in network meta-analysis (NMA). Existing population adjustment NMA methods use individual patient data to adjust for EM but disregard available subgroup information from aggregated data in the evidence network. Additionally, these methods often rely on the shared effect modification (SEM) assumption. In this paper, we propose Network Meta-Interpolation (NMI): a method using subgroup analyses to adjust for EM that does not assume SEM.

METHODS: NMI balances effect modifiers across studies by turning treatment effect (TE) estimates at the subgroup- and study level into TE and standard errors at EM values common to all studies. In an extensive simulation study, we simulate two evidence networks consisting of four treatments, and assess the impact of departure from the SEM assumption, variable EM correlation across trials, trial sample size and network size. NMI was compared to standard NMA, network meta-regression (NMR) and Multilevel NMR (ML-NMR) in terms of estimation accuracy and credible interval (CrI) coverage.

RESULTS: In the base case non-SEM dataset, NMI achieved the highest estimation accuracy with root mean squared error (RMSE) of 0.228, followed by standard NMA (0.241), ML-NMR (0.447) and NMR (0.541). In the SEM dataset, NMI was again the most accurate method with RMSE of 0.222, followed by ML-NMR (0.255). CrI coverage followed a similar pattern.

CONCLUSIONS: NMI’s dominance in terms of estimation accuracy and CrI coverage appeared to be consistent across all scenarios. NMI represents an effective option for NMA in the presence of study imbalance and available subgroup data. This article is protected by copyright. All rights reserved.

PMID:36283960 | DOI:10.1002/jrsm.1608

Ultrasound Med Biol. 2022 Oct 22:S0301-5629(22)00532-4. doi: 10.1016/j.ultrasmedbio.2022.08.007. Online ahead of print.

ABSTRACT

Ultrasound (US) is an increasingly prevalent and effective diagnostic modality for neuromuscular imaging. Gray-scale B-mode imaging has been the dominant US approach to evaluating nerves qualitatively or making morphometric measurements of nerves, providing important insights into pathological changes for conditions such as carpal tunnel syndrome. Among more recent ultrasound strategies, high-frequency ultrasound (often defined as >15 MHz for clinical applications), quantitative ultrasound and image textural analysis offer promising enhancements for improved and more objective approaches to nerve imaging. In this study, we evaluated the repeatability and reproducibility of backscatter coefficient (BSC) and imaging texture features extracted by gray-level co-occurrence matrices (GLCMs) in homogeneous tissue-mimicking reference phantoms and in median nerves in the wrists of healthy participants. We also investigated several practical sources of variability in the assessment of quantitative parameters, including influences of operators, and participant-to-participant variability. Overall, BSC- and GLCM-based outcomes are highly repeatable and reproducible after operator training, based on measurement of descriptive statistics, repeatability coefficient (RC) and reproducibility coefficient recommended by Quantitative Imaging Biomarker Alliance (QIBA RDC). GLCM parameters appear more reproducible and repeatable than BSC-based parameters in healthy participants in vivo. However, such variability noted here must be compared with the value ranges and variability of the results in pathological nerves, including median nerves afflicted by trauma, overuse syndromes such as carpal tunnel syndrome and after surgical repair.

PMID:36283940 | DOI:10.1016/j.ultrasmedbio.2022.08.007

Ultrasound Med Biol. 2022 Oct 23:S0301-5629(22)00578-6. doi: 10.1016/j.ultrasmedbio.2022.09.018. Online ahead of print.

ABSTRACT

In patients with breast cancer undergoing anthracycline-based chemotherapy, we investigated the deformational parameters of the left ventricle, right ventricle and left atrium, as well as the relationship between these parameters. Ninety-five patients with breast cancer who were treated with anthracycline-based chemotherapy were enrolled. The control group included 116 healthy female volunteers. Parameters including left ventricular global longitudinal strain (LV-GLS); right ventricular free wall longitudinal strain (RVFWSL) and global longitudinal strain (RV4CSL); and peak strain of the left atrium during LV systole (LASR), early LV diastole (LASCD) and late LV diastole (LASCT) were analyzed by speckle tacking echocardiography. LV-GLS, LASR, LASCD, RVFWSL and RV4CSL in the chemotherapy group decreased significantly by 15.6%, 13.8%, 19.8%, 21.8% and 13.2% (p < 0.05), respectively, when compared with the control group. LASCT was slightly increased in the chemotherapy group but the increase was not statistically significant (p > 0.05). Formulas for the influencing factors of LV-GLS were LV-GLS = -18.73738541 + 0.13961 × LVIDd + 0.09672 × LASCD + 0.18113 × RVFWSL in the control group and LV-GLS = -8.026302253 + 0.20811 × LASCD + 0.11084 × LASCT + 0.12153 × RVFWSL in the chemotherapy group. Both LV contraction and RV contraction were impaired after the completion of anthracycline-based therapy, and RVFWSL may be superior to LV-GLS in assessing cardiotoxicity. LA reserve and channel function were significantly reduced, while pump function was slightly increased. Compared with the results among healthy people, the influencing factor of LV-GLS varied after anthracycline treatment, and LA function had a greater impact on LV-GLS.

PMID:36283937 | DOI:10.1016/j.ultrasmedbio.2022.09.018

Reprod Biomed Online. 2022 Sep 21:S1472-6483(22)00709-X. doi: 10.1016/j.rbmo.2022.09.015. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Do internal levels of persistent organic pollutants (POP) in serum and follicular fluid affect ovarian function of women attending IVF?

DESIGN: This cohort study included 136 women undergoing IVF in the assisted reproductive technology (ART) service of University Hospital from Nantes (France). Representative POP were measured using gas and liquid chromatography coupled with tandem mass spectrometry. Polyfluoroalkylated and perfluoroalkylated substances were measured in serum and polychlorinated biphenyls and organochlorinated pesticides in follicular fluid. Statistical associations between POP and ovarian reserve markers (anti-Müllerian Hormone [AMH] and antral follicle count [AFC], and ovarian responsiveness markers (Ovarian Sensitivity Index [OSI] and Follicular Output RaTe [FORT]), were explored in single and multipollutant regression models.

RESULTS: Twenty-seven out of 53 POP congeners were frequently detected in almost all women attending IVF. Adjusted models did not show statistically significant associations between POP and ovarian reserve markers. Positive associations were found between some POP, i.e. hexachlorobenzene with FORT (β 0.42, 95% CI 0.13 to 0.71, P = 0.005) or PCB52 with Ovarian Sensitivity Index (β 0.22; 95% CI, 0.07 to 0.38, P = 0.005). Negative associations between some polyfluoroalkylated and perfluoroalkylated substances, PCB189 and trans-nonachlor with AFC and AMH were found among current smokers.

CONCLUSIONS: Globally, associations between POP and the markers of ovarian function or responsiveness were lacking. Nonetheless, the stratification analysis suggested that current smoking could be a risk modifier, and extension of the study to a larger population sample size is needed.

PMID:36283934 | DOI:10.1016/j.rbmo.2022.09.015

J Surg Educ. 2022 Oct 23:S1931-7204(22)00249-5. doi: 10.1016/j.jsurg.2022.09.014. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to examine the mortality difference and other outcome measures amongst trauma patients with residents involved in the initial management versus those that were managed by attending physicians only without resident involvement.

DESIGN: Retrospective review. Chi-square, Fisher’s tests were used to analyze the outcomes, diagnostics, and interventions using the presence of residents in the initial care of patients as an independent variable. Linear and logistic regression were used to estimate adjusted outcomes.

SETTING: Riverside Community Hospital, Riverside California (State-designated level I trauma center) PARTICIPANTS: Data on all trauma patients ≥18 years old that were admitted between July 1, 2018 and June 30, 2020 was collected retrospectively (total 2644 trauma patients). Trauma patients that were transferred from outside facilities were excluded from the study.

RESULTS: There was no significant difference in mortality associated with resident involvement in both unadjusted and adjusted analysis. Patients treated by residents, however, had more comorbidities (higher CCI) and were more severely injured (higher ISS). On adjusted analysis, higher ISS was independently associated with resident presence. There was also a statistically significant increase in the use of diagnostic studies and therapeutic interventions in the resident-present group.

CONCLUSIONS: Involvement of residents in the initial management of our trauma patient population was associated with no difference in overall mortality or morbidity, despite higher injury severity in the resident treated patient group.

PMID:36283922 | DOI:10.1016/j.jsurg.2022.09.014