Plasma hPG80 (Circulating Progastrin) as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Alpha-fetoprotein (AFP) is the most widely used biomarker for hepatocellular carcinoma (HCC) prognosis. However, AFP is not useful in establishing a prognosis for patients with a tumor in the early stages. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including HCC. In this study, we evaluated the prognostic value of plasma hPG80 in patients with HCC, alone or in combination with AFP. A total of 168 HCC patients were tested prospectively for hPG80 and analyzed retrospectively. The prognostic impact of hPG80 and AFP levels on patient survival was assessed using Kaplan-Meier curves and log-rank tests. hPG80 was detected in 84% of HCC patients. There was no correlation between hPG80 and AFP levels in the training and validation cohorts. Both cohorts showed higher sensitivity of hPG80 compared to AFP, especially at early stages. Patients with high hPG80 (hPG80+) levels (optimal cutoff value 4.5 pM) had significantly lower median overall survival (OS) compared to patients with low hPG80 (hPG80−) levels (12.4 months versus not reached respectively, p < 0.0001). Further stratification by combining hPG80 and AFP levels (cutoff 100 ng/mL) improved prognosis in particular for those patients with low AFP level (hPG80−/AFP+ and hPG80−/AFP−, 13.4 months versus not reached respectively, p < 0.0001 and hPG80+/AFP+ and hPG80+/AFP−, 5.7 versus 26 months respectively, p < 0.0001). This was corroborated when analyses were performed using the BCLC staging especially at early stages. Our findings show that hPG80 could serve as a new prognostic biomarker in HCC. Used in combination with AFP, it improves the stratification of the patients in good and poor prognosis, especially for those patients with negative AFP and early-stage HCC.

Determination of the Effect of Two Different Methods of Dental Anaesthesia on Pain Level in Pediatric Patients: A Cross-Over, Randomised Trial

ObjectiveTo compare intraosseous (IOA) and needle-free dental anaesthesia (NFA) methods that painless anaesthesia.Materials and MethodsTwenty patients aged 8–10 years were included in this cross-over study. To determine the anxiety levels and pain experienced by the patients, Face, Legs, Activity, Cry, Consolability (FLACC) and Frankl Behavioural scales were used. The pulse rate (PR) and salivary opiorphin levels (SOL) determined. The Friedman and Wilcoxon signed-rank tests were used. p<0.01 was considered significant.ResultsAccording to FLACC scores, IOA and NFA exhibited significantly pain alteration patterns in during local and topical anaesthesia, respectively (p=0.004,0.001; p<0.01). Also, only NFA showed significantly decreased SOL values in 5- and 10- minutes after local anaesthesia periods compared to the before levels (p=0.004, p=0.001; p<0.01).ConclusionsPatients feel similar pain perceptions during local anaesthesia application in both injection systems. According to the SOL values, NFA may provide more higher anaesthetic efficiency than IOA.Clinical RelevanceThis study provides to compare two different new anaesthetic systems for pain reduction during local anesthesia for pediatric population.

Phenotypic Spectrum of Dystrophinopathy Due to Duchenne Muscular Dystrophy Exon 2 Duplications

Background and Objectives:To describe the phenotypic spectrum of dystrophinopathy in a large cohort of individuals with DMD exon 2 duplications (Dup2), whom may be particularly amenable to therapies directed at restoring expression of either full-length dystrophin, or nearly full-length dystrophin through utilization of the DMD exon 5 internal ribosome entry site (IRES).Methods:In this retrospective observational study, we analyzed data from large genotype-phenotype databases (the United Dystrophinopathy Project [UDP] and the Italian DMD network) and classified subjects into Duchenne (DMD), intermediate (IMD), or Becker (BMD) phenotypes. Log-rank tests for time-to event variables were used to compare age at loss of ambulation (LOA) in Dup2 subjects versus non-Dup2 controls in the UDP database, and for comparisons between steroid-treated vs. steroid-naive Dup2 subjects.Results:Among 66 Dup2 subjects (UDP=40, Italy=26), 61% percent were classified as DMD, 9% as IMD, and 30% as BMD. Median age at last observation was 15.4 years [IQR 8.79-26.0], and 75% had been on corticosteroids for at least 6 months. Age at LOA differed significantly between Dup2 DMD subjects and historical non-Dup2 DMD controls (p<0.001). Valid spirometry was limited but suggested a delay in the typical age-related decline in forced vital capacity, and 24 of 55 subjects with adequate cardiac data had cardiomyopathy.Discussion:Some Dup2 patients display a milder disease course than non-Dup2 DMD controls, and prolonged ambulation with corticosteroids suggests the potential of IRES activation as a molecular mechanism. As Dup2-targeted therapies reach clinical applications, this information is critical to aid in the interpretation of the efficacy of new treatments.

DCE-MRI is more sensitive than IVIM-DWI for assessing anti-angiogenic treatment-induced changes in colorectal liver metastases

Background Diffusion weighted imaging (DWI) with intravoxel incoherent motion (IVIM) modelling can inform on tissue perfusion without exogenous contrast administration. Dynamic-contrast-enhanced (DCE) MRI can also characterise tissue perfusion, but requires a bolus injection of a Gadolinium-based contrast agent. This study compares the use of DCE-MRI and IVIM-DWI methods in assessing response to anti-angiogenic treatment in patients with colorectal liver metastases in a cohort with confirmed treatment response. Methods This prospective imaging study enrolled 25 participants with colorectal liver metastases to receive Regorafenib treatment. A target metastasis > 2 cm in each patient was imaged before and at 15 days after treatment on a 1.5T MR scanner using slice-matched IVIM-DWI and DCE-MRI protocols. MRI data were motion-corrected and tumour volumes of interest drawn on b=900 s/mm2 diffusion-weighted images were transferred to DCE-MRI data for further analysis. The median value of four IVIM-DWI parameters [diffusion coefficient D (10−3 mm2/s), perfusion fraction f (ml/ml), pseudodiffusion coefficient D* (10−3 mm2/s), and their product fD* (mm2/s)] and three DCE-MRI parameters [volume transfer constant Ktrans (min−1), enhancement fraction EF (%), and their product KEF (min−1)] were recorded at each visit, before and after treatment. Changes in pre- and post-treatment measurements of all MR parameters were assessed using Wilcoxon signed-rank tests (P<0.05 was considered significant). DCE-MRI and IVIM-DWI parameter correlations were evaluated with Spearman rank tests. Functional MR parameters were also compared against Response Evaluation Criteria In Solid Tumours v.1.1 (RECIST) evaluations. Results Significant treatment-induced reductions of DCE-MRI parameters across the cohort were observed for EF (91.2 to 50.8%, P<0.001), KEF (0.095 to 0.045 min−1, P<0.001) and Ktrans (0.109 to 0.078 min−1, P=0.002). For IVIM-DWI, only D (a non-perfusion parameter) increased significantly post treatment (0.83 to 0.97 × 10−3 mm2/s, P<0.001), while perfusion-related parameters showed no change. No strong correlations were found between DCE-MRI and IVIM-DWI parameters. A moderate correlation was found, after treatment, between Ktrans and D* (r=0.60; P=0.002) and fD* (r=0.67; P<0.001). When compared to RECIST v.1.1 evaluations, KEF and D correctly identified most clinical responders, whilst non-responders were incorrectly identified. Conclusion IVIM-DWI perfusion-related parameters showed limited sensitivity to the anti-angiogenic effects of Regorafenib treatment in colorectal liver metastases and showed low correlation with DCE-MRI parameters, despite profound and significant post-treatment reductions in DCE-MRI measurements. Trial registration NCT03010722 clinicaltrials.gov; registration date 6th January 2015.

The Importance of Mentors and How to Handle More Than One Mentor

Introduction: Working with multiple mentors is a critical way for students to expand their network, gain opportunities, and better prepare for future scholastic or professional ventures. However, students from underrepresented groups (UR) are less likely to be mentored or have access to mentors, particularly in science, technology, engineering, and mathematics (STEM) fields. We developed and implemented a workshop, to provide the necessary foundation for students to be better prepared for establishing future mentorships throughout graduate and professional school. Methods: Faculty well-versed in the area of effective mentorship from multiple universities developed and delivered a 1.5-hour workshop to address the roles of a mentor, especially when it comes to UR students, and how students may effectively work with multiple mentors. This workshop was delivered to a group of students from the HBCU Winston Salem State University, and a pre/post- Likert scale-based survey was administered. Results: We analyzed the raw data with nonparametric tests for comparison within paired samples. Wilcoxon matched-pairs and signed-rank tests showed statistically significant growth in student self-ratings related to the workshop learning objectives. Conclusions: The How to Handle More than One Mentor to Achieve Excellence workshop was well received as a component of pre-graduate and pre-professional training. Incorporating workshops like this may increase student preparedness around developing and cultivating healthy mentorship relationships throughout STEM training.

The Effect of Storytelling Using Finger Puppets on Anxiety in Hospitalized Preschool Children

Introduction: The prevalence rates of disease at preschool age are higher than toddlers and school age. The coping mechanism has not developed at that age, thus contributing to increased anxiety levels during hospitalization. Interventions are needed to overcome anxiety problems so that children are more comfortable and cooperative in undergoing treatment in the hospital more effectively. The research aims to examine the effect of storytelling using finger puppets on anxiety in hospitalized preschool children. Methods: Quasi-experiment research with pre and post-test design, 40 preschool children were selected with purposive sampling with inclusion and exclusion criteria, 20 respondents of treatment groups, and 20 respondents of control groups. The instrument used FAS. Data analysis used is the Mann Whitney and Wilcoxon Sign Rank Tests. Results: Mann-Whitney results showed the difference in anxiety between treatment and control group in post-test (p=0.023), and Wilcoxon results showed Z count -3.827 a< Z table -1.96 value asymp sig. (2-tailed) where z arithmetic ≤ z table which means there is influence or probability value p= 0.000 (p< α= 0,05) which means H1 accepted. Conclusion: It is expected that in the future, it can be used as an alternative method to reduce anxiety. And then it’s hoped that researchers can further examine more deeply the effectiveness of parental involvement in storytelling play therapy.

Parents’ Report of Canadian Elementary School Children’s Physical Activity and Screen Time during the COVID-19 Pandemic: A Longitudinal Study

COVID-19 public health protocols have altered children’s daily routines, limiting their physical activity opportunities. The purpose of this study was to examine how the COVID-19 pandemic affected children’s (ages 10–12 years) physical activity and screen time, and to explore the impact of gender, socioeconomic status (SES), and public health constraints (i.e., facility use and social interaction) on the changes in children’s health behaviors. Online surveys were disseminated to parents at two time points: before COVID-19 (May 2019 to February 2020) and during COVID-19 (November to December 2020). Wilcoxon signed-rank tests were used to assess changes in physical activity and screen time, and for subgroup analyses. Parents (n = 95) reported declines in children’s physical activity (Z = −2.53, p = 0.01, d = 0.18), and increases in weekday (Z = −4.61, p < 0.01, d = 0.33) and weekend screen time (Z = −3.79, p < 0.01, d = 0.27). Significant changes in physical activity and screen time behaviors were identified between gender, SES, and facility use groups. All social interaction groups underwent significant changes in screen time. Overall, COVID-19 protocols have negatively influenced children’s physical activity and screen time. Due to the negative consequences of inactivity and excessive screen time, resources must be made available to support families during the pandemic.