Development and Validation of the Mental Health Scale for Maltreated Children.

OBJECTIVE: This study aimed to develop and validate a comprehensive self-report questionnaire to assess emotional and behavioral problems and psychological trauma in maltreated children. METHODS: The Mental Health Scale for Maltreated Children (MHS-MC) was constructed to encompass five major symptoms (depression, anxiety, inattention/hyperactivity/impulsivity, aggression/defiance, and psychological trauma) prevalent in maltreated children. Critical items and ego-resilience subscale were also devised to increase clinical utility. After informed consent, 205 children (maltreated children, n=157, 76.6%) were recruited nationwide, and they answered a package of self-report measures, including the MHS-MC. Reliability, construct validity, concurrent validity, and criterion-related validity were examined to explore the psychometric properties. RESULTS: The reliability was good to excellent. Confirmatory factor analysis yielded a five-factorial solution for the symptom subscales supporting construct validity. In logistic regression, the total scores of the MHS-MC predicted membership in the maltreated group. Criterion-related validity was generally satisfactory in that all subscales of the MHS-MC showed significant correlations with relevant measures in the expected direction. CONCLUSION: This is the first attempt to develop a comprehensive psychological scale based on nationwide data collected from maltreated Korean children. We hope that the continued standardization of this scale will contribute to evidence-based clinical and policy decisionmaking for maltreated children.

SYNGAP1-related developmental and epileptic encephalopathy: Genotypic and phenotypic characteristics and longitudinal insights.

The clinical and genetic characteristics of SYNGAP1 mutations in Korean pediatric patients are not well understood. We retrospectively analyzed 13 individuals with SYNGAP1 mutations from a longitudinal aspect. Clinical data, genetic profiles, and electroencephalography (EEG) patterns were examined. Genotypic analyses included gene panels and whole-exome sequencing. All patients exhibited global developmental delay from early infancy, with motor development eventually reaching independent ambulation by 3 years of age. Language developmental delay varied significantly from nonverbal to simple sentences, which plateaued in all patients. Patients with the best language outcomes typically managed 2-3-word sentences, corresponding to a developmental age of 2-3 years. Epilepsy developed in 77% of patients, with onset consistently following developmental delays at a median age of 31 months. Longitudinal EEG data revealed a shift from occipital to frontal epileptiform discharges with age, suggesting a correlation with synaptic maturation. These findings suggest that the critical developmental plateau occurs between the ages of 2 and 5 years and is potentially influenced by epilepsy. By analyzing longitudinal data, our study contributes to a deeper understanding of SYNGAP1-related DEE, provides potential EEG biomarkers, and underlines the importance of early diagnosis and intervention to address this complex disorder.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

Oligohydramnios affects pulmonary functional/structural abnormalities in school-aged children with bronchopulmonary dysplasia.

Background: The relationship between early life factors and childhood pulmonary function and structure in preterm infants remains unclear. Purpose: This study investigated the impact of bronchopulmonary dysplasia (BPD) and perinatal factors on childhood pulmonary function and structure. Methods: This longitudinal cohort study included preterm participants aged ≥5 years born between 2005 and 2015. The children were grouped by BPD severity according to National Institutes of Health criteria. Pulmonary function tests (PFTs) were performed using spirometry. Chest computed tomography (CT) scans were obtained and scored for hyperaeration or parenchymal lesions. PFT results and chest CT scores were analyzed with perinatal factors. Results: A total 150 children (66 females) aged 7.7 years (6.4-9.9 years) were categorized into non/mild BPD (n=68), moderate BPD (n=39), and severe BPD (n=43) groups. The median z score for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced midexpiratory flow (FEF25%-75%) were significantly lower in the severe versus non/mild BPD group (-1.24 vs. -0.18, -0.22 vs. 0.41, -1.80 vs. -1.12, and -1.88 vs. -1.00, respectively; all P<0.05). The median z scores of FEV1, FEV1/ FVC, and FEF25%-75% among asymptomatic patients were also significantly lower in the severe versus non/mild BPD group (-0.82 vs. 0.09, -1.68 vs. -0.87, -1.59 vs. -0.61, respectively; all P<0.05). The severe BPD group had a higher median (range) CT score than the non/mild BPD group (6 [0-12] vs. 1 [0-10], P<0.001). Prenatal oligohydramnios was strongly associated with both low pulmonary function (FEV1/FVC

Pulmonary function characteristics in children with suspected asthma: implications for asthma diagnosis.

BACKGROUND: In children suspected of asthma, diagnosis is confirmed via variable expiratory airflow limitation. However, there is no single gold standard test for diagnosing asthma. OBJECTIVE: This study aimed to evaluate the pulmonary function characteristics in children suspected of asthma without bronchodilator response (BDR) and bronchial hyperresponsiveness (BHR). METHODS: We utilized two separate real-world retrospective observational cohorts of children who underwent both spirometry and bronchial provocation testing for asthma. Spirometry parameters were collected and compared between definite asthma, probable asthma, and non-asthma groups. The original cohort comprised 1199 children who visited the Severance Hospital (Seoul, Korea) between January 2017 and December 2019. The external cohort included 105 children who visited the Gangnam Severance Hospital between January 2019 and December 2019. RESULTS: Probable asthma accounted for 16.8% and 32.4% of the original and external cohorts, respectively. This group showed a significantly higher FeNO level and prevalence of allergic sensitization. Baseline forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF25-75), and FEF75 showed stepwise decrements from non-asthma, probable asthma, to definite asthma patients (P < 0.001). The probable asthma group showed significantly higher odds of abnormal FEV1/FVC (OR, 2.24 [95%CI, 1.43-3.52])and FEF25-75 (2.05 [1.13-3.73]) than the non-asthma group and lower odds of abnormal FEV1(0.05 [0.01-0.19]),FEV1 /FVC (0.27 [0.18-0.41]), FEF25-75 (0.17 [0.11-0.28]), and FEF75 (0.14 [0.08-0.24]) compared to the definite asthma group. The external cohort was consistent with the original cohort. CONCLUSION: We show evidence of airway dysfunction in children for whom a high clinical suspicion of asthma exists without evidence of BDR and BHR. Repeated pulmonary function tests that closely monitor for subtle lung function impairments and active utilization of additional tests, such as allergic screening and FeNO, should be considered to close the gap in diagnosing asthma.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial.

PURPOSE: Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. METHODS: The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuum-assisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years. DISCUSSION: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05505357. Registered on August 17, 2022. Clinical Research Information Service Identifier: KCT0007638. Registered on July 25, 2022.

Heart rate variability and its association with symptoms of orthostatic hypotension in spinal cord injury.

CONTEXT/OBJECTIVE: To assess differences in autonomic function using heart rate variability (HRV) parameters between people with and without orthostatic hypotension (OH), and to determine symptoms of OH in people with spinal cord injury (SCI). METHODS: R-R interval and blood pressure (BP) data were recorded using Finometer PRO® in both the supine position and at a 60-degree tilt using a tilt table, each lasting for 6 minutes. R-R interval data were processed using the Kubios HRV analysis software to convert R-R interval into time and frequency domains for further analysis. RESULTS: Compared to the non-OH group, the SCI group with OH exhibited lower values for root mean square of the successive differences (RMSSD) and standard deviation of normal-to-normal interval (SDNN), along with an elevated heart rate during tilt-up. Participants with OH symptoms had a lower average heart rate in the supine and 60-degree positions compared to asymptomatic participants. Logistic regression analysis indicated that SDNN in the supine position correlated with the presence of OH, and that the mean heart rate in the 60-degree position was related to the presence of symptoms. CONCLUSIONS: Differences in HRV parameters were observed in people with SCI and OH, suggesting a reduced parasympathetic activity in the supine position, likely as a response to maintain homeostasis in BP regulation. Despite the presence or absence of OH symptoms, there was no difference in HRV parameters. This finding suggests that autonomic function may not be the primary determinant of these symptoms, with other factors likely being more influential.

Predicting the Outcome of Pediatric Oral Food Challenges for Determining Tolerance Development.

PURPOSE: Despite the risk of anaphylaxis, oral food challenges (OFCs) are performed clinically for various indications, particularly to confirm tolerance development. This study aimed to assess OFCs by relevant indications and build an outcome prediction model to help determine when to perform OFCs in children who are likely to have developed immune tolerance. METHODS: In total, 432 pediatric OFCs were retrospectively analyzed according to indications. Clinical characteristics, serum total immunoglobulin (Ig) E, blood eosinophils, and specific IgE and IgG4 levels for food allergens were noted and compared. Machine learning was utilized to select the most important variables in determining the passage of the OFCs, and prediction models were constructed using the selected variables. RESULTS: OFCs were most commonly performed to confirm tolerance development (number, %; 267, 61.8%). The most common food allergens tested were egg (191, 44.2%) and milk (135, 31.3%). Children who passed the egg challenges for confirming tolerance acquisition had significantly lower egg white-specific IgE level (P = 0.008). Similarly, those who passed milk challenges had significantly lower cow's milk-specific IgE (P = 0.002) and casein-specific IgE levels (P = 0.005). We developed a nomogram to predict the outcome of OFCs to determine the tolerance acquisition with the selected variables; lower food-specific IgE, higher total IgE, and younger age indicated a higher probability of passage. The area under the curve (95% confidence interval) was 0.623 (0.503-0.743) for egg and 0.734 (0.628-0.840) for milk. CONCLUSIONS: Serum total IgE and food-specific IgE combined with age showed trends toward passing OFCs for confirming tolerance development. The constructed model may be used by clinicians as a practical guide for minimizing the risks of OFCs and a timely reintroduction for children with food allergies.

Mammographic density changes after neoadjuvant chemotherapy in triple-negative breast cancer: Association with treatment and survival outcome.

PURPOSE: To investigate the association of mammographic breast density with treatment and survival outcomes in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC). METHODS: This retrospective study evaluated 306 women with TNBC who underwent NAC followed by surgery between 2010 and 2019. The baseline density and the density changes after NAC were evaluated. Qualitative breast density (a-d) was evaluated using the Breast Imaging Reporting and Data System. Quantitative breast density (%) was evaluated using fully automated software (the Laboratory for Individualized Breast Radiodensity Assessment) in the contralateral breast. Multivariable logistic regression analysis was used to evaluate the association between breast density and pathologic complete response (pCR), stratified by menopausal status. Cox proportional hazard regression analysis was used to evaluate the association among breast density, the development of contralateral breast cancer, and the development of locoregional recurrence and/or distant metastasis. RESULTS: Contralateral density reduction ≥10 % was independently associated with pCR in premenopausal women (odds ratio [OR], 2.5; p = 0.022) but not in postmenopausal women (OR, 0.9; p = 0.823). During a mean follow-up of 65 months, 10 (3 %) women developed contralateral breast cancer, and 68 (22 %) women developed locoregional recurrences and/or distant metastases. Contralateral density reduction ≥10 % showed no association with the occurrence of contralateral breast cancer (hazard ratio [HR], 3.1; p = 0.308) or with locoregional recurrence and/or distant metastasis (HR, 1.1; p = 0.794). CONCLUSION: In premenopausal women, a contralateral breast density reduction of ≥10 % after NAC was independently associated with pCR, although it did not translate into improved outcomes.

Diagnostic uplift through the implementation of short tandem repeat analysis using exome sequencing.

To date, approximately 50 short tandem repeat (STR) disorders have been identified; yet, clinical laboratories rarely conduct STR analysis on exomes. To assess its diagnostic value, we analyzed STRs in 6099 exomes from 2510 families with mostly suspected neurogenetic disorders. We employed ExpansionHunter and REViewer to detect pathogenic repeat expansions, confirming them using orthogonal methods. Genotype-phenotype correlations led to the diagnosis of thirteen individuals in seven previously undiagnosed families, identifying three autosomal dominant disorders: dentatorubral-pallidoluysian atrophy (n = 3), spinocerebellar ataxia type 7 (n = 2), and myotonic dystrophy type 1 (n = 2), resulting in a diagnostic gain of 0.28% (7/2510). Additionally, we found expanded ATXN1 alleles (≥39 repeats) with varying patterns of CAT interruptions in twelve individuals, accounting for approximately 0.19% in the Korean population. Our study underscores the importance of integrating STR analysis into exome sequencing pipeline, broadening the application of exome sequencing for STR assessments.

Modes of responsibility in disclosing cancer genetic test results to relatives: An analysis of Swiss and Korean narrative data.

OBJECTIVE: We examined how responsibility (the "duty to inform relatives about genetic testing results") is understood and enacted among Swiss and Korean women carrying BRCA1 or BRCA2 pathogenic variants. METHODS: In-depth interviews and/or focus groups with 46 Swiss and 22 Korean carriers were conducted, using an identical interview guide. Data were analyzed inductively and translated into English for cross-country comparisons. RESULTS: We identified five modes of responsibility in both samples: Persuader, Enabler, Relayer, Delayer, and Decliner. The Enabler and Relayer modes were the most common in both countries. They followed the rational imperative of health and norms of competence and self-determination, respectively. The Relayer mode transmitted information without trying to influence relatives' decisions. The Delayer and Decliner modes withheld information, deeming it the best way to safeguard the family during that specific moment of its trajectory. Responsibility to disclose testing results was influenced by culturally diverging conceptions of the family unit and socio-contextual norms. CONCLUSION: Responsibility primarily reflects the imperative of health prevention; findings demonstrate various interpretations, including the sense of family caring achieved through controlled disclosure of genetic information. PRACTICE IMPLICATIONS: Findings offer healthcare providers socio-anthropological insights to assist probands navigate the disclosure of genetic information within their families. TRIAL REGISTRATION NUMBER: NCT04214210 (registered Nov 2, 2020), KCT 0005643 (registered Nov 23, 2020).

Variants in the WDR44 WD40-repeat domain cause a spectrum of ciliopathy by impairing ciliogenesis initiation.

WDR44 prevents ciliogenesis initiation by regulating RAB11-dependent vesicle trafficking. Here, we describe male patients with missense and nonsense variants within the WD40 repeats (WDR) of WDR44, an X-linked gene product, who display ciliopathy-related developmental phenotypes that we can model in zebrafish. The patient phenotypic spectrum includes developmental delay/intellectual disability, hypotonia, distinct craniofacial features and variable presence of brain, renal, cardiac and musculoskeletal abnormalities. We demonstrate that WDR44 variants associated with more severe disease impair ciliogenesis initiation and ciliary signaling. Because WDR44 negatively regulates ciliogenesis, it was surprising that pathogenic missense variants showed reduced abundance, which we link to misfolding of WDR autonomous repeats and degradation by the proteasome. We discover that disease severity correlates with increased RAB11 binding, which we propose drives ciliogenesis initiation dysregulation. Finally, we discover interdomain interactions between the WDR and NH2-terminal region that contains the RAB11 binding domain (RBD) and show patient variants disrupt this association. This study provides new insights into WDR44 WDR structure and characterizes a new syndrome that could result from impaired ciliogenesis.

Unenhanced Breast MRI With Diffusion-Weighted Imaging for Breast Cancer Detection: Effects of Training on Performance and Agreement of Subspecialty Radiologists.

OBJECTIVE: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). MATERIALS AND METHODS: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). RESULTS: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training (P = 0.002). CONCLUSION: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Adjustment to "new normal" after cancer among non-small cell lung cancer survivors: A qualitative study.

OBJECTIVES: Cancer is a life-changing experience, and side effects from treatment can make it difficult for survivors to return to their pre-cancer "normal life." We explored the "new normal" and barriers to achieving it among lung cancer survivors who underwent surgery. METHODS: Semi-structured interviews were conducted with 32 recurrence-free non-small cell lung cancer survivors. We asked survivors how life had changed; how they defined the "new normal"; barriers that prevent them from achieving a "normal" life; and unmet needs or support for normalcy. Thematic analysis was performed. RESULTS: Defining "new normal" subjectively depends on an individual's expectation of recovery: (1) being able to do what they want without pain or discomfort; (2) being able to do activities they could accomplish before their surgery; and (3) being able to work, earn money, and support their family. We found that (1) persistent symptoms, (2) fear of cancer recurrence, (3) high expectations in recovery, and (4) psychosocial stress and guilty feelings were barriers to achieving a "new normal." The needs and support for normalcy were information on expected trajectories, postoperative management, and support from family and society. SIGNIFICANCE OF RESULTS: Survivors defined the "new normal" differently, depending on their expectations for recovery. Informing survivors about the "new normal" so they could expect possible changes and set realistic goals for their life after cancer. Health professionals need to communicate with survivors about expectations for "normality" from the beginning of treatment, and it should be included in comprehensive survivorship care.

A Case of Multiple Mitochondrial Dysfunctions Syndrome 4 with Novel ISCA2 Variants, Mimicking Post-Infectious Encephalitis.

ISCA2 loss of function leads to leukodystrophy and developmental regression (multiple mitochondrial dysfunctions syndrome 4 (MMDS4)). We present a first Korean case of MMDS4 presenting with rapid developmental regression and leukodystrophy after febrile episode, mimicking post-infectious encephalitis. The patient had displayed normal development until 12 months of age. At 13 months of age, one month after experiencing a post-vaccination fever, she quickly progressed to being unable to sit unassisted nor speak any words. Analysis of the cerebrospinal fluid (CSF) revealed lympho-dominant pleocytosis. Amino acid analysis of both the serum and CSF demonstrated elevated glycine exclusively in the CSF. Diffuse leukodystrophy was noted in the brain magnetic resonance image. Whole exome sequencing revealed compound heterozygous ISCA2 variants of c.166T>G, p.C56G and c.422A>C, p.Q141P. No evidence of mitochondrial disease other than bilateral optic atrophy was noted. In cases of early onset rapid developmental regression with leukodystrophy, MMDS4 should be considered.

Long Term Effects of a Social Capital-Based Exercise Adherence Intervention for Breast Cancer Survivors With Moderate Fatigue: A Randomized Controlled Trial.

OBJECTIVES: This study reports on the long-term effects of the Better Life After Cancer: Energy, Strength, and Support (BLESS) program, a 12-week social capital-based exercise adherence program for breast cancer survivors (BCS), implemented using a randomized controlled trial design. The study investigated outcomes related to cancer-related fatigue (CRF), quality of life (QOL), physical activity, depression, anxiety, sleep quality, and social capital. METHODS: Participants who had moderate or greater CRF were randomly assigned to the intervention (n = 24), consisting of supervised and home-based exercise, or the control (n = 26), who received exercise leaflets. Generalized estimating equations models were fitted for the outcome variables. The assessment points were baseline (M1), immediately after completing the intervention at 12 weeks (M2), 1 month (M3), and 6 months post-intervention (M4). RESULTS: A significant reduction in the total CRF score was found for both groups. We observed a significant time by group effect at M2, indicating a reduction of behavioral/severity CRF scores and a higher increase of physical activity. Also, there was an increase in the QOL score of both groups at M2, M3, and M4, compared to M1. Both groups had reduced anxiety at M3 and M4 compared to M1. The time by group effect for depression, sleep quality and social capital was not statistically significant. CONCLUSION: This 12-week exercise adherence program improved behavioral/severity CRF and physical activity post-intervention. Both the experimental group and control group showed significant improvements in CRF, QOL, and anxiety domains compared to the baseline, which extended to 6 months post-intervention. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0005763).

Therapeutic role of 2-stearoxyphenethyl phosphocholine targeting microtubule dynamics and Wnt/ß-catenin/EMT signaling in human colorectal cancer cells.

The inhibition of cell death, perturbation of microtubule dynamics, and acceleration of Wnt/ß-catenin/epithelial-mesenchymal transition (EMT) signaling are fundamental processes in the progression and metastasis of colorectal cancer (CRC). To explore the role of 2-stearoxyphenethyl phosphocholine (stPEPC), an alkylphospholipid-based compound, in CRC, we conducted an MTT assay, cell cycle analysis, western blot analysis, immunoprecipitation, immunofluorescence staining, Annexin V/propidium iodide double staining, small interfering RNA gene silencing, a wound-healing assay, an invasion assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay in the human CRC cell lines HT29 and HCT116. stPEPC showed anti-proliferative properties and mitotic cell accumulation via upregulated phosphorylation of BUBR1 and an association between mitotic arrest deficiency 2 (MAD2) and cell division cycle protein 20 homolog (CDC20). These results suggest that activation of the mitotic checkpoint complex and tubulin polymerization occurred, resulting in mitotic catastrophe in HT29 and HCT116 cells. In addition, stPEPC attenuated cell migration and invasion by regulating proteins mediated by EMT, such as E-cadherin and occludin. stPEPC altered the protein expression of Wnt3a and phosphorylation of low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase 3ß (GSK3ß), and ß-catenin as well as their target genes, including cMyc and cyclin D1, in CRC cells. Thus, stPEPC may be useful for developing new drugs to treat human CRC.

Development and Validation of a Clinical Practicum Transition Shock Scale (CPT-Shock) for Korean Nursing Students.

Clinical practice is an important educational tool for nursing students, and their emotions during clinical practice should be accurately understood. This study aimed to develop and verify the validity and reliability of a clinical practicum transition shock scale (CPT-shock) to measure Korean nursing students' emotional responses when transitioning from a theoretical learning process to clinical practice. This research design was a methodological study and the content, construct, criterion validity, and reliability of the items were verified. Content validity was evaluated by seven experts. The preliminary survey was conducted on 24 nursing students, and the factor analysis was conducted on 331 nursing students in various regions of Korea. Confirmatory factor analysis confirmed the model fit (χ2/df = 1.741, GFI = 0.930, AGFI = 0.902, NFI = 0.869, TLI = 0.923, CFI = 0.938, RMR = 0.035, RMSEA = 0.047) and established discrimination and convergence validity. Positive and negative correlations were found with existing transition shock (r = 0.779) and clinical practice adaptation (r = -0.505), respectively (p < 0.001), thus establishing criterion validity. The reliability was good, with a Cronbach's α of 0.85. The clinical practicum transition shock scale reflects nursing students' practice environment and is expected to accurately measure nursing students' unique emotional shock.

Expansion of clinico-genetic spectrum of PRDX3 disease: a literature review with two additional cases.

Graphical Abstract.