The effect of complex posttraumatic stress and poverty on quality of life among adult survivors of childhood institutional maltreatment: evidence from survivors of the 'Hyeongje Welfare Institution' in South Korea.

Background: Childhood institutional maltreatment (IM) is associated with both complex posttraumatic stress disorder (CTPSD) and poverty in adulthood life, each of which may impact an individual's quality of life (QoL). To find implications for clinical practice and policy making for adult survivors with childhood IM experiences, it is necessary to conduct research examining their current QoL and identifying related factors.Objective: By applying the model of the conservation of resources theory, we focused on how adulthood QoL can be indicated by childhood IM as well as the life outcomes of IM such as additional lifetime trauma, CPTSD, and poverty.Methods: In a cross-sectional study, self-report data were collected from 127 adults who were survivors of the 'Hyeongje' childhood IM in South Korea. We conducted regression analyses of childhood IM experiences, trauma experiences after escape from the institution, current CPTSD symptoms, and current poverty experiences on current QoL.Results: The duration of placement at the 'Hyeongje' (ß = .24, p = .009) was associated with trauma experiences after escape from the institution. Trauma experiences after escape from the institution (ß = .25, p = .007) were associated with CPTSD symptoms. CPTSD symptoms (ß = .26, p = .005) were associated with poverty, and both CPTSD symptoms (ß = -.52, p < .001) and poverty (ß = -.26, p = .003) were negatively associated with current QoL.Conclusions: Prolonged childhood IM brings about loss spirals by increasing an individual's exposure to experiences of further cumulative trauma, CPTSD, and poverty. There is a need for due diligence-based policy making and public support from the government to help create upward spirals for QoL. This may include the imminent detection and rescue of children as well as providing a safe environment, offering multidisciplinary interventions including evidence-based treatment for CPTSD, and considering economic support including collective reparations.

Duration of placement at the 'Hyeongje' institution was associated with additional trauma experience after escaping the institution.Cumulative trauma after escape was associated with CPTSD symptoms; CPTSD symptoms were associated with poverty; and both CPTSD symptoms and poverty were associated with poor current QoL.Multidisciplinary interventions including evidence-based treatment for CPTSD and considering economic resources for childhood IM survivors would be crucial in increasing QoL.

Spatial architectures of somatic mutations in normal prostate, benign prostatic hyperplasia and coexisting prostate cancer.

This study aimed to identify somatic mutations in nontumor cells (NSMs) in normal prostate and benign prostatic hyperplasia (BPH) and to determine their relatedness to prostate cancer (PCA). From 22 PCA patients, two prostates were sampled for 3-dimensional mapping (50 normal, 46 BPH and 1 PCA samples), and 20 prostates were trio-sampled (two normal or BPH samples and one PCA sample) and analyzed by whole-genome sequencing. Normal and BPH tissues harbored several driver NSMs and copy number alterations (CNAs), including in FOXA1, but the variations exhibited low incidence, rare recurrence, and rare overlap with PCAs. CNAs, structural variants, and mutation signatures were similar between normal and BPH samples, while BPHs harbored a higher mutation burden, shorter telomere length, larger clone size, and more private NSMs than normal prostates. We identified peripheral-zonal dominance and right-side asymmetry in NSMs, but the asymmetry was heterogeneous between samples. In one normal prostate, private oncogenic RAS-signaling NSMs were detected, suggesting convergence in clonal maintenance. Early embryonic mutations exhibited two distinct distributions, characterized as layered and mixed patterns. Our study identified that the BPH genome differed from the normal prostate genome but was still closer to the normal genome than to the PCA genome, suggesting that BPH might be more related to aging or environmental stress than to tumorigenic processes.

Frameshift mutations of immunomodulatory BTN2A1, BTN2A2, and BTNL3 genes in colon cancers.

The butyrophilin family genes are immunoregulatory genes with either immune stimulatory or inhibitory functions. In the present study, we analyzed three butyrophilin genes, BTN2A1 (immune-stimulatory), BTN2A2 (inhibitory), and BTNL3 (stimulatory) genes in sporadic colon cancers (CCs). By the mutation analysis, we identified the frameshift mutations of BTN2A1, BTN2A2, and BTNL3 genes in 2, 4, and 8 CCs in microsatellite instability-high (MSI-H) CCs (2.1-8.4% of MSI-H), respectively, but not the microsatellite stable (MSS) CCs. Four of 16 MSI-H CCs (25%) exhibited regional heterogeneous mutations (RHM) of BTN2A1, BTN2A2, and BTNL3 genes. In immunohistochemistry, BTNL3 expression was lost in approximately 30% of CCs, and BTN2A2 loss was minimal in CCs (around 3%) irrespective of the MSI status. Our study revered that butyrophilin family genes BTN2A1, BTN2A2, and BTNL3 harbored multiple levels of gene alterations at frameshift mutations, RHMs, and expression losses in CCs, suggesting that butyrophilin family genes could contribute to CC pathogenesis by altering immune responses.

Genes with dual proto-oncogene and tumor suppressor gene activities are frequently altered by protein losses in colon cancers.

Cancer genes are largely categorized into tumor suppressor gene (TSG) and proto-oncogene, but many have dual activities depending on the cellular context. In the present study, we analyzed DYRK1B, ESRP1, MTSS1, ADAMTS1, and INPP5F genes known to possess the dual activities in sporadic colon cancers (CCs). By the mutation analysis, we identified DYRK1B, ESRP1, MTSS1, ADAMTS1, and INPP5F frameshift mutations in 2, 2, 3, 3, and 1 CCs in instability-high (MSI-H) cases (1.1-3.2% of MSI-H CCs), respectively, but not microsatellite stable (MSS) cases. One CC showed regional heterogeneous mutations (RHM) of ESRP1 mutation. Immunohistochemistry identified protein expression of ESRP1, MTSS1, and ADAMTS1 in the CCs, revealing that approximately 30% of CCs lost the protein expression irrespective of the MSI status. Our study showed that dual TSG and proto-oncogene genes DYRK1B, ESRP1, MTSS1, ADAMTS1, and INPP5F harbored low incidences of inactivating mutations, but that the protein losses were frequent in CCs. Our study suggests a possibility that the dual-function genes could be altered mainly at the expression level, which might contribute to CC pathogenesis.

Concurrent inactivating mutations and expression losses of RGS2, HNF1A, and CAPN12 candidate tumor suppressor genes in colon cancers.

Microsatellite instability-high (MSI-H) colorectal cancer (CRC) is different from microsatellite stable (MSS) CRC concerning biological, and clinical features. In MSI-H CRCs, defects of mismatch repair genes produce increased mutation accumulation in repetitive DNA sequences. To see whether candidate tumor suppressor genes (TSGs) are altered in MSI-H CRC, we studied frameshift mutation and protein expression of candidate TSGs of RGS2, HNF1A, HNF1B, CAPN12, RCBTB2, ATE1, PKNOX1, and USP19. We found frameshift mutations of RGS2 in 5 (5%), HNF1A in 6 (6%), HNF1B in 2 (2%), CAPN12 in 3 (3%), RCBTB2 in 4 (4%), ATE1 in 2 (2%), PKNOX1 in 2 (2%), and USP19 in 2 (2%) MSI-H CRCs. However, we found no such mutations in MSS CRCs. RCBTB2, CAPN12, HNF1A, and HNF1B frameshift mutations revealed the regional difference in the same tumors. In addition, we identified loss of RGS2, HNF1A, and CAPN12 protein expression irrespective of MSI phenotype in 13-29% of CRCs. The results indicate that many TSGs harbor concurrent inactivating mutations and protein loss in MSI-H CRCs with intratumoral mutational heterogeneity, and that MSS CRCs are altered by protein losses. These alterations could contribute to CRC development and underlying mechanisms and consequences of the TSG alterations remain to be clarified.

qMTNet: Accelerated quantitative magnetization transfer imaging with artificial neural networks.

PURPOSE: To develop a set of artificial neural networks, collectively termed qMTNet, to accelerate data acquisition and fitting for quantitative magnetization transfer (qMT) imaging. METHODS: Conventional and interslice qMT data were acquired with two flip angles at six offset frequencies from seven subjects for developing the networks and from four young and four older subjects for testing the generalizability. Two subnetworks, qMTNet-acq and qMTNet-fit, were developed and trained to accelerate data acquisition and fitting, respectively. qMTNet-2 is the sequential application of qMTNet-acq and qMTNet-fit to produce qMT parameters (exchange rate, pool fraction) from undersampled qMT data (two offset frequencies rather than six). qMTNet-1 is one single integrated network having the same functionality as qMTNet-2. qMTNet-fit was compared with a Gaussian kernel-based fitting. qMT parameters generated by the networks were compared with those from ground truth fitted with a dictionary-driven approach. RESULTS: The proposed networks achieved high peak signal-to-noise ratio (>30) and structural similarity index (>97) in reference to the ground truth. qMTNet-fit produced qMT parameters in concordance with the ground truth with better performance than the Gaussian kernel-based fitting. qMTNet-2 and qMTNet-1 could accelerate data acquisition at threefold and accelerate fitting at 5800- and 4218-fold, respectively. qMTNet-1 showed slightly better performance than qMTNet-2, whereas qMTNet-2 was more flexible for applications. CONCLUSION: The proposed single (qMTNet-1) and two joint neural networks (qMTNet-2) can accelerate qMT workflow for both data acquisition and fitting significantly. qMTNet has the potential to accelerate qMT imaging for clinical applications, which warrants further investigation.

Case Reports of Tectal Plate Gliomas Showing Indolent Course.

From 2004 to 2020, we studied three pediatric patients (age: 9-13 years, all male) and one adult patient (age: 29 years, female) with tectal plate glioma with obstructing hydrocephalus on MRI. One patient had neurofibromatosis type 1. All patients complained about headaches and vomiting, and one patient had diplopia. Endoscopic third ventriculostomy (ETV) was underwent in all patients and a biopsy was obtained from two patients. Pathologic diagnoses were a pilocytic astrocytoma and a low-grade glioma. After ETV with or without biopsy, neurological symptoms were improved in all patients. Three patients did the clinical and radiological follow-up without adjuvant treatment. One patient underwent gamma knife radiosurgery. In two pediatric patients and the adult patient, there was no clinical and radiological progression after 6.2, 6.9, and 8.0 years, respectively. One pediatric patient whose lesion had focal enhancement had radiologic progression without any neurologic symptoms after 5.1 years. Without adjuvant treatment for this lesion, there was no clinical deterioration neither further radiological progression for 6.2 years after radiological aggravation. Tectal plate gliomas showed indolent clinical courses, even after radiologic tumor progression. After the treatment of obstructing hydrocephalus, clinical and radiologic follow-up can be recommended for indolent tectal plate gliomas.

Effect of the Sodium-Glucose Cotransporter 2 Inhibitor, Dapagliflozin, on Genitourinary Infection in an Animal Model of Type 2 Diabetes.

PURPOSE: To investigate the effect of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, on inflammatory cytokines of urogenital tissue in a rat model of type 2 diabetes (T2DM) to infer pharmaceutical influence of dapagliflozin on genitourinary infection or inflammation. METHODS: Study animals were divided into the following 4 groups of 10 animals each: (1) the Otsuka Long-Evans Tokushima Fatty (OLETF)-DA group treated with dapagliflozin at 1.0 mg/kg/day, (2) the OLETF-VO group treated with voglibose at 0.6 mg/kg/day, (3) the control group (OLETF-CO) given water, and (4) the Long-Evans Tokushima Otsuka (LETO) rats were included as nondiabetic control group. Changes in blood glucose, 24-hour urine volume, and urine glucose were measured. The interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) levels in the bladder and the urethra were quantified, respectively. RESULTS: The urine glucose level and the 24-hour urine volume at 12 weeks of treatment were significantly higher in the OLETF-DA group than that in any other group (P<0.05). The cytokine analysis of the bladder and urethra showed higher IL18 and IL-1ß in the OLETF-DA and the OLETF-CO groups than that in the OLETF-VO and LETO groups (P<0.05). The cytokine levels did not differ between the OLETF-DA and the OLETF-CO groups, and the level of IL-18 in the OLETF-DA group was higher in the urethra than in the bladder. CONCLUSION: This study revealed that dapagliflozin increased the urine glucose concentration, resulting in an inflammatory response remain in the urogenital tract as the untreated diabetic rats. Therefore, when treating patients with T2DM with dapagliflozin, careful attention should be paid to genitourinary infection or inflammation.

Rapid framework for quantitative magnetization transfer imaging with interslice magnetization transfer and dictionary-driven fitting approaches.

PURPOSE: To develop a rapid framework for quantitative magnetization transfer (qMT) imaging based on the 2D interslice MT and dictionary-driven fitting approaches. METHODS: Sequential balanced steady-state free precession (bSSFP) scanning was performed on a whole human brain in a total of 12 conditions from six different interslice gaps and two different flip angles. To obtain qMT maps, the acquired 12 datasets were fitted to a dictionary predefined by using Bloch equation simulations based on the two-pool MT model. The proposed qMT method was compared to the conventional qMT methods, in terms of qMT parameter maps and processing time. RESULTS: The proposed method yielded qMT maps similar to those of the conventional method, indicating feasibility of modulating MT saturation frequency and power with the interslice gap and flip angle. The whole-brain qMT imaging could be completed in 8 min because of the absence of separate MT pulses. The time for processing qMT parameters was significantly reduced through the dictionary-driven approach; it is 1000 times shorter than that without the dictionary-driven approach and 3 times shorter than that with the spoiled gradient recalled echo-qMT method that uses an analytical solution. CONCLUSION: The proposed dictionary-driven interslice qMT imaging provides qMT maps close to those from the conventional method with significantly reduced scan time and postprocessing time, which can make qMT imaging more clinically acceptable.

Phase imaging with multiple phase-cycled balanced steady-state free precession at 9.4 T.

While phase imaging with a gradient echo (GRE) sequence is popular, phase imaging with balanced steady-state free precession (bSSFP) has been underexplored. The purpose of this study was to investigate anatomical and functional phase imaging with multiple phase-cycled bSSFP, in expectation of increasing spatial coverage of steep phase-change regions of bSSFP. Eight different dynamic 2D pass-band bSSFP studies at four phase-cycling (PC) angles and two TE /TR values were performed on rat brains at 9.4 T with electrical forepaw stimulation, in comparison with dynamic 2D GRE. Anatomical and functional phase images were obtained by averaging the dynamic phase images and mapping correlation between the dynamic images and the stimulation paradigm, and were compared with their corresponding magnitude images. Phase imaging with 3D pass-band and 3D transition-band bSSFP was also performed for comparison with 3D GRE phase imaging. Two strategies of combining the multiple phase-cycled bSSFP phase images were also proposed. Contrast between white matter and gray matter in bSSFP phase images significantly varied with PC angle and became twice as high as that of GRE phase images at a specific PC angle. With the same total scan time, the combined bSSFP phase images provided stronger phase contrast and visualized neuronal fiber-like structures more clearly than the GRE phase images. The combined phase images of both 3D pass-band and 3D transition-band bSSFP showed phase contrasts stronger than those of the GRE phase images in overall brain regions, even at a longer TE of 20 ms. In contrast, phase functional MRI (fMRI) signals were weak overall and mostly located in draining veins for both bSSFP and GRE. Multiple phase-cycled bSSFP phase imaging is a promising anatomical imaging technique, while its usage as fMRI does not seem desirable with the current approach.

The effect of abdominal drawing-in exercise and myofascial release on pain, flexibility, and balance of elderly females.

[Purpose] This study is designed to compare the effects of abdominal drawing-in exercise and myofascial release on pain, flexibility, and balance of elderly females. [Subjects and Methods] Forty elderly females aged 65 or older who had complained of low back pain for three months or longer were selected as the subjects. They were randomly and equally assigned to either an abdominal drawing-in group or a myofascial release group. The subjects conducted exercise three times per week, 40 minutes each time, for eight weeks. As evaluation tools, visual analogue scale for pain, remodified schober test for flexibility, and upright posture with eye opening on hard platform, upright posture with eye closing on hard platform, upright posture with eye opening on soft platform, upright posture with eye closing on soft platform using tetrax for balance were used. [Results] The abdominal drawing-in exercise group saw significant difference in pain and balance after the exercise compared to before the exercise. The myofascial release group saw significant difference in pain and flexibility after exercise compared to before the exercise. [Conclusion] The above study showed that abdominal drawing-in exercise affected elderly females regarding pain and balance and myofascial release influenced their pain and flexibility.

Preliminary Observations on Sensitivity and Specificity of Magnetization Transfer Asymmetry for Imaging Myelin of Rat Brain at High Field.

Magnetization transfer ratio (MTR) has been often used for imaging myelination. Despite its high sensitivity, the specificity of MTR to myelination is not high because tissues with no myelin such as muscle can also show high MTR. In this study, we propose a new magnetization transfer (MT) indicator, MT asymmetry (MTA), as a new method of myelin imaging. The experiments were performed on rat brain at 9.4 T. MTA revealed high signals in white matter and significantly low signals in gray matter and muscle, indicating that MTA has higher specificity than MTR. Demyelination and remyelination studies demonstrated that the sensitivity of MTA to myelination was as high as that of MTR. These experimental results indicate that MTA can be a good biomarker for imaging myelination. In addition, MTA images can be efficiently acquired with an interslice MTA method, which may accelerate clinical application of myelin imaging.

The effects of target distance on pivot hip, trunk, pelvis, and kicking leg kinematics in Taekwondo roundhouse kicks.

The study purpose was to investigate the effects of target distance on pivot hip, trunk, pelvis, and kicking leg movements in Taekwondo roundhouse kick. Twelve male black-belt holders executed roundhouse kicks for three target distances (Normal, Short, and Long). Linear displacements of the pivot hip and orientation angles of the pelvis, trunk, right thigh, and right shank were obtained through a three-dimensional video motion analysis. Select displacements, distances, peak orientation angles, and angle ranges were compared among the conditions using one-way repeated measure ANOVA (p < 0.05). Several orientation angle variables (posterior tilt range, peak right-tilted position, peak right-rotated position, peak left-rotated position, and left rotation range of the pelvis; peak hyperextended position and peak right-flexed position of the trunk; peak flexed position, flexion range and peak internal-rotated position of the hip) as well as the linear displacements of the pivot hip and the reach significantly changed in response to different target distances. It was concluded that the adjustment to different target distances was mainly accomplished through the pivot hip displacements, hip flexion, and pelvis left rotation. Target distance mainly affected the reach control function of the pelvis and the linear balance function of the trunk.