The longitudinal behavioral effects of acute exposure to galactic cosmic radiation in female C57BL/6J mice: implications for deep space missions, female crews, and potential antioxidant countermeasures.

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment is lacking. Here we asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received the antioxidant CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and either Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: 1) location discrimination reversal (which tests behavior pattern separation and cognitive flexibility, two abilities reliant on the dentate gyrus) and 2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment end (14.25-month post-IRR), neurogenesis was assessed (doublecortin-immunoreactive [DCX+] dentate gyrus neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. Notably, one radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had worse stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice show normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change in neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

Volumetric Measurement of Relative CBV Using T1-Perfusion-Weighted MRI with High Temporal Resolution Compared with Traditional T2*-Perfusion-Weighted MRI in Postoperative Patients with High-Grade Gliomas.

BACKGROUND AND PURPOSE: T1-PWI with high temporal resolution may provide a reliable relative CBV value as a valid alternative to T2*-PWI under increased susceptibility. The purpose of this study was to assess the technical and clinical performance of T1-relative CBV in patients with postoperative high-grade gliomas. MATERIALS AND METHODS: Forty-five MRIs of 34 patients with proved high-grade gliomas were included. In all MRIs, T1- and T2*-PWIs were both acquired and processed semiautomatically to generate relative CBV maps using a released commercial software. Lesion masks were overlaid on the relative CBV maps, followed by a histogram of the whole VOI. The intraclass correlation coefficient and Bland-Altman plots were used for quantitative and qualitative comparisons. Signal loss from both methods was compared using the Wilcoxon signed-rank test of zero voxel percentage. The MRIs were divided into a progression group (n = 20) and a nonprogression group (n = 14) for receiver operating characteristic curve analysis. RESULTS: Fair intertechnique consistency was observed between the 90th percentiles of the T1- and T2*-relative CBV values (intraclass correlation coefficient = 0.558, P < .001). T2*-PWI revealed a significantly higher percentage of near-zero voxels than T1-PWI (17.7% versus 3.1%, P < .001). There was no statistically significant difference between the area under the curve of T1- and T2*-relative CBV (0.811 versus 0.793, P = .835). T1-relative CBV showed 100% sensitivity and 57.1% specificity for the detection of progressive lesions. CONCLUSIONS: T1-relative CBV demonstrated exquisite diagnostic performance for detecting progressive lesions in postoperative patients with high-grade gliomas, suggesting the potential role of T1-PWI as a valid alternative to the traditional T2*-PWI.

Intraindividual Comparison between the Contrast-Enhanced Golden-Angle Radial Sparse Parallel Sequence and the Conventional Fat-Suppressed Contrast-Enhanced T1-Weighted Spin-Echo Sequence for Head and Neck MRI.

BACKGROUND AND PURPOSE: The golden-angle radial sparse parallel-volumetric interpolated breath-hold (GRASP-VIBE) sequence is a recently introduced imaging technique with high resolution. This study compared the image quality between conventional fat-suppressed T1-weighted TSE and GRASP-VIBE after gadolinium enhancement in the head and neck region. MATERIALS AND METHODS: Data from 65 patients with clinical indications for head and neck MR imaging between September 2020 and January 2021 were retrospectively reviewed. Two radiologists assessed the overall image quality, overall artifacts, and image conspicuities in the oropharynx, hypopharynx, and cervical lymph nodes according to 5-point scores (best score: 5). Interobserver agreement was assessed using weighted κ statistics. The SNR and contrast-to-noise ratio were calculated and compared between the 2 sequences using a paired Wilcoxon signed rank test. RESULTS: The analysis included 52 patients (mean age, 60 [SD, 14 ] years; male, 71.2% [37/52]) who were mostly diagnosed with head and neck malignancies (94.3% [50/52]). κ statistics ranged from slight agreement in cervical lymph node conspicuity (κ = 0.18) to substantial agreement in oropharyngeal mucosal conspicuity (κ = 0.80) (κ range, 0.18-0.80). Moreover, GRASP-VIBE demonstrated significantly higher mean scores in overall image quality (4.68 [SD, 0.41] versus 3.66 [SD, 0.73]), artifacts (4.47 [SD, 0.48] versus 3.58 [SD, 0.71]), oropharyngeal mucosal conspicuity (4.85 [SD, 0.41] versus 4.11 [SD, 0.79]), hypopharyngeal mucosal conspicuity (4.84 [SD, 0.34] versus 3.58 [SD, 0.81]), and cervical lymph node conspicuity (4.79 [SD, 0.32] versus 4.08 [SD, 0.64]) than fat-suppressed T1-weighted TSE (all, P < .001). Furthermore, GRASP-VIBE demonstrated a higher SNR (22.8 [SD, 11.5] versus 11.3 [SD, 5.6], P < .001) and contrast-to-noise ratio (4.7 [SD, 5.4] versus 2.3 [SD, 2.7], P = .059) than fat-suppressed T1-weighted TSE. CONCLUSIONS: GRASP-VIBE provided better image quality with fewer artifacts than conventional fat-suppressed T1-weighted TSE for the head and neck regions.

Prediction of Human Papillomavirus Status and Overall Survival in Patients with Untreated Oropharyngeal Squamous Cell Carcinoma: Development and Validation of CT-Based Radiomics.

BACKGROUND AND PURPOSE: Human papillomavirus is a prognostic marker for oropharyngeal squamous cell carcinoma. We aimed to determine the value of CT-based radiomics for predicting the human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Eighty-six patients with oropharyngeal squamous cell carcinoma were retrospectively collected and grouped into training (n = 61) and test (n = 25) sets. For human papillomavirus status and overall survival prediction, radiomics features were selected via a random forest-based algorithm and Cox regression analysis, respectively. Relevant features were used to build multivariate Cox regression models and calculate the radiomics score. Human papillomavirus status and overall survival prediction were assessed via the area under the curve and concordance index, respectively. The models were validated in the test and The Cancer Imaging Archive cohorts (n = 78). RESULTS: For prediction of human papillomavirus status, radiomics features yielded areas under the curve of 0.865, 0.747, and 0.834 in the training, test, and validation sets, respectively. In the univariate Cox regression, the human papillomavirus status (positive: hazard ratio, 0.257; 95% CI, 0.09-0.7; P = .008), T-stage (≥III: hazard ratio, 3.66; 95% CI, 1.34-9.99; P = .011), and radiomics score (high-risk: hazard ratio, 3.72; 95% CI, 1.21-11.46; P = .022) were associated with overall survival. The addition of the radiomics score to the clinical Cox model increased the concordance index from 0.702 to 0.733 (P = .01). Validation yielded concordance indices of 0.866 and 0.720. CONCLUSIONS: CT-based radiomics may be useful in predicting human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma.

Simulation of laser-tattoo pigment interaction in a tissue-mimicking phantom using Q-switched and long-pulsed lasers.

BACKGROUND: Laser therapy is the treatment of choice in tattoo removal. However, the precise mechanisms of laser-tattoo pigment interactions remain to be evaluated. METHODS: We evaluated the geometric patterns of laser-tattoo pigment particle interactions using a tattoo pigment-embedded tissue-mimicking (TM) phantom. RESULTS: A Q-switched (QS) neodymium-doped yttrium aluminum garnet laser was used at settings of 532-, 660-, and 1064-nm wavelengths, single-pulse and quick pulse-to-pulse treatment modes, and spot sizes of 4 and 7 mm. Most of the laser-tattoo interactions in the experimental conditions formed cocoon-shaped or oval photothermal and photoacoustic injury zones, which contained fragmented tattoo particles in various sizes depending on the conditions. In addition, a long-pulsed 755-nm alexandrite laser was used at a spot size of 6 mm and pulse widths of 3, 5, and 10 ms. The finer granular pattern of tattoo destruction was observed in TM phantoms treated with 3- and 5-ms pulse durations compared to those treated with a 10-ms pulse. CONCLUSION: We outlined various patterns of laser-tattoo pigment interactions in a tattoo-embedded TM phantom to predict macroscopic tattoo and surrounding tissue reactions after laser treatment for tattoo removal.

DCE and DSC MR perfusion imaging in the differentiation of recurrent tumour from treatment-related changes in patients with glioma.

AIM: To retrospectively compare the utility of perfusion magnetic resonance imaging (MRI) in distinguishing treatment-related changes from recurrent disease in glioma patients. MATERIALS AND METHODS: Thirty-one patients with histologically diagnosed gliomas and increased enhancement after or during concurrent (chemo-) radiation therapy were enrolled. They underwent dynamic contrast-enhanced (DCE) permeability MRI followed by dynamic susceptibility contrast (DSC) perfusion MRI. The vascular transfer constant (rK(trans)) and initial areas under the concentration curve (riAUC) were obtained from DCE MRI, and cerebral blood volume (rCBV) was obtained from DSC MRI. Patients were classified as having treatment-related changes or recurrent tumours based on clinicoradiological results or pathological results from surgery. RESULTS: Nineteen patients were diagnosed as having recurrences and 12 patients as having treatment-related changes. The rK(trans), riAUC, and rCBV values in the recurrent group were significantly higher than the values in the group with treatment-related changes (p < 0.05). For all 31 patients, there was no significant difference between DSC MRI and DCE MRI for the differentiating power between recurrence and treatment-related changes (p = 0.7227). However, when including only the 24 patients with concordant values of rK(trans) and riAUC, DCE MRI showed a significant AUC value of 0.786 in the receiver operating characteristic (ROC) curve analysis (p = 0.003), whereas DSC MRI did not (AUC = 0.643, p = 0.229). CONCLUSION: MRI perfusion images appear to show promise in distinguishing treatment-related changes from recurrent tumours. When both rK(trans) and riAUC show concordant values, DCE MRI seems to be more powerful than DSC MRI in the differentiation of recurrence from treatment-related changes.

Potential role of advanced MRI techniques for the peritumoural region in differentiating glioblastoma multiforme and solitary metastatic lesions.

Differentiation between solitary metastatic lesions and glioblastomas, two of the most common malignant brain neoplasms, is often a diagnostic challenge. The purpose of this review is to emphasize the potential roles of advanced magnetic resonance imaging (MRI) techniques, including diffusion-based techniques, such as diffusion-weighted imaging (DWI), exponential DWI, and diffusion tensor imaging, MR perfusion, and MR spectroscopy, as well as conventional MRI, in making a distinction between glioblastomas and solitary metastases in peritumoural regions. Integration of advanced MRI features with conventional MRI, may provide valuable information for differentiating glioblastoma from solitary metastatic lesions.

Both the sera of patients with Behçet's disease and Streptococcus sanguis stimulate membrane expression of hnRNP A2/B1 in endothelial cells.

OBJECTIVES: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 has been identified as a target antigen of anti-endothelial cell immunglobulin (Ig)A antibodies in patients with Behçet's disease (BD). The aim was to investigate the effects of the sera from BD patients and Streptococcus sanguis on the subcellular expression of hnRNP A2/B1 in human dermal microvascular endothelial cells (HDMECs). METHOD: The sera of BD patients and healthy controls (HC) as well as cultured S. sanguis were used to stimulate HDMECs. Subcellular fractions were obtained from stimulated HDMECs and were subjected to immunoblot analyses. The distribution of hnRNP A2/B1 was investigated by immunocytochemistry and direct immunofluorescence study was performed in biopsy specimens of mucosal ulcers from BD patients. RESULTS: BD patients' sera increased the membrane expression of hnRNP A2/B1 in HDMECs after 12 and 24 h of incubation compared with HDMECs incubated with endothelial cell culture media and HC sera. S. sanguis also increased hnRNP A2/B1 in the cellular membrane. hnRNP A2/B1 mRNA level was also significantly upregulated in HDMECs incubated with BD patients' sera and S. sanguis. Immunocytochemistry demonstrated marked expression of hnRNP A2/B1 in the cytoplasm and cellular membrane of HDMECs incubated with BD patients' sera or S. sanguis. In addition, direct immunofluorescence experiments revealed the co-localization of serum IgA antibodies and monoclonal antibodies (mAbs) against hnRNP A2/B1 in tissue sections from ulcers of BD patients. CONCLUSIONS: Our data indicate that both the sera of BD patients with active disease and S. sanguis infection are inflammatory stimuli that can induce membranous hnRNP A2/B1 expression in HDMECs.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Immediate pigment darkening and persistent pigment darkening as means of measuring the ultraviolet A protection factor in vivo: a comparative study.

BACKGROUND: Persistent pigment darkening (PPD) is a widely used in vivo method for measurement of ultraviolet (UV) A protection factor (UVAPF). However, with increased emphasis on UVA protection and sunscreen products with higher UVAPF gaining popularity, the immediate pigment darkening (IPD) method is drawing attention again. Furthermore, only about a quarter of the recommended quantity of sunscreen is used during daily activities. However, there is as yet no clearly defined relationship between the UVAPF and the amount of sunscreen applied. OBJECTIVES: To analyse the differences between the IPD and PPD methods, and to establish a relationship between the quantity of sunscreen application and the UVAPF. METHODS: Different doses of sunscreen were applied on the back of 15 healthy volunteers, and the UVAPF was measured using both the IPD and the PPD methods. RESULTS: Both methods proved to be effective for measuring the UVAPF. However, all the UVAPF values determined by the PPD method were lower than those determined by the IPD method. Additionally, an exponential relationship between the amount of sunscreen applied and the UVAPF was observed. CONCLUSIONS: The IPD method can also be used as an appropriate endpoint in the determination of UVA protection. It is time saving, and thus considerably lowers the risk of UV exposure, particularly when testing sunscreen products with higher UVAPF. We further state that in order to achieve the desired protective effect of the sunscreen, the quantity of application is also very important.

Change of biophysical properties of the skin caused by ultraviolet radiation-induced photodamage in Koreans.

BACKGROUND/PURPOSE: Ultraviolet (UV) irradiation affects the function and complexion of the skin by inducing changes in physical properties through formation of erythema, proliferation of epithelial cells, DNA damage, activation or inactivation of various enzymes and proteins, and free radical formation. In this study, the authors intended to observe the overall course of changes in barrier function and reflectance of the skin induced by photodamage, and healing reaction in the course of time, and alteration of the skin complexion. METHODS: The subjects were chosen from 15 healthy Korean men 20-35 in age, that fall into the category of Fitzpatrick's skin types II, III, and IV without history of recent exposure to sunlight, photosensitivity, or having taken any drugs that induce phototoxicity or photoallergic reactions. The subjects were artificially exposed to suberythemogenic dose [0.5 minimal erythemal dose (MED), 0.75 MED], 1 MED and high dose (2.5 MED) by solar simulator, and changes in skin barrier function and skin reflectance were assessed with a Tewameter, a Corneometer, and a Colorimeter for 4 weeks. RESULTS: Transepidermal water loss (TEWL) increased abruptly at Day 1 of single solar UV (SSUV) exposure, and slowly returned to the original level from Day 2/Day 3. In the case of exposure with 0.75 MED, it returned to the original level at Day 4 of exposure, and at Days 7 and 28 in the cases of 1 MED and 2.5 MED exposure, respectively. Water-holding capacity sharply declined at Day 1 of exposure, hitting the lowest point at Day 2, and then slowly recovered starting on Day 3. In the case of exposure with 0.75 MED and 1 MED, it returned to the original level at Days 7 and 28 in the case of 2.5 MED exposure. The a(*) values abruptly increased and reached the peak at Day 1 and slowly returned to the original level at Day 2, while the b(*) values slowly increased at Day 3, peaking at Day 7 and slowly returning to the original level thereafter. The L(*) values abruptly declined at Day 1, maintaining plateau through Day 7 and slowly returning to the baseline level thereafter. The individual typology angle (ITA degrees ) were compatible with L(*) values change. The erythema index increased abruptly at Day 1 of SSUV exposure, peaking at Day 2 and slowly returned to the original level starting at Day 3. Melanin index slowly started to increase on Day 3 of SSUV exposure, peaking at Day 7 and gradually returned to the original level thereafter. However, L(*), a(*), b(*), erythema index, and melanin index did not return to the original level during the 28-day course of this study. CONCLUSION: This study shows that in the skin of Korean subjects, changes in skin barrier function and delayed melanization do occur even in exposure to a suberythemogenic dose of SSUV. Also, given the fact that restoration of barrier function occurs as the process of melanization begins, melanization is considered to be a useful predictive indicator of the restoration of the skin barrier function after sunburn.

The difference between the constitutive and facultative skin color does not reflect skin phototype in Asian skin.

BACKGROUND/PURPOSE: The assessment of the sensitivity of human skin to ultraviolet (UV) radiation is important in the area of phototherapy, photodermatoses, photo-aging, photo-carcinogenesis, and photo-protection. Some reports have shown that quantitatively measured skin color is a good indicator for predicting UV sensitivity to human skin in Caucasians. In this study, our aim was to define the correlation between skin color and the skin phototype assessed by the Fitzpatrick method in Asian brown skin. METHODS: A total of 180 medical students with similar life styles were included in this study. Their skin phototype was classified according to the system introduced by Fitzpatrick. Then, using a Minolta Spectrophotometer CM-2002, their skin color was determined on the buttocks and forehead. The buttock color was taken as the constitutive skin color, and the forehead color as the facultative skin color. Using these measured values, we compared the skin color with the skin phototype to find their correlation. Also, we investigated whether the difference between the constitutive and facultative skin colors of each individual had a relationship with his or her skin phototype. RESULTS: The constitutive skin color became darker with increasing skin phototype, and this change was statistically significant. As for the facultative skin color, it also became darker with increasing skin phototype, but was less well correlated with the skin phototype than the constitutive skin color. However, the difference between the constitutive and facultative skin colors did not show consistent results in predicting the skin phototype. CONCLUSION: In this study, we found that the constitutive skin color can be a good indicator of the skin phototype. However, the difference between the constitutive and facultative skin colors of each individual does not give any meaningful information for the assessment of his or her skin phototype in Asian skin.

Diffusion-weighted MRI and ADC mapping in FK506 neurotoxicity.

FK506 is a newly developed potent immunosuppressant for preventing rejection after organ transplantation. However, FK506 can induce central nervous system toxicity. Until now the pathogenic mechanism of FK506 neurotoxicity was unclear. We report the findings of diffusion-weighted MRI and apparent diffusion coefficient (ADC) mapping of a FK506 neurotoxicity patient who showed increased signal intensities in both parieto-occipital lobes on T(2) weighted images, diffusion-weighted images and ADC maps. These findings suggest that a vasogenic oedema rather than a cytotoxic oedema may play a pivotal role in FK506 neurotoxicity pathogenesis.

CD40L activation in circulating platelets in patients with acute coronary syndrome.

The CD40-CD40L interaction, which was initially shown to have important roles in the T cell-mediated activation of B cells during humoral immune responses, is now known to have roles in activation of endothelial cells, smooth muscle cells, and macrophages within atherosclerotic plaques. Recently, CD40L expression was found in activated platelets in the thrombus in vivo and CD40L was reported to be responsible for the platelet-mediated activation of endothelial cells in vitro. To investigate the activation status of platelets in coronary artery disease patients, we tested expression levels of CD40L, and platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) in platelets isolated from peripheral blood, using flow cytometric analysis. Twenty-nine patients with acute coronary syndrome (10 acute myocardial infarction and 19 unstable angina patients) were compared with 14 normal subjects or 14 stable angina patients. In platelets isolated from normal subjects, the expression of CD40L was not detected in all subjects. In the patients with acute coronary syndrome, the average level of CD40L showed a significant increase (p = 0.0028), while stable angina patients did not have any increase when compared to normal subjects. Patients with more complex lesions or vessel occlusion tended to have a high platelet CD40L level compared to patients who do not. The expression levels of CD31 were increased in a small portion of the ACS patients. These data indicate that the rupture of plaque and subsequent formation of thrombus may lead to the activation of CD40L expression in circulating platelets of ACS patients.

Computed tomographic correlation with pituitary function in Sheehan's syndrome.

Twenty six patients with Sheehan's syndrome were studied with high-resolution computed tomography (CT) and the sequential pituitary stimulation test in order to correlate the CT findings of the sella turcica with the pituitary reserve functions. CT revealed 21 completely empty sella (CES), 4 partially empty sella (PES) and 1 normal sella. Panhypopituitarism occurred in 1 of 4 patients with PES and 20 of 21 with CES. One patient showing normal sella had a normal preservation of prolactin (PRL), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH) and lutenizing hormone (LH). In all patients with PES and CES, growth hormone (GH) responses to hypoglycemia and PRL responses to thyrotropin releasing hormone (TRH) were blunted. Three (75.0%) with PES had normal basal cortisol levels, which were more frequent than two (9.6%) with CES; however, most of the PES (3 of 4) and CES (20 of 21) demonstrated blunted cortisol responses to hypoglycemia. Three (75.0%) with PES and only one (4.8%) with CES had normal thyroxine levels and TSH responses to TRH. None with PES showed decreased basal and stimulated levels of FSH and LH, whereas 15 of 21 with CES did. The pituitary functions of the patients having considerable amounts of pituitary remnants visualized by CT were relatively preserved for TSH, cortisol, FSH and LH. Considering the above results, changes in the amounts of pituitary remnants detected by CT might correlate with hormonal secretory capacity.