OBJECTIVE: To evaluate the ultrasonography (US) features and clinical characteristics of columnar cell variant of papillary thyroid carcinoma (CCV-PTC) that can predict disease progression. MATERIALS AND METHODS: Six cases of CCV-PTC were identified via surgical pathology analysis at our institution from 1994 to 2016. The histological, architectural, and cytological features met the diagnostic criteria of CCV-PTC. We reviewed the US features and clinicopathological findings in the six cases. RESULTS: An indolent clinical course was observed in four young female patients aged 27–34 years (median: 32 years), while two older patients aged 55 years or 70 years had an aggressive clinical course. All patients underwent total thyroidectomy and radioiodine therapy. The indolent group included patients with T1 and nodal metastasis, where the disease was not observed during the follow-up period (range: 8–17 years). On the other hand, a larger tumor size (1.8 cm and 6.0 cm), gross extrathyroidal extension to the muscle and lymph node, and distant metastasis were observed in the aggressive group. In one male patient, recurrence occurred immediately after operation, and this patient died 4 years after the diagnosis of thyroid cancer. Based on US, the individuals from the indolent group had a smooth margin, except for one. Both cases in the aggressive group had a microlobulated margin. CONCLUSION: Favorable prognosis in CCV-PTC is observed in young patients with T1 staging and demonstrates a smooth margin at US. These US findings might help exclude the same treatment as the aggressive type in the indolent type of CCV-PTC.
Diagnosis ; Disease Progression ; Female ; Follow-Up Studies ; Hand ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Pathology, Surgical ; Prognosis ; Recurrence ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Ultrasonography

PURPOSE: This study aimed to examine the following questions: to what extent do patients and caregivers perceive their family members to be avoidant of communication regarding patient's cancer, and to what extent do these perceptions interrelate; and how do such perceptions influence their own and each other's communication behaviors, communication outcome, mental health, and quality of life. MATERIALS AND METHODS: A national survey was performed with 990 patient-caregiver dyads (participation rate, 76.2%). To examine the dyadic interaction, we developed linked patient and family member questionnaires, including the Family Avoidance of Communication about Cancer (FACC) scale. RESULTS: The mean scores (standard deviations) of patient- and caregiver-perceived FACC were low at 10.9 (15.5) and 15.5 (17.5), respectively (p < 0.001), and concordance was low, a well (Spearman's rho, 0.23). Patient-perceived FACC was associated with lower levels of disclosure and behaviors of holding back communication, as well as lower levels of mental health outcome and quality of life. The same was true for caregivers (all p < 0.05). Patient-perceived FACC was associated with caregiver holding back, caregiver's depression level, and caregiver quality of life (all p < 0.05). Both patient- and caregiver-perceived FACC were independently associated with communication difficulty within the family. CONCLUSION: Future research would benefit from the measurement of FACC from both patients and caregivers, and promote family intervention to enhance openness to communication, which would be helpful for improving mental health and quality of life for both patients and caregivers.
Caregivers ; Depression ; Disclosure ; Humans ; Mental Health ; Quality of Life

Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds in mice with HCF-PRP resulted in much faster wound closure as well as dermal and epidermal regeneration at day 12 compared to treatment with either C-PRP or F-PRP. Enhanced skin regeneration observed in HCF-PRP group may have been at least partially due to enhanced angiogenesis in the wound beds. Therefore, this method could be useful for skin wound treatment.
Animals ; Blotting, Western ; *Cell Proliferation ; Dermis/cytology/metabolism ; Female ; Fibrin/*metabolism ; Fibroblast Growth Factor 2/genetics/metabolism ; Heparin/metabolism ; Immunoenzyme Techniques ; Intercellular Signaling Peptides and Proteins/*secretion ; Mice ; Mice, Inbred BALB C ; Platelet-Rich Plasma/*metabolism ; Proto-Oncogene Proteins c-sis/genetics/metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Regeneration ; Skin/*cytology/*metabolism ; Vascular Endothelial Growth Factor A/genetics/metabolism ; Wound Healing/*physiology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces excessive pro-inflammatory cytokine release and cell death, leading to organ damage and mortality.High-mobility group box 1 (HMGB1) is one of the damage-associated molecular patterns that can be secreted by pro-inflammatory stimuli, including viral infections, and its excessive secretion levels are related to a variety of inflammatory diseases. Here, the aim of the study was to show that SARS-CoV-2 infection induced HMGB1 secretion via active and passive release. Active HMGB1 secretion was mediated by post-translational modifications, such as acetylation, phosphorylation, and oxidation in HEK293E/ACE2-C-GFP and Calu-3 cells during SARS-CoV-2 infection. Passive release of HMGB1 has been linked to various types of cell death; however, we demonstrated for the first time that PANoptosis, which integrates other cell death pathways, including pyroptosis, apoptosis, and necroptosis, is related to passive HMGB1 release during SARS-CoV-2 infection. In addition, cytoplasmic translocation and extracellular secretion or release of HMGB1 were confirmed via immunohistochemistry and immunofluorescence in the lung tissues of humans and angiotensin-converting enzyme 2-overexpressing mice infected with SARS-CoV-2.

Background: Recent evidence has reported the relationships between 25-hydroxyvitamin D (25[OH]D) insufficiency and chronic diseases. This study examined the association of physical activity and sitting time with vitamin D status. Methods: This study analyzed the data of 1,598 adults aged ≥19 who participated in the 2014 Korea National Health and Nutrition Examination Survey. Vitamin D insufficiency was defined as a serum 25(OH)D level of ≤20 ng/mL. The odds ratios and 95% confidence intervals of vitamin D insufficiency according to physical activity and sitting time were calculated using a multivariable logistic regression analysis. Results: The mean levels of serum 25(OH)D were 16.5 ng/mL in males and 15.2 ng/mL in females, respectively and was significantly higher in the participants with sitting times of <5 hours/day than those with sitting times of ≥5 hours/day. After adjusting for confounding variables, sitting time of <5 hours/day was associated with decreased odds of vitamin D insufficiency as compared with sitting time of ≥5 hours/day in the total participants and females. In addition, the odds ratio for vitamin D insufficiency was significantly lower in the group with sitting times of <5 hours/ day than in the group with sitting times of ≥5 hours/day even among people with low physical activity in the total participants and females. Conclusion Serum 25(OH)D level was insufficient in the Korean adults and shorter sitting time was related to lower odds ratio of vitamin D insufficiency. Our findings suggest that sitting time is an independent factor of serum vitamin D status.

Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model. Dextran sulfate sodium-induced colitis mice were administered RIPK3 inhibitor (3 mg/ml) 3 times and their tissues were analyzed by immunohistochemistry. RIPK3, mixed lineage kinase domain-like (MLKL), phosphorylated MLKL, IL-17, and CD4 in colitis patient colon tissues were detected using confocal microscopy. Protein levels were measured using immunohistochemistry and ELISA. The differentiation of Th17 cells was evaluated using flow cytometry. The expression of proinflammatory cytokines and necroptosis in peripheral blood mononuclear cells from UC patients was decreased markedly by RIPK3 inhibitor treatment. We also observed that the injection of RIPK3 inhibitor improves colitis severity and protects intestinal destruction. RIPK3 inhibitor reduced necroptosis factors and proinflammatory cytokines in the colon and consequently protected colon devastation. The expression of inflammatory mediators in experimental colitis mice splenocytes was decreased significantly by RIPK3 inhibitor treatment. These results suggest that RIPK3 inhibitor ameliorates severity of experimental colitis and reduces inflammation through the inhibition of inflammatory response and necroptosis and support RIPK3-targeting substances for treatment of UC.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.