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

BACKGROUND AND PURPOSE: Nicergoline is an ergoline derivative that is used to treat cognitive deficits in cerebrovascular disease and various forms of dementia. Although therapeutic effects of nicergoline have been established, little is known about its effects on cerebral perfusion in Alzheimer's disease (AD). The aim of this study was to examine the role of nicergoline in regional cerebral blood flow (rCBF) of AD patients using technetium-99m hexa-methyl-propylene-amine-oxime single photon emission computed tomography (SPECT). METHODS: Sixteen patients with early AD underwent a comprehensive clinical assessment including cognitive testing and SPECT scans before and after nicergoline treatment. Nicergoline (30 mg twice daily) was administered for an average duration of 1.5 years. Clinical and cognitive functioning was assessed using the Mini-Mental State Examination, Clinical Dementia Rating (CDR), CDR-Sum of Boxes, Global Deterioration Scale, Barthel Activities of Daily Living Index, Instrumental Activities of Daily Living, and Geriatric Depression Scale. RESULTS: Nicergoline treatment induced changes in the severity of dementia, cognitive function, activities of daily living, and depressive symptoms, which were not statistically significant. During the follow-up, the patients showed significant increases in their relative rCBF in the superior frontal gyrus, precentral gyrus, and postcentral gyrus. CONCLUSIONS: Nicergoline treatment improves perfusion of the frontal and parietal regions in early AD patients. It is possible that the increased perfusion in the superior frontal gyrus may be related to the mechanisms that delay or prevent progressive deterioration of cognitive functions in AD.
Activities of Daily Living ; Alzheimer Disease* ; Cerebrovascular Circulation ; Cerebrovascular Disorders ; Cognition ; Cognition Disorders ; Dementia ; Depression ; Ergolines ; Follow-Up Studies ; Frontal Lobe ; Humans ; Nicergoline* ; Parietal Lobe ; Perfusion* ; Pilot Projects* ; Prefrontal Cortex ; Somatosensory Cortex ; Therapeutic Uses ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: AND PURPOSE: Similar-sized stroke lesions at similar locations can have different prognoses in clinical practice. Lesion-network mapping elucidates network-level effects of lesions that cause specific neurologic symptoms and signs, and also provides a group-level understanding. This study visualized the effects of stroke lesions on the functional brain networks of individual patients. METHODS: We enrolled patients with ischemic stroke who were hospitalized within 1 week of the stroke occurrence. Resting-state functional magnetic resonance imaging was performed 3 months after the index stroke. For image preprocessing, acute stroke lesions were visually delineated based on diffusion-weighted images obtained at admission, and the lesion mask was drawn using MRIcron software. Correlation matrices were calculated from 280 brain regions using the Brainnetome Atlas, and connectograms were visualized using in-house MATLAB code. RESULTS: We found characteristic differences in connectograms between pairs of patients who had comparable splenial, frontal cortical, cerebellar, and thalamocapsular lesions. Two representative patients with bilateral thalamic infarctions showed significant differences in their reconstructed connectograms. The cognitive function had recovered well at 3 months after stroke occurrence in patients with well-maintained interhemispheric and intrahemispheric connectivities. CONCLUSIONS This pilot study has visualized the effects of stroke lesions on the functional brain networks of individual patients. Consideration of the neurobiologic mechanisms underlying the differences between their connectograms has yielded new hypotheses about differences in the effects of stroke lesions.

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: 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.