No abstract available.
Pulmonary Aspergillosis*

Treatment options for patients with chronic kidney disease (CKD) are currently limited; therefore, there has been significant interest in applying mesenchymal stem/stromal cell (MSC)-based therapy to treat CKD. However, MSCs harvested from CKD patients tend to show diminished viability and proliferation due to sustained exposure to uremic toxins in the CKD environment, which limits their utility for cell therapy. The application of melatonin has been demonstrated to improve the therapeutic efficacy of MSCs derived from and engrafted to tissues in patients suffering from CKD, although the underlying biological mechanism has not been elucidated. In this study, we observed overexpression of hexokinase-2 (HK2) in serum samples of CKD patients and MSCs harvested from an adenine-fed CKD mouse model (CKD-mMSCs). HK2 upregulation led to increased production levels of methylglyoxal (MG), a toxic metabolic intermediate of abnormal glycolytic processes. The overabundance of HK2 and MG was associated with impaired mitochondrial function and low cell proliferation in CKD-mMSCs. Melatonin treatment inhibited the increases in HK2 and MG levels, and further improved mitochondrial function, glycolytic metabolism, and cell proliferation. Our findings suggest that identifying and characterizing metabolic regulators such as HK2 in CKD may improve the efficacy of MSCs for treating CKD and other kidney disorders.

Osteoporosis is characterized by impaired osteogenesis. BMD is a major determinant of bone strength. The role of the VDR gene in predisposition to primary osteoporosis has been recognized. However, population-based case-control studies have been reported controversial results for known candidate genes in an ethnically distinct group. To determine the genetic effects of VDR variants on osteoporosis and BMD, we directly sequenced the VDR gene in 24 unrelated Korean individuals and identified eighteen sequence variants. We investigated the potential involvement of eight SNPs in osteoporosis in postmenopausal women (n = 729). Two SNPs (LD) in intron 2, -5294G > C (rs2238135) and -4817G > A (rs17882443) showed the evidence of association with enhanced BMD of the femoral neck (p(additive) =0.031 for rs2238135; p(additive)=0.017 and p(dominant)= 0.019 for 17882443). Moreover, VDR -4817G > A was significantly associated with protective effect on all fracture risk (p(recessive)=0.035, OR=0.2, 95% CI=0.05~0.89), and tended to be higher BMD values at various proximal femur sites. Therefore, we suggest that the -4817G > A may be useful genetic marker for vitamin D-related metabolism and may have an important role in the increased BMD of the proximal femur in postmenopausal Korean women.
Bone Density ; Case-Control Studies ; Female ; Femur ; Femur Neck ; Genetic Markers ; Humans ; Introns ; Osteogenesis ; Osteoporosis ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol ; Vitamin D ; Vitamins

A 15-year-old castrated mixed breed dog presented due to a 5-month history of cough and difficulty in ambulation. Necropsy showed multiple periosteal and intramedullary infiltrative masses in the appendicular skeleton. In addition, single and multiple neoplastic nodules were observed in several organs, including the lungs, liver, kidney, and heart. Microscopically, several skeletal neoplastic masses and nodules in the parenchymal organs revealed similar changes. The neoplastic cells were spindle- to polygonal-shaped with prominent osteoid production and occasional cartilaginous and bone formation. Based on the gross findings and histopathology results, the case was diagnosed as multicentric osteosarcoma with systemic metastases.
Adolescent ; Animals ; Cough ; Dogs* ; Heart ; Humans ; Kidney ; Liver ; Lung ; Neoplasm Metastasis* ; Osteogenesis ; Osteosarcoma* ; Skeleton ; Walking

To investigate the influence of leukoaraiosis (LA) on the functional outcomes of subcortical stroke in the subacute phase after onset. We retrospectively analyzed 41 patients with subacute subcortical infarct at a single center from 2011 to 2015. We explored the relationship between LA severity at admission/transfer (initial evaluation) and functional outcome at the time of discharge (follow-up evaluation), as assessed using the modified Rankin Scale (mRS), Functional Ambulation Category (FAC), and modified Barthel Index (mBI). LA severity was graded as mild, moderate, or severe according to the Fazekas scale. Scores of the mRS, FAC, and mBI were compared in patients grouped based on LA severity: no LA (n = 12), mild LA (n = 19), and moderate-to-severe LA (n = 10). Significant inter-group differences were observed in all 3 scores at both the initial and follow-up evaluations. After adjustment for age, scores at follow-up evaluation were significantly different between the 2 groups. LA is related to functional outcomes of subcortical stroke in the subacute phase after onset. After adjustment for age, severe LA was correlated with poor functional outcomes in the subacute phase.
Cerebral Infarction ; Follow-Up Studies ; Humans ; Leukoaraiosis* ; Retrospective Studies ; Stroke ; Walking

BACKGROUND AND OBJECTIVES: Cancer of the thyroid is the sixth common cancer in Korea, and fourth common among the Korean women, in particular. Aming the prevalent carcinomas of thyroid, the papillary thyroid carcinoma is the most frequent type. Genomic instability is the characteristic of nearly all tumors as well as thyroid cancers. However, despite the high frequency of papillary thyroid carcinomas, their chromosomal alterations are poorly characterized in Korea. Comparative genomic hybridization (CGH) is a new fluorescence in situ hybridization (FISH) technique to identify genomic imbalances in cancers. In this study, CGH was carried out with the aim of analyzing non-random chromosomal aberrations involved in papillary thyroid carcinomas. MATERIALS AND METHOD: CGH was carried out. Biotin-labeled tumor DNA and digoxigenin-labeled normal DNA were co-hybridized to normal metaphase cells. Then, the ratio of fluorescence was analyzed by an image analyzer. In array-CGH, Cy3 labeled tumor DNA and Cy5 labeled normal DNA were hybridized to microarray template, and then image analysis was performed by microarray image analyzer. RESULTS: Gains of 22q13, 6p24, 7p13, 7q21, 7q31, 8q24, 17q24 and 19p13.3 were found frequently. CONCLUSION: Non-random aberrations which were disclosed in this study might be candidate regions for the abnormal genes involved in papillary thyroid cancer.
Carcinoma, Papillary* ; Chromosome Aberrations* ; Comparative Genomic Hybridization* ; DNA ; Female ; Fluorescence ; Genomic Instability ; Humans ; Hybridization, Genetic ; In Situ Hybridization ; Korea ; Metaphase ; Thyroid Gland* ; Thyroid Neoplasms

PURPOSE: Alagille syndrome is a complex hereditary disorder that is associated with cardiac, hepatic, skeletal, ocular, and facial abnormalities. Mutations in the Notch signaling pathway, such as in JAG1 and NOTCH2, play a key role in embryonic development. A cardiac or hepatic presentation is a critical factor for determining the prognosis. METHODS: We conducted a retrospective study of 41 patients with Alagille syndrome or a JAG1 mutation between 1983 and 2013. RESULTS: The first presentations were jaundice, murmur, cyanosis, and small bowel obstruction at a median age of 1.0 months (range, 0-24 months). The JAG1 mutation was found in 27 of the 28 genetically-tested patients. Cardiovascular anomalies were identified in 36 patients, chronic cholestasis was identified in 34, and liver transplantation was performed in 9. There was no significant correlation between the severity of the liver and cardiac diseases. The most common cardiovascular anomaly was peripheral pulmonary stenosis (83.3%), with 13 patients having significant hemodynamic derangement and 12 undergoing surgical repair. A total bilirubin level of >15 mg/dL with a complex surgical procedure increased the surgical mortality (P=0.022). Eight patients died after a median period of 2.67 years (range, 0.33-15 years). The groups with fetal presentation and with combined severe liver and heart disease had the poorest survival (P<0.001). CONCLUSION: The group with combined severe liver and heart disease had the poorest survival, and a multidisciplinary approach is necessary to improve the outcome.
Alagille Syndrome* ; Bilirubin ; Cardiovascular Diseases ; Cholestasis ; Cyanosis ; Embryonic Development ; Female ; Heart Diseases ; Hemodynamics ; Humans ; Jaundice ; Labor Presentation ; Liver ; Liver Transplantation ; Mortality ; Pregnancy ; Prognosis ; Pulmonary Valve Stenosis ; Retrospective Studies

Pericardial mesothelioma is a rare neoplasm in dogs. This report describes a case of pericardial mesothelioma in a 13-year-old Shih Tzu that presented with a clinical history of dyspnea. Hemorrhagic pericardial effusion and chylous pleural effusion with reactive mesothelial cells were identified by radiograph and cytology. Necropsy revealed multiple round nodules throughout the pericardium and regional lymph nodes in addition to chylothorax. Histopathology revealed invasive neoplasm on the pericardial surface with metastasis to the lymph nodes. The neoplastic cells were immunopositive to both cytokeratin and vimentin. Diagnosis of pericardial mesothelioma with regional lymph node metastasis was made.

A female domestic ferret (Mustela putorius furo) presented to a veterinary clinic with a clinical history of anorexia and poor body condition. Due to gradual deterioration of the body condition, explorative laparotomy was performed. Diffusely, the mesentery was severely thickened and adhered with prominent mesenteric lymph nodes. A portion of the mesentery and mesenteric lymph nodes were biopsied and fixed. Microscopic analysis revealed severe pyogranulomatous peritonitis and lymphadenitis, but staining revealed no bacterial organisms. However, immunohistochemistry for feline coronavirus exhibited strong immunoreactivity, primarily in the macrophages. Based on these results, the case was diagnosed as ferret coronavirus infection.

Background: The coronavirus disease 2019 (COVID-19) pandemic is a major public health problem of international concern. It is important to estimate its impact of COVID-19 for health policy decision-making. We estimated the years of life lost (YLLs) due to COVID-19 in high-incidence countries. Methods: We collected the YLLs due to COVID-19 in 30 high-incidence countries as of April 13, 2020 and followed up as of July 14, 2020. Incidence and mortality were collected using each country's formal reports, articles, and other electronic sources. The life expectancy of Japanese females by age and the UN population data were used to calculate YLLs in total and per 100,000. Results: As of April 22, 2020, there were 1,699,574 YLLs due to COVID-19 in 30 high-incidence countries. On July 14, 2020, this increased to 4,072,325. Both on April 22 and July 14, the total YLLs due to COVID-19 was highest in the USA (April 22, 534,481 YLLs; July 14, 1,199,510 YLLs), and the YLLs per 100,000 population was highest in Belgium (April 22, 868.12 YLLs/100,000;July 14, 1,593.72 YLLs/100,000). YLLs due to COVID-19 were higher among males than among females and higher in those aged ≥ 60 years than in younger individuals. Belgium had the highest proportion of YLLs attributable to COVID-19 as a proportion of the total YLLs and the highest disability-adjusted life years per 100,000 population. Conclusion This study estimated YLLs due to COVID-19 in 30 countries. COVID-19 is a high burden in the USA and Belgium, among males and the elderly. The YLLs are very closely related with the incidence as well as the mortality. This highlights the importance of the early detection of incident case that minimizes severe acute respiratory syndrome coronavirus-2 fatality.