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Abstract Background Disruption of mitochondrial genes may become a powerful tool for elucidating precisely the functions of individual mitochondrial genes. However, it is generally difficult to manipulate genetically mitochondrial genes, because 1) a mitochondrion is surrounded by inner and outer membranes, and 2) there are a large number of mtDNA copies in a single cell. This is the reason why we tried to establish a novel method for disrupting a certain mitochondrial gene (rps4), using Dictyostelium cells. Results Here, we have developed a new method for specifically disrupting a mitochondrial gene (rps4 ; ribosomal protein subunit S4), by a combination of homologous recombination and delivery of an appropriate restriction endonuclease (SfoI) into mitochondria. First, mitochondrially targeted SfoI whose expression is under control of the tetracycline (Tet)-regulated gene expression system was introduced into cells heteroplasmic with respect to the rps4 gene. Then, the heteroplasmic cells were produced by homologous recombination by use of the construct in which the unique SfoI site and the 5'-half of the rps4 coding region were deleted not to be digested by SfoI, and therefore their mitochondria have both the wild-type mtDNA and the mutant mtDNA with the disrupted rps4 gene. In response to removal of Tet from growth medium, SfoI was selectively delivered into mitochondria and digested only the wild-type mtDNA but not the mutated rps4. Thus one can gain rps4-null cells with only the mutated mtDNA, under the Tet-minus condition. Conclusion The mitochondrial gene-disruption method presented here must be widely useful for precisely determining the functions of individual mitochondrial genes. This is the first report to demonstrate complete and specific mitochondrial gene disruption.

Background: In the coming years, surrogate decision-making is expected to become highly prevalent in Japanese clinical practice. Further, there has been a recent increase in activities promoting advance care planning, which potentially affects the manner in which judgements are made by surrogate decision-makers. This study aims to clarify the grounds on which surrogate decision-makers in Japan base their judgements.Methods: In this qualitative study, semi-structured interviews were conducted to examine the judgement grounds in surrogate decision-making for critical life-sustaining treatment choices in acute care hospitals.Results: A total of 228 participants satisfied the inclusion criteria, and 15 were selected for interviews. We qualitatively analysed the content of 14 interview transcripts, excluding one that did not meet the inclusion criteria. Based on this analysis, we extracted 4 core categories, 17 categories, 35 subcategories, and 55 codes regarding judgement grounds in surrogate decision-making. The four core categories were as follows: patient preference-oriented factor (Type 1), patient interest-oriented factor (Type 2), family preference-oriented factor (Type 3), and balanced patient/family preference-oriented factor (Type 4). The Type 4 core category represented attempts to balance the preferences of the patient with those of the surrogate decision-maker.Conclusions: Surrogate decision-makers based their decisions on important aspects related to a patient's life, and they considered not only the patient's preferences and best interests but also their own preferences. As the need for surrogate decisions will increase in the future, decision-makers will need to consider judgement grounds from a more diverse perspective. [ABSTRACT FROM AUTHOR]

Nanostructure control is of fundamental and technological importance because various properties such as vortex pinning in superconductors are determined by the nanostructure. While the nanostructure in superconducting oxides is well controlled, the nanostructure control of iron-based superconductors is required. The nanostructure has not yet been well controlled even in Fe(Te,Se) with the simplest structure among Fe-based superconductors because the anion may be non-stoichiometric and anionic substitution is possible. In this study, we observed the compositional inhomogeneity originating from phase separation in Fe(Te,Se) films, which were prepared by pulsed laser deposition. The films deposited at lower temperature do not show nanoscale compositional inhomogeneity. On the other hand, the high-temperature deposited films contain an inhomogeneous anion distribution with the size of ∼8 nm due to phase separation. The spacing of the compositional inhomogeneity is ∼16 nm. This structure obtained by phase separation is expected to be an effective pinning center in high magnetic fields after further optimization. Thus, the method of nanostructure control other than nanocomposite formation in oxides is demonstrated for Fe(Te,Se). [ABSTRACT FROM AUTHOR]

Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital condition that can cause sudden death in young people. When it is associated with acute aortic dissection, acute myocardial infarction can occur due to enlargement of the sinus of Valsalva. We report the case of a 71‐year‐old man with anomalous origin of the right coronary artery from the left sinus of Valsalva, who developed right ventricular infarction due to the compression of the right coronary artery between the aorta and pulmonary artery trunk. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Our aims were to examine the add‐on effects of a sodium–glucose cotransporter 2 inhibitor, dapagliflozin, compared with existing antidiabetes treatments, on anthropometric/metabolic parameters, the levels of an endocrine regulator, fibroblast growth factor 21 (FGF21); a skeletal muscle mass (SMM) negative regulator, myostatin; and a metabolic regulator, irisin, in patients with type 2 diabetes. Materials and Methods: A total of 54 patients with type 2 diabetes were randomly divided into dapagliflozin and control groups. The dapagliflozin group received dapagliflozin 5 mg/day in addition to conventional therapy for 24 weeks. The primary outcome was the change in the level of serum FGF21 from baseline. The secondary outcomes included changes from baseline in anthropometric/metabolic parameters and serum levels of myostatin and irisin. Results: Bodyweight decreased in the dapagliflozin group compared with the control group (P < 0.001), but the changes in SMM were not significant between the groups (P = 0.611), thereby elevating the ratio of SMM‐to‐bodyweight in the dapagliflozin group (P = 0.028). Myostatin levels were significantly decreased (P = 0.010), and irisin levels showed a nearly significant reduction (P = 0.052) in the dapagliflozin group compared with the control group, whereas FGF21 levels did not change significantly from baseline to the end of the intervention in both the dapagliflozin (P = 0.673) and the control (P = 0.823) groups. Conclusions: Dapagliflozin add‐on therapy in patients with type 2 diabetes reduced myostatin levels significantly and maintained SMM, without significant changes in FGF21 levels. [ABSTRACT FROM AUTHOR]

Aims Anomalous origin of the coronary artery (AOCA) with an inter-arterial course (IAC) between the great vessels poses a risk for a life-threatening cardiovascular event. We assessed, in a registry-based study, the clinical features, treatment strategies, and prognoses of life-threatening cardiovascular events ensuant to AOCA. Methods and results Included were 65 AOCA patients (48 men/17 women, aged 41 ± 23 years) from 40 clinical centres who had experienced sudden cardiac arrest (SCA) (n  = 30), acute myocardial infarction (AMI) (n  = 5), angina (n  = 23), or syncope (n  = 7). The anomalous vessel was the right coronary artery in 72% of patients and left coronary artery in 28%; the ostium was slit-like in 42%. Coronary luminal narrowing ≥75% was absent in patients with SCA or syncope (86% and 57%, respectively), but occlusion or narrowing was seen in those with AMI (100%) or angina (52%). Age ≤40 years, male sex, sporting activity, absence of prodromal symptoms, acutely angled (≤30°) take-off from the aorta, and absence of luminal narrowing of the IAC segment were associated with SCA in this patient group. Coronary vasospasm was inducible in 12 of 17 patients without coronary narrowing. Management included surgical revascularization (n  = 26) percutaneous coronary intervention (n  = 9), and medical treatment (n  = 26). Four SCA patients died while hospitalized; no others died during the median 5.0 (range, 1.8–7.0)-year follow-up period. Conclusions In patients with AOCA, age ≤40 years, male sex, sporting activity, and an acute take-off angle appear to be risk factors for SCA. Appropriate management can be beneficial. Confirmation in a large-scale study is warranted. [ABSTRACT FROM AUTHOR]

The clinicopathological significance of carbohydrate antigen 19‐9 (CA19‐9) in gastric cancer (GC) remains obscure. Therefore, the current study aimed to clarify the clinicopathological value of CA19‐9 in GC utilizing autopsy cases. We examined the expression of CA19‐9 and mucin core proteins in GC immunohistochemically, and analyzed serum CA19‐9 levels and clinicopathological variables or complications. We also investigated whether fucosyltransferases 2 and 3 (FUT2/3) allelic variants influence CA19‐9 expression in GC. Compared to GC cases with negative CA19‐9 expression (tCA19‐9‐N), those with positive CA19‐9 expression (tCA19‐9‐P) demonstrated significant differences in characteristic features such as lymph node and distant organ metastases, lymphatic and venous permeation, and higher Tumor, Node, Metastasis (TNM) stages. Moreover, compared to GC cases with low serum CA19‐9 levels (sCA19‐9‐L), those with high serum CA19‐9 levels (sCA19‐9‐H) were related to venous permeation, higher proportion of lymph node and distant organ metastases, and higher TNM stages. Both tCA19‐9‐P GC and sCA19‐9‐H GC cases were significantly associated with coagulation abnormalities. sCA19‐9‐H GC cases correlated significantly with MUC1 and MUC5AC expression. FUT2/3 genotypes were not associated with CA19‐9 expression in GC. These results suggest that CA19‐9 can predict the risk of lymph node and distant metastases as well as of coagulation abnormalities. [ABSTRACT FROM AUTHOR]

We develop a simple growth model featuring individuals' choices between general and specific skills, endogenous technological innovation, and a government subsidy for education. The two types of skills differ by their productivity and transferability: general skills are transferable across firms, while each firm-specific skill has a productivity advantage in the firm. Firms face uncertainty in their innovation activities, and the resulting heterogeneity in their labor demand makes the transferability of general skill valuable. We theoretically show that as a country catch up to the world technology frontier, firms invest more in innovation activities. This rises firms' technological uncertainty and, thus, their demands for general skills increases. As a result, especially in more advanced economies, education subsidies may enhance GDP by increasing the supply of general skills. Using aggregated data for 12 European OECD counties, we calibrate the model and compare the theoretical prediction with the data. In cross-country comparisons, we find that the returns on general skills and the impact of general education expenditure on GDP are higher in countries with higher total factor productivity. These findings support our theoretical argument of the positive relationship between firms' demand for general skills and countries' stages of development. [ABSTRACT FROM AUTHOR]

Rat-bite fever (RBF) is characterized by fever, rash and arthritis, mainly caused by Streptobacillus moniliformis. We present a case of inflammatory erosive polyarthritis with sepsis caused by Streptobacillus notomytis, a novel species isolated from S. moniliformis. A 67-year-old man presented with fever, purpura and peripheral arthritis. After blood cultures were performed, loxoprofen administration was initiated. Arthritis partially improved, but left first metatarsophalangeal (MTP) arthritis persisted. A gram-negative rod was detected in the blood culture, and meropenem administration was started that improved arthritis. Ultrasonography and computed tomography revealed bone erosion in the left first MTP joint, leading to the diagnosis of septic arthritis. 16S rRNA gene sequence analysis revealed that this strain was S. notomytis. Further questioning revealed the patient may have had contact with rats. It is essential to consider Streptobacillus infection in the differential diagnosis of erosive polyarthritis. [ABSTRACT FROM AUTHOR]