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ASOs targeting TG/TRL, such as angiopoietin-like 3 or 4 (ANGPTL3 or ANGPTL4), apolipoprotein C-III (APOC3), or Lp(a) have effectively lowered the corresponding lipid profiles without requiring high or frequent doses. Clinical outcomes from these novel therapeutics are yet to be proven. Here, we review current and emerging therapeutics targeting LDL-C, TG, TRL, and Lp(a) to reduce the residual CV risk.

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevated low-density lipoprotein cholesterol concentration and premature acute coronary syndrome (ACS). However, hereditary diseases may have regional characteristics, and few data are available regarding the prevalence of FH throughout particular regions in Japan. This study investigated the prevalence and prognosis of FH in patients with ACS in Mie Prefecture, Japan.Methods and ResultsThis study investigated 738 ACS patients from the Mie ACS Registry in Mie Prefecture, and 706 (95.7%) with sufficient data to diagnose FH were enrolled for analysis. Eighteen patients (2.5%) were diagnosed with FH, which was similar to findings of another multidistrict registry conducted in Japan. Patients with FH were significantly younger and had a higher prevalence of premature onset of ACS than patients with non-FH (P<0.01). Incidence of major adverse cardiac and cerebrovascular events (MACCE) was not statistically different between patients with FH and non-FH in this study population, even in the propensity score-matched analysis.

Prevalence of FH in ACS patients from the Mie Prefecture was similar to that found in another Japanese multidistrict registry. Among ACS patients, short-term incidence of MACCE was not statistically different between patients with FH and non-FH in this study population.

Prevalence of FH in ACS patients from the Mie Prefecture was similar to that found in another Japanese multidistrict registry. Among ACS patients, short-term incidence of MACCE was not statistically different between patients with FH and non-FH in this study population.

Quantitative ultrasound (QUS) and resonance frequency analyses (RFA) are promising methods to assess the stability of dental implants. The aim of this in vivo preclinical study is to compare the results obtained with these two techniques with the bone-implant contact (BIC) ratio, which is the gold standard to assess dental implant stability.

Twenty-two identical dental implants were inserted in the tibia and femur of 12 rabbits, which were sacrificed after different healing durations (0, 4, 8 and 13 weeks). For each implant, the ultrasonic indicator (UI) and the implant stability quotient (ISQ) were retrieved just before the animal sacrifice using the QUS and RFA techniques, respectively. Histomorphometric analyses were carried out to estimate the bone-implant contact ratio.

UI values were found to be better correlated to BIC values (R²=0.47) compared to ISQ values (R²=0.39 for measurements in one direction and R²=0.18 for the other direction), which were shown to be dependent on the direction of measurements. Errors realized on the UI were around 3.3 times lower to the ones realized on the ISQ.

QUS provide a better estimation of dental implant stability compared to RFA. This study paves the way for the future clinical development of a medical device aiming at assessing dental implant stability in a patient-specific manner. Clinical studies should confirm these results in the future.

QUS provide a better estimation of dental implant stability compared to RFA. This study paves the way for the future clinical development of a medical device aiming at assessing dental implant stability in a patient-specific manner. Clinical studies should confirm these results in the future.

A decrease in posterior occlusal support is considered to increase the load on remaining teeth and thus accelerate tooth loss. Therefore, a follow-up study was carried out to perform a longitudinal analysis of the association between the posterior occlusal support region and tooth loss.

The participants of the study were 806 Suita Study participants who underwent physical health checkups both at baseline and at follow-up. The participants were classified into three groups by posterior occlusal support area (POSA) using the Eichner Index at baseline Perfect POSA group, Eichner A; Decreased POSA group, Eichner B1-3; and Lost POSA group, Eichner B4 and Eichner C1-2. Participants were also classified into two groups according to whether they had tooth loss during the follow-up period. Tooth loss risk factors were investigated through the construction of logistic regression models with tooth loss as the dependent variable and posterior occlusal support, sex, age, periodontal disease, stimulated salivary flow rate, smoking habit, drinking habit, denture wearing, utilization of dental services, brushing habits, diabetes mellitus, osteoporosis and number of years of follow-up as independent variables.

In the results of the logistic regression model, the adjusted odds ratio (95%CI) for tooth loss with the Perfect POSA group as the reference was 3.19 (1.98-5.14) for the Decreased POSA group and 4.57 (1.97-10.62) for the Lost POSA group.

This study showed that decreased POSA accelerated tooth loss in the general urban population.

This study showed that decreased POSA accelerated tooth loss in the general urban population.

This study aimed to evaluate the trueness and precision of complete-arch models printed with three-dimensional printers via three different printing technologies.

An arch-shaped master model was designed using software (RapidForm XOR2, 3D Systems Inc., USA), and the digital master model was printed 10 times with three-dimensional printers using stereolithography (SLA), direct light processing (DLP), and Polyjet technology (n = 30). The printed models were then scanned with an industrial scanner to create the respective digital models. All digital models were compared with the master model, and an evaluation of the trueness was performed by model superimposition with Geomagic Control software (3D Systems, Rock Hill, SC, USA). Precision was determined for each case by superimposing some combination of the 10 datasets in each group.

The trueness of the printed models was 46.2 µm for the DLP printer, 51.6 µm for the SLA printer, and 58.6 µm for the Polyjet printer. The DLP models were significantly better than the Polyjet models (p = .005). However, the Polyjet models (30.4 µm) were more precise than the SLA (37.6 µm) and DLP (43.6 µm) models (p < .001, p = .016). Furthermore, the SLA (11.8 µm) was the most accurate printer in the Z-direction (p = .016, p = .002).

The 3D printing technologies showed significant differences in the precision and trueness of complete-arch measurements. Although DLP was more accurate other tested 3D printers, the accuracy of all 3D printed models was within clinical tolerance, and they were clinically acceptable and could be used for the production of fixed restorations.

The 3D printing technologies showed significant differences in the precision and trueness of complete-arch measurements. Although DLP was more accurate other tested 3D printers, the accuracy of all 3D printed models was within clinical tolerance, and they were clinically acceptable and could be used for the production of fixed restorations.γ-Glutamyltranspeptidase (GGT) has been widely used as a marker enzyme of hepatic and biliary diseases and relations between various diseases and its activity have been studied extensively. Nevertheless, several of its fundamental enzymatic characteristics had not been elucidated. We obtained homogeneous preparation of GGTs from bacteria, characterized them, and elucidated its physiological function that is common to mammalian cells, using GGT-deficient E. coli. Prior to GGT of all living organisms, we also identified catalytic nucleophile of E. coli GGT and revealed the post-translational processing mechanism for its maturation, and also its crystal structure was determined. The reaction intermediate was trapped and the structure-based reaction mechanism was presented. As for its application, using its transferase activity, we developed the enzymatic synthesis of various γ-glutamyl compounds that are promising in food, nutraceutical and medicinal industries. We found GGT of Bacillus subtilis is salt-tolerant and can be used as a glutaminase, which is important in food industry, to enhance umami of food, such as soy sauce and miso. We succeeded in converting bacterial GGT to glutaryl-7-aminocephalosporanic acid acylase, which is an important enzyme in cephem antibiotics production, by site-directed and random mutagenesis.Ubiquitin is a small protein used for posttranslational modification and it regulates every aspect of biological functions. Through a three-step cascade of enzymatic action, ubiquitin is conjugated to a substrate. Because ubiquitin itself can be post-translationally modified, this small protein generates various ubiquitin codes and triggers differing regulation of biological functions. For example, ubiquitin itself can be ubiquitinated, phosphorylated, acetylated, or SUMOylated. Via the type three secretion system, some bacterial effectors also modify the ubiquitin system in host cells. This review describes the general concept of the ubiquitin system as well as the fundamental functions of ubiquitin in the regulation of cellular responses during inflammation and bacterial infection.While exploring phytotoxic metabolites from phytopathogenic fungi in the 1970s, we became interested in biosynthetic enzymes that catalyze Diels-Alder reactions involving biosynthesis of several phytotoxins that we isolated. Target enzymes were successfully characterized, and this triggered the identification of various Diels-Alderases in a recent decade. selleck products Through our Diels-Alderase project in 1990s, we recognized a highly efficient expression system of various biosynthetic genes with Aspergillus oryzae as a host. With the development of tools such as genomic data and bioinformatics analysis to identify biosynthetic gene clusters for natural products, we developed a highly reliable methodology such as hot spot knock-in to elucidate the biosynthetic pathways of representative fungal metabolites including phytotoxic substances. This methodology allows total biosynthesis of natural products and genome mining using silent biosynthetic gene clusters to obtain novel bioactive metabolites. Further applications of this technology are discussed.To address the climate change caused by anthropogenic emissions of greenhouse gases into the atmosphere, it is essential to understand and quantitatively elucidate their cycling on the Earth's surface. This paper first presents an overview of the global cycling of three greenhouse gases, carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O), followed by a description of their variations in the atmosphere. This paper then presents the recent global budgets of these greenhouse gases estimated using two different approaches, top-down and bottom-up. Discussions on our current knowledge regarding the global cycling of the three gases are also presented.

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