Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells.

CRISPR/Cas9-mediated gene editing has great potential utility for treating genetic diseases. However, its therapeutic applications are limited by unintended genomic alterations arising from DNA double-strand breaks and random integration of exogenous DNA. In this study, we propose NICER, a method for correcting heterozygous mutations that employs multiple nicks (MNs) induced by Cas9 nickase and a homologous chromosome as an endogenous repair template.

Outcome of extracorporeal membrane oxygenation use in severe accidental hypothermia with cardiac arrest and circulatory instability: A multicentre, prospective, observational study in Japan (ICE-CRASH study).

Aim: To elucidate the effectiveness of extracorporeal membrane oxygenation (ECMO) in accidental hypothermia (AH) patients with and without cardiac arrest (CA), including details of complications.

Methods: This study was a multicentre, prospective, observational study of AH in Japan. All adult (aged ≥18 years) AH patients with body temperature ≤32 °C who presented to the emergency department between December 2019 and March 2022 were included.

Switching From Daily DPP-4 Inhibitor to Once-Weekly GLP-1 Receptor Activator Dulaglutide Significantly Ameliorates Glycemic Control in Subjects With Poorly Controlled Type 2 Diabetes Mellitus: A Retrospective Observational Study.

Aim: At present, daily DPP-4 inhibitors are quite frequently prescribed in subjects with type 2 diabetes mellitus (T2DM). Recently, it has been drawing much attention that once-weekly incretin-based injection dulaglutide was developed. In this study, we aimed to examine the possible effects of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide on glycemic control as well as various metabolic parameters.

Anesthetic management of a patient with severe aortic regurgitation undergoing reoperation for ascending aorta false aneurysm using hypothermia: prevention of ventricular fibrillation by nifekalant.

Background: To prevent cardiac collapse and to protect cerebral function, hypothermic cardiopulmonary bypass is established before resternotomy. However, ventricular fibrillation under hypothermia facilitates left ventricular distension, which causes irreversible myocardial damage when the patient has aortic regurgitation. We report a case of successful management in preventing ventricular fibrillation under hypothermia by using nifekalant.

Analysis of difficulty in placement of pulmonary artery catheter through the left internal jugular vein.

Purpose: The left internal jugular vein may be an alternative route for the placement of a pulmonary artery catheter when the right jugular vein is not available. Although the placement through the left internal jugular vein is expected to be more difficult, little has been written regarding difficulties in achieving proper placement of the catheter through the left internal jugular vein.

Methods: This prospective and observational study includes patients undergoing cardiac surgery with the catheter placement by monitoring the pressure waveform for 2 years.

Comparison of HbA1c levels and body mass index for prevention of diabetic kidney disease: A retrospective longitudinal study using outpatient clinical data in Japanese patients with type 2 diabetes mellitus.

Aim: This study examined the association among the onset of diabetic kidney disease (DKD), blood glucose levels (HbA1), and body mass index (BMI) in Japanese patients with type 2 diabetes mellitus.

Methods: Patients eligible for this study included those with type 2 diabetes who visited the outpatient clinic at Kawasaki Medical School Hospital between 2000 and 2018 and were followed up for more than two years. The Cox proportional hazards model was used in four categories of subjects: at the beginning of the follow-up period, "controlled" or "uncontrolled" glycemic control based on HbA1c and "overweight" or "non-overweight" based on BMI.

Delayed diagnosis of traumatic ventricular septal perforation in penetrating chest injury: hematoma formation in the ventricular septum in CT suggests perforation.

Background: Ventricular septal perforation (VSP) can be caused by a penetrating cardiac injury. Diagnosis of VSP tends to be delayed because a shunt might not be detected by color flow Doppler at an early stage following injury.

Case Presentation: A 60-year-old man with depression was admitted to the emergency center after a knife injury in the chest.

Eicosapentaenoic acid/arachidonic acid ratio and weight loss during hospitalization for glycemic control among overweight Japanese patients with type 2 diabetes: a retrospective observational study.

Background: The study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes.

Methods: The study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models.

Cortical and Subcortical Projections from Granular Insular Cortex Receiving Orofacial Proprioception.

We have recently revealed that the proprioceptive signal from jaw-closing muscle spindles (JCMSs) is conveyed to the dorsal part of granular insular cortex rostroventrally adjacent to the rostralmost part of secondary somatosensory cortex (dGIrvs2) via the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM) in rats. However, it remains unclear to which cortical or subcortical structures the JCMS proprioceptive information is subsequently conveyed from the dGIrvs2. To test this issue, we injected an anterograde tracer, biotinylated dextranamine, into the electophysiologically identified dGIrvs2, and analyzed the resultant distribution profiles of labeled axon terminals in rats.

Survey of Denture Repair Cases: Denture Reinforcement Makes Patients Able to Use Their Dentures for Longer Periods.

Purpose: To evaluate the long-term effects of preventive measures against denture fracture using clinical surveys of denture fracture cases from 1984 and 2009.

Materials And Methods: This study included 128 patients who presented with a chief complaint of denture fracture and received denture repair treatment in 2009. The following data were collected: denture repair procedure; location of denture base fracture (with or without reinforcement); and period of denture use from insertion to repair.

Effect of Attachment Type on Implant Strain in Maxillary Implant Overdentures: Comparison of Ball, Locator, and Magnet Attachments. Part 2: Palateless Dentures.

Purpose: Palateless maxillary implant overdentures are often used for patients experiencing problems with a full-palate denture. However, palateless overdentures are reported to be a risk factor for implant complications. The purpose of this study was to examine the strain on implants beneath palateless overdentures with unsplinted attachments under various implant distributions.

Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168.

The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168 by ubiquitylated targets involves two distinct regions, Ub-dependent DSB recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the complex between UDM1 and Lys63-linked diUb (K63-Ub) and that between the C-terminally truncated UDM2 (UDM2ΔC) and K63-Ub.

Precise and efficient nucleotide substitution near genomic nick via noncanonical homology-directed repair.

CRISPR/Cas9, which generates DNA double-strand breaks (DSBs) at target loci, is a powerful tool for editing genomes when codelivered with a donor DNA template. However, DSBs, which are the most deleterious type of DNA damage, often result in unintended nucleotide insertions/deletions (indels) via mutagenic nonhomologous end joining. We developed a strategy for precise gene editing that does not generate DSBs.

Abiotic Stress Phenotypes Are Associated with Conserved Genes Derived from Transposable Elements.

Plant phenomics offers unique opportunities to accelerate our understanding of gene function and plant response to different environments, and may be particularly useful for studying previously uncharacterized genes. One important type of poorly characterized genes is those derived from transposable elements (TEs), which have departed from a mobility-driven lifestyle to attain new adaptive roles for the host (exapted TEs). We used phenomics approaches, coupled with reverse genetics, to analyze T-DNA insertion mutants of both previously reported and novel protein-coding exapted TEs in the model plant .

Thalamo-insular pathway conveying orofacial muscle proprioception in the rat.

Little is known about how proprioceptive signals arising from muscles reach to higher brain regions such as the cerebral cortex. We have recently shown that a particular thalamic region, the caudo-ventromedial edge (VPMcvm) of ventral posteromedial thalamic nucleus (VPM), receives the proprioceptive signals from jaw-closing muscle spindles (JCMSs) in rats. In this study, we further addressed how the orofacial thalamic inputs from the JCMSs were transmitted from the thalamus (VPMcvm) to the cerebral cortex in rats.

Influence of Abutment Angle on Implant Strain When Supporting a Distal Extension Removable Partial Dental Prosthesis: An In Vitro Study.

Purpose: This study evaluated the impact of angled abutments on strain in implants supporting a distal extension removable partial denture.

Materials And Methods: An in vitro model of an implant supporting a distal extension removable partial denture was developed. The implant was positioned with a 17- or 30-degree mesial inclination, with either a healing abutment or a corrective multiunit abutment.

Root Fracture of Abutment Teeth for Partial Removable Dental Prostheses.

Purpose: Root fracture is a common and serious cause of abutment tooth loss. No studies to date have comprehensively assessed the individual contributions of the factors that increase stress on abutment teeth. The purpose of this study was to analyze the stress distribution in abutment teeth based on a three-dimensional finite element model and to analyze the factors that affect stress distribution.

Influence of Palatal Coverage and Implant Distribution on Denture Strain in Maxillary Implant Overdentures.

Purpose: As maxillary implant overdentures are being increasingly used in clinical practice, prosthodontic complications related to these dentures are also reported more often. The purpose of this study was to examine the influence of palatal coverage and implant distribution on the shear strain of maxillary implant overdentures.

Materials And Methods: A maxillary edentulous model with implants inserted in the anterior, premolar, and molar areas was fabricated.

Loading Variables on Implant-Supported Distal-Extension Removable Partial Dentures: An In Vitro Pilot Study.

Purpose: The aim of this study was to investigate strain on implants used for adjunctive support of distal extension removable partial dentures.

Materials And Methods: An implant with strain gauges was used for testing purposes in two positions, parallel and inclined. Three loading scenarios--loading apparatus (LA), artificial teeth via cotton roll (CR), and artificial teeth (UT)--were studied and strains compared via the Kruskal-Wallis test (P=.

A Comprehensive Approach to Assess Arabidopsis Survival Phenotype in Water-Limited Condition Using a Non-invasive High-Throughput Phenomics Platform.

With the rapid rise in global population and the challenges caused by climate changes, the maximization of plant productivity and the development of sustainable agriculture strategies are vital for food security. One of the resources more affected in this new environment will be the limitation of water. In this study, we describe the use of non-invasive technologies exploiting sensors for visible, fluorescent, and near-infrared lights to accurately screen survival phenotypes in Arabidopsis thaliana exposed to water-limited conditions.

The Influence of Loading Variables on Implant Strain When Supporting Distal-Extension Removable Prostheses: An In Vitro Study.

Purpose: The purpose of this study was to determine the implant stress under distalextension removable prostheses (DERPs).

Materials And Methods: A mandibular distal-extension cast and denture were fabricated. Strain gauges were attached to the implant, which was placed either parallel to the distal abutment or perpendicular to the ridge crest (inclined).

A diffraction-quality protein crystal processed as an autophagic cargo.

Crystallization of proteins may occur in the cytosol of a living cell, but how a cell responds to intracellular protein crystallization remains unknown. We developed a variant of coral fluorescent protein that forms diffraction-quality crystals within mammalian cells. This expression system allowed the direct determination of its crystal structure at 2.

Rapid evaluation of a protein-based voltage probe using a field-induced membrane potential change.

The development of a high performance protein probe for the measurement of membrane potential will allow elucidation of spatiotemporal regulation of electrical signals within a network of excitable cells. Engineering such a probe requires a functional screen of many candidates. Although the glass-microelectrode technique generally provides an accurate measure of a given test probe, throughputs are limited.