Efficacy and Tolerability of Lacosamide in Pediatric and Young Adult Epilepsy Patients with Severe Motor and Intellectual Disabilities.

Objective:  Epilepsy is common among patients with severe motor and intellectual disabilities (SMID) patients, often taking a prolonged and intractable course. Lacosamide (LCM) is widely used to treat epilepsy in both adults and children. We assess the efficacy and tolerability of LCM among pediatric and young adult epilepsy patients with SMID who suffer from intractable seizures.

Effects of quorum sensing-interfering agents, including macrolides and furanone C-30, and an efflux pump inhibitor on nitrosative stress sensitivity in .

Long-term administration of certain macrolides is efficacious in patients with persistent pulmonary infection, despite how limited the clinically achievable concentrations are, being far below their MICs. An increase in the sub-MIC of macrolide exposure-dependent sensitivity to nitrosative stress is a typical characteristic of . However, a few clinical isolates do not respond to sub-MIC of macrolide treatment.

BRZ-INSENSITIVE-LONG HYPOCOTYL8 inhibits kinase-mediated phosphorylation to regulate brassinosteroid signaling.

Glycogen synthase kinase 3 (GSK3) is an evolutionarily conserved serine/threonine protein kinase in eukaryotes. In plants, the GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 (BIN2) functions as a central signaling node through which hormonal and environmental signals are integrated to regulate plant development and stress adaptation. BIN2 plays a major regulatory role in brassinosteroid (BR) signaling and is critical for phosphorylating/inactivating BRASSINAZOLE-RESISTANT 1 (BZR1), also known as BRZ-INSENSITIVE-LONG HYPOCOTYL 1 (BIL1), a master transcription factor of BR signaling, but the detailed regulatory mechanism of BIN2 action has not been fully revealed.

One-pot synthesis of 2,5-diketopiperazine with high titer and versatility using adenylation enzyme.

2,5-Diketopiperazine (DKP) is a cyclic peptide composed of two amino acids and has been recently reported to exhibit various biological activities. DKPs have been synthesized using various methods. In chemical synthesis, a multi-step reaction requiring purification and racemization is problematic.

Enhanced production of Shiga toxin 1 in enterohaemorrhagic by oxygen.

Enterohaemorrhagic (EHEC) produces Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). Although and were found within the late operons of the Stx-encoding phages (Stx-phages), could mainly be transcribed from the promoter (), which represents the functional operator-binding site (Fur box) for the transcriptional regulator Fur (ferric uptake regulator), upstream of . In this study, we found that the production of Stx1 by EHEC was affected by oxygen concentration.

Pd-Catalyzed Indolization/-C-H Annulation/-Dealkylation Cascade to Cyclopenta-Fused Acenaphtho[1,2-]indole Scaffold.

A novel Pd-catalyzed cascade reaction of ,-dialkyl-substituted -alkynylanilines involving an indolization/-C-H annulation/-dealkylation sequence has been developed to construct a cyclopenta-fused acenaphtho[1,2-]indole (ANI) scaffold. A variety of aromatic hydrocarbons having a -C-H bond at the alkynyl terminus, such as naphthalene, phenanthrene, pyrene, and fluoranthene, were employed, affording the corresponding π-extended ANI derivatives. The ANI molecules showed relatively narrow energy gaps by increasing HOMOs and lowering LUMOs, implying their potential applications as π-segments in low-band-gap materials.

A pilot study verifying the effectiveness of high-frequency repetitive transcranial magnetic stimulation in combination with intensive speech-language-hearing therapy in patients with chronic aphasia.

Background: A lot of research on the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in patients with aphasia in the chronic stage deals with low-frequency stimulation, and reports on high-frequency stimulation (HF-rTMS) are scarce.

Objective: The purpose of this study was to evaluate retrospectively the effectiveness of high-frequency rTMS in combination with intensive speech-language-hearing therapy (ST) following the identification of the stimulation site using functional magnetic resonance imaging (fMRI) before, after the procedure and at 3 months in patients with aphasia in the chronic stage.

Methods: 20 patients with aphasia in the chronic stage who met the eligibility criteria for rTMS therapy and who underwent HF-rTMS for the first time were included in the present study.

Digital therapeutics for essential hypertension using a smartphone application: A randomized, open-label, multicenter pilot study.

Hypertension is the most considerable but treatable risk factor for cardiovascular disease. Although physicians prescribe multiple antihypertensive drugs and promote lifestyle modifications, the real-world blood pressure (BP) control rate remains poor. To improve BP target achievement, we developed a novel digital therapeutic-the HERB software system -to manage hypertension.

Synthesis of Decaarylanthracene with Nine Different Substituents.

A synthesis of decaarylanthracene with nine different substituents has been accomplished by a coupling/ring-transformation strategy. The oxidation of tetraarylthiophenes with four different substituents to the corresponding thiophene -oxides and a [4 + 2] cycloaddition with a double benzyne precursor afforded a multiply arylated naphthalene derivative. Subsequently, the naphthalene derivative was converted into a naphthalyne, and then a [4 + 2] cycloaddition of another thiophene -oxide provided decaarylanthracenes with nine different aryl groups.

A multicenter clinical trial to assess the efficacy of the digital therapeutics for essential hypertension: Rationale and design of the HERB-DH1 trial.

Digital therapeutics is a new approach to treat hypertension via using software programs such as smartphone apps and/or device algorithms. We develop a HERB system-new interactive smartphone app (HERB Mobile) with web-based patient management console (HERB Console)-to lower blood pressure (BP) based on an algorithm that helps users to promote lifestyle modifications in conjunction with medically validated non-pharmacological interventions. The app can assess the personalities, behavior characteristics, and hypertension determinants of each patient with hypertension to provide adequate guidance.

Repetitive peripheral magnetic stimulation combined with intensive physical therapy for gait disturbance after hemorrhagic stroke: an open-label case series.

In this pilot study, we aimed to determine the safety and feasibility of a 15-day protocol consisting of in-hospital repetitive peripheral magnetic stimulation (rPMS) combined with intensive physical therapy for the recovery of the gait disturbance in chronic stroke patients with lower limb hemiparesis. Seven hemorrhagic stroke patients with lower limb hemiparesis and gait disturbance (age: 50-78; time from onset of stroke: 7-107 months) were enrolled. rPMS was applied to the muscles of the paretic lower limb with a parabolic coil.

Dose-response of rPMS for upper Limb hemiparesis after stroke.

Introduction: Repetitive peripheral magnetic stimulation (rPMS) therapy is an innovative and minimally invasive neurorehabilitative technique and has been shown to facilitate neural plasticity. However, there is at present no research that clarifies the dose-response of rPMS therapy on the recovery of upper limb hemiparesis after stroke. This trial aims to clarify the dose-response of rPMS therapy combined with intensive occupational therapy (OT) for chronic stroke patients with moderate to severe upper limb hemiparesis.

A randomized controlled trial of a smoking cessation smartphone application with a carbon monoxide checker.

Evidence of the long-term efficacy of digital therapies for smoking cessation that include a smartphone application (app) is limited. In this multi-center randomized controlled trial, we tested the efficacy of a novel digital therapy for smoking cessation: the "CureApp Smoking Cessation (CASC)" system, including a CASC smartphone app, a web-based patient management PC software for primary physicians, and a mobile exhaled carbon monoxide (CO) checker. A total of 584 participants with nicotine dependence were recruited from October 2017 to January 2018, and allocated 1:1 to the CASC intervention group or the control group.

Synthesis of d-Amino Acid-Containing Dipeptides Using the Adenylation Domains of Nonribosomal Peptide Synthetase.

Recent papers have reported dipeptides containing d-amino acids to have novel effects that cannot be observed with ll-dipeptides, and such dipeptides are expected to be novel functional compounds for pharmaceuticals and food additives. Although the functions of d-amino acid-containing dipeptides are gaining more attention, there are few reports on the synthetic enzymes that can accept d-amino acids as substrates, and synthetic methods for d-amino acid-containing dipeptides have not yet been constructed. Previously, we developed a chemoenzymatic system for amide synthesis that comprised enzymatic activation and a subsequent nucleophilic substitution reaction.

Impact of a Novel Smartphone App (CureApp Smoking Cessation) on Nicotine Dependence: Prospective Single-Arm Interventional Pilot Study.

Background: Mobile apps have been considered to provide active and continuous support for smoking cessation. However, it is yet to be known whether a smoking cessation smartphone app improves long-term abstinence rates in nicotine-dependent patients.

Objective: This study aimed to evaluate the long-term abstinence effect of a novel smartphone app, CureApp Smoking Cessation (CASC), in patients with nicotine dependence.

A Novel Smoking Cessation Smartphone App Integrated With a Mobile Carbon Monoxide Checker for Smoking Cessation Treatment: Protocol for a Randomized Controlled Trial.

Background: Smoking cessation treatment programs have been widely available for patients with nicotine dependence. Despite intensive programs, the continuous abstinence rate (CAR) from weeks 9-12 is still about 50%. Recently, a smartphone app emerged as a novel tool for therapeutic interventions, including nicotine dependence.

Modular synthesis of heptaarylindole.

The first synthesis of heptaarylindole (HAI) has been accomplished using a coupling/ring transformation strategy. Four readily prepared modular units (diarylthiophenes, 2-arylaziridines, arylboronic acids, and arylalkynes) were joined together to provide key ynamide intermediates. Subsequent inverse electron-demand intramolecular [4 + 2] cycloaddition furnished pentaarylindoles (PAIs) regioselectively.

Pd-Catalyzed Decarbonylative C-H Coupling of Azoles and Aromatic Esters.

A decarbonylative C-H coupling of azoles and aromatic esters by palladium catalysis is described. Our previously reported Ni-catalyzed C-H coupling of azoles and aromatic esters has a significant drawback regarding the substrate scope. Herein, we employ palladium catalysis instead of nickel, resulting in a broader substrate scope in terms of azoles and aromatic esters.

A chemoenzymatic process for amide bond formation by an adenylating enzyme-mediated mechanism.

Amide bond formation serves as a fundamental reaction in chemistry, and is practically useful for the synthesis of peptides, food additives, and polymers. However, current methods for amide bond formation essentially generate wastes and suffer from poor atom economy under harsh conditions. To solve these issues, we demonstrated an alternative synthesis method for diverse tryptophyl-N-alkylamides by the combination of the first adenylation domain of tyrocidine synthetase 1 with primary or secondary amines as nucleophiles.

Production of aminoacyl prolines using the adenylation domain of nonribosomal peptide synthetase with class III polyphosphate kinase 2-mediated ATP regeneration.

An ATP regeneration system is advantageous for industrial processes that are coupled with ATP-dependent enzymes. For ATP regeneration from AMP, a few methods have been reported; however, these methods employ multiple enzymes. To establish an ATP regeneration system using a single enzyme, we focused on class III polyphosphate kinase 2 (class III PPK2) that can synthesize ATP from AMP and polyphosphate.

Synthesis of Octaaryl Naphthalenes and Anthracenes with Different Substituents.

A synthesis of multiply arylated naphthalenes and anthracenes with eight different substituents has been accomplished. The key intermediates are tetraarylthiophene S-oxides, which are synthesized through a method involving sequential C-H arylation and cross-coupling from 3-methoxythiophene, followed by oxidation of the sulfur atom. The resulting tetraarylthiophene S-oxides can be converted into a tetraaryl benzynes or naphthalynes and then merged through [4+2] cycloaddition reaction with another tetraarylthiophene S-oxide, thereby resulting in the programmed synthesis of octaarylnaphthalenes and octaarylanthracenes.

Ligand Promoted meta-C-H Chlorination of Anilines and Phenols.

Pd-catalyzed meta-C-H chlorination of anilines and phenols is developed using norbornene as the mediator. Heterocycles, including indole, thiophene, and indazole, are tolerated. The identification of a new pyridone-based ligand is crucial for the success of this meta-C-H chlorination reaction.