A novel 7-phenoxy-benzimidazole derivative as a potent and orally available BRD4 inhibitor for the treatment of melanoma.

The bromodomain-containing protein 4 (BRD4), which is a key epigenetic regulator in cancer, has emerged as an attractive target for the treatment of melanoma. In this study, we investigate 7-phenoxy-benzimidazole derivative 12, which is a novel BRD4 inhibitor for the treatment of melanoma, by performing scaffold hopping on the previously reported benzimidazole derivative 1. Despite their good oral and intravenous exposure, the compounds obtained by modifying derivate 1 exhibit mutagenicity, which was confirmed by the positive Ames test results.

Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study.

Introduction: We hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).

Research Design And Methods: We conducted an efficacy-implementation pilot study of MPE for T2D and CKD for primary care provider (PCP)-patient dyads at an academic health system. MPE included (1) a dashboard to identify patients without a prescription for sodium-glucose cotransporter-2 inhibitors (SGLT2i) and without a maximum dose prescription for renin-angiotensin-aldosterone system inhibitors (RAASi), (2) a multidisciplinary team of specialists to provide recommendations using e-consult templates, and (3) a workflow to deliver timely e-consult recommendations to PCPs.

Reduced menthol sensitivity in a prodromal Parkinson's disease model induced by intranasal rotenone treatment.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms, and it is associated with several prodromal non-motor symptoms, including an impaired sense of smell, taste and touch. We previously reported that bitter taste impairments occur independently of olfactory impairments in an early-stage PD animal model using short-term intranasal rotenone-treated mice. Cool temperatures also affect bitter taste perception, but it remains unclear whether or not bitter taste impairments result from an altered sensitivity for intraoral cool stimuli.

Discovery of a potent, orally available tricyclic derivative as a novel BRD4 inhibitor for melanoma.

The epigenetic regulation of the protein bromodomain-containing protein 4 (BRD4) has emerged as a compelling target for cancer treatment. In this study, we outline the discovery of a novel BRD4 inhibitor for melanoma therapy. Our initial finding was that benzimidazole derivative 1, sourced from our library, was a powerful BRD4 inhibitor.

Validity of computed mean compressed fibroglandular tissue thickness and breast composition for stratification of masking risk in Japanese women.

Background: The volumetric measurement system for mammographic breast density is a high-precision objective method for evaluating the percentage of fibroglandular tissue volume (FG%). Nonetheless, FG% does not precisely correlate with subjective visual estimation (SVE) and shows poor evaluation performance regarding masking risk in patients with comparatively thin compressed breast thickness (CBT), commonly found in Japanese women. We considered that the mean compressed fibroglandular tissue thickness (mCGT), which incorporates the CBT element into the evaluation of breast density, may better predict masking risk.

Effects of jaw movement in bimaxillary orthognathic surgery on the upper airway: Computational fluid dynamics analysis.

Maxillomandibular repositioning in orthognathic surgeries has both morphologic and functional effects. These surgeries are thought to change the pharyngeal space and cause obstructive sleep apnoea syndrome, however. The primary purpose of this study is to evaluate the effects of jaw movement in bimaxillary orthognathic surgery on airway function and to identify the morphometric factors that can predict postoperative airway function.

Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation).

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C).

Aerosol-generating procedures, how best did anesthesiologists use available personal protective equipment during early COVID-19 pandemic in a tertiary care center of southern India? A prospective cross-sectional study.

Background And Aims: Anesthesiologists are involved in high-risk procedures for transmission of SARS-CoV-2 like aerosol-generating procedures (AGPs). The present study was conducted to assess the compliance toward the use of personal protective equipment (PPE) and proposed modifications in anesthesia techniques to prevent dissemination of the virus among healthcare workers.

Material And Methods: This prospective cross-sectional study was conducted during the first wave of the COVID-19 pandemic and included all elective surgeries involving AGPs inside operation theatres and remote areas.

Silent Corticotroph and Somatotroph Double Pituitary Adenoma: A Case Report and Review of Literature.

Clinically silent double pituitary adenomas consisting of corticotroph and somatotroph cells are an exceedingly rare clinical finding. In this report, we present the case of a 28-year-old man with a 1-year history of recurrent headaches. Imaging revealed a 2.

Photo-modulation of supramolecular polymorphism in the self-assembly of a scissor-shaped azobenzene dyad into nanotoroids and fibers.

Recent advances in the research field of supramolecularly engineered dye aggregates have enabled the design of simple one-dimensional stacks such as fibers and of closed structures such as nanotoroids (nanorings). More complex and advanced supramolecular systems could potentially be designed using a molecule that is able to provide either of these distinct nanostructures under different conditions. In this study, we introduced bulky but strongly aggregating cholesterol units to a scissor-shaped azobenzene dyad framework, which affords either nanotoroids, nanotubes, or 1D fibers, depending on the substituents.

Non-surgical Interventions for Pituitary Lesions.

There have been numerous advancements in the variety of nonsurgical therapies available to achieve control of pituitary tumor size and hormone production. Medical therapies may target the pituitary tumor directly or the downstream hormonal pathways and receptors. Combination therapies may further improve clinical outcomes.

Three-dimensional Analysis of Factors Related to the Effective Alveolar Molding in Presurgical Infant Orthopedics: Findings From a Pilot Study.

Objective: Presurgical infant orthopedics (PIO) reduces the severity of the original cleft and burden on patients and their parents, provides better esthetics and function, and enables surgeons to achieve better surgical repair. To reduce the alveolar cleft width and to predict treatment difficulty using PIO, various measures were examined in pretreatment cast models.

Design: Retrospective case-control pilot study.

Development of a flavor hop (Humulus lupulus L.) cultivar, 'Furano Magical', with cones rich in 4-methyl-4-sulfunylpentan-2-one.

Background: Flavor hops (Humulus lupulus L.) are recognized as key raw materials that impart unique flavors to beer, especially in the emerging craft-beer industry. In this study the sensory evaluation of hop cone aromas using hop water extract by boiling (HWEB) was applied to develop new flavor hop cultivars in a screening from tens of varieties and breeding lines.

Effects of episodic slow slip on seismicity and stress near a subduction-zone megathrust.

Slow slip phenomena deep in subduction zones reveal cyclic processes downdip of locked megathrusts. Here we analyze seismicity within a subducting oceanic slab, spanning ~50 major deep slow slip with tremor episodes over 17 years. Changes in rate, b-values, and stress orientations of in-slab seismicity are temporally associated with the episodes.

Clinical and Bacteriologic Characteristics of Six Cases of Bifidobacterium breve Bacteremia Due to Probiotic Administration in the Neonatal Intensive Care Unit.

Background: Bifidobacterium breve is widely used as a probiotic in preterm infants and children with congenital surgical conditions, however, some cases of probiotics-induced bacteremia have been reported recently.

Objectives: To examine the clinical and bacteriologic features of Bifidobacterium breve bacteremia caused by a probiotic (BBG-01) in term and preterm infants.

Methods: We included 298 patients who were admitted to the neonatal intensive care unit of Miyagi Children's Hospital and were given BBG-01 as a probiotic within the period June 2014 to February 2019.

Biasing the Hierarchy Motifs of Nanotoroids: from 1D Nanotubes to 2D Porous Networks.

Hierarchical organization of self-assembled structures into superstructures is omnipresent in Nature but has been rarely achieved in synthetic molecular assembly due to the absence of clear structural rules. We herein report on the self-assembly of scissor-shaped azobenzene dyads which form discrete nanotoroids that further organize into 2D porous networks. The steric demand of the peripheral aliphatic units diminishes the trend of the azobenzene dyad to constitute stackable nanotoroids in solution, thus affording isolated (unstackable) nanotoroids upon cooling.

Role of reduced enamel epithelium in root resorption.

Background: The precise mechanism of root resorption in human primary teeth is unclear. However, research has suggested that the enamel organ and dental follicle of the successive (permanent) teeth are important for this process. This review focuses on the mechanism of root resorption.

Orthodontic treatment of a skeletal Class III malocclusion with severe root resorption of the maxillary anterior teeth. Autotransplantation using a 3-dimensional printed replica of the donor tooth.

This case report describes the successful orthodontic treatment of a 12-year-old girl with skeletal Class III malocclusion and severe root resorption of the maxillary anterior teeth. Ectopic eruption and mesial inclination of the bilateral maxillary canines caused severe root resorption of the right central and lateral incisors and the left lateral incisor. These 3 teeth were extracted, and traction was applied to the maxillary right and left canines toward the extracted right central incisor and left lateral incisor, respectively.

Scissor-Shaped Photochromic Dyads: Hierarchical Self-Assembly and Photoresponsive Property.

Unique relationships between hierarchically organized biological nanostructures and functions have motivated chemists to construct sophisticated artificial nanostructured systems from small and simple synthetic molecules through self-assembly. As one of such sophisticated systems, we have investigated scissor-shaped photochromic dyads that can hierarchically self-assemble into discrete nanostructures showing photoresponsive properties. We synthesized various azobenzene dyads and found that these dyads adopt intramolecularly folded conformation like a closed scissor, and then self-assemble into toroidal nanostructures by generating curvature.