RNA binding protein CUGBP2/ETR-3 regulates STAT3 alternative splicing.

Signal transducer and activator of transcription 3 (STAT3) is a multifactorial regulator involved in many biological responses. Alternative splicing of STAT3 pre-mRNA leads to an internal 50-nucleotide deletion of exon 23 selecting an alternative 3' acceptor site, resulting in the generation of two splicing isoforms, STAT3α and STAT3β. STAT3β lacks 55 amino acid-residue transactivation domain at the C-terminal of STAT3α replacing seven unique amino acids.

Treatment strategies for insomnia in Japanese primary care physicians' practice: A Web-based questionnaire survey.

Background: It is unclear how primary care physicians manage insomnia after the introduction of novel hypnotics such as orexin receptor antagonists and melatonin receptor agonists. This Web-based questionnaire survey aimed to examine treatment strategies for insomnia in Japanese primary care practice.

Methods: One-hundred-and-seventeen primary care physicians were surveyed on the familiarity of each management option for insomnia on a binary response scale (0 = "unfamiliar"; 1 = "familiar") and how they managed insomnia using a nine-point Likert scale (1 = "I never prescribe/perform it"; 9 = "I often prescribe/perform it").

Clinical practice for unspecified anxiety disorder in primary care.

Aim: Clinicians face difficulties in making treatment decisions for unspecified anxiety disorder due to the absence of any treatment guidelines. The objective of this study was to investigate how familiar and how often primary care physicians use pharmacological and nonpharmacological approaches to manage the disorder.

Methods: A survey was conducted among 117 primary care physicians in Japan who were asked to assess the familiarity of using each treatment option for unspecified anxiety disorder on a binary response scale (0 = "unfamiliar," 1 = "familiar") and the frequency on a nine-point Likert scale (1 = "never used," 9 = "frequently used").

Development of Fortified Breads Enriched with Plant-Based Bioactive Peptides Derived from the Chia ( L.) Expeller.

By-products from the industrialization of oilseeds, particularly chia, can be sustainably used for the development of new functional products. In this work, wheat breads supplemented with up to 10 mg of chia expeller hydrolysate/g of flour were prepared, obtaining fortified breads with acceptability for consumption, according to a preliminary consumer research study based on an affective test employing a five-point hedonic scale of global acceptance. In this context, protein hydrolysates of the chia expeller were produced using Alcalase, reaching a degree of hydrolysis of 54.

Exploring the experiences and learning of young primary care physicians in disaster-affected areas: A qualitative study on the Great East Japan Earthquake.

Background: Primary care physicians (PCPs) play a critical role in disaster medicine. However, it is unclear how PCPs who provide chronic support to disaster-affected areas learn from their experiences.

Methods: This qualitative study investigates the learnings of young PCPs who provided medical care during the chronic phase of the Great East Japan Earthquake disaster.

Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET The Neurodiagnostic Society.

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These societies recognize that neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths.

Design and Pharmacological Chaperone Effects of -(4'-Phenylbutyl)-DAB Derivatives Targeting the Lipophilic Pocket of Lysosomal Acid α-Glucosidase.

This study provides the first example of a strategy to design a practical ligand toward lysosomal acid α-glucosidase (GAA) focusing on -alkyl derivatives of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB). The optimized -4'-(-trifluoromethylphenyl)butyl-DAB () showed a value of 0.73 μM, which was 353-fold higher affinity than -butyl-DAB () without a terminal phenyl group.

Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET - The Neurodiagnostic Society.

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET - The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These Societies recognize that Neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths.

Guidelines for Qualifications of Neurodiagnostic Personnel: A Joint Position Statement of the American Clinical Neurophysiology Society, the American Association of Neuromuscular & Electrodiagnostic Medicine, the American Society of Neurophysiological Monitoring, and ASET-The Neurodiagnostic Society.

The Guidelines for Qualifications of Neurodiagnostic Personnel (QNP) document has been created through the collaboration of the American Clinical Neurophysiology Society (ACNS), the American Society of Neurophysiological Monitoring (ASNM), the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM), and ASET-The Neurodiagnostic Society (ASET). The quality of patient care is optimized when neurophysiological procedures are performed and interpreted by appropriately trained and qualified practitioners at every level. These societies recognize that neurodiagnostics is a large field with practitioners who have entered the field through a variety of training paths.

Mental health training in family medicine residencies: International curriculum overview.

Integration of mental health into primary care has become a global trend, and many countries have developed mental health training in primary care. However, systematic mental health training for family physicians is insufficient in Japan. The newly established Japan Primary Care Association Mental Health Committee surveyed the current status of mental health training curricula in family medicine residency internationally.

Physicians' attitudes toward hypnotics for insomnia: A questionnaire-based study.

Introduction: Benzodiazepines and non-benzodiazepines are still widely prescribed despite safety concerns and the introduction of novel hypnotics (orexin receptor antagonists [ORA] and melatonin receptor agonists [MRA]), which may be influenced by physicians' attitudes toward hypnotics.

Methods: A questionnaire survey was administered to 962 physicians between October 2021 and February 2022, investigating frequently prescribed hypnotics and the reasons for their selection.

Results: ORA were the most frequently prescribed at 84.

Management of unspecified anxiety disorder: Expert consensus.

Aims: Treatment guidelines with respect to unspecified anxiety disorder have not been published. The aim of this study was to develop a consensus among field experts on the management of unspecified anxiety disorder.

Methods: Experts were asked to evaluate treatment choices based on eight clinical questions concerning unspecified anxiety disorder using a nine-point Likert scale (1 = "disagree" to 9 = "agree").

Nanomolar β-glucosidase and β-galactosidase inhibition by enantiomeric α-1-C-alkyl-1,4-dideoxy-1,4-imino-arabinitol derivatives.

A series of α-1-C-alkyl DAB (1,4-dideoxy-1,4-imino-d-arabinitol) and LAB (1,4-dideoxy-1,4-imino-l-arabinitol) derivatives with aryl substituents have been designed as analogues of broussonetine W (12), and assayed as glycosidase inhibitors. While the inhibition spectrum of α-1-C-alkyl DAB derivative 16 showed a good correlation to that of broussonetine W (12), introduction of substituents on the terminal aryl (17a-f) or hydroxyl groups at C-1' position of the alkyl chains (18a-e) decreased their α-glucosidase inhibitions but greatly improved their inhibitions of bovine liver β-glucosidase and β-galactosidase. Furthermore, epimerization of C-1' configurations of compounds 18a-e clearly lowered their inhibition potency of bovine liver β-glucosidase and β-galactosidase.

Intake of SBT2055 improves subjective symptoms of common cold during winter season in healthy adults: A randomized, double-blind, placebo-controlled parallel-group comparative study.

Objective: SBT2055 (LG2055) has been reported to show immunostimulating effects. This study aimed to investigate the effects of LG2055 on the subjective symptoms of the physical condition in healthy adults.

Materials And Methods: In this randomized, double-blind, placebo-controlled, parallel-group comparative study, Japanese individuals aged 20-64 years were recruited.

Attitudes and Difficulties Associated with Benzodiazepine Discontinuation.

Long-term use of benzodiazepine receptor agonists (BZDs) may depend on clinicians' BZD discontinuation strategies. We aimed to explore differences in strategies and difficulties with BZD discontinuation between psychiatrists and non-psychiatrists and to identify factors related to difficulties with BZD discontinuation. Japanese physicians affiliated with the Japan Primary Care Association, All Japan Hospital Association, and Japanese Association of Neuro-Psychiatric Clinics were surveyed on the following items: age group, specialty (psychiatric or otherwise), preferred time to start BZD reduction after improvement in symptoms, methods used to discontinue, difficulties regarding BZD discontinuation, and reasons for the difficulties.

C-6 fluorinated casuarines as highly potent and selective amyloglucosidase inhibitors: Synthesis and structure-activity relationship study.

A series of C-6 fluorinated casuarine derivatives have been synthesized via organocatalytic stereoselective α-fluorination of iminosugar-based aldehydes or direct nucleophilic fluorination of polyhydroxylated pyrrolizidines. Glycosidase assays against various glycosidases allowed systematic structure-activity relationship (SAR) study using molecular docking calculations. Introduction of fluorine atom(s) at C-6 position removed the trehalase and maltase inhibitory activities of all casuarine derivatives, and greatly increased their specificity towards amyloglucosidase.

trans, trans-2-C-Aryl-3,4-dihydroxypyrrolidines as potent and selective β-glucosidase inhibitors: Pharmacological chaperones for Gaucher disease.

Enantiomeric series of C-4 hydroxymethyl depleted DAB and LAB derivatives (trans, trans-2-C-aryl-3,4-dihydroxypyrrolidines), designed as β-glucosidase inhibitors by molecular docking calculations, have been synthesized in 2 steps from l- and d-tartaric acid derived enantiomeric cyclic nitrones 29L and 29D, respectively. Both series of C-4 hydroxymethyl depleted DAB and LAB derivatives 28Da-e and 28La-e, which are structurally trans, trans-2-C-aryl-3,4-dihydroxypyrrolidines, were potent and selective human lysosome acid β-glucosidase (GCase) inhibitors, of which 28Dd and 28Ld with C-4 biphenyls showed the highest potency relative to other compounds of the same series. The work provided a series of pyrrolidine-type potent and selective GCase inhibitors with minimal hydroxyl substitutions and synthetic procedures.

Diastereoselective Synthesis, Glycosidase Inhibition, and Docking Study of C-7-Fluorinated Casuarine and Australine Derivatives.

C-7-fluorinated derivatives of two important polyhydroxylated pyrrolizidines, casuarine and australine, were synthesized with organocatalytic stereoselective α-fluorination of aldehydes as the key step. The strategy is extensively applicable to some synthetically challenging fluorinated iminosugars and carbohydrates. The docking studies indicated that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are due to the interaction modes dominated by fluorine atoms in these iminosugars with the amino acids' residues of the corresponding enzymes.

Design, synthesis and glycosidase inhibition of C-4 branched LAB and DAB derivatives.

Two series of C-4 alkylated and arylated LAB (1,4-dideoxy-1,4-imino-l-arabinitol) and DAB (1,4-dideoxy-1,4-imino-d-arabinitol) derivatives, synthesized in 6 steps from enantiomeric cyclic nitrones derived from l- and d-tartaric acid, were designed and assayed against various glycosidases. C-4 Branched LAB alkyl and phenyl derivatives 5La-d showed potent α-glucosidase inhibition, particularly against human lysosomal acid α-glucosidase; C-4 DAB derivatives 5Da-d, with small alkyl groups, showed enhanced inhibition of rat intestinal maltase and sucrase. Both enantiomeric C-4 arylated derivatives 5Lf-l and 5Df-l exhibited potent and selective α-glucosidase inhibition; and compound 5Li with a para-electron donating group (EDG) on its C-4 aryl group, showed the most potent rat intestinal sucrase inhibition.

Synthesis, conformational analysis and glycosidase inhibition of bicyclic nojirimycin C-glycosides based on an octahydrofuro[3,2-b]pyridine motif.

A set of bicyclic iminosugar C-glycosides, based on an octahydrofuro[3,2-b]pyridine motif, has been synthesized from a C-allyl iminosugar exploiting a debenzylative iodocycloetherification and an iodine nucleophilic displacement as the key steps. The halogen allowed the introduction of a range of aglycon moieties of different sizes bearing several functionalities such as alcohol, amine, amide and triazole. In these carbohydrate mimics the fused THF ring forces the piperidine to adopt a flattened C conformation according to NMR and DFT calculations studies.

Stereocomplementary synthesis of casuarine and its 6--, 7--, and 6,7-di-stereoisomers.

Four diastereomers belonging to the family of casuarines, including casuarine (1), 6--casuarine (2), 7--casuarine (13) and 6,7-di-casuarine (14), have been synthesized from D-arabinose-derived cyclic nitrone 7 and nitrone-derived aldehyde 4 by a stereocomplementary strategy. Glycosidase inhibition comparison showed that 6--casuarine (2) exhibits enhanced inhibition of trehalase (IC = 9.7 μM) and 6,7-di-casuarine (14) leads to specific inhibition of trehalase.

Social Isolation and Patient Experience in Older Adults.

Purpose: Social isolation has been identified as a major health problem, particularly in the elderly. In the present study, we examine the association between social isolation and patient experience in elderly primary care patients.

Methods: This cross-sectional study was conducted in a primary care practice-based research network (28 clinics) in Japan.