Booster COVID-19 mRNA vaccination ameliorates impaired B-cell but not T-cell responses in older adults.

Age-associated differences in the effect of repetitive vaccination, particularly on memory T-cell and B-cell responses, remain unclear. While older adults (aged ≥65 years) exhibited enhanced IgG responses following COVID-19 mRNA booster vaccination, they produced fewer spike-specific circulating follicular helper T cells-1 than younger adults. Similarly, the cytotoxic CD8 T-cell response remained diminished with reduced PD-1 expression even after booster vaccination compared with that in younger adults, suggesting impaired memory T-cell activation in older adults.

Mexiletine Block of Voltage-Gated Sodium Channels: Isoform- and State-Dependent Drug-Pore Interactions.

Mexiletine is a class Ib antiarrhythmic drug and is also used clinically to reduce or prevent myotonia. In addition, mexiletine has neuroprotective effects in models of brain ischemia. We compared state-dependent affinities of mexiletine for Na1.

The Validity and Reproducibility of Dietary Non-enzymatic Antioxidant Capacity Estimated by Self-administered Food Frequency Questionnaires.

Background: High dietary non-enzymatic antioxidant capacity (NEAC) has been inversely related to the incidence of degenerative diseases. However, few studies have investigated the validity and reproducibility of dietary NEAC estimated from a food frequency questionnaire (FFQ). We assessed the validity and reproducibility of FFQ-based dietary NEAC against a dietary record (DR).

The Impact of Menstrual Cycle Phases on Cardiac Autonomic Nervous System Activity: An Observational Study Considering Lifestyle (Diet, Physical Activity, and Sleep) among Female College Students.

Studies examining the impact of menstrual cycle phases on the cardiac autonomic nervous system have produced inconsistent results. This study aimed to investigate this relationship, controlling for the confounding effects of diet, physical activity, and sleep, which can be affected by the menstrual cycle. Fifteen female college students with regular menses were enrolled.

Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study.

Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse. We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.

Association of eating behaviours with diurnal preference and rotating shift work in Japanese female nurses: a cross-sectional study.

Objectives: Our study examines differences in eating behaviour between day workers and rotating shift workers, and considers whether diurnal preference could explain the differences.

Methods: Japanese female nurses were studied (39 day workers and 123 rotating shift workers, aged 21-63 years) using self-administered questionnaires. The questionnaires assessed eating behaviours, diurnal preference and demographic characteristics.

Validity of a Semi-Quantitative Food Frequency Questionnaire for Collegiate Athletes.

Background: Food frequency questionnaires (FFQs) have been developed and validated for various populations. To our knowledge, however, no FFQ has been validated for young athletes. Here, we investigated whether an FFQ that was developed and validated to estimate dietary intake in middle-aged persons was also valid for estimating that in young athletes.

[THE OPINION OF POPULATION CONCERNING ISSUE OF DRUG USE AS A SOCIAL HYGIENIC FACTOR].

The article indicates that in modern society the trends of reevaluation and redefinition of moral and social limits, regulating legitimate and non-legitimate pleasure. The popularity of programs of decreasing of narcotization harm is increasing to the prejudice of comprehensive conception of necessity of social prevention of drug abuse as a system of influence of public authorities and institutions of civil society with purpose to minimize drug effect. The modeling of such exposition pressure directing individual to "drug-independent" behavior by all totality of mechanisms society dispose is one of major tasks of drug abuse control.

Examining the relationship between vegetable intake of mothers and that of their children: a cross-sectional study of 10- to 12-year-old schoolchildren in Japan.

Objective: The present study aimed to investigate the correlation between mothers' and children's vegetable intake and whether children are conscious about their vegetable intake.

Design: Cross-sectional study. Self-administered questionnaires for mothers and children, consisting of items regarding diet history, were distributed to children via homeroom teachers.

Relationship Between Dietary Factors and Bodily Iron Status Among Japanese Collegiate Elite Female Rhythmic Gymnasts.

This cross-sectional study explored the prevalence of iron deficiency (ID) and associations between dietary factors and incidence of ID in female rhythmic gymnasts during preseason periods. Participants were 60 elite collegiate rhythmic gymnasts (18.1 ± 0.

Association of body mass index with lifestyle and rotating shift work in Japanese female nurses.

Objective: Higher body mass index (BMI) values have been reported in rotating shift workers compared with regular daytime workers. This study examines the relationship between work schedule and BMI, and considers whether lifestyle habits could explain the relationship.

Methods: Japanese female nurses (1179 day workers and 1579 rotating shift workers, aged 20-59) were studied using self-administered questionnaires.

Effects of feeding schedule changes on the circadian phase of the cardiac autonomic nervous system and serum lipid levels.

Purpose: The purpose of this study was to investigate whether scheduling meals earlier in the day affects the circadian phase of the cardiac autonomic nervous system as assessed by heart rate variability (HRV) and serum lipid levels.

Methods: Healthy men aged 21.4 ± 0.

Influence of dietary behavior on the circadian rhythm of the autonomic nervous system as assessed by heart rate variability.

Background: Misalignment of circadian systems is detrimental to human health. However, only a few studies have examined the influence of late meals on the human circadian system. The purpose of this study was to investigate whether delayed meals affect circadian rhythm as assessed by heart rate variability (HRV).

A genetically encoded bioluminescent indicator for the sodium channel activity in living cells.

We have developed a genetically encoded bioluminescent indicator for the Na(+) channel, in which Na(+)-sensitive Gaussia luciferase is fused with the voltage-gated Na(+) channel. This indicator is capable of detecting Na(+) flow through the pores of Na(+) channels. Because of high sensitivity and low background in luminescence assays, the absence of toxicity, and a wide linear dynamic range, this luciferase can be used to generate a novel, genetically encoded Na(+) channel indicator.

The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.

Phenotypic overlap of type 3 long QT syndrome (LQT3) with Brugada syndrome (BrS) is observed in some carriers of mutations in the Na channel SCN5A. While this overlap is important for patient management, the clinical features, prevalence, and mechanisms underlying such overlap have not been fully elucidated. To investigate the basis for this overlap, we genotyped a cohort of 44 LQT3 families of multiple ethnicities from 7 referral centers and found a high prevalence of the E1784K mutation in SCN5A.

Accessibility of mid-segment domain IV S6 residues of the voltage-gated Na+ channel to methanethiosulfonate reagents.

The inner pore of the voltage-gated Na+ channel is predicted by the structure of bacterial potassium channels to be lined with the four S6 alpha-helical segments. Our previously published model of the closed pore based on the KcsA structure, and our new model of the open pore based on the MthK structure predict which residues in the mid-portion of S6 face the pore. We produced cysteine mutants of the mid-portion of domain IV-S6 (Ile-1575-Leu-1591) in NaV 1.

Unexpected mexiletine responses of a mutant cardiac Na+ channel implicate the selectivity filter as a structural determinant of antiarrhythmic drug access.

Gating properties of Na(+) channels are the critical determinants for the state-dependent block by class I antiarrhythmic drugs; however, recent site-directed mutagenesis studies have shown that the Na(+) channel selectivity filter region controls drug access to and dissociation from the binding site. To validate these observations, we have exploited a naturally occurring cardiac Na(+) channel mutation, S1710L, located next to the putative selectivity filter residue of domain 4, and evaluated the pharmacological properties to mexiletine using whole-cell, patch-clamp recordings. Consistent with the large negative shift of steady-state inactivation and the enhanced slow inactivation, the S1710L channel showed greater mexiletine tonic block than wild-type (WT) channel.

Electrophysiological effects of ginseng and ginsenoside Re in guinea pig ventricular myocytes.

Panax ginseng is a folk medicine with various cardiovascular actions; however, its underlying mechanisms of action are not well known. In the present study, we examined the effects of ginseng and its main component, ginsenoside Re, on action potentials and membrane currents recorded from isolated guinea pig ventricular myocytes with the whole-cell patch clamp technique. Ginseng (1 mg/ml) shortened the action potential duration in a rate-dependent manner.

Involvement of local anesthetic binding sites on IVS6 of sodium channels in fast and slow inactivation.

Local anesthetics (LAs) block Na(+) channels with a higher affinity for the fast or slow inactivated state of the channel. Their binding to the channel may stabilize fast inactivation or induce slow inactivation. We examined the role of the LA binding sites on domain IV, S6 (IVS6) of Na(+) channels in fast and slow inactivation by studying the gating properties of the mutants on IVS6 affecting LA binding.

Cardiac-specific external paths for lidocaine, defined by isoform-specific residues, accelerate recovery from use-dependent block.

Local anesthetic antiarrhythmic drugs block voltage-gated Na(+) channels from the cytoplasmic side. In addition, cardiac Na(+) channels can be also blocked by the membrane-impermeant local anesthetic QX via external paths not present in skeletal muscle or brain channels. Introduction of cardiac isoform-specific residues into wild-type skeletal muscle or brain channels creates access paths for external QX block.

Structural and gating changes of the sodium channel induced by mutation of a residue in the upper third of IVS6, creating an external access path for local anesthetics.

Membrane-impermeant quaternary amine local anesthetics QX314 and QX222 can access their binding site on the cytoplasmic side of the selectivity filter from the outside in native cardiac Na(+) channels. Mutation of domain IV S6 Ile-1760 of rat brain IIA Na(+) channel or the equivalent (Ile-1575) in the adult rat skeletal muscle isoform (mu 1) creates an artificial access path for QX. We examined the characteristics of mutation of mu 1-I1575 and the resulting QX path.

A critical residue for isoform difference in tetrodotoxin affinity is a molecular determinant of the external access path for local anesthetics in the cardiac sodium channel.

Membrane-impermeant quaternary derivatives of lidocaine (QX222 and QX314) block cardiac Na(+) channels when applied from either side of the membrane, but they block neuronal and skeletal muscle channels poorly from the outside. To find the molecular determinants of the cardiac external QX access path, mutations of adult rat skeletal muscle (micro1) and rat heart (rH1) Na(+) channels were studied by two-electrode voltage clamp in Xenopus oocytes. Mutating the micro1 domain I P-loop Y401, which is the critical residue for isoform differences in tetrodotoxin block, to the heart sequence (Y401C) allowed outside QX222 block, but its mutation to brain type (Y401F) showed little block.

Sodium channel selectivity filter regulates antiarrhythmic drug binding.

Local anesthetic antiarrhythmic drugs block Na+ channels and have important clinical uses. However, the molecular mechanism by which these drugs block the channel has not been established. The family of drugs is characterized by having an ionizable amino group and a hydrophobic tail.