Oral frailty is defined as a decrease in oral function accompanied by a decrease in mental and physical functions. Studies showing that people with oral frailty are at high risk of physical frailty, sarcopenia, severe conditions requiring nursing care and death have been reported in Japan. An increase in life expectancy and maintenance of teeth result in a decrease in the effect of the number of teeth. In contrast, a decrease in oral function as a result of aging has been suggested to have major effects on dysfunction and mortality risk. The present report is a narrative review of major clinical studies on the relationships of the number of teeth, dentures, occlusion and oral function with longevity, with the aim of providing information for future studies centered on oral function in Japan or overseas. This review clearly shows the relationships of the number of teeth, dentures, and occlusion with health and longevity. Recent studies have shown that, besides maintenance of the number of teeth, attempting to maintain or increase oral function, having a good diet and maintaining nutritional status are all linked to general health. Decreased oral function is a major risk factor for developing malnutrition and sarcopenia. Oral frailty, a new concept that has been recently introduced in Japan, is considered to have major effects on dental and oral health policies in Japan, in the old‐age group, and is expected to be reflected in the dental and oral health policies of various countries, as they also predict increased life expectancies. Geriatr Gerontol Int 2020; ••: ••–••.
The quality of chimeric antigen receptor (CAR)-T cell products, including the expression of memory and exhaustion markers, has been shown to influence their long-term functionality. The manufacturing process of CAR-T cells should be optimized to prevent early T cell exhaustion during expansion. Activation of T cells by monoclonal antibodies is a critical step for T cell expansion, which may sometimes induce excess stimulation and exhaustion of T cells. Given that
piggyBac
transposon (PB)-based gene transfer could circumvent the conventional pre-activation of T cells, we established a manufacturing method of PB-mediated HER2-specific CAR-T cells (PB-HER2-CAR-T cells) that maintains their memory phenotype without early T cell exhaustion. Through stimulation of CAR-transduced T cells with autologous peripheral blood mononuclear cell-derived feeder cells expressing both truncated HER2, CD80, and 4-1BBL proteins, we could effectively propagate memory-rich, PD-1-negative PB-HER2-CAR-T cells. PB-HER2-CAR-T cells demonstrated sustained antitumor efficacy
in vitro
and debulked the HER2-positive tumors
in vivo
. Mice treated with PB-HER2-CAR-T cells rejected the second tumor establishment owing to the
in vivo
expansion of PB-HER2-CAR-T cells. Our simple and effective manufacturing process using PB system and genetically modified donor-derived feeder cells is a promising strategy for the use of PB-CAR-T cell therapy.
We examined factors related to dietary intake status (food form) of long-term care facility (LTCF) residents to identify factors related to proper food form choice for older individuals requiring nursing care. We surveyed 888 residents from 37 LTCFs in Japan. We evaluated basic information (age, sex, body mass index [BMI]), food form (swallowing-adjusted diet class), Barthel Index (BI), Clinical Dementia Rating (CDR), simply evaluated eating and swallowing functions, the number of present/functional teeth, oral diadochokinesis, repetitive saliva swallowing test (RSST), and modified water swallowing test. To clarify factors associated with food form, participants who had good nutrition by oral intake were categorized into the dysphagic diet (DD) and normal diet (ND) groups. Multi-level analyses were used to detect oral functions associated with food form status. Among objective assessments, BMI (odds ratio
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