Association between Kihon check list score and geriatric depression among older adults from ORANGE registry

Objective Older adults in Japan are tackling health-related challenges brought by comprehensive geriatric symptoms, such as physical and cognitive problems and social-psychological issues. In this nationwide study, we mainly focused on the Kihon checklist (KCL) as certificated necessity of long-term care for Japanese older adults and investigated whether the KCL score was associated with geriatric depression. In addition, we aimed to identify critical factors that influence the relationship between the KCL score and geriatric depression. Methods This survey was a cross-sectional observational study design, performed from 2013 to 2019. A total of 8,760 participants aged 65 years and over were recruited from five cohorts in Japan, consisting of 6,755 persons in Chubu, 1,328 in Kanto, 481 in Kyushu, 49 in Shikoku and 147 in Tohoku. After obtaining informed consent from each participant, assessments were conducted, and outcomes were evaluated according to the ORANGE protocol. We collected data on demographics, KCL, physical, cognitive and mental evaluations. To clarify the relationship between the KCL and geriatric depression or critical factors, a random intercept model of multi-level models was estimated using individual and provincial variables depending on five cohorts. Results The KCL score was correlated with depression status. Moreover, the results of a random intercept model showed that the KCL score and geriatric depression were associated, and its association was affected by provincial factors of slow walking speed, polypharmacy and sex difference. Conclusions These results suggest that provincial factors of low walking performance, polypharmacy and sex difference (female) might be clinically targeted to improve the KCL score in older adults

20１１ネン カラ ２０１３ネン ノ ヤマガタケン ニ オケル ミッツ ノ コトナル イデンシガタ ノ ハイエン マイコプラズマ ノ チイキテキ ヒロガリ ト マクロライド タイセイ カブ シュツゲン ノ タイミング ニ カンスル ケントウ

Background: We previously revealed that several multiple-locus variable-number tandem-repeat analyses（MLVA）and P1 types of Mycoplasma pneumoniae（M. pneumoniae）cocirculated between 2011 and 2013 in Yamagata, Japan. However, the regional spread of M. pneumoniae infection by genotype is not reported yet. It remains unclear whether there is a difference in the spread of macrolide-resistant M. pneumoniae among genotypes. Methods: Genotypes were labeled according to 4-locus（Mpn 13, 14, 15, and 16）MLVA and P1 types. A total of 208 strains belonging to three major genotypes, i.e., type 4-5-7-2, 1; 4-5-7-3, 1; and 3-5-6-2, 2c, were analyzed by combining with the information of macrolide resistance-associated mutation and the patients’ information including residence. Results and Discussion: The three genotypes were widely distributed over more than four cities and towns in Yamagata Prefecture, cocirculating between late 2011 and early 2013, and there was little difference in the duration of their epidemics. Timing of macrolide-resistant strain appearance during the epidemic period differed between type 4-5-7-2, 1 and type 4-5-7-3, 1, and it did not appear throughout type 3-5-6-2, 2c epidemic. These genotypic differences can account for the variation in the prevalence of macrolide resistance-associated mutations in each of the studied areas

Characterization of medaka PTEN genes and design of TALEN constructs.

<p><b>(A</b>) RT-PCR analysis of total RNA isolated from whole embryos of medaka was performed with two sets of primers designed to amplify almost the entire open reading frames of <i>ptena</i> (lane 1) and <i>ptenb</i> (lane 2). The arrow indicates the specific amplification products, with the faster-migrating bands being found to represent technical artifacts by sequencing analysis. Lane M, molecular size markers. (<b>B</b>) Products of medaka <i>ptena</i> and <i>ptenb</i> predicted from the sequences of the amplified cDNAs and database information. Arrowheads labeled #1 and #2 indicate the localization of the TALEN target sequences shown in (C). (<b>C</b>) TALEN target sites in <i>ptena</i> and <i>ptenb</i>.</p

Effects of LY294002 on vascular development and blood cell flow in <i>pten</i> dko embryos.

<p>(<b>A</b>) Wild-type or <i>pten</i> dko embryos were exposed (or not) to 15 μM LY294002 for 48 h beginning at 30 or 48 hpf. (<b>B</b>) At 7 dpf, the embryos were photographed and genotyped. The dko embryos treated with LY294002 developed partial Cuvierian ducts (4 of 4 treated at 30 hpf, and 2 of 3 treated at 48 hpf). The dko embryos not exposed to the drug (2/2) did not manifest vasculogenesis. X, no duct. (<b>C</b>) Snapshots from a movie of a 4-dpf dko embryo that had been treated with LY294002 for 48 h beginning at 30 hpf. Blood cells can be seen flowing through the Cuvierian duct (arrow). Times are indicated in seconds.</p

Effects of rapamycin on <i>pten</i> dko embryos.

<p>(<b>A</b>) A total of 41 embryos obtained from <i>ptena</i>^+/−<i>ptenb</i>^−/− parents was treated with 5 μM rapamycin for 96 h beginning at 26 hpf. (<b>B</b>) At 7 dpf, the embryos were photographed and genotyped. Eight of the 41 embryos had the <i>ptena</i>^−/−<i>ptenb</i>^−/− genotype (images 1–8), nine were <i>ptena</i>^+/−<i>ptenb</i>^−/−(image 9), and 10 were <i>ptena</i>^+/+<i>ptenb</i>^−/−(image 10). Partial Cuvierian ducts developed in seven of the eight dko embryos. X, no duct. (<b>C</b>) Snapshots from movies of the dko embryos shown in images 2 (upper) and 4 (lower) in (B). Blood cells can be seen flowing through the Cuvierian duct (upper) and the tail vascular duct (lower) indicated by the arrows. Times are in seconds.</p

PI3K-AKT signaling pathway activity in adult <i>pten</i> mutant medaka.

<p>Extracts (20 μg of protein) derived from the dorsal muscle of 7- to 10-mpf fish were subjected to immunoblot analysis with antibodies to phosphorylated (p) or total forms of AKT as well as with those to α-tubulin (loading control). Each lane corresponds to an individual. The pAKT/AKT ratio for individual fish of the indicated <i>pten</i> genotypes was determined by densitometry. There were another two independent replications that showed much the same results.</p

Establishment of <i>pten</i> knockout medaka with transcription activator–like effector nucleases (TALENs) as a model of PTEN deficiency disease

<div><p>Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)–AKT signaling pathway. The <i>PTEN</i> gene is a major tumor suppressor, with mutations of this gene occurring frequently in tumors of humans and mice. We have now developed mutant medaka deficient in PTEN with the use of transcription activator–like effector nuclease (TALEN) technology. Medaka possesses two <i>pten</i> genes, <i>ptena</i> and <i>ptenb</i>, similar to zebrafish. We established 16 <i>ptena</i> mutant lines and two <i>ptenb</i> mutant lines. Homozygous single <i>pten</i> mutants were found to be viable and fertile. In contrast, <i>pten</i> double-knockout (dko) embryos manifested severe abnormalities in vasculogenesis, eye size, and tail development at 72 hours post fertilization(hpf) and died before hatching. Immunoblot analysis revealed that the ratio of phosphorylated to total forms of AKT (pAKT/AKT) in <i>pten</i> dko embryos was four times that in wild-type embryos, indicative of up-regulation of signaling by the PI3K-AKT pathway. Treatment of <i>pten</i> dko embryos with the PI3K inhibitor LY294002 reduced the pAKT/AKT ratio by about one-half and partially rescued the defect in vasculogenesis. Additional inhibitors of the PI3K-AKT pathway, including rapamycin and <i>N</i>-α-tosyl-L-phenylalanyl chloromethyl ketone, also partially restored vasculogenesis in the dko embryos. Our model system thus allows <i>pten</i> dko embryos to be readily distinguished from wild-type embryos at an early stage of development and is suitable for the screening of drugs able to compensate for PTEN deficiency.</p></div