Association between Oral Frailty and Dietary Variety among Community-Dwelling Older Persons: A Cross-Sectional Study.

OBJECTIVE: To examine the association between the severity of oral frailty (OF), which is one of the comprehensive oral functions evaluated, and dietary variety in community-dwelling older persons. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: A total of 769 community-dwelling older persons aged 65 and over. INTERVENTIONS: We examined basic demographic information, functional status, cognitive status, depressive symptoms, medical history, and oral functions of the participants. MEASUREMENTS: OF was defined by 1-2 and 3 or more of 6 items of oral function evaluation in the pre-oral frailty and oral frailty groups, respectively. Dietary variety was assessed using the dietary variety score (DVS). The participants were categorized into 3 groups for evaluation: those with a low score (0-2), medium score (3-5), and high score (≥6). Ordinal logistic regression analysis was performed to examine the association between OF and DVS. RESULTS: The rate of OF in the participants was 21.6%, and its severity was significantly associated with DVS after adjusting for potential confounders (Pre-OF; adjusted odds ratio [OR] = 1.687, 95% confidence interval [CI] = 1.219-2.335, OF; adjusted OR = 2.857, 95% CI = 1.489-5.484). CONCLUSION: The severity of OF was significantly associated with DVS in community-dwelling older persons. This suggests that DVS may be useful in understanding the effects of OF on the nutritional status. Further longitudinal studies are needed to elucidate the association between OF and DVS.

Association between Oral Frailty and Nutritional Status among Community-Dwelling Older Adults: the Takashimadaira Study.

OBJECTIVES: Recently, the concept of oral frailty, defined as accumulated deficits in oral health, has been introduced in Japan. However, data about its association with nutritional status are limited. Thus, this cross-sectional study aimed to investigate the association between oral frailty and malnutrition among community-dwelling older adults. DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: One thousand and fifty-four individuals (428 men and 626 women, mean age: 77.0 years) from the Takashimadaira Study. MEASUREMENTS: Based on a multifaceted oral health assessment, oral frailty was defined as greater than or equal to three of the following components: (1) low number of remaining teeth, (2) decreased masticatory performance, (3) reduced articulatory oral motor skill, (4) low tongue pressure, and difficulties in (5) eating and (6) swallowing. The nutritional status was evaluated using the Mini Nutritional Assessment®-Short Form (MNA®-SF) and serum albumin. An ordinal logistic regression model was used to evaluate the association between oral frailty and nutritional status. RESULTS: Oral frailty was observed in 217 (20.4%) participants. After adjusting for potential confounders, the participants with oral frailty had higher odds of more severe malnutrition evaluated using MNA®-SF (adjusted odds ratio: 2.17; 95% confidence interval: 1.58-2.98) and serum albumin level (adjusted odds ratio: 1.59; 95% confidence interval: 1.10-2.31). CONCLUSION: Oral frailty was associated with nutritional status among Japanese older adults. Maintaining comprehensive oral health and function may be effective for malnutrition prevention in community-dwelling older adults. However, further studies must be conducted to validate the generalizability of the results of the current study.

Association of Dietary Variety and Appetite with Sleep Quality in Urban-Dwelling Older Japanese Adults.

OBJECTIVES: Although it has been shown that specific foods and nutrients are associated with sleep quality, few studies have examined the association of dietary variety and appetite with sleep quality in older adults. DESIGN AND SETTING: A cross-sectional study was conducted that examined the association of dietary variety and appetite with sleep quality in Japanese adults aged ≥70 years who resided in the metropolitan area of Tokyo, Japan. PARTICIPANTS: Data were collected in two steps: a mailed interview survey and an on-site survey. Those who responded to the surveys and met the inclusion criteria were included. MEASUREMENTS: Dietary variety, appetite, and sleep quality were assessed using a Dietary Variety Score (DVS), Council on Nutrition Appetite Questionnaire (CNAQ) score, and sleep efficiency, respectively. The sleep efficiency is the ratio of sleep duration to total time in bed (retiring time-awakening time). We defined the individuals with a sleep efficiency less than 75% as having poor sleep quality. RESULTS: Mean DVS and CNAQ score were 3.8 and 29.6 points, respectively. The rate of individuals with poor sleep quality was 11.7%. In the fully adjusted model, the odds ratios (OR) for low sleep efficiency in the middle and highest group categories of the DVS were 0.83 (95% confidence interval [CI], 0.54-1.29) and 0.50 (95% CI, 0.28-0.90), respectively, in reference to the lowest group category (p for trend = 0.023). The OR for low sleep efficiency in the middle and highest group categories of the CNAQ score were 0.73 (95% CI, 0.47-1.14) and 0.54 (95% CI, 0.30-0.96), respectively, in reference to the lowest group category (p for trend = 0.031). CONCLUSIONS: The higher DVS and CNAQ scores were significantly associated with higher sleep efficiency. Thus, dietary variety and good appetite might help maintain good sleep quality in urban-dwelling older Japanese adults.

Self-Feeding Ability as a Predictor of Mortality Japanese Nursing Home Residents: A Two-Year Longitudinal Study.

OBJECTIVES: To examine the ability of different elements of the Self-Feeding Assessment Tool for Elderly with Dementia (SFED) to predict mortality risk in nursing home residents. DESIGN AND SETTING: Data from 387 residents in five nursing homes for the elderly in Japan were obtained using a baseline survey. This measure's ability to predict mortality risk was examined over a two-year observation period. Participants and Measurement: Demographic information (sex, age, height, weight, medical history) on 387 initial participants was gathered. A total of 10 individuals were excluded from the analysis because of the inability to eat by mouth at baseline, while 36 were excluded owing to missing mortality data during the observation period. The resulting 341 residents were divided into a death group or survival group according to whether they were still alive after two-year observation period. In addition to basic information and the SFED, the baseline survey included the Barthel Index (BI), Clinical Dementia Rating (CDR), and Mini Nutritional Assessment-Short Form (MNA®-SF). The ability of SFED to predict time-to-event mortality was examined using Cox proportional hazards regression analysis, including other measures associated with mortality as confounding variables. RESULTS: In total, 129 participants (37.8%) died during the observation period, and their mean SFED score was significantly lower than that of surviving ones (11.1 ± 6.7 vs. 15.0 ± 5.6, P<0.001). SFED score was significantly associated with two-year mortality in the Cox proportional hazards regression analysis after adjusting for sex, age, medical history, BI, CDR, and MNA®-SF (hazard ratio = 0.941, 95% confidence interval = 0.898-0.985, P = 0.010). Additionally, three SFED categories were significantly associated with mortality risk: movement ("able to eat without dropping food"), concentration ("able to maintain attention to meal"), and safety ("able to swallow without choking, with no change in vocal quality after eating"). CONCLUSIONS: Self-feeding ability as measured by SFED score was associated with long-term mortality in elderly living in nursing homes. Accordingly, adjusting feeding assistance based on regular SFED-based assessments may help maintain self-feeding ability and enhance quality of life in this population, as well as providing evidence for end-of-life care options and greatly improving care quality.

Differentiation of feline immunodeficiency virus vaccination, infection, or vaccination and infection in cats.

BACKGROUND: Serodiagnosis of feline immunodeficiency virus (FIV) is complicated by the use of a formalin-inactivated whole-virus FIV vaccine. Cats respond to immunization with antibodies indistinguishable from those produced during natural infection by currently available diagnostic tests, which are unable to distinguish cats that are vaccinated against FIV, infected with FIV, or both. HYPOTHESIS: An enzyme-linked immunosorbent assay (ELISA) detecting antibodies against formalin-treated FIV whole virus and untreated transmembrane peptide will distinguish uninfected from infected cats, regardless of vaccination status. ANIMALS: Blood samples were evaluated from uninfected unvaccinated cats (n = 73 samples), uninfected FIV-vaccinated cats (n = 89), and FIV-infected cats (n = 102, including 3 from cats that were also vaccinated). METHODS: The true status of each sample was determined by virus isolation. Plasma samples were tested for FIV antibodies by a commercial FIV diagnostic assay and an experimental discriminant ELISA. RESULTS: All samples from uninfected cats were correctly identified by the discriminant ELISA (specificity 100%). Of the samples collected from FIV-infected cats, 99 were correctly identified as FIV-infected (sensitivity 97.1%). CONCLUSIONS AND CLINICAL IMPORTANCE: With the exception of viral isolation, the discriminant ELISA is the most reliable assay for diagnosis of FIV. A practical strategy for the diagnosis of FIV infection would be to use existing commercial FIV antibody assays as screening tests. Negative results with commercial assays are highly reliable predictors for lack of infection. Positive results can be confirmed with the discriminant ELISA. If the discriminant ELISA is negative, the cat is probably vaccinated against FIV but not infected. Positive results are likely to represent infection.

Frailty Severity and Dietary Variety in Japanese Older Persons: A Cross-Sectional Study.

Providing older person individuals with an appropriate intervention at the time of frailty onset is important to prevent the progression of the condition and the need for long-term care. However, the proper timing of starting nutritional and dietary interventions for frail older person subjects has not been fully elucidated. Therefore, in this cross-sectional study, we aimed to clarify the association between frailty and dietary variety among older persons in Japan. We surveyed sex, age, body height, body weight, body mass index, serum albumin level, dietary variety, and nutritional intake indexes in 747 community-dwelling older person individuals who underwent a comprehensive health examination in October 2014. Frailty was determined using the Kihon Checklist (25 questions). Kihon Checklist is widely used to assess frailty in Japan, and their physical, cognitive and social function was evaluated. After excluding those who did not complete the Kihon Checklist and those who required long-term care, frailty status was analyzed in 665 older person individuals. The numbers and percentages of frail, pre-frail and robust older persons were found to be 77 (11.6%), 182 (27.4%) and 406 (61.0%) respectively. Significant differences among robust, pre-frail, and frail subjects were observed in terms of age, serum albumin level, alcohol consumption, smoking, and history of diabetes. Among the nutrition-related indexes, only the dietary variety showed a significant difference. The results of ordinal logistic regression analysis showed a significant association between frailty and sex, age, smoking status, diabetes, and dietary variety score. Dietary variety was significantly associated with the progression of frailty among older persons in the community.

1-Oxacephalosporins: enhancement of beta-lactam reactivity and antibacterial activity.

The effect of replacement of sulfur in the cephem nucleus by oxygen upon the beta-lactamase stability, infrared carbonyl frequency of the beta-lactam ring, and antibacterial activity was investigated. The replacement reduced the stability of beta-lactam compounds to beta-lactamases, increased the IR frequencies, and enhanced the intrinsic antibacterial activity against bacterial strains without beta-lactamase. The instability of 1-oxacephalosporins to beta-lactamases, in other words, high reactivity to the enzymes, seemed to be due to the enhanced chemical reactivity of their beta-lactam rings which was indicated by their higher IR beta-lactam carbonyl frequencies. Based on a view that acylation of the enzyme by beta-lactam compounds occurred in both cases of beta-lactamase hydrolysis and target enzyme inhibition, the suggestion was made that one of the factors which conferred the higher intrinsic antibacterial activity on 1-oxacephalosporins was their high reactivity to the target enzyme(s), as was the case with beta-lactamases.

Genetic subtyping and epidemiological study of feline immunodeficiency virus by nested polymerase chain reaction-restriction fragment length polymorphism analysis of the gag gene.

Genetic subtyping of feline immunodeficiency virus (FIV) was carried out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. A 329-base pair fragment in the FIV gag gene was amplified by nested PCR, then digested with restriction enzymes, HindIII, PvuII and BamHI. Using these restriction enzymes, FIV isolates belonging to subtypes A, B and D, which had been classified on the basis of the env gene V3-V5 sequence, could be discriminated. Genetic subtypes of FIV prevalent in Japan were investigated using the gag-nested PCR-RFLP analysis. Of 88 FIV-infected cats, PCR products of 70 cats showed a subtype B RFLP pattern (digestion only with PvuII), those of nine cats had a subtype D RFLP pattern (digestion only with BamHI), and those of seven cats had a subtype A RFLP pattern (digestion only with HindIII). The PCR products of the remaining two cats had subtype A and B RFLP patterns (digestion with both HindIII and PvuII). The digestion pattern of the gag-nested PCR-RFLP analysis was unchanged after in vivo passages of the virus. These results suggest that the gag-nested PCR-RFLP analysis is useful as a simple method for FIV genetic subtyping.

Effect of dual-subtype vaccine against feline immunodeficiency virus infection.

Dual-subtype feline immunodeficiency virus (FIV) vaccine, consisting of inactivated cells infected with subtypes A (Petaluma strain) and D (Shizuoka strain), was developed and tested for its vaccine efficacy against FIV infection in specific pathogen free (SPF) cats. Animals were monitored for proviral DNA by FIV-specific PCR and for FIV-specific antibody profiles by ELISA and virus-neutralization assays. In addition, blood from challenged cats was inoculated into naive SPF cats to confirm the viral status of the vaccinated cats. All cats immunized with Petaluma vaccine alone were protected against homologous Petaluma challenge, but only one of four cats was protected against heterologous Shizuoka challenge. More importantly, all cats immunized with the dual-subtype vaccine were protected against both Petaluma and Shizuoka challenges. These results suggest that a multi-subtype vaccine approach may provide the broad-spectrum immunity necessary for vaccine protection against strains from different subtypes.

Antibiotic A-130, isolation and characterization.

An antibiotic, A-130, was isolated from a strain identified as Streptomyces hygroscopicus, strain A-130. The antibiotic belongs to the nigericin group and like dianemycin, has an alpha, beta-unsaturated ketone chromophore in its molecule. A-130 is active against gram-positive organisms.

A novel 1 beta-methylcarbapenem antibiotic, S-4661. Synthesis and structure-activity relationships of 2-(5-substituted pyrrolidin-3-ylthio)-1 beta-methylcarbapenems.

The synthesis and biological activity of (1R,5S,6S)-2-[(3S,5S)-5-substituted pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1- methylcarbapen-2-em-3-carboxylic acids are described. These compounds exhibit potent antibacterial activity against a wide range of both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. Of these new carbapenems, (1R,5S,6S)-2-[(3S,5S)-5-sulfamoylaminomethyl pyrrolidin-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarb apen- 2-em-3-carboxyli c acid (S-4661) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.

Orally active cephalosporins. III. Synthesis and structure-activity relationships of new 3-heterocyclicthiomethylthio-7 beta-[(Z)- 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-cephem-4 -carboxylic acids.

3-Heterocyclicthiomethylthio-7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2- hydroxyiminoacetamido]-3-cephem-4-carboxylic acids (2) were synthesized. Their antibacterial activity and oral absorbability were much influenced by the structure of heteroaromatic moiety in the side chain at the 3-position of a cephem nucleus. In this cephalosporin series, 3-thiadiazolylthiomethylthiocephalosporins (2k, 2l and 2m) exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria, whereas 3-(2-methyl-1,2,3-triazol-4-yl)thiomethylthiocephalosporin (2b) and 3-(pyridin-2-yl)thiomethylthiocephalosporin (2n) showed better oral absorption in mice than the other cephalosporins prepared. The structure-activity relationships of 2 are presented.

Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoyl-amino]-3- desacetoxymethylcephalosporins.

Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice.

Synthesis and modification of a novel 1 beta-methyl carbapenem antibiotic, S-4661.

We describe an efficient method for introducing a sulfamoylamino group into the C-2' position of pyrrolidine using the Mitsunobu reaction. S-4661, its N-methyl analogues and stereoisomers were synthesized using this method and their structure-activity relationships were investigated.

Orally active cephalosporins. II. Synthesis and structure-activity relationships of new 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-cephalospori ns with 1,2,3-triazole in C-3 side chain.

The synthesis, antibacterial activity and oral absorbability of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3 -(1H-1,2, 3-triazol-4-yl)thiomethylthio-3-cephem-4-carboxylic acid (1g) and related compounds are described. Their oral absorbability was influenced by the spacer length between C-3 of a cephem nucleus and C-4' of 1,2,3-triazole. The SCH2S structure was also found to contribute to their good oral absorption. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a-1n) is discussed.

Asparenomycins A, B and C, new carbapenem antibiotics. IV. Antibacterial activity.

Asparenomycins (ASM) A, B and C, new members of the carbapenem family of antibiotics, are broad spectrum antibiotics with activity against Gram-positive and Gram-negative bacteria. ASM A was bactericidal to both aerobic and anaerobic bacteria, although morphological alterations of ASM A exposed cells differed significantly between Escherichia coli and Bacteroides fragilis; with the former ovoidal forms were produced while with the latter elongated forms were seen. Synergistic activities were observed with a combination of ASM A and ampicillin (ABPC) against various ABPC-resistant bacteria presumably as a result of the inhibition by ASM A of beta-lactamases. ASM A showed relatively weak therapeutic activity against E. coli infected mice, because of instability in body fluids, a common property of the carbapenem family of antibiotics.

Isolation and characterization of new peptide antibiotics, plusbacins A1-A4 and B1-B4.

New antibiotics, plusbacins A1-A4 and B1-B4, were isolated from the culture broth of a strain of Pseudomonas sp. These antibiotics were isolated as a complex by column chromatographies on Diaion HP-20 and silica gel, and then separated by HPLC. They are amphoteric in nature. The hydrochlorides are obtained as colorless powders, soluble in methanol and alkaline water. From their physico-chemical properties, these antibiotics are presumed to be acyloctapeptides containing a lactone linkage, and their differences occur in amino acid and fatty acid residues. The antibiotics are active against Gram-positive bacteria in vitro and in vivo.

Synthesis and structure-activity relationships of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino]-3-cephems with C-3 substitutions.

Synthesis and biological activity of a series of 7 beta-[(Z)-2-(2- aminothiazol-4-yl)-3-(substituted)-2-propenoylamino]-3-cephe m-4-carboxylic acids with C-3 substitutions and their pivaloyloxymethyl esters are described. These acid compounds exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Pivaloyloxymethyl esters of selected compounds in this series were found to be well absorbed from small intestine in mice. Pivaloyloxymethyl 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-3- carbamoyloxymethyl-3-cephem-4-carboxylase hydrochloride hydrate (S-1108) was finally selected as the candidate for clinical evaluation.

Virus neutralizing antibody titer to feline immunodeficiency virus isolates of subtypes A, B and D in experimentally or naturally infected cats.

Six strains of feline immunodeficiency virus (FIV) classified into subtypes A, B and D were examined by cross-neutralization test using Kumi-1 cells (CD4+, CD8+, and CD9+), an interleukin-2 dependent feline T-lymphocyte cell line. Neutralizing activities against these six FIV strains were also investigated in 50 FIV-antibody-positive serum samples collected from different geographical regions in Japan. The cross-neutralization test revealed that antisera against the six strains tended to possess high neutralizing activity against the homologous strain. These antisera were also capable of neutralizing viral strains of the same subtype. However, some of the antisera were broadly crossreactive with all six FIV strains. Serum samples collected from naturally infected cats in the field showed various neutralization patterns for the six FIV strains. These observations reflect the antigenic diversity in FIV strains prevailing in the field. There were also broadly crossreactive serum samples, and 36% (18/50 samples) showed neutralization for all six FIV strains.

[Orally active cephalosporins. I. Synthesis and structure-activity relationships of 7 beta-[2-(R)-amino-2-phenylacetamido]-3-(1H- 1,2,3-triazol-4-yl)alkylthiomethyl-3-cephem-4-carboxylic acid and related compounds].

The synthesis, antibacterial activity and oral absorbability of 7 beta-[2-(R)-amino-2-phenylacetamido]-3-(1H-1H-1,2,3-triazol- 4-yl)methylthiomethyl-3-cephem-4-carboxylic acid (1a) and related compounds (1b-p and 2) are described. The replacement of 1,2,3-triazole at the C-3 position of 1a with other heteroaromatics such as 1,2,4-triazole, imidazole and so on decreased its oral absorbability in mice (1b-j). The oral absorbability was also influenced by the spacer length between C-3 of cephem nucleus and C-4 of 1,2,3-triazole. The quantitative relationship between the bioavailability and the spacer length of cephalosporins (1a and 1k-p) is discussed. These results suggest that 1,2,3-triazole in the side chain at the C-3 position of cephems plays an important role in good oral absorption through its interaction with the transport system of small intestine.