TRENDS IN THE PREVALENCE OF FRAILTY IN JAPAN: A META-ANALYSIS FROM THE ILSA-J.

OBJECTIVE: To examine whether age-specific prevalence of frailty in Japan changed between 2012 and 2017. DESIGN: This study performed meta-analyses of data collected from 2012 to 2017 using the Integrated Longitudinal Studies on Aging in Japan (ILSA-J), a collection of representative Japanese cohort studies. SETTING: The ILSA-J studies were conducted on community-living older adults. PARTICIPANTS: ILSA-J studies were considered eligible for analysis if they assessed physical frailty status and presence of frailty in the sample. Seven studies were analyzed for 2012 (±1 year; n = 10312) and eight studies were analyzed for 2017 (±1 year; n = 7010). Five studies were analyzed for both 2012 and 2017. MEASUREMENTS: The study assessed the prevalence of frailty and frailty status according to 5 criteria: slowness, weakness, low activity, exhaustion, and weight loss. RESULTS: The overall prevalence of physical frailty was 7.0% in 2012 and 5.3% in 2017. The prevalence of frailty, especially in people 70 years and older, tended to decrease in 2017 compared to 2012. Slight decreases were found in the prevalence of frailty subitems including weight loss, slowness, exhaustion, and low activity between 2012 and 2017, but change in the prevalence of weakness was weaker than other components. CONCLUSIONS: The prevalence of physical frailty decreased from 2012 to 2017. There are age- and gender-related variations in the decrease of each component of frailty.

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.

Renal Infiltration of Macrophages in Canine and Feline Chronic Kidney Disease.

During the progression of chronic kidney disease (CKD), macrophage infiltration is a crucial event leading to tubulointerstitial fibrosis. In the present study, macrophages infiltrating renal tissue in dogs and cats with CKD were analysed immunohistochemically. Iba-1 was used as a pan-macrophage marker, CD204 was used as a marker of M2 macrophages and tumour necrosis factor (TNF)-α was used as a marker of M1 macrophages. Signals for Iba1 and CD204 were observed in the interstitium of all tested kidney samples. In dogs, the signals were diffusely scattered. In cats, both diffuse and focal signals were observed. Cells that were positive for Iba1 and CD204 were also observed in the tubular lumina in cats. Co-expression of Iba1 and CD204 was also observed in the infiltrating cells by immunofluorescence labelling, and these cells were negative for TNF-α. By quantitative analysis, the indices for Iba1- and CD204-positive cells were significantly correlated with the concentrations of plasma creatinine and/or urea and the extent of interstitial fibrosis in both dogs and cats. These results demonstrated that renal infiltration of M2 macrophages plays an important role in the progression of CKD in dogs and cats. The distribution pattern of the kidney-infiltrating macrophages was unique in cats and may be associated with a cat-specific renal fibrotic process.

Factors related to dissociation between objective and subjective masticatory function in Japanese community-dwelling elderly adults.

Clinicians' evaluations of older adults sometimes reveal inconsistencies between objective and subjective dental status. This study investigated which factors contribute both to good objective masticatory function (OMF) and the poor subjective masticatory function (SMF) that often becomes a clinical issue. Study participants included 635 elderly community-dwelling Japanese adults who underwent a comprehensive geriatric health examination in 2012. SMF was assessed with a question from the Kihon Checklist on eating difficulties (poor or good). OMF was assessed by a colour-changing gum (poor or good). Also investigated were age, sex, depressive symptoms, instrumental activities of daily living (I-ADLs), number of people who joined the participant at dinner, grip strength, usual walking speed, number of remaining teeth, number of functional teeth and their occlusal force. The group with good OMF and good SMF, defined as group 1, and the group with good OMF but poor SMF, group 2, were compared. Logistic regression analyses confirmed that the number of remaining and functional teeth participants had was statistically unrelated to differences between OMF and SMF. Instead, differences were related to stronger depressive symptoms (OR = 1.67, CI = 1.14-2.44), less ability to conduct I-ADL activities (OR = 0.73, CI = 0.59-0.91), slower usual walking speeds (OR = 0.18, CI = 0.06-0.58) and less occlusal force (OR = 0.99, CI = 0.99-1.00). Depressive symptoms, I-ADLs, and physical function are shown to be significantly related to divergence between objective and subjective masticatory function in elderly Japanese. This suggests that dissociations between objective and subjective dental evaluations of elderly adults indicate need for assessment of their mental and physical function.

T-cell-replete haploidentical stem cell transplantation is highly efficacious for relapsed and refractory childhood acute leukaemia.

BACKGROUND: Despite improvements in first-line therapies, the outcomes of relapsed or refractory childhood acute leukaemia that has not achieved complete remission after relapse, has relapsed after stem cell transplantation (SCT), has primary induction failure and has relapsed with a very unfavourable cytogenetic risk profile, are dismal. OBJECTIVES AND METHODS: We evaluated the feasibility and efficacy of T-cell-replete haploidentical peripheral blood stem cell transplantation (haplo-SCT) with low-dose anti-human thymocyte immunoglobulin (ATG), tacrolimus, methotrexate and prednisolone (PSL) in 14 paediatric patients with high-risk childhood acute leukaemia. RESULTS: All patients achieved complete engraftment. The median time to reaching an absolute neutrophil count of more than 0.5 × 10(9) L(-1) was 14 days. Acute graft-vs-host disease (aGVHD) of grades II-IV and III-IV developed in 10 (71%) and 2 (14%) patients, respectively. Treatment-related mortality and relapse occurred in one (7%) patient and six (43%) patients, respectively. Eleven patients were alive and seven of them were disease-free with a median follow-up of 36 months (range: 30-159 months). The probability of event-free survival after 2 years was 50%. CONCLUSION: These findings indicate that T-cell-replete haplo-SCT, with low-dose ATG and PSL, provides sustained remission with an acceptable risk of GVHD in paediatric patients with advanced haematologic malignancies.

Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1.

BACKGROUND: Impaired drug transport is an important factor that reduces the efficacy of anticancer agents against pancreatic cancer. Here, we report a novel combination chemotherapy using gemcitabine (GEM) and internalised-RGD (iRGD) peptide, which enhances tumour-specific drug penetration by binding neuropilin-1 (NRP1) receptor. METHODS: A total of five pancreatic cancer murine models (two cell line-based xenografts (CXs) and three tumour grafts (TGs)) were treated with either GEM (100 mg kg(-1), q3d × 4) alone or GEM plus iRGD peptide (8 µmol kg(-1)). Evaluation of NRP1 expression in xenografts and 48 clinical cancer specimens was performed by immunohistochemistry (IHC). RESULTS: We identified a subset of pancreatic cancer models that showed NRP1 overexpression sensitive to iRGD co-administration. Treatment with GEM plus iRGD peptide resulted in a significant tumour reduction compared with GEM monotherapy in CXs, but not remarkable in TGs. Potential targets of iRGD were characterised as cases showing NRP1 overexpression (IHC-2+/3+), and these accounted for 45.8% of the clinical specimens. CONCLUSIONS: Internalised RGD peptide enhances the effects of co-administered drugs in pancreatic cancer models, its efficacy is however only appreciable in those employing cell lines. Therefore, the clinical application needs to be given careful consideration.

Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis.

The prognosis of lupus nephritis (LN) has improved since the introduction of immunosuppressant therapies, but the safety and effectiveness of treatments can also be improved. We retrospectively assessed the treatment courses of 12 patients with systemic lupus erythematosus who were treated with glucocorticoid, mizoribine (MZR) and tacrolimus. This regimen was used as initial therapy for active LN in six patients (mean glucocorticoid dose, 66.6 mg); four of these six patients also received pulse methylprednisolone therapy. The starting doses of MZR and tacrolimus were 150 and 3 mg, respectively, and they were titrated as required. Five of six patients achieved complete remission and one achieved partial remission at 6 months. Five patients who completed 12-month analysis achieved complete remission. Another six patients were given the combination regimen for treating minor flares or for steroid sparing. The mean prednisolone doses were reduced from 11.0 mg at baseline to 6.6 mg at 12 months. Six patients experienced minor adverse events, including three minor infections. One patient stopped tacrolimus because of suspected toxicity. All 12 patients were successfully treated, and none experienced severe adverse events. Multitarget therapy combining glucocorticoid, MZR and tacrolimus may have the potential to become a treatment option which is effective and safe.

Protective effect of sivelestat sodium (Eraspol) on postoperative lung dysfunction in patients with type A acute aortic dissection: a pilot study.

AIM: The authors evaluated the protective effect of sivelestat sodium on postoperative lung dysfunction in patients with type A acute aortic dissection who underwent aortic arch surgery with cardiopulmonary bypass (CPB) under deep hypothermia with circulatory arrest (DHCA). METHODS: Twelve patients with type A acute aortic dissection who underwent aortic arch replacement under CPB with DHCA and were pretreated with or without sivelestat sodium (sivelestat group, N.=7 patients; control group, N.=5 patients) were observed. The ratio of arterial oxygen tension to inspired oxygen fraction (P/F ratio) was measured as a parameter of pulmonary function before and after operation. The number of white blood cells was also counted as an index of inflammatory reaction before and after the operation. RESULTS: The P/F ratio decreased significantly after operation in the control group. However, the P/F ratio was unchanged between before and after operation in the sivelestat group. The number of white blood cells tended to increase after operation in the control group, whereas it decreased significantly after operation in the sivelestat group. CONCLUSION: The present study demonstrated the protective effect of sivelestat sodium on postoperative lung injury in patients with acute type A aortic dissection undergoing aortic arch surgery under CPB with DHCA.

Acute hyperglycaemia prevents the protective effect of pre-infarction angina on microvascular function after primary angioplasty for acute myocardial infarction.

BACKGROUND: Acute hyperglycaemia has been associated with impaired microvascular function after acute myocardial infarction (AMI), whereas pre-infarction angina (PIA) occurring shortly before the onset of AMI has been shown to reduce microvascular injury after reperfusion. OBJECTIVE: To examine whether acute hyperglycaemia prevents the protective effect of PIA on microvascular function after AMI. METHODS: We studied 205 patients with a first anterior wall AMI who underwent primary angioplasty within 12 hours of onset. Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire. Severe microvascular injury was defined as the presence of systolic flow reversal and diastolic deceleration time <600 ms. Echocardiographic wall motion was analysed before revascularisation and 4 weeks later. RESULTS: Acute hyperglycaemia, defined as a blood glucose level of >or=198 mg/dl on admission, was found in 67 (33%) patients. In patients without acute hyperglycaemia, PIA was associated with a lower incidence of systolic flow reversal, a longer diastolic deceleration time and a higher coronary flow reserve. However, in patients with acute hyperglycaemia there was no significant difference in these same parameters between patients with and without PIA. In the presence of acute hyperglycaemia PIA did not improve the change in wall motion score. In a multivariate model, the absence of PIA was an independent determinant of severe microvascular injury in patients without acute hyperglycaemia (odds ratio 6.28, p = 0.001), but not in patients with acute hyperglycaemia. CONCLUSION: The protective effect of PIA on microvascular function was attenuated in patients with acute hyperglycaemia, resulting in unfavourable functional recovery.

Demonstration of inter- and intracellular distribution of boron and gadolinium using micro-proton-induced X-ray emission (Micro-PIXE).

Micro-proton-induced X-ray emission (Micro-PIXE) was applied to determine inter- and intracellular distribution of boron (10B) and gadolinium (157Gd), the capture atoms used to kill tumor cells in neutron capture therapy (NCT). Cultured 9L gliosarcoma cells on Mylar film were exposed to sodium borocaptate (BSH) and gadobenate dimeglumine (Gd-BOPTA). To analyze the inter- and intracellular distribution of 10B and 157Gd in 9L gliosarcoma cells, the cells were irradiated using a proton beam of 1.7 or 3 MeV energy collimated to 1 microm diameter and emission X-ray was detected. The distribution of 10B and 157Gd in 9L gliosarcoma cells was then examined. In this study, we could directly analyze the inter- and intracellular distribution of 10B and 157Gd elements in 9L gliosarcoma cells directly using Micro-PIXE. This is the first report on the distribution of 10B employing a method to detect gamma-rays resulting from the nuclear reaction of 10B using particle-induced gamma-ray emission (PIGE). These results show that the distribution of 157Gd elements was correctly measured using micro-PIXE. 157Gd should have the same tendency as 10B in cultured 9L gliosarcoma cells and agree with the distribution in 9L gliosarcoma cells. Further investigation is necessary for a higher spatial resolution and optimization of the measurement time or improvement of the sampling method. In the future, it will be possible to employ this method to analyze the intracellular microdistribution of the capture element and in the development of new drugs for NCT.

Relation between the TIMI frame count and the degree of microvascular injury after primary coronary angioplasty in patients with acute anterior myocardial infarction.

OBJECTIVE: To investigate the relation between thrombolysis in myocardial infarction (TIMI) frame count (TFC) and coronary blood flow velocity (CBFV) parameters reflecting the degree of microvascular injury in patients with acute myocardial infarction. RESULTS: TFC and CBFV were measured after primary coronary angioplasty in 103 consecutive patients with their first anterior wall acute myocardial infarction. TFC correlated inversely with the averaged peak velocity (r = -0.43, p < 0.0001). However, TFC did not correlate significantly with diastolic deceleration time and with the averaged systolic peak velocity (r = -0.16, p = 0.22, and r = -0.23, p = 0.16, respectively). The patients were divided into two groups according to presence (35 patients) or absence (68 patients) of systolic flow reversal. There was no significant difference in TFC between the two groups (29 (16) v 25 (13), p = 0.20). CONCLUSIONS: These findings suggest that the TFC reflects epicardial CBFV. However, it is not accurate enough to assess the degree of microvascular injury after primary coronary angioplasty.

Rapid determination of bovine lactoferrin in dairy products by an automated quantitative agglutination assay based on latex beads coated with F(ab')2 fragments.

UNLABELLED: This study evaluated an automated immunoassay for bovine lactoferrin (LF) in dairy products based on latex beads coated with F(ab')2 fragments. METHODS: F(ab')2 fragments were obtained by pepsin digestion of rabbit anti-bovine LF (IgG fraction) and polystyrene latex beads were coated with the F(ab')2 fragments. We used the beads to develop a rapid and homogeneous light scatter immunoassay employing an autoanalyzer (the Automated Latex assay). The Automated Latex assay was easy to perform and could rapidly determine bovine lactoferrin in lactoferrin-supplemented products. It was sensitive enough for testing products and showed good precision.

[Surgery for acute aortic dissection concomitant with preceding axillofemoral bypass to prevent malperfusion of visceral organs and limb ischemia].

A 52-year-old man was admitted with sudden onset of epigastralgia. Abdominal X-ray showed dilated intestine and computed tomography (CT) revealed extended type A aortic dissection. Marked abdominal distention and weak pulse of right femoral artery were recognized so malperfusion of visceral organs due to narrowing true lumen compressed by thrombosed false lumen was suggested. In the operation, right axillo-right femoral bypass was established preceding to median sternotomy. This graft was used as an arterial perfusion site of cardiopulmonary bypass, and replacement of the ascending aorta was performed under hypothermic circulatory arrest and retrograde cerebral perfusion. Sign of malperfusion of visceral organs was showed for several days after the operation but it disappeared without further intervention. Axillofemoral inflow of cardiopulmonary bypass may be effective procedure in these cases.

Genetic organization of the Francisella plasmid pFNL10.

We report here the molecular characterization of pFNL10, a 3990-bp cryptic plasmid of Francisella novicida-like F6168. The plasmid was maintained in F. novicida Utah 112 and F. tularensis LVS strains. We sequenced the entire plasmid and found six open reading frames (ORFs)-ORF1, ORF2, ORF3, ORF4, ORF5, and ORFm. ORF3, ORF4, ORF5, and ORFm are located on the same strand, and we designated it the plus strand. ORF1 and ORF2 are on the complementary strand. The ORFs appear to be arranged in two operons, one comprising ORF5 and ORF4 and the other ORF1 and ORF2. There exist two distinct promoters similar to the Escherichia coli sigma(70) promoter, one 5' to ORF1-ORF2 operon and the other 5' to ORF5-ORF4 operon. We found that in both promoters the transcriptional start is an adenosine. ORF3 is positioned in tandem with ORF5-ORF4, but has its own transcriptional start, a thymidine. However, sequence analysis revealed no recognizable promoter in physical proximity to ORF3. Sequence analysis revealed transcriptional terminators immediately downstream of the two operons. Experimental results showed that the ORF1-ORF2 terminator is authentic. But we could not definitively confirm the ORF5-ORF4 terminator. Two sets of direct repeats, one 31 and the other 13 bp, characteristic of ori are positioned between the two promoters. ORF1 encodes a protein that bears homology to the replication initiation protein RepA of various bacteria, and disruption of this ORF indeed blocked pFNL10 replication. In contrast, ORF2 disruption caused formation of plasmid multimers, suggesting aberrant replication. Our analysis also suggests that pFNL10 replicates by the theta mode. The ORF5-ORF4 operon resembles the phd-doc operon of Escherichia coli bacteriophage P1, but the significance of this similarity is unclear.

Association of L* protein of Theiler's murine encephalomyelitis virus with microtubules in infected cells.

We used an antibody raised against a synthetic peptide corresponding to amino acid residues 70-88 for characterizing the L* protein of Theiler's murine encephalomyelitis virus (TMEV), which is only synthesized in DA subgroup strains from an alternative AUG and is out of frame with the viral polyprotein; evidence suggests that L* protein is critical to viral persistence, demyelination, and growth in murine macrophage cell lines. It was synthesized with kinetics similar to that of other viral proteins, although less in amount. After synthesis, it remained stable in the cytoplasm and was not incorporated into virions. Immunofluorescent staining and immunoblotting of microtubule preparations demonstrated that it is associated with microtubules. Expression of L* protein also demonstrated that the 5' one third of the coding region may be responsible for the association. The association of L* protein with microtubules may be important in the disease-inducing and in vitro characters of L* protein.

Nucleotide sequence, structural organization, and functional characterization of the small recombinant plasmid pOM1 that is specific for Francisella tularensis.

pOM1 is a recombinant 4442-bp plasmid that includes the replicon of the Francisella novicida-like strain F6168 cryptic plasmid pFNL10 and the tetracycline resistance gene (tetC) of plasmid pBR328. pOM1 can stably replicate and is maintained in Francisella tularensis biovars tularensis, palaearctica, and palaearctica var. japonica. The replicon of pOM1 includes the ori region and the repA gene. The ori region, located upstream of the repA gene includes two sets of 31- and 13-bp direct repeats (DR), with AT-rich regions preceding each of the DRs. Two putative promoters of the repA gene were found connected with the DR regions. A 40-kDa protein was encoded by the repA gene and found essential for replication. Expression of the tetC gene is regulated by an Escherichia coli sigma(70)-like promoter and is dependent on the F. tularensis strain and its environment.