Pneumonia incidence and oral health management by dental hygienists in long-term care facilities: A 1-year prospective multicentre cohort study.

OBJECTIVE: To investigate the association between oral health management (OHM) by dental hygienists and the occurrence of pneumonia, and determine the effectiveness of OHM in pneumonia prevention. BACKGROUND: In long-term care facilities in Japan, the need for professional OHM is increasing with an increase in the number of severely debilitated residents. MATERIALS AND METHODS: A 1-year prospective multicentre cohort study was conducted using data from 504 residents (63 men; mean age: 87.4 ± 7.8 years) in Japanese long-term care facilities. Basic information, medical history, willingness to engage in oral hygiene behaviour, need for OHM and oral conditions were investigated at baseline. In addition, information on the occurrence of pneumonia was collected using a follow-up survey after one year. A Poisson regression analysis with robust standard errors was conducted, with pneumonia as the dependent variable, and factors associated with OHM and pneumonia occurrence as explanatory variables. RESULTS: Overall, 349 (69.2%) residents required OHM by dental hygienists during that year of follow-up. Of those, 238 (68.2%) were provided with OHM, and 18 (7.5%) developed pneumonia. Among the 111 patients (31.8%) who were not provided with OHM, 21 (18.9%) developed pneumonia. The OHM group had lower pneumonia rates than the non-OHM group (prevalence rate ratio: 0.374; 95% CI: 0.210-0.665). CONCLUSION: Oral health management by dental hygienists was associated with a lower incidence of pneumonia among residents of long-term care facilities, underlining the importance of professional OHM for such individuals. It is recommended that OHM be practised routinely in long-term care facilities.

Bactericidal Activity of Bulk Nanobubbles through Active Oxygen Species Generation.

We investigated the bactericidal activity of bulk nanobubbles (NBs) using E. coli, a model bacterium. Bulk NBs were produced by forcing gas through a porous alumina membrane with an ordered arrangement of nanoscale straight holes in contact with water. NBs with different gas contents, including CO2, O2, and N2, were generated and evaluated for their bactericidal effects. The survival rate of E. coli was significantly reduced in a suspension of CO2-containing NB (CO2-NB water). The N2-NB water demonstrated a small amount of bactericidal behavior, but its impact was not as significant as that of CO2-NB water. When E. coli was retained in O2-NB water, the survival rate was even higher than that in pure water (PW). We investigated the generation of reactive oxygen species (ROS) in NB suspensions by electron spin resonance spectroscopy. The main ROS generated in the NB water were hydroxyl radicals and OH·, and the production of ROS was the strongest in CO2-NB water, which was consistent with the results of the bactericidal effect measurements. We assumed that NB mediated by ROS would exhibit bactericidal behavior and proposed a kinetic model to explain the retention time variation of the survival rate. The results calculated based on the proposed model matched closely with the experimental results.

Bactericidal Activity of TiO2 Nanotube Thin Films on Si by Photocatalytic Generation of Active Oxygen Species.

The photocatalytic bactericidal activity of titanium dioxide (TiO2) thin films has been extensively studied. In this study, we investigated the bactericidal activities of TiO2 nanotube (NT) thin films using Escherichia coli and Staphylococcus aureus cells as the model bacteria. Metallic titanium (Ti) thin films were anodized on a silicon (Si) wafer substrate to form TiO2 NT thin films. To evaluate the bactericidal activity of the TiO2 NT thin films, bacteria on the TiO2 NT thin films were irradiated with near-ultraviolet light (UV-A) at a wavelength of 365 nm. The bactericidal activity was estimated by the survival rate derived from the number of live cells, which form colonies on the cell culture medium. We demonstrated that the survival rate of the two types of bacteria investigated in this study was significantly reduced by UV light irradiation and that there was a difference in the temporal change in the survival rate between the two types of bacteria. Furthermore, we investigated the generation of reactive oxygen species (ROSs) by UV light irradiation of TiO2 NT thin films using electron spin resonance spectroscopy and fluorescence analysis. We found that the main ROS generated on the surface of the TiO2 NT film was the hydroxyl radical, OH•. In addition, the generation of ROSs increased with an increase in the UV irradiation time. We proposed a kinetic model that reproduces the dependence of bacterial viability on the UV light irradiation time by considering the temporal change in the amount of ROSs generated by UV light irradiation. A comparison of the calculated and experimental results revealed that the bactericidal effect consisted of the direct photolysis of bacteria and the photocatalysis via the generation of hydroxyl radicals, with the latter exhibiting a stronger bactericidal effect than the former.

Qualitative analysis of the vocabulary used in work logs of a preventive programme for elderly oral function and nutrition.

BACKGROUND: In Japan, day care services for elders include programmes aimed at improving nutrition and oral and motor functions. Few studies have qualitatively assessed these interventions. OBJECTIVE: To qualitatively search for the characteristic words used in the work logs of a preventive programme on oral function and nutrition for elders by intervention period and intervention type． METHODS: We included 83 participants (81.3 ± 8.2 years) from four day care services in Japan and divided them into the following groups randomly: those who received oral function intervention only, nutritional intervention only and those who received combined oral function plus nutritional intervention. The interventions were conducted twice per month for 24 months. Data from handwritten work logs were entered into a computer as text files. Monitoring of frequently appearing words, co-occurrence analysis and cross-tabulation by intervention period and intervention types was conducted using text mining analysis. RESULTS: Correspondence analysis revealed that the words used during 1-6 months and 7-12 months were similar in participants' subjective content, and those used in objective content in 13-18 months and 19-24 months were similar. These results indicate that subjective improvements increased after 13 months, and it was maintained within 24 months. The combined intervention type is ideal for oral and nutrition problems. CONCLUSION: Because this text mining approach revealed the changes in the words used and could be used to monitor any subjective improvement, this approach may help evaluate the effects of preventive care.

Robust label-free microRNA detection using one million ISFET array.

Detection of nucleic acid molecules is one of the most pervasive assays in biology, medicine, and agriculture applications. Currently, most comely used DNA/RNA detection platforms use fluorescence labeling and require lab-scale setting for performing the assay. There is a need for developing less expensive, label-free, and rapid detection of biomolecules with minimal utilization of resources. Use of electrical approaches for detection of biomolecules by utilizing their inherent charge is a promising direction for biosensing assays. Here, we report a 1024 × 1024 array of Ion Sensitive Field Effect Transistors (ISFET) as label free sensors for detection of nucleic acid molecules. Using PNA probe functionalized on these ISFET array, we robustly detected miRNA Let-7b by measuring changes in drain current after hybridization of target molecules with concentration as low as 1 nM. We demonstrate that mismatched or non-complementary target molecules resulted in statistically smaller changes. Most importantly, the high-density sensor array shows unprecedented reliability and robustness with P values <0.0001 for all experiments. Practical implementation of this platform could have a wide range of applications in high-throughput nucleic acid genotyping, detection of amplified pathogenic nucleic acid, detection of cell-free DNA, and electrical readouts for current hybridization-based DNA biomolecular assays.

The catalytic mechanism of decarboxylative hydroxylation of salicylate hydroxylase revealed by crystal structure analysis at 2.5 Å resolution.

The X-ray crystal structure of a salicylate hydroxylase from Pseudomonas putida S-1 complexed with coenzyme FAD has been determined to a resolution of 2.5 Å. Structural conservation with p- or m-hydroxybenzoate hydroxylase is very good throughout the topology, despite a low amino sequence identity of 20-40% between these three hydroxylases. Salicylate hydroxylase is composed of three distinct domains and includes FAD between domains I and II, which is accessible to solvent. In this study, which analyzes the tertiary structure of the enzyme, the unique reaction of salicylate, i.e. decarboxylative hydroxylation, and the structural roles of amino acids surrounding the substrate, are considered.

[Neuroendovascular Treatment for Cerebral Embolism in a Patient just after Aortic Valve Replacement；Report of a Case].

A 67-year-old woman suffered from severe aortic stenosis and atrial fibrillation, and underwent aortic valve replacement with a St. Jude Medical Regent 23-mm valve and pulmonary vein isolation using an AtriCure Isolator Synergy.At 6 days after the operation, she experienced sudden onset of atrial fibrillation, left side paralysis, and dysarthria. Right internal carotid artery embolism was diagnosed via magnetic resonance imaging, and we promptly performed neuroendovascular therapy with a Solitaire FR. Neuroendovascular treatment succeeded, and her neurological function was restored to near-normal. Her post-treatment course was uneventful, and she is currently well without neurological dysfunction.

Arterial location-specific calcification at the carotid artery and aortic arch for chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia.

Several risk factors for arterial calcification have been reported but controversial. The aim of this study was to clarify the interactions among chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and dyslipidemia in altering the risk of arterial calcification in the three different arterial locations and the intramural location at the internal carotid artery (ICA) origins. Calcified burdens at the ICA origins, the aortic arch, and its orifices were evaluated in a retrospective fashion by using computed tomography angiography in 397 patients. The multivariate analyses were adjusted for age, gender, CKD, DM, hypertension, dyslipidemia, and current smoking status. Additionally, subgroup analyses in each variable were conducted. Our multivariate logistic regression analyses revealed that CKD was significantly associated with the outside-wall calcification at the ICA origins, whereas DM was only associated with the inside-ICA-wall calcification. Additionally, we found that DM increased the association between CKD and arterial calcification at the aortic arch and its orifices, and the outside-wall at the ICA origins. Hypertension was significantly associated with the calcification at the orifices of the aortic arch branches synergistically with CKD. Dyslipidemia did not have any significant association with calcification in any of the three vascular beds. CKD had the highest prevalence risk of calcification in common with the three different vascular beds. CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices.

Enhancement of anticancer effect of interferon-γ gene transfer against interferon-γ-resistant tumor by depletion of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) negatively affect the therapeutic effects of anticancer agents. To examine the role of TAMs in interferon (IFN)-γ gene therapy, we selected two types of solid tumors, which varied in the number of TAMs, and investigated the effects of IFN-γ gene transfer on tumor growth. Many TAMs were detected in the solid tumors of murine adenocarcinoma colon-26 cells, whereas few TAMs were detected in murine melanoma B16-BL6 cells. IFN-γ gene transfer hardly suppressed the growth of colon-26 tumors, whereas it was effective in suppressing the growth of B16-BL6 tumors. The antiproliferative effects of IFN-γ on cultured colon-26 cells were similar to those on cultured B16-BL6 cells. To evaluate the role of TAMs, we injected clodronate liposomes (CLs) modified with poly(ethylene glycol) (PEG) to functionally deplete TAMs in tumor-bearing mice. Repeated injections of PEG-CLs significantly retarded the growth of colon-26 tumors and combination with IFN-γ gene transfer further inhibited the growth. In contrast, PEG-CLs hardly retarded the growth of B16-BL6 tumors. These results clearly indicate that TAM depletion is effective in enhancing the therapeutic effect of IFN-γ in TAM-repleted and IFN-γ-resistant tumors.

Validity of salt intake assessment system based on a 24-h dietary recall method using a touch panel computer.

BACKGROUND: An electronic system for salt intake assessment using a 24-h dietary recall method has been developed in Japan. We evaluated the validity of this salt intake system for assessing salt intake. METHODS: We prospectively obtained data on estimated salt intake using 24-hour urinary sodium excretion (24-hUNaCl) and salt intake by the salt intake assessment system from 203 consecutive outpatients with essential hypertension (age: 67.8 ± 10.7 years; 53.7% men). RESULTS: Mean values were 9.7 ± 2.9 g/day for 24-hUNaCl and 9.1 ± 2.9 g/day for the salt intake assessment system before corrections. The salt intake estimated by the present system was significantly correlated with 24-hUNaCl (r = 0.66, p < 0.0001). After corrections for habitual use of discretionary seasonings, habitual intake of salty foods, and physical activity, correlation coefficients between salt intake and 24-hUNaCl increased from 0.60 to 0.66 in men <65 years, from 0.80 to 0.81 in men ≥ 65 years, from 0.64 to 0.75 in women <65 years, and from 0.52 to 0.59 in women ≥ 65 years. After further correction for regional differences in average salt intake, the correlation coefficient reached 0.72 in all patients. CONCLUSION: After correction for dietary habits, lifestyle factors, and differences in average salt intake by region, this system may be a useful tool in Japan to encourage salt restriction in the clinical treatment of hypertension and improve public health in terms of salt restriction overall.

Diagnosing vascular variability anomalies, not only MESOR-hypertension.

Chronobiology is the study of biological rhythms. Chronomics investigates interactions with environmental cycles in a genetically coded autoresonance of the biosphere with wrangling space and terrestrial weather. Analytical global and local methods applied to human blood pressure records of around-the-clock measurements covering decades detect physiological-physical interactions, a small yet measurable response to solar and terrestrial magnetism. The chronobiological and chronomic interpretation of ambulatory blood pressure monitoring (C-ABPM) records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability anomalies (VVAs) for an assessment of cardio-, cerebro-, and renovascular disease risk. Even within the conventionally accepted normal range, VVAs have been associated with a statistically significant increase in risk. Long-term C-ABPM records help to "know ourselves," serving for relief of psychological and other strain once transient VVAs are linked to the source of a load, prompting adjustment of one's lifestyle for strain reduction. Persistent circadian VVAs can be treated, sometimes by no more than a change in timing of the daily administration of antihypertensive medication. Circadian VVA assessment is an emergency worldwide, prompted in the United States by 1,000 deaths per day every day from problems related to blood pressure. While some heads of state met under United Nation and World Health Organization sponsorship to declare that noncommunicable diseases are a slow-motion disaster, a resolution has been drafted to propose C-ABPM as an added tool complementing purely physical environmental monitoring to contribute also to the understanding of social and natural as well as personal cataclysms.

Toward a personalized chronotherapy of high blood pressure and a circadian overswing.

Timing can greatly affect the response to a stimulus, including antihypertensive medications. Herein, we assess the response of 30 patients to losartan/hydrochlorothiazide (L/H), administered for at least 1 month at a given circadian stage to each patient, this stage being changed during consecutive spans to cover six treatment times from awakening to bedtime at approximately 3-hour intervals. At the end of each stage, each patient underwent a 7-day around-the-clock ambulatory blood pressure (BP) profile, analyzed chronobiologically. A larger reduction of the midline estimating statistic of rhythm (MESOR; a rhythm-adjusted mean) of diastolic BP was achieved by L/H administration in the early morning for more patients (P < .05), while treatment upon awakening was the best choice for most patients to reduce the circadian amplitude of BP the most (P < .01). The optimal treatment time varied considerably among patients, however. Special attention should be given to the effect on the circadian amplitude since treatment can increase it above a threshold, beyond which there is a marked increase in cardiovascular disease risk. The results indicate the desirability to individualize the optimization of the antihypertensive effect of L/H by timing along the circadian scale.

Administration of angiotensin receptor II blockade improves vascular function, urinary albumin excretion, and left ventricular hypertrophy in low-risk essential hypertensive patients receiving antihypertensive treatment with calcium channel blockers.

We examined calcium channel blockers (CCBs) and angiotensin receptor II blockers in low-risk hypertensives to evaluate renal, vascular function and left ventricular mass (LVM) from the viewpoint of salt intake (SI). Low-risk hypertensives who had not met blood pressure (BP) goals with CCB were administered telmisaltan. Office and home BP, urinary albumin excretion (uAE), brachial ankle pulse wave velocity (baPWV) and LVM were significantly reduced. uAE and baPWV correlated with SI. It is therefore necessary to evaluate the organ-protecting effects from the viewpoint of SI. In low-risk hypertensives, telmisartan with CCB improves renal, vascular function and LVM.

Association between Death or Hospitalization and Observable Variables of Eating and Swallowing Function among Elderly Residents in Long-Term Care Facilities: A Multicenter Prospective Cohort Study.

This 1-year multicenter prospective cohort study aimed to determine the association between observable eating and swallowing function factors and outcomes (death/hospitalization or survival) among elderly persons in long-term care insurance facilities in Japan. Baseline assessments of factors, such as language, drooling, halitosis, hypersalivation, tongue movement, perioral muscle function, coughing, respiration after swallowing, rinsing, and oral residue, among others, were conducted. A score of 0 was considered positive, and a score of 1 or 2 was considered negative. Patient age, sex, body mass index, Barthel index, and Clinical Dementia Rating were recorded. The death/hospitalization or survival rates over 1 year were recorded, and patients were allocated into groups depending on the respective outcome (death/hospitalization group or survival group) and baseline characteristics. A total of 986 residents from 32 facilities were included, with 216 in the death/hospitalization group and 770 in the survival group. Language, salivation, halitosis, perioral muscle, coughing, respiration after swallowing, rinsing, and oral residue were significantly associated with the outcomes (p < 0.05). Therefore, routine performance of these simple assessments by caregivers may allow early detection and treatment to prevent death, pneumonia, aspiration, and malnutrition in elderly persons.

Association between denture use and food form in older adults requiring long-term care: A multicenter cross-sectional study.

PURPOSE: This study aimed to determine whether denture use contributes to maintaining and improving food forms in long-term care facility (LTCFs) residents. METHODS: In 888 residents of 37 LTCFs in Japan, the following were investigated: nutritional intake status, food forms, age, sex, Barthel index (BI), clinical dementia rating (CDR), number of teeth present, number of occlusal supports, swallowing function, and use of dentures. Among all residents, those who were well-nourished and had ≤9 occlusal supports were analyzed. Based on standardized criteria, the food forms consumed by the subjects were divided into two groups: dysphagia and normal diet, which were further classified into four levels. Analysis was performed using a generalized estimation equation with the four levels of food forms as dependent variables and age, sex, BI, CDR, presence of dysphagia, number of teeth present, and use of dentures as independent variables. RESULTS: The final analysis included 622 (70.0%) residents. Of these, 380 (61.1%) used dentures. The analyses revealed that food form was significantly associated with age (adjusted odds ratio [OR], 0.98), BI (OR, 1.04), number of teeth present (OR, 1.03), presence of dysphagia (OR, 0.44), and use of dentures (OR, 2.82). CONCLUSIONS: Denture use was associated with food forms among Japanese LTCF residents. This indicates that the use of dentures is related to the maintenance of food forms, even in the elderly who participate in few activities of daily living, have reduced cognitive function, and require long-term care.

Constant and steady transgene expression of interferon-γ by optimization of plasmid construct for safe and effective interferon-γ gene therapy.

BACKGROUND: Hydrodynamic injection of pmCMV(enh) -hEF-1(prom) -muIFN-γ, a plasmid DNA (pDNA) expressing murine interferon (IFN)-γ with a murine cytomegalovirus (mCMV) enhancer and a human elongation factor (EF)-1 promoter, has been proven effective for the treatment of cancer and atopic dermatitis in mice. However, the initial peak of IFN-γ soon after injection was quite high compared to the steady level for subsequent periods, which could cause unwanted adverse effects. Therefore, in the present study, aiming to optimize the efficacy/side-effect ratio of IFN-γ gene transfer, we have developed plasmid vectors encoding murine IFN-γ under the control of different combinations of promoter and enhancer sequences. METHODS: The promoter and enhancer sequence of pmCMV(enh) -hEF-1(prom) -huIFN-γ, a prototype plasmid expressing human IFN-γ, was replaced or deleted to obtain various pDNAs. To assess the transgene expression profile, each pDNA was delivered to mice by hydrodynamic injection and the serum IFN-γ concentration was measured periodically. On the basis of the results obtained, murine IFN-γ expressing pDNAs were constructed and the body weight change was monitored as an indicator of adverse effects. RESULTS: The prototype pmCMV(enh) -hEF-1(prom) -huIFN-γ showed a high but declining concentration of IFN-γ. Those containing hROSA26 promoter expressed the transgene in a more constant manner with no initial high concentrations and scarcely reduced the body weight. CONCLUSIONS: These results indicate that hROSA26 promoter, irrespective of the presence and type of enhancers, is suitable for achieving constant and steady level of transgene expression and effective in avoiding the body weight loss caused by high concentrations of IFN-γ.

Sustained exogenous expression of therapeutic levels of IFN-gamma ameliorates atopic dermatitis in NC/Nga mice via Th1 polarization.

The short in vivo half-life of IFN-gamma can prevent the cytokine from inducing immunological changes that are favorable for the treatment of Th2-dominant diseases, such as atopic dermatitis. To examine whether a sustained supply of IFN-gamma is effective in regulating the balance of Th lymphocyte subpopulations, plasmid vector encoding mouse IFN-gamma, pCpG-Mugamma, or pCMV-Mugamma was injected into the tail vein of NC/Nga mice, a model for human atopic dermatitis. A single hydrodynamic injection of a CpG motif reduced pCpG-Mugamma at a dose of 0.14 microg/mouse resulted in a sustained concentration of IFN-gamma in the serum, and the concentration was maintained at >300 pg/ml over 80 d. The pCpG-Mugamma-mediated IFN-gamma gene transfer was associated with an increase in the serum concentration of IL-12, reduced production of IgE, and inhibition of mRNA expression of IL-4, -5, -10, -13, and -17 and thymus and activation-regulated chemokine in the spleen. These immunological changes were not clearly observed in mice receiving two injections of 20 microg pCMV-Mugamma, a CpG-replete plasmid DNA, because of the transient nature of the expression from the vector. The mice receiving pCpG-Mugamma showed a significant reduction in the severity of skin lesions and in the intensity of their scratching behavior. Furthermore, high transepidermal water loss, epidermal thickening, and infiltration of lymphocytes and eosinophils, all of which were obvious in the untreated mice, were significantly inhibited. These results indicate that an extraordinary sustained IFN-gamma expression induces favorable immunological changes, leading to a Th1-dominant state in the atopic dermatitis model.

Overweight and obesity accelerate the progression of IgA nephropathy: prognostic utility of a combination of BMI and histopathological parameters.

BACKGROUND: Although more than 40 years have passed since IgA nephropathy (IgAN) was first reported, predicting the renal outcome of individual IgAN patients remains difficult. Emerging epidemiologic evidence indicates that overweight and obesity are risk factors for end-stage renal disease. We aimed to elucidate the outcome of overweight IgAN patients and improve our ability to predict the progression of IgAN based on a combination of body mass index (BMI) and histopathological parameters, including maximal glomerular area (Max GA). METHODS: Forty-three adult IgAN patients whose estimated glomerular filtration rate was ≥50 ml/min/1.73 m(2) were enrolled in this study. Renal biopsy specimens were evaluated according to the Oxford classification of IgAN. A Kaplan-Meier analysis and the multivariate Cox proportional hazards method were used to evaluate 10-year kidney survival and the impact of covariates. The ability of factors to predict the progression of IgAN was evaluated by their diagnostic odds ratio (DOR). RESULTS: A BMI ≥25 kg/m(2) was found to be an independent predictor of a ≥1.5-fold increase in serum creatinine value (DOR 7.4). The combination of BMI ≥25 kg/m(2), Max GA ≥42,900 µm(2), and presence of mesangial hypercellularity (Oxford M1) optimally raised predictive power for disease progression of IgAN (DOR 26.0). CONCLUSION: A combination of BMI ≥25 kg/m(2), the Oxford classification M1, and a Max GA ≥42,900 µm(2) can serve as a predictor of long-term renal outcome of IgAN.