Effects of a financial incentive scheme for dementia care on medical and long-term care expenditures: A propensity score-matched analysis using LIFE study data.

OBJECTIVE: Japan introduced a financial incentive scheme in April 2016 to improve hospital-based dementia care, but its effectiveness remains unclear. This study aimed to investigate the scheme's impact on medical and long-term care (LTC) expenditures, as well as on changes in care needs levels and daily living independence levels among older persons one year after hospital discharge. METHODS: We linked medical and LTC claims databases, and retrospectively identified patients who received LTC needs certification and daily living independence assessments in Fukuoka, Japan. Case patients (received care under the new scheme) were those admitted from April 2016 to March 2018, and control patients were those admitted from April 2014 to March 2016 (before the scheme was implemented). Through propensity score matching, we identified 260 case patients and 260 control patients, and compared using t-tests, and chi-square tests. RESULTS: The analyses found no significant differences between the case and control groups in medical expenditure (US$26,685 vs US$24,823, P = 0.37), LTC expenditure (US$16,870 vs US$14,374, P = 0.08), daily living independence level changes (26.5% vs 20.4%, P = 0.12), or care needs level changes (36.9% vs 30%, P = 0.11). CONCLUSIONS: The financial incentive scheme for dementia care did not demonstrate any beneficial effects on patients' healthcare expenditures or health conditions. Further studies are needed to examine the scheme's long-term effects.

Structure and Stereochemistry of Amphidinolide N Congeners from Marine Dinoflagellate Amphidinium Species.

Two highly potent cytotoxic 26-membered macrolides, isocaribenolide-I (1) and a chlorohydrin 2, together with known amphidinolide N (3), have been isolated from a free-swimming dinoflagellate Amphidinium species (KCA09053 and KCA09056 strains) collected off Iriomote Island, Japan. The structures of 1 and 2 were determined to be a congener of 3 with an isobutyl terminus and the chlorohydrin form of 3, respectively, by detailed analyses of spectroscopic data. The relative stereochemistries of 1 and 2 were elucidated by the conformational analyses based on NMR data.

Silychristin derivatives conjugated with coniferylalcohols from silymarin and their pancreatic α-amylase inhibitory activity.

Silymarin is a mixture of flavonolignans extracted from the fruit of Silybum marianum (milk thistle). The latter is used as a medicinal plant to treat liver and gallbladder disorders. Recently, silymarin has been investigated for its effects against diabetes mellitus, and shown to reduce serum levels of glucose in model animals and in clinical trials. This effect can be explained mainly by the protective effect of silymarin against pancreatic beta-cells, but the involvement of other mechanisms is possible. We demonstrated the α-amylase inhibitory activity of silymarin and investigated the components responsible for this effect. Two major flavonolignans, silibinin and silychristin, did not show inhibition against α-amylase, but two novel silychristin derivatives conjugated with dehydrodiconiferyl alcohol were isolated as the mildly inhibiting components of silymarin. Further analyses indicated the presence of various silychristin derivatives in silymarin that may act synergistically to show α-amylase inhibitory activity.[Formula: see text].

Optimal beam quality for chest flat panel detector system: realistic phantom study.

OBJECTIVE: To investigate optimal beam quality for chest flat panel detector (FPD) system by semi-quantitatively assessment using a realistic lung phantom. MATERIALS AND METHODS: Chest FPD radiographs were obtained on a realistic lung phantom with simulated lung opacities using various X-ray tube voltage levels (90-140 kV) with/without copper filter. Entrance skin dose was set to maintain identical for all images (0.1 mGy). Three chest radiologists unaware of the exposure settings independently evaluated the image quality of each simulated opacity and normal structure using a 5-point scale (+ 2: clearly superior to the standard; + 1: slightly superior to the standard; 0: equal to the standard; - 1: slightly inferior to the standard; - 2: clearly inferior to the standard). The traditional FPD image obtained at a tube voltage of 120 kV was used as the standard. The scores of image quality were statistically compared using the Wilcoxon rank test with Bonferroni correction. RESULTS: FPD images using 90-kV shot with copper filter were superior to the traditional 120-kV shot without filter with respect to the visibility of vertebra, pulmonary vessels, and nodules overlapping diaphragm and heart (p < 0.05). There was no significant difference with respect to the visibility of all other simulated lung opacities (lung nodules except for overlying diaphragm/heart and honeycomb opacity) between each tube voltage level with/without copper filter and the traditional 120-kV shot without filter. CONCLUSION: Image quality of FPD images using 90 kV with copper filtration is superior to that using standard tube voltage when dose is identical. KEY POINTS: • FPD image quality using 90 kV with filter is superior to that using traditional beam. • Ninety-kilovolt shot with copper filter may be suitable for chest FPD image. • Clinical study dealing with chest FPD beam optimization would be warranted.

Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range. Evaluation of macrocarpal C solution by turbidity, nuclear magnetic resonance spectroscopy and mass spectrometry indicated its aggregation, which may explain the characteristics of the inhibition curve. These findings will be valuable for further study of potential small molecule DPP-4 inhibitors.

Ability of higenamine and related compounds to enhance glucose uptake in L6 cells.

ß2-Adrenergic receptor (ß2AR) agonists are employed as bronchodilators to treat pulmonary disorders, but are attracting attention for their modulation of glucose handling and energy expenditure. Higenamine is a tetrahydroisoquinoline present in several plant species and has ß2AR agonist activity, but the involvement of each functional groups in ß2AR agonist activity and its effectiveness compared with endogenous catecholamines (dopamine, epinephrine, and norepinephrine) has rarely been studied. Glucose uptake of muscle cells are known to be induced through ß2AR activation. Here, the ability to enhance glucose uptake of higenamine was compared with that of several methylated derivatives of higenamine or endogenous catecholamines. We found that: (i) the functional groups of higenamine except for the 4'-hydroxy group are required to enhance glucose uptake; (ii) higenamine shows a comparable ability to enhance glucose uptake with that of epinephrine and norepinephrine; (iii) the S-isomer shows a greater ability to enhance glucose uptake compared with that of the R-isomer.

Synthesis and Detailed Examination of Spectral Properties of (S) and (R)-Higenamine 4'-O-ß-d-Glucoside and HPLC Analytical Conditions to Distinguish the Diastereomers.

Higenamine is a tetrahydroisoquinoline present in several plants that has ß-adrenergic receptor agonist activity. Study of the biosynthesis of higenamine has shown the participation of norcoclaurine synthase, which controls the stereochemistry to construct the (S)-isomer. However, when isolated from nature, higenamine is found as the racemate, or even the (R)-isomer. We recently reported the isolation of higenamine 4'-O-ß-d-glucoside. Herein, its (R)- and (S)-isomers were synthesized and compared to precisely determine the stereochemistry of the isolate. Owing to their similar spectral properties, determination of the stereochemistry based on NMR data was considered inappropriate. Therefore, a high-performance liquid chromatography method was established to separate the isomers, and natural higenamine 4'-O-ß-d-glucoside was determined to be a mixture of isomers.

Isolation and lipolytic activity of eurycomanone and its epoxy derivative from Eurycoma longifolia.

Eurycomanone (1) and 13ß,21-epoxyeurycomanone (2) were isolated from Eurycoma longifolia for studies of lipolytic activity. Compound 1 enhanced lipolysis in adipocytes with an EC50 of 14.6µM, while its epoxy derivate, compound 2, had a stronger activity with an EC50 of 8.6µM. Based on molecular mechanistic study using several specific inhibitors to lipolytic signaling pathways, it was found that PKA inhibitor totally diminished the lipolytic activity of 1 and 2. Further immunoblotting analysis confirmed the activation of phosphorylated PKA by both 1 and 2. With the growing need to develop new anti-obesity agents, eurycomanone and its epoxy derivate can be used as promising lead compounds to target lipid catabolism.

Astilbe thunbergii reduces postprandial hyperglycemia in a type 2 diabetes rat model via pancreatic alpha-amylase inhibition by highly condensed procyanidins.

Type 2 diabetes mellitus (T2DM) is a common global health problem. Prevention of this disease is an important task, and functional food supplements are considered an effective method. We found potent pancreatic α-amylase inhibition in Astilbe thunbergii root extract (AT) and confirmed that AT treatment in a T2DM rat model reduces post-starch administration blood glucose levels. Activity-guided isolation revealed procyanidin (AT-P) as the α-amylase inhibitory component with IC50 = 1.7 µg/mL against porcine pancreatic α-amylase. Structure analysis of AT-P revealed it is a B-type procyanidin comprised of four types of flavan-3-ols, some with a galloyl group, and catechin attached as the terminal unit. The abundant AT-P content and its comparable α-amylase inhibition to acarbose, the anti-diabetic medicine, suggest that AT is a promising food supplement for diabetes prevention.

Iriomoteolides-9a and 11a: two new odd-numbered macrolides from the marine dinoflagellate Amphidinium species.

Iriomoteolides-9a (1) and 11a (2), new 15- and 19-membered macrolides, respectively, have been isolated from the marine dinoflagellate Amphidinium species (strain KCA09052). Compounds 1 and 2 were obtained from the extracts of the algal cells inoculated in the PES and TKF seawater medium, respectively. The structures of 1 and 2 were assigned on the basis of detailed NMR analyses. Compounds 1 and 2 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa cells.

Structural Analysis of Novel Low-Digestible Sucrose Isomers Synthesized from D-Glucose and D-Fructose by Thermal Treatment.

The synthesis of the saccharide ß-D-fructopyranosyl-(2→6)-D-glucopyranose, which was isolated from Super Ohtaka®, has recently been reported. During the synthesis of this saccharide, the formation of two novel saccharides from D-glucose and D-fructose was observed. The present study aimed to confirm the structures of the two disaccharides synthesized from D-glucose and D-fructose by thermal treatment. Furthermore, various properties of the saccharides were investigated. Both saccharides were isolated from the reaction mixture by carbon-Celite column chromatography and an HPLC system and were determined to be novel sucrose-isomers, ß-D-fructopyranosyl-(2↔1)-ß-D-glucopyranoside (1) and ß-D-fructofuranosyl-(2↔1)-ß-D-glucopyranoside (2), by MALDI-TOF MS and NMR analyses. Both saccharides showed low digestibility in vitro, and the sweetness of saccharide 2 was 0.45 times that of sucrose.

Structural Analysis of a Novel Oligosaccharide Isolated from Fermented Beverage of Plant Extracts.

A fermented beverage of plant extracts (Super Ohtaka®) was prepared from about 50 kinds of fruits and vegetables. This natural fermentation was performed by yeast (Zygosaccharomyces spp. and Pichia spp.) and lactic acid bacteria (Leuconostoc spp.) and resulted in the production of a novel fructopyranose-containing saccharide, which was subsequently isolated using carbon-Celite column chromatography and preparative-HPLC. The structure of the saccharide was determined using MALDI-TOF MS and NMR, and the saccharide was identified as ß-D-fructopyranosyl-(2→6)-ß-D-fructofuranosyl-(2↔1)-α-D-glucopyranoside. This is the first description of this novel saccharide and its isolation from a natural source.

Isolation of rugosin A, B and related compounds as dipeptidyl peptidase-IV inhibitors from rose bud extract powder.

Dipeptidyl peptidase-IV (DPP-IV) is a protease responsible for the degradation of the incretin hormone. A number of DPP-IV inhibitors have been approved for use in the treatment of type 2 diabetes. While these inhibitors are effective for this treatment, methods for the prevention of this disease are also required as diabetes patient numbers are currently increasing rapidly worldwide. We screened the DPP-IV inhibitory activities of edible plant extracts with the intention of using these extracts in a functional food supplement for the prevention of diabetes. Rose (Rosa gallica) bud extract powder was a promising material with high inhibitory activity. In this study, seven ellagitannins were isolated as active compounds through activity-guided fractionations, and their DPP-IV inhibitory activities were measured. Among them, rugosin A and B showed the highest inhibitory activities and rugosin B was shown as the major contributing compound in rose bud extract powder.

Iriomoteolides-10a and 12a, Cytotoxic Macrolides from Marine Dinoflagellate Amphidinium Species.

Two new macrolides, iriomoteolides-10a (1) and -12a (2), have been isolated from a marine dinoflagellate Amphidinium sp. (KCA09053 strain), and their structures were elucidated on the basis of a detailed two dimensional (2D)-NMR analysis. Compound 1 is a novel 21-membered Amphidinium macrolide, which contains one tetrahydrofuran ring, two ketone carbonyls, two hydroxyl groups, and six one-carbon branches. Compound 2 is a new 12-membered macrolide related to amphidinolide Q. Compound 1 exhibited cytotoxic activity against human cervix adenocarcinoma HeLa and murine hepatocellular carcinoma MH134 cells.

Structural analysis of novel kestose isomers isolated from sugar beet molasses.

Eight kestose isomers were isolated from sugar beet molasses by carbon-Celite column chromatography and HPLC. GC-FID and GC-MS analyses of methyl derivatives, MALD-TOF-MS measurements and NMR spectra were used to confirm the structural characteristics of the isomers. The (1)H and (13)C NMR signals of each isomer saccharide were assigned using COSY, E-HSQC, HSQC-TOCSY, HMBC and H2BC techniques. These kestose isomers were identified as α-D-fructofuranosyl-(2- > 2)-α-D-glucopyranosyl-(1 < ->2)-ß-D-fructofuranoside, α-D-fructofuranosyl-(2- > 3)-ß-D-fructofuranosyl-(2 < ->1)-α-D-glucopyranoside, α-D-fructofuranosyl-(2- > 4)-ß-D-fructofuranosyl-(2 < ->1)-α-D-glucopyranoside, ß-D-fructofuranosyl-(2- > 4)-ß-D-fructofuranosyl-(2 < ->1)-α-D-glucopyranoside, ß-D-fructofuranosyl-(2- > 3)-α-D-glucopyranosyl-(1 < ->2)-ß-D-fructofuranoside, α-D-fructofuranosyl-(2- > 1)-ß-D-fructofuranosyl-(2 < ->1)-α-D-glucopyranoside, α-D-fructofuranosyl-(2- > 6)-α-D-glucopyranosyl-(1 < ->2)-ß-D-fructofuranoside, and α-D-fructofuranosyl-(2- > 6)-ß-D-fructofuranosyl-(2 < ->1)-α-D-glucopyranoside. The former five compounds are novel saccharides.

Structural confirmation of novel oligosaccharides isolated from sugar beet molasses.

Eleven oligosaccharides were isolated from sugar beet molasses using carbon-Celite column chromatography and HPLC. The constituent sugars and linkage positions were determined using methylation analysis, MALDI-TOF-MS, and NMR measurements. The configurations of isolated oligosaccharides were confirmed based on detailed NMR analysis. Based on our results, three of the 11 oligosaccharides were novel.

Higenamine 4'-O-ß-d-glucoside in the lotus plumule induces glucose uptake of L6 cells through ß2-adrenergic receptor.

Hypoglycemic effect is an efficient means to modulate elevated blood glucose levels in patients with diabetes. We found that the extract of lotus plumule (the germ of Nelumbo nucifera Gaertn. seed) showed potent glucose uptake enhancement activity against L6 myotubes, which results in a hypoglycemic effect. This activity was further investigated, and an active constituent was identified as a single bioactive compound, higenamine 4'-O-ß-d-glucoside. Mechanistic studies employing phosphatidylinositol 3-kinase (PI3K) inhibitor, AMP-activated protein kinase (AMPK) inhibitor, or adrenergic receptor antagonist showed that the compound induced its activity through ß2-adrenergic receptor. Patients with type II diabetes mellitus frequently develop insulin resistance. Owing to the differences between the mechanism of action of insulin and of the isolated compound, the compound or lotus plumule itself may have the possibility of modulating blood glucose levels in insulin-resistant patients effectively.

Uncovering potential of Indonesian medicinal plants on glucose uptake enhancement and lipid suppression in 3T3-L1 adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: As obesity is a key factor in the development of type 2 diabetes, lowering lipid accumulation in adipose tissues is as important as increasing insulin sensitivity in diabetic patients. The selected plant extracts used in this screen have been traditionally used in Indonesian medicine for the treatment of diabetes and its complications. AIM OF THE STUDY: To investigate the ability of the selected plants to both increase insulin sensitivity through the enhancement of glucose uptake after insulin induction in adipocytes and suppress lipid production in the same target cells. MATERIALS AND METHODS: Dried Indonesian medicinal plants were extracted with 50% (v/v) aq. methanol. The extracts were dissolved in 50% DMSO when tested in 3T3-L1 adipocytes. The screening platform consists of insulin-induced glucose uptake, lipid accumulation, and cell viability. Initially, an enzymatic fluorescence assay was designed to demonstrate the enhancement of 2-deoxyglucose (2-DG) uptake after insulin induction. Different concentrations of the extracts that enhanced glucose uptake were subjected to lipid accumulation assay using Oil Red O staining. Potential extracts based on lipid suppression were subsequently assessed by CCK-8 cell viability assay to distinguish lipid reduction activity from cytotoxicity. RESULTS: Out of 59 plants, 13 plants demonstrated their ability to increase glucose uptake in 3T3-L1 adipocytes after insulin induction, and 4 of these plants' extracts suppressed lipid production of the cells. The CCK-8 assay results of those 4 plant extracts suggest that the lipid inhibition activity of Eurycoma longifolia Jack (root) and Piper nigrum L. (fruits) extracts is not attributed to their cytotoxicity in the adipose cells. Both of the plant extracts increased glucose uptake by more than 200% at 50 µg/mL and suppressed lipid accumulation in a concentration-dependent manner. CONCLUSIONS: Screening of selected Indonesian medicinal plants has uncovered the potentials of E. longifolia Jack (root) and P. nigrum L. (fruits) with dual active functions, increasing insulin sensitivity through the enhancement of glucose uptake and reducing lipid accumulation in adipose cells. These findings suggest that the ability of both plants to suppress lipid production would provide additional benefits in the treatment of diabetes.

Amphirionin-2, a novel linear polyketide with potent cytotoxic activity from a marine dinoflagellate Amphidinium species.

A novel linear polyketide, amphirionin-2 (1), with two unique hexahydrofuro[3,2-b]furan moieties has been isolated from the cultivated algal cells of a benthic dinoflagellate Amphidinium sp. (strain KCA09051). The structure was elucidated on the basis of detailed analyses of 2D NMR data, and the absolute configuration of C-5 was determined by using modified Mosher's method. Amphirionin-2 (1) exhibited potent cytotoxic activity against human colon carcinoma Caco-2 cells and human lung adenocarcinoma A549 cells.

Amphirionin-4 with potent proliferation-promoting activity on bone marrow stromal cells from a marine dinoflagellate amphidinium species.

A linear polyketide, amphirionin-4 (1), has been isolated from cultivated algal cells of the marine dinoflagellate Amphidinium species. The structure was elucidated on the basis of detailed analyses of 1D and 2D NMR data, and the absolute configurations of C-4 and C-8 were determined using the modified Mosher's method. Amphirionin-4 (1) exhibited extremely potent proliferation-promoting activity on murine bone marrow stromal ST-2 cells (950% promotion) at a concentration of 0.1 ng/mL.