Ultrasonography is an effective tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

BACKGROUND: Individuals with severe motor and intellectual disabilities have become an aging population, and high cancer morbidity and mortality are critical issues affecting their survival. Cancer screening is a crucial method of resolving this issue; however, a suitable screening method for them has not been established. METHODS: We used ultrasonography alone and performed breast cancer screening for women over 30 years old in our facility from 2016 to 2023. We observed the outcomes and calculated the recall/detection rate in this screening. RESULTS: Three cases among 379 tested positive in this screening, all of which underwent radical surgery. They are alive and well without relapse present. We detected these breast cancer cases with a low recall rate. CONCLUSION: We were able to successfully detect breast cancer cases using ultrasonography alone. Ultrasonography is an effective and feasible tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

Quantitative and time-course analysis of microbial degradation of 1H,1H,2H,2H,8H,8H-perfluorododecanol in activated sludge.

A methylene group in the fluorinated carbon backbone of 1H,1H,2H,2H,8H,8H-perfluorododecanol (degradable telomer fluoroalcohol, DTFA) renders the molecule cleavable by microbial degradation into two fluorinated carboxylic acids. Several biodegradation products of DTFA are known, but their rates of conversion and fates in the environment have not been determined. We used liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) to quantitatively investigate DTFA biodegradation by the microbial community in activated sludge in polyethylene terephthalate (PET) flasks, which we also determined here showed least adsorption of DTFA. A reduction in DTFA concentration in the medium was accompanied by rapid increases in the concentrations of 2H,2H,8H,8H-perfluorododecanoic acid (2H,2H,8H,8H-PFDoA), 2H,8H,8H-2-perfluorododecenoic acid (2H,8H,8H-2-PFUDoA), and 2H,2H,8H-7-perfluorododecenoic acid and 2H,2H,8H-8-perfluorododecenoic acid (2H,2H,8H-7-PFUDoA/2H,2H,8H-8-PFUDoA), which were in turn followed by an increase in 6H,6H-perfluorodecanoic acid (6H,6H-PFDeA) concentration, and decreases in 2H,2H,8H,8H-PFDoA, 2H,8H,8H-2-PFUDoA, and 2H,2H,8H-7-PFUDoA/2H,2H,8H-8-PFUDoA concentrations. Accumulation of perfluorobutanoic acid (PFBA), a presumed end product of DTFA degradation, was also detected. Our quantitative and time-course study of the concentrations of these compounds reveals main routes of DTFA biodegradation, and the presence of new biodegradation pathways.

Interaction of Organogermanium Compounds with Saccharides in Aqueous Solutions: Promotion of Aldose-to-ketose Isomerization and Its Molecular Mechanism.

This review discusses sugar isomerization with organogermanium compounds. Organogermanium compounds markedly increase the aldose-ketose (glucose-fructose or lactose-lactulose) isomerization ratio, double the initial reaction rate, and significantly reduce the base-catalyzed degradation of sugars. 1H-nuclear magnetic resonance analysis reveals that the affinity of organogermanium compounds with a 3-(trihydroxygermyl)propanoic acid (THGP) structure toward ketoses is 20-40 times stronger than that toward aldoses; thus, such organogermanium compounds form complexes more readily with ketoses than with aldoses. Stable ketose complexes, which contain multiple cis-diol structures and high fractions of furanose structures, suppress the reverse ketose-aldose reaction, thereby shifting the equilibrium toward the ketose side. These complexes also protect sugar molecules from alkaline degradation owing to the repulsion between anionic charges. The increased rate of the initial reaction in the alkaline isomerization process results from stabilizing the transition state by forming a complex between THGP and a cis-enediol intermediate. The cyclic pentacoordinate or hexacoordinate THGP structures give rise to a conjugated system of germanium orbitals, which is extended through dπ-pπ interactions, thereby improving the stability of the complex. Based on these results, we have developed a bench-scale lactulose syrup manufacturing plant incorporating a system to separate, recover, and reuse organogermanium poly-trans-[(2-carboxyethyl)germasesquioxane]. This manufacturing plant can be used as a model of an alkaline isomerization accelerator for continuous industrial production.

An Organogermanium Compound Enhances the Initial Reaction Rate of Alkaline Isomerization of an Aldose into a Ketose through Enediol Complex Formation.

We previously demonstrated that the organogermanium compound 3-(trihydroxygermyl)propanoic acid (THGP) enhances the enzymatic and alkaline isomerization of an aldose to a ketose through cis-diol complex formation by multiple mechanisms. Its higher affinity for the ketose than the aldose protects the ketose complex from alkaline decomposition. Furthermore, it has been reported that the aldose-ketose alkaline isomerization pathway includes 1,2-enediol. Therefore, we speculated that the complex-forming ability of THGP could also be applied to enediol, a transient intermediate of alkaline isomerization. To test this prediction, we analyzed the initial rates of glucose or lactose isomerization in a region where there was no substantial difference in pH with and without THGP addition. The results showed that THGP enhanced the rate of fructose or lactulose formation per unit time by approximately 2-fold compared to the control. This finding indicated that THGP could form a complex with the transition state of aldose-ketose alkaline isomerization.

Quantitative assessment of the interactions between the organogermanium compound and saccharides using an NMR reporter molecule.

Poly-trans-[(2-carboxyethyl)germasesquioxane], Ge-132, is a water-soluble organogermanium compound reported to have physiological effects such as immunostimulatory and antiviral effects. The hydrolysate of Ge-132, 3-(trihydroxygermyl)propanoic acid (THGP), can interact with diols; therefore, it likely can interact with diol-containing sugars in sugar chains, glycoproteins, and glycolipids, which have important physiological functions. In this study, we quantitatively assessed the ability of THGP to interact with saccharides using nuclear magnetic resonance (NMR) spectroscopy and THGP derivatives. THGP was complexed by binding its trihydroxy group with saccharides in aqueous solutions via the cis-diol group rather than the trans-diol group. The spectra of THGP and monosaccharides indicated that THGP has a higher affinity for ketose than aldose. Moreover, the complexation ability between THGP and saccharides was influenced by the number of cis-diol groups on the saccharide structure. Thus, interactions of THGP with important biological sugars might be involved in the physiological functions of Ge-132.

Microbial biodegradation of a novel fluorotelomer alcohol, 1H,1H,2H,2H,8H,8H-perfluorododecanol, yields short fluorinated acids.

The accumulation of perfluorooctanoic acid (PFOA) has been detected in wildlife, soil, and water. Further, 8:2 fluorotelomer alcohol (8:2 FTOH) is used for the industrial synthesis of other fluorotelomer compounds, surfactants, and polymeric materials; however, it was recently found to be a potential source of PFOA contamination in the environment. 1H,1H,2H,2H,8H,8H-perfluorododecanol (degradable telomer fluoroalcohol (DTFA)), which is a newly developed fluorotelomer, contains the -CH2- group in the fluorinated carbon backbone, making it potentially degradable through biological reactions. In this study, we investigated the biodegradation of DTFA in a mixed bacterial culture obtained from activated sludge. Optimized quantitative liquid chromatography-mass spectrometry analysis of the predicted metabolites generated in the culture revealed accumulations of the transformation products from DTFA to 2H,2H,8H,8H-PFDoA and 2H,8H,8H-2-PFUDoA via multiple processes. Furthermore, the production of short fluorinated compounds, perfluorobutanoic acid, perfluoropentanoic acid, and perfluoropentanedioic acid, which are believed to have lower accumulation potential and toxicity toward organisms than PFOA, was determined.

Efficient Continuous Production of Lactulose Syrup by Alkaline Isomerization Using an Organogermanium Compound.

Lactulose, a keto-type disaccharide widely used in pharmaceuticals and functional foods, is produced by the isomerization of lactose. The organogermanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) is an effective reaction promoter for the conversion of lactose to lactulose because of its high affinity to ketoses. Herein, an effective method for the continuous production of lactulose syrup was developed using Ge-132 through the alkaline isomerization of lactose in a bench-scale plant. This plant carried out a continuous isomerization process using Ge-132, continuous two-step separation process for separating the sugar and Ge-132, a continuous purification and concentration processes for the lactulose syrup, and separation and purification processes for the recovery of Ge-132. In this bench-scale plant, lactulose-containing syrup (350 g/L lactulose, 92 g/L lactose, and 31 g/L galactose) was prepared. The syrup was produced at a rate of 37.7 mL/h, and the content of residual Ge-132 in the syrup was 2 mg/L. The separation process was a two-step separation system requiring an ordinary electrodialyzer and an electro deionizer, which allowed the separation of more than 99.6 % Ge-132 from the reaction mixture. Moreover, the majority of Ge-132 and sodium hydroxide were recovered through electrodialysis using a bipolar membrane. The proposed system is the first to represent the novel development of an effective continuous production system for lactulose-containing syrup on the basis of the use of organogermanium compounds and incorporation of the electrodialysis technology.

The Organogermanium Compound Ge-132 Interacts with Nucleic Acid Components and Inhibits the Catalysis of Adenosine Substrate by Adenosine Deaminase.

Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) is a water-soluble organogermanium compound that exerts various physiological effects, including anti-inflammatory activity and pain relief. In water, Ge-132 is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP), which in turn is capable of interacting with cis-diol compounds through its trihydroxy group, indicating that this compound could also interact with diol-containing nucleic acid constituents. In this study, we evaluated the ability of THGP to interact with nucleosides or nucleotides via nuclear magnetic resonance (NMR) analysis. In addition, we evaluated the effect of added THGP on the enzymatic activity of adenosine deaminase (ADA) when using adenosine or 2'-deoxyadenosine as a substrate. In solution, THGP indeed formed complexes with nucleotides or nucleosides through their cis-diol group. Moreover, the ability of THGP to form complexes with nucleotides was influenced by the number of phosphate groups present on the ribose moiety. Notably, THGP also inhibited the catalysis of adenosine by ADA in a concentration-dependent manner. Thus, interactions between THGP and important biological nucleic acid constituents might be implicated in the physiological effects of Ge-132.

Efficient Alkaline Isomerization of Lactose to Lactulose in the Presence of an Organogermanium Compound.

Lactulose, a disaccharide widely used in pharmaceuticals and functional foods, is produced by lactose isomerization. Lactose and lactulose have an aldose-ketose relationship. Less than 25 % conversion of lactose into lactulose is achieved using the Lobry de Bruyn-Alberda van Ekenstein transformation with heating, whereas the conversion is increased to 80 % by the addition of an approximately equimolar concentration of the organogermanium compound 3-(trihydroxygermyl)propanoic acid (THGP) to the reaction mixture. To further understand this phenomenon, in this study, we analyzed the affinity between THGP and sugar isomers using 1H nuclear magnetic resonance spectroscopy. For the dimethyl derivative of THGP with lactose and lactulose, the complex formation ratios at 0.1 M (1:1 mixing ratio) were 14 and 59 %, respectively, with complex formation constants of 1.8 and 43 M-1, respectively. The complex formation capacity was approximately 24-fold higher for lactulose than for lactose. Moreover, THGP is considered to protect lactulose from alkaline degradation, resulting in high production yield of lactulose. Therefore, we concluded that high affinity for the isomerization product may promote isomerization and that promotion of sugar isomerization using an organogermanium compound is an effective method for converting lactose to lactulose.

Efficient Conversion of D-Glucose to D-Fructose in the Presence of Organogermanium Compounds.

D-Glucose and D-fructose are isomers of commonly consumed monosaccharides. The ratio of conversion of D-glucose to D-fructose by glucose isomerase (xylose isomerase) is not more than 50 %. However, addition of an equimolar ratio of the organogermanium compound poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) or its derivative increases the conversion ratio to 80 %. In contrast, use of the Lobry de Bruyn-Alberda van Ekenstein transformation with heating results in a lower conversion ratio, less than 30 %, whereas addition of an equimolar concentration of Ge-132 or its derivative to this reaction mixture increases the ratio to 73 %. Therefore, in this study, we aimed to further analyze the affinity between organogermanium compounds (i.e., Ge-132 and its derivatives) and sugar using 1H-nuclear magnetic resonance (NMR) spectrometry. For the dimethyl derivative of Ge-132, the complex formation ratios at 0.25 M (mixing ratio 1:1) were 19 and 74 % for D-glucose and D-fructose, respectively. Additionally, the complex formation constants between monosaccharides and Ge-132 were 1.2 and 46 M-1 for D-glucose and D-fructose, respectively. The complex formation capacity was approximately 40-fold higher for D-fructose than for D-glucose. Therefore, we concluded that the high affinity for the product of isomerization may promote isomerization, and that promotion of sugar isomerization using organogermanium compounds is an effective method for conversion of D-glucose to D-fructose.

Nuclear magnetic resonance studies of the interactions between the organic germanium compound Ge-132 and saccharides.

Poly-trans-[(2-carboxyethyl)germasesquioxane], Ge-132, is a water-soluble organic germanium compound with many reported physiological functions. The hydrolysate of Ge-132, 3-(trihydroxygermyl)propanoic acid, can interact with diol compounds; therefore, it can possibly interact with diol-containing sugar compounds, which have important physiological functions in sugar chains, glycoproteins, and glucolipids. In this study, we examined the interaction between sodium 3-(trihydroxygermyl)propanoate and monosaccharides using nuclear magnetic resonance. When 1,4-anhydroerythritol was mixed with sodium 3-(trihydroxygermyl)propanoate, a pattern of signals different from that obtained for each solute alone was observed. Some signals were broader, and novel signals with different chemical shifts appeared to originate from complex formation. Spectral observations for sodium 3-(trihydroxygermyl)propanoate and the sugar isomers of glucose and fructose indicated that sodium 3-(trihydroxygermyl)propanoate has a higher affinity for fructose (a ketose) than glucose (an aldose). Moreover, the ß-furanosyl conformation of fructose was the structure that interacted most with sodium 3-(trihydroxygermyl)propanoate. These results demonstrate the ability of aqueous Ge-132 to form complexes with the cis-diol structures of saccharides. Thus, interactions among 3-(trihydroxygermyl)propanoic acid and the important biological sugar compounds might be implicated in the physiological function of Ge-132.

Organogermanium compound, Ge-132, forms complexes with adrenaline, ATP and other physiological cis-diol compounds.

BACKGROUND: In mammals, adrenaline and ATP are life-essential vicinal diol and cis-diol functional groups. Here, we show that interactions between a safe organogermanium compound and these cis-diol compounds have the potential to regulate physiological functions. In addition, we represent a possible new druggable target for controlling the action of cis-diol compounds. RESULTS: We analyzed a single crystal structure of organogermanium 3-(trihydroxygermyl)propanoic acid (THGPA), a hydrolysate of safe Ge-132, in complex with catecholamine (adrenaline and noradrenaline), and evaluated the affinity between several cis-diol compounds and THGPA by NMR. An in vitro study using normal human epidermal keratinocytes was performed to investigate the inhibition of cis-diol compound-stimulated receptors by THGPA. At high concentration, THGPA inhibited the calcium influx caused by adrenaline and ATP. CONCLUSION: This study demonstrates that THGPA can modify cis-diol-mediated cell-to-cell signaling.

Cercariometry for detection of transmission sites for schistosomiasis.

Cercariometry provided information on diurnal fluctuation, seasonal and spatial distribution of cercariae in the suitable natural water bodies. There was an apparent mismatch between the results of cercariometry and snail sampling. Water, which cercariometry showed to contain cercariae was potentially infective, although the resultant worm load of sentinel rodents may not bear a linear relationship with cercarial density. Cercariometry has some weakness in practices and analysis of data, however, it provides the valuable information on the active transmission sites of schistosomiasis.

Evaluation of the effects of dietary organic germanium, ge-132, and raffinose supplementation on caecal flora in rats.

Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) is the most common organic germanium compound. The ingestion of Ge-132 promotes bile secretion. We assessed the rat caecal characteristics after the administration of Ge-132 and raffinose, a prebiotic oligosaccharide, because both Ge-132 and some prebiotics can change the fecal color to yellow. We also compared the changes in the caecal flora caused by the two compounds. In addition, we evaluated the simultaneous administration of Ge-132 and raffinose and their effects on ß-glucuronidase activity, which is known to be a factor related to colon cancer. Male Wistar rats (three weeks old) were given one of the following diets: 1) a control diet (control group), 2) a diet containing 0.05% Ge-132 (Ge-132 group), 3) a diet containing 5% raffinose (RAF group) or 4) a diet containing 0.05% Ge-132 + 5% raffinose (GeRAF group). The Bifidobacterium, Lactobacillus and total bacteria counts were significantly increased by the dietary raffinose, and Ge-132 did not suppress this increase. The raffinose intake increased caecal acetic acid production significantly. The activity of ß-glucuronidase in the caecal contents was increased by dietary Ge-132, whereas dietary raffinose decreased the ß-glucuronidase activity significantly. These results indicate that the simultaneous intake of dietary raffinose and Ge-132 does not inhibit the effects of either compound on intestinal fermentation and bile secretion. Additionally, the simultaneous intake of both raffinose and Ge-132 could abrogate the increase in ß-glucuronidase activity induced by Ge-132 alone.