Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity.

Innate immune signaling via TLR4 plays critical roles in pathogenesis of metabolic disorders, but the contribution of different lipid species to metabolic disorders and inflammatory diseases is less clear. GM3 ganglioside in human serum is composed of a variety of fatty acids, including long-chain (LCFA) and very-long-chain (VLCFA). Analysis of circulating levels of human serum GM3 species from patients at different stages of insulin resistance and chronic inflammation reveals that levels of VLCFA-GM3 increase significantly in metabolic disorders, while LCFA-GM3 serum levels decrease. Specific GM3 species also correlates with disease symptoms. VLCFA-GM3 levels increase in the adipose tissue of obese mice, and this is blocked in TLR4-mutant mice. In cultured monocytes, GM3 by itself has no effect on TLR4 activation; however, VLCFA-GM3 synergistically and selectively enhances TLR4 activation by LPS/HMGB1, while LCFA-GM3 and unsaturated VLCFA-GM3 suppresses TLR4 activation. GM3 interacts with the extracellular region of TLR4/MD2 complex to modulate dimerization/oligomerization. Ligand-molecular docking analysis supports that VLCFA-GM3 and LCFA-GM3 act as agonist and antagonist of TLR4 activity, respectively, by differentially binding to the hydrophobic pocket of MD2. Our findings suggest that VLCFA-GM3 is a risk factor for TLR4-mediated disease progression.

Real-time wireless compliance monitoring system using calendar-type pill organizer.

BACKGROUND: Accurate information about patients' use of medication is crucially important for medical treatment. Real-time information can prevent treatment failure resulting from medication delays or failures. OBJECTIVE: In this study, a compliance-monitoring system is developed for physicians to ascertain their patients' drug-taking behaviors at home in real time. Its operation is then evaluated. METHODS: The authors produced a device that uses wireless communication to notify a physician that drugs are taken out of a package by a patient. The device has sensors to detect the package opening. A wireless module is installed in a drug-containing calendar-type pill organizer. RESULTS: Experimental trials confirmed that a physician can monitor the kind and number of drugs removed from the package on a real-time basis. Furthermore, a practical system can be produced by measuring the distance and consumption current of the produced device, which allows wireless communication. CONCLUSIONS: This system enables a doctor to intervene immediately when any compliance lapse occurs, thereby preventing treatment failure caused by delayed response.

Compliance monitoring system using screen printing technology based on conductive ink.

We developed a compliance monitoring system that electrically detects which drug among the multiple prescribed drugs a patient has taken and the date of drug-taking by a patient to prevent the patient from missing doses and taking drugs incorrectly at home. A conductive pattern is screen printed using conductive ink (silver paste) on the surface of a calendar-type pill organizer containing medications for as long as 1 week (4 times per day × 7 days, 28 doses) to create a sensor for detecting the opening of a pill organizer. Whenever the patient opens the pill organizer and removes a dose of the drug (pill), information about which of the 28 locations is opened and the date of opening are recorded in nonvolatile memory. This system is applicable to patients who take multiple drugs, for whom recording of drug-taking behavior is reportedly difficult. Specific benefits are that the user needs no additional manipulation to use the system: the user can take the drug from the pill organizer according to usual procedures.

Assisting the diagnosis of overt hypothyroidism with pattern recognition methods, making use of a set of routine tests, and their multiple correlation with total T4.

In our previous papers we proposed a novel screening method that assists the diagnosis of patients with overt Graves' hyperthyroidism by making use of routine test data and pattern recognition methods. This method can be applied by non-specialists during physical check-ups at low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists, that is, to improve patients' QOL. In this report, we investigate whether a similar screening method is also applicable for overt hypothyroidism. Fifty-six subjects with 12 routine test data with a known diagnosis (30 patients with overt hypothyroidism and 52 healthy female volunteers, and 26 patients with overt hypothyroidism and 48 healthy male volunteers) were used as training data. Then, test samples of patients who had also undergone the same routine tests at the Tohoku university hospital were screened by our method for overt hypothyroidism. The present examination of the screening method showed its high screening ability with the set of four parameters used (lactate dehydrogenase [LDH], total cholesterol [TC], red blood cell [RBC] and serum creatinine [S-Cr]). It was found that there was a strong multiple correlation between the set of routine test parameters and serum total thyroxine (TT4) in the patients with overt hypothyroidism, which supports the usefulness of our screening method.

Assisting the diagnosis of Graves' hyperthyroidism with pattern recognition methods and a set of three routine tests parameters, and their correlations with free T4 levels: Extension to male patients.

In our previous paper, we proposed a novel screening method that aids the diagnosis of female patients with Graves' hyperthyroidism via two types of neural networks and the use of routine test data. This method can be applied by non-specialists during physical checkups at a low cost and is expected to lead to rapid referrals for examination and treatment by thyroid specialists; i.e., to improve patients' QOL. In this report, we investigate whether the screening method is also applicable to males since sex differences exist in routine test data. The values of 14 routine test parameters for 78 subjects with definite diagnoses (31 patients with Graves' hyperthyroidism and 48 healthy volunteers) were adopted as training data, and 133 individuals who had also undergone the same routine tests at Tohoku University Hospital were screened for Graves' hyperthyroidism using our method. The present examination of our screening method in males showed its high screening ability with the set of parameters used (low serum creatinine, elevated alkaline phosphatase, and low total cholesterol). It was also found that there is strong multiple correlation between a set of three parameters and serum free thyroxine (FT4) in male patients with Graves' hyperthyroidism. A formula for FT4 consisting of three parameters was obtained, and this can be utilized in place of the true FT4 value. This result also supports the usefulness of our screening method.