Background and Aims Methylglyoxal-derived hydroimidazolone (MG-H1), one of the advanced glycation end-products (AGEs), has been a potential biomarker of type 2 diabetes (T2DM), which is strongly related to insulin resistance. However, the relationship between the dynamics of MG-H1 and insulin resistance has not been characterized, and its mechanism on insulin resistance is unknown. In this study, we aimed to investigate the relationship between MG-H1 and insulin resistance in the clinical study of Japanese individuals and identify the molecular mechanisms underlying MG-H1 associated phenomena in vitro. Methods We performed the meal tolerance test (MTT) and hyper-insulinemic-euglycemic clamp analysis in 19 patients with T2DM and 19 participants without diabetes (non-DM). We measured their fasting and postprandial MG-H1 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the effects of MG-H1 on glucose uptake and insulin signalling in C2C12 skeletal myocytes. Results The postprandial MG-H1 and the area under the curve (AUC) of MG-H1 in MTTs were significantly negatively correlated with the glucose disposal rate (GDR) in clamp studies both in the T2DM (r = -0.72 [p < 0.001]) and non-DM (r = -0.54 [p < 0.05]) groups. In cultured C2C12 skeletal myocytes, pre-treatment with MG-H1 inhibited insulin-stimulated phosphorylation of Akt and glucose uptake, via the activation of mechanistic target of rapamycin complex 2 (mTORC2). Conclusions In clinical study findings revealed that postprandial MG-H1 was a novel marker of insulin resistance in Japanese individuals, and in vitro findings using cultured C2C12 skeletal myocytes suggested that MG-H1 disturbs insulin signalling via the mechanisms of mTORC2 activation.

Background Schistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones. Moreover, crude antigens such as soluble egg antigen (SEA) show cross-reactivity with other parasitic infections, and it is difficult to formulate the standard preparations. To resolve these issues, the performances of recombinant antigens have been evaluated. The antibody responses against recombinant S. haematobium serine-protease inhibitor (ShSerpin) and RP26 were previously shown to reflect active schistosome infection in humans. Furthermore, antibody detection using multiple recombinant antigens has been reported to improve the accuracy of antibody-based assays compared to single-target assays. Therefore, we examined the performances of ShSerpin, RP26 and the mixture of these antigens for detecting S. haematobium low-intensity infection and assessed the potential for transmission monitoring. Methodology/principal findings We collected urine and plasma samples from school-aged children in Kwale, Kenya and evaluated S. haematobium prevalence by number of eggs in urine and worm-derived circulating anodic antigen (CAA) in plasma. Among 269 pupils, 50.2% were CAA-positive by the lateral flow test utilizing up-converting phosphor particles (UCP-LF CAA), while only 14.1% were egg-positive. IgG levels to S. haematobium SEA (ShSEA), ShSerpin, RP26, and the mixture of ShSerpin and RP26 were measured by ELISA. The mixture of ShSerpin and RP26 showed the highest sensitivity, 88.7%(125/141)among the four antigens in considering indecisive UCP-LF CAA results as negative. Conclusion/significance IgG detection against the ShSerpin-RP26 mixture demonstrated better sensitivity for detection of active S. haematobium infection. This recombinant antigen mixture is simpler to produce with higher reproducibility and can potentially replace ShSEA in monitoring transmission under near-elimination settings.

The purpose of this study is to examine the pregestational BMI value that results in insulin use in Japanese patients with gestational diabetes mellitus (GDM) and to assess whether the type of GDM treatment affects postpartum glucose tolerance. This retrospective study included 21 GDM patients treated until parturition at our department from 2013 to 2017. We calculated the pregestational BMI related to insulin treatment and the significant elevation in homeostasis model assessment of insulin resistance (HOMA-IR) by receiver operating characteristics curve (ROC) analysis. We also analyzed whether the insulin treatment caused a difference in postpartum glucose tolerance. Seven of the eight patients who needed insulin treatment had a pregestational BMI over 23 kg/m2. The pregestational BMI cutoff value related to insulin treatment was 22.5 kg/m2 (sensitivity 100%, specificity 46.2%, area under the curve 0.668, and Confidence Interval=0.429-0.907) in ROC analysis. Insulin utilization was significantly higher in the group with a pregestational BMI of 22.5 or more (p=0.045). HOMA-IR at postpartum was higher in patients whose pregestational BMI was 22.5kg/m2 or more. Blood glucose levels, HOMA-IR, homeostasis model assessment of β-cell function (HOMA-β), and the insulinogenic index (IGI) after delivery did not differ between the diet and insulin treatment groups. In conclusion, Japanese women with GDM and a pregestational BMI over 23 kg/m2 may increase the risk of requiring insulin treatment during pregnancy. Postpartum glucose tolerance did not differ between patients treated with diet or insulin treatment for GDM.

Fatty acid-binding protein 4 (FABP4) has been reported to act as a hepatic insulin resistance factor. We previously reported that fasting FABP4 was correlated with insulin resistance measurements derived from the glucose clamp, and another study reported that postprandial FABP4 levels were decreased in healthy volunteers but were not reported (or known) in participants with type 2 diabetes. We have limited knowledge about the direct effect of FABP4 on muscle cells. We investigated the postprandial FABP4 levels in participants with type 2 diabetes, and the basic mechanism of muscle insulin resistance and FABP4. We performed a meal tolerance test and hyperinsulinaemic–euglycaemic clamp in 22 participants with type 2 diabetes and 26 participants without diabetes. We measured fasting and postprandial serum FABP4. We cultured mouse C2C12 muscle cells, and investigated the effect of FABP4 on glucose uptake. We analysed insulin signalling by western blot and insulin binding assay. The postprandial FABP4 level in participants with type 2 diabetes was higher than that in participants without diabetes. Participants without diabetes had lower postprandial FABP4 than fasting except for one participant, whereas one-third of participants with type 2 diabetes had higher postprandial FABP4 than fasting. Postprandial FABP4 was correlated with the muscle insulin resistance M/I value from a glucose clamp in participants without diabetes (r=−0.42, p<0.05). The increase in FABP4 after a meal correlated with the muscle insulin resistance M/I value (r=−0.44, p<0.05) and the difference between fasting and postprandial glucagon in participants with type 2 diabetes (r=0.36, p<0.05). FABP4 alone appears to increase glucose uptake, and the combination of FABP4 and insulin decreases glucose uptake when compared with insulin alone. FABP4 inhibits insulin signalling of muscle cells through decreases in phosphorylation of insulin receptor substrate 1 and Akt. The physiological concentration of FABP4 did not inhibit insulin binding to muscle cells. These results suggested that the postprandial FABP4 level is associated with insulin resistance, and FABP4 may suppress insulin signals.

Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas.

Leishmaniasis is a tropical disease caused by Leishmania parasites and currently has no licensed vaccines. We developed a dermotropic Leishmania major centrin gene-deleted strain (LmCen-/-) as a live attenuated vaccine. Recent studies have shown that type I interferons (IFNs) play important roles in immunity to parasitic and viral pathogens. However, their relevance in protective immunity following vaccination is not understood. We found that immunization with LmCen-/- induces a transient increase in type I IFN response along with its regulatory factor IRF7 that is downregulated 7-21 days post-immunization, coincided with the induction of a robust Th1 adaptive immune response. Challenge infection with virulent L. donovani parasites showed a significant reduction of splenic and hepatic parasite burden in IRF7-/- mice than wild type mice following immunization with LmCen-/-, suggesting that ablation of type I IFN response is a pre-requisite for the induction of LmCen-/- mediated Th1 immunity against L. donovani infection.

Background Hepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes mellitus (T2DM). HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. HIC is originally calculated by post-load insulin and C-peptide from the oral glucose tolerance test (OGTT). However, OGTT or meal tolerance tests are a burden for patients, and OGTT is not suitable for overt diabetes due to the risk of hyperglycemia. If we can calculate the HIC from the fasting state, it is preferable. We hypothesized that fasting HIC correlates with postprandial HIC in both participants with T2DM and without diabetes. We investigated whether fasting HIC correlates with postprandial HIC in overt T2DM and nondiabetes subjects (non-DM) evaluated by using glucose clamp and meal load. Methods We performed a meal tolerance test and hyperinsulinemic–euglycemic clamp in 70 subjects, 31 patients with T2DM and 39 non-DM subjects. We calculated the postprandial C-peptide AUC-to-insulin AUC ratio as the postprandial HIC and the fasting C-peptide-to-insulin ratio as the fasting HIC. We also calculated whole-body insulin clearance from the glucose clamp test. Results The fasting HIC significantly correlated with postprandial HIC in T2DM ( r_S = 0.82, P < 0.001). Nondiabetes subjects also showed a significant correlation between fasting and postprandial HIC ( r_S = 0.71, P < 0.001). Fasting HIC in T2DM was correlated with BMI, HbA1c, gamma-glutamyl transpeptidase, HOMA-IR, HOMA-beta, M/I, and whole-body insulin clearance. Fasting HIC in nondiabetes subjects was correlated with HOMA-IR and HOMA-beta. Conclusions These results suggest that fasting HIC is strongly correlated with postprandial HIC in both overt T2DM and non-DM patients, as evaluated by the meal test and glucose clamp method. Fasting HIC could be a convenient marker of HIC.

Background: Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme involved in alcohol metabolism. ALDH2 polymorphism has been reported as a risk factor for type 2 diabetes mellitus (T2DM) and is associated with liver insulin resistance due to alcohol consumption in non-diabetic individuals. Herein, we investigated the association between ALDH2 polymorphisms and insulin resistance in patients with T2DM. Methods: We performed a meal tolerance test and the hyperinsulinemic-euglycemic clamp on 71 Japanese participants: 34 patients with T2DM, and 37 non-diabetic participants. We analyzed the ALDH2 polymorphism (ALDH2 rs67); GG type was defined as the T2DM high-risk group, compared with the low-risk AG and AA groups. Results: Glucose levels were similar in the high- and low-risk T2DM groups. The high-risk group for T2DM showed a significantly higher BMI (p < 0.005), insulin resistance in HOMA-IR (p < 0.05), and Insulin sensitivity index (p < 0.05); however, there were no significant differences in insulin resistance in the clamp test (p = 0.10). Alcohol consumption did not differ significantly between groups (p = 0.66). Non-diabetic participants also showed higher HOMA-IR insulin resistance in the high-risk group (p < 0.05), but insulin resistance levels in the glucose clamp tests (p = 0.56) and insulin secretion were not significant. Conclusion: The results suggest that ALDH2 is an important gene associated with insulin resistance and obesity in Japanese patients with type 2 diabetes.

OBJECTIVE:Galectins are sugar-binding proteins that participate in many biological processes, such as immunity, by regulating host immune cells and their direct interaction with pathogens. They are involved in mediating infection by Schistosoma mansoni, a parasitic trematode that causes schistosomiasis. However, their direct effects on schistosomes have not been investigated.RESULTS:We found that galectin-2 recognizes S. mansoni glycoconjugates and investigated whether galectin-1, 2, and 3 can directly affect S. mansoni in vitro. Adult S. mansoni were treated with recombinant galectin-1, 2, and 3 proteins or praziquantel, a positive control. Treatment with galectin-1, 2, and 3 had no significant effect on S. mansoni motility, and no other differences were observed under a stereoscopic microscope. Hence, galectin-1, 2, and 3 may have a little direct effect on S. mansoni. However, they might play a role in the infection in vivo via the modulation of the host immune response or secretory molecules from S. mansoni. To the best of our knowledge, this is the first study to investigate the direct effect of galectins on S. mansoni and helps in understanding the roles of galectins in S. mansoni infection in vivo.

[This corrects the article DOI: 10.1371/journal.pntd.0008518.].

Infection of C57BL/6 wild-type mice with Leishmania major 5-ASKH or Friedlin strains results in relatively similar pathogenicity with self-healing lesions within weeks. Parasite clearance depends on nitric oxide production by activated macrophages in response to cytokines produced mainly by CD4(+) Th1 cells. In contrast, C57BL/6 Rag2 knockout mice, which lack T and B lymphocytes, show distinct pathologies during infection with these strains. Despite of the similar parasite number, the 5-ASKH infection induced severe inflammation rather than the Friedlin. To determine the immunological factors behind this phenomenon, we infected C57BL/6 Rag2 knockout mice with these two strains and compared immune cell kinetics and macrophage activation status. Compared with the Friedlin strain, the 5-ASKH strain elicited increased pathology associated with the accumulation of CD11b(high), Ly6G(high) neutrophils by week four and increased the expression of macrophage activation markers. We then analyzed the differentially expressed transcripts in infected bone marrow-derived macrophages by RNA sequencing. It showed upregulation of multiple inflammatory transcripts, including Toll-like receptor 1/2 (TLR1/2), CD69, and CARD14, upon 5-ASKH infection. Our findings suggest that different L. major strains can trigger distinct macrophage activation, contributing to the disease outcome observed in the absence of lymphocytes but not in the presence of lymphocytes. IMPORTANCE Disease manifestations of cutaneous leishmaniasis (CL) range from self-healing cutaneous lesions to chronic forms of the disease, depending on the infecting Leishmania sp. and host immune protection. Previous works on mouse models of CL show the distinct pathogenicity of Leishmania major strains in the absence of lymphocytes. However, the mechanisms of this pathology remain uncovered. In the trial to understand the immunological process involved in lymphocyte-independent pathology, we have found a specific induction of macrophages by different L. major strains that affect their ability to mount innate responses leading to neutrophilic pathology when lymphocytes are ablated.

Introduction Pancreatic and duodenal homeobox factor-1 ( PDX-1 ) is an imperative gene for insulin secretion in maturity-onset diabetes of the young 4. PDX-1 gene polymorphism was associated with lower first-phase insulin secretion in a genome-wide association study of intravenous glucose tolerance test. It was not associated with type 2 diabetes risk and insulin secretion in a genome-wide oral glucose tolerance test study. However, there have been no reports of overt type 2 diabetes and insulin resistance evaluation using a glucose clamp. We investigated PDX-1 polymorphism, insulin secretion, and insulin resistance in overt type 2 diabetes. Research design and methods We performed a meal tolerance test (MTT) and hyperinsulinemic–euglycemic clamping on 63 Japanese subjects, 30 with type 2 diabetes and 33 non-diabetic. We analyzed the rs1124607 PDX-1 gene polymorphism and defined A/C and C/C as the high-risk group and A/A as the low-risk group. Results HOMA-beta (homeostatic model assessment beta-cell function) was significantly lower in the high-risk group than in the low-risk group for all subjects (72.9±54.2% vs 107.0±63.5%, p<0.05). Glucose levels and glucose area under the curve (AUC) were not significantly different between both the risk groups. The insulin levels at 60 and 120 min and the insulin AUC after MTT were remarkably lower in the high-risk group than those in the low-risk group for all subjects (AUC 75.7±36.7 vs 112.7±59.5, p<0.05). High-risk subjects with type 2 diabetes had significantly lower insulin levels at 30 and 60 min and insulin AUC than low-risk subjects. Non-diabetic high-risk subjects depicted significantly lower insulin levels at 120 and 180 min. There were negligible differences in insulin resistance between the risk groups. Conclusions These results suggest that the PDX-1 genetic polymorphism is crucial for insulin secretion in Japanese patients with type 2 diabetes.

Background Dipeptidyl peptidase 4 inhibitor (DPP4i) is an effective medicine for type 2 diabetes mellitus (T2DM). Some articles reported DPP4i improves insulin secretion and insulin resistance. However, these effects are not well established by glucose clamp test and test meal in Japanese. We investigated the effect of DPP4i on insulin resistance and insulin secretion by using the glucose clamp test and meal tolerance test (MTT). Methods We performed a MTT, and the hyperinsulinemic-euglycemic clamp in 8 Japanese patients with T2DM. This study was a single-arm study. We measured fasting and postprandial glucose, insulin, incretins, and glucagon levels. We also measured serum adiponectin levels. Results HbA1c was significantly decreased after 3 months. The fasting and postprandial glucose levels were significantly decreased. Fasting and postprandial insulin levels were not changed. The insulin resistance derived from the glucose clamp test was significantly improved. HOMA-IR was not significantly changed. GLP-1 and GIP were significantly increased but glucagon did not change. Adiponectin was not significantly changed. Conclusions Although the number of patients was very small, these results suggested that DPP4i treatment might improve insulin resistance without changing insulin secretion.

BackgroundPrevious studies have attempted to characterize depression using electroencephalography (EEG), but results have been inconsistent. New noise reduction technology allows EEG acquisition during conversation.MethodsWe recorded EEG from 40 patients with depression as they engaged in conversation using a single-channel EEG device while conducting real-time noise reduction and compared them to those of 40 healthy subjects. Differences in EEG between patients and controls, as well as differences in patients' depression severity, were examined using the ratio of the power spectrum at each frequency. In addition, the effects of medications were examined in a similar way.ResultsIn comparing healthy controls and depression patients, significant power spectrum differences were observed at 3 Hz, 4 Hz, and 10 Hz and higher frequencies. In the patient group, differences in the power spectrum were observed between asymptomatic patients and healthy individuals, and between patients of each respective severity level and healthy individuals. In addition, significant differences were observed at multiple frequencies when comparing patients who did and did not take antidepressants, antipsychotics, and/or benzodiazepines. However, the power spectra still remained significantly different between non-medicated patients and healthy individuals.LimitationsThe small sample size may have caused Type II error. Patients' demographic characteristics varied. Moreover, most patients were taking various medications, and cannot be compared to the non-medicated control group.ConclusionA study with a larger sample size should be conducted to gauge reproducibility, but the methods used in this study could be useful in clinical practice as a biomarker of depression.

Sodium–glucose cotransporter 2 inhibitor (SGLT2i) treatment is a therapeutic approach for type 2 diabetes mellitus (T2DM). Some reports have shown that SGLT2i treatment improves insulin resistance; however, few studies have evaluated insulin resistance by the glucose clamp method. Hepatic insulin clearance (HIC) is a new pathophysiological mechanism of T2DM. The effect of SGLT2i treatment on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i treatment on insulin resistance, insulin secretion, incretin levels, body composition, and hepatic insulin clearance. We conducted a meal tolerance test (MTT) and a hyperinsulinemic-euglycemic clamp test in 9 T2DM patients. Ipragliflozin (50 mg/day) was administered, and the MTT and clamp test were performed after 4 months. We calculated HIC as the postprandial C-peptide AUC-to-insulin AUC ratio. We also measured GLP-1, GIP, and glucagon levels during the MTT. Body weight and HbA1c were decreased, although not significantly, after 4 months of treatment. Postprandial glucose, fasting insulin and postprandial insulin were significantly decreased. Insulin resistance with the glucose clamp was not changed, but the HOMA-IR and insulin sensitivity indices were significantly improved. Incretin and glucagon levels were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. The FIB-4 index and fatty liver index were significantly reduced. The HOMA-beta and insulinogenic indices were not changed, but the C-peptide index was significantly increased. Although the number of patients was small, these results suggested that SGLT2i treatment improved liver function, decreased hepatic insulin resistance, and increased hepatic insulin clearance, despite the small weight reduction.

Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a medication for type 2 diabetes mellitus (T2DM). Some reports showed SGLT2i improved insulin resistance, however, the effect on insulin resistance is not well established. Hepatic insulin clearance (HIC) is new pathophysiology of T2DM. The effect of SGLT2i on hepatic insulin clearance and insulin resistance is not well known. We investigated the effect of SGLT2i on insulin resistance, insulin secretion, incretins, body composition, and hepatic insulin clearance. Materials and Methods: We conducted a meal tolerance test (MTT), and the hyperinsulinemic-euglycemic clamp in 9 T2DM patients. 50 mg/day ipragliflozin was admitted, MTT and clamp were performed after 4 months. We calculated the postprandial C-peptide AUC to insulin AUC ratio as the HIC. We also measured GLP1, GIP, and glucagon levels during MTT. Results: Body weight, HbA1c, and body composition were not significantly changed after 4 months of treatment. Postprandial glucose, fasting, and postprandial insulin were significantly decreased. The insulin resistance of the glucose clamp was not changed, but HOMA-IR and insulin sensitivity index (ISI) were significantly improved. Incretins and glucagon were not changed. Hepatic insulin clearance was significantly increased, but whole-body insulin clearance was not changed. Fib 4 index and fatty liver index were significantly reduced. HOMA-beta and insulinogenic index was not changed but the C-peptide index was significantly increased. Conclusions: Although patients’ number was small, these results suggest that SGLT2i treatment decreased hepatic insulin resistance, increased hepatic insulin clearance, and decreased hyperinsulinemia, it might protect beta-cell function.

Background: Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be eliminated in the environment with host excreta to maintain their life cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, immune molecules that orchestrate such immunity remain unclear. IL-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. This study aimed at determining its role in the maturation, reproduction, and excretion of S. mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.Methods: Using S. mansoni-infected IL-33-deficient (IL-33-/-) and wild-type (WT) mice, worm morphology, reproduction, and egg excretion were studied at different time points of infection. IL-5 and IL-13 production in spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of non- and infected mice.Results: Morphology-wise, worms from IL-33-/- and WT mice at the fourth and sixth weeks of infection did not differ. The worms' reproduction, expressed as eggs per worm pair, as well as the excretion of eggs, expressed as the number of eggs in intestinal tissues, did not differ between IL-33-/- and WT mice. In the sixth week of infection, IL-33-/- mice presented impaired type 2 immunity in intestines, characterized by decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. Besides, there was no difference between IL-33-/- and WT mice in the levels of IL-25 and TSLP in intestinal tissues.Conclusions: Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation, reproduction, and egg excretion. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally induced type 2 immunity in intestinal tissues in schistosome infection. Further studies are needed to decipher the role of each of them in schistosomiasis and clarify the possible interactions that might exist between them.

Schistosomiasis remains a worldwide public health problem, especially in sub-Saharan Africa. The World Health Organization targets the goal for its elimination as a public health problem in the 2030 Neglected Tropical Diseases (NTDs) Roadmap. Concerted action and agile responses to challenges will be necessary to achieve the targets. Better diagnostic tests can accelerate progress towards the elimination by monitoring disease trends and evaluating the effectiveness of interventions; however, current examinations such as Kato-Katz technique are of limited power to detect light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) test shows a higher sensitivity compared to the reference standard, Kato-Katz technique, but it still lacks sufficient sensitivity with low infection intensity. In this study, we examined antibody reactions against recombinant protein antigens; Schistosoma mansoni serine protease-inhibitor (SmSerpin) and RP26, by enzyme-linked immunosorbent assay (ELISA) in plasma samples with light-intensity infection. The sensitivity using the cocktail antigen of recombinant SmSerpin and RP26 showed 83.7%. The sensitivity using S. mansoni soluble egg antigen (SmSEA) was 90.8%, but it showed poor specificity (29.7%), while the cocktail antigen presented improved specificity (61.4%). We conclude that antibody detection to the SmSerpin and RP26 protein antigens is effective to detect S. mansoni light-intensity infections. Our study indicates the potential of detecting antibody against recombinant protein antigens to monitor the transmission of schistosomiasis in low endemicity contexts.

IntroductionHepatic insulin clearance (HIC) is an important pathophysiology of type 2 diabetes. HIC was reported to decrease in patients with type 2 diabetes and metabolic syndrome. However, hyperglycemia was suggested to enhance HIC, and it is not known whether poorly controlled diabetes increases HIC in patients with type 2 diabetes. We investigated whether HIC was increased in patients with poorly controlled diabetes, and whether HIC was associated with insulin resistance and incretins.Research design and methodsWe performed a meal tolerance test and the hyperinsulinemic–euglycemic clamp in 21 patients with type 2 diabetes. We calculated the postprandial C-peptide area under the curve (AUC)-to-insulin AUC ratio as the HIC; measured fasting and postprandial glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon levels and analyzed serum adiponectin and zinc transporter-8 (ZnT8) gene polymorphism.ResultsThe HIC significantly correlated with glycated hemoglobin (HbA1c) (r_S=0.58, p<0.01). In patients with high HIC above the median of 6.5, the mean HbA1c was significantly higher compared with low HIC below the median. Homeostatic model assessment (HOMA)-beta (r_S=−0.77, p<0.01) and HOMA-IR (r_S=−0.66, p<0.005) were correlated with HIC. The M/I value in the clamp study was correlated with HIC. GLP-1-AUC and GIP-AUC were not correlated with HIC. Glucagon-AUC was negatively correlated with HIC, but there were no significant differences between the high and low HIC groups. Adiponectin was positively correlated with HIC. The ZnT8 gene polymorphism did not affect HIC.ConclusionsThese results suggest that HIC was increased in patients with high HbA1c type 2 diabetes, low insulin secretion, low insulin resistance and high adiponectin conditions.

Entamoeba histolytica, a protozoan parasite in the lumen of the human large intestine, occasionally spreads to the liver and induces amebic liver abscesses (ALAs). Upon infection with E. histolytica, high levels of type 2 cytokines are induced in the liver early after infection. However, the sources and functions of these initial type 2 cytokines in ALA formation remain unclear. In this study, we examined the roles of group 2 innate lymphoid cells (ILC2s) in ALA formation. Hepatic ILC2 numbers were significantly increased and they produced robust levels of IL-5. The in vivo transfer of ILC2s into Rag2(-/-) common gamma chain (gamma(c))(-/-) KO mice aggravated ALA formation accompanied by eosinophilia and neutrophilia. Furthermore, IL-33-deficient mice and IL-5-neutralized mice had less ALA formations. These results suggest that ILC2s contribute to exacerbating the pathogenesis of ALA by producing early type 2 cytokines and promoting the accumulation of eosinophils and neutrophils in the liver.