Effects of cooked rice containing high resistant starch on postprandial plasma glucose, insulin, and incretin in patients with type 2 diabetes.

BACKGROUND AND OBJECTIVES: Few studies exist on resistant starch in rice grains. The Okinawa Institute of Science and Technology Graduate University (OIST) has developed a new rice (OIST rice, OR) rich in resistant starch. This study aimed to clarify the effect of OR on postprandial glucose concentrations. METHODS AND STUDY DESIGN: This single-center, open, randomized, crossover comparative study included 17 patients with type 2 diabetes. All participants completed two meal tolerance tests using OR and white rice (WR). RESULTS: The median age of the participants was 70.0 [59.0-73.0] years, and the mean body mass index was 25.9±3.1 kg/m2. The difference in total area under the curve (AUC) of plasma glucose was -8223 (95% confidence interval [CI]: -10100 to -6346, p<0.001) mg·min/dL. The postprandial plasma glucose was significantly lower with OR than with WR. The difference in the AUC of insulin was -1139 (95% CI: -1839 to -438, p=0.004) µU·min/mL. The difference in the AUC of total gastric inhibitory peptide (GIP) and total glucagon-like peptide-1 (GLP-1) was -4886 (95% CI: -8456 to -1317, p=0.011) and -171 (95% CI: -1034 to 691, p=0.673) pmol·min/L, respectively. CONCLUSIONS: OR can be ingested as rice grains and significantly reduced postprandial plasma glucose compared to WR independent of insulin secretion in patients with type 2 diabetes. OR could have escaped absorption not only from the upper small intestine but also from the lower small intestine.

LUBAC accelerates B-cell lymphomagenesis by conferring resistance to genotoxic stress on B cells.

The linear ubiquitin chain assembly complex (LUBAC) is a key regulator of NF-κB signaling. Activating single-nucleotide polymorphisms of HOIP, the catalytic subunit of LUBAC, are enriched in patients with activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), and expression of HOIP, which parallels LUBAC activity, is elevated in ABC-DLBCL samples. Thus, to clarify the precise roles of LUBAC in lymphomagenesis, we generated a mouse model with augmented expression of HOIP in B cells. Interestingly, augmented HOIP expression facilitated DLBCL-like B-cell lymphomagenesis driven by MYD88-activating mutation. The developed lymphoma cells partly shared somatic gene mutations with human DLBCLs, with increased frequency of a typical AID mutation pattern. In vitro analysis revealed that HOIP overexpression protected B cells from DNA damage-induced cell death through NF-κB activation, and analysis of the human DLBCL database showed that expression of HOIP positively correlated with gene signatures representing regulation of apoptosis signaling, as well as NF-κB signaling. These results indicate that HOIP facilitates lymphomagenesis by preventing cell death and augmenting NF-κB signaling, leading to accumulation of AID-mediated mutations. Furthermore, a natural compound that specifically inhibits LUBAC was shown to suppress the tumor growth in a mouse transplantation model. Collectively, our data indicate that LUBAC is crucially involved in B-cell lymphomagenesis through protection against DNA damage-induced cell death and is a suitable therapeutic target for B-cell lymphomas.

Two bacterial glycosphingolipid synthases responsible for the synthesis of glucuronosylceramide and α-galactosylceramide.

Bacterial glycosphingolipids such as glucuronosylceramide and galactosylceramide have been identified as ligands for invariant natural killer T cells and play important roles in host defense. However, the glycosphingolipid synthases required for production of these ceramides have not been well-characterized. Here, we report the identification and characterization of glucuronosylceramide synthase (ceramide UDP-glucuronosyltransferase [Cer-GlcAT]) in Zymomonas mobilis, a Gram-negative bacterium whose cellular membranes contain glucuronosylceramide. On comparing the gene sequences that encode the diacylglycerol GlcAT in bacteria and plants, we found a homologous gene that is widely distributed in the order Sphingomonadales in the Z. mobilis genome. We first cloned the gene and expressed it in Escherichia coli, followed by protein purification using nickel-Sepharose affinity and gel filtration chromatography. Using the highly enriched enzyme, we observed that it has high glycosyltransferase activity with UDP-glucuronic acid and ceramide as sugar donor and acceptor substrate, respectively. Cer-GlcAT deletion resulted in a loss of glucuronosylceramide and increased the levels of ceramide phosphoglycerol, which was expressed in WT cells only at very low levels. Furthermore, we found sequences homologous to Cer-GlcAT in Sphingobium yanoikuyae and Bacteroides fragilis, which have been reported to produce glucuronosylceramide and α-galactosylceramide, respectively. We expressed the two homologs of the cer-glcat gene in E. coli and found that each gene encodes Cer-GlcAT and Cer-galactosyltransferase, respectively. These results contribute to the understanding of the roles of bacterial glycosphingolipids in host-bacteria interactions and the function of bacterial glycosphingolipids in bacterial physiology.

Genetic landscape of Rett syndrome-like phenotypes revealed by whole exome sequencing.

BACKGROUND: Rett syndrome (RTT) is a characteristic neurological disease presenting with regressive loss of neurodevelopmental milestones. Typical RTT is generally caused by abnormality of methyl-CpG binding protein 2 (MECP2). Our objective to investigate the genetic landscape of MECP2-negative typical/atypical RTT and RTT-like phenotypes using whole exome sequencing (WES). METHODS: We performed WES on 77 MECP2-negative patients either with typical RTT (n=11), atypical RTT (n=22) or RTT-like phenotypes (n=44) incompatible with the RTT criteria. RESULTS: Pathogenic or likely pathogenic single-nucleotide variants in 28 known genes were found in 39 of 77 (50.6%) patients. WES-based CNV analysis revealed pathogenic deletions involving six known genes (including MECP2) in 8 of 77 (10.4%) patients. Overall, diagnostic yield was 47 of 77 (61.0 %). Furthermore, strong candidate variants were found in four novel genes: a de novo variant in each of ATPase H+ transporting V0 subunit A1 (ATP6V0A1), ubiquitin-specific peptidase 8 (USP8) and microtubule-associated serine/threonine kinase 3 (MAST3), as well as biallelic variants in nuclear receptor corepressor 2 (NCOR2). CONCLUSIONS: Our study provides a new landscape including additional genetic variants contributing to RTT-like phenotypes, highlighting the importance of comprehensive genetic analysis.

Association of the muscle/fat mass ratio with insulin resistance in gestational diabetes mellitus.

This study assessed the association of muscle mass with insulin resistance, evaluated from the insulin sensitivity index (ISI), in Japanese patients with gestational diabetes mellitus (GDM). Consecutive patients with GDM (n = 96) admitted to St. Marianna University Hospital between October 2015 and March 2018 for initial education and glycemic control were enrolled in a prospective observational study. Insulin resistance was evaluated by measuring the ISI and body composition was assessed by bioelectrical impedance analysis. The subjects were aged 34.4 ± 4.8 years (mean ± SD) and their body mass index (BMI) before pregnancy was 22.3 ± 4.0 kg/m2. Fifty-three patients (55.2%) had a history of diabetes in first-degree relatives. The ISI was 7.2 ± 3.3, appendicular skeletal muscle mass (ASM) was 17.0 ± 2.1 kg, and fat mass (FM) was 18.8 ± 8.2 kg. The ASM/FM ratio was 1.02 ± 0.34. There was a positive correlation between FM and ASM (r = 0.734, p < 0.001). To adjust for confounders when evaluating the association of ASM with ISI, multivariate analysis was conducted using age, family history of diabetes, and BMI as variables. In this analysis, the ASM/FM ratio showed a significant positive correlation with ISI (ß = 0.303, p = 0.020). These findings suggest that inadequate ASM/FM ratio is important for the development of insulin resistance in Japanese patients with GDM. Excessive emphasis on dieting rather than health might increase the risk of GDM by reducing the muscle mass below the level that maintains normal glucose metabolism.

Identifying the factors and root causes associated with the unintentional usage of an adrenaline auto-injector in Japanese children and their caregivers.

BACKGROUND: The unintentional usage of adrenaline auto-injectors may cause injury to caregivers or patients. To prevent such incidents, we assessed the causative factors of these incidents. METHODS: The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which adrenaline auto-injectors were unintentionally used. One hundred cases were reported from June 2015 to March 2016. We identified the root causes of 70 child and 25 adult cases, separately. RESULTS: The incidents occurred with repeated prescriptions as well as the first prescription. Three cases resulted in a failure to administer an adrenaline auto-injector to children with anaphylaxis. Four caregivers used it with improper application (epilepsy or enteritis). Among the child cases, the median age at the time of the incident was 5.5 years (range, 2-14 years). Five children injected the adrenaline auto-injector on their own body trunk. Twenty children were not the allergic patients themselves. Improper management protocol of the device and the child's development were concomitantly involved in most of the cases. A variety of human behaviors were identified as the root causes in the adult cases. At least 34 cases were associated with mix-ups between the actual and training device. CONCLUSIONS: Health workers should provide sufficient education regarding safety use of adrenaline auto-injector for caregivers tailored to their experience levels at both first and repeated prescriptions. Such education must cover anticipatory behavior based on normal child development. Devices should also be further improved to prevent such incidents.

Surveillance of the use of adrenaline auto-injectors in Japanese children.

BACKGROUND: The appropriate usage of an adrenaline auto-injector (AAI, Epipen®) is a key aspect of patient and social education in the management of anaphylaxis. However, although AAIs are being prescribed increasingly frequently, there are few reports on their actual use. METHODS: The Anaphylaxis Working Group of the Japanese Society of Pediatric Allergy and Clinical Immunology requested that society members register cases in which AAIs were used. Two hundred and sixty-six cases were collected from March 2014 to March 2016. RESULTS: The cases included 240 events of immediate-type food allergies caused by cow's milk (n = 100), hen's egg (n = 42), wheat (n = 40), and peanuts (n = 11). Exercise-related events were reported in 19 cases; however, the diagnosis of food-dependent exercise-induced anaphylaxis with a specific causative food was only made in 4 cases (wheat, n = 2; fish, n = 1; squid, n = 1). The frequent reasons for the causative intake included programmed intake (n = 48), failure to check the food labeling (n = 43), and consuming an inappropriate food (n = 26). AAIs were used at schools or nurseries in 67 cases, with school or nursery staff members administering the AAI in 39 cases (58%). On arriving at the hospital, the symptom grade was improved in 71% of the cases, while grade 4 symptoms remained in 20% of the cases. No lethal cases or sequelae were reported. CONCLUSIONS: AAIs were used effectively, even by school teachers. The need to visit a hospital after the use of an AAI should be emphasized because additional treatment might be required.

[THE CLINICAL CHARACTERISTICS OF PEANUT ALLERGY AND THE DIAGNOSTIC ACCURACY OF THE SPECIFIC IgE TO Ara h 2].

BACKGROUND: This study aimed to evaluate the clinical accuracy of specific IgE (sIgE) to Ara h 2 in the diagnosis of peanut allergy (PA). We also investigated the prevalence of complications with other nut allergies in PA patients. METHODS: The Ara h 2-sIgE titer was examined in patients with positive results for sIgE to peanut from April 2014 to March 2015. The presence or absence of PA was diagnosed based on an oral food challenge or a convincing clinical history. The characteristics of 217 patients (including 90 PA patients) were retrospectively evaluated. RESULTS: At ≥0.35UA/mL, Ara h 2 showed 85.6% sensitivity in the diagnosis of PA. At the clinically-designated positive cut-off value (≥4.0UA/mL), the positive predictive value was 93.1% and the specificity was 96.9%. However, the Ara h 2-sIgE levels were not correlated with the threshold dose or the severity of the symptoms that were provoked in the peanut challenge (n=42). Nine (10%) of the PA patients also had allergies to other tree nuts. CONCLUSION: The re-evaluation of the clinically-designated positive Ara h 2-sIgE cut-off value revealed that the cut-off value was appropriate. The differential diagnosis of tree nut allergies was suggested to be important in PA patients.

SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex.

Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders.

SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis.

SHARPIN is a ubiquitin-binding and ubiquitin-like-domain-containing protein which, when mutated in mice, results in immune system disorders and multi-organ inflammation. Here we report that SHARPIN functions as a novel component of the linear ubiquitin chain assembly complex (LUBAC) and that the absence of SHARPIN causes dysregulation of NF-κB and apoptotic signalling pathways, explaining the severe phenotypes displayed by chronic proliferative dermatitis (cpdm) in SHARPIN-deficient mice. Upon binding to the LUBAC subunit HOIP (also known as RNF31), SHARPIN stimulates the formation of linear ubiquitin chains in vitro and in vivo. Coexpression of SHARPIN and HOIP promotes linear ubiquitination of NEMO (also known as IKBKG), an adaptor of the IκB kinases (IKKs) and subsequent activation of NF-κB signalling, whereas SHARPIN deficiency in mice causes an impaired activation of the IKK complex and NF-κB in B cells, macrophages and mouse embryonic fibroblasts (MEFs). This effect is further enhanced upon concurrent downregulation of HOIL-1L (also known as RBCK1), another HOIP-binding component of LUBAC. In addition, SHARPIN deficiency leads to rapid cell death upon tumour-necrosis factor α (TNF-α) stimulation via FADD- and caspase-8-dependent pathways. SHARPIN thus activates NF-κB and inhibits apoptosis via distinct pathways in vivo.

Development of a prediction model of severe reaction in boiled egg challenges.

BACKGROUND: We have proposed a new scoring system (Anaphylaxis SCoring Aichi: ASCA) for a quantitative evaluation of the anaphylactic reaction that is observed in an oral food challenge (OFC). Furthermore, the TS/Pro (Total Score of ASCA/cumulative protein dose) can be a marker to represent the overall severity of a food allergy. We aimed to develop a prediction model for a severe allergic reaction that is provoked in a boiled egg white challenge. METHODS: We used two separate datasets to develop and validate the prediction model, respectively. The development dataset included 198 OFCs, that tested positive. The validation dataset prospectively included 140 consecutive OFCs, irrespective of the result. A 'severe reaction' was defined as a TS/Pro higher than 31 (the median score of the development dataset). A multivariate logistic regression analysis was performed to identify the factors associated with a severe reaction and develop the prediction model. RESULTS: The following four factors were independently associated with a severe reaction: ovomucoid specific IgE class (OM-sIgE: 0-6), aged 5 years or over, a complete avoidance of egg, and a total IgE < 1000 IU/mL. Based on these factors, we made a simple scoring prediction model. The model showed good discrimination in a receiver operating characteristic analysis; area under the curve (AUC) = 0.84 in development dataset, AUC = 0.85 in validation dataset. The prediction model significantly improved the AUC in both datasets compared to OM-sIgE alone. CONCLUSIONS: This simple scoring prediction model was useful for avoiding risky OFC.

[AN EVALUATION OF SPONTANEOUS HISTAMINE RELEASE AND THE LOW RESPONDERS IN A BASOPHIL HISTAMINE RELEASE TEST].

BACKGROUND: We evaluated the clinical significance of the spontaneous histamine release ratio (SHR/T) and low responders in the automated basophil histamine release test (AllerportⓇ HRT). METHODS: This study analyzed the outcomes of 101 oral food challenges (OFC) with egg, milk or wheat (challenge-positive: n=79) in relation to the SHR/T. The traditional HRT low responders (n=27) were separated into two groups:"LOW"responders (n=10), who showed a ≥10% concentration-dependent maximum histamine release in response to the anti-human IgE stimulation, and"NON"responders who did not fulfill the criteria (n=17). RESULTS: Among the 34 patients with ≥20% SHR/T, 32 patients (94%) had a positive OFC with a low threshold dose which provoked severe symptoms. Among the"LOW"responders, four cases showed ≥10% allergen-specific maximum histamine release. On the other hand, concentration-dependent histamine release was not seen in the"NON"responders, suggesting the basophil function was not detected in this subgroup. CONCLUSION: The present study suggested that SHR/T could be an indicator of basophil activation and hypersensitivity in vivo. We also suggested that significant basophil functions might be detected among the "LOW"responders, but not among the"NON"responders.

Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN.

Linear ubiquitin chains generated by the linear ubiquitin chain assembly complex (LUBAC) play an important role in NF-κB activation. However, the regulation of linear ubiquitin chain generation by LUBAC is not well characterized. Here, we identified two deubiquitinating enzymes (DUBs), ovarian tumor DUB with linear linkage specificity (OTULIN/Gumby/FAM105B) and cylindromatosis (CYLD) that can cleave linear polyubiquitin chains and interact with LUBAC via the N-terminal PNGase/UBA or UBX (PUB) domain of HOIP, a catalytic subunit of LUBAC. HOIP interacts with both CYLD and OTULIN even in unstimulated cells. The interaction of CYLD and OTULIN with HOIP synergistically suppresses LUBAC-mediated linear polyubiquitination and NF-κB activation. Moreover, introduction of a HOIP mutant unable to bind either deubiquitinase into HOIP-null cells augments the activation of NF-κB by TNF-α stimulation. Thus, the interactions between these two deubiquitinases and the LUBAC ubiquitin ligase are involved in controlling the extent of TNF-α-induced NF-κB activation in cells by fine-tuning the generation of linear ubiquitin chains by LUBAC. The interaction of HOIP with OTULIN is also involved in OTULIN suppressing the canonical Wnt signaling pathway activation by LUBAC. Our observations provide molecular insights into the roles of ligase-deubiquitinase interactions in regulating molecular events resulting from linear ubiquitin conjugation.

Sun exposure inversely related to food sensitization during infancy.

BACKGROUND: Autumn and winter birth (AWB) has been reported to be a risk factor for the development of food allergies. However, the association between seasonal factors and allergic sensitization during early infancy remains unclear. METHODS: We collected data from 732 patients regarding the total and specific immunoglobulin E (tIgE, sIgE) levels in infants younger than 6 months old from November 2001 to October 2012 from the institutional clinical database system. We then analyzed the relationship between the birth month and the value of each parameter. Furthermore, we identified any correlations between the number of sensitized patients and the monthly climatological parameters. RESULTS: The number of tIgE samples obtained from AWB patients (n = 482) was 2.1 times higher than that from patients born in the spring and summer (SSB, n = 225). The number of sIgE samples to egg white, cow's milk, and wheat, the sensitized ratio and the median sIgE titer were also all higher in AWB. The number of sensitized AWB patients to these allergens was 2.75, 3.05, and 3.97 times higher, respectively. A periodic change in the number of sensitized patients was observed annually (highest in October-November and lowest in May). Among the climatological parameters examined, the average solar radiation during the 3-month period after birth showed the strongest negative correlation with the number of sensitized patients (egg white: r = -0.976, cow's milk: r = -0.969, wheat: r = -0.975). CONCLUSIONS: The amount of solar radiation immediately after birth had a strong negative correlation with allergen sensitization before 6 months of age.

The relationship between the season of birth and early-onset food allergies in children.

BACKGROUND: This study examined the relationship between the season of birth (SoB) and other factors with the development of FA. METHODS: A multicenter, cross-sectional pilot study recruited 1197 patients with FA. The main study recruited 440 incident cases (FA group) definitively diagnosed as FA at 0-1 year of age. In both studies, the frequency of autumn-winter births (AWBs) in FA patients was compared to the regional control population. In the main study, we analyzed the differences in the SoB and other factors between patients in the FA group and those in the non-FA group (n = 332) in allergy clinics. RESULTS: The pilot study showed that the frequency of AWB (57.6%) in the FA patients was significantly higher than that of the regional control population (50.4%, OR, 1.34; p < 0.001). The main study also showed the dominance of AWB (62.7%) in the FA group in comparison with that in the regional control population (50.2%, OR, 1.70; p < 0.001). Preterm birth (OR, 0.43; p = 0.027) and the presence of two or more elder siblings (OR, 0.27; p = 0.012) were significantly associated with a lower frequency of FA than those of non-FA. AWB (RR, 1.21; p = 0.020) and preterm birth (RR, 0.55; p = 0.017) were significantly associated with a number of trigger foods. The SoB effect was observed in FA patients irrespective of the presence of infantile eczema. CONCLUSIONS: AWB was predominant in the patients with newly diagnosed food allergies.

A workshop with practical training for anaphylaxis management improves the self-efficacy of school personnel.

BACKGROUND: School personnel are required to guarantee a secure school environment for children suffering from severe food allergies. We organized a workshop for school personnel to learn the appropriate management of anaphylaxis that included practical training with an adrenaline auto-injector (AAI). The objective of this study was to evaluate the workshop in terms of the improvement of self-efficacy (SE) of participants to deal with anaphylaxis. METHODS: All 93 school nurses, 73 schoolteachers and 110 childcare workers participating in the study completed a questionnaire before and after the workshop. The SE of the participants was evaluated using an original 15-item questionnaire. RESULTS: Before the workshop, the SE of school nurses was the highest among the profession groups, and being involved with children prescribed an AAI was a common factor associated with a high SE. After the workshop, the SE increased in all groups, but most apparently in school nurses and those involved with children prescribed an AAI. The presence of an emergency plan was positively associated with the SE of schoolteachers only after the workshop, even though no such association existed beforehand. CONCLUSIONS: Practical instruction of school nurses and school personnel involved with children prescribed an AAI resulted in dramatic improvement of the SE. These people are expected to play a central role in the development of an anaphylaxis management plan in their schools.

[Utility of the allerport® HRT in the diagnosis of hen's egg allergy: a pediatric multicenter challenge study].

Purpose This study aimed to evaluate the utility of the Allerport® HRT in the diagnosis of hen's egg allergy. Method We enrolled 51 subjects who underwent the Allerport® HRT before an oral food challenge (OFC) consisting of heated egg. Blood samples were collected within three months prior to OFC to measure histamine release (HR) and specific IgE antibody titers. We examined whether the Allerport® HRT was useful as a means of diagnosing hen's egg allergy and predicting severity of induced symptoms. Of 51 subjects, three whose OFC results were not valid**1** and 13 who were classified as "low responders" to the Allerport® HRT (%HR due to anti-IgE below 20%) were excluded. Of the remaining 35 subjects (average age: 4 years), 23 showed positive reactions to the OFC. Quantities of histamine released in spontaneous HR and egg white (EW)- and ovomucoid (OVM)-induced HR were significantly higher in patients with positive reactions. In our receiver operating characteristic analysis, the area under the curve for %HR against 6 ng/ml of EW was 0.9601 and that against 3 ng/ml of OVM was 0.9022. The cutoff value was 15.0% for EW and 3.7% for OVM. The sensitivity was 95.7% for EW and 91.3% for OVM, and the specificity was 83.3% for EW and 58.3% for OVM. %HR correlated well with the severity of induced symptoms in the OFC. Conclusion Allerport® HRT is useful for the diagnosis of hen's egg allergy, and may also aid in predicting the severity of induced symptoms.

[SIX CASES OF WHEAT-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS IN CHILDREN].

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is often reported in adults for whom the specific IgE to ω-5 gliadin can be a useful diagnostic test. However, few cases of WDEIA in children have been reported. We herein report six cases (aged 7-16 years) of children with WDEIA, who had no clinical history of immediate-type wheat allergy but who were diagnosed by a wheat ingestion + exercise provocation test. The specific IgE to wheat ranged <0.35-3.49 (median 1.64) UA/ml. Skin prick tests using wheat extract were performed on 3 patients who showed either a negative or low specific IgE titer to wheat, and all of them resulted in negative findings. The specific IgE to ω-5 gliadin was below the detection limit in all cases. Aspirin-supplemented provocation tests were performed to 4 cases who had negative results in the wheat + exercise test. All of these resulted in a positive reaction, and two of them provoked the occurrence of anaphylactic shock, which was relieved by the intramuscular injection of adrenaline. WDEIA in children cannot be ruled out by serological tests alone. On the other hand, severe symptoms might be provoked by the provocation test. Therefore, a safe procedure is warranted for the diagnosis of WDEIA in children.

Correction: Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

[This corrects the article DOI: 10.1007/s13340-023-00646-w.].

Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

The significance of diagnosing gestational diabetes mellitus (GDM) in early pregnancy is controversial. We used the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria to investigate whether clinical background and neonatal outcomes differ depending on when GDM is diagnosed in early or late pregnancy. This was a single-center, observational study conducted between November 2012 and March 2020 at St. Marianna University Hospital (Kawasaki, Japan). We compared the background and perinatal outcomes of patients with GDM depending on the time of diagnosis (at < 24 gestational weeks or ≥ 24 weeks). Insulin sensitivity index, homeostasis model assessment of insulin resistance, and ß-cell function were calculated from a 75-g oral glucose tolerance test. Stratified analysis was performed by pre-pregnancy BMI in patients with early GDM. As a result, in the 507 patients, 89.9% gave birth at our hospital. The pre-pregnancy BMI was significantly higher in patients with early GDM than in those with late GDM (the median [interquartile range], 22.7 [20.3, 26.3] and 21.5 [19.3, 23.8] kg/m2, respectively; p = 0.001). Perinatal outcomes were not different between the two groups. However, in the subgroup analysis of patients with early GDM, the prevalence of large-for-gestational-age infants was significantly higher in the group with overweight (15.4% vs 2.1%, respectively; p = 0.008). In conclusion, patients with GDM using the IADPSG criteria in early pregnancy may be treated, especially in patients with pre-pregnancy overweight.