Could neurofeedback improve therapist-patient communication? Considering the potential for neuroscience informed examinations of the psychotherapeutic relationship.

Empathic communication between a patient and therapist is an essential component of psychotherapy. However, finding objective neural markers of the quality of the psychotherapeutic relationship have been elusive. Here we conceptualize how a neuroscience-informed approach involving real-time neurofeedback, facilitated via existing functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) technologies, could provide objective information for facilitating therapeutic rapport. We propose several neurofeedback-assisted psychotherapy (NF-AP) approaches that could be studied as a way to optimize the experience of the individual patient and therapist across the spectrum of psychotherapeutic treatment. Finally, we consider how the possible strengths of these approaches are balanced by their current limitations and discuss the future prospects of NF-AP.

Designing gradient coils with the shape derivative and the closed B-spline curves.

This study proposes a versatile and efficient optimisation method for discrete coils that induce a magnetic field by their steady currents. The prime target is gradient coils for MRI (Magnetic Resonance Imaging). The derivative (gradient) of the z-component the magnetic field, which is calculated by the Biot-Savart's law, with respect to the z-coordinate in the Cartesian xyz coordinate system is considered as the objective function. Then, the derivative of the objective function with respect to a change of coils in shape is formulated according to the concept of shape optimisation. The resulting shape derivative (as well as the Biot-Savart's law) is smoothly discretised with the closed B-spline curves. In this case, the control points (CPs) of the curves are naturally selected as the design variables. As a consequence, the shape derivative is discretised to the sensitivities of the objective function with respect to the CPs. Those sensitivities are available to solve the present shape-optimisation problem with a certain gradient-based nonlinear-programming solver. The numerical examples exhibit the mathematical reliability, computational efficiency, and engineering applicability of the proposed methodology based on the shape derivative/sensitivities and the closed B-spline curves.

Reliability and validity of the Japanese version of the camouflaging autistic traits questionnaire.

This study investigated the factor structure and determined the reliability and validity of the Camouflaging Autistic Traits Questionnaire-Japanese version (CAT-Q-J) among 204 autistic and 410 non-autistic people. Since a confirmatory factor analysis revealed no factor validity of the CAT-Q-J for both autistic and non-autistic adults, an exploratory factor analysis was conducted to ensure the psychometric properties matched those of the original scale as much as possible. The results showed the CAT-Q-J comprised three subscales, a four-item compensation subscale, a five-item masking scale, and a five-item assimilation subscale. The overall CAT-Q-J and all three subscales showed sufficient internal consistency and moderate-to-good and stable test-retest reliability in both the autistic and non-autistic samples. Convergent validity was also supported by the correlations found with measures of autistic traits, well-being, anxiety, and depression. Different from the original CAT-Q, compensation/masking for the autistic sample was not correlated with mental health or autistic traits. The reliability and the validity of the overall CAT-Q-J were confirmed; however, caution should be exercised when interpreting its subscales.

Cross-cultural variation in experiences of acceptance, camouflaging and mental health difficulties in autism: A registered report.

Recent findings suggest that stigma and camouflaging contribute to mental health difficulties for autistic individuals, however, this evidence is largely based on UK samples. While studies have shown cross-cultural differences in levels of autism-related stigma, it is unclear whether camouflaging and mental health difficulties vary across cultures. Hence, the current study had two aims: (1) to determine whether significant relationships between autism acceptance, camouflaging, and mental health difficulties replicate in a cross-cultural sample of autistic adults, and (2) to compare these variables across cultures. To fulfil these aims, 306 autistic adults from eight countries (Australia, Belgium, Canada, Japan, New Zealand, South Africa, the United Kingdom, and the United States) completed a series of online questionnaires. We found that external acceptance and personal acceptance were associated with lower levels of depression but not camouflaging or stress. Higher camouflaging was associated with elevated levels of depression, anxiety, and stress. Significant differences were found across countries in external acceptance, personal acceptance, depression, anxiety, and stress, even after controlling for relevant covariates. Levels of camouflaging also differed across countries however this effect became non-significant after controlling for the covariates. These findings have significant implications, identifying priority regions for anti-stigma interventions, and highlighting countries where greater support for mental health difficulties is needed.

Tackling social anxiety with targeted brain stimulation: investigating the effects of transcranial static magnetic field stimulation on self-focused attention.

Previous studies suggested that self-focused attention (SFA), implicated in social anxiety disorder (SAD), correlates with heightened activity in the right frontopolar area (rFPA), which is the right prefrontal cortex just behind the forehead. Transcranial static magnetic field stimulation (tSMS) is a non-invasive brain stimulation method capable of temporarily suppressing brain function beneath the magnet. We explored whether tSMS on individuals with tendencies toward SAD elicited (1) suppressing rFPA activation during the resting-state and (2) reducing SFA during a subsequent speech task. Twenty-three university students with social anxiety performed two speech tasks. Between tasks, the tSMS group received neodymium magnet stimulation while the sham group received fake magnet stimulation on the rFPA for 20 min. Resting-state rFPA activities was measured using functional near-infrared spectroscopy (fNIRS), while SFA (body sensations and observer perspective), field perspective, and detached mindfulness (DM) perspective were assessed via questionnaires during both speech tasks. The observer perspective means SFA to self-imagery from others' viewpoint, while the field and DM perspectives mean appropriately focusing on the external environment. The results indicated that tSMS intervention decreased rFPA activity from pre- to post-intervention rest. Then, tSMS reduced SFA to bodily sensations and increased DM perspective from pre- to post-intervention speech, especially in those with high levels of social anxiety. Furthermore, tSMS enhanced the field perspective regardless of social anxiety tendency. The results suggest that tSMS may suppress overactivity in rFPA, reduce SFA to body sensation, and increase adaptive attention in highly socially anxious individuals. Our study suggests the possibility of the clinical application of tSMS for treating SAD.

VIABAHN® Stent Graft Implantation for Iatrogenic Arteriovenous Fistula and Pseudoaneurysm of the Deep Femoral Artery.

Femoral arteriovenous access is most commonly used in endovascular diagnosis and treatment. Complications arising during femoral arteriovenous access include hematoma, retroperitoneal hemorrhage, pseudoaneurysm, and arteriovenous fistula. A 66-year-old woman diagnosed with paroxysmal atrial fibrillation was treated with catheter ablation. This patient had a high femoral artery bifurcation, and we punctured the femoral vein by the conventional Merkmal method, which led to a femoral vein puncture through the deep femoral artery. The next day, echography revealed a pseudoaneurysm communicating with the deep femoral artery. We performed a thrombin injection without complication, and the pseudoaneurysm was occluded. However, echography three days after thrombin embolization showed a recurrence of the pseudoaneurysm and an arteriovenous fistula connecting to the common femoral vein. The first choice for the treatment of pseudoaneurysms and arteriovenous fistula is surgical treatment, but in addition to the lack of vascular surgery in our hospital, the patient did not want an invasive treatment and strongly preferred to be treated with a catheter. We performed endovascular treatment by VIABAHN® stent graft insertion. VIABAHN® stent graft was implanted at the deep femoral artery, and the patient was discharged without complications. VIABAHN® stent graft placement in the deep femoral artery sealed the entrance of the pseudoaneurysm and the arteriovenous fistula at once, which simultaneously treated both the pseudoaneurysm and AV fistula, and helped avoid the use of an invasive surgical procedure.

Arthroscopic superior capsule reconstruction augmentation using a semitendinosus autograft in massive reparable rotator cuff tears.

Background: Arthroscopic superior capsule reconstruction (SCR) augmentation is a viable treatment option for massive reparable cuff tears. This study aimed to retrospectively compare clinical and imaging outcomes of patients with reparable massive rotator cuff tears after arthroscopic rotator cuff repair (ARCR) with those after SCR augmentation using a semitendinosus autograft. Methods: We retrospectively compared 50 patients with massive reparable rotator cuff tears who underwent ARCR and SCR augmentation (n = 25 each). Patients were clinically followed up for at least 2 years, and the American Shoulder and Elbow index, other patient-reported outcomes, active range of motion, and radiography and magnetic resonance imaging findings were assessed. Results: At the final follow-up, both patient groups showed significant improvements in forward elevation in range of motion and visual analog scale scores. Improvements in the American Shoulder and Elbow scores in the SCR augmentation group were significantly superior to those in the ARCR group (48.3 and 28.9, P < .01). There was a significant difference in the retear rate between the SCR augmentation group and ARCR group (20% and 56%, respectively; P = .009). Conclusion: Our study demonstrated that patient-reported outcomes and retear rates in patients who underwent SCR augmentation with rotator cuff repair for massive rotator cuff tears significantly improved compared with those in patients who underwent ARCR without augmentation. Augmentation with semitendinosus autografting during rotator cuff repair represents a solution for patients with massive reparable rotator cuff tears.

The topology of interpersonal neural network in weak social ties.

The strategies for social interaction between strangers differ from those between acquaintances, whereas the differences in neural basis of social interaction have not been fully elucidated. In this study, we examined the geometrical properties of interpersonal neural networks in pairs of strangers and acquaintances during antiphase joint tapping. Dual electroencephalogram (EEG) of 29 channels per participant was measured from 14 strangers and 13 acquaintance pairs.Intra-brain synchronizations were calculated using the weighted phase lag index (wPLI) for intra-brain electrode combinations, and inter-brain synchronizations were calculated using the phase locking value (PLV) for inter-brain electrode combinations in the theta, alpha, and beta frequency bands. For each participant pair, electrode combinations with larger wPLI/PLV than their surrogates were defined as the edges of the neural networks. We calculated global efficiency, local efficiency, and modularity derived from graph theory for the combined intra- and inter-brain networks of each pair. In the theta band networks, stranger pairs showed larger local efficiency than acquaintance pairs, indicating that the two brains of stranger pairs were more densely connected. Hence, weak social ties require extensive social interactions and result in high efficiency of information transfer between neighbors in neural network.

Development of a fluorometric Cuboni test for the semi-quantitative measurement of urinary estrogen levels and pregnancy detection in mares.

The aim of the present study was to develop a semi-quantitative urine pregnancy test for mares based on the Cuboni reaction and to verify the reliability of this test. The urine specimens were hydrolyzed by heating in the presence of hydrochloric acid. The resulting free estrogens were extracted from the urine matrix using toluene. Sulfuric acid was added to the toluene extract and the mixture was heated again. The lower layer in the test tube containing sulfuric acid was used for fluorescence measurements with excitation at 355 nm and measurement at 535 nm. The fluorometric Cuboni test revealed that the fluorescence counts in urine samples collected after the second trimester of gestation were significantly higher than those obtained from barren mares. The levels of estrogens, including equilin, estrone and estardiol-17ß exhibited a dose-dependent increase in fluorescence counts, whereas other steroids, such as progesterone, testosterone, and cortisol, did not affect fluorescence. Heat treatment of urine samples with hydrochloric acid significantly increased the fluorescence counts in those collected after the second trimester of gestation compared to non-pregnant samples, implying the presence of large amounts of conjugated estrogens in pregnant mare urine. Fluorescence counts in urine samples obtained during pregnancy showed a positive relationship with estrone concentrations as measured by enzyme immunoassay. The results of the present study showed that the fluorometric Cuboni test facilitates urine fluorescence counts depending on the urinary estrogen content and is capable of discriminating between pregnancy and non-pregnancy states beyond the second trimester of gestation in mares.

The association between social camouflage and mental health among autistic people in Japan and the UK: a cross-cultural study.

BACKGROUND: To examine the relationship between social camouflage and mental health in Japanese autistic adults and make an international comparison with a sample from the UK. METHODS: This study analysed secondary data of participants with a self-reported diagnosis of autism from Japan (N = 210; 123 men and 87 women) and the UK (N = 305; 181 women, 104, men, and 18 nonbinary). The relationships between the quadratic term of the Camouflaging Autistic Traits Questionnaire and mental health scales, including depression and anxiety, were assessed. RESULTS: The UK sample showed linear relationships, whereas the Japanese sample showed significant nonlinear relationships. The quadratic terms of the Camouflaging Autistic Traits Questionnaire slightly explained generalised anxiety (ß = .168, p = .007), depression (ß = .121, p = .045), and well-being (ß = - .127, p = .028). However, they did not explain the association between social anxiety and the Camouflaging Autistic Traits Questionnaire. LIMITATIONS: Participants had self-reported diagnoses, and while the autism-spectrum quotient provides a cut-off value for screening, it does not enable confirming diagnoses. Mean scores of the Japanese version of the Camouflaging Autistic Traits Questionnaire were lower as compared to the original CAT-Q, which implies that the social camouflage strategy types used by autistic people in Japan and the UK could differ. The cross-sectional design limits causal inferences. CONCLUSION: In the UK, more social camouflage was associated with poorer mental health scores, whereas too little or too much social camouflage was associated with a low mental health score in Japan. The Japanese population is seemingly less aware of and educated on autistic characteristics and considers 'average' behaviour a good thing. This could influence Japanese autistic people's social camouflage use, differing from that of autistic people in the UK. The differences in the relationship between social camouflage and mental health between Japan and the UK could be associated with national-level divergence regarding the culture of autism.

Interferon-Stimulated Gene Expression in Peripheral Blood Leucocytes as a Convenient Prediction Marker for Embryo Status in Embryo-Transferred Japanese Black Cows during the Peri-Implantation Period.

Pregnancy diagnosis during early gestation is important for cattle reproduction. The expression of interferon-stimulated genes (ISGs) in peripheral blood leukocytes (PBLs) was studied in embryo-transferred (ET) Japanese Black cattle. ISGs in PBLs-ISG15, MX1, MX2, and OAS1-were detected in multiple ovulation ET cattle using a real-time quantitative polymerase chain reaction, and receiver operating characteristic (ROC) curve analysis was performed. Gestational status was predicted using the average ISG levels during the normal estrous cycle (AVE) and the Youden index from the ROC curve analysis as cutoff values. The ISG15, MX1, and MX2 levels were significantly higher in pregnant cattle (n = 10) than in non-pregnant cattle (n = 23) on gestation day 21, whereas the levels of all ISGs were similar between non-pregnant and non-pregnant cattle with late embryonic death (n = 7). ISG15, MX1, and MX2 appropriately predicted the gestational status of ET cows. The statistical evaluation of the diagnostic accuracy in ET cows on day 21 of gestation presented higher values of sensitivity, specificity, accuracy, and positive predictive values of ISG15, MX1, and MX2 using the Youden index than using the AVE. Therefore, ISG15, MX1, and MX2 are excellent biomarkers of gestational status during the peri-implantation period in ET cattle.

Drug-dependent analgesic efficacy in interscalene block for postoperative pain after arthroscopic rotator cuff repair: a comparison between ropivacaine and levobupivacaine.

Background: Interscalene brachial plexus block (ISB) for arthroscopic rotator cuff repair (ARCR) provides high analgesic efficacy for postoperative pain. However, different drug efficacies remain unclear. This retrospective study compared the efficacy of ropivacaine and levobupivacaine in a single-dose ISB for pain control after ARCR. Methods: This study included 173 patients who underwent ARCR; they were divided into the ISBR group (n = 61) that received ISB with 20 mL 0.375% ropivacaine and 3.3 mg dexamethasone, and the ISBL group (n = 112) that received ISB with 20 mL 0.25% levobupivacaine and 3.3 mg dexamethasone. Visual analog scale (VAS) pain scores were evaluated at 1, 4, 8, 12, 24, and 48 hours, postoperatively. Rebound pain was defined as a difference of ≥ 5 points between the highest and lowest VAS pain scores. Results: The mean VAS pain scores at 1 hour were not significantly different between the groups. ISBL administration resulted in significantly lower VAS pain scores at 4, 8, 12, and 24 hours than ISBR administration. Rebound pain rates in the ISBR and ISBL groups were 41.0% and 17.9%, respectively. Rebound pain was more frequent in the ISBR than in the ISBL group. Conclusion: ISB with levobupivacaine and dexamethasone can provide more effective postoperative pain control after ARCR than ropivacaine and dexamethasone.

Early-onset Marfan syndrome with a novel missense mutation: A case report.

Early-onset Marfan syndrome (eoMFS) progresses rapidly, starting during the neonatal period, causes severe clinical disease, and has a poor prognosis. The genetic abnormality associated with eoMFS is located in a so-called critical neonatal region in exons 25-26 of the fibrillin-1 (FBN1) gene. A female neonate was delivered by emergency cesarean section at 37 weeks gestation due to fetal distress with bradycardia, cyanosis, and no spontaneous breathing. On examination, the patient had multiple musculoskeletal deformities, including loose redundant skin, arachnodactyly, flat soles, and joint contractures. Echocardiography showed poor cardiac contractility with multiple valvular abnormalities. She died 13 h after birth. We identified a novel missense variant c.3218A>G (p.Glu1073Gly) in exon 26 of the FBN1 gene by targeted next-generation sequencing. A literature review revealed that arachnodactyly and aortic root dilatation in the fetus are predictive of eoMFS. However, the predictive potential of ultrasonography alone is limited. Genetic testing of the FBN1 gene restriction region associated with short life expectancy and characteristic fetal ultrasound findings could be important for prenatal diagnosis of eoMFS, postnatal management, and parental preparedness. Learning objective: We identified a novel missense mutation located in exons 25-26 of the Fibrillin-1 gene in a neonate with early-onset Marfan syndrome (eoMFS) who died of severe early heart failure shortly after birth. This mutation was located in a narrowly defined critical neonatal region, recently reported to cause eoMFS, and its clinical profile was consistent with early-onset severe heart failure. In addition to ultrasonography, genetic analysis of this region is important for predicting prognosis in eoMFS.

The effect of Aspergillus luchuensis pectin methylesterase genes pmeA and pmeB on methanol production in sweet potato shochu.

To reduce the methanol content in sweet potato shochu, we studied the pectin methylesterase genes of the shochu-koji mold Aspergillus luchuensis. We found the following three homologs of pectin methyleseterase in the genome of A. luchuensis: pmeA, pmeB, and pmeC. Using pectin as a substrate, the methanol-producing activity of the recombinant of each gene expressed in A. luchuensis was examined and found to be present in recombinant PmeA and PmeB. Additionally, small-scale fermentation of sweet potato shochu using disruptions of pmeA and pmeA-pmeB in A. luchuensis (∆pmeA and ∆pmeApmeB) resulted in significant reduction of the methanol content. Taken together, we revealed that the A. luchuensis pmeA gene was mainly involved in methanol production in sweet potato shochu.

Moderating effect of attention deficit hyperactivity disorder tendency on the relationship between delay discounting and procrastination in young adulthood.

Among adults with ADHD, one of the most common problems in daily life is procrastination. ADHD is characterized by attention as well as suboptimal decision-making deficits, indicating difficulty in making long-term reward choices. However, little is known about the relationship between suboptimal decision-making or temporal discounting (TD) and procrastination among adults with ADHD. This study aimed to investigate whether ADHD symptoms enhance the relationship between TD and procrastination. Fifty-eight university participants completed questionnaires about procrastination and an experimental task which measured TD rates in reward and punishment conditions. Only the reward condition showed that ADHD symptoms significantly strengthened the association between the TD rate and procrastination. This study revealed that even when ADHD symptoms were high, higher TD rates were associated with more procrastination, while lower TD rates were associated with less procrastination. The results suggest that procrastination interventions for adult ADHD-prone individuals need to pay attention to reward responses.

Purification and characterization of a serine protease from the fruit of Ficus carica cultivar Masui Dauphine.

Ficus carica produces, in addition to the cysteine protease ficin, a serine protease (FSP). Here, we purified FSP to homogeneity from the fruit of F. carica cultivar Masui Dauphine. An 81-fold enrichment in specific activity of FSP with 2.1% recovery was attained. Three protein bands (70, 62, and 60 kDa) were identified on SDS-PAGE. Each band was identified as a subtilisin-like protease (661 amino acids) by trypsin digestion, LC-MS/MS analysis, and the partial N-terminal amino acid sequence analysis. Gelatin zymography revealed that the active FSP exists as a dimer. The optimum hydrolysis pH of FSP was 7.5, and the pHs at which the enzyme retained its initial activity by 70% in 24 h were 8.0-11.0. The optimum hydrolysis temperature of FSP was 50-60 °C, and the temperature required to reduce the initial activity by 50% in 15 min was 70 °C. These results will inform the industrial use of FSP.

Dexmedetomidine improves acute lung injury by activating autophagy in a rat hemorrhagic shock and resuscitation model.

Dexmedetomidine (DEX) can reduce lung injury in a hemorrhagic shock (HS) resuscitation (HSR) model in rats by inhibiting inflammation. Here, we aimed to investigate if these effects of DEX are due to autophagy activation. Therefore, we established HSR rat models and divided them into four groups. HS was induced using a blood draw. The rats were then resuscitated by reinjecting the drawn blood and saline. The rats were sacrificed 24 h after resuscitation. Lung tissues were harvested for histopathological examination, determination of wet/dry lung weight ratio, and detection of the levels of autophagy-related marker proteins LC3, P62, Beclin-1, and the ATG12-ATG5 conjugate. The morphological findings of hematoxylin and eosin staining in lung tissues and the pulmonary wet/dry weight ratio showed that lung injury improved in HSR + DEX rats. However, chloroquine (CQ), an autophagy inhibitor, abolished this effect. Detecting the concentration of autophagy-related proteins showed that DEX administration increased LC3, ATG12-ATG5, and Beclin-1 expression and decreased P62 expression. The expression levels of these proteins were similar to those in the HSR group after CQ + DEX administration. In summary, DEX induced autophagic activation in an HSR model. These findings suggest that DEX administration partially ameliorates HSR-induced lung injury via autophagic activation.

Effect of a Mindfulness-Based Intervention on Self-Compassionate Behaviors: A Randomized Controlled Trial.

Self-compassion is regarded as a mediating or moderating variable in mindfulness-based interventions (MBI). However, few studies have investigated the role of self-compassion on MBI. Therefore, we conducted a randomized controlled trial to examine whether (1) MBI decreases depression and trait anxiety, while increasing trait mindfulness, trait self-compassion, self-compassionate behaviors (SC behaviors), mindful behaviors, and mood after behaviors; and (2) SC behaviors moderate the effect of mindful behaviors on mood in daily life. Participants were patients with depression and/or anxiety (N=19) in Japan. Of the 27 participants recruited, 19 participated in the study. Using stratified randomization, we allocated 10 participants to the intervention group, with an 8-week standard MBI, and nine to the waitlist control group. Depression, trait anxiety, trait mindfulness, and trait self-compassion were assessed using questionnaires, while SC behaviors, mindful behaviors, and mood were measured using an ecological momentary assessment-a method used to repeatedly record events and behaviors in daily life. The results revealed that depression, trait anxiety, trait mindfulness, and trait self-compassion did not significantly change. However, SC behaviors, mindful behaviors, and mood significantly improved with MBI. Moreover, the interaction between SC behaviors and mindful behaviors was significantly shown in the pre-intervention, suggesting that SC behaviors moderate the effect of mindful behaviors on mood in daily life.

Lower leg blood pressure decreases while calf external pressure increases with the angulation of the Trendelenburg position in the lithotomy position with calf- and foot-supported leg holders.

Patients who underwent lower abdominopelvic surgeries in the lithotomy position (LP) and the Trendelenburg position (TP) with the leg holder are at risk of developing well leg compartment syndrome (WLCS). However, contributing factors related to the LP with TP associated with WLCS are unknown. This study aimed to investigate the associations between external pressure at the calf in the LPs at different angulations of the TP and physiological characteristics. Eighty-four university students (age, 21.7 ± 0.9; 42 men and 42 women) voluntarily participated in the study. The awake participants were placed in the LPs using the calf- and foot-supported leg holder at 0° (horizontal level), 5°, 10°, and 20° head-down tilts by moving the electric operating table. The peak contact pressure (pCP) was measured at the calf as a representative external pressure using the pressure distribution measurement system BIG-MAT®. Lower leg blood pressure significantly decreased with TP angulation, while calf pCP significantly increased with it at 0°, 5°, 10°, and 20° head-down tilts (39.4 ± 15.2, 46.5 ± 17.7, 47.2 ± 16.9, and 50.3 ± 17.6 mmHg, respectively). The calf pCP with a 10° head-down tilt was correlated positively with the calf total force (P < 0.001) and negatively with the calf contact area (P < 0.001). Blood hypoperfusion due to low lower leg blood pressure secondary to lower leg elevation and head-down tilt, and high calf external pressure due to direct external compression from the leg holder where it is loaded may contribute to WLCS.

Targeted gene panel analysis of Japanese patients with maturity-onset diabetes of the young-like diabetes mellitus: Roles of inactivating variants in the ABCC8 and insulin resistance genes.

AIMS/INTRODUCTION: To investigate the genetic background of Japanese patients with suspected maturity-onset diabetes of the young (MODY). MATERIALS AND METHODS: On 340 proband patients referred from across Japan, genomic variants were analyzed using a targeted multigene panel analysis combined with the multiplex ligation probe amplification (MLPA) analysis, mitochondrial m.3243A > G analysis and methylation-specific polymerase chain reaction of the imprinted 6q24 locus. Pathogenic/likely pathogenic variants were listed according to the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Additionally, variants with a population frequency <0.001 and Combined Annotation Dependent Depletion score >20 (CS >20) were listed as rare variants of uncertain significance-CS >20. RESULTS: A total of 157 pathogenic/likely pathogenic variants and 44 rare variants of uncertain significance-CS >20 were identified. In the pathogenic/likely pathogenic variants, alterations in the GCK gene were the most common (82, 52.2%) followed by HNF1A (29, 18.5%), HNF4A (13, 8.3%) and HNF1B (13, 8.3%). One patient was a 29.5% mosaic with a truncating INSR variant. In the rare variants of uncertain significance-CS >20, 20 (45.5%) were in the genes coding for the adenosine triphosphate-sensitive potassium channel, KCNJ11 or ABCC8, and four were in the genes of the insulin-signaling pathway, INSR and PIK3R1. Four variants in ABCC8 were previously reported in patients with congenital hyperinsulinism, suggesting the inactivating nature of these variants, and at least two of our patients had a history of congenital hyperinsulinism evolving into diabetes. In two patients with INSR or PIK3R1 variants, insulin resistance was evident at diagnosis. CONCLUSIONS: Causative genomic variants could be identified in at least 46.2% of clinically suspected MODY patients. ABCC8-MODY with inactivating variants could represent a distinct category of MODY. Genes of insulin resistance should be included in the sequencing panel for MODY.