Acute Effects of Combination Therapy by Triceps Surae Stretching and Electrical Stimulation to the Tibialis Anterior on Medial Forefoot Plantar Pressure During Gait in Patients With Diabetes Mellitus.

High plantar flexor moment and limited ankle mobility are known to cause high plantar pressure under the forefoot. Stretching is an effective physical therapy for the limited ankle range of motion (ROM), and electrical stimulation is used to regulate the activity of antagonistic muscle via the action of reciprocal inhibition. Additionally, stretching paired with electrical stimulation has been reported to improve the limited ROM significantly. This study aims to investigate the influences of stretching on triceps surae (STR), electrical stimulation to tibialis anterior (ES), and the combination (ES+STR) on the ROM, kinematic parameters, and plantar pressure distribution during gait in patients with diabetes mellitus. Planter pressure and other parameters were measured before and after the intervention of ES, STR, ES+STR, or the rest sitting on the bed (CON) for 10 min. Pressure time integral under the medial forefoot decreased in the ES+STR compared to CON (P< .05). Interestingly, ES+STR increased passive and dynamic ROM on ankle dorsiflexion during gait and increased the lateral center of pressure excursion (P < .05). Furthermore, these changes were followed by decreased contact duration under the medial forefoot (P < .05). The combined therapy improves ankle mobility during gait and reduces the contact duration and the plantar pressure under the medial forefoot in patients with diabetes mellitus.

Hypercalcemia Associated with the Ectopic Expression of 25-hydroxyvitamin D3-1α-hydroxylase in Diffuse Large B-cell Lymphoma.

An 82-year-old man was transferred to our hospital due to impaired consciousness. His albumin-corrected calcium level was 14.2 mg/dL, intact parathyroid hormone (PTH) and PTH-related protein levels were reduced, and his 1,25-dihydroxyvitamin D [1,25 (OH) 2VitD] level was elevated at 71.5 pg/mL. Computed tomography revealed masses on the bilateral ribs. The mass on the rib was biopsied and diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunostaining of the biopsy sample with the anti-CYP27B1 antibody revealed the ectopic expression of 1α-hydroxylase in the lesion. We herein report a rare case of hypercalcemia induced by the overproduction of 1,25 (OH) 2VitD in DLBCL ectopically expressing 1α-hydroxylase.

Chronic Subdural Hematoma after Craniotomy with Preoperative Embolization of Middle Meningeal Artery: A Case Report.

Endovascular embolization of the middle meningeal artery (MMA) has been reported as an effective method for treating chronic subdural hematoma (CSDH); however, its preventive effect on CSDH following craniotomy is unknown. We present a case in which MMA embolization was ineffective in preventing CSDH following craniotomy. A 56-year-old man who complained of diplopia was diagnosed with sphenoid ridge meningioma with a 3-cm diameter. MMA embolization prior to the operation and total surgical removal of the tumor were performed. Two months postoperatively, the patient complained of headache and hemiparesis of the left side. CSDH with a 15-mm thickness and a midline shift was observed. MMA embolization before inflammation may not play a role in preventing CSDH development because MMA embolization is considered effective in CSDH because it is associated with the blood supply of neovessels that are newly formed due to inflammation. Therefore, MMA embolization might not be effective in preventing the occurrence of CSDH following craniotomy.

Fluid-attenuated inversion recovery vascular hyperintensity-diffusion-weighted imaging mismatch and functional outcome after endovascular reperfusion therapy for acute ischemic stroke.

BACKGROUND: Fluid-attenuated inversion recovery vascular hyperintensity (FVH) outside of the diffusion-weighted imaging (DWI) lesion, termed FVH-DWI mismatch, may represent penumbral tissue with good collateral status. METHODS: Consecutive patients who underwent endovascular reperfusion therapy (EVT) for acute internal carotid artery (ICA) or middle cerebral artery (MCA)-M1 occlusion were enrolled. FVH-DWI mismatch score was defined as the number of cortical Alberta Stroke Program Early CT Score areas (I and M1 to M6) that involved FVH but no DWI lesion (0 to 7 points). The outcome measure was set as good functional outcome, defined as a modified Rankin Scale score of 0 to 2, at 90 days after onset. RESULTS: Of 196 consecutive patients who underwent EVT for acute ICA or MCA-M1 occlusion, 32 without brain MRI before EVT were excluded, and the remaining 164 were analyzed. The median FVH-DWI mismatch score was 2 (interquartile range, 0 to 4). At 90 days after EVT, 2 patients were lost-to follow-up, and 73 had good functional outcome. The frequency of good functional outcome at 90 days after EVT increased significantly with increasing FVH-DWI mismatch score (P for trend <0.001). FVH-DWI mismatch score was independently associated with good functional outcome at 90 days after onset (adjusted odds ratio per 1 point,1.46; 95% confidence interval, 1.15-1.89). CONCLUSIONS: Patients with large FVH-DWI mismatch had good functional outcome after EVT for acute ICA or MCA-M1 occlusion.

Intraplaque high-intensity signal on time-of-flight magnetic resonance angiography and restenosis after carotid artery stenting.

OBJECTIVE: To test the hypothesis that intraplaque hemorrhage is a predictor of restenosis after carotid artery stenting (CAS), the association between intraplaque high-intensity signal (HIS) on time-of-flight MR angiography (TOF-MRA), as a marker of intraplaque hemorrhage, and restenosis after CAS was assessed in the present observational study. METHODS: Consecutive patients who underwent initial CAS for atherosclerotic stenosis in the cervical internal carotid artery in the authors' department were enrolled. Of these, patients without preprocedural cervical TOF-MRA were excluded. Outcome measures were ≥ 50% restenosis, defined as a peak systolic velocity of > 1.3 m/sec; or occlusion and ≥ 70% restenosis, defined as a peak systolic velocity of > 2.1 m/sec; or occlusion on carotid duplex ultrasound. RESULTS: Of 230 consecutive patients who underwent initial CAS, 22 without preprocedural cervical TOF-MRA were excluded. Of the remaining 208 patients (mean age 73 years; 33 women), 46 had intraplaque HIS. Ultrasound follow-up was not performed in 4 patients. The median follow-up duration was 3.2 years (interquartile range 1.7-5.1 years). During the follow-up period, 102 patients had ≥ 50% restenosis and 36 had ≥ 70% restenosis. Intraplaque HIS was significantly associated with increased risk of ≥ 50% restenosis (adjusted hazard ratio 2.18; 95% CI 1.28-3.68) and ≥ 70% restenosis (adjusted hazard ratio 3.12; 95% CI 1.32-7.52). CONCLUSIONS: Intraplaque HIS on TOF-MRA was associated with increased risk of restenosis after CAS. The present results indicate that intraplaque hemorrhage is a predictor of restenosis after CAS.

Efficacy of combined use of a stent retriever and aspiration catheter in mechanical thrombectomy for acute ischemic stroke.

BACKGROUND: The efficacy of combined stent retriever (SR) and aspiration catheter (AC; combined technique: CBT) use for acute ischemic stroke (AIS) is unclear. We investigated the safety and efficacy of single-unit CBT (SCBT)-retrieving the thrombus as a single unit with SR and AC into the guide catheter-compared with single use of either SR or contact aspiration (CA). METHODS: We analysed 763 consecutive patients who underwent mechanical thrombectomy for AIS between January 2013 and January 2020, at six comprehensive stroke centers. Patients were divided into SCBT and single device (SR/CA) groups. The successful recanalization with first pass (SRFP) and other procedural outcomes were compared between groups. RESULTS: Overall, 240 SCBT and 301 SR/CA (SR 128, CA 173) patients were analyzed. SRFP (modified Thrombolysis In Cerebral Infarction (mTICI) ≥2c, 43.3% vs 27.9%, p<0.001; mTICI 3, 35.8% vs 25.5%, p=0.009) and final mTICI ≥2b recanalization (89.1% vs 82.0%, p=0.020) rates were significantly higher, puncture-to-reperfusion time was shorter (median (IQR) 43 (31.5-69) vs 55 (38-82.2) min, p<0.001), and the number of passes were fewer (mean±SD 1.72±0.92 vs 1.99±1.01, p<0.001) in the SCBT group. Procedural complications were similar between the groups. In subgroup analysis, SCBT was more effective in women, cardioembolic stroke patients, and internal carotid artery and M2 occlusions. CONCLUSIONS: SCBT increases the SRFP rate and shortens the puncture-to-reperfusion time without increasing procedural complications.

High Adherence to the Food Pyramid's Recommendations Avoids the Risk of Insufficient Nutrient Intake among Farmers in Peri-Urban Kenya.

This study aimed to investigate whether the Kenyan Food Pyramid (FP) can evaluate excess or insufficient nutrient intake. Participants were farmers (56 men and 64 women, aged 18-60 years) in Wangige Village, Kiambu County-a peri-urban area of Kenya. Cross-sectional data were collected for demographic characteristics, physical measurements, and 2-day and 24-h dietary recalls. The average adherence level to the FP (hereafter, "FP score") was 25.0 out of 50.0, with a minimum and maximum of 14.1 and 41.5, respectively. Energy and protein % energy ratio were significantly higher (p for trend < 0.05) in the higher FP score group. A higher FP score was also associated with a higher energy-adjusted micronutrient intake, and it was more likely to meet nutrient requirements. However, the higher FP score group had a higher risk of excess sodium intake (p for trend < 0.001). The Kenyan FP could be a useful tool for avoiding the risk of insufficient nutrient intake, but not for avoiding high energy and sodium intake. It is necessary to include appropriate evaluations to limit energy, sugar, and salt. Food groups and recommendations of the FP should be optimised according to the dietary environment of the target population so as to promote their health.

Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model.

BACKGROUND: Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. METHODS: In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/-, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. RESULTS: Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/- mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/- mice. CONCLUSIONS: Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice.

Analysis of time-dependent alterations of parameters related to erythrocytes after ipragliflozin initiation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors often increase the hematocrit. It remains unclear whether this increase would be observed in all patients administered SGLT2 inhibitors, however. We therefore used the data from the previous study and investigated time-dependent alterations of various outcomes related to erythrocytes, erythropoiesis, and clinical outcome in type 2 diabetes subjects (n = 89) treated with ipragliflozin for 16 weeks. Among a total of 89 participants, 71 subjects (80.0% of total participants) showed the elevation of the hematocrit and 18 subjects (20.0% of total participants) did not at 16 weeks. Although the hematocrit levels at baseline were significantly lower in hematocrit-elevated group than non-elevated group, they reached the same levels 4 weeks after the onset of treatment. Binomial logistic regression analysis demonstrated that a lower baseline hematocrit level was related to the elevation of hematocrit at 16 weeks. Optimal cutoff hematocrit levels at baseline to predict hematocrit elevation were 46.9% (male) and 41.7% (female) in ROC analysis. Random intercept model analysis revealed the serum erythropoietin level increased in both hematocrit-elevated and non-elevated groups, whereas only the former group showed an increase in the percentage of reticulocytes during the first 4 weeks. These results suggest that the ipragliflozin-induced increase in hematocrit which is affected by the baseline hematocrit level is attributable to the responsiveness to, but not to the production of, erythropoietin. Collectively, Ht elevation observed in administration of SGLT2 inhibitors can result from erythropoietin-induced erythropoiesis, which is determined by the pre-treatment Ht level. Trial registration: This trial has been registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR no. 000015478).

Mechanical thrombectomy and carotid artery stenting for stenosis of the internal carotid artery with free-floating thrombosis: illustrative case.

BACKGROUND: The authors report a case in which mechanical thrombectomy and carotid artery stenting (CAS) were performed for acute cerebral infarction with free-floating thrombosis (FFT) in left internal carotid artery (ICA) stenosis. Good results were obtained. OBSERVATIONS: A 63-year-old man developed sudden disturbance of consciousness and right hemiplegia. He was transported to the authors' hospital by an emergency vehicle. Head magnetic resonance imaging showed acute cerebral infarction in the left middle cerebral artery region, and magnetic resonance angiography showed poor vascular flow beyond the left ICA. Emergency angiography revealed severe stenosis at the origin of the left ICA and a free-floating thrombus attached to the stenosis and extending to the peripheral side. Percutaneous transluminal angioplasty (PTA) was performed on the stenosis with proximal protection, the thrombus was aspirated under reversal flow, and CAS was performed without exacerbation of clinical symptoms. LESSONS: PTA, thrombus aspiration, and CAS under reversal flow may be effective treatments for FFT caused by ICA stenosis.

Ischemic Stroke Caused by Carotid Stump at the Common Carotid Artery.

An 84-year-old man developed motor aphasia and right hemiparesis on postoperative day 1 after orchiectomy for suspected malignant lymphoma. He had a history of thoracic endovascular aortic repair for aortic aneurysm using a bypass graft from the right subclavian artery to the left common carotid artery (CCA); however, the graft had become occluded six months later. Brain magnetic resonance imaging revealed acute cerebral infarctions in the left frontal lobe. Carotid ultrasonography revealed a stump at the left CCA, just below the bifurcation, formed by the occluded graft with an oscillating thrombus. This case was rare in that a CCA stump was identified as the embolic source of ischemic stroke.

Epidemic Myalgia Associated with Human Parechovirus Type 3 Infection.

A 42-year-old man was hospitalized due to a fever, orchiodynia, and extremely severe myalgia predominantly in the extremities, which made it difficult for him to stand or walk. He had a history of contact with his son who had acute upper respiratory infection. Based on the characteristic clinical symptoms and detection of the partial sequence of human parechovirus type 3 (HPeV3) in throat swabs as well as stool and serum samples, he was diagnosed with epidemic myalgia associated with HPeV3 infection. Because HPeV3 infection is widespread among children in Japan, HPeV3-associated myalgia should be considered when adult patients manifest such distinguishing clinical characteristics.

A case of pulmonary tuberculosis diagnosed in a patient with manifestations of haemophagocytic lymphohistiocytosis.

An 80-year-old woman was admitted with continuous fever, hepatic dysfunction and cytopaenia. The presence of hepatosplenomegaly, hyperferritinaemia, hypofibrinogenaemia and phagocytosis by macrophages in the bone marrow was consistent with a diagnosis of haemophagocytic lymphohistiocytosis (HLH). We suspected that HLH was induced by pre-existing tuberculosis, and antitubercular agents were started. Positive nucleic acid amplification and sputum culture for Mycobacterium tuberculosis resulted in a diagnosis of pulmonary tuberculosis. The patient improved with three months of treatment. In this patient, manifestations of HLH preceded those of pulmonary tuberculosis. A diagnosis of HLH should increase suspicion of disseminated tuberculosis and thus contribute to early detection.

Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open-label study (SOAR-KOBE Study).

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT-2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT-2 inhibitor, ipragliflozin, including those on appetite-regulating hormones, in individuals with suboptimally controlled type 2 diabetes. MATERIALS AND METHODS: The present prospective, multicenter, open-label study was carried out with 96 patients with a body mass index of ≥22 kg/m2 who were treated with ipragliflozin (50 mg/day) for 16 weeks. Parameters including glycated hemoglobin level, bodyweight, circulating leptin and active ghrelin concentrations, and appetite as assessed with a visual analog scale were measured before and during treatment. RESULTS: Both glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks. CONCLUSIONS: The present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.

Effects of Insulin Degludec and Insulin Glargine U300 on Day-to-Day Fasting Plasma Glucose Variability in Individuals with Type 1 Diabetes: A Multicenter, Randomized, Crossover Study (Kobe Best Basal Insulin Study 2).

INTRODUCTION: Administered basal insulin markedly influences the fasting plasma glucose (FPG) level of individuals with type 1 diabetes. Insulin degludec (IDeg) and insulin glargine U300 (IGlar U300) are now available as ultra-long-acting insulin formulations, but whether or how their glucose-stabilizing effects differ remains unclear. We will compare the effects of these basal insulins on parameters related to blood glucose control, with a focus on day-to-day glycemic variability, in individuals with type 1 diabetes treated with multiple daily injections. METHODS: A multicenter, randomized, open-label, crossover, comparative study (Kobe Best Basal Insulin Study 2) will be performed at 13 participating institutions in Japan. A total of 46 C-peptide-negative adult outpatients with type 1 diabetes will be randomly assigned 1:1 by a centralized allocation process to IGlar U300 (first period)/IDeg (second period) or IDeg (first period)/IGlar U300 (second period) groups, in which subjects will be treated with the corresponding basal insulin for consecutive 4-week periods. The basal insulin will be titrated to achieve an FPG of less than 130 mg/dL initially and then less than 110 mg/dL if feasible. In the last week of each period, plasma glucose will be determined seven times a day by self-monitoring of blood glucose (SMBG) and intraday and day-to-day glucose excursions will be determined by flash glucose monitoring (FGM). The primary end point is comparison of day-to-day glycemic variability as evaluated by the standard deviation (SD) of FPG during the last week of each treatment period. Secondary end points include the coefficient of variance of FPG, the frequency of severe hypoglycemia as evaluated by SMBG, the duration of hypoglycemia as evaluated by FGM, intraday glycemic variability calculated from both SMBG and FGM data, and the administered insulin dose. PLANNED OUTCOMES: The results of the study will be submitted for publication in a peer-reviewed journal to report differences in the effects of two ultra-long-acting basal insulins, IDeg and IGlar U300. CONCLUSION: This head-to-head comparison will be the first study to compare the effects of IDeg and IGlar U300 on day-to-day FPG variability in C-peptide-negative individuals with type 1 diabetes. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry as 000029630 on 20 June 2017. FUNDING: Novo Nordisk Pharma Ltd.

Comprehensive Evaluation of Combination Therapy with Basal Insulin and Either Lixisenatide or Vildagliptin in Japanese Patients with Type 2 Diabetes: A Randomized, Open-Label, Parallel-Group, Multicenter Study.

INTRODUCTION: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes. METHODS: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 µg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA1c) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA1c level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose. RESULTS: The change in HbA1c level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA1c level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups. CONCLUSION: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control. TRIAL REGISTRATION: This trial has been registered with UMIN (No. 000010769).

A case of pernicious anemia requiring differential diagnosis of autoimmune hemolytic anemia complication.

An 80-year-old female was admitted to our hospital due to malaise. The initial diagnosis on admission was pernicious anemia (PA), Hashimoto thyroiditis and autoimmune atrophic gastritis. Autoimmune hemolytic anemia was suspected because direct antiglobulin test (DAT) was positive. Treatment with vitamin B12 improved anemia, with the disappearance of hemolysis. In some cases, PA patients with positive DAT may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT for the prevention of unnecessary administration of steroid therapy.

Roles of mTOR in ageing and longevity.

The large Ser/Thr protein kinase mTOR signals through two physically distinct multipro- tein complexes called mTOR complexes 1 and 2(mTORC1 and mTORC2). The mTORC1 pathway integrates inputs from nutrients and growth factors for protein synthesis, autophagy, cell growth and proliferation. Dietary restriction delays ageing and extends life span in diverse species including yeast, worm, fly, and mammals such as mouse and monkey. Because in- cidences of many diseases such as cancer, cardiovascular disease, metabolic disease and dementia rise rapidly with age, interventions that delay ageing would greatly benefit health. It has become apparent in recent years that the nutrient sensing mTOR pathways are well con- served among such various species and important regulators of ageing and longevity.

The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic ß cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A) may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD) mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C)) was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C). In addition, injection of high-dose poly(I: C) to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C) than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C) treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.