Evaluation of muscle mass and intramuscular fatty infiltration in dogs with hypercortisolism and their association with prognosis.

BACKGROUND: Muscle atrophy and intramuscular fatty infiltration, as well as their association with prognosis, have not been quantified in dogs with spontaneous hypercortisolism (HC). OBJECTIVE: To quantitatively evaluate muscle atrophy and IM fatty infiltration in dogs with HC and determine their prognostic impact. ANIMALS: Fifty-three dogs with HC and 66 control dogs without HC. METHODS: Retrospective cohort study. Medical records and computed tomography images obtained between 2014 and 2021 were evaluated. Kaplan-Meier curves and log-rank tests were used to analyze the effect of muscle atrophy and IM fatty infiltration on the prognosis of dogs with HC. RESULTS: Dogs with HC showed lower visually measured cross-sectional area (VCSA) and cross-sectional area based on attenuation (HCSA) than control dogs (median [interquartile range {IQR}]: 50.3 mm2/mm [36.2-67.8] vs 66.7 mm2/mm [48.0-85.9]; P < .001; 30.4 mm2/mm [13.7-57.2] vs 54.8 mm2/mm [39.7-71.5]; P < .001, respectively). Dogs with HC had lower epaxial muscle attenuation (L3HU) than control dogs (median [IQR]: 21.2 Hounsfield [HU] [12.4-28.2] vs 33.2 HU [22.6-43.6]; P < .001). Dogs with HC with lower HCSA or L3HU had shorter survival (median [IQR]: 670 days [222-673] vs 949 days [788-1074], P < .01; 523 days [132-670] vs 949 days [756-1074], P < .01, respectively) but not lower VCSA (median [IQR]: 673 days [132-788] vs 949 days [523 to not applicable]; P = .30). CONCLUSION AND CLINICAL IMPORTANCE: Hypercortisolism in dogs causes muscle atrophy and IM fatty infiltration and is associated with poor prognosis.

Human Crowds as Social Networks: Collective Dynamics of Consensus and Polarization.

A ubiquitous type of collective behavior and decision-making is the coordinated motion of bird flocks, fish schools, and human crowds. Collective decisions to move in the same direction, turn right or left, or split into subgroups arise in a self-organized fashion from local interactions between individuals without central plans or designated leaders. Strikingly similar phenomena of consensus (collective motion), clustering (subgroup formation), and bipolarization (splitting into extreme groups) are also observed in opinion formation. As we developed models of crowd dynamics and analyzed crowd networks, we found ourselves going down the same path as models of opinion dynamics in social networks. In this article, we draw out the parallels between human crowds and social networks. We show that models of crowd dynamics and opinion dynamics have a similar mathematical form and generate analogous phenomena in multiagent simulations. We suggest that they can be unified by a common collective dynamics, which may be extended to other psychological collectives. Models of collective dynamics thus offer a means to account for collective behavior and collective decisions without appealing to a priori mental structures.

Lifestyle parameters of Japanese agricultural and non-agricultural workers aged 60 years or older and less than 60 years: A cross-sectional observational study.

OBJECTIVES: Improving the lifestyle of occupational workers is essential for extending healthy life expectancy. We investigated various lifestyle-related items in a rural Japanese population and compared them between agricultural and non-agricultural workers. METHODS: This cross-sectional study was conducted as a part of the "Iwaki Health Promotion Project." Lifestyle-related items such as sleep, work hours, nutrition, health-related quality of life, and proportion of time spent performing each daily activity were compared between agricultural and non-agricultural workers in the ≥60 years (n = 251) and <60 years (n = 560) age groups. RESULTS: Agricultural workers had significantly lower Pittsburgh Sleep Quality Index total scores than non-agricultural workers in the <60 years group. The proportion of participants with more than 5 weekly working days was high among agricultural workers in both groups. Additionally, the proportion of people who worked more than 8 h per day was high among agricultural workers in both age groups. Energy intake per day was high among agricultural workers in the <60 years group. In both age groups, agricultural workers slept and woke up approximately 40 min earlier than did non-agricultural workers. CONCLUSIONS: Agricultural workers have better sleep habits but work longer than non-agricultural workers, with some differences in energy intake and proportion of time spent on each daily activity. These differences should be considered when planning lifestyle intervention programs for agricultural workers.

Nighttime hypoglycemia in Japanese children with type 1 diabetes mellitus treated with multiple daily injection insulin therapy.

Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.

Efficacy of Low-dose Dapagliflozin in Young People with Type 1 Diabetes.

Objective Young people with type 1 diabetes are likely to gain body weight and not achieve optimal glycemic control with only high doses of insulin. This study examined the efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin as an adjunct-to-insulin therapy in young Japanese subjects with type 1 diabetes who had been diagnosed before 15 years old, were overweight, and had inadequate control despitereceiving intensive insulin therapy. Methods Twenty-two patients with type 1 diabetes (12 boys and 10 girls 16.0-33.9 years old) were involved in the study. All patients had a body mass index (BMI) >25 kg/m2, glycated hemoglobin (HbA1c) level >7.0%, and daily insulin dose >0.5 units/kg. They were treated with a low dose of dapagliflozin (5.0 mg/day) as an adjunctive therapy to insulin. Fourteen patients were treated with multiple daily injections of insulin, while eight used an insulin pump. Results The body weights and BMIs were significantly reduced during the 12-month study period (change of -4.4 kg and -1.7 kg/m2, p<0.001, respectively). Their insulin dose was significantly decreased (-0.17 units/kg, P <0.001), and glycemic control was significantly improved (fasting plasma glucose: -18.7 mg/dL, HbA1c: -0.62%, p<0.001) during the study period. There was one episode of diabetic ketoacidosis, with no other problematic adverse events, including severe hypoglycemia, observed. Conclusion The use of low-dose dapagliflozin as an adjunct therapy may be beneficial in overweight young people with poorly controlled type 1 diabetes.

A clinical practice review of therapeutic movement-based anterior cruciate ligament reconstruction return to sports bridge program: the biological, biomechanical and behavioral rationale.

This clinical practice review describes the biological, biomechanical and behavioral rationale behind a return to sport bridge program used predominantly with non-elite, youth and adolescent high school and college athletes following anterior cruciate ligament (ACL) reconstruction. Post-physiotherapy, this program has produced outcomes that meet or exceed previous reports. With consideration for athletic identity and the Specific Adaptations to Imposed Demands (SAID) principle, the early program focus was on restoring non-impaired bilateral lower extremity joint mobility and bi-articular musculotendinous extensibility. Building on this foundation, movement training education, fundamental bilateral lower extremity strength and power, and motor learning was emphasized with use of external focus cues and ecological dynamics-social cognition considerations. Plyometric and agility tasks were integrated to enhance fast twitch muscle fiber recruitment, anaerobic metabolic energy system function, and fatigue resistance. The ultimate goal was to achieve the lower extremity neuromuscular control and activation responsiveness needed for bilateral dynamic knee joint stability. The rationale and conceptual basis of selected movement tasks and general philosophy of care concepts are described and discussed in detail. Based on the previously reported efficacy of this movement-based therapeutic exercise program we recommend that supplemental programs such as this become standard practice following release from post-surgical physiotherapy and before return to sports decision-making.

History of Ulnar Collateral Ligament Injury and College Pitcher Fastball Profiles: A Retrospective, Observational, Live Pitching Analysis.

PURPOSE: The aim of this study was to retrospectively compare the fastball profiles of pitchers who had previously sustained grade I or II ulnar collateral ligament (UCL) injuries, were rehabilitated, and released back for competition with those of pitchers with no history of elbow injury. METHODS: Eighteen pitchers from the pitching staff of 1 National Collegiate Athletic Association Division III team participated in this study. Group 1 had a history of grade I or II UCL injury (n = 8), and group 2 (n = 10) did not. A computerized pitch tracking device was used to analyze ball movement and pitching mechanics. The hypothesis was that the pitchers with a history of injury (group 1) would display differing fastball velocity-ball movement relationships compared to those without (group 2). RESULTS: The groups had similar heights, weights, pitching experiences, and arm slot positions at ball release. The pitching coach-determined preinjury arm slot position and the postinjury computerized pitch tracking device measurements after return to competition displayed strong agreement (r = 0.83), suggesting comparable pre and postinjury pitching techniques. The groups had comparable glenohumeral joint range of motion and fastball profiles, except that group 1 released the ball at a 2.5 times lesser horizontal distance away from the pitching rubber center. Group 2 also displayed consistently more robust and more frequent fastball movement relationships with velocity, horizontal break, and vertical break than group 1. CONCLUSIONS: Reduced horizontal ball release distances at comparable vertical ball release heights without changes in the arm slot position suggest that pitchers with a history of grade I or II UCL injury have greater contralateral trunk tilt and elbow flexion at ball release. Increased contralateral trunk tilt may occur to increase pitch velocity at the expense of ball movement while placing the pitching elbow in a potentially injurious position. Computerized fastball profile analysis using a computerized pitch tracking device, in conjunction with coach pitching technique observation, and team medical staff clinical examination may help better identify pitchers with an increased risk of UCL injury. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype.

Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo-NP class, whereby indole- and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo-IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo-IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research.

Comparison of the clinical effects of intermittently scanned and real-time continuous glucose monitoring in children and adolescents with type 1 diabetes: A retrospective cohort study.

AIMS/INTRODUCTION: The aim of the study was to compare two continuous glucose monitoring (CGM) systems, intermittently scanned CGM (isCGM) and real-time CGM (rtCGM), to determine which system achieved better glycemic control in pediatric patients. MATERIALS AND METHODS: We carried out a retrospective cohort study of children and adolescents with type 1 diabetes, and compared the time in range (70-180 mg/dL), time below range (<70 mg/dL) and time above range (>180 mg/dL), and estimated glycated hemoglobin levels between patients on isCGM and rtCGM. RESULTS: Of the 112 participants, 76 (67.9%) used isCGM and 36 (32.1%) used rtCGM for glycemic management. Patients on rtCGM had significantly greater time in range (57.7 ± 12.3% vs 52.3 ± 12.3%, P = 0.0368), and had significantly lower time below range (4.3 ± 2.7% vs 10.2% ± 5.4%, P < 0.001) than those on isCGM, but there was no significant difference in the time above range (37.4 ± 12.9% vs 38.0% ± 12.5%, P = 0.881) or the glycosylated hemoglobin A1c levels (7.4 ± 0.9% vs 7.5 ± 0.8%, P = 0.734) between the two groups. CONCLUSIONS: Pediatric patients with type 1 diabetes on rtCGM also showed more beneficial effects for increase of time in range, with a notable reduction of time below range compared with those on isCGM. Real-time CGM might provide better glycemic control than isCGM in children with type 1 diabetes.

Myc Supports Self-Renewal of Basal Cells in the Esophageal Epithelium.

It is widely believed that cellular senescence plays a critical role in both aging and cancer, and that senescence is a fundamental, permanent growth arrest that somatic cells cannot avoid. Here we show that Myc plays an important role in self-renewal of esophageal epithelial cells, contributing to their resistance to cellular senescence. Myc is homogeneously expressed in basal cells of the esophageal epithelium and Myc positively regulates their self-renewal by maintaining their undifferentiated state. Indeed, Myc knockout induced a loss of the undifferentiated state of esophageal epithelial cells resulting in cellular senescence while forced MYC expression promoted oncogenic cell proliferation. A superoxide scavenger counteracted Myc knockout-induced senescence, therefore suggesting that a mitochondrial superoxide takes part in inducing senescence. Taken together, these analyses reveal extremely low levels of cellular senescence and senescence-associated phenotypes in the esophageal epithelium, as well as a critical role for Myc in self-renewal of basal cells in this organ. This provides new avenues for studying and understanding the links between stemness and resistance to cellular senescence.

Quantitative assessment of muscle mass and gene expression analysis in dogs with glucocorticoid-induced muscle atrophy.

The present study aimed to quantitatively evaluate muscle mass and gene expression in dogs with glucocorticoid-induced muscle atrophy. Five healthy beagles received oral prednisolone for 4 weeks (1 mg/kg/day), and muscle mass was then evaluated via computed tomography. Histological and gene expression analyses were performed using biopsy samples from the biceps femoris before and after prednisolone administration. The cross-sectional area of the third lumbar paraspinal and mid-femoral muscles significantly decreased after glucocorticoid administration (from 27.5 ± 1.9 to 22.6 ± 2.0 cm2 and from 55.1 ± 4.7 to 50.7 ± 4.1 cm2, respectively; P<0.01). The fast- and slow-twitch muscle fibers were both atrophied (from 2,779 ± 369 to 1,581 ± 207 µm2 and from 2,871 ± 211 to 1,971 ± 169 µm2, respectively; P<0.05). The expression of the growth factor receptor-bound protein 10 (GRB10) significantly increased after prednisolone administration (P<0.05). Because GRB10 suppresses insulin signaling and the subsequent mammalian target of rapamycin complex 1 activity, increased expression of GRB10 may have resulted in a decrease in protein anabolism. Taken together, 1 mg/kg/day oral prednisolone for 4 weeks induced significant muscle atrophy in dogs, and GRB10 might participate in the pathology of glucocorticoid-induced muscle atrophy in canines.

Radial nerve palsy following humeral shaft fracture: a theoretical PNF rehabilitation approach for tendon and nerve transfers.

BACKGROUND: Humerus fracture-induced radial nerve injury can create severe and permanent disabilities. PURPOSE: Surgical management often relies on either tendon or nerve transfer. Regardless of which procedure is selected, physical therapists are challenged to restore functional outcomes without jeopardizing repair healing. Through synergistic, multi planar upper extremity movement patterns, neuromuscular irradiation, or overflow, and neuroplasticity, proprioceptive neuromuscular facilitation (PNF) may improve strength, range of motion and tone. METHODS: After reviewing the literature, a five phase PNF-based treatment approach is proposed with timing differences based on the selected procedure. FINDINGS: Phase I (2 or 4 weeks pre-surgery for tendon or nerve transfer, respectively) consists of comprehensive patient education; Phase II (4-6 or 1-2 weeks post-surgery for tendon or nerve transfer, respectively) explores variable duration peripheral and central nervous system motor learning during isometric activation to enhance central neuroplasticity; Phase III (7-12 or 3-20 weeks post-surgery for tendon or nerve transfer, respectively) incorporates low-intensity motor control including contralateral isotonic upper extremity loading to maximize overflow and neuroplastic effects; Phase IV (13-26 or 21-52 weeks post-surgery for tendon or nerve transfer, respectively) adds high-intensity strength and motor control using ipsilateral isotonic upper extremity loading to maximize overflow and neuroplastic effects. Phase V (27-52 or 53-78 weeks post-surgery for tendon or nerve transfer, respectively) progresses to more activity of daily living, vocational, or sport-specific training with higher intensity strength and motor control tasks. CONCLUSIONS: Through manually guided synergistic, multi planar movement, overflow, and neuroplasticity, a PNF treatment approach may optimize neuromuscular recovery. Validation strategies to confirm clinical treatment efficacy are discussed.

Frequent scanning using flash glucose monitoring contributes to better glycemic control in children and adolescents with type 1 diabetes.

AIMS/INTRODUCTION: We examined the impact of scanning frequency with flash glucose monitoring on glycemic control in children and adolescents with type 1 diabetes. MATERIALS AND METHODS: The study included 85 patients, aged 14.0 ± 0.5 years, with type 1 diabetes. The median time in the target glucose range (TIR) and glycosylated hemoglobin (HbA1c) values were 50.0 ± 1.4% and 7.5 ± 0.1%, respectively. RESULTS: The median scanning frequency using flash glucose monitoring was 12.0 ± 0.4 times/day. Scanning frequency showed a significant positive correlation with TIR and an inverse correlation with HbA1c. Scanning frequency was identified to be the determinant of TIR and HbA1c by using multivariate analysis. The participants whose scanning frequency was <12 times/day were categorized as the low-frequency group (n = 40), and those who carried out the scanning >12 times/day were categorized as the high-frequency group (n = 45). Patients in the high-frequency group were more likely to be treated with insulin pumps compared with those in the low-frequency group; however, this difference was not significant (21.3 vs 5.3%, P = 0.073). The high-frequency group showed significantly greater TIR than the low-frequency group (57 ± 1.6 vs 42 ± 1.7%, P = 0.002). Furthermore, the high-frequency group showed significantly lower HbA1c levels than the low-frequency group (6.8 ± 0.1 vs 8.0 ± 0.1%, P < 0.001). CONCLUSIONS: These findings showed that patients with a higher scanning frequency had better glycemic control, with greater TIRs and lower HbA1c levels, compared with those with a lower scanning frequency. Scanning frequency of >12 times/day might contribute to better glycemic outcomes in real-world practice in children with type 1 diabetes.

A case report with functional characterization of a HNF1B mutation (p.Leu168Pro) causing MODY5.

We previously performed next-generation sequencing-based genetic screening in patients with autoantibody-negative type 1 diabetes, and identified the p.Leu168Pro mutation in HNF1B. Here,we report the clinical course of the patient and the results of functional characterization of this mutation. The proband had bilateral renal hypodysplasia and developed insulin-dependent diabetes during childhood. The pathogenicity of Leu168Pro-HNF1B was evaluated with three-dimensional structure modeling, Western blotting, immunofluorescence analysis and luciferase reporter assays using human embryonic kidney 293 cells. Three-dimensional structure modeling predicted that the Leu168 residue is buried in the DNA-binding Pit-Oct-Unc-specific (POUS) domain and forms a hydrophobic core. Western blotting showed that the protein expression level of Leu168Pro-HNF1B was lower than that of wild-type (WT) HNF1B. Immunofluorescence staining showed that both WT- and Leu168Pro-HNF1B were normally localized in the nucleus. The cells transfected with WT-HNF1B exhibited 5-fold higher luciferase reporter activity than cells transfected with an empty vector. The luciferase activities were comparable between WT-HNF1B/Leu168Pro-HNF1B and WT-HNF1B/empty vector co-transfection. In conclusion, Leu168Pro is a protein-destabilizing HNF1B mutation, and the destabilization is likely due to the structural changes involving the hydrophobic core of POUS. The disease-causing Leu168Pro HNF1B mutation is a loss-of-function mutation without a dominant-negative effect.

Rotational Medicine Ball Throw Velocity Relates to NCAA Division III College Baseball Player Bat Swing, Batted Baseball, and Pitching Velocity.

ABSTRACT: Taniyama, D, Matsuno, J, Yoshida, K, Pyle, B, and Nyland, J. Rotational medicine ball throw velocity relates to NCAA Division III college baseball player bat swing, batted baseball, and pitching velocity. J Strength Cond Res 35(12): 3414-3419, 2021-Previous studies have evaluated relationships between baseball batting or pitching and whole-body power tests such as rotational medicine ball throw velocity (RMBTV) (transverse plane), lateral-to-medial hop for distance (frontal plane), and two-legged standing broad jump for distance (sagittal plane). However, no previous report has evaluated all 3 whole-body power tests in the same study to determine their relationship to bat swing velocity or pitching velocity. The purpose of this descriptive study was to determine correlational relationship strength between bat swing velocity, batted baseball velocity, and throwing velocity with 2-legged standing broad jump for distance, lateral-to-medial jump for distance, and RMBTV whole-body power tests in collegiate baseball players. Thirty-five NCAA Division III players (15 pitchers and 23 hitters; 3 players played pitcher and other positions) participated in this study. An alpha value of p < 0.05 was selected to indicate statistical significance. Moderate relationships were observed between bat swing velocity and RMBTV (r = 0.65, p = 0.003), explaining 39% of the variance, and between pitching velocity and RMBTV (r = 0.62, p = 0.02), explaining 38% of the variance. A moderate correlation was also observed between batted baseball velocity and RMBTV (r = 0.53, p = 0.02), explaining 28% of the variance. Only the RMBTV whole-body power test displayed significant relationships with bat swing velocity, batted baseball velocity, and pitching velocity. Significant relationships were not identified for either the two-legged standing broad jump for distance or the lateral-to-medial jump for distance whole-body power tests and bat swing velocity or pitching velocity. Further studies should evaluate whether the coordination developed during RMBTV movements can decrease baseball shoulder and elbow injuries associated with repetitive, poorly timed, sequential lower extremity-trunk-upper extremity whole-body movements.

Role of Liquid-Liquid Separation in Endocrine and Living Cells.

CONTEXT: Recent studies have revealed that every eukaryotic cell contains several membraneless organelles created via liquid-liquid phase separation (LLPS). LLPS is a physical phenomenon that transiently compartmentalizes the subcellular space and thereby facilitates various biological reactions. LLPS is indispensable for cellular functions; however, dysregulated LLPS has the potential to cause irreversible protein aggregation leading to degenerative disorders. To date, there is no systematic review on the role of LLPS in endocrinology. EVIDENCE ACQUISITION: We explored previous studies which addressed roles of LLPS in living cells, particularly from the viewpoint of endocrinology. To this end, we screened relevant literature in PubMed published between 2009 and 2021 using LLPS-associated keywords including "membraneless organelle," "phase transition," and "intrinsically disordered," and endocrinological keywords such as "hormone," "ovary," "androgen," and "diabetes." We also referred to the articles in the reference lists of identified papers. EVIDENCE SYNTHESIS: Based on 67 articles selected from 449 papers, we provided a concise overview of the current understanding of LLPS in living cells. Then, we summarized recent articles documenting the physiological or pathological roles of LLPS in endocrine cells. CONCLUSIONS: The discovery of LLPS in cells has resulted in a paradigm shift in molecular biology. Recent studies indicate that LLPS contributes to male sex development by providing a functional platform for SOX9 and CBX2 in testicular cells. In addition, dysregulated LLPS has been implicated in aberrant protein aggregation in pancreatic ß-cells, leading to type 2 diabetes. Still, we are just beginning to understand the significance of LLPS in endocrine cells.

Glucagon stimulation test as a possible predictor of residual ß-cell function.

BACKGROUND: We aimed to investigate the significance of the C-peptide levels on a glucagon stimulation test (GST) conducted soon after diagnosis as a predictive marker for residual ß-cell function over time in Japanese children with type 1 diabetes (TD1). METHODS: We retrospectively enrolled 65 Japanese children (25 male, 40 female; age <16 years) with new-onset TD1. A GST was conducted within 1 month of diagnosis, when glucose toxicity improved. One- to 2-h postprandial serum C-peptide values were measured at 0, 3, 6, 12, 24, 36, 60, and 120 months after diagnosis. RESULTS: Receiver operating characteristic analysis showed that the cutoff values of peak serum C-peptide levels used to predict the complete destruction of ß-cells at 3, 6, and 12 months after diagnosis were all 0.20 ng/mL (area under the curve [AUC] 0.867, 95% confidence interval [CI] 0.745-0.990; AUC 0.774, 95% CI 0.634-0.914; and AUC 0.804, 95% CI 0.695-0.914, respectively); the values at 24, 36, and 60 months were 0.69 ng/mL (AUC 0.828, 95% CI 0.721-0.936), 0.60 ng/mL (AUC 0.777, 95% CI 0.636-0.918), and 0.70 ng/mL (AUC 0.848, 95% CI 0.715-0.982), respectively. On multivariate analysis, peak serum C-peptide level on a GST, diabetic ketoacidosis, age, and HbA1c level at diagnosis were associated with residual ß-cell function over time. CONCLUSIONS: Peak serum C-peptide levels on a GST conducted soon after diagnosis in Japanese children with TD1 could predict the time to decrease in postprandial serum C-peptide values to < 0.20 ng/mL.

Association between scanning frequency of flash glucose monitoring and continuous glucose monitoring-derived glycemic makers in children and adolescents with type 1 diabetes.

BACKGROUND: We assessed the association between scanning frequency of flash glucose monitoring (FGM) and continuous glucose monitoring (CGM)-derived glycemic markers in children and adolescents with type 1 diabetes. METHODS: Subjects consisted of 85 children and adolescents with type 1 diabetes using FGM. We assessed the association between scanning frequencies of FGM- and CGM-derived metrics: Time in range (TIR) (70-180 mg/dL), time below range (TBR) (<70 mg/dL), time above range (>180 mg/dL), and other glycemic markers - laboratory-measured HbA1c and CGM-estimated glucose and HbA1c (eA1c) levels in the subjects. RESULTS: The mean number of scans was 11.5 ± 3.5 (5-20) times per day, and scanning was most frequently conducted during a period of 18-24 h. Scanning frequency showed significant positive correlation with TIR (r = 0.719, P < 0.0001) and inverse correlation with time above range (r = -0.743, P < 0.0001), but did not correlate with TBR. There were also significant inverse correlations between scanning frequency and glucose, HbA1c, and eA1c levels (r = -0.765, -0.815, and -0.793, respectively, P < 0.0001). CONCLUSIONS: Frequent glucose testing with FGM decreased hyperglycemia with increased TIR, but did not reduce TBR. Coping with a rapid fall of glucose and unexpected hypoglycemia with more advanced technology might contribute to a reduction in TBR.

A Concise Enantioselective Total Synthesis of (-)-Deoxoapodine.

We have established a highly convergent 10-step route for the total synthesis of (-)-deoxoapodine, which is a hexacyclic aspidosperma alkaloid. The quaternary C5 center of the characteristic tetrahydrofuran ring was constructed by a chiral-phosphoric-acid-catalyzed enantioselective bromocycloetherification in a 5-endo fashion and subsequent allylation by using the Keck protocol. Construction of the aspidosperma skeleton features the formation of a nine-membered lactam by a catalytic C-H palladation/alkylation cascade at the indole 2-position and an iron-catalyzed oxidative transannular reaction at a late-stage of the synthesis.

Significance of "Time below Range" as a Glycemic Marker Derived from Continuous Glucose Monitoring in Japanese Children and Adolescents with Type 1 Diabetes.

INTRODUCTION: We evaluated the frequencies of various glycemic markers derived from continuous glucose monitoring in Japanese children and adolescents with type 1 diabetes and assessed the significance of hypoglycemia duration. METHODS: We enrolled 85 children and adolescents (36 boys and 49 girls) with type 1 diabetes who used FreeStyle® Libre in the present study. Frequencies of blood glucose levels as time within target range (TIR; 70-180 mg/dL), time below target range (TBR; <70 mg/dL), time below extreme hypoglycemia range (TBER; <54 mg/dL), and time above range (TAR; >180 mg/dL) were assessed during a 3-month study period. Furthermore, we evaluated the intraday frequencies of TBR and TBER. RESULTS: The mean frequencies of TIR, TBR, and TAR were 52.7 ± 11.3%, 10.8 ± 5.4%, and 36.5 ± 10.8%, respectively, whereas the mean frequency of TBER was 1.1 ± 0.9% (0-3.0%); there was no clinical episode of severe hypoglycemia. The mean frequency of TBR was significantly greater in 0-6 h (16.9 ± 5.2%) than in 6-12 h (7.8 ± 2.9%) and 18-24 h (6.8 ± 4.8%; p < 0.01) time zones, respectively. DISCUSSION/CONCLUSION: We found similar TIR and comparatively higher TBR frequencies, particularly during sleep, than those that were previously reported. Possible reasons for the higher frequency of TBR include differences in the quality of insulin treatment and diabetes care between the present study and the European studies. The utilization of advanced technologies, such as a predictive low-glucose suspend-function pump or closed-loop therapy, can reduce the frequency of TBR, with a consequent increase in TIR frequency and comprehensive improvement in glycemic control.