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Type 2 diabetes (T2D) is a multifaceted metabolic disorder associated with distinctive pathophysiological disturbances. One of the pathophysiological risk factors observed in T2D is dysregulation of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Both hormones stimulate insulin secretion by acting postprandially on pancreatic β-cell receptors. Oral glucose administration stimulates increased insulin secretion in comparison with isoglycemic intravenous glucose administration, a phenomenon known as the incretin effect. While the evidence for incretin defects in individuals with T2D is growing, the etiology behind this attenuated incretin effect in T2D is not clearly understood. Given their central role in T2D pathophysiology, incretins are promising targets for T2D therapeutics. The present review synthesizes the recent attempts to explain the biological importance of incretin hormones and explore potential pharmacological approaches that target the incretins.

The present study hypothesized that treatment with GW501516 (a selective PPAR-δ agonist) lowers lipids by increasing fatty acid oxidation without adverse effects on oxidative stress. Caucasian men (age 18-50 years, n=18) were randomly assigned to treatment with GW501516, GW590735, or placebo for two weeks while residing in a clinical research facility. A meal tolerance test, skeletal muscle biopsy, and blood/breath sampling were conducted. The study reported that treatment with GW501516 ameliorated multiple metabolic abnormalities associated with metabolic syndrome including oxidative stress, obesity, dyslipidemia, and insulin resistance, all while increasing fatty acid oxidation. Notably, no adverse effects were reported. However, the restricted living conditions and/or diets that the participants were subjected to likely do not resemble their normal lifestyle. Therefore, the beneficial effects of GW501516 on metabolic health observed in the study should further be investigated in a real-life setting. During participant recruitment, the use of dietary supplements were minimally considered, thereby increasing the risk for confounding effects on the metabolic parameters assessed in the study. Also, recruiting a larger and more diverse population would allow for a more detailed analysis that may benefit a broader range of people (i.e., examining the effects of GW501516 in certain ethnic groups or with/without exercise programs). Additional research on GW501516 and other PPAR-δ agonists is encouraged since it appears that this class of drugs can ameliorate multiple metabolic syndrome features. Future studies should consider additional metrics relevant to metabolic syndrome such as C-reactive protein, cortisol, and homocysteine.

Previous studies in adults have found a correlation between nonalcoholic fatty liver disease (NAFLD) and sarcopenia. The present study evaluated the relationship between NFALD and skeletal muscle mass in overweight/obese youth. A total of 234 children and adolescents (age 8-16) was stratified into tertiles based on relative muscle mass (RMM). Total, regional lean body mass, and total fat mass were obtained by dual-energy X-ray absorptiometry. RMM was defined as the percent of muscle mass (kg) relative to the sum of muscle and fat mass (kg). NAFLD was diagnosed via ultrasononography and a subset of participants with NAFLD (n=40) underwent a liver biopsy. The lowest tertile had a significantly higher risk for obesity, dyslipidemia, insulin resistance, metabolic syndrome, NAFLD, and nonalcoholic steatohepatitis (NASH). The present study demonstrated an association between low muscle mass, NAFLD, and NASH in overweight/obese youth. Despite the strong scientific merits of the present study, a lack of race/ethnic description could be a major critique as different ethnic background (specifically in the minorities) may be disproportionately impacted by fat distribution and relative muscle mass. Even though there is a clear relationship between sarcopenia and NAFLD in the elderly, this association may not stem from the same origin in the pediatric population. Lastly, but not least, future studies should evaluate NAFLD in obese youth with varying degrees of metabolic disorders (i.e., metabolic syndrome).

OBJECTIVE To prospectively assess the efficacy of a biodegradable collagen matrix (ologen) in dogs with uncontrolled glaucoma receiving an Ahmed glaucoma valve (AGV) implant. ANIMAL STUDIED Five client-owned dogs with glaucoma (five eyes). PROCEDURES Five eyes treated for uncontrolled glaucoma underwent AGV implantation with ologen. Ologen was placed on the AGV plate and tube with a scleral flap. Complete ophthalmological examinations were performed preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1, 2, 3, and 6 months postoperatively. Surgical outcomes were assessed based on the intraocular pressure (IOP), vision, frequency of anti-glaucoma eye drops, and bleb morphology; complications, if any, were recorded. The number of dogs with an IOP

Background : The oral glucose tolerance test (OGTT)-glucose response curves (GRCs; incessant increase, monophasic, and biphasic) reflect insulin sensitivity and β-cell function, being worse in the former and superior in the latter. Here, we examined if the OGTT-GRC pattern is worse in obese antibody (glutamic acid decarboxylase 65-kDa [GAD65] and insulinoma-associated protein-2 [IA-2])-positive (Ab+) vs. -negative (Ab-) youth clinically diagnosed with type 2 diabetes (CDX-T2D). Methods : Forty-seven obese youth, 15 Ab+ and 32 Ab-, were divided into three OGTT-GRC groups: incessant increase, monophasic, and biphasic. The prevalence of OGTT-GRC, clamp-measured insulin sensitivity, and β-cell function was compared. Results : Incessant increase OGTT-GRC is the most frequent curve type and is three-fold higher in Ab+ vs. Ab- youth CDX-T2D. In Ab+ youth, there was up to 40% lower second-phase insulin secretion in the incessant increase group vs. the other two groups combined (monophasic and biphasic). In Ab- youth, while first- and second-phase insulin secretion was significantly lower in the incessant increase vs. the other two groups combined, overall β-cell function was less impaired than in Ab+ youth. In neither Ab- or Ab+ youth was OGTT-GRC related to hepatic or peripheral insulin sensitivity. Conclusion : Severe insulin deficiency, a characteristic of type 1 diabetes, seems to be related to higher prevalence of incessant increase in Ab+ vs. Ab- obese youth.

OBJECTIVE We examined the glucose response curves (biphasic [BPh], monophasic [MPh], incessant increase [IIn]) during an oral glucose tolerance test (OGTT) and their relationship to insulin sensitivity (IS) and β-cell function (βCF) in youth versus adults with impaired glucose tolerance or recently diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS This was both a cross-sectional and a longitudinal evaluation of participants in the RISE study randomized to metformin alone for 12 months or glargine for 3 months followed by metformin for 9 months. At baseline/randomization, OGTTs (85 youth, 353 adults) were categorized as BPh, MPh, or IIn. The relationship of the glucose response curves to hyperglycemic clamp–measured IS and βCF at baseline and the change in glucose response curves 12 months after randomization were assessed. RESULTS At randomization, the prevalence of the BPh curve was significantly higher in youth than adults (18.8% vs. 8.2%), with no differences in MPh or IIn. IS did not differ across glucose response curves in youth or adults. However, irrespective of curve type, youth had lower IS than adults (P < 0.05). βCF was lowest in IIn versus MPh and BPh in youth and adults (P < 0.05), yet compared with adults, youth had higher βCF in BPh and MPh (P < 0.005) but not IIn. At month 12, the change in glucose response curves did not differ between youth and adults, and there was no treatment effect. CONCLUSIONS Despite a twofold higher prevalence of the more favorable BPh curve in youth at randomization, RISE interventions did not result in beneficial changes in glucose response curves in youth compared with adults. Moreover, the typical β-cell hypersecretion in youth was not present in the IIn curve, emphasizing the severity of β-cell dysfunction in youth with this least favorable glucose response curve.

A castrated, mixed‐breed, 10‐year‐old male dog developed a skin fistula from a ruptured periorbital swelling on the right eye; the patient was successfully treated with dacryoendoscope‐guided cannulation using a nasolacrimal tube. On presentation, computed tomography with concurrent dacryocystography (CT‐DCG) revealed obstruction of the right nasolacrimal duct and abnormal flow of contrast agents towards the root of tooth 109 at the right maxillary bone; however, the origin of the fistula remained unclear on CT‐DCG. Dacryoendoscopy was used to confirm the physical association between the fistula and the nasolacrimal duct; the fistula end was found to be near the right upper gum mucosa around tooth 107. CT‐DCG and dacryoendoscopy revealed that the periorbital swelling occurred owing to an infection or inflammation of the accessory nasolacrimal duct. The fistula end was connected to the oral cavity through a nasolacrimal tube installed in the oral mucosa. The tube was removed a week later, and the clinical symptoms completely resolved., This report describes a case of dacryocystitis in a male dog, who was brought to our hospital with an 8‐month history of right‐sided epiphora and a periorbital swelling, which had ruptured, despite multiple rounds of antibiotic administration. A fistula was discovered beneath a scab associated with the swelling and pus drainage. Computed tomography with concurrent dacryocystography was performed to determine if there was a connection between the fistula and the nasolacrimal drainage system; right nasolacrimal duct obstruction was identified, as well as abnormal flow of contrast agents, but this imaging technique was not sufficient for determining the fistula's origin. Diagnostic dacryoendoscopy with nasolacrimal tube insertion was then performed, resulting in successful diagnosis and appropriate treatment. No recurrence of symptoms was observed within a 1‐year follow‐up period. We, therefore, suggest that dacryoendoscopy may be recommended for making more accurate diagnoses of nasolacrimal diseases, which in turn will facilitate more effective treatment of patients.

Parallel with the current pediatric obesity epidemic, the escalating rates of youthonset type 2 diabetes mellitus (T2DM) have become a major public health burden. Although lifestyle modification can be the first-line prevention for T2DM in youths, there is a lack of evidence to establish optimal specific exercise strategies for obese youths at high risk for T2DM. The purpose of this narrative review is to summarize the potential impact of exercise on 2 key pathophysiological risk factors for T2DM, insulin sensitivity and β-cell function, among obese youths. The studies cited are grouped by use of metabolic tests, i.e., direct and indirect measures of insulin sensitivity and β-cell function. In general, there are an increasing number of studies that demonstrate positive effects of aerobic exercise, resistance exercise, and the 2 combined on insulin sensitivity. However, a lack of evidence exists for the effect of any exercise modality on β-cell functional improvement. We also suggest a future direction for research into exercise medical prevention of youth-onset T2DM. These suggestions focus on the effects of exercise modalities on emerging biomarkers of T2DM risk.

Incretin hormones have recently been considered an important pathophysiological factor for T2D in adults and youth due to their role in augmenting insulin secretion (Michaliszyn et al., 2014). It is recognized that glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are glucose-dependent hormones released from the gut that stimulate insulin release from pancreatic β-cells (Muscelli et al., 2006). Thus, the insulin response to oral glucose is significantly greater than the intravenous (IV) glucose administration response; this is known as the incretin effect (Michaliszyn et al., 2014). To date, adults with T2D demonstrate a remarkable decrease in the incretin effect (Nauck et al., 1986), whereas there is lack of evidence in pediatric populations. The incretin effect is also associated with β-cell glucose sensitivity (βCGS), attesting incretins as a high-promising target for T2D treatment (Michaliszyn et al., 2014). Utilizing GLP-1 receptor agonists can be advantageous as a therapeutic option for both adults and youth (Tamborlane et al., 2019; Vanderheiden et al., 2016; Yeow et al., 2017). While metformin and insulin were the sole treatment options for Y-T2D prior to FDA approval (in 2019) for the use of GLP-1 agonists, a recent RISE (Restoring Insulin Secretion) clinical trial reported disappointing results that both metformin alone and insulin glargine for three months followed by metformin for nine months were not effective in restoring/preserving β-cell function in youth with prediabetes and T2D (RISE Consortium & RISE Consortium Investigators, 2019). On the contrary, the role of GLP-1 and the efficacy of the GLP-1 receptors in T2D signifies a strong target for potential treatment. Additional clinical trials are warranted to see if monotherapy of GLP-1 agonist vs. combined (metformin + liraglutide) therapy is effective to reserve Y-T2D to prediabetes and/or normal state. More importantly, future research should focus on disease prevention rather than treatment to avoid aggressive complications and metabolic degradations of Y-T2D (RISE Consortium & RISE Consortium Investigators, 2019). Altogether, it would be germane to investigate whether lifestyle changes (diet, physical activity, exercise medicine) can improve the incretin effect in conjunction with glycemic control in youth.

Type 2 diabetes is traditionally diagnosed by the use of an oral glucose tolerance test and/or HbA1c, both of which require serum collection. Various biomarkers, which are measurable biological substances that provide clinical insight on disease state, have also been effective in the early identification and risk prediction of inflammatory diseases. Measuring biomarker concentrations has traditionally been obtained through serum collection as well. However, numerous biomarkers are detectable in saliva. Salivary analysis has more recently been introduced into research as a potential non-invasive, cost-effective diagnostic for the early identification of type 2 diabetes risk in adults and youth. Therefore, the purpose of this review was to compare 6 established inflammatory biomarkers of type 2 diabetes, in serum and saliva, and determine if similar diagnostic effectiveness is seen in saliva. A lack of standardized salivary analysis, processing, and collection accounts for errors and inconsistencies in conclusive data amongst studies. Proposing a national standardization in salivary analysis, coupled with increased data and research on the utility of saliva as a diagnostic, poses the potential for salivary analysis to be used in diagnostic settings.

The aim of this study was to determine whether serum symmetric dimethylarginine (SDMA) and cystatin C (CysC) levels can be utilized as more accurate markers of early kidney dysfunction in dogs. Forty-one client-owned dogs with chronic kidney disease (CKD), which were clinically stable, and ten beagles as healthy controls were included. All dogs underwent physical examination, systemic blood pressure measurement, complete blood cell count, and plasma biochemistry analyses. Frozen serum was used for SDMA and CysC analyses. Data analysis was performed using Kruskal Wallis, Pearson's correlation, Bland-Altman plots, and receiver operating characteristic curve. SDMA and CysC levels were significantly higher in patients with CKD at various International Renal Interest Society (IRIS) stages than in the healthy controls. In particular, CysC level was the only biomarker that could indicate the earliest stage of CKD (IRIS stage I). Similar to these results, CysC level showed better sensitivity and specificity compared to the other biomarkers in early CKD dogs.

BACKGROUND: Individuals with obesity have metabolic inflexibility with diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) in insulin-stimulated states. However, it is unclear if metabolic inflexibility is a characteristic of obesity per se or is unique to youth who have metabolically unhealthy obesity (MUO) compared with metabolically healthy obesity (MHO). OBJECTIVE: We investigated metabolic flexibility in youth with MUO, MHO and normal weight (NW) and compared their metabolic characteristics. PATIENTS/DESIGN: Youth (n=188) were divided, based on cut-off points for in vivo insulin sensitivity (IS) of adolescents with NW, into 137 with MUO and 51 with MHO. Fasting hepatic IS (HIS) from hepatic glucose production by [6,6-(2)H(2)]glucose, adipose tissue IS (ATIS) from whole-body lipolysis by [(2)H(5)]glycerol, RQ (indirect calorimetry) during fasting and a hyperinsulinemic (80mu/m(2)/min)-euglycemic clamp were measured. RESULTS: Youth with MUO vs. MHO had blunted ΔRQ (p=0.035) and lower HIS and ATIS (both p

BACKGROUND: Glucose concentrations during an oral glucose tolerance test (OGTT) have been used as biomarkers to differentiate type 2 diabetes risk phenotypes. No studies have examined changes in OGTT-glucose phenotypes following lifestyle intervention among high-risk youth. OBJECTIVE: To examine changes in OGTT-glucose phenotypes following lifestyle intervention and to explore differences in insulin sensitivity and β-cell function among post-intervention phenotypes. METHODS: Latino adolescents with obesity (n = 48, age 15.4 ± 1.0, BMI% 98.2 ± 1.4, female 56.3%) completed a 12-week lifestyle intervention that included weekly nutrition education and physical activity. At baseline and 12 weeks, youth completed a 2-h OGTT with glucose and insulin concentrations assessed at 0′, 30′, 60′, 90′ and 120′. Glucose concentrations during the OGTT were used to identify biomarkers, 1-h glucose, glucose response curve and time to glucose peak. Using these respective biomarkers, high-risk (1-h glucose ≥ 155 mg/dl, Monophasic, Late Peak) and lower-risk phenotypes (1-h glucose < 155 mg/dl, Biphasic, Early Peak) were categorized. Insulin sensitivity was estimated by whole-body insulin sensitivity index (WBISI) and β-cell function by oral disposition index (oDI). RESULTS: Following intervention, the prevalence of Monophasic phenotypes decreased from 81% to 67% (p = 0.048) and 1-h glucose ≥ 155 mg/dl from 38% to 10% (p = 0.054). Although Late Peak phenotypes did not significantly change (from 58% to 29%, p = 0.200), Early Peak phenotypes at post-intervention demonstrated significantly higher WBISI compared to Late Peak (2.3 ± 0.1 vs 1.7 ± 0.2, p = 0.023). CONCLUSIONS: OGTT-glucose phenotypes improve following lifestyle intervention among high-risk youth. These findings further support their potential utility as clinical biomarkers to identify diabetes risk and risk reduction in youth.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by a progressive loss of ß-cell function relative to insulin resistance. Once thought to be an adult disease, T2D has emerged as an increasingly prevalent health concern in obese youth, suggesting that early identification of those who are at high-risk for T2D is critical. Traditionally, either fasting glucose and/or 2-hr glucose concentrations during an oral glucose tolerance test has been used to identify prediabetes (i.e., intermediate stage of T2D). However, the fact that multiple blood collections are required during the test hinders necessary screening of high-risk youth with obesity and metabolic syndrome, primarily due to the invasive methods (i.e., fear of needles). For this reason, there is increasing interest in salivary biomarkers that can identify metabolic abnormalities. Goodson et al. provided critical evidence for future use of salivary samples for T2D risk detection as investigating saliva-based inflammatory biomarkers in an at-risk population of children. A total of 744 children (mean age 11 years) were divided into 4 groups based on their weight status using the age- and sex-standardized BMI z-score: underweight, normal healthy weight, overweight, and obese (n=186 for each group). Fasting saliva samples were collected from all participants to examine 20 biomarkers and the biomarkers were analyzed on a Luminex 200 platform (Luminex Corporation, Austin, TX, USA). Of the 20 biomarkers tested, 16 showed no significant differences between obese and normal weight subjects. However, 4 biomarkers did show significant differences between obese and normal weight subjects. Salivary C-reactive protein (CRP), a pro-inflammatory biomarker, was 6 times higher in obese youth compared with their normal weight peers (median 435 pg/ml vs. 76 pg/ml, P

Frequent/intense training increases the risk of overtraining in athletes.When overtrained, despite high effort in training, performance stagnates and/or deteriorates (Cadegiani & Kater, 2018). A growing body of literature has attempted to decipher the pathophysiology of overtraining. However, the majority of these literatures focus on the metabolic, biochemical, hormonal, and immunological aspects of overtraining. Few studies have analyzed more applicable biomarkers of overtraining such as eating and sleeping patterns, body composition, mood, and libido with conclusive results. A previous study entitled “Endocrine and Metabolic Responses on Overtraining Syndrome (EROS)” has attracted researchers’ attention as they measured relevant/applicable biomarkers for overtraining. The purpose of the study by Cadegiani and Kater (2018) is to elaborate the EROS study and understand the mechanisms of overtraining more comprehensively. Male volunteers (age 18-50 years) were screened based on health history, drug use, exercise patterns, and overtraining symptoms (i.e., unexplained performance decreases). After prescreening, selected participants (n=51) were further tested on their sleeping, eating, and social patterns (self-reported), and psychological state by the POMS (Profile of Mood States) questionnaire. Based on these answers, participants were divided into three groups: healthy athletes (ATL), overtrained athletes (OTS), and non-physically active controls (NCS). Using bioimpedance and air-displacement, body hydration and composition were measured. Daily caloric/macronutrient intake, POMS, time spent studying/working (hours/day), libido on a scale 1-10, and basal metabolic rate (BMR) by indirect calorimetry were also measured for analysis. Compared to ATL, OTS reported reduced relative calorie intake (26.4 kcal/kg/day in OTS vs. 52.7 kcal/kg/day in ATL), worse sleep quality on a scale 1-10 (6.5 vs. 8.0), worse mood (POMS scores of 15.0 vs. 5.0 on anger, 5.0 vs. 2.0 on confusion, 7.5 vs. 0.0 on depression, 20.0 vs. 2.0 on fatigue, 16.5 vs. 6.0 on tension, and 9.5 vs. 26.0 vigor), lower measured-to-predicted BMR (100.5% vs. 109.0%), higher body fat (15.3% vs. 10.3%), and diminished libido on a scale 1-10 (7.0 vs. 8.0) and hydration (60.8% vs. 64.9% body water) (all P

BACKGROUND The American Diabetes Association recommends risk-based screening for dysglycaemia (prediabetes and type 2 diabetes) in youth with overweight/obesity plus ≥1 risk factor. However, evidence for these recommendations is lacking. OBJECTIVES Examine the association between the number of risk factors and the prevalence of dysglycaemia in youth with overweight/obesity at initial presentation. METHODS In a paediatric obesity registry, youth (>10 and

Background: Previous studies have identified biomarkers derived from glucose concentrations during a 2-h Oral Glucose Tolerance Test (OGTT) that differentiate type 2 diabetes risk phenotypes. Such markers include 1-h glucose concentrations (1hG), shape of the glucose response curve (GRC), and time to glucose peak (TGP). Lifestyle intervention is the first line approach to diabetes prevention, yet no studies have examined changes in OGTT-glucose phenotypes. Methods: Latino adolescents with obesity (n=48, age 15.4±1.0, BMI% 98.2±1.4, Girls 56.3%) completed a 12-week lifestyle intervention that included physical activity (3 d/wk) and nutrition education (1 d/wk). At baseline and 12 weeks, youth completed a 2-h OGTT with glucose concentrations assessed at 0’, 30’, 60’, 90’, and 120’ to derive the 3 biomarkers used to classify low and high risk phenotypes. For 1hG, ≥155mg/dL served as the threshold that classified 1hG Results: At baseline, there was substantial heterogeneity in the prevalence of OGTT-glucose phenotypes with 38% 1hG≥155mg/dL, 81% Monophasic, and 58% Late Peak. In response to the intervention, the prevalence of Monophasic decreased to 14% (p=0.048), while the prevalence of 1hG≥155mg/dL decreased to 28% (p=0.054). The decrease in prevalence of Late Peak phenotypes was not significant (-29%, p=0.200). Conclusion: Lifestyle intervention may improve OGTT-glucose phenotypes among high-risk youth populations. Whether changes in OGTT-glucose phenotypes are associated with changes in type 2 diabetes risk factors has yet to be established. Disclosure A. Pena: None. J. Kim: None. J. A. Reyes: None. K. B. Vander wyst: None. M. Olson: None. S. Ayers: None. A. Williams: None. G. Q. Shaibi: None. Funding National Institutes of Health (P20MD002316U54, MD002316R01, DK107579F31, DK125037)

In this report, we provide clinical information on the diagnosis of postretinal blindness in veterinary ophthalmology. We have diagnosed three dogs with postretinal blindness (bilateral in one case and in the left eye in two cases). The electroretinogram results were normal and the optic axis was relatively clear in all cases. Our findings indicate that the reason for the blindness in these dogs was an intracranial lesion. Fundus photography did not reveal any significant changes, except in the optic disc. A normal optic disc, an optic disc that appeared to be smaller than that in the other eye, and a severely hyperemic and edematous optic disc were seen in cases 1, 2, and 3, respectively. On magnetic resonance imaging, two dogs had optic chiasm lesions (one a tumor, one inflammation) and the remaining dog had inflammation in the right optic tract and occipital lobe even though bright flash electroretinograms were normal. Magnetic resonance imaging and electroretinography can be used as diagnostic tools for detection and localization of central nervous system lesions in the visual pathways.

In OY it is not clear what degree of βCF impairment translates to increases in OGTT glucose area under the curve (G-AUC) commensurate with transition from NGT to IGT to T2D, and whether there are racial differences. Given the high rates of T2D in Black (BY) vs. White youth (WY), we hypothesized that βCF decline in BY is more detrimental and results in larger increases in G-AUC than in WY. Here we report the quantitative relationship between differences in clamp disposition index (DI=insulin sensitivity [IS] by a 3-hr hyperinsulinemic (80 mu/m2/min)-euglycemic clamp x 1st-phase insulin by a 2-hr hyperglycemic (225 mg/dL) clamp) and OGTT G-AUC in 152 OY. Two-way ANOVA (race x glycemic status) showed that in BY vs. WY larger decrements in DI from NGT to IGT and from NGT to T2D (all p Disclosure J. Kim: None. H.M. Tfayli: None. F. Bacha: Research Support; Self; AstraZeneca, Takeda Development Center Americas, Inc. N. Gebara: None. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

It has been shown that gintonin, isolated from Panax ginseng, can promote rapid corneal wound healing. We aimed to elucidate the underlying mechanism and investigated whether gintonin affects the concentration of the extracellular matrix remodelling factor matrix metalloproteinase-9 (MMP-9) in tears during rabbit corneal wound healing in vivo. Twelve eyes (six rabbits) were divided equally into three groups. All eyes underwent corneal de-epithelialisation. The control group received Tearin Free sodium hyaluronate 0.1%, the solcoseryl group received solcoseryl-120 concentrate, and the gintonin group received 2.5 mg gintonin in sodium hyaluronate 0.1%. All preparations were administered for 5 days and the concentration of MMP-9 was measured in tears via ELISA on days 0, 1, and 5. MMP-9 concentrations in all groups were increased at day 1 and reduced at day 5. Of note, we found a significant change over the time frame for the gintonin group (P < 0.05) but not for the control or solcoseryl groups (P > 0.05) Moreover, increased MMP-9 levels between days 0 and 1, and their reduction between days 1 and 5, were significant in the gintonin group compared to those in the other groups (P < 0.05); however, and once more, these changes were not significant between the control and solcoseryl groups (P > 0.05). In conclusion, gintonin increases the concentration of MMP-9 rapidly within a day of injury, and decreasing it thereafter.

Obese individuals have metabolic inflexibility evidenced by diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) from fasting to insulin-stimulated state. Metabolically unhealthy obese (MUHO) adolescents, unlike their metabolically healthy obese (MHO) peers, have unfavorable metabolic characteristics despite having comparable adiposity. We investigated if metabolic inflexibility is a characteristic of obesity per se or is unique to MUHO compared with MHO youth. Obese youth (n=188; age 14.1 ± 0.1 yrs [SE]; BMI 33.6 ± 0.4 kg/m2) were divided into 137 MUHO (age 14.1 ± 0.2 yrs; BMI 35.4 ± 0.5 kg/m2) and 51 MHO (age 13.9 ± 0.3 yrs; BMI 29.0 ± 0.7 kg/m2) based on cut points for in vivo insulin sensitivity (IS) [MHO within 1.5 SD and MUHO MUHO vs. MHO youth had blunted ∆RQ (0.088 ± 0.004 vs. 0.107 ± 0.007, p=0.035), but MHO was not different from NW (0.098 ± 0.004, p=0.893). Further, MUHO vs. MHO youth had lower HIS (15.3 ± 0.7 vs. 24.3 ± 1.6 (mg/kg/min·uU/mL)-1, p The present study reveals that metabolic inflexibility is not a feature of obesity, rather it is a characteristic of MUHO youth who have significantly lower ∆RQ compared with MHO youth, with no difference between MHO and NW youth. Moreover, MUHO compared with MHO youth have worse metabolic profile, represented in lower HIS and ATIS.

Various cosmetics having a single function are increasingly being used, but cosmetics having multifunctional activities remain limited. We aimed to develop a multifunctional cosmetic cream having antioxidant, anti-tyrosinase, anti-aging and antimicrobial activities. Antimicrobial activities were performed by disc-diffusion method. Cell toxicity and cell proliferations were evaluated in a 96-well plate with different cell lines such as HaCaT, RAW264.7, CCD-986Sk, B16F1, and B16F10. Mushroom tyrosinase inhibition, elastase inhibition, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities were evaluated and IC50 was calculated. Mesoporous silica particle was synthesized using Pluronic P123 and tetraethyl ortho-silicate (TEOS). Facial pictures were captured by VISIA-CR (Facial Imaging System for Clinical Research). Roughness of image was analysed by PRIMOS software and brightness of image was analyzed by Chromameter CR-400. The crude product of strain T65 inhibited the different human pathogenic bacteria such as Bacillus subtilis, Escherichia coli, Propionibacterium acnes, Staphylococcus aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The IC50 of T65 crude product for mushroom tyrosinase, elastase, and DPPH radical scavenging activities were 58.73, 14.68, and 6.31 &micro, g/mL, respectively. T65 crude product proliferated collagen type I in CCD-986Sk cell up to 145.91% &plusmn, 9.11% (mean &plusmn, SD, mean of 24, 48, and 72 h) at 250 pg/mL. Synthesized mesoporous particles (SBA-15) confirmed the sustainable performance by control-release for three days. Formulated functional cosmetic cream containing T65 embedded SBA-15, significantly decreased the skin roughness by 4.670% and increased the skin brightness by 0.472% after application of 4 weeks. T65 crude product inhibited both Gram-positive and Gram-negative pathogens. Synthesized mesoporous particle, SBA-15, confirmed the physiologically active substance was released in sustainable release condition. T65 crude product showed impeccable antimicrobial, antioxidant, anti-aging, and whitening activities with non-cytotoxic effects to different cell lines related to the human skin.

OBJECTIVE Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: 1) adipose insulin resistance index (Adipose-IR) (calculated as fasting insulin × free fatty acids [FFAs]) in youth across the spectrum of adiposity from normal weight to obese and the spectrum from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes, 2) the relationship of Adipose-IR with physical and metabolic characteristics, and 3) the predictive power of Adipose-IR for determining dysglycemia in youth. RESEARCH DESIGN AND METHODS A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, visceral adipose tissue (VAT), leptin, and adiponectin evaluated. RESULTS Adipose-IR was 2.2-fold higher in obese NGT, 4.3-fold higher in IGT, and 4.6-fold higher in type 2 diabetes compared with that in normal-weight peers (all P < 0.05). Females with dysglycemia (IGT and type 2 diabetes) had higher Adipose-IR than their male counterparts (P < 0.001). Adipose-IR correlated positively with total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin and negatively with adiponectin. Receiver operating characteristic curve analysis yielded an optimal cutoff for Adipose-IR of 9.3 μU/mL × mmol/L for determining dysglycemia with 80% predictive power. CONCLUSIONS Adipose-IR is a simple surrogate estimate that reflects pathophysiological alterations in adipose tissue insulin sensitivity in youth, with progressive deterioration from normal weight to obese and from NGT to IGT to type 2 diabetes. Adipose-IR can be applied in large-scale epidemiological/observational studies of the natural history of youth-onset type 2 diabetes and its progression or reversal with intervention strategies.

Context Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation manifested in increased respiratory quotient (RQ). Little is known about adipose tissue metabolism and metabolic flexibility in adolescent girls with polycystic ovary syndrome (PCOS). Objective We investigated whole-body lipolysis, substrate oxidation, and metabolic flexibility in obese girls with PCOS vs obese girls without PCOS. Patients/Design Twenty-one obese girls with PCOS and 21 obese girls without PCOS were pair-matched for age and race. Body composition, abdominal visceral adipose tissue (VAT), sex hormones, lipid profile, and adiponectin were measured. Whole-body lipolysis ([2H5]glycerol turnover), RQ, and substrate oxidation (indirect calorimetry) were evaluated during fasting and a hyperinsulinemic-euglycemic clamp together with assessment of insulin sensitivity (IS). Results Despite similar body mass index and percent body fat, girls with PCOS vs girls without PCOS had lower fasting lipolysis and fat oxidation, less increase in RQ during hyperinsulinemia with impaired suppression in lipolysis and lipid oxidation, and lower IS. In multiple regression, the best predictors of metabolic flexibility were [using clinical parameters: adiponectin, fasting triglycerides, and insulin (R2 = 0.618, P < 0.0001); using research parameters: IS, VAT, and baseline RQ (R2 = 0.756, P < 0.0001)]. Conclusions Obese girls with PCOS vs obese girls without PCOS have decreased lipid mobilization, diminished fat oxidation, and metabolic inflexibility. Whether this metabolic phenotype of adipose tissue dysfunction, which is conducive to fat accretion, plays a role in the induction and maintenance of obesity in adolescent girls with PCOS remains to be determined.

Early diagnosis of chronic kidney disease (CKD) could facilitate timely and appropriate monitoring and therapy. Traditional biomarkers have limitations. Thus, new biomarkers are needed. The objective of the present study was to compare renal biomarkers (including symmetric dimethylarginine [SDMA], cystatin C [CysC], and urine neutrophil gelatinase-associated lipocalin [NGAL]-creatinine ration [UNCR]) and creatinine (CREA) for early detection of CKD in dogs. Nine healthy dogs and 32 dogs with CKD were included in this study. All dogs underwent physical examination, blood analysis (included CREA and SDMA), urinalysis, and imaging examinations. CysC and NGAL levels were measured in serum and urine, respectively. SDMA, CysC, and UNCR were significantly elevated in dogs with CKD and IRIS stage Ι (P < .0001) than in controls. CysC demonstrated a strong correlation with CREA (r2 = 0.6556, P < .0001). CysC (sensitivity 93.55%, specificity 100%) had the highest sensitivity for detecting CKD, followed by UNCR (sensitivity 90%, specificity 100%), SDMA (sensitivity 84.37%, specificity 100%), and CREA (sensitivity 43.75%, specificity 100%). Additionally, CysC and UNCR (sensitivity 88.89%, specificity 100%) exhibited higher sensitivity and specificity than CREA (sensitivity 88.89%, specificity 66.67%) and SDMA (sensitivity 88.89%, specificity 88.89%) in dogs with CKD International Renal Interest Society (IRIS) stage Ι. CysC as a marker of glomerular filtration rate (GFR) and urinary NGAL as a marker of tubular damage could be used to detect CKD early in dogs better than CREA and SDMA.

In obese non-diabetic youth, glucose response curve (GRC) and 1-hr glucose concentration during an oral glucose tolerance test (OGTT) represent novel biomarkers for T2D risk. Obese youth with monophasic- vs. biphasic-GRC and 1-hr glucose concentration of ≥155 (Above155) vs.

Background The diagnosis of coronary artery abnormalities (CAA), including dilation and aneurysm, in patients with Kawasaki disease is paramount to treatment planning. CAA are defined using various standards, which makes diagnosis difficult. The aims of this study were to determine the variability of CAA prevalence according to existing guidelines and Z score formulas and to examine the discrepancies in widely used Z score formulas. Methods Using data from a Korean national survey on Kawasaki disease, 6,889 patients were included and analyzed. The overall prevalence of CAA and the prevalence for subgroups were compared on the basis of aneurysm severity, age, and body surface area. Finally, discrepancies among five Z score formulas were evaluated by comparing two of the formulas in pairs. Results According to the Japanese criteria, the prevalence of CAA was 18%. According to the American Heart Association criteria, the prevalence of dilation or aneurysm was about 21% to 42%, and that of aneurysm of the left anterior descending artery or right coronary artery was about 8% to 27%. The prevalence of CAA and that of left anterior descending or right coronary artery aneurysm was significantly different, with discrepancies between the Japanese and AHA Z score criteria, as well as among the five Z score formulas. Additionally, misclassification of aneurysm severity was observed for each criterion or Z score formula. There was significant variation among calculated Z scores. The more extreme the Z score values, the more discrepancy was observed. Conclusions Different guidelines and Z score formulas yield significantly different prevalence rates and classifications of CAA. In addition, more discrepancies were observed with higher Z score values. As CAA or aneurysm severity could be changed by guidelines or Z score formulas, they should be chosen carefully, and when a particular formula is chosen, consistency is needed.

Objective Youth type 2 diabetes mellitus (T2DM) occurs decades earlier than adult T2DM and is characterized by high therapeutic failure rates and decreased response to insulin sensitizers suggesting a more severe disease process than in adults. To explain these observations, we hypothesized that insulin resistance is worse in obese youth than adults with impaired glucose tolerance (IGT), a state of high-risk for T2DM. As proof-of-concept, we compared insulin sensitivity between BMI-, sex-, and race-matched obese youth vs adults with IGT. Methods This retrospective analysis of IGT youth and adults included 34 obese adolescents matched (2:1) for BMI, sex, and race to 17 adults. Hepatic and peripheral insulin sensitivity were measured by [6,6-2H2]glucose and hyperinsulinemic-euglycemic clamp. Body composition (DEXA) and serum lipid profile were examined. Results Despite similar percent body fat, obese adolescents had 2-fold higher fasting insulin concentration, lower hepatic (~53%) and peripheral (~42%) insulin sensitivity and lower HDL compared with adults (all P

Anti-Müllerian hormone (AMH) is proposed as a biomarker of polycystic ovary syndrome (PCOS). This study investigated: (1) AMH concentrations in obese adolescents with PCOS versus without PCOS; (2) the relationship of AMH to sex steroid hormones, adiposity, and insulin resistance; and (3) the optimal AMH value and the multivariable prediction model to determine PCOS in obese adolescents.AMH levels were measured in 46 obese PCOS girls and 43 obese non-PCOS girls. Sex steroid hormones, clamp-measured insulin sensitivity and secretion, body composition, and abdominal adiposity were evaluated. Logistic regression and receiver-operating characteristic curve analyses were used, and multivariate prediction models were developed to test the utility of AMH for the diagnosis of PCOS.AMH levels were higher in obese PCOS versus non-PCOS girls (8.3 ± .6 vs. 4.3 ± .4 ng/mL, p .0001), of comparable age and puberty. AMH concentrations correlated positively with age in both groups, total and free testosterone in PCOS girls only, abdominal adipose tissue in non-PCOS girls, with no correlation to in vivo insulin sensitivity and secretion in either groups. A multivariate model including AMH (cutoff 6.26 ng/mL, area under the curve .788) together with sex hormone-binding globulin and total testosterone exhibited 93.4% predictive power for diagnosing PCOS.AMH may be a useful biomarker for the diagnosis of PCOS in obese adolescent girls.

The goal of auricular cartilage harvest is to obtain a sufficient amount for reconstruction and to minimize the change in ear shape. The cartilage can be harvested by a posterior or anterior approach, and each method has advantages and disadvantages. The posterior approach presents the advantage of scar concealment, but there are limits to the amount of cymba cartilage that may be harvested. In contrast, the anterior approach may cause a noticeable scar. However, as cartilage is collected, the anterior approach provides a view that facilitates the preservation ear structure. In addition, it is possible to obtain a greater amount of cartilage. From January 2014 to December 2015, we harvested auricular cartilage graft material in 17 patients. To prevent the development of trapdoor scars or linear scar contracture, short incisions were made on the superior border of the cymba and cavum. Two small and narrow incisions were made, resulting in suboptimal exposure of the surgical site, which heightens the potential for damaging the cartilage when using existing tools. To minimize this, the authors used a newly invented ball-type elevator. All patients recovered without complications after surgery and reported satisfaction with the shape of the ear.

A 10-month-old male Welsh Corgi with a history of acute blindness underwent neuro-ophthalmological testing and magnetic resonance imaging (MRI). Vision testing revealed complete visual deficits but the electroretinograph and pupillary light reflex were normal in both eyes. The motor and sensory functions of the eyelids and eyes were also normal. The MRI revealed compression of the optic chiasm caused by severe ventriculomegaly in the lateral and third ventricles. Such lesions are associated with inflammatory stenotic lesions in the mesencephalic aqueduct. Moderate neutrophilic pleocytosis was observed during cerebrospinal fluid analysis and Acinetobacter lwoffii was isolated, leading to a diagnosis of Acinetobacter-positive obstructive hydrocephalus. This is the first reported case of culture-proven Acinetobacter-associated postencephalitic hydrocephalus with acute blindness in a dog.

The purpose of this methodological study was to develop a convolutional neural network (CNN), which is a recently developed deep-learning-based image recognition method, to determine corneal ulcer severity in dogs. The CNN model was trained with images for which corneal ulcer severity (normal, superficial, and deep) were previously classified by veterinary ophthalmologists’ diagnostic evaluations of corneal photographs from patients who visited the Veterinary Medical Teaching Hospital (VMTH) at Konkuk University and 3 different veterinary ophthalmology specialty hospitals in Korea. The original images (depicting normal corneas (36) and corneas with superficial (47) ulcers, deep (47) ulcers), flipped images (total 520), rotated images (total 520), and both flipped and rotated images (total 1,040) were labeled, learned and evaluated with GoogLeNet, ResNet, and VGGNet models, and the severity of each corneal ulcer image was determined. To accomplish this task, models based on TensorFlow, an open-source software library developed by Google, were used, and the labeled images were converted into TensorFlow record (TFRecord) format. The models were fine-tuned using a CNN model trained on the ImageNet dataset and then used to predict severity. Most of the models achieved accuracies of over 90% when classifying superficial and deep corneal ulcers, and ResNet and VGGNet achieved accuracies over 90% for classifying normal corneas, corneas with superficial ulcers, and corneas with deep ulcers. This study proposes a method to effectively determine corneal ulcer severity in dogs by using a CNN and concludes that multiple image classification models can be used in the veterinary field.

Background In adults, the time-to-glucose-peak at or after 30 minutes during an oral glucose tolerance test (OGTT) identifies physiologically distinct groups with differences in insulin sensitivity, β-cell function and risk for type 2 diabetes. In obese non-diabetic adolescents, we investigated if the OGTT-time-to-glucose-peak also reflects incretin and free fatty acid (FFA) responses besides insulin sensitivity and β-cell function, measured by the clamp. Methods Obese adolescents (n = 278) were categorized according to their OGTT-time-to-glucose-peak by Early-peak (at 30 minutes) vs Late-peak (>30 minutes) groups. Body composition, visceral adipose tissue, oral disposition index and OGTT-area under the curve (AUC) were examined. A subset of 102 participants had both hyperinsulinemic-euglycemic and hyperglycemic clamps to measure in vivo insulin sensitivity, insulin secretion, and β-cell function relative to insulin sensitivity. Results Compared with the Early-peak group, the Late-peak group had impaired β-cell function relative to insulin sensitivity, lower glucose-dependent insulinotropic polypeptide-AUC, and higher FFA-AUC despite higher insulin- and C-peptide-AUC. They also had lower hepatic and peripheral insulin sensitivity despite similar percent body fat and visceral adipose tissue, and had higher prevalence of impaired glucose tolerance (all P Conclusions In obese non-diabetic youth, those with a Late-peak vs an Early-peak glucose during an OGTT showed diminished β-cell function, blunted incretin secretion, and lower insulin sensitivity of glucose and FFA metabolism. It remains to be determined if Late-peak glucose predicts the future development of type 2 diabetes in these high-risk youth.

The OGTT-GRCs [Incessant Increase (IIn), Monophasic (Mph), and Biphasic (Bph)] reflect insulin sensitivity (IS) and β-cell function (BCF), being worse in the former and best in the latter. Accordingly, the prevalence of these GRCs differ in diabetic and nondiabetic individuals (Table). While islet cell Ab- obese youth CDX-T2D have worse IS, Ab+ youth have severe impairment in BCF [Diabetes 58: 2009]. Here, we examined the prevalence of OGTT-GRC patterns, clamp-measured IS, and BCF in obese Ab+ (GAD65 and IA2) vs. Ab- youth CDX-T2D. The dominant GRC was IIn in Ab+ and Mph in Ab- youth while Bph was scarce in both (Table). In Ab+ youth, 1st- (32.5 ± 5.6 vs. 40.2 ± 8.0 µU/mL, p=0.13) and 2nd-phase insulin (39.6 ± 8.6 vs. 62.8 ± 12.2 µU/mL, p=0.04), were 20% and 40% lower in IIn vs. the other two combined. In Ab-, while 1st- (67.3 ± 19.1 vs. 122.4 ± 28.3 µU/mL, p=0.049) and 2nd-phase insulin (110.3 ± 31.4 vs. 171.6 ± 28.6 µU/mL, p=0.054) were lower in IIn vs. Mph, overall BCF was less impaired than in Ab+ youth. IS did not differ by GRC type in either group but was lower in Ab- vs. Ab+ irrespective of GRC type. The prevalence of IIn-GRC is 3-fold higher in Ab+ vs. Ab- obese youth CDX-T2D, and the prevalence in Ab- youth is similar to that in the TODAY study (Table). The higher prevalence of IIn-GRC in Ab+ obese youth signifies the severe insulin deficiency characteristic of type 1 diabetes. Disclosure J. Kim: None. N. Gebara: None. H. Tfayli: Other Relationship; Self; Sanofi. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. S.A. Arslanian: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503 to S.A.A.); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)

Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation manifested in increased respiratory quotient (∆RQ). Obese adolescent girls with PCOS have metabolic inflexibility compared with their non-PCOS obese peers (JCEM 2018, PMID 29220530). To examine if metabolic inflexibility is also present in lean PCOS or is unique to obese PCOS, we investigated metabolic flexibility in lean and obese women (ages 18-42 yrs.) with PCOS. Data in 24 obese (body mass index, BMI 33.4 ± 4.7 [SD] kg/m2) and 15 lean (BMI 22.7 ± 2.0 kg/m2) PCOS women (diagnosed by the Rotterdam criteria), and 14 obese (BMI 32.5 ± 5.0 kg/m2) and 16 lean (22.9 ± 1.4 kg/m2) control women without PCOS were examined. RQ and lipid oxidation, by indirect calorimetry, were analyzed at fasting and during a hyperinsulinemic-euglycemic clamp. The relationship between metabolic flexibility (assessed as ∆RQ from fasting to hyperinsulinemia) and clamp insulin sensitivity (IS), sex hormones, C-reactive protein (CRP), BMI and leptin concentrations was evaluated. Despite similar BMI and leptin levels, obese PCOS women had lower ∆RQ compared with obese control women (0.07 ± 0.04 vs. 0.11 ± 0.04, p< 0.0001). However, ∆RQ was not different between obese and lean PCOS women, nor was fasting lipid oxidation and suppression in lipid oxidation during hyperinsulinemia. Insulin sensitivity was lower (3.9 ± 1.4 vs. 7.4 ± 2.6 mg/Kg/min per mU/L, p< 0.0001), and CRP and leptin concentrations were higher in obese PCOS vs. lean PCOS (3.34 ± 1.87 vs. 1.29 ± 1.18 mg/L; and 33.6 ± 11.0 vs. 12.4 ± 8.5 ng/L, respectively, all p< 0.05). In the total cohort, ∆RQ correlated with free androgen index (r = -0.359), androstenedione (r = -0.271), and IS (r = 0.452) (all p< 0.05). Multiple regression analysis in the total cohort revealed that the best predictor of metabolic flexibility was PCOS status (partial r = -0.243, p= 0.05) independent of BMI and age. In PCOS women, IS (partial r = 0.503, p= 0.002) and baseline RQ (partial r = -0.489, p= 0.003) explained 46% of the variance in metabolic flexibility with no significant effect of BMI and age. Findings were similar in non-PCOS women (model R2 = 0.750, p= 0.001). Replacing BMI with leptin in the models for PCOS or control women did not change the results. In conclusion, our data suggest that PCOS status, rather than adiposity plays a role in the metabolic inflexibility observed in women with PCOS. It remains to be determined if the lack of a difference in metabolic inflexibility between obese and lean PCOS women applies across the lifespan and holds true in adolescents too, or if metabolic flexibility differs early in the course of PCOS between obese and lean adolescents, but the difference fades as they get older and enter womanhood. Sources of Research Support: Juselius Foundation and Academy of Finland

A small pupil and poor pupil dilation are well-known risk factors faced by veterinary ophthalmologists during and after cataract surgery. We here describe two cases of phacoemulsification performed using an iris expander (Visitec I-Ring Pupil Expander, Beaver-Visitec International, USA) for treating cataracts in dogs with small pupils. Using this technique, we performed cataract extraction effectively in dogs with insufficiently dilated pupils. This case report provides useful information on the use of an iris expander for phacoemulsification in eyes with a small pupil, which can be applied in veterinary settings.

An Ahmed valve implantation with an Ologen® Collagen Matrix (Ologen® CM, Aeon Astron, Leiden, the Netherlands) was performed for the treatment of uncontrolled glaucoma in a cat. This cat was a 5-year-old castrated Russian Blue male with a 12-week history of conjunctival hyperemia and mydriasis of the left eye. During the ophthalmic examination, the intraocular pressure (IOP) oculus sinister (OS) was 52 mmHg, and a narrow iridocorneal angle (ICA) was detected by gonioscopy. Medical treatment with Cosopt® (2% dorzolamide and 0.5% timolol) failed to decrease the IOP. The left eye still had vision, and an Ahmed valve implantation was performed. During the gonioimplantation, Ologen® CM was used to inhibit scar formation around the valve. Following the operation, the IOP was stable at an approximate average of 15 mmHg during the 7-month follow-up period, and vision in the left eye was retained without medication. An adequate subconjunctival filtering bleb was formed after 140 days. This is the first case report in which an Ahmed valve gonioimplant with an Ologen® CM has been used for the surgical treatment of glaucoma in a cat.

Numerous methods to achieve occipitocervical stabilization have been described, including the use of occipital plate/screw constructs. Bicortical screws may increase the pullout strength, but intracranial injuries to venous sinuses have been reported. This study was performed to analyze the variations in occipital sinuses to prevent sinus injury caused by the bicortical screw.Occipital sinuses of 1720 patients were examined using digital subtraction angiography. The data collected included patient age and sex, occipital sinus type, distance between occipital sinus and midline, depth from inion to occipital sinus, and distance between occipital sinus and midline occiput at different levels.The mean age of patients was 57 years ± 13. There were 807 (46.9%) men and 913 (53.1%) women. The most common occipital sinus type was single occipital sinus off-midline (type B2). The least common occipital sinus type was absent occipital sinuses (type A; 8.7% of patients). There was no significant difference between age and occipital sinus type (P = 0.310). Also, the difference between sexes was not significant in regard to occipital sinus type in general. However, in subgroup analysis of type B1 and B2, there was a significant difference between sexes (P0.01). The mean depth from bone to occipital sinus was 19.913 mm ± 7.437.The occipital sinus shows several variations, and many morphologic differences can be seen. Preoperative detailed examination by magnetic resonance venography or vertebral angiography may be required for cases in which bicortical occipital screw fixation is necessary to avoid occipital sinus-related complications.