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Objective: The objective of this study was to study how acid accumulation (lower plasma bicarbonate and higher anion gap [AG] and corrected anion gap [CAG]) correlates with metabolic parameters, food intake, and 24‐h energy expenditure (EE). Methods: Acid accumulation was measured in 286 healthy adults with estimated glomerular filtration rate > 60 mL/min/1.73 m2. Measurements included body composition by dual‐energy x‐ray absorptiometry scan, ad libitum energy intake by a vending machine paradigm over 3 days, and 24‐h EE in a whole‐room indirect calorimeter. Results: Lower bicarbonate, higher AG, and higher CAG were correlated with higher waist and thigh circumferences, body fat (percentage), fat mass, triglycerides, and lower high‐density lipoprotein cholesterol. Acid accumulation markers were correlated with higher total energy (CAG partial r = 0.17; p = 0.02), fat (CAG partial r = 0.17; p = 0.02), protein intake (CAG partial r = 0.20; p = 0.006), and 24‐h EE (CAG partial r = 0.24; p = 0.0007). A mediation analysis of CAG and total energy intake found that 24‐h EE was a partial mediator (40%), but the association remained significant (β = 0.15; p < 0.0001). Conclusions: In healthy individuals, acid accumulation was associated with an unfavorable metabolic phenotype; higher 24‐h EE; and increased total energy, fat, and protein intake. Acid accumulation markers, as putative markers of higher dietary acid load (e.g., from protein), may affect energy balance physiology promoting weight gain. [ABSTRACT FROM AUTHOR]

Author(s): Douglas C. Chang [sup.1], Alessio Basolo [sup.1], Paolo Piaggi [sup.1], Susanne B. Votruba [sup.1], Jonathan Krakoff [sup.1] Author Affiliations: (1) Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and [...], Background/Objective Evidence from non-human species indicate that hydration and arginine vasopressin (AVP) influence fuel selection, energy expenditure (EE), and food intake, but these relationships are unclear in humans. We sought to assess whether hydration biomarkers [24-h urine volume (UVol) and urine urea nitrogen concentration (UUN)] and copeptin (a surrogate for AVP) are associated with 24-h EE, respiratory quotient (RQ), and daily energy intake (DEI). Subjects/Methods In a secondary analysis of collected data, we selected healthy adults (Group 1, n = 177) who had 24-h whole-room indirect calorimetry measurements in energy balance with 24-h urine collection and fasting copeptin measurements (n = 117), followed by 3 days ad libitum food intake. A separate group (Group 2, n = 284) with hydration markers and calorimetry measurements was also studied. The main outcome measures were 24-h RQ, 24-h EE, DEI, substrate oxidation. Results In Group 1, lower 24-h UVol and higher 24-h UUN, indicating lower hydration, were correlated with lower 24-h RQ (r = 0.35, p < 0.0001, and r = -0.29, p = 0.0001, respectively; results similar in Group 2) and predicted subsequent reduced DEI (r = 0.20, p = 0.01, and r = -0.27, p = 0.0003, respectively), adjusted for confounders. Copeptin was independently associated with 24-h lipid oxidation (r = -0.23, p = 0.01). In Group 2, lower hydration was associated with reduced 24-h EE (24-h UVol: r = 0.29, p < 0.0001; 24-h UUN: r = -0.25, p < 0.0001). Conclusions Hydration biomarkers were associated with metabolic differences characterized by altered food intake, fuel selection, and possibly EE. Independently, copeptin was associated with higher lipid oxidation.

Objective: We investigated how changes in 24‐h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake. Methods: Forty‐four healthy, weight‐stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m2) underwent 24‐h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24‐h fasting. Immediately after each chamber stay, participants were allowed 24‐h ad libitum food intake from computerized vending machines. Results: Twenty‐four‐hour RER decreased by 9.4% (95% CI: −10.4% to −8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], −2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24‐h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24‐h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting (r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = −0.27, p = 0.07, respectively). Conclusions: Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake. [ABSTRACT FROM AUTHOR]

Aim: Reduced renal insulin signalling is implicated in the pathogenesis of albuminuria. We sought to investigate whether insulin action and secretion, measured before diabetes onset, are associated with the development of albuminuria after diabetes onset. Materials and Methods: Baseline body composition, insulin sensitivity by hyperinsulinaemic‐euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m2/min; M‐low and M‐high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] were measured in 170 Southwestern Indigenous American adults who subsequently developed diabetes. After diabetes onset and during the median follow‐up of 13.6 years, 81 participants (48%) developed albuminuria (urine albumin‐to‐creatinine ratio ≥30 mg/g). Separate associations of M‐low, M‐high and AIR (per 1‐SD change) with the risk of albuminuria were assessed by Cox regression models adjusted for age, sex and body fat (%). Results: Participants who developed albuminuria were of similar age (26.4 ± 5.4 vs. 27.5 ± 6.1 years), sex (46% vs. 48% male), body fat (36.4 ± 7.5 vs. 35.7 ± 7.9%) and AIR [2.3 ± 0.3 vs. 2.3 ± 0.3, pmol/L (log)] as those who did not develop albuminuria but had lower insulin sensitivity [M‐low: 0.33 ± 0.08 vs. 0.36 ± 0.12, p =.03; M‐high: 0.87 ± 0.11 vs. 0.91 ± 0.12, p =.02; mg/kg‐metabolic body size/min (log)]. In separate adjusted models, lower M‐low and M‐high were both associated with an increased risk for albuminuria [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.14, 2.00, p =.004; HR 1.31, 95% CI 1.06, 1.63, p =.01), whereas AIR was not (HR 1.15, 95% CI 0.87, 1.56, p =.3). Conclusions: Lower insulin sensitivity is associated with the development of albuminuria, suggesting a role for insulin signalling in the pathogenesis of proteinuria. [ABSTRACT FROM AUTHOR]

We examined whether perceived stress, anhedonia, and food insecurity were associated with dietary adherence during a 6-week intervention. Sixty participants (23 m; 53 ± 14 y) completed psychosocial measures and were provided with full meals. Individuals with obesity were randomized to a weight-maintaining energy needs (WMENs) (n = 18; BMI 33 ± 4) or a 35% calorie-reduced diet (n = 19; BMI 38 ± 9); normal-weight individuals (n = 23; BMI 23 ± 2) were assigned to a WMENs diet. Adherence scores were determined via weekly assessments and daily ecological momentary assessments (EMAs) of real-time behavior in a natural environment. Perceived stress and anhedonia were associated with % body fat (all r-values > 0.25, all p-values < 0.05), but food insecurity and adherence were not. Higher perceived stress (r = −0.31, p = 0.02), anhedonia (r = −0.34, p = 0.01), and food insecurity (r = −0.27, p = 0.04) were associated with lower adherence scores, even after adjusting for age, sex, and % body fat. In all adjusted models, % body fat was not associated with adherence. Higher measures of stress, anhedonia, and food insecurity predicted lower adherence independently of body fat, indicating that psychosocial factors are important targets for successful adherence to dietary interventions, regardless of body size. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to test proportional‐integral‐derivative (PID) control of air inflow rate in a whole‐room indirect calorimeter to improve accuracy in measuring oxygen (O2) consumption (V̇O2) and carbon dioxide (CO2) production (V̇CO2). Methods: A precision gas blender infused nitrogen (N2) and CO2 into the calorimeter over 24 hours based on static and dynamic infusion profiles mimicking V̇O2 and V̇CO2 patterns during resting and non‐resting conditions. Constant (60 L/min) versus time‐variant flow set by a PID controller based on the CO2 concentration was compared based on errors between measured versus expected values for V̇O2,V̇CO2, respiratory exchange ratio, and metabolic rate. Results: Compared with constant inflow, the PID controller allowed both a faster rise time and long‐term maintenance of a stable CO2 concentration inside the calorimeter, resulting in more accurate V̇CO2 estimates (mean hourly error, PID: −0.9%, 60 L/min = −2.3%, p < 0.05) during static infusions. During dynamic infusions mimicking exercise sessions, the PID controller achieved smaller errors for V̇CO2 (mean: −0.6% vs. −2.7%, p = 0.02) and respiratory exchange ratio (mean: 0.5% vs. −3.1%, p = 0.02) compared with constant inflow conditions, with similar V̇O2 (p = 0.97) and metabolic rate (p = 0.76) errors. Conclusions: PID control in a whole‐room indirect calorimeter system leads to more accurate measurements of substrate oxidation during dynamic metabolic studies. [ABSTRACT FROM AUTHOR]

Acanthamoeba keratitis (AK), a painful corneal infection that may lead to vision loss or enucleation, is caused by the ubiquitous free-living Acanthamoeba spp. (1-4). AK occurs primarily among users of [...]

Objective: Physiological systems responsible for water homeostasis and energy metabolism are interconnected. This study hypothesized altered responses to dehydration including thirst, ad libitum water intake, and copeptin in men with obesity.Methods: Forty-two men (22 lean and 20 with obesity) were stimulated by a 2-hour hypertonic saline infusion and a 24-hour water deprivation. In each dehydrating condition, thirst, ad libitum water intake after dehydration, and urinary and hormonal responses including copeptin were assessed.Results: After each dehydration condition, ad libitum water intake was similar between both groups (p > 0.05); however, those with obesity reported feeling less thirsty (p < 0.05) and had decreased copeptin response and higher urinary sodium concentrations when stressed (p < 0.05). Angiotensin II, aldosterone, atrial and brain natriuretic peptides, and apelin concentrations did not differ by adiposity group and did not explain the different thirst or copeptin responses in men with obesity. However, leptin was associated with copeptin response in lean individuals during the hypertonic saline infusion (p < 0.05), but the relationship was diminished in those with obesity.Conclusions: Diminished thirst and copeptin responses are part of the obesity phenotype and may be influenced by leptin. Adiposity may impact pathways regulating thirst and vasopressin release, warranting further investigation. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the agreement of commonly reported energy metabolism measurements obtained from two different whole-room indirect calorimeters (WRICs).Methods: Nine healthy adult volunteers were evaluated over four separate 24-hour periods in a crossover design, twice in two different WRICs of different sizes, each operated according to the Room Indirect Calorimetry Operating and Reporting Standards published in 2020. The reproducibility of repeated measurements was quantified by the coefficient of variation (CV) and intraclass correlation coefficient (ICC).Results: The CVs between and within each WRIC for average 24-hour carbon dioxide production rate (VCO2 ) and oxygen consumption rate (VO2 ), 24-hour energy expenditure (EE), and respiratory exchange ratio ranged from 1.5% to 3.6%, whereas sleep EE ranged from 3.1% to 5.5%. CVs for macronutrient oxidation rates and spontaneous physical activity were higher, ranging from 9.2% to 38.1%. ICCs of VCO2 , VO2 , 24-hour EE, and energy expenditure at zero activity were >0.95, indicating excellent reproducibility, whereas ICCs for lipid oxidation, awake and fed thermogenesis, and sleep EE ranged from 0.55 to 0.92, indicating moderate to high reproducibility. ICCs for respiratory exchange ratio and carbohydrate and protein oxidation rates were lower (<0.70). Spontaneous physical activity showed high reproducibility within chambers (ICC = 0.88) but differed substantially between chambers (ICC = 0.23).Conclusions: Cross-chamber reproducibility is high for common outcome measures assessed in the respiratory chamber. The results support efforts to promote standardization across WRICs to allow multicenter studies. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis is a common cause of community-acquired pneumonia (CAP) in disease-endemic areas. Because testing rates influence interpretation of reportable-disease data and quality of CAP patient care, we determined the proportion [...]

The specific activities, contact lens hygiene practices, or products associated with Fusarium keratitis outbreak are defined. It is indicated that this outbreak of Fusarium keratitis is associated with the use of ReNu with MoistureLoc contact lens solution.

Objective: Food insecurity is known to be associated with obesity, but its association with physiological measures is unclear. Therefore, it was hypothesized that, compared with food-secure individuals, those with food insecurity would have higher 24-hour energy expenditure (EE [kilocalories per day]) and 24-hour respiratory quotient (RQ [ratio]). Subsequently, hormones involved in appetite regulation, substrate oxidation, and EE were explored.Methods: A total of 113 healthy participants without diabetes (75 men; mean [SD], age 40 [12] years; BMI 30 [8] kg/m2 ) were included in this analysis. Participants completed the Food Security Short Form, underwent a dual-energy x-ray absorptiometry scan, and spent 24 hours in a human respiratory chamber following a weight-maintaining diet.Results: Compared with individuals with food security, participants with food insecurity had no difference in 24-hour EE. However, they had higher carbohydrate oxidation rates (p = 0.03) and lower lipid oxidation rates (p = 0.02), resulting in higher 24-hour RQ (p < 0.01). They also had lower fasting glucagon-like peptide 1 (p = 0.03) concentrations.Conclusions: Food insecurity is associated with higher 24-hour RQ and lower fasting glucagon-like peptide 1 concentrations, metabolic and hormonal differences previously shown to drive greater calorie intake in the setting of unrestricted food availability. These findings therefore provide new insight into the paradoxical link between restricted food access and increased adiposity. [ABSTRACT FROM AUTHOR]

Objective: Fidgeting, a type of spontaneous physical activity (SPA), has substantial thermogenic potential. This research aims to examine secular trends in SPA and energy expenditure (EE) inside a respiratory chamber. Methods: From 1985 to 2005, healthy adults (n = 678; mean age: 28.8 years; men: 60%; 522 Indigenous American, 129 White, and 27 Black) had a 24‐hour stay in the respiratory chamber equipped with radar sensors. Body composition, glucose tolerance, fasting insulin, insulin action (hyperinsulinemic‐euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were measured as covariates. Results: SPA, adjusted for age, sex, race, and body composition, declined (r = −0.30, p < 0.0001), with a concomitant rise in the energy cost of SPA (r = 0.30, p < 0.0001). The 24‐hour EE adjusted for covariates increased (r = 0.31, p < 0.0001), which was reflected in increases in EE during sleep (r = 0.18, p < 0.0001) and during the awake, fed condition (r = 0.28, p < 0.0001). The secular trends in SPA or 24‐hour EE were unchanged with adjustment for measures related to glucose metabolism. Conclusions: Secular trend analyses showed a decline in fidgeting. However, this decline in SPA was partially counterbalanced by an increase in energy cost of this activity and a rise in EE. Nevertheless, our results support public health efforts to promote small but sustained changes in these behaviors. [ABSTRACT FROM AUTHOR]

Objective: Circulating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined. Methods: In study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition. Results: After adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p<0.0001). Lower albumin concentrations were associated with greater weight [β=3.53 kg, p=0.039 (adjusted for age, sex, follow up time), CI 0.16 to 6.21 per 1 g/dl difference albumin concentration] and fat mass (β=2.3 kg, p=0.022), respectively, but not with changes in fat free mass (p=0.06). Conclusions: Lower albumin concentrations were associated with increased ad libitum food intake and weight gain, indicating albumin as a marker of energy intake regulation. Clinical Trial Registration: ClinicalTrials.gov, identifiers NCT00340132, NCT00342732. [ABSTRACT FROM AUTHOR]

A greater decrease in 24-h energy expenditure (24 EE) during 24-h fasting defines a "thriftier" metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24 EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24-h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male; aged 36.6 ± 11.4 years; percentage body fat 34.8 ± 10.5%). Greater decrease in 24 EE during fasting (thriftier phenotype) was associated with less increase in 24 EE during COLD (i.e., less cold-induced thermogenesis). Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24-h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated with and mediated by the liver-derived hormone FGF21. Thus, the 24 EE response to COLD further identifies the "thrifty" versus "spendthrift" phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change. [ABSTRACT FROM AUTHOR]

Objective: The relationship between adipocyte size and ad libitum energy intake has not been previously examined. This study hypothesized an inverse relationship between adipocyte size and daily energy intake (DEI).Methods: Seventy healthy adults (39 men and 31 women; BMI 30.0  [SD 6.3]) underwent dual-energy x-ray absorptiometry and subcutaneous fat biopsies from the abdomen and thigh. Osmium-fixed adipocytes were sized with a Coulter counter. Volunteers self-selected food from a vending machine paradigm as the only source of energy intake over 3 days as inpatients. Volunteers also had 24-hour respiratory quotient (RQ) measured in a whole-room indirect calorimeter.Results: In women, the large cell peak diameter of the thigh depot was greater than that of the abdominal depot (Δ = +15.8 μm; P < 0.0001). In women, thigh peak diameter was inversely associated with DEI (β = -264.7 kcal/d per 10-μm difference; P = 0.03) after adjusting for demographics and body composition. The thigh peak diameter in women was associated with 24-hour RQ (r = -0.47, P = 0.04) after adjusting for demographics, body composition, and 24-hour energy balance. These associations did not extend to men or the abdominal depot.Conclusions: In women, thigh adipocyte size was associated with reduced DEI and 24-hour RQ, indicating a special role for thigh fat in women. This depot-specific sexual dimorphism indicates common regulation of energy intake and adipocyte size in the thigh region of women. [ABSTRACT FROM AUTHOR]

Context Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated. Design In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m2) with varying degrees of glucose tolerance. A calibration model was used to assess the ability of OGTT-derived, tissue-specific surrogate indices [hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI)] to predict insulin sensitivity/resistance indices derived from the reference glucose clamp [Hepatic-IRbasal, a product of fasting plasma insulin and hepatic glucose production (HGP), Hepatic-IRclamp, reciprocal of the percent suppression of HGP during the insulin clamp corrected for plasma insulin concentration, and Muscle-ISclamp, a measure of peripheral glucose disposal]. Predictive accuracy was assessed by root mean squared error of prediction and leave-one-out, cross-validation-type square root of the mean squared error of prediction. Results HIRI and MISI were correlated with their respective clamp-derived indices. HIRI was negatively related to Muscle-ISclamp (r = –0.62, P < 0.0001) and MISI correlated with Hepatic-IR derived from the clamp (Hepatic-IRbasal: r = –0.48, P < 0.0001 and Hepatic-IRclamp: r = –0.41, P < 0.0001). However, the accuracy of HIRI and MISI to predict Hepatic-IR (basal or during clamp) was not significantly different. Likewise, the ability of HIRI and MISI to predict Muscle-ISclamp was also similar. Conclusion Our findings indicate that the surrogate indices derived from an OGTT are accurate in predicting insulin sensitivity but are not tissue specific. [ABSTRACT FROM AUTHOR]

Objective: We compared the ability of 1- and 2-h plasma glucose concentrations (1h-PG and 2h-PG, respectively), derived from a 75-g oral glucose tolerance test (OGTT), to predict retinopathy. 1h-PG and 2h-PG concentrations, measured in a longitudinal study of an American Indian community in the southwestern U.S., a population at high risk for type 2 diabetes, were analyzed to assess the usefulness of the 1h-PG to identify risk of diabetic retinopathy (DR).Research Design and Methods: Cross-sectional (n = 2,895) and longitudinal (n = 1,703) cohorts were assessed for the prevalence and incidence of DR, respectively, in relation to deciles of 1h-PG and 2h-PG concentrations. Areas under the receiver operating characteristic (ROC) curves for 1h-PG and 2h-PG were compared with regard to predicting DR, as assessed by direct ophthalmoscopy.Results: Prevalence and incidence of DR, based on direct ophthalmoscopy, changed in a similar manner across the distributions of 1h-PG and 2h-PG concentrations. ROC analysis showed that 1h-PG and 2h-PG were of similar value in identifying prevalent and incident DR using direct ophthalmoscopy. 1h-PG cut points of 230 and 173 mg/dL were comparable to 2h-PG cut points of 200 mg/dL (type 2 diabetes) and 140 mg/dL (impaired glucose tolerance), respectively.Conclusions: 1h-PG is a useful predictor of retinopathy risk, has a predictive value similar to that of 2h-PG, and may be considered as an alternative glucose time point during an OGTT. [ABSTRACT FROM AUTHOR]

Such interindividual ranges and the evidence by Martins et al. that the effect of MA may be masked until other measures such as adherence are accounted for raise the following question: has the effect of MA been underestimated? Metabolic adaptation (MA, also known as adaptive thermogenesis) defines the greater-than-expected decline in energy expenditure (EE) with weight loss and is generally accepted physiology (1). MA is calculated as the measured EE - predicted EE after weight loss, with predicted EE based on regression equations at baseline. [Extracted from the article]

New biomarkers for type 2 diabetes mellitus (T2DM) may aid diagnosis, drug development or clinical treatment. Evidence is increasing for the adaptive immune system’s role in T2DM and suggests the presence of unidentified autoantibodies. While high-density protein microarrays have emerged as a useful technology to identify possible novel autoantigens in autoimmune diseases, its application in T2DM has lagged. In Pima Indians, the HLA haplotype (HLA-DRB1*02) is protective against T2DM and, when studied when they have normal glucose tolerance, subjects with this HLA haplotype have higher insulin secretion compared to those without the protective haplotype. Possible autoantibody biomarkers were identified using microarrays containing 9480 proteins in plasma from Pima Indians with T2DM without the protective haplotype (n = 7) compared with those with normal glucose regulation (NGR) with the protective haplotype (n = 11). A subsequent validation phase involving 45 cases and 45 controls, matched by age, sex and specimen storage time, evaluated 77 proteins. Eleven autoantigens had higher antibody signals among T2DM subjects with the lower insulin-secretion HLA background compared with NGR subjects with the higher insulin-secretion HLA background (p<0.05, adjusted for multiple comparisons). PPARG2 and UBE2M had lowest p-values (adjusted p = 0.023) while PPARG2 and RGS17 had highest case-to-control antibody signal ratios (1.7). A multi-protein classifier involving the 11 autoantigens had sensitivity, specificity, and area under the receiver operating characteristics curve of 0.73, 0.80, and 0.83 (95% CI 0.74–0.91, p = 3.4x10-8), respectively. This study identified 11 novel autoantigens which were associated with T2DM and an HLA background associated with reduced insulin secretion. While further studies are needed to distinguish whether these antibodies are associated with insulin secretion via the HLA background, T2DM more broadly, or a combination of the two, this study may aid the search for autoantibody biomarkers by narrowing the list of protein targets. [ABSTRACT FROM AUTHOR]

Context: Fusarium keratitis is a serious corneal infection, most commonly associated with corneal injury. Beginning in March 2006, the Centers for Disease Control and Prevention received multiple reports of Fusarium keratitis among contact lens wearers. Objective: To define the specific activities, contact lens hygiene practices, or products associated with this outbreak. Design, Setting, and Participants: Epidemiological investigation of Fusarium keratitis occurring in the United States. A confirmed case was defined as keratitis with illness onset after June 1, 2005, with no history of recent ocular trauma and a corneal culture growing Fusarium species. Data were obtained by patient and ophthalmologist interviews for case patients and neighborhood-matched controls by trained personnel. Available Fusarium isolates from patients' clinical and environmental specimens were genotyped by multilocus sequence typing. Environmental sampling for Fusarium was conducted at a contact lens solution manufacturing plant. Main Outcome Measures: Keratitis infection with Fusarium species. Results: As of June 30, 2006, we identified 164 confirmed case patients in 33 states and 1 US territory. Median age was 41 years (range, 12-83 years). Corneal transplantation was required or planned in 55 (34%). One hundred fifty-four (94%) of the confirmed case patients wore soft contact lenses. Forty-five case patients and 78 controls were included in the casecontrol study. Case patients were significantly more likely than controls to report using a specific contact lens solution, ReNu with MoistureLoc (69% vs 15%; odds ratio, 13.3; 95% confidence interval, 3.1-119.5). The prevalence of reported use of ReNu MultiPlus solution was similar between case patients and controls (18% vs 20%; odds ratio, 0.7; 95% confidence interval, 0.2-2.8). Fusarium was not recovered from the factory, warehouse, solution filtrate, or unopened solution bottles; production of implicated lots was not clustered in time. Among 39 isolates tested, at least 10 different Fusarium species were identified, comprising 19 unique multilocus genotypes. Conclusions: The findings from this investigation indicate that this outbreak of Fusarium keratitis was associated with use of ReNu with MoistureLoc contact lens solution. Contact lens users should not use ReNu with MoistureLoc. [ABSTRACT FROM AUTHOR]

Context: Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated., Design: In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m 2 ) with varying degrees of glucose tolerance. A calibration model was used to assess the ability of OGTT-derived, tissue-specific surrogate indices [hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI)] to predict insulin sensitivity/resistance indices derived from the reference glucose clamp [Hepatic-IR basal , a product of fasting plasma insulin and hepatic glucose production (HGP), Hepatic-IR clamp , reciprocal of the percent suppression of HGP during the insulin clamp corrected for plasma insulin concentration, and Muscle-IS clamp , a measure of peripheral glucose disposal]. Predictive accuracy was assessed by root mean squared error of prediction and leave-one-out, cross-validation-type square root of the mean squared error of prediction., Results: HIRI and MISI were correlated with their respective clamp-derived indices. HIRI was negatively related to Muscle-IS clamp ( r = -0.62, P < 0.0001) and MISI correlated with Hepatic-IR derived from the clamp (Hepatic-IR basal : r = -0.48, P < 0.0001 and Hepatic-IR clamp : r = -0.41, P < 0.0001). However, the accuracy of HIRI and MISI to predict Hepatic-IR (basal or during clamp) was not significantly different. Likewise, the ability of HIRI and MISI to predict Muscle-IS clamp was also similar., Conclusion: Our findings indicate that the surrogate indices derived from an OGTT are accurate in predicting insulin sensitivity but are not tissue specific.

In 2005 and 2006, outbreaks of Fusarium keratitis associated with soft contact lens use occurred in multiple U.S. states and Puerto Rico. A case-control study conducted by the Centers for Disease Control and Prevention (CDC) showed a significant association between infections and the use of one particular brand of lens solution. To characterize the full spectrum of the causal agents involved and their potential sources, partial DNA sequences from three loci (RPB2, EF-1alpha, and nuclear ribosomal rRNA) totaling 3.48 kb were obtained from 91 corneal and 100 isolates from the patient's environment (e.g., contact lens and lens cases). We also sequenced a 1.8-kb region encoding the RNA polymerase II second largest subunit (RPB2) from 126 additional pathogenic isolates to better understand how the keratitis outbreak isolates fit within the full phylogenetic spectrum of clinically important fusaria. These analyses resulted in the most robust phylogenetic framework for Fusarium to date. In addition, RPB2 nucleotide variation within a 72-isolate panel was used to design 34 allele-specific probes to identify representatives of all medically important species complexes and 10 of the most important human pathogenic Fusarium in a single-well diagnostic assay, using flow cytometry and fluorescent microsphere technology. The multilocus data revealed that one haplotype from each of the three most common species comprised 55% of CDC's corneal and environmental isolates and that the corneal isolates comprised 29 haplotypes distributed among 16 species. The high degree of phylogenetic diversity represented among the corneal isolates is consistent with multiple sources of contamination.