Aging and caloric restriction impact adipose tissue, adiponectin, and circulating lipids.

Adipose tissue expansion has been associated with system-wide metabolic dysfunction and increased vulnerability to diabetes, cancer, and cardiovascular disease. A reduction in adiposity is a hallmark of caloric restriction (CR), an intervention that extends longevity and delays the onset of these same age-related conditions. Despite these parallels, the role of adipose tissue in coordinating the metabolism of aging is poorly defined. Here, we show that adipose tissue metabolism and secretory profiles change with age and are responsive to CR. We conducted a cross-sectional study of CR in adult, late-middle-aged, and advanced-aged mice. Adiposity and the relationship between adiposity and circulating levels of the adipose-derived peptide hormone adiponectin were age-sensitive. CR impacted adiposity but only levels of the high molecular weight isoform of adiponectin responded to CR. Activators of metabolism including PGC-1a, SIRT1, and NAMPT were differentially expressed with CR in adipose tissues. Although age had a significant impact on NAD metabolism, as detected by biochemical assay and multiphoton imaging, the impact of CR was subtle and related to differences in reliance on oxidative metabolism. The impact of age on circulating lipids was limited to composition of circulating phospholipids. In contrast, the impact of CR was detected in all lipid classes regardless of age, suggesting a profound difference in lipid metabolism. These data demonstrate that aspects of adipose tissue metabolism are life phase specific and that CR is associated with a distinct metabolic state, suggesting that adipose tissue signaling presents a suitable target for interventions to delay aging.

Pubertal Height Growth and Adult Height in Cystic Fibrosis After Newborn Screening.

BACKGROUND: To examine long-term growth benefit of newborn screening (NBS), adolescent peak height velocity (PHV), and adult height were compared between the screened (diagnosed early via NBS) and the control (identified generally by symptoms) in the Wisconsin Randomized Clinical Trial. METHODS: Data from 107 children born in 1985-1994 and followed through 2012 were analyzed. PHV was estimated by a semiparametric growth curve model and compared with Tanner reference. RESULTS: Meconium ileus (MI; n = 25) was associated with the worst pubertal growth and adult height, including 1 child who did not experience apparent PHV; children with pancreatic sufficiency (n = 18) achieved the best growth (normal PHV and adult height). In children with pancreatic insufficiency without meconium ileus (n = 64), the subgroup most likely to benefit from NBS, screened children had similar PHV but better adult height compared with controls. Specifically, in boys, the screened group (n = 22) achieved normal PHV (9.5 cm at 13.5 years); the control group (n = 19) had similar onset age (13.6 years) but 0.6-cm lower magnitude (P = .08). In girls, the screened group (n = 10) had somewhat later (12.5 years vs 11.7 years, P = .12) and lower PHV (7.3 cm vs 7.9 cm, P = .33) than the controls (n = 13), coinciding with later menarche (13.6 years vs 12.2 years, P = .10). Adult height was taller in the screened than the control (50th vs 29th percentile, P = .02), even after adjusted for genetic potential (32nd vs15th percentile, P = .006). Differences in adult height were primarily attributable to NBS and better prepubertal growth. CONCLUSIONS: Early linear growth benefits of NBS were sustained through puberty, leading to better adult height in cystic fibrosis.

Clinical Features, Virus Identification, and Sinusitis as a Complication of Upper Respiratory Tract Illness in Children Ages 4-7 Years.

OBJECTIVE: To determine the rate of sinusitis complicating upper respiratory tract illnesses (URIs) in children. We prospectively identified the clinical, virologic, and epidemiologic characteristics of URIs in a population of 4- to 7-year-old children followed for 1 year. STUDY DESIGN: This was an observational cohort study in 2 primary care pediatric practices in Madison, Wisconsin. Nasal samples were obtained during 4 asymptomatic surveillance visits and during symptomatic URIs. A polymerase chain reaction-based assay for 9 respiratory viruses was performed on nasal samples. A diagnosis of sinusitis was based on published criteria. RESULTS: Two hundred thirty-six children ages 48-96 months were enrolled. A total of 327 URIs were characterized. The mean number of URIs per child was 1.3 (range 0-9) per year. Viruses were detected in 81% of URIs; rhinovirus (RV) was most common. Seventy-two percent of URIs were resolved clinically by the 10th day. RV-A and RV-C were detected more frequently at URI visits; RV-B was detected at the same rate for both asymptomatic surveillance visits and URI visits. Sinusitis was diagnosed in 8.8% of symptomatic URIs. Viruses were detected frequently (33%) in samples from asymptomatic children. CONCLUSIONS: Sinusitis occurred in 8.8% of symptomatic URIs in our study. The virus most frequently detected with URIs in children was RV; RV-A and RV-C detection but not RV-B detection were associated with illness. Viruses, especially RV, are detected frequently in asymptomatic children. Most URIs have improved or resolved by the 10th day after onset. Children experienced a mean of 1.3 URIs per year, which was lower than expected.

Cross-Sectional Survey on Newborn Screening in Wisconsin Amish and Mennonite Communities.

Old Order Amish and Mennonites, or Plain populations, are a growing minority in North America with unique health care delivery and access challenges coupled with higher frequencies of genetic disorders. The objective of this study was to determine newborn screening use and attitudes from western Wisconsin Plain communities. A cross-sectional survey, with an overall response rate of 25 %, provided data representing 2010 children. In households with children (n = 297), the rate of newborn screening was 74 % and all children were screened in 40 % of these households. Lack of access to testing was the most common reason for not screening all children and parental age was inversely associated with testing. The majority of respondents reported some or more knowledge of screening, viewed screening as important, and had access to screening in their communities. Households with children who had never received newborn screening (26 %) reported lower frequencies of favorable responses in all categories compared to households that had at least one child screened. The difference in access to newborn screening was less marked between the groups compared to differences on knowledge and consideration of its importance. Moreover, 55 % of households who had never screened any of their children reported being unlikely or unsure of screening any future children. A focus on improving access to newborn screening alongside establishing approaches to change parental perceptions on the importance of newborn screening is necessary for increasing newborn screening in these Plain communities.

Antimüllerian hormone as a predictor of good-quality supernumerary blastocyst cryopreservation among women with levels <1 ng/mL versus 1-4 ng/mL.

OBJECTIVE: To determine whether antimüllerian hormone (AMH) levels predict the availability of good-quality supernumerary blastocysts for cryopreservation. DESIGN: Retrospective study. SETTING: Two fertility centers. PATIENT(S): First fresh IVF cycles (n = 247) grouped as follows: 40 women <35 year old with AMH <1 ng/mL and 77 women with AMH 1-4 ng/mL; 62 women ≥35 year old with AMH <1 ng/mL, and 68 women with AMH 1-4 ng/mL. INTERVENTION(S): AMH level measured before IVF with ovarian stimulation protocols based on patient age and AMH level, including short gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, or GnRH agonist microdose flare; supernumerary good-quality blastocysts cryopreserved on days 5 or 6 after retrieval. MAIN OUTCOME MEASURES(S): Supernumerary good-quality blastocysts for cryopreservation in relation to AMH levels. RESULT(S): Among women <35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocysts for cryopreservation between the groups with AMH <1 ng/mL and AMH 1-4 ng/mL (30.0% vs. 58.4%) when adjusted for age. Among women ≥35 years of age, there was a statistically significant difference in the number of patients with supernumerary good-quality blastocyst cryopreservation between groups with AMH <1 ng/mL and AMH 1-4 ng/mL (16.1% vs. 42.6%), when adjusted for age. CONCLUSION(S): Low AMH levels are associated with a statistically significantly lower likelihood of blastocysts for cryopreservation as compared with higher AMH levels. This effect was seen among women both <35 and ≥35 years of age. Patient counseling should include realistic expectations for the probability of good-quality supernumerary blastocysts available for cryopreservation.

Plasma diacylglycerol composition is a biomarker of metabolic syndrome onset in rhesus monkeys.

Metabolic syndrome is linked with obesity and is often first identified clinically by elevated BMI and elevated levels of fasting blood glucose that are generally secondary to insulin resistance. Using the highly translatable rhesus monkey (Macaca mulatta) model, we asked if metabolic syndrome risk could be identified earlier. The study involved 16 overweight but healthy, euglycemic monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years while the other half remained healthy. We conducted a series of biometric and plasma measures focusing on adiposity, lipid metabolism, and adipose tissue-derived hormones, which led to a diagnosis of metabolic syndrome in the insulin-resistant animals. Plasma fatty acid composition was determined by gas chromatography for cholesteryl ester, FFA, diacylglycerol (DAG), phospholipid, and triacylglycerol lipid classes; plasma lipoprotein profiles were generated by NMR; and circulating levels of adipose-derived signaling peptides were determined by ELISA. We identified biomarker models including a DAG model, two lipoprotein models, and a multiterm model that includes the adipose-derived peptide adiponectin. Correlations among circulating lipids and lipoproteins revealed shifts in lipid metabolism during disease development. We propose that lipid profiling may be valuable for early metabolic syndrome detection in a clinical setting.

The accuracy of conventional 2D video for quantifying upper limb kinematics in repetitive motion occupational tasks.

Marker-less 2D video tracking was studied as a practical means to measure upper limb kinematics for ergonomics evaluations. Hand activity level (HAL) can be estimated from speed and duty cycle. Accuracy was measured using a cross-correlation template-matching algorithm for tracking a region of interest on the upper extremities. Ten participants performed a paced load transfer task while varying HAL (2, 4, and 5) and load (2.2 N, 8.9 N and 17.8 N). Speed and acceleration measured from 2D video were compared against ground truth measurements using 3D infrared motion capture. The median absolute difference between 2D video and 3D motion capture was 86.5 mm/s for speed, and 591 mm/s(2) for acceleration, and less than 93 mm/s for speed and 656 mm/s(2) for acceleration when camera pan and tilt were within ± 30 degrees. Single-camera 2D video had sufficient accuracy (< 100 mm/s) for evaluating HAL. Practitioner Summary: This study demonstrated that 2D video tracking had sufficient accuracy to measure HAL for ascertaining the American Conference of Government Industrial Hygienists Threshold Limit Value(®) for repetitive motion when the camera is located within ± 30 degrees off the plane of motion when compared against 3D motion capture for a simulated repetitive motion task.

A frequency-duty cycle equation for the ACGIH hand activity level.

A new equation for predicting the hand activity level (HAL) used in the American Conference for Government Industrial Hygienists threshold limit value®(TLV®) was based on exertion frequency (F) and percentage duty cycle (D). The TLV® includes a table for estimating HAL from F and D originating from data in Latko et al. (Latko WA, Armstrong TJ, Foulke JA, Herrin GD, Rabourn RA, Ulin SS, Development and evaluation of an observational method for assessing repetition in hand tasks. American Industrial Hygiene Association Journal, 58(4):278-285, 1997) and post hoc adjustments that include extrapolations outside of the data range. Multimedia video task analysis determined D for two additional jobs from Latko's study not in the original data-set, and a new nonlinear regression equation was developed to better fit the data and create a more accurate table. The equation, HAL = 6:56 ln D[F(1:31) /1+3:18 F(1:31), generally matches the TLV® HAL lookup table, and is a substantial improvement over the linear model, particularly for F>1.25 Hz and D>60% jobs. The equation more closely fits the data and applies the TLV® using a continuous function.

A behavioral paradigm to evaluate hippocampal performance in aged rodents for pharmacological and genetic target validation.

Aged-related cognitive ability is highly variable, ranging from unimpaired to severe impairments. The Morris water maze (a reliable tool for assessing memory) has been used to distinguish aged rodents that are superior learners from those that are learning impaired. This task, however, is not practical for pre- and post-pharmacological treatment, as the memory of the task is long lasting. In contrast, the object location memory task, also a spatial learning paradigm, results in a less robust memory that decays quickly. We demonstrate for the first time how these two paradigms can be used together to assess hippocampal cognitive impairments before and after pharmacological or genetic manipulations in rodents. Rats were first segregated into superior learning and learning impaired groups using the object location memory task, and their performance was correlated with future outcome on this task and on the Morris water maze. This method provides a tool to evaluate the effect of treatments on cognitive impairment associated with aging and neurodegenerative disorders.

Gene delivery of Homer1c rescues spatial learning in a rodent model of cognitive aging.

Homer1c has been shown to play a role in learning and memory. Overexpression of Homer1c in the hippocampus can improve memory in normal rats and can also rescue spatial learning deficits in Homer1 knockout mice. In a previous study, we found that Homer1c mRNA is upregulated after a spatial learning paradigm in aged rats that successfully learn the task, when compared to aged rats that are learning-impaired (AI). This study was designed to validate the role of Homer1c in successful cognitive aging. In this article, we report that gene delivery of Homer1c into the hippocampus of aged learning-impaired rats significantly improves individual performance on an object location memory task. The learning ability of these rats on the Morris Water Maze was also superior to that of AI control rats. In summary, using 2 independent spatial memory tasks, we demonstrate that Homer1c is sufficient to improve the spatial learning deficits in a rodent model of cognitive aging. These results point to Homer1c as a potential therapeutic target for improving age-related cognitive impairment.

Pubertal height velocity and associations with prepubertal and adult heights in cystic fibrosis.

OBJECTIVES: To test the hypothesis that pubertal peak height velocity (PHV) in cystic fibrosis (CF) has improved and is influenced by prepubertal growth and genetic potential. STUDY DESIGN: PHV from 1862 children born in 1984-87 and documented in the 1986-2008 US CF Foundation Registry was determined by statistical modeling and classified into normal, delayed (2-SD > average age), attenuated (magnitude <5th percentile), or both delayed and attenuated (D&A). Genetic potential for height was estimated by parental stature. RESULTS: PHV averaged 8.4 cm/year at age 14.0 years in boys and 7.0 cm/year at age 12.1 years in girls, ∼6-month delay and ∼15% reduction compared with healthy children. PHV was normal in 60%, delayed in 9%, attenuated in 21%, and D&A in 5%. Patients with delayed PHV reached similar adult height percentile (boys: 34th, girls: 46th) to those with normal PHV (boys: 33rd, girls: 34th); both were significantly taller than the attenuated (boys: 11th, girls: 19th) and D&A PHV subgroups (boys: 8th, girls: 14th). Pancreatic-sufficient patients had taller prepubertal and adult heights but similar PHV compared with pancreatic-insufficient or meconium ileus patients. Adjusting for genetic potential reduced adult height percentiles more in boys (from 25th to 16th) than girls (from 28th to 24th). Height at age 7 years, PHV age and magnitude, and parental stature significantly predicted adult height. CONCLUSIONS: Pubertal PHV has improved in children with CF born after mid-1980s compared with older cohorts but remains below normal. Suboptimal prepubertal and pubertal growth led to adult height below genetic potential in CF.

High catalytic rates for hydrogen production using nickel electrocatalysts with seven-membered cyclic diphosphine ligands containing one pendant amine.

A series of Ni-based electrocatalysts, [Ni(7P(Ph)2N(C6H4X))2](BF4)2, featuring seven-membered cyclic diphosphine ligands incorporating a single amine base, 1-para-X-phenyl-3,6-triphenyl-1-aza-3,6-diphosphacycloheptane (7P(Ph)2N(C6H4X), where X = OMe, Me, Br, Cl, or CF3), have been synthesized and characterized. X-ray diffraction studies have established that the [Ni(7P(Ph)2N(C6H4X))2](2+) complexes have a square planar geometry, with bonds to four phosphorus atoms of the two bidentate diphosphine ligands. Each of the complexes is an efficient electrocatalyst for hydrogen production at the potential of the Ni(II/I) couple, with turnover frequencies ranging from 2400 to 27,000 s(-1) with [(DMF)H](+) in acetonitrile. Addition of water (up to 1.0 M) accelerates the catalysis, giving turnover frequencies ranging from 4100 to 96,000 s(-1). Computational studies carried out on the [Ni(7P(Ph)2N(C6H4X))2](2+) family indicate the catalytic rates reach a maximum when the electron-donating character of X results in the pKa of the Ni(I) protonated pendant amine matching that of the acid used for proton delivery. Additionally, the fast catalytic rates for hydrogen production by the [Ni(7P(Ph)2N(C6H4X))2](2+) family relative to the analogous [Ni(P(Ph)2N(C6H4X)2)2](2+) family are attributed to preferred formation of endo protonated isomers with respect to the metal center in the former, which is essential to attain suitable proximity to the reduced metal center to generate H2. The results of this work highlight the importance of precise pKa matching with the acid for proton delivery to obtain optimal rates of catalysis.

Predictors of recurrent ingestion of gastrointestinal foreign bodies.

BACKGROUND: Gastrointestinal foreign bodies are commonly encountered; however, little knowledge exists as to the causes of foreign body ingestions and why they occur repeatedly in some patients. OBJECTIVE: To identify and define patients at high risk for recurrent foreign body ingestion. METHODS: A retrospective chart review of foreign body ingestion was conducted at a tertiary care medical centre over an 11-year period. Variables analyzed included age, sex, incarceration status, Diagnostic and Statistical Manual of Mental Disorders-IV diagnosis, success of endoscopy, type of sedation used, method of extraction, complications, presence of gastrointestinal pathology, and incidence of recurrent food impaction or foreign body. RESULTS: A total of 159 patients with a foreign body ingestion were identified. One hundred fourteen (77%) experienced a single episode of ingestion and 45 (23%) experienced multiple ingestions. Of the patients with multiple ingestions, 27 (60%) had recurrent food impactions while 18 (40%) ingested foreign objects. In the recurrent ingestor group, a psychiatric disorder had been diagnosed in 16 patients (35.6%) and there were 13 incarcerated individuals (28.9%). The average number of recurrences was 2.6 per patient (117 total recurrences). Individuals with a psychiatric disorder experienced 3.9 recurrences per patient, while prisoners averaged 4.1 recurrences per patient. The combination of a psychiatric disorder and being incarcerated was associated with the highest recurrence rate (4.33 per patient). Multivariable logistic regression revealed that male sex (OR 2.9; P=0.022), being incarcerated (OR 3.0; P=0.024) and the presence of a psychiatric disorder (OR 2.5; P=0.03) were risk factors for recurrent ingestion. CONCLUSION: Risk factors for recurrent ingestion of foreign bodies were male sex, being incarcerated and the presence of a psychiatric disorder.

Diagnostics for repeated measurements in linear mixed effects models.

Most currently available methods for detecting discordant subjects and observations in linear mixed effects model fits adapt existing methods for single-level regression data. The most common methods are generalizations of deletion-based approaches, primarily Cook's distance. This article describes the limitations of modifications to Cook's distance and local influence, and suggests a new nondeletion subject-level method, studentized residual sum of squares (TRSS) plots. We also suggest a new observation-level deletion method that detects discordant observations as an application of TRSS plots. The proposed method provides greater information on repeated measurements by utilizing revised residuals and efficiently evaluating the effect of discordant subjects and observations on the estimation of parameters including variance components. We compare the performance of the proposed methods with current methods by using the orthodontic growth data: a longitudinal dataset with 27 subjects each observed four times. TRSS plots successfully identified discordant subjects that were missed by modified Cook's distance methods and the local influence approach. Extensions of TRSS plots are also described.

Speech in ALS: Longitudinal Changes in Lips and Jaw Movements and Vowel Acoustics.

PURPOSE: The goal of this exploratory study was to investigate longitudinally the changes in facial kinematics, vowel formant frequencies, and speech intelligibility in individuals diagnosed with bulbar amyotrophic lateral sclerosis (ALS). This study was motivated by the need to understand articulatory and acoustic changes with disease progression and their subsequent effect on deterioration of speech in ALS. METHOD: Lip and jaw movements and vowel acoustics were obtained for four individuals with bulbar ALS during four consecutive recording sessions with an average interval of three months between recordings. Participants read target words embedded into sentences at a comfortable speaking rate. Maximum vertical and horizontal mouth opening and maximum jaw displacements were obtained during corner vowels. First and second formant frequencies were measured for each vowel. Speech intelligibility and speaking rate score were obtained for each session as well. RESULTS: Transient, non-vowel-specific changes in kinematics of the jaw and lips were observed. Kinematic changes often preceded changes in vowel acoustics and speech intelligibility. CONCLUSIONS: Nonlinear changes in speech kinematics should be considered in evaluation of the disease effects on jaw and lip musculature. Kinematic measures might be most suitable for early detection of changes associated with bulbar ALS.

Endoscopic ultrasound fine-needle aspiration characteristics of primary adenocarcinoma versus other malignant neoplasms of the pancreas.

BACKGROUND: Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic). OBJECTIVE: To compare and characterize primary pancreatic adenocarcinoma versus other malignant neoplasms, hereafter referred to as nonprimary pancreatic adenocarcinoma (NPPA), diagnosed by EUS-guided FNA. METHODS: The present study was a retrospective analysis of a prospectively maintained database. The setting was a tertiary care, academic medical centre. Patients referred for suspected pancreatic neoplasms were evaluated. Based on EUS-FNA characteristics, primary pancreatic adenocarcinoma was differentiated from other malignant neoplasms. The subset of other neoplasms was defined as malignant lesions that were 'NPPAs' (ie, predominantly solid or solid/cystic based on EUS appearance and primary malignant lesions or metastatic lesions to the pancreas). Pancreatic masses that were benign cystic lesions (pseudocyst, simple cyst, serous cystadenoma) and focal inflammatory lesions (acute, chronic and autoimmune pancreatitis) were excluded. RESULTS: A total of 230 patients were evaluated using EUS-FNA for suspected pancreatic mass lesions. Thirty-eight patients were excluded because they were diagnosed with inflammatory lesions or had purely benign cysts. One hundred ninety-two patients had confirmed malignant pancreatic neoplasms (ie, pancreatic adenocarcinoma [n=144], NPPA [n=48]). When comparing adenocarcinoma with NPPA lesions, there was no significant difference in mean age (P=0.0675), sex (P=0.3595) or average lesion size (P=0.3801). On average, four FNA passes were necessary to establish a cytological diagnosis in both lesion subtypes (P=0.396). Adenocarcinomas were more likely to be located in the pancreatic head (P=0.0198), whereas masses in the tail were more likely to be NPPAs (P=0.0006). Adenocarcinomas were also more likely to exhibit vascular invasion (OR 4.37; P=0.0011), malignant lymphadenopathy (P=0.0006), pancreatic duct dilation (OR 2.4; P=0.022) and common bile duct dilation (OR 2.87; P=0.039). CONCLUSIONS: Adenocarcinoma was more likely to be present in the head of the pancreas, have lymph node and vascular involvement, as well as evidence of pancreatic duct and common bile duct obstruction. Of all malignant pancreatic lesions analyzed by EUS-FNA, 25% were NPPA, suggesting that FNA is crucial in establishing a diagnosis and may be helpful in preoperative planning.

Investigating the role of the outer-coordination sphere in [Ni(P(Ph)2N(Ph­R)2)2]2+ hydrogenase mimics.

A series of dipeptide substituted nickel complexes with the general formula, [Ni(P(Ph)(2)N(NNA-amino acid/ester)(2))(2)](BF(4))(2), have been synthesized and characterized (P(2)N(2) = 1,5-diaza-3,7-diphosphacyclooctane, and the dipeptide consists of the non-natural amino acid, 3-(4-aminophenyl)propionic acid (NNA), coupled to amino acid/esters = glutamic acid, alanine, lysine, and aspartic acid). Each of these complexes is an active electrocatalyst for H(2) production. The effects of the outer-coordination sphere on the catalytic activity for the production of H(2) were investigated; specifically, the impact of sterics, the ability of the side chain or backbone to protonate and the pK(a) values of the amino acid side chains were studied by varying the amino acids in the dipeptide. The catalytic rates of the different dipeptide substituted nickel complexes varied by over an order of magnitude. The amino acid derivatives display the fastest rates, while esterification of the terminal carboxylic acids and side chains resulted in a decrease in the catalytic rate by 50-70%, implicating a significant role of protonated sites in the outer-coordination sphere on catalytic activity. For both the amino acid and ester derivatives, the complexes with the largest substituents display the fastest rates, indicating that catalytic activity is not hindered by steric bulk. These studies demonstrate the significant contribution that the outer-coordination sphere can have in tuning the catalytic activity of small molecule hydrogenase mimics.

Comparison of hepatitis C virus treatment between incarcerated and community patients.

UNLABELLED: The prevalence of chronic hepatitis C virus (HCV) infection among incarcerated individuals in the United States is estimated to be between 12% and 31%. HCV treatment during incarceration is an attractive option because of improved access to health care and directly observed therapy. We compared incarcerated and nonincarcerated HCV-infected patients evaluated for treatment at a single academic center between January 1, 2002 and December 31, 2007. During this period, 521 nonincarcerated and 388 incarcerated patients were evaluated for HCV treatment. Three hundred and nineteen (61.2%) nonincarcerated patients and 234 (60.3%) incarcerated patients underwent treatment with pegylated interferon and ribavirin. Incarcerated patients were more likely to be male, African-American race, and have a history of alcohol or intravenous drug use. Treated incarcerated patients were less likely to have genotype 1 virus and were less likely to have undergone previous treatment. There was a similar prevalence of coinfection with human immunodeficiency virus (HIV) in both groups. A sustained viral response (SVR) was achieved in 97 (42.9%) incarcerated patients, compared to 115 (38.0%) nonincarcerated patients (P = 0.304). Both groups had a similar proportion of patients that completed a full treatment course. Stepwise logistic regression was conducted, and the final model included full treatment course, non-genotype 1 virus, younger age at treatment start, and negative HIV status. Incarceration status was not a significant predictor when added to this model (P = 0.075). CONCLUSION: In a cohort of HCV-infected patients managed in an academic medical center ambulatory clinic, incarcerated patients were as likely to be treated for HCV and as likely to achieve an SVR as nonincarcerated patients.

MRI appearance of the proximal hamstring tendons in patients with and without symptomatic proximal hamstring tendinopathy.

OBJECTIVE: The purpose of our study was to determine if six MRI findings of the proximal hamstrings differ in frequency in hamstrings with and without symptoms of tendinopathy. MATERIALS AND METHODS: We reviewed the MRI examinations of 118 consecutive patients who had undergone pelvis MRI and evaluation by a musculoskeletal clinical specialist. The proximal hamstrings were evaluated at four consecutive axial locations for tendon size, internal T1 and T2 signal, peritendinous T2 signal, and ischial tuberosity edema. Statistical analysis was performed to determine the association of the MRI findings with symptomatic hamstring tendinopathy. RESULTS: Twenty-one patients had a clinical diagnosis of unilateral proximal hamstring tendinopathy. The mean width or anteroposterior size was significantly larger in symptomatic hamstrings at all three proximal levels (p = 0.002-0.040). More than 90% of hamstring tendons had increased internal T1 or T2 signal that was not associated with hamstring symptoms. Both hamstrings with and without symptoms of tendinopathy had peritendinous T2 signal, but this was significantly more common in hamstrings with tendinopathy symptoms at the three most distal levels (p = 0.001-0.041). Ischial tuberosity edema and a feathery appearance of the peritendinous T2 signal distally were significantly more common in symptomatic hamstrings (p = 0.004 and 0.001, respectively). CONCLUSION: Increased T1 and T2 signal is commonly seen within the proximal hamstrings but is not associated with symptoms of hamstring tendinopathy. Increased tendon size, peritendinous T2 signal with a distal feathery appearance, and ischial tuberosity edema are significantly associated with symptomatic hamstring tendinopathy but can be seen in asymptomatic individuals.

Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response.

OBJECTIVE: Previous studies of the HLA-B27-transgenic rat model of ankylosing spondylitis (AS) suggested that macrophages develop an intracellular stress response called the unfolded protein response (UPR) and, as a result, secrete increased amounts of cytokines in response to Toll-like receptor agonists such as lipopolysaccharide (LPS). Our objective was to determine whether macrophages from AS patients also undergo a UPR and secrete increased cytokines/chemokines in response to LPS. METHODS: Peripheral blood monocytes isolated from 10 AS patients and 10 healthy controls were differentiated in vitro with macrophage colony-stimulating factor. Select samples were treated with interferon-γ (IFNγ) to up-regulate class I major histocompatibility complex (HLA-B) expression prior to stimulation with LPS for either 3 hours (for RNA) or 8-24 hours (for supernatant). UPR induction was assessed by measuring the expression of messenger RNA for ERdj4, BiP, and CCAAT/enhancer binding protein homologous protein 10 (CHOP). RESULTS: Although IFNγ treatment up-regulated HLA-B expression (2-fold; P < 0.0001), neither IFNγ nor LPS substantially enhanced BiP or CHOP expression (<1.3-fold). ERdj4 expression increased weakly, but not significantly, in AS samples treated with IFNγ plus LPS (2.2-fold; P = 0.31). In response to LPS, AS macrophages secreted more CXCL9, interleukin-10 (IL-10), IL-12p70, IL-23, and tumor necrosis factor α than did control macrophages (P ≤ 0.025). The most striking difference was observed for IL-23 (median 265 pg/ml in AS patients versus 9 pg/ml in controls; P = 0.0007). We did not detect significant differences in IL-6, IL-8, or IFNß production. CONCLUSION: The greater production of IL-23 by AS patient macrophages in response to LPS provides further support for the development of Th17/IL-23-directed therapy. Since significant UPR induction was not detected in AS patient macrophages, the relationship between UPR and inflammatory cytokine production remains unclear.