Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric.

PURPOSE: A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure. METHODS: Twenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared. RESULTS: Individual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed. CONCLUSIONS: SFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression.

Predictive value of sleep apnea screenings in cardiac surgery patients.

INTRODUCTION: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased cardiovascular risks. We explored the predictive value of OSA screening instruments in cardiac disease patients awaiting cardiac surgery. METHODS: In this prospective cohort, 107 participants awaiting cardiac surgery from Cleveland Clinic and Johns Hopkins underwent polysomnography after completing Epworth Sleepiness Scale (ESS), Sleep Apnea/Sleep Disorder Questionnaire (SA/SDQ), STOP, STOPBAG2 and Berlin questionnaires. Score comparisons between groups based on apnea-hypopnea index (AHI) ≥15 were performed. Logistic regression with receiver operating characteristic (ROC) analysis was used to investigate optimal threshold. RESULTS: Prevalence of OSA (AHI ≥5) was 71.9% (77/107) and 51 (47.7%) had moderate-to-severe disease (AHI ≥15). Participants were primarily male (57%) and Caucasian (76.6%). Mean age was 67.3 ± 13.3 years and BMI was 26.5 ± 6.6. Of the five screening tools, STOPBAG2 with a cut-point of 0.381 provided 78% sensitivity and 38% specificity (AUC 0.66, 95%CI 0.55-0.77). SA/SDQ yielded a cut-point of 32 for all subjects (AUC: 0.62, 95%CI 0.51-0.73) with sensitivity and specificity of 60% and 62% respectively, while STOP score ≥2 provided sensitivity and specificity of 67% and 52% respectively (AUC: 0.61, 95%CI 0.51-0.72). Among STOP items, "observed apnea" had the strongest correlation with AHI ≥15 (OR 3.67, 95%CI 1.57-8.54, p = 0.003). The ESS and Berlin were not useful in identifying moderate-to-severe OSA. CONCLUSION: Common screening tools had suboptimal performance in cardiac surgery patients. STOPBAG2 was better at predicting the probability of moderate-to-severe OSA in patients undergoing cardiac surgery compared to ESS, SA/SDQ, STOP and Berlin questionnaires.

How Can Intranasal Oxytocin Research Be Trusted? A Systematic Review of the Interactive Effects of Intranasal Oxytocin on Psychosocial Outcomes.

Over the past two decades, research about the role of oxytocin (OT) in human behavior has grown exponentially. However, a unified theory of OT effects has yet to be developed. Relatedly, growing concerns about the robustness of conclusions drawn in the field have been raised. The current article contributes to this debate by reporting on and discussing key conclusions from a systematic review of published studies addressing the interactive effects of intranasal OT (IN-OT) administration on psychosocial outcomes in a healthy population. The review indicates that (a) tested interactive IN-OT effects were highly heterogeneous; (b) for most published interactions, no replication was attempted; (c) when attempted, replications were largely unsuccessful; (d) significance was unrelated to sample size; (e) statistical power was critically low and unrelated to the rate of significant results; and (f) research practices were characteristic of an exploratory approach. This concerning state of affairs makes it virtually impossible to tease apart true from false interactive IN-OT effects. We provide constructive directions on the basis of this observation and positive predictive value simulations for future research that should help extract true effects from noise and move the IN-OT field forward.

Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status after bariatric surgery.

AIM: To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. METHODS: A total of 40 adults [mean ± sd body mass index 36 ± 3 kg/m(2) , age 48 ± 9 years, glycated haemoglobin (HbA1c) 9.7 ± 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-α, high-sensitivity C-reactive protein (hs-CRP)] were also assessed. RESULTS: At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and ß-cell function (C-peptide0-120 /glucose0-120 × Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced ß-cell function, lower triglyceride levels and fat loss. CONCLUSIONS: Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key to achieving higher type 2 diabetes remission rates after bariatric surgery.

Comparison of clinical evaluation of genitourinary symptoms in female adolescents among primary care versus emergency department physicians.

OBJECTIVE: To compare clinical approaches to assessment and treatment of female adolescents with genitourinary symptoms among primary care and emergency department (ED) physicians. DESIGN: A chart review was performed of the evaluation and treatment of 472 patients presenting between July 1, 2005, and June 30, 2006. SETTING: Suburban and tertiary care EDs and primary care settings. PARTICIPANTS: Female patients age 13-21 years with genitourinary symptoms. INTERVENTIONS: None. OUTCOME MEASURES: Physician assessment of sexual history, performance of pelvic exam and sexually transmitted infection (STI) tests, empiric treatment of suspected STIs. RESULTS: Patients seen in primary care settings were more likely to be asked about sexual history, including contraceptive use, than patients in the ED (P<0.001). After adjustment for age and race, there was no statistically significant difference between the ED and primary care sites in performance of pelvic exams or gonorrhea and chlamydia tests. However, there was a higher likelihood that older adolescents would undergo pelvic exams (P=0.001), and STI testing (P=0.002) than younger patients. There was no significant difference in empiric treatment of patients with positive STI tests between ED and primary care sites or across the age spectrum. CONCLUSIONS: ED physicians should obtain sexual histories on patients with genitourinary symptoms. Both primary care and ED clinicians should consistently test for STIs in sexually active patients who have genitourinary symptoms. Physicians in both settings should have a low threshold for testing and empirically treating adolescents with symptoms or physical exam findings consistent with STIs.

Transobturator slings for stress incontinence: using urodynamic parameters to predict outcomes.

The purpose of this study is to evaluate the ability of preoperative urodynamic urethral function parameters to predict the success rate of transobturator slings (TOS). Seventy women urodynamically diagnosed with stress incontinence with urethral hypermobility underwent a Monarc TOS (American Medical Systems, Minnetonka, USA). Postoperative continence status was correlated with preoperative urodynamic urethral function parameters. Mathematical modeling was used to determine whether urodynamic parameters can be used to predict postoperative continence. Average follow-up was 8.1 (6-12) months; 56 (80%) patients were continent based on a standardized stress test and subjective report. The median Valsalva leak point pressure at 150 cc (VLPP150) in the failures and successes was not different (p = 0.12). The median VLPP at cystometric capacity (VLPPcap) in the failures was 32 cmH2O compared to 71 cmH2O in the successes (p < 0.001). The maximum urethral closure pressure (MUCP) had a median of 20 cmH2O in the failures and 45 cmH2O in the successful patients (p < 0.001). No correlation existed between the degree of urethral hypermobility, as measured by the cotton swab test, and surgical success (p = 0.17). There was no correlation between level of preoperative urethral function and persistent overactive bladder symptoms, post-void residual, voids/day, and nocturia. Using a combined model, the cutoff values of VLPPcap > 60 cmH2O and MUCP > 40 cmH2O were the most predictive of surgical success, revealing a sensitivity of 83% (0.55, 0.95) and specificity of 79% (0.67, 0.88). A combination of urodynamic parameters can be used to predict continence rates after a TOS. A TOS should be used with caution in women with impaired urethral function.

Comparison of unintentional fatal occupational injuries in the Republic of Korea and the United States.

OBJECTIVES: To compare the profile of unintentional fatal occupational injuries in the Republic of Korea and the United States to help establish prevention strategies for Korea and to understand country specific differences in fatality risks in different industries. METHODS: Occupational fatal injury data from 1998-2001 were collected from Korea's Occupational Safety and Health Agency's Survey of Causes of Occupational Injuries (identified by the Korea Labor Welfare Corporation) and from the United States Census of Fatal Occupational Injuries. Employment estimates were obtained in both countries. Industry coding and external cause of death coding were standardized. Descriptive analyses of injury rates and Poisson regression models to examine time trends were conducted. RESULTS: Korea exhibited a significantly higher fatal injury rate, at least two times higher than the United States, after accounting for different employment patterns. The ordering of industries with respect to risk is the same in the two countries, with mining, agriculture/forestry/fishing, and construction being the most dangerous. Fatal injury rates are decreasing in these two countries, although at a faster rate in Korea. CONCLUSIONS: Understanding industrial practices within different countries is critical for fully understanding country specific occupational injury statistics. However, differences in surveillance systems and employment estimation methods serve as caveats to any transnational comparison, and need to be harmonized to the fullest extent possible.

Deindustrialisation and the long term decline in fatal occupational injuries.

AIMS: To examine the extent to which deindustrialisation accounts for long term trends in occupational injury risk in the United States. METHODS: Rates of fatal unintentional occupational injury were computed using data from death certificates and the population census. Trends were estimated using Poisson regression. Standardisation and regression methods were used to adjust for the potential effect of structural change in the labour market. RESULTS: The fatal occupational injury rate for all industries declined 45% from 1980 to 1996 (RR (rate ratio) 0.55, 95% CI 0.52 to 0.57). Adjustment for structural changes in the workforce shifted the RR to 0.62 (95% CI 0.60 to 0.65). Expanding industries enjoyed more rapid reduction in risk (-3.43% per year, 95% CI -3.62 to -3.24) than those that contracted (-2.65% per year, 95% CI -2.88 to -2.42). CONCLUSIONS: Deindustrialisation contributed to the decline of fatal occupational injury rates in the United States, but explained only 10-15% of the total change.

Diversity of trends in occupational injury mortality in the United States, 1980-96.

OBJECTIVES: Although the United States has generally enjoyed declining rates of fatal occupational injury, the rate of decline has not been uniform. To examine the heterogeneity of trends, changes in fatal occupational injury rates from 1980 to 1996 were estimated by occupation, industry, geographic region, and demographic group. METHODS: Deaths due to injury at work during 1980-96 were identified from the US National Traumatic Occupational Fatality database and populations at risk were estimated from the census of population. Mortality rates were computed for unintentional injuries, homicides, and all injuries combined. The annual rate of change was estimated using Poisson regression to model the death rate as a function of time. RESULTS: The estimated average rates for all fatal occupational injuries and for unintentional injuries declined by 3% per year, while the estimated rate of homicide declined <1% per year. The improvement was faster for men (3% per year) than for women (<1% per year) and for younger relative to older workers (7% per year v 2%-3% per year). Trends were also geographically heterogeneous, with the most rapid declines (7%-8% per year) in the South and West. Injury rates for most occupations and industries declined at near the average rate, but some experienced no change or an increase. The rate of homicide also increased in a number of occupations and industries. CONCLUSIONS: Broad downward trends in occupational fatality rates may be explained by several factors, including organized safety efforts, product and process changes, and the ongoing shift of employment toward safer sectors. Disparities in fatal injury trends draw attention to potential opportunities to reduce risk: work settings with increasing injury rates are of particular concern.

Separation of newborn BALB/c thymocytes by a density gradient method.

The recognition of T-lymphocyte subpopulations has led to a search for methods to separate lymphoid subsets on the basis of physical, biochemical and biological differences. The analysis of these properties of thymic cells made it possible to distinguish two main subsets: a major population of immunologically inactive cells, and a minor subpopulation of immunocompetent T cells. In the present paper a method for the separation of thymic lymphoid cell subpopulations in mice aged 5 to 10 days is reported. The cells resulting from this procedure were analyzed according to different criteria. From a morphological point of view, the existence of a large blast-like cell (termed I) and a smaller cell (termed III) was evident. These two cell subclasses were investigated in order to characterize their division rate, in vitro sensitivity to dexamethasone and peanut lectin agglutination pattern. It was found that subpopulation I had a faster division rate than subpopulation III, as measured in vitro by [3H]thymidine (dThd) incorporation and mitotic index with colchicine. When these different cells were incubated in the presence of dexamethasone at different concentrations, no significant difference was seen in [3H]dThd incorporation at the age of 5 days, while on the tenth day subpopulation I became more resistant to the hormone than subpopulation III. When incubated with peanut lectin, it was evident that subpopulation I was mainly constituted by PNA-unagglutinable cells. On the other hand, subpopulation III consisted mostly of PNA-agglutinable cells.