Kvistmathis6826

Pregnancy-associated plasma protein-A (PAPP-A) has been suggested as a proatherogenic enzyme by its ability to locally increase insulin-like growth factor (IGF) activity through proteolytic cleavage of IGF binding protein-4 (IGFBP-4). Recently, stanniocalcin-2 (STC2) was discovered as an inhibitor of PAPP-A. This study aimed to investigate IGFBP-4, PAPP-A, and STC2 as local regulators of IGF bioactivity in the cardiac microenvironment by comparing levels in the pericardial fluid with those in the circulation of patients with cardiovascular disease.

Plasma and pericardial fluid were obtained from 39 patients undergoing elective cardiothoracic surgery, hereof 15 patients with type 2 diabetes. Concentrations of IGF-I, intact and fragmented IGFBP-4, PAPP-A, and STC2 were determined by immunoassays and IGF bioactivity by a cell-based assay.

In pericardial fluid, the concentrations of total IGF-I, intact IGFBP-4, and STC2 were 72 ± 10%, 91 ± 5%, and 40 ± 24% lower than in plasma, while PAPP-A was 15 times more concentrated. The levels of the 2 IGFBP-4 fragments generated by PAPP-A and reflecting PAPP-A activity were elevated by more than 25%. IGF bioactivity was 62 ± 81% higher in the pericardial fluid than plasma. Moreover, pericardial fluid levels of both IGFBP-4 fragments correlated with the concentration of PAPP-A and with the bioactivity of IGF. All protein levels were similar in pericardial fluid from nondiabetic and diabetic subjects.

PAPP-A increases IGF bioactivity by cleavage of IGFBP-4 in the pericardial cavity of cardiovascular disease patients. This study provides evidence for a distinct local activity of the IGF system, which may promote cardiac dysfunction and coronary atherosclerosis.

PAPP-A increases IGF bioactivity by cleavage of IGFBP-4 in the pericardial cavity of cardiovascular disease patients. This study provides evidence for a distinct local activity of the IGF system, which may promote cardiac dysfunction and coronary atherosclerosis.

This study aimed to evaluate the impact of intravenous opioid product restrictions at an academic medical institution in an urban setting during the time of critical opioid shortages. We assessed the effect of ordering restrictions on inpatient opioid utilization measured by 1) changes in intermittent oral and injectable opioid product administration; 2) changes in total institutional opioid administration; and 3) changes in the utilization of individual restricted opioid agents.

This study is a single-center retrospective analysis by interrupted time series of institutional opioid utilization from 07/2017 to 06/2018. Utilization was quantified using milligrams of intravenous morphine equivalent administered or dispensed per admitted patient. Restrictions were grouped into 10 distinct phases, which informed the interruptions in linear regression models.

Sequential restrictions during the study period led to shifts in use of individual agents but did not have a significant impact on overall total opioid strictions in response to future shortages.Although posterior cortical atrophy is often regarded as the canonical 'visual dementia', auditory symptoms may also be salient in this disorder. Patients often report particular difficulty hearing in busy environments; however, the core cognitive process-parsing of the auditory environment ('auditory scene analysis')-has been poorly characterized. In this cross-sectional study, we used customized perceptual tasks to assess two generic cognitive operations underpinning auditory scene analysis-sound source segregation and sound event grouping-in a cohort of 21 patients with posterior cortical atrophy, referenced to 15 healthy age-matched individuals and 21 patients with typical Alzheimer's disease. After adjusting for peripheral hearing function and performance on control tasks assessing perceptual and executive response demands, patients with posterior cortical atrophy performed significantly worse on both auditory scene analysis tasks relative to healthy controls and patients with typical Alzheimer's disease (all P  less then  0.05). Our findings provide further evidence of central auditory dysfunction in posterior cortical atrophy, with implications for our pathophysiological understanding of Alzheimer syndromes as well as clinical diagnosis and management.Polyunsaturated fatty acids (PUFAs) are critical for brain development and have been linked with neurodevelopmental outcomes. We conducted a population-based case control study in California to examine the association between PUFAs measured in mid-pregnancy serum samples and child autism spectrum disorder (ASD). ASD cases (n = 499) were identified through the Department of Developmental Services and matched to live-birth population controls (n = 502) on birth month, year (2010-2011), and sex. Crude and adjusted logistic regression models were used to examine associations. Secondary analyses examined ASD with and without co-occurring intellectual disability (ID; n = 67 and 432 respectively), and effect modification by sex and ethnicity. No clear patterns emerged, though there was a modest inverse association with the top quartile of linoleic acid (highest versus lowest quartile, adjusted OR = 0.74, 95% CI 0.49, 1.11; P for trend = 0.10). Lower levels of total and ω 3 PUFAs were associated with ASD with ID (lowest decile versus deciles 4-7, total PUFA adjusted OR = 2.78 95% CI 1.13, 6.82) but not ASD without ID. We did not observe evidence of effect modification by factors examined. Findings do not suggest a strong association between mid-pregnancy PUFA levels and ASD. Further work should consider associations with ASD with ID and in other time windows.It is well known that alcohol consumption is associated with type 2 diabetes mellitus. However, the association of age at initiation of alcohol consumption and duration of alcohol drinking with type 2 diabetes mellitus among Chinese adults is not fully understood. This study was based on data from the China Kadoorie Biobank, which included 512,712 participants aged 30-79 years who were living in China in 2004-2008. GSK583 A Cox proportional hazards model was used to estimate the association of AAI and drinking duration with type 2 diabetes. After adjustment for potential covariates, ages at alcohol initiation (AAIs) of 18.1-29.0 years, 29.1-39.0 years, and >39.0 years were associated with 22% (95% confidence interval (CI) 14, 30), 25% (95% CI 17, 33), and 32% (95% CI 24, 39) lower hazards of type 2 diabetes compared with abstaining, respectively. Drinking durations of 30.0 years were associated with 18% (95% CI 4, 33) and 20% (95% CI 3, 40) higher hazards of type 2 diabetes, compared with AAI 18.1-29.0 years and drinking duration less then 10.