Acromegaly is characterized by an excess of growth hormone (GH) and insulin like growth-factor 1 (IGF1), and it is strongly associated with cardiovascular diseases (CVD). Both acute and long-lasting ...pro-inflammatory effects have been attributed to IGF1. Previous results suggest the presence of systemic inflammation in treated patients. Here we assessed the association between treatment of acromegaly, systemic inflammation and vascular function.
Ex vivo cytokine production and circulating inflammatory markers were assessed in peripheral blood from treated and untreated acromegaly patients (N = 120), and compared them with healthy controls. A more comprehensive prospective inflammatory and vascular assessment was conducted in a subgroup of six treatment-naive patients with follow-up during treatment.
Circulating concentrations of VCAM1, E-selectin and MMP2 were higher in patients with uncontrolled disease, whereas the concentrations of IL18 were lower. In stimulated whole blood, cytokine production was skewed towards a more pro-inflammatory profile in patients, especially those with untreated disease. Prospective vascular measurements in untreated patients showed improvement of endothelial function during treatment.
Acromegaly patients are characterized by a pro-inflammatory phenotype, most pronounced in those with uncontrolled disease. Treatment only partially reverses this pro-inflammatory bias. These findings suggest that systemic inflammation could contribute to the increased risk of CVD in acromegaly patients.
•Acromegaly patients are characterized by a pro-inflammatory phenotype.•This phenotype is most pronounced in those with uncontrolled disease.•Treatment only partially reverses this pro-inflammatory phenotype.•Systemic inflammation could contribute to the increased risk of CVD in acromegaly.
To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development.
A ...double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at </=9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG n=80) or fish oil and fungal oil (fish/fungal n = 82) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha-linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament.
AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated.
These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha-linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth.infant development, breast feeding, infant formula, long-chain polyunsaturated fatty acids, docosahexaenoic acid.
To discern whether the characteristics and outcome of invasive aspergillosis in liver transplant recipients have evolved during the past decade, 26 patients who underwent transplantation during ...1990–1995 (known as “the earlier cohort”) were compared with 20 patients who underwent transplantation during 1998–2001 (known as “the later cohort”). Twenty-three percent of the Aspergillus infections in the earlier cohort occurred ⩾90 days after transplantation, compared with 55% of such infections in the later cohort (P =.026). The earlier cohort was significantly more likely to have disseminated infection (P =.034) and central nervous system (CNS) involvement (P =.0004) than was the later cohort. The mortality rate was significantly higher for the earlier cohort (92%) than for the later cohort (60%; P =.012). Only disseminated infection (not the year of transplantation) approached statistical significance as an independent predictor of outcome. In the current era, invasive aspergillosis occurs later in the posttransplantation period, is less likely to be associated with CNS infection, and is associated with a lower mortality rate, compared with invasive aspergillosis in the early 1990s.
The mechanical environment of the skeleton plays an important role in the establishment and maintenance of structurally competent bone. Biophysical signals induced by mechanical loading elicit a ...variety of cellular responses in bone cells, however, little is known about the underlying mechanotransduction mechanism. We hypothesized that bone cells detect and transduce biophysical signals into biological responses via a mechanism requiring annexin V (AnxV). AnxV, a calcium-dependent phospholipid binding protein, has several attributes, which suggest it is ideally suited for a role as a mechanosensor, possibly a mechanosensitive ion channel. These include the ability to function as a Ca
2+ selective ion channel, and the ability to interact with both extracellular matrix proteins and cytoskeletal elements. To test the hypothesis that AnxV has a role in mechanosensing, we studied the response of osteoblastic cells to oscillating fluid flow, a physiologically relevant physical signal in bone, in the presence and absence of AnxV inhibitors. In addition, we investigated the effects of oscillating flow on the cellular location of AnxV. Oscillating fluid flow increased both Ca
2+
i levels and c-fos protein levels in osteoblasts. Disruption of AnxV with blocking antibodies or a pharmacological inhibitor, K201 (JTV-519), significantly inhibited both responses. Additionally, our data show that the cellular location of AnxV was modulated by oscillating fluid flow. Exposure to oscillating fluid flow resulted in a significant increase in AnxV at both the cell and nuclear membranes. In summary, our data suggest that AnxV mediates flow-induced Ca
2+ signaling in osteoblastic cells. These data support the idea of AnxV as a Ca
2+ channel, or a component of the signaling pathway, in the mechanism by which mechanical signals are transduced into cellular responses in the osteoblast. Furthermore, the presence of a highly mobile pool of AnxV may provide cells with a powerful mechanism by which cellular responses to mechanical loading might be amplified and regulated.
Methods: We analyzed data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R and K656N) of LEPR with body mass index (BMI; kg/m2) and ...waist circumference (WC). A total of 3263 related and unrelated subjects from diverse ethnic backgrounds including African-American, Caucasian, Danish, Finnish, French Canadian and Nigerian were studied. We tested effects of individual alleles, joint effects of alleles at multiple loci, epistatic effects among alleles at different loci, effect modification by age, sex, diabetes and ethnicity, and pleiotropic genotype effects on BMI and WC. Results: We found that none of the effects were significant at the 0.05 level. Heterogeneity tests showed that the variations of the non-significant effects are within the range of sampling variation. Conclusions: We conclude that, although certain genotypic effects could be population-specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or WC in the overall population.
BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal ...and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice.
Most observers in behaviour studies are aware of relevant information about the animals being observed. We investigated whether observer expectations influence subjective scoring methods during a ...class practicum. Veterinary students were trained in recording negative and positive interactions between pigs, in scoring the degree of panting in cattle and in applying qualitative behaviour assessment (QBA) using a fixed set of terms for assessing hens' behaviour. The students applied these methods in three trials in which they were shown duplicated video recordings of the same animals: the original and a slightly modified version (to prevent recognition at second viewing). When scoring the duplicated recordings they were told either correct or false information about the conditions in which the animals had been filmed. The false information reflected plausible study scenarios in ethology and was used to create expectations about the outcome. As in reality the students scored the identical behaviour twice, the difference in the scores for the original and modified recordings reflects expectation bias due to providing different contextual information. In all trials there was evidence of expectation bias: students scored the ratio of positive to negative interactions higher when told that the observed pigs had been selected for high social breeding value, they scored cattle panting higher when told that the ambient temperature was 5°C higher than in reality, and in the QBA they indicated more positive and fewer negative emotions when told that the hens were from an organic instead of a conventional farm. The magnitude of the bias in the QBA trial was related to the opinion of the students about hen welfare in organic versus conventional farms. Although veterinary students may not be representative of practising ethologists, these findings do indicate that observer bias could influence subjective scores of animal behaviour and welfare.
•Blinding observers is not common in ethology.•Subjective scoring methods are commonly used in ethology.•Expectation bias during subjective outcome assessments was demonstrated.•Observer expectations may invalidate subjective recordings of behaviour.
Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse ...summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
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