a randomized clinical trial

The objective of the present study was to evaluate the effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production. Cows entering their second or greater lactation (n = 158) were randomly assigned to a control group (CON) or one of 2 treatment groups receiving either 6 × 106 IU (6VitD) or 12 × 106 IU (12VitD) cholecalciferol intramuscularly on d 275 ± 1.2 (SD) of gestation. Concentrations of serum total Ca (tCa), phosphate, and Mg were determined on 1, 2, 3, 5, 7, and 10 d in milk (DIM). For a subsample of 30 cows entering the third lactation (n = 10/group), these samples were analyzed for cholecalciferol, 25-hydroxycholecalciferol (25-OHD3), and 24,25-dihydroxycholecalciferol (24,25-[OH]2D3). In these cows, we also determined 1,25-dihydroxycholecalciferol (1,25-[OH]2D3), the biologically most active metabolite, on 1, 2, 3, and 5 DIM. Repeated measures ANOVA was performed to evaluate the effect of different dosages of cholecalciferol on blood minerals, vitamin D metabolites, and milk yield over the first 5 test days after calving. Binary outcomes such as retained placenta and metritis were analyzed using a chi-squared test. Although the 12VitD treatment increased tCa concentrations on 1, 2, and 3 DIM compared with CON, administration of 6VitD increased tCa concentrations only on 1 DIM. Compared with CON cows and 6VitD cows, 12VitD cows had greater serum phosphate concentration during the first 10 DIM. Furthermore, 6VitD cows had greater serum phosphate concentrations compared with CON cows. On the contrary, 12VitD cows had lower serum Mg concentrations during the first 10 DIM compared with CON and 6VitD cows. Cholecalciferol was increased by the treatment and decreased quickly until 10 DIM. In respect to 25-OHD3, the 6VitD treatment resulted in a 4.1-fold increase in comparison to the CON group, while a 6.5-fold increase was observed in 12VitD animals. The vitamin D metabolite 24,25-(OH)2D3 increased linearly with 25-OHD3 serum levels, resulting in the highest concentrations in the 12VitD group. An increase of 1,25-(OH)2D3 until 3 DIM was observed in all cows. However, this rise was most pronounced in the CON group. The incidence of retained placenta was 1.9%, 11.5%, and 29.6%, and that of metritis was 11.5%, 15.4%, and 31.5% for CON, 6VitD, and 12VitD cows, respectively. Although none of the treated cows exerted clinical signs of hypocalcemia, one cow in CON incurred clinical hypocalcemia. Cows of the 12VitD group had a lower milk yield over the first 5 monthly test days compared with the control and 6VitD group (42.2 ± 0.5, 42.0, ± 0.5 and 40.7 ± 0.5 kg for control cows, 6VitD cows and 12VitD cows, respectively). Although no negative side effects were observed in 6VitD cows, we do not recommend the general application of 6 × 106 IU cholecalciferol before calving as positive effects on calcium homeostasis were marginal and restricted to the first DIM. The present findings confirm that the application of 12 × 106 IU cholecalciferol negatively affected milk production on this farm

Postglacial expansion of the arctic keystone copepod calanus glacialis

Calanus glacialis, a major contributor to zooplankton biomass in the Arctic shelf seas, is a key link between primary production and higher trophic levels that may be sensitive to climate warming. The aim of this study was to explore genetic variation in contemporary populations of this species to infer possible changes during the Quaternary period, and to assess its population structure in both space and time. Calanus glacialis was sampled in the fjords of Spitsbergen (Hornsund and Kongsfjorden) in 2003, 2004, 2006, 2009 and 2012. The sequence of a mitochondrial marker, belonging to the ND5 gene, selected for the study was 1249 base pairs long and distinguished 75 unique haplotypes among 140 individuals that formed three main clades. There was no detectable pattern in the distribution of haplotypes by geographic distance or over time. Interestingly, a Bayesian skyline plot suggested that a 1000-fold increase in population size occurred approximately 10,000 years before present, suggesting a species expansion after the Last Glacial Maximum.GAME from the National Science Centre, the Polish Ministry of Science and Higher Education Iuventus Plus [IP2014 050573]; FCT-PT [CCMAR/Multi/04326/2013]; [2011/03/B/NZ8/02876

Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients

BACKGROUND: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. METHODS: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV(1 )94% of predicted) at three times over a three year period. RESULTS: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV(1), MEF(75/25%VC), and MEF(25%VC). The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. CONCLUSION: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease

Comparison of four mathematical models to analyze indicator-dilution curves in the coronary circulation

While several models have proven to result in accurate estimations when measuring cardiac output using indicator dilution, the mono-exponential model has primarily been chosen for deriving coronary blood/plasma volume. In this study, we compared four models to derive coronary plasma volume using indicator dilution; the mono-exponential, power-law, gamma-variate, and local density random walk (LDRW) model. In anesthetized goats (N = 14), we determined the distribution volume of high molecular weight (2,000 kDa) dextrans. A bolus injection (1.0 ml, 0.65 mg/ml) was given intracoronary and coronary venous blood samples were taken every 0.5–1.0 s; outflow curves were analyzed using the four aforementioned models. Measurements were done at baseline and during adenosine infusion. Absolute coronary plasma volume estimates varied by ~25% between models, while the relative volume increase during adenosine infusion was similar for all models. The gamma-variate, LDRW, and mono-exponential model resulted in volumes corresponding with literature, whereas the power-model seemed to overestimate the coronary plasma volume. The gamma-variate and LDRW model appear to be suitable alternative models to the mono-exponential model to analyze coronary indicator-dilution curves, particularly since these models are minimally influenced by outliers and do not depend on data of the descending slope of the curve only

Intraoperative Multispectral Fluorescence Imaging for the Detection of the Sentinel Lymph Node in Cervical Cancer: A Novel Concept

PURPOSE: Real-time intraoperative near-infrared fluorescence (NIRF) imaging is a promising technique for lymphatic mapping and sentinel lymph node (SLN) detection. The purpose of this technical feasibility pilot study was to evaluate the applicability of NIRF imaging with indocyanin green (ICG) for the detection of the SLN in cervical cancer. PROCEDURES: In ten patients with early stage cervical cancer, a mixture of patent blue and ICG was injected into the cervix uteri during surgery. Real-time color and fluorescence videos and images were acquired using a custom-made multispectral fluorescence camera system. RESULTS: Real-time fluorescence lymphatic mapping was observed in vivo in six patients; a total of nine SLNs were detected, of which one (11%) contained metastases. Ex vivo fluorescence imaging revealed the remaining fluorescent signal in 11 of 197 non-sentinel LNs (5%), of which one contained metastatic tumor tissue. None of the non-fluorescent LNs contained metastases. CONCLUSIONS: We conclude that lymphatic mapping and detection of the SLN in cervical cancer using intraoperative NIRF imaging is technically feasible. However, the technique needs to be refined for full applicability in cervical cancer in terms of sensitivity and specificity

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) is caused by mutations in the <it>CFTR </it>gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl^-channel, would improve the intestinal phenotype in CF mice.</p> <p>Methods</p> <p><it>Cftr^tm1UNC</it>(CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16<it>S </it>gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR.</p> <p>Results</p> <p>Crypt width in control CF mice was 700% that of WT mice (<it>P </it>< 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (<it>P </it>= 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (<it>P </it>= 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (<it>P </it>= 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (<it>P </it>< 0.001) and CF mice (<it>P </it>< 0.001). Lubiprostone enhanced small intestinal transit in WT mice (<it>P </it>= 0.024) but not in CF mice (<it>P </it>= 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels.</p> <p>Conclusions</p> <p>These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.</p

Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node

Purpose: At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection Methods: The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised. Results: Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy. Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection. © The Author(s) 2012

European Cystic Fibrosis Society standards of care: best practice guidelines

Specialised CF care has led to a dramatic improvement in survival in CF: in the last four decades, well above what was seen in the general population over the same period. With the implementation of newborn screening in many European countries, centres are increasingly caring for a cohort of patients who have minimal lung disease at diagnosis and therefore have the potential to enjoy an excellent quality of life and an even greater life expectancy than was seen previously. To allow high quality care to be delivered throughout Europe, a landmark document was published in 2005 that sets standards of care. Our current document builds on this work, setting standards for best practice in key aspects of CF care. The objective of our document is to give a broad overview of the standards expected for screening, diagnosis, pre-emptive treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support. For comprehensive details of clinical care of CF, references to the most up to date European Consensus Statements, Guidelines or Position Papers are provided in Table 1. We hope that this best practice document will be useful to clinical teams both in countries where CF care is developing and those with established CF centres

The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis

OBJECTIVE: To meta-analyse the diagnostic accuracy of US, CT, MRI and (1)H-MRS for the evaluation of hepatic steatosis. METHODS: From a comprehensive literature search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles were selected that investigated the diagnostic performance imaging techniques for evaluating hepatic steatosis with histopathology as the reference standard. Cut-off values for the presence of steatosis on liver biopsy were subdivided into four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30 and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and specificity were calculated. The natural-logarithm of the diagnostic odds ratio (lnDOR) was used as a single indicator of test performance. RESULTS: 46 articles were included. Mean sensitivity estimates for subgroups were 73.3-90.5% (US), 46.1-72.0% (CT), 82.0-97.4% (MRI) and 72.7-88.5% ((1)H-MRS). Mean specificity ranges were 69.6-85.2% (US), 88.1-94.6% (CT), 76.1-95.3% (MRI) and 92.0-95.7% ((1)H-MRS). Overall performance (lnDOR) of MRI and (1)H-MRS was better than that for US and CT for all subgroups, with significant differences in groups 1 and 2. CONCLUSION: MRI and (1)H-MRS can be considered techniques of choice for accurate evaluation of hepatic steatosi