Contrast media and cutaneous reactions. Part 2: Delayed hypersensitivity reactions to iodinated contrast media.

Contrast media (CM) are an indispensable part of modern medical imaging. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 covers the classification of CM, immediate hypersensitivity reactions to CM and the newly described condition, gadolinium deposition disease. Given that there has only been two case reports to our knowledge of a delayed adverse reaction to gadolinium-based CM, this second part will focus on cutaneous delayed reactions caused by iodinated CM (ICM). Delayed hypersensitivity reactions to ICM commonly present as maculopapular exanthems, but more rarely, they can manifest as fixed drug eruptions, acute generalized exanthematous pustulosis, drug-related eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis, symmetrical drug-related intertriginous and flexural exanthema, graft-versus-host disease, vasculitis and iododerma. Delayed reactions to ICM may be underdiagnosed, as cutaneous symptoms may be attributed to oral medications, particularly if patients are on multiple drugs.

Contrast media and cutaneous reactions. Part 1. Immediate hypersensitivity reactions to contrast media and gadolinium deposition.

Contrast media (CM) are commonly used worldwide to enhance the quality of imaging, which is invaluable for diagnostic accuracy. Adverse reactions to CM are uncommon, but frequently involve cutaneous symptoms. This two-part article reviews adverse events secondary to CM that are relevant to the practising dermatologist. Part 1 will classify CM, address immediate hypersensitivity reactions and review the newly described condition, gadolinium deposition disease. Part 2 will cover the delayed hypersensitivity reactions of iodinated contrast medium including severe cutaneous adverse reactions and iododerma.

pH sensing through a single optical fibre using SERS and CMOS SPAD line arrays.

Full exploitation of fibre Raman probes has been limited by the obstruction of weak Raman signals by background fluorescence of the sample and the intrinsic Raman signal of the delivery fibre. Here we utilised functionalised gold nanoshells (NS) to take advantage of the surface-enhanced Raman spectroscopy (SERS) effect to enhance the pH responsive spectrum of 4-mercaptobenzoic acid (MBA). However, the fibre background is still dominant. Using the photon arrival time-resolving capability of a CMOS single-photon avalanche diode (SPAD) based line sensor, we recover the SERS spectrum without a fibre background in a 10 s measurement. In this manner, pH sensing through a multimode fibre at a low excitation power that is safe for future in vivo applications, with short acquisition times (10 or 60 s), is demonstrated. A measurement precision of ± 0.07 pH units is thus achieved.

The development of chlorophyll-based markers in poultry diets to aid detection of fluorescent fecal contamination.

Incidents of foodborne illness associated with consuming undercooked or raw chicken are often linked to 2 causative pathogens: Campylobacter spp. or Salmonella spp. Numerous studies have shown that contamination of carcasses results when pathogens are transferred from the intestinal tract or fecal material on feet and feathers to the dressed carcass. Ultraviolet spectral imaging to detect surface fecal and ingesta contamination on poultry carcasses may provide a solution to aid detection. However, poultry diets do not provide sufficiently high levels of natural fluorophores for this system to be reliable. This study investigated the potential of chlorophyll-based feed additives to improve fluorescence of the feces and narrow the excitation and emission wavelengths to aid in the development of a simple visualization system. Twenty-four hens (Gallus gallus domesticus) were allocated at random to 1 of 4 treatments: control (C, no marker), Zn chlorophyllin, Mg chlorophyllin, or Fe chlorophyllin. All markers were incorporated into mash before pelleting at a rate of 1 g/kg of DM. The experiment consisted of two 4 × 4 Latin squares with each period consisting of 2 wk. Feces were collected and extracted in acetone:water (50:50; vol/vol) with fecal fluorescence emission spectra determined using a Jasco FP-6200 Spectrofluorometer with excitation at 382 nm. A main peak evolved at wavelength 670 nm with the total area under the peak used as fluorescence intensity. Following 7 d of marker supplementation, the 3 markers improved the fluorescence intensity by ×14.8, 12.8, and 6.9 for Fe, Mg, and Zn chlorophyllin, respectively, compared with the control. The addition of feces containing Mg chlorophyllin to chicken carcass increased detection of the feces compared with feces with no marker. Also, due to the plain background of chicken skin, a simple image at 675 nm with appropriate thresholds would allow detection of contaminated carcasses at the current slaughter line speed without the need of expensive hyperspectral imaging.

Performance and enteric methane emissions from housed beef cattle fed silage produced on pastures with different forage profiles.

Methane (CH4) produced by ruminants is a significant source of greenhouse gases from agriculture in the United Kingdom (UK), accounting for approximately 50% of the emissions in this sector. Ration modification is linked to changes in rumen fermentation and can be an effective means of CH4 abatement. In temperate climate countries, forage silage represents a major feed component for cattle during the housing period. The objective of this study was, therefore, to compare enteric CH4 emission from cattle offered silage produced from different types of grassland. Beef cattle, steers (n = 89) and heifers (n = 88) with average liveweight (LW) of 328 ± 57.1 kg were evaluated during two housing seasons (2016-2017 and 2017-2018) from November to April, at the Rothamsted Research North Wyke Farm Platform (UK). The treatments corresponded to three diet types, comprising silage harvested from three different pastures: MRG, monoculture of perennial ryegrass (PRG, Lolium perenne L.cv. AberMagic), bred to express the high-sugar phenotype; RG-WC, a mixed sward comprised of the same perennial ryegrass cultivar with white clover (Trifolium repens L.) with a target clover proportion of 30% as land cover; and permanent pasture (PP) dominated by PRG and a small number of non-introduced species. MRG and PP received 160-200 kg N/ha/year. Cattle were weighed every 30 days, and the enteric CH4 emission was determined using GreenFeed automated systems. No significant differences in enteric CH4 emission per head or per kg LW were observed between treatments. However, emission expressed per average daily gain (ADG) in LW was greater (P < 0.001) for MRG compared with RG-WC and PP, at 270, 248 and 235 g CH4/kg ADG, respectively. This related to a lower ADG (P = 0.041) for the animals fed MRG silage compared with RG-WC and PP which were similar, with respective values of 0.67, 0.71 and 0.74 kg/day. The forages compared in this study showed little or no potential to reduce enteric CH4 emission when fed as silage to growing beef cattle during the winter housing period.

The impact of feeding supplemental minerals to sheep on the return of micronutrients to pasture via urine and faeces.

The form (organic versus inorganic) of minerals (Se, Zn, Cu and Mn), supplemented to sheep (Charolais × Suffolk-Mule (mean weight = 57 ± 2.9 kg) at two European industrial doses, on the return of micronutrients to pasture via nutrient partitioning and composition in sheep urine and faeces was investigated. This gave four treatments in total with 6 animals per treatment (n = 24). The form of the supplemented minerals did not influence the excretory partitioning of micronutrients (Se, Zn, Cu and Mn) between urine and faeces, nor on their concentrations in the excreta. The two doses trialed however, may influence the Se flux in the environment through altering the ratios of Se:P and Se:S ratios in the faeces and Se:S ratio in the urine. Administration of the mineral supplements also improved the retention of P in sheep reducing its excretion via urine. Although the concentrations of readily bioavailable micronutrients in the faeces were not affected by the mineral forms, there were differences in the more recalcitrant fractions of Se, Zn and Cu (as inferred via a sequential extraction) in faeces when different forms of supplemental minerals were offered. The potential impact of these differences on micronutrient flux in pasture requires further investigation.

Data to identify key drivers of animal growth and carcass quality for temperate lowland sheep production systems.

With the growing demand for animal-sourced foods and a serious concern over climate impacts associated with livestock farming, the sheep industry worldwide faces the formidable challenge of increasing the overall product supply while improving its resource use efficiency. As an evidence base for research to identify key drivers behind animal growth and carcass quality, longitudinal matched data of 741 ewes and 2978 lambs were collected at the North Wyke Farm Platform, a farm-scale grazing trial in Devon, UK, between 2011 and 2019. A subset of these data was subsequently analysed in a study to assess the feasibility of using a lamb's early-life liveweight as a predictor of carcass quality [1]. The data also have the potential to offer insight into key performance indicators (KPIs) for the sheep industry, or what variables farmers should measure and target to increase profitability.

Using a lamb's early-life liveweight as a predictor of carcass quality.

The commercial value of lamb carcasses is primarily determined by their weight and quality, with the latter commonly quantified according to muscle coverage and fat depth. The ability to predict these quality scores early in the season could be of substantial value to sheep producers, as this would enable tailored flock management strategies for different groups of animals. Existing methods of carcass quality prediction, however, require either expensive equipment or information immediately before slaughter, leaving them unsuitable as a decision support tool for small to medium-scale enterprises. Using seven-year high-resolution data from the North Wyke Farm Platform, a system-scale grazing trial in Devon, UK, this paper investigates the feasibility of using a lamb's early-life liveweight to predict the carcass quality realised when the animal reaches the target weight. The results of multinomial regression models showed that lambs which were heavier at weaning, at 13 weeks of age, were significantly more likely to have leaner and more muscular carcasses. An economic analysis confirmed that these animals produced significantly more valuable carcasses at slaughter, even after accounting for seasonal variation in lamb price that often favours early finishers. As the majority of heavier-weaned lambs leave the flock before lighter-weaned lambs, an increase in the average weaning weight could also lead to greater pasture availability for ewes in the latter stage of the current season, and thus an enhanced ewe condition and fertility for the next season. All information combined, therefore, a stronger focus on ewes' nutrition before and during lactation was identified as a key to increase system-wide profitability.

The accuracy of standard multiple sclerosis MRI brain sequences for the diagnosis of optic neuropathy.

BACKGROUND: Detection of optic neuropathy on MRI has potential implications for the diagnosis and management of Multiple Sclerosis (MS). OBJECTIVE: This study assessed the accuracy of T2 sagittal MRI brain for detection of optic neuropathy, compared to coronal STIR orbit. METHODS AND MATERIALS: Retrospective single-center blinded diagnostic accuracy study of 100 consecutive patients who underwent both T2 sagittal brain and coronal STIR orbit MRI. All were performed on 1.5T scanners. T2 sagittal slice thickness was 4 mm for the first 50 patients (group1) and 3 mm for the second 50 (group2). The MRIs were reviewed in a blinded fashion to determine the presence of optic neuropathy. Coronal STIR orbit sequences were considered the diagnostic reference standard. RESULTS: The sensitivity of T2 sagittal brain imaging for ON was 44% in group 1 and 85% in group 2 (p = 0.007). The specificities were 98% and 97% respectively (p = 0.9). Sensitivity was poorest for evaluation of the intraorbital nerve segment (56% grp1, 69% grp2, p = 0.4). CONCLUSION: T2 sagittal MRI brain has high specificity for the detection of optic neuropathy when compared to coronal STIR orbit. Sensitivity is increased when slice thickness is reduced, but remains poor for evaluation of the intraorbital segment.

Synthetic and living micropropellers for convection-enhanced nanoparticle transport.

Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable "living ferrofluid" by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.

Preoperative CT in patients with surgically resectable pancreatic adenocarcinoma: does the time interval between CT and surgery affect survival?

PURPOSE: The preoperative imaging-to-surgery time interval (ISI) influences the risk of unexpected progression (UP) found at surgery for pancreatic adenocarcinoma. We aimed to assess whether ISI influences disease recurrence and/or survival. METHODS AND MATERIALS: A single-institution, ethics board-approved retrospective analysis of all patients who underwent attempted resection of pancreatic (PDAC) or periampullary adenocarcinoma (AmpAC) between 1st January 2010 and 31st December 2015 was performed. All patients underwent preoperative abdominal computed tomography (CT). Exclusion criteria were borderline resectable disease and neoadjuvant chemo/radiotherapy. Patients were followed up until 30th June 2016. The population was divided into ISI ≥/<25 days. Kaplan-Meier and Cox regression survival analyses were performed. RESULTS: 239 patients underwent surgical exploration. UP was found in 29 (12.1%) and these patients had longer ISI (median 46 vs. 29 days, p < 0.05). When intention-to-treat analysis was performed, there was no difference in overall survival (OS) between patients with ISI ≥/<25. In those who underwent resection, ISI did not influence disease-free survival (DFS) or OS for PDAC (n = 174). For AmpAC (n = 36), ISI ≥ 25 days was associated with longer OS (p < 0.05) but did not influence DFS. Longer ISI was independently associated with improved OS on regression analysis for AmpAC. CONCLUSION: Performing surgery for resectable pancreatic adenocarcinoma within 25 days of abdominal CT reduces the chance of UP but does not confer a survival benefit. For those who undergo resection of AmpAC, a longer ISI was associated with longer OS. This probably represents a more biologically indolent disease in this cohort.

Highlights from Faraday Discussion FDSERS17: Surface Enhanced Raman Scattering - SERS, Glasgow, UK, 30th August-1st September 2017.

The 2017 Faraday Discussion on Surface Enhanced Raman Scattering (SERS) attracted more than a hundred delegates from a broad spectrum of backgrounds and experience levels, bringing together leading scientists involved in the long living field of SERS. The meeting gave an overview of the liveliness of the topic, characterised by open questions and fascinating science still to discover. In the following, we discuss the topics covered during this meeting and briefly highlight the content of each presentation.

Extracellular matrix microarrays to study inductive signaling for endoderm specification.

During tissue development, stem and progenitor cells are faced with fate decisions coordinated by microenvironmental cues. Although insights have been gained from in vitro and in vivo studies, the role of the microenvironment remains poorly understood due to the inability to systematically explore combinations of stimuli at a large scale. To overcome such restrictions, we implemented an extracellular matrix (ECM) array platform that facilitates the study of 741 distinct combinations of 38 different ECM components in a systematic, unbiased and high-throughput manner. Using embryonic stem cells as a model system, we derived definitive endoderm progenitors and applied them to the array platform to study the influence of ECM, including the interactions of ECM with growth factor signaling, on the specification of definitive endoderm cells towards the liver and pancreas fates. We identified ECM combinations that influence endoderm fate decisions towards these lineages, and demonstrated the utility of this platform for studying ECM-mediated modifications to signal activation during liver specification. In particular, defined combinations of fibronectin and laminin isoforms, as well as combinations of distinct collagen subtypes, were shown to influence SMAD pathway activation and the degree of hepatic differentiation. Overall, our systematic high-throughput approach suggests that ECM components of the microenvironment have modulatory effects on endoderm differentiation, including effects on lineage fate choice and cell adhesion and survival during the differentiation process. This platform represents a robust tool for analyzing effects of ECM composition towards the continued improvement of stem cell differentiation protocols and further elucidation of tissue development processes. STATEMENT OF SIGNIFICANCE: Cellular microarrays can provide the capability to perform high-throughput investigations into the role of microenvironmental signals in a variety of cell functions. This study demonstrates the utility of a high-throughput cellular microarray approach for analyzing the effects of extracellular matrix (ECM) in liver and pancreas differentiation of endoderm progenitor cells. Despite an appreciation that ECM is likely involved in these processes, the influence of ECM, particularly combinations of matrix proteins, had not been systematically explored. In addition to the identification of relevant ECM compositions, this study illustrates the capability of the cellular microarray platform to be integrated with a diverse range of cell fate measurements, which could be broadly applied towards the investigation of cell fate regulation in other tissue development and disease contexts.

Sequence analysis of the Lactobacillus plantarum bacteriophage PhiJL-1.

The complete genomic sequence of a Lactobacillus plantarum virulent phage PhiJL-1 was determined. The phage possesses a linear, double-stranded, DNA genome consisting of 36,677 bp with a G+C content of 39.36%. A total of 52 possible open reading frames (ORFs) were identified. According to N-terminal amino acid sequencing and bioinformatic analyses, proven or putative functions were assigned to 21 ORFs (41%), including 5 structural protein genes. The PhiJL-1 genome shows functionally related genes clustered together in a genome structure composed of modules for DNA replication, DNA packaging, head and tail morphogenesis, and lysis. This type of modular genomic organization was similar to several other phages infecting lactic acid bacteria. The structural gene maps revealed that the order of the head and tail genes is highly conserved among the genomes of several Siphoviridae phages, allowing the assignment of probable functions to certain uncharacterized ORFs from phage PhiJL-1 and other Siphoviridae phages.

Effect of breed and pasture type on methane emissions from weaned lambs offered fresh forage.

To investigate the extent to which enteric methane (CH4) emissions from growing lambs are explained by simple body weight and diet characteristics, a 2 × 2 Latin square changeover design experiment was carried out using two sheep breeds and two fresh pasture types. Weaned lambs of two contrasting breed types were used: Welsh Mountain (WM, a small, hardy hill breed) and Welsh Mule × Texel (TexX, prime lamb) (n = 8 per breed). The lambs were zero-grazed on material cut from recently reseeded perennial ryegrass and extensively managed permanent pasture. In each experimental period, individual ad libitum dry matter intake (DMI) was determined indoors following an adaptation period of 2 weeks, and CH4 emissions were measured individually in open-circuit respiration chambers over a period of 3 days. Although total daily CH4 emissions were lower for the WM lambs than for the TexX lambs (13·3 v. 15·7 g/day, respectively) when offered fresh forage, the yield of CH4 per unit DMI was similar for the two breed types (16·4 v. 17·7 g CH4/kg DMI). Total output of CH4 per day was higher when lambs were offered ryegrass compared with permanent pasture (16·1 v. 12·9 g/day, respectively), which was probably driven by differences in DMI (986 v. 732 g/day). Methane emissions per unit DMI (16·4 v. 17·7 g CH4/kg DMI) and proportion of gross energy intake excreted as CH4 (0·052 v. 0·056 MJ/MJ) were both higher on the permanent pasture. No forage × breed type interactions were identified. The results indicate that forage type had a greater impact than breed type on CH4 emissions from growing weaned lambs. It can be concluded that when calculating CH4 emissions for inventory purposes, it is more important to know what forages growing lambs are consuming than to know what breeds they are.

Can live weight be used as a proxy for enteric methane emissions from pasture-fed sheep?

To test the hypothesis that sheep live weight (LW) could be used to improve enteric methane (CH4) emission calculations, mature ewes of 4 different breeds representative of the UK sheep industry were studied: Welsh Mountain, Scottish Blackface, Welsh Mule and Texel (n = 8 per breed). The ewes were housed and offered ad libitum access to fresh cut pasture of three different types, varying in digestibility: (a) a relatively high digestibility monoculture of perennial ryegrass (Lolium perenne), (b) a medium digestibility permanent pasture comprising a range of grass species, and (c) a relatively low digestibility native grassland pasture comprising mainly Molinia caerulea. Individual LW, feed dry matter intake (DMI), and CH4 emissions in chambers were measured. The linear functional relationship between DMI and CH4 emissions was positive (r = 0.77) with little breed effect. The relationships between LW and DMI, and LW and CH4 emissions were also positive but weaker, regardless of pasture type. It is concluded that change to LW was a poor indicator of DMI and has limited value in the prediction of enteric CH4 emissions from mature ewes.

Effects of cyclic nucleotides on estradiol binding in human endometrium.

The addition of molybdate to intact or homogenized cells of the endometrial adenocarcinoma line HEC-1 during incubation with [3H]estradiol ([3H]E2) at 4 C causes substantial increases in cytoplasmic E2 binding levels. A similar effect can be observed in homogenates of normal human endometrium. These effects of molybdate appear to involve activation of E2-binding sites. Fractionation of the homogenates and recombination of different fractions revealed that activation of specific E2-binding sites by by MoO4= requires cytosolic factors as well as factors associated with the cell membrane. In homogenates of neoplastic cells (HEC-1) and normal endometrium, the addition of ATP, GTP, or cGMP was also found to increase E2 binding to levels as high as those obtained by the addition of MoO4=. In contrast, the addition of cAMP was found to lower specific E2 binding levels and to counteract the effects of MoO4=, ATP, GTP, and cGMP. Levels of intracellular cAMP and cGMP can change rapidly in cells in culture. Since cGMP causes E2 binding levels to increase while cAMP causes them to decrease, changes in the levels of these two cyclic nucleotides may explain the fluctuation in concentrations of specific estrogen binders that we have previously reported to occur in cultured endometrial cells.

Major histocompatibility complex restriction and transplantation immunity. A possible solution to the allograft problem.

Studies of the survival of weakly histoincompatible skin grafts in which the Langerhans' cells (LC)5 have been replaced with major histocompatibility complex (MHC)-compatible or incompatible LC, as well as studies of the fate of cultured endocrine allografts in MHC-compatible and incompatible mice and rats, indicate that allografts are only recognized as foreign if they possess donor macrophages (or cells of this family), or if antigen presenting cells MHC-compatible with the graft can be provided by the host.

Sodium salicylate centrally augments ventilation through cholinergic mechanisms.

Several different stimuli, including hydrogen ions, may exert their effect on central ventilatory control through cholinergic mechanisms. Salicylates are known to be central respiratory stimulants. Therefore this study explored whether the ventilatory effect of sodium salicylate (SAL) is through cholinergic mechanisms. Ventriculocisternal perfusion was used in spontaneously breathing anesthetized (pentobarbital sodium, 30 mg/kg) mongrel dogs to study the effects of SAL (50 mM), atropine (ATR, 4.8 mM), and SAL-ATR on ventilation. After 15 min of perfusion with mock cerebrospinal fluid, each test agent was perfused for 15 min at a rate of 1 ml/min. Cardiovascular and ventilatory parameters were monitored. Values at 15 min of test agent perfusion were compared with values at 15 min of mock cerebrospinal fluid perfusion, with each animal used as its own control. Body temperature was kept between 37.5 and 39.0 degrees C. Perfusion with SAL increased minute ventilation (VE) by 54% (P less than 0.005) and respiratory frequency by 50% (P less than 0.005). Tidal volume was not changed, but mean inspiratory flow rate increased (P less than 0.05). Perfusion with ATR decreased VE by 22% (P less than 0.1), and perfusion with SAL-ATR decreased VE by 20% (P = 0.01). No significant cardiovascular changes were noted in any group. We conclude that SAL increases VE centrally, primarily by increasing respiratory frequency. Because ATR blocked this effect, cholinergic mechanisms are probably involved in the salicylates' central stimulation of ventilation.