What's new in atopic eczema? An analysis of systematic reviews published in 2019. Part 2: treatment.

This review forms part of a series of annual evidence updates on atopic eczema (AE), and provides a summary of key findings from systematic reviews (SRs) published or indexed in 2019 related to AE treatment. Several SRs assessed the efficacy of topical corticosteroids (TCS), topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors and topical Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors. However, there is a lack of good-quality trials comparing topical treatment agents with TCS, which remain the standard of care for patients with AE. Most of the included trials lack meaningful comparisons as they used vehicle as a comparator. There is also lack of harmonization of outcome measures for AE across studies. Large, well-designed RCTs are needed to further determine whether any specific emollients offer superior benefit. There is evidence highlighting limited benefit of oral H1 antihistamines as 'add-on' therapy to topical treatment of eczema. Mycophenolate mofetil may have a role in patients with refractory AE. Among biologic therapies, most of the efficacy data relate to dupilumab. Furthermore, there is growing evidence for the efficacy and safety of systemic JAK/STAT pathway inhibitors, but the existing data are of low quality.

Thematic synthesis of the experiences of people with hidradenitis suppurativa: a systematic review.

BACKGROUND: Although hidradenitis suppurativa (HS) is known to affect quality of life, little summative knowledge exists on how HS impacts people living with the condition. OBJECTIVES: To synthesize experiences of people with HS within published qualitative research. METHODS: Searches on databases MEDLINE, PsycINFO, Embase and CINAHL were conducted on 17 April 2020. Two independent reviewers screened 5512 publications. Study quality was assessed using the National Institute for Health and Care Excellence quality appraisal checklist for qualitative studies. Thematic synthesis generated descriptive and analytic themes. RESULTS: Fourteen studies were included: four studies fulfilled most quality criteria, eight fulfilled some quality criteria, and two fulfilled few quality criteria. There were three final themes. (i) Putting the brakes on life. The physical, psychological and social consequences of HS resulted in people missing out on multiple life events. This could have a cumulative effect that influences the trajectory of someone's life. (ii) A stigmatized identity: concealed and revealed. People try to conceal their HS, visually and verbally, but this results in anticipation and fear of exposure. Social support and psychological acceptance helped people cope. Connecting to others with HS may have a specific role in preserving a positive self-identity. (iii) Falling through the cracks. Delayed diagnosis, misdiagnosis and lack of access to care were reported. People felt unheard and misunderstood by healthcare professionals, and healthcare interactions could enhance feelings of shame. CONCLUSIONS: There need to be improvements to clinical care to allow people with HS to live their life more fully.

Dermatological games: Part 2. What has changed 40 years on?

In this two-part report, we review and critically appraise 'Dermatological games' by J. A. Cotterill, a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. Part 1 described and critically appraised the educational value of Cotterill's original list of games in relation to how they apply to dermatology practice. In Part 2, a list of new 'games' that might be observed in current dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his article remains relevant to dermatology practice and training today is scrutinized, in order to stimulate discussion and improve patient care.

Dermatological games: Part 1. Original description and critique.

'Dermatological games' by J. A. Cotterill was a seminal article published in 1981, which attempted to explain the interaction between dermatologists and patients using Berne's game theory. In Part 1 of this series of two reviews, we review Cotterill's original list of games and how they applied to dermatology in the context of when they were written. We then critically appraise Cotterill's article and arguments. Although the article was deliberately provocative, we found Cotterill's arguments to be well-structured and logical, and the 'games' described are well-conceived. Cotterill's candid analysis of doctors' motivations and the potential impact on the patient is refreshing and insightful. It is striking that, 40 years on, many of the original 'games' described remain recognizable in current practice. In Part 2, a list of new 'games' that might be observed in modern dermatological practice is introduced. The relevance of Cotterill's paper and an explanation for why his educational article remains relevant to dermatology practice and training today is scrutinized in order to stimulate discussion, promote education and improve patient care.

Effects of clay on toxin binding capacity, ruminal fermentation, diet digestibility, and growth of steers fed high-concentrate diets.

Three experiments were conducted to determine the effect of increasing concentrations of a smectite clay on toxin binding capacity, ruminal fermentation, diet digestibility, and growth of feedlot cattle. In Exp. 1, 72 Angus × Simmental steers were blocked by BW (395 ± 9.9 kg) and randomly allotted to 3 treatments (4 pens/treatment and 6 steers/pen) to determine the effects of increasing amounts of clay (0, 1, or 2%) on performance. The clay was top-dressed on an 80% concentrate diet at a rate of 0, 113, or 226 g/steer daily to achieve the 0, 1, and 2% treatments, respectively. Steers were slaughtered at a target BW of 606 kg. In Exp. 2, 6 steers (596 ± 22.2 kg initial BW) were randomly allotted to the same 3 treatments in a replicated 3 × 3 Latin square design (21-d periods) to determine the effects of increasing amounts of clay on ruminal pH, VFA, and nutrient digestibility. In Exp. 3, 150 mg of clay was incubated in 10 mL of rumen fluid with 3 incremental concentrations (6 replicates per concentration) of aflatoxin B (AFB) or ergotamine tartate (ET) to determine binding capacity. During the first 33-d period, there was a quadratic effect of clay on ADG ( < 0.01) and G:F ( < 0.01), increasing from 0 to 1% clay and then decreasing from 1 to 2% clay. However, during the second 30-d period, clay linearly decreased ADG and G:F ( ≤ 0.03) and overall ADG, DMI, and G:F were not impacted ( ≥ 0.46). Clay linearly decreased marbling score ( = 0.05). Hepatic enzyme activity did not differ among treatments on d 0 or at slaughter ( ≥ 0.15). Clay linearly decreased ruminal lactate and propionate, linearly increased formate and the acetate:propionate ratio ( ≤ 0.04), and tended ( = 0.07) to linearly increase butyrate. Clay tended to linearly increase ( = 0.06) OM and CP apparent digestibility. Ruminal pH, urine pH, and other digestibility measures did not differ among treatments ( ≥ 0.15). Clay was able to effectively bind AFB and ET at concentrations above the normal physiological range (52 and 520 µg/mL), but proportional adsorption was decreased to 35.5 and 91.1% at 5,200 µg/mL ( < 0.01) for AFB and ET, respectively. In conclusion, clay effectively binds ruminal toxins, decreases ruminal lactate, and improves performance only during adaptation to a high-concentrate feedlot diet.

Using Kamlet-Taft solvent descriptors to explain the reactivity of anionic nucleophiles in ionic liquids.

In this paper, we report the effect of ionic liquids on substitution reactions using a variety of anionic nucleophiles. We have combined new studies of the reactivity of polyatomic anions, acetate, trifuoroacetate, cyanide, and thiocyanide, with our previous studies of the halides in [C4C1py][Tf2N], [C4C1py][TfO], and [C4C1im][Tf2N] (where [C4C1im]+ is 1-butyl-3-methylimidazolium and [C4C1py]+ is 1-butyl-1-methylpyrrolidinium) and compared their reactivities, k2, to the same reactions in the molecular solvents dichloromethane, dimethylsulfoxide, and methanol. The Kamlet-Taft solvent descriptors (alpha, beta, pi) have been used to analyze the rates of the reactions, which were found to have a strong inverse dependency on the alpha value of the solvent. This result is attributed to the ability of the solvent to hydrogen bond to the nucleophile, so reducing its reactivity. The Eyring activation parameters (DeltaH++ and DeltaS++), while confirming the reaction mechanism, do not offer obvious correlations with the Kamlet-Taft solvent descriptors.

Acetyl nitrate nitrations in [bmpy][N(Tf)2] and [bmpy][OTf], and the recycling of ionic liquids.

In this work we have examined the nitration by acetyl nitrate of a range of activated and deactivated aromatic substrates in two ionic liquids and compared the results to the same reaction in dichloromethane. Both ionic liquids are stable to the reaction conditions, and in both ionic liquids the yields of reaction are higher after unit time than the same reactions in dichloromethane, although the regioselectivity is little affected by solvent choice. This result gives further support to the suggestion that in the ionic liquid, acetyl nitrate dissociates to give the nitronium ion, and that this is the effective nitrating agent here. However, it is shown that [bmpy][N(Tf)(2)] is a better solvent for aromatic nitration than [bmpy][OTf]. This is due to the ease of formation of nitronium ion in the former ionic liquid, and is consistent with the fact that [bmpy][N(Tf)(2)] is a weaker hydrogen bond acceptor solvent than [bmpy][OTf]. Finally, a method by which [bmpy][N(Tf)(2)] may be recovered and reused for aromatic nitration has been demonstrated.

Precise temperature control in microfluidic devices using Joule heating of ionic liquids.

Microfluidic devices for spatially localised heating of microchannel environments were designed, fabricated and tested. The devices are simple to implement, do not require complex manufacturing steps and enable intra-channel temperature control to within +/-0.2 degrees C. Ionic liquids held in co-running channels are Joule heated with an a.c. current. The nature of the devices means that the internal temperature can be directly assessed in a facile manner.

Nucleophilicity in ionic liquids. 3. Anion effects on halide nucleophilicity in a series of 1-butyl-3-methylimidazolium ionic liquids.

We have continued the study of halide nucleophilicity in ionic liquids, concentrating on the effect of changing the anion ([BF(4)](-), [PF(6)](-), [SbF(6)](-), [OTf](-), and [N(Tf)(2)](-)) when the cation is [bmim](+) (where bmim = 1-butyl-3-methylimidazolium). It was found that the nucleophilicities of all the halides were lower in all of the ionic liquids than in dichloromethane. Changing the anion affected the order of halide nucleophilicity, e.g., in [bmim][BF(4)] the order of nucleophilicity was Cl(-)>Br(-)>I(-) while in [bmim][N(Tf)(2)] the order was Cl(-)

Manipulating solute nucleophilicity with room temperature ionic liquids.

In this work we report the effect of ionic liquids on a class of charge-neutral nucleophiles. We have studied the reactions of (n)butylamine, di-(n)butylamine, and tri-(n)butylamine with methyl p-nitrobenzenesulfonate in [bmpy][N(Tf)(2)], [bmpy][OTf], and [bmim][OTf] (bmpy = 1-butyl-1-methylpyrrolidinium; bmim = 1-butyl-3-methylimidazolium) and compared their reactivities, k(2), to those for the same reactions in the molecular solvents dichloromethane and acetonitrile. It was shown that all of the amines are more nucleophilic in the ionic liquids than in the molecular solvents studied in this work. Comparison is also made with the effect of ionic liquids on the reactivity of chloride ions, which are deactivated in ionic liquids. The Eyring activation parameters revealed that changes in the activation entropies are largely responsible for the effects seen. This can be explained in part by the differing hydrogen-bonding properties, as shown by the Kamlet-Taft solvent parameters, of each of these solvents and the formation of hydrogen bonds between the solvents and the nucleophiles.

Aromatic nitrations in ionic liquids: the importance of cation choice.

Aromatic substrates can be nitrated in high yields and with efficient use of the nitrating agent in ionic liquids, although a suitably inert ionic liquid cation must be used.

Nucleophilicity in ionic liquids. 2.(1) Cation effects on halide nucleophilicity in a series of bis(trifluoromethylsulfonyl)imide ionic liquids.

In this work, the nucleophilicities of chloride, bromide, and iodide have been determined in the ionic liquids [bmim][N(Tf)(2)], [bm(2)im][N(Tf)(2)], and [bmpy][N(Tf)(2)] (where bmim = 1-butyl-3-methylimidazolium, bm(2)im = 1-butyl-2,3-dimethylimidazolium, bmpy = 1-butyl-1-methylpyrrolidinium, and N(Tf)(2) = bis(trifluoromethylsulfonyl)imide). It was found that in the [bmim](+) ionic liquid, chloride was the least nucleophilic halide, but that changing the cation of the ionic liquid affected the relative nucleophilicities of the halides. The activation parameters DeltaH(), DeltaS(), and DeltaG() have been estimated for the reaction of chloride in each ionic liquid, and compared to a similar reaction in dichloromethane, where these parameters were found for reaction by both the free ion and the ion pair.

The sedimentary structure of linear sand dunes

Linear sand dunes--dunes that extend parallel to each other rather than in star-like or crescentic forms--are the most abundant type of desert sand dune. But because their development and their internal structure are poorly understood, they are rarely recognized in the rock record. Models of linear dune development have not been able to take into account the sub-surface structure of existing dunes, but have relied instead either on the extrapolation of short-term measurements of winds and sediment transport or on observations of near-surface internal sedimentary structures. From such studies, it has not been clear if linear dunes can migrate laterally. Here we present images produced by ground penetrating radar showing the three-dimensional sedimentary structure of a linear dune in the Namib sand sea, where some of the world's largest linear dunes are situated. These profiles show clear evidence for lateral migration in a linear dune. Moreover, the migration of a sinuous crest-line along the dune produces divergent sets of cross-stratification, which can become stacked as the dune height increases, and large linear dunes can support superimposed dunes that produce stacked sets of trough cross-stratification. These clear structural signatures of linear dunes should facilitate their recognition in geological records.

Nordihydroguaiaretic acid attenuates NMDA neurotoxicity--action beyond the receptor.

There is widespread interest in the neurotoxicity of the endogenous excitatory amino acid neurotransmitter glutamate. Excessive glutamate release or accumulation leads to neuronal injury or death in a variety of experimental models of ischemia, anoxia and hypoglycemia. This injury appears to be caused by overactivation of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors since a variety of competitive and uncompetitive NMDA antagonists can attenuate this process, sometimes in a dramatic fashion. Given the clinical context in which this form of neuronal injury occurs, it would be desirable if we could identify agents that blocked NMDA toxicity, after initial receptor binding and ion channel fluxes had transpired. Because NMDA receptor activation initiates the arachidonic acid cascade, we have recently looked at whether the phospholipase A2 and lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) can reduce NMDA neurotoxicity in vitro. In the concentration range 1-30 microM, NDGA diminished the death of cultured rodent hippocampal neurons produced by 100 microM NMDA. When 30 microM NDGA was present both before and after NMDA exposure, death declined by over 50%. NDGA did not block NMDA-induced inward currents in voltage-clamped neurons, so the drug is not a direct NMDA receptor antagonist. It also had no effect on the elevation in intracellular calcium produced by NMDA exposure. It is likely that NDGA acts at a site(s) distal to the NMDA receptor and the neuronal membrane to limit NMDA toxicity. We are hopeful that strategies for limiting excitotoxicity, which halt destructive intracellular events, can be developed for use in human neurological diseases linked to excessive stimulation of glutamate receptors.

Distribution of apolipoproteins A-I and B among intestinal lipoproteins.

Chylomicrons and very low density lipoproteins (VLDL) are produced by the intestine and these nascent particles are thought to be similar to their counterparts in intestinal lymph. To study the relationship between these lipoproteins within the cell and those secreted into the lamina propria and lymph, we have isolated enterocytes, lamina propria, and mesenteric lymph from rats while fasted and after corn oil feeding. Apolipoprotein A-I and B content were measured by radioimmunoassay in cell, lamina propria, and lymph fractions separated by Sepharose 6B and 10% agarose chromatography, and by KBr isopycnic density centrifugation. ApoA-I in the cell and the underlying lamina propria was found partly in those fractions in which chylomicron and very low density lipoproteins (chylo-VLDL) and high density lipoproteins (HDL) elute, but more abundantly where unassociated 125I-labeled apoA-I was eluted. In the lymph, however, 74% of apoA-I eluted in the HDL region and no peak of free apoA-I was found. ApoB and apoC-III within the enterocyte were found distributed in the position of particles eluting not only with chylomicrons and VLDL, but also in the regions corresponding to LDL and HDL. In the lamina propria and lymph, on the other hand, most of the apoB was found in the region of VLDL and chylomicrons. These results indicate that the patterns in lymph lipoproteins and the lamina propria do not exactly mirror the distribution of apoA-I and B among lipoproteins inside the cell. This may be because intracellular apoproteins may be unassociated with lipoproteins, or they could be associated with lipoproteins in various stages of assembly of protein with lipids. Furthermore, the apoprotein composition of intestinal lipoproteins is altered after secretion from the enterocyte. Finally, not all apoproteins seem to be secreted in association with identifiable lipoprotein particles from the enterocyte.

The effects of fat feeding on apolipoprotein AI secretion from rat small intestinal epithelium.

The small intestine is known to be an important synthetic site for certain apolipoproteins, which are subsequently secreted from the enterocyte into the mesenteric lymph. We have studied apolipoprotein AI and CIII content of the enterocyte during the course of fat feeding in order to determine their relative synthetic and secretory rates. Rat intestinal enterocytes were isolated from the entire jejunal villus after fat feeding in vivo. The apo AI content fell 50% as determined by RIA one and two hours after fat feeding. By four hours, the intracellular cellular levels had returned to prefeeding levels. These changes in apolipoprotein AI levels were not seen in the terminal ileum. Apolipoprotein CIII levels remained unchanged afer fat feeding. To determine the effect of free fatty acids on apolipoprotein AI secretion, organ culture explants were incubated for four hours in the presence and absence of 360 microM oleic acid bound to albumin. Apolipoprotein AI detected in the incubation media reflected release from the lamina propria (which was not colchicine sensitive), and secretion from the enterocyte (which was inhibited by colchicine). In the absence of oleic acid, enterocyte secretion of apolipoprotein AI accounted for about half of the apo AI recovered in the medium. In the presence of oleic acid, the total apolipoprotein AI content of the tissue increased by 50 percent. A similar increase in colchicine sensitive secretion was observed. The secretion of apolipoprotein AI from explants was more rapid in the presence of oleic acid and began without the half hour lag noted when oleic acid was absent. The mid intestine was most active in the secretion of apolipoprotein AI. These data are consistent with the hypothesis that in the first few hours after feeding the rate of secretion of apolipoprotein AI exceeds the synthetic capacity of the small intestinal epithelium.