A digital therapeutic for management of psychosocial aspects of psoriasis: A pre-post proof of concept study.

Background: Despite the psychosocial challenges of living with psoriasis many patients may not be able to access appropriate services to manage these challenges. Mobile health interventions may be helpful as a means to support patients in managing the impact of their condition. Objective: To conduct a preliminary examination of the feasibility and acceptability of a bespoke psoriasis-specific digital therapeutic solution (hereafter termed Allay), and to provide initial data on psychological changes pre-post. Methods: Phase one proof of concept pre-post study. Eligible patients were provided with Allay on their smartphone and assessed at baseline and at 12 weeks on a range of indices of well-being. Participants experiences on usability were collected by telephone interview at 4 weeks, 8 and 12 weeks. Results: Out of 66 participants recruited, 59 persisted in using Allay after the familiarisation phase, and 34 participants completed the 12 weeks programme. Participants showed a statistically significant improvement between induction and the end of the 12 weeks programme on Quality of life, Resilience, Perceptions of 'Overall impact' of psoriasis, and 'Emotional impact'. There was a significant change over the course of using Allay for symptoms of depression but not anxiety. While there was an interaction effect of changes in severity of psoriasis symptoms over the course of the study for dermatology-specific measures, there was no interaction between such changes in psoriasis symptoms and changes in depression, resilience or beliefs in emotional impact. Conclusions: Study results suggest that the use of Allay as an adjunct to medical management of psoriasis may help patients improve resilience, mood, beliefs about their condition and enhance their quality of life. Given that this is a phase one proof of concept study, and our rates of attrition further research is necessary to examine comparative effectiveness and stability of these findings.

Tuberculosis and oral healthcare provision.

Tuberculosis (TB) is a preventable and curable infection, but remains a significant cause of death. The dental team is likely to encounter patients with a history of TB, however, at present there is limited guidance available to inform the provision of oral healthcare for this patient group. This may lead to confusion with delays in care. There is a potential health risk posed to patients and co-workers by a member of the dental team who becomes infected. TB has the potential to be a major issue for oral healthcare in the United Kingdom (UK). This paper discusses the implications for both patient care and management of the dental team.

Outcome of repeat anaesthesia after investigation for perioperative anaphylaxis.

BACKGROUND: Perioperative anaphylaxis (POA) is infrequent, but remains an important and potentially life-threatening complication of general anaesthesia. The diagnostic uncertainty surrounding the investigation of anaesthetic allergy poses numerous challenges. We aimed to inform practice by auditing the outcomes of repeat anaesthesia, after an investigation for previous POA. METHODS: One-hundred and seventy-four subjects were investigated after suspected POA between December 2002 and August 2015. Outcome data were obtained for a total of 70 patients who underwent repeat anaesthesia after investigation in the drug-allergy clinic. RESULTS: Sixty-seven out of the 70 patients studied underwent repeat anaesthesia without further complications. Three individuals experienced a further episode of anaphylaxis. In two cases, incomplete referral information led to the offending drugs being omitted from initial testing. The third was found to have underlying systemic mastocytosis (SM). CONCLUSIONS: In our cohort, the incidence of repeat anaphylaxis after a comprehensive assessment in the drug-allergy clinic for suspected POA was 4%. Important risk factors include the completeness of referral information provided to the assessor and the role of exacerbating disorders, particularly SM.

Role of the MT1 and MT2 melatonin receptors in mediating depressive- and anxiety-like behaviors in C3H/HeN mice.

Melatonin is a neurohormone primarily synthesized by the pineal gland following a circadian rhythm with a high level during the night and a low level during the day. Alterations in the synthesis and secretion of melatonin have been reported in various mood disorders, including major depressive disorder. However, the role of endogenous melatonin in the pathophysiology of depressive disorder is unclear. Melatonin primarily acts through two G protein-coupled receptors, termed MT1 and MT2 . The present study investigated the effect of genetic deletion of the MT1 and/or MT2 receptors on tests associated with depression- and anxiety-like behaviors in C3H/HeN mice. Deletion of the MT1 and/or MT2 receptors caused a deficit in hedonic and social interaction behavior, and increased anxiety-like behavior. It is likely that dysregulations of the MT1 and/or MT2 melatonin receptors could be involved in the pathophysiology of depression and anxiety.

Resistance of soybean genotypes to Sclerotinia sclerotiorum isolates in different incubation environments.

Sclerotinia sclerotiorum is an important soybean pathogen. The objectives of this study were to evaluate levels of resistance of soybean genotypes to the fungus, and to determine the effects of different incubation environments on host resistance and pathogen aggressiveness. Two experiments were conducted using 103 genotypes from the seed collection of Laboratório de Desenvolvimento de Germoplasma, Universidade Federal de Uberlândia (LAGER-UFU). The first experiment was conducted in a greenhouse, and the second in a growth chamber. Inoculations were performed by the straw test method using two Brazilian isolates of the fungus, one from Uberaba, Minas Gerais, and the other from Jataí, Goiás. The average stem-lesion length (cm) at 5 days post-inoculation was used to determine levels of resistance. Overall, the most resistant genotype was EMGOPA-316, and the most susceptible genotype was LAGER-29. Incubation in a growth chamber and use of the Jataí isolate generated the most reliable data, and multivariate analysis indicated that the genotypes were divergent under the growth chamber conditions. Therefore, when studying host resistance of soybean genotypes to S. sclerotiorum, it is important to use environmental conditions favorable to the fungus and aggressive isolates.

Reducing health inequalities in people with learning disabilities: a multi-disciplinary team approach to care under general anaesthesia.

Background There remains significant inequality in health and healthcare in people with learning disabilities (LD). A lack of coordination and the episodic nature of care provision are contributory factors. Recognising the need to improve outcomes for this group, we evaluate a multi-disciplinary team (MDT) approach to care whereby additional medical procedures are carried out under the same episode of general anaesthesia (GA) as dental treatment for people with severe LD. This is the first published evaluation of its kind in the UK.Aim To evaluate the need and outcomes of an MDT approach to care among people with severe LD receiving dental treatment under GA.Method One hundred patients with severe LD and behaviour that challenges attended Barts Health Dental Hospital for dental assessment and subsequent treatment under GA. Details of failed or forthcoming medical interventions were determined. Where appropriate, care was coordinated with the relevant medical team.Findings Twenty-one percent (n = 21/100) had recent medical interventions attempted that had been abandoned, and 7.0% (n = 7/100) had future investigations or treatment planned under GA with medical specialties. An MDT approach was indicated in 28.0% (n = 28/100). For such complex cases, a successful MDT outcome was achieved in 89.3% (n = 25/28). This included ophthalmological/orthoptic, ENT and gastroenterological interventions in addition to medical imaging.Conclusion An MDT approach to care for people with LD offers improved patient-centred outcomes in addition to financial and resource efficiency. It requires a high level of cooperation between specialties, with consideration of the practicalities of a shared surgical space and equipment needs. Re-shaping of services and contractual flexibility are essential to support the future implementation of MDTs and to ensure long-term sustainability. Adoption of a holistic culture in the care of this vulnerable patient group is encouraged.

Medical risk assessment in dentistry: use of the American Society of Anesthesiologists Physical Status Classification.

BACKGROUND: Medical risk assessment is essential to safe patient management and the delivery of appropriate dental care. The American Society of Anesthesiologists Physical Status (ASA PS) Classification is widely used within medicine and dentistry, but has received significant criticism. This is the first UK survey to assess the consistency of medical risk assessment in dentistry. AIMS: (i) To determine the use and consistency of the ASA PS among dentists and anaesthetists. (ii) To consider the appropriateness of the ASA PS in relation to dental treatment planning and delivery of care. METHOD: A cross-sectional online questionnaire was distributed to anaesthetists and dental practitioners in general practice, community and hospital dental services. Questions focused on professional backgrounds, use of the ASA PS, alternative approaches to risk assessment in everyday practice and scoring of eight hypothetical patients using ASA PS. RESULTS: There were 101 responses, 82 were complete. Anaesthetists recorded ASA PS score more frequently than dental practitioners and found it more useful. Inconsistencies were evident in the assignment of ASA PS scores both between and within professional groups. CONCLUSION: Many dental practitioners did not use or find ASA PS helpful, with significant inconsistencies in its use. An awareness of alternative assessment scales may be useful across settings. Accepting its limitations, it would be helpful for all dentists to be educated in ASA PS and its use in medical risk assessment, particularly in relation to conscious sedation.

"These boots were made for walking": the isotopic analysis of a C(4) Roman inhumation from Gravesend, Kent, UK.

As part of the road widening scheme between London and Dover, Oxford Archaeology South uncovered a large boundary ditch of Iron Age origin that contained Iron Age and Roman inhumations, adjacent to which was a small mid-late Roman cemetery, interpreted as a rural cemetery for Romano-British farmers. Grave goods in the cemetery were restricted to a few individuals with hobnailed boots. Bulk bone collagen isotopic analysis of 11 skeletons of Iron Age and Roman date gave a typical C(3) terrestrial signal (average δ(13) C = -19.8‰, δ(15) N = 9.3‰), but also revealed one (SK12671) with a diet which included a substantial C(4) component (δ(13) C = -15.2‰, δ(15) N = 11.2‰). This is only the second such diet reported in Roman Britain. Subsequent δ(18) O(c) and (87) Sr/(86) Sr measurements on the dental enamel in this individual were, however, consistent with a "local" origin, indicating that either C(4) protein was consumed in Late Roman Britain, or that he came from somewhere else, but where conditions gave rise to similar isotopic values. If we accept the latter, then it indicates that using oxygen and strontium isotopes alone to identify "incomers" may be problematic. The provision of hobnailed boots for the dead appears to have had a strong symbolic element in Late Roman Britain. We suggest that in this case the boots may be significant, in that he was being equipped for the long march home.

A second T-region of the soybean-supervirulent chrysopine-type Ti plasmid pTiChry5, and construction of a fully disarmed vir helper plasmid.

Agrobacterium tumefaciens Chry5, which is particularly virulent on soybeans, induces tumors that produce a family of Amadori-type opines that includes deoxyfructosyl glutamine (Dfg) and its lactone, chrysopine (Chy). Cosmid clones mapping to the right of the known oncogenic T-region of pTiChry5 conferred Amadori opine production on tumors induced by the nopaline strain C58. Sequence analysis of DNA held in common among these cosmids identified two 25-bp, direct repeats flanking an 8.5-kb segment of pTiChry5. These probable border sequences are closely related to those of other known T-regions and define a second T-region of pTiChry5, called T-right (TR), that confers production of the Amadoriopines. The oncogenic T-left region (TL) was located precisely by identifying and sequencing the likely border repeats defining this segment. The two T-regions are separated by approximately 15 kb of plasmid DNA. Based on these results, we predicted that pKYRT1, a vir helper plasmid derived from pTiChry5, still contains all of TR and the leftmost 9 kb of TL. Consistent with this hypothesis, transgenic Arabidopsis thaliana plants selected for with a marker encoded by a binary plasmid following transformation with KYRT1 co-inherited production of the Amadori opines at high frequency. All opine-positive transgenic plants also contained TR-DNA, while those plants that lacked TR-DNA failed to produce the opines. Moreover, A. thaliana infected with KYRT1 in which an nptII gene driven by the 35S promoter of Cauliflower mosaic virus was inserted directly into the vir helper plasmid yielded kanamycin-resistant transformants at a low but detectable frequency. These results demonstrate that pKYRT1 is not disarmed, and can transfer Ti plasmid DNA to plants. A new vir helper plasmid was constructed from pTiChry5 by two rounds of sacB-mediated selection for deletion events. This plasmid, called pKPSF2, lacks both of the known T-regions and their borders. pKPSF2 failed to transfer Ti plasmid DNA to plants, but mobilized the T-region of a binary plasmid at an efficiency indistinguishable from those of pKYRT1 and the nopaline-type vir helper plasmid pMP90.

The Arabidopsis dnd1 "defense, no death" gene encodes a mutated cyclic nucleotide-gated ion channel.

Gene-for-gene disease resistance typically includes a programmed cell death response known as the hypersensitive response (HR). The Arabidopsis thaliana dnd1 mutant was previously isolated as a line that failed to produce the HR in response to avirulent Pseudomonas syringae pathogens; plants homozygous for the recessive dnd1-1 mutation still carry out effective gene-for-gene resistance. The dnd1-1 mutation also causes constitutive systemic resistance and elevated levels of salicylic acid. In the present study, a positional cloning approach was used to isolate DND1. DND1 encodes the same protein as AtCNGC2, a cyclic nucleotide-gated ion channel of previously unknown organismal function that can allow passage of Ca(2+), K(+) and other cations [Leng, Q., Mercier, R. W., Yao, W. & Berkowitz, G. A. (1999) Plant Physiol. 121, 753-761]. By using a nahG transgene, we found that salicylic acid is required for the elevated resistance caused by the dnd1 mutation but that removal of salicylic acid did not completely eliminate the dwarf and loss-of-HR phenotypes of mutant dnd1 plants. A stop codon that would severely truncate the DND1 gene product was identified in the dnd1-1 allele. This demonstrates that broad-spectrum disease resistance and inhibition of the HR can be activated in plants by disruption of a cyclic nucleotide-gated ion channel.

Female reproductive tissues are the primary target of Agrobacterium-mediated transformation by the Arabidopsis floral-dip method.

The floral-dip method for Agrobacterium-mediated transformation of Arabidopsis allows efficient plant transformation without need for tissue culture. To facilitate use with other plant species, we investigated the mechanisms that underlie this method. In manual outcrossing experiments, application of Agrobacterium tumefaciens to pollen donor plants did not produce any transformed progeny, whereas application of Agrobacterium to pollen recipient plants yielded transformants at a rate of 0.48%. Agrobacterium strains with T-DNA carrying gusA (encoding beta-glucuronidase [GUS]) under the control of 35S, LAT52, or ACT11 promoters revealed delivery of GUS activity to developing ovules, whereas no GUS staining of pollen or pollen tubes was observed. Transformants derived from the same seed pod contained independent T-DNA integration events. In Arabidopsis flowers, the gynoecium develops as an open, vase-like structure that fuses to form closed locules roughly 3 d prior to anthesis. In correlation with this fact, we found that the timing of Agrobacterium infection was critical. Transformants were obtained and GUS staining of ovules and embryo sacs was observed only if the Agrobacterium were applied 5 d or more prior to anthesis. A 6-fold higher rate of transformation was obtained with a CRABS-CLAW mutant that maintains an open gynoecium. Our results suggest that ovules are the site of productive transformation in the floral-dip method, and further suggest that Agrobacterium must be delivered to the interior of the developing gynoecium prior to locule closure if efficient transformation is to be achieved.

Identification of Arabidopsis mutants exhibiting an altered hypersensitive response in gene-for-gene disease resistance.

A mutational study was carried out to isolate Arabidopsis thaliana plants that exhibit full or partial disruption of the RPS2-mediated hypersensitive response (HR) to Pseudomonas syringae that express avrRpt2. Five classes of mutants were identified including mutations at RPS2, dnd mutations causing a "defense, no death" loss-of-HR phenotype, a lesion-mimic mutant that also exhibited an HR- phenotype, and a number of intermediate or partial-loss-of-HR mutants. Surprisingly, many of these mutants displayed elevated resistance to virulent P. syringae and, in some cases, to Peronospora parasitica. Constitutively elevated levels of pathogenesis-related (PR) gene expression and salicylic acid were also observed. In the lesion-mimic mutant, appearance of elevated resistance was temporally correlated with appearance of lesions. For one of the intermediate lines, resistance was shown to be dependent on elevated levels of salicylic acid. A new locus was identified and named IHR1, after the mutant phenotype of "intermediate HR." Genetic analysis of the intermediate-HR plant lines was difficult due to uncertainties in distinguishing the partial/intermediate mutant phenotypes from wild type. Despite this difficulty, the intermediate-HR mutants remain of interest because they reveal potential new defense-related loci and because many of these lines exhibit partially elevated disease resistance without dwarfing or other apparent growth defects.

Unification of the quantum and classical theories of methyl NMR.

The existing low and high temperature theories of methyl NMR are not linked because two conditions imposed on state functions in the low temperature theory are not compatible with the classical rotations on which the high temperature theory is based. The conditions do not occur in a geometrical theory of quantum phenomena in which particles and waves have separate roles. When applied to methyl dynamics, this theory covers the whole temperature range.

Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana.

The Agrobacterium vacuum infiltration method has made it possible to transform Arabidopsis thaliana without plant tissue culture or regeneration. In the present study, this method was evaluated and a substantially modified transformation method was developed. The labor-intensive vacuum infiltration process was eliminated in favor of simple dipping of developing floral tissues into a solution containing Agrobacterium tumefaciens, 5% sucrose and 500 microliters per litre of surfactant Silwet L-77. Sucrose and surfactant were critical to the success of the floral dip method. Plants inoculated when numerous immature floral buds and few siliques were present produced transformed progeny at the highest rate. Plant tissue culture media, the hormone benzylamino purine and pH adjustment were unnecessary, and Agrobacterium could be applied to plants at a range of cell densities. Repeated application of Agrobacterium improved transformation rates and overall yield of transformants approximately twofold. Covering plants for 1 day to retain humidity after inoculation also raised transformation rates twofold. Multiple ecotypes were transformable by this method. The modified method should facilitate high-throughput transformation of Arabidopsis for efforts such as T-DNA gene tagging, positional cloning, or attempts at targeted gene replacement.

NMR and relative quantum theory.

Assumptions on which NMR dynamical studies have been based for nearly 50 years are consistent with a relative quantum theory based on Minkowski spacetime. A symmetry condition required by the existence of reference frames takes over the usual role of particle permutation symmetry, leaving a quantum theory of relative motion which only involves observables.

A two-component system in Ralstonia (Pseudomonas) solanacearum modulates production of PhcA-regulated virulence factors in response to 3-hydroxypalmitic acid methyl ester.

Expression of virulence factors in Ralstonia solanacearum is controlled by a complex regulatory network, at the center of which is PhcA, a LysR family transcriptional regulator. We report here that expression of phcA and production of PhcA-regulated virulence factors are affected by products of the putative operon phcBSR(Q). phcB is required for production of an extracellular factor (EF), tentatively identified as the fatty acid derivative 3-hydroxypalmitic acid methyl ester (3-OH PAME), but a biochemical function for PhcB could not be deduced from DNA sequence analysis. The other genes in the putative operon are predicted to encode proteins homologous to members of two-component signal transduction systems: PhcS has amino acid similarity to histidine kinase sensors, whereas PhcR and OrfQ are similar to response regulators. PhcR is quite unusual because its putative output domain strongly resembles the histidine kinase domain of a sensor protein. Production of the PhcA-regulated factors exopolysaccharide I, endoglucanase, and pectin methyl esterase was reduced 10- to 100-fold only in mutants with a nonpolar insertion in phcB [which express phcSR(Q) in the absence of the EF]; simultaneously, expression of phcA was reduced fivefold. Both a wild-type phenotype and phcA expression were restored by addition of 3-OH PAME to growing cultures. Mutants with polar insertions in phcB or lacking the entire phcBSR(Q) region produced wild-type levels of PhcA-regulated virulence factors. The genetic data suggest that PhcS and PhcR function together to regulate expression of phcA, but the biochemical mechanism for this is unclear. At low levels of the EF, it is likely that PhcS phosphorylates PhcR, and then PhcR interacts either with PhcA (which is required for full expression of phcA) or an unknown component of the signal cascade to inhibit expression of phcA. When the EF reaches a threshold concentration, we suggest that it reduces the ability of PhcS to phosphorylate PhcR, resulting in increased expression of phcA and production of PhcA-regulated factors.

Differential Expression of Virulence Genes and Motility in Ralstonia (Pseudomonas) solanacearum during Exponential Growth.

A complex network regulates virulence in Ralstonia solanacearum (formerly Pseudomonas solanacearum); central to this system is PhcA, a LysR-type transcriptional regulator. We report here that two PhcA-regulated virulence factors, endoglucanase (Egl) and acidic exopolysaccharide I (EPS I), and motility are expressed differentially during exponential growth in batch cultures. Tests with strains carrying lacZ fusions in a wild-type genetic background revealed that expression (on a per-cell basis) of phcA was constant but expression of egl and epsB increased 20- to 50-fold during multiplication from 1 x 10(sup7) to 5 x 10(sup8) CFU/ml. Expression of xpsR, an intermediate regulator downstream of PhcA in the regulatory cascade for eps expression, was similar to that of epsB and egl. Motility track photography revealed that all strains were essentially nonmotile at 10(sup6) CFU/ml. As cell density increased, 30 to 50% of wild-type cells were motile between 10(sup7) and 10(sup8) CFU/ml, but this population was again nonmotile at 10(sup9) CFU/ml. In contrast, about 60% of the cells of phcB and phcA mutants remained motile at 10(sup9) CFU/ml. Expression of phcB, which is not positively regulated by PhcA, was the inverse of epsB, egl, and xpsR (i.e., it decreased 20-fold at high cell density). PhcB is essential for production of an extracellular factor, tentatively identified as 3-hydroxypalmitic acid methyl ester (3-OH PAME), that might act as an exponential-phase signal to activate motility or expression of virulence genes. However, growth of the lacZ fusion strains in medium containing excess 3-OH PAME did not result in motility or expression of virulence genes at dramatically lower cell densities, suggesting that 3-OH PAME is not the only factor controlling these traits.