Occupational contact urticaria to cannabis sativa.

Cannabis allergy is not commonly reported, perhaps due to the legal status of cannabis use and the difficulties of obtaining permission to test it. We report 3 cases of work-related cannabis allergy with features suggestive of a dermatitis, rather than a contact urticaria. Only prick tests were able to confirm the diagnosis. Identification of the cause of the rash was essential to direct work re-deployment.

Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses.

Antiviral therapies that impede virus entry are attractive because they act on the first phase of the infectious cycle. Drugs that target pathways common to multiple viruses are particularly desirable when laboratory-based viral identification may be challenging, e.g., in an outbreak setting. We are interested in identifying drugs that block both Ebola virus (EBOV) and Lassa virus (LASV), two unrelated but highly pathogenic hemorrhagic fever viruses that have caused outbreaks in similar regions in Africa and share features of virus entry: use of cell surface attachment factors, macropinocytosis, endosomal receptors, and low pH to trigger fusion in late endosomes. Toward this goal, we directly compared the potency of eight drugs known to block EBOV entry with their potency as inhibitors of LASV entry. Five drugs (amodiaquine, apilimod, arbidol, niclosamide, and zoniporide) showed roughly equivalent degrees of inhibition of LASV and EBOV glycoprotein (GP)-bearing pseudoviruses; three (clomiphene, sertraline, and toremifene) were more potent against EBOV. We then focused on arbidol, which is licensed abroad as an anti-influenza drug and exhibits activity against a diverse array of clinically relevant viruses. We found that arbidol inhibits infection by authentic LASV, inhibits LASV GP-mediated cell-cell fusion and virus-cell fusion, and, reminiscent of its activity on influenza virus hemagglutinin, stabilizes LASV GP to low-pH exposure. Our findings suggest that arbidol inhibits LASV fusion, which may partly involve blocking conformational changes in LASV GP. We discuss our findings in terms of the potential to develop a drug cocktail that could inhibit both LASV and EBOV.IMPORTANCE Lassa and Ebola viruses continue to cause severe outbreaks in humans, yet there are only limited therapeutic options to treat the deadly hemorrhagic fever diseases they cause. Because of overlapping geographic occurrences and similarities in mode of entry into cells, we seek a practical drug or drug cocktail that could be used to treat infections by both viruses. Toward this goal, we directly compared eight drugs, approved or in clinical testing, for the ability to block entry mediated by the glycoproteins of both viruses. We identified five drugs with approximately equal potencies against both. Among these, we investigated the modes of action of arbidol, a drug licensed abroad to treat influenza infections. We found, as shown for influenza virus, that arbidol blocks fusion mediated by the Lassa virus glycoprotein. Our findings encourage the development of a combination of approved drugs to treat both Lassa and Ebola virus diseases.

Patch testing with the European baseline series fragrance markers: a 2016 update.

BACKGROUND: Fragrance contact allergy is common and is currently screened for using the following European baseline series fragrance markers: fragrance mix (FM)I, FMII, Myroxylon pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde. OBJECTIVES: To investigate the validity of patch testing using these fragrance markers in detecting fragrance allergy to 26 individual fragrance substances for which cosmetic ingredient labelling is mandatory within the European Union. METHODS: We conducted a retrospective review of the patch test records of all patients with eczema who underwent testing using the European baseline series, extended with the individual fragrance substances during the period from 2015 to 2016. RESULTS: Overall, 359 patients (17·2%) reacted to one or more allergens from the labelled fragrance substance series and/or a fragrance marker from the European baseline series. The allergens that were positive with the greatest frequencies were oxidized linalool [n = 154; 7·4%, 95% confidence interval (CI) 6·3-8·6], oxidized limonene (n = 89; 4·3%, 95% CI 3·4-5·2) and Evernia furfuracea (n = 44; 2·1%, 95% CI 1·5-2·8). Of the 319 patients who reacted to any of the labelled fragrance substances, only 130 (40·8%) also reacted to a baseline series fragrance marker. The sensitivity of our history-taking for detecting fragrance allergy was 25·7%. CONCLUSIONS: Given the evolving trends in fragrance allergy, patch testing with FMI, FMII, M. pereirae and hydroxyisohexyl 3-cyclohexene carboxaldehyde is no longer sufficient for screening for fragrance allergy.

Predictors of coverage of the national maternal pertussis and infant rotavirus vaccination programmes in England.

This study assessed variation in coverage of maternal pertussis vaccination, introduced in England in October 2012 in response to a national outbreak, and a new infant rotavirus vaccination programme, implemented in July 2013. Vaccine eligible patients were included from national vaccine coverage datasets and covered April 2014 to March 2015 for pertussis and January 2014 to June 2016 for rotavirus. Vaccine coverage (%) was calculated overall and by NHS England Local Team (LT), ethnicity and Index of Multiple Deprivation (IMD) quintile, and compared using binomial regression. Compared with white-British infants, the largest differences in rotavirus coverage were in 'other', white-Irish and black-Caribbean infants (-13·9%, -12·1% and -10·7%, respectively), after adjusting for IMD and LT. The largest differences in maternal pertussis coverage were in black-other and black-Caribbean women (-16·3% and -15·4%, respectively). Coverage was lowest in London LT for both programmes. Coverage decreased with increasing deprivation and was 14·0% lower in the most deprived quintile compared with the least deprived for the pertussis programme and 4·4% lower for rotavirus. Patients' ethnicity and deprivation were therefore predictors of coverage which contributed to, but did not wholly account for, geographical variation in coverage in England.

Neutrophilic urticarial dermatosis: a novel association with poststreptococcal rheumatic disease.

Neutrophilic urticarial dermatosis (NUD), a particular clinical and histological entity, can provide a strong pointer to underlying systemic disease, most frequently rheumatological diseases. We report the first case of NUD in association with a post-streptococcal rheumatic disease, with symptoms including recurrent sore throat, raised antistreptolysin O titre, persistent transient urticaria, polyarthralgia, rheumatic mitral valve disease and Jaccoud arthropathy. Histologically, NUD is characterized by an intense superficial and deep neutrophilic interstitial and perivascular infiltrate, without significant oedema or blood vessel damage. These neutrophils may have a tendency to concentrate along the basement membrane and extend into the epidermis, hair follicles, sebaceous glands and sweat glands (a feature termed 'neutrophilic epitheliotropism'). Clinicians should remain cognizant of NUD, and in particular its frequent association with an underlying inflammatory disorder.

A dynamic landscape of allergen associations in delayed-type cutaneous hypersensitivity.

BACKGROUND: Delayed-type hypersensitivity represents a significant clinical and public health challenge. Patients undergoing patch testing may exhibit positive reactions to more than one allergen. It is recognized that reactions to specific pairs of allergens are associated, reflecting a combination of exposure patterns and structural similarity. OBJECTIVES: To explore the influence of time of testing, age, sex and atopy status on allergen pair associations in a series of 45 110 consecutive patients tested over 30 years. METHODS: Patch test records of all patients undergoing testing with a modified European baseline series between 1985 and 2014 were retrieved from a database at St John's Institute of Dermatology. Reactions were read on days 2 and 4. For each allergen it was recorded whether the allergen was tested and whether the result was positive or negative. RESULTS: This is the largest reported study of patch test allergen pair relationships. Our analysis shows a high degree of variability in allergen pair associations. Rigorous statistical analysis reveals a large number of differences between groups, including a significant increase in the association between formaldehyde and multiple formaldehyde-releasing preservatives over the study period, in addition to pair associations with cobalt and formaldehyde-releasing preservatives. These were present to a significantly greater extent in men than in women. CONCLUSIONS: These observations extend our understanding of cutaneous allergy, with implications for both clinical practice and mechanisms of cutaneous hypersensitivity.

Bi-2223 Test Coils for High Resolution NMR Magnets.

Recently, significant improvement in the strain tolerance of Bi-2223 conductor has been achieved by lamination with high strength nickel alloy. The conductor, supplied by Sumitomo Electric and designated Type HT-NX, is now commercially available in lengths sufficient for manufacture of high-homogeneity solenoids. A program to fully exploit the improved conductor properties is now underway at the National High Magnetic Field Laboratory (NHMFL). Five coils are being made, the last of which is to demonstrate an NMR measurement approaching 1 GHz and 1 ppm over 10 mm volume. In so doing, we expect to demonstrate critical current fraction, and strain similar to that expected in 30 T NMR magnets. The coils will be tested inside an existing 16 Tesla large-bore background magnet at the NHMFL. The design of the NMR demonstration coil is presented first, with expected values for field, homogeneity and strain given. A technology development program is then outlined, which includes fabrication of four test coils to test various design features, develop fabrication tooling and train personnel.

Tetra-porphyrin molecular tweezers: two binding sites linked via a polycyclic scaffold and rotating phenyl diimide core.

The synthesis of a tetra-porphyrin molecular tweezer with two binding sites is described. The bis-porphyrin binding sites are aligned by a polycyclic scaffold and linked via a freely rotating phenyl diimide core. Synthesis was achieved using a divergent approach employing a novel coupling method for linking two polycyclic units to construct the core, with a copper(ii)-mediated phenyl boronic acid coupling found to extend to our polycyclic imide derivative. We expect this chemistry to be a powerful tool in accessing functional polycyclic supramolecular architectures in applications where north/south reactivity and/or directional interactions between modules are important. Porphyrin receptor functionalisation was undertaken last, by a four-fold ACE coupling reaction on the tetra-epoxide derivative of the core.

Current epidemiology of tetanus in England, 2001-2014.

Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average annual incidence was 0·13/million (95% confidence interval 0·10-0·16) of which 50·0% were male. Where reported, 70·3% of injuries occurred in the home/garden (45/64). Overall, 40·3% (31/77) cases were in people who inject drugs (PWID), including a cluster of 22 cases during 2003-2004. Where known (n = 68), only 8·8% were age-appropriately immunized. The overall case-fatality rate was 11·0% (9/82). All tetanus-associated deaths occurred in adults aged >45 years, none of whom were fully immunized. Due to the success of the childhood immunization programme, tetanus remains a rare disease in England with the majority of cases occurring in older unimmunized or partially immunized adults. Minor injuries in the home/garden were the most commonly reported likely sources of infection, although cases in PWID increased during this period. It is essential that high routine vaccine coverage is maintained and that susceptible individuals, particularly older adults, are protected through vaccination and are offered timely post-exposure management following a tetanus-prone wound.

Oxidative damage of aromatic dipeptides by the environmental oxidants NO2˙ and O3.

Irreversible oxidative damage at both aromatic side chains and dipeptide linkage occurs in the aromatic N- and C-protected dipeptides 7-11 upon exposure to the environmental pollutants NO2˙ and O3. The reaction proceeds through initial oxidation of the aromatic ring by in situ generated NO3˙, or by NO2˙, respectively, which leads to formation of nitroaromatic products. The indole ring in Phe-Trp undergoes oxidative cyclization to a pyrroloindoline. An important reaction pathway for dipeptides with less oxidisable aromatic side chains proceeds through fragmentation of the peptide bond with concomitant acyl migration. This process is likely initiated by an ionic reaction of the amide nitrogen with the NO2˙ dimer, N2O4.

Energy transfer in PPV-based conjugated polymers: a defocused widefield fluorescence microscopy study.

Both pendant and main chain conjugated MEH-PPV based polymers have been studied at the level of single chains using confocal and widefield fluorescence microscopy techniques. In particular, defocused widefield fluorescence is applied to reveal the extent of energy transfer in these polymers by identifying whether they act as single emitters. For main chain conjugated MEH-PPV, molecular weight and the surrounding matrix play a primary role in determining energy transport processes and whether single emitter behaviour is observed. Surprisingly in polymers with a saturated backbone but containing the same pendant MEH-PPV oligomer on each repeating unit, intra-chain energy transfer to a single emitter is also apparent. The results imply there is chromophore heterogeneity that can facilitate energy funneling to the emitting site. Both main chain conjugated and pendant MEH-PPV polymers exhibit changes in orientation of the emission dipole during a fluorescence trajectory of many seconds, whereas a model MEH-PPV oligomer does not. The results suggest that, in the polymers, the nature of the emitting chromophores can change during the time trajectory.

Risk Factors and Innovations in Risk Assessment for Melanoma, Basal Cell Carcinoma, and Squamous Cell Carcinoma.

Skin cancer is the most frequently diagnosed cancer globally and is preventable. Various risk factors contribute to different types of skin cancer, including melanoma, basal cell carcinoma, and squamous cell carcinoma. These risk factors encompass both extrinsic, such as UV exposure and behavioral components, and intrinsic factors, especially involving genetic predisposition. However, the specific risk factors vary among the skin cancer types, highlighting the importance of precise knowledge to facilitate appropriate early diagnosis and treatment for at-risk individuals. Better understanding of the individual risk factors has led to the development of risk scores, allowing the identification of individuals at particularly high risk. These advances contribute to improved prevention strategies, emphasizing the commitment to mitigating the impact of skin cancer.

Treatment planning in dentistry using an electronic health record: implications for undergraduate education.

OBJECTIVE: Treatment planning, an essential component of clinical practice, has received little attention in the dental literature and there appears to be no consistent format being followed in the teaching and development of treatment plans within dental school curricula. No investigation, to our knowledge, has been carried out to explore the subject of treatment planning since the advent of electronic health record (EHR) use in dentistry. It is therefore important to examine the topic of treatment planning in the context of EHRs. METHODS: This paper reports on how 25 predoctoral dental students from two U.S. schools performed when asked to complete diagnosis and treatment planning exercises for two clinical scenarios in an EHR. Three calibrated clinical teaching faculty scored diagnosis entry, diagnosis-treatment (procedure) pairing, and sequencing of treatment according to criteria taught in their curriculum. Scores were then converted to percent correct and reported as means (with standard deviations). RESULTS: Overall, the participants earned 48.2% of the possible points. Participants at School 2 earned a mean of 54.3% compared with participants at School 1, who earned 41.9%. Students fared better selecting the appropriate treatment (59.8%) compared with choosing the correct diagnoses (41.9%) but performed least favorably when organizing the sequence of their treatment plans (41.7%). CONCLUSION: Our results highlight the need to improve the current process by which treatment planning is taught and also to consider the impact of technology on the fundamental skills of diagnosis and treatment planning within the modern educational setting.

Patch testing: what allergists should know.

Patch testing is a standardized, in vivo diagnostic test for type IV hypersensitivity reactions, resulting in allergic contact dermatitis, which clinically resembles eczema. Common allergens include fragrance chemicals, hair dyes, metals, rubber accelerators and preservatives. Known allergens at particular concentrations in optimal vehicles are tested on the upper back under occlusion for 2 days. Readings according to international criteria are usually performed on days 2 and 4. Irritant reactions can closely resemble allergic ones, and further tests may be necessary to discriminate. Interpretation of the relevance of the reactions can also be difficult, perhaps requiring repeated open application testing, work-site visits etc. Monitoring of trends in patch test positivity can be effective in primary prevention of type IV allergy.

A randomized clinical trial of anticaries therapies targeted according to risk assessment (caries management by risk assessment).

This randomized parallel group clinical trial assessed whether combined antibacterial and fluoride therapy benefits the balance between caries pathological and protective factors. Eligible, enrolled adults (n = 231), with 1-7 baseline cavitated teeth, attending a dental school clinic were randomly assigned to a control or intervention group. Salivary mutans streptococci (MS), lactobacilli (LB), fluoride (F) level, and resulting caries risk status (low or high) assays were determined at baseline and every 6 months. After baseline, all cavitated teeth were restored. An examiner masked to group conducted caries exams at baseline and 2 years after completing restorations. The intervention group used fluoride dentifrice (1,100 ppm F as NaF), 0.12% chlorhexidine gluconate rinse based upon bacterial challenge (MS and LB), and 0.05% NaF rinse based upon salivary F. For the primary outcome, mean caries increment, no statistically significant difference was observed (24% difference between control and intervention groups, p = 0.101). However, the supplemental adjusted zero-inflated Poisson caries increment (change in DMFS) model showed the intervention group had a statistically significantly 24% lower mean than the control group (p = 0.020). Overall, caries risk reduced significantly in intervention versus control over 2 years (baseline adjusted generalized linear mixed models odds ratio, aOR = 3.45; 95% CI: 1.67, 7.13). Change in MS bacterial challenge differed significantly between groups (aOR = 6.70; 95% CI: 2.96, 15.13) but not for LB or F. Targeted antibacterial and fluoride therapy based on salivary microbial and fluoride levels favorably altered the balance between pathological and protective caries risk factors.

The Hapten-Atopy hypothesis II: the 'cutaneous hapten paradox'.

One explanation for the striking increase in atopic disease in developed countries over the last 50 years has been the 'Hygiene Hypothesis'; a reduced exposure to pathogenic microorganisms. We have postulated previously that oral and cutaneous exposure to chemicals generally and to haptens in particular, may have also contributed to the increased prevalence of atopic disease; the 'Hapten-Atopy Hypothesis'. The purpose here is to extend further that hypothesis by consideration of the impact interplay between the innate and adaptive immune systems may have on the development of atopic allergy. It is clear that experimental cutaneous exposure to hapten can generate immune responses of different types with regard to T-helper (Th) cell phenotype. Allergic contact dermatitis is frequently associated with a selective Th1 (and Tc1)-driven inflammation, whereas atopic dermatitis is characterized by preferential Th2 cell responses. We postulate here that initial innate immune responses to chemical haptens result in the promotion of Th1 cell responses secondary to stimulation of Toll-like receptor. However, we argue also that under conditions where there is prolonged skin exposure to hapten there will be a shift of Th cell phenotype to selective Th2-type responses. The significance of such interactions is the possibility that repeated low-level skin exposure to certain types of hapten may result in the creation of an immunological environment in which the development of Th2 immune responses to third party antigens is favoured. The hypothesis is advanced that the nature and conditions of skin exposure to common haptens may impact on the quality of cutaneous immune responses such that in some circumstances the development atopic disease is favoured.

Structure, function and evolutionary relationship of proteins containing a disintegrin domain.

Disintegrins are soluble integrin ligands from snake venoms that disrupt cell-matrix interactions. Recently, the nuclear magnetic resonance structures of two disintegrins were determined, providing provocative molecular insight into how a disintegrin may engage an integrin. In addition, it has recently been realized that disintegrins are derived from larger multifunctional proteins, and that there is a family of membrane-anchored, disintegrin domain-containing proteins that may promote important cell-cell interactions.

ADAMs: focus on the protease domain.

ADAMs are proteins containing a disintegrin and metalloproteinase domain. Several important insights were provided in the past year regarding ADAM metalloproteinases. ADAM 10 was implicated in the Notch signaling pathway. ADAM 17 was shown to be the long sought after tumor necrosis factor-alpha convertase and the crystal structure of its metalloproteinase domain was determined.

ADAMs and cell fusion.

Members of the ADAM family (membrane proteins with a disintegrin and metalloprotease domain) have been implicated in several cell-interactive events, including cell-cell fusion. Recent evidence implicates three ADAMs, fertilin-alpha, fertilin-beta, and meltrin-alpha, in sperm-egg fusion and myoblast fusion. In light of the large number and wide tissue distribution of the ADAMs, they may also participate in other cell-cell fusion events. As ADAMs are also found in both vertebrates and invertebrates, some features of cell-cell fusion reactions may be conserved throughout the animal kingdom.