Enhanced inhibition of Pseudomonas aeruginosa virulence factor production and biofilm development by sublethal concentrations of eugenol and phenyllactic acid.

Biofilm development in Pseudomonas aeruginosa is regulated by its quorum sensing (QS) systems. It has three major QS systems: LasI/R, RhlI/R and PQS/MvfR. Previous studies showed that phenyllactic acid (PLA) binds to RhlR and PqsR and inhibits the Rhl and PQS QS; and eugenol at sublethal concentration inhibits Las and PQS QS systems. Here, we have demonstrated that a combination of sublethal doses of eugenol and PLA enhanced the inhibition of the QS mediated production of the virulence factors and biofilm development of this pathogen. A combination of 50 µmol l-1 eugenol and 0·3 mmol l-1 PLA significantly inhibited the pyocyanin production, protease activity, swarming motility and cytotoxic activities of P. aeruginosa strain PAO1, whereas eugenol and PLA when added individually to PAO1 cultures were less effective in inhibiting its virulence factor expression. Biofilm formation of PAO1 was reduced by 32, 19 and 87% on glass surfaces; and 54, 49 and 93% on catheter surfaces when treated using 50 µmol l-1 eugenol or 0·3 mmol l-1 PLA and their combinations, respectively. The in vitro finding in the reduction of biofilm development was further validated in vivo using a catheter associated medaka fish biofilm model. Our results indicate that a combination of QS inhibitors targeting different QS pathways should be selected while designing therapeutic molecules to achieve maximum QS mediated biofilm inhibition and clinical outcome against P. aeruginosa.

Measurement of the Electrical Properties of a Thundercloud Through Muon Imaging by the GRAPES-3 Experiment.

The GRAPES-3 muon telescope located in Ooty, India records rapid (∼10 min) variations in the muon intensity during major thunderstorms. Out of a total of 184 thunderstorms recorded during the interval of April 2011-December 2014, the one on December 1, 2014 produced a massive potential of 1.3 GV. The electric field measured by four well-separated (up to 6 km) monitors on the ground was used to help estimate some of the properties of this thundercloud, including its altitude and area that were found to be 11.4 km above mean sea level and ≥380 km^{2}, respectively. A charging time of 6 min to reach 1.3 GV implied the delivery of a power of ≥2 GW by this thundercloud that was moving at a speed of ∼60 km h^{-1}. This work possibly provides the first direct evidence for the generation of gigavolt potentials in thunderclouds that could also possibly explain the production of highest-energy (100 MeV) gamma rays in the terrestrial gamma-ray flashes.

Transient Weakening of Earth's Magnetic Shield Probed by a Cosmic Ray Burst.

The GRAPES-3 tracking muon telescope in Ooty, India measures muon intensity at high cutoff rigidities (15-24 GV) along nine independent directions covering 2.3 sr. The arrival of a coronal mass ejection on 22 June 2015 18:40 UT had triggered a severe G4-class geomagnetic storm (storm). Starting 19:00 UT, the GRAPES-3 muon telescope recorded a 2 h high-energy (∼20 GeV) burst of galactic cosmic rays (GCRs) that was strongly correlated with a 40 nT surge in the interplanetary magnetic field (IMF). Simulations have shown that a large (17×) compression of the IMF to 680 nT, followed by reconnection with the geomagnetic field (GMF) leading to lower cutoff rigidities could generate this burst. Here, 680 nT represents a short-term change in GMF around Earth, averaged over 7 times its volume. The GCRs, due to lowering of cutoff rigidities, were deflected from Earth's day side by ∼210° in longitude, offering a natural explanation of its night-time detection by the GRAPES-3. The simultaneous occurrence of the burst in all nine directions suggests its origin close to Earth. It also indicates a transient weakening of Earth's magnetic shield, and may hold clues for a better understanding of future superstorms that could cripple modern technological infrastructure on Earth, and endanger the lives of the astronauts in space.

Effects of rituximab-based B-cell depletion therapy on skin manifestations of lupus erythematosus--report of 17 cases and review of the literature.

Cutaneous manifestations occur frequently in systemic lupus erythematosus (SLE) and are pathognomonic in subacute-cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Although B-cell depletion therapy (BCDT) has demonstrated efficacy in SLE with visceral involvement, its usefulness for patients with predominant skin manifestations has not been fully established. In this single-centre, retrospective study 14 consecutive SLE, one CCLE and two SCLE patients with recalcitrant skin involvement were treated with 2 × rituximab 1 g, and 1 × cyclophosphamide 750 mg. Six months after BCDT, nine of 17 (53%) patients were in complete (CR) or partial remission (PR). Relapses occurred in 12 patients (71%) at a mean time of 10 ± 1.8 months after BCDT. A second cycle of BCDT achieved a more sustained remission in seven of nine patients (78%) lasting for a mean time of 18.4 ± 2.7 months. Minor adverse events were experienced by three patients. Mean follow-up was 30 months. Our own results and the literature review demonstrate that BCDT based on rituximab is well tolerated and may be effective for cutaneous lesions of lupus erythematosus. Randomized controlled trials are necessary to further evaluate the value of BCDT for this group of patients.

Occupational exposure to ionizing radiation has no effect on T- and B-cell total counts or percentages of helper, cytotoxic and activated T-cell subsets in the peripheral circulation of male radiation workers.

PURPOSE: To investigate changes in immune cell subsets in the peripheral circulation of a male population occupationally exposed to ionizing radiation. MATERIALS AND METHODS: Peripheral blood samples were taken from 194 male workers with cumulative exposures of >200 mSv (mean exposure 331.5 mSv, mean age 51 years) and from a reference population of 131 male workers with cumulative exposures of <27.5 mSv (mean exposure 13.9 mSv, mean age 47 years). Samples were analysed by flow cytometry for T- and B-cell total counts and for the T-cell subset percentages of CD4+ (helper T-cells), CD8+ (cytotoxic T-cells) and CD3+/HLA-DR+ (activated T-cells). RESULTS: Comparison of the >200 and <27.5 mSv exposure groups using linear regression analysis showed no statistically significant differences between the two groups for T-cell total count, B-cell total count or for percentages of the T-cell subsets CD4+, CD8+ or CD3+/HLA-DR+ and CD4+:CD8+. However, statistically significant increases in both T- and B-cell total counts were observed within the two exposure groups and data pooled from both groups when non-smokers (never and ex-smokers) were compared with current smokers. For pooled data T-cell total count increased in smokers by 35% (p=0.0001) and B-cell total count increased by 37% (p=0.0004). CONCLUSIONS: No significant immunological effects were observed in male radiation workers with cumulative exposures of >200 mSv when compared with a reference population with cumulative exposures of <27.5 mSv, although highly significant increases in both T- and B-cell total counts were observed in smokers compared with non-smokers.

Persistent anticonvulsant hypersensitivity syndrome responding to ciclosporin.

The drug hypersensitivity syndrome is a severe, multisystem reaction that typically develops within 2 months of starting a drug. We describe a case which has been unusually persistent, requiring prolonged treatment with systemic corticosteroids and after 1 year, ciclosporin. To the best of our knowledge, the use of ciclosporin for the treatment of the drug hypersensitivity syndrome has not been described previously.

Psoriasis bullosa acquisita.

We report a 51-year-old man with a 20-year history of chronic plaque psoriasis who developed an autoimmune subepidermal blistering eruption that had clinical features of bullous pemphigoid, erythema multiforme and epidermolysis bullosa acquisita. Investigations revealed a 1 : 400 titre circulating and in vivo bound IgG autoantibody that mapped to the dermal side of 1 m NaCl-split skin and localized to the lower lamina lucida/upper lamina densa on immunogold electron microscopy. Immunoblotting, using dermal extracts, showed serum binding to antigens of approximately 200- and approximately 260 kDa. Indirect immunofluorescence microscopy, using the patient's serum on archival skin sections taken from selected individuals with different forms of inherited epidermolysis bullosa as substrate, showed normal basement membrane labelling on all samples apart from recessive dystrophic epidermolysis bullosa skin (with inherent mutations in the type VII collagen gene): in these cases there was a complete absence of immunostaining. Clinically, the patient responded rapidly to combination treatment with intravenous immunoglobulin and oral corticosteroids, dapsone and mycophenolate mofetil. Autoimmune subepidermal blistering has been reported in other patients with psoriasis, although no specific target antigen has ever been determined. Our study provides preliminary evidence that, for this patient at least, the autoantibody may be targeted against a skin component closely associated with type VII collagen (the epidermolysis bullosa acquisita antigen). Therefore, we propose the term 'psoriasis bullosa acquisita' for this and possibly other patients with similar skin eruptions.

Ferrochelatase gene polymorphism analysis for accurate genetic counselling in erythropoietic protoporphyria.

It has recently been shown that most cases of clinically overt erythropoietic protoporphyria (EPP) result from coinheritance of a mutated ferrochelatase gene and a commonly occurring low-expression normal variant allele. The identification of two polymorphic variant sequences associated with this low-expression allele now enables improved predictive counselling for couples where one partner has EPP. We describe a patient and his spouse in whom we have used such genetic analysis to provide an accurate estimate of the chance that their future offspring may suffer from EPP.

An unusual presentation of diffuse granuloma annulare in an HIV-positive patient - immunohistochemical evidence of predominant CD8 lymphocytes.

Over the past decade there have been several reports in the literature of atypical forms of granuloma annulare (GA) occurring in HIV positive patients. We now report a case of diffuse granuloma annulare in an HIV positive patient with unusual clinical and immunohistological features. Our patient presented with a persistent extensive macular erythematous eruption on his face and upper trunk with bizarre sparing around the nipples and axillae. The histology showed an interstitial pattern of GA, with a predominance of CD8 positive cells, in contrast to the usual CD4 positive infiltrate typically seen in GA.

Heat shock proteins and the skin.

Heat shock proteins are of fundamental importance in cutaneous biology, from protection against UV-induced damage to wound healing and repair. Heat shock proteins have important regulatory roles in the control of apoptosis, regulation of steroid aporeceptors, kinases, and other protein remodelling events. They are also implicated in the control of cell growth, and as such, are potential targets for cancer diagnosis and treatment. Currently, emphasis is being placed on the potential use of these proteins in the prevention and treatment of disease. Therapeutic manipulation of these proteins may ultimately lead to novel treatments for diseases as diverse as melanoma to epidermolysis bullosa.

Comparative frequency of patch test reactions to topical antibiotics.

BACKGROUND: Neomycin, clioquinol and fusidic acid are all topical antibiotics widely used in dermatological practice in the U.K., either as a single agent or in combination with topical corticosteroids. However, an adverse effect of topical antibiotics is contact sensitization. OBJECTIVES: To examine the frequency of positive patch test reactions to fusidic acid, clioquinol and neomycin. METHODS: To compare the frequency of allergic patch test reactions over 1 year, we patch tested all patients attending the St John's Institute of Dermatology contact dermatitis clinic for one calendar year with fusidic acid, neomycin and clioquinol. RESULTS: We patch tested 1119 patients. Positive patch test reactions to neomycin were noted in 40 patients (3.6%), compared with eight patients (0.7%) to clioquinol and three patients (0.3%) to fusidic acid. The frequency of medicament allergy to neomycin was thus five times more common than to clioquinol and ten times more common than to fusidic acid. Although fusidic acid is not part of our extended standard series, it is in our medicaments series. Therefore, in the second part of our study, we reviewed all cases of positive patch test reactions to fusidic acid over the last 20 years. We found that the frequency of hypersensitivity has decreased since the early 1980s despite increasing usage; the current average frequency being 1.62 patch-tested patients per year (1.45%) of those patch tested to the medicaments series). The most common diagnosis in such patients was stasis dermatitis (54.2%). CONCLUSIONS: The frequency of fusidic acid allergy in an eczema population is low and is comparable with published data from over 10 years ago.

Factors influencing pediatric injury in side impact collisions.

BACKGROUND: Side impact collisions pose a great risk to children in crashes, but information about the injury mechanisms is limited. METHODS: This study involves a case series of children in side impact collisions who were identified through Partners for Child Passenger Safety, a large, child-focused crash surveillance system. The aim of the current study was to use in-depth crash investigations to identify injury mechanisms to children in side impact collisions. RESULTS: Ninety-three children in 55 side impact crashes were studied. Twenty-three percent (n = 22) of the children received an Abbreviated Injury Scale (AIS) score > or = 2 (clinically significant) injury. In these 22 children, head (40%), extremity (23%), and abdominal injuries (21%) were the most common significant injuries. Cases that illustrate body region-specific injury mechanisms are discussed. CONCLUSION: The cases revealed that serious injuries, particularly head injuries, occur even in minor crashes, and efforts should be made to make the interiors of vehicles more child occupant friendly. Lower extremity and abdominal injuries occurred because of contact with the intruding door. Design of vehicles to minimize crush should mitigate the occurrence and severity of these injuries.

Child occupant protection: a summary of current safety recommendations.

In 1998, 140 children younger than 1 year of age were killed in motor vehicle crashes, and nearly half of those children killed were restrained. Used correctly, child safety seats dramatically reduce a child's risk of death in a motor vehicle crash, but unfortunately, incorrect use of child seats is widespread. Obstetricians and gynecologists have a unique opportunity to counsel parents on the correct restraint for their infants and to provide recommendations for the proper restraint of older children as well. The recommendations for child occupant protection are updated with new information constantly. This article will provide an overview of the current recommendations for restraining children in motor vehicles and identify sources for up-to-date information for physicians and families.

Assessing child restraint misuse by parental survey.

OBJECTIVE: To determine the extent to which child restraint system (CRS) misuse can be evaluated by parental survey. METHODS: A cross sectional survey was conducted at eight CRS clinics from May to October, 1998. Before CRS inspection, parents were administered a structured interview to identify distinct characteristics of restraint use and misuse. After the interview, a certified child passenger safety technician team independently evaluated the restraint system and identified specific modes of misuse. Parent descriptions of CRS use were compared with observations of the technician and the degree of agreement between the two was assessed for several specific attributes of use. RESULTS: A total of 100 children restrained in convertible CRSs were included in the study. Parents were able to accurately report several aspects of child restraint use-in particular, the attachment and fit of the CRS, the use of the harness clip, and the CRS incline. Parents were less accurate in their characterization of the fit of the child in the CRS. For nearly every item assessed, parents were more accurate in their description of correct compared with incorrect use. CONCLUSIONS: Interview tools can be developed that enable parents to describe aspects of CRS use and that screen for correct CRS use. These tools could be administered by telephone to obtain a more representative estimate of the prevalence of CRS misuse or to screen for CRS misuse. This screening would assist in targeting time consuming and costly CRS clinics to those parents who need them the most.