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Background: Chronic urticaria patients who demonstrate autoantibodies against the high-affinity receptor of IgE (FceRI) or IgE itself tend to have a high itch and wheal score, and systemic symptoms may have a significant bearing on their management in terms of super pharmacologic doses of antihistamines needed or use of immunomodulators. Most studies have used histamine release assays rather than autologous serum skin tests (ASSTs) for correlating urticaria severity and histamine releasing activity. Methods: An ASST was performed in 100 (M:F, 31:69) chronic urticaria patients aged between 14 and 63 (mean, 32.69 ± 13) years with an objective to study the clinicoepidemiologic features like age, sex, age of onset and duration, frequency and distribution of wheals, urticaria severity, angioedema and systemic manifestations in ASST-positive and ASST-negative patients. Results: ASST was positive in 46% of the patients and negative in 54% of the patients, respectively. Both groups showed no statistically significant difference for epidemiological details. However, the ASST-positive patients had a higher mean urticaria activity score, frequent involvement of more body sites, particularly palms and soles, presence of throat angioedema and general constitutional, respiratory or gastrointestinal symptoms in comparison with the ASST-negative patients. Conclusions: Apparently, ASST-positive patients have more severe clinical manifestations of chronic urticaria. The knowledge will be useful for the treating dermatologists and patients alike in view of its therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: There is a strong need to develop a photopatch test tray suitable for Indian patients of photodermatitis as European/Scandinavian photopatch test trays may not be wholly relevant for them. Aim: We carried out this study using photoallergens relevant in the Indian context to determine their relevance in patients of photodermatitis. Methods: Thirty patients (M:F, 23:7) between 19 and 76 years of age of photodermatitis and 10 controls were patch- and photopatch tested with 20 common photoallergens. In addition, the patients were also (photo) patch tested with articles of daily use as and when these were suspected to be the cause. Results: Forty-three positive reactions to one or more antigens were seen in 22 (74%) patients. Fourteen positive photopatch tests to seven allergens were observed in 10 (33%) patients, and nine (30%) of them had a definite relevance. The most common contact allergen was fragrance mix (FM) (30%), followed by p-phenylenediamine (20%) and Parthenium hysterophorous (17%). The definite relevance of the patch- and photopatch tests could be correlated in 47% of these patients. Conclusions: FM is the most common contact and photocontact allergen among the various photopatch test antigens. Although differences in technique and evaluation make direct comparison between different centers difficult, still photopatch testing remains an integral part and gold standard for the work-up of the photosensitive patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Elimination of allergens/topical medications causing contact dermatitis in venous eczema, which poses a significant problem in its chronicity and treatment, provides the basis for better therapeutic outcome. Our objective was to determine the pattern of contact sensitization in venous eczema patients in Himachal Pradesh (India).Methods: Thirty-four patients (M:F, 31:3) and 10 controls (M:F, 6:4) were patch tested with Indian standard series and 10 commonly used topical medicaments.Results: Positive patch test results were seen in 50% (M:F, 16:1) of the patients. Common allergens were Fragrance mix (15%), p-phenylendiamine (15%), nickel (9%), wool alcohol (9%), chinoform (9%), balsum of Peru (5%), cobalt chloride (5%), potassium dichromate (3%), epoxy resin (3%), thiuram mix (3%) and formaldehyde (3%). Only sisomycin and miconazole among the topical medications elicited a positive patch test reaction in 3 and 5% patients, respectively. Neomycin contact sensitivity was not seen in any of the patients. One patient who had exacerbation of venous eczema following accidental application of topical diclofenac showed a positive patch test reaction to it.Conclusions: Patch test should be used to identify the topical agents that may be responsible for perpetuation or aggravation of eczema, especially in patients who do not improve despite adequate treatment of other underlying cause(s). [ABSTRACT FROM AUTHOR]

A quiz about the case of a 10-year-old child who presented with photosensitivity and recurrent blistering on exposed areas is presented.

Extensive chromium (Cr) release into water and soil severely impairs crop productivity worldwide. Nanoparticle (NP) technology has shown potential for reducing heavy metal toxicity and improving plant physicochemical profiles. Herein, we investigated the effects of exogenous zinc oxide NPs (ZnO-NPs) on alleviating Cr stress in Cr-sensitive and tolerant chickpea genotypes. Hydroponically grown chickpea plants were exposed to Cr stress (0 and 120 μM) and ZnO-NPs (25 μM, 20 nm size) twice at a 7-day interval. Cr exposure reduced physiochemical profiles, ion content, cell viability, and gas exchange parameters, and it increased organic acid exudate accumulation in roots and the Cr content in the roots and leaves of the plants. However, ZnO-NP application significantly increased plant growth, enzymatic activities, proline, total soluble sugar, and protein and gas exchange parameters and reduced malondialdehyde and hydrogen peroxide levels, Cr content in roots, and organic acid presence to improve root cell viability. This study provides new insights into the role of ZnO-NPs in reducing oxidative stress along with Cr accumulation and mobility due to low levels of organic acids in chickpea roots. Notably, the Cr-tolerant genotype exhibited more pronounced alleviation of Cr stress by ZnO-NPs. These findings highlight the potential of ZnO-NP in regulating plant growth, reducing Cr accumulation, and promoting sustainable agricultural development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Chromium (Cr), a highly toxic redox-active metal cation in soil, seriously threatens global agriculture by affecting nutrient uptake and disturbing various physio-biochemical processes in plants, thereby reducing yields. Here, we examined the effects of different concentrations of Cr alone and in combination with hydrogen sulfide (H 2 S) application on the growth and physio-biochemical performance of two mungbeans (Vigna radiata L.) varieties, viz. Pusa Vishal (PV; Cr tolerant) and Pusa Ratna (PR; Cr sensitive), growing in a pot in hydroponics. Plants were grown in the pot experiment to examine their growth, enzymatic and non-enzymatic antioxidant levels, electrolyte balance, and plasma membrane (PM) H + -ATPase activity. Furthermore, root anatomy and cell death were analysed 15 days after sowing both varieties in hydroponic systems. The Cr-induced accumulation of reactive oxygen species caused cell death and affected the root anatomy and growth of both varieties. However, the extent of alteration in anatomical features was less in PV than in PR. Exogenous application of H 2 S promoted plant growth, thereby improving plant antioxidant activities and reducing cell death by suppressing Cr accumulation and translocation. Seedlings of both cultivars treated with H 2 S exhibited enhanced photosynthesis, ion uptake, glutathione, and proline levels and reduced oxidative stress. Interestingly, H 2 S restricted the translocation of Cr to aerial parts of plants by improving the nutrient profile and viability of root cells, thereby relieving plants from oxidative bursts by activating the antioxidant machinery through triggering the ascorbate-glutathione cycle. Overall, H 2 S application improved the nutrient profile and ionic homeostasis of Cr-stressed mungbean plants. These results highlight the importance of H 2 S application in protecting crops against Cr toxicity. Our findings can be utilised to develop management strategies to improve heavy metal tolerance among crops., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Extensive use of chromium (Cr) in anthropogenic activities leads to Cr toxicity in plants causing serious threat to the environment. Cr toxicity impairs plant growth, development, and metabolism. In the present study, we explored the effect of NaHS [a hydrogen sulfide; (H 2 S), donor] and silicon (Si), alone or in combination, on two chickpea ( Cicer arietinum ) varieties (Pusa 2085 and Pusa Green 112), in pot conditions under Cr stress. Cr stress increased accumulation of Cr reduction of the plasma membrane (PM) H + -ATPase activity and decreased in photosynthetic pigments, essential minerals, relative water contents (RWC), and enzymatic and non-enzymatic antioxidants in both the varieties. Exogenous application of NaHS and Si on plants exposed to Cr stress mitigated the effect of Cr and enhanced the physiological and biochemical parameters by reducing Cr accumulation and oxidative stress in roots and leaves. The interactive effects of NaHS and Si showed a highly significant and positive correlation with PM H + -ATPase activity, photosynthetic pigments, essential minerals, RWC, proline content, and enzymatic antioxidant activities (catalase, peroxidase, ascorbate peroxidase, dehydroascorbate reductase, superoxide dismutase, and monodehydroascorbate reductase). A similar trend was observed for non-enzymatic antioxidant activities (ascorbic acid, glutathione, oxidized glutathione, and dehydroascorbic acid level) in leaves while oxidative damage in roots and leaves showed a negative correlation. Exogenous application of NaHS + Si could enhance Cr stress tolerance in chickpea and field studies are warranted for assessing crop yield under Cr-affected area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Singh, Siddiqui, Alamri, Sarkar, Rathore, Prasad, Singh, Sharma, Kalaji and Brysiewicz.)

Chromium (Cr) accumulation in crops reduces yield. Here, we grew two chickpea cultivars, Pusa 2085 (Cr-tolerant) and Pusa Green 112 (Cr-sensitive), in hydroponic and pot conditions under different Cr treatments: 0 and 120 µM Cr and 120 µM Cr + 100 mM glycine betaine (GB). For plants grown in the hydroponic media, we evaluated root morphological attributes and plasma membrane integrity via Evans blue uptake. We also estimated H + -ATPase activity in the roots and leaves of both cultivars. Plants in pots under conditions similar to those of the hydroponic setup were used to measure growth traits, oxidative stress, chlorophyll contents, enzymatic activities, proline levels, and nutrient elements at the seedling stage. Traits such as Cr uptake in different plant parts after 42 days and grain yield after 140 days of growth were also evaluated. In both cultivars, plant growth traits, chlorophyll contents, enzymatic activities, nutrient contents, and grain yield were significantly reduced under Cr stress, whereas oxidative stress and proline levels were increased compared to the control levels. Further, Cr uptake was remarkably decreased in the roots and leaves of Cr-tolerant than in Cr-sensitive cultivars. Application of GB led to improved root growth and morpho-physiological attributes and reduced oxidative stress along with reduced loss in plasma membrane integrity and subsequently increase in H + -ATPase activity. An increment in these parameters shows that the exogenous application of GB improves the Cr stress tolerance in chickpea plants., (© 2022. The Author(s).)

Chromium (Cr) presently used in various major industries and its residues possess a potent environmental threat. Contamination of soil and water resources due to Cr ions and its toxicity has adversely affected plant growth and crop productivity. Here, deleterious effects of different levels of Cr (VI) treatments i.e., 0, 30, 60, 90, and 120 μM on two mungbean cultivars, Pusa Vishal (PV) and Pusa Ratna (PR), in hydroponic and pot conditions were evaluated. Germination, seedling growth, biomass production, antioxidant enzyme, electrolytic leakage, oxidative stress (hydrogen peroxide and malondialdehyde), and proline content were determined to evaluate the performance of both cultivars under hydroponic conditions for 15 days. The hydroponic results were further compared with the growth and seed yield attributes of both the genotypes in pot experiments performed over 2 years. Seedling growth, biomass production, total chlorophyll (Chl), Chl- a , Chl- b , nitrogen content, plant height, seed protein, and seed yield decreased significantly under the 120 μM Cr stress level. Activities of antioxidant enzymes superoxide dismutase, catalase, ascorbate peroxidase and peroxidase increased in the leaves following Cr exposure at 60-90 μM but declined at 120 μM. Cr-induced reductions in growth and seed yield attributes were more in the sensitive than in the tolerant cultivar. Cr accumulation in the roots, stems, leaves, and seeds increased with an increase in Cr concentrations in the pot conditions. Furthermore, for both cultivars, there were significant negative correlations in morpho-physiological characteristics under high Cr concentrations. Overall results suggest that (PR) is more sensitive to Cr stress (PV) at the seedling stage and in pot conditions. Furthermore, (PV) can be utilized to study the mechanisms of Cr tolerance and in breeding programs to develop Cr-resistant varieties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Singh, Sharma, Singh, Yerramilli, Narayan, Sarkar and Singh.)

The ever-increasing industrial activities over the decades have generated high toxic metal such as chromium (Cr) that hampers the crop productivity. This study evaluated the effect of Cr on two chickpea (Cicer arietinum L.) varieties, Pusa 2085 and Pusa Green 112, in hydroponic and pot-grown conditions. First, growth parameters (seed germination, seedling growth, and biomass production) and physio-biochemical parameters (oxidative stress and the content of antioxidants and proline) were measured to evaluate the performance of both varieties grown hydroponically for 21 days at concentrations of 0, 30, 60, 90 and 120 μM Cr in the form of potassium dichromate (K2Cr2O7). In both varieties, significantly deleterious effects on germination and seedling growth parameters were observed at 90 and 120 μM, while growth was stimulated at 30 μM Cr. Significant increases in malondialdehyde and hydrogen peroxide content and electrolyte leakage demonstrated enhanced oxidative injury to seedlings caused by higher concentrations of Cr. Further, increasing concentrations of Cr positively correlated with increased proline content, superoxide dismutase activity, and peroxide content in leaves. There was also an increase in peroxisomal ascorbate peroxidase and catalase in the leaves of both varieties at lower Cr concentrations, whereas a steep decline was recorded at higher Cr concentrations. In the pot experiments conducted over two consecutive years, growth, yield, yield attributes, grain protein, and Cr uptake and accumulation were measured at different Cr concentrations. Pusa Green 112 showed a significant reduction in plant growth, chlorophyll content, grain protein, pod number, and grain yield per plant when compared with Pusa 2085. Overall, our results indicate that Pusa 2085 has a higher Cr tolerance than Pusa Green 112. Therefore, Pusa 2085 could be used to further elucidate the mechanisms of Cr tolerance in plants and in breeding programmes to produce Cr-resistant varieties., Competing Interests: The authors have declared that no competing interests exist.

The objectives of this study are to determine the current treatment policies of UK shock-wave lithotripsy centres. Fixed-site lithotripter centres in the UK were identified via the national Therapeutic Interventions for Stones of the Ureter (TISU) study (n = 25). Questionnaires were completed regarding current SWL protocols for each centre, including management of anticoagulation, use of antibiotics and analgesia, urine testing, pacemakers, and arterial aneurysms. Data were collected regarding service delivery. Responses were obtained for 21 centres. Most centres use the Storz Modulith (85.7 %). Wide variation was observed in clinical contraindications to SWL, with 47.6 % centres performing SWL in patients with an abdominal aortic aneurysm, 66.7 % performing SWL in patients with a pacemaker, and 66.7 % of centres not performing SWL in asymptomatic patients with a urine dipstick positive for nitrites and leucocytes. The management of anticoagulation pre- and post-SWL showed wide variation, with the omission of anticoagulation ranging from 0 to 10 days pre-SWL. Seventeen distinct analgesia regimens were reported and prophylactic antibiotics are routinely administered in 25.0 % of centres. Tamsulosin is prescribed to all patients in 20.0 % of centres and a further 15.0 % of centres routinely prescribe tamsulosin post-SWL of ureteric stones. The included centres undertake SWL a median of 4 days per week and treat a median of six patients per list. Emergency SWL is unavailable in 30.0 % of centres. This observational real-life study has identified a significant disparity in the delivery of SWL throughout the UK, despite high numbers of patients with renal and ureteric stones being treated with this modality. Further studies should address the key areas of controversy, including an assessment of technical training, and facilitate the development of national guidelines to ensure a high level of standardized care for SWL patients.

Due to increased sensitivity, the expression of circulating nucleotides is rapidly gaining popularity in cancer diagnosis. Whole blood mRNA has been used in studies on a number of cancers, most notably two separate studies that used whole blood mRNA to define non-overlapping signatures of prostate cancer that has become castration independent. Prostate cancer is known to rely on androgens for initial growth, and there is increasing evidence on the importance of the androgen axis in advanced disease. Using whole blood mRNA samples from patients with prostate cancer, we have identified the four-gene panel of FAM129A, MME, KRT7 and SOD2 in circulating mRNA that are differentially expressed in a discovery cohort of metastatic samples. Validation of these genes at the mRNA and protein level was undertaken in additional cohorts defined by risk of relapse following surgery and hormone status. All the four genes were downregulated at the mRNA level in the circulation and in primary tissue, but this was not always reflected in tissue protein expression. MME demonstrated significant differences in the hormone cohorts, whereas FAM129A is downregulated at the mRNA level but is raised at the protein level in tumours. Using published ChIP-seq data, we have demonstrated that this may be due to AR binding at the FAM129A and MME loci in multiple cell lines. These data suggest that whole blood mRNA of androgen-regulated genes has the potential to be used for diagnosis and monitoring of prostate cancer., (© 2016 Society for Endocrinology.)

Background: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome., Methods: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone., Findings: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions., Interpretation: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Treatment possibilities for clinically localised prostate cancer include radical prostatectomy (RP), external beam radiotherapy, brachytherapy, focal therapy and active surveillance. Conflicting and methodologically flawed observational data from the last two decades have led to uncertainty as to the best oncological option. However, recently, there has been a series of high-quality studies that point to disease specific and overall survival advantages for those men undergoing RP. This article reviews the latest evidence and argues that at the current time, RP must be considered the gold standard treatment for the majority of men with clinically localised prostate cancer.

Background: Subcutaneous phaeohyphomycosis usually results from traumatic inoculation with the fungus and generally occurs in immunosuppressed men. Cladosporium, Exophiala, and Alternaria spp. are commonly implicated pathogens., Objectives: We present a case of subcutaneous phaeohyphomycosis caused by Rhytidhysteron sp. that was refractory to conventional antifungal therapy., Case Report: A 72-year-old man with hypertension and diabetes presented with a multiloculated, large cystic swelling over the right dorsal foot. Laboratory findings and x-rays of the chest and left foot were normal., Results: Adequate control of the patient's diabetes was achieved, and the swelling was excised under itraconazole/terbinafine coverage. Histology showed multiple areas of neutrophilic abscess, epithelioid cells, foreign body giant cells, and multiple septate hyphae and yeast-like cells. Dematiaceous fungus was cultured but failed to produce spores. Sequencing of the isolate showed a match of > 99% with Rhytidhysteron rufulum. The patient demonstrated no response after one year of therapy with itraconazole/terbinafine. Weekly infiltration of the lesion with liposomal amphotericin B resulted in its complete resolution within 15 weeks., Conclusions: Lesions of phaeohyphomycosis appear morphologically similar regardless of the organism implicated. Hence, their diagnosis rests entirely on the clinicopathological and microbiological presentation. Molecular studies may be required to identify a fungus if attempts to grow it in artificial culture media fail. Rhytidhysteron spp. are not known as pathogens in humans, and no treatment protocol exists. Intralesional amphotericin was highly effective in our patient and caused no systemic adverse effects. Voriconazole and posaconazole are effective against disseminated/visceral phaeohyphomycotic infections, but their efficacy against Rhytidhysteron spp. remains unstudied., (© 2014 The International Society of Dermatology.)

Purpose: In a recent phase II clinical trial, low-dose (100 mg/m(2)) gemcitabine showed promise as a radiosensitizer in bladder cancer, but underlying mechanisms lack elucidation. Here, we investigated the mechanism of radiosensitization by low-dose gemcitabine in bladder cancer cell lines., Experimental Design: Four bladder cancer cell lines were screened for radiosensitization by low-dose gemcitabine using clonogenic assay, and gemcitabine-resistant RT112gem and CALgem cells created by exposure to increasing gemcitabine doses. Four key gemcitabine-regulatory genes were knocked down by transient siRNA. Nude mice carrying CALgem subcutaneous xenografts were exposed to 100 mg/kg gemcitabine ± ionizing radiation (IR) and response assessed by tumor growth delay., Results: Gemcitabine was cytotoxic in the low nanomolar range (10-40 nmol/L) in four bladder cancer cell lines and radiosensitized all four lines. Sensitizer enhancement ratios at 10% survival were: RT112 1.42, CAL29 1.55, T24 1.63, and VMCUB1 1.47. Transient siRNA knockdown of deoxycytidine kinase (dCK) significantly reduced radiosensitization by gemcitabine (P = 0.02). RT112gem and CALgem cells displayed robust decreases of dCK mRNA and protein levels; reexpression of dCK restored gemcitabine sensitivity. However, CALgem xenografts responded better to combination gemcitabine/IR than either treatment alone (P < 0.001) with dCK strongly expressed in the tumor vasculature and stroma., Conclusions: Gemcitabine resistance in bladder cancer cell lines was associated with decreased dCK expression, but gemcitabine-resistant xenografts were responsive to combination low-dose gemcitabine/IR. We propose that dCK activity in tumor vasculature renders it gemcitabine sensitive, which is sufficient to invoke a tumor response and permit tumor cell kill in gemcitabine-resistant tumors., (©2014 American Association for Cancer Research.)

In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Dermatophytosis is defined as the fungal infection of the skin, hair and nails by a group of keratinophillic fungi known as dermatophytes., Aims and Objectives: This study is an attempt to find out various species of dermatophytes in clinically suspected cases of dermatophytosis., Materials and Methods: One hundred samples were subjected to direct microscopy by potassium hydroxide wet mount (KOH) and isolation on culture with Sabourauds dextrose agar., Results: Out of these 80 (80%) samples were KOH positive while 20 (20%) were KOH negative. Overall culture positivity rate was 68%. Dermatophytosis was more common in males, the M:F ratio was 4:1., Conclusion: Total seven species were isolated on culture. Trichophyton rubrum (66.17%) was the commonest isolate followed by Trichophyton mentagrophytes (19.11%), Trichophyton violaceum (7.35%), Trichophyton tonsurans (2.94%) and one isolate each of Epidermophyton floccosum and Microsporum gypseum (1.47%).

Castrate-resistant prostate cancer (CRPC) is poorly characterized and heterogeneous and while the androgen receptor (AR) is of singular importance, other factors such as c-Myc and the E2F family also play a role in later stage disease. HES6 is a transcription co-factor associated with stem cell characteristics in neural tissue. Here we show that HES6 is up-regulated in aggressive human prostate cancer and drives castration-resistant tumour growth in the absence of ligand binding by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. In the clinical setting, we have uncovered a HES6-associated signature that predicts poor outcome in prostate cancer, which can be pharmacologically targeted by inhibition of PLK1 with restoration of sensitivity to castration. We have therefore shown for the first time the critical role of HES6 in the development of CRPC and identified its potential in patient-specific therapeutic strategies.

Psoriatic arthritis (PsA) is increasingly being recognized to cause progressive joint damage and disability. PsA unresponsive to non-steroidal anti-inflammatory drugs (NSAIDs), the conventional first-line choice of treatment, is usually managed with disease-modifying antirheumatic drugs (DMARDs) especially methotrexate. An 18-year-old HIV-negative male had progressively severe PsA of 4-month duration that was nearly confining him to a wheel chair. He did not respond to multiple NSAIDs, alone or in combination with methotrexate (15 mg/week), given for 4 weeks. Addition of prednisolone (10 mg on alternate days) controlled his symptoms within a week. The NSAIDs could be withdrawn after 4 weeks as the treatment progressed. The doses were tapered for methotrexate (5 mg/week) and prednisolone (2.5 mg on alternate days) every 8 weekly subsequently during 15 months of follow-up without recurrence/deformities or drug toxicity. For years, the use of corticosteroids in psoriasis has been criticized for their propensity to exacerbate the skin disease on withdrawal. However, monitored use of corticosteroids, even in low doses, combined with DMARDs may be a good therapeutic option in early stage of the PsA rather than 'steroid rescue' later. This will help in early control of joint inflammation, prevent joint damage and maintain long-term good functional capacity and quality of life. This may be useful when the cost or availability of biologics precludes their use. However, we discourage the use of corticosteroids as monotherapy.

The most significant and debilitating complication of herpes zoster (HZ) is herpetic neuralgia that accompanies and may persist in 10-15% of all zoster patients, particularly those over 60 years of age. The described 3 cases had an uncommon complication of spontaneous tooth exfoliation after trigeminal HZ that rarely finds mention in dermatology literature.

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A growing body of evidence supports the anti-cancer effect of histone deacetylase inhibitors (HDACi) in vitro, via multiple pathways, and many Phase I clinical trials have shown them to be well-tolerated in a range of malignancies. Combined therapies, including with radiation, present an exciting area of current and planned study. This review summarises the evidence to date, including pre-clinical data and clinical trials, of the anti-cancer effect of HDACi in urological cancers. It provides an overview of epigenetics and the mechanisms of action of HDACi. It suggests areas of future development, including the current challenges for the successful introduction of HDACi into clinical therapy. Epigenetic modifications are known to play a critical role in the development and progression of many cancers. The opposing actions of histone deacetylases (HDACs) and histone acetyltransferases (HATs) modify chromatin and lead to epigenetic gene regulation, in addition to wider effects on non-histone proteins. There is growing interest in the clinical application of HDAC inhibitors (HDACi) in cancer. HDACi have been shown to inhibit cancer cell growth both in vitro and in vivo and recent clinical trials have shown encouraging results in various urological cancers. In this review, we discuss the existing evidence and potential role for HDACi in urological malignancies, including in combined therapies., (© 2013 BJU International.)

Many cancers display increased expression of histone deacetylases (HDACs) and therefore transcriptionally inactive chromatin, resulting in the downregulation of genes including tumour suppressor and DNA repair genes. Histone deacetylase inhibitors (HDACi) are a heterogeneous group of epigenetic therapeutics, showing promising anticancer effects in both pre-clinical and clinical settings, in particular the effect of radiosensitisation when administered in combination with radiotherapy. Radiotherapy remains one of the most common forms of cancer treatment, leading to cell death through the induction of DNA double-strand breaks (DSBs). Cells have developed mechanisms to repair such DSB through two major pathways: non-homologous end-joining and homologous recombination. Here, we explore the current evidence for the use of HDACi in combination with irradiation, focusing on the effects of HDACi on DNA damage signalling and repair in vitro. In addition, we summarise the clinical evidence for using HDACi with radiotherapy, a growing area of interest with great potential clinical utility.

The androgen receptor (AR) regulates prostate cell growth in man, and prostate cancer is the commonest cancer in men in the UK. We present a comprehensive analysis of AR binding sites in human prostate cancer tissues, including castrate-resistant prostate cancer (CRPC). We identified thousands of AR binding sites in CRPC tissue, most of which were not identified in PC cell lines. Many adjacent genes showed AR regulation in xenografts but not in cultured LNCaPs, demonstrating an in-vivo-restricted set of AR-regulated genes. Functional studies support a model of altered signaling in vivo that directs AR binding. We identified a 16 gene signature that outperformed a larger in-vitro-derived signature in clinical data sets, showing the importance of persistent AR signaling in CRPC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: Structured mentor-led training programmes permit the safe introduction of novice trainees to robotic-assisted laparoscopic prostatectomy (RALP). We outline the first description of parallel learning curves for individual surgical steps and quantify the relative difficulty of each step to propose an order of training in our structured mentoring programme., Patients and Methods: A prospective ethically approved database was used to evaluate the operating times of each individual surgical step, in the first 150 RALP cases performed independently by a robotic-naive laparoscopic surgeon. Linear regression analysis was used to quantify the effect of surgeon experience on the operating time for each individual surgical step., Results: Univariate linear regression analysis revealed significant reductions in operating time over the first 150 cases for all of the RALP steps, with the exception of the Rocco stitch. Multivariate linear regression analysis compensated for confounding variables and led to the identification of five surgical steps in which the operating time of each was significantly influenced by experience of the procedure. The most substantial improvement in operating time was seen in the bladder take down step. After taking into account the multivariate regression model, standardized univariate coefficients allowed an order of training to be identified for future RALP novices, of increasing complexity rather than order of surgery, beginning with the bladder take down step and ending with the vesico-urethral anastomosis., Conclusions: We can begin the training of new robotic-naive surgeons at simpler surgical steps, in which the greatest gains in expediency are made. We anticipate that identifying the more challenging surgical steps from this study and targeting training towards them may expedite our future trainees' proficiency at RALP., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Mercury poisoning was once common in the 19th century. With its declining use, now clinicians and the public in general are often unaware and unsuspecting of mercury toxicity. A 40-year-old woman and her two children were hospitalized with a 1-week history of a generalized lichenoid eruption. Clinical improvement occurred without a diagnosis; however, on returning home, features of acrodynia with digital gangrene developed in the woman, leading to suspicion of heavy metal poisoning. There was no recurrence after moving from their contaminated house., (© 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.)

Objective: • To study the outcomes and learning curve of robotic-assisted laparoscopic radical prostatectomy (RALP) in a single centre by two surgeons., Patients and Methods: • In total, 500 consecutive patients underwent RALP between 2005 and 2009 carried out by two surgeons. Using an ethically-approved database, prospective data collection of demographic, surgical, oncological and functional outcomes (patient reported) was performed, with up to 4 years of follow-up. • The learning curves of both surgeons were analyzed and, in addition, the first 100 and last 100 patients were compared to determine the effect of surgeon experience., Results: • The mean age of the patients was 61.5 years and mean preoperative prostate-specific antigen was 7.0 µg/L. Clinical stages were T1 in 63.2%, T2 in 33.8% and T3 in 3.0% of patients. Median (range) operating time was 170 (63-420) min and median (range) blood loss was 200 (20-3000) mL, with significant improvements for both surgeons with increasing experience (P < 0.001 and P= 0.029, respectively). • Pathological stages were pT2 in 53.4%, pT3a in 41.6%, pT3b in 4.0% and pT4 in 0.6% of patients. Overall, the positive margin rate (PMR) was 24.0% and stage-specific rates were 16.1%, 30.4%, 55.0% and 100.0% for pT2, pT3a, pT3b and pT4 disease, respectively. In the last 50 cases performed by each surgeon, the PMRs for pT2 and pT3a disease were 8.0% and 19.1% (surgeon 1) and 12.9% and 23.5% (surgeon 2). • At 12 months of follow-up, 91.3% of patients were continent and, by 48 months of follow-up, 75% of men with preoperative potency who underwent bilateral nerve-sparing RALP were potent., Conclusion: • This is the first report of two surgeons' learning curves in a single centre and shows that key learning curve outcomes continued to improve during the series, suggesting that the learning curve for RALP may be longer than has been previously suggested., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by a unique susceptibility to cutaneous infection by a group of phylogenetically related human papilloma viruses (HPVs). These patients show a defect in cell-mediated immunity specific toward the causative HPVs that lead to lifelong disease. The defect is usually inherited as autosomal recessive trait and presents clinically with plane warts, pityriasis versicolor-like lesions and reddish verrucous plaques. Dysplastic and malignant changes in the form of actinic keratoses, Bowen's disease and squamous cell carcinoma (SCC) are common but metastasis occurs rarely. A totally effective treatment against EV is as yet highly desirable. Two siblings having autosomal dominant EV presented with multiple actinic keratoses in addition to classic lesions. One of them had also developed well-differentiated SCC over forehead with metastases to regional lymph nodes. They were treated with combination of excision of small malignant/premalignant lesions, topical 5-flurouracil and sun protection. Additionally, elective excision/grafting of large SCC was performed after chemotherapy/radiotherapy in patient with metastatic SCC. Oral acitretin (25 mg/day) was of benefit in the other patient. Overall clinicotherapeutic experience in both the patients is discussed here.

Three unusual clinical forms of sporotrichosis described in this paper will be a primer for the clinicians for an early diagnosis and treatment, especially in its unusual presentations. Case 1, a 52-year-old man, developed sporotrichosis over pre-existing facial nodulo-ulcerative basal cell carcinoma of seven-year duration, due to its contamination perhaps from topical herbal pastes and lymphocutaneous sporotrichosis over right hand/forearm from facial lesion/herbal paste. Case 2, a 25-year-old woman, presented with disseminated systemic-cutaneous, osteoarticular and possibly pleural (effusion) sporotrichosis. There was no laboratory evidence of tuberculosis and treatment with anti-tuberculosis drugs (ATT) did not benefit. Both these cases were diagnosed by histopathology/culture of S. schenckii from tissue specimens. Case 3, a 20-year-old girl, had multiple intensely pruritic, nodular lesions over/around left knee of two-year duration. She was diagnosed clinically as a case of prurigo nodularis and histologically as cutaneous tuberculosis, albeit, other laboratory investigations and treatment with ATT did not support the diagnosis. All the three patients responded well to saturated solution of potassium iodide (SSKI) therapy. A high clinical suspicion is important in early diagnosis and treatment to prevent chronicity and morbidity in these patients. SSKI is fairly safe and effective when itraconazole is not affordable/available.