Quality of life impact in patients with cutaneous toxicities caused by EGFR inhibitors and immunotherapy.

BACKGROUND: novel oncologic therapies, including epidermal growth factor receptor inhibitors (EGFR-Is) and immune checkpoint inhibitors (ICIs), are associated with a new spectrum of adverse reactions, with prominent cutaneous toxicities. The impact of cutaneous adverse events (cAEs) on patients' quality of life (QoL) represents an unmet clinical need. OBJECTIVES: 1) to assess whether cutaneous toxicities directed therapies are effective in reducing the QoL burden via the submission of two patient reported outcome measures (PROMs); 2) to investigate whether class of oncologic therapy, type of cAE and toxicity severity differently impact on patients' QoL. METHODS: a prospective observational study was conducted at the Dermatology department of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, from October 2018 to October 2019. Patients aged ≥ 18 years, under therapy with EGFR-Is or ICIs and experiencing a treatment-related cAE were eligible for the study. Dermatology Life Quality Index (DLQI) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 version 3.0 (EORTC QLQ-C30) were administered to patients at first clinical visit (T0), at 1-month (T1), and at 3-month (T2) dermatological follow-up. RESULTS: Sixty cAEs of 51 patients have been recorded. A significant difference in the mean score for both DLQI and EORTC QLQ-C30 was found along the 3-months dermatological follow-up (p <0.0001). A similar QoL improvement was reported for PROMs stratified by class of therapy and toxicity severity (p <0.0001). No difference was reported for patients with pyogenic granuloma-like lesions and psoriasiform eruption as per DLQI. Class of therapy and toxicity severity did not differently impact on patients' QoL at selected timepoints; we reported a higher EORTC QLQ-C30 score at T2 for patients developing psoriasiform eruption compared to other types of cAEs. CONCLUSIONS: Early patients' referral to dermatologists and tailored management could result in better QoL.

Clinical, epidemiological, and therapeutic hallmarks of pyoderma gangrenosum: a case series of 35 patients.

BACKGROUND: Over the past few decades, advances in medical research and diagnostic tools have shed light on some aspects of pyoderma gangrenosum (PG). Nevertheless, the multifactorial etiology, pathogenesis, and optimal management strategies for PG need to be further investigated. To address these knowledge gaps and contribute to a better understanding of this complex dermatological disorder, we collected epidemiological, clinical, and therapeutic aspects of a case series of PG patients occurring in our department over the past 10 years. METHODS: We performed a single-centered, retrospective, observational study analyzing all cases with a diagnosis of PG observed at the Dermatology clinic of the Fondazione Policlinico A. Gemelli IRCCS Catholic University from January 1, 2013, to January 1, 2023. For each case, we retrieved demographic data, the presence of other skin and systemic conditions, and the histopathological and clinical characteristics of PG, such as clinical variant, number of lesions, disease localization, previous therapy, response to treatment, and occurrence of relapse. RESULTS: We included 35 patients, 22 females and 13 males with a mean age of 40.0 years. Twenty patients (57.1%) had multiple localizations of disease, and the most commonly involved site was the lower limbs (85.7%). The lesions were mainly associated with inflammatory bowel diseases (51.4%) and hidradenitis suppurativa (37.1%). Clinical resolution with complete re-epithelialization was achieved in 25 patients (71.4%) with an average time of 20.8 months. On average, patients who underwent therapy with biological drugs had better outcomes. CONCLUSIONS: PG is a severe, rare, and pleomorphic disease associated with a broad spectrum of conditions. Corticosteroids remain the primary first-line approach for severe forms, but using biological immunosuppressants is promising.

Differential genetic expression within reward-specific ensembles in mice.

Maladaptive reward seeking is a hallmark of cocaine use disorder. To develop therapeutic targets, it is critical to understand the neurobiological changes specific to cocaine-seeking without altering the seeking of natural rewards, e.g., sucrose. The prefrontal cortex (PFC) and the nucleus accumbens core (NAcore) are known regions associated with cocaine- and sucrose-seeking ensembles, i.e., a sparse population of co-activated neurons. Within ensembles, transcriptomic alterations in the PFC and NAcore underlie the learning and persistence of cocaine- and sucrose-seeking behavior. However, transcriptomes exclusively driving cocaine seeking independent from sucrose seeking have not yet been defined using a within-subject approach. Using Ai14:cFos-TRAP2 transgenic mice in a dual cocaine and sucrose self-administration model, we fluorescently sorted (FACS) and characterized (RNAseq) the transcriptomes defining cocaine- and sucrose-seeking ensembles. We found reward- and region-specific transcriptomic changes that will help develop clinically relevant genetic approaches to decrease cocaine-seeking behavior without altering non-drug reward-based positive reinforcement.

Transcriptomic landscape of the interaction between the entomopathogenic fungus Beauveria bassiana and its tolerant host Tribolium castaneum revealed by dual RNA-seq.

Entomopathogenic fungi such as Beauveria bassiana are the only insect pathogens able to start the infection process by penetrating through the host cuticle. However, some insects try to avoid fungal infection by embedding their cuticle with antifungal compounds. This is the case of the red flour beetle Tribolium castaneum, which generates economical loss of great significance in stored product environments worldwide. In this study, T. castaneum adults were fed during different time periods (from 3 to 72 h) on B. bassiana conidia-covered corn kernels. The progression of fungal infection was monitored using the dual RNA-seq technique to reconstruct the temporal transcriptomic profile and to perform gene enrichment analyses in both interacting organisms. After mapping the total reads with the B. bassiana genome, 904 genes were identified during this process. The more expressed fungal genes were related to carbon catabolite repression, cation binding, peptidase inhibition, redox processes, and stress response. Several immune-related genes from Toll, IMD, and JNK pathways, as well as genes related to chitin modification, were found to be differentially expressed in fungus-exposed T. castaneum. This study represents the first dual transcriptomic approach to help understand the interaction between the entomopathogenic fungus B. bassiana and its tolerant host T. castaneum.

Mutations in abnormal spindle disrupt temporal transcription factor expression and trigger immune responses in the Drosophila brain.

The coordination of cellular behaviors during neurodevelopment is critical for determining the form, function, and size of the central nervous system (CNS). Mutations in the vertebrate Abnormal Spindle-Like, Microcephaly Associated (ASPM) gene and its Drosophila melanogaster ortholog abnormal spindle (asp) lead to microcephaly (MCPH), a reduction in overall brain size whose etiology remains poorly defined. Here, we provide the neurodevelopmental transcriptional landscape for a Drosophila model for autosomal recessive primary microcephaly-5 (MCPH5) and extend our findings into the functional realm to identify the key cellular mechanisms responsible for Asp-dependent brain growth and development. We identify multiple transcriptomic signatures, including new patterns of coexpressed genes in the developing CNS. Defects in optic lobe neurogenesis were detected in larval brains through downregulation of temporal transcription factors (tTFs) and Notch signaling targets, which correlated with a significant reduction in brain size and total cell numbers during the neurogenic window of development. We also found inflammation as a hallmark of asp mutant brains, detectable throughout every stage of CNS development, which also contributes to the brain size phenotype. Finally, we show that apoptosis is not a primary driver of the asp mutant brain phenotypes, further highlighting an intrinsic Asp-dependent neurogenesis promotion mechanism that is independent of cell death. Collectively, our results suggest that the etiology of the asp mutant brain phenotype is complex and that a comprehensive view of the cellular basis of the disorder requires an understanding of how multiple pathway inputs collectively determine tissue size and architecture.

The preclinical discovery and development of deucravacitinib for the treatment of psoriasis.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease that most commonly presents as plaque psoriasis. The understanding of the pivotal pathogenetic role of the IL-23/IL-17 axis has dramatically changed the therapeutic approach to the disease. The identification of intracellular signaling pathways mediating IL-23 activity provided the rationale for targeting TYK2. AREAS COVERED: This review assesses the underlying rationale that led to development of deucravacitinib, a novel oral TYK2 inhibitor, as a therapeutic option for the treatment of moderate-to-severe psoriasis, primarily focusing on pre-clinical and early phase clinical studies. EXPERT OPINION: Innovative therapies used in patients with moderate-to-severe psoriasis include biologic agents and small molecules, which are associated with less adverse events than traditional systemic agents. Deucravacitinib, which selectively targets TYK2, has demonstrated to be effective in treating psoriasis, preserving a more favorable safety profile compared to other JAK inhibitors approved for the treatment of other immune diseases that block the ATP-binding site. Because of its oral administration, deucravacitinib represents an intriguing option in the therapeutic armamentarium of psoriasis, though the evaluation of long-term efficacy and safety is necessary to establish its place-in-therapy.

The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients.

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e. progression-free survival (PFS) and OS) and disease progression. Plasma samples of Stage III-IV melanoma patients were collected at baseline (treatment initiation) and thereafter every 3 months. Circulating BRAFV600E/K and NRASQ61R/K mutations were analysed through droplet digital PCR (ddPCR, Bio-Rad) in a total of 177 plasma samples from 48 melanoma patients (19 Stage III, 29 Stage IV). Baseline ctDNA concentration was significantly associated with OS (HR = 1.003, 95% CI = 1.000-1.006, p = 0.043) and PFS (HR = 1.004, 95% CI = 1.000-1.007, p = 0.029) independent of clinical-prognostic confounders. For each unit increase in the ∆ctDNA (concentration difference between the last follow-up and baseline) there was a 24% increased risk of disease progression, irrespective of treatment type and stage at diagnosis (OR = 1.24, 95% CI = 1.03-1.49, p = 0.020, AUC = 0.93). Patients with reduction of ctDNA level from baseline to the last follow-up had longer OS (HR = 0.14; 95% CI = 0.05-0.44, p = 0.001) and PFS (HR = 0.08; 95% CI = 0.03-0.27, p < 0.0001) compared to patients with increased ctDNA, including adjustment for confounding factors. Our findings suggest that variation of ctDNA over time during melanoma treatment reflects the clinical outcome and tumour response to therapy and might be helpful in clinical monitoring.

Cyclin-Dependent Kinase 4/6 Inhibitors and Dermatologic Adverse Events: Results from the EADV Task Force "Dermatology for Cancer Patients" International Study.

BACKGROUND: The introduction of cyclin-dependent kinase inhibitors (CDK4/6i) was a great advance in therapeutics for patients with estrogen receptor+/human epidermal growth factor receptor (HER2) locally advanced and metastatic breast cancer. Despite the increasing use of these agents, their adverse drug-related events have not yet been fully characterized. We describe the spectrum of cutaneous adverse reactions occurring in advanced breast cancer patients treated with cyclin-dependent kinase inhibitors, analyzing types, severity, time to onset, and possible treatment outcomes. METHODS: We performed a multicentric retrospective study including patients with advanced breast cancer who developed cutaneous lesions during treatment with CDK4/6i in the period from June 2020 to June 2021. Patients > 18 years were recruited at eleven onco-dermatology units located in Albania (1), Argentina (1), France (1), Greece (3), Italy (3), and Spain (2). We evaluated patients' epidemiological and clinical characteristics, types of cutaneous adverse events, their time to onset, and treatment outcomes. The severity of the skin reactions was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 score. RESULTS: Seventy-nine patients (median age: 62.3 years; range 39-83 years) were included in the study, and, collectively, we recorded a total of 165 cutaneous adverse events during follow-up visits. The most frequent cutaneous reactions were pruritus (49/79 patients), alopecia (25/79), and eczematous lesions (24/79). Cutaneous toxicities were usually mild in severity (>65%) and occurred after a median of 6.5 months. Only four patients (5%) required treatment discontinuation due to the severity of the skin lesions. The majority of the skin reactions were managed with topical treatments. CONCLUSIONS: To the best of our knowledge, we present the largest case series of cutaneous adverse events developing in advanced breast cancer patients treated with CDK4/6i. We showed that cutaneous toxicities are usually mild in severity, and manageable with standard supportive care; however, in selected cases, they can lead to treatment discontinuation with possible implications for patients' clinical outcomes.

Clinical Characteristics of an Italian Patient Population with Advanced BCC and Real-Life Evaluation of Hedgehog Pathway Inhibitor Safety and Effectiveness.

BACKGROUND: Advanced basal cell carcinoma (aBCC) represents a complex and clinically heterogeneous group of lesions for which curative surgery and/or radiotherapy is unlikely. Systemic therapy with hedgehog pathway inhibitors (HHIs) changed the treatment landscape for this complex patient population. OBJECTIVES: The aims of the present study are to describe the clinical characteristics of a real-life Italian cohort diagnosed with aBCC and to investigate effectiveness and safety of HHI. METHODS: A multicenter observational study was performed by twelve Italian centers in the period January 1, 2016 - October 15, 2022. Patients aged ≥18 years and diagnosed with aBCC (locally advanced [laBCC] and metastatic BCC [mBCC]) were eligible for the study. Methods for investigating tumor response to HHI included clinical and dermatoscopic evaluation, radiological imaging, and histopathology. For HHI safety assessment, therapy-related adverse events (AEs) were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We enrolled 178 patients under treatment with HHI: 126 (70.8%) and 52 patients (29.2%) received sonidegib and vismodegib, respectively. Comprehensive data on HHI effectiveness and disease outcome were available for 132 (74.1%) of 178 patients: 129 patients had a diagnosis of laBCC (n = 84, sonidegib; n = 45, vismodegib) and 3 patients of mBCC (n = 2, vismodegib; n = 1, sonidegib, off-label). Objective response rate was 76.7% (95% confidence interval [CI]: 82.3-68.7) and 33.3% (95% CI: 88.2-1.7) for laBCC (complete response [CR]: 43/129; PR: 56/129) and mBCC (CR: 0/3; PR: 1/3), respectively. High-risk aBCC histopathological subtypes and occurrence of >2 therapy-related AEs were significantly associated with nonresponse to HHI therapy ([OR: 2.61; 95% CI: 1.09-6.05; p: 0.03] and [OR: 2.74; 95% CI: 1.03-7.9; p: 0.04]), respectively. Majority of our cohort (54.5%) developed at least 1 therapy-related AE, most of which were mild-moderate in severity. CONCLUSIONS: Our results demonstrate the effectiveness and safety profile of HHI and confirm the reproducibility of pivotal trial results in real-life clinical setting.

Advanced Cutaneous Squamous Cell Carcinoma: Italian Multicentric Retrospective Analysis of Patient Profiles and Therapeutic Approaches.

BACKGROUND: Advanced cutaneous squamous cell carcinoma (aCSCC) represents an area of unmet clinical need, with no standardized treatments until the recent approval of immune checkpoint inhibitors (ICIs). OBJECTIVES: The aim of the study was to describe clinical characteristics and therapeutic strategies of a real-life Italian cohort of aCSCC patients managed at the beginning of cemiplimab approval as compassionate use in Italy. METHODS: A multicenter retrospective study was performed by 10 Italian centers in the period January 1, 2018-May 31, 2020. Patients aged ≥18 years and diagnosed with aCSCC (locally aCSCC and metastatic CSCC) were eligible for the study. Analysis of patients' characteristics and treatment strategies was performed. RESULTS: 239 patients were initially recruited in the study: 19 patients were excluded due to incomplete data collection, yielding a final cohort of 220 patients, of which 191 and 220 were included for patients' clinical characteristics and therapeutic intervention analysis, respectively. Median age at the time of diagnosis was 81 years (range: 72-86); nodal metastases were detected in 64/220 (29%) patients, and distant metastatic spread was reported in 33/220 (15%) patients. Most of our patients referred chronic occupational and/or recreational sun exposure, experienced ≥1 sunburn during their lifetime, never wore hats or used photoprotective filters, and presented with signs of cumulative sun damage (solar lentigines and/or actinic keratosis). Majority of our cohort received at least one intervention directed to the primary tumor (n = 212, 96.3%); surgery and radiotherapy were the most common therapeutic choices. Immunotherapy was administered to a small number of patients as compassionate use, especially in the metastatic setting. CONCLUSIONS: Our study outlines the complex and heterogeneous clinical and therapeutic landscape of aCSCC patients at the beginning of ICI era, highlighting the need of a standardized care for this fragile and high-need patient population.

Investigational systemic drugs for moderate to severe plaque psoriasis: What's new?

INTRODUCTION: The therapeutic armamentarium for the treatment of psoriasis, a chronic inflammatory skin disease, is now reasonably broad and structured, with several therapeutic agents that demonstrated a successful long-term control of this condition. However, there are still unfulfilled gaps resulting from the inherent limitations of existing therapies, which have paved the way for the identification of new therapeutic strategies or the improvement of the existing ones. AREAS COVERED: The aim of this review is to thoroughly explore new therapeutic strategies and novel drugs that are currently in the pipeline for the treatment of psoriasis, focusing primarily on agents that are currently in phase I/II of clinical development. Some of which retrace already existing therapeutic approaches, such as the IL23/Th17 pathway inhibition, while others unveil new and yet unexplored ones. EXPERT OPINION: Since the therapeutic landscape of psoriasis is wide, it is not yet clear whether novel agents will fill the remaining gaps in the context of a broader and more diversified set of oral and biologic therapies. Nevertheless, with the development of precision medicine approaches, the development of innovative targeted drugs will still have a therapeutic rationale in psoriasis.

The neurodevelopmental transcriptome of the Drosophila melanogaster microcephaly gene abnormal spindle reveals a role for temporal transcription factors and the immune system in regulating brain size.

The coordination of cellular behaviors during neurodevelopment is critical for determining the form, function, and size of the central nervous system. Mutations in the vertebrate Abnormal Spindle-Like, Microcephaly Associated (ASPM) gene and its Drosophila melanogaster ortholog abnormal spindle (asp) lead to microcephaly, a reduction in overall brain size whose etiology remains poorly defined. Here we provide the neurodevelopmental transcriptional landscape for a Drosophila model for autosomal recessive primary microcephaly (MCPH) and extend our findings into the functional realm in an attempt to identify the key cellular mechanisms responsible for Asp-dependent brain growth and development. We identify multiple transcriptomic signatures, including new patterns of co-expressed genes in the developing CNS. Defects in optic lobe neurogenesis were detected in larval brains through downregulation of temporal transcription factors (tTFs) and Notch signaling targets, which correlated with a significant reduction in brain size and total cell numbers during the neurogenic window of development. We also found inflammation as a hallmark of asp MCPH brains, detectable throughout every stage of CNS development, which also contributes to the brain size phenotype. Finally, we show that apoptosis is not a primary driver of the asp MCPH phenotype, further highlighting an intrinsic Asp-dependent neurogenesis promotion mechanism that is independent of cell death. Collectively, our results suggest that the etiology of asp MCPH is complex and that a comprehensive view of the cellular basis of the disorder requires an understanding of how multiple pathway inputs collectively determine the microcephaly phenotype.

Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis.

Topical agents that are currently available for the treatment of atopic dermatitis may represent a valid approach in the management of mild or mild-moderate cases, whereas they are often supplemented with systemic therapies for handling more complex or unresponsive cases. The most used compounds include topical corticosteroids and calcineurin inhibitors, although their use might be burdened by side effects, poor response, and low patient compliance. Consequently, new innovative drugs with higher efficacy and safety both in the short and long term need to be integrated into clinical practice. A deeper understanding of the complex pathogenesis of the disease has led to identifying new therapeutic targets and to the development of innovative therapeutics. This narrative review aims to collect data on selected promising topical drugs that are in an advanced stage of development.

Self-Assessment Questionnaire on Patient-Physician Concordance on Nevus Self-Count and Models Development to Predict High-Risk Phenotype >50 Nevi.

BACKGROUND: Cutaneous melanoma accounts for the majority of skin cancer-related deaths. Readily identifiable phenotypic characteristics and total body nevus count (TBNC) >50 are among the most important risk factors for cutaneous melanoma. Implementation of nevus self-count procedures and self-assessment of phenotypic traits as part of skin self-examination could be an excellent screening tool for identifying an at-risk target population. OBJECTIVES: Objectives of the study were to assess the skills of a central Italian and eastern Spanish population sample to recognize their skin lesions via the submission of a self-assessment questionnaire and to explore which self-assessment questionnaire item combination best predicts the high-risk condition of TBNC >50. METHODS: Patients aged ≥18 years filled a self-assessment questionnaire, autonomously and prior to the dermatological visit. Subsequently, dermatologists performed total body skin examination and reported patients' skin lesions on a separate questionnaire. RESULTS: We reported fair to moderate patient-dermatologist agreement for skin lesion self-assessment. The item number of nevi on the back was the single questionnaire item most accurately predicting TBNC >50. The high-sensitivity and high-specificity classification and regression tree models for the prediction of TBNC >50 displayed different items combinations; the item nevus on the back was always the first and most important predictor in both our models. CONCLUSIONS: Patients were partially able to provide correct estimation of their whole-body nevus self-count. The item nevi on the back seems to be the first and most important predictor of TBNC >50 across our models. Delivery of high-sensitivity and high-specificity prediction models based on our questionnaire item combination may help defining a high-risk target population.

Proposal of a ranking methodology for plant threats in the EU.

Following a request of the European Commission, EFSA and ANSES, beneficiary of the EFSA tasking grant on horizon scanning for plant pests (GP/EFSA/ALPHA/2017/02), developed a methodology to order by risk non-regulated pests recently identified through the monitoring of media and scientific literature. The ranking methodology proposed at the end of the pilot phase was based on the scoring of pests under evaluation following 16 criteria related to the steps of the pest risk assessment scheme. The multicriteria matrix of scores obtained was then submitted to the multicriteria analysis method PROMETHEE. The pilot methodology was tested on a limited number of pests (14 pests identified during the monitoring activity, and 4 'control' pests whose well-known risk should be reflected either in a positive or negative score), then applied on all non-regulated pests identified through the media and scientific literature monitoring in the first 2 years of the project. After having collected feedback from the targeted final users (EU risk managers), the methodology underwent a few refinements: (i) implementation of the methodology to a set of already assessed reference pests from EFSA opinions, (ii) exclusions of three criteria from the scoring phase, (iii) identification of pests proposed for further action ('positive' pests), using a threshold defined after scoring the reference pests.

Advances in the drug management of basal cell carcinoma.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin cancer in humans. Recently, BCCs were suggested to be classified into 'easy to treat' and 'difficult to treat,' and different therapeutic options are suggested for their management. AREAS COVERED: In this review, the authors discuss treatment options that are approved, recommended for, or are still in development for treatment of BCC. The review covers approved local therapies, such as imiquimod and 5-fluorouracil, and systemic therapies, such as hedgehog inhibitors. New medical agents, investigated in clinical trials, are reviewed. These include: targeted therapies, such as GLI antagonists or anti-VEGFR agents, immunotherapies, such as checkpoint inhibitors, recombinant cytokines or silencing RNA, as well as intralesional virotherapies with modified adeno- or herpes viruses. EXPERT OPINION: The progress made in recent years has improved the management of patients with advanced BCC; however, neither tumor targeting nor immune system engaging agents provide a cure. New treatment approaches directed not only to known targets but also the tumor microenvironment are in development and are anticipated to improve the management of difficult to treat BCC.

Isolation of Beauveria bassiana from the Chagas Disease Vector Triatoma infestans in the Gran Chaco Region of Argentina: Assessment of Gene Expression during Host-Pathogen Interaction.

A native strain of the entomopathogenic fungus Beauveria bassiana (Bb-C001) was isolated from a naturally infected Triatoma infestans, Klug (Hemiptera: Reduviidae) adult cadaver in the Gran Chaco region, Salta province, Argentina. The isolate was both phenotypic and molecularly characterized in a context of fungus-insect interaction, by measuring the expression pattern of toxin genes during infection and immune response of T. infestans. The commercial strain GHA of B. bassiana, which was previously used in field interventions to control these vectors, was used as reference in this study. The phylogenetic trees based on both ribosomal internal transcribed spacer (ITS) and elongation factor 1-alpha (EF1-α) indicated that Bb-C001 fits into a B. bassiana cluster, and the sequence-characterized amplified regions (SCAR) showed that Bb-C001 is different from the GHA strain. There were no differences between both strains regarding viability, radial growth, and conidia production, either in the median survival time or insect mortality. However, Bb-C001 showed a higher expression than GHA of the bassianolide synthetase gene (BbbslS) during infection, and similar levels of the beauvericin synthetase gene (BbbeaS). Immune-related genes of T. infestans nymphs (limpet-2 and defensin-1, -2, and -6) were later expressed and thus insects failed to stop the infection process. These results showed that B. bassiana Bb-C001 is a promised fungal strain to be incorporated in the current biological control programs of T. infestans in Salta province, Argentina.

Efficacy of topical beta-blockers in the management of EGFR-inhibitor induced paronychia and pyogenic granuloma-like lesions: case series and review of the literature.

Nail toxicities, such as paronychia and pyogenic granuloma-like lesions, are well-recognized side effects of epidermal growth factor receptor inhibitor (EGFR-I) therapy that can significantly impair patient's quality of life and compliance to anticancer treatment. Numerous therapeutic options are available, with variable rates of success. Recently, topical ß-blockers have emerged as a novel, non-invasive treatment strategy. We tested the effectiveness of topical timolol 0.5% gel, twice daily, under occlusion for 30 days, on paronychia and periungual pyogenic granuloma-like lesions in 9 patients being treated with EGFR-I. We also reviewed the available literature on this topic, which is the use of topical ß-blockers in the management of EGFR-I-induced nail toxicities. We assessed 25 lesions consistent with the diagnosis of EGFR-I-induced pyogenic granuloma-like lesions and paronychia (21 diagnosed as pyogenic granuloma-like, and four as paronychia). Thirteen of the 25 lesions achieved complete resolution, 9/25 reached at least improvement, and only 3/25 did not respond to the intervention. As for the review, four papers met the scope of our research. The results confirmed at least partial benefit in the majority of treated patients. Among current strategies, high-potency topical corticosteroids are a well-known treatment option especially for paronychia, targeting the inflammatory component of such lesions; nevertheless, the management of pyogenic granuloma-like lesion is often more complex and the success rate is variable. Nail plate avulsion and phenol chemical matricectomy are not highly effective and display some degree of invasiveness. Topical ß-blockers seem to be promising alternatives, especially in fragile cancer patients who may be unsuitable candidates for an invasive procedure.

A New Online Resource to Monitor New or Emerging Plant Pests: MEDISYS Media Monitoring and the Case of Xylella fastidiosa.

The European Food Safety Authority has established a horizon scanning exercise for plant pests by automated monitoring of open-source media. The news sources are screened using the publicly accessible MEDISYS (Medical Information System) platform of the Joint Research Centre of the European Commission. Here, we report the example of monitoring for Xylella fastidiosa, a highly polyphagous plant-pathogenic bacterium. Since its first occurrence in Europe, news sources have reported findings and latest developments. Media monitoring-related data can support surveillance or plant pests' management programs by early warning and can help understand the impacts of plant pests and the societal response to new plant health threats.

Multivariate analysis of historical data (2004-2013) in assessing the possible environmental impact of the Bellolampo landfill (Palermo).

Multivariate analysis was performed on a large data set of groundwater and leachate samples collected during 9 years of operation of the Bellolampo municipal solid waste landfill (located above Palermo, Italy). The aim was to obtain the most likely correlations among the data. The analysis results are presented. Groundwater samples were collected in the period 2004-2013, whereas the leachate analysis refers to the period 2006-2013. For groundwater, statistical data evaluation revealed notable differences among the samples taken from the numerous wells located around the landfill. Characteristic parameters revealed by principal component analysis (PCA) were more deeply investigated, and corresponding thematic maps were drawn. The composition of the leachate was also thoroughly investigated. Several chemical macro-descriptors were calculated, and the results are presented. A comparison of PCA results for the leachate and groundwater data clearly reveals that the groundwater's main components substantially differ from those of the leachate. This outcome strongly suggests excluding leachate permeation through the multiple landfill lining.