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Contradictory aspects apparently coexist in relation to the causes of bronchial allergic inflammation in agriculture. It's worth notion that either exposure to inhalable dust and endotoxins or exposure to molecular patterns play a role in such a pathology; in particular endotoxins should protect against the onset of allergic diseases. Likewise, the exposure to pesticides would not lead to allergic asthma, but could facilitate the onset of pollinosis and contact dermatitis in gardeners. Moreover, the risk of anaphylaxis from bee sting would be lower in repeatedly bitten beekeepers if compared to sensitized and less exposed population, while atopy by itself is not evaluable as a risk factor for sensitization to hymenoptera. In conclusion either frequency and strength of exposure or distinctive feature of the subject are able to determine the occurrence of allergic disease in an almost different manner. [ABSTRACT FROM AUTHOR]

The article explores climate sensitivity in the Anthropocene to avoid dangerous anthropogenic interference with the climate system. It discusses climate sensitivity which depends on climate feedbacks' sign and strength. It defines climate feedback which is induced by a climate forcing. It also discusses related topics including Earth's energy balance, feedback sensitivity, and carbon cycle feedbacks.

The article cites a research study where occupational allergens were estimated to determine cases of asthma in adult workers. In Italy, the Italian National Insurance Against Professional Disease (INAIL) compensates very low cases that legally identified 90 cases in 1996 and only 9 cases in 2000. The study found three main causes for a real negative trend in making diagnosis and compensating workers for occupational asthma.

Drug reactions in pharmaceutical industry workers represent a quiet different problem in terms of evaluation and job ability, if related to hospitalized patients with adverse reaction to drug administration. The modern approach of GRADE (Grading Recommendation Assessment Development and Evaluation) was applied to 8 workers who had suspected occupational drug reactions, and were clinically examined in order to exclude any possible adverse event. Such a method allows to draw the relationship between adverse reaction to drugs, aetiology, risk evaluation and clinical events. Therefore, the adverse events are classified in type A (incongruous exposure), type B (hypersensitivity reactions) and not A not B (not work related). Both medical history/clinical evaluation and GRADE seem to give a correct view of the single case. Moreover, a high score suggests an occupational pathology, whilst low scores for evidence of drug reaction and occupational risk can avoid the use of diagnostic procedures. [ABSTRACT FROM AUTHOR]

Background FOLFIRINOX-regime is a combination-chemotherapy that provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients, but is associated with severe toxicity. Aim of this study is to explore the role of miRNAs as modulators of chemosensitivity and their potential as biomarkers of sensitivity to FOLFIRINOX-therapy. Methods HTS of 997 LNA-MIR-inhibitors was performed in PDAC cell lines treated with a combination of Fluorouracil (F), Oxaliplatin (O) and Irinotecan (I) that mimics FOLFIRINOX-regime. Validation experiments were performed with miRvana probes. Apoptosis was measured by flow-cytometry and western-blotting. Knock-out of microRNA was achieved by CRISPR-CAS9 in MiaPaca2 cells. HITS-CLIP assay was used to identify MIR1307 target site. Drug sensitivity was tested in xenograft models. Plasma MIR1307 was assessed by ddPCR. Results 41 and 84 miRNA-inhibitors enhanced FOI activity by > 30% (p < 0.001) in Capan1 and MiaPaCa2. These included MIR1307-inhibitor that was validated in 6 PDAC cell lines. The effect of FOI in comparison to DMSO was greater in cells transfected with MIR1307 inhibitor vs control, making the effect of this MIR specific for chemotherapy. MIR1307 was over-expressed in tumours of 40/60 human PC cases, confirming clinical relevance. DNA damage markers were upregulated (pH2AX2, 8OHdG, DNA breaks) in KO cells treated with FOI and therapy-induced apoptosis was higher in KO cells. Re-expression of MIR1307 in KO cells increased resistance to FOI chemotherapy and protected from FOI-induced DNA damage. HITS-CLIP assay identified binding of MIR1307 to CLIC5, whose expression was increased in KO cells and reduced by rescued expression of MIR1307. Both WT and KO xenografts responded to FOI chemotherapy but response was transient in WT mice, while we noticed a prolonged response in KO tumours. Baseline plasma level of MIR1307 correlated with overall survival in patients receiving FOLFIRINOX chemotherapy. Conclusions We identified MIR1307 as a potential modulator of sensitivity to FOI-chemotherapy in PC. MIR1307 inhibition impairs the ability of the cells to recover from chemotherapy damage and therefore enhances its activity. Legal entity responsible for the study The authors. Funding Pancreatic Cancer UK Research Innovation Fund, Cancer Research UK. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate inflammatory markers and pro-inflammatory CD14 and Toll-like Receptor 4 (TLR4) polymorphisms in workers exposed to flour dust., Methods: Polymorphisms in TLR4 and CD14 were identified in our study population of 167 workers that included 63 healthy subjects (HS), 45 atopic subjects (A), and 59 subjects diagnosed clinically with occupational asthma/rhinitis (OAR). Endpoint measures in this study included fractional exhaled nitric oxide and serum concentrations of interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α)., Results: We identified a polymorphism in CD14 (rs2569190) that may be differentially expressed (P = 0.06). IL-6 concentrations in the serum were significantly higher in the A and OAR groups (P < 0.01) than in subjects in the HS group, while IL-8 concentrations were significantly elevated only in the OAR group (P < 0.01). Interestingly, TNF-α concentrations in the OAR group were significantly reduced when compared with subjects in the HS group (P < 0.01)., Conclusion: Cytokines are likely a defensive response in atopic and healthy workers. A protective genotype is hypothesized for occupational asthma.

Background: Piperacillin, unlike other antibiotics, rarely causes immediate allergic reactions. Only two cases related to occupational exposure are reported in the literature., Objectives: Adoption of new methods for diagnosis of occupational allergy to drugs., Methods: An atopic nurse, aged 30 years, was referred to our hospital for an allergic work-related reaction to piperacillin. The patient had suffered two successive episodes with immediate cutaneous reaction, angioedema and dyspnoea after preparing piperacillin. Almost four years previously she had suffered from similar symptoms after taking amoxicillin. She was submitted to a clinical examination and a routine allergic test, performing also specific IgE (Phadia Pharmacia ImmunoCap) and BAT (Basophil Activation Test) for Beta-lactam antibiotics., Results: A positive response to piperacillin was observed in our case using BAT a new non-invasive and safe method, that proved useful for diagnosis of allergy. Moreover, we observed a change from an allergic reaction for therapeutic use of amoxicillin to a work-related adverse reaction to another beta-lactam, piperacillin., Conclusions: In previous clinical cases cutaneous and specific challenge tests were performed for diagnosis. At present, availability of an in vitro test, such as BAT may provide new diagnostic opportunities, and a useful tool for studying clinical cases other than, in perspective, monitoring exposed workers. Preventive measures were taken in the workplace to lower the risk of sensitization and allergic response. The nurse was transferred to a well controlled job.

Contradictory aspects apparently coexist in relation to the causes of bronchial allergic inflammation in agriculture. It's worth notion that either exposure to inhalable dust and endotoxins or exposure to molecular patterns play a role in such a pathology; in particular endotoxins should protect against the onset of allergic diseases. Likewise, the exposure to pesticides would not lead to allergic asthma, but could facilitate the onset of pollinosis and contact dermatitis in gardeners. Moreover, the risk of anaphylaxis from bee sting would be lower in repeatedly bitten beekeepers if compared to sensitized and less exposed population, while atopy by itself is not evaluable as a risk factor for sensitization to hymenoptera. In conclusion either frequency and strength of exposure or distinctive feature of the subject are able to determine the occurrence of allergic disease in an almost different manner.

Drug reactions in pharmaceutical industry workers represent a quiet different problem in terms of evaluation and job ability, if related to hospitalized patients with adverse reaction to drug administration. The modern approach of GRADE (Grading Recommendation Assessment Development and Evaluation) was applied to 8 workers who had suspected occupational drug reactions, and were clinically examined in order to exclude any possible adverse event. Such a method allows to draw the relationship between adverse reaction to drugs, aetiology, risk evaluation and clinical events. Therefore, the adverse events are classified in type A (incongruous exposure), type B (hypersensitivity reactions) and not A not B (not work related). Both medical history/clinical evaluation and GRADE seem to give a correct view of the single case. Moreover, a high score suggests an occupational pathology, whilst low scores for evidence of drug reaction and occupational risk can avoid the use of diagnostic procedures.

The occupational allergens are estimated to determine 1 out 10 cases of asthma in adult workers. In Italy very low cases are compensated by the Italian National Insurance Against Professional Disease (INAIL), that legally recognized 90 cases in 1996 and only 9 cases in 2000. A real negative trend in making diagnosis and compensating workers for occupational asthma is due to three main causes. (1) Delayed diagnosis. Lack of protocols or lack of accuracy in applying them. Scarce collaboration of the general practitioners. (2) Unsatisfactory bill on compensation that misunderstands moderate asthma under drug control and asthma with scarce symptoms and occasional therapy. (3) Lack of prevention in industrial medicine. Occupational doctors play a role more relevant in legal activities than in clinical ones.

Background: Hairdressers are exposed to irritants and allergenic compounds that may cause contact dermatitis, rhinitis and asthma., Objectives: In this paper we describe the case of a female, age 33 years, who developed contact dermatitis after 10 years of exposure to ammonium persulfate., Methods: After 7 months of progressively extensive and persistent skin lesions, respiratory symptoms appeared that were related to the occupational exposure (on-off test). SIDAPA and specific occupational patch test for hairdressers and occupational challenge with ammonium persulfate were performed. Clinical parameters of inflammation, ECP (eosinophil cationic protein) and exhaled nitric oxide (FeNO) were detected before and after the specific bronchial challenge., Results: The patch test was positive to ammonium persulfate (++), and bronchial challenge for ammonium persulfate showed a significant late response (FEV1 decrease--33%). Both FeNO and ECP showed a significant increase after 24 hours. Dermatitis, urticaria and angioedema occurred on the uncovered skin due to airborne contact. Topic steroids and anti-histaminic drugs resolved the clinical symptoms., Conclusions: Bronchial challenge is, in fact, considered to be the gold standard for the diagnosis of occupational asthma, although new inflammatory parameters can contribute to the diagnosis and can be useful for monitoring after a specific inhalation test with occupational agents. The described case summarizes the evolution from contact dermatitis to inhalation allergy, suggesting the occurrence of an allergic "march" for occupational allergy.

This consensus document was prepared by an Italian working group including occupational health professionals involved for many years in the management of glove- and latex-related problems in health care settings. The aim of this document was to address the most significant technical, epidemiological, clinical, environmental and prevention problems related to the use of gloves and latex. The group's recommendations are based on scientific evidence and practical experience but they cannot be considered as final. These topics need to be periodically revised. The following points should be taken into account: glove quality seems to have improved considerably but the information on glove features provided by the manufacturers is often still inaccurate or incomplete; the regulations in force provide that the manufacturers perform tests to supply evidence for the quality of the products but they do not indicate which analytical method should be used and they do not require that the results be reported in the technical data sheets. Thus the manufacturers have only to declare that their products are "in accordance with the rules"; therefore, purchasers should require the manufacturing companies to supply detailed information and verify their reliability. Moreover, the rules should be adapted to higher quality standards; occupational physicians must be involved for the correct choice and purchase of protective gloves; the use of gloves (in particular latex gloves) and latex devices in health care settings should be based on specific criteria: procedures must be available stating which kind of gloves are suitable for specific tasks. When exposure to latex cannot be avoided it is necessary to choose products that have good biocompatibility (e.g., powder free-gloves with low allergen content); once and for all latex powdered gloves should no longer be commercially available! labels for latex devices (including gloves) should report the extractable latex allergen content. Limit values for extractable latex allergens should be established; the use of synthetic rubber gloves should be encouraged since some materials (e.g., neoprene and nitrile rubber) appear to have physical properties and protective efficacy similar to latex, plus good biocompatibility; more studies should be promoted to verify the protective efficacy of new synthetic materials; health care workers should be informed about the advisability and usefulness of using materials other than latex; health care services should not cause additional risks but rather highlight the advantages for workers and patients if the use of latex gloves and devices is minimized.

Background: Exposure to nickel sulphate, other than contact dermatitis, can potentially cause respiratory symptoms. Although few cases of occupational rhinitis and asthma are reported in literature, a prolonged exposure can determine sensitization and evolution to respiratory symptoms., Objectives: Clinical evaluation of a case of occupational rhinitis and asthma due to nickel sulphate., Methods: A female worker, aged 43 years, has been occupationally exposed to nickel for 22 years. After 1 year she experienced asthma, apparently not work related. She treated the respiratory symptoms for many years, but a slow and progressive increase of the disease was observed. During the last five years a straight relationship between work and symptoms was observed. On-off test was positive. The diagnosis of occupational respiratory disease was based on the work-related symptoms and the specific nasal challenge test result., Results: An early response was observed with nasal symptoms (score 4), increase of anterior nasal airflow resistance (33%), severe dyspnea, haematic eosinophilia, and fall in FEV-1 of 18%., Conclusions: The prolonged exposure to nickel determined impairment of respiratory function. Nasal challenge, more safe and useful than bronchial challenge, can be considered gold standard for the diagnosis of occupational rhinitis and asthma due to occupational allergens.

Background: Latex is a relevant occupational and environmental allergen, strongly related to the extensive use of natural rubber products., Objectives: Threshold Limit Values have to be identified, as well as biocompatible materials in order to avoid sensitization or appearance of allergic symptoms., Methods: In this paper we consider the main methods, which have been used to detecting latex allergens for environmental monitoring of airborne and latex products., Results: We report our experience in such afield, and our approach to the latex problem, suggesting that quantification of allergens, which is currently applicable according to well standardized methods, should be adopted by manufacturers, agency and consumer organization.

Background: Baker's asthma is related to wheat flour exposure and to other cereal dust exposure., Objectives: The cockroach is considered a significant allergen and can occasionally trigger asthma in bakery workers., Methods: The case of a 33-year-old male, suffering from asthma in the workplace with previous equivocal tests for cereal dust was investigated Clinical assessment of the worker consisted of cutaneous and blood screening for common and occupational allergens, including cockroach. The subject was monitored for aspecific bronchial reactivity and peak flow in a cockroach disinfected workplace, and these data were compared to data obtained after previous workplace exposure., Results: The worker was not allergic to wheat and other cereal dusts or alpha-amylase, but was sensitized to cockroach. His asthmatic symptoms disappeared, and bronchial reactivity varied after a long period outside the bakery workplace. PEF monitoring, that had showed diurnal variability > 20% and differences between working and non-working periods, demonstrated both normal values and daily variations less than 10% when he returned to the cockroach disinfected workplace., Conclusions: The cockroach is a common allergen, however no case of work-related baker's asthma due to the cockroach has been previously described. Clinical history and analysis of the allergens at the workplace must direct the clinical approach of the investigators, in order to correctly evaluate the subject and enable him/her to resume work.

Background: An increased use of acrylic compounds is observed in different industries, home repairs and hobbies. These compounds are known to cause skin sensitisation, irritation of mucous membranes and bronchial asthma. Methyl cyanoacrylate is moderately likely to be a sensitizer, while ethyl cyanoacrylate might be a weak sensitizer., Objectives: Clinical evaluation of a case of occupational asthma due to cyanoacrylate., Methods: A female worker, aged 32 years, used ethyl cyanoacrylate daily. After 2 months she experienced dry cough and shortness breath. Some weeks later she developed bronchial asthma. The diagnosis of occupational asthma was based on the work-related symptoms and the inhalation challenge test result., Results: A late asthmatic response was observed with a maximum fall in FEV1 of 26% 345 minutes after exposure. Complete clinical and functional recovery was observed after inhalation of a broncho-dilating agent., Conclusions: Acrylates are new occupational sensitising agents, causing rhinitis and asthma. It is not possible to perform prick tests or specific IgE measurements for these compounds. The bronchial challenge test is therefore the sole valid test for the diagnosis of occupational asthma.

Numerous studies and documents have been recently produced on the topic of latex allergy but the unpredictable nature of the clinical reactions and the widespread use of natural rubber products in health care has led to incorrect use due to inadequate risk assessment. This article is intended to supply a clinical and epidemiological outline of latex allergy and its management and prevention. The aim is to promote communication between specialists in various disciplines in order to protect patients and health care workers from the risk of latex allergy. The feasibility analysis of a latex-free stream in a hospital was made by a board composed of an allergist, occupational health physicians, a surgeon and an anaesthetician to evaluate the various phases of the project. The equipment available at the hospital (certified latex-free materials to equip pre and post operation trolleys, latex free gloves) and a correct work organization (definition and work procedures, check list of materials, alarm bracelet, warning signals) will make it possible to achieve a latex-free stream for symptomatic and sensitized patients at risk. The use of non-powdered gloves with low levels of protein residue, particularly in areas like operating theatres, can minimise the occurrence of sensitization to latex, protecting health care workers from serious consequences. Also, such measures reduce the cost of health surveillance, allow latex-safe areas to be maintained which can be inter-connected so that the best possible management ot latex-allergic patients during hospitalization is ensured.

The availability of specific monoclonal and policlonal antibodies and the standardization of allergen extracts enables to quantify the exposure to airborne allergens in the domestic environment and at the workplace. In this article we report our experience coming from three studies based upon the measurement of airborne allergens in different environments. In a pharmaceutical factory we measured levels of laboratory animals allergens and evaluated the prevalence of sensitization to the same allergens among the workers. Airborne latex allergens and latex allergens content in latex gloves were measured in hospitals. In bakeries we evaluated the prevalence of sensitization to flour and measured flour allergens levels. The results of our studies give information useful to improve methods of prevention, diagnosis, and therapy of occupational allergic diseases.