Monolithically integrated low linewidth comb source using gain switched slotted Fabry-Perot lasers.

A monolithically integrated low linewidth optical comb is demonstrated by gain switching of a three-section laser device. The device consists of a slave and master section separated by a shared slotted mirror section. Wavelength tunability has been demonstrated by varying the electrical bias of each section. The number of comb lines is shown to almost double with the addition of optical injection from the master section into the slave. The unmodulated device has a full width half max linewidth of ∼ 500 kHz, while the comb line set were measured to be ∼ 600 kHz, with little degradation as a result of gain switching. The FSR (free spectral range) of the demonstrated comb is 4 GHz, which is tunable within the bandwidth of the device, with a central wavelength of 1580.3 nm.

IL-33/ST2 pathway and classical cytokines in end-stage heart failure patients submitted to left ventricular assist device support: a paradoxic role for inflammatory mediators?

BACKGROUND: Inflammation is a critical process contributing to heart failure (HF). We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. METHODS: IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post-LVAD). RESULTS: Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVAD than in the HT group. LVAD determined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. CONCLUSIONS: IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course. Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies.

[A clinical case of occupational allergy to piperacilline. A novel diagnostic method: basophil activation test (BAT)]. / Utilizzo del test di attivazione dei basofili (BAT) per la diagnosi di reazione allergica a piperacillina in ambito professionale: descrizione di un caso clinico.

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.

[Drug allergy: new methodological approaches in occupational clinical evaluations]. / Farmacoallergia. Disamina di una casistica e nuovi approcci metodologici in ambito occupazionale.

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.

Patient specific multiscale modelling for plaque formation and progression.

We present a three-dimensional model of plaque formation and progression that was tested in a set of patients who underwent coronary Computed Tomography angiography (CTA) for anginal symptoms. The 3D blood flow is described by the Navier-Stokes equations, together with the continuity equation. Mass transfer within the blood lumen and through the arterial wall is coupled with the blood flow and is modeled by a convection-diffusion equation. The Low Density Lipoprotein (LDL) transports in lumen of the vessel and through the vessel tissue (which has a mass consumption term) are coupled by Kedem-Katchalsky equations. The inflammatory process is modeled using three additional reaction-diffusion partial differential equations. A full three-dimensional model was created. Furthermore, features potentially affecting plaque growth, such as patient risk score, circulating biomarkers, localization and composition of the initial plaque, and coronary vasodilating capability were also investigated. The proof of concept of the model effectiveness was assessed 6 months after the baseline evaluation.

[Baker's asthma. Experimental studies]. / Asma del panificatore. Studi sperimentali.

UNLABELLED: Baker's asthma is one of the most commonly reported occupational lung diseases in countries, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. The development of a mouse model could be useful in order to characterize the development and progression of baker's asthma. RESULTS: Experimental studies evidenced that flour dust elicits neutrophilic inflammation in a tlr4-independent manner, suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance pre-existing allergic asthma in OVA sensitized and challenged mice. CONCLUSIONS: Bakery flour dust is strongly pro-inflammatory, can cause non-allergic airway inflammation, and can enhance allergen-mediated airway inflammation.

[Occupational allergic "march". Rapid evolution of contact dermatitis to ammonium persulfate into airborne contact dermatitis with rhinitis and asthma in a hairdresser]. / La marcia dell'allergia. Rapida evoluzione di una dermatite da contatto da ammonio persolfato in airborne contact dermatitis con rinite ed asma bronchiale.

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.

[Respiratory allergy to nickel. Description of an atypical clinical case]. / Allergia do nichel. Descrizione di un caso di rinite ed asma professionale atipico.

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.

Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice.

BACKGROUND: Baker's asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker's asthma, yet the aetiology and pathogenesis of baker's asthma remain poorly understood. OBJECTIVE: We sought to develop a mouse model of baker's asthma that could be used to characterize the development and progression of baker's asthma. METHODS: We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of ovalbumin (OVA) sensitization and challenge. RESULTS: Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a Toll-like receptor 4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA-sensitized and challenged mice. CONCLUSIONS: Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation.

[Monitoring latex risk: detection of airborne and glove allergens]. / Monitoraggio del rischio latice: campionamenti dell'allergene su particolato aerodisperso e su manufatti in gomma.

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.

The possible role of cockroaches in baker's asthma.

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.

Construction and characterization of a Coffea canephora BAC library to study the organization of sucrose biosynthesis genes.

The first bacterial artificial chromosome (BAC) library of Robusta coffee (Coffea canephora) was constructed, with the aim of developing molecular resources to study the genome structure and evolution of this perennial crop. Clone 126, which is highly productive and confers good technological and organoleptic qualities of beverage, was chosen for development of this library. The BAC library contains 55,296 clones, with an average insert size of 135 Kb per plasmid, therefore representing theoretically nine haploid genome equivalents of C. canephora. Its validation was achieved with a set of 13 genetically anchored single-copy and 4 duplicated RFLP probes and yielded on average 9 BAC clones per probe. Screening of this BAC library was also carried out with partial cDNA probes coding for enzymes of sugar metabolism like invertases and sucrose synthase, with the aim of characterizing the organization and promoter structure of this important class of genes. It was shown that genes for both cell wall and vacuolar forms of invertases were probably unique in the Robusta genome whereas sucrose synthase was encoded by at least two genes. One of them (CcSUS1) was cloned and sequenced, showing that our BAC library is a valuable tool to rapidly identify genes of agronomic interest or linked to cup quality in C. canephora.

[Indoor allergens in office. Evaluation of the work station]. / Il rischio da allergeni indoor negli uffici. Valutazione delle postazioni di lavoro.

House dust mite and other indoor allergens play a prominent role in the pathogenesis of asthma and other allergic diseases. Several studies have shown a close relationship between sensitisation and/or onset of asthmatic symptoms and levels of indoor allergen exposure. Aim of the study was to investigate the concentration of specific markers of the indoor allergenic pollution, such as Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2. Dust samples were taken using a standard method by means of a 1200 W vacuum cleaner connected with a dust-sampling device (MITEST). A standard A4 size area has been vacuumed four times during 2 min. The concentrations of Der p 1, Der f 1, Mite Group 2, Fel d 1 and Bla g 2 were determined in dust samples from 53 different sources (office chair and carpet) using a commercial kit (DUSTSCREEN). House dust mite allergens were not always detectable in the offices. Indoor allergen concentrations (Der p 1, Der f 1, Mite Group 2, Fel d 1) were significant higher in the work station (chair) than in the carpet (p < 0.0001). Der 1 exceeded the current threshold for sensitization in about 1/4 of the samples. Der f 1 was predominant over Der p 1 according to other studies. A good correlation between the results of Der p 1 and Der f 1 was observed both in carpet and work station. Cat allergen was ubiquitous and predominantly detected in the chairs because of the employees' clothes. No appreciable levels for Mite Gr 2 and Bla g 2 were detected. Such an exposure for 8 hours in every working day may be an important occupational risk for the development of sensitization/elicitation symptoms to house dust mite. To reduce mite allergen levels are necessary preventive measure by means of specific techniques and products as barriers for preventing the direct contact with allergens.

[Occupational asthma due to cyanoacrylate: a case-report]. / Un caso di asma professionale da acrilati.

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.

Urinary determination of N-acetyl- S-( N-methylcarbamoyl)cysteine and N-methylformamide in workers exposed to N, N-dimethylformamide.

OBJECTIVES: We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (NMF) (mainly from N-hydroxy- N-methylformamide) and N-acetyl- S-( N-methylcarbamoyl)cysteine (AMCC), and levels of exposure to N, N-dimethylformamide (DMF) among occupationally exposed subjects. METHODS: Exposure levels were determined by personal sampling: breathing zone air samples were collected by means of passive samplers. DMF collected by the charcoal in personal samplers was analysed after extraction with methanol by a gas chromatograph. For the purpose of biological monitoring the levels of NMF and AMCC were measured in pre-shift and post-shift samples. Determinations were carried out by, respectively, gas chromatography and high performance liquid chromatography (HPLC). RESULTS AND CONCLUSIONS: The mean time-weighted average (TWA) exposure was approximately half (13.5 mg/m(3)) of the current threshold limit value, the range of the values was from 0.4 to 75.2 mg/m(3). Environmental DMF concentrations exhibited a significant correlation with the specific mercapturic acid (AMCC) collected at the end of the working week (AMCC Friday morning mg/l=1.384xDMF (mg/m(3))+8.708; r(2)=0.47; P<0.008]; hence urinary AMCC represents an index of the average exposure during several preceding working days, making it possible to calculate the approximate relationship between DMF uptake and excretion of this metabolite. A significant correlation was found also between the daily excretion of NMF and the corresponding levels of DMF in air. The equation of the regression line was: NMF (mg/g creatinine)=0.936xDMF (mg/m(3))+7.306; r(2)=0.522 ( P<0.0001).

[Latex protein allergy and preventive measures]. / Allergia alle proteine del lattice e percorsi di prevenzione.

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.

Molecular and biochemical characterization of endo-beta-mannanases from germinating coffee (Coffea arabica) grains.

The activity of endo-beta-mannanase ([1-->4]-beta-mannan endohydrolase EC 3.2.1.78) is likely to be central to the metabolism of cell wall mannans during the germination of grains of coffee (Coffea spp.). In the present paper, we report the cloning and sequencing of two endo-beta-mannanase cDNAs (manA and manB) by different strategies from Coffea arabica L.. The manA cDNA was obtained by the use of oligonucleotides homologous to published sequences of other endo-beta-mannanases and manB by the use of oligonucleotides deduced from a purified enzyme from coffee. ManA and B proteins share about 56% sequence homology and include highly conserved regions found in other mannan endohydrolases. Purification of the activity by chromatography followed by separation by two-dimensional electrophoresis and amino acid sequencing demonstrated the existence of at least seven isomers of the ManB form. The existence of multiple manB genes was also indicated by Southern analysis, whereas only one or two gene copies were detected for manA. Northern hybridizations with manA- and manB-specific probes showed that mRNA transcripts for both cDNAs were present at the same periods of bean germination with transcript peaks at 20 days after imbibition of water (DAI). Transcripts were not detected during grain maturation or in the other tissues such as roots, stems, flowers and leaves. The peak endo-beta-mannanase activity occurred at approximately 28 DAI and was not detected in grains prior to imbibition. Activity and mRNA levels appeared to be tightly co-ordinated. Tests of substrate specificity with the purified ManB enzyme showed that activity required a minimum of five mannose units to function efficiently.

[Sampling of airborne allergens: practical experience]. / Il campionamento degli allergeni aerodispersi: esperienze pratiche.

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.

[Measurement of N-methylformamide in occupational exposure to N,N-dimethylformamide]. / Il dosaggio della N-metilformamide nella esposizione professionale a N,N-dimetilformamide.

N,N-dimethylformamide (DMF) is a solvent that is widely used in industry. The major occupational sources of exposure results from production of synthetic leather. The main metabolite formed in both man and animals is N-hydroxymethyl-N-methylformamide. Demethylation leads to N-methylformamide (NMF) and formamide and also to a small extent to hydroxy-methylformamide. All the metabolites are excreted in urine, as are very small amounts of the unchanged substance. N-acetyl-S-(N-methyl-carbamoyl)-cysteine can be determined in urine as a further metabolite. We conducted this biomonitoring study with the aim of evaluating the correlation between the excretion of N-methylformamide (mainly from N-hydroxymethylformamide) and levels of exposure to N,N-dimethylformamide among occupationally exposed people. The mean time-weighted average (TWA) exposure was about half (13.5 mg/m3) of the current threshold limit value, the range of the values varying from 0.4 to 75.2 mg/m3. A linear equation existed between urinary NMF concentration and DMF concentration in the environment. The findings show that the urinary NMF concentration can be used as an appropriate biological exposure index. The authors suggest for occupationally exposed subjects, a urinary NMF concentration corresponding to the time-weighted average of the threshold limit value of 39.9 mg/l (37.2 mg/g creatinine) and a 95% lower confidence limit (biological threshold) of 23.4 mg/l (22.2 mg/g creatinine).