[Update 2022: interdisciplinary statement on airway management with supraglottic airway devices in pediatric emergency medicine-The laryngeal mask is and remains state of the art : Joint statement of the Institute for Emergency Medicine and Medicine Management (INM), the University Clinic Munich, LMU Munich, Germany, the Working Group for Pediatric Critical Care and Emergency Medicine of the German Interdisciplinary Society for Critical Care and Emergency Medicine (DIVI), the Medical Directors of Emergency Medical Services in Bavaria (ÄLRD), the Scientific Working Group for Pediatric Anesthesia (WAKKA) of the German Society for Anesthesiology and Intensive Care Medicine (DGAI), the Scientific Working Group for Emergency Medicine of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) and the Society of Neonatology and Pediatric Critical Care Medicine (GNPI)]. / Update 2022: Interdisziplinäre Stellungnahme zum Atemwegsmanagement mit supraglottischen Atemwegshilfen in der Kindernotfallmedizin ­ die Larynxmaske ist und bleibt State of the Art : Gemeinsame Stellungnahme des Instituts für Notfallmedizin und Medizinmanagement (INM), Klinikum der Universität München, der Sektion Pädiatrische Intensiv- und Notfallmedizin der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI), des Ärztlicher Leiter Rettungsdienst Bayern (ÄLRD Bayern), des Wissenschaftlichen Arbeitskreises Kinderanästhesie (WAKKA) der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI), des Wissenschaftlichen Arbeitskreises Notfallmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI) und der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI).

BACKGROUND: Airway management with supraglottic airway devices (SGA) in life-threatening emergencies in children is increasingly being used. Different specifications of laryngeal masks (LM) and the laryngeal tube (LT) are commonly used devices for this purpose. We present a literature review and interdisciplinary consensus statement of different societies on the use of SGA in pediatric emergency medicine. MATERIAL AND METHODS: Literature review in the PubMed database and classification of studies according to the criteria of the Oxford Centre for Evidence-based Medicine. Levels and consensus finding within the group of authors. RESULTS: The evidence for successful applications of the various types of LM is significantly higher than for LT application. Reported smaller series of successful applications of LT are currently limited to selected research groups and centers. Especially for children below 10 kg body weight there currently exists insufficient evidence for the successful application of the LT and therefore its routine use cannot be recommended. SGAs used for emergencies should have a gastric drainage possibility. DISCUSSION: Considering the scientific data and the large clinical experience with the LM in medical routine and emergency situations in children currently only the LM can be recommended for alternative (i.e., non-intubation) emergency airway management in children. If alternative airway management is part of a local emergency strategy, the LM should be provided in all pediatric sizes (1, 1½, 2, 2½, 3) for out of hospital use and in hospital emergency use and all users should regularly be trained in its application.

Genomic comparison of two strains of Mycobacterium avium subsp. paratuberculosis with contrasting pathogenic phenotype.

In a previous study, we evaluated the degree of virulence of Mycobacterium avium subsp. paratuberculosis (Map) strains isolated from cattle in Argentina in a murine model. This assay allowed us to differentiate between high-virulent MapARG1347 and low-virulent MapARG1543 strains. To corroborate whether the differences in virulence could be attributed to genetic differences between the strains, we performed Whole Genome Sequencing and compared the genomes and gene content between them and determined the differences related to the reference strain MapK10. We found 233 SNPs/INDELS in one or both strains relative to Map K10. The two strains share most of the variations, but we found 15 mutations present in only one of the strains. Considering NS-SNP/INDELS that produced a severe effect in the coding sequence, we focus the analysis on four predicted proteins, putatively related to virulence. Survival of MapARG1347 strain in bMDM was higher than MapARG1543 and was more resistant to acidic pH and H2O2 stresses than MapK10. The genomic differences between the two strains found in genes MAP1203 (a putative peptidoglycan hydrolase), MAP0403 (a putative serine protease) MAP1003c (a member of the PE-PPE family) and MAP4152 (a putative mycofactocin binding protein) could contribute to explain the contrasting phenotype previously observed in mice models.

[Arterial ischemic stroke in childhood and adolescence]. / Arteriell ischämischer Schlaganfall im Kindes- und Jugendalter: Zeitkritischer Notfall in der Pädiatrie.

Childhood arterial ischemic stroke is one of the most time-critical pediatric emergencies but is often diagnosed with a prognostically relevant time delay. The reasons are low awareness, sometimes unspecific clinical presentation with a wide variety of critical differential diagnoses and less coordinated acute care structures. The revascularization strategies established for adults also show sometimes spectacular success in children. These should therefore also be made available for affected children if possible, although the evidence is nowhere near comparable. In the postacute phase the etiological work-up is complex due to the risk factors which need to be considered, but identification of the individual risk profile is essential as it defines secondary prevention, risk of recurrence and outcome. The long-term care in a multiprofessional, interdisciplinary team must take into account all bio-psycho-social aspects of the child in the current developmental phase.

[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.

Respiratory diseases and allergy in farmers working with livestock: a EAACI position paper.

Farmers constitute a large professional group worldwide. In developed countries farms tend to become larger, with a concentration of farm operations. Animal farming has been associated with negative respiratory effects such as work-related asthma and rhinitis. However, being born and raised or working on a farm reduces the risk of atopic asthma and rhinitis later in life. A risk of chronic bronchitis and bronchial obstruction/COPD has been reported in confinement buildings and livestock farmers. This position paper reviews the literature linking exposure information to intensive animal farming and the risk of work-related respiratory diseases and focuses on prevention. Animal farming is associated with exposure to organic dust containing allergens and microbial matter including alive microorganisms and viruses, endotoxins and other factors like irritant gases such as ammonia and disinfectants. These exposures have been identified as specific agents/risk factors of asthma, rhinitis, chronic bronchitis, COPD and reduced FEV1. Published studies on dust and endotoxin exposure in livestock farmers do not show a downward trend in exposure over the last 30 years, suggesting that the workforce in these industries is still overexposed and at risk of developing respiratory disease. In cases of occupational asthma and rhinitis, avoidance of further exposure to causal agents is recommended, but it may not be obtainable in agriculture, mainly due to socio-economic considerations. Hence, there is an urgent need for focus on farming exposure in order to protect farmers and others at work in these and related industries from developing respiratory diseases and allergy.

Relevance of TH2 Markers in the Assessment and Therapeutic Management of Severe Allergic Asthma: A Real-Life Perspective.

BACKGROUND: Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. METHODS: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. RESULTS: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. CONCLUSIONS: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab.

Relevance of TH2 markers in the assessment and therapeutic management of severe allergic asthma: a real-life perspective

BACKGROUND: Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. METHODS: Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. RESULTS: We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. CONCLUSIONS: Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab

ANTECEDENTES: Aunque los eosinófilos en la sangre actualmente son reconocidos como el principal marcador clínico de la inflamación Th2, su relevancia en la identificación de la gravedad del asma sigue siendo un tema de debate. MÉTODOS: Nuestro estudio retrospectivo de la vida real sobre asmáticos graves, incluido en la base de datos italiana de NEONet, tuvo como objetivo investigar la relevancia del recuento de eosinófilos en sangre y el FeNO en la evaluación clínica del asma grave y su función como posible factor predictivo de la capacidad de respuesta al tratamiento con anti-IgE. Como valores de corte se eligieron 300 eosinófilos/mm3en sangre y 30 ppm para FeNO. RESULTADOS: En total se evaluaron 132 pacientes adultos. No se pudieron observar diferencias significativas entre los grupos de eosinófilos basales altos y bajos, en términos de datos demográficos, IgE total, función pulmonar, resultados informados por el paciente (PRO) o comorbilidades nasales. Los pacientes con ≥ FeNO 30 ppb mostraron una puntuación de ACT peor y una puntuación AQLQ más baja en comparación con los de FeNO <30 ppb. En el subgrupo de FeNO alto, se registraron ingresos hospitalarios con más frecuencia y un mayor número de días de trabajo perdidos en el último año. Una puntuación combinada que incluye tanto a los eosinófilos como el FeNO no mejoró la precisión de los parámetros individuales. En el subgrupo de eosinófilos altos, la proporción de pacientes que respondieron al tratamiento con omalizumab fue mayor y aumentó significativamente en cada punto de tiempo de seguimiento. CONCLUSIONES: De acuerdo con nuestros hallazgos, los eosinófilos en sangre no representan un marcador unívoco de la gravedad del asma, mientras que un nivel más alto de FeNO se asocia con más ingresos hospitalarios y más días de trabajo perdidos. Los eosinófilos de la sangre parecen actuar como predictores de la respuesta del tratamiento al omalizumab

Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients.

Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.

Blood-Brain Barrier in a Haemophilus influenzae Type a In Vitro Infection: Role of Adenosine Receptors A2A and A2B.

The blood-brain barrier (BBB) is mainly made up of tightly connected microvascular endothelial cells (BMECs), surrounded by pericytes (BMPCs) which regulate BBB tightness by providing soluble factors that control endothelial proliferation. Haemophilus influenzae type a (Hia) is able to reach the BBB, crossing it, thus causing meningitis. In this study, by using an in vitro model of BBB, performed with human BMECs and human BMPCs in co-culture, we demonstrated that, after Hia infection, the number of hBMPCs decreased whereas the number of hBMECs increased in comparison with non-infected cells. SEM and TEM images showed that Hia was able to enter hBMECs and reduce TEER and VE-cadherin expression. When the cells were infected in presence of SCH58261 and PSB603 but not DPCPX, an increase in TEER values was observed thus demonstrating that A2A and A2B adenosine receptors play a key role in BBB dysfunction. These results were confirmed by the use of adenosine receptor agonists CGS21680, CCPA, and NECA. In infected co-cultures cAMP and VEGF increased and TEER reduction was counter-balanced by VEGF-R1 or VEGF-R2 antibodies. Moreover, the phosphorylated CREB and Rho-A significantly increased in infected hBMECs and hBMPCs and the presence of SCH58261 and PSB603 significantly abrogated the phosphorylation. In conclusion, this study demonstrated that the infection stimulated A2A and A2B adenosine receptors in hBMECs and hBMPCs thus inducing the pericytes to release large amounts of VEGF. The latter could be responsible for both, pericyte detachment and endothelial cell proliferation, thus provoking BBB impairment.

[Childhood stroke : What are the special features of childhood stroke?] / "Childhood stroke" : Was macht den Schlaganfall beim Kind besonders?

Childhood arterial ischemic stroke differs in essential aspects from adult stroke. It is rare, often relatively unknown among laypersons and physicians and the wide variety of age-specific differential diagnoses (stroke mimics) as well as less established care structures often lead to a considerable delay in the diagnosis of stroke. The possible treatment options in childhood are mostly off-label. Experiences in well-established acute treatment modalities in adult stroke, such as thrombolysis and mechanical thrombectomy are therefore limited in children and only based on case reports and case series. The etiological clarification is time-consuming due to the multitude of risk factors which must be considered. Identifying each child's individual risk profile is mandatory for acute treatment and secondary prevention strategies and has an influence on the individual outcome. In addition to the clinical neurological outcome the residual neurological effects of stroke on cognition and behavior are decisive for the integration of the child into its educational, later professional and social environment.

Proteome Analysis of Urticating Setae From Thaumetopoea pityocampa (Lepidoptera: Notodontidae).

Thaumetopoea pityocampa (Denis & Schiffermüller) (Lepidoptera: Notodontidae) is harmful to conifer trees because of defoliation and to public health because of the release of urticating setae from the caterpillars. Contact with setae by humans and domestic animals induces dermatitis, usually localized to the exposed areas. Recent studies demonstrated the presence of a complex urticating mechanism where proteins present in the setae may play a role as activators of immune responses. Yet, limited information is available at present about the proteins occurring in the setae of T. pityocampa. Using a refined method for protein extraction from the setae, and a combination of liquid chromatography tandem-mass spectrometry (LC-MS/MS), de novo assembly of transcriptomic data, and sequence similarity searches, an extensive data set of 353 proteins was obtained. These were further categorized by molecular function, biological process, and cellular location. All the 353 proteins identified were found to match through BLAST search with at least one Lepidoptera sequence available in databases. We found the previously known allergens Tha p 1 and Tha p 2 described from T. pityocampa, as well as enzymes involved in chitin biosynthesis, one of the principal components of the setae, and serine proteases that were responsible for inflammatory and allergic reactions in other urticating Lepidoptera. This new proteomic database may allow for a better understanding of the complexity of allergenic reactions due to T. pityocampa and to other Lepidoptera sharing similar defense systems.

Building dampness and mold in European homes in relation to climate, building characteristics and socio-economic status: The European Community Respiratory Health Survey ECRHS II.

We studied dampness and mold in homes in relation to climate, building characteristics and socio-economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self-reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self-reported water damage (OR=1.63 per 10°C; 95% CI 1.02-2.63), damp spots (OR=2.95; 95% CI 1.98-4.39), and mold (OR=2.28; 95% CI 1.04-4.67). Precipitation was associated with water damage (OR=1.12 per 100 mm; 95% CI 1.02-1.23) and damp spots (OR=1.11; 95% CI 1.02-1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53-0.89) but more mold (OR=1.27; 95% CI 1.03-1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.

Drop-out rate among patients treated with omalizumab for severe asthma: Literature review and real-life experience.

BACKGROUND: In patients with asthma, particularly severe asthma, poor adherence to inhaled drugs negatively affects the achievement of disease control. A better adherence rate is expected in the case of injected drugs, such as omalizumab, as they are administered only in a hospital setting. However, adherence to omalizumab has never been systematically investigated. The aim of this study was to review the omalizumab drop-out rate in randomized controlled trials (RCTs) and real-life studies. A comparative analysis was performed between published data and the Italian North East Omalizumab Network (NEONet) database. RESULTS: In RCTs the drop-out rate ranged from 7.1 to 19.4 %. Although the reasons for withdrawal were only occasionally reported, patient decision and adverse events were the most frequently reported causes. In real-life studies the drop-out rate ranged from 0 to 45.5 %. In most cases lack of efficacy was responsible for treatment discontinuation. According to NEONet data, 32 % of treated patients dropped out, with an increasing number of drop outs observed over time. Patient decision and lack of efficacy accounted for most treatment withdrawals. CONCLUSIONS: Treatment adherence is particularly crucial in patients with severe asthma considering the clinical impact of the disease and the cost of non-adherence. The risk of treatment discontinuation has to be carefully considered both in the experimental and real-life settings. Increased knowledge regarding the main reasons for patient withdrawal is important to improve adherence in clinical practice.

The risk of respiratory symptoms on allergen exposure increases with increasing specific IgE levels.

BACKGROUND: The relation between IgE sensitization and allergic respiratory symptoms has usually been evaluated by dichotomizing specific IgE levels. The aim of this study was to evaluate the association between specific IgE levels and risk of symptoms on allergen-related exposure, with special reference to allergen-related asthma-rhinitis comorbidity. METHODS: We considered 6391 subjects enrolled within the European Community Respiratory Health Survey 2, having information on cat/grass/D. pteronyssinus IgE levels and symptoms on exposure to animals/pollen/dust. The risk of oculonasal/asthmalike/both symptoms was evaluated by a multinomial logistic model. RESULTS: A clear positive association was observed between specific IgE levels to cat/grass/mite and the risk of symptoms on each allergen-related exposure (test for trend with P < 0.001). This trend was particularly pronounced when considering the coexistence of asthmalike and oculonasal symptoms. Compared to non-sensitized subjects, subjects with specific IgE to cat >= 3.5 kU/l presented relative risk ratios of 11.4 (95% CI 6.7-19.2), 18.8 (8.2-42.8), and 55.3 (30.5-100.2) when considering, respectively, only oculonasal symptoms, only asthmalike symptoms, or both. A similar pattern was observed when considering specific IgE to grass/mite and symptoms on exposure to pollen/dust. Also the proportion of people using inhaled medicines or visiting a general practitioner for breathing problems in the previous year increased with increasing sum of specific IgE to cat/grass/mite. CONCLUSION: Specific IgE level is the most important predictor of allergen-related symptoms. The risk of both oculonasal/asthmalike symptoms increases with specific IgE levels, suggesting that specific IgE contributes to the 'united airways disease'.

Real-time sonoelastography as novel follow-up method in Achilles tendon surgery.

PURPOSE: To evaluate the sonoelastographic features of Achilles tendon healing after percutaneous treatment using real-time sonoelastography, a new tool able to quantify deformation in biological tissues. METHODS: Patients with atraumatic Achilles tendon ruptures, treated with a percutaneous technique, were assessed. Sonoelastographic evaluations were performed at the myotendinous junction, tendon body/lesion site and osteotendinous junction, both for the operated and contralateral side, at 40 days, 6 months and 1 year after surgery. Using standard regions of interest, the "strain index" (SI) was calculated as an indicator of tendon elasticity. Clinical outcomes were assessed by the ATRS questionnaire at 6 months and 1 year post-operatively and correlated with sonoelastographic findings. Sixty healthy tendons from 30 volunteers were used to provide a healthy control range. RESULTS: Twenty-five patients were recruited for this study. The SI in treated tendons showed progressive stiffening over time, especially at myotendinous junction and at the site of the sutured lesion, resulting in significantly higher stiffness than both the contralateral tendon and healthy volunteers. Peak thickness of treated tendons occurred at 6 months, with a tendency to reduce at 1 year, while never achieving a normal physiological state. Greatest remodelling was seen at the lesion site. The contralateral tendon showed significant thickening at the myotendinous and osteotendinous junctions. The SI of the contralateral tendon was found to be stiffer than physiological values found in the control group. ATRS score improved significantly between 6 months and 1 year, being negatively correlated with the SI (p < 0.001). CONCLUSION: RTSE showed that operatively treated Achilles tendons become progressively stiffer during follow-up, while the ATRS score improved. From a biomechanical point of view, at 1 year after surgery Achilles tendons did not show a "restitutio ad integrum". Real-time sonoelastography provides more qualitative and quantitative details in the diagnostics and follow-up of Achilles tendon conditions as the post-operative evolution of the repairing tissue. LEVEL OF EVIDENCE: Diagnostic and therapeutic study, Level III.

Role of cytosolic and calcium independent phospholipases A(2) in insulin secretion impairment of INS-1E cells infected by S. aureus.

Cytosolic PLA2 (cPLA2) and Ca(2+)-independent PLA2 (iPLA2) play a significant role in insulin ß-cells secretion. Bacterial infections may be responsible of the onset of diabetes. The mechanism by which Staphylococcus aureus infection of INS-1 cells alters glucose-induced insulin secretion has been examined. After acute infection, insulin secretion and PLA2 activities significantly increased. Moreover, increased expressions of phospho-cPLA2, phospho-PKCα and phospho-ERK 1/2 were observed. Chronic infection causes a decrease in insulin release and a significant increase of iPLA2 and COX-2 protein expression. Moreover, insulin secretion in infected cells could be restored using specific siRNAs against iPLA2 isoform and specific COX-2 inhibitor.

Asthenozoospermia and membrane remodeling enzymes: a new role for phospholipase A2.

Phosholipase A2 (PLA2 ) activity in the seminal plasma and in sperm heads is closely related to sperm motility and male fertility. Therefore, the purpose of this study was to investigate the possible involvement of different isoforms of phospholipase in asthenozoospermia. To accomplish this, cPLA2 , phospho-cPLA2 , iPLA2 , and sPLA2 were evaluated by immunofluorescence and immunoblot analyses in spermatozoa obtained from 22 normozoospermic men and 28 asthenozoospermic patients. We found significant differences in cPLA2 and its phosphorylated/activated form, iPLA2 , and sPLA2 content and distribution in normal and asthenozoospermic patients. cPLA2 was localized in heads, midpieces, and tails of all spermatozoa as constitutive enzyme, less expressed in the tail of spermatozoa with low progressive motility. While active phospho-cPLA2 distribution was homogeneous throughout the cell body of control-donor spermatozoa, lower levels were detected in the tails of asthenozoospermic patients, as opposed to its strong presence in heads. Low immunofluorescence signal for iPLA2 was found in astenozoospermic patients, whereas sPLA2 was significantly lower in the heads of asthenozoospermic patients. Spermatozoa with low progressive motility showed differences both in terms of total specific activity and of intracellular distribution. cPLA2 , iPLA2 , and sPLA2 specific activities correlated positively and in a significantly manner with sperm progressive motility both in normozoospermic men and asthenozoospermic patients. In conclusion, PLA2 s are expressed in different areas of human spermatozoa. Spermatozoa with low motility showed differences in total specific activity and enzyme distributions. We speculated that PLA2 expression and/or different distribution could be potential biomarkers of asthenozoospermia, one of the major causes of male factor infertility.

Adult eczema in Italy: prevalence and associations with environmental factors.

BACKGROUND: Studies on the prevalence of eczema and atopic dermatitis (AD), and on the factors associated with these diseases, have been mostly performed in children, whereas studies on adult populations are lacking. OBJECTIVES: To determine the prevalence of eczema and AD in the Italian adult population, and to investigate risk factors associated with the disease. METHODS: A postal screening questionnaire was administered to 18 357 randomly selected subjects aged 20-44 years in the Gene-Environment Interaction in Respiratory Diseases study, which involved seven centres distributed across northern, central and southern Italy. The questionnaire included items on the occurrence of doctor-diagnosed eczema, asthma and hay fever, socio-demographic characteristics and environmental exposures. RESULTS: In all, 10 464 (57.0%) subjects responded to the questionnaire. The prevalence of current eczema was 8.1% (95% CI: 7.6-8.7%), while the prevalence of eczema with asthma and/or hay fever (EAH), which was adopted as proxy of AD, was 3.4% (95% CI: 3.1-3.8%). About 60% of the subjects with current eczema reported the onset of the disease in adulthood. In multi-variable models, the prevalence of eczema was significantly associated with female sex, older age, living close to industrial plants, high levels of heavy traffic near home and living in central-southern Italy. CONCLUSIONS: Eczema and EAH are highly prevalent in Italian young adults, especially in women. Our results suggest that adult onset is not unusual, and that environmental factors may influence the occurrence of eczema and EAH.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.

[Therapy of inherited diseases of platelet function. Interdisciplinary S2K guideline of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)]. / Therapie hereditärer Thrombozytopathien. Interdisziplinäre S2K-Leitlinie der Ständigen Kommission Pädiatrie der Gesellschaft für Thrombose- und Hämostaseforschung e. V.

Inherited disorders of platelet function are a heterogeneous group. For optimal prevention and management of bleeding, classification and diagnosis of the underlying defect are highly recommended. An interdisciplinary guideline for a diagnostic approach has been published (AWMF # 086-003 S2K; Hämostaseologie 2014; 34: 201-212). Underlying platelet disorder, platelet count, age and clinical situation modify treatment. Exclusive transfusion of platelet concentrates may be inappropriate as potentially adverse effects can outweigh its benefit. A stepwise and individually adjusted approach for restitution and maintenance of haemostasis is recommended. Administration of antifibrinolytics is generally endorsed, but is of particular use in Quebec disease. Restricted to older children, desmopressin is favourable in storage pool disease and unclassified platelet disorders. Although licensed only for patients with Glanzmann thrombasthenia and alloantibodies, in clinical practice rFVIIa is widely used in inherited platelet disorders with severe bleeding tendency. This guideline aims at presenting the best available advice for the management of patients with inherited platelet function disorders.