Clinical severity of LTP syndrome is associated with an expanded IgE repertoire, FDEIA, FDHIH, and LTP mono reactivity.

Summary: Background. LTP allergy is often a challenge for clinicians. We evaluated a multiplex diagnostic approach with diverse cofactors to stratify LTP syndrome risk. Methods. Of the 1,831 participants screened with 'Allergy Explorer-ALEX-2', 426 had reactions to at least one LTP. Data was gathered and recorded via an electronic database. Results. Reactivity to peach Pru p 3 was found in 77% of individuals with LTP allergy. Higher levels of specific IgE and concurrent sensitization to more than 5 molecules (50% of all LTP-sensitised participants, 62% of symptomatic cases) were significantly associated with an increased risk of severe reactions (p = 0.001). Several cofactors, either alone or in combination, also influenced patients' clinical outcomes. Some cofactors increased the risk of severe reactions, such as mono reactivity to LTP in 44.6% of cases (p = 0.001), FDEIA in 10.8% of patients (p = 0.001), and FDNIH in 11.5% (p = 0.005). On the other hand, reactivity to PR10 (24.2%; p = 0.001), profilin hypersensitivity (10.3%; p = 0.001), and/or atopic dermatitis (16.7%; p = 0.001) had a mitigating effect on symptom severity. Conclusions. Clinical severity of LTP syndrome is associated with an expanded IgE repertoire in terms of the number of LTP components recognized and increased IgE levels in individual molecules. Ara h 9, Cor a 8, and Mal d 3 showed the strongest association with clinical severity. In addition, several cofactors may either exacerbate (FDEIA, FDHIH, and LTP monoreactivity) or ameliorate (atopic dermatitis and co-sensitization to profilin and/or PR10) individual patient outcomes. These factors may be utilized for the daily clinical management of LTP syndrome.

A new digital health tool for the telemonitoring of patients with scleroderma during iloprost administration: a feasibility and acceptability study.

OBJECTIVE: To assess the feasibility of a new device for telemonitoring vital parameters during iloprost infusion. MATERIALS AND METHODS: In a pilot study, patients with systemic sclerosis received iloprost infusion while being telemonitored with Umana T1 Heart Monitor, within the hospital, under the supervision of family/community nurses and rheumatologists. Patients were administered a questionnaire to obtain information on satisfaction, practicability, and compliance with the new monitoring device. RESULTS: Data recorded by the device for blood pressure, heart rate, and oximetry were concordant with those registered directly by nurses. Most patients found the device useful and thought it could be used at home, even while working. CONCLUSIONS: Umana Heart Monitor T1 could be a valuable aid in at-home iloprost therapy in patients with systemic sclerosis.

Trace metals and polycyclic aromatic hydrocarbons in the Eastern Mediterranean sediments: Concentration ranges as a tool for quality control of large data collections.

Assessing the status of marine pollution at regional and sub-regional scales requires the use of comparable and harmonized data provided by multiple institutions, located in several countries. Standardized data management and quality control are crucial for supporting a coherent evaluation of marine pollution. Taking the Eastern Mediterranean Sea as a case study, we propose an approach to improve the quality control procedures used for sediment pollution data, thus supporting a harmonized environmental assessment. The regional ranges of contaminant concentrations in sediments were identified based on an in-depth literature review, and the lowest measured concentrations were evaluated to determine the "background concentrations" of chemical substances not yet targeted in the Mediterranean Sea. In addition, to verify the suitability of the approach for validating large data collections provided by multiple sources, the determined ranges were used to validate a regional dataset available through EMODnet data infrastructure.

Polylactide Nanocapsules Attenuate Adverse Cardiac Cellular Effects of Lyso-7, a Pan-PPAR Agonist/Anti-Inflammatory New Thiazolidinedione.

Lyso-7 is a novel synthetic thiazolidinedione, which is a receptor (pan) agonist of PPAR α,ß/δ,γ with anti-inflammatory activity. We investigated the cardiotoxicity of free Lyso-7 in vitro (4.5-450 nM), and Lyso-7 loaded in polylactic acid nanocapsules (NC) in vivo (Lyso-7-NC, 1.6 mg/kg). In previous work, we characterized Lyso-7-NC. We administered intravenously Lyso-7, Lyso-7-NC, control, and blank-NC once a day for seven days in mice. We assessed cell contraction and intracellular Ca2+ transients on single mice cardiomyocytes enzymatically isolated. Lyso-7 reduced cell contraction and accelerated relaxation while lowering diastolic Ca2+ and reducing Ca2+ transient amplitude. Lyso-7 also promoted abnormal ectopic diastolic Ca2+ events, which isoproterenol dramatically enhanced. Incorporation of Lyso-7 in NC attenuated drug effects on cell contraction and prevented its impact on relaxation, diastolic Ca2+, Ca2+ transient amplitude, Ca2+ transient decay kinetics, and promotion of diastolic Ca2+ events. Acute effects of Lyso-7 on cardiomyocytes in vitro at high concentrations (450 nM) were globally similar to those observed after repeated administration in vivo. In conclusion, we show evidence for off-target effects of Lyso-7, seen during acute exposure of cardiomyocytes to high concentrations and after repeated treatment in mice. Nano-encapsulation of Lyso-7 in polymeric NC attenuated the unwanted effects, particularly ectopic Ca2+ events known to support life-threatening arrhythmias favored by stress or exercise.

Phthalocyanine photosensitizer in polyethylene glycol-block-poly(lactide-co-benzyl glycidyl ether) nanocarriers: Probing the contribution of aromatic donor-acceptor interactions in polymeric nanospheres.

For best photosensitizer activity phthalocyanine dyes used in photodynamic therapy should be molecularly dispersed. Polyethylene glycol-block-polylactide derivatives presenting benzyl side-groups were synthesized to encapsulate a highly lipophilic phthalocyanine dye (AlClPc) and evaluate the effect of π-π interactions on the nanocarrier colloidal stability and dye dispersion. Copolymers with 0, 1, 2 and 6 mol% of benzyl glycidyl ether (BGE) were obtained via polyethylene glycol initiated ring-opening copolymerization of D,l-lactide with BGE. The block copolymers formed stable, monodisperse nanospheres with low in vitro cytotoxicity. AlClPc loading increased the nanosphere size and affected their colloidal stability. The photo-physical properties of the encapsulated dye, studied in batch and after separation by field flow fractionation, demonstrated the superiority of plain PEG-PLA over BGE-containing copolymers in maintaining the dye in its monomeric (non-aggregated) form in aqueous suspension. High dye encapsulation and sustained dye release suggest that these nanocarriers are good candidates for photodynamic therapy.

An atlas of IgE sensitization patterns in different Italian areas. A multicenter, cross-sectional study.

Summary: Background. The development of recombinant technology supported the allergy diagnostic work-up in the daily clinical practice, representing a useful tool for epidemiological studies. Methods. An atlas of the IgE sensitization profiles found throughout Italy was prepared from a nationwide, multicenter, cross-sectional study. Results. 6052 unselected consecutive individuals, belonging to North-West [NW], North-East [NE], Centre [C], South [S], and Islands subset [Is] were evaluated by means of the ImmunoCAP ISAC test. The top-ranked sensitizations found were Cup a 1 in [C] (58.1%) and [S] (53.6%), Phl p 1 in the North (from 46.1% to 49%), and Cyn d 1 in [Is] (44.2%). High frequency of house dust mite group 2 molecules sensitization was found in [C] (36.9%) and [S] Italy (40.8%), whilst low level of reactivity was recorded in [NW] (20%). Pellitory hypersensitivity was mainly found in [C], [S], and [Is], whilst ragweed Amb a 1 sensitivity was particularly found in [NW] Italy. IgE recognition of PR-10, Profilin, and nsLTP was mutually exclusive in 69.1% of cases, PR-10 reactivity mostly occurring in [NE], Profilin in [NW], and nsLTP molecules recognition mainly recorded in [C] and [S]. Conclusions. Divergent IgE sensitization patterns were found along Italy, possibly linked to the distinct geographical locations, indicating multiplex system IgE analysis as a reliable approach for epidemiological evaluation even in small geographical areas.

Storage molecules from tree nuts, seeds and legumes: relationships and amino acid identity among homologue molecules.

Summary: The families of seed storage proteins, together with profilins, oil-bodies-associated oleosins, and pathogenesis-related (PR) proteins like PR-10 (Bet v 1-like), PR-12 (defensins) and PR-14 (non-specific lipid transfer protein), are the main causes of IgE sensitization to tree nuts, legumes and seeds. All these allergens, with the exclusion of profilins and of PR-10, are heat-stable and possibly responsible for fatal or almost fatal adverse reactions to such foods. In this short review, we will discuss the relationship and amino acid identities among some of the seed storage homologue molecules identified to date from tree nuts, seeds and legumes.

Early stages of clathrin aggregation at a membrane in coarse-grained simulations.

The self-assembly process of clathrin coated pits during endocytosis has been simulated by combining and extending coarse grained models of the clathrin triskelion, the adaptor protein AP2, and a flexible network membrane. The AP2's core, upon binding to membrane and cargo, releases a motif that can bind clathrin. In conditions where the core-membrane-cargo binding is weak, the binding of this motif to clathrin can result in a stable complex. We characterize the conditions and mechanisms resulting in the formation of clathrin lattices that curve the membrane, i.e., clathrin coated pits. The mechanical properties of the AP2 ß linker appear crucial to the orientation of the curved clathrin lattice relative to the membrane, with wild-type short linkers giving rise to the inward curving buds enabling endocytosis while long linkers produce upside-down cages and outward curving bulges.

Pla a 2 and Pla a 3 reactivities identify plane tree-allergic patients with respiratory symptoms or food allergy.

Nine hundred and thirty-nine rPla a 1, nPla a 2, and rPla a 3 ImmunoCAP ISAC reactors were studied. nPla a 2pos MUXF3pos but Pla a 1/2neg subjects were excluded from the study because they were cross-reactive carbohydrate determinant reactors. Among the 764 remaining participants, 71.9% were Pla a 3pos , 54.1% Pla a 2pos , and 10.9% Pla a 1pos . Among Pla a 3 reactors, 89.6% were Pru p 3pos and 86.8% Jug 3pos , but the strongest IgE recognition relationship was observed between Pla a 3 and Jug r 3. Distinctive clinical subsets could be documented among plane tree-allergic patients. Pla a 3 reactors had both local and systemic food-induced reactions, but lower past respiratory symptoms occurrence. Pla a 2 reactivity was associated with respiratory symptoms but inversely related to systemic reactions to food. Cosensitization to Pla a 2 and Pla a 3 was associated with a lower past incidence of severe food-induced reactions.

Determination of hydrocarbons transported by urban runoff in sediments of São Gonçalo Channel (Pelotas - RS, Brazil).

A high concentration of hydrocarbons in the environment is indicative of pollution. To evaluate the effect of hydrocarbons transported by urban runoff, the present study analyzed total petroleum hydrocarbons (TPHs), aliphatic hydrocarbons (AHs), unresolved complex mixture (UCM), and n-alkanes of the sediments of the canal that cross the urban area of Pelotas, Rio Grande do Sul, Brazil. The carbon preference index (CPI), terrigenous/aquatic ratio (TAR), and pristane/phytane ratio were determined. The TPH content ranged from 177,043.7µg·kg-1±13.4% to 5,892,667.0µg·kg-1±5.9%. The total aliphatic content ranged from 116,268.8µg·kg-1±11.1% to 2,393,592.6µg·kg-1±7.7%, indicating chronic contamination of n-alkanes petrogenic and biogenic sources. The levels of hydrocarbons (TPH, AHs, and n-alkanes) were considered relatively high, confirming the effect of urban runoff on the drainage system of cities and their consequent effect on the estuarine region of Patos Lagoon and other water resources.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

Lipid transfer protein sensitization: reactivity profiles and clinical risk assessment in an Italian cohort.

BACKGROUND: Nonspecific lipid transfer proteins (nsLTPs) represent a major cause of systemic food allergic reactions in the Mediterranean area. This study investigate hierarchical patterns and cluster relationships of IgE sensitization to different nsLTPs, and the relationship to clinical allergy in a large Italian cohort. METHODS: A total of 568 nsLTP-positive subjects after IgE ImmunoCAP-ISAC microarray analysis with Ara h 9, Art v 3, Cor a 8, Jug r 3, Pla a 3, Pru p 3 and Tri a 14 allergens were studied. IgE inhibition experiments were carried out with mugwort and plane tree pollen extracts. RESULTS: Eighty-two per cent of nsLTP-positive participants (94% if <6 years old) were Pru p 3(pos) , and 71% were Jug r 3(pos) . Participants who reacted to >5 nsLTPs reported a higher incidence of food-induced systemic reactions. Only Art v 3 and Pla a 3 (mugwort and plane tree nsLTPs, respectively) were associated with respiratory symptoms, and a correlation was observed between sensitization to pollen and plant food nsLTPs, particularly between Pla a 3 and tree nut/peanut nsLTPs. Co-sensitization to Par j 2 and PR-10 or profilin pan-allergens was associated with a lower prior prevalence of severe food-induced reactions. In inhibition assays, plane and mugwort pollen extracts inhibited 50-100% of IgE binding to food nsLTPs in microarrays. CONCLUSIONS: Testing IgE reactivity to a panel of nsLTP allergens unveils important associations between nsLTP sensitization profiles and clinical presentation and allows the identification of novel cluster patterns indicating likely cross-reactivities and highlighting potential allergens for nsLTP immunotherapy.

Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases.

The mode of inheritance of Alport syndrome (ATS) has long been controversial. In 1927, the disease was hypothesized as a dominant condition in which males were more severely affected than females. In 1990, it was considered an X-linked (XL) semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal dominant (AD) form was testified more recently by the description of some large pedigrees but the real existence of this form is still questioned by many and its exact prevalence is unknown. The introduction of next generation sequencing (NGS) allowed us to perform an unbiased simultaneous COL4A3-COL4A4-COL4A5 analysis in 87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of them (55%), a mutation in one of the three genes was identified: the inheritance was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15 families). The AD form must therefore be seriously taken into account in all pedigrees with affected individuals in each generation. Furthermore, a high frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical criteria, suggesting NGS as first-level analysis in cases with a clinical suspicion of ATS.

Performance of different PEEP valves and helmet outlets at increasing gas flow rates: a bench top study.

BACKGROUND: Aim of the paper was to assess the performance of different expiratory valves and the resistance of helmet outlet ports at increasing gas flow rates. METHODS: A gas flow-meter was connected to 10 different expiratory peep valves: 1 water-seal valve, 4 precalibrated fixed PEEP valves and 5 adjustable PEEP valves. Three new valves of each brand, set at different pressure levels (5-7.5-10-12.5-15 cmH(2)O, if available), were tested at increasing gas flow rates (from 30 to 150 L/min). We measured the pressure generated just before the valves. Three different helmets sealed on a mock head were connected at the inlet port with a gas flow-meter while the outlet was left clear. We measured the pressure generated inside the helmet (due to the flow-resistance of the outlet port) at increasing gas flow rates. RESULTS: Adjustable valves showed a variable degree flow-dependency (increasing difference between the measured and the expected pressure at increasing flow rates), while pre-calibrated valves revealed a flow-independent behavior. Water seal valve showed low degree flow-dependency. The pressures generated by the outlet port of the tested helmets ranged from 0.02 to 2.29 cmH(2)O at the highest gas flow rate. CONCLUSION: Adjustable PEEP valves are not suggested for continuous-flow CPAP systems as their flow-dependency can lead to pressures higher than expected. Precalibrated and water seal valves exhibit the best performance. Different helmet outlet ports do not significantly affect the pressure generated during helmet CPAP. In order to avoid iatrogenic complications gas flow and pressure delivered during helmet CPAP must always be monitored.

Winter to spring variations of chromophoric dissolved organic matter in a temperate estuary (Po River, northern Adriatic Sea).

The light absorbing fraction of dissolved organic carbon (DOC), known as chromophoric dissolved organic matter (CDOM) showed wide seasonal variations in the temperate estuarine zone in front of the Po River mouth. DOC concentrations increased from winter through spring mainly as a seasonal response to increasing phytoplankton production and thermohaline stratification. The monthly dependence of the CDOM light absorption by salinity and chlorophyll a concentrations was explored. In 2003, neither DOC nor CDOM were linearly correlated with salinity, due to an exceptionally low Po river inflow. Though the CDOM absorbance coefficients showed a higher content of chromophoric dissolved organic matter in 2004 with respect to 2003, the spectroscopic features confirmed that the qualitative nature of CDOM was quite similar in both years. CDOM and DOC underwent a conservative mixing, only after relevant Po river freshets, and a change in optical features with an increase of the specific absorption coefficient was observed, suggesting a prevailing terrestrial origin of dissolved organic matter.

Skin reactions triggered by the use of cosmetic products in nonspecific lipid transfer protein-sensitive patients.

Nonspecific lipid transfer proteins (nsLTPs) are members of the prolamine superfamily and they are found in pollen and food, as well as in latex. Due to the strong stability both against pepsin digestion and thermal denaturation, sensitisation towards these proteins is often associated with severe systemic reactions (angioedema, urticaria, asthma, anaphylaxis, etc.) following the ingestion of both raw or fresh food and cooked or preserved food. Many studies have shown reactivity towards nsLTPs both via inhalation and orally and in this study we present two cases of nsLTPs-sensitive patients who manifested the immediate onset of skin reactions following the use of cosmetic products containing these proteins. Thus, in order to prevent immediate reactions linked to their use, it is necessary to recommend nsLTPssensitive patients to avoid the topical use of products containing these proteins (and obviously the ingestion of foods containing these proteins).

Systemic lupus erythematosus and Wiskott-Aldrich syndrome in an Italian patient.

Systemic lupus erythematosus has not yet been associated with mutations in the Wiskott-Aldrich syndrome gene; moreover, the time courses of platelet number and size in patients with Wiskott-Aldrich syndrome are unknown. In this case, we present the time trends of platelet count and volume and the histopathology of the kidney of a patient with systemic lupus erythematosus and a mutation in the Wiskott-Aldrich syndrome gene. The patient suffered from congenital recessive X-linked thrombocytopenia, and he developed systemic lupus erythematosus at the age of 12 years. Thus, his disease was reclassified as Wiskott-Aldrich syndrome, class 5. The g.257G > A mutation in the Wiskott-Aldrich syndrome gene and reduced expression of the specific messenger were revealed by molecular analyses.

Evaluation by double-blind placebo-controlled oral challenge of the clinical relevance of IgE antibodies against plant glycans.

BACKGROUND: The clinical relevance of immunoglobulin E (IgE) to plant glycans is a longstanding debate. We sought to evaluate their clinical reactivity using the human glycoprotein lactoferrin expressed in rice. METHODS: Allergic patients with IgE antibodies against plant glycans were analyzed for the presence of IgE against rice-produced lactoferrin. The potency of IgE to induce mediator release was assessed by basophil histamine release and skin prick tests (SPTs). Clinical relevance was evaluated by double-blind placebo-controlled oral challenge (DBPCOC). RESULTS: Twenty-four of 29 sera (82.7%) with IgE antibodies against plant glycans demonstrated IgE binding to transgenic lactoferrin. In three of five cases transgenic lactoferrin induced histamine release. Compared to a control major grass pollen allergen lactoferrin concentrations needed for biological activity of IgE were 5-6 orders of magnitude higher. Skin prick test and DBPCOC were negative in five patients with potential clinical reactivity that volunteered to undergo these in vivo challenges. CONCLUSIONS: Poor or no biological activity and lack of clinical relevance of IgE-binding plant glycans (five out of five) was demonstrated using human lactoferrin expressed in rice as a model.