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The integration of Artificial Intelligence (AI) into the discovery of new materials offers significant potential for advancing sustainable technologies. This paper presents a novel approach leveraging AI-driven methodologies to identify a new malate structure derived from the treatment of spent lithium-ion batteries. By analysing bibliographic data and incorporating domain-specific knowledge, AI facilitated the identification and structure refinement of a new malate complex containing different metals (Ni, Mn, Co, and Cu). The synthesized compound was investigated through chemical and physical analyses, confirming its unique structure and composition. The present work proposes a significant difference from the classical use of AI in materials science, typically rooted in data-driven approaches relying on extensive datasets. This hybrid approach, combining AI's computational power with human expertise, not only expedited the structure determination process but also ensured the reliability and accuracy of the results. Finally, AI-driven material discovery highlights that waste materials can be transformed into valuable chemical products, suggesting their possible reuse, with several expected benefits, emphasising the role of AI in fostering not only innovation but also sustainability in material science., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Left bundle branch block (LBBB) causes left atrial (LA) dyssynchrony. It is unknown if LA dyssynchrony impacts long-term prognosis., Objectives: The purpose of this study was to determine mechanisms of LA dyssynchrony in LBBB and if LA dyssynchrony impacts long-term prognosis., Methods: In a prospective multicenter study of 168 heart failure patients with LBBB, echocardiographic strain imaging was done before and after 6 months with cardiac resynchronization therapy (CRT). Outcome was assessed after 6 years. Dyssynchrony was measured relative to septum as delay in left ventricular (LV) lateral wall shortening and LA lateral wall stretch. Response to CRT was defined as at least 15% reduction in LV end-systolic volume., Results: Before CRT, there was marked LA dyssynchrony of 105 ± 76 ms, which decreased to 37 ± 68 ms in CRT-responders (P < 0.001), whereas nonresponders showed only a modest reduction in LA dyssynchrony (P < 0.05). There was strong association between LA and LV dyssynchrony (r = 0.70), consistent with direct LV-LA mechanical interaction. CRT caused modest increase in LA reservoir strain (P < 0.01) and marked increase of LV filling time (P < 0.001) in responders. Mortality after 6 years was 21% (35 deaths). LA dyssynchrony did not independently predict mortality. However, the combination of preserved LA reservoir strain (≥18%) and resolved LA dyssynchrony (≤53 ms) after 6 months with CRT was associated with excellent long term-prognosis: HR: 0.11 (95% CI: 0.03-0.42) vs preserved reservoir strain and persistent LA dyssynchrony., Conclusions: LA dyssynchrony in LBBB was attributed to direct LV-LA mechanical interactions. CRT improved diastolic function by increasing LV filling time. Patients with preserved LA reservoir strain and resolution of LA dyssynchrony by CRT had excellent long-term prognosis. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185)., Competing Interests: Funding Support and Author Disclosures Dr Smiseth is co-inventor of “Method for myocardial segment work analysis,” has a patent on “Estimation of blood pressure in the heart” and has received 1 speaker honorarium from GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The characterization and selection of heart failure (HF) patients for cardiac resynchronization therapy (CRT) remain challenging, with around 30% non-responder rate despite following current guidelines. This study aims to propose a novel hybrid approach, integrating machine-learning and personalized models, to identify explainable phenogroups of HF patients and predict their CRT response., Methods: The paper proposes the creation of a complete personalized model population based on preoperative CRT patient strain curves. Based on the parameters and features extracted from these personalized models, phenotypes of patients are identified thanks to a clustering algorithm and a random forest classification is provided., Results: A close match was observed between the 162 experimental and simulated myocardial strain curves, with a mean RMSE of 4.48% (±1.08) for the 162 patients. Five phenogroups of personalized models were identified from the clustering, with response rates ranging from 52% to 94%. The classification results show a mean area under the curves (AUC) of 0.86 ± 0.06 and provided a feature importance analysis with 22 features selected. Results show both regional myocardial contractility (from 22.5% to 33.0%), tissue viability and electrical activation delays importance on CRT response for each HF patient (from 55.8 ms to 88.4 ms)., Discussion: The patient-specific model parameters' analysis provides an explainable interpretation of HF patient phenogroups in relation to physiological mechanisms that seem predictive of the CRT response. These novel combined approaches appear as promising tools to improve understanding of LV mechanical dyssynchrony for HF patient characterization and CRT selection., Competing Interests: Declaration of competing interest No conflict of interest exists. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: The prediction of ventricular arrhythmia (VA) in hypertrophic cardiomyopathy (HCM) remains challenging. We sought to characterize the VA risk profile in HCM patients through clustering analysis combining clinical and conventional imaging parameters with information derived from left ventricular longitudinal strain analysis (LV-LS)., Methods: A total of 434 HCM patients (65% men, mean age 56 years) were included from two referral centers and followed longitudinally (mean duration 6 years). Mechanical and temporal parameters were automatically extracted from the LV-LS segmental curves of each patient in addition to conventional clinical and imaging data. A total of 287 features were analyzed using a clustering approach (k-means). The principal endpoint was VA., Results: 4 clusters were identified with a higher rhythmic risk for clusters 1 and 4 (VA rates of 26%(28/108), 13%(13/97), 12%(14/120), and 31%(34/109) for cluster 1,2,3 and 4 respectively). These 4 clusters differed mainly by LV-mechanics with a severe and homogeneous decrease of myocardial deformation for cluster 4, a small decrease for clusters 2 and 3 and a marked deformation delay and temporal dispersion for cluster 1 associated with a moderate decrease of the GLS (p < 0.0001 for GLS comparison between clusters). Patients from cluster 4 had the most severe phenotype (mean LV mass index 123 vs. 112 g/m 2 ; p = 0.0003) with LV and left atrium (LA) remodeling (LA-volume index (LAVI) 46.6 vs. 41.5 ml/m 2 , p = 0.04 and LVEF 59.7 vs. 66.3%, p < 0.001) and impaired exercise capacity (% predicted peak VO 2 58.6 vs. 69.5%; p = 0.025)., Conclusion: Processing LV-LS parameters in HCM patients 4 clusters with specific LV-strain patterns and different rhythmic risk levels are identified. Automatic extraction and analysis of LV strain parameters improves the risk stratification for VA in HCM patients., Competing Interests: Declaration of competing interest General Electric Healthcare is providing research facilities to Rennes University Hospital., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Response to cardiac resynchronization therapy (CRT) is reduced in patients with high left ventricular (LV) scar burden, in particular when scar is located in the LV lateral wall or septum. Late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) can identity scar, but is not feasible in all patients. This study investigates if myocardial metabolism by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contractile function by echocardiographic strain are alternatives to LGE-CMR., Methods: In a prospective multicenter study, 132 CRT candidates (91% with left bundle branch block) were studied by speckle tracking strain echocardiography, and 53 of these by FDG-PET. Regional myocardial FDG metabolism and peak systolic strain were compared to LGE-CMR as reference method., Results: Reduced FDG metabolism (<70% relative) precisely identified transmural scars (≥50% of myocardial volume) in the LV lateral wall, with area under the curve (AUC) 0.96 (95% confidence interval (CI) 0.90-1.00). Reduced contractile function by strain identified transmural scars in the LV lateral wall with only moderate accuracy (AUC = 0.77, CI 0.71-0.84). However, absolute peak systolic strain >10% could rule out transmural scar with high sensitivity (80%) and high negative predictive value (96%). Neither FDG-PET nor strain identified septal scars (for both, AUC < 0.80)., Conclusions: In CRT candidates, FDG-PET is an excellent alternative to LGE-CMR to identify scar in the LV lateral wall. Furthermore, preserved strain in the LV lateral wall has good accuracy to rule out transmural scar. None of the modalities can identify septal scar., Clinical Trial Registration: The present study is part of the clinical study "Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy (CRID-CRT)", which was registered at clinicaltrials.gov (identifier NCT02525185)., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Functional tricuspid regurgitation (FTR) is an independent risk factor for morbidity and mortality. New pathophysiological concepts but also new therapeutic options are justifying new knowledges for characterizing FTRs and their prognoses., Aim: To study echocardiographic criteria associated with prognosis in FTR-patients using a clustering method in two cohorts., Methods and Results: Two hundred forty-one patients with at least severe (≥grade 3) TR were enrolled: 92 in the retrospective cohort (mean age 77.9 ± 13 years) and 149 in the prospective validation cohort. Hierarchical clustering analysis was conducted. Four parameters explained the clustering categorization according to a multinomial regression (right ventricular (RV) end-diastolic mid-cavity diameter, RV free-wall strain, right atrial (RA) volume index, RA strain; p = 0.0039). Three clusters were identified in the retrospective cohort: Cluster 1 had better right ventricular, left ventricular, and right atrial function than Cluster 2 (reduced RV and RA strain despite similar sizes). Cluster 3 included patients with severely dilated heart chambers associated to RV and RA dysfunctions. When applying the model in the validation (external) cohort, the rate of the primary endpoint (hospitalization for heart failure and/or death from any cause) was lowest in Cluster 1 (30.8% versus 48% and 58.8% in Clusters 2 and 3, respectively; p < 0.05)., Conclusion: In FTR patients, different profiles of RV and RA remodeling are associated with different outcomes. Therefore, the diagnostic work-up in this clinical setting should include RV and RA characteristics. Under noninterventional management, the phenotype corresponding to preserved RV size and preserved RA and RV functions appears to have a better prognosis., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT)., Background: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT., Methods: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EF preserved ), 36% to 49% (EF mid ), and ≤35% (EF low ). Sixty-four patients underwent CRT and were re-examined after 6 months., Results: Septal work was successively reduced from controls, through EF preserved , EF mid , and EF low (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EF preserved and EF mid versus controls, and did not significantly correlate with LVEF in these groups. In EF low, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005)., Conclusions: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT., Competing Interests: Funding Support and Author Disclosures Drs Sletten and Aalen were supported by grants from the Norwegian Health Association. Dr Larsen was a recipient of a clinical research fellowships form the South-Eastern Norway Regional Health Authority. Prof Voigt holds a personal research mandate of the Flemish Research Council. Prof Voigt and Dr Duchenne were further supported by a grant of the University of Leuven. Dr Smiseth is co-inventor, but since May 24, 2017 has had no financial relations to the patent “Method for myocardial segment work analysis,” which was used to calculate the myocardial work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose, (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Conflicting data exist about the relationship between cardiac resynchronization therapy (CRT) and diastolic function. Aims of the study are to assess diastolic patterns in patients undergoing CRT according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging and to evaluate the prognostic value of diastolic dysfunction (DD) in CRT candidates. METHODS AND RESULTS: One-hundred ninety-three patients (age: 67 ± 11 years, QRS width: 167 ± 21 ms) were included in this multicentre prospective study. Mitral filling pattern, mitral tissue Doppler velocity, tricuspid regurgitation velocity, and indexed left atrial volume were used to classify DD from grade I to III. CRT-response, defined as a reduction of left ventricular (LV) end-systolic volume > 15% at 6-month follow-up (FU), occurred in 132 (68%) patients. The primary endpoint was a composite of heart transplantation, LV assisted device implantation, or all-cause death during FU and occurred in 29 (15%) patients. CRT was associated with a degradation of DD in non-responders. At multivariable analysis corrected for clinical variables, QRS duration, mitral regurgitation, CRT-response and LV dyssynchrony, grade I DD was associated with a better outcome (HR 0.37, 95% CI: 0.14-0.96). Non-responders with grade II-III DD had the worse prognosis (HR 4.36, 95%CI: 2.10-9.06). CONCLUSIONS: The evaluation of DD in CRT candidates allows the prognostic stratification of patients, independently from CRT-response., Competing Interests: Declaration of Competing Interest Nothing to disclose., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sodium lauryl ether sulphate (SLES) is the anionic surfactant commonly utilized as the main synthetic chemical component in most foaming agents used in mechanized tunnelling. This produces huge amounts of soil debris which can contain residual concentrations of SLES. The absence of environmental quality standards for soil and water and the limited information about SLES persistence in real excavated soils do not facilitate any re-use of soil debris as by-products. The environmental risk assessment (ERA) of foaming agents containing SLES can be a valid tool for this purpose. In this study, an ERA analysis of SLES in 12 commercial formulations (cf) used for tunnelling excavation was performed. Various soils from different tunnel excavation sites were conditioned with the selected foaming agents containing SLES. Predicted or measured environmental concentrations (PECs, MECs) were determined and then compared with the Predicted No Effect Concentrations (PNECs) for both the terrestrial and aquatic compartments. The results indicate a reduction of the potential risk over time for these ecosystems, with differences depending on both the commercial foaming formulation and the spoil material characteristics. However, because potential threats to the natural environment cannot be excluded, some risk management and mitigation actions are discussed., (Copyright © 2019. Published by Elsevier B.V.)

The management of atrial fibrillation (AF) is not only a clinical challenge but also an imaging challenge. The role of different imaging modalities to estimate the thromboembolic risk in AF is a key clinical question. The present review summarizes the advances of myocardial imaging in the stratification of thromboembolic risk, diagnosis, and management of left atrial thrombosis in patients with AF. These imaging techniques are also important for understanding arrhythmias and their consequences. It is becoming fundamental for guiding therapy. Still, large studies are required, but be sure that left atrial imaging will become more and more clinically fundamental., (Copyright © 2019 American College of Cardiology Foundation. All rights reserved.)

Aims: The current algorithm in transthoracic echocardiography (TTE) proposed in the 2016 ASE/EACVI recommendation for the estimation of left ventricular filling pressure (LVFP) is quite complex and time-consuming. B-lines, in lung ultrasonography (LUS), could constitute an interesting tool for LVFP evaluation in clinical practice, although data regarding their association with invasive haemodynamics are lacking. The purpose of this study was to explore the diagnostic accuracy of B-lines in identifying elevated left ventricular end-diastolic pressure (LVEDP)., Method and Results: 81 adults with significant dyspnoea (NYHA ≥ 2) were prospectively analyzed by LUS in four areas in each hemithorax and a complete TTE within four hours prior to coronary angiography. Twenty-eight patients had elevated LVEDP. Clinical variables yielded a C-index of 79% to identify elevated LVEDP. The number of total B-lines was higher in the elevated LVEDP group (1.0vs17.0, p < 0.0001) and significantly increased the diagnostic accuracy (C-index increase = 10.5%, p = 0.002) and net reclassification index (NRI = 145.4, 113.0-177.9, p < 0.0001) on top of clinical variables., Conclusion: This study demonstrates the substantial diagnostic capacity of B-lines to identify elevated LVEDP, which appears superior to that of classical echocardiographic strategies. This tool should be considered in a multi-parametric approach in patients with heart failure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV)., Methods: We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library., Results: The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17-68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0-4) was lower than that prior to treatment (median 3; range 1-5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p = .006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment., Conclusions: Our data support a potential role for RTX treatment in selected patients with PCNSV., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the last decades the increasing rate of obesity in children and adolescents worldwide has led to the onset in paediatric age of metabolic syndrome, a disease commonly associated to adulthood. Central obesity, dyslipidaemia, hyperglycaemia, and hypertension are typical features of metabolic syndrome that seem to hesitate often in type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, and many other clinical conditions. Thus preventing and curing metabolic syndrome in paediatric patients is becoming an urgent need for public health. While diagnostic criteria and therapy of metabolic syndrome in adults are very well defined, there is no consensus on the definition of metabolic syndrome in children and adolescents as well as on healing approaches. The aim of this review is to describe the recent advances on the pathogenesis and clinical outcomes of paediatric metabolic syndrome. We then detail the therapeutic strategies (i.e. dietary regimens, physical exercise, nutraceuticals, and medications) employed to manage the disease. Finally, we analyse the safety profile of the drugs used in children and adolescents by performing a retrospective review of paediatric adverse reactions reported in the FDA's Adverse Event Reporting System database., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

For the first time a laccase from Trametes versicolor was immobilized on a natural clinoptilolite with Si/Al=5 to obtain a biocatalyst for environmental applications. Immobilization procedures exploiting adsorption and covalent binding were both tested, and only the last provided enough activity for practical applications. The optimal conditions for the immobilization of the enzyme on the support and the kinetic parameters for the free and covalent bonded laccase were determined. The laccase bonded to the zeolitic support showed a lower activity than the free laccase, but the pH and thermal stability were greater. 20 mg of dry biocatalyst containing 1 U of laccase were able to remove in 50h 73-78% of 2-chlorophenol and 2,4-dichlorophenol in relatively concentrated aqueous solutions (100 μmol L(-1))., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The assessment of myocardial function in the context of valvular heart disease remains highly challenging. The myocardium deforms simultaneously in 3 dimensions, and global left ventricular (LV) function parameters such as volume and ejection fraction may remain compensated despite the changes in myocardial deformation properties. Current guidelines recommend valve replacement/repair in the presence of symptoms or reduced LV ejection fraction, but the resolution of symptoms or recovery of LV function post-surgery may not be reliably predicted. A wealth of evidence currently suggests that LV dysfunction is frequently subclinical despite normal ejection fraction. It may precede the onset of symptoms and portend a poor outcome due to progressive myocardial remodeling and dysfunction during the post-operative period. The advent of novel tissue-tracking echocardiography techniques has unleashed new opportunities for the clinical identification of early abnormalities in LV function. This review gathers and summarizes current evidence regarding the use of these techniques to assess myocardial deformation in patients with valvular heart disease., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Oxytetracycline (OTC) is administered in high doses to livestocks and enters the environmental compartments as a consequence of animal waste disposal. As a first step in setting up a useful mycoremediation technique, an OTC lab degradation test was performed in liquid medium using the ligninolytic fungus Pleurotus ostreatus. OTC disappearance in culture medium was clearly evident as early as the third day of exposure onwards, with an almost complete removal after 14d. The drug removal was mediated by fungal absorption in the mycelia, where the OTC molecule underwent a degradation step, as demonstrated by mass spectrometry analyses. A putative degradation product, ADOTC (2-acetyl-2-decarboxamido-oxytetracycline) is proposed. Experimental conditions excluded OTC abiotic degradation; the degradation by extracellular laccase was also experimentally discarded., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Atopic dermatitis (AD) and psoriasis are common skin diseases characterized by cutaneous inflammation and disturbed epidermal differentiation. Genome-wide analyses have shown overlapping susceptibility loci, such as the epidermal differentiation complex on chromosome 1q21. Recently, a deletion on 1q21 (LCE3C&#95;LCE3B-del), comprising LCE3B and LCE3C, two members of the late cornified envelope (LCE) gene cluster, was found to be associated with psoriasis. Although the mechanistic role of LCE proteins in psoriasis has not been identified, these proteins are putatively involved in skin barrier formation and repair. Considering the potential genetic overlap between the two diseases and the recent finding that mutations in the skin barrier protein filaggrin are associated with AD, we investigated a possible association between LCE3C&#95;LCE3B-del and AD. Evaluation of four different cohorts of European ancestry, containing a total of 1075 AD patients and 1658 controls, did not provide evidence for such an association. Subgroup analysis did not reveal an association with concomitant asthma. Our data suggest that the potential roles of skin barrier defects in the pathogenesis of AD and psoriasis are based on distinct genetic causes.

Chitinous material was isolated from the mycelium of seven species of Basidiomycetes to evaluate the possibility of using fungal biomass as a source of chitin and chitosan. Such material was characterised for its purity, degree of acetylation and crystallinity. Chitin yields ranged between 8.5 and 19.6% dry weight and the chitosan yield was approximately 1%. The characteristics of the fungal chitins were similar to those of commercial chitin. Chitosans, with a low degree of acetylation, comparable with that of commercial chitosan, were obtained by the chemical deacetylation of fungal chitins.

A high-field NMR study of the polysaccharidic fraction extracted from Lentinula edodes mycelium grown on olive mill waste waters is reported. Diffusion-ordered NMR spectroscopy (DOSY) was applied to the polysaccharidic fraction. The results showed the presence of two polysaccharides of different sizes, whose structures were revealed using one- and two-dimensional NMR techniques. These two polysaccharides were identified as xylan and lentinan.

Rhodococcus opacus R7 was isolated from a soil contaminated with polycyclic aromatic hydrocarbons for its ability to grow on naphthalene. The strain was also able to degrade o-xylene, the isomer of xylenes most recalcitrant to microbial degradation. The catabolic pathways for naphthalene and o-xylene were investigated by identification of metabolites in R. opacus R7 cultures performed with the two hydrocarbons and by evaluation of some enzymes involved in the metabolism of these compounds. 1,2-Dihydro-1,2-dihydroxynaphthalene, salicylic and gentisic acids were identified as metabolites in cultures exposed to naphthalene. This suggests that the degradation occurs through the dioxygenation of the aromatic ring with the formation of 1,2-dihydro-1,2-dihydroxynaphthalene, dehydrogenated to the corresponding 1,2-dihydroxy derivative which is further oxidized to salicylic acid, a key intermediate of naphthalene metabolism; this compound is converted to gentisic acid cleaved by a gentisate 1,2-dioxygenase. From R. opacus R7 cultures supplied with o-xylene, 2,3-dimethylphenol and 3,4-dimethylcatechol were observed. The pathway of o-xylene involves the monooxygenation of the benzene nucleus leading to dimethylphenol which is further metabolised to 3,4-dimethylcatechol, followed by a meta cleavage reaction, catalyzed by the catechol 2,3-dioxygenase. R. opacus R7 is the first strain thus far described both in Gram-negative and Gram-positive bacteria which has the ability to degrade both a polycyclic aromatic hydrocarbon such as naphthalene and a monocyclic aromatic hydrocarbon such as o-xylene.

We developed biocatalysts carrying naphthalene dioxygenase and dihydrodiol dehydrogenase genes cloned from plasmid pN3 of Pseudomonas fluoresceins N3 involved in naphthalene degradation, as an alternative approach to the production of hydroxylated compounds by chemical synthesis. Naphthalene dioxygenase is responsible for hydroxylation of the hydrocarbon into the corresponding 1,2-dihydro-1,2-dihydroxy derivative and dihydrodiol dehydrogenase is involved in the subsequent transformation into the 1,2-dihydroxy derivative. The first reaction strictly requires the presence of oxygen, essential for the dioxygenation reaction, while the second one can also be performed in anaerobic conditions that are optimal to avoid the easy oxidation of bioconversion products. Consequently, we constructed biocatalysts carrying the genes responsible for the biotransformation of hydrocarbons, inducible under aerobic and anaerobic conditions. We cloned the dioxygenase gene under its promoter, inducible by salicylic acid and the dihydrodiol dehydrogenase under the Pnar promoter of Escherichia coli, inducible by nitrate, in a nitrogen atmosphere, in order to develop biological systems with the possibility of controlling the expression of the cloned genes by the shift from aerobic to anaerobic conditions. Bioconversion experiments performed in aerobic conditions showed dihydrodiol production and dehydrogenase repression; as soon as cultures were switched to nitrogen, dihydrodiol dehydrogenation with an efficient production of 1,2-dihydroxyderivatives was observed.

Whole-cell bioconversion of naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene by Escherichia coli JM109(pPS1778) recombinant strain, carrying naphthalene dioxygenase and regulatory genes cloned from Pseudomonas fluorescens N3, in direct micellar systems is optimized as an example of fine chemicals bioproduction from scarcely water-soluble substrates. The oxygen insertion into the aromatic substrate, which stops at the enantiomerically pure cis dihydroxylated product, is performed in direct microemulsion systems, where a non-ionic surfactant stabilizes naphthalene containing oil droplets in an aqueous medium. These media provide an increased substrate solubility so that a homogeneous reaction can be carried out, while not affecting bacteria viability and performances. The influence of the chemical nature of the oil is investigated. The phase behavior of the direct microemulsion system was monitored for three different oils as a function their volume fraction and characterized through light scattering. The addition of isopropyl palmitate, oleic acid, or glyceryl trioleate, 0.6-1.2% v/v to the micellar systems, led to an increase of the substrate concentration in the solution and particularly its bioavailability, allowing faster catalytic conversions. All these systems resulted in being suitable for catalytic conversions of aromatic compounds. Although the nature of the oil does have a deep effect on the phase behavior of the micellar systems, in the present investigation no differences in the yields and in the rates of product formation of the enzymatic system were observed on changing the oil, thus showing that in this case the substrate concentration or bioavailability is not the rate-limiting step.

Naphthalene dioxygenase, a key enzyme in the dihydroxylation of naphthalene, is encoded by the plasmid pN3, responsible for naphthalene metabolism in Pseudomonas fluorescens N3. The naphthalene dioxygenase, including all the sequences for its expression and the regulatory region, has been localized on the 4.3-kb HindIII-ClaI fragment and on the 3.5-kb HindIII fragment of the plasmid pN3, by Southern analysis using as probes nahA and nahR genes, the homologous genes of the plasmid NAH7 from Pseudomonas putida G7. We cloned in Escherichia coli JM109 the dioxygenase gene and its regulatory region and developed an efficient bacterial system inducible by salicylic acid, able to produce dihydrodiols. E. coli containing recombinant plasmids carrying the dioxygenase gene were analysed for their potential as a biocatalytic tool to produce dihydrodiols from different naphthalenes with the substituent on the aromatic ring at the alpha or beta position. The dihydrodiols, identified by HPLC (high-performance liquid chromatography) and 1H-NMR (nuclear magnetic resonance) were produced with yields ranging from 50 to 94%. The degree of bioconversion efficiency depends on the nature and the position of the substituent and indicates the broad substrate specificity of this dioxygenase and its potential for the production of a wide variety of fine chemicals.

To evaluate the involvement of indole-3-acetic acid (IAA) in promotion of root development, the effects of inoculation of wheat seedlings with Azospirillum brasilense SpM7918, a very low-IAA producer, were estimated. Compared with the wild-type strain Sp6, SpM7918 showed a reduced ability to promote root system development in terms both of number and length of lateral roots and of distribution of root hairs.

We studied the production within the CNS of anti-HIV antibodies, of non-specific IgG, and the presence of HIV antigens in the serum and CSF of 28 HIV infected patients belonging to group IV in the Center for Disease Control classification. CSF and serum were diluted under optimal conditions to equalize their IgG content, to enable us to better interpret serum and CSF reactivity by means of Western blot and ELISA. Under these conditions, no patient displayed a limited immunological response profile in CSF as compared to serum. On the contrary, there was intrathecal synthesis (ITS) of anti HIV-antibodies in Western blot test in 21 patients for gp160 and ITS was demonstrable for env, gag, and pol products. ITS of anti-HIV antibodies occurred in 17 patients when measured by ELISA. ITS of non specific IgG and HIV-antigens in CSF were less frequent. A marked anti-HIV response is evident in the CSF-CNS compartment in the later phases of the HIV infection.

Pyridine and nitrilotriacetic acid sodium salt as models of soluble compounds and linear dodecylbenzene, branched dodecylbenzene, and stearic acid as models of insoluble compounds were compared for their biodegradability in three tests: the ODCE modified test and the Sturm and enrichment culture tests. The degradation of soluble compounds was measured as dissolved organic carbon removal and CO2 evolution, while for the insoluble compounds, which were tested only in the Sturm test, CO2 evolution was determined. The individual tests were characterized by comparing their results with those obtained in the others. Comparable biodegradation values higher than 90% were obtained for the soluble compounds. The Sturm test proved to be very suitable for the evaluation of biodegradability of either soluble or insoluble compounds.

The xylenes (o, m, p), which are produced in large amounts and widely used, must be considered as environmental contaminants, as they have been identified in the atmosphere of many countries. Their acute and chronic toxicity in mammals is moderate. Mutagenic and teratogenic properties can be excluded. Carcinogenic potential has been at present inadequately studied. In man some disturbances are evident at the concentration of 45 ppm. Hepatic metabolism is a valid process of detoxification and its high rate limits the risk of accumulation of the xylenes in adipose tissue. Ecotoxicological data refer almost exclusively to water. No long-term tests have been made. However, the high volatility, elevated elimination, and the low factor of accumulation suggest the impact on aquatic environment should be limited. Xylenes are easily biodegraded by many microorganisms. Photoxydation is one of the main degradation processes, responsible for the disappearance of the xylenes from the atmosphere.

26 patients with primary immunodeficiencies (3 infants with severe combined immunodeficiency [SCID] 3 with DiGeorge syndrome, 6 with T-cell defect or SCID with B cells, 4 with common variable hypogammaglobulinaemia and associated T-cell defect, 5 with ataxia-telangiectasia, and 5 with hyper-IgE syndrome) were treated with thymopoietin pentapeptide (TP-5) at a dose of 0 . 5 mg/kg daily for 2 weeks and then 3 times a week at 0 . 5 mg/kg for 10 weeks, 3 patients with DiGeorge syndrome and 3 with primary T-cell defect demonstrated pronounced clinical and immunological improvement during treatment. None of the patients with SCID and 3 of 6 patients with SCID with B cells or primary T-cell defect showed any clinical or immunological changes during therapy. In 5 patients with ataxia-telangiectasia clinical manifestations and immunological tests were unchanged by TP-5. Abnormality of T cells in cases of hyper-IgE syndrome was not corrected by TP-5 treatment.