Search

The solvent driven aggregation of porphyrin derivatives, covalently linked to a L- or D-prolinate enantiomer, results in the stereospecific formation of species featuring remarkable supramolecular chirality, as a consequence of reading and amplification of the stereochemical information stored in the proline-appended group. Spectroscopic, kinetic, and topographic SEM studies gave important information on the aggregation processes, and on the structures of the final chiral architectures. The results obtained may be the seeds for the construction of stereoselective sensors aiming at the detection, for example, of novel emergent pollutants from agrochemical, food, and pharmaceutical industry., (Copyright © 2020 Stefanelli, Savioli, Zurlo, Magna, Belviso, Marsico, Superchi, Venanzi, Di Natale, Paolesse and Monti.)

An overview of the solvent-driven aggregation of a series of chiral porphyrin derivatives studied by optical methods (UV/Vis, fluorescence, CD and RLS spectroscopies) is herein reported. The investigated porphyrins are characterized by the presence in the meso-positions of glycol-, steroidal- and glucosteroidal moieties, conferring amphiphilicity and solubility in aqueous media to the primarily hydrophobic porphyrin platform. Aggregation of the macrocycles is driven by a change in bulk solvent composition, forming architectures with supramolecular chirality, steered by the stereogenic centers on the porphyrin peripheral positions. The aggregation behavior and chiroptical properties of the final aggregated species strongly depend on the number and stereogenicity of the ancillary groups that dictate the mutual spatial arrangement of the porphyrin chromophores and their further organization in larger structures, usually detectable by different microscopies, such as AFM and SEM. Kinetic studies are fundamental to understand the aggregation mechanism, which is frequently found to be dependent on the substrate concentration. Additionally, Molecular Mechanics calculations can give insights into the intimate nature of the driving forces governing the self-assembly process. The critical use of these combined methods can shed light on the overall self-assembly process of chirally-functionalized macrocycles, with important implications on the development of chiral porphyrin-based materials.

As the coronavirus epidemic continues, a host of new cutaneous complications is seen on the faces of frontline healthcare workers wearing personal protective equipment on a daily basis. To minimize the risk of COVID-19 infection, healthcare workers wear tight-fitting masks that lead to an excessive amount of pressure on the facial skin. Mechanical pressure, mask materials, and perspiration can all lead to various types of cutaneous lesions such as indentations of the face, skin tears, post-inflammatory hyperpigmentation, ulceration, crusting, erythema, and infection. The objective of this article is to provide effective and straightforward recommendations to those health care providers using facial masks in order to prevent skin-related complications. J Drugs Dermatol. 2020;19(9):858-864. doi:10.36849/JDD.2020.5259.

Background: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders., Aims: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol)., Methods: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine)., Results: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) μg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 μg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively., Discussion: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects., Conclusion: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Owing to the attractive potential applications of porphyrin assemblies in photocatalysis, sensors, and material science, studies presently concerning porphyrin aggregation are widely diffused. π-π stacking, H-bonding, metal coordination, hydrophobic effect, and electrostatic forces usually drive porphyrin interaction in solution. However, theoretical studies of such phenomena are still limited. Therefore, a computational examination of the different porphyrin aggregation approaches is proposed here, taking into account amphiphilic [5-{4-(3-trimethylammonium)propyloxyphenyl}-10,15,20-triphenylporphyrin] chloride, whose aggregation behavior has been previously experimentally investigated. Different functionals have been adopted to investigate the porphyrin dimeric species, considering long-range interactions. Geometry optimization has been performed, showing that for the compound under analysis, H-type and cation-π dimers are the most favored structures that likely co-exist in aqueous solution. Of note, frontier orbital delocalization showed an interesting interaction between the porphyrin units in the dimer at the supramolecular level.

The interest in assembling porphyrin derivatives is widespread and is accounted by the impressive impact of these suprastructures of controlled size and shapes in many applications from nanomedicine and sensors to photocatalysis and optoelectronics. The massive use of porphyrin dyes as molecular building blocks of functional materials at different length scales relies on the interdependent pair properties, consisting of their chemical stability/synthetic versatility and their quite unique physicochemical properties. Remarkably, the driven spatial arrangement of these platforms in well-defined suprastructures can synergically amplify the already excellent properties of the individual monomers, improving conjugation and enlarging the intensity of the absorption range of visible light, or forming an internal electric field exploitable in light-harvesting and charge-and energy-transport processes. The countless potentialities offered by these systems means that self-assembly concepts and tools are constantly explored, as confirmed by the significant number of published articles related to porphyrin assemblies in the 2015-2019 period, which is the focus of this review.

Acute mastoiditis (AM) is the most common complication of acute otitis media (AOM) and is one of the most severe acute bacterial diseases in infants and children. In some geographic areas, the incidence of AM is increasing, and the causative role of some bacterial pathogens could be greater than previously thought. In this paper, the results of a study that evaluated the epidemiology and microbial etiology of paediatric AM in Umbria, which is a region of central Italy, are reported. This is a retrospective study of patients aged 0-14 years with AM admitted to the pediatric wards of the hospitals of Umbria, Italy, between June 1 and September 30 in four consecutive years (2015-2018). A total of 108 children were enrolled. The prevalence of AM in males during the four years of analysis was significantly higher than that in females at 63% (95% confidence intervals [CI]: 0.54-0.72). The most frequently affected age groups were 5-9 years (45.4%) and 10-14 years (31.5%), with statistically significant differences in comparison with children aged <1 year (5.6%, 95% CI: 0.01-0.10) and 1-4 years (17.6%, 95% CI: 0.10-0.25). In most cases (64, 59.3%), AM was associated with spontaneous tympanic membrane perforation (STP). The culture of the middle ear fluid revealed the presence of Pseudomonas aeruginosa in 56 cases (51.6%). The mean incidence rates of pediatric AM in Umbria during the study increased significantly with time, as it was 18.18/100,000 children/year in 2015-2016 and 29.24/100,000 children/year in 2017-2018 (CI difference: +2.5 - +19.9, p < 0.05). The incidence rates of Pseudomonas aeruginosa detection in pediatric AM associated with STP significantly increased with time. The incidence was 6.06/100,000 children/year in 2015-2016 and 18.61/100,000 children/year in 2017-2018 (CI difference: +6.1 - +19.0, p < 0.001). This study demonstrated the high and increasing incidence of AM in the Umbria region during the summer months and the frequent detection of P. aeruginosa as an etiologic agent of the disease in the presence of STP. Confirmation of these results with a larger study population, in different settings, and throughout the whole year is needed to define the first-line approach of AM with STP in pediatrics.

Silver corrolates are attractive compounds from both practical and theoretical points of view. Indeed, they play a key role in peripheral functionalization reactions occurring at the macrocycle, enabling high-yield and regioselective group insertions useful to further elaborate the molecular skeleton. In parallel, the Janus innocent or noninnocent behavior of the corrole ligand in these complexes makes their description particularly challenging. Herein, we report properties for a series of silver 3,17-disubstituted triarylcorrole complexes with various functionalities (halogens or different phenylethynyl units) that deeply affect the electron density in the macrocyclic ligand, with obvious repercussions on the observed spectral characteristics. The compounds were obtained in yields of 54-92% by applying the Stille coupling reaction with the appropriate tributylethynyl stannane. Among the complexes prepared was a derivative bearing two terminal acetylenic units which opens the way to "click" reactions for new corrole-based architectures. This corrole was structurally characterized by single crystal X-ray crystallography. The addition of substituted ethynyl groups resulted in red-shifts of the electronic absorption spectra, the largest of which was observed for the compound with two β-NO2-Ph-C[triple bond, length as m-dash]C substituents. The remarkable influence of the NO2 groups on the electron density of this macrocycle was further demonstrated by electrochemical measurements, where an easier reduction of this complex derivative was observed as compared to the others. DFT calculations showed full delocalization over the entire p-nitrophenylethynyl unit of 5, largely affecting orbital distributions and the corresponding electronic absorptions. Although a variation of the β-substituents dramatically modifies the Soret- and Q-band positions towards lower energies for all the examined complexes, the saddling of the macrocycle resulting from functionalization is only moderate. The collected results suggest the description of these compounds as AgIII-corrolate3-, a metallocorrole with an innocent macrocyclic ligand.

In the injured central nervous system, myeloid cells, including macrophages and microglia, are key contributors to both myelin injury and repair. This immense plasticity emphasizes the need to further understand the precise molecular mechanisms that contribute to the dynamic regulation of myeloid cell polarization and function. Herein, we demonstrate that miR-223 is upregulated in multiple sclerosis (MS) patient monocytes and the alternatively-activated and tissue-regenerating M2-polarized human macrophages and microglia. Using miR-223 knock-out mice, we observed that miR-223 is dispensable for maximal pro-inflammatory responses, but is required for efficient M2-associated phenotype and function, including phagocytosis. Using the lysolecithin animal model, we further demonstrate that miR-223 is required to efficiently clear myelin debris and promote remyelination. These results suggest miR-223 constrains neuroinflammation while also promoting repair, a finding of important pathophysiological relevance to MS as well as other neurodegenerative diseases., (© 2018 Wiley Periodicals, Inc.)

Objective: Poor fitness among people with Multiple Sclerosis (MS) aggravates disease symptoms. Whether low fitness levels accompany brain functioning changes is unknown., Methods: MS patients (n = 82) completed a graded maximal exercise test, blood was drawn, and transcranial magnetic stimulation determined resting and active motor thresholds, motor evoked potential latency, and cortical silent period (CSP)., Results: Sixty-two percent of participants had fitness levels ranked below 10th percentile. Fitness was not associated with disability measured using the Expanded Disability Status Scale (EDSS). Regression analyses revealed that, cardiorespiratory fitness, when controlling for disease demographics, contributed 23.7% (p < 0.001) to the model explaining variance in CSP. Regression analysis using cardiorespiratory fitness and CSP as predictors showed that CSP alone explained 19.9% of variance in subjective fatigue (p = 0.002). Tumor necrosis factor was not associated with any variable., Conclusion: Low fitness was associated with longer CSP in MS. Longer CSP was, in turn, related to greater MS fatigue., Significance: MS patients had extremely low levels of cardiorespiratory fitness. Poor fitness predicted longer CSP, a marker of greater intracortical inhibition, which was linked to MS fatigue. Future research should examine whether aerobic training could shorten CSP and potentially lessen inhibition of cortical networks., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Recognition of enantiomers is one of the most arduous challenges in chemical sensor development. Although several chiral systems exist, their effective exploitation as the sensitive layer in chemical sensors is hampered by several practical implications that hinder stereoselective recognition in solid state. In this paper, we report a new methodology to efficiently prepare chiral solid films, by using a hybrid material approach where chiral porphyrin derivatives are grafted onto zinc oxide nanoparticles. Circular dichroism (CD) evidences that the solid-state film of the material retains supramolecular chirality due to porphyrin interactions, besides an additional CD feature in correspondence of the absorbance of ZnO (375 nm), suggesting the induction of chirality in the underlying zinc oxide nanoparticles. The capability of hybrid material to detect and recognize vapors of enantiomer pairs was evaluated by fabricating gas sensors based on quartz microbalances. Chiral films of porphyrin on its own were used for comparison. The sensor based on functionalized nanostructures presented a remarkable stereoselectivity in the recognition of limonene enantiomers, whose ability to intercalate in the porphyrin layers makes this terpene an optimal chiral probe. The chiroptical and stereoselective properties of the hybrid material confirm that the use of porphyrin-capped ZnO nanostructures is a viable route for the formation of chiral selective surfaces.

Objectives: Investigate whether asymmetrical corticospinal excitability exists in Multiple Sclerosis (MS) and its association with MS symptoms., Methods: Bilateral resting and active motor thresholds (RMT, AMT) were gathered using transcranial magnetic stimulation among 82 MS patients. Corticospinal excitability (CSE) asymmetry was expressed as the ratio between weaker and stronger sides' RMT and AMT. Stronger and weaker side was determined by pinch and grip strength. We examined whether CSE asymmetry predicted symptoms., Results: AMT asymmetry ratio revealed atypical CSE asymmetry whereby the hemisphere associated with the weaker hand was more excitable in early MS. After controlling for MS disease demographics, shifting of CSE asymmetry towards greater excitability in the stronger side significantly predicted more severe symptoms including Expanded Disease Severity Scale, nine-hole peg test, cognitive processing speed, walking speed, heat sensitivity, fatigue, and subjective impact of MS., Conclusion: CSE asymmetry significantly predicted the severity of MS-related physical and objective cognitive symptoms. The phenomenon may be related to neuroinflammation-mediated hyperexcitability. Shifting of asymmetry toward less excitability on the weaker side may suggest the onset of a more neurodegenerative phase of the disease., Significance: Shifting of hemispheric excitability, detected using a CSE asymmetry ratio, may be a useful biomarker to track disease progression and understand the benefits of treatments., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The self-aggregation of inherently chiral, (l)-proline functionalised Cu and Zn porphyrin derivatives has been investigated in different aqueous organic solvent media. The results indicate that the title species form self-assembled structures expressing supramolecular chirality by the amplification of the stereochemical information stored on the l-prolinate functionality. A substantial difference of the aggregation modes, and the chiroptical features of the final supramolecular species for the two investigated complexes, is clearly imputable to the metal ions, having a different coordination ability toward solvent molecules. Detailed kinetic investigation performed by combining different spectroscopy techniques allowed the definition of the reaction mechanisms involved in these processes. The results described are of importance, for example, for the achievement of stereoselective devices and sensors.

The importance of allosteric proteasome inhibition in the treatment of cancer is becoming increasingly evident. Motivated by this urgent therapeutic need, we have recently identified cationic porphyrins as a highly versatile class of molecules able to regulate proteasome activity by interfering with gating mechanisms. In the present study, the mapping of electrostatic contacts bridging the regulatory particles with the α-rings of the human 20S proteasome led us to the identification of (meso-tetrakis(4-N-methylphenyl pyridyl)-porphyrin (pTMPyPP4) as a novel non-competitive inhibitor of human 20S proteasome. pTMPyPP4 inhibition mechanism implies a positive cooperative binding to proteasome, which disappears when a permanently open proteasome mutant (α-3ΔN) is used, supporting the hypothesis that the events associated with allosteric proteasome inhibition by pTMPyPP4 interfere with 20S gating and affect its "open-closed" equilibrium. Therefore, we propose that the spatial distribution of the negatively charged residues responsible for the interaction with regulatory particles at the α-ring surface of human 20S may be exploited as a blueprint for the design of allosteric proteasome regulators.

Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

Porphyrins and related macrocycles have been intensively exploited as sensing materials in chemical sensors, since in these devices they mimic most of their biological functions, such as reversible binding, catalytic activation, and optical changes. Such a magnificent bouquet of properties allows applying porphyrin derivatives to different transducers, ranging from nanogravimetric to optical devices, also enabling the realization of multifunctional chemical sensors, in which multiple transduction mechanisms are applied to the same sensing layer. Potential applications are further expanded through sensor arrays, where cross-selective sensing layers can be applied for the analysis of complex chemical matrices. The possibility of finely tuning the macrocycle properties by synthetic modification of the different components of the porphyrin ring, such as peripheral substituents, molecular skeleton, coordinated metal, allows creating a vast library of porphyrinoid-based sensing layers. From among these, one can select optimal arrays for a particular application. This feature is particularly suitable for sensor array applications, where cross-selective receptors are required. This Review briefly describes chemical sensor principles. The main part of the Review is divided into two sections, describing the porphyrin-based devices devoted to the detection of gaseous or liquid samples, according to the corresponding transduction mechanism. Although most devices are based on porphyrin derivatives, seminal examples of the application of corroles or other porphyrin analogues are evidenced in dedicated sections.

Reaction of 2-amino-3-(pyrrol-1-yl)-5,10,15-tris(4-tert-butylphenyl)corrolato copper(II) with arylaldehydes affords novel π-extended β,β'-pyrrolo(1,2-a)pyrazino-fused corroles via a Pictet-Spengler reaction. Corrole shows an unprecedented reaction pathway, leading to a mixture of phenyl-substituted and nonsubstituted pyrrolopyrazino annulated species as reaction products.

Vico Lake, a volcanic meso-eutrophic lake in Central Italy, whose water is used for drinking and recreational activities, experienced the presence of the microcystins (MC) producing cyanobacterium Planktothrix rubescens. In order to assess the human health risks and to provide the local health authorities with a scientific basis for planning tailored monitoring activities, we studied P. rubescens ecology and toxicity for two years. P. rubescens generally dominated the phytoplankton community, alternating with Limnothrix redekei, potentially toxic. P. rubescens was distributed throughout the water column during winter; in summer it produced intense blooms where drinking water is collected (-20 m); here MC were detected all year round (0.5-5 μg/L), with implications for drinking water quality. In surface waters, MC posed no risk for recreational activities in summer, while in winter surface blooms and foams (containing up to 56 μg MC/L) can represent a risk for people and children practicing water sports and for animals consuming raw water. Total phosphorus, phosphate and inorganic nitrogen were not relevant to predict densities nor toxicity; however, a strong correlation between P. rubescens density and aminopeptidase ectoenzymatic activity, an enzyme involved in protein degradation, suggested a role of organic nitrogen for this species. The fraction of potentially toxic population, determined both as mcyB(+)/16SrDNA (10-100%) and as the MC/mcyB(+) cells (0.03-0.79 pg MC/cell), was much more variable than usually observed for P. rubescens. Differently from other Italian and European lakes, the correlation between cell density or the mcyB(+) cells and MC explained only ∼50 and 30% of MC variability, respectively: for Vico Lake, monitoring only cell or the mcyB(+) cell density is not sufficient to predict MC concentrations, and consequently to protect population health. Finally, during a winter bloom one site has been sampled weekly, showing that monthly sampling during such a phase could greatly underestimate the 'hazard'. Our results highlight the need to adopt a stepwise monitoring activity, considering the lake and the cyanobacteria specific features. This activity should be complemented with communication to the public and involvement of stakeholders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The metabolic syndrome (MetS) presents an increasing prevalence in elderly people. A significant role in MetS is played by the stress response and cortisol. The hypothalamic-pituitary-adrenal (HPA) axis activity is increased by central (loss of hippocampal glucocorticoid receptors) and peripheral (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1, hyperactivity) mechanisms. The HPA hyperactivity has been found in chronic diseases affecting the endocrine (abdominal obesity with MetS, type 2 diabetes), cardiovascular (atherosclerosis, essential hypertension), and nervous systems (dementia, depression), in aging. A novel therapeutic approach (11β-HSD1 inhibition) is promising in treating the HPA axis hyperactivity in chronic diseases with MetS. A large-scale national clinical trial (AGICO, AGIng, and COrtisol study) has been proposed by our group to evaluate the role of cortisol and MetS in the main pathologies of aging (vascular and degenerative dementia, cardiovascular diseases, type 2 diabetes, abdominal obesity).

The hepatitis C virus (HCV) infection is an important public health problem and it is associated with hepatic and extrahepatic manifestations. Autoimmune thyroid diseases are common in HCV infected patients and the standard interferon-based treatment is associated with an increase of the immune-mediated thyroid damage. Recent evidence in the literature analyzed critical points of the mechanisms of thyroid damage, focusing on the balance between the two sides of the interaction: The environment (virus infection with potential cross-reaction) and the host (susceptibility genes with consistent immune response). The spectrum of antiviral treatment for chronic HCV infection is rapidly expanding for the development of dual o triple therapy. The availability of interferon-free combined treatment with direct antiviral agents for HCV is very promising, in order to ameliorate the patient compliance and to reduce the development of thyroid autoimmunity.

Background: In reconstructing anterior defects of the ear, postauricular flaps represent a popular option. The pedicle of such transauricular flaps can be superior, inferior, medial, or lateral. The postauricular helix-based adipodermal-pedicle turnover (PHAT) flap is an original single-stage transauricular technique for defects of the antihelix and scapha. Its skin paddle is on the posterior aspect of the ear. Its lateral de-epithelialized pedicle in front of the helix allows for it to easily reach peripheral anterior defects. In cases in which the underlying cartilage is involved, the extended PHAT (ePHAT) flap allows for restoring the contours of the ear without a cartilage graft., Materials and Methods: Between 2009 and 2011, a PHAT flap was used in 5 cases of defects of the antihelix or the scapha after tumor resection, 3 of which are in an extended version (ePHAT flap)., Results: There were no complications and a satisfactory aesthetic result was achieved in all cases., Conclusion: The PHAT flap is an original single-stage procedure for anterior auricular defects located on the antihelix or scapha. The single-layer PHAT flap is indicated in purely skin defect. The triple-layer ePHAT flap includes two subcutaneous extensions which increase its thickness and is indicated to restore the ear contours when cartilage has been removed.

Objective: Ulcerative colitis is a chronic disease that could be triggered by acute stressful events, such as gastrointestinal infections or emotional stress., Patients and Methods: We reported the case of the onset of an ulcerative colitis after a thyrotoxicosis crisis and reviewed the literature about the relationships between thyroid dysfunctions and ulcerative colitis., Results: A 38-year-old woman was diagnosed with ulcerative colitis after her third thyrotoxicosis crisis, two years after the diagnosis of Graves' disease. In this case, thyrotoxicosis acted as a trigger for ulcerative colitis onset., Conclusions: Hyperthyroidism could be a trigger able to elicit ulcerative colitis in susceptible patients.

Aim: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population., Methods: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time., Results: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs., Conclusion: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Complexes of 5,10,15-triferrocenylcorrole were synthesized from the crude free-base corrole product obtained by the reaction of ferrocenyl aldehyde and pyrrole. Direct formation of the complex in this manner leads to an increase of the reaction yield by protecting the corrole ring toward oxidative decomposition. The procedure was successful and gave the expected product in the case of the copper and triphenylphosphinecobalt complexes, but an unexpected result was obtained in the case of the nickel derivative, where metal insertion led to a ring opening of the macrocycle at the 5 position, giving as a final product a linear tetrapyrrole nickel complex bearing two ferrocenyl groups. The purified 5,10,15-triferrocenylcorrole complexes have been fully characterized by a combination of spectroscopic methods, electrochemistry, spectroelectrochemistry, and density functional theory calculations. Copper derivatives of 10-monoferrocenyl- and 5,15-diferrocenylcorrole were prepared to investigate how the number and position of the ferrocenyl groups influenced the spectroscopic and electrochemical properties of the resulting complexes. A complete assignment of resonances in the (1)H and (13)C NMR spectra was performed for the cobalt and nickel complexes, and detailed electrochemical characterization was carried out to provide additional insight into the degree of communication between the meso-ferrocenyl groups on the conjugated macrocycle and the central metal ion of the ferrocenylcorrole derivatives.

The insertion of a -NO2 group onto the corrole framework represents a key step for subsequent synthetic manipulation of the macrocycle based on the chemical versatility of such a functionality. Here we report results of the investigation of a copper 3-NO2-triarylcorrolate in nucleophilic aromatic substitution reactions with "active" methylene carbanions, namely diethyl malonate and diethyl 2-chloromalonate. Although similar reactions on nitroporphyrins afford chlorin derivatives, nucleophilic attack on carbon-2 of corrole produces 2,3-difunctionalized Cu corrolates in acceptable yields (ca. 30%), evidencing once again the erratic chemistry of this contracted porphyrinoid.

Background: Following the initial reports of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and the purported curative potential of venoplasty, (coined the 'liberation' procedure) Canadians living with multiple sclerosis (MS) began to travel abroad to receive the unregulated procedure, often placing them at odds with their health providers. The purpose of this study was to determine the factors influencing older MS patients' decision to undergo the procedure in order to develop more specific and targeted health information., Methods: We performed secondary analysis of data collected as part of the 'Canadian Survey of Health Lifestyle and Aging with MS' from people over the age of 55 years with MS symptoms for 20 or more years. The survey consisted of self-reported information on impairments, disability, participation, demographics, personal and environmental factors. In order to compare respondents who underwent the procedure to those who did not and to develop a predictive model, we created a comparison group using a case-control algorithm, controlling for age, gender and education, and matching procedure cases to controls 1:3. We used multivariate stepwise least likelihood regression of 'a priori' variables to determine predictive factors., Results: The prevalence of the 'liberation' procedure in our sample was 12.8% (95/743), substantially lower than reported in previous studies of complementary/alternative treatments in MS. The predictive model contained five factors; living alone (Odds ratio 0.24, 95%CI 0.09-0.63), diagnosis of anxiety (Odds ratio 0.29, 95%CI 0.10 - 0.84), rating of neurologist's helpfulness (Odds ratio 0.56, 95%CI 0.44 -0 .71), Body Mass Index (Odds ratio 0.93, 95%CI, 0.89 - 0.98) and perceived physical impact of MS (Odds ratio 1.02, 95%CI 1.01 - 1.04)., Conclusions: Predictive factors differed from previous studies of complementary/alternative treatment use likely due to both the invasiveness of the procedure and the advanced age of our study cohort. Our findings suggest that health professionals should target information on the risks and benefits of unregulated procedures to those patients who feel dissatisfied with their neurologist and they should include family members in discussions since they may be providing the logistical support to travel abroad and undergo the 'liberation' procedure. Our findings may be applicable to others with chronic disabling conditions who contemplate the user-pay unregulated invasive procedures available to them.

Background: Nasolabial flaps based on the lateral side of the nose for the reconstruction of lateral nasal defects in a single-stage procedure have been described. Similarly, in midline defects, nasolabial flaps can be used but a 2-stage procedure is classically required. The Midline-based Nasolabial Transposition (MNT) flap is presented as a new single-stage procedure for nasal tip reconstruction., Materials and Methods: Between 2009 and 2011, an MNT flap was used as a single-stage procedure in 3 cases of large nasal defects of the tip where the forehead flap was either contraindicated or rejected as an option by the patient., Results: There were no complications and a satisfactory aesthetic result was achieved in all cases., Conclusions: The MNT flap is a new single-stage procedure for large nasal tip defects and as such represents an interesting alternative to the classical 2-stage forehead and nasolabial flaps, especially in elderly patients.

Background & Aims: Homozygous individuals with alpha-1-antitrypsin deficiency (AATD) type PiZ have an increased risk of chronic liver disease and hepatocellular carcinoma (HCC). It is noteworthy that HCCs are composed by hepatocytes without accumulation of AAT, but the reason for this remains unclear. The aim of this study was to determine liver pathology in PiZ mice, focusing the attention on the distribution of AAT globules in normal liver, regenerative foci and neoplastic nodules., Methods: Liver of 79 PiZ mice and 18 wild type (Wt) was histologically analysed for steatosis, clear cell foci, hyperplasia and neoplasia. The expression of human-AAT transgene and murine AAT, in non-neoplastic liver and in hyperplastic/neoplastic nodules was tested by qPCR and qRT-PCR. RT-PCR was used to study expression of hepatic markers: albumin, α-foetoprotein, transthyretin, AAT, glucose-6-phospate, tyrosine aminotransferase., Results: Liver pathology was seen more frequently in PiZ (47/79) than in Wt (5/18) and its development was age related. In older PiZ mice (18-24 m), livers showed malignant tumours (HCC and angiosarcoma) (17/50), hyperplastic nodules (28/50), non-specific changes (33/50), whereas only 9/50 were normal. Both human-AATZ DNA and mRNA showed no differences between tumours/nodules and normal liver, while murine-AAT mRNA was reduced in tumours/nodules., Conclusion: Accumulation of AAT is associated with an increased risk of liver nodules. The presence of globule-devoid hepatocytes and the reduced expression of murine-AAT mRNA in hyperplastic and neoplastic nodules suggest that these hepatic lesions in AATD could originate from proliferating dedifferentiated cells, lacking AAT storage and becoming capable of AFP re-expression., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatic glycogenosis (HG) in type 1 diabetes is a underrecognized complication. Mauriac firstly described the syndrome characterized by hepatomegaly with altered liver enzymes, growth impairment, delay puberty and Cushingoid features, during childhood. HG in adulthood is characterized by the liver disorder (with circulating aminotransferase increase) in the presence of poor glycemic control (elevation of glycated hemoglobin, HbA1c levels). The advances in the comprehension of the metabolic pathways driving to the hepatic glycogen deposition point out the role of glucose transporters and insulin mediated activations of glucokinase and glycogen synthase, with inhibition of glucose-6-phosphatase. The differential diagnosis of HG consists in the exclusion of causes of liver damage (infectious, metabolic, obstructive and autoimmune disease). The imaging study (ultrasonography and/or radiological examinations) gives information about the liver alterations (hepatomegaly), but the diagnosis needs to be confirmed by the liver biopsy. The main treatment of HG is the amelioration of glycemic control that is usually accompanied by the reversal of the liver disorder. In selected cases, more aggressive treatment options (transplantation) have been successfully reported.

Despite the absence of scientific evidence demonstrating the efficacy of the "liberation procedure" in treating multiple sclerosis (MS), thousands of MS patients worldwide have undergone the procedure. The study objective was to explore the experience of liberation procedure decision making for individuals with MS. Fifteen adults in Newfoundland and Labrador, Canada, each participated in an in-depth interview. The data analysis revealed three groups of people: "waiters," "early embracers," and "late embracers." Using van Manen's hermeneutic phenomenological approach, we identified three themes each in the stories of the early and late embracers and four themes in the waiters' stories. A characteristic of the late embracers and waiters was skepticism, whereas desperation set the embracers apart from the waiters. With a deeper understanding of the experience, nurses can be more attuned to the perspectives of MS patients while helping them make informed decisions about undergoing the liberation procedure., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The debate within the multiple sclerosis (MS) community initiated by the chronic cerebrospinal venous insufficiency (CCSVI) hypothesis and the subsequent liberation procedure placed some people with MS at odds with health care professionals and researchers., Objective: This study explored decision making regarding the controversial liberation procedure among people with MS., Subjects and Methods: Fifteen people with MS (procedure, n=7; no procedure, n=8) participated in audiotaped semistructured interviews exploring their thoughts and experiences related to the liberation procedure. Data were transcribed and analyzed using an iterative, consensus-based, thematic content-analysis approach., Results: Participants described an imbalance of motivating factors affirming the procedure compared to hesitating factors that provoked the participant to pause or reconsider when deciding to undergo the procedure. Collegial conversational relationships with trusted sources (eg, MS nurse, neurologist) and ability to critically analyze the CCSVI hypothesis were key hesitating factors. Fundraising, family enthusiasm, and the ease of navigation provided by medical tourism companies helped eliminate barriers to the procedure., Conclusion: Knowledge of factors that helped to popularize the liberation procedure in Canada may inform shared decision making concerning this and future controversies in MS.

β-Nitrocorroles are potentially valuable platforms for the preparation of a wide range of more elaborated corrole derivatives possessing unique chemical functionalities and electronic properties. Here we report our results on the chemical manipulation of a copper 3-NO2-triarylcorrolate using different organic reactions, all involving the reduction of -NO2 to -NH2 at an early stage, followed by further transformations. By way of a β-acylated copper corrolate, a novel corrole derivative bearing an alkyl azide group on the peripheral positions was obtained and exploited in the Huisgen 1,3-dipolar cycloaddition.

The reaction of 5,10,15-tris(4-tert-butylphenyl)corrole with 2,3-bis(bromomethyl)-5,6-dicyanopyrazine provides a new example of corrole ring expansion to a hemiporphycene derivative. The ring expansion is regioselective, with insertion of the pyrazine derivative at the 5-position of the corrole ring, affording the corresponding 5-hemiporphycene. Different macrocyclic products accompany formation of the 5-hemiporphycene, depending on the reaction experimental conditions. Br-substitued 5-hemiporphycenes and the 2-Br substituted corrole were obtained in 1,2,4-trichlorobenzene, while in refluxing toluene traces of an inner core substituted corrole were observed together with a significant amount of the unreacted corrole. These results provide an important indication of the reaction pathway. The coordination behavior of the 5-hemiporphycene, together with detailed electrochemical characterization of the free-base and some metal complexes, provides evidence for the reactivity of the peripheral pyrazino group.

Objective: People with multiple sclerosis (MS) are living longer so strategies to enhance long-term health are garnering more interest. We aimed to create a profile of ageing with MS in Canada by recruiting 1250 (5% of the Canadian population above 55 years with MS) participants and focusing data collection on health and lifestyle factors, disability, participation and quality of life to determine factors associated with healthy ageing., Design: National multicentre postal survey., Setting: Recruitment from Canadian MS clinics, MS Society of Canada chapters and newspaper advertisements., Participants: People aged 55 years or older with MS symptoms more than 20 years., Outcome Measures: Validated outcome measures and custom-designed questions examining MS disease characteristics, living situation, disability, comorbid conditions, fatigue, health behaviours, mental health, social support, impact of MS and others., Results: Of the 921 surveys, 743 were returned (80.7% response rate). Participants (mean age 64.6±6.2 years) reported living with MS symptoms for an average of 32.9±9.5 years and 28.6% were either wheelchair users or bedridden. There was only 5.4% missing data and 709 respondents provided optional qualitative information. According to data derived from the 2012 Canadian Community Health Survey of Canadians above 55 years of age, older people with MS from this survey sample are about eight times less likely to be employed full-time. Older people with MS were less likely to engage in regular physical activity (26.7%) compared with typical older Canadians (45.2%). However, they were more likely to abstain from alcohol and smoking., Conclusions: Despite barriers to participation, we were able to recruit and gather detailed responses (with good data quality) from a large proportion of older Canadians with MS. The data suggest that this sample of older people with MS is less likely to be employed, are less active and more disabled than other older Canadians., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Cyanotoxins (CTX) are widely produced by several cyanobacteria (CB), increasingly spreading in most water bodies and terrestrial habitats, and represent a risk for human health. CB are prokaryotes, and although mostly autotrophic, several examples of heterotrophy in symbiotic relationship with different organisms have been described. In addition to the known routes of exposure, it has been hypothesized that CB might 'colonize' human intestine with relevant implications for human health. Colonization is a complex process and requires specific features of the possible invaders. Still, a short-term persistence as living and toxin-producing organisms within the intestinal lumen of the host could represent an 'internal' source of exposure to CTX. In this work we ran microcosm experiments (4-18days), looking at Microcystis aeruginosa PCC7806 resistance and cyanotoxin-producing capabilities in darkness, 37°C, pH 2, and subsequent recovery in a rich medium, in darkness, 37°C, in the presence of enteric bacteria, mimicking few important features of the gastrointestinal environment. We measured cyanobacterial populations and growth, microcystin (MC) production and the presence of mcyB gene. M. aeruginosa could grow in the dark at 37°C up to 17days, and survive at pH 2 at a rate between 30% and 70%, depending on the age and toxicity of the starting culture. Cell lysis resulted in a substantial amounts of MC released, not degraded at gastric pH. Following the acidic passage, still in the dark at 37°C, M. aeruginosa restarted to grow within 24h for the next 3-4days, independently on the presence of intestinal bacteria, maintaining the MC cell quota and mcyB gene. Our results show new features of CB: a significant resistance of M. aeruginosa in conditions far from its optimal one, that is an environment mimicking some of the important characteristics of human gastrointestinal tract, suggesting the possibility of an internal source of exposure to CTX, with implications for the risk assessment., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The association between diabetes and neurodegenerative diseases is increasing with aging. Several common mechanisms are involved in both these diseases. The endothelial cells of the blood brain barrier, neurons and glia express typical and different receptors of the glucose metabolism (glucose transporters, insulin receptors and glucagon-like peptide-1 receptors). The impairment in insulin signaling leads to an impairment of neuronal function and increases neurodegeneration, and, conversely, neurodegeneration causes a reduction of insulin signaling on neurons. Increased detailed knowledge of common physiological processes opens up the opportunities for developing new treatments that may prevent or reduce the onset of neurodegenerative diseases. The aim of the review is to discuss the potential neuroprotective effects of the antidiabetic drugs. The article presents some promising patents on the treatment of insulin resistance in the neurodegeneration.

Objective: Anisakidosis is a parasitic infection caused by the ingestion of row or uncooked fish, containing larval nematodes from the Anisakidae family. Intestinal anisakidosis represents about 4% of all cases, the majority being localized in the small bowel, with rare colonic involvement. Here we present an infrequent case of chronic anisakidosis, presenting with intestinal intussusception., Case Report: A 52 years old woman, chronically treated with immunosuppressants, presented to our Institution with acute abdominal pain and vomiting, due to colocolic intussusception. Colonoscopy successfully reduced the intussusception and revealed the presence of a voluminous colonic submucosal mass, near the hepatic flexure. Therefore, the patient underwent laparoscopic right hemicolectomy. The diagnosis of anisakidosis was made when the histological examination of the surgical specimen revealed the infestation of the intestinal wall by a nematode of the Anisakidae family, with an intense erosive-inflammatory adjacent reaction.

5,10,15-Triaryltetrabenzocorroles functionalized with different electron-withdrawing groups on the β,β'-fused rings have been prepared by a cross-coupling Heck procedure between octabrominated copper corrole and a terminal alkene bearing electron-withdrawing moieties. The spectroscopic characterization of these complexes showed red-shifted UV-vis absorption bands characterized by a significant band broadening. The same feature was observed in the case of NMR spectra, where low-resolution groups of signals were observed. This behavior derives from a strong tendency of these macrocycles to aggregate in solution, as has been demonstrated by an (1)H NMR study performed on one of these tetrabenzocorroles. The influence of the substituents on the fused benzene ring on the properties of the tetrabenzocorroles was investigated by electrochemistry and spectroelectrochemistry, and comparisons were made between properties of the newly synthesized compounds and those of the tetrabenzocorroles reported earlier in the literature.

The β-nitration reaction carried out on the corrole macrocycle has been shown to be extremely regioselective, although the reduced symmetry of the macrocycle could potentially lead to a huge number of possible regioisomers. We recently reported that the careful use of AgNO 2 /NaNO 2 as a nitrating system enabled the achievement in good yields of mono- and dinitro-derivatives on both corrole free base and its copper complex, proving to be an efficient and cost-effective method. In this work, we present a detailed study of the scope of this method using TtBuCorrH 3 as a model corrole. A further increase of the oxidant pushes the nitration up to the functionalization of three β-pyrrolic positions, although concomitant decomposition of the macrocycle is also observed. The application of the proven nitration method with a five-fold excess of both silver and sodium nitrites with respect to corrole, afforded the 2,3,17-(NO 2 ) 3 -TtBuPCorrCu as the main product, in 25% yield, together with traces of another compound identified by X-ray crystallographic analysis as the 3,8,17-(NO 2 ) 3 -TtBuPCorrCu isomer. In light of these recent results, we also reinvestigated the characterization of the nitration products obtained from bis-substitution reactions, allowing among others the identification of the copper 3,8-(NO 2 ) 2 corrolate.

The stress response during chronic conditions increases vulnerability to diseases through the activation of adaptive systems, in particular, the hypothalamus-pituitary-adrenal (HPA) axis. Dysregulation in HPA activity (central and peripheral) has been reported in chronic diseases, like metabolic syndrome, type-2 diabetes mellitus, atherosclerosis-related disease, essential hypertension, dementia, depression, particularly during comorbid conditions. Different targets of anti-glucocorticoid treatment have been proposed, acting at supra-hypothalamic, HPA axis, glucocorticoid receptor and post-receptor levels. The recent promising patents on the therapy against glucocorticoid-mediated damage will be presented and discussed.

Rationale: It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of 'liberation therapy' (venoplasty) following the initial report by Zamboni et al in 2009. That study also led to public pressure upon Departments of Health in Canadian Provinces to fund the procedure. The present study was done in order to advise the Government of Newfoundland and Labrador as to whether or not it should do so., Methods: We conducted an observational study of 30 MS subjects who had submitted to venoplasty, using objective, semi-objective and subjective measures., Results: Significant subjective improvement was reported by half of the subjects at three months, although the degree of perceived improvement was less at 12 months. The objective and semi-objective tests employed did not indicate improvement in any area over the one-year follow-up period. Seven of the 29 subjects in whom CT venography was performed at the end of the study year were found to have uni- or bilateral occlusion or >50% stenosis of at least one cervical draining vein, but they showed no deterioration in their clinical status compared to those in whom no venous occlusion nor stenosis was found., Conclusion: No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.

Purpose: This qualitative study sought to explore older people's experience of ageing with multiple sclerosis (MS) and to describe the natural history of self-management from their points of view., Methods: Eighteen people over age 55 and living with MS for at least 20 years were recruited from an MS clinic and rehabilitation outpatient records. Interviews (60-80 min), using open-ended questions, explored participants' lifelong experiences of MS. Following interview transcription, data were coded and analyzed; themes, subthemes, and their relationships were described based on consensus., Results: Participants recounted their diagnosis process, their life experience with MS, and how they eventually accepted their disease, adapted, and moved toward self-management. The findings included vivid descriptions of social relationships, health care interactions, overcoming barriers, and the emotions associated with living with MS. A conceptual model of phases of self-management, from diagnosis to integration of MS into a sense of self, was developed., Conclusions: Study participants valued self-management and described its phases, facilitators, and inhibitors from their points of view. Over years and decades, learning from life experiences, trial and error, and interactions with health care professionals, participants seemed to consolidate MS into their sense of self. Self-determination, social support, strong problem-solving abilities, and collaborative relationships with health professionals aided adaptation and coping. Findings from this study make initial steps toward understanding how MS self-management evolves over the life course and how self-management programmes can help people with MS begin to manage wellness earlier in their lives.

Functionalization of the β-pyrrolic positions of the corrole macrocycle with -NO(2) groups is limited at present to metallocorrolates due to the instability exhibited by corrole free bases under oxidizing conditions. A careful choice of the oxidant can limit the transformation of corroles into decomposition products or isocorrole species, preserving the corrole aromaticity, and thus allowing the insertion of nitro groups onto the corrole framework. Here we report results obtained by reacting 5,10,15-tritolylcorrole (TTCorrH(3)) with the AgNO(2)/NaNO(2) system, to give mono- and dinitrocorrole derivatives when stoichiometry is carefully controlled. Reactions were found to be regioselective, affording the 3-NO(2)TTCorrH(3) and 3,17-(NO(2))(2)TTCorrH(3) isomers as the main products in the case of mono- and disubstitution, in 53 and 20% yields, respectively. In both cases, traces of other mono- and disubstituted isomers were detected, which were structurally characterized by X-ray crystallography. The influence of the β-nitro substituents on the corrole properties is studied in detail by UV-visible, electrochemical, and spectroelectrochemical characterization of these functionalized corroles. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations of the ground and excited state properties of these β-nitrocorrole derivatives also afforded significant information, closely matching the experimental observations. It is found that the β-NO(2) substituents conjugate with the π-aromatic system of the macrocycle, which initiates significant changes in both the spectroscopic and redox properties of the so functionalized corroles. This effect is more pronounced when the nitro group is introduced at the 2-position, because in this case the conjugation is, for steric reasons, more efficient than in the 3-nitro isomer.

Two different methods for the regioselective nitration of different meso-triarylcorroles leading to the corresponding β-substituted nitrocorrole iron complexes have been developed. A two-step procedure affords three Fe(III) nitrosyl products-the unsubstituted corrole, the 3-nitrocorrole, and the 3,17-dinitrocorrole. In contrast, a one-pot synthetic approach drives the reaction almost exclusively to formation of the iron nitrosyl 3,17-dinitrocorrole. Electron-releasing substituents on the meso-aryl groups of the triarylcorroles induce higher yields and longer reaction times than what is observed for the synthesis of similar triarylcorroles with electron-withdrawing functionalities, and these results can be confidently attributed to the facile formation and stabilization of an intermediate iron corrole π-cation radical. Electron-withdrawing substituents on the meso-aryl groups of triarylcorrole also seem to labilize the axial nitrosyl group which, in the case of the pentafluorophenylcorrole derivative, results in the direct formation of a disubstituted iron μ-oxo dimer complex. The influence of meso-aryl substituents on the progress and products of the nitration reaction was investigated. In addition, to elucidate the most important factors which influence the redox reactivity of these different iron nitrosyl complexes, selected compounds were examined by cyclic voltammetry and thin-layer UV-visible or FTIR spectroelectrochemistry in CH(2)Cl(2)., (© 2012 American Chemical Society)

This paper describes emerging issue related to cyanobacterial dynamics and toxicity and human health risks. Data show an increasing cyanobacteria expansion and dominance in many environments. However there are still few information on the toxic species fitness, or on the effects of specific drivers on toxin production. Open research fields are related to new exposure scenario (cyanotoxins in water used for haemodialysis and in food supplements); to new patterns of co-exposure between cyanotoxins and algal toxins and/or anthropogenic chemicals; to dynamics affecting toxicity and production of different cyanotoxin variants under environmental stress; to the accumulation of cyanotoxins in the food web. In addition, many data gaps exist in the characterization of the toxicological profiles, especially about long term effects.

Purpose: The purpose of this study was to describe the factors influencing healthy aging from the perspective of the older person with multiple sclerosis (MS) in order to build curricula for MS self-management programs., Method: We sourced participants, older than 55 years with MS for more than 20 years, from a database of MS clinic and outpatient rehabilitation visits. Recruitment continued until data saturation was reached (n = 18). Semi-structured interviews explored perspectives on aging and health and lifestyle habits. Demographic, lifestyle and perceived health status information was also gathered. We analyzed the transcribed text for themes and theme relationships., Results: Work and social engagement, effective and accessible health care, healthy lifestyle habits, and maintaining independence at home were found to be critical proximal factors for healthy aging. The presence of financial flexibility, social support, cognitive and mental health, and resilience provided a supporting foundation to these critical proximal factors. These factors comprised a two-tiered model of healthy aging with MS., Conclusions: This two-tiered conceptual model of health aging, based on the perspectives of older persons with MS, provides a potential framework for the development of MS self-management program curricula aimed at optimizing quality of life. Further empirical testing may validate its utility in predicting healthy aging with MS.

A comparative study of Pt(II)- and Pt(IV)-porphyrins as novel ionophores for anion-selective polymeric membrane electrodes is performed. Polymeric membranes of different compositions, prepared by varying plasticizers, cationic and anionic additives and Pt porphyrins, have been examined by potentiometric and optical techniques. Pt porphyrin-based devices were found to exhibit enhanced potentiometric selectivity toward iodide ion compared to electrodes based on a typical anion-exchanger (e.g. tridodecylmethylammonium chloride). It is shown that Pt(II)-porphyrins function as neutral anion carriers within the electrode membranes, while those based on Pt(IV)TPPCl(2) operate via a mixed mode carrier mechanism, evidencing also a partial reduction of the starting ionophore to Pt(II)TPP. Spectrophotometric measurements of thin polymeric films indicate that no spontaneous formation of hydroxide ion bridged porphyrin dimers occurs in the membrane plasticized both with high or low dielectric constant plasticizer, due to a low oxophilicity of central Pt. The computational study of various anion-Pt(IV)TPPCl(2) complex formation by means of semi-empirical and density functional theory (DFT) methods revealed a good correlation between calculated and measured ionophore selectivity.