On the integration of LiDAR and field data for riparian biomass estimation.

The role of vegetation in supporting life on Earth is widely known. Nevertheless, the relevance of riparian corridors has been overlooked for a long time, leading to a dramatic reduction of vegetated buffers alongside them. Vegetation monitoring systems, including those for biomass estimation, are required to manage riparian corridors properly. Field surveys may support monitoring, but their usefulness is reduced by numerous drawbacks, therefore needing coupling with other data sources. The present work shows how Light Detection And Ranging (LiDAR) datasets can integrate targeted field measurements to estimate above-ground biomass at temperate or boreal latitudes and generate accurate biomass maps over large areas. By referring to the case study of the Orco river (northwest Italy), we defined a technique to reconstruct the geometry of an individual shrub from LiDAR point clouds. We tested the technique by comparing field measurements with Terrestrial and Airborne Laser Scanner data (TLS and ALS, respectively), assessing the former's superiority but the broader range of applicability of the latter. After these preliminary tests, we coupled the presented technique with a literature algorithm for individual tree detection, providing a more generalized procedure for the overall mapping and budgeting of riparian biomass based on ALS data. We applied the procedure to a fluvial bar of the Orco river, achieving a quantitative assessment of the shrub and tree biomass budget for 2019 and 2021 and visualizing the changes that occurred in that period. These results allowed us to shed light on the prevailing natural and anthropogenic processes in the investigated area and provide insights into the strengths and weaknesses of the proposed procedure.

Updated European Consensus Statement on diagnosis and treatment of adult ADHD.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

The Fertility Quality of Life Questionnaire (FertiQoL) Relational subscale: psychometric properties and discriminant validity across gender.

STUDY QUESTION: Is the Fertility Quality of Life Questionnaire (FertiQoL)-Relational Scale a valid measure to assess the relational domain regarding quality of life in women and men undergoing infertility treatment? SUMMARY ANSWER: The FertiQoL-Relational scale (FertiQoL-REL) showed good psychometric properties and captured core aspects of couple relationships. WHAT IS KNOWN ALREADY: FertiQoL has become a gold standard for the assessment of infertility-related quality of life in patients undergoing assisted reproduction treatment (ART). Despite its growing importance, no previous studies have examined the convergent validity of the FertiQoL-REL and its discriminant validity across gender. STUDY DESIGN, SIZE, DURATION: Baseline cross-sectional data as part of a longitudinal study of infertile couples undergoing an ART between February 2013 and January 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Five hundred and eighty-nine patients (301 females and 288 males), prior to starting an ART in a private clinic, filled in the Fertility Quality of Life Questionnaire (FertiQoL) and several measures of the marital relationship (Dyadic Adjustment Scale, Marital Commitment Inventory and ENRICH Marital Satisfaction Scale) and infertility-related distress (Fertility Problem Inventory). MAIN RESULTS AND THE ROLE OF CHANCE: Confirmatory factor analysis showed that the FertiQoL four-factor solution provided a good fit for the observed data. Reliability of the FertiQoL-REL was higher for women than men. Significant correlations between the FertiQoL-REL scores and all the other measures of marital relationship were found for both women and men. FertiQoL-REL scores did not differ significantly in women and men. The FertiQoL-REL was able to differentiate subjects as regards the Dyadic Adjustment Scale and ENRICH Marital Satisfaction Scale threshold. LIMITATIONS, REASONS FOR CAUTION: Findings are limited because the data were obtained from only one Italian private clinic. WIDER IMPLICATIONS OF THE FINDINGS: FertiQoL-REL threshold scores are useful for identifying those patients undergoing ART who are more likely to report poor or good relationship quality. Clinicians should tailor their counselling strategies to the positive qualities in a couple's relationship, so as to reinforce the overall quality of life, especially among women, and to support patients in tackling the psychological burden, so that they can either continue treatment or choose discontinuation. STUDY FUNDING/COMPETING INTERESTS: This research was supported by funds provided by Centro Andros S.r.l., Palermo, Italy. The authors declare no financial or commercial conflicts of interest in this study. TRIAL REGISTRATION NUMBER: Not necessary.

PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Empirical examination of the interpersonal maintenance model of anorexia nervosa.

OBJECTIVE: A cognitive interpersonal maintenance model of anorexia nervosa (AN) was first proposed in 2006 and updated in 2013 (Schmidt and Treasure, J Br J Clin Psychol, 45, 343-366, 2006; Treasure and Schmidt, J Eat Disorders, in press.). The aim of this study was to test the interpersonal component of this model in people with AN requiring intensive hospital treatment (inpatient/day patient). METHOD: On admission to hospital women with AN or eating disorder not otherwise specified (AN subtype; n = 152; P) and their primary carers (n = 152; C) completed questionnaires on eating symptoms (P), depression and anxiety (P, C), accommodation and enabling (C), and psychological control (C). Structural equation modeling was used to examine relationships among these components. RESULTS: Carers' expressed emotion and level of psychological control were significantly related to carers' distress, which in turn, was related to patients' distress. This pathway significantly predicted eating symptoms in patients. DISCUSSION: The cognitive interpersonal maintenance model of eating disorders (EDs) was confirmed in part and suggests that interventions targeting interpersonal maintaining factors such as carer distress might impact on patient outcomes.

A focus on heme oxygenase-1 (HO-1) inhibitors.

The aim of this review is to highlight the advances in the field of heme oxygenase-1 (HO-1) inhibitors over the past years, particularly from a medicinal chemistry point of view; progresses made in the field strongly helped to clarify physiological roles of the heme oxygenase (HO) system. HO is a family of ubiquitously expressed enzymes which regulate the regiospecific catabolism of heme leading to the formation of equimolar amounts of carbon monoxide (CO), ferrous iron (Fe⁺⁺), and biliverdin. HO exists in two distinct, catalytically active isoforms: HO-1 and HO-2. HO-1 is an inducible 32-kDa protein, while HO-2 is a constitutively synthesized 36-kDa protein and generally is unresponsive to any of the inducers of HO-1. A third isoform, HO-3, is still an elusive protein. The HO system, along with its catabolism products, is involved in a variety of crucial physiological functions, including cytoprotection, inflammation, anti-oxidative effects, apoptosis, neuro-modulation, immune-modulation, angiogenesis, and vascular regulation. The use of selective HO inhibitors is a very important tool to clarify the role of the HO system and the mechanisms underlying its physiological effects and pathological involvement; due to the inducible nature of HO-1, selective inhibition of HO-1 isoform is generally preferable. Notably, HO-1 inhibitors may be also beneficial in therapeutic applications and have been mainly studied for treatment of hyperbilirubinemia and certain types of cancer. Historically, the first molecules used as non selective HO-1 inhibitors were metalloporphyrins (Mps). The subsequent development of the imidazole-dioxolane derivatives afforded the first generation of non-porphyrin based, isozyme selective HO-1 inhibitors.

Serotonin 5-HT3 and 5-HT4 ligands: an update of medicinal chemistry research in the last few years.

The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) is one of the most studied neurotransmitters in the central nervous system. It acts through the activation of at least fourteen 5-HT receptor subtypes. Over the last two decades, high attention was devoted to the 5-HT(3) and 5-HT(4) receptors due to their colocalization in the gastrointestinal tract and because their ligands are useful in the treatment of intestinal serotonergic system dysfunctions. The focus of this review is to discuss the literature concerning recent advances on 5-HT(3)R and 5-HT(4)R ligands and their structure-activity relationships from a medicinal chemistry perspective. During the last few years, new and significant progresses have been made in the field of novel potent and selective ligands, mixed ligands, agonists, partial agonists, and antagonists, and a number of patents have been filed. Furthermore several ligands targeting the 5-HT(3)R and 5-HT(4)R have been proposed for novel therapeutic indications such as the treatment of various psychiatric disorders.

Synthesis of 1,2,4-triazole derivatives: binding properties on endothelin receptors.

In the present study we describe the synthesis of a new series of 1,2,4-triazoles: [3-(arylmethyl)thio-5-aryl-4H-[1,2,4]triazol-4-yl]acetic acids 5a-g, [5-(arylmethyl)thio-3-aryl-1H-[1,2,4]triazol-1-yl]acetic acids 8a-d, and [3-(aryl-methyl)thio-5-aryl-1H-[1,2,4]triazol-1-yl] acetic acids 9a-d. These compounds were tested in binding assays to evaluate their ability as ligands for human ET(A) and ET(B) receptors stably expressed in CHO cells; some of the tested compounds showed affinity in the micromolar range.

Imidazole derivatives as antioxidants and selective inhibitors of nNOS.

The reperfusion of ischemic tissue often delays its physiological and functional recovery; this paradoxical effect is ascribed to increased release of free radicals including O(2)(-) and NO. For these reasons, scavenging reactive oxygen species or inhibition the NO synthesis has been shown to result in an enhanced neuronal survival after cerebral ischemia. Many authors believe that therapy for stroke patients would be a cocktail of drugs with various mechanisms of action. Combination therapy is a difficult and complicated avenue for drug development because of the possibility of drug-drug interactions. An alternative approach would be to combine multiple activities within the same compound. In consideration of the free-radical scavenging and inhibitory effect on NOS of various natural and synthetic compounds, the aim of this study was to analyze the antioxidant properties of some imidazole derivatives previously synthesized in our laboratory. Results obtained in the present study provide evidence that tested compounds exhibit interesting antioxidant properties, expressed either by their capacity to scavenge free radicals or their ability to reduce lipid peroxidation. In particular, compounds A and B represent chemical structures which can be easily modified to improve the observed antioxidant properties and to provide new therapeutic strategies focused on multiple downstream events.

Novel inhibitors of neuronal nitric oxide synthase.

Selective inhibitors of neuronal nitric oxide synthase (nNOS), which are devoid of any effect on the endothelial isoform (eNOS), may be required for the treatment of some neurological disorders. In our search for novel nNOS inhibitors, we recently described some 1-[(Aryloxy)ethyl]-1H-imidazoles as interesting molecules for their selectivity for nNOS against eNOS. This work reports a new series of 1-[(Aryloxy)alkyl]-1H-imidazoles in which a longer methylene chain is present between the imidazole and the phenol part of molecule. Some of these molecules were found to be more potent nNOS inhibitors than the parent ethylenic compounds, although this increase in potency resulted in a partial loss of selectivity. The most interesting compound was investigated to establish its mechanism of action and was found to interact with the tetrahydrobiopterin (BH(4)) binding site of nNOS, without interference with any other cofactors or substrate binding sites.

Progress in the development of selective nitric oxide synthase (NOS) inhibitors.

Nitric oxide (NO), a molecular messenger synthesized by nitric oxide synthase (NOS) from L-arginine and molecular oxygen, is involved in a number of physiological and pathological processes in mammalians. Three structurally distinct isoforms of NOS have been identified: neuronal (nNOS), endothelial (eNOS) and inducible (iNOS). Although NO mediates several physiological functions, overproduction of NO by nNOS has been reported in a number of clinical disorders including acute (stroke) and chronic (schizophrenia, Alzheimer s, Parkinson s and AIDS dementia) neurodegenerative diseases, convulsions and pain; overproduction of NO by iNOS has been implicated in various pathological processes including septic shock, tissue damage following inflammation and rheumatoid arthritis. On the contrary, NO produced by eNOS has only physiological roles such as maintaining physiological vascular tone. Accordingly, selective inhibition of nNOS or iNOS vs eNOS may provide a novel therapeutic approach to various diseases; in addition selective inhibitors may represent useful tools for investigating other biological functions of NO. For these reasons, after the identification of N-methyl-L-arginine (L-NMA) as the first inhibitor of NO biosynthesis, design of selective NOS inhibitors has received much attention. In this article the recent developments of new molecules endowed with inhibitory properties against the various isoforms of NOS are reviewed. Major focus is placed on structure-activity-selectivity relationships especially concerning compounds belonging to the non-amino acid-based inhibitors.

Inhibition of neuronal nitric oxide synthase by N-phenacyl imidazoles.

Nitric oxide (NO) mediates a series of physiological processes, including regulation of vascular tone, macrofage-mediated neurotoxicity, platelet aggregation, learning and long-term potentiation, and neuronal transmission. Although NO mediates several physiological functions, overproduction of NO can be detrimental and play multiple roles in several pathological diseases. Accordingly, more potent inhibitors, more selective for neuronal nitric oxide synthase (nNOS) than endothelial NOS (eNOS) or inducible NOS (iNOS), could be useful in the treatment of cerebral ischemia and other neurodegenerative diseases. We recently described the synthesis of a series of imidazole derivatives. Among them N-(4-nitrophenacyl) imidazole (A) and N-(4-nitrophenacyl)-2-methyl-imidazole (B) were considered selective nNOS inhibitors. In the present study the action mechanism of compounds A and B was analyzed. Spectral changes observed in the presence of compound A indicate that this inhibitor exerts its effect without interaction with heme iron. Moreover compounds A and B, inhibit nNOS "noncompetitively" versus arginine, but "competitively" versus BH(4).

Long-term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase.

OBJECTIVE: To examine the long-term effects of treatment with recombinant human CuZn superoxide dismutase (rhSOD) in infants enrolled previously in two placebo-controlled trials. STUDY DESIGN: Records for 46 (88%) infants were examined, with 19 infants having received either single or multiple intratracheal (i.t.) doses of placebo, 12 having received a single i.t. dose of rhSOD, and 15 having received multiple i.t. doses of rhSOD. Mean age at follow-up was 28 months corrected age. Records were examined for neurologic dysfunction, developmental delay, and any significant medical disorders. RESULTS: Four placebo infants (21%) had evidence of neurodevelopmental abnormalities and four infants developed asthma. Four single-dose rhSOD infants (33%) had neurodevelopmental abnormalities and two infants developed asthma. One multiple-dose rhSOD infant had evidence of neurodevelopmental abnormalities and one developed asthma. No other differences were found between the placebo and rhSOD groups. CONCLUSION: Preliminary data suggest that rhSOD is safe and not associated with any long-term adverse effects. Further results will depend on the results of multicenter trials of rhSOD in preterm infants.

Synthesis of novel 4,5-diphenylthiazole derivatives as potential acyl-CoA:cholesterol O-acyltransferase inhibitors.

Several novel N-(4,5-diphenylthiazol-2-yl)-N'-aryl or alkyl (thio)ureas and N-(4,5-diphenylthiazol-2-yl)alkanamides were prepared as potential acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors. Synthesis was accomplished by reaction of 2-amino-4,5-diphenylthiazole with the suitable isocyanate, isothiocyanate or acyl chloride. Some analogues without the 5-phenyl substituent or both the phenyl groups in 4 and 5 position of the thiazole ring were also prepared. Moreover, some bioisosters of the title compounds in which the thiazole ring was replaced by an imidazole were synthesized starting from the 2-amino-4,5-diphenyl-1H-imidazole. The ability of synthesized compounds to inhibit ACAT was evaluated in vitro by measuring the formation of cholesteryl[14C]oleate from cholesterol and [1-14C]oleoyl-CoA in rat liver microsomes. Among the tested compounds, only some thiazole ureas were able to inhibit ACAT in a reasonable degree. N-(4,5-diphenylthiazol-2-yl)- N'-[2,6-bis(2-methylethyl)phenyl] urea (11) and N-(4,5-diphenylthiazol-2-yl)-N'-n-butyl urea (16) were the most active compounds in the series showing IC50 values in the low micromolar range.

[The clinical usefulness of cyclosporine therapeutic monitoring]. / Utilità clinica del monitoraggio terapeutico della ciclosporina.

PURPOSE: To review the cyclosporine therapy indications and evaluate determine the incidence of cyclosporine blood levels outside the therapeutic range in patients under treatment, to evaluate the practical utility of the drug monitoring. PATIENTS AND METHODS: The blood concentration of monoclonal cyclosporine was monitored in 225 patients by FPIA method, using the trough concentration. RESULTS: 58% of patients had a drug blood level within the therapeutic range, 26% and 16% of them had respectively, a value below and down this range. After correcting the drug dosage, 75% and 68% of the patients of the two subgroups had a cyclosporine blood value within the therapeutic range. CONCLUSIONS: Cyclosporine is increasingly used in transplant recipients as well as in patients with other immunological diseases. Since the number of patients, with inappropriate serum levels of cyclosporine is high, therapeutic monitoring of blood levels of the drug are of paramount importance.

Micro-albuminuria in obese subjects: relationship among body fat distribution, blood pressure and left ventricular structure and function.

OBJECTIVE: To evaluate the relationships among micro-albuminuria, blood pressure and measurements of left ventricular structure and function in centrally and peripherally obese subjects compared with members of a lean control group. METHODS: Centrally obese subjects were subdivided according to whether they had levels of micro-albuminuria higher than 30 mg/24 h (micro-albuminuric group) or lower than or equal to 30 mg/24 h (normo-albuminuric group). For all the subjects we measured heart rate, casual mean blood pressure (MBP), 24 h MBP, total cholesterol level, high-density lipoprotein cholesterol, lipoprotein (a) level, fasting immunoreactive insulin level, plasma renin activity, plasma aldosterone level and micro-albminuria (UAE) by current methods. Left ventricular mass indexed for body height, left ventricular diastolic and systolic diameters, interventricular septal thickness and left ventricular ejection fraction were measured by echocardiography. Peak filling rate was also calculated by radionuclide study. Family history of cardiovascular disease was evaluated for all the obese subjects.RESULTS: Lipoprotein (a) level, total cholesterol level, 24 h MBP and interventricular septal thickness were significantly (P < 0.05) greater for micro-albuminuric than they were for normo-albuminuric centrally obese subjects, whereas high-density lipoprotein cholesterol level and left ventricular ejection fraction were significantly (P < 0.05 lower. In addition, UAE levels of centrally obese subjects were significantly (P < 0.05) higher than those of peripherally obese subjects. UAE of all the centrally obese subjects was correlated directly to lipoprotein (a) level (r = 0.33, P < 0.009), 24 h MBP (r = 0.41, P < 0.002), interventricular septal thickness (= 0.36, P < 0.005) and family history of cardiovascular disease (r = 0.33, P < 0.007). Multiple regression analysis indicated that UAE was independently related to 24 h MBP and family history of cardiovascular disease. CONCLUSION: Our data indicated that measurement of micro-albuminuria is useful for evaluating cardiovascular risk profiles of obese subjects with a central fat distribution.

Transport of alpha-tocopherol and its derivatives through erythrocyte membranes.

PURPOSE: To investigate the transport of alpha-tocopherol (T), tocopherol succinate (TS) and tocopherol succinate-3-glucose (a newly synthetized, less hydrophobic T ester; TSG) through bovine erythrocyte membranes. METHODS: Our experiments were carried out on erythrocytes (obtained from heparinized fresh bovine blood), because they represent a suitable model for investigations of membrane transport. RESULTS: T was shown to reside almost completely in the suspension medium, while the greater part of TS disappeared from the suspension medium and was mainly incorporated into erythrocyte membranes. In comparison with T, a larger amount of TSG was incorporated into erythrocyte membranes and taken up by cells; however the TSG intracellular accumulation was significantly lower than that observed with TS. Furthermore, the transport of TS and TSG was partially inhibited by p-chloromercuribenzenesulfonate (which inhibits monocarboxylate uptake; PCMBS) and by maltose (a competitive inhibitor of glucose transport) respectively, with a concomitant increase in drug membrane incorporation. No significant change in drug transport was observed in the presence of 4,4'-diisothiocyanostilbene-2,2'-disulfonate, a selective and irreversible blocker of band 3 protein (DIDS). CONCLUSIONS: Our results show 1) the existence of large differences in membrane incorporation of T, TS and TSG (very likely caused by differing abilities to fill spaces in the lipid bilayer) and 2) a specific contribution of the monocarboxylate transport protein and of the glucose transport protein in the cellular uptake of TS and TSG, respectively. A tempting suggestion is that the unique cytoprotective properties of TS may be related to the differences in the transmembrane mobility observed between T and its succinate ester. Furthermore, T conjugation to a monocarboxylate or glycoside moiety could provide suitable substrates for active membrane transport, thus appearing as a promising pharmaceutical strategy for the improved delivery of tocopherol derivatives.

[Current clinical interest in monitoring digoxinemia]. / Attualità dell'importanza clinica del monitoraggio della digossinemia.

After a short introduction about the current role of digitalis in the treatment of the supraventrical arrhythmias and about the factors that make often problematic the achievement of an optimal posology of the drug, the results relative to more recent 340 digoxinaemia determinations in patients of Policlinico in Palermo or in outpatients are presented. Just the 43.8% of the patients had a digoxinaemia value in the range considered therapeutic; just 45 patients (32.1%), out of the 140 in which the digoxinaemia had been monitored for, at least, 5 days, were in the therapeutic range at the first determination; the 47.8% of the patients were underdosed and the 38.8% of them showed higher values than the therapeutic range. Determination 5 or more days later showed digoxinaemia values in the therapeutic range in 112 patients (80%). According to the reported results, it may be presumed that the posology correction effectuated by the physician on these patients might have been driven by the digoxinaemia values, whose determination must be considered an unavoidable guide to the digitalis treatment.