The role of melatonin in mood disorders

Melatonin (N-acetyl-5-methoxytryptamine) has been discovered as a hormone secreted by the pineal gland, even though it is also synthetized in various other organs, tissues, and cells. The circadian rhythm of melatonin is often used as an indicator phase position since it is a well-defined, high-amplitude rhythm controlled by the hypothalamic suprachiasmatic nuclei. Melatonin production is controlled by this endogenous circadian timing system. It peaks during the night and is suppressed by daylight. Mood spectrum disorders, including bipolar disorder (BD), major depressive disorder (MDD), and seasonal affective disorder (SAD), have been observed to be accompanied by circadian dysregulation as well as dysregulation in melatonin secretion. Simultaneously, it has also been documented that disruptions in circadian rhythms, including the sleep/wake cycle, though environmental means can produce mood-related problems in vulnerable individuals. These findings suggested that altered circadian rhythms might be biological markers of these disorders. As melatonin is considered a chronobiotic factor, ie, able to entrain the circadian rhythms of several biological functions (eg, activity/rest, sleep/wake, body temperature, endocrine rhythms, etc), its use may provide a new therapeutic approach for the treatment of affective disorders. However, the available evidence is controversial. This review summarizes the data published so far about reliable evidence on the role of melatonin in affective disorder

Alexithymia, responsibility attitudes and suicide ideation among outpatients with obsessive-compulsive disorder: An exploratory study

Abstract Aims Obsessive-compulsive disorder (OCD) is psychiatric disorder with a significant suicide risk, and the presence of alexithymia may increase this risk. As several studies attribute an important role, in OCD, to responsibility, the aims of this study were to evaluate possible clinical differences between patients positive or not for alexithymia concerning disorder severity, responsibility attitudes and suicide ideation and investigate which variables were associated with increased suicide ideation. Methods 104 adult outpatients with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale (TAS-20), attitude about responsibility was tested with Responsibility Attitude Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI) and depressive symptoms were evaluated with Montgomery Asberg Depression Rating Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of insight. Results Patients positive for alexithymia showed higher responsibility attitudes and more severe suicide ideation. In a blockwise regression model, the presence of lower insight, higher RAS scores and difficulty in identifying feelings dimension of TAS-20 were associated with higher SSI scores. Conclusions OCD patients with alexithymia may show higher disorder severity, lower insight and inflated responsibility, all related to suicide ideation, independently from depressive symptoms. Implications were discussed and study limitations considered and reported

Variabilit? naturale e legata a fattori antropici nei siti lacustri studiati

The natural variability of the biotic components, in particular of those showing seasonal cycles, often leads to significant changes of biomass as well as specific composition. This means that the choice of sampling frequency and distribution during the year may be crucial when assessing the ecological quality of a waterbody, starting from the structure of biotic communities. Among the four biological quality elements used to classify the lakes, three of them (phytoplankton, macrophytes and macroinvertebrates) show a marked seasonality and/or a certain degree of spatial variability. This document has the aim to evaluate how the metrics used are sensitive to the natural variability, especially respect to their response to the pressure gradients. The analysis was carried out on data collected during the project and is limited to phytoplankton and macrophytes, because the examination of autumn samples of macroinvertebrates, is still in progress. Regarding phytoplankton, three metrics defined by Italian national legislation (composition indices, chlorophyll and biovolume) were analyzed, comparing the variability due to anthropogenic origin (expressed by the gradient of total phosphorus) with the natural one (seasonal variations on different time scales) and estimating the uncertainty in the classification using different sampling frequencies. In the case of macrophytes, monitoring methods and classification were analyzed respect to their accuracy in assessing if the variability between sites, explained by a different anthropogenic pressure, is actually greater than the variance within the individual lake. In addition, we want to determine if the sampling effort, as established by the monitoring protocols, is adequate to the needs of the classification. Our analysis showed that the variability of phytoplankton metrics reflects the trophic gradient and is more significant than that explained by seasonal fluctuations, demonstrating the robustness of the indicators used. Moreover, the phytoplankton assemblages reveal a high stability in interannual patterns of succession. Conversely, the general formulation of the macrophytic index may need to be redefined to better understand the differences in ecological quality between lakes. Furthermore, as concerns macrophytes, a significant reduction of the sampling effort does not seem to be possible without compromising the quality of classification, while, as regards phytoplankton, it would be acceptable to reduce the number of annual samples from 6 to 4 without compromising the result of the classification, while observing the seasonality, because our analysis suggests that phytoplankton samples concentrated in a single season lead to increased uncertainty in the classification.La variabilit? naturale delle componenti biotiche, in modo particolare di quelle che mostrano cicli su base stagionale, porta a cambiamenti spesso significativi della composizione specifica e della biomassa. Questo significa che la scelta della frequenza di campionamento e la distribuzione dei prelievi nel corso dell\u27anno possono rappresentare dei fattori critici quando si tratta di valutare la qualit? ecologica a partire dalla struttura delle comunit? biotiche. Delle quattro componenti biologiche usate per classificare i laghi, tre (fitoplancton, macrofite e macroinvertebrati) mostrano una spiccata stagionalit? e/o una certa variabilit? spaziale. Il presente documento ? stato redatto con lo scopo di valutare quanto le metriche utilizzate siano sensibili alla variabilit? di origine naturale, soprattutto in relazione alla loro risposta rispetto ai gradienti di pressione. L?analisi ? stata condotta sui dati raccolti nel corso del progetto ed ? limitata al fitoplancton ed alle macrofite, poich? l?esame dei campioni autunnali dei macroinvertebrati ? tuttora in corso. Per quanto riguarda il fitoplancton sono state analizzate tre metriche indicate dalla normativa nazionale (indici di composizione, clorofilla e biovolume), confrontandone la variabilit? di origine antropica (espressa dal gradiente di fosforo totale) con quella naturale (stagionalit? su diverse scale temporali) e stimando l?incertezza nella classificazione con frequenze di prelievo diverse. Nel caso delle macrofite, i metodi di monitoraggio e di classificazione sono stati analizzati rispetto alla loro accuratezza nel valutare se la variabilit? tra ambienti, dovuta alla diversa pressione antropica, sia effettivamente maggiore rispetto alla varianza all?interno del singolo lago. Inoltre, si vuole valutare se lo sforzo di campionamento, previsto dai protocolli di monitoraggio, sia adeguato alle esigenze della classificazione. La nostra analisi ha messo in evidenza che la variabilit? delle metriche fitoplanctoniche rispecchia il gradiente trofico ed ? pi? significativa rispetto a quella spiegata dalle fluttuazioni stagionali, dimostrando la robustezza degli indicatori utilizzati e che le associazioni fitoplanctoniche rilevano un grande stabilit? negli schemi di successione interannuali. Viceversa, la formulazione generale dell?indice macrofitico potrebbe necessitare di una ridefinizione per meglio cogliere le differenze di qualit? ecologica tra i laghi. Inoltre, nel caso delle macrofite, una riduzione significativa dello sforzo di campionamento non pare possibile senza compromettere la qualit? della classificazione, mentre, per quanto riguarda il fitoplancton, sarebbe accettabile ridurre il numero dei prelievi annuali da 6 a 4 senza compromettere il risultato della classificazione, rispettando comunque la stagionalit?, poich? prelievi di fitoplancton concentrati in una sola stagione determinano una maggiore incertezza nella classificazione

Molecular and pathological characterization of the EZH2 rs3757441 single nucleotide polymorphism in colorectal cancer

Background The enhancer of zeste-homolog 2 (EZH2) is involved in cancer development through gene silencing by trimethylation of lysine 27 of histone 3 (H3K27me3). The C/C genotype for the EZH2 rs3757441 single-nucleotide polymorphism (SNP) is linked with poor prognosis in metastatic colorectal cancer (CRC), but molecular and pathological characterization of this SNP is lacking. Methods 119 primary CRCs were analyzed. SNP was evaluated by real-time PCR from colonic healthy tissue, while EZH2 and H3K27me3 expression were studied by immunohistochemistry. We primarily looked for correlation between EZH2 rs3757441 genotypes and EZH2/H3K27me3 expression. Potential associations between EZH2/H3K27me3 expression and clinico-pathological features or KRAS exon 2 and BRAF exon 15 mutations were secondary endpoints. Statistical analysis was performed by chi-square test, T-test or ANOVA. Results The C/C genotype was significantly associated with higher EZH2 (100 vs. 44 %; P = 0.019) and H3K27me3 (100 vs. 38 %; P = 0.009) staining intensity compared with C/T and T/T. EZH2 3+ staining significantly correlated with stronger H3K27me3 expression (P = 0.039). KRAS and BRAF mutations were not associated with EZH2 or H3K27me3 expression. Conclusion EZH2 rs3757441 C/C genotype is associated with stronger EZH2 and H3K27me3 immunoreactivity in primary CRC: this SNP may serve as a promising biomarker for EZH2-targeting agents and may add independent information to KRAS and BRAF testing

Banca dati relativa al monitoraggio dei laghi

A relational database was set up to host the high resolution biological, cvhemical and hydromorphological data produced within the InHabit project. Based on previous partial databases (Deliverables I1d2 and I1d3) the database was built using PostgreSQL, an Open Source Relational Database Management system. The data base contains information on the habitat surveys, information on lake water chemistry and the four biological quality elements quoted in the Annex V of the Directive 2000/60/EC (Water Framework Directive) for lakes: phytoplankton, macrophytes, benthic macroinvertebrates and fishes. With respect to the previous databases, more temporal and taxonomical resolution is provided. At the moment, Lake Habitat survey information are available for 13 lakes and or reservoirs, totaling 170 habitat plots an 170 inter-plot shore descriptions. Chemical data are available for 13 lakes and 258 samples. For what concern the biological quality elements, phytoplankton (58 samples and 281 taxa), macrophyte (94 samples and 20 taxa) and benthos (28 sample and 177 taxa) data are stored at the species level, while fish data are stored at the speciemen level (607 specimen, belonging to 29 species in 16 samples).Questo rapporto descrive la banca dati relazionale predisposta per i dati ad alta risoluzione provenienti dai laghi all?interno del progetto InHabit. Per evitare l?uso di software proprietario, la banca dati ? stata scritta usando il software PostgreSQL, un gestore di database relazionali disponibile con licenza Open Source. La banca dati ? predisposta sulla base dei precedenti database parziali (deliverables I1d2 e I1d3) per contenere i dati relativi alla descrizione degli habitat lacustri secondo il metodo del Lake Habitat Survey, e i dati ad alta risoluzione raccolti nella campagna di monitoraggio, con una risoluzione tassonomica e temporale maggiroe rispetto alle banche dati precedenti. Al momento di scrivere questo rapporto, erano disponibili informazioni di tipo idromorfologico per 13 laghi o invasi, per un totale di 170 osservazioni puntuali di habitat e 170 descrizioni della sponda tra un punto di rilevamento e l?altro. Inoltre, la banca dati contiene i risultati delle analisi chimiche di 258 campioni di acqua dei 13 laghi del progetto. Per gli elementi biologici di qualit?, i dati sono stati archiviati a livello di specie per il fitoplancton (58 campioni e 281 taxa), le macrofite (94 campioni e 20 taxa) e il benthos (28 campioni e 177 taxa), mentre nel caso dei pesci sono stati archiviati i dati a livello di singolo individuo campionato, (607 pesci di 29 specie 16 campioni)

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons

Analisi della relazione tra le concentrazione di azoto e la composizione delle comunit? acquatiche

This report presents an analysis of the relationships between environmental variables and organisms belonging to the four biotic communities used to define the lake\u27s ecological quality, according to provisions of the Italian legislation (D.Lgs. 260, November 2010) and the European Water Framework 2000/6. The data analyzed were collected during the sampling surveys carried out within InHabit Project in 13 water bodies, 7 in Piedmont and 6 in Sardinia respectively. In particular, the aim of the study was to evaluate the possible effects of nitrogen on biotic communities. Phytoplankton community shown the clearer responses: according to the result of multivariate analysis, total nitrogen and ammonium nitrogen are among the most significant factors explaining the relationships among phytoplankton orders, species and environmental variables. In particular, cyanobacteria increased considerably with increasing availability of ammonium nitrogen. Conversely, high concentrations of this compound suppress the development of diatoms. Other algal groups show a nonlinear response with respect to nitrogen, with a possible limitation under low levels of nitrogen and an inhibition at higher levels. A comparative analysis, carried out to evaluate the response to the gradient of total phosphorus, shows that this nutrient is not as selective as nitrogen in controlling the structure of the algal assemblage in different environmental conditions. Other biotic communities did not show a clear relationship with nitrogen, but they rather responded to the trophic gradient as a whole: responses by macroinvertebrates seem, especially in the analysis of functional groups, complex and difficult to discriminate, highlighting a possible shifting of the food web towards the presence of large carnivores at high trophic status. Regarding the fish, the results show that nitrogen alone does not seem to be an important controlling factor for the fish communities. However together with the phosphorus, is one of the main elements controlling both biomass and size of the fish fauna, as well as the presence of tolerant, omnivorous or benthofagous species. In conclusion, the results of our analysis highlight the need for a greater emphasis on nitrogen inputs, which, especially in cases of nitrogen carried by atmospheric deposition, may even affect lake ecosystems relatively distant from direct impacts of human activities, thus altering the structure of biotic communities.A partire dai dati raccolti con le campagne di campionamento effettuate nell?ambito del progetto InHabit, questo documento presenta un?analisi delle relazioni tra le variabili ambientali e gli organismi appartenenti alle quattro comunit? biotiche utilizzate per la definizione della qualit? ecologica degli ambienti lacustri, secondo quanto previsto dal D.Lgs. 260 del novembre 2010, che recepisce la Direttiva Europea sulle Acque 2000/60. I campionamenti sono stati condotti in 13 ambienti lacustri, 7 in Piemonte e 6 in Sardegna. In particolare, lo scopo del lavoro ? stato valutare i possibili effetti sulla comunit? biotiche di concentrazioni variabili dei composti azotati inclusi tra le variabili considerate. La comunit? che mostra le risposte pi? chiare ? quella fitoplanctonica: come risulta dall?analisi multivariata, sia azoto ammoniacale che azoto totale compaiono tra le variabili significative per spiegare l?ordinamento di ordini e specie fitoplanctoniche. Tra questi, sono soprattutto i cianobatteri che aumentano sensibilmente all?aumentare della disponibilit? di azoto ammonicale. Al contrario, elevate concentrazioni di questo composto deprimono lo sviluppo delle diatomee. Altri gruppi algali mostrano una risposta non lineare rispetto ai composti azotati, con una possibile limitazione a bassi livelli di azoto ed una inibizione a livelli troppo elevati. L?analisi della risposta rispetto al gradiente di fosforo totale, mostra che questo nutriente non ? selettivo come l?azoto nel controllare la struttura delle associazioni algali in diverse condizioni ambientali. Le altre comunit? non hanno mostrato una relazione evidente con i composti azotati, ma, piuttosto, con il gradiente trofico complessivo: le risposte evidenziate dalla fauna macroinvertebrata, sembrano, soprattutto nell?analisi dei gruppi funzionali, complesse e difficili da discriminare, evidenziando un possibile spostamento degli equilibri della rete trofica verso i carnivori in presenza di elevati livelli trofici. Relativamente alla fauna ittica, i risultati mostrano che da solo l?azoto non sembra essere un fattore di controllo importante per la comunit? ittiche. Tuttavia insieme al fosforo, ? uno degli elementi principali a cui si associano positivamente la biomassa e le dimensioni della fauna ittica, nonch? la presenza di specie tolleranti, onnivore o bentofaghe. In conclusione, i risultati della nostra analisi, sottolineano ulteriormente la necessit? di porre una maggiore attenzione agli apporti di azoto, che, soprattutto nei casi di azoto veicolato da deposizioni atmosferiche, potrebbero interessare anche ecosistemi lacustri relativamente distanti da impatti diretti delle attivit? antropiche, alterandone la struttura delle comunit? biotiche

Effetti dell\u27inquinamento da azoto nei laghi e nei fiumi e suggerimento per il miglioramento dei PdG

This report summarizes the finding of the InHabit project on the importance of atmospheric nitrogen deposition in affecting the chemical composition of lake water and in eventually altering the biological communities living in them. Previous deliverables (I2d5, Id26 and I2d7) have shown that; 1. in both regions studied in the InHabit project (Piedmont and Sardinia), atmospheric deposition of nitrogen compounds is relevant; 2. the flux of nitrogen from the atmosphere to the ecosystem is markedly larger in Piedmont than in Sardinia; 3. models of the dynamic behavior of nitrogen in forested catchments indicates that Piedmon soils are mainly N-saturated, so that nitrogen carried by atmospheric deposition can be released form forest soil to the surface water; 4. in Sardinia, soil are less saturated, but a part of the deposited nitrogen is still carried to surface water; 5. trend analysis of deposition and stream water revealed that nitrogen deposition is stable or slightly decreasing in recent years, both in atmospheric deposition and in stream water; 6. the importance relative importance of N deposition is relevant for sites in or close to reference conditions; 7. the relationships between environmental variables and organisms belonging to the four biotic communities used to define the lake\u27s ecological quality, according to provisions of the Italian legislation (D.Lgs. 260, November 2010) and the European Water Framework 2000/60 differ depending on the biological quality element considered; 8. phytoplankton community shows the clearer responses: according to the result of multivariate analysis, total nitrogen and ammonium nitrogen are among the most significant factors explaining the relationships among phytoplankton orders, species and environmental variables. In particular, cyanobacteria increased considerably with increasing availability of ammonium nitrogen. Conversely, high concentrations of this compound suppress the development of diatoms. On the basis of those results, which are summarized in this deliverable, we focused on the effect of different levels of nitrogen in lakes with low phosphorus concentration, slightly affected by direct trophic pressure and close to the reference conditions. The comparison between two lakes in Piedmont with low P concentration and high N concentration with two reservoirs in Sardinia with low levels of both nutrients shows that the formers are dominated by diatoms and the latter by dynophytes. Two reservoirs in Piedmont with high N levels are also dominated by diatoms. In spite of the small number of lakes studied, it seems that dynophytes are more fitted to low N lakes, probably because of their ability to use an heterotrophic metabolism, while lakes in reference conditions are generally considered to be dominated by oligotrophic diatoms, Our findings call for deeper studies on reference conditions in the Mediterranean ecoregion, because they suggest that lakes not affected by direct trophic pressure, i.e. reference lakes, may host different diatom communities depending on the amount of nitrogen deposition they receive

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial

Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia