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ABSTRACTIntroductionAdverse events (AEs) monitoring of mood stabilizers (MS) is essential during the treatment of mood disorders as safety and tolerability profiles of MS may greatly influence treatment adherence, patient’s compliance, and discontinuation rate. Therefore, clinicians should be aware of their AEs profile and tapering a variety of strategies to manage them, according to an evidence-based approach.Areas coveredWe aimed at critically summarizing the tolerability and safety profile for each nonantipsychotic MS, providing evidence-based strategies able to manage these AEs, in order to increase clinically useful strategies which may allow clinicians enhancing adherence and therapeutic compliance, the impact on quality of life and treatment efficacy in psychiatric conditions.Expert opinionThe management of the safety and tolerability profile of each MS comprises an initial assessment of the symptoms/signs to be observed/measured during the therapy, including a psychoeducational activity, a periodical monitoring with a specific timing depending on clinical parameters and each prescribed MS, but also an evaluation if a treatment modification (in terms of dose adjustment, discontinuation or additional medication to be prescribed) is required as well as which combination therapy is allowed and which caution should be posed by clinicians in some special conditions, including pregnancy and breastfeeding.

Background: NPS belonging to the benzodiazepine (BZD) class, e.g., ‘legal/designer BZDs’/‘research chemicals’, have recently emerged in the drug (mainly online/virtual) market. Objective: While certain NPS belonging to the BZD class possess pharmacological profiles similar to controlled pharmaceutical BZDs, clinical and pharmacological profiles of current emerging BZDs are still not well-described. Therefore, there is a need to increase clinicians’/public health knowledge/awareness, to incentive harm reduction strategies. Method: A comprehensive overview was carried out by using the EMCDDA/EDND database regularly monitored by our research team, by specifically looking at the ‘new BZDs’ so far notified. Furthermore, given the limitation of peer-reviewed data published so far, a nonparticipant multilingual qualitative netnographic study was conducted to obtain further clinical/pharmacological/ toxicological data, including psychonauts’ online trip reports. Results: First designer BZDs appeared as NPS around 2007. So far, 29 designer BZDs have been notified to the EMCDDA, being some of them extremely powerful, also at lower dosages. They are sold as tablets/powder/pellets/capsules/blotters/liquids, at very affordable prices, and variably administered. Some are also sold on the illicit drugmarket as counterfeit forms of traditional BZDs or as either adulterants or diluents in heroin or other synthetic opioids/cannabinoids. Nowadays, there is no guarantee of the quality of designer BZDs composition/purification and, hence, most NPS consumers may be inadvertently exposed to unsafe and harmful compounds. Conclusion: Given the limited information on their pharmacology/toxicity, variations in dosage, onset of effects, combination of substances, potency, and general patient or individual variability, the concomitant use of these substances with other drugs entails several and unpredictable risks.

ABSTRACTIntroductionThere are several new and emerging antipsychotic medication strategies recently marketed or under clinical development for the treatment of several mental disorders. There is the need to provide an up-to-date overview on the safety of this new generation of antipsychotic medications, which includes also the third-generation antipsychotics (TGA).Areas coveredThe authors aimed at providing a synthesis of the most current evidence about the safety profile of the recently developed and/or marketed antipsychotics. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library from inception until March 2020, combining free terms and MESH headings for the topics of TGA and recently developed and/or marketed antipsychotics as following: ((safetyOR adverse eventsOR side effects) AND ((brexpiprazoleOR cariprazineOR inhaled loxapineOR lumateperone(ITI-007) OR lurasidoneOR pimavanserinOR roluperidone(MIN-101) OR transdermal patch asenapine)).Expert opinionOverall, newer antipsychotics display a good safety profile, with a well-demonstrated lower metabolic liability compared to second-generation antipsychotics. Furthermore, TGA appear to specifically target negative symptomatology and improving cognitive domains.AbbreviationsAps=Antipsychotic Drugs; AEs = Adverse Effects; EPS = Extrapyramidal Symptoms; NMS = Neuroleptic malignant syndrome; D = Dopamine; Ki= Inhibitory Constant; 5-HT = Serotonin; ECG = Electrocardiogram; H = Histamine; M = Muscarinic; BMI = Body Mass Index

Background: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. Objective: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. Methods: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. Results: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. Conclusion: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

Snow initialization has been previously investigated as a potential source of predictability at the subseasonal‐to‐seasonal (S2S) timescale in winter and spring, through its local radiative, thermodynamical, and hydrological feedbacks. However, previous studies were conducted with low‐top models over short periods only. Furthermore, the potential role of the land surface‐stratosphere connection upon the S2S predictability had remained unclear. To this end, we have carried out twin 30‐member ensembles of 2‐month (November and December) retrospective forecasts over the period 1985–2016, with either realistic or degraded snow initialization. A high‐top version of the Norwegian Climate Prediction Model is used, based on the Whole Atmosphere Community Climate Model, to insure improved coupling with the stratosphere. In a composite difference of high versus low initial Eurasian snow, the surface temperature is strongly impacted by the presence of snow, and wave activity fluxes into the stratosphere are enhanced at a 1‐month lag, leading to a weakened polar vortex. Focusing further on 7 years characterized by a strongly negative phase of the Arctic Oscillation, we find a weak snow feedback contributing to the maintenance of the negative Arctic Oscillation. By comparing the twin forecasts, we extracted the predictive skill increment due to realistic snow initialization. The prediction of snow itself is greatly improved, and there is increased skill in surface temperature over snow‐covered land in the first 10 days, and localized skill increments in the mid‐latitude transition regions on the southern flanks of the snow‐covered land areas, at lead times longer than 30 days. Eurasian snow strongly impacts surface temperature and upward wave activity fluxHigh initial Eurasian snow favors the maintenance of the negative Arctic Oscillation though a land surface–stratosphere feedbackLocalized skill increments in surface temperature over the midlatitude snow transition regions even at lead times longer than 30 days

The clinical manifestation of COVID‐19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV‐2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can “be protective” as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection. A kidney‐transplanted patient infected with SARS‐CoV‐2 shows a mild disease despite immune suppression, leading the authors to think it may be possible that immunosuppression can be protective, as the cytokine storm is an important factor in the disease story.

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further “neurobiological targeted” approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.

Systemic mastocytosis can give very different bone pictures: from osteosclerosis to osteoporosis. Osteoporosis is one of the most frequent manifestations particularly in adults and the most clinical relevant. It is often complicated by a high recurrence of mainly vertebral fragility fractures. The main factor of bone loss is the osteoclast with a relative or absolute predominance of bone resorption. The RANK-RANKL pathway seems of key importance, but histamine and other cytokines also play a significant role in the process. The predominance of resorption made bisphosphonates, as anti-resorptive drugs, the most rational treatment of bone involvement in systemic mastocytosis.

While observed mesospheric polar nitric acid enhancements have been attributed to energetic particle precipitation through ion cluster chemistry in the past, this phenomenon is not reproduced in current whole‐atmosphere chemistry‐climate models. We investigate such nitric acid enhancements resulting from energetic electron precipitation events using a recently developed variant of the Whole Atmosphere Community Climate Model (WACCM) that includes a sophisticated ion chemistry tailored for the D‐layer of the ionosphere (50–90 km), namely, WACCM‐D. Using the specified dynamics mode, that is, nudging dynamics in the troposphere and stratosphere to meteorological reanalyses, we perform a 1‐year‐long simulation (July 2009–June 2010) and contrast WACCM‐D with the standard WACCM. Both WACCM and WACCM‐D simulations are performed with and without forcing from medium‐to‐high energy electron precipitation, allowing a better representation of the energetic electrons penetrating into the mesosphere. We demonstrate the effects of the strong particle precipitation events which occurred during April and May 2010 on nitric acid and on key ion cluster species, as well as other relevant species of the nitrogen family. The 1‐year‐long simulation allows the event‐related changes in neutral and ionic species to be placed in the context of their annual cycle. We especially highlight the role played by medium‐to‐high energy electrons in triggering ion cluster chemistry and ion‐ion recombinations in the mesosphere and lower thermosphere during the precipitation event, leading to enhanced production of nitric acid and raising its abundance by 2 orders of magnitude from 10−4to a few 10−2ppb. D‐layer ion chemistry enhances production of mesospheric nitric acid through ion cluster recombination with a seasonal maximum in winterMedium‐to‐high energy electrons precipitating into the mesosphere in April–May 2010 further enhance the formation of nitric acidOccurring at a time of year with low background abundance, the enhancement brought nitric acid abundance close to its annual cycle maximum

Energetic electrons from the magnetosphere deposit their energy in the atmosphere and lead to production of nitric oxide (NO) in the mesosphere and lower thermosphere. We study the atmospheric NO response to a geomagnetic storm in April 2010 with WACCM (Whole Atmosphere Community Climate Model). Modeled NO is compared to observations by Solar Occultation For Ice Experiment/Aeronomy of Ice in the Mesosphere at 72–82°S latitudes. We investigate the modeled NOs sensitivity to changes in energy and chemistry. The electron energy model input is either a parameterization of auroral electrons or a full range energy spectrum (1–750 keV) from National Oceanic and Atmospheric Administration/Polar Orbiting Environmental Satellites and European Organisation for the Exploitation of Meteorological Satellites/Meteorological Operational satellites. To study the importance of ion chemistry for the production of NO, WACCM‐D, which has more complex ion chemistry, is used. Both standard WACCM and WACCM‐D underestimate the storm time NO increase in the main production region (90–110 km), using both electron energy inputs. At and below 80 km, including medium‐energy electrons (>30 keV) is important both for NO directly produced at this altitude region and for NO transported from other regions (indirect effect). By using WACCM‐D the direct NO production is improved, while the indirect effects on NO suffer from the downward propagating deficiency above. In conclusion, both a full range energy spectrum and ion chemistry is needed throughout the mesosphere and lower thermosphere region to increase the direct and indirect contribution from electrons on NO. Energetic electron precipitation (EEP) in April 2010 enhanced the level of mesospheric and thermospheric nitric oxide (NO) observed by SOFIEIncluding MEE and Dregion ions increases directly produced NO and improves agreement with observations between 60 and 80 kmNeither specifications of energy input nor chemistry was able to eliminate a persistent model deficit in NO between 90 and 110 km

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

The Arctic sea ice cover has been rapidly declining in the last two decades, concurrent with a shift in the Atlantic Multidecadal Oscillation (AMO) to its warm phase around 1996/1997. Here we use both observations and model simulations to investigate the modulation of the atmospheric impacts of the decreased sea ice cover in the Atlantic sector of the Arctic (AASIC) by the AMO. We find that the AASIC loss during a cold AMO phase induces increased Ural blocking activity, a southeastward-extended snowpack, and a cold continent anomaly over Eurasia in December through northerly cold air advection and moisture transport from the Arctic. The increased Ural blocking activity and more extended Eurasian snowpack strengthen the upward propagation of planetary waves over the Siberian-Pacific sector in the lower stratosphere and hence lead to a weakened stratospheric polar vortex and a negative Arctic Oscillation (AO) phase at the surface in February. However, corresponding to the AASIC loss during a warm AMO phase, one finds more widespread warming over the Arctic and a reduced snowpack over Northern Eurasia in December. The stratosphere-troposphere coupling is suppressed in early winter and no negative AO anomaly is found in February. We suggest that the cold AMO phase is important to regulate the atmospheric response to AASIC decline, and our study provides insight to the ongoing debate on the connection between the Arctic sea ice and the AO. The AASIC loss during a cold AMO phase favors increased Ural blockings, a southeastward-extended snowpack, and cold Eurasia in DecemberThe anomalous blockings and snowpack weaken the stratospheric polar vortex via vertical wave propagation, with a negative AO in FebruaryThe AASIC loss during a warm AMO phase does not exhibit cold Eurasia in December, nor a significant negative AO in February

ObjectiveAgomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients.Methods30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in “real-world,” everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment.ResultsAgomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose.ConclusionsAgomelatine’s antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

In April 2010, a coronal mass ejection and a corotating interaction region on the Sun resulted in an energetic electron precipitation event in the Earth's atmosphere. We investigate direct and indirect nitric oxide (NO) response to the electron precipitation. By combining electron fluxes from the Total Energy Detector and the Medium Energy Proton and Electron Detector on the National Oceanic and Atmospheric Administration's Polar‐orbiting Operational Environmental Satellites, we obtain a continuous energy spectrum covering 1–750 keV. This corresponds to electrons depositing their energy at atmospheric altitudes 60–120 km. Based on the electron energy deposition, taking into account loss due to photolysis, the accumulated NO number density is estimated. When compared to NO measured at these altitudes by the Solar Occultation for Ice Experiment instrument on board the Aeronomy of Ice in the Mesosphere satellite, the NO direct effect was detected down to 55 km. The main variability at these altitudes is, however, dominated by the indirect effect, which is downward transported NO. We estimate the source of this descending NO to be in the upper mesosphere at ∼75–90 km. During the April 2010 geomagnetic storm, direct production of nitric oxide is observed down to 55 km in the polar atmosphereThe main nitric oxide number density variability at 55 km is seen 15 days after storm onset and is caused by the indirect effectThe source region for descending nitric oxide is in the upper mesosphere (∼75‐90 km), associated with medium‐energy electrons (>10 keV)

Background: A new trend among users of new psychoactive substances’ the consumption of “herbal highs”: plant parts containing psychoactive substances. Most of the substances extracted from herbs, in old centuries were at the centre of religious ceremonies of ancient civilizations. Currently, these herbal products are mainly sold by internet web sites and easily obtained since some of them have no legal restriction. Objective: We reviewed psychoactive effects and neuropharmacology of the most used “herbal highs” with characterized active principles, with studies reporting mechanisms of action, pharmacological and subjective effects, eventual secondary effects including intoxications and/or fatalities Method: The PubMed database was searched using the following key.words: herbal highs, Argyreia nervosa, Ipomoea violacea and Rivea corymbosa; Catha edulis; Datura stramonium; Piper methysticum; Mitragyna speciosa. Results: Psychoactive plants here reviewed have been known and used from ancient times, even if for some of them limited information still exist regarding subjective and neuropharmacological effects and consequent eventual toxicity when plants are used alone or in combination with “classical” drugs of abuse. Conclusion: Some “herbal highs” should be classified as harmful drugs since chronic administration has been linked with addiction and cognitive impairment; for some others taking into consideration only the recent trends of abuse, studies investigating these aspects are lacking.

Background: Evolutionary research on drug abuse has hitherto been restricted to proximate studies, considering aetiology, mechanism, and ontogeny. However, in order to explain the recent emergency of a new behavioral pattern (e.g. ‘the e-psychonaut style’) of novel psychoactive substances’ (NPS) intake, a complementary evolutionary model may be needed. Objective: A range of evolutionary interpretations on the ‘psychonaut style’ and the recent emergency of NPS were here considered. Method: The PubMed database was searched in order to elicit evolutionary theory-based documents commenting on NPS/NPS users/e-psychonauts. Results: The traditional ‘shamanic style’ use of entheogens/plant-derived compounds may present with a range of similarities with the ‘e-psychonauts’ use of mostly of hallucinogen/psychedelic NPS. These users consider themselves as ‘new/technological’ shamans. Conclusion: Indeed, a range of evolutionary mechanisms, such as: optimal foraging, costly signaling, and reproduction at the expense of health may all cooperate to explain the recent spread and diffusion of the NPS market, and this may represent a reason of concern.

One of the most challenging aspects of using nanofibrillated cellulose (NFC) for membranes production is their limited permeance. When NFC membranes are produced from aqueous suspensions, depending on their grammage, the permeances are in the range of a few decades of L/(hm2MPa) not matching satisfactory filtration times. We present a fast and sustainable solution to increase the permeances of such membranes through a combination of solvent exchange of the NFC suspension with ethanol and the use of a removable template, a mixture of calcium compounds (CC). The effect of the CC/NFC ratio was screened for various concentrations. The permeance of water could be increased by as much as 2–3 times as compared to nontemplated membranes. Further, the membranes showed the ability for penetration of water-soluble macromolecules, contaminant rejection of suspended solid particles, and thus fluids (such as orange juice) could be concentrated, with a view to applications in food industry.

Major depressive disorder is a chronic and invalidating psychiatric illness and is associated with a greater risk of suicidal behaviors. In recent decades many data have supported a biological link between depressive states and inflammation. Pro-inflammatory cytokines have been found to rise, first of all TNF-a and IL-6. Suicidal behaviors have been consistently associated with increased levels of IL-6 and decreased levels of IL-2. The aim of this review is to investigate the relationship between inflammatory markers in depressed patients with or without suicidal attempts compared to healthy controls.

Objectives Ascending aorta has an increased stiffness (AoSI) in rheumatoid arthritis (RA) patients due to their chronic inflammatory status. We assessed prevalence and factors associated with increased AoSI and its prognostic role in a large cohort of RA patients.Methods We prospectively analysed 226 RA patients without overt cardiac disease compared with 226 non-RA patients matched for cardiovascular risk factors (non-RA controls). Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation as part of a thorough echocardiography performed in all patients.Results AoSI was significantly higher in the RA patients than non-RA controls (6.3 ± 4.5% vs. 4.6 ± 3.5%, p< 0.001); it was related to older age, higher systolic blood pressure and RA disease. Predictors of AoSI in RA patients were older age, higher systolic blood pressure and the non-prescription of non-steroidal anti-inflammatory drug and/or immunomodulatory/anti-cytotoxic agents. Abnormally high AoSI was diagnosed in 41% RA patients and 21% non-RA controls (p< 0.001). The RA phenotype with abnormally high AoSI was a > 60 years old subject with systolic blood pressure > 129 mmHg, mitral annular calcification who was not receiving non-steroidal anti-inflammatory drug. By multivariate Cox regression analysis abnormally high AoSI independently predicted death or all-cause hospitalization (hazard ratio 2.85 (95% confidence interval 1.03–7.85)) at 12-month follow-up.Conclusions Increased AoSI is common, can be predicted by an ordinary clinical assessment and is a strong predictor of adverse clinical outcome at mid-term follow-up in patients with RA.

ABSTRACTIntroduction:The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/‘typical’ APs.Areas covered: We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)).Expert opinion:A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

ABSTRACTIntroduction: Among other approaches, the modulation of the dopaminergic pathway has been advocated in the therapeutic management of Alcohol Use Disorders (AUD). A potential avenue toward the modulation of the dopaminergic pathway across varying substance disorders seems to be provided by aripiprazole, a second-generation antipsychotic characterized by a peculiar pharmacodynamics signature.Areas covered: In this review, the authors provided a qualitative synthesis and a critical perspective on the efficacy of aripiprazole in relapse prevention and craving in AUD. A systematic search was carried out through MEDLINE/Embase/PsycINFO/Cochrane Library from inception until September 2015, combining free terms and MESH headings for the topics of AUD and aripiprazole as following: (((Alcohol use Disorder) OR (Alcoholuse)) AND aripiprazole).Expert opinion: Based both on a qualitative synthesis and a critical interpretation of the evidence, the authors submit that aripiprazole would promote alcohol abstinence and reduce the alcohol seeking behaviour possibly via dopaminergic and serotoninergic modulations at the fronto-subcortical circuits underpinning alcohol reward and craving, impulsive behaviour as well as reduce alcohol-related anxiety/low mood and anhedonia. However, due to the lack of published studies, a conclusive statement about any direct effect of aripiprazole in the prevention of craving and/or alcohol consumption is not possible.

Based on a climate‐chemistry model (constrained by reanalyses below ~50 km), the zonal‐mean composite response of the mesosphere and lower thermosphere (MLT) to major sudden stratospheric warming events with elevated stratopauses demonstrates the role of planetary waves (PWs) in driving the mean circulation in the presence of gravity waves (GWs), helping the polar vortex recover and communicating the sudden stratospheric warming (SSW) impact across the equator. With the SSW onset, strong westward PW drag appears above 80 km primarily from the dissipation of wave number 1 perturbations with westward period of 5–12 days, generated from below by the unstable westward polar stratospheric jet that develops as a result of the SSW. The filtering effect of this jet also allows eastward propagating GWs to saturate in the winter MLT, providing eastward drag that promotes winter polar mesospheric cooling. The dominant PW forcing translates to a net westward drag above the eastward mesospheric jet, which initiates downwelling over the winter pole. As the eastward polar stratospheric jet returns, this westward PW drag persists above 80 km and acts synergistically with the return of westward GW drag to drive a stronger polar downwelling that warms the pole adiabatically and helps reform the stratopause at an elevated altitude. With the polar wind reversal during the SSW onset, the westward drag by the quasi‐stationary PW in the winter stratosphere drives an anomalous equatorial upwelling and cooling that enhance tropical stratospheric ozone. Along with equatorial wind anomalies, this ozone enhancement subsequently amplifies the migrating semidiurnal tide amplitude in the winter midlatitudes. Westward traveling planetary waves important to the elevated stratopause (ES) evolution and the stratopause recoveryThe impact of ES events extends well across the equator, altering the tropical wind, temperature, and ozoneAfter ES events, the migrating semidiurnal tides amplify due to tropical stratospheric ozone and wind anomalies

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm and microvascular involvement. Iloprost (ILO), a prostaglandin analogous, is used for the treatment of SSc-related Raynaud’s phenomenon and digital ulcers. The suggested dose is 0.5–2 ng/kg/min for 6–8 h, and the maximum dose is decided upon the patient’s tolerance.Objectives: This study aims to analyze ILO infusion tolerance and possible predictive factors in patients with SSc.Design: This is a retrospective observational study.Method: We evaluated 113 patients with SSc beginning ILO intravenous (IV) infusion treatment between 2004 and 2021. We assessed the maximum tolerated ILO IV infusion rate, the incidence of adverse events (AEs), and the need for symptomatic therapy during the dose-finding sessions. We collected relevant demographic and medical and employed generalized linear models to assess possible predictors of maximum tolerated ILO infusion rate and AEs and logistic regression to assess predictors of AEs.Results: The median ILO infusion rate at the end of the dose-finding process was 0.88 ng/kg/min [interquartile range (IQR) = 0.37]. We found a significant inverse correlation between ILO infusion rate and body mass index (BMI) at the beginning of treatment. BMI was negatively associated with ILO infusion rate (β= −0.21, p= 0.02) after correction for relevant confounding factors. Overweight patients (BMI >26) presented a 13-fold increased risk of developing AEs during ILO titration [adjusted odds ratio = 13.979, 95% confidence interval (CI) = 2.359–82.845]. AEs during ILO titration occurred in 47.8% of patients, of whom 22.2% presented hypotension. Other AEs were headache, nausea, vomiting, diarrhea, and edema. Symptomatic therapy was needed in half of the patients at least once.Conclusion: This study showed that higher BMI was statistically associated with lower ILO infusion rate tolerance and higher AEs rate, underlying a possible BMI-dependent endothelial dysfunction. Individual ILO regimens still need to be tailored to the patient.Plain Language Summary Introduction:Systemic sclerosis is a rare a rheumatic disease characterized by skin thickening, vasospasm, and digital ulcers (DUs), as well as other organs involvement. Iloprost, which is administered as intravenous infusion, is one of the main treatments for this disease, and it is effective in reducing vasospasm and the frequency of DUs. Even if there is a suggested dose range, the exact dose must be tailored on each patient, because the tolerance to the drug is variable. Tolerance is limited by dose-dependent unwanted effects, as headache, low blood pressure, dizziness, and sickness. This study aimed to identify possible predictors of such tolerance. Materials and Methods:We collected data from our patients with systemic sclerosis beginning the treatment with iloprost between January 2004 and November 2021 at our hospital facility in Verona, Italy, and analyzed different factors that could be associated with a better tolerance, as age, sex, disease duration, smoking habit, body mass index (a measure of body fatness), blood pressure, concomitant medications, and different patterns of the disease. Results:We found that a higher body mass index was associated with lower iloprost tolerance and higher adverse events rate in patients with systemic sclerosis, while we did not find a correlation with other factors. We believe overweight and obese patients (who have a higher body mass index) have a defect in the vasodilatation mechanism and can therefore be more susceptible to the effect of this medication. Conclusions:While preliminary, our results could provide a good starting point to develop a predictive tool to limit adverse events during this therapy.