Electrophysiological Impact of SARS-CoV-2 Envelope Protein in U251 Human Glioblastoma Cells: Possible Implications in Gliomagenesis?

SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.

Single-Port Transvesical Vesico-Vaginal Fistula Repair: An Initial Experience.

INTRODUCTION: Vesicovaginal fistula (VVF) is the most common urogenital fistula due to iatrogenic cause, primarily associated with gynecologic surgery (1). Although both conservative and surgical management may be considered, the optimal treatment is still uncertain and several studies were published using different techniques (open, laparoscopic or robotic) and approaches (extravesical, transvesical or transvaginal) (2-5). In this context, we aim to report our initial experience repairing VVF with Single-Port (SP) Transvesical (TV) access. MATERIALS AND METHODS: Four patients with a diagnosis of VVF underwent SP-TV VVF repair between May 2022 and December 2023. Diagnosis was confirmed by cystoscopy, cystogram and in two cases by CT Urogram. Under general anesthesia, before robotic time, patients were placed in lithotomy position and a preliminary cystoscopy was performed. Fistula was noted and a 5fr stent was placed through the fistulous tract. Two ureteral stents were placed. Then, with patient supine, a transverse suprapubic 3cm incision and 2cm cystotomy were made for SP access. First step was to mark and remove fistula tract to the vagina. The edges of the vagina and bladder were dissected in order to have a closure free of tension and to create three different layers to close: vagina, muscularis layer of the bladder and mucosal layer of the bladder. A bladder catheter was placed, and the two ureteral stents were removed at the end of procedure. RESULTS: Mean age was 53 years old and three out of 4 patients developed VVF after gynecologic surgery. Two patients underwent VVF repair 6 and 8 months after total hysterectomy. One patient developed VVF after total hysterectomy and oophorectomy followed by radiation therapy. Last patient developed VVF after previous urological procedure. Fistula diameter was between 11 and 15mm. Operative time was 211 min, including preliminary cystoscopy, stents placement and SP-access. All patients were discharged on the same day with a bladder catheter, successfully removed between post-operative day 14-18 after negative cystogram. Only in one case a ureteral stent was left because the fistula was closed to the ureteral orifice and we reported one case of UTI twelve days after surgery, treated with outpatient antibiotics. Mean follow-up was 8 months, patients were scheduled for regular follow-up visits and no recurrence was reported. All patients have at least 3 months of post-operative follow-up. CONCLUSIONS: Our experience suggests that SP Transvesical VVF repair may be considered as a safe and feasible minimally invasive treatment for small/medium fistulae (10-15mm).

Political terrorism and affective polarization in "black" and "red" terrorists in Italy during the years 1968-1988.

Psychiatric evaluations of violent political crime were mostly performed on a case-by-case basis in a forensic environment, which made them unduly dependent on categories of presumed dangerousness and legal responsibility, rather than on a clinical definition of their mental status. In referring to such "clinical" definitions, the disorder we have in mind is not limited to the major, agitated psychotic manias or mixed states. The presence of a dominant temperament, or protracted hypomania, is enough by itself to explain an individual's engagement in a wide range of activities, not necessarily sociopathic or violent. We put forward the hypothesis that formal and transpolitical radical choices, either in favor of an illegal lifestyle or of activities involving a high level of risk, may be linked with certain mental states, especially when considering small clandestine groups showing a high level of internal ideological consensus, and a no-return attitude toward a commitment to radical choices. Available data about the psycho(patho)logical profile of terrorists are still hard to come by. The only available studies are those on identified living terrorists (judging by the trials of those who personally admitted to having been terrorists), and statistical data imply a number of documented cases belonging to the same terrorist organization. In Italy, the period often called the "years of lead [bullets]" displays an interesting viewpoint for the study of terrorist psychology, for two main reasons: first of all, it is a historically defined period (1968-1988), and second, the number of ascertained participants in terrorist activities was quite large.

Former Heroin-Dependent Alcohol Use Disorder Patients. Prevalence, Addiction History and Clinical Features.

AIMS: To examine the prevalence of former heroin dependence (FHA) in Alcohol Use Disorder (AUD) patients; to compare the clinical characteristics of FHA-AUD patients versus AUD patients without any past use of heroin at alcohol treatment entry; to document the heroin dependence history of FHA-AUD patients, and review treatment strategies for this group. METHODS: Retrospective case review of 448 consecutive AUD patients. RESULTS: The annual entry of FHA-AUD showed stability over the study period of 3 years overall 60/448 (13.3%). FHA-AUD patients showed higher concomitant use of cocaine, benzodiazepines, cannabis and hallucinogens than other heroin addicts. They consumed higher amounts of alcohol at the beginning of their alcohol dependence history, and reached a high maximum level of alcohol consumption, than other AUD patients, and tended to have more physical disorders. The most important signals of FHA-AUD were polyabuse and older age at the time of presentation. FHA-AUD patients tended to have had a severe pattern of heroin dependence associated with inadequate agonist opiate treatment. CONCLUSIONS: The prevalence of FHA-AUD patients is not negligible. This may relate to previous inadequate treatment of heroin addiction contributing to the development of severe AUD. For these patients we propose a reconsideration of 'soft' (low dose) agonist opiate treatment.

Anticonvulsants for alcohol dependence.

BACKGROUND: Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Besides psychosocial interventions, different pharmacological interventions have been or currently are under investigation through Cochrane systematic reviews. OBJECTIVES: The primary aim of the review is to assess the benefits/risks of anticonvulsants for the treatment of alcohol dependence. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Trials Register (October 2013), PubMed (1966 to October 2013), EMBASE (1974 to October 2013) and CINAHL (1982 to October 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing anticonvulsants alone or in association with other drugs and/or psychosocial interventions versus placebo, no treatment and other pharmacological or psychosocial interventions. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: A total of 25 studies were included in the review (2641 participants). Most participants were male, with an average age of 44 years. Anticonvulsants were compared with placebo (17 studies), other medications (seven studies) and no medication (two studies). The mean duration of the trials was 17 weeks (range four to 52 weeks). The studies took place in the USA, Europe, South America, India and Thailand. Variation was reported in the characteristics of the studies, including their design and the rating instruments used. For many key outcomes, the risk of bias associated with unclear or unconcealed allocation and lack of blinding affected the quality of the evidence.Anticonvulsants versus placebo: For dropouts (16 studies, 1675 participants, risk ratio (RR) 0.94, 95% confidence interval (Cl) 0.74 to 1.19, moderate-quality evidence) and continuous abstinence (eight studies, 634 participants, RR 1.21, 95% Cl 95% 0.97 to 1.52, moderate-quality evidence), results showed no evidence of differences. Moderate-quality evidence suggested that anticonvulsants reduced drinks/drinking days (11 studies, 1126 participants, mean difference (MD) -1.49, 95% Cl -2.32 to -0.65) and heavy drinking (12 studies, 1129 participants, standardised mean difference (SMD) -0.35, 95% Cl -0.51 to -0.19). Moreover, withdrawal for medical reasons (12 studies, 1410 participants, RR 1.22, 95% Cl 0.58 to 2.56, moderate-quality evidence) showed no evidence of difference, but for specific adverse effects (nine studies, 1164 participants), two of 18 adverse event outcomes favoured placebo. The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate.Anticonvulsants versus naltrexone: No evidence of difference was shown in dropout rates (five studies, 528 participants, RR 0.74, 95% CI 0.52 to 1.06), severe relapse rates (four studies, 427 participants, RR 0.69, 95% Cl 0.44 to 1.07) and continuous abstinence rates (five studies, 528 participants, RR 1.21, 95% Cl 0.99 to 1.49); anticonvulsants were associated with fewer heavy drinking days (three studies, 308 participants, MD -5.21, 95% Cl -8.58 to -1.83), more days to severe relapse (three studies, 244 participants, MD 11.88, 95% Cl 3.29 to 20.46) and lower withdrawal for medical reasons (three studies, 245 participants, RR 0.13, 95% Cl 0.03 to 0.58). AUTHORS' CONCLUSIONS: At the current stage of research, randomised evidence supporting the clinical use of anticonvulsants to treat alcohol dependence is insufficient. Results are conditioned by heterogeneity and by the low number and quality of studies comparing anticonvulsants with other medications. The uncertainty associated with these results leaves to clinicians the need to balance possible benefits/risks of treatment with anticonvulsants versus other medications as supported by evidence of efficacy.

Is early continence recovery related to the length of spared urethra? A prospective multicenter study comparing preoperative MRI and histologic specimen measurements after robotic radical prostatectomy.

BACKGROUND: Urinary incontinence (UI) is a common complication after radical prostatectomy, significantly affecting patients' quality of life. This study aimed to correlate the length of preserved urethra in robotic radical prostatectomy (RALP) patients with short-term urinary continence rates within 90 days post-surgery. METHODS: A prospective multicentric study enrolled 190 prostate adenocarcinoma patients undergoing RALP. Using preoperative magnetic resonance imaging (mpMRI), urethral length was measured from the external urethral sphincter to the bladder neck. After surgery, histological measurements of the removed urethra were compared to the preoperative mpMRI data. Patients were categorized into two groups at the three-month follow-up based on urinary continence assessed through Urodynamic Study (UDS): Group A (94 patients without UI) and Group B (96 patients with UI). RESULTS: Results revealed a significant difference in mean UI recovery time (Group A: 12.35 days, SD: 3.09 vs. Group B: 93.86 days, SD: 34.8, p < 0.0001). A ROC curve identified a 16.5% cut-off value (p < 0.000, sensitivity 87.5%, specificity 91.8%). Both groups showed a significant negative correlation between preserved urethral percentage and UI recovery time (Group A: r -0.655, p < 0.0001; Group B: r -0.340, p: 0.017). Group A had an average of 21.52% preserved urethra, while Group B had 13.86% (p < 0.0001). At one-year follow-up, 93.2% overall patients reported urinary continence without pads. CONCLUSIONS: This study emphasizes the positive correlation between preserved urethra percentage in RALP and early urinary continence recovery, highlighting its surgical significance.

QTc interval screening for cardiac risk in methadone treatment of opioid dependence.

BACKGROUND: Methadone represents today the gold standard of efficacy for the pharmacological treatment of opioid dependence. Methadone, like many other medications, has been implicated in the prolongation of the rate-corrected QT (QTc) interval of the electrocardiogram (ECG), which is considered a marker for arrhythmias such as torsade de pointes (TdP). Indications on the association between methadone, even at therapeutic dosages, and TdP or sudden cardiac death have been reported. On these bases, consensus and recommendations involving QTc screening of patients receiving methadone treatment have been developed to identify patients with QTc above the thresholds considered at risk for cardiac arrhythmias, and they provide these individuals with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors). OBJECTIVES: To evaluate the efficacy and acceptability of QTc screening for preventing cardiac-related morbidity and mortality in methadone-treated opioid dependents. SEARCH METHODS: We searched MEDLINE, EMBASE, CINAHL (to April 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library Cochrane Drug and Alcohol Review Group Specialised Register (Issue 3, 2013), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers. SELECTION CRITERIA: Randomised controlled trials (RCTs), controlled clinical trials (CCTs) and non-randomised studies (cohort studies, controlled before and after studies, interrupted time series studies, case control studies) examining the efficacy of QTc screening for the prevention of methadone-related mortality and morbidity in opioid addicts. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and extracted data from studies. MAIN RESULTS: The search strategy led to the identification of 872 records. Upon full-text assessment, no study was found to meet the quality criteria used for this review. AUTHORS' CONCLUSIONS: It is not possible to draw any conclusions about the effectiveness of QTc screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying the associated benefits and harms.

Negative dimension in psychiatry. Amotivational syndrome as a paradigm of negative symptoms in substance abuse.

Negative symptoms, conceptualized as clinical manifestations of schizophrenia, and subsequently described in other psychiatric disorders, include the loss of normal arousal, drive and affective reactivity. In the field of substance abuse, an interesting analogy can be detected between negative symptoms, in their classical meaning, and the amotivational syndrome (AS), which has been described as a form of chronic cannabis intoxication. AS also shows a close resemblance to the reward deficiency syndrome (RDS) of alcoholics and stimulant abusers, and to the post-withdrawal syndrome (PWS) of detoxified heroin addicts. A variety of substances share a common tropism for the dopaminergic system, leading to a state of hypophoria, which seems to represent a common pathway for chronic substance abusers. In the light of these convergences, a common treatment principle for addictive disorders can be enunciated. This consists in resorting to pro-dopaminergic drugs, that are supposed to replace damaged functions and control craving, and in avoiding anti-dopaminergic drugs, that are expected to exacerbate craving and impede the reversal of the reward deficiency.

Characteristics of Stress Sensitivity in Heroin Use Disorder Patients during Their Opioid Agonist Treatment.

In the present study, performed on a sample of Heroin Use Disorder (HUD) patients undergoing Opioid Agonist Treatment (OAT), we attempted to explore the relationships between stress sensitivity and heroin addiction-related clinical aspects. HUD patients' stress sensitivity was evaluated with the Heroin/PTSD-Spectrum questionnaire (H/PSTD-S). The Drug Addiction History Questionnaire (DAH-Q), the Symptomatological Check List-90 (SCL-90), and The Behavioural Covariate of Heroin Craving inventory (CRAV-HERO) were all used, as were the Deltito Subjective Wellness Scale (D-SWS), a self-report scale evaluating subjective well-being; the Cocaine Problem Severity Index (CPSI), a questionnaire determining the extent of a cocaine problem; and the Marijuana Craving Questionnaire (MC-Q), an instrument assessing craving for cannabinoids. We checked correlations between stress sensitivity and the extent of HUD clinical features and compared patients with and without problematic stress sensitivity. H/PTSD-S was positively correlated with patients' income, altered mental status, legal problems, the lifetime different treatments index, the current treatment load index, and all SCL-90 indexes and factors. Regarding subjective well-being, stress sensitivity negatively correlated with the contrast best week (last five years) index. Patients with high-stress sensitivity were females with a low income. They exhibited a more severe mental status at treatment entry, greater difficulty in working adaptation, and legal problems during treatment. Additionally, these patients showed a higher level of psychopathology, more impairment in well-being, and more risky behaviours during treatment. Stress sensitivity, as H/PTSD-S, must be considered an outcome of HUD. HUD's addiction history and clinical features are significant risk factors for H/PTSD-S. Therefore, social and behavioural impairment in HUD patients could be considered the clinical expression of the H/PTSD spectrum. In summary, the long-term outcome of HUD is not represented by drug-taking behaviours. Rather, the inability to cope with the contingent environmental conditions is the key feature of such a disorder. H/PTSD-S, therefore, should be seen as a syndrome caused by an acquired inability (increased salience) concerning regular (daily) life events.

Fluorescence Confocal Microscopy in Urological Malignancies: Current Applications and Future Perspectives.

Fluorescence confocal microscopy (FCM) represents a novel diagnostic technique able to provide real-time histological images from non-fixed specimens. As a consequence of its recent developments, FCM is gaining growing popularity in urological practice. Nevertheless, evidence is still sparse, and, at the moment, its applications are heterogeneous. We performed a narrative review of the current literature on this topic. Papers were selected from the Pubmed, Embase, and Medline archives. We focused on FCM applications in prostate cancer (PCa), urothelial carcinoma (UC), and renal cell carcinoma (RCC). Articles investigating both office and intraoperative settings were included. The review of the literature showed that FCM displays promising accuracy as compared to conventional histopathology. These results represent significant steps along the path of FCM's formal validation as an innovative ready-to-use diagnostic support in urological practice. Instant access to a reliable histological evaluation may indeed significantly influence physicians' decision-making process. In this regard, FCM addresses this still unmet clinical need and introduces intriguing perspectives into future diagnostic pathways. Further studies are required to thoroughly assess the whole potential of this technique.

Clinical presentations of substance abuse in bipolar heroin addicts at time of treatment entry.

BACKGROUND: Studies on the 'self-medication hypothesis' have focused on substance abuse as an attempt to alleviate emotional suffering. METHODS: We have investigated concomitant substances of abuse in 150 bipolar heroin addicts clustered according to their clinical presentation at treatment entry (depressive episode, hypomanic episode, manic episode and mixed episode). Bipolar heroin addicted patients were chosen because they tend to have a concomitant poly-substance abuse and because, as compared with patients suffering for other mental illnesses, they more clearly reveal a variety of identifiable affective states. RESULTS: Patients with a depressive episode more frequently used non-prescribed anxiolytic-hypnotics. They were found to use cocaine-amphetamines more frequently during a hypomanic episode, whereas the use of cannabis and cocaine-amphetamines occurred more frequently during a manic episode. The associated use of alcohol, cocaine-amphetamines and cannabinoids was more frequently encountered during a mixed episode. LIMITATIONS: apart from the difficulty in determining whether the substance use modifies the mood or the mood state determines the substance used, this is a report on a retrospective analysis, rather than a study specifically designed to elucidate the issue; in addition, no information was available on the temperament of our subjects. Assessments of the same subject in various clinical presentations would have provided a better level of information. CONCLUSIONS: Besides one expected result - the prominent use of CNS stimulants during a depressive phase of bipolar patients - this study supports the hypothesis that mood elation is a pleasurable, rewarding experience that, in bipolar patients, can be started or prolonged by means of CNS stimulant drugs. Stimulant use was, therefore, more prevalent during the 'up' rather than the 'down' phase of the illness.

Effect of psychiatric severity on the outcome of methadone maintenance treatment.

While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.

Do methadone and buprenorphine have the same impact on psychopathological symptoms of heroin addicts?

BACKGROUND: The idea that the impact of opioid agonist treatment is influenced by the psychopathological profile of heroin addicts has not yet been investigated, and is based on the concept of a specific therapeutic action displayed by opioid agents on psychopathological symptoms. In the present report we compared the effects of buprenorphine and methadone on the psychopathological symptoms of 213 patients (106 on buprenorphine and 107 on methadone) in a follow-up study lasting 12 months. METHODS: Drug addiction history was collected by means of the Drug Addiction History Rating Scale (DAH-RS) and psychopathological features were collected by means of the Symptom Checklist-90 (SCL-90), using a special five-factor solution. Toxicological urinalyses were carried out for each patient during the treatment period. RESULTS: No statistically significant differences were detected in psychopathological symptoms, including 'worthlessness-being trapped', 'somatization', and 'panic-anxiety'. Methadone proved to be more effective on patients characterized by 'sensitivity-psychoticism', whereas buprenorphine was more effective on patients displaying a 'violence-suicide' symptomatology. CONCLUSIONS: Heroin-dependent patients with psychiatric comorbidities may benefit from opioid agonist treatment not only because it targets their addictive problem, but also, precisely due to this, because it is effective against their mental disorder too.

Mood stabilizers in the treatment of substance use disorders.

Individuals suffering from drug addiction may also manifest features of bipolar spectrum disorders. Hyperthymic and cyclothymic temperaments may render individuals vulnerable to later development of substance abuse. Bipolar disorders themselves may be altered or precipitated by substance use, most notably by stimulants (amphetamines), alcohol, and cannabinoids. The clinical usefulness of mood stabilizers, particularly antiepileptics, has been established as safe and effective in substance abusers with and without comorbid mood disorders. Most studies on this issue have been of short duration and focused on the resolution of a currently manifest period of illness. Few studies have been conducted on the usefulness of these drugs on the long-term longitudinal course of these diseases, such as frequently encountered recurrent relapses into states of agitation, impulsivity, and/or dissatisfaction. As opposed to the clinical experience with traditional antidepressants and neuroleptics, antiepileptics do not induce counter-polar states (depressed patients abruptly turning manic or hypomanic; nor patients currently hypomanic or manic turning abruptly depressed). Many clinicians consider antiepileptic mood stabilizers to be the preferred category of medications for the treatment of such patients. Valproate appears to be a potentially fruitful medication to study in these dual diagnosis patients due to preliminary evidence demonstrating its anticraving efficacy.

Subtyping patients with heroin addiction at treatment entry: factor derived from the Self-Report Symptom Inventory (SCL-90).

BACKGROUND: Addiction is a relapsing chronic condition in which psychiatric phenomena play a crucial role. Psychopathological symptoms in patients with heroin addiction are generally considered to be part of the drug addict's personality, or else to be related to the presence of psychiatric comorbidity, raising doubts about whether patients with long-term abuse of opioids actually possess specific psychopathological dimensions. METHODS: Using the Self-Report Symptom Inventory (SCL-90), we studied the psychopathological dimensions of 1,055 patients with heroin addiction (884 males and 171 females) aged between 16 and 59 years at the beginning of treatment, and their relationship to age, sex and duration of dependence. RESULTS: A total of 150 (14.2%) patients with heroin addiction showed depressive symptomatology characterised by feelings of worthlessness and being trapped or caught; 257 (24.4%) had somatisation symptoms, 205 (19.4%) interpersonal sensitivity and psychotic symptoms, 235 (22.3%) panic symptomatology, 208 (19.7%) violence and self-aggression. These dimensions were not correlated with sex or duration of dependence. Younger patients with heroin addiction were characterised by higher scores for violence-suicide, sensitivity and panic anxiety symptomatology. Older patients with heroin addiction showed higher scores for somatisation and worthlessness-being trapped symptomatology. CONCLUSIONS: This study supports the hypothesis that mood, anxiety and impulse-control dysregulation are the core of the clinical phenomenology of addiction and should be incorporated into its nosology.

Differential substance abuse patterns distribute according to gender in heroin addicts.

This study attempts to analyse potential gender differences among a group of heroin addicts seeking treatment at a university-based medical centre. The central modality of treatment at this centre is the use of methadone maintenance. Among those patients entering this program there seems to be an emerging pattern of males who tend to use heroin as their opiate of choice, and are more likely to combine it with cannabis, while females are more likely to use to street methadone, with adjunctive use of ketamine, benzodiazepines, hypnotic drugs and/or amphetamines. Women are at higher risk of abusing opioids through a pathway of initial prescription painkiller use, and later to resort to street methadone to cope with prescription pain killer addiction. This latter pattern seems to result in an increased risk for fatal accidental overdoses. The use of these longer-acting agents in women may be influenced by psychosocial and hormonal factors.

The Conceptual Framework of Dual Disorders and Its Flaws.

When psychiatric illness and substance use disorder coexist, the clinical approach to the patient is, unsurprisingly, awkward. This fact is due to a cultural context and, more directly, to the patient's psychiatric condition and addiction behaviors-a situation that does not favor a scientific approach. In dual disorder facilities, several types of professionals work together: counselors, social workers, psychologists, and psychiatrists. Treatment approaches vary from one service to another and even within the same service. It is crucial to provide dual disorder patients with multiple treatments, comprising hospitalization, rehabilitative and residential programs, case management, and counselling. Still, when treating dual disorder (DD) heroin use disorder (HUD) patients, it is advisable to follow a hierarchical algorithm. First, we must deal with addiction: by detoxification, whenever possible. This means starting most patients on anti-craving pharmacological maintenance, though aversion therapy may be appropriate for a few of them. Opiate antagonists may be used with heroin-addicted patients as long as those patients are only mildly ill. In contrast, agonist opioid medications, i.e., buprenorphine and methadone suit moderately and severely ill patients, respectively. Achieving control of mood instability or psychotic episodes is the next step, to be followed by a prevention strategy to counteract residual cravings and dominate mood disorders or psychotic episodes through long-term pharmacological maintenance that is focused on a double target.

Delineating the Psychic Structure of Substance Use and Addictions, from Neurobiology to Clinical Implications: Ten Years Later.

The diagnosis of substance use disorder is currently based on the presence of specifically identified behavioral symptoms. In addition, other psychiatric signs and symptoms accompany addictive behavior, contributing to the full picture of patients' psychopathologic profile. Historically, such symptoms were confined within the framework of "comorbidity", as comorbid psychiatric disorders or personality traits. However, an alternative unitary view of the psychopathology of addiction, inclusive of related psychiatric symptoms, has been claimed, with the support of epidemiological, neurobiological, and neuropsychological evidence. In the present article, we highlight the research advancements that strengthen this unified perspective. We then give an account of our group's definition of a specific SCL-90-based construct of the psychopathology of addiction. Lastly, we discuss the benefits that can be expected to be acquired in the evaluation and treatment of patients with a longitudinal approach including psychological/psychiatric predisposing features, addictive behavior, and psychiatric manifestations.

What we have learned from the Methadone Maintenance Treatment of Dual Disorder Heroin Use Disorder patients.

Mental Disorders and Heroin Use Disorder (HUD) often co-occur and constitute correlated risk factors that the authors believe are best considered from a unitary perspective. In this article we review and discuss data collected by the V.P. Dole Research Group in Dual Disorder (V.P. Dole DD-RG) patients according to the following six discussion points: (1) Treatment of personality disorders during Methadone Maintenance Treatment (MMT); (2) Treatment of Mood Disorders during MMT; (3) Treatment of Anxiety Disorders during MMT; (4) Treatment of Psychotic Disorders during MMT; (5) Treatment of violence during MMT; (6) Treatment of Alcohol Use Disorder (AUD) during MMT. In treating Mood Disorder in HUD patients, we must bear in mind the interactions (potentiation and side effects) between psychopharmacology, used substances and agonist opioid medications; the use of psychiatric medications as an anti-craving drug, and the possible use of agonist and antagonist opioid medications in treating the other mental disorders. In treating chronic psychosis in HUD patients, we must consider the potentiation and side effects of antipsychotic drugs consequent on HUD treatment, worsening addiction hypophoria and inducing a more severe reward deficiency syndrome (RDS) in hypophoric patients. Violence and AUD during MMT can benefit from adequate dosages of methadone and co-medication with Sodium gamma-hydroxybutyrate (GHB). The experience of our V.P. Dole DD-RG suggests the following: (a) DD is the new paradigm in neuroscience in deepening our understanding of mental health; (b) To successfully treat DD patients a double competence is needed; (c) In managing DD patients priority must be given to Substance Use Disorder (SUD) treatment (stabilizing patients); (d) Antidepressant use is ancillary to SUD treatment; antipsychotic use must be restricted to acute phases; mood stabilizers must be preferred; any use of Benzodiazepines (BDZs) must be avoided.

Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health.

Background: In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim: To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use. Methods: An electronic search was carried out on the Medline/PubMed and Google Scholar databases to find selected search terms. Results: Some NPSs are already controlled, while others can be legally sold directly on the drug market (mainly via internet, less so by drug dealers) or be used as precursors for the synthesis of other designer drugs that mimic the psychoactive effects of controlled substances. Potential side-effects of NSOs include miosis, sedation, respiratory depression, hypothermia, inhibition of gastrointestinal propulsion, death (from opioid overdose). Conclusions: The severity of the opioid crisis has intensified with the introduction of highly potent NSOs on the drug market. As long as addicts are dying from overdose or similar causes, there is something more constructive to do than waiting for addicts to overdose on heroin at a place located near a remedy, as if to say, within reach of naloxone.