Physical and cognitive correlates, inflammatory levels, and treatment response in post-COVID-19 first-onset vs. recurrent depressive episodes.

Psychiatric symptoms have been frequently reported in patients affected by COVID-19, both as new occurring and recurrences of pre-existing diseases. Depressive symptoms are estimated to affect at least 30% of patients following infection, with specific physical and cognitive features and relevant immune-inflammatory alterations. This study aimed to retrospectively characterize post-COVID-19 first-onset and recurrent major depressive episodes (MDE) and to evaluate the effects of antidepressants on physical and cognitive correlates of depression, in addition to mood, anxiety, and underlying inflammatory status. We evaluated 116 patients (44.8% males, 51.1 ± 17 years) with post-COVID-19 first-onset (38.8%) and recurrent (61.2%) MDE at baseline and after one- and three-month treatment with antidepressants (31% SSRIs, 25.9% SNRIs, 43.1% others). We assessed sociodemographic and clinical features and psychopathological dimensions through: Hamilton Depression and Anxiety Rating Scales; Short Form-36 Health Survey Questionnaire; Perceived Deficits Questionnaire-Depression 5-items. The systemic immune-inflammatory index was calculated to measure inflammation levels. Alongside the reduction of depression and anxiety (p < 0.001), physical and cognitive symptoms improved (p < 0.001) and inflammatory levels decreased (p < 0.001) throughout treatment in both groups. Post-COVID-19 recurrent MDE showed a significantly more severe course of physical and cognitive symptoms and persistently higher levels of inflammation than first-onset episodes. Antidepressants proved to be effective in both post-COVID-19 first-onset and recurrent MDE. However, a sustained inflammatory status might blunt treatment response in patients with recurrent depression in terms of physical correlates and cognition. Therefore, personalized approaches, possibly involving combinations with anti-inflammatory compounds, could promote better outcomes in this clinical population.

Evaluating Craving in Alcohol Use Disorder: Psychometric Characteristics of the Craving Typology Questionnaire-15 (CTQ-15).

AIMS: The Craving Typology Questionnaire (CTQ) is a psychometric instrument used to assess alcohol craving in normal controls and subjects with alcohol use disorder (AUD). It allows a dimensional self-rating assessment of craving according to a three-pathway psychobiological model of craving distinguishing craving into a reward, relief and obsessive component. The aim of the present study is to evaluate psychometric properties of the CTQ-15, a revised version of CTQ with 15 items. METHODS: The CTQ-15 was firstly administered to two groups of control subjects, one (414 subjects) used for the exploratory factor analysis and the other one (415 subjects) for the confirmatory factor analysis. A three-factor model was assessed and compared to alternative models. RESULTS: The resulting structure was in line with the original scale CTQ. Obsessive craving accounted for 15.20% of the total variance, relief craving for the 13.99% and reward craving for 13.13% of the total variance. The three-factor model (M1) reached good fit indices (CFI = 0.96, TLI = 0.95, RMSEA = 0.06 and SRMR = 0.05) and was significantly better than other alternative models. Reliability showed good internal consistency for each scale, i.e. obsessive craving (α = 0.92), relief craving (α = 0.82) and reward craving (α = 0.81). CONCLUSIONS: The CTQ-15 proved to be reliable and practical for identifying the three dimensions of craving in clinical practice. Craving plays a crucial role in the mechanisms of dependence and relapse; thus, characterizing the craving can be fundamental to a targeted drug therapy.

Effect of vortioxetine in subjects with major depressive and alcohol use disorders: a 6-month retrospective analysis.

BACKGROUND: Major depressive disorder (MDD) and alcohol use disorder (AUD) are highly comorbid, with greater clinical complexity and psychosocial impairment. Several antidepressants have been used in this population, with mixed results. This preliminary study aims to investigate the effects of the multimodal antidepressant vortioxetine in MDD + AUD subjects. METHODS: We retrospectively evaluated 57 MDD + AUD and 56 MDD outpatients, matched for baseline characteristics. Patients were assessed after 1, 3, and 6 months treatment with vortioxetine (10-20 mg/d, flexibly dosed) in combination with continuous psychosocial support. The primary outcome was improvement in depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale. We also investigated changes in anxiety, anhedonia, cognition, functioning, quality of life, and clinical global severity using the following instruments: Hamilton Anxiety Rating Scale, Snaith-Hamilton Pleasure Scale, Digit Symbol Substitution Test, Perceived Deficits Questionnaire-Depression, Functioning Assessment Short Test, Quality of Life Index, and Clinical Global Impression-Severity Scale. RESULTS: Vortioxetine significantly improved mood in MDD + AUD patients (P < .001), with no differences when compared to MDD (P = .36). A substantial rate (45.6%) of comorbid subjects obtained clinical remission at endpoint (P = .36 vs MDD). We additionally observed baseline to endpoint improvements on all secondary outcomes (P < .001), with no significant difference between groups. Overall, vortioxetine was safe and well tolerated. CONCLUSIONS: Given its effectiveness on mood, cognition, and functioning, its good safety and tolerability profile, and low potential for abuse, vortioxetine could represent a valid pharmacological intervention in MDD + AUD patients as part of an integrated therapeutic-rehabilitation program.

Predictors of clinical severity in subjects attending the Emergency Department for substance use: a ten-year cross-sectional study.

OBJECTIVE: Substance-related referrals to the Emergency Department (ED) are rising. Multiple substance use is frequent, and psychiatric patients represent a high-risk population. Our study aimed at identifying risk factors for increased severity in ED attendances for substance use. METHODS: We retrospectively evaluated consecutive patients attending the ED over ten years for substance-related problems, subdivided according to the triage code as having a life-threatening (LT), potentially life-threatening (P-LT), and non-life-threatening (N-LT) condition. RESULTS: Substance/drug intake for deliberate self-harm was a risk factor for being classified as LT compared to both P-LT (OR = 6.357; p ≤ 0.001) and N-LT (OR = 28.19; p ≤ 0.001). Suicide attempts (OR = 4.435; p = 0.022) and multiple substance use (OR = 1.513; p = 0.009) resulted as risk factors for P-LT, compared to N-LT. Psychiatric diagnosis (OR = 1.942; p = 0.042) and multiple substance use (OR = 1.668; p = 0.047) were risk factors for being classified as LT rather than N-LT. CONCLUSIONS: In our sample, self-harming overdoses were the strongest risk factor for highest overall severity in a real-world setting. Psychiatric disorders and multiple substance use also increased the risk for greater severity at presentation. Substance use worsens patients' clinical picture and management, suggesting the need for consultation-liaison psychiatry services in emergency contexts and highlighting the role of EDs as key sites for identification and early intervention.

Emotional dysregulation mediates the impact of childhood trauma on psychological distress: First Italian data during the early phase of COVID-19 outbreak.

BACKGROUND: The coronavirus disease 2019 pandemic represents an unprecedented traumatic stressor to mental health. Psychological distress is considered a reliable proxy for psychopathology and can be negatively influenced by childhood trauma through sensitization effects. Emotion dysregulation has been proposed as a potential mediator of this mechanism. We aimed to test this hypothesis in a national Italian sample assessed in the early phase of the coronavirus disease 2019 outbreak. METHODS: We investigated the relationship between psychological distress and childhood trauma in 500 healthy participants assessed through a survey-based study, after the coronavirus disease 2019 pandemic lockdown in Italy. Levels of psychological distress and history of childhood trauma were obtained using the Kessler-10 (K10) and the Childhood Trauma Questionnaire, respectively. We used bootstrapped mediation analysis to test the mediator role of emotional dysregulation, measured through the Difficulties in Emotion Regulation Scale, on the effect of childhood trauma on psychological distress. RESULTS: In total, 190 (38%) reported psychological distress related to the coronavirus disease 2019 outbreak. Individuals with psychological distress experienced more childhood trauma, specifically emotional abuse (F = 23.51, df = 1, p < 0.001) and neglect (F = 10.98, df = 1, p = 0.001). After modelling the effect of emotional dysregulation, the impact of childhood trauma on coronavirus disease 2019-related psychological distress resulted in indirect effects and mediated by deficits in emotion regulation mechanisms (bootstrapped lower level of confidence interval = 0.345, upper level of confidence interval = 0.598). CONCLUSION: Childhood trauma is associated with increased vulnerability to the stressful effect of the coronavirus disease 2019 outbreak. Our data suggest that emotional dysregulation may represent a dimension mediating the impact of childhood trauma on coronavirus disease 2019-related psychological distress and may be considered as specific target for interventions aiming at empowering resilience.

Affective temperament, attachment style, and the psychological impact of the COVID-19 outbreak: an early report on the Italian general population.

The outbreak of COVID-19 is severely affecting mental health worldwide, although individual response may vary. This study aims to investigate the psychological distress perceived by the Italian general population during the early phase of the COVID-19 pandemic, and to analyze affective temperament and adult attachment styles as potential mediators. Through an online survey, we collected sociodemographic and lockdown-related information and evaluated distress, temperament, and attachment using the Kessler 10 Psychological Distress Scale (K10), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire short version (TEMPS-A) and the Attachment Style Questionnaire (ASQ). In our sample (n = 500), 62% of the individuals reported no likelihood of psychological distress, whereas 19.4% and 18.6% displayed mild and moderate-to-severe likelihood. Cyclothymic (OR: 1.24; p < 0.001), depressive (OR: 1.52; p < 0.001) and anxious (OR: 1.58; p = 0.002) temperaments, and the ASQ "Need for approval" (OR: 1.08; p = 0.01) were risk factors for moderate-to-severe psychological distress compared to no distress, while the ASQ "Confidence" (OR: 0.89; p = 0.002) and "Discomfort with closeness" were protective (OR: 0.92; p = 0.001). Cyclothymic (OR: 1.17; p = 0.008) and depressive (OR: 1.32; p = 0.003) temperaments resulted as risk factors in subjects with moderate-to-severe psychological distress compared to mild distress, while the ASQ "Confidence" (OR: 0.92; p = 0.039) and "Discomfort with closeness" (OR: 0.94; p = 0.023) were protective. Our data indicated that a relevant rate of individuals may have experienced psychological distress following the COVID-19 outbreak. Specific affective temperament and attachment features predict the extent of mental health burden. To the best of our knowledge, these are the first data available on the psychological impact of the early phase of the COVID-19 pandemic on a sizeable sample of the Italian population. Moreover, our study is the first to investigate temperament and attachment characteristics in the psychological response to the ongoing pandemic. Our results provide further insight into developing targeted intervention strategies.

Elimination of Pseudomonas aeruginosa through Efferocytosis upon Binding to Apoptotic Cells.

For opportunistic pathogens such as Pseudomonas aeruginosa, the mucosal barrier represents a formidable challenge. Infections develop only in patients with altered epithelial barriers. Here, we showed that P. aeruginosa interacts with a polarized epithelium, adhering almost exclusively at sites of multi-cellular junctions. In these sites, numerous bacteria attach to an extruded apoptotic cell or apoptotic body. This dead cell tropism is independent of the type of cell death, as P. aeruginosa also binds to necrotic cells. We further showed that P. aeruginosa is internalized through efferocytosis, a process in which surrounding epithelial cells engulf and dispose of extruded apoptotic cells. Intracellularly, along with apoptotic cell debris, P. aeruginosa inhabits an efferocytic phagosome that acquires lysosomal features, and is finally killed. We propose that elimination of P. aeruginosa through efferocytosis is part of a host defense mechanism. Our findings could be relevant for the study of cystic fibrosis, which is characterized by an exacerbated number of apoptotic cells and ineffective efferocytosis.

ProEx C as Diagnostic Marker for Detection of Urothelial Carcinoma in Urinary Samples: A Review.

The gold standard for the detection of urothelial carcinoma is represented by urethro-cystoscopy and biopsy. Both procedures are invasive and expensive and therefore cytology is often used as first approach to investigate on a possible neoplasia, being a safe and cost-effective diagnostic modality of evaluation. Because cytology alone is not highly sensitive for detection of low grade urothelial carcinoma and recurrence of the disease, several adjunct markers and urine based tests for urothelial carcinoma have been developed, which can help in the final diagnosis. In particular, ProEx C is an immunohistochemical cocktail containing antibodies direct against topoisomerase IIα (TOP2A) and minichromosome maintenance 2 (MCM2) proteins. It proved to be a valid biomarker especially in detecting squamous intraepithelial lesions in cervical liquid-based samples and in discerning these lesions from their mimickers, as well as in ovarian, endometrial, vulvar, primary and metastatic melanomas, breast, pancreatic and renal cell carcinomas. This brief review covers the effective utility of ProEx C as adjunct tool in assessing the urothelial lesions in urine cytology, also providing prognostic and therapeutic information to help in clinical decisions.

Influence of temperament and emotional dysregulation on depressive symptoms in adults with attention-deficit/hyperactivity disorder: A structural equation modelling analysis.

OBJECTIVE: Depressive symptoms in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) are common. Clinical evidence suggests that affective temperaments and emotional dysregulation are reasonable putative explanatory factors of this association. In this study, we thus investigated the role of these features in influencing concomitant depressive symptoms in adults with ADHD. METHODS: Outpatients with ADHD were consecutively enrolled. Depressive symptoms were measured by the Symptom Checklist-90 Revised (SCL-90-R), while the Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) was used to assess the affective temperament dimensions. We tested emotional dysregulation using the Difficulties in Emotion Regulation Scale (DERS). Structural equation modeling was performed to test the interplay between temperament, emotional dysregulation, and depressive symptoms, accounting for other clinical variables that showed an association with depressive symptoms at univariate level. RESULTS: A total of 164 individuals with ADHD (mean age of 29.8 ± 10.7 years), of which 61 (37.2%) women, were recruited. Data showed that, accounting for the possible influence of psychopharmacological treatment and ADHD severity, both emotional dysregulation (p < 0.001) and dysthymic temperament (p = 0.003), though not other affective temperament dimensions, might influence depressive symptoms in people with ADHD. CONCLUSIONS: Despite some limitations, our study emphasizes the role of dysthymic temperament and emotional dysregulation in contributing to levels of depressive symptoms among individuals with ADHD. A comprehensive temperament assessment in adults with ADHD can offer valuable insights for developing tailored treatment strategies and enhancing overall patient care.

Childhood sexual abuse and suicide attempts in patients with substance use disorders: The mediating role of emotion dysregulation.

BACKGROUND: Suicide attempts (SA) are a public health concern because of increasing prevalence and clinical implications. Childhood trauma (CT) and emotion dysregulation (ED) have been proposed as predictors of SA, but few data are available in patients with Substance Use Disorder (SUD). OBJECTIVE: Our study aims to investigate the association of sociodemographic/clinical variables, CT typologies, and ED features with SA in SUD patients. PARTICIPANTS AND SETTING: Subjects with SUD were screened in an outpatient setting. The final sample consisted of 226 patients, subdivided according to the presence of lifetime SA (SUD, n = 163 vs. SUD-SA, n = 63). METHODS: Participants were compared for sociodemographic and clinical information. CT and ED were assessed through the Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Difficulties in Emotion Regulation Scale (DERS), respectively. We performed a mediation analysis to test the effect of CT and ED on SA. RESULTS: Patients with a history of SA (27.9 %) displayed more psychiatric comorbidities (p = 0.002) and hospitalizations (p < 0.001), higher scores at CTQ-SF sexual abuse (p < 0.001) and DERS 'impulse' (p = 0.002), 'goals', 'non-acceptance', 'strategies' (p < 0.001) subscales. The relationship between CTQ-SF sexual abuse and SA was significantly mediated by DERS 'strategies' (p = 0.04; bootstrapped 95 % LLCI-ULCI = 0.004-0.024). CONCLUSIONS: CT and different dimensions of ED were associated with SA in SUD patients. In our sample, the effects of childhood sexual abuse on SA were mediated by limited access to emotion regulation strategies. SUD patients are burdened with higher all-cause mortality, and CT and lifetime SA can worsen clinical outcomes. Clarifying the reciprocal interactions of psychopathological dimensions may help deliver targeted interventions and reduce suicide risk in specific populations.

3-Methoxy-Phencyclidine Induced Psychotic Disorder: A Literature Review and an 18F-FDG PET/CT Case Report.

New Psychoactive Substances (NPS) are modifying the drug scenario worldwide and have become a public health concern because of their toxicological profiles and their harmful physical/psychological effects. 3-Methoxy-Phencyclidine (3-MeO-PCP), a non-competitive antagonist of glutamate N-methyl-D-aspartate (NMDA) receptors, belongs to the phencyclidine-like subfamily of arylcyclohexylamines and has gained attention for its toxic, sometimes fatal, effects. Despite several cases of intoxication and death reported in the literature, little is known about substance-induced psychotic disorders (SIP) and potential cognitive impairment following 3-MeO-PCP intake. This literature review aimed to summarize available evidence about 3-MeO-PCP mechanisms of action and physical and psychotropic effects and to spread preliminary findings about persistent psychotic symptoms and impaired cognitive functioning. Additionally, the case of an SIP is reported in a 29-year-old man with small oral intakes of 3-MeO-PCP over two weeks until a high dose ingestion. Psychometric and neuropsychological assessment and brain [18F]-fluorodeoxyglucose positron emission tomography integrated with computed tomography were used to support clinical description. Identifying and addressing the characteristic clinical features and neural substrates of NPS-induced psychoses might help clinicians with a more precise differentiation from other psychotic disorders. Although further studies are required, phenotyping the cognitive profile of NPS users might provide targets for tailored therapeutic approaches.

Substance use disorders in adults with attention-deficit/hyperactivity disorder: The role of affective temperament.

OBJECTIVE: Substance Use Disorders (SUD) are common in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Although predictors of SUD in this population are relevant for prevention and treatment, they need further clarification. Affective temperaments potentially associated with SUD in adult ADHD patients were explored. METHODS: ADHD patients with and without SUD were compared for sociodemographic, clinical, and psychological characteristics through: Adult ADHD Self-Report Scale; Wender Utah Rating Scale; Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire. Logistic regression investigated factors associated with SUD. RESULTS: We included one-hundred and thirty-six ADHD patients with (n = 51, 37.5 %) and without SUD (n = 85, 62.5 %). The presence of SUD was associated with irritable temperament (p = 0.009), as well as more frequent school failure (p = 0.038), legal problems (p = 0.039), and lifetime suicide attempts (p = 0.014). LIMITATIONS: The cross-sectional design, the relatively small sample size, and the use of self-administered questionnaires. CONCLUSIONS: This study confirms the greater overall severity of adult ADHD-SUD compared with ADHD-only patients and suggests the potential role of irritable temperament as a predictor of substance-related problems.

Heart Rate Variability as a Potential Predictor of Response to Intranasal Esketamine in Patients with Treatment-Resistant Depression: A Preliminary Report.

Background: Esketamine has received approval as a nasal spray (ESK-NS) for treatment-resistant depression (TRD) and evidence from real-world investigations has confirmed the effectiveness of ESK-NS, albeit with interindividual differences in response. Heart rate variability (HRV), defined as the fluctuation in time interval between consecutive heartbeats, can be used to measure autonomic dysfunction in psychiatric disorders and its role has been investigated in diagnosis and prognosis of depression. Methods: This preliminary report aims to evaluate HRV parameters and their association with treatment outcome in 18 patients (55.6% males, 55.6 ± 9.39 years old) with TRD treated with a target dose of ESK-NS for one month (mean dose: 80.9 ± 9.05 mg). The Beck Depression Inventory (BDI) and a 3 min resting electrocardiogram were used to assess changes in depressive symptoms and HRV measurements before and after treatment. Results: Responders (n = 8, 44.5%; based on ≥30% BDI scores reduction) displayed lower HRV values than non-responders at baseline (p = 0.019), which increased at one month (p = 0.038). Receiver-Operating Characteristic (ROC) curves obtained from a logistic regression displayed a discriminative potential for baseline HRV in our sample (AUC = 0.844). Conclusions: These preliminary observations suggest a mutual interaction between esketamine and HRV, especially in relation to treatment response. Further studies are required to investigate electrophysiological profiles among predictors of response to ESK-NS and allow for personalized intervention strategies in TRD that still represent a public health concern.

Examining Lurasidone Efficacy in Patients with Schizophrenia Spectrum Illness and Concurrent Alcohol and Substance Use Disorder: A Prospective, Multicentric, Real-World Investigation.

Background: Dual disorders (DD) entail the coexistence of a substance use disorder (SUD) and another mental health condition, often within psychotic and affective disorders. This study aims to evaluate lurasidone, an innovative atypical antipsychotic, in individuals diagnosed with schizophrenia spectrum disorder and concurrent comorbidities of alcohol use disorder/substance use disorder (AUD/SUD). Methods: A cohort of 23 subjects diagnosed with schizophrenia spectrum disorder and comorbid AUD/SUD underwent psychometric assessments at baseline (T0) and one-month (T1) post-lurasidone initiation. Results: Lurasidone exhibited significant reductions in psychopathological burden, evidenced by decreased total PANSS scores (Z = 2.574, p = 0.011). Positive symptoms, substance craving (VAS Craving; Z = 3.202, p = 0.001), and aggressivity (MOAS scale; Z = 2.000, p = 0.050) were notably reduced. Clinical Global Impression (CGI) scores significantly improved (Z = 2.934, p = 0.003). Quality of life enhancements were observed in SF-36 subscales (energy, emotional well-being, and social functioning) (p < 0.05) and Q-LES-Q-SF scale (Z = -2.341, p = 0.021). A safety analysis indicated lurasidone's good tolerability, with only 8.7% reporting discontinuation due to side effects. Conclusions: This study offers initial evidence supporting lurasidone's efficacy and safety in dual diagnoses, highlighting positive effects on psychopathology, substance craving, and quality of life. These findings emphasize the need for tailored, comprehensive treatment strategies in managing the complexities of this patient population.

Investigating the Effectiveness of Brexpiprazole in Subjects with Schizophrenia Spectrum Illness and Co-Occurring Substance Use Disorder: A Prospective, Multicentric, Real-World Study.

BACKGROUND: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. METHODS: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. RESULTS: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). CONCLUSIONS: This study provides initial evidence supporting brexpiprazole's efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed.

Automatic detection of the nipple in screen-film and full-field digital mammograms using a novel Hessian-based method.

Automatic detection of the nipple in mammograms is an important step in computerized systems that combine multiview information for accurate detection and diagnosis of breast cancer. Locating the nipple is a difficult task owing to variations in image quality, presence of noise, and distortion and displacement of the breast tissue due to compression. In this work, we propose a novel Hessian-based method to locate automatically the nipple in screen-film and full-field digital mammograms (FFDMs). The method includes detection of a plausible nipple/retroareolar area in a mammogram using geometrical constraints, analysis of the gradient vector field by mean and Gaussian curvature measurements, and local shape-based conditions. The proposed procedure was tested on 566 mammographic images consisting of 372 randomly selected scanned films from two public databases (mini-MIAS and DDSM), and 194 digital mammograms acquired with a GE Senographe 2000D FFDM system. A radiologist independently marked the centers of the nipples for evaluation of the results. The average error obtained was 6.7 mm (22 pixels) with reference to the center of the nipple as identified by the radiologist. Only two out of the 566 detected nipples (0.35 %) had an error larger than 50 mm. The method was also directly compared with two other techniques for the detection of the nipple. The results indicate that the proposed method outperforms other algorithms presented in the literature and can be used to identify accurately the nipple on various types of mammographic images.

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series.

BACKGROUND: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine. METHODS: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI). FINDINGS: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores. CONCLUSIONS: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

Vortioxetine improves physical and cognitive symptoms in patients with post-COVID-19 major depressive episodes.

Major Depressive Episodes (MDE) following COVID-19 are frequent, can have a characteristic clinical picture, and are associated with immune-inflammatory changes. Vortioxetine is known to improve physical and cognitive performance in patients with depression and shows anti-inflammatory and anti-oxidative activities. This study aimed to retrospectively evaluate the effects of vortioxetine after 1 and 3 months of treatment in 80 patients (44.4% males, 54±17.2 years) with post-COVID-19 MDE. The primary outcome was improvement in physical and cognitive symptoms measured by specific items of Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS), Short Form-36 Health Survey Questionnaire (SF-36), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire for Depression (PDQ-D5). Changes in mood, anxiety, anhedonia, sleep, and quality of life were also investigated, as well as the underlying inflammatory status. Results show that, alongside reduction of depressive symptoms (HDRS, p<0.001), vortioxetine (mean dose: 10.1±4.1 mg/day) significantly improved physical features (all measurements p<0.001) and cognitive functioning (DDST, p=0.02; PDQ-D5, p<0.001) throughout treatment. We also observed significant reductions in inflammatory indexes. Therefore, vortioxetine might be a favorable therapeutic choice in post-COVID-19 patients with MDE because of its beneficial effects on physical complaints and cognition, features that appear to be specifically affected in relation to SARS-CoV-2 infection, and its good safety/tolerability profile. High prevalence and clinical and socioeconomic implications of COVID-19 consequences are a major public health concern and developing tailored, safe interventions is crucial to promote full functional recovery.

Update on Pharmacological Treatment for Comorbid Major Depressive and Alcohol Use Disorders: The Role of Extended-release Trazodone.

BACKGROUND: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are major public health concerns because of their high prevalence and clinical and functional severity. MDD and AUD commonly co-occur, but effective therapeutic approaches for comorbidity are still scarce. Available evidence on selective serotonin reuptake inhibitors and tricyclic antidepressants held mixed results, and further pharmacological categories have been less investigated. Trazodone is an approved antidepressant drug for adults and has shown efficacy on symptoms like anxiety and insomnia observed in AUD patients as well. Thus, this study aims to evaluate the effect of extended-release trazodone on clinical and functional features in MDD + AUD subjects. METHODS: One hundred MDD + AUD outpatients were retrospectively evaluated at 1, 3, and 6 months of treatment with extended-release trazodone (150-300 mg/day, flexibly dosed). Improvement in depressive symptoms was the primary outcome measure. Changes in anxiety, sleep, functioning, quality of life, clinical global severity, and alcohol craving were also investigated. RESULTS: Trazodone reduced depressive symptoms (p < 0.001) with 54.5% remission at the endpoint. Similar improvements were observed in all secondary outcomes, including anxiety, sleep alterations, and craving (p < 0.001). Only mild side effects were reported and disappeared over time. CONCLUSION: Extended-release trazodone displayed good antidepressant properties in MDD + AUD patients, ameliorating overall symptomatology, functioning, and quality of life, with a good safety/ tolerability profile. Further, it significantly improved sleep disturbances and craving symptoms, which are associated with drinking relapse and worse outcomes. Therefore, trazodone might represent a promising pharmacological option for MDD + AUD patients.

Adaptation of the binding domain of Lactobacillus acidophilus S-layer protein as a molecular tag for affinity chromatography development.

Introduction: The S-layer proteins are a class of self-assembling proteins that form bi-dimensional lattices named S-Layer on the cell surface of bacteria and archaea. The protein SlpA, which is the major constituent of the Lactobacillus acidophilus S-layer, contains in its C-terminus region (SlpA284 - 444), a protein domain (named here as SLAPTAG) responsible for the association of SlpA to the bacterial surface. SLAPTAG was adapted for the development of a novel affinity chromatography method: the SLAPTAG-based affinity chromatography (SAC). Methods: Proteins with different molecular weights or biochemical functions were fused in-frame to the SLAPTAG and efficiently purified by a Bacillus subtilis-derived affinity matrix (named Bio-Matrix or BM). Different binding and elution conditions were evaluated to establish an optimized protocol. Results: The binding equilibrium between SLAPTAG and BM was reached after a few minutes of incubation at 4°C, with an apparent dissociation constant (KD) of 4.3µM. A reporter protein (H6-GFP-SLAPTAG) was used to compare SAC protein purification efficiency against commercial immobilized metal affinity chromatography. No differences in protein purification performance were observed between the two methods. The stability and reusability of the BM were evaluated, and it was found that the matrix remained stable for more than a year. BM could be reused up to five times without a significant loss in performance. Additionally, the recovery of bound SLAP-tagged proteins was explored using proteolysis with a SLAP-tagged version of the HRV-3c protease (SLAPASE). This released the untagged GFP while the cut SLAPTAG and the SLAPASE were retained in the BM. As an alternative, iron nanoparticles were linked to the BM, resulting in BMmag. The BMmag was successfully adapted for a magnetic SAC, a technique with potential applications in high-throughput protein production and purification. Discussion: The SAC protocol can be adapted as a universal tool for the purification of recombinant proteins. Furthermore, the SAC protocol utilizes simple and low-cost reagents, making it suitable for in-house protein purification systems in laboratories worldwide. This enables the production of pure recombinant proteins for research, diagnosis, and the food industry.