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First- and second-generation antipsychotics are highly accountable for causing a plethora of medical side effects, ranging from metabolic imbalances to sexual dysfunction (SD), that frequently undermine patient-doctor relationships. Nevertheless, to date antipsychotics are one of the best treatment options for dealing with numerous either acute or chronic conditions like agitation, suicidality, depression, dementia, and of course psychosis. For these reasons, clinicians need to handle them wisely to preserve patients' sexual health, avoid poor therapeutic adherence and prevent high rates of therapy drop-out.This article reviews the literature on pharmacologic approaches for management strategies in men who are administered with antipsychotics and developed SD. The etiology of antipsychotic-induced SD is also discussed.Clinicians must consider sexual life as a major health domain. To do so, a first step would be to measure and monitor sexual function by means of psychometric tools. Secondly, primary prevention should be conducted when choosing antipsychotics, i.e. picking sex-sparing compounds like aripiprazole or brexpiprazole. Thirdly, if sexolytic compounds cannot be dismissed, such as first-generation antipsychotics, risperidone, paliperidone, or amisulpride, then aripiprazole 5-20 mg/day adjunctive therapy has proven to be most effective in normalizing prolactin levels and consequently treating antipsychotic-induced SD.

Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are highly versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. Thus, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than a serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by nonpsychiatrists. Thus, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.

Objectives: To detect seed-based functional connectivity (FC) between various cortical sub-regions and the thalamus in lifelong premature ejaculation (LPE) patients and explore whether specific thalamocortical networks are significantly altered in PE patients compared to healthy controls (HCs) Methods: Fifty non-medicated LPE patients and 40 age-matched HCs underwent a resting-state functional MRI. FC was adopted to identify specific thalamocortical connectivity between the thalamus and six cortical regions of interest (i.e. the motor cortex/supplementary motor, the prefrontal cortex, the temporal lobe, the posterior parietal cortex, the somatosensory cortex and the occipital lobe). In LPE patients, regression analysis was subsequently conducted to assess relationships of thalamocortical connectivity with the Premature Ejaculation Diagnostic Tool (PEDT) score and the Intravaginal Ejaculatory Latency Time (IELT). Results: LPE patients had significantly decreased FC between the motor cortex and bilateral ventral thalamus, between the prefrontal cortex and left dorsomedial thalamus, as well as between the temporal cortex and bilateral ventromedial thalamus. In LPE patients, PEDT score was significantly positively associated with the thalamus-posterior parietal cortex FC, and negatively associated with the thalamus-temporal cortex FC, while IELT was positively associated with the thalamus-temporal cortex and thalamus-motor cortex FC. Conclusion: These results enrich the imaging evidence for the understanding of the neurobiological mechanisms and/or consequences of LPE.

A PHQ-9 score ≥ 15, represented as PHQ-9The nomogram was constructed by analysing data of 802 patients from Xijing Hospital and Northwest Women'sChildren's Hospital. The LASSO and multivariable logistic regressions were used to identify independent predictors of PHQ-9The duration of PE, IELT, a history of PE exacerbation, IIEF-5 score, urinary frequency and physical pain score were identified as independent predictors. The nomogram showed excellent calibration, discrimination and clinical usefulness in the derivation and validation cohorts, with a predictive accuracy of 0.781 and 0.763, respectively. Based on this nomogram, patients were divided into not recommended, recommended and strongly recommended PHQ-9 filling groups, with PHQ-9A nomogram to discern LPE patients with low risks of PHQ-9

Peter Abelard (1079-1142) is still considered one of the giants of philosophy, theology, and psychology, and the unsurpassed master of dialectical debate. Born in Le Pallet, near Nantes, Abelard became an academic and wandering cleric of great fame, founder of several schools that attracted students from all countries, arousing the admiration of his contemporaries and the profound envy of his colleagues. Around 1115, Abelard became master of the school of the Cathedral of Notre-Dame. Shortly after, the canon Fulbert asked him to take his niece, the equally famous and highly cultured Héloïse d'Argenteuil (1092-1164), as a pupil. Thus a relationship began, celebrated for centuries to come, characterized by burning sexual and intellectual passion, by the famous correspondence, which will be the archetype of sentimental education and the template of romantic love letters, bythe birth of a son and consequent marriage, and by the cowardly revenge of Fulbert, who, together with a band of servants, mutilated "those parts of my body with which I had done what was the cause of their pain," as Abelard wrote. While this unclear self-description has suggested to contemporaries and to posterity that Abelard was castrated, we aim to question this belief by analyzing in-depth this historical-andrological clinical case to understand if there is any evidence that could suggest that Abelard was instead the victim of an even more brutal punishment: penectomy. Signs and symptoms gleaned from the personal writings and historical perspectives of Abelard and his time are used here to provide a possible answer to a thousand-year-old question: what makes a man … a man?

Priapism is defined as a prolonged penile erection in absence of sexual arousal, leading also to serious sexual and urological problems such as erectile dysfunction and penile fibrosis. Amongst many different etiologies, priapism may be caused by a wide range of antipsychotic medications, mainly due to the α1-adrenergic receptor antagonism. On the other hand, only a couple of cases of opioid compounds have been linked to the onset of priapism, with evidence coming only from methadone and buprenorphine. Here we describe the case of a patient treated with antipsychotics who developed priapism four times following rapid discontinuation of buprenorphine/naloxone (Suboxone®).S.C. is a 30-year-old Caucasian man suffering from chronic buprenorphine/naloxone (Suboxone®) abuse, borderline personality disorder, antisocial traits, and multiple suicide attempts. During the acute and the first part of post-acute Suboxone® withdrawal, four episodes of priapism developed while he was treated with clotiapine, clozapine, and chlorpromazine. However, after the last episode of priapism, despite he was either on haloperidol or zuclopenthixol and chlorpromazine, no other urological event occurred during the following 6 months of observation.As opioids may have dampened the patient's sexual function due to chronic consumption, a rapid drug suspension coupled with an antipsychotic therapy might have created the conditions to facilitate the occurrence of close clustered priapism events.

BackgroundAlthough erectile dysfunction (ED) often occurs simultaneously with depression, not all patients with ED suffer major depression (MD), with a PHQ-9 score ≥15 indicating MD. Because the PHQ-9 questionnaire includes phrases such as “I think I am a loser” and “I want to commit suicide,” the psychological burdens of ED patients are likely to increase inevitably after using the PHQ-9, which, in turn, may affect ED therapeutic effects. Accordingly, we endeavored to develop a nomogram to predict individual risk of PHQ-9 score ≥15 in these patients.MethodsThe data of 1,142 patients with ED diagnosed in Xijing Hospital and Northwest Women and Children's Hospital from January 2017 to May 2020 were analyzed. While the Least Absolute Shrinkage and Selection Operator regression was employed to screen PHQ-9 score ≥15 related risk factors, multivariate logistic regression analysis was performed to verify these factors and construct the nomogram. The training cohort and an independent cohort that comprised 877 prospectively enrolled patients were used to demonstrate the efficacy of the nomogram.ResultsThe IIEF-5 score, PEDT score, physical pain score, frequent urination, and feeling of endless urination were found to be independent factors of PHQ-9 score ≥15 in patients with ED. The nomogram developed by these five factors showed good calibration and discrimination in internal and external validation, with a predictive accuracy of 0.757 and 0.722, respectively. The sensitivity and specificity of the nomogram in the training cohort were 0.86 and 0.52, respectively. Besides, the sensitivity and specificity of the nomogram in the validation cohort were 0.73 and 0.62, respectively. Moreover, based on the nomogram, the sample was divided into low-risk and high-risk groups.ConclusionThis study established a nomogram to predict individual risk of PHQ-9 score ≥15 in patients with ED. It is deemed that the nomogram may be employed initially to avoid those with a low risk of MD completing questionnaires unnecessarily.

Key Points Question What are the mental health outcomes among Italian health care workers during the COVID-19 pandemic? Findings In this longitudinal cohort study of 2856 health care workers in Italy during the COVID-19 pandemic the prevalence of depression symptoms, anxiety symptoms, insomnia symptoms, and posttraumatic stress symptoms decreased among Italian health care workers 14 months after the beginning of the COVID-19 pandemic. Prolonged work with patients with COVID-19 was significantly associated with mental health outcomes, whereas quitting work as a frontline health care worker was significantly associated with decrease in mental health issues. Meaning These findings help to identify the potential risk factors for health care workers exposed to direct contact with patients with COVID-19 and could help inform better preventive policies regarding mental health in this particular population., Importance Health care workers (HCWs) exposed to COVID-19 have high rates of mental health issues. However, longitudinal data on the evolution of mental health outcomes in HCWs are lacking. Objective To evaluate the mental health outcomes among Italian HCWs 14 months after the beginning of the COVID-19 pandemic. Design, Setting, and Participants This longitudinal cohort study collected data from March 1 to April 30, 2020 (T1) and from April 1 to May 31, 2021 (T2), from 2856 Italian HCWs aged 18 years or older who responded to an online questionnaire. Participants were also recruited via snowballing, a technique in which someone who receives the invitation to participate forwards it to his or her contacts. Exposures Frontline vs second-line position, job type, hospitalization for COVID-19, and colleagues or family members affected by COVID-19. Main Outcomes and Measures Outcomes are depression symptoms, anxiety symptoms, insomnia symptoms, and posttraumatic stress symptoms (PTSSs). Four different trajectories are described for each condition: resilient, remittent, incident, and persistent. Results Of the 2856 HCWs, 997 (34.9%) responded to the follow-up assessment (mean [SD] age, 42.92 [10.66] years; 816 [82.0%] female). Depression symptoms (b = −2.88; 95% CI, −4.05 to −1.71), anxiety symptoms (b = −2.01; 95% CI, −3.13 to −0.88), and PTSSs (b = −0.77; 95% CI, −1.13 to −0.42) decreased over time; insomnia symptoms increased (b = 3.05; 95% CI, 1.63-4.47). Serving as a frontline HCW at T1 was associated with decreased symptoms of depression (b = −1.04; 95% CI, −2.01 to −0.07), and hospitalization for COVID-19 was associated with increased depression symptoms (b = 5.96; 95% CI, 2.01-9.91); younger age (b = −0.36; 95% CI, −0.70 to −0.03) and serving as a frontline HCW at T1 (b = −1.04; 95% CI, −1.98 to −0.11) were associated with decreased anxiety symptoms. Male sex was associated with increase in insomnia symptoms (b = 1.46; 95% CI, 0.39-2.53). Serving as a frontline HCW at T1 (b = −0.42; 95% CI, −0.71 to −0.13) and being a physician (b = −0.52; 95% CI, −0.81 to −0.24) were associated with a decrease in PTSSs, whereas younger age (b = 0.35; 95% CI, 0.09-0.61) and male sex (b = 0.12; 95% CI, 0.01-0.22) were associated with an increase in PTSSs. Depression trajectories were 629 resilient (65.5%), 181 remittent (18.8%), 58 incident (6.0%), and 92 persistent (9.6%). Anxiety trajectories were 701 resilient (73.3%), 149 remittent (15.6%), 45 incident (4.7%), and 61 persistent (6.4%). Insomnia trajectories were 858 resilient (88.9%), 77 remittent (8.0%), 20 incident (2.1%), and 10 persistent (1.0%). The PTSS trajectories were 363 resilient (38.5%), 267 remittent (28.3%), 86 incident (9.1%), and 226 persistent (24.0%). Conclusions and Relevance In this cohort study, relative to the beginning of the COVID-19 pandemic, mental health among HCWs has improved. Factors associated with change in mental health outcomes could help in the design of prevention strategies for HCWs., This cohort study assesses the prevalence and associated risk or protective factors of symptoms of depression, anxiety, insomnia, and posttraumatic stress among Italian health care workers in the 14 months after the COVID-19 pandemic began.

Background and purpose Dysphagia occurs in up to 50% of all patients with acute stroke. There is debate regarding which is the most effective screening tool in identifying aspiration in patients with acute stroke. We assessed the accuracy of the Sapienza Global Bedside Evaluation of Swallowing after Stroke (GLOBE-3S), which combines the Toronto Bedside Swallowing Screening Test (TOR-BSST©) with oxygen desaturation and laryngeal elevation measurement during swallowing. Methods We prospectively enrolled consecutive patients with stroke within 72 h of symptom onset. All patients with stroke firstly underwent a standard neurological examination, then the GLOBE-3S evaluation and finally the fiberoptic endoscopic evaluation of swallowing (FEES). Two different assessors, a neurologist and a speech pathologist, blind to both the clinical data and each other's evaluation, administered the GLOBE-3S and FEES examination. We assessed the accuracy of the GLOBE-3S in detecting post-stroke swallow impairment with aspiration using the FEES as the standard. Results We enrolled 50 patients with acute stroke, 28 of whom (56%) had swallowing impairment with aspiration at FEES evaluation. A total of 33 patients (66%) failed the GLOBE-3S evaluation. The GLOBE-3S reached a sensitivity of 100% and a specificity of 77.3% (negative predictive value, 100%; positive likelihood ratio, 4.34). The median time required for the GLOBE-3S to be performed was 297 s. Conclusions GLOBE-3S is quick to perform at the bedside and can accurately identify aspiration in patients with acute stroke. By including the measurement of laryngeal elevation and monitoring of oxygen desaturation, it could represent a highly sensitive instrument to avoid the misdiagnosis of silent aspirators.

To develop a comprehensive next-generation sequencing panel assay that screens genes known to cause developmental eye disorders and inherited eye disease and to evaluate its diagnostic yield in a pediatric cohort with malformations of the globe, anterior segment anomalies, childhood glaucoma, or a combination thereof.Evaluation of diagnostic test.Two hundred seventy-seven children, 0 to 16 years of age, diagnosed with nonsyndromic or syndromic developmental eye defects without a genetic diagnosis.We developed a new oculome panel using a custom-designed Agilent SureSelect QXT target capture method (Agilent Technologies, Santa Clara, CA) to capture and perform parallel high-throughput sequencing analysis of 429 genes associated with eye disorders. Bidirectional Sanger sequencing confirmed suspected pathogenic variants.Collated clinical details and oculome molecular genetic results.The oculome design covers 429 known eye disease genes; these are subdivided into 5 overlapping virtual subpanels for anterior segment developmental anomalies including glaucoma (ASDA; 59 genes), microphthalmia-anophthalmia-coloboma (MAC; 86 genes), congenital cataracts and lens-associated conditions (70 genes), retinal dystrophies (RET; 235 genes), and albinism (15 genes), as well as additional genes implicated in optic atrophy and complex strabismus (10 genes). Panel development and testing included analyzing 277 clinical samples and 3 positive control samples using Illumina sequencing platforms; more than 30× read depth was achieved for 99.5% of the targeted 1.77-Mb region. Bioinformatics analysis performed using a pipeline based on Freebayes and ExomeDepth to identify coding sequence and copy number variants, respectively, resulted in a definitive diagnosis in 68 of 277 samples, with variability in diagnostic yield between phenotypic subgroups: MAC, 8.2% (8 of 98 cases solved); ASDA, 24.8% (28 of 113 cases solved); other or syndromic, 37.5% (3 of 8 cases solved); RET, 42.8% (21 of 49 cases solved); and congenital cataracts and lens-associated conditions, 88.9% (8 of 9 cases solved).The oculome test diagnoses a comprehensive range of genetic conditions affecting the development of the eye, potentially replacing protracted and costly multidisciplinary assessments and allowing for faster targeted management. The oculome enabled molecular diagnosis of a significant number of cases in our sample cohort of varied ocular birth defects.

Irreversible photoreceptor cell death is a major cause of blindness in many retinal dystrophies. A better understanding of the molecular mechanisms underlying the progressive loss of photoreceptor cells remains therefore crucial. Abnormal expression of microRNAs (miRNAs) has been linked with the aetiology of a number of retinal dystrophies. However, their role during the degenerative process remains poorly understood. Loss of cone photoreceptors in the human macula has the greatest impact on sight as these cells provide high acuity vision. Using a Chrnb4-cre; Dicerflox/flox conditional knockout mouse (Dicer CKO) to delete Dicer1 from cone cells, we show that cone photoreceptor cells degenerate and die in the Dicer-deleted retina. Embryonic eye morphogenesis appeared normal in Dicer CKO mice. Cone photoreceptor abnormalities were apparent by 3 weeks of age, displaying either very short or absent outer segments. By 4 months 50% of cones were lost and cone function was impaired as assessed by electroretinography (ERG). RNAseq analysis of the Dicer CKO retina revealed altered expression of genes involved in the visual perception pathway. These data show that loss of Dicer1 leads to early-onset cone cell degeneration and suggest that Dicer1 is essential for cone photoreceptor survival and homeostasis.