Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol.

Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01-2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research".

Efficacy and safety of ketamine and esketamine for unipolar and bipolar depression: an overview of systematic reviews with meta-analysis.

Background: Unipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile. Methods: Following PRIOR guidelines, this OoR's protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted. Results: Our analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence. Limitations: This study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression. Conclusion: While ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression. Systematic review registration: [https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).

PERCEPTIONS AND EXPERIENCES OF M-HEALTH TECHNOLOGIES AND SOCIAL MEDIA: A QUALITATIVE STUDY IN PATIENTS WITH SCHIZOPHRENIA.

The growing influence of technology in the realm of mental health presents promising prospects for patients with psychiatric disorders like schizophrenia. The objective of this study is to investigate the perceptions of individuals with schizophrenia spectrum disorder regarding the utilization of technology and social media. The qualitative methodology used consists of an individual structured interview and the data were subjected to thematic analysis. The results show that the participants use digital tools for various activities such as work, searching for information, entertainment, and socialising. Their perceptions confirm the usefulness and easy accessibility of these tools, which enable positive changes in the organisation of daily life and social relationships. In general, it is possible to identify both positive and negative aspects of technology and social media, such as abuse and addictive behaviour, network and information overload problems, and the risk that privacy may not be guaranteed; among the positive ones, the promotion of remote sociability, speed in carrying out tasks and acquiring useful information emerge. Most of the participants express a positive perception of the possibility that digital tools can help in the field of mental health.

What Evidence-based Medicine (EBM) Doesn't Say About Allergen-specific Immunotherapy (AIT).

Evidence-based allergology for the treatment of allergic rhinitis with allergen-specific immunotherapy (AIT) has been used in publications by the companies manufacturing AIT. The purpose of randomized controlled trials (RCTs) is to provide physicians, health authorities, patients, and their families with the best evidence upon which to base treatment decisions. However, some RCT results may do more harm than good because they serve the commercial interests of the companies producing and marketing AIT more than the interests of patients. Allergic rhinitis is a trivial disease that is not life-threatening and is easily controlled by drugs. In this paper, we analyze some of the more controversial points underlying the EBM supporting the use of AIT. The paradox behind RCT-based practice is that AIT is based on the results of incorrectly interpreted RCTs. International scientific societies and drug regulatory bodies should analyze trials more carefully, considering potential conflicts of interest.

Mental Pain Correlates with Mind Wandering, Self-Reflection, and Insight in Individuals with Psychotic Disorders: A Cross-Sectional Study.

Understanding the cognitive processes that contribute to mental pain in individuals with psychotic disorders is important for refining therapeutic strategies and improving patient outcomes. This study investigated the potential relationship between mental pain, mind wandering, and self-reflection and insight in individuals diagnosed with psychotic disorders. We included individuals diagnosed with a 'schizophrenia spectrum disorder' according to DSM-5 criteria. Patients in the study were between 18 and 65 years old, clinically stable, and able to provide informed consent. A total of 34 participants, comprising 25 males and 9 females with an average age of 41.5 years (SD 11.5) were evaluated. The Psychache Scale (PAS), the Mind Wandering Deliberate and Spontaneous Scale (MWDS), and the Self-Reflection and Insight Scale (SRIS) were administered. Statistical analyses involved Spearman's rho correlations, controlled for potential confounders with partial correlations, and mediation and moderation analyses to understand the indirect effects of MWDS and SRIS on PAS and their potential interplay. Key findings revealed direct correlations between PAS and MWDS and inverse correlations between PAS and SRIS. The mediation effects on the relationship between the predictors and PAS ranged from 9.22% to 49.8%. The largest statistically significant mediation effect was observed with the SRIS-I subscale, suggesting that the self-reflection and insight component may play a role in the impact of mind wandering on mental pain. No evidence was found to suggest that any of the variables could function as relationship moderators for PAS. The results underscore the likely benefits of interventions aimed at reducing mind wandering and enhancing self-reflection in psychotic patients (e.g., metacognitive therapy, mindfulness). Further research will be essential to elucidate the underlying mechanisms.

Reflective functioning and dissociative experiences: A comparison study between adolescents at "high-risk" of psychosis and healthy controls.

Background: Despite the established contribution to psychological well-being in young subjects, the investigation of reflective functioning and dissociative experiences in help-seekers adolescents still appears an unmet need. Objective: The study aimed to assess reflective functioning and dissociative symptoms in help-seekers adolescents, and compare them to gender-matched healthy controls. Methods: The Reflecting Functioning Questionnaire (RFQ) was used to investigate mentalizing; the Adolescent Dissociative Experience Scale (A-DES) was used to explore dissociative symptoms. Results: The study involved 102 adolescents (mean age 18.06 ± 1.78 years), split into "help-seekers" (N= 51; mean age 19 ± 1.98 years) and healthy controls (N= 51; mean age 17.12 ± 0.84). "Help-seekers" adolescents showed lower RFQ-certainty scores (mean 3.39 ± 2.47), compared to healthy controls (mean 6.73 ± 5.01). Furthermore, "help-seekers" adolescents reported higher scores on RFQ-uncertainty (mean 7.73 ± 4.38), compared to healthy controls (mean 5.14 ± 4.17), which indicates a greater lack of knowledge about mental states (hypomentalizing). Eventually, "help-seekers" adolescents showed significantly worse dissociative symptoms (A-DES total mean score 3.49 ± 2.04), compared to healthy controls (A-DES total mean score 2.06 ± 1.43). Conclusion: The importance of an assessment in early adolescence denotes a topic of increasing concern, in order to identify failures in reflective functioning and the onset of dissociative experiences among help-seekers adolescents, toward the implementation of tailored psychological interventions.

The international platform of registered systematic review and meta-analysis protocols (INPLASY) at 3 years: an analysis of 4,658 registered protocols on inplasy.com, platform features, and website statistics.

Background: INPLASY® is an international platform for registering systematic reviews and meta-analysis protocols that was launched in March 2020. INPLASY® provides an online database in which the protocols are maintained as permanent public records and can be accessed on its website (www.inplasy.com). Methods: We described the database features and registered information of all records published since the launch of the registry on March 31, 2023. Additionally, we analyzed the website statistics dataset to explore user experience and promote data transparency. Results: Four thousand six hundred fifty-eight records were registered in INPLASY®, and more than 94% of the protocols were published within 24 h. Most of the submissions were from China, followed by Portugal, Taiwan, Malaysia, and Brazil. The INPLASY® website received 386,395 page views from 64,568 visitors during the first three years. The accesses were obtained from 170 countries. Most of the accesses were from China, followed by the US, the UK, and Portugal. The review status "completed and published" was observed in 898 protocols, and these studies were published in 372 different scientific peer-reviewed journals. The features of INPLASY® include the following: (i) INPLASY® identifier, a unique protocol number; (ii) the digital object identifier (DOI) number, the URL of the protocol linked to a specific DOI; (iii) ORCID update, INPLASY® automatically updates authors' ORCID page, including their protocol; and (iv) search tools, the protocols are freely accessible on www.inplasy.com. Conclusions: INPLASY® has several practical and useful features that should be considered when planning the registration of a systematic review protocol. Furthermore, the sharp increase in the number of protocols registered in INPLASY® in the first three years and the database statistics demonstrate that INPLASY® has become an important source of systematic review protocols. Therefore, authors should access INPLASY® before planning a future review study to avoid unintended duplication of efforts and to obtain timely registration.

Personality Traits and Fatigue in Multiple Sclerosis: A Narrative Review.

(1) Background: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease. Fatigue is a prevalent and debilitating symptom that significantly impacts the quality of life of these patients. A relationship between personality traits and fatigue in MS has been hypothesized but not clearly defined. (2) Methods: A literature search was carried out from databases up to April 2023 for studies correlating personality traits and fatigue in patients suffering from MS. (3) Results: A total of ten articles was included; most of the studies depict a neuroticism-fatigue correlation; however, they were not consistent in terms of the fatigue, personality, and covariate assessments. (4) Conclusions: The clinical and methodological heterogeneity of the included studies prevented us from drawing any firm conclusion on the link between personality traits and fatigue in MS. Several models of personality and different fatigue assessments have been found. Despite this, a common pathway shows that the neuroticism trait or similar personality patterns has a role in fatigue diagnosis. This may be a useful target to improve the quality of life and enhance the modification of the disease treatment results. Further homogeneous and longitudinal studies are needed.

The association between polygenic risk scores for mental disorders and social cognition: A scoping review.

People with mental disorders, such as psychosis or autism spectrum disorder (ASD), often present impairments in social cognition (SC), which may cause significant difficulties in real-world functioning. SC deficits are seen also in unaffected relatives, indicating a genetic substratum. The present review evaluated the evidence on the association between SC and the polygenic risk score (PRS), a single metric of the molecular genetic risk to develop a specific disorder. In July 2022, we conducted systematic searches in Scopus and PubMed following the PRISMA-ScR guidelines. We selected original articles written in English reporting results on the association between PRSs for any mental disorder and domains of SC either in people with mental disorders or controls. The search yielded 244 papers, of which 13 were selected for inclusion. Studies tested mainly PRSs for schizophrenia, ASD, and attention-deficit hyperactivity disorder. Emotion recognition was the most investigated domain of SC. Overall, evidence revealed that currently available PRSs for mental disorders do not explain variation in SC performances. To enhance the understanding of mechanisms underlying SC in mental disorders, future research should focus on the development of transdiagnostic PRSs, study their interaction with environmental risk factors, and standardize outcome measurement.

Is It Time for a Paradigm Shift in the Treatment of Schizophrenia? The Use of Inflammation-Reducing and Neuroprotective Drugs-A Review.

Comprehending the pathogenesis of schizophrenia represents a challenge for global mental health. To date, although it is evident that alterations in dopaminergic, serotonergic, and glutamatergic neurotransmission underlie the clinical expressiveness of the disease, neuronal disconnections represent only an epiphenomenon. In recent years, several clinical studies have converged on the hypothesis of microglia hyperactivation and a consequent neuroinflammatory state as a pathogenic substrate of schizophrenia. Prenatal, perinatal, and postnatal factors can cause microglia to switch from M2 anti-inflammatory to M1 pro-inflammatory states. A continuous mild neuroinflammatory state progressively leads to neuronal loss, a reduction in dendritic spines, and myelin degeneration. The augmentation of drugs that reduce neuroinflammation to antipsychotics could be an effective therapeutic modality in managing schizophrenia. This review will consider studies in which drugs with anti-inflammatory and neuroprotective properties have been used in addition to antipsychotic treatment in patients with schizophrenia.

Exploring Personal Recovery in Schizophrenia: The Role of Mentalization.

Recovery is a broadly debated concept in the field of psychiatry research and in schizophrenia. Our study aims to understand the correlation between personal recovery from schizophrenia and factors such as mentalization, disability, quality of life, and antipsychotic side effects; Methods: Participants with schizophrenia (according to DSM-5 criteria) were consecutively recruited from the Psychiatry Unit of the University of Catania, Italy. Participants were assessed with the Recovery Assessment Scale (RAS), the Multidimensional Mentalizing Questionnaire (MMQ), the brief version of the WHO Disability Assessment Schedule (WHO-DAS), the EuroQoL-5 dimensions-5 levels, the Insight Orientation Scale (IOS) and the Glasgow Antipsychotic Side Effect Scale (GASS); Results: 81 patients were included. Our findings showed a positive correlation between RAS total scores and MMQ scores, especially in "good mentalizing" subdomains. IOS scores also had a positive association with RAS and MMQ scores. In contrast, poor mentalizing abilities negatively correlated with WHO-DAS 2.0 scores. While antipsychotic side effects influenced functioning, they did not impact perceived recovery. Conclusions: The study's results identified potential predictors of personal recovery from schizophrenia. These findings could contribute to creating tailored interventions to facilitate the recovery process.

A Clinical Psychological View about Delusional Characterizations in Subjects with Schizophrenia Spectrum Disorder during the COVID-19 Period.

(Background) The period experienced during the COVID-19 virus and the respective social regulations associated with it caused enormous psychosocial stress. (Objective) The objective of the present work was to observe whether the lived period induced a change in delusional characterizations in subjects with schizophrenia spectrum disorder. (Methods) A systematic literature review was conducted following the PRISMA 2020 guidelines for systematic reviews of the PRISMA GROUP. The literature search was conducted from November 2021 to May 2022, using various scientific platforms including PubMed. (Results) A total of 865 articles were found, from which 176 duplicates were removed. The remaining articles were reviewed by reading the titles and abstracts; fourteen were included. (Conclusions) During this research, it was possible to confirm the initial thesis, namely that delirium absorbs external reality by being modified by it. It was observed that the speed of absorption is estimated to be directly proportional to the speed of the modification of social reality and to the impact that the latter has on the subject's private sphere. Moreover, the situation of radical change represented a condition of abnormal psychosocial stress, which led to an increase in diagnoses of schizophrenia spectrum disorders and, specifically, a weighty increase in diagnoses of brief psychotic disorder (BDP). In the coming years, it is estimated that there will be an increase in diagnoses of schizophrenia spectrum disorder caused by both environmental and biological factors.

How should patient decision aids for schizophrenia treatment be designed? - A scoping review.

Despite the clear rationale for applying shared decision-making in the context of the preference sensitive decision for or against antipsychotics and the upswing of patient decision aids (pDAs) to support this process, there is still a lack of knowledge regarding which key features are crucial for pDAs in schizophrenia treatment. A scoping review according to the PRISMA-SRc was conducted to inform on crucial key features and quality indicators. The review focussed on the following seven aspects for investigating pDAs: (1) Types of decision aids, (2) Values, (3) Decision Guidance, (4) Output of the decision aid, (5) Target group, (6) Effectiveness according to publication and (7) Decision aid evaluation. Eleven studies which addressed six unique decision aids met the eligibility criteria. There were major differences in the design as well as in the development of the decision aids. Three aspects emerged that should be given special consideration in the design of such tools for antipsychotics: the evidence used by the decision aid, the algorithm for translating evidence into a decision aid and finally the presentation of the evidence. We recommend the use of data with a high level of evidence and to combine it with individualized treatment by taking into account patient preferences and previous experiences as well as comparing them with clinical assessments. Fully computerized decision aids that use complicated algorithms, for example, by merging treatment effects with patient characteristics to suggest an appropriate treatment at the end, tend to be paternalistic and thus not appropriate for SDM, in our view. In addition, possible cognitive deficits need to be considered when presenting the output of decision aids for antipsychotics.

Challenging the Pleiotropic Effects of Repetitive Transcranial Magnetic Stimulation in Geriatric Depression: A Multimodal Case Series Study.

BACKGROUND: Although the antidepressant potential of repetitive transcranial magnetic stimulation (rTMS), the pleiotropic effects in geriatric depression (GD) are poorly investigated. We tested rTMS on depression, cognitive performance, growth/neurotrophic factors, cerebral blood flow (CBF) to transcranial Doppler sonography (TCD), and motor-evoked potentials (MEPs) to TMS in GD. METHODS: In this case series study, six drug-resistant subjects (median age 68.0 years) underwent MEPs at baseline and after 3 weeks of 10 Hz rTMS on the left dorsolateral prefrontal cortex. The percentage change of serum nerve growth factor, vascular endothelial growth factor, brain-derived growth factor, insulin-like growth factor-1, and angiogenin was obtained. Assessments were performed at baseline, and at the end of rTMS; psychocognitive tests were also repeated after 1, 3, and 6 months. RESULTS: Chronic cerebrovascular disease was evident in five patients. No adverse/undesirable effect was reported. An improvement in mood was observed after rTMS but not at follow-up. Electrophysiological data to TMS remained unchanged, except for an increase in the right median MEP amplitude. TCD and neurotrophic/growth factors did not change. CONCLUSIONS: We were unable to detect a relevant impact of high-frequency rTMS on mood, cognition, cortical microcircuits, neurotrophic/growth factors, and CBF. Cerebrovascular disease and exposure to multiple pharmacological treatments might have contributed.

Neurobiology and Applications of Inositol in Psychiatry: A Narrative Review.

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged.

Transcranial Magnetic Stimulation for the Treatment of Gambling Disorder: A Systematic Review.

BACKGROUND: Gambling Disorder (GD) is a behavioral addiction listed within the diagnostic category of substance-related and addictive disorders. Recently, transcranial magnetic stimulation (TMS), which non-invasively stimulates the brain and has neuromodulatory properties, has emerged as an innovative treatment tool for GD, thus offering a new option for the management of this complex disorder. The present review explored the efficacy of TMS as a possible non-pharmacological treatment for GD. METHODS: An exhaustive search was performed across the MEDLINE, Web of Science, and EMBASE databases using a specific search string related to GD and TMS. A total of 20 papers were selected for full-text examination, out of which eight fulfilled the inclusion criteria and were therefore systematically analyzed in the present review. RESULTS: This review included eight studies: three randomized-controlled trials (RCTs), three non-controlled studies, one case series, and one case report. Two cross-over RCTs described a decrease in craving after high-frequency (excitatory), repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) and the medial prefrontal cortex (PFC), respectively; another study applying low-frequency (inhibitory) rTMS on the right DLPFC did not find any positive effect on craving. Among uncontrolled studies, one demonstrated the beneficial effect of high-frequency rTMS over the left DLPFC, while another showed the efficacy of a continuous theta burst stimulation protocol directed over the pre-supplementary motor area, bilaterally. CONCLUSION: The included studies showed the promising effect of excitatory stimulation over the left PFC. However, further investigation is needed, particularly in terms of standardizing stimulation protocols and psychometric assessments.

Allergic Diseases in the Elderly.

Recent increases in allergic diseases are thought to be caused by better hygiene, Westernized diets, air pollution, climate change, and other factors that influence host microbiota, a key player in the induction and maintenance of immunoregulatory circuits and tolerance. The increase of allergic diseases in the elderly is also related to additional factors, such as various comorbidities that may interfere with the development and the type of allergic reactions. Immunosenescence plays a central role in these reactions, altering microbiota responses and triggering inflammageing. In addition, in the elderly, there is a shift from Th1 to Th2 immunity, thus favoring allergic responses. A better understanding of the mechanisms responsible for immunosenescence and its effects on allergic inflammation will most certainly lead to improved therapies.

Flourishing or Languishing? Predictors of Positive Mental Health in Medical Students during the COVID-19 Pandemic.

During the COVID-19 pandemic, medical students were burdened with high levels of stress, anxiety, and depression. The objective of the present study was to investigate predictors of positive mental health among medical students during the COVID-19 pandemic. We conducted an online survey from September 2021 to March 2022. We applied the snowball recruitment technique involving medical students from the University of Catania, Italy. We administered, anonymously, a questionnaire about demographic characteristics, the Depression Anxiety Stress Scale (DASS-21), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A), and the short form of the Mental Health Continuum (MHC-SF). Participants showed moderate anxiety, depression, and stress levels, and more than half had positive mental health status overall. This finding was inversely related to age, depression severity, cyclothymic, and depressive temperaments. Our results showed that medical students with depressive and cyclothymic temperaments were more at risk of worsening mental health status during the pandemic. Our findings may allow for further developments about the impact of personological characteristics on students' mental health to enable more efficient support for the most vulnerable.