Effects of transcranial magnetic stimulation on cocaine addiction: A systematic review of randomized controlled trials.

OBJECTIVE: While pharmacological strategies appear to be ineffective in treating long-term addiction, repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. METHOD: A systematic review of randomized controlled trials (RCTs) was conducted on the efficacy and tolerability of rTMS in treating cocaine use disorder (CUD). Relevant papers published in English through November 30th 2022 were identified, searching the electronic databases MEDLINE, Embase, PsycINFO and the Cochrane Library. RESULTS: Eight studies matched inclusion criteria. The best findings were reported by the RCTs conducted at high-frequency (≥5 Hz) multiple sessions of rTMS delivered over the left dorsolateral prefrontal cortex (DLPFC): a significant decrease in self-reported cue-induced cocaine craving and lower cocaine craving scores and a considerable amelioration in the tendency to act rashly under extreme negative emotions (impulsivity) were found in the active group compared to controls. CONCLUSION: Although still scant and heterogeneous, the strongest evidence so far on the use of rTMS on individuals with CUD support the high frequency stimulation over the left DLPFC as a well tolerated treatment of cocaine craving and impulsivity.

One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Hyper/neuroinflammation in COVID-19 and suicide etiopathogenesis: Hypothesis for a nefarious collision?

Accumulating scientific and clinical evidence highlighted pathological hyperinflammation as a cardinal feature of SARS-CoV-2 infection and acute COVID-19 disease. With the emergence of long COVID-19 syndrome, several chronic health consequences, including neuropsychiatric sequelae, have gained attention from the public and medical communities. Since inflammatory mediators have also been accredited as putative biomarkers of suicidal ideations and behaviors, hyper- and neuroinflammation might share some colliding points, overlapping and being interconnected in the context of COVID-19. This review aims to provide a summary of current knowledge on the molecular and cellular mechanisms of COVID-19-associated hyper/neuroinflammation with focus on their relevance to the inflammatory hypothesis of suicide development. Subsequently, strategies to alleviate COVID-19 hyper/neuroinflammation by immunomodulatory agents (many of which at experimental stages) as well as psychopharmacologic/psychotherapeutic approaches are also mentioned. While suicide risk in COVID-19 survivors - until now little known - needs further analysis through longitudinal studies, current observations and mechanistic postulates warrant additional attention to this possibly emerging mental health concern.

Topical Tacrolimus 0.1% for treatment of cutaneous microcystic lymphatic malformations.

Microcystic lymphatic malformations as described in the international literature form a subgroup of low-flow congenital vascular malformations (VM) resulting from irregular embryological development. Microcystic lesions normally manifest as an accumulation of lymph- and blood-filled vesicles that, when externalized, cause skin maceration with consequent pain and potential infection resulting in the impairment of the patient's quality of life. There is no consensus on a standardized algorithm nor clear guidelines for successful treatment of this type of lymphatic malformation, and treatment options employed often result in ambivalent and transient outcomes with a high rate of recurrence. The topical formulation of tacrolimus is a well-known FDAapproved anti-T cell agent that was recently identified as a potent activator of ALK1, which is involved in several processes and functions including angiogenesis. We investigated if topical administration of tacrolimus may be an effective therapy for directly targeting cutaneous microcystic lymphatic malformations as a complement to systemic treatment. The study enrolled four patients with cutaneous microcystic lymphatic malformations: three male (ages: 13,15,18) and one female (age: 30). Two of the patients presented lesions on their backs, one patient on the left hand and one on the left lower limb. All four patients received treatment with topical tacrolimus 0.1% twice a day for 10 weeks on a previously selected area for application. Weekly clinical follow-ups were conducted along with close physician-patient contact. All patients displayed a satisfactory response after treatment. Lymphorrhea and bleeding were stopped in all cases and the esthetic aspect of lesions improved in two patients. To date, all patients presented no clinically significant changes to the size or extension of the lesion. Topical tacrolimus treatment is a promising and reasonable option for microcystic lymphatic malformations. Our results encourage further exploration in larger populations with the consideration that it is a safe and effective alternative or complementary therapy to systemic treatment.

Physical Exercise for Late-Life Major Depression.

(Reprinted with permission from Br J Psychiatry 2005; 207: 235-242).

Molecular detection of Chlamydia abortus in a stranded Mediterranean striped dolphin Stenella coeruleoalba.

This study reports gross, histopathological, and molecular features of a Chlamydia abortus infection in a stranded female striped dolphin Stenella coeruleoalba from the Tyrrhenian coast of southern Italy. Post-mortem examination revealed liver congestion, splenic lymphoid depletion with capsular petechiae, and pneumonia. Histology revealed disseminated intravascular coagulation with vasculitis and congestion. Hepatocellular and acute myocardial degeneration were also observed. Basophilic, coccobacillary inclusions consistent with Chlamydia spp. were observed histologically in the type II pneumocytes, myocardial fibers, and hepatocytes, and in macrophages and plasma cells of liver, spleen, and prescapular lymph nodes. Chlamydial antigen was detected by immunofluorescence assay using genus-specific anti-Chlamydia antibodies. PCR assay revealed C. abortus in spleen, liver, heart, and lungs. C. abortus was the only pathogen detected. The main pathological changes suggest that Chlamydia infection may have been the cause of stranding and death of the striped dolphin. This case represents the first molecular detection of a member of the Chlamydiaceae in a marine mammal.

Plantar lymphatic network.

Anatomical descriptions of the lymphatic system of the foot remain imprecise. In the present report, we aim to elucidate the anatomical lymphatic plantar network in order to improve current clinical practice on the foot. Lower limbs from a total of 25 human cadavers, 4 amputated limbs, and 8 term fetuses were studied. All cadavers were subjected to injection procedures, formalized, immersed in a solution of hydrogen peroxide, and finally dissected. On 6 of the fetal samples, the diaphanization Spatelholz technique was followed. The superficial lymphatic network of the sole is morphologically divided into three plexuses: anterior, medium, and posterior, with the medium differing from the rest. The anterior plexus presents lymphatic vessels forming scarce polygonal figures of considerable size that converge towards the medial edge to constitute ascending trunks. The middle plexus is characterized by the presence of transverse interconnected trunks that extend from one edge to the other of the sole. The posterior plexus presents polygonal figures of smaller size and greater number than the anterior plexus and forms ascending trunks that are directed to the dorsal surface of the foot. These observations demonstrate that the plantar lymphatic network display important differences among the caliber of the lymphatic vessels as well as in the communication and morphological shape of their plexus. Finally, a comparative distribution and organization between the lymphatic and the venous networks was also examined.

Conceptualizations of suicide through time and socio-economic factors: a historical mini-review.

OBJECTIVES: Suicide is a complex phenomenon determined by the interplay of an articulated network of factors including socio-economic factors which have a decisive role. This paper investigates the development of the modern conceptualization of suicide in Europe, its sociological understandings and its intertwinement with economic cycles throughout time. METHODS: MEDLINE, SCHOLAR, EMBASE using the keywords 'socioeconomic factors AND suicide'; 'economic cycles AND suicide'; 'history AND suicide' without timeframe limitations. Moreover, journal-by-journal search in journals of related areas was performed. RESULTS: In total, 51 historical studies focusing on the subjects in European countries were included. Three main areas arose: (a) development of the conceptualization of suicide over time; (b) sociological understandings of suicide according to the structure of society and its economy of power; (c) economic theories explaining the intertwinement of economic cycles and suicides. CONCLUSIONS: Suicide is a deeply human phenomenon inescapably linked to and grounded in society and economic cycles. Understandings from the past show the importance of accurate analysis of socio-economic contexts that shape societies together with man's own sense of self in order to organize multi-layered tangible and intangible support strategies to better understand and prevent suicide in this day and age.

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition.

OBJECTIVE: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. METHOD: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. RESULTS: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). CONCLUSION: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®.

The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used asa fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.

Pathology and molecular analysis of Hapalotrema mistroides (Digenea: Spirorchiidae) infecting a Mediterranean loggerhead turtle Caretta caretta.

Turtle blood flukes belonging to the family Spirorchiidae (Digenea) represent a major threat for sea turtle health and are considered the most important parasitic cause of turtle stranding and mortality worldwide. Despite the large diversity of spirorchiid species found globally, there are only 2 records for free-ranging Mediterranean sea turtles that date back to the late 1800s involving just Hapalotrema mistroides Monticelli, 1896. This study describes the first fatal confirmed case of spirorchiidiasis in a free-ranging Mediterranean loggerhead turtle Caretta caretta (Linnaeus) and, owing to the complexities of taxonomic identification of these parasites, provides the first molecular characterization and phylogenetic analysis of H. mistroides from the Mediterranean Sea. The loggerhead turtle showed cachexia and digestive disorders associated with severe damage to the pancreas and intestinal ganglia, caused by deposition of Hapalotrema eggs forming granulomas. Massive Hapalotrema egg emboli in several tissues and organs and encephalitis were the most probable contributions to the death of the turtle. The congruence between the phylogenetic analysis of both the ITS2 and 28S rDNA resolved the Italian and USA H. mistroides as the same species, confirming the parasite identification. The case here described clearly indicates that the blood flukes should be considered in the differential diagnosis of Mediterranean sea turtle diseases.

A new combined operative technique using crossed inguinal lymphatic rescue for pediatric patients with mixed lymphatic and venous malformations.

Truncular venous malformations and acquired functional or anatomical venous occlusions (or sub-occlusions) can be the cause of secondary lymphedema and even the cause of primary lymphedema when they are associated with lymphatic malformations (lymphangiodysplasia - LAD I, lymphadenodysplasia - LAD II, or a combination of both) in pediatric patients. This understanding recognizes the shared and successive embryogenesis of both systems. These conditions can exhibit hypertension in the venous pedicles intended for lymph-venous anastomosis, and this finding would be a formal contraindication to the procedure. However, this hypertension is a rarely considered condition and is not commonly identified. As a technique to solve this problem, we have combined Nielubowicz, Olszewski, Campisi, and Palma's proposals and created a lymph-venous anastomosis from the side with lymphedema and venous hypertension (lymphatic donor and venous recipient) with an internal suprapubic saphenous venous bridge (from the normal side to the lymphedematous side with venous hypertension) to enable a crossed inguinal lymphatic/venous rescue. We believe this newly synthesized approach will allow better clinical care of pediatric patients with complex and combined lymphatic-venous malformations and is worthy of further investigation.

Social cognition in people with schizophrenia: a cluster-analytic approach.

BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. CONCLUSIONS: If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

Abnormal functional-structural cingulum connectivity in mania: combined functional magnetic resonance imaging-diffusion tensor imaging investigation in different phases of bipolar disorder.

OBJECTIVE: The objective of the study was to investigate the relationship between structural connectivity (SC) and functional connectivity (FC) in the cingulum in bipolar disorder (BD) and its various phases. METHOD: We combined resting-state functional magnetic resonance imaging and probabilistic tractographic diffusion tensor imaging to investigate FC and SC of the cingulum and its portions, the SC-FC relationship, and their correlations with clinical and neurocognitive measures on sustained attention in manic (n = 21), depressed (n = 20), and euthymic (n = 20) bipolar patients and healthy controls (HC) (n = 42). RESULTS: First, we found decreased FC between the anterior and posterior parts of the cingulum in manic patients when compared to depressed patients and HC. Second, we observed decreased SC of the cingulum bundle, particularly in its anterior part, in manic patients when compared to HC. Finally, alterations in the cingulum FC (but not SC) correlated with clinical severity scores while changes in the cingulum SC (but not FC) were related with neurocognitive deficits in sustained attention in BD. CONCLUSION: We demonstrate for the first time a reduction in FC and concomitantly in SC of the cingulum in mania, which correlated with psychopathological and neurocognitive parameters, respectively, in BD. This supports the central role of cingulum connectivity specifically in mania.

The communication of suicidal intentions: a meta-analysis.

BACKGROUND: Among the myths that are often cited about suicide is that 'people who talk about killing themselves rarely die by suicide', but the evidence seems to contradict this statement. The aim of this study was to conduct a meta-analysis of studies reporting a prevalence of suicide communication (SC), and to examine the diagnostic accuracy of SC towards suicide in case-control reports. METHOD: Eligible studies had to examine data relative to completed suicides and report the prevalence of SC. Data relative to sample characteristics, study definition, modality and recipient of the SC were coded. RESULTS: We included 36 studies, conducted on a total of 14 601 completed suicides. The overall proportion of SC was 44.5% [95% confidence interval (CI) 35.4-53.8], with large heterogeneity (I 2 = 98.8%) and significant publication bias. The prevalence of SC was negatively associated with the detection of verbal communication as the sole means of SC and, positively, with study methodological quality. Based on seven case-control studies, SC was associated with an odds ratio of 4.66 for suicide (95% CI 3.00-7.25) and was characterized by sufficient diagnostic accuracy only if studies on adolescents were removed. CONCLUSION: Available data suggest that SC occurs in nearly half of subjects who go on to die by suicide, but this figure is likely to be an underestimate given the operational definitions of SC. At present, SC seems associated with overall insufficient accuracy towards subsequent suicide, although further rigorous studies are warranted to draw definite conclusions on this issue.