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PurposeSecretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms.MethodsWe describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity.ResultsTo the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy’s genomic profile revealed not only positivity for the typical SBC’s translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity.ConclusionsSBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management.

PurposeThe purpose of this study is to describe ultra-processed food and drinks (UPFDs) consumption, and associations with intake of total sugar and dietary fibre, and high BMI in adults across Europe.MethodsUsing food consumption data collected by food records or 24-h dietary recalls available from the European Food Safety Authority (EFSA) Comprehensive European Food Consumption Database, the foods consumed were classified by the level of processing using the NOVA classification. Diet quality was assessed by data linkage to the Dutch food composition tables (NEVO) and years lived with disability for high BMI from the Global Burden of Disease Study 2019. Bivariate groupings were carried out to explore associations of UPFDs consumption with population intake of sugar and dietary fibre, and BMI burden, visualised by scatterplots.ResultsThe energy share from UPFDs varied markedly across the 22 European countries included, ranging from 14 to 44%, being the lowest in Italy and Romania, while the highest in the UK and Sweden. An overall modest decrease (2–15%) in UPFDs consumption is observed over time, except for Finland, Spain and the UK reporting increases (3–9%). Fine bakery wares and soft drinks were most frequently ranked as the main contributor. Countries with a higher sugar intake reported also a higher energy share from UPFDs, as most clearly observed for UPF (r = 0.57, p value = 0.032 for men; and r = 0.53, p value = 0.061 for women). No associations with fibre intake or high BMI were observed.ConclusionPopulation-level UPFDs consumption substantially varied across Europe, although main contributors are similar. UPFDs consumption was not observed to be associated with country-level burden of high BMI, despite being related to a higher total sugar intake.

Necrotising fasciitis involving the periorbita is a devastating infection. Potential outcomes range from severe disfigurement, loss of the eye and even to death. Early recognition is critical, although its initially non-distinctive appearance frequently delays diagnosis and treatment. Herein, the authors have performed a systematic review of previously published cases including clinical features, diagnoses and differential diagnoses, pathological characteristics and management. Periorbital necrotising fasciitis is seen mainly in adults with a female predominance (54%); about one-half (47%) of the patients were previously healthy. The infection can follow local blunt trauma (17%), penetrating injuries (22%) and face surgery (11%), but in about one-third of cases (28%) no cause was identified. Non-specific erythema and localised painful swelling of the eyelids characterise the earliest manifestation of the disease, followed by formation of blisters and necrosis of the periorbital skin and subcutaneous tissues. The causative organism in periorbital infection was mainly β-haemolytic Streptococcus alone (50%), occasionally in combination with Staphylococcus aureus (18%). The overall mortality rate was 14.42%. The main risk factor for mortality was the type of causative organism, since all reported cases of death were caused by β-haemolytic Streptococcus alone or associated with other organisms. Unlike necrotising fasciitis affecting other body sites, there was not a strong correlation with age >50 years or the presence of associated chronic illness. Management of periorbital necrotising fasciitis is then based on early distinction of symptoms and signs and aggressive multidisciplinary treatment. Thus, the delay between initial debridement and initiating parenteral broad-spectrum antibiotic therapy should be considered the most critical factor influencing morbidity and mortality.

The neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = −0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.

RationaleStress is a risk factor for psychosis and treatments which mitigate its harmful effects are needed. Cannabidiol (CBD) has antipsychotic and anxiolytic effects.ObjectivesWe investigated whether CBD would normalise the neuroendocrine and anxiety responses to stress in clinical high risk for psychosis (CHR) patients.MethodsThirty-two CHR patients and 26 healthy controls (HC) took part in the Trier Social Stress Test (TSST) and their serum cortisol, anxiety and stress associated with public speaking were estimated. Half of the CHR participants were on 600 mg/day of CBD (CHR-CBD) and half were on placebo (CHR-P) for 1 week.ResultsOne-way analysis of variance (ANOVA) revealed a significant effect of group (HC, CHR-P, CHR-CBD (p = .005) on cortisol reactivity as well as a significant (p = .003) linear decrease. The change in cortisol associated with experimental stress exposure was greatest in HC controls and least in CHR-P patients, with CHR-CBD patients exhibiting an intermediate response. Planned contrasts revealed that the cortisol reactivity was significantly different in HC compared with CHR-P (p = .003), and in HC compared with CHR-CBD (p = .014), but was not different between CHR-P and CHR-CBD (p = .70). Across the participant groups (CHR-P, CHR-CBD and HC), changes in anxiety and experience of public speaking stress (all p’s < .02) were greatest in the CHR-P and least in the HC, with CHR-CBD participants demonstrating an intermediate level of change.ConclusionsOur findings show that it is worthwhile to design further well powered studies which investigate whether CBD may be used to affect cortisol response in clinical high risk for psychosis patients and any effect this may have on symptoms.

The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain.

Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown. Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest. Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients. This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.

Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested. A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; = -0.251, s.d. = 1.242) and those not sensitive ( = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug ( (14) = 2.459, = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; = -275.4, s.d. = 207.519) and those not sensitive ( = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug ( (13) = 3.068, = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

Background: Cannabis use can increase the risk of psychosis, and the acute administration of its key psychoactive ingredient, delta-9-tetrahydrocannabinol (∆9-THC), can induce transient psychotomimetic symptoms. Methods: A double-blind, randomized, placebo-controlled crossover design was used to investigate the symptomatic effects of acute intravenous administration of ∆9-THC (1.19 mg/2 mL) in 16 healthy participants (seven males) with modest previous cannabis exposure. Results: In the 20 min following acute ∆9-THC administration, symptomatic effects of at least mild severity were present in 94% of the cohort, with moderate to severe symptoms having a much lower prevalence (19%). Nearly one-third (31%) of the volunteers were still experiencing protracted mild symptomatic effects 2.5 h after exposure to ∆9-THC. Compared to the Δ9-THC challenge, most of the study participants did not experience any symptomatic effects following placebo administration (62%). Acute physical reactions were 2.5 times more frequent after Δ9-THC (31%) than placebo (12%). Male and female participants differed in terms of acute Δ9-THC effects, with some negative symptoms occurring more frequently in female (56% to 89%) than male participants (0% to 29%), and acute physical reactions occurring exclusively in the female gender (56%). Conclusions: These results have implications for future research, also in light of cannabis being the most widely used illicit drug.

A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.