High-fat diet (HFD) consumption during pregnancy can shape fetal brain development, increasing susceptibility to mental disorders. Nevertheless, the mechanisms underlying these negative outcomes remain unclear.

We hypothesize that mHFD induces inflammation and oxidative stress (OS) in the fetal brain, disrupting excitatory/inhibitory (E/I) balance in the adult brain. This results in altered hypothalamic-pituitary-adrenal (HPA) axis reactivity, emotional regulation, and cognitive function. We tested the ability of N-acetyl-cysteine (NAC) - a powerful anti-oxidant and anti-inflammatory compound - to counteract mHFD effects.

Our mHFD model consists of female C57BL/6N mice fed either HFD (fat 58%, carbohydrate 25.5%, and protein 16.4%) or control diet (CD, fat 10.5%, carbohydrate 73.1% and protein 16.4%) before and during pregnancy (13 weeks). After 5 weeks on diets, half of them received NAC (1g/kg) for 8 weeks, until delivery.

Gene expression of Il-1b, Cd68, Tmem119, iNOS, and Arg1 was measured in fetal brains. Cognitive function and emotional phenotype were assessed in adult male and female offspring through the Morris Water Maze (MWM) and the Emergence test, respectively. HPA axis functionality was assessed by measuring plasma corticosterone levels by ELISA following acute stress. Gene expression of vesicular glutamate transporter 1 (Vglut1) and vesicular GABA transporter (Vgat) were assessed as markers of E/I balance.

Exposure to mHFD induced inflammation and OS in the fetal brain of both sexes, by increasing Il-1b and iNOS/Arg1. Additionally, Cd68 and Tmem119 were specifically increased in females. In adulthood, mHFD reduced latency to emerge from the shelter in the Emergence test in both sexes. In females, mHFD impaired cognitive function, reducing time spent in the MWM target zone, and increased HPA reactivity in response to acute stress. Furthermore, mHFD decreased Vgat expression in both sexes, resulting in an imbalanced Vglut1/Vgat ratio towards excessive excitatory input. Maternal NAC supplementation rescued this imbalance.

Overall, these data show that mHFD increases inflammation and OS in fetal brains, with greater effects in female offspring, inducing alterations in the E/I neuronal balance with concomitant disruptions of the neuroendocrine system and the emotional and cognitive profiles during adulthood. The supplementation with NAC was effective in rescuing the E/I imbalance as well as the behavioral phenotype.

None Declared

Stressful experiences in utero can produce physiological changes which become embedded biological traces affecting fetal brain development and ultimately leading to increased vulnerability for psychiatric disorders.

We hypothesized that stressors as diverse as maternal obesity and maternal psychophysical stress might disrupt fetal programming resulting in long-lasting effects on offspring brain development by acting through shared oxidative stress (OS)-mediated mechanisms.

We compared a mouse model (C57Bl/6N) of maternal high-fat diet (HFD) consumption (13 weeks, until delivery) to prenatal restraint stress (PNS) repeatedly administered during the last week of pregnancy. To counteract the negative effects of both stressors, the antioxidant N-acetyl-cysteine (NAC, 1 g/kg) was administered to female breeders for 8 weeks until delivery. Emotionality was assessed in adolescent male and female offspring through the elevated-plus-maze (EPM). Moreover, hippocampal gene expression levels of Brain-Derived-Neurotrophic-Factor (Bdnf), Nuclear factor erythroid 2–related factor 2 (Nrf-2) and Kelch-like ECH-associated protein 1 (Keap-1) were measured, by qPCR, as markers of brain plasticity and antioxidant capacity.

Prenatal exposure to both HFD and PNS enhanced behavioral disinhibition, increasing time spent in the open arms of the EPM and decreasing the frequency of risk-assessment behaviors, especially in female offspring. Moreover, both prenatal stressors led to decreased Bdnf (in females) and Nrf-2 levels, and disrupted Keap-1 levels. Prenatal NAC was able to counteract these effects on the brain.

Our data support the hypothesis of a “funnel effect” model explaining how different prenatal stressors result in long-term negative effects on the adolescent offspring, increasing risk assessment behaviors and affecting brain plasticity and antioxidant defenses. The beneficial preventive effects of NAC suggest that OS may be a common mechanism, playing a pivotal role in fetal programming of mental disorders. ERANET-NEURON-JTC-2018-Mental Disorders-“EMBED” and Bando Ricerca Indipendente ISS 2021-2023; MOMINFLAM. Unique signatures underlying placental-fetal brain crosstalk in maternal obesity to F Cirulli.

None Declared

Bipolar disorder (BD) is a psychiatric disease whose heterogeneity in phenotypic manifestations and disease severity hampers the diagnosis and the achievement of adequate therapeutic management. Increased pro-inflammatory cytokines and cortisol levels (CORT) have been observed in BD patients that might affect brain plasticity by decreasing Brain-Derived-Neurotrophic Factor (BDNF) levels. However, BD etiopathological mechanisms are still largely unclear and little is known about the interaction among these biomarkers and affective episodes.

To assess changes in peripheral endocrine and inflammatory markers, CORT awakening response, BDNF and cytokines levels during an acute phase of the disease and during euthymia and to evaluate whether these changes might be exploited as a biosignature of the disease.

The study will be carried out on BD patients aged 18-65 who will be recruited during affective episodes (depressive, manic/hypomanic phase). In addition, a control group of 40 healthy subjects, age- and sex-matched will be also enrolled. All assessments will be carried out at the time of recruitment and after 3 and 6 months. Blood samples will be collected to evaluate cytokines (IL-1, IL-2, IL-6, IL-10, TNF-alpha, IFN-gamma) and BDNF. Hypothalamic-pituitary-adrenal (HPA) axis response will be assessed by measuring salivary cortisol levels upon awakening (cortisol awakening response – CAR). The psychopathological assessment will include the use of MADRS, YMRS and HAM-A for the assessment of psychiatric symptoms; PSP and C-SSRS for the assessment of global functioning and suicidal risk; IPSS and SRRS for the assessment of stress levels; CIRS for the evaluation of physical comorbidities.

We expect that 1) changes in inflammatory markers can predict the onset of acute phases of BD; 2) to observe significant differences in the levels of pro-inflammatory cytokines, CORT and BDNF between BD patients (during euthymia) and control subjects.

Using a longitudinal approach, we will be able to evaluate whether the presence of affective symptoms in the BD patient is correlated with fluctuations in the levels of pro-inflammatory cytokines and chemokines, salivary cortisol and BDNF. Furthermore, the enrolment of control subjects will allow to evaluate if the inflammatory state and the activation of the HPA axis are steadily elevated in BD patients.

“Funded by: Bando Ricerca Indipendente ISS 2021-2023 to A. Berry project code ISS20-9286e4091f8e”

None Declared

To report a case of fluctuating hearing due to auditory aura, as an unusual presentation of temporal lobe epilepsy.

Case report and review of English language literature on temporal lobe epilepsy and auditory aura.

A 31-year-old man presented with intermittent symptoms of bilateral fullness in the ears associated with deafness. He was subsequently diagnosed with temporal lobe epilepsy. Further enquiry revealed a family history of epilepsy.

Auditory aura as a presentation of temporal lobe epilepsy is rarely encountered in otolaryngological practice. This case highlights the importance of obtaining detailed information on epilepsy, including any family history of epilepsy, as a routine part of history-taking in patients presenting with fluctuating hearing loss.

Precise delineation of the extent of frontal sinus pneumatisation is a crucial step in osteoplastic flap frontal sinus surgery. The authors present a novel method of achieving this objective.

First, models of the frontal area are generated using three-dimensional printing based on pre-operative computed tomography image data. These models are then used to create an onlay template of the frontal sinus, which is used intra-operatively.

In a series of 10 patients undergoing osteoplastic flap frontal sinus surgery, the described frontal sinus templates were consistently accurate to within 1 mm.

Frontal sinus templates are potentially useful adjuncts to current techniques employed to guide frontal sinus surgery.

To ascertain which components of healthcare worker (HCW) influenza vaccination programs are associated with higher vaccination rates.

Survey.

University-affiliated hospitals.

Participating hospitals were surveyed with regard to their institutional HCW influenza vaccination program for the 2007-2008 influenza season. Topics assessed included vaccination adherence and availability, use of declination statements, education methods, accountability, and data reporting. Factors associated with higher vaccination rates were ascertained.

Fifty hospitals representing 368,696 HCWs participated in the project. The median vaccination rate was 55.0% (range, 25.6%-80.6%); however, the types of HCWs targeted by vaccination programs varied. Programs with the following components had significantly higher vaccination rates: weekend provision of vaccine (58.8% in those with this feature vs 43.9% in those without; P = .01), train-the-trainer programs (59.5% vs 46.5%; P = .005), report of vaccination rates to administrators (57.2% vs 48.1%; P = .04) or to the board of trustees (63.9% vs 53.4%; P = .01), a letter sent to employees emphasizing the importance of vaccination (59.3% vs 47%; P = .01), and any form of visible leadership support (57.9% vs 36.9%; P = .01). Vaccination rates were not significantly different between facilities that did and those that did not require a signed declination form for HCWs who refused vaccination (56.9% vs 55.1%; P = .68), although the precise content of such statements varied.

Vaccination programs that emphasized accountability to the highest levels of the organization, provided weekend access to vaccination, and used train-the-trainer programs had higher vaccination coverage. Of concern, the types of HCWs targeted by vaccination programs differed, and uniform definitions will be essential in the event of public reporting of vaccination rates.

We present a rare and clinically relevant anomaly of the sphenopalatine artery in relation to its blood supply of the nasal mucosa, with implications for the management of epistaxis.

Case report and review of the world literature, using Medline through Pub Med (1950–2005), EMBASE (1980–2005) and Ovid (1958–2005), searching for papers using a combination of terms including ‘spheno-palatine artery’, ‘anterior ethmoidal artery’ and ‘epistaxis’.

In the presented case of refractory epistaxis, endoscopic and subsequent endovascular management failed to identify a significant supply from the sphenopalatine arteries bilaterally. The main supply was found to be from the anterior ethmoidal arteries.

After a detailed search, the authors failed to locate any similar case in the English literature.