Antiepileptogenesis after stroke—trials and tribulations: Methodological challenges and recruitment results of a Phase II study with eslicarbazepine acetate

There is currently no evidence to support the use of antiseizure medications to prevent unprovoked seizures following stroke. Experimental animal models suggested a potential antiepileptogenic effect for eslicarbazepine acetate (ESL), and a Phase II, multicenter, randomized, double-blind, placebo-controlled study was designed to test this hypothesis and assess whether ESL treatment for 1 month can prevent unprovoked seizures following stroke. We outline the design and status of this antiepileptogenesis study, and discuss the challenges encountered in its execution to date. Patients at high risk of developing unprovoked seizures after acute intracerebral hemorrhage or acute ischemic stroke were randomized to receive ESL 800 mg/d or placebo, initiated within 120 hours after primary stroke occurrence. Treatment continued until Day 30, then tapered off. Patients could receive all necessary therapies for stroke treatment according to clinical practice guidelines and standard of care, and are being followed up for 18 months. The primary efficacy endpoint is the occurrence of a first unprovoked seizure within 6 months after randomization (“failure rate”). Secondary efficacy assessments include the occurrence of a first unprovoked seizure during 12 months after randomization and during the entire study; functional outcomes (Barthel Index original 10-item version; National Institutes of Health Stroke Scale); post-stroke depression (Patient Health Questionnaire-9; PHQ-9); and overall survival. Safety assessments include the evaluation of treatment-emergent adverse events; laboratory parameters; vital signs; electrocardiogram; suicidal ideation and behavior (PHQ-9 question 9). The protocol aimed to randomize approximately 200 patients (1:1), recruited from 21 sites in seven European countries and Israel. Despite the challenges encountered, particularly during the COVID-19 pandemic, the study progressed and included a remarkable number of patients, with 129 screened and 125 randomized. Recruitment was stopped after 30 months, the first patient entered in May 2019, and the study is ongoing and following up on patients according to the Clinical Trial Protocol

A Specialized Odor Memory Buffer in Primary Olfactory Cortex

The neural substrates of olfactory working memory are unknown. We addressed the questions of whether olfactory working memory involves a verbal representation of the odor, or a sensory image of the odor, or both, and the location of the neural substrates of these processes.We used functional magnetic resonance imaging to measure activity in the brains of subjects who were remembering either nameable or unnameable odorants. We found a double dissociation whereby remembering nameable odorants was reflected in sustained activity in prefrontal language areas, and remembering unnameable odorants was reflected in sustained activity in primary olfactory cortex.These findings suggest a novel dedicated mechanism in primary olfactory cortex, where odor information is maintained in temporary storage to subserve ongoing tasks

Dissociated Representations of Pleasant and Unpleasant Olfacto-Trigeminal Mixtures: An fMRI Study

How the pleasantness of chemosensory stimuli such as odorants or intranasal trigeminal compounds is processed in the human brain has been the focus of considerable recent interest. Yet, so far, only the unimodal form of this hedonic processing has been explored, and not its bimodal form during crossmodal integration of olfactory and trigeminal stimuli. The main purpose of the present study was to investigate this question. To this end, functional magnetic resonance imaging (fMRI) was used in an experiment comparing brain activation related to a pleasant and a relatively unpleasant olfacto-trigeminal mixture, and to their individual components (CO2 alone, Orange alone, Rose alone). Results revealed first common neural activity patterns in response to both mixtures in a number of regions: notably the superior temporal gyrus and the caudate nucleus. Common activations were also observed in the insula, although the pleasant mixture activated the right insula whereas the unpleasant mixture activated the left insula. However, specific activations were observed in anterior cingulate gyrus and the ventral tegmental area only during the perception of the pleasant mixture. These findings emphasized for the firs time the involvement of the latter structures in processing of pleasantness during crossmodal integration of chemosensory stimuli

Is Promiscuity Associated with Enhanced Selection on MHC-DQα in Mice (genus Peromyscus)?

Reproductive behavior may play an important role in shaping selection on Major Histocompatibility Complex (MHC) genes. For example, the number of sexual partners that an individual has may affect exposure to sexually transmitted pathogens, with more partners leading to greater exposure and, hence, potentially greater selection for variation at MHC loci. To explore this hypothesis, we examined the strength of selection on exon 2 of the MHC-DQα locus in two species of Peromyscus. While the California mouse (P. californicus) is characterized by lifetime social and genetic monogamy, the deer mouse (P. maniculatus) is socially and genetically promiscuous; consistent with these differences in mating behavior, the diversity of bacteria present within the reproductive tracts of females is significantly greater for P. maniculatus. To test the prediction that more reproductive partners and exposure to a greater range of sexually transmitted pathogens are associated with enhanced diversifying selection on genes responsible for immune function, we compared patterns and levels of diversity at the Class II MHC-DQα locus in sympatric populations of P. maniculatus and P. californicus. Using likelihood based analyses, we show that selection is enhanced in the promiscuous P. maniculatus. This study is the first to compare the strength of selection in wild sympatric rodents with known differences in pathogen milieu

Un inusuale rituale omicidiario: l’incaprettamento, commesso da un ex componente della Legione Straniera. An unusual homicide by ligature strangulation (“incaprettamento” a.k.a. “trussed goat”) committed by a retired Foreign Legionnaire.

The case presented here concerns an unusual type of strangulation homicide whereby a rope is passed around the victim’s wrists, ankles, and throat resulting in suffocation by auto-asphyxia. The literature usually refers to this method as “incaprettamento” (i.e. “trussed up like a goat”), a method employed by organized crime groups such as the Italian Mafia, but also used in the execution of war crimes, or in various other cultural-anthropological contexts, This method of killing is meant to impart a particularly degrading and humiliating revenge on the victim. It also serves as sign of intimidation and a warning to others.To all appearances, the case presented here is different than those usually reported in the literature. The unusual way in which the killing took place, along with its symbolic meaning, seems to have both military and anthropological origins that reflect the culture to which the perpetrator belonged. This case study, offers the opportunity to analyze the interaction between these factors and those derived from the experience of a rigid military environment such as that of the Foreign Legion