Feasibility and Safety of the "One-Week Breast Radiation Therapy" Program.

AIMS: FAST-Forward and UK-FAST-trials have demonstrated the safety and efficacy of five-fraction breast adjuvant radiation therapy (RT) and have become the standard of care for selected early breast cancer patients. In response to the additional burden caused by the COVID-19 pandemic, we implemented "One-Week Breast RT," an innovative program delivering five-fraction whole breast RT in a complete 5-day workflow. The primary objective of this study was to demonstrate the feasibility and safety of our program. The secondary objective was to evaluate cosmetic results. MATERIAL AND METHODS: A total of 120 patients treated from February 2021 to March 2022, received whole breast RT without lymph node irradiation nor boost, with 26 Gy in five fractions over one week. Inverse planning with restricted optimization parameters offers systematic deep inspiration breath-hold aimed to provide treatment plans compliant with FAST-Forward recommendations. Toxicity and cosmetic evaluations were prospectively registered prior (pre-RT), at the end (end-RT), and 6 months after RT (6 months) based on Common Terminology Criteria for Adverse Events v. 4.03 and Harvard scale. RESULTS: With a median age of 70 years (interquartile range (IQR): 66-74) and a median follow-up of 6 months (IQR: 6.01-6.25), most patients (93.3%) completed their RT in one week from baseline to the end of the treatment consultation. The most common acute toxicities (at end-RT) were skin-related: radio-dermatitis (72%), induration (35%), hyperpigmentation (8%), and breast edema (16%). The rate of radio-dermatitis decreased from end-RT to 6 months (71.7% vs 5.4%, P< 0.001). No patient experienced grade ≥3 toxicity. At 6 months, cosmetic results were generally good or excellent (94.1%). CONCLUSION: This study confirms the feasibility and acute safety of the "One-Week Breast RT" in real life. Favorable toxicity profiles and good cosmetic outcomes are in line with FAST-Forward results. A prospective national cohort, aimed at decreasing treatment burden, maintaining safety, efficacy, and improving RT workflow efficiency with longer follow-up is ongoing.

Selenoprotein T, a potential treatment of attention-deficit/hyperactivity disorder and comorbid pain in neonatal 6-OHDA lesioned mice.

pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain. Growing evidence suggests that oxidative stress may be crucial in both pathologies. Recent studies revealed that a small peptide encompassing the redox-active site of selenoprotein T (PSELT), protects dopaminergic neurons and fibers as well as lesioned nerves in animal models. The current study aims to examine the effects of PSELT treatment on ADHD-like symptoms and pain sensitivity, as well as the role of catecholaminergic systems in these effects. Our results demonstrated that intranasal administration of PSELT reduced the hyperactivity in the open field, decreased the impulsivity displayed by 6-OHDA-lesioned male mice in the 5-choice serial reaction time task test and improved attentional performance. In addition, PSELT treatment significantly increased the nociception threshold in both normal and inflammatory conditions. Furthermore, anti-hyperalgesic activity was antagonized with sulpiride pre-treatment, but not by phentolamine, or propranolol pre-treatments. The present study suggests that PSELT reduces the severity of ADHD symptoms in mice and possesses potent antinociceptive effects which could be related to the involvement of D2/D3 dopaminergic receptors.

Exposure to metam sodium-based pesticide impaired cognitive performances in adult mice: Involvement of oxidative damage and glial activation.

Cognitive integrity is a critical aspect of neurological function, and a decline in cognitive function is a hallmark of neurotoxicity. Oxidative stress is a significant pathological feature contributing to cognitive deficits that can arise from exposure to environmental pollutants such as pesticides. Among these, Metam sodium-based pesticides (MS-BP) are an emergent type of pesticide widely used in the agriculture and public health sectors for controlling pests and diseases. Our prior research has shown that animals exposed to MS-BP during the early stages of brain development caused cognitive impairments. In the present study, we tested whether exposure to this compound in a fully matured brain would affect cognitive performance and induce oxidative damage to the central nervous system. In this context, adult mice received chronic treatment with increasing doses of MS-BP and subjected to a set of behavioral paradigms. Following behavioral assessment, oxidative stress and glial activation were evaluated. Our main findings showed that MS-BP chronic exposure impaired recognition and short- and long-term memory. These alterations were accompanied by increased superoxide dismutase activity and malondialdehyde level and a marked decrease in catalase activity in specific brain areas. Moreover, exposure to MS-BP is associated with a significant rise in the density of astrocytic and microglial markers, indicating a possible glial cell response within the prefrontal cortex and hippocampus. The present work demonstrated that MS-BP altered cognitive performance likely through oxidative damage to the brain.

Effects of topiramate on morphological and structural alterations of the anterior cingulate cortex in aggressive socially isolated mice.

RATIONALE: Topiramate, an approved antiepileptic drug, was found effective in treating aggressive symptoms in humans and rodents. However, the effects and mechanisms of Topiramate on aggressive behavior are still unclear. Our previous study indicated that intraperitoneal administration of Topiramate successfully decreased aggression and reinforced sociability in socially aggressive mice, and increased cFos-expressing neurons in the anterior cingulate cortex (ACC). In addition to its pharmacological properties, previous studies have approved the neuroprotective effects of Topiramate. These suggest a potential effect of Topiramate on ACC's structure and function. OBJECTIVES AND RESULTS: In the present study, we first investigated the structural characteristics of ACC in the social isolation-induced aggression paradigm. The results showed that hyper-aggressive behavior in socially aggressive mice was associated with several structural alterations in ACC: increased neuron death combined with decreased neuron density, increased damaged neuronal morphology and increased neuroinflammation markers. Based on these observations, we next investigated the potential neuroprotective effect of Topiramate against structural alterations of ACC observed in socially aggressive mice. Results indicated that intraperitoneal administration of Topiramate (30 mg/kg) decreased aggression and enhanced sociability without affecting locomotor activity. Interestingly, the anti-aggressive effect of Topiramate was associated with decreased neuronal death, ameliorated damaged neuronal morphology, and decreased reactive microglia markers in ACC. CONCLUSIONS: Our results provide insights into the structural alterations of ACC in aggressive socially aggressive mice. Moreover, the present study suggested that the anti-aggressive effect of Topiramate could be related to its neuroprotective effects against the structural alterations of ACC.

The role of the anterior cingulate cortex in aggression and impulsivity.

Aggression is a complex social behavior that evolved in the context of defending a territory, fighting for limited resources, and competing for mates and protection. Although aggression considered as a negative or undesirable emotion is an essential part of many species' repertoire of social behaviors. For humans, the motivations, actions, and limits of aggressive acts are not always clear. However, uncontrolled aggression may have destructive consequences, and it develops inappropriately into violence. At the neural level, several studies demonstrated that aggression is related to cortical abnormalities, including the anterior cingulate cortex (ACC). This review summarizes the state of the literature regarding the involvement of ACC in the neurobiology of aggression and impulsivity. We will first review structural and neuroanatomical studies, including volumetric and functional investigations of aggression. Next, we will discuss the neurochemical and neuropharmacological studies of aggression related to the ACC. We will focus mainly on the gamma-aminobutyric acid/glutamate balance, as well as the serotoninergic system. Finally, we will try to integrate these results and reconcile discrepancies in the field and suggest recommendations for future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of atomoxetine on ADHD-pain hypersensitization comorbidity in 6-OHDA lesioned mice.

BACKGROUND: Methylphenidate and atomoxetine are used for the treatment of attention-deficit/hyperactivity disorder (ADHD). Our previous studies established the validity of the 6-hydroxydopamine (6-OHDA) mouse model of ADHD and demonstrated hypersensitivity to pain, in line with clinical reports in ADHD patients. Acute methylphenidate treatment reduces hyperactivity and increases attention, but does not affect pain behaviors in this mouse model. Whereas atomoxetine has been shown to be effective against some symptoms of ADHD, nothing is known about its possible action on comorbid pain hypersensitivity. The objectives of the present research are (1) to investigate the effects of acute and chronic treatment with atomoxetine on ADHD-like symptoms and nociceptive thresholds, and (2) to explore the catecholaminergic systems underlying these effects. METHODS: Sham and 6-OHDA cohorts of male mice were tested for hyperactivity (open field), attention and impulsivity (5-choice serial reaction time task test), and thermal (hot plate test) and mechanical (von Frey test) thresholds after acute or repeated treatment with vehicle or atomoxetine (1, 3 or 10 mg/kg). RESULTS: Acute administration of atomoxetine (10 mg/kg) reduced the hyperactivity and impulsivity displayed by 6-OHDA mice, without affecting attention or nociception. However, atomoxetine administered at 3 mg/kg/day for 7 days alleviated the ADHD-like core symptoms and attenuated the hyperalgesic responses. Furthermore, hyperlocomotion and anti-hyperalgesic activity were antagonized with phentolamine, propranolol, and sulpiride pre-treatments. CONCLUSION: These findings demonstrated that when administered chronically, atomoxetine has a significant effect on ADHD-associated pain hypersensitization, likely mediated by both α- and ß-adrenergic and D2/D3 dopaminergic receptors, and suggest new indications for atomoxetine that will need to be confirmed by well-designed clinical trials.

Chronic exposure to metam sodium-based pesticide in mice during adulthood elevated anxiety and depression-like behaviors: Involvement of serotoninergic depletion and gut microbiota dysbiosis.

Metam sodium-based pesticide (MS-BP) is widely used in agriculture and public health. We have previously demonstrated that maternal exposure to MS-BP resulted in sensorimotor alterations in mice offspring with long-lasting deficits including anxiety- and depression-like behaviors. Here, we project to verify whether these two neurobehavioral effects occur during adulthood following direct exposure to MS-BP and whether it results in changes in the serotoninergic system and gut microbiota. Our findings showed that chronic exposure to MS-BP increased anxiety- and depression-like behaviors, accompanied by a depletion of serotonin-like neurons within the dorsal raphe nucleus and a reduction in serotoninergic terminals in the infralimbic cortex and the basolateral amygdala. In addition, all MS-BP-exposed animals exhibited a reduced total bacterial number and diversity of gut microbiota. Taken together, our data demonstrated that MS-BP-induced behavioral changes could be related to the impairment of the serotoninergic system and gut microbiota dysbiosis.

Facteurs associés à l'hospitalisation prolongée et à la mortalité au niveau du service de néphrologie de l'hôpital Aristide Le Dantec de Dakar / Factors associated with prolonged hospitalization and mortality in the nephrology department of the Aristide Le Dantec hospital in Dakar

Introduction : L'hospitalisation en néphrologie n'avait pas fait l'objet de plusieurs études au Sénégal et les données sont limitées. Notre travail avait pour but de déterminer les facteurs associés à l'hospitalisation prolongée et à la mortalité en néphrologie. Patients et méthodes : Il s'agissait d'une étude observationnelle prospective de 5 mois incluant tous les patients hospitalisés dans le service durant au moins 24H. La durée d'hospitalisation (la période allant du jour d'admission dans la chambre d'hospitalisation au jour de sortie du patient) était dite prolongée si > 12 jours. Résultats : Quatre-vingt-dix-neuf patients ont été analysés durant cette période avec une durée moyenne en hospitalisation de 11,14 ± 9,89 jours. L'âge moyen était de 45,22 ± 18,03 ans avec un sex-ratio (H/F) de 0,62. Les anomalies biologiques étaient : l'hyponatrémie (62,36%), l'hypokaliémie (23,91%), l'hypocalcémie (25%), l'hyperphosphatémie (51,21%), l'anémie (92,30%), la CRP élevée (90,90%) et l'hypoalbuminémie (80,76%). La protéinurie moyenne était de 3,38 ± 3,35 g/24h avec 34,61% de protéinurie néphrotique. La mortalité hospitalière était de 25,25%. En analyse univariée, l'hospitalisation prolongée était associée à l'âge ≤ 45 ans (p = 0,018), aux patients non dialysés chroniques (p=0,034), à la transfusion sanguine (p=0,008) tandis que la mortalité était liée à l'âge de plus de 45 ans (p=0,032), le diabète (p=0,014), l'hypokaliémie (p=0,045) et l'hospitalisation prolongé (p=0,007). En analyse multivariée, les patients présentant des œdèmes et ceux ayant été transfusés avaient respectivement 2,89 et 3,9 fois plus de risque d'avoir une hospitalisation prolongée. Les patients diabétiques avaient 4,63 fois plus de risque de décès et ceux ayant été hospitalisés de plus de 12 jours avaient 0,14 fois de risque de décès. Conclusion : La durée d'hospitalisation était relativement prolongée avec une mortalité élevée. Cependant l'impact de certains facteurs a été démontré permettant ainsi de réduire la durée d'hospitalisation et le nombre de décès.

Introduction: Hospitalization in nephrology had not been the subject of several studies in Senegal and the data are limited. Our work aimed to determine the factors associated with prolonged hospitalization and mortality in nephrology. Patients and methods: This was a 5-month prospective observational study including all patients hospitalized in the department for at least 24 hours. The duration of hospitalization (the period from the day of admission to the hospital room to the day of the patient's discharge) was said to be prolonged if > 12 days. Results: Ninety-nine patients were analyzed during this period with an average hospital stay of 11.14 ± 9.89 days. The mean age was 45.22 ± 18.03 years with a sex ratio (M/F) of 0.62. The biological abnormalities were: hyponatremia (62.36%), hypokalemia (23.91%), hypocalcemia (25%), hyperphosphatemia (51.21%), anemia (92.30 %), elevated CRP (90.90%) and hypoalbuminemia (80.76%). The mean proteinuria was 3.38 ± 3.35 g/24h with 34.61% nephrotic proteinuria. Hospital mortality was 25.25%. In univariate analysis, prolonged hospitalization was associated with age ≤ 45 years (p = 0.018), chronic non-dialysis patients (p = 0.034), blood transfusion (p = 0.008) while mortality was related to age over 45 (p=0.032), diabetes (p=0.014), hypokalaemia (p=0.045) and prolonged hospitalization (p=0.007). In multivariate analysis, patients with edema and those who had been transfused were respectively 2.89 and 3.9 times more likely to have prolonged hospitalization. Diabetic patients had a 4.63 times greater risk of death and those who had been hospitalized for more than 12 days had a 0.14 times greater risk of death. Conclusion: The duration of hospitalization was relatively prolonged with high mortality. However, the impact of certain factors has been demonstrated, thus making it possible to reduce the duration of hospitalization and the number of deaths

Temporal judgments of actions following unilateral brain damage.

Sense of time is a complex construct, and its neural correlates remain to date in most part unknown. To complicate the frame, physical attributes of the stimulus, such as its intensity or movement, influence temporal perception. Although previous studies have shown that time perception can be compromised after a brain lesion, the evidence on the role of the left and right hemispheres are meager. In two experiments, the study explores the ability of temporal estimation of multi-second actions and non-biological movements in 33 patients suffering from unilateral brain lesion. Furthermore, the modulatory role of induced embodiment processes is investigated. The results reveal a joint contribution of the two hemispheres depending not only on different durations but also on the presence of actions. Indeed, the left hemisphere damaged patients find it difficult to estimate 4500 ms or longer durations, while the right hemisphere damaged patients fail in 3000 ms durations. Furthermore, the former fail when a biological action is shown, while the latter fail in non-biological movement. Embodiment processes have a modulatory effect only after right hemisphere lesions. Among neuropsychological variables, only spatial neglect influences estimation of non-biological movement.

A Bibliometric Analysis of the Trends in the Research on Wearable Technologies for Cardiovascular Diseases.

In this paper, a bibliometric analysis of research on wearable technologies for cardiovascular diseases was conducted with Bibliometrix and based on 1675 papers collected in Scopus from 2000 to 2022, and interesting results were presented. The US and China stood out for their sustained productivity in the field of cardiovascular diseases. The examination of the authors' keywords revealed that between 2000-01 and 2009-12, "Respiration" and "personalized applications" were the most popular research topics, however from 2010-01 to 2019-12, attention was given to "ECG," "Wearable devices," "Wearable sensors," and "heart rate". This study suggests that in the present decade, researchers should focus on topics related to artificial intelligence, hypertension, ECG, wearable sensors, and African countries must address their technological gap in the coming years.

The socially enriched environment test: a new approach to evaluate social behavior in a mouse model of social anxiety disorder.

Social anxiety disorder (SAD) is a common anxiety disorder characterized by a marked fear of social situations. Treatments for SAD, including exposure therapy and medication, are not satisfactory for all patients. This has led to the development of several paradigms to study social fear in rodents. However, there are still some social impairments observed in SAD patients that have never been examined in rodent models. Indeed, social situations avoided by SAD patients include not only social interactions but also public performances and being observed by others. Nevertheless, tests used to assess sociability in rodents evaluate mostly social interaction in pairs. Thus, we developed a new test-a socially enriched environment test-that evaluates sociability within a group of three unfamiliar conspecifics in an enriched environment. In this study, we induced a SAD-like behavior (i.e., social fear) in male mice using social fear conditioning (SFC) and then tested social fear using the socially enriched environment test and the three-chamber test. Finally, we tested the effects of fear extinction and acute diazepam treatment in reversing social fear. Results revealed, in conditioned mice, decreased object exploration in proximity to conspecifics, social interaction, and mouse-like object exploration. Extinction training, but not acute diazepam treatment, reversed SFC-induced behavioral changes. These findings demonstrate that the socially enriched environment test provides an appropriate behavioral approach to better understand the etiology of SAD. This test may also have important implications in the exploration of new treatments.

Knowledge of COVID-19 and the impact on indigents' access to healthcare in Burkina Faso.

BACKGROUND: COVID-19 constitutes a global health emergency of unprecedented proportions. Preventive measures, however, have run up against certain difficulties in low and middle-income countries. This is the case in socially and geographically marginalized communities, which are excluded from information about preventive measures. This study contains a dual objective, i) to assess knowledge of COVID-19 and the preventive measures associated with it concerning indigents in the villages of Diebougou's district in Burkina Faso. The aim is to understand if determinants of this understanding exist, and ii) to describe how their pathways to healthcare changed from 2019 to 2020 during the COVID-19 pandemic. METHODS: The study was conducted in the Diebougou healthcare district, in the south-west region of Burkina Faso. We relied on a cross-sectional design and used data from the fourth round of a panel survey conducted among a sample of ultra-poor people that had been monitored since 2015. Data were collected in August 2020 and included a total of 259 ultra-poor people. A multivariate logistic regression to determine the factors associated with the respondents' knowledge of COVID-19 was used. RESULTS: Half of indigents in the district said they had heard about COVID-19. Only 29% knew what the symptoms of the disease were. The majority claimed that they protected themselves from the virus by using preventive measures. This level of knowledge of the disease can be observed with no differences between the villages. Half of the indigents who expressed themselves agreed with government measures except for the closure of markets. An increase of over 11% can be seen in indigents without the opportunity for getting healthcare compared with before the pandemic. CONCLUSIONS: This research indicates that COVID-19 is partially known and that prevention measures are not universally understood. The study contributes to reducing the fragmentation of knowledge, in particular on vulnerable and marginalized populations. Results should be useful for future interventions for the control of epidemics that aim to leave no one behind.

Pain hypersensitivity in a pharmacological mouse model of attention-deficit/hyperactivity disorder.

Clinical evidence suggests that pain hypersensitivity develops in patients with attention-deficit/hyperactivity disorder (ADHD). However, the mechanisms and neural circuits involved in these interactions remain unknown because of the paucity of studies in animal models. We previously validated a mouse model of ADHD obtained by neonatal 6-hydroxydopamine (6-OHDA) injection. Here, we have demonstrated that 6-OHDA mice exhibit a marked sensitization to thermal and mechanical stimuli, suggesting that phenotypes associated with ADHD include increased nociception. Moreover, sensitization to pathological inflammatory stimulus is amplified in 6-OHDA mice as compared to shams. In this ADHD model, spinal dorsal horn neuron hyperexcitability was observed. Furthermore, ADHD-related hyperactivity and anxiety, but not inattention and impulsivity, are worsened in persistent inflammatory conditions. By combining in vivo electrophysiology, optogenetics, and behavioral analyses, we demonstrated that anterior cingulate cortex (ACC) hyperactivity alters the ACC-posterior insula circuit and triggers changes in spinal networks that underlie nociceptive sensitization. Altogether, our results point to shared mechanisms underlying the comorbidity between ADHD and nociceptive sensitization. This interaction reinforces nociceptive sensitization and hyperactivity, suggesting that overlapping ACC circuits may be targeted to develop better treatments.

Phenotypic characterization of human peripheral γδT-cell subsets in glioblastoma.

The antitumoral contribution of γδT cells depends on their activation and differentiation into effectors. This depends on different molecules and membrane receptors, which conditions their physiology. This study aimed to determine the phenotypic characteristics of γδT cells in glioblastoma (GBM) according to five layers of membrane receptors. Among ten GBM cases initially enrolled, five of them who had been confirmed by pathological examination and ten healthy controls underwent phenotyping of peripheral γδT cells by flow cytometry, using the following staining: αßTCR, γδTCR, CD3, CD4, CD8, CD16, CD25, CD27, CD28, CD45, CD45RA, CD56, NKG2D, CD272(BTLA), and CD279(PD-1). Compared with the controls, the results showed no significant change in the number of γδT cells. However, there was a decrease of double-negative (CD4- CD8- ) Tγδ cells and an increase of naive γδT cells, a lack of CD25 expression, a decrease of the expression of CD279, and a remarkable, but not significant, increase in the expression of the CD27 and CD28 costimulation markers. Among the γδT cell subsets, the number of Vδ2 decreased in glioblastoma and showed no significant difference in the expression of CD16, CD56, and NKG2D. In contrast, the number of Vδ1 increased in glioblastoma with overexpression of CD16, CD56, and NKG2D. Our results showed that γδT cells are prone to adopt a pro-inflammatory profile in the glioblastoma context, which suggests that they might be a potential tool to consider in T cell-based immunotherapy in glioblastoma. However, this requires additional investigation on a larger sample size.

Anxiety and Gene Expression Enhancement in Mice Exposed to Glyphosate-Based Herbicide.

Growing evidence demonstrates that serotonin (5-HT) depletion increases activity in the amygdala and medial prefrontal cortex (mPFC), ultimately leading to anxiety behavior. Previously, we showed that glyphosate-based herbicides (GBHs) increased anxiety levels and reduced the number of serotoninergic fibers within the mPFCs and amygdalas of exposed mice. However, the impact of this 5-HT depletion following GBH exposure on neuronal activity in these structures is still unknown. In this study, we investigated the effects of GBH on immediate early gene (IEG) activation within the mPFCs and amygdalas of treated mice from juvenile age to adulthood and its subsequent effects on anxiety levels. Mice were treated for subchronic (6 weeks) and chronic (12 weeks) periods with 250 or 500 mg/kg/day of GBH and subjected to behavioral testing using the open field and elevated plus maze paradigms. Then, we analyzed the expression levels of c-Fos and pCREB and established the molecular proxies of neuronal activation within the mPFC and the amygdala. Our data revealed that repeated exposure to GBH triggers anxiogenic behavior in exposed mice. Confocal microscopy investigations into the prelimbic/infralimbic regions of the mPFC and in basolateral/central nuclei of the amygdala disclosed that the behavioral alterations are paralleled by a robust increase in the density and labelling intensity of c-Fos- and pCREB-positive cells. Taken together, these data show that mice exposed to GBH display the hyperactivation of the mPFC-amygdala areas, suggesting that this is a potential mechanism underlying the anxiety-like phenotype.

Immune tumoral microenvironment in gliomas: focus on CD3+ T cells, Vδ1+ T cells, and microglia/macrophages.

Gliomas are histologically defined as low-grade gliomas (LGG) and high-grade gliomas (HGG). The most common type of HGG is the glioblastoma (GBM). We aimed to determine the immunological characteristics of CD3 T-cells, Vδ1 T-cells, and microglia/macrophages infiltrating brain gliomas. We collected 24 formalin-fixed paraffin-embedded samples issued from 19 cases of GBM and 5 cases of LGG. An immunohistochemical analysis was performed using anti-CD3, anti-Vδ1, and anti-iba-1 antibodies. Labelling indexes (LI) of CD3 and Vδ1 were evaluated quantitatively, and other CD3, Vδ1, and iba-1 staining characteristics were evaluated qualitatively. The median age of patients was 49 years in GBM and 52 years in LGG. The sex ratio was 1.4 and GBM predominated in males (p = 0.05). In GBM, the medians of CD3-LI and Vδ1-LI were 30 and 3.5 respectively. CD3-LI inversely correlated with survival in GBM cases (r = - 0.543; p = 0.016). CD3 staining intensity correlated with CD3-LI (p < 0.0001) and with the survival in GBM cases (p = 0.003). Compared to LGG, the CD3-LI, the intensity of intra-tumoral Vδ1 staining, and the amount of iba-1 were higher in GBM (p = 0.042; p = 0.014; and p = 0.001 respectively). The iba-1 organization was more amoeboid in older patients and more branched in younger patients (p = 0.028) and tended to be more amoeboid in cases with high iba-1 amount (p = 0.09). Our results suggest that a high level of CD3-LI and a strong intra-tumoral infiltration of Vδ1 T-cells as well as a high involvement of TAM can be considered potential markers of poor prognosis of GBM. However, this requires further studies on more balanced GBM-LGG sample, including an expanded panel of biomarkers.

Clinical features and prognosis of severe scorpion envenomation in children.

BACKGROUND: Scorpionism is endemic and represents a real public health problem in Morocco. The most dangerous arthropod in the central area is Androctonus mauretanicus (Am) scorpion. Its venom can be lethal, especially for children. This study aimed to determine a clinico-epidemiological profile of severe scorpion envenomation among children and identify risk factors for mortality. METHODS: This retrospective cohort study included 606 children admitted for severe scorpion envenomation (SSE) from January 2010 to July 2015 in the Pediatric Intensive Care Unit (PICU) of Mohammed VI Teaching Hospital. RESULTS: The mean age of envenomed children was 6.3 ± 4.2 years. Seventy-four percent of them came from rural settings. Envenomation occurred mostly during the summer months and 78.4% of stings were nocturnal. The time between the sting and evaluation was greater than 2 h in 83% of cases. Bivariate analysis indicated that from 1 to 24 months of age (P = 0.001), hyperthermia (P = 0.022), episodes of diarrhea (P < 0.001), tachycardia (P < 0.001), abdominal distention (P < 0.001), skin marbling (P < 0.001), signs of respiratory distress (P < 0.001), irritability (P < 0.001), generalized seizures (P = 0.053), and Glasgow Coma Score (GCS) of 3 to 9 (P < 0.001) were significantly correlated with mortality. On multivariate analysis, diarrhea (P = 0.007), skin marbling (P = 0.006), and respiratory distress (P = 0.002), and GCS 3-9 (P = 0.007) were found to be independent risk factors for mortality in our patient population. CONCLUSIONS: Children are at high risk of developing serious complications, even death, from severe scorpion envenomation. Here we identified multiple factors that appear to increase the mortality risk in children after scorpion envenomation, including previously described central nervous system alterations.

Chronic thinner inhalation alters olfactory behaviors in adult mice.

Volatile solvents exposure can result in various behavioral impairments that have been partly associated to altered adult hippocampal neurogenesis. Despite recent evidence supporting this association, few studies have been devoted to examine the impact on olfactory functioning and olfactory bulb (OB) neurogenesis, although olfactory system is directly in contact with volatile molecules. Thus, this study was designed to evaluate in adult mice the potential modifications of the olfactory functioning after acute (1 day), subchronic (6 weeks) and chronic (12 weeks) exposure to thinner vapor at both behavioral and cellular levels. Firstly, behavioral evaluations showed that chronic thinner exposure impacts on odor detection ability of treated mice but does not affect mice ability to efficiently discriminate between two different odors. Moreover, chronic thinner exposure produces impairment in the olfactory-mediated associative memory. Secondly, analysis of the effects of thinner exposure in the subventricular zone (SVZ) of the lateral ventricle and in the OB revealed that thinner treatments do not induce apoptosis nor glial activation. Thirdly, immunohistochemical quantification of different markers of adult olfactory neurogenesis showed that inhalant treatments do not change the number of proliferating progenitors in the SVZ and the rostral migratory stream (RMS), as well as the number of newborn cells reaching and integrating in the OB circuitry. Altogether, our data highlight that the impaired olfactory performances in chronically-exposed mice are not associated to an alteration of adult neurogenesis in the SVZ-OB system.

Repeated ethanol exposure following avoidance conditioning impairs avoidance extinction and modifies conditioning-associated prefrontal dendritic changes in a mouse model of post-traumatic stress disorder.

Treatment of post-traumatic stress disorder is complicated by the presence of alcohol use disorder comorbidity. Little is known about the underlying brain mechanisms. We have recently shown, in mice, that the post-traumatic stress disorder-like phenotype is characterised by the increase and decrease in total dendritic number and length in the prelimbic and infralimbic areas of the medial prefrontal cortex, respectively. Here, we examined whether repeated ethanol exposure would exacerbate these changes and whether this would be associated with difficulty to extinguish passive avoidance behaviour, as an indicator of treatment resistance. We also analysed whether other known trauma-associated changes, like increased or decreased corticosterone and decreased brain-derived neurotrophic factor levels, would also be exacerbated. Male mice underwent trauma exposure (1.5-mA footshock), followed, 8 days later, by a conditioned place preference training with ethanol. Tests for fear sensitization, passive avoidance, anxiety-like behaviour, extinction acquisition and relapse susceptibility were used to assess behaviour changes. Plasma corticosterone and brain-derived neurotrophic factor levels and prefrontal dendritic changes were subsequently measured. Trauma-susceptible mice exposed to ethanol acquired a strong place preference and behaved differently from those not exposed to ethanol, with delayed avoidance extinction and higher avoidance relapse vulnerability. Ethanol potentiated trauma-associated dendritic changes in the prelimbic area and suppressed trauma-associated dendritic changes in the infralimbic area. However, ethanol had no effect on trauma-induced increased corticosterone and decreased brain-derived neurotrophic factor levels. These data suggest that the modification of prefrontal trauma-related changes, due to alcohol use, can characterise, and probably support, treatment-resistant post-traumatic stress disorder.