Apport de l’IRM structurelle multimodale dans la chirurgie d’épilepsie : le cas de l’épilepsie insulaire

L’épilepsie insulaire (ÉI) est une forme rare d’épilepsie focale qui, en raison des défis liés à son diagnostic, est difficilement cernable. De plus, la prise en charge des patients avec ÉI s’avère complexifiée par le fait que cette pathologie est fréquemment résistante aux médicaments anti-crises. Pour ces cas médico-réfractaires, la chirurgie insulaire est une option viable. Cela dit, les patients subissant une telle intervention développent fréquemment des déficits neurologiques postopératoires; heureusement, la grande majorité de ceux-ci récupèrent complètement et rapidement. Or, le mécanisme sous-tendant ce singulier rétablissement fonctionnel demeure à ce jour mal compris. Deux modalités modernes d’IRM structurelle, soit l’analyse d’épaisseur corticale et la tractographie, ont permis, dans les dernières années, de décrire les altérations architecturales caractéristiques et potentiellement diagnostiques de divers types d’épilepsie ainsi que de caractériser les remodelages plastiques qui suivent la chirurgie de l’épilepsie extra-insulaire. Cependant, à ce jour, aucune étude ne s’est encore penchée sur le cas de l’ÉI. De ce fait, les études qui constituent cette thèse exploitent l’IRM structurelle afin, d’une part, de dépeindre les altérations d’épaisseur du cortex et de connectivité de matière blanche associées à l’ÉI et, d’autre part, de définir les réarrangements de connectivité subséquents à la chirurgie insulaire pour contrôle épileptique. Les deux premières études de cette thèse ont révélé que l’ÉI était associée à un pattern majoritairement ipsilatéral d’atrophie corticale et d’hyperconnectivité impliquant principalement des sous-régions insulaires et des régions connectées à l’insula. De manière intéressante, la topologie de ces changements correspondait, au moins en partie, à celle du réseau épileptique de l’ÉI. Ensuite, la troisième étude visait à décrire, par le biais d’une méta-analyse, l’histoire naturelle postopératoire des patients subissant une chirurgie pour ÉI. Cette analyse a, entre autres, confirmé que cette chirurgie était efficace (66.7% de disparition des crises) et qu’elle était fréquemment accompagnée de complications neurologiques (42.5%) qui, dans la plupart des cas, étaient transitoires (78.7% des complications) et récupéraient entièrement dans les trois mois postopératoires (91.6% des complications transitoires). Finalement, la quatrième étude a révélé que la chirurgie pour ÉI était suivie d’altérations de connectivité diffuses et bilatérales. Notamment, les connexions présentant une augmentation de connectivité concernaient particulièrement des régions localisées soit près de la cavité chirurgicale ou dans l’hémisphère controlatéral à l’intervention. De plus, la majorité de ces renforcements structurels se sont produits dans les six premiers mois suivant la chirurgie, un délai comparable à celui durant lequel la majeure partie de la récupération fonctionnelle postopératoire a été observée dans notre méta-analyse. En somme, nos résultats suggèrent que les altérations morphologiques en lien avec l’ÉI peuvent correspondre à son réseau épileptique sous-jacent. La topologie de ces changements pourrait constituer un biomarqueur structurel diagnostique qui aiderait à la reconnaissance de l’ÉI et, concomitamment, favoriserait possiblement un traitement chirurgical plus adapté et plus efficace. De plus, les augmentations de connectivité postopératoires pourraient correspondre à des réponses neuroplastiques permettant de prendre en charge les fonctions altérées par la chirurgie. Nos constats ont ainsi contribué à la caractérisation des mécanismes étayant la singulière récupération fonctionnelle accompagnant la chirurgie pour ÉI. À plus grande échelle, nos travaux offrent un aperçu du potentiel de l’IRM structurelle à assister au diagnostic de l’épilepsie focale ainsi qu’à participer à la description des changements plastiques subséquents à une résection neurochirurgicale.Insular epilepsy (IE) is a rare type of focal epilepsy that is difficult to diagnose. In addition to the challenging nature of IE detection, management of patients with this condition is complicated by the tendency of insular seizures to be resistant to anti-seizure medications. For such medically refractory cases, insular surgery constitutes a viable and long-lasting therapeutic option. That said, patients who undergo an insular resection for seizure control frequently develop postoperative neurological deficits; fortunately, most of these impairments recover fully and rapidly. While this favorable postoperative course contributes to improving the outcome of IE surgery, the mechanism underlying the functional recovery remains unknown. Two contemporary structural MRI modalities, namely cortical thickness analysis and tractography, have recently been used to describe characteristic structural alterations of focal epilepsies and to elucidate the postoperative plastic remodeling associated with surgery for extra-insular epilepsy. While these analyses added to our understanding of several localization-related epilepsies, none specifically studied IE. In this thesis, we exploit structural MRI techniques to, first, depict the alterations of cortical thickness and white matter connectivity in IE and, second, define the progressive rearrangements that follow insular surgery for epilepsy. The first two studies of the current thesis showed that IE is associated with a primarily ipsilateral pattern of cortical thinning and hyperconnectivity that mainly involves insular subregions and insula-connected regions. Interestingly, the topology of these changes corresponded, at least in part, to the epileptic network of IE. Furthermore, the third study aimed to describe, via a meta-analysis, the postoperative outcome of patients undergoing surgery for IE. Among other findings, the analysis revealed that insular surgery was effective (66.7% seizure freedom rate) but was associated with a significant risk of neurological complications (42.5%) which, in most cases, were transient (78.7% of all complications) and recovered fully within three months (91.6% of transient complications). Finally, the fourth study showed that surgery for IE was followed by a diffuse pattern of bilateral structural connectivity changes. Notably, connections exhibiting an increase in connectivity were specifically located near the surgical cavity and in the contralateral healthy hemisphere. In addition, the majority of the structural strengthening occurred in the first six months following surgery, a time course that is consistent with the short delay during which most of the postoperative functional recovery was observed in our meta-analysis. Our results suggest that the morphological alterations in IE may reflect its underlying epileptic network. The topology of these changes may constitute a structural biomarker that could help diagnose IE more readily and, concomitantly, potentially enable a more targeted and more effective surgical treatment. Moreover, the postoperative increases in connectivity may be compatible with compensatory neuroplastic responses, a process that arose to recoup the functions of the injured insular cortex. Our findings have therefore contributed to the characterization of the driving process that supports the striking functional recovery seen following surgery for IE. On a larger scale, our work provides insights into the potential of structural MRI to assist in the diagnosis of focal epilepsy and to describe plastic changes following neurosurgical resections

Impact of age dominating over the pre-existing comorbidities influencing the D-Dimer levels in SARS-COV-2 infection

COVID-19-related disease severity is more commonly seen in elderly patients with comorbidities, and hypercoagulability has been demonstrated to be involved in the disease progression. This study aimed to evaluate the level of D-Dimer in hospitalized SARS-COV-2 infected patients and to determine the influence of age, gender, Body Mass Index (BMI), and comorbidities on D-dimer value and correlate it with disease severity. This case-control retrospective study retrieved patient data on demographic characteristics, vital functions, comorbidities, disease severity [National Institutes of Health (NIH) classification], and D-dimer from medical records of Thumbay University Hospital, Ajman, United Arab Emirates. SPSS-Version-28 was used for data analysis; a Chi-Square test was done to compare the distribution of comorbidities and disease severity between demographic categories. An independent sample t-test and one-way ANOVA were done to compare mean levels of D-Dimer between two or more categories, respectively. The majority of patients were males, ˃40 years of age, overweight/obese, with 30% having one comorbidity and 20% having ≥2 comorbidities. Among the total, three-quarters had moderate, and one-quarter had severe disease conditions, irrespective of gender or BMI, with an increasing trend of severe cases in the older age group and with comorbidities. Increased D-dimer levels were seen in the majority of SARS-COV-2-infected hospitalized patients, with age as the primary determinant, irrespective of absence or presence of comorbidity, though the trend of higher prevalence of elevated D-dimer value in the multiple comorbid groups and more severe condition was observed. Supporting SAR-COV-2 as a coagulopathic condition, D-dimer concentrations can be a helpful marker of disease progression and can be considered to guide the clinical treatment

Evaluation of anti-fungal activity derivative from Premna odorata Blanco extract by deep eutectic solvents

Fungal organisms are an opportunistic pathogen commonly found in different parts in human body like oral cavity and vagina. Recent study has revealed a critical need for novel antifungal medicines developed from medicinal plant extracts due to concerns about fungal pathogen resistance to commercial medication. In the present work, Premna odorata Blanco, belonging to the family Lamiaceae was evaluated in vitro antifungal activity against two fungal organism isolated from clinical cases. With the aim to replace toxic conventional solvents through deep eutectic solvents was used and phytochemical compounds were determined (total phenol content, total flavonoid content). ChMa extracts of Premna odorata Blanco demonstrate a significant antifungal activity against Candida albicans, Monilinia spp. Higher than water extract. While the DES2 extract reported the highest phenolic contents (3.58 mg GAE/100 g DW) and total flavonoid content (0.028 mg RE/100 g DW) compared with water extract. In conclusion, the study suggests that the Premna odorata Blanco extracts by deep eutectic solvents are promising for the development of treatments against various fungal diseases with a friendly green procedure, low toxicity and new application in pharmaceutical industry

Synergistic Effect of Azotobacter nigricans and Nitrogen Phosphorus Potassium Fertilizer on Agronomic and Yieldtraits of Maize (Zea mays L.)

Peer reviewe

Control of a population of battery energy storage systems for frequency response

The control of multiple battery energy storage systems (BESSs) to provide frequency response will be a challenge in future smart grids. This paper proposes a hierarchical control of BESSs with two decision layers: the aggregator layer and the BESS control layer. The aggregator layer receives the states of charge (SoC) of BESSs and sends a command signal to enable/disable the BESS control layer. The BESS controller was developed to enable the BESSs to respond from the highest to lowest SoC when the frequency drops, and from lowest to highest when it rises. Hence, the BESS’s response is prioritised to reduce the impact on the power system and end-users during the service. The BESS controller works independently when a failure occurs in the communication with the aggregator. The dynamic behaviour of the population of the controllable BESSs was modelled based on a Markov chain. The model demonstrates the value of aggregation of BESSs for providing frequency response and evaluates the effective capacity of the service. The model was demonstrated on the 14-machine South-East Australian power system with a 14.5 GW load. 254 MW of responsive capacity of aggregated batteries was effective in reducing the system frequency deviation below 0.2 Hz following a sequence of disturbances

Potential of demand side response aggregation for the stabilization of the grids frequency

The role of ancillary services related to the frequency control have become increasingly important in the smart grids. Demand Side Response is a competitive resource that can be used to regulate the grid frequency. This paper describes the use of heat pumps and fridges to provide ancillary services of frequency response so that to continuously balance the supply with demand. The power consumption of domestic units is usually small and, therefore, the aggregation of large numbers of small units should be able to provide sufficient capacity for frequency response. In this research, dynamic frequency control was developed to evaluate the capacity that can be gathered from the aggregation of domestic heat pumps and fridges for frequency response. The potential of frequency response was estimated at a particular time during winter and summer days. We also investigated the relationship between both loads (domestic heat pumps and fridges) to provide Firm Frequency Response service. A case study on the simplified Great Britain power system model was developed. Based on this case study, three scenarios of load combination were simulated according to the availability of the load and considering cost savings. It was demonstrated that the aggregation of heat pumps and fridges offered large power capacity and, therefore, an instantaneous frequency response service was achievable. Finally, the economic benefit of using an aggregated load for Firm Frequency Response service was estimated

Efficacy of biological agents and fillers seed coating in improving drought stress in anise

Many plants, including anise, have tiny, non-uniform seeds with low and light nutrient reserves. The seeds also show a weak establishment, especially under stressful conditions where their accurate planting in the soil and optimal yield are tough. This study sought to improve anise seeds' physical and physiological characteristics under drought stress. To this end, two factorial experiments under laboratory and greenhouse conditions were performed in a completely randomized design with 4 and 3 replications, respectively. Five levels of seed inoculation (inoculation with T36 and T43 of Trichoderma harzianum, and CHA0 and B52 of Pseudomonas fluorescent, and non-inoculation which means that control seeds were not treated with microbial inoculant), three levels of coating (K10P20, K10P10V5, and non-coating), and three levels of drought stress (0, -3, and -6 bars) were considered as the factorial experiment [vermiculite (V), kaolin (K), and perlite (P) numbers refer to the amount of material used in grams]. The laboratory experiment revealed that the combined treatments of bio-agents with coating increased the physical and germination characteristics of anise seeds compared to the control treatment. The greenhouse experiment showed that drought stress reduced the initial growth indices. Still, the combination treatments of biological agents and coating (fillers) could alleviate the destructive effects of drought stress to some extent and improve these indices. The best treatment was provided by T36 and K10P20 in both experiments, which significantly increased morphological indices.Peer reviewe

Interstitial imaging with multiple diffusive reflectance spectroscopy projections for in vivo blood vessels detection during brain needle biopsy procedures

Blood vessel injury during image-guided brain biopsy poses a risk of hemorrhage. Approaches that reduce this risk may minimize related patient morbidity. We present here an intraoperative imaging device that has the potential to detect the brain vasculature in situ. The device uses multiple diffuse reflectance spectra acquired in an outward-viewing geometry to detect intravascular hemoglobin, enabling the construction of an optical image in the vicinity of the biopsy needle revealing the proximity to blood vessels. This optical detection system seamlessly integrates into a commercial biopsy system without disrupting the neurosurgical clinical workflow. Using diffusive brain tissue phantoms, we show that this device can detect 0.5-mm diameter absorptive carbon rods up to approximately 2 mm from the biopsy window. We also demonstrate feasibility and practicality of the technique in a clinical environment to detect brain vasculature in an in vivo model system. In situ brain vascular detection may add a layer of safety to image-guided biopsies and minimize patient morbidity

Dose optimization of β-lactams antibiotics in pediatrics and adults:A systematic review

Background: β-lactams remain the cornerstone of the empirical therapy to treat various bacterial infections. This systematic review aimed to analyze the data describing the dosing regimen of β-lactams. Methods: Systematic scientific and grey literature was performed in accordance with Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The studies were retrieved and screened on the basis of pre-defined exclusion and inclusion criteria. The cohort studies, randomized controlled trials (RCT) and case reports that reported the dosing schedule of β-lactams are included in this study. Results: A total of 52 studies met the inclusion criteria, of which 40 were cohort studies, 2 were case reports and 10 were RCTs. The majority of the studies (34/52) studied the pharmacokinetic (PK) parameters of a drug. A total of 20 studies proposed dosing schedule in pediatrics while 32 studies proposed dosing regimen among adults. Piperacillin (12/52) and Meropenem (11/52) were the most commonly used β-lactams used in hospitalized patients. As per available evidence, continuous infusion is considered as the most appropriate mode of administration to optimize the safety and efficacy of the treatment and improve the clinical outcomes. Conclusion: Appropriate antibiotic therapy is challenging due to pathophysiological changes among different age groups. The optimization of pharmacokinetic/pharmacodynamic parameters is useful to support alternative dosing regimens such as an increase in dosing interval, continuous infusion, and increased bolus doses

A Systematic Review on Clinical Safety and Efficacy of Vancomycin Loading Dose in Critically Ill Patients

Background: The clinical significance of utilizing a vancomycin loading dose in critically ill patients remains unclear. Objective: The main aim of this systematic review is to evaluate the clinical safety and efficacy of the vancomycin loading dose in critically ill patients. Methods: We performed a systematic review using PRISMA guidelines. PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar, the Saudi Digital Library and other databases were searched. Studies that reported clinical outcomes among patients receiving the vancomycin LD were considered eligible. Data for this study were collected using PubMed, the Web of Science, MEDLINE, Scopus, Google Scholar and the Saudi Digital Library using the following terms: “vancomycin”, “safety”, “efficacy” and “loading dose” combined with the Boolean operator “AND” or “OR”. Results: A total of 17 articles, including 2 RCTs, 11 retrospective cohorts and 4 other studies, met the inclusion/exclusion criteria out of a total 1189 studies. Patients had different clinical characteristics representing a heterogenous group, including patients in critical condition, with renal impairment, sepsis, MRSA infection and hospitalized patients for hemodialysis or in the emergency department. Conclusions: The study shows that the target therapeutic level is achieved more easily among patients receiving a weight-based LD as compared to patients received the usual dose without an increased risk of new-onset adverse drug reactions