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1.
Glia ; 71(7): 1699-1714, 2023 07.
Article in English | MEDLINE | ID: mdl-36951238

ABSTRACT

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.


Subject(s)
Epilepsy , Microglia , Humans , Brain , Seizures/drug therapy
2.
bioRxiv ; 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36945556

ABSTRACT

Seizure disorders are common, affecting both the young and the old. Currently available antiseizure drugs are ineffective in a third of patients and have been developed with a focus on known neurocentric mechanisms, raising the need for investigations into alternative and complementary mechanisms that contribute to seizure generation or its containment. Neuroinflammation, broadly defined as the activation of immune cells and molecules in the central nervous system (CNS), has been proposed to facilitate seizure generation, although the specific cells involved in these processes remain inadequately understood. The role of microglia, the primary inflammation-competent cells of the brain, is debated since previous studies were conducted using approaches that were less specific to microglia or had inherent confounds. Using a selective approach to target microglia without such side effects, we show a broadly beneficial role for microglia in limiting chemoconvulsive, electrical, and hyperthermic seizures and argue for a further understanding of microglial contributions to contain seizures.

3.
Cureus ; 14(3): e23259, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35449613

ABSTRACT

Tuberculosis septic shock (TBSS) is a rare diagnosis due to inherent diagnostic difficulty or attribution to alternate causes. We report six cases of TBSS, along with comorbidities, clinical characteristics, hospital course, and in-hospital outcomes. All patients were middle-aged, with a median age of 54.5 years (interquartile range (IQR): 47-62). Four patients were males, whereas two were females. Majority (n = 4, 66.7%) of patients had comorbidities. Diabetes mellitus (n = 3, 50%), systemic hypertension (n = 2, 33.3%), and chronic obstructive pulmonary disease (n = 1, 16.7%) were the reported comorbidities in included patients. Median Acute Physiology and Chronic Health Evaluation (APACHE) II score at admission was 12 (IQR: 12-16). All patients had a microbiologic diagnosis of tuberculosis (TB). Four patients (66.7%) had respiratory secretions positive for Mycobacterium tuberculosis (MTB) by acid-fast bacilli (AFB) smear or cartridge-based nucleic acid amplification test (CBNAAT), two had sputum positivity, one had induced sputum positivity, whereas another had bronchoalveolar lavage specimen positive for MTB. One patient had lymph node aspirate positivity, and another had chest wall abscess positive for MTB. All had drug-sensitive TB. Five patients could be prescribed all four primary antitubercular drugs; one patient had deranged liver enzymes, requiring initiation of modified antitubercular therapy (ATT). Five patients were discharged successfully, whereas one patient died during the hospital stay. In-hospital mortality was 16.7%.

4.
Cureus ; 13(10): e18469, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34754635

ABSTRACT

Introduction Sclerotherapy offers an alternative to surgery to treat an aneurysmal bone cyst (ABC). The present study's main objective was to assess the radiological efficacy of sclerotherapy in the healing of the cyst cavity secondary to biopsy-proven ABC on X-rays and assess clinical efficacy on pain, recurrence, and complications. Materials and methods Between 2016 and 2018, 26 patients (12 females, 14 males) with biopsy-proven ABC treated by sclerotherapy were included. All patients received an injection of polidocanol 3% intralesional as standard treatment under fluoroscopic guidance. Ossification was assessed on plain X-ray, and the pain was evaluated on a visual analog scale (VAS). Results Ossification was complete in 24 (92.3%) patients and partial in two (7.7%) patients. Eighteen patients (70%) were pain-free at the end of three months. There was an improvement in the VAS score, and clinically, there was a significant reduction in pain and swelling. Two patients developed recurrence within two years of follow-up, treated successfully by the re-application of intralesional polidocanol 3% injection. Discussion Sclerotherapy provides an effective, minimally invasive treatment for ABC and is particularly useful for deep lesions, challenging access for surgery and potentially damaging vital structures. The use of percutaneous polidocanol 3% under fluoroscopic control seems to improve the risk/benefit ratio. Its clinical and radiological efficacy makes sclerotherapy an alternative treatment option in ABC.  Level of evidence IV, prospective study.

5.
Front Immunol ; 8: 1203, 2017.
Article in English | MEDLINE | ID: mdl-29046674

ABSTRACT

TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.

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