Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sudden unexpected death in epilepsy (SUDEP) is the major cause of death that affects patients with epilepsy. The risk of SUDEP increases according to the frequency and severity of uncontrolled seizures; therefore, SUDEP risk is higher in patients with refractory epilepsy (RE), in whom most antiepileptic drugs (AEDs) are ineffective for both seizure control and SUDEP prevention. Consequently, RE and SUDEP share a multidrug resistance (MDR) phenotype, which is mainly associated with brain overexpression of ABC-transporters such as P-glycoprotein (P-gp). The activity of P-gp can also contribute to membrane depolarization and affect the normal function of neurons and cardiomyocytes. Other molecular regulators of membrane potential are the inwardly rectifying potassium channels (Kir), whose genetic variants have been related to both epilepsy and heart dysfunctions. Although it has been suggested that dysfunctions of the cardiac, respiratory, and brainstem arousal systems are the causes of SUDEP, the molecular basis for explaining its dysfunctions remain unknown. In rats, repetitive seizures or status epilepticus induced high expression of P-gp and loss Kir expression in the brain and heart, and promoted membrane depolarization, malignant bradycardia, and the high rate of mortality. Here we reviewed clinical and experimental evidences suggesting that abnormal expression of depolarizing/repolarizing factors as P-gp and Kir could favor persistent depolarization of membranes without any rapid functional recovery capacity. This condition induced by convulsive stress could be the molecular mechanism leading to acquired severe bradycardia, as an ineffective heart response generating the appropriate scenario for SUDEP development. This article is part of the Special Issue "NEWroscience 2018".
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PMID:The role of P-glycoprotein (P-gp) and inwardly rectifying potassium (Kir) channels in sudden unexpected death in epilepsy (SUDEP). 3170 19

Transplantation of appropriate neuronal precursors after injury is a promising strategy to reconstruct cortical circuits, but the efficiency of these approaches remains limited. Here, we applied targeted apoptosis to selectively ablate layer II/III pyramidal neurons in the rat juvenile cerebral cortex and attempted to replace lost neurons with their appropriate embryonic precursors by transplantation. We demonstrate that grafted precursors do not migrate to replace lost neurons but form vascularized clusters establishing reciprocal synaptic contacts with host networks and show functional integration. These heterotopic neuronal clusters significantly enhance the activity of the host circuits without causing epileptic seizures and attenuate the apoptotic injury-induced functional deficits in electrophysiological and behavioral tests. Chemogenetic activation of grafted neurons further improved functional recovery, and the persistence of the graft was necessary for maintaining restored functions in adult animals. Thus, implanting neuronal precursors capable to form synaptically integrated neuronal clusters combined with activation-based approaches represents a useful strategy for helping long-term functional recovery following brain injury.
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PMID:Transplanted Embryonic Neurons Improve Functional Recovery by Increasing Activity in Injured Cortical Circuits. 3226 29

Chimeric Antigen Receptor (CAR) T-cell therapy can have severe toxicities, which include CAR-T-cell-related encephalopathy syndrome (CRES). The patient may present with altered mental status, encephalopathy, seizures, and cerebral edema. Depending on the severity, the recovery process will require rehabilitation. We present a case and explain how communication between cancer physiatrists, oncologists, and patients can affect the expectations for functional recovery, and the importance of setting goals for recovery in a medically complex population. We present a patient who underwent aggressive chimeric antigen receptor T cell therapy, causing encephalopathy and complications. He initially required total assistance for mobility and activities of daily living. Physiatry was consulted to assist with the rehabilitation plan of care and disposition. Initially, the oncologist conveyed to the patient he would be walking in two weeks, which was unrealistically optimistic. The patient's physiatrist intervened and discussed these expectations with him, alleviating his emotional distress. His condition improved with inpatient rehabilitation, and he was able to ambulate short distances with modified independence in four weeks. The involvement of a cancer physiatrist allows for recognition and treatment of complications related to cancer and aggressive therapies, along with an accurate functional prognosis assessment. With improved communication and patient involvement, the patient underwent a successful rehabilitation.
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PMID:A Case Report on the Communication between Oncologists and Physiatrists in the Establishment of Functional Prognosis while Undergoing Chimeric Antigen Receptor T-cell Therapy. 3234 8

Cerebral venous sinus thrombosis (CVT) is notoriously known for its varied presentations and extremely high risk of mortality, if remains undetected and untreated. On the other hand, life can be saved with full functional recovery if CVT can be identified with high index of clinical suspicion with supportive imaging and treatment with appropriate anticoagulation. It is important for clinicians to be meticulous to screen for both the potential reversible and heritable causes of CVT so that appropriate measures can be taken to prevent such catastrophe. Here we report a case of CVT involving right sigmoid and transverse sinuses presenting with acute onset left sided hemiplegic without antecedent headache or seizures. Patient was successfully treated with anticoagulants with nearly full functional recovery. Multiple predisposing factors were identified. As per our knowledge, this is the first case of CVT with underlying conglomeration of multiple acquired (lactation, folate deficiency, hyperhomocysteinemia, depot medroxyprogesterone acetate injection) and hereditary risk factors (deficiency of protein C, protein S and antithrombin-III) in a single patient.
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PMID:Cerebral venous sinus thrombosis-A primer for emergency physician. 3267 Sep 74

Traumatic brain injury (TBI) and spinal cord injury (SCI) cause millions of deaths and permanent or prolonged physical disabilities around the globe every year. It generally happens due to various incidents, such as accidents during sports, war, physical assault, and strokes which result in severe damage to brain and spinal cord. If this remains untreated, traumatic CNS injuries may lead to early development of several neurodegenerative diseases like Alzheimer's, Parkinson, multiple sclerosis, and other mental illnesses. The initial physical reaction, which is also termed as the primary phase, includes swelling, followed by inflammation as a result of internal haemorrhage causing damage to indigenous tissue, i.e., axonal shear injury, rupture of blood vessels, and partial impaired supply of oxygen and essential nutrients in the neurons, thereby initiating a cascade of events causing secondary injuries such as hypoxia, hypotension, cognitive impairment, seizures, imbalanced calcium homeostasis and glutamate-induced excitotoxicity resulting in concomitant neuronal cell death and cumulative permanent tissue damage. In the modern era of advanced biomedical technology, we are still living with scarcity of the clinically applicable comparative non-invasive therapeutic strategies for regeneration or functional recovery of neurons or neural networks after a massive CNS injury. One of the key reasons for this scarcity is the limited regenerative ability of neurons in CNS. Growth-impermissive glial scar and the lack of a synthetic biocompatible platform for proper neural tissue engineering and controlled supply of drugs further retard the healing process. Injectable or implantable hydrogel materials, consisting majorly of water in its porous three-dimensional (3D) structure, can serve as an excellent drug delivery platform as well as a transplanted cell-supporting scaffold medium. Among the various neuro-compatible bioinspired materials, we are limiting our discussion to the recent advancement of engineered biomaterials comprising mainly of peptides and proteins due to their growing demand, low immunogenicity and versatility in the fabrication of neuro regenerative medicine. In this article, we try to explore all the recent scientific avenues that are developing gradually to make peptide and peptide-conjugated biomaterial hydrogels as a therapeutic and supporting scaffold for treating CNS injuries.
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PMID:Recent trends in the development of peptide and protein-based hydrogel therapeutics for the healing of CNS injury. 3272 81

Low physical activity (PA) levels are common in hospitalized patients. Digital health tools could be valuable in preventing the negative effects of inactivity. We therefore developed Hospital Fit; which is a smartphone application with an accelerometer, designed for hospitalized patients. It enables objective activity monitoring and provides patients with insights into their recovery progress and offers a tailored exercise program. The aim of this study was to investigate the potential of Hospital Fit to enhance PA levels and functional recovery following orthopedic surgery. PA was measured with an accelerometer postoperatively until discharge. The control group received standard physiotherapy, while the intervention group used Hospital Fit in addition to physiotherapy. The time spent active and functional recovery (modified Iowa Level of Assistance Scale) on postoperative day one (POD1) were measured. Ninety-seven patients undergoing total knee or hip arthroplasty were recruited. Hospital Fit use, corrected for age, resulted in patients standing and walking on POD1 for an average increase of 28.43 min (95% confidence interval (CI): 5.55-51.32). The odds of achieving functional recovery on POD1, corrected for the American Society of Anesthesiologists classification, were 3.08 times higher (95% CI: 1.14-8.31) with Hospital Fit use. A smartphone app combined with an accelerometer demonstrates the potential to enhance patients' PA levels and functional recovery during hospitalization.
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PMID:Smartphone App with an Accelerometer Enhances Patients' Physical Activity Following Elective Orthopedic Surgery: A Pilot Study. 3274 76


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