Regional and global resting-state functional MR connectivity in temporal lobe epilepsy: Results from the Epilepsy Connectome Project.

Temporal lobe epilepsy (TLE) has been conceptualized as focal disease with a discrete neurobiological focus and can respond well to targeted resection or ablation. In contrast, the neuro-cognitive deficits resulting from TLE can be widespread involving regions beyond the primary epileptic network. We hypothesize that this seemingly paradoxical findings can be explained by differences in connectivity between the primary epileptic region which is hyper-connected and its secondary influence on global connectome organization.

Antioxidant Combo Therapy Protects White Matter After Traumatic Brain Injury.

Following traumatic brain injury (TBI), increased production of reactive oxygen species (ROS) and the ensuing oxidative stress promotes the secondary brain damage that encompasses both grey matter and white matter. As this contributes to the long-term neurological deficits, decreasing oxidative stress during the acute period of TBI is beneficial. While NADPH oxidase (NOX2) is the major producer of ROS, transcription factor Nrf2 that induces antioxidant enzymes promotes efficient ROS disposal.

Therapeutic potential of nutraceuticals to protect brain after stroke.

Stroke leads to significant neuronal death and long-term neurological disability due to synergistic pathogenic mechanisms. Stroke induces a change in eating habits and in many cases, leads to undernutrition that aggravates the post-stroke pathology. Proper nutritional regimen remains a major strategy to control the modifiable risk factors for cardiovascular and cerebrovascular diseases including stroke.

Microarray Profiling Reveals Distinct Circulating miRNAs in Aged Male and Female Mice Subjected to Post-stroke Social Isolation.

Social isolation (SI) increases ischemic injury and significantly delays recovery after experimental stroke. Changes in circulating microRNAs (miRNAs) have been implicated in several neurological disorders, including stroke. However, potential biomarkers to elucidate the mechanisms that underlie the detrimental effects of post-stroke isolation are unknown.

Impact of Age and Sex on α-Syn (α-Synuclein) Knockdown-Mediated Poststroke Recovery.

Background And Purpose: Increased expression of α-Syn (α-Synuclein) is known to mediate secondary brain damage after stroke. We presently studied if α-Syn knockdown can protect ischemic brain irrespective of sex and age.

Methods: Adult and aged male and female mice were subjected to transient middle cerebral artery occlusion.

TET3 regulates DNA hydroxymethylation of neuroprotective genes following focal ischemia.

The 5-hydroxymethylcytosine (5hmC) epigenetic modification is highly enriched in the CNS and a critical modulator of neuronal function and development. We found that cortical 5hmC was enhanced from 5 min to three days of reperfusion following focal ischemia in adult mice. Blockade of the 5hmC-producing enzyme ten-eleven translocase 3 (TET3) increased edema, infarct volume, and motor function impairments.

Effect of a Standard vs Enhanced Implementation Strategy to Improve Antibiotic Prescribing in Nursing Homes: A Trial Protocol of the Improving Management of Urinary Tract Infections in Nursing Institutions Through Facilitated Implementation (IMUNIFI) Study.

Importance: Suspicion of urinary tract infection (UTI) is the major driver of overuse and misuse of antibiotics in nursing homes (NHs). Effects of interventions to improve the recognition and management of UTI in NHs have been mixed, potentially owing to differences in how interventions were implemented in different studies. An improved understanding of how implementation approach influences intervention adoption is needed to achieve wider dissemination of antibiotic stewardship interventions in NHs.

Chronic kidney disease in the pathogenesis of acute ischemic stroke.

Chronic kidney disease has a graded and independent inverse impact on cerebrovascular health. Both thrombotic and hemorrhagic complications are highly prevalent in chronic kidney disease patients. Growing evidence suggests that in chronic kidney disease patients, ischemic strokes are more common than hemorrhagic strokes.

Induction of DNA Hydroxymethylation Protects the Brain After Stroke.

Background and Purpose- Epigenetics play a significant role in brain pathologies. We currently evaluated the role of a recently discovered brain-enriched epigenetic modification known as 5-hydroxymethylcytosine (5hmC) in regulating transcriptomic and pathogenic mechanisms after focal ischemic injury. Methods- Young and aged male and female mice were subjected to transient middle cerebral artery occlusion, and the peri-infarct region was analyzed at various times of reperfusion.

Age and sex differences in the pathophysiology of acute CNS injury.

Despite the immeasurable burden on patients and families, no effective therapies to protect the CNS after an acute injury are available yet. Furthermore, the underlying mechanisms that promote neuronal death and functional deficits after injury remain to be poorly understood. The prevalence, age of onset, pathophysiology, and symptomatology of many CNS insults differ significantly between males and females.

The microRNA miR-7a-5p ameliorates ischemic brain damage by repressing α-synuclein.

Ischemic stroke, which is caused by a clot that blocks blood flow to the brain, can be severely disabling and sometimes fatal. We previously showed that transient focal ischemia in a rat model induces extensive temporal changes in the expression of cerebral microRNAs, with a sustained decrease in the abundance of miR-7a-5p (miR-7). Here, we evaluated the therapeutic efficacy of a miR-7 mimic oligonucleotide after cerebral ischemia in rodents according to the Stroke Treatment Academic Industry Roundtable (STAIR) criteria.

Inhibition of the Epigenetic Regulator REST Ameliorates Ischemic Brain Injury.

Cerebral ischemia is known to activate the repressor element-1 (RE1)-silencing transcription factor (REST) which silences neural genes via epigenetic remodeling and promotes neurodegeneration. We presently determined if REST inhibition derepresses target genes involved in synaptic plasticity and promotes functional outcome after experimental stroke. Following transient focal ischemia induced by middle cerebral artery occlusion (MCAO) in adult rats, REST expression was upregulated significantly from 12 h to 1 day of reperfusion compared to sham control.

Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice.

Background And Purpose: Social isolation increases mortality and impairs recovery after stroke in clinical populations. These detrimental effects have been recapitulated in animal models, although the exact mechanism mediating these effects remains unclear. Dysregulation of microRNAs (miRNAs) occurs in both strokes as well as after social isolation, which trigger changes in many downstream genes.

The microRNA miR-21 conditions the brain to protect against ischemic and traumatic injuries.

Ischemic and traumatic injuries to CNS remain leading causes of death and disability worldwide, despite decades of research into risk factors, therapies, and preventative measures. Recent studies showed that CNS injuries significantly alter the cerebral microRNAome that impact the secondary brain damage as well as plasticity and recovery. Many microRNA based therapies are currently in various clinical trials for different pathologic conditions indicating their therapeutic potential.

A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury.

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice.

Mitochondrial fission and fusion in secondary brain damage after CNS insults.

Mitochondria are dynamically active organelles, regulated through fission and fusion events to continuously redistribute them across axons, dendrites, and synapses of neurons to meet bioenergetics requirements and to control various functions, including cell proliferation, calcium buffering, neurotransmission, oxidative stress, and apoptosis. However, following acute or chronic injury to CNS, altered expression and function of proteins that mediate fission and fusion lead to mitochondrial dynamic imbalance. Particularly, if the fission is abnormally increased through pro-fission mediators such as Drp1, mitochondrial function will be impaired and mitochondria will become susceptible to insertion of proapototic proteins.

The Top Three Health Care Developments Impacting the Practice of Interventional Radiology in the Next Decade.

Objective: We discuss three health care trends that will have a profound impact on interventional radiology (IR) in the next decade.

Conclusion: Precision medicine, representing the next frontier of medicine, will bring opportunities and challenges to the field. Significant changes in payment models may prove beneficial to the subspecialty if proactive steps are taken by its members.

Poststroke Induction of α-Synuclein Mediates Ischemic Brain Damage.

Unlabelled: α-Synuclein (α-Syn), one of the most abundant proteins in the CNS, is known to be a major player in the neurodegeneration observed in Parkinson's disease. We currently report that transient focal ischemia upregulates α-Syn protein expression and nuclear translocation in neurons of the adult rodent brain. We further show that knockdown or knock-out of α-Syn significantly decreases the infarction and promotes better neurological recovery in rodents subjected to focal ischemia.

Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles.

The health benefits of the plant-derived polyphenol resveratrol were established in multiple disease systems. Notably, pre-treatment with resveratrol was shown to be neuroprotective in several models of cerebral ischemia. Mechanisms of resveratrol-mediated neuroprotection have been explored in the context of canonical resveratrol targets, but epigenetic and non-coding RNA processes have not yet been evaluated.

Randomized controlled equivalence trial comparing videoconference and in person delivery of cognitive processing therapy for PTSD.

Introduction: In an effort to improve access to and utilization of health care, the Veterans Health Administration (VHA) continues to investigate the effectiveness of video-teleconferencing (VTC) technologies for service delivery. While previous research focused on the efficacy of VTC treatment for post-traumatic stress disorder (PTSD) in Vietnam era veterans, few studies have evaluated the efficacy of this modality and treatment for the Iraq/Afghanistan era veterans. The aim of this randomized clinical trial was to evaluate equivalence between in person and VTC psychotherapy for PTSD in this newer cohort.

An economic analysis of sublobar resection versus thermal ablation for early-stage non-small-cell lung cancer.

Purpose: To compare medical costs for a matched-pair cohort of Medicare patients with early-stage non-small-cell lung cancer (NSCLC) who underwent treatment with sublobar resection or thermal ablation.

Materials And Methods: Patients at least 65 years of age with stage IA/IB NSCLC treated with sublobar resection or thermal ablation from 2007 to 2009 were identified from Surveillance, Epidemiology, and End Results/Medicare-linked data and matched by propensity scores. The primary outcome of interest, cost from the payer's perspective, was derived from Medicare claims data.

Physiology in medicine: obstructive sleep apnea pathogenesis and treatment--considerations beyond airway anatomy.

We review evidence in support of significant contributions to the pathogenesis of obstructive sleep apnea (OSA) from pathophysiological factors beyond the well-accepted importance of airway anatomy. Emphasis is placed on contributions from neurochemical control of central respiratory motor output through its effects on output stability, upper airway dilator muscle activation, and arousability. In turn, we consider the evidence demonstrating effective treatment of OSA via approaches that address each of these pathophysiologic risk factors.