Focused Ultrasound Neuromodulation: Exploring a Novel Treatment for Severe Opioid Use Disorder.

Background: Opioid use disorder remains a critical healthcare challenge as current therapeutic strategies have limitations resulting in high recurrence and deaths. We evaluated safety and feasibility of focused ultrasound (FUS) neuromodulation to reduce substance cravings and use in severe opioid- and co-occurring substance use disorders.

Methods: This prospective, open-label, single-arm study enrolled 8 participants with severe, primary opioid use disorder with co-occurring substance use.

The early-onset Alzheimer's disease MRI signature: a replication and extension analysis in early-stage AD.

Early-onset Alzheimer's disease (EOAD) is less investigated than the more common late-onset Alzheimer's disease (LOAD) despite its more aggressive course. A cortical signature of EOAD was recently proposed and may facilitate EOAD investigation. Here, we aimed to validate this proposed MRI biomarker of EOAD neurodegeneration in an Appalachian clinical cohort.

Memory consolidation, temporal and parietal atrophy, and metabolism in amyloid-β positive and negative mild cognitive impairment.

Background: Alzheimer's disease (AD) is classically characterized by alterations in memory consolidation. With the advent of diagnostic biomarkers, some patients clinically diagnosed with AD display biomarkers inconsistent with the diagnosis.

Objective: We aimed to explore differences in memory consolidation and neurodegeneration of the temporal and parietal lobes as a function of amyloid-β status in amnestic mild cognitive impairment (aMCI).

Executive function and cortical thickness in biomarker aMCI.

Introduction: Memory deficits are the primary symptom in amnestic Mild Cognitive Impairment (aMCI); however, executive function (EF) deficits are common. The current study examined EF in aMCI based upon amyloid status (A+/A-) and regional atrophy in signature areas of Alzheimer's disease (AD).

Method: Participants included 110 individuals with aMCI (A+ = 66; A- = 44) and 33 cognitively healthy participants (HP).

Cortical Thickness Correlates of Go/No-go and Motor Sequencing in Mild Cognitive Impairment and Suspected Alzheimer Disease Dementia.

Background: While the cognitive hallmark of typical Alzheimer disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted.

Objective: We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group.

Methods: First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task.

Precision targeting in the globus pallidus interna: insights from the multicenter, prospective, blinded VA/NINDS CSP 468 study.

Objective: Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson's disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets.

β,γ-Methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD rats.

Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with CKD. Extracellular nucleotides (ie, ATP or UTP) regulate the arterial calcification process by interacting with (1) purinergic receptors and (2) breakdown via ecto-nucleotidases, such as ectonucleotide pyrophosphatase/phosphodiesterase NPP1 or NPP3, affecting the local levels of calcification inhibitor, pyrophosphate, and stimulator inorganic phosphate (PP/P ratio). Also, it has been shown that ATP analogs (ie, β,γ-methylene-ATP [β,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro.

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities.

Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions.

Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD.

Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aβ) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aβ was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography.

Navigational Bronchoscopy versus Computed Tomography-guided Transthoracic Needle Biopsy for the Diagnosis of Indeterminate Lung Nodules: protocol and rationale for the VERITAS multicenter randomized trial.

Background: Lung nodule incidence is increasing. Many nodules require biopsy to discriminate between benign and malignant etiologies. The gold-standard for minimally invasive biopsy, computed tomography-guided transthoracic needle biopsy (CT-TTNB), has never been directly compared to navigational bronchoscopy, a modality which has recently seen rapid technological innovation and is associated with improving diagnostic yield and lower complication rate.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients.

Background: Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year.

Methods: Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209).

Chronic dehydration induces injury pathways in rats, but does not mimic histopathology of chronic interstitial nephritis in agricultural communities.

CINAC-patients present renal proximal tubular cell lysosomal lesions which are also observed in patients experiencing calcineurin inhibitor (CNI) nephrotoxicity, suggesting that CINAC is a toxin-induced nephropathy. An alternative hypothesis advocates chronic dehydration as a major etiological factor for CINAC. Here, we evaluated histological and molecular changes in dehydrated versus toxin exposed rats.

Surface-based correlates of cognition along the Alzheimer's continuum in a memory clinic population.

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits.

Intraoperative physiology augments atlas-based data in awake deep brain stimulation.

Background: Deep brain stimulation (DBS) is commonly performed with patients awake to perform intraoperative microelectrode recordings and/or macrostimulation testing to guide final electrode placement. Supplemental information from atlas-based databases derived from prior patient data and visualised as efficacy heat maps transformed and overlaid onto preoperative MRIs can be used to guide preoperative target planning and intraoperative final positioning. Our quantitative analysis of intraoperative testing and corresponding changes made to final electrode positioning aims to highlight the value of intraoperative neurophysiological testing paired with image-based data to optimise final electrode positioning in a large patient cohort.

Comprehensiveness of online sources for patient education on hereditary hearing impairment.

Introduction: The present study aimed at investigating the readability of online sources on hereditary hearing impairment (HHI).

Methods: In August 2022, the search terms "hereditary hearing impairment", "genetic deafness", hereditary hearing loss", and "sensorineural hearing loss of genetic origin" were entered into the Google search engine and educational materials were determined. The first 50 websites were determined for each search.

Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study.

Background: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure.

Safety and feasibility clinical trial of nucleus accumbens deep brain stimulation for treatment-refractory opioid use disorder.

Objective: There were more than 107,000 drug overdose deaths in the US in 2021, the most ever recorded. Despite advances in behavioral and pharmacological treatments, over 50% of those receiving treatment for opioid use disorder (OUD) experience drug use recurrence (relapse). Given the prevalence of OUD and other substance use disorders (SUDs), the high rate of drug use recurrence, and the number of drug overdose deaths, novel treatment strategies are desperately needed.

Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer's disease.

Background: Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is under investigation as a therapeutic modality for neurodegeneration, yet its effects in humans are incompletely understood. Here, we assessed physiologic responses to FUS administered in multifocal brain sites of persons with Alzheimer's disease (AD).

Methods: At a tertiary neuroscience institute, eight participants with AD (mean age 65, 38% F) enrolled in a phase 2 clinical trial underwent three successive targeted BBB opening procedures at 2 week intervals using a 220 kHz FUS transducer in combination with systemically administered microbubbles.

Metformin and Canagliflozin Are Equally Renoprotective in Diabetic Kidney Disease but Have No Synergistic Effect.

Diabetic Kidney Disease (DKD) is a major microvascular complication for diabetic patients and is the most common cause of chronic kidney disease (CKD) and end-stage renal disease. Antidiabetic drugs, such as metformin and canagliflozin, have been shown to exert renoprotective effects. Additionally, quercetin recently showed promising results for the treatment of DKD.

Androgen therapy does not prevent bone loss and arterial calcifications in male rats with chronic kidney disease.

Patients suffering from chronic kidney disease (CKD) often experience bone loss and arterial calcifications. It is unclear if hypogonadism contributes to the development of these complications and whether androgen therapy might prevent them. Male adult rats were randomized into four groups.

Management of fracture risk in CKD-traditional and novel approaches.

The coexistence of osteoporosis and chronic kidney disease (CKD) is an evolving healthcare challenge in the face of increasingly aging populations. Globally, accelerating fracture incidence causes disability, impaired quality of life and increased mortality. Consequently, several novel diagnostic and therapeutic tools have been introduced for treatment and prevention of fragility fractures.

A Proteomic Screen to Unravel the Molecular Pathways Associated with Warfarin-Induced or TNAP-Inhibited Arterial Calcification in Rats.

Arterial media calcification refers to the pathological deposition of calcium phosphate crystals in the arterial wall. This pathology is a common and life-threatening complication in chronic kidney disease, diabetes and osteoporosis patients. Recently, we reported that the use of a TNAP inhibitor, SBI-425, attenuated arterial media calcification in a warfarin rat model.