A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid.

Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the characterization of fragile CSF cells by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh CSF was collected from twenty-one participants at two independent sites.

Hypogonadism in men with multiple sclerosis: Prevalence and clinical associations.

It has been hypothesized that multiple sclerosis (MS) has hormonal influences, and testosterone may have anti-inflammatory functions in this context. Given prior reports of lower testosterone levels in men with MS in archival serum samples, we evaluated the prevalence of hypogonadism in the clinical setting and its association with disability in men with MS. Subjects were screened for symptoms of hypogonadism using a clinical instrument, and those with positive screens had total and free morning testosterone levels checked.

Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases.

Objective: To report initial results of a planned multicenter year-long prospective study examining the risk and impact of COVID-19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS).

Methods: In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID-19 in persons with NID (PwNID) and change in their neurological care.

Results: Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020.

Intra- and inter-fractional liver and lung tumor motions treated with SBRT under active breathing control.

Purpose: To assess intra- and inter-fractional motions of liver and lung tumors using active breathing control (ABC).

Methods And Materials: Nineteen patients with liver cancer and 15 patients with lung cancer treated with stereotactic body radiotherapy (SBRT) were included in this retrospective study. All patients received a series of three CTs at simulation to test breath-hold reproducibility.

Endothelial Wnt/β-catenin signaling reduces immune cell infiltration in multiple sclerosis.

Disruption of the blood-brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis. Although wingless integrated MMTV (Wnt)/β-catenin signaling plays an essential role in BBB formation and maintenance in healthy CNS, its role in BBB repair in neurologic diseases such as MS remains unclear.

Chronic cerebrospinal venous insufficiency: pitfalls and perils of sonographic assessment.

Objectives: Duplex sonography has been proposed as a diagnostic modality for detection of chronic cerebrovascular venous insufficiency, a recently proposed hypothesis of multiple sclerosis (MS) pathogenesis. We reviewed potential challenges of duplex sonography for diagnosis of chronic cerebrovascular venous insufficiency and used interim pooled data from a study aimed to apply cerebrovascular venous insufficiency criteria to a group of patients with MS and control patients without MS.

Methods: Duplex sonography for chronic cerebrovascular venous insufficiency was performed in patients with MS and controls.

Esophageal dose tolerance to hypofractionated stereotactic body radiation therapy: risk factors for late toxicity.

Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT).

Methods And Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.

Hydration status substantially affects chronic cerebrospinal venous insufficiency assessments.

We sought to determine the effect of hydration on the criteria for chronic cerebrospinal venous insufficiency (CCSVI), a proposed hypothesis for the etiology of multiple sclerosis (MS). Sixteen subjects (11 MS and 5 controls) were asked to fast overnight. The following morning, 2 CCSVI ultrasound examinations were performed: 1 in the mildly dehydrated state, and another 30-45 minutes after rehydrating with 1.

A technical approach to dissecting and assessing cadaveric veins pertinent to chronic cerebrospinal venous insufficiency in multiple sclerosis.

Objective: To establish a detailed technical procedure for studying the anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers of multiple sclerosis and control subjects, and to present our findings of the normal anatomic venous structures, with reference to previous descriptions from the literature.

Methods: This study examined the internal jugular veins (IJVs), the brachiocephalic veins, and the azygos vein from 20 cadavers (10 control and 10 multiple sclerosis). These veins were exposed, isolated by clamps from the rest of the venous system, flushed with water, and then injected with fluid silicone from the superior ends of both IJVs.

Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality.

Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord.

Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves.

BACE1 is a promising therapeutic and preventive target for Alzheimer's disease because it is essential for amyloid deposition. However, the recent demonstration of BACE1 in modulating developmental myelination in both peripheral and central nervous systems raises a concern of its effect on myelin maintenance or remyelination, and inhibition of these processes will potentially be detrimental to the BACE1 inhibitor users who are susceptible to myelination diseases such as adult peripheral nerve injury or multiple sclerosis. In this report, we investigated the role of BACE1 during peripheral nerve remyelination in wild-type (WT) and BACE1-null mice.

The cis-regulatory logic of the mammalian photoreceptor transcriptional network.

The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3.