Clinical Problem Solving: Two Patients With Gait Instability and Difficulty With Hand Coordination.

Subacute-to-chronic gait instability has a broad differential diagnosis. The neurological exam can help elucidate the localization and suggest an underlying etiology of the symptomatology, which can lead to a more focused diagnostic approach. Two patients are described - 1 with a month of worsening difficulty with ambulation that evolved to bilateral hand discoordination and another with 18 months of progressive difficulty with ambulation that also then progressed to involve her bilateral hands.

Symmetric leukoencephalopathy associated with systemic lupus erythematosus: A systematic review of a distinctive neurorheumatologic syndrome.

Background: A symmetric leukoencephalopathy can occur in the context of systemic lupus erythematosus (SLE), often as a first manifestation of underlying rheumatologic disease. Recognition of this distinctive syndrome can prompt investigation for SLE when undiagnosed, or prompt treatment initiation when the diagnosis is already known. Earlier recognition of this syndrome could lead to more effective treatment of the disease.

Age-related and amyloid-beta-independent tau deposition and its downstream effects.

Amyloid-β (Aβ) is hypothesized to facilitate the spread of tau pathology beyond the medial temporal lobe. However, there is evidence that, independently of Aβ, age-related tau pathology might be present outside of the medial temporal lobe. We therefore aimed to study age-related Aβ-independent tau deposition outside the medial temporal lobe in two large cohorts and to investigate potential downstream effects of this on cognition and structural measures.

Deep label fusion: A generalizable hybrid multi-atlas and deep convolutional neural network for medical image segmentation.

Deep convolutional neural networks (DCNN) achieve very high accuracy in segmenting various anatomical structures in medical images but often suffer from relatively poor generalizability. Multi-atlas segmentation (MAS), while less accurate than DCNN in many applications, tends to generalize well to unseen datasets with different characteristics from the training dataset. Several groups have attempted to integrate the power of DCNN to learn complex data representations and the robustness of MAS to changes in image characteristics.

Self- and Partner-Reported Subjective Memory Complaints: Association with Objective Cognitive Impairment and Risk of Decline.

Background: Episodic memory decline is a hallmark of Alzheimer's disease (AD). Subjective memory complaints (SMCs) may represent one of the earliest signs of impending cognitive decline. The degree to which self- or partner-reported SMCs predict cognitive change remains unclear.

Agreement between attended home and ambulatory blood pressure measurements in adolescents with chronic kidney disease.

Background: This study aimed to compare attended home blood pressure (BP) measurements (HBPM) with ambulatory BP monitor (ABPM) readings and examine if level of agreement between measurement modalities differs overall and by subgroup.

Methods: This was a secondary analysis of data from a 2-year, multicenter observational study of children 11-19 years (mean 15, SD = 2.7) with chronic kidney disease.

STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation.

Genetic diseases involving overactivation of the mechanistic target of rapamycin (mTOR) pathway, so-called "mTORopathies," often manifest with malformations of cortical development (MCDs), epilepsy, and cognitive impairment. How mTOR pathway hyperactivation results in abnormal human cortical development is poorly understood. To study the effect of mTOR hyperactivity on early stages of cortical development, we focused on Pretzel Syndrome (polyhydramnios, megalencephaly, symptomatic epilepsy; PMSE syndrome), a rare mTORopathy caused by homozygous germline mutations in the STRADA gene.

Looking at education through the microscope.

Advanced research microscopes in universities can be used to enhance the education of STEM students, as demonstrated by initiatives at Johns Hopkins University that give students the opportunity to get hands-on experience with sophisticated microscopes.

Engagement and Affective Communication During Pediatric Nephrology Clinic Visits: Associations with Medication Adherence.

Objective: To evaluate whether engagement and affective communication among adolescents and young adults (AYAs) with chronic kidney disease (CKD), caregivers, and pediatric nephrology providers during outpatient clinic visits predicts antihypertensive medication adherence.

Methods: AYAs (n = 60, M age = 15.4 years, SD = 2.

Rapid Generation of Human Genetic Loss-of-Function iPSC Lines by Simultaneous Reprogramming and Gene Editing.

Specifically ablating genes in human induced pluripotent stem cells (iPSCs) allows for studies of gene function as well as disease mechanisms in disorders caused by loss-of-function (LOF) mutations. While techniques exist for engineering such lines, we have developed and rigorously validated a method of simultaneous iPSC reprogramming while generating CRISPR/Cas9-dependent insertions/deletions (indels). This approach allows for the efficient and rapid formation of genetic LOF human disease cell models with isogenic controls.