Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.

Background: Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN.

Efferent Activity Controls Hair Cell Response to Mechanical Overstimulation.

The efferent pathway strengthens the auditory system for optimal performance by fine-tuning the response and protecting the inner ear from noise-induced damage. Although it has been well documented that efference helps defend against hair cell and synaptic extinction, the mechanisms of its otoprotective role have still not been established. Specifically, the effect of efference on an individual hair cell's recovery from mechanical overstimulation has not been demonstrated.

Brain Mechanisms of Pain and Dysautonomia in Diabetic Neuropathy: Connectivity Changes in Thalamus and Hypothalamus.

Context: About one-third of diabetic patients suffer from neuropathic pain, which is poorly responsive to analgesic therapy and associated with greater autonomic dysfunction. Previous research on diabetic neuropathy mainly links pain and autonomic dysfunction to peripheral nerve degeneration resulting from systemic metabolic disturbances, but maladaptive plasticity in the central pain and autonomic systems following peripheral nerve injury has been relatively ignored.

Objective: This study aimed to investigate how the brain is affected in painful diabetic neuropathy (PDN), in terms of altered structural connectivity (SC) of the thalamus and hypothalamus that are key regions modulating nociceptive and autonomic responses.

ncRNA BC1 influences translation in the oocyte.

Regulation of translation is essential for the diverse biological processes involved in development. Particularly, mammalian oocyte development requires the precisely controlled translation of maternal transcripts to coordinate meiotic and early embryo progression while transcription is silent. It has been recently reported that key components of mRNA translation control are short and long noncoding RNAs (ncRNAs).

Brain imaging signature of neuropathic pain phenotypes in small-fiber neuropathy: altered thalamic connectome and its associations with skin nerve degeneration.

Small-fiber neuropathy (SFN) has been traditionally considered as a pure disorder of the peripheral nervous system, characterized by neuropathic pain and degeneration of small-diameter nerve fibers in the skin. Previous functional magnetic resonance imaging studies revealed abnormal activations of pain networks, but the structural basis underlying such maladaptive functional alterations remains elusive. We applied diffusion tensor imaging to explore the influences of SFN on brain microstructures.

Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.

Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is strongly associated with favorable outcome. We examined the utility of serial circulating tumor DNA (ctDNA) testing for predicting pCR and risk of metastatic recurrence.

Patients And Methods: Cell-free DNA (cfDNA) was isolated from 291 plasma samples of 84 high-risk early breast cancer patients treated in the neoadjuvant I-SPY 2 TRIAL with standard NAC alone or combined with MK-2206 (AKT inhibitor) treatment.

Effects of Efferent Activity on Hair Bundle Mechanics.

Hair cells in both the auditory and vestibular systems receive efferent innervation. A number of prior studies have indicated that efferent regulation serves to diminish the overall sensitivity of the auditory system. The efferent pathway is believed to affect the sensitivity and frequency selectivity of the hair cell by modulating its membrane potential.

Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer.

Importance: Novel sensitive methods for detection and monitoring of residual disease can improve postoperative risk stratification with implications for patient selection for adjuvant chemotherapy (ACT), ACT duration, intensity of radiologic surveillance, and, ultimately, outcome for patients with colorectal cancer (CRC).

Objective: To investigate the association of circulating tumor DNA (ctDNA) with recurrence using longitudinal data from ultradeep sequencing of plasma cell-free DNA in patients with CRC before and after surgery, during and after ACT, and during surveillance.

Design, Setting, And Participants: In this prospective, multicenter cohort study, ctDNA was quantified in the preoperative and postoperative settings of stages I to III CRC by personalized multiplex, polymerase chain reaction-based, next-generation sequencing.

Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma.

Purpose: Novel sensitive methods for early detection of relapse and for monitoring therapeutic efficacy may have a huge impact on risk stratification, treatment, and ultimately outcome for patients with bladder cancer. We addressed the prognostic and predictive impact of ultra-deep sequencing of cell-free DNA in patients before and after cystectomy and during chemotherapy.

Patients And Methods: We included 68 patients with localized advanced bladder cancer.

Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence.

Purpose: Up to 30% of patients with breast cancer relapse after primary treatment. There are no sensitive and reliable tests to monitor these patients and detect distant metastases before overt recurrence. Here, we demonstrate the use of personalized circulating tumor DNA (ctDNA) profiling for detection of recurrence in breast cancer.

Contextual interference enhances motor learning through increased resting brain connectivity during memory consolidation.

Increasing contextual interference (CI) during practice benefits learning, making it a desirable difficulty. For example, interleaved practice (IP) of motor sequences is generally more difficult than repetitive practice (RP) during practice but leads to better learning. Here we investigated whether CI in practice modulated resting-state functional connectivity during consolidation.

Benefit of interleaved practice of motor skills is associated with changes in functional brain network topology that differ between younger and older adults.

Practicing tasks arranged in an interleaved manner generally leads to superior retention compared with practicing tasks repetitively, a phenomenon known as the contextual interference (CI) effect. We investigated the brain network of motor learning under CI, that is, the CI network, and how it was affected by aging. Sixteen younger and 16 older adults practiced motor sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on day 5 to evaluate learning.

Next-generation sequencing applied to rare diseases genomics.

Genomics has revolutionized the study of rare diseases. In this review, we overview the latest technological development, rare disease discoveries, implementation obstacles and bioethical challenges. First, we discuss the technology of genome and exome sequencing, including the different next-generation platforms and exome enrichment technologies.

Enhanced motor learning in older adults is accompanied by increased bilateral frontal and fronto-parietal connectivity.

We recently demonstrated that older adults can benefit as much as younger adults from learning skills in an interleaved manner. Here we investigate whether optimized learning through interleaved practice (IP) is associated with changes in inter-regional brain connectivity and whether younger and older adults differ in such brain-behavior correlations. Younger and older adults practiced a set of three 4-element motor sequences in a repetitive or in an interleaved order for 2 consecutive days.

Interleaved practice enhances skill learning and the functional connectivity of fronto-parietal networks.

Practice of tasks in an interleaved order generally induces superior learning compared with practicing in a repetitive order, a phenomenon known as the contextual-interference (CI) effect. Increased neural activity during interleaved over repetitive practice has been associated with the beneficial effects of CI. Here, we used psychophysiological interaction (PPI) analysis to investigate whether the neural connectivity of the dorsal premotor (PM) and the dorsolateral prefrontal (DLPFC) cortices changes when motor sequences are acquired through interleaved practice.

Brain-behavior correlates of optimizing learning through interleaved practice.

Understanding how to make learning more efficient and effective is an important goal in behavioral neuroscience. The notion of "desirable difficulties" asserts that challenges for learners during study result in superior learning. One "desirable difficulty" that has a robust benefit on learning is contextual interference (CI), in which different tasks are practiced in an interleaved order rather than in a repetitive order.

Contextual interference effects in sequence learning for young and older adults.

Practice of different tasks in a random order induces better retention than practicing them in a blocked order, a phenomenon known as the contextual interference (CI) effect. Our purpose was to investigate whether the CI effect exists in sequence learning, such that practicing different sequences in a random order will result in better learning of sequences than practicing them in blocks, and whether this effect is affected by aging. Subjects practiced a serial reaction time task where a set of three 4-element sequences were arranged in blocks or in a random order on 2 successive days.

Neural correlates of the contextual interference effect in motor learning: a transcranial magnetic stimulation investigation.

The authors applied transcranial magnetic stimulation (TMS) to investigate the causal role of the primary motor cortex (M1) for the contextual-interference effect in motor learning. Previous work using a nonfocal TMS coil suggested a casual role for M1 during high-interference practice conditions, but this hypothesis has not yet been proven. In the 1st experiment, participants practiced 3 rapid elbow flexion-extension tasks in either a blocked or random order, with learning assessed by a delayed retention test.

Age affects the attentional demands of stair ambulation: evidence from a dual-task approach.

Background: Approximately 75% of all injury-producing falls on steps for people of all ages occur in people 65 years of age and older. Diminished attentional capacity contributes to fall risk in older adults, particularly when task demands are high.

Objective: The purpose of this study was to compare the attentional demands of ascending and descending a set of stairs (stair ambulation) in older adults and younger adults.

Efficacy of 2 non-weight-bearing interventions, proprioception training versus strength training, for patients with knee osteoarthritis: a randomized clinical trial.

Study Design: Randomized clinical trial.

Objective: To investigate the clinical and functional efficacy of 2 different non-weight-bearing exercise regimens, proprioceptive training (PrT) versus strength training (ST), for patients with knee osteoarthritis (OA).

Background: Both strength and proprioceptive training are important interventions for individuals with knee OA.

Differences in sonographic characteristics of the vastus medialis obliquus between patients with patellofemoral pain syndrome and healthy adults.

Background: There is controversy regarding the relationship between patellofemoral pain syndrome (PFPS) and insufficiency of the vastus medialis obliquus (VMO). The conventional clinical practice of VMO strengthening for PFPS has been challenged for lack of evidence. The purpose of this study was to observe the difference in sonographic findings of the VMO between patients with PFPS and healthy adults.

Neural correlate of the contextual interference effect in motor learning: a kinematic analysis.

The contextual interference (CI) effect affirms that learning is enhanced when interference during practice is high, such as when participants practice multiple tasks in a random order. Previous research showed a distinct response in the cortical motor (CM) regions of participants performing under high CI practice conditions compared with low CI conditions. Specifically, there was increased corticomotor activity in a high CI condition when participants practiced 3 arm tasks, each with specific spatial and temporal requirements.

The effects of quadriceps contraction on different patellofemoral alignment subtypes: an axial computed tomography study.

Study Design: Controlled laboratory study.

Background: The effect of quadriceps contraction on patellar alignment in patients with patellofemoral pain syndrome (PFPS) is debated and may vary based on patellar alignment subtypes measured with the quadriceps relaxed.

Objectives: To determine if the effects of quadriceps contraction on patellar alignment differs (1) with respect to patellar alignment subtype in individuals with PFPS and (2) between symptomatic and asymptomatic knees in individuals with unilateral PFPS.

Contextual interference effect: elaborative processing or forgetting-reconstruction? A post hoc analysis of transcranial magnetic stimulation-induced effects on motor learning.

The elaborative-processing and forgetting-reconstruction hypotheses are the 2 principal explanations for the contextual interference (CI) effect. The present authors' purpose was to identify which of these 2 hypotheses better accounts for the CI effect. They synchronized single transcranial magnetic stimulation (TMS) pulses to each intertrial interval to modulate information processing during Blocked and Random Practice conditions.