Dye-less quantification of tissue perfusion by laser speckle contrast imaging is equivalent to quantified indocyanine green in a porcine model.

Introduction: Subjective surgeon interpretation of near-infrared perfusion video is limited by low inter-observer agreement and poor correlation to clinical outcomes. In contrast, quantification of indocyanine green fluorescence video (Q-ICG) correlates with histologic level of perfusion as well as clinical outcomes. Measuring dye volume over time, however, has limitations, such as it is not on-demand, has poor spatial resolution, and is not easily repeatable.

Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy - could it end the controversy?

Unlabelled: The Gross Motor Function Measure is used in most studies measuring gross motor function in children with cerebral palsy. In many studies, including those evaluating the effect of hyperbaric treatment, the Gross Motor Function Measure variations were potentially misinterpreted because of the lack of control groups. The Gross Motor Function Measure Evolution Ratio (GMFMER) uses historical data from the Gross Motor Function Classification System curves and allows to re-analyze previous published studies which used the Gross Motor Function Measure by considering the natural expected evolution of the Gross Motor Function Measure.

Simultaneous Quantification of Psychotropic Drugs in Human Plasma and Breast Milk and Its Application in Therapeutic Drug Monitoring and Peripartum Treatment Optimization.

Background: Therapeutic drug monitoring is recommended for several psychotropic drugs, particularly in sensitive situations such as the peripartum period. This study aimed to develop an ultra-high-performance liquid chromatography-tandem spectrometry method for the simultaneous quantification of 14 psychotropic drugs in human plasma and 4 in breast milk.

Methods: The samples were precipitated with methanol containing the stable isotope-labeled analogs.

A birefringent spectral demultiplexer enables fast hyper-spectral imaging of protoporphyrin IX during neurosurgery.

Hyperspectral imaging and spectral analysis quantifies fluorophore concentration during fluorescence-guided surgery. However, acquisition of the multiple wavelengths required to implement these methods can be time-consuming and hinder surgical workflow. To this end, a snapshot hyperspectral imaging system capable of acquiring 64 channels of spectral data simultaneously was developed for rapid hyperspectral imaging during neurosurgery.

The atypic antipsychotic clozapine inhibits multiple cardiac ion channels.

Clozapine is an atypical neuroleptic used to manage treatment-resistant schizophrenia which is known to inhibit cardiac hERG/K11.1 potassium channels, a pharmacological property associated with increased risk of potentially fatal Torsades de Pointes (TdP) and sudden cardiac death (SCD). Yet, the long-standing clinical practice of clozapine does not show a consistent association with increased incidence of TdP, although SCD is considerably higher among schizophrenic patients than in the general population.

Spatial modeling reveals nuclear phosphorylation and subcellular shuttling of YAP upon drug-induced liver injury.

The Hippo signaling pathway controls cell proliferation and tissue regeneration via its transcriptional effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The canonical pathway topology is characterized by sequential phosphorylation of kinases in the cytoplasm that defines the subcellular localization of YAP and TAZ. However, the molecular mechanisms controlling the nuclear/cytoplasmic shuttling dynamics of both factors under physiological and tissue-damaging conditions are poorly understood.

Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy.

Aims/hypothesis: The individual risk of progression of diabetic peripheral neuropathy is difficult to predict for each individual. Mutations in proteins that are responsible for the process of myelination are known to cause neurodegeneration and display alteration in experimental models of diabetic neuropathy. In a prospective observational human pilot study, we investigated myelin-specific circulating mRNA targets, which have been identified in vitro, for their capacity in the diagnosis and prediction of diabetic neuropathy.

Chronic pain treatment preferences change following participation in N-of-1 trials, but not always in the expected direction.

Objective: To examine pain treatment preferences before and after participation in an N-of-1 trial.

Study Design And Setting: In this observational study nested within a randomized trial, we examined chronic pain patients' preferences before and after treatment in relation to N-of-1 trial results; assessed the influence of different schemes for defining comparative "superiority" on potential conclusions; and generated classification trees illustrating the relationship between pre-treatment preferences, N-of-1 trial results, and post-treatment preferences.

Results: Treatment preferences differed pre- and post-trial for 40% of participants.

RNA therapeutics for mood disorders: current evidence toward clinical trials.

Introduction: Mood disorders are severe yet frequent psychiatric disorders worldwide, comprising major depressive disorder (MDD) and bipolar disorders (BD). Their treatment remains poorly effective. Recently, growing evidence for epigenetic mechanisms has emerged.

Innovative approaches in CNS clinical drug development: Quantitative systems pharmacology.

Clinical trials involving brain disorders are notoriously difficult to set up and run. Innovative ways to develop effective prevention and treatment strategies for central nervous system (CNS) diseases are urgently needed. New approaches that are likely to renew or at least modify the paradigms used so far have been recently proposed.

Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro.

Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD.

Effect of Mobile Device-Assisted N-of-1 Trial Participation on Analgesic Prescribing for Chronic Pain: Randomized Controlled Trial.

Objectives: Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for chronic musculoskeletal pain, despite limited evidence of effectiveness and well-documented adverse effects. We assessed the effects of participating in a structured, personalized self-experiment ("N-of-1 trial") on analgesic prescribing in patients with chronic musculoskeletal pain.

Methods: We randomized 215 patients with chronic pain to participate in an N-of-1 trial facilitated by a mobile health app or to receive usual care.

First experience imaging short-wave infrared fluorescence in a large animal: indocyanine green angiography of a pig brain.

The potential to image subsurface fluorescent contrast agents at high spatial resolution has facilitated growing interest in short-wave infrared (SWIR) imaging for biomedical applications. The early but growing literature showing improvements in resolution in small animal models suggests this is indeed the case, yet to date, images from larger animal models that more closely recapitulate humans have not been reported. We report the first imaging of SWIR fluorescence in a large animal model.

Patient Perceptions of Their Own Data in mHealth Technology-Enabled N-of-1 Trials for Chronic Pain: Qualitative Study.

Background: N-of-1 (individual comparison) trials are a promising approach for comparing the effectiveness of 2 or more treatments for individual patients; yet, few studies have qualitatively examined how patients use and make sense of their own patient-generated health data (PGHD) in the context of N-of-1 trials.

Objective: The objective of our study was to explore chronic pain patients' perceptions about the PGHD they compiled while comparing 2 chronic pain treatments and tracking their symptoms using a smartphone N-of-1 app in collaboration with their clinicians.

Methods: Semistructured interviews were recorded with 33 patients, a consecutive subset of the intervention group in a primary study testing the feasibility and effectiveness of the Trialist N-of-1 app.

Effect of Mobile Device-Supported Single-Patient Multi-crossover Trials on Treatment of Chronic Musculoskeletal Pain: A Randomized Clinical Trial.

Importance: Individually designed single-patient multi-crossover (n-of-1) trials can facilitate tailoring of treatments directed at various conditions, including chronic musculoskeletal pain (CMSP) but are potentially burdensome, which may limit uptake in research and practice.

Objectives: To determine whether patients randomized to participate in an n-of-1 trial supported by a mobile health (mHealth) app would experience less pain and improved global health, adherence, satisfaction, and shared decision making compared with patients assigned to usual care.

Design, Setting, And Participants: This randomized clinical trial compared participation in an individualized, mHealth-supported n-of-1 trial vs usual care.

Optimal wavelength selection for optical spectroscopy of hemoglobin and water within a simulated light-scattering tissue.

An algorithm that selects optimal wavelengths for spectral fitting of diffuse light reflectance spectra using a nonnegative least squares method is presented. Oxyhemoglobin, deoxyhemoglobin, and water are considered representative absorbers, but the approach is not constrained or limited by absorber selection provided native basis spectra are available. The method removes wavelengths iteratively from a scattering-modulated absorption matrix by maximizing the product of its singular values and offers considerable improvements over previously published wavelength selection schemes.

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis.

Sensorimotor adaptation of whole-body postural control.

The aim of the present study was to examine the modification of postural symmetry during quiet standing using a sensorimotor adaptation paradigm. A group of neurologically typical adult participants performed a visually guided mediolateral (left-right) weight shifting task requiring precise adjustments in body orientation. During one phase of the task, the visual feedback of center of pressure (COP) was systematically biased toward the left or the right, requiring an adjustment in posture to compensate.

Does bovine besnoitiosis affect the sexual function of chronically infected bulls?

Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage.

Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms.

Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation.

Gross Motor Function Measure Evolution Ratio: Use as a Control for Natural Progression in Cerebral Palsy.

Objective: To develop a new way to interpret Gross Motor Function Measure (GMFM-66) score improvement in studies conducted without control groups in children with cerebral palsy (CP).

Design: The curves, which describe the pattern of motor development according to the children's Gross Motor Function Classification System level, were used as historical control to define the GMFM-66 expected natural evolution in children with CP. These curves have been modeled and generalized to fit the curve to particular children characteristics.