Measurements of chromatic adaptation and luminous efficiency while wearing colored filters.

The visual system adapts dynamically to stabilize perception over widely varying illuminations. Such adaptation allows the colors of objects to appear constant despite changes in spectral illumination. Similarly, the wearing of colored filters also alters spectral content, but this alteration can be more extreme than typically encountered in nature, presenting a unique challenge to color constancy mechanisms.

Potent activity of polymyxin B is associated with long-lived super-stoichiometric accumulation mediated by weak-affinity binding to lipid A.

Polymyxins are gram-negative antibiotics that target lipid A, the conserved membrane anchor of lipopolysaccharide in the outer membrane. Despite their clinical importance, the molecular mechanisms underpinning polymyxin activity remain unresolved. Here, we use surface plasmon resonance to kinetically interrogate interactions between polymyxins and lipid A and derive a phenomenological model.

BDNF in Neuropathic Pain; the Culprit that Cannot be Apprehended.

In males but not in females, brain derived neurotrophic factor (BDNF) plays an obligatory role in the onset and maintenance of neuropathic pain. Afferent terminals of injured peripheral nerves release colony stimulating factor (CSF-1) and other mediators into the dorsal horn. These transform the phenotype of dorsal horn microglia such that they express P2X4 purinoceptors.

Lipid Tales: Optimizing Arylomycin Membrane Anchors.

Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts, no new antibiotic class with activity against Gram-negative bacteria has been approved in over 50 years. LepB inhibitors (LepBi) based on the arylomycin class of natural products are a novel class of antibiotics and function by inhibiting the bacterial type I signal peptidase (SPase) in Gram-negative bacteria. One critical aspect of LepBi development involves optimization of the membrane-anchored lipophilic portion of the molecule.

Growth Arrest in Type IV Osteogenesis Imperfecta After Fassier-Duval Rod Insertion Treated by a Lengthening Magnetic Intramedullary Nail: A Case Report.

Case: A child with Type IV Osteogenesis Imperfecta (OI) sustained a growth arrest of the distal femur after fixation of a left femur fracture with a Fassier-Duval expanding rod at 3 years old. Despite bar resection with fat interposition, the discrepancy progressed to 7.5 cm at maturity.

Neuropathic pain; what we know and what we should do about it.

Neuropathic pain can result from injury to, or disease of the nervous system. It is notoriously difficult to treat. Peripheral nerve injury promotes Schwann cell activation and invasion of immunocompetent cells into the site of injury, spinal cord and higher sensory structures such as thalamus and cingulate and sensory cortices.

Biomechanical Implications of Congenital Conditions of the Foot/Ankle.

Segmental foot and ankle models are often used as part of instrumented gait analysis when planning interventions for complex congenital foot conditions. More than 40 models have been used for clinical analysis, and it is important to understand the technical differences among models. These models have been used to improve clinical planning of pediatric foot conditions including clubfoot, planovalgus, and equinovarus.

The Known Biology of Neuropathic Pain and Its Relevance to Pain Management.

Patients with neuropathic pain are heterogeneous in pathophysiology, etiology, and clinical presentation. Signs and symptoms are determined by the nature of the injury and factors such as genetics, sex, prior injury, age, culture, and environment. Basic science has provided general information about pain etiology by studying the consequences of peripheral injury in rodent models.

Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β.

Intractable neuropathic pain is a frequent consequence of nerve injury or disease. When peripheral nerves are injured, damaged axons undergo Wallerian degeneration. Schwann cells, mast cells, fibroblasts, keratinocytes and epithelial cells are activated leading to the generation of an "inflammatory soup" containing cytokines, chemokines and growth factors.

Peripheral Voltage-Gated Cation Channels in Neuropathic Pain and Their Potential as Therapeutic Targets.

The persistence of increased excitability and spontaneous activity in injured peripheral neurons is imperative for the development and persistence of many forms of neuropathic pain. This aberrant activity involves increased activity and/or expression of voltage-gated Na and Ca channels and hyperpolarization activated cyclic nucleotide gated (HCN) channels as well as decreased function of K channels. Because they display limited central side effects, peripherally restricted Na and Ca channel blockers and K channel activators offer potential therapeutic approaches to pain management.

What are the long-term outcomes of lateral column lengthening for pes planovalgus in cerebral palsy?

Background: Lateral column lengthening (LCL) is commonly performed on children and adolescents with cerebral palsy (CP) for correction of pes planovalgus (PPV). There are limited reports of the long-term outcomes of this procedure. The purpose of this study was to examine the long-term results of LCL for correction of PPV in individuals with CP by evaluating subjects when they had transitioned to adulthood and were entering the workforce.

Potent Killing of Pseudomonas aeruginosa by an Antibody-Antibiotic Conjugate.

Pseudomonas aeruginosa causes life-threatening infections that are associated with antibiotic failure. Previously, we identified the antibiotic G2637, an analog of arylomycin, targeting bacterial type I signal peptidase, which has moderate potency against P. aeruginosa.

Are sensory neurons exquisitely sensitive to interleukin 1β?

Peripheral nerve injury frequently evokes chronic neuropathic pain. This is initiated by a transient inflammatory response that leads to persistent excitation of dorsal root ganglion (DRG) neurons by inflammatory cytokines such as interleukin 1β(IL-1β). In non-neuronal cells such as lymphocytes, interleukin 1 exerts actions at attomolar (aM; 10 M) concentrations.

Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity.

Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca]) fluctuations.

Single-molecule nanopore sequencing reveals extreme target copy number heterogeneity in arylomycin-resistant mutants.

Tandem gene amplification is a frequent and dynamic source of antibiotic resistance in bacteria. Ongoing expansions and contractions of repeat arrays during population growth are expected to manifest as cell-to-cell differences in copy number (CN). As a result, a clonal bacterial culture could comprise subpopulations of cells with different levels of antibiotic sensitivity that result from variable gene dosage.

K Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain.

Sensory abnormalities generated by nerve injury, peripheral neuropathy or disease are often expressed as neuropathic pain. This type of pain is frequently resistant to therapeutic intervention and may be intractable. Numerous studies have revealed the importance of enduring increases in primary afferent excitability and persistent spontaneous activity in the onset and maintenance of peripherally induced neuropathic pain.

A Multicenter Study of Intramedullary Rodding in Osteogenesis Imperfecta.

Background: Osteogenesis imperfecta (OI), a heritable connective tissue disorder with wide clinical variability, predisposes to recurrent fractures and bone deformity. Management requires a multidisciplinary approach in which intramedullary rodding plays an important role, especially for moderate and severe forms. We investigated the patterns of surgical procedures in OI in order to establish the benefits of rodding.

Do Bisphosphonates Alleviate Pain in Children? A Systematic Review.

Purpose Of Review: The goal of this systematic review is to analyze the effectiveness of bisphosphonates (BPs) to treat bone pain in children and adolescents who have diseases with skeletal involvement.

Recent Findings: We included 24 studies (2 randomized controlled trials, 3 non-randomized controlled trials, 10 non-randomized open-label uncontrolled studies, 8 retrospective studies, and 1 study with design not specified). The majority of included studies assessed pain from a unidimensional approach, with pain intensity the most frequently evaluated dimension.

Time Course of Inflammation in Dorsal Root Ganglia Correlates with Differential Reversibility of Mechanical Allodynia.

Some individuals recover from the pain of nerve trauma within 12 months or less whereas others experience life-long intractable pain. This transition between reversible pain and the establishment of chronic neuropathic pain is poorly understood. We examined the role of persistent inflammation in the dorsal root ganglia (DRG) in the long-term maintenance of mechanical allodynia; an index of neuropathic pain.

Effect of Bisphosphonates on Function and Mobility Among Children With Osteogenesis Imperfecta: A Systematic Review.

Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder that results in bone fragility and deformity. Management is multi-disciplinary. Although pharmacologic intervention with bisphosphonates (BP) is a standard of care for individuals with severe OI, no consensus or reviews were found that focus on the effects of bisphosphonates on function and mobility.