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Literacy expectations for persons with cognitive impairments, including impairments caused by traumatic brain injury (TBI), have remained quite low. Some researchers have suggested that educators move from a focus on teaching functional skills to teaching basic reading skills in a manner similar to instruction for nondisabled learners. The purpose of this study was to examine the effectiveness of basic reading strategies on reading skills for an adult with cognitive impairments caused by TBI while using formative assessment to inform instructional decision making. The findings suggest that persons with traumatic brain injury resulting in cognitive and memory impairments may have the potential to learn basic reading skills, even years after a TBI has occurred. [ABSTRACT FROM AUTHOR]

Ex vivo 3D culture of human tissue explants addresses many limitations of traditional monolayer cell culture techniques, namely the lack of cellular heterogeneity and absence of 3D intercellular spatial relationships, but presents challenges with regard to repeatability owing to the difficulty of acquiring multiple tissue samples from the same donor. In this study, we used a cryopreserved bank of human lung microexplants, ∼1 mm 3 fragments of peripheral lung from donors undergoing lung resection surgery, and a liquid-like solid 3D culture matrix to describe a method for the analysis of non-small-cell lung cancer adhesion to human lung tissue. H226 (squamous cell carcinoma), H441 (lung adenocarcinoma), and H460 (large cell carcinoma) cell lines were cocultured with lung microexplants. Confocal fluorescence microscopy was used to visualize the adherence of each cell line to lung microexplants. Adherent cancer cells were quantified following filtration of nonadherent cells, digestion of cultured microexplants, and flow cytometry. This method was used to evaluate the role of integrins in cancer cell adherence. A statistically significant decrease in the adherence of H460 cells to lung microexplants was observed when anti-integrins were administered to H460 cells before coculture with lung microexplants.

Severe inflammatory stress often leads to vessel rarefaction and fibrosis, resulting in limited tissue recovery. However, signaling pathways mediating these processes are not completely understood. Patients with ischemic and inflammatory conditions have increased systemic Activin A level, which frequently correlates with the severity of pathology. Yet, Activin A's contribution to disease progression, specifically to vascular homeostasis and remodeling, is not well defined. This study investigated vasculogenesis in an inflammatory environment with an emphasis on Activin A's role. Exposure of endothelial cells (EC) and perivascular cells (adipose stromal cells, ASC) to inflammatory stimuli (represented by blood mononuclear cells from healthy donors activated with lipopolysaccharide, aPBMC) dramatically decreased EC tubulogenesis or caused vessel rarefaction compared to control co-cultures, concurrent with increased Activin A secretion. Both EC and ASC upregulated Inhibin Ba mRNA and Activin A secretion in response to aPBMC or their secretome. We identified TNFα (in EC) and IL-1β (in EC and ASC) as the exclusive inflammatory factors, present in aPBMC secretome, responsible for induction of Activin A. Similar to ASC, brain and placental pericytes upregulated Activin A in response to aPBMC and IL-1β, but not TNFα. Both these cytokines individually diminished EC tubulogenesis. Blocking Activin A with neutralizing IgG mitigated detrimental effects of aPBMC or TNFα/IL-1β on tubulogenesis in vitro and vessel formation in vivo. This study delineates the signaling pathway through which inflammatory cells have a detrimental effect on vessel formation and homeostasis, and highlights the central role of Activin A in this process. Transitory interference with Activin A during early phases of inflammatory or ischemic insult, with neutralizing antibodies or scavengers, may benefit vasculature preservation and overall tissue recovery., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Depriving microbes of iron is critical to host defense. Hemeproteins, the largest source of iron within vertebrates, are abundant in infected tissues in aspergillosis due to hemorrhage, but Aspergillus species have been thought to lack heme import mechanisms. We hypothesized that heme provides iron to Aspergillus during invasive pneumonia, thereby worsening the outcomes of the infection., Methods: We assessed the effect of heme on fungal phenotype in various in vitro conditions and in a neutropenic mouse model of invasive pulmonary aspergillosis., Results: In mice with neutropenic invasive aspergillosis, we found a progressive and compartmentalized increase in lung heme iron. Fungal cells cultured under low iron conditions took up heme, resulting in increased fungal iron content, resolution of iron starvation, increased conidiation, and enhanced resistance to oxidative stress. Intrapulmonary administration of heme to mice with neutropenic invasive aspergillosis resulted in markedly increased lung fungal burden, lung injury, and mortality, whereas administration of heme analogs or heme with killed Aspergillus did not. Finally, infection caused by fungal germlings cultured in the presence of heme resulted in a more severe infection., Conclusions: Invasive aspergillosis induces local hemolysis in infected tissues, thereby supplying heme iron to the fungus, leading to lethal infection., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: To systematically summarize the evidence on costs related to chronic pelvic pain (CPP) for women., Data Sources: Electronic databases (MEDLINE, EMBASE, PubMed, and Cochrane Library) were searched for English and French articles published from 1990 to January 2021 STUDY SELECTION: Of 1304 articles screened, 67 were screened in full-text form, and a total of 13 articles were included in the final analysis. Articles included involved cost studies that estimated hospital or health system costs for pelvic pain, dysmenorrhea, dyspareunia, endometriosis with pain, interstitial cystitis, or painful bladder syndrome., Data Extraction and Synthesis: A standardized form was created to extract study setting, design, and population; patient demographics; study duration; and reported costs of CPP components and amounts. Two independent reviewers completed the data extraction, and discrepancies were resolved through discussion with a third reviewer., Conclusion: Estimated health care costs ranged from US$1367 to US$7043 per woman per year. Prescription costs ranged from US$193 to US$2457 per woman per year. Indirect costs ranged from US$4216 to US$12 789 per woman per year. Combined costs ranged from US$1820 to US$20 898 per woman per year. The yearly costs of CPP varied according to country; yearly costs were estimated to be $2.8 billion, ¥191,680 to ¥246,488, and $16 970 to $20 898 per woman per year in the United Sates, Japan, and Australia, respectively. The literature suggests that CPP represents a considerable economic burden on women and health care systems internationally, with indirect costs contributing a significant portion of total costs., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) patients exhibit skeletal muscle atrophy, denervation, and reduced mitochondrial oxidative capacity. Whilst chronic tobacco smoke exposure is implicated in COPD muscle impairment, the mechanisms involved are ambiguous. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that activates detoxifying pathways with numerous exogenous ligands, including tobacco smoke. Whereas transient AHR activation is adaptive, chronic activation can be toxic. On this basis, we tested the hypothesis that chronic smoke-induced AHR activation causes adverse muscle impact., Methods: We used clinical patient muscle samples, and in vitro (C2C12 myotubes) and in vivo models (mouse), to perform gene expression, mitochondrial function, muscle and neuromuscular junction morphology, and genetic manipulations (adeno-associated virus-mediated gene transfer)., Results: Sixteen weeks of tobacco smoke exposure in mice caused muscle atrophy, neuromuscular junction degeneration, and reduced oxidative capacity. Similarly, smoke exposure reprogrammed the muscle transcriptome, with down-regulation of mitochondrial and neuromuscular junction genes. In mouse and human patient specimens, smoke exposure increased muscle AHR signalling. Mechanistically, experiments in cultured myotubes demonstrated that smoke condensate activated the AHR, caused mitochondrial impairments, and induced an AHR-dependent myotube atrophy. Finally, to isolate the role of AHR activity, expression of a constitutively active AHR mutant without smoke exposure caused atrophy and mitochondrial impairments in cultured myotubes, and muscle atrophy and neuromuscular junction degeneration in mice., Conclusions: These results establish that chronic AHR activity, as occurs in smokers, phenocopies the atrophy, mitochondrial impairment, and neuromuscular junction degeneration caused by chronic tobacco smoke exposure., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objective: Pudendal neuralgia is a recognized cause of chronic pelvic pain. The diagnosis is complex, and there is no consensus on ideal management. Many current methods do not provide adequate relief. Pulsed radiofrequency is a minimally invasive option that has been reported for its use in other neuropathies. This study aimed to evaluate the feasibility and safety of using transvaginal pulsed radiofrequency for the treatment of pudendal neuralgia and to generate a hypothesis on its efficacy., Methods: A retrospective review was conducted of women who were treated with pulsed radiofrequency for chronic pelvic pain owing to pudendal neuralgia between January 2012 and December 2017 at an academic tertiary care centre. (Canadian Task Force Classification II-3)., Results: A total of seven patients were included. The mean age was 43.7 (standard deviation 7.97). The average number of pulsed radiofrequency treatments was 4.43 (range 1-12), and the duration of effect averaged 11.4 weeks (standard deviation 3.09). There were no major or minor complications at the time of procedure or at follow-up visits., Conclusions: Pulsed radiofrequency may be an effective and safe treatment option for the management of pudendal neuralgia for women in whom conservative management has not been effective. Future controlled studies are needed to confirm this hypothesis., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the hospital-related costs incurred by women requiring surgery or inpatient admission for chronic pelvic pain in Canada., Methods: We conducted a population-based, cross-sectional study, focusing on women ages 15-59 with a most responsible International Classification of Diseases diagnosis of pelvic and perineal pain, dysmenorrhea, or dyspareunia who had surgery or inpatient admission with a discharge date between April 1, 2008 and March 31, 2012. This study was based on the Canadian Institute for Health Information Discharge Abstract database and the National Ambulatory Care Reporting System. Clinical diagnoses and interventions and resource intensity weights (RIW) were extracted. Hospital costs were estimated by multiplying cost per weighted case (CPWC) calculated at the national level with respective RIWs., Results: Over four years, there were 34 346 cases of surgery or inpatient admission for chronic pelvic pain amounting to $100.5 million with an average cost of $25 million per year. Pelvic and perineal pain accounted for 61.5% (n = 21 127) of the cases, while dysmenorrhea accounted for 31.8% (n = 10 936), and dyspareunia accounted for 6.6% (n = 2283). The vast majority of the cases (92.9%, n = 31 923) were associated with surgical interventions, with the most common surgeries being hysterectomy (47.1%, n = 16 189), followed by laparoscopy (25.8%, n = 8850), adnexal surgery (6.8%, n = 2349), and other procedures (11.6%, n = 3968)., Conclusion: While these estimates do not take into account non-hospital related costs, such as outpatient treatment, loss of productivity, and impact on quality of life, this study demonstrates that chronic pelvic pain represents a considerable economic burden to Canada's health care system., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

The intrathecal drug-delivery system (IDDS) is one mode of infusing analgesic medications directly into the cerebrospinal fluid in close proximity to their site of action. This modality has been employed in patients with refractory pain either due to malignant or non-malignant causes for over 30 years. Unfortunately, and despite the number of years it has been in use, there is still a scarcity of rigorous evidence to guide its integration into clinical practice. Current best evidence is inconclusive as to the comparative effectiveness and harms of the IDDS relative to routine medical care of patients. There are far more systematic reviews than high-quality primary comparative studies of the IDDS vs. conventional pain treatment. Existing clinical practice recommendations are best viewed as expert opinion with competing interests. This article will review the existing literature for indications, contraindications, consensus statements, different technologies, and complications of the IDDS. Although approved analgesics for IDDS delivery are limited to morphine and ziconotide, many other analgesics, alone or in combination, are routinely used in this setting. This review will also focus on the pharmacology, clinical efficacy, and safety of intrathecal medications extensively used in clinical practice; including agents approved, unapproved, and under development.

Immobilized proteins present a unique interface with water. The water translational diffusive motions affect the high-frequency dynamics and the nuclear spin-lattice relaxation as with all surfaces; however, rare binding sites for water in protein systems add very low-frequency components to the dynamics spectrum. Water binding sites in protein systems are not identical, thus distributions of free energies and consequent dynamics are expected. (2)H(2)O spin-lattice relaxation rate measurements as a function of magnetic field strength characterize the local rotational fluctuations for protein-bound water molecules. The measurements are sensitive to dynamics down to the kilohertz range. To account for the data, we show that the extreme-values statistics of rare events, i.e., water dynamics in rare binding sites, implies an exponential distribution of activation energies for the strongest binding events. In turn, for an activated dynamical process, the exponential energy distribution leads to a Pareto distribution for the reorientational correlation times and a power law in the Larmor frequency for the (2)H(2)O spin-lattice relaxation rate constants at low field strengths. The most strongly held water molecules escape from rare binding sites in times on the order of microseconds, which interrupts the intramolecular correlations and causes a plateau in the spin-lattice relaxation rate at very low magnetic field strengths. We examine the magnetic relaxation dispersion (MRD) data using two simple but related models: a protein-bound environment for water characterized by a single potential well and a protein-bound environment characterized by a double potential well where the potential functions for the local motions of the bound-state water are of different depth. This analysis is applied to D(2)O deuterium spin-lattice relaxation on cross-linked albumin and lysozyme, which is dominated by the intramolecular relaxation driven by the dynamical modulation of the nuclear electric quadrupole coupling. We also separate the intramolecular from the intermolecular contribution to water proton spin-lattice relaxation by isotope dilution and show that the intramolecular proton data map onto the deuterium relaxation by a scale factor implied by the relative strength of the quadrupole and dipolar couplings. The temperature and pH dependence of the magnetic relaxation dispersion are complex and accounted for by changing only the weighting factors in a superposition of contributions from single-well and double-well contributions. These experiments show that the reorientational dynamics spectrum for water, in and on a protein, is characterized by a strongly asymmetric distribution with a long-time tail that extends at least to microseconds.

The paramagnetic contributions to water-proton-spin-lattice relaxation rate constants in protein systems spin-labeled with nitroxide radicals were re-examined. As noted by others, the strength of the dipolar coupling between water protons and the protein-bound nitroxide radical often appears to be larger than physically reasonable when the relaxation is assumed to be controlled by 3-dimensional diffusive processes in the vicinity of the spin label. We examine the effects of the surface in biasing the diffusive exploration of the radical region and derive a relaxation model that incorporates 2-dimensional dynamics at the interfacial layer. However, we find that the local 2-dimensional dynamics changes the shape of the relaxation dispersion profile but does not necessarily reproduce the low-field relaxation efficiency found by experiment. We examine the contributions of long-range dipolar couplings between the paramagnetic center and protein-bound-water molecules and find that the contributions from these several long range couplings may be competitive with translational contributions because the correlation time for global rotation of the protein is approximately 1000 times longer than that for the diffusive motion of water at the interfacial region. As a result the electron-proton dipolar coupling to rare protein-bound-water-molecule protons may be significant for protein systems that accommodate long-lived-water molecules. Although the estimate of local diffusion coefficients is not seriously compromised because it derives from the Larmor frequency dependence, these several contributions confound efforts to fit relaxation data quantitatively with unique models., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The (1)H nuclear magnetic relaxation dispersion profiles were measured from 10 kHz to 30 MHz as a function of temperature for polyglycine, polyalanine, polyvaline, and polyphenylalanine to examine the contributions of different side chain motions to the polypeptide proton relaxation rate constants. The spin-fracton theory for (1)H relaxation is modified to account for high frequency motions of side chains that are dynamically connected to the linear polymer backbone. The (1)H relaxation is dominated by propagation of rare disturbances along the backbone of the polymer. The side-chain dynamics cause an off-set in the field dependence of the (1)H spin-lattice relaxation rate constants which obey a power law in the Larmor frequency in the limit of low and high magnetic field strength., (Copyright 2007 Wiley Periodicals, Inc.)

Proton spin-lattice relaxation by paramagnetic centers may be dramatically enhanced if the paramagnetic center is rotationally immobilized in the magnetic field. The details of the relaxation mechanism are different from those appropriate to solutions of paramagnetic relaxation agents. We report here large enhancements in the proton spin-lattice relaxation rate constants associated with organic radicals when the radical system is rigidly connected with a rotationally immobilized macromolecular matrix such as a dry protein or a cross-linked protein gel. The paramagnetic contribution to the protein-proton population is direct and distributed internally among the protein protons by efficient spin diffusion. In the case of a cross-linked-protein gel, the paramagnetic effects are carried to the water spins indirectly by chemical exchange mechanisms involving water molecule exchange with rare long-lived water molecule binding sites on the immobilized protein and proton exchange. The dramatic increase in the efficiency of spin relaxation by organic radicals compared with metal systems at low magnetic field strengths results because the electron relaxation time of the radical is orders of magnitude larger than that for metal systems. This gain in relaxation efficiency provides completely new opportunities for the design of spin-lattice relaxation based contrast agents in magnetic imaging and also provides new ways to examine intramolecular protein dynamics.

The nuclear magnetic relaxation dispersion profiles of lyophilized globular proteins were measured in the frequency range of 10 kHz-30 MHz at temperatures from 156 to 302 K. The existent theory of proton relaxation in immobilized protein systems was critically tested and expended to include contributions of rapid motions of protein side-chain groups. The new theory takes into account the strong coupling between the side-chain protons and the protein backbone, when correlation function cannot be written as a product of the contributions. The measurements showed that while the relaxation rate constant of the protein backbone protons is a linear function of the absolute temperature the side-chain groups exhibit an exponential temperature dependence corresponding to an activated process. Measurements carried out on simple homopolypeptides, polyglycine and polyalanine, provide strong support of the proposed new theory.