Longitudinal peripheral tissue RNA-Seq transcriptomic profiling, hyperalgesia, and wound healing in the rat plantar surgical incision model.

Postoperative pain and delayed healing in surgical wounds, which require complex management strategies have understudied complicated mechanisms. Here we investigated temporal changes in behavior, tissue structure, and transcriptomic profiles in a rat model of a surgical incision, using hyperalgesic behavioral tests, histological analyses, and next-generation RNA sequencing, respectively. The most rapidly (1 hour) expressed genes were the chemokines, Cxcl1 and Cxcl2. Consequently, infiltrating leukocytes were abundantly observed starting at 6 and peaking at 24 hours after incising which was supported by histological analysis and appearance of the neutrophil markers, S100a8 and S100a9. At this time, hyperalgesia was at a peak and overall transcriptional activity was most highly activated. At the 1-day timepoint, Nppb, coding for natriuretic peptide precursor B, was the most strongly upregulated gene and was localized by in situ hybridization to the epidermal keratinocytes at the margins of the incision. Nppb was basically unaffected in a peripheral inflammation model transcriptomic dataset. At the late phase of wound healing, five secreted, incision-specific peptidases, Mmp2, Aebp1, Mmp23, Adamts7, and Adamtsl1, showed increased expression, supporting the idea of a sustained tissue remodeling process. Transcripts that are specifically upregulated at each timepoint in the incision model may be potential candidates for either biomarkers or therapeutic targets for wound pain and wound healing. This study incorporates the examination of longitudinal temporal molecular responses, corresponding anatomical localization, and hyperalgesic behavioral alterations in the surgical incision model that together provide important and novel foundational knowledge to understand mechanisms of wound pain and wound healing.

Concurrent validity of biofilm detection by wound blotting on hard-to-heal wounds.

OBJECTIVE: Wound biofilms delay healing of hard-to-heal wounds. Convenient biofilm identification tools for clinical settings are currently not available, hindering biofilm-based wound management. Wound blotting with biofilm staining is a potential tool for biofilm detection, owing to its convenience. Although predictive validity of wound blotting has been established, it is necessary to confirm its concurrent validity. Furthermore, current staining systems employing ruthenium red have some disadvantages for clinical use. This study aimed to evaluate the usability of alcian blue as a substitute for ruthenium red. METHOD: Both in vitro and in vivo clinical samples were used to investigate validity and usability. RESULTS: The in vitro study showed that proteins and extracellular DNA in biofilms did not affect staining ability of ruthenium red and alcian blue in the detection of biofilms. In the in vivo study, using a wound biofilm model with Pseudomonas aeruginosa, the staining sensitivity of ruthenium red was 88.9% and 100% for alcian blue, with correlation coefficients of signal intensities with native polyacrylamide gel electrophoresis (PAGE) of r=0.67 (p=0.035) and r=0.67 (p=0.036) for ruthenium red and alcian blue, respectively. Results from clinical samples were r=0.75 (p=0.001) for ruthenium red and r=0.77 (p<0.001) for alcian blue. The sensitivities of wound blotting staining by ruthenium red and alcian blue were very high and had a good correlation with native PAGE analysis. CONCLUSION: Because the alcian blue procedure is more convenient than the ruthenium red procedure, wound blotting with alcian blue staining would be a promising tool to guide clinicians in delivering biofilm-based wound management.

Wound Pain and Wound Healing Biomarkers From Wound Exudate: A Scoping Review.

PURPOSE: Effective management of wound pain is essential for optimal wound healing. Nevertheless, the outcomes of wound pain interventions are based on subjective measures, which can prove problematic in patients with cognitive impairment. Identification of biomarkers associated with wound pain and wound healing can be used to more objectively estimate wound pain and contribute to the development of precise management options to reduce wound pain and promote wound healing. This scoping review aimed to identify wound pain and wound healing biomarkers from wound exudates and to describe different wound collection methods to identify these biomarkers. METHODS: We searched the literature (PROSPERO database registration number: CRD42018103843) via a scoping review. SEARCH STRATEGY: The PubMed database was searched for articles that explored relationships between cutaneous wound pain, wound healing, and biomolecules. Inclusion criteria were articles that reported original data, used adult human samples, and were published in English. FINDINGS: Twenty-one articles were retrieved: 17 investigated molecules from wound exudate associated with wound healing status, and 4 reported molecules associated with wound pain. The most frequently observed wound pain biomarkers were proinflammatory cytokines; the most frequently observed wound healing biomarkers were proteases including those in the matrix metalloproteinase family. Six wound exudate collection methods were identified to extract potential wound pain and wound healing biomarkers from wound exudate. IMPLICATIONS: The results can guide future wound exudate research to validate these wound pain and wound healing biomarkers and to develop therapies targeting these biomarkers to reduce wound pain and promote wound healing.

Recording and reconstruction of volumetric magnetic hologram using multilayer medium with heat dissipation layers.

Hologram memory is a strong candidate for optical storage due to its high recording density and high data transfer rate. We have studied and engineered a magnetic hologram memory medium using a stable magnetic garnet as recording material. To record a deep and clear magnetic hologram, it is important to control the heat diffusion generated during recording. Numerical simulation suggested that a multilayer structure with transparent heat-dissipation layers would be effective to address this. We fabricated a multilayer magnetic medium for a collinear magnetic hologram. This medium exhibited a diffraction efficiency as high as that of the single layered one, and errorless recording and reconstruction was achieved with the magnetic assist technique.

Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full-thickness cutaneous wound model in rats.

Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic-pituitary-adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full-thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6-epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6-EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = -.630). Finally, the mechanical withdrawal threshold in the 5,6-EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6-EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.

Measurement of mechanical withdrawal threshold on full-thickness cutaneous wounds in rats using the von Frey test.

OBJECTIVE: A method for measuring mechanical withdrawal threshold of full-thickness cutaneous wound pain in animal models is lacking. This study aimed to confirm the validity and reactivity of the von Frey test in full-thickness cutaneous wounds in rats. METHOD: A 1.5cm-diameter wound was established on the dorsal areas of male Sprague-Dawley rats and subcutaneously injected with either morphine hydrochloride (5.0mg/kg) or indomethacin (2.5mg/kg) with a 27-gauge needle on day three post-wounding. On day five post-wounding, an injection of morphine hydrochloride, indomethacin or lambda-carrageenan (1.0%) into the granulation tissue was also administered. The withdrawal threshold of mechanical stimulation of the wound edge was compared in each group before treatment with injection and at two, four, eight and 24 hours after injection. RESULTS: A total of 40 rats were used in the study. Since more severe inflammation in and around the wound was induced on day three post-wounding than that of day five, the withdrawal threshold measured on day three post-wounding was significantly lower than that of day five. The decrease of the withdrawal threshold was depressed by morphine hydrochloride and indomethacin treatment on day three post-wounding. While there was no significant difference between the changes in the withdrawal threshold after indomethacin treatment on day five post-wounding, we observed an increased withdrawal threshold after morphine hydrochloride treatment and decreased withdrawal threshold after lambda-carrageenan treatment on day five post-wounding. CONCLUSION: The results suggest that the von Frey test can be applied to measure the mechanical withdrawal threshold of full-thickness dorsal wounds in rats.

Multiferroic nanocomposite fabrication via liquid phase using anodic alumina template.

We report a novel and inexpensive fabrication process of multiferroic nanocomposite via liquid phase using an anodic alumina template. The sol-gel spin-coating technique was used to coat the template with ferrimagnetic CoFe2O4. By dissolving the template with NaOH aqueous solution, a unique nanotube array structure of CoFe2O4 was obtained. The CoFe2O4 nanotube arrays were filled with, and sandwiched in, ferroelectric BaTiO3 layers by a sol-gel spin-coating method to obtain the composite. Its multiferroicity was confirmed by measuring the magnetic and dielectric hysteresis loops.

Error-free reconstruction of magnetic hologram via improvement of recording conditions in collinear optical system.

Magnetic holographic memory is expected as a rewritable high-capacity data storage technology. To improve the reconstructed image, we investigate recording conditions by numerical simulation and experiments. We found experimentally that four diffracted beams from a digital micromirror device interfere with each other at a suitable defocus recording point, and such overlapping is favorable to obtain clear reconstruction images without diffuser. Subsequently, we modify the shape of the reference beam to ensure more effective interference. As a result, we achieve error-free image reconstruction from the magnetic hologram. Our results indicate that magnetic holograms can potentially be utilized as holographic memory.

Thermomagnetic writing into magnetophotonic microcavities controlling thermal diffusion for volumetric magnetic holography.

Holographic memory is expected to become a high-capacity data storage. Magnetic volumetric holograms are rewritable holograms that are recorded as magnetization directions through thermomagnetic recording. However, the effective depth of magnetic holograms is limited by thermal diffusion that causes merging of magnetic fringes. In this study, we propose the insertion of heat-sink layers (HSLs) for retaining well-defined magnetic fringes during volumetric writing. Magnetophotonic microcavity media were used for demonstrating the HSL effect, and the structural design principle was established in numerical calculations. The results indicate that deep and clear magnetic fringes and an improvement in the diffraction efficiency can be achieved by the insertion of HSLs.

Magnetophotonic crystal with cerium substituted yttrium iron garnet and enhanced Faraday rotation angle.

Magnetophotonic crystals (MPCs) comprising cerium-substituted yttrium iron garnet (CeYIG) sandwiched by two Bragg mirrors were fabricated by vacuum annealing. CeYIG was deposited on Bragg mirrors at room temperature and annealed in 5 Pa of residual air. No ceria or other non-garnet phases were detected. Cerium 3 + ions substituted on the yttrium sites and no cerium 4 + ions were found. The Faraday rotation angle of the MPC was -2.92° at a wavelength of λ = 1570 nm was 30 times larger than that of the CeYIG film. These results showed good agreement with calculated values derived using a matrix approach.

Magneto-optical Q-switching using magnetic garnet film with micromagnetic domains.

High-power giant pulses can be used applied in various applications with Q-switched micro-lasers. This method can shorten the pulse duration; however, active control is currently impossible in micro-lasers. To achieve precise pulse control while maintaining compactness and simplicity, we exploit the magneto-optical effect in magnetic garnet films with micromagnetic domains that can be actively controlled by a pulsed magnetic field. Our Q-switching technique enhances the output power by a factor of 4 × 103. Moreover, the device itself is smaller than other Q-switching devices. This novel type of active Q-switch can be combined with a micro-laser to obtain megawatt-order pulses.

Lower temperature at the wound edge detected by thermography predicts undermining development in pressure ulcers: a pilot study.

Undermined pressure ulcers (PUs) are troublesome complications that are likely to delay wound healing. Early skin incision and debridement can prevent the deterioration of undermined PUs, thus it is necessary to identify devitalised tissue areas to determine the appropriate timing for such interventions. This retrospective cohort study evaluated whether a lower temperature at the wound edge than the wound bed and periwound skin, detected by thermography, can predict undermining development in PUs 1 week after the assessment. Twenty-two participants with category III, IV, or unstageable PUs who were examined by interdisciplinary PU team and were followed up for at least two consecutive weeks were analysed. We found 9/11 PUs without a lower temperature at the wound edge did not develop undermining development, whereas 8/11 PUs with the lower temperature did develop undermining. The relative risk of undermining development after 1 week in PUs with the lower temperature was 4·00 (95% confidence intervals: 1·08-14·7). The sensitivity, specificity, positive predictive value and negative predictive value were 0·80, 0·75, 0·73 and 0·81, respectively. A thermal imaging assessment focusing on a lower temperature pattern at the wound edge may provide sufficient information to predict undermining development.

Collinear volumetric magnetic holography with magnetophotonic microcavities.

Hologram memory is a candidate for high-capacity data storage. Magnetic holograms formed as magnetization directions have been studied to realize rewritable hologram media. Recently, we reported that the magnetophotonic microcavity (MPM) can improve diffraction efficiency because of enhanced Faraday rotation angle and deep hologram writing. In this study, we demonstrated a clear reconstructed image from magnetic holograms in an MPM medium. The structural condition of MPMs for high diffraction efficiency was investigated, and the MPM medium was actually fabricated. The image reconstructed from the MPM medium had approximately twice the brightness of that reconstructed using a monolayer film.

Oxygen partial pressure dependence of magnetic, optical and magneto-optical properties of epitaxial cobalt-substituted SrTiO3 films.

Cobalt-substituted SrTiO3 films (SrTi0.70Co0.30O(3-δ)) were grown on SrTiO3 substrates using pulsed laser deposition under oxygen pressures ranging from 1 µTorr to 20 mTorr. The effect of oxygen pressure on structural, magnetic, optical, and magneto-optical properties of the films was investigated. The film grown at 3 µTorr has the highest Faraday rotation (FR) and magnetic saturation moment (M(s)). Increasing oxygen pressure during growth reduced M(s), FR and optical absorption in the near-infrared. This trend is attributed to decreasing Co2+ ion concentration and oxygen vacancy concentration with higher oxygen partial pressure during growth.

SrGa(0.7)Co(0.3)O(3-δ) perovskite-cobalt oxide-metal nanocomposite films: magnetic and optical properties.

Two-phase nanocomposite films consisting of metallic Co nanoparticles below 50 nm diameter in a perovskite matrix were grown by pulsed laser deposition onto (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) and silicon substrates from a target of SrGa0.73Co0.27O3. The particles made up about 6% by volume of the film and were present within the film and at the substrate interface. The saturation magnetization of the film was up to 85 emu cm(-3) at 80 nm thickness and the Faraday rotation (FR) tracked the out-of-plane hysteresis loop, reaching 3000 deg cm(-1) at 10 kOe for 1550 nm wavelength. The magneto-optical figure of merit defined as FR divided by optical absorption was 0.04-0.06 deg dB(-1) due to the high optical absorption of the Co particles.

Integration of bulk-quality thin film magneto-optical cerium-doped yttrium iron garnet on silicon nitride photonic substrates.

Cerium substituted yttrium iron garnet (Ce:YIG) films were grown on yttrium iron garnet (YIG) seed layers on silicon nitride films using pulsed laser deposition. Optimal process conditions for forming garnet films on silicon nitride are presented. Bulk or near-bulk magnetic and magneto-optical properties were observed for 160 nm thick Ce:YIG films grown at 640 °C on rapid thermal annealed 40 nm thick YIG grown at 640 °C and 2 Hz pulse rate. The effect of growth temperature and deposition rate on structural, magnetic and magneto-optical properties has been investigated.

A nonreciprocal racetrack resonator based on vacuum-annealed magnetooptical cerium-substituted yttrium iron garnet.

Vacuum annealed polycrystalline cerium substituted yttrium iron garnet (CeYIG) films deposited by radio frequency magnetron sputtering on non-garnet substrates were used in nonreciprocal racetrack resonators. CeYIG annealed at 800°C for 30 min provided a large Faraday rotation angle, close to the single crystal value. Crystallinity, magnetic properties, refractive indices and absorption coefficients were measured. The resonant transmission peak of the racetrack resonator covered with CeYIG was non-reciprocally shifted by applying an in-plane magnetic field.

Mechanistic insights into behavioral clusters associated with cancer-related systemic inflammatory response.

PURPOSE OF REVIEW: This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions. RECENT FINDINGS: GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster. SUMMARY: GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications.

Cancer-Related Cognitive Impairment Associated with APOE rs7412 and BDNF rs6265 in Breast Cancer Survivors.

OBJECTIVES: Cancer-related cognitive impairment (CRCI) is a highly prevalent and debilitating symptom reported by breast cancer survivors (BCS). The etiology of CRCI remains unclear, leading to poor symptom management. Building from prior studies, BCS with the C/C genotype of apolipoprotein E (APOE) rs7412 and the T/T genotype of brain-derived neurotrophic factor (BDNF) rs6265 were hypothesized to experience more severe CRCI. Therefore, we investigated the relationships between the severity of CRCI and polymorphisms of APOE and BDNF among BCS. METHODS: This was a subanalysis of data from a larger descriptive, correlational, and cross-sectional study. Subjective and objective CRCI were measured using the Patient-Reported Outcomes Measurement Information System and CANTAB Cambridge Cognitive assessment, respectively. Buccal swab samples were collected to evaluate the single nucleotide polymorphisms. Multivariable generalized linear regression models were used to analyze data. RESULTS: APOE rs7412 and BDNF rs6265 were significantly associated with lower self-reported cognitive abilities in a total of 353 BCS. Age was positively associated with self-reported cognitive scores, indicating that younger BCS perceived lower cognitive abilities. Individuals carrying genotype of C/T for APOE with the C/C or C/T for BDNF showed positive associations with cognitive abilities. CONCLUSIONS: Younger BCS with the C/C genotype for APOE rs7412 and the T/T genotype for BDNF rs6265 may be at risk for CRCI. Knowledge regarding predictive markers for CRCI symptoms is essential for precision symptom management. Further investigation with a longitudinal and translational design is necessary to explore the etiologies for CRCI. IMPLICATIONS FOR NURSING PRACTICE: Integrating genetic phenotyping into routine clinical practice will provide nurses with unique opportunities to understand individual susceptibilities, and how symptoms may trigger other symptoms. Further, findings from these innovative investigations will provide symptom interventionists and implementation scientists with critical data to optimize individualized strategies for symptom prevention, detection, and management.

Associations of brain-derived neurotrophic factor rs6265 polymorphism and cognitive function in breast cancer survivors from a cross-sectional study.

BACKGROUND: Breast cancer survivors (BCS) often complain of cancer-related cognitive impairment (CRCI) during and even months after completing primary cancer treatments, particularly chemotherapy. The etiology of CRCI is unknown, but associations of CRCI with germline genetic polymorphisms have been reported, including Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism. The current study investigated the associations of specific BDNF rs6265 with CRCI. METHODS: Cancer-related cognitive impairment was assessed using subjective reports of cognitive symptoms (the version 1.0, 8-item short-forms of the Patient-Reported Outcomes Measurement Information System®) and computerized objective cognitive function scores (CANTAB®). BDNF rs6265 genotypes were determined from buccal swabs. The associations of specific BDNF rs6265 with CRCI were examined by either one-way analysis of variance or the Kruskal-Wallis test followed by post hoc tests and rank-based regression analysis. RESULTS: We examined 356 female BCS. The mean (SD) age was 55.6 (9.8) years old, the median (IQR) years since cancer diagnosis were 4.0 (6.0), and 331 (92.7%) were self-described as White. BCS carrying the Met/Met genotype showed poorer results on 'visual episodic memory and new learning' and 'spatial working memory and executive function.' This relationship was observed regardless of prior chemotherapy. CONCLUSION: Our findings suggest that carrying the BDNF rs6265 Met/Met genotype increases the risk for CRCI in BCS. These results are foundational in nature and provide important information to identify mechanisms underpinning CRCI.