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The microcirculation of the wound bed is a key parameter for improving granulation tissue formation and, hence, wound healing. The aim of this study was to determine whether a wound dressing comprising collagen/oxidized regenerated cellulose has effects over a short term on wound healing. Wounds were evaluated using a clinical wound score; pain associated with wounds was measured using a visual analogue scale. Wound microcirculation was evaluated using a technique based on noncontact remission spectroscopy. A prospective trial was performed in 40 patients with chronic venous leg ulcers (mean age 74 years; range, 43-93 years; 25 females and 15 males). Patients in group A were treated with PROMOGRAN Matrix (Johnson& Johnson, New Brunswick, NJ) combined with 'good' ulcer care for 2 weeks. Control group B consisted of 10 patients who received only good ulcer care. The authors measured a favorable clinical response in 76.9% (group A) versus 66.7% (group B). The mean reduction of ulcer area was statistically significant in group A (P < .05). The wound score improved in group A from 2.28 +/- 1.24 (before treatment) increasing to 3.72 +/- 1.57 (after 1 week; P < .00023) and 4.92 +/- 1.68 (after 2 weeks; P < .000027). In group B, the score improved from 1.44 +/- 1.33 (before treatment) to 3.22 +/- 1.30 (after 1 week; P < .0077). The mean visual analogue pain score before treatment was 8.72 (group A) and 7.88 (group B) (ns, P > .05). After 1 week of treatment, the score dropped to 5.76 (group A) and 6.66 (group B). In the second week, group A patients had a mean pain score of 3.84 compared with the pain score before treatment (P < .05). After 1 week of treatment, in group A there was a decrease in remission spectroscopy, which is considered to reflect an improvement in microcirculation. [ABSTRACT FROM AUTHOR]

BACKGROUND : Spider leg veins are common. Their treatment with laser or intensed light therapy shows generally variable success rates and often adverse side effects such as hyper- or hypopigmentation. This study was performed to investigate whether pulsed diode laser (810 nm) treatment is effective and safe. METHODS : Thirty-five female patients with spider leg veins were included in this prospective trial. They were treated twice with a pulsed diode laser (810 nm; spot size 12 mm, frequency 2-4 Hz, pulse width 60 msec, fluence 80-100 Jcm -2 ). Laser therapy was performed on day 0 and day 14. Clinical assessments were carried out before and immediately after the first laser therapy, after 2 weeks, 8 weeks, and one year. Skin biopsies were taken before and immediately after the first laser treatment, and after 10 weeks. Contact-free remittance spectroscopy was performed before laser treatment, immediately after the first treatment, after 2 weeks and 8 weeks. RESULTS : After the first treatment 15 patients showed a complete disappearance (CR) of spider leg veins; in the remaining 20 patients a remarkable improvement (RI) was noted ( n =35). After six months of follow-up CR was seen in 6 patients, RI in 6, a stable situation in 9, and scar formation in 1 patient ( n =21). The effect was almost completely stable during one year of follow-up. The examination of histological specimens before and after laser treatment showed no cellular inflammatory reaction. The mean vascular area was significantly reduced after the first ( p <0.05) and after the second ( p <0.05) laser treatment. Spectral analysis showed a marked decrease of peaks for oxygenized haemoglobin immediately after laser treatment and during the follow-up. Safety profile was excellent without purpuric reaction or pigmentary changes. Mild scarring was observed in two patients at the end of follow-up. CONCLUSIONS : Pulsed diode laser therapy (810 nm) is an effective and safe treatment option for spider leg veins. The effects can be seen immediately. Objective monitoring by non-invasive remission spectroscopy and histology of biopsy specimens demonstrates selectivity of the laser action. [ABSTRACT FROM AUTHOR]

Abstract Background The human skin is an easily accessible organ on which non-invasive examination methods can be applied. Remittance spectroscopy uses registration of the proportion of reflected light from the skin surface. Optical characteristics of skin are determined by scattering, reflection and absorption. The remittance is influenced by various test conditions and topography. Spectroscopic methods are applied for determination of microcirculation, measuring of erythema and pigmentation and in pharmacology and toxicology of applied drugs. Conclusion The standardization of spectroscopic measurement of human skin is essential to reduce error sources. In future a better investigation of skin structures and molecules, which are responsible for optical characteristics of skin and a more precise evaluation of spectroscopic signals are necessary to get more information about the state of skin and to develop new fields of applications, such as early diagnosis of skin diseases or monitoring of metabolic processes. [ABSTRACT FROM AUTHOR]

Polymethine dyes are used as colourants and as spectral sensitizers. Thiacarbocyanine and thiadicarbocyanine dyes were studied in solution, on electronically inert (CaF) and active surfaces (AgCl, ZnO), using steady state and time resolved fluorescence spectroscopy. Fluorescence lifetimes are strongly dependent on the environment. Deactivation processes such as nonradiative decay and fluorescence are discussed. The widely accepted model for the S deactivation of polymethines is torsion of the polymethine chain. In the adsorbed state, the quantum yield of fluorescence increases and shows a strong concentration dependence. We studied 3,3′-diethylthiacarbocyanine iodide (DTCC) and 3,3′-diethylthiadicarbocyanine chloride (DTDC) in different solvents and on CaF. The adsorption isotherms of DTCC and DTDC on CaF are of non-Langmuir type. The fluorescence lifetimes of adsorbed polymethines are not constant and start to decrease even at surface concentrations which are much less than one monolayer. The quenching was observed at concentrations lower than those at which dimer formation could be spectroscopically detected. Förster energy transfer between the adsorbed molecules was therefore taken into account. On active surfaces, electron transfer and Förster energy transfer were investigated as competing processes. The results were related to the mechanistic aspects of the spectral sensitization of silver halides. [ABSTRACT FROM AUTHOR]

Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival., Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs., Results: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations., Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer., (© 2024. The Author(s).)

Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with 'normal' stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC., (© 2023. Springer Nature Limited.)

Multiplex Immunohistochemistry (mIHC) is a cost-effective and accessible method for in situ labeling of multiple protein biomarkers in a tissue sample. By assigning a different stain to each biomarker, it allows the visualization of different types of cells within the tumor vicinity for downstream analysis. However, to detect different types of stains in a given mIHC image is a challenging problem, especially when the number of stains is high. Previous deep-learning-based methods mostly assume full supervision; yet the annotation can be costly. In this paper, we propose a novel unsupervised stain decomposition method to detect different stains simultaneously. Our method does not require any supervision, except for color samples of different stains. A main technical challenge is that the problem is underdetermined and can have multiple solutions. To conquer this issue, we propose a novel inversion regulation technique, which eliminates most undesirable solutions. On a 7-plexed IHC images dataset, the proposed method achieves high quality stain decomposition results without human annotation.

Quantitative assessment of spatial relations between tumor and tumor-infiltrating lymphocytes (TIL) is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network analysis pipelines to generate combined maps of cancer regions and TILs in routine diagnostic breast cancer whole slide tissue images. The combined maps provide insight about the structural patterns and spatial distribution of lymphocytic infiltrates and facilitate improved quantification of TILs. Both tumor and TIL analyses were evaluated by using three convolutional neural network networks (34-layer ResNet, 16-layer VGG, and Inception v4); the results compared favorably with those obtained by using the best published methods. We have produced open-source tools and a public data set consisting of tumor/TIL maps for 1090 invasive breast cancer images from The Cancer Genome Atlas. The maps can be downloaded for further downstream analyses., (Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Oxygen is critical for optimal bone regeneration. While axolotls and salamanders have retained the ability to regenerate whole limbs, mammalian regeneration is restricted to the distal tip of the digit (P3) in mice, primates, and humans. Our previous study revealed the oxygen microenvironment during regeneration is dynamic and temporally influential in building and degrading bone. Given that regeneration is dependent on a dynamic and changing oxygen environment, a better understanding of the effects of oxygen during wounding, scarring, and regeneration, and better ways to artificially generate both hypoxic and oxygen replete microenvironments are essential to promote regeneration beyond wounding or scarring. To explore the influence of increased oxygen on digit regeneration in vivo daily treatments of hyperbaric oxygen were administered to mice during all phases of the entire regenerative process. Micro-Computed Tomography (μCT) and histological analysis showed that the daily application of hyperbaric oxygen elicited the same enhanced bone degradation response as two individual pulses of oxygen applied during the blastema phase. We expand past these findings to show histologically that the continuous application of hyperbaric oxygen during digit regeneration results in delayed blastema formation at a much more proximal location after amputation, and the deposition of better organized collagen fibers during bone formation. The application of sustained hyperbaric oxygen also delays wound closure and enhances bone degradation after digit amputation. Thus, hyperbaric oxygen shows the potential for positive influential control on the various phases of an epimorphic regenerative response.

Amputation of the digit tip within the terminal phalangeal bone of rodents, monkeys, and humans results in near-perfect regeneration of bone and surrounding tissues; however, amputations at a more proximal level fail to produce the same regenerative result. Digit regeneration is a coordinated, multifaceted process that incorporates signaling from bioactive growth factors both in the tissue matrix and from several different cell populations. To elucidate the mechanisms involved in bone regeneration we developed a novel multi-tissue slice-culture model that regenerates bone ex vivo via direct ossification. Our study provides an integrated multi-tissue system for bone and digit regeneration and allows us to circumvent experimental limitations that exist in vivo. We used this slice-culture model to evaluate the influence of oxygen on regenerating bone. Micro-computed tomography (µCT) and histological analysis revealed that the regenerative response of the digit is facilitated in part by a dynamic oxygen event, in which mutually exclusive high and low oxygen microenvironments exist and vacillate in a coordinated fashion during regeneration. Areas of increased oxygen are initially seen in the marrow and then surrounding areas of vasculature in the regenerating digit. Major hypoxic events are seen at 7 days postamputation (DPA 7) in the marrow and again at DPA 12 in the blastema, and manipulation of oxygen tensions during these hypoxic phases can shift the dynamics of digit regeneration. Oxygen increased to 21% oxygen tension can either accelerate or attenuate bone mineralization in a stage-specific manner in the regenerative timeline. These studies not only reveal a circumscribed frame of oxygen influence during bone regeneration, but also suggest that oxygen may be one of the primary signaling influences during regeneration., (© 2014 American Society for Bone and Mineral Research.)

We describe the development and operation of a two-laser, large-field hyperspectral scanner for analysis of multicolor genotyping microarrays. In contrast to confocal microarray scanners, in which wavelength selectivity is obtained by positioning band-pass filters in front of a photomultiplier detector, hyperspectral microarray scanners collect the complete visible emission spectrum from the labeled microarrays. Hyperspectral scanning permits discrimination of multiple spectrally overlapping fluorescent labels with minimal use of optical filters, thus offering important advantages over standard filter-based multicolor microarray scanners. The scanner uses two-sided oblique line illumination of microarrays. Two lasers are used for the excitation of dyes in the visible and near-infrared spectral regions. The hyperspectral scanner was evaluated with commercially available two-color calibration slides and with in-house-printed four-color microarrays containing dyes with spectral properties similar to their commercial genotyping array counterparts.

Objective: Nonmelanoma skin cancer (NMSC) is one of the most common malignancies in men. Objective evaluation by digital dermoscopy, as for pigmented lesions, does not provide sufficient data to discriminate between benign and malignant lesions. Therefore, other techniques have to be developed., Setting: Hospitalized patients of an academic teaching hospital were evaluated., Patients and Methods: Because the simultaneous measurement of fluorescence and remission of skin is impossible, a principle of subsequent measurement of remission and fluorescence had been developed by our group. This was combined with dermoscopic imaging. VIS-NIR remission spectroscopy was performed using the laboratory device TIDAS. Fluorescence spectroscopy was realized using a SKINSKAN. Fluorescence emission was detected by a highly sensitive PMT-detector. Based on this evaluation, we developed an optimized measuring device (FRIS, fluorescence-remission-imaging sensor) combining sensors for fluorescence, remission and digital imaging with a white light ring illumination, a drilled mirror and fibre optics. FRIS consists of an industrial personal computer with a touch screen combining three UV-VIS spectrometer modules and a white light source for remission measurements and referencing. Furthermore, included are a CCD coloured camera module and an LED white light ring-illumination. Fluorescence emission is realized by a UV-LED with a peak wavelength of 370 nm. System control uses Window frames and a specifically developed software Skinrem3.exe . Using this technology, we performed a pilot study in 19 patients with 30 NMSC-suspicious lesions including: actinic keratosis (n=10), basal cell carcinoma (BCC; n=16) and squamous cell carcinoma (SCC; n=4 with two in situ carcinomas)., Results: Reproducibility measured or FRIS by relative standard deviation of repeated spectroscopic measurements was <0.1% for remission and 2% for fluorescence. The technology was able to generate typical pattern of remission-corrected fluorescence data. The fluorescence differences at 430 nm allow a differentiation between actinic keratoses and BCC. A decrease of the corrected lesional fluorescence >2 AU indicates BCC. To substantiate the diagnostic potency of this technology, further studies are needed., Conclusions: A combination of fluorescence and remission readings of skin provides objective data in NMSC. We developed the FRIS equipment that allows a reproducible measurement and easy handling.

Background: Maggot therapy (biosurgery) has received increasing interest for the debridement of chronic wounds and for the improvement of wound healing. The purpose of this study was to investigate the clinical effects, side-effects, and possible mechanisms of action of biosurgery., Methods: Biosurgery was used for debridement in 30 patients with chronic leg ulcers of mixed origin. The effect of a single application of maggots for 1-4 days was evaluated by a clinical wound score and contact-free spectroscopy. Side-effects were recorded., Results: Debridement was rapid and selective. The wound secretion was temporarily increased. We observed a significant improvement of the wound score with a decrease from 13.5 +/- 1.8 to 6.3 +/- 2.7 (P < 0.001). The treatment was well tolerated in most patients. Twelve out of 30 patients reported temporary pain, but only two needed analgesic treatment. Other side-effects included venous bleeding in one patient. The remittance spectra showed an improvement of tissue oxygenation as revealed by the characteristic oxygen doublet peak (548 and 575 nm)., Conclusions: Biosurgery is an effective and rapid treatment for the debridement of chronic wounds and the improvement of wound healing. A possible mode of action is the increase in tissue oxygenation. More studies are needed.

Objective wound monitoring is an essential tool for evidence-based medicine in leg ulcers and other chronic wounds. Non-invasive and contact-free optical remittance spectroscopy seems to be a useful approach as it can provide additional information with respect to more traditional techniques of wound scoring. Twenty-three patients with chronic venous, arterial, and mixed leg ulcers were enrolled in this study. The clinical state of the ulcers was documented by a clinical wound score (quantity, color, and consistency of granulation tissue). The spectroscopic readings were performed with a novel diode-array spectrometer system in the visible and near-infrared range of the spectrum (400-1600 nm) with a resolution of 5 nm. The wound spectra mainly depend on the absorption of hemoglobin and water. The maximum correlation coefficients of mean remittance spectra with the clinical wound scores did not exceed +/- 0.5. Discriminant and cluster analysis were applied for spectral classification of wound scores. By using cross-validation the percentage of correct predicted wound scores was about 69%. Our results indicate that the application of optical visible and near-infrared spectroscopy could be a valuable remedy for the clinician.

Officials in 36 states responded to a survey of state policies, procedures, and regulations for the use of seclusion in the psychiatric treatment of children. Thirty-five of the states permit its use in emergencies, and 18 allow its use as part of a therapeutic treatment program. Only six states responding have regulations specifically addressing the use of seclusion with children. The authors summarize state regulations, including duration and frequency of seclusion episodes; orders required to implement seclusion and who may authorize it; rules about observation, documentation, and termination of episodes and breaks during episodes; design of seclusion rooms; and staff training. The authors present a model policy and procedure statement based on clinical and developmental considerations.

Knowledge and attitudes about AIDS were surveyed in 147 children between the ages of 6 and 12. Awareness of and accurate information about AIDS increased steadily through the early school years. From third grade on, over 90% of children had heard of AIDS, with the majority capable of providing additional accurate information. Significant misconceptions were also identified in all age groups. Television was found to be the major source of information about AIDS for most children.

Computer technology is becoming an integral aspect of many medical specialties. Current applications range from the collection and interpretation of patient data to hospital billing and inventory control. Within the field of psychiatry, the role of computers continues to evolve. One area of considerable interest and attention has been the automated patient interview. This article describes the development, present status, and future potential of this technology. Implications for psychiatric practice are examined.