Intraoperative Near-infrared Spectroscopy Can Predict Skin Flap Necrosis.

Background: The study aimed to validate the previously identified capacity of near-infrared spectroscopy (NIRS) to detect clinically relevant differences in tissue perfusion intraoperatively. Methods: Consecutive patients undergoing oncologic resection requiring flap reconstruction were analyzed. Clinicians were blinded to tissue oxygen saturation (StO2) measurements taken intraoperatively. Measurements were taken at (1) control areas not affected by the procedure, (2) areas at risk of necrosis based on distal location, and (3) areas of skin flap necrosis (SFN) identified during the follow-up period. Mean StO2 values were compared using a single-sample t test and analysis of variance (ANOVA) to determine differences in oxygenation. Results: There were 102 patients included from April 2018 to May 2019. Reconstruction was undertaken following resection for breast cancer (46), melanoma (35), sarcoma (9), and other cutaneous malignancies (12). Breast reconstruction involved 38 alloplastic reconstructions and eight autologous free flaps. Other skin flap reconstruction involved 42 local/regional skin flaps, 13 pedicled flaps, and one free flap. Eighteen patients (17.6%) developed SFN. Mean intraoperative StO2 measurements for control areas, areas at risk, and areas of SFN were 74.8%, 70.9%, and 54.3%, respectively. StO2 values equal to or less than 60% were highly specific (96%) for SFN, whereas StO2 values above 85% were highly sensitive (96%) to rule out SFN. Conclusion: These results further support the use of NIRS to objectively assess variations in skin flap oxygenation and tissue perfusion that are correlated with the development of postoperative SFN.

Locoregional management of in-transit metastasis in melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline.

Objective: The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastasis (itm) from melanoma. Methods: The guideline was developed by the Program in Evidence-Based Care (pebc) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group. Recommendations were drafted by a Working Group based on a systematic review of publications in the medline and embase databases. The document underwent patient- and caregiver-specific consultation and was circulated to the Melanoma Disease Site Group and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations: "Minimal itm" is defined as lesions in a location with limited spread (generally 1-4 lesions); the lesions are generally superficial, often clustered together, and surgically resectable. "Moderate itm" is defined as more than 5 lesions covering a wider area, or the rapid development (within weeks) of new in-transit lesions. "Maximal itm" is defined as large-volume disease with multiple (>15-20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.■ In patients presenting with minimal itm, complete surgical excision with negative pathologic margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.■ In patients presenting with moderate unresectable itm, consider using this approach for localized treatment: intralesional interleukin 2 or talimogene laherparepvec as 1st choice, topical diphenylcyclopropenone as 2nd choice, or radiation therapy as 3rd choice. Evidence is insufficient to recommend intralesional bacille Calmette- Guérin or CO2 laser ablation outside of a research setting.■ In patients presenting with maximal itm confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.■ In cases in which local, regional, or surgical treatments for itm might be ineffective or unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.

Management of uveal melanoma: a consensus-based provincial clinical practice guideline.

INTRODUCTION: Survival in uveal melanoma has remained unchanged since the early 1970s. Because outcomes are highly related to the size of the tumour, timely and accurate diagnosis can increase the chance for cure. METHODS: A consensus-based guideline was developed to inform practitioners. PubMed was searched for publications related to this topic. Reference lists of key publications were hand-searched. The National Guidelines Clearinghouse and individual guideline organizations were searched for relevant guidelines. Consensus discussions by a group of content experts from medical, radiation, and surgical oncology were used to formulate the recommendations. RESULTS: Eighty-four publications, including five existing guidelines, formed the evidence base. SUMMARY: Key recommendations highlight that, for uveal melanoma and its indeterminate melanocytic lesions in the uveal tract, management is complex and requires experienced specialists with training in ophthalmologic oncology. Staging examinations include serum and radiologic investigations. Large lesions are still most often treated with enucleation, and yet radiotherapy is the most common treatment for tumours that qualify. Adjuvant therapy has yet to demonstrate efficacy in reducing the risk of metastasis, and no systemic therapy clearly improves outcomes in metastatic disease. Where available, enrolment in clinical trials is encouraged for patients with metastatic disease. Highly selected patients might benefit from surgical resection of liver metastases.

Model development to study strategies of younger and older adults getting up from the floor.

BACKGROUND: Long lies after a fall remain a public health challenge. Many successful fall prevention programmes have been developed but only few of them include recovery strategies after a fall. Once better understood, such movement strategies could be implemented into training interventions. AIMS: A model of motion sequences describing successful movement strategies for rising from the floor in different age groups was developed. Possible risk factors for poor rising performance such as flexibility and muscle power were evaluated. METHODS: Fourteen younger subjects between 20 and 50 years of age and 10 healthy older subjects (60+ years) were included. Movement strategies and key components of different rising sequences were determined from video analyses. The temporal parameters of transfers and number of components within the motion sequences were calculated. Possible explanatory variables for differences in rising performance were assessed (leg extension power, flexibility of the knee- and hip joints). RESULTS: Seven different components were identified for the lie-to-stand-walk transfer, labelled as lying, initiation, positioning, supporting, elevation, or stabilisation component followed by standing and/or walking. Median time to rise was significantly longer in older subjects (older 5.7s vs. younger 3.7s; p < 0.001), and leg extension power (left p = 0.002, right p = 0.013) and knee flexibility (left p = 0.019, right p = 0.025) were significantly lower. The number of components for rising was correlated with hip flexibility (r = 0.514) and maximal power (r = 0.582). The time to rise was correlated with minimal goniometric knee angle of the less flexible leg (r = 0.527) and maximal leg extension power (r = 0.725). CONCLUSIONS: A motion sequence model containing seven different components identified by individual key-frames could be established. Age-related differences in rising strategies and performance were identified.

Regulation of the DNA Damage Response to DSBs by Post-Translational Modifications.

Damage to the genetic material can affect cellular function in many ways. Therefore, maintenance of the genetic integrity is of primary importance for all cells. Upon DNA damage, cells respond immediately with proliferation arrest and repair of the lesion or apoptosis. All these consequences require recognition of the lesion and transduction of the information to effector systems. The accomplishment of DNA repair, but also of cell cycle arrest and apoptosis furthermore requires protein-protein interactions and the formation of larger protein complexes. More recent research shows that the formation of many of these aggregates depends on post-translational modifications. In this article, we have summarized the different cellular events in response to a DNA double strand break, the most severe lesion of the DNA.

Lysosomal membrane permeabilization and cathepsin release is a Bax/Bak-dependent, amplifying event of apoptosis in fibroblasts and monocytes.

Apoptotic stimuli have been shown to trigger lysosomal membrane permeability (LMP), leading to the release of cathepsins, which activate death signaling pathways in the cytosol. However, it is unknown whether this process is an initiating or amplifying event in apoptosis. In this study, we used fibroblasts and monocytes exposed to etoposide, ultraviolet light, FasL or deprived of interleukin-3 (IL-3) to show that LMP and the cytosolic release of cathepsins B, L and D consistently depends on Bax/Bak and components of the apoptosome. Neither Bax nor Bak resided on the lysosomes, indicating that lysosomes were not directly perforated by Bax/Bak but by effectors downstream of the apoptosome. Detailed kinetic analysis of cells lacking cathepsin B or L or treated with the cysteine protease inhibitor, E64d, revealed a delay in these cells in etoposide- and IL-3 deprivation-induced caspase-3 activation and apoptosis induction but not clonogenic survival, indicating that cathepsins amplify rather than initiate apoptosis.

Development of conductive polymer analysis for the rapid detection and identification of phytopathogenic microbes.

ABSTRACT Conductive polymer analysis, a type of electronic aroma detection technology, was evaluated for its efficacy in the detection, identification, and discrimination of plant-pathogenic microorganisms on standardized media and in diseased plant tissues. The method is based on the acquisition of a diagnostic electronic fingerprint derived from multisensor responses to distinct mixtures of volatile metabolites released into sampled headspace. Protocols were established to apply this technology specifically to plant disease diagnosis. This involved development of standardized cultural methods, new instrument architecture for sampling, sample preparation, prerun procedures, run parameters and schedules, recognition files and libraries, data manipulations, and validation protocols for interpretations of results. The collective output from a 32-sensor array produced unique electronic aroma signature patterns diagnostic of individual microbial species in culture and specific pathogen-host combinations associated with diseased plants. The level of discrimination applied in identifications of unknowns was regulated by confidence level and sensitivity settings during construction of application-specific reference libraries for each category of microbe or microbe-host combination identified. Applications of this technology were demonstrated for the diagnosis of specific disease systems, including bacterial and fungal diseases and decays of trees; for host identifications; and for determinations of levels of infection and relatedness between microbial species. Other potential applications to plant pathology are discussed with some advantages and limitations for each type of diagnostic application.

The antiproliferative alkylphospholipid S-1-O-phosphocholine-2-N-acetyl-octadecane induces apoptosis in leukemia cell lines.

Lipids are involved in a multitude of important cellular functions. They act as signaling molecules and can even provoke apoptosis. In this context we investigated the efficacy of synthetic alkylphosphocholines (APCs) as potential anti-cancer membrane-affecting drugs. Leading to novel therapeutic strategies for cancer treatment, the new agents interact with the cell membrane and do not affect the DNA. The data presented here show a cell death-inducing capacity for 1-O-phosphocholine-2[S]-O-acetyl-octadecane and 1-O-phosphocholin-2[S]-N-acetyl-octadecane in Jurkat T cells as well as in BJAB cells. The activation of caspases is generally required for the induction of apoptosis as shown by experiments with specific caspase inhibitors. The results point on the one hand to the formation of a functional DISC after APC-treatment as indicated by the clustering of receptor molecules and on the other hand to the dependency on the instrinsic apoptotic machinery and the downstream of mitochondria-activated apoptosome.

A PvuII polymorphism of the bcr region in patients with hematopoietic disorders and their families.

The BCR gene on chromosome 22 has received increasing attention because of its involvement in the Philadelphia (Ph') translocation. For most restriction enzymes, this locus has been found to be nonpolymorphic. Two alleles have only been found when Taql-digested DNA is hybridized to a 5' bcr-specific probe. We describe another two-allele polymorphism detected by the same probe in PvuII-digested DNA. The polymorphism is characterized by an additional PvuII site in the bcr region: this causes the appearance of an additional band of about 2.3 kb or 2.5 kb besides a 4.8-kb fragment in hybridizations with the 5' bcr or a 3' bcr probe. The incidence of the second allele is very low. It has only been found in some patients with hematopoietic malignancies and in a group of volunteers having a leukemia patient in their families.