Imaging features of myxoid soft-tissue tumours.

Myxoid soft-tissue tumours are mesenchymal neoplasms, which are characterised by the production of abundant extracellular myxoid matrix. Imaging plays an important role in the diagnosis of these tumours as well as treatment planning. The imaging features as well as the clinical course for these lesions are highly variable, depending on both the anatomical location of the tumour and the histopathological subtype. This article, illustrated by histopathologically proven cases from our tertiary referral soft-tissue sarcoma centre, reviews the spectrum of imaging findings and characteristic signs seen with different types of benign and malignant myxoid soft-tissue neoplasms.

Processing DNA lesions during mitosis to prevent genomic instability.

Failure of cells to process toxic double-strand breaks (DSBs) constitutes a major intrinsic source of genome instability, a hallmark of cancer. In contrast with interphase of the cell cycle, canonical repair pathways in response to DSBs are inactivated in mitosis. Although cell cycle checkpoints prevent transmission of DNA lesions into mitosis under physiological condition, cancer cells frequently display mitotic DNA lesions. In this review, we aim to provide an overview of how mitotic cells process lesions that escape checkpoint surveillance. We outline mechanisms that regulate the mitotic DNA damage response and the different types of lesions that are carried over to mitosis, with a focus on joint DNA molecules arising from under-replication and persistent recombination intermediates, as well as DNA catenanes. Additionally, we discuss the processing pathways that resolve each of these lesions in mitosis. Finally, we address the acute and long-term consequences of unresolved mitotic lesions on cellular fate and genome stability.

[To sedate or to confront? Sedation in adult dental treatment]. / Sederen of confronteren? Sedatie bij de tandheelkundige behandeling van volwassenen.

When patients are unable to undergo diagnostics or treatments for various reasons, sedation can be applied. A psychological approach and/or non-pharmacological sedation is preferred. When this is not possible, pharmacological sedation may be considered. In principle, the level of sedation applied, will be no deeper than is necessary for the patient to undergo the treatment and for the practitioner to be able to perform the treatment. Sedation is aimed at reducing agitation, anxiety, and/or lowering consciousness. However, it is not a pain treatment. Pain treatment will therefore always require adequate local anaesthesia. This article highlights the different levels of sedation, areas of indication, and sedatives used in dentistry. The application of pharmacological sedation will always have to be considered for each individual situation, within a total treatment plan that is aimed at lastingly increasing treatability.

An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018.

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

Phylogenomics and barcoding of Panax: toward the identification of ginseng species.

BACKGROUND: The economic value of ginseng in the global medicinal plant trade is estimated to be in excess of US$2.1 billion. At the same time, the evolutionary placement of ginseng (Panax ginseng) and the complex evolutionary history of the genus is poorly understood despite several molecular phylogenetic studies. In this study, we use a full plastome phylogenomic framework to resolve relationships in Panax and to identify molecular markers for species discrimination. RESULTS: We used high-throughput sequencing of MBD2-Fc fractionated Panax DNA to supplement publicly available plastid genomes to create a phylogeny based on fully assembled and annotated plastid genomes from 60 accessions of 8 species. The plastome phylogeny based on a 163 kbp matrix resolves the sister relationship of Panax ginseng with P. quinquefolius. The closely related species P. vietnamensis is supported as sister of P. japonicus. The plastome matrix also shows that the markers trnC-rps16, trnS-trnG, and trnE-trnM could be used for unambiguous molecular identification of all the represented species in the genus. CONCLUSIONS: MBD2 depletion reduces the cost of plastome sequencing, which makes it a cost-effective alternative to Sanger sequencing based DNA barcoding for molecular identification. The plastome phylogeny provides a robust framework that can be used to study the evolution of morphological characters and biosynthesis pathways of ginsengosides for phylogenetic bioprospecting. Molecular identification of ginseng species is essential for authenticating ginseng in international trade and it provides an incentive for manufacturers to create authentic products with verified ingredients.

Impact of Endoscopic Ultrasonography on 18F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment.

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. METHODS: During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid 18F-FDG-PET/CT or 18F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. RESULTS: EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. CONCLUSIONS: EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes.

Controlling the response to DNA damage by the APC/C-Cdh1.

Proper cell cycle progression is safeguarded by the oscillating activities of cyclin/cyclin-dependent kinase complexes. An important player in the regulation of mitotic cyclins is the anaphase-promoting complex/cyclosome (APC/C), a multi-subunit E3 ubiquitin ligase. Prior to entry into mitosis, the APC/C remains inactive, which allows the accumulation of mitotic regulators. APC/C activation requires binding to either the Cdc20 or Cdh1 adaptor protein, which sequentially bind the APC/C and facilitate targeting of multiple mitotic regulators for proteasomal destruction, including Securin and Cyclin B, to ensure proper chromosome segregation and mitotic exit. Emerging data have indicated that the APC/C, particularly in association with Cdh1, also functions prior to mitotic entry. Specifically, the APC/C-Cdh1 is activated in response to DNA damage in G2 phase cells. These observations are in line with in vitro and in vivo genetic studies, in which cells lacking Cdh1 expression display various defects, including impaired DNA repair and aberrant cell cycle checkpoints. In this review, we summarize the current literature on APC/C regulation in response to DNA damage, the functions of APC/C-Cdh1 activation upon DNA damage, and speculate how APC/C-Cdh1 can control cell fate in the context of persistent DNA damage.

Human cranial vault thickness in a contemporary sample of 1097 autopsy cases: relation to body weight, stature, age, sex and ancestry.

The relation between human cranial vault thickness (CVT) and various elements of the physical anthropological biological profile is subject of ongoing discussion. Some results seem to indicate no correlation between CVT and the biological profile of the individual, whereas other results suggest that CVT measurements might be useful for identification purposes. This study assesses the correlation between CVT and body weight, stature, age, sex, and ancestry by reviewing data of 1097 forensic autopsies performed at the Netherlands Forensic Institute (NFI). In subadults (younger than 19 years of age at the time of death), all frontal, temporal, and occipital CVT measurements correlated moderately to strongly with indicators of growth (body weight, stature, and age). Neither sex nor ancestry correlated significantly with cranial thickness. In adults, body weight correlated with all CVT measurements. No meaningful correlation was found between CVT and stature or age. Females showed to have thicker frontal bones, and the occipital region was thicker in the Negroid subsample. All correlation in the adult group was weak, with the distribution of cranial thickness overlapping for a great deal between the groups. Based on these results, it was concluded that CVT generally cannot be used as an indicator for any part of the biological profile.

Diagnostic dry bone histology in human paleopathology.

Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

Economic evaluation of occupational health and safety programmes in health care.

BACKGROUND: Evidence-based resource allocation in the public health care sector requires reliable economic evaluations that are different from those needed in the commercial sector. AIMS: To describe a framework for conducting economic evaluations of occupational health and safety (OHS) programmes in health care developed with sector stakeholders. To define key resources and outcomes to be considered in economic evaluations of OHS programmes and to integrate these into a comprehensive framework. METHODS: Participatory action research supported by mixed qualitative and quantitative methods, including a multi-stakeholder working group, 25 key informant interviews, a 41-member Delphi panel and structured nominal group discussions. RESULTS: We found three resources had top priority: OHS staff time, training the workers and programme planning, promotion and evaluation. Similarly, five outcomes had top priority: number of injuries, safety climate, job satisfaction, quality of care and work days lost. The resulting framework was built around seven principles of good practice that stakeholders can use to assist them in conducting economic evaluations of OHS programmes. CONCLUSIONS: Use of a framework resulting from this participatory action research approach may increase the quality of economic evaluations of OHS programmes and facilitate programme comparisons for evidence-based resource allocation decisions. The principles may be applicable to other service sectors funded from general taxes and more broadly to economic evaluations of OHS programmes in general.

Dioecy is associated with higher diversification rates in flowering plants.

In angiosperms, dioecious clades tend to have fewer species than their nondioecious sister clades. This departure from the expected equal species richness in the standard sister clade test has been interpreted as implying that dioecious clades diversify less and has initiated a series of studies suggesting that dioecy might be an 'evolutionary dead end'. However, two of us recently showed that the 'equal species richness' null hypothesis is not valid in the case of derived char acters, such as dioecy, and proposed a new test for sister clade comparisons; preliminary results, using a data set available in the litterature, indicated that dioecious clades migth diversify more than expected. However, it is crucial for this new test to distinguish between ancestral and derived cases of dioecy, a criterion that was not taken into account in the available data set. Here, we present a new data set that was obtained by searching the phylogenetic literature on more than 600 completely dioecious angiosperm genera and identifying 115 sister clade pairs for which dioecy is likely to be derived (including > 50% of the dioecious species). Applying the new sister clade test to this new dataset, we confirm the preliminary result that dioecy is associated with an increased diversification rate, a result that does not support the idea that dioecy is an evolutionary dead end in angiosperms. The traits usually associated with dioecy, that is, an arborescent growth form, abiotic pollination, fleshy fruits or a tropical distribution, do not influence the diversification rate. Rather than a low diversification rate, the observed species richness patterns of dioecious clades seem to be better explained by a low transition rate to dioecy and frequent losses.

Priapism following continuous thoracic epidural anaesthesia: emergency or a benign condition?

Priapism is a rare complication of epidural anaesthesia, and the pathophysiology is poorly understood. In general, 95% of all priapism episodes are ischemic because of decreased penile blood flow, and therefore requires immediate treatment. A case is reported of a 45-year-old male patient in which a clear relation is demonstrated between continuous thoracic epidural analgesia and priapism after transabdominal nephrectomy. The level of epidural anaesthesia supports the theory that the erection is a consequence of increased penile blood flow, thus a relatively harmless condition. However, confirmation by serial cavernous blood gas analysis or colour duplex ultrasonography is mandatory. Until this hypothesis is confirmed, termination of epidural infusion is advised as a primary treatment.

RAD52-dependent mitotic DNA synthesis is required for genome stability in Cyclin E1-overexpressing cells.

Overexpression of Cyclin E1 perturbs DNA replication, resulting in DNA lesions and genomic instability. Consequently, Cyclin E1-overexpressing cancer cells increasingly rely on DNA repair, including RAD52-mediated break-induced replication during interphase. We show that not all DNA lesions induced by Cyclin E1 overexpression are resolved during interphase. While DNA lesions upon Cyclin E1 overexpression are induced in S phase, a significant fraction of these lesions is transmitted into mitosis. Cyclin E1 overexpression triggers mitotic DNA synthesis (MiDAS) in a RAD52-dependent fashion. Chemical or genetic inactivation of MiDAS enhances mitotic aberrations and persistent DNA damage. Mitosis-specific degradation of RAD52 prevents Cyclin E1-induced MiDAS and reduces the viability of Cyclin E1-overexpressing cells, underscoring the relevance of RAD52 during mitosis to maintain genomic integrity. Finally, analysis of breast cancer samples reveals a positive correlation between Cyclin E1 amplification and RAD52 expression. These findings demonstrate the importance of suppressing mitotic defects in Cyclin E1-overexpressing cells through RAD52.

Conversion from calcineurin inhibitors to belatacept-based immunosuppressive therapy skews terminal proliferation of non-classical monocytes and lowers lymphocyte counts.

Belatacept, a modified form of CTLA-Ig that blocks CD28-mediated co-stimulation of T cells, is an immune-suppressant that can be used as an alternative to calcineurin inhibitors (CNIs). In kidney transplant recipients, belatacept has been associated with improved renal function and reduced cardiovascular toxicity. Monocytes as well as T-lymphocytes play causal roles in the pathophysiology of atherosclerotic disease. We hypothesized that the beneficial impact of the use of belatacept over CNIs on cardiovascular risk could be partly explained by the impact of belatacept therapy on these circulating leukocytes. Hence, we phenotyped circulating leukocytes in transplanted patients with a stable renal function that were randomized between either continuation of CNI or conversion to belatacept in two international studies in which we participated. In 41 patients, we found that belatacept-treated patients consistently showed lower numbers of B-lymphocytes, T-lymphocytes as well as CD14-negative monocytes (CD14NM), especially in non-diabetic patients. Our observation that this decrease was associated to plasma concentrations of TNFα is consistent with a model where CD14NM-production of TNFα is diminished by belatacept-treatment, due to effects on the antigen-presenting cell compartment.

Microvascular damage in type 1 diabetic patients is reversed in the first year after simultaneous pancreas-kidney transplantation.

Simultaneous pancreas-kidney transplantation (SPK) is an advanced treatment option for type 1 diabetes mellitus (DM) patients with microvascular disease including nephropathy. Sidestreamdarkfield (SDF) imaging has emerged as a noninvasive tool to visualize the human microcirculation. This study assessed the effect of SPK in diabetic nephropathy (DN) patients on microvascular alterations using SDF and correlated this with markers for endothelial dysfunction. Microvascular morphology was visualized using SDF of the oral mucosa in DN (n = 26) and SPK patients (n = 38), healthy controls (n = 20), DM1 patients (n = 15, DM ≥ 40 mL/min) and DN patients with a kidney transplant (KTx, n = 15). Furthermore, 21 DN patients were studied longitudinally up to 12 months after SPK. Circulating levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble thrombomodulin (sTM) were measured using ELISA. Capillary tortuosity in the DN (1.83 ± 0.42) and DM ≥ 40 mL/min (1.55 ± 0.1) group was increased and showed reversal after SPK (1.31 ± 0.3, p < 0.001), but not after KTx (1.64 ± 0.1). sTM levels were increased in DN patients and reduced in SPK and KTx recipients (p < 0.05), while the Ang-2/Ang-1 ratio was normalized after SPK and not after KTx alone (from 0.16 ± 0.04 to 0.08 ± 0.02, p < 0.05). Interestingly, in the longitudinal study, reversal of capillary tortuosity and decrease in Ang-2/Ang-1 ratio and sTM was observed within 12 months after SPK. SPK is effective in reversing the systemic microvascular structural abnormalities in DN patients in the first year after transplantation.

Stellate-ganglion block as a treatment for severe postmenopausal flushing.

OBJECTIVE: Hormone replacement therapy is the most effective treatment for postmenopausal flushing. Unfortunately, its use is often contraindicated. A limited amount of uncontrolled data suggests that stellate-ganglion block (SGB) may be useful for the treatment of hot flushes. In the present study, we examined whether previously reported results could be reproduced in women with severe postmenopausal flushing. METHODS: Twenty postmenopausal women with a baseline hot flush score ≥ 15 were treated with SGB in an open, uncontrolled setting. This mean daily hot flush score was calculated as the product of flush frequency and flush severity over a period of 1 week. The response to treatment was evaluated by flush scores and assessment of quality of life at baseline and 4 weeks after SGB. RESULTS: The per-protocol analysis included 19 women. One woman was excluded because of lack of Horner syndrome after SGB. Four weeks after SGB, the mean flush score had decreased by 34 ± 7.4% (95% confidence interval (CI) 18-49%; p < 0.005). Nine women had a decrease in flush score between 40 and 90%, with a mean response of 65 ± 4.9% (95% CI 53-76%). The other ten women were non-responders with a decrease in flush score between 0 and 11%. Quality of life and sleep, both assessed by questionnaire, improved significantly. CONCLUSIONS: The results of this study support the observation that SGB may be a useful therapy for a subset of women with severe postmenopausal flushing. A sham-controlled, single-blinded study is warranted to improve the evidence of efficacy.

Re-examining so-called 'secondary identifiers' in Disaster Victim Identification (DVI): Why and how are they used?

Disaster victim identification (DVI) refers to the identification of multiple deceased persons following an event that has a catastrophic effect on human lives and living conditions. Identification methods in DVI are typically described as either being primary, which include nuclear genetic markers (DNA), dental radiograph comparisons, and fingerprint comparisons, or secondary, which are all other identifiers and are ordinarily considered insufficient as a sole means of identification. The aim of this paper is to review the concept and definition of so-called 'secondary identifiers" and draw on personal experiences to provide practical recommendations for improved consideration and use. Initially, the concept of secondary identifiers is defined and examples of publications where such identifiers have been used in human rights violation cases and humanitarian emergencies are reviewed. While typically not investigated under a strict DVI framework, the review highlights the idea that non-primary identifiers have proven useful on their own for identifying individuals killed as a result of political, religious, and/or ethnic violence. The use of non-primary identifiers in DVI operations in the published literature is then reviewed. Because there is a plethora of different ways in which secondary identifiers are referenced it was not possible to identify useful search terms. Consequently, a broad literature search (rather than a systematic review) was undertaken. The reviews highlight the potential value of so-called secondary identifiers but more importantly show the need to scrutinise the implied inferior value of non-primary methods which is suggested by the terms "primary" and "secondary". The investigative and evaluative phases of the identification process are examined, and the concept of "uniqueness" is critiqued. The authors suggest that non-primary identifiers may play an important role in providing leads to formulating an identification hypothesis and, using the Bayesian approach of evidence interpretation, may assist in establishing the value of the evidence in guiding the identification effort. A summary of contributions non-primary identifiers may make to DVI efforts is provided. In conclusion, the authors argue that all lines of evidence should be considered because the value of an identifier will depend on the context and the victim population. A series of recommendations are provided for consideration for the use of non-primary identifiers in DVI scenarios.

FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics.

Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA+ ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability.