While most melanomas can be distinguished from nevi by histopathology, the histology is ambiguous for some melanocytic tumors, contributing to diagnostic uncertainty. Therefore molecular assays, ...including FISH or SNP array, and more recently a gene expression test (myPath, Myriad Genetics) have been proposed to aid in the work-up of ambiguous tumors. Two hundred and sixty-eight prospectively submitted cases were gathered, with the goal of comparing the myPath assay to morphologic diagnosis in (1) morphologically unequivocal cases (198), and to morphologic diagnosis and FISH in (2) morphologically ambiguous cases (70). Melanoma FISH was performed using probes for 6p25, 6q23, 11q13, Cep6, 9p21, and Cep9 and scored according to established criteria. The myPath assay was scored by the manufacturer as benign, indeterminate, or malignant. In the unequivocal group, myPath assay showed 75% agreement with morphologic diagnosis, with 67% sensitivity and 81% specificity. In the ambiguous group, FISH and myPath showed 69% inter-test agreement. For these cases agreement with histopathologic interpretation was 84% for FISH and 74% for myPath. Sensitivity and specificity of FISH was 61 and 100%, 50 and 93% for myPath, respectively. Cases from both groups in which myPath was discordant with either morphologic diagnosis and/or FISH (81/268 cases), were submitted for evaluation by two experienced dermatopathologist and also by SNP-array. SNP-array results correlated better than FISH, which correlated better than myPath, with the morphologic interpretation. Our findings document that molecular diagnostics show good correlation with consensus diagnoses, but discordant results occur, and vary in level of correlation with consensus interpretations. Studies with long-term outcomes data within specific ambiguous lesion subsets are required to establish the accuracy of this test, as each molecular diagnostic technique has limitations based on both lack of clinical outcomes data in ambiguous melanocytic tumors and in terms of their sensitivity and specificity in melanocytic lesion subtypes.
Abstract
A cooperative study involving 189 litters from 114 sows initial breeding body weight (BW), 200.8 ± 37.1 kg was conducted at two experiment stations to investigate the effects of OmniGen AF ...(OG; Phibro Animal Health Corporation) supplementation in sow diets on reproductive performance and milk composition. Diets were: 1) corn-soybean meal-based control diet that met NRC (2012) requirement estimates or 2) control plus 0.75% OG. A common diet formulation was used by both stations. Sow allotment was balanced for breed, parity, and BW. Sows were allotted to diets at least 21 days prebreeding and were fed the diets continuously at 1.82 kg daily in gestation and ad libitum in lactation. Sow BWs were measured at breeding, prefarrowing, postfarrowing and weaning. Litter size responses were recorded within 24 h postpartum and individual pig weights were measured at birth and weaning. Milk samples were collected twice during lactation on d 5–7 and d 14–17. Supplementation with OG resulted in less (P < 0.05) BW change of sows during lactation (-12.1 vs. -8.2 kg). Total born (12.9 vs. 13.0), live born (11.7 vs. 12.0), and weaned (10.3 vs. 10.5) were similar for control and OG sows, respectively. Sows fed OG-based diets had greater (P < 0.05) litter weight for total born (18.3 vs. 19.3 kg) and weaned (63.2 vs. 67.0 kg), and lactation litter gain (47.8 vs. 50.7 kg). Lactation feed intake for control and OG sows (5.32 vs 5.52 kg, respectively) did not differ. Supplementing sow diets with OG increased (P = 0.057) lactose content (5.78 vs. 5.84%) and reduced (P = 0.047) protein content (4.77 vs. 4.68%) in milk. The results of this study demonstrated that supplemental OG at 0.75% in sow diets reduced weight loss during lactation and improved litter weights with marginal effects on milk composition of sows.
Listening to music is a common method of regulating unpleasant emotions such as sadness, but music listening has not been compared to prototypical interpersonal emotion-regulation strategies. We ...examined music’s response-independent benefits (i.e., benefits that do not require a response from another person) and response-dependent benefits (i.e., benefits that do require a response from another person) and compared those to other regulation strategies such as talking to a friend and asking someone for advice. College students (N = 353) completed an online survey in which they rated their likelihood of using eight different strategies to regulate sadness and the benefits of using each strategy. Repeated-measures ANOVAs revealed listening to music was the most likely strategy used when sad. Moreover, listening to music provided the most response-independent benefits of any strategy we examined, including talking to a friend and asking someone for advice. Talking to a friend provided more interpersonal support than listening to music did, but listening to music did not provide any less of a shared experience than talking to a friend or asking someone for advice. These findings suggest that listening to music shares much in common with interpersonal emotion-regulation strategies such as talking with other people when sad.
Pediatric Orthopaedic Oncology is a developing subspecialty within the field of Pediatric Orthopaedics. Traditionally, the field of Orthopaedic Oncology has been focused on the skeletally mature ...individual, and the research tends to be all encompassing rather than truly evaluating isolated populations. The purpose of this review is to summarize the most clinically relevant literature in the field of Pediatric Orthopaedic Oncology over the last 6 years.
We evaluated the PubMed database utilizing keywords for pediatric orthopaedic oncology: sarcoma, osteosarcoma, Ewing sarcoma, bone cyst. In additionally, we further broadened our search by searching for relevant articles in the contents sections of major orthopaedic surgery journals that routinely publish both pediatric and orthopaedic oncology literature. In keeping with "What's New," we selected the most clinically relevant articles published in the last 6 years from January 1, 2014 through February 2020. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included.
Our search yielded 60 articles that met general criteria, from which 14 were determined to be most relevant to the goals of this paper. Of the papers presented in this review, there were papers related to management of benign tumors/tumor-like conditions, bone cysts, limb salvage procedures, and amputation procedures. Ultimately included in the review were 5 studies related to limb salvage, 4 related to bone cysts, 1 related to multiple hereditary exostoses, 2 related to osteofibrous dysplasia, 1 related to chondroblastoma, and 1 discussing cementation in skeletally immature patients. They were level III, IV, and V studies. Basic science and systemic therapies literature was widely reviewed and the research and clinical trials most relevant to pediatric sarcoma and neoplastic processes found in the pediatric population were included. Our search of the basic science and systemic therapies literature yielded 19 sources were found to be pertinent to our aims and 18 of those sources were published between 2015 and 2020.
There are many, varied, and creative procedures in the realm of limb salvage, though there remains a lack of high-level evidence to support some of the more novel procedures. In regards to benign bone tumors, despite a more solid base of literature, there still does not seem to be consensus as to the best treatment. In particular, there continue to be many schools of thought on the treatment of benign bone cysts. Research in the basic science arena and systemic therapies are advancing in exciting ways in regards to pediatric sarcoma. Orthopaedic oncologic research specific to the pediatric population overall continues to be impeded by low sample sizes and inadequate levels of evidence, which limits the ability of surgeons to draw definitive conclusions from the literature.
The purpose of this study was to investigate balance and motor control in dancers and non-dancers with different foot positions. Physically active female dancers (
= 11) and non-dancers (
= 9) ...randomly completed two balance tests in a single visit: 1) Y-balance test (YBT), and 2) motor control test (MCT). Each test was completed with two different foot positions: 1) first ballet position in which heels were touching and feet were externally rotated to 140 degrees, and 2) sixth ballet position in which heels were spaced 10 cm apart and forward parallel. For the YBT, participants completed three attempts at anterior, posteromedial, and posterolateral reaches, which were averaged and standardized to limb length for a composite score. For the MCT, participants completed a multi-directional target test on a Biosway balance system, and accuracy and time to completion were analyzed. Findings revealed no differences in YBT score (
= 0.255), MCT score (
= 0.383), or MCT time (
= 0.306) between groups in the sixth position. However, dancers displayed better YBT scores (
= 0.036), MCT scores (
= 0.020), and faster MCT times (
= 0.009) in the first position. Results suggest that superior balance and motor control in dancers may be limited to less innate dance-specific foot positions.
The non-specific symptoms of Ebola Virus Disease (EVD) pose a major problem to triage and isolation efforts at Ebola Treatment Centres (ETCs). Under the current triage protocol, half the patients ...allocated to high-risk "probable" wards were EVD(-): a misclassification speculated to predispose nosocomial EVD infection. A better understanding of the statistical relevance of individual triage symptoms is essential in resource-poor settings where rapid, laboratory-confirmed diagnostics are often unavailable.
This retrospective cohort study analyses the clinical characteristics of 566 patients admitted to the GOAL-Mathaska ETC in Sierra Leone. The diagnostic potential of each characteristic was assessed by multivariate analysis and incorporated into a statistically weighted predictive score, designed to detect EVD as well as discriminate malaria. Of the 566 patients, 28% were EVD(+) and 35% were malaria(+). Malaria was 2-fold more common in EVD(-) patients (p<0.05), and thus an important differential diagnosis. Univariate analyses comparing EVD(+) vs. EVD(-) and EVD(+)/malaria(-) vs. EVD(-)/malaria(+) cohorts revealed 7 characteristics with the highest odds for EVD infection, namely: reported sick-contact, conjunctivitis, diarrhoea, referral-time of 4-9 days, pyrexia, dysphagia and haemorrhage. Oppositely, myalgia was more predictive of EVD(-) or EVD(-)/malaria(+). Including these 8 characteristics in a triage score, we obtained an 89% ability to discriminate EVD(+) from either EVD(-) or EVD(-)/malaria(+).
This study proposes a highly predictive and easy-to-use triage tool, which stratifies the risk of EVD infection with 89% discriminative power for both EVD(-) and EVD(-)/malaria(+) differential diagnoses. Improved triage could preserve resources by identifying those in need of more specific differential diagnostics as well as bolster infection prevention/control measures by better compartmentalizing the risk of nosocomial infection.
Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK ...pathway. SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinical studies. The long-term effectiveness of tyrosine kinase inhibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non-small cell lung cancer (NSCLC) is limited by acquired resistance. Multiple clinically identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude drug binding as well as EGFR-independent activation of the MAPK pathway through alternate RTK (RTK-bypass). It has also been noted that frequently a tumor from a single patient harbors more than one resistance mechanism, and the plasticity between multiple resistance mechanisms could restrict the effectiveness of therapies targeting a single node of the oncogenic signaling network. Here, we report the discovery of IACS-13909, a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway. IACS-13909 potently impeded proliferation of tumors harboring a broad spectrum of activated RTKs as the oncogenic driver. In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation
and caused tumor regression
. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFRi-resistant NSCLC. SIGNIFICANCE: These findings highlight the discovery of IACS-13909 as a potent, selective inhibitor of SHP2 with drug-like properties, and targeting SHP2 may serve as a therapeutic strategy to overcome tumor resistance to osimertinib.
The purpose of this pilot study was to determine if the efficacy of imaginal exposure for symptoms of posttraumatic stress disorder (PTSD) could be improved by adding aerobic exercise. We ...hypothesized that aerobic exercise would enhance the efficacy of exposure therapy. Active duty service members with clinically significant symptoms of posttraumatic stress (PTSD Checklist-Stressor-Specific Version, PCL-S, ≥25) were randomized into one of four conditions: exercise only; imaginal exposure only; imaginal exposure plus exercise; no exercise/no exposure therapy (control). Participants (N = 72) were primarily male, Army, noncommissioned officers ranging in age from 22 to 52. PTSD symptom severity decreased over time (p < .0001); however, there were no significant differences between the experimental conditions. The prediction that imaginal exposure augmented with aerobic exercise would be superior to either imaginal exposure alone or aerobic exercise alone was not supported, suggesting that engaging in exercise and imaginal exposure simultaneously may not be any better than engaging in either activity alone. A better understanding of individually administered and combined exercise and exposure therapy interventions for PTSD is warranted.
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