Juvenile hormones (JHs) are key regulators of both metamorphosis and adult reproductive processes. Farnesoic acid
O-methyltransferase (FAMeT) is thought to be an important enzyme in the JH ...biosynthetic pathway, catalyzing methylation of farnesoic acid (FA) to methyl farnesoate (MF). Previous evidence in other insects suggested that FAMeT is rate limiting and regulated by a neuropeptide family, the allatostatins. A full-length cDNA encoding a 296 amino acid putative FAMeT has been isolated. A recombinant (r)FAMeT was cloned, expressed and a specific antiserum generated. rFAMeT was assayed for enzymatic activity using a radiochemical assay. In this assay, no activity was detected either with rFAMeT alone or when added to a corpus allatum CA extract. Immunohistochemical analysis was used to confirm the presence of FAMeT in the CA of
Drosophila melanogaster ring gland. Analysis of MF, JHIII and JHB
3 release in wild type and mutant stocks in the presence and absence of Drome AST (PISCF-type) suggest that
Drosophila FAMeT has little if any effect on sesquiterpenoid biosynthesis. Drome AST appears to have a select effect on JH bisepoxide biosynthesis and not MF or JHIII. Additional analysis of MF, JHIII and JHB
3 release in strains with a deficiency or decrease of FAMeT compared to wild type shows no significant decrease in MF, JHIII or JH bisepoxide synthesis. Deficiency strains that reduce the level of FAMeT showed reduced longevity relative to wildtype but this result may be due to other genetic influences.
Background
Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy.
Methods
A ...collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis.
Results
Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow‐up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5–262·0) cm3. The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P < 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan–Meier long‐term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively.
Conclusion
Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.
Antecedentes
Los schwannomas son tumores raros que plantean un importante desafío para su tratamiento en el abdomen, retroperitoneo y pelvis. No existen datos disponibles que informen de la estrategia de tratamiento.
Métodos
Se llevó a cabo un estudio de cohortes colaborativo internacional, entre unidades especializadas en sarcomas, que incluía a pacientes adultos con schwannomas de la cavidad abdominal, retroperitoneo o pelvis con confirmación histológica que se presentaron entre 2000 y 2017.
Resultados
De 485 pacientes de los 12 centros, 38 (7,8%) fueron dados de alta sin seguimiento, 199 (41,0%) fueron sometidos a resección precoz y 248 (51,1%) pacientes se incluyeron en seguimiento radiológico, de estos últimos 96 pacientes (38,7%) fueron sometidos finalmente a cirugía, con una tasa global de resección del 60,8% (295/485). Al inicio, la mediana del volumen tumoral fue 90,1 cm3 (rango intercuartílico: 26,5‐262,0). La tasa media de crecimiento fue 10,5% por año (i.c. del 95%: 9,4%‐11,6%), siendo uniforme en el seguimiento a corto (durante los 2 años del diagnóstico) y largo plazo (más allá de los 2 años, rho: 0,405, P = 0,021). La decisión de establecer la indicación quirúrgica fue más frecuente en pacientes sintomáticos (P < 0,001) y en tumores con crecimiento rápido (> 20% por año, P = 0,025). Se consiguió una resección R0/R1 en el 91,6%. Las tasas de recidiva a largo plazo de Kaplan‐Meier tras resección R0/R1 fueron 2% y 7% a 3 y 5 años, respectivamente.
Conclusión
Las recomendaciones específicas incluyen: indicaciones para la cirugía precoz, predicción del crecimiento en el seguimiento radiológico, fomentar la resección submacroscópica selectiva, y cese del seguimiento postoperatorio con pruebas de imagen.
Schwannomas present a significant management challenge, and surgery can result in morbidity. Individualized growth rates predicted after a period of radiological monitoring can help guide decision‐making. There is no role for surveillance after resection.
Practical guidelines
Background
Desmoid tumors (DT) occur sporadically, in familial adenomatous polyposis, or in association with pregnancy. Initial observation has been proposed in the management of DT. An advantage of ...this approach is to select patients who have indolent disease versus those who require intervention. Here we report our multidisciplinary experience of abdominal DT as it relates to nonoperative management.
Methods
Patients seeking care from 1980 to 2012 with pathologically confirmed DT were identified from clinical research databases. Clinicopathologic data and management strategies were collected, and statistical analyses were performed by Chi square and
t
tests.
Results
A total of 213 patients were identified; DT occurred in abdominal wall (
n
= 103, 48 %), intra-abdominally (
n
= 92, 43 %), or at both sites (
n
= 18, 9 %). Patients were predominantly female (72 %); disease was sporadic (48 %), associated with familial adenomatous polyposis (38 %), or associated with pregnancy (14 %). Patient presentation was stratified into 3 groups: untreated (group A;
n
= 176), DT resected elsewhere (group B;
n
= 19), or recurrent DT (group C;
n
= 18). In group A, 109 patients were initially observed, with 51 patients requiring intervention as a result of progression or symptoms. Of the 58 patients who underwent only observation, 93 % experienced spontaneous regression or stable disease (median follow-up 38 months). Of the 67 patients in group A who underwent resection, 28 % experienced recurrence (median 22 months). Abdominal wall DT >7 cm and intra-abdominal DT were more likely to recur (
P
< 0.01).
Conclusions
Initial observation has been implemented for abdominal DT at our institution. Over half of patients observed required no intervention with prolonged follow-up. Tumor size and site may predict progression during observation, therefore representing higher-risk groups.
Arteriosclerosis causes significant morbidity and mortality worldwide. Central to this process is the development of subclinical non-atherosclerotic intimal lesions before the appearance of ...pathologic intimal thickening and advanced atherosclerotic plaques. Intimal thickening is associated with several risk factors, including oxidative stress due to reactive oxygen species (ROS), inflammatory cytokines and lipid. The main ROS producing systems
are reduced nicotinamide dinucleotide phosphate (NADPH) oxidase (NOX). ROS effects are context specific. Exogenous ROS induces apoptosis and senescence, whereas intracellular ROS promotes stem cell differentiation, proliferation, and migration. Lineage tracing studies using murine models of subclinical atherosclerosis have revealed the contributory role of medial smooth muscle cells (SMCs), resident vascular stem cells, circulating bone-marrow progenitors and endothelial cells that undergo endothelial-mesenchymal-transition (EndMT). This review will address the putative physiological and patho-physiological roles of ROS in controlling vascular cell fate and ROS contribution to vascular regeneration and disease progression.
Background
Concern persists regarding percutaneous core needle biopsy (CNB) of a potentially malignant lesion of the retroperitoneum due to the perceived risk of immediate complications and adverse ...oncologic outcomes, including needle tract seeding (NTS).
Objective
The aim of this study was to evaluate the incidence of (1) early complications and (2) NTS following CNB of suspected retroperitoneal sarcoma (RPS).
Methods
Patients who underwent CNB of an RP mass with pre-biopsy suspicion of sarcoma were identified from a prospective database at two centers: (1) Princess Margaret Cancer Centre/Mount Sinai Hospital, Toronto (2009–2015); and (2) The Ottawa Hospital (1999–2015). Early complications, including bleeding, pain, infection, and organ injury, were recorded. Instances of NTS were identified from long-term follow-up of patients who underwent resection of primary RPS at these two centers after initial CNB (1996–2013).
Results
Of 358 percutaneous CNBs of suspected RPS performed over the study period, 7 (2.0%) resulted in minor bleeding with no transfusion, 3 (0.8%) resulted in significant pain, 1 (0.3%) resulted in unplanned admission to hospital for observation, and 1 (0.3%) resulted in a pneumothorax. There were no infections. In 203 patients who underwent resection of RPS following CNB, crude cumulative local recurrence was 24% at 5 years. At a median follow-up of 44 months, there was one case of NTS (approximately 0.5%).
Conclusion
This large bi-institutional experience with CNB of an RP mass demonstrates that both the early complication rate and the incidence of NTS are very low. Physicians and patients can be reassured that the benefits of CNB in diagnosing sarcoma and determining its histologic subtype and grade far outweigh the risks.
The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial ...thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which seven members have been characterized. The Nox family are critical determinants of the redox state within the vessel wall that dictate, in part the pathophysiology of several vascular phenotypes. This review highlights the putative role of ROS in controlling vascular fate by promoting endothelial dysfunction, altering vascular smooth muscle phenotype and dictating resident vascular stem cell fate, all of which contribute to intimal medial thickening and vascular disease progression.
The use of archaeology for economic development represents a non- traditional use of resources normally valued for their cultural aspects. Economic benefits and uses are often presented in opposition ...to cultural ones in much of heritage management theory and practice. This divide has lead to a lack of data and an inadequate consideration of the economic value of archaeology and its place in economic development. Based on research in Scotland and in Jordan, this paper presents concepts to help bridge the gap between these values and provide a more holistic view of archaeological resources which considers the relationships between cultural and economic values.
Background
Retroperitoneal sarcoma (RPS)-specific nomograms provide estimates of survival and recurrence risk following resection in the individual patient. The effect of preoperative treatment on ...nomogram performance has not been previously examined. Our aim was to evaluate the predictive accuracy of existing RPS-specific nomograms in patients managed at our center, where the majority of patients received preoperative radiation.
Patients and Methods
All patients who underwent curative treatment for primary RPS at Mount Sinai Hospital/Princess Margaret Hospital between 1996 and 2016 were identified. The performance of four previously published nomograms was assessed by measuring the agreement between nomogram-predicted and observed outcomes using Harrell’s C-Index and level of calibration. Outcomes included in each of the nomograms overall survival (OS), disease-free survival (DFS), disease-specific death (DSD), local recurrence (LR), distant recurrence (DR) at each of the specified post-resection timepoints were examined.
Results
In total, 253 patients were included. When observed outcomes were compared with those predicted by each of the four nomograms, the C-Index ranged from 0.60 to 0.81, representing a wide range of predictive accuracy. The lowest C-Index was for prediction of LR. Calibration plots revealed that the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram predicted a 5-year LR of 45%, whereas the observed LR was 24%. Overprediction of LR was detected in patients who had undergone preoperative radiotherapy, but not in patients treated with surgery alone.
Conclusions
Preoperative radiotherapy appeared to preclude the use of the LR component of existing nomograms for primary RPS. Updated nomograms should be created to reflect this variable, particularly in light of the recently published STRASS trial results.
As the world strives towards its goal of net zero carbon emissions, it is vital that renewable energy sources be optimized to their full potential. A key source of renewable energy is hydropower, ...more specifically, the Pelton turbine—a highly efficient, widely used, and well-researched piece of turbomachinery. This review proposes a methodology that will aid future research on Pelton turbines and compares relevant literature to assess effective ways to improve upon the Pelton design. The methodology evaluates how both experimental and computational analysis can be utilized in parallel to accelerate the progress of research, giving an example of the adopted workflow presented in a case study. The literature study in this paper focuses on how a variety of bucket parameters can be optimized to improve the efficiency of a Pelton turbine and analyses the accuracy of CFD compared to experimental data from previous research involving Pelton and Turgo turbines. The findings revealed that a water exit angle of 169°–170° proved to be optimal, while modifications to the depth and internal geometry of the bucket seemed to have the greatest impact on the efficiency of Pelton turbines. A short discussion on the potential for utilizing the strengths of both Pelton and Turgo turbines is included to highlight the need for further research in this field. A combination of both simulation and experimental results running in parallel with each other during optimization is found to be beneficial due to advancements in rapid prototyping. By comparing experimental data with simulated data throughout the optimization process, mistakes can be realized early on in the process, reducing time in later stages. Having experimental data throughout the turbine’s development aids the computational process by highlighting issues that may have been missed when only using CFD.
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