Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

Induction of β-family chemokines mRNA in human embryonic astrocytes by inflammatory cytokines

The cellular infiltration found during CNS inflammation consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during inflammatory responses. Astrocyte chemokine expression might contribute to site-specific leukocyte infiltration within the CNS. To investigate the factors that regulate astrocyte chemokine expression, we examined the ability of human fetal astrocytes to induce -family chemokine mRNA. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1 (MIP-1), and MIP-1 mRNA were easily induced by lipopolysaccharide and/or the proinflammatory cytokines (IFN and/or TNF-), respectively. Addition of both IFN and TNF- together did not lead to an additive effect but resulted in the inhibition of MCP-1 and MIP-1 mRNA expression, indicating that interaction between chemokines and cytokines may play a key role in regulating the local immune response of resident and infiltrating cells at the site of lesion. Interestingly, ultraviolet light-inactivated measles virus, but not cytomegalovirus, strongly induced expression of MCP-1, RANTES, MIP-1, and MIP-1 mRNA in human embryonic astrocytes, especially MCP-1 and MIP-1. An association occurs between the -family chemokine expression in astrocytes and inflammatory factors/virus, suggesting a possible role for -family chemokines in the pathogenesis of CNS inflammatory disease.     

Characterization of long‐term outcomes for pediatric patients with epithelioid hemangioma

Epithelioid hemangioma (EH) is a rare benign vascular tumor that occurs in soft tissues and bone and presents between the third and sixth decades of life. Little is known about the clinical course and outcomes of pediatric EH. We report 11 patients diagnosed with EH at a median age of 14.4 years. One patient treated with interferon and one with sirolimus exhibited partial response for >2 years. Although a benign neoplasm, EH is difficult to manage without standard protocols and portends considerable morbidity. Our findings suggest medical management, particularly sirolimus, may benefit these patients; however, long‐term follow‐up is needed.     

Gestational lead exposure induces developmental abnormalities and up-regulates apoptosis of fetal cerebellar cells in rats

Lead (Pb), a known environmental toxicant, adversely affects almost all organ systems. In this study, we investigated the effects of maternal lead exposure on fetal rat cerebellum. Female Sprague–Dawley rats were given lead nitrate in drinking water (0, 0.5, and 1%) for two weeks before conception, and during pregnancy. Fetuses were collected by caesarian section on gestational day 21 and observed for developmental abnormalities. The fetal cerebellar sections from control and 1% lead group were stained with cresyl violet. Immunohistochemical expressions of p53, Bax, Bcl-2, and caspase 3 were quantified by AnalySIS image analyzer (Life Science, Germany). Lead exposure induced developmental abnormalities of eyes, ear, limbs, neck and ventral abdominal wall; however, these abnormalities were commonly seen in the 1% lead-treated group. In addition, lead also caused fetal mortality and reduced body growth in both dose groups and reduced brain weight in the 1% lead-treated group. The fetal cerebella from the 1% lead-treated group showed unorganized cerebellar cortical layers, and degenerative changes in granule and Purkinje cells such as the formation of clumps of Nissl granules. An increase in Bax and caspase 3, and a decrease in Bcl-2 (p?相似文献   

Eating habits are associated with subjective sleep quality outcomes among university students: findings of a cross-sectional study

Sleep and Breathing - This study investigated the relationships between eating habits and sleep quality among university students. In a cross-sectional study, university students completed a...     

Therapy-induced bone changes in oncology imaging with 18F-sodium fluoride (NaF) PET–CT

Annals of Nuclear Medicine - 18F-Sodium fluoride (18F-NaF) is a PET tracer that is mostly used in the evaluation of bone metastasis in oncology cases. Recently, 18F-NaF PET/CT is gaining wide...     

Modification of Serum Galectin-3 and Reversal of Cardiac Remodeling Following Pediatric Transcatheter Atrial Septal Defect Closure

Objectives: We aimed to evaluate the effect of percutaneous atrial septal defect (ASD) closure in children using right heart indices and serum galectin-3 (Gal-3), as potential biomarkers of right heart remodeling. Methods: This case–control prospective study included 40 children with ASD and 25 control subjects. An echocardiographic evaluation was performed before the procedure, as well as 24 h, 1 month, and 6 months after intervention. Serum Gal-3 was measured before, and 1 month after the procedure. Results: Serum Gal-3 concentration, right atrial (RA) dimensions, right ventricular (RV) dimensions, indexed RA area, and right index of myocardial performance (RIMP) were significantly increased in children with ASD compared with control subjects while tricuspid annular plane systolic excursion (TAPSE) was significantly decreased. Six months after closure, RA, and RV dimensions significantly decreased and RV function improved (RIMP decreased and TAPSE increased). Gal-3 oncentration significantly decreased 1 month after ASD closure, but it did not reach normal range compared with control subjects. A positive correlation between Gal-3 and age at closure, RA area, RV dimensions, and RIMP was observed. A positive correlation was observed between the decrease in Gal-3 concentration and the decrease in RA area and RV dimensions 1 month after ASD closure. A significant negative correlation was observed between TAPSE and Gal-3 concentration before and after intervention. Conclusions: Percutaneous ASD closure can improve right-sided indices and decrease serum Gal-3 concentration. Gal-3 can be used as a sensitive biomarker of right heart remodeling, with a decrease in Gal-3 concentration suggesting reversal of maladaptive remodeling.     

A review on non-edible oil as a potential feedstock for biodiesel: physicochemical properties and production technologies

There is increasing concern regarding alleviating world energy demand by determining an alternative to petroleum-derived fuels due to the rapid depletion of fossil fuels, rapid population growth, and urbanization. Biodiesel can be utilized as an alternative fuel to petroleum-derived diesel for the combustion engine. At present, edible crops are the primary source of biodiesel production. However, the excessive utilization of these edible crops for large-scale biodiesel production might cause food supply depletion and economic imbalance. Moreover, the utilization of edible oil as a biodiesel feedstock increases biodiesel production costs due to the high price of edible oils. A possible solution to overcome the existing limitations of biodiesel production is to utilize non-edible crops oil as a feedstock. The present study was conducted to determine the possibility and challenges of utilizing non-edible oil as a potential feedstock for biodiesel production. Several aspects related to non-edible oil as a biodiesel feedstock such as overview of biodiesel feedstocks, non-edible oil resources, non-edible oil extraction technology, its physicochemical and fatty acid properties, biodiesel production technologies, advantages and limitation of using non-edible oil as a feedstock for biodiesel production have been reviewed in various recent publications. The finding of the present study reveals that there is a huge opportunity to utilize non-edible oil as a feedstock for biodiesel production.

There is increasing concern regarding alleviating world energy demand by determining an alternative to petroleum-derived fuels due to the rapid depletion of fossil fuels, rapid population growth, and urbanization.     

The Saudi Critical Care Society extracorporeal life support chapter guidance on utilization of veno-venous extracorporeal membrane oxygenation in adults with acute respiratory distress syndrome and special considerations in the era of coronavirus disease 2019

Extracorporeal membrane oxygenation (ECMO) is considered as a supportive treatment that provides circulatory and ventilatory support and can be thought off as a bridge to organ recovery. Since 2009, it has been applied as a rescue treatment for patients with severe adult respiratory distress syndrome (ARDS) mainly due to viral causes. In December 2019, several patients presented with a constellation of symptoms of viral pneumonia in China. A new strain of the corona virus family, called COVID-19, has been discovered to be the cause of this severe mysterious illness that was named severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). This new virus continued to spread across the globe leading to the World Health Organization announcing it as a pandemic in the early 2020. By the end of March 2021, the number of COVID-19 cases worldwide exceeded 126 million cases. In Saudi Arabia, the first confirmed case of COVID-19 was reported in the 2nd March 2020. By the end of March 2021, the total number of confirmed COVID-19 cases in Saudi Arabia is just above 360,000. In anticipation of the need of ECMO for the treatment of patients with SARS‑CoV‑2 based on the previous Middle East respiratory syndrome coronavirus pandemic experience, the Saudi Extra-Corporeal Life Support (ECLS) chapter that is under the umbrella of the Saudi Critical Care Society (SCCS) convened a working group of ECMO experts. The mission of this group was to formulate a guidance for the use of ECMO as a last resort for patients with severe ARDS, especially with COVID-19 based on available evidence. The ECLS-SCCS chapter wanted to generate a document that can be used to simple guide, with a focus on safety, to provide ECMO service for patients with severe ARDS with a special focus on SARS‑CoV‑2.     

Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

Background  

Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.