Oncologic outcomes of surgically managed primary pelvic soft tissue sarcoma; tumour biology or surgical constraints of the true pelvis?

Background: Pelvic soft tissue sarcomas are rare. Potentially curative resection remains challenging due to anatomical constraints of true pelvis and tumour spread through various anatomical hiatus. We sought to review the oncological outcomes of surgically managed cases at our centre and determine whether outcomes differ for patients with localised (limited to pelvis) versus extensive disease (with extra-pelvic extension).

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma.

Background: As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between ageing and prognosis are lacking. Our study aimed to investigate whether ageing is associated with inferior short-term survival outcomes after RPS surgery.

Definity, an affinity for painful crisis: a case series describing vaso-occlusive pain crises in sickle cell patients undergoing echocardiogram with Definity contrast.

Background: Individuals with sickle cell disease (SCD) are at risk for painful crises and long-term cardiopulmonary morbidity. Echocardiogram is recommended if signs or symptoms of cardiopulmonary disease develop in previously asymptomatic patients, or worsen in those with known disease. Second-generation echocardiogram contrast agents (ECAs) improve the diagnostic capacity of echocardiogram; however, these agents have risks in SCD populations that have yet to be investigated.

Maternal Transfer of Cetirizine Into Human Milk.

Introduction: Cetirizine hydrochloride is a second-generation H1 histamine antagonist with Food and Drug Administration approval for treatment of allergic rhinitis and urticaria. Currently, the Food and Drug Administration does not recommend use of cetirizine during breastfeeding, as there are insufficient studies on both the transference of cetirizine into human milk and the effects of cetirizine in infants.

Main Issue: To determine the concentration of cetirizine in human milk, samples were analyzed using high performance liquid chromatography mass spectrometry.

Human herpesvirus 6 meningitis in an adult.

Many cases of viral meningitis are idiopathic, but increased utilization of polymerase chain reaction testing has enabled physicians to better recognize rare causes of viral meningitis. This will likely continue to improve the rate of causative agent identification in seemingly idiopathic viral meningitis, including this case of human herpesvirus 6 (HHV-6) meningitis in an immunocompetent adult patient. More common viral etiologies need to be excluded before diagnosing HHV-6 meningitis, as this maximizes pretest probability and therefore increases validity of a positive result.

The pulmonary inflammatory response to multiwalled carbon nanotubes is influenced by gender and glutathione synthesis.

Inhalation of multiwalled carbon nanotubes (MWCNTs) during their manufacture or incorporation into various commercial products may cause lung inflammation, fibrosis, and oxidative stress in exposed workers. Some workers may be more susceptible to these effects because of differences in their ability to synthesize the major antioxidant and immune system modulator glutathione (GSH). Accordingly, in this study we examined the influence of GSH synthesis and gender on MWCNT-induced lung inflammation in C57BL/6 mice.

Chronic low-level domoic acid exposure alters gene transcription and impairs mitochondrial function in the CNS.

Domoic acid is an algal-derived seafood toxin that functions as a glutamate agonist and exerts excitotoxicity via overstimulation of glutamate receptors (AMPA, NMDA) in the central nervous system (CNS). At high (symptomatic) doses, domoic acid is well-known to cause seizures, brain lesions and memory loss; however, a significant knowledge gap exists regarding the health impacts of repeated low-level (asymptomatic) exposure. Here, we investigated the impacts of low-level repetitive domoic acid exposure on gene transcription and mitochondrial function in the vertebrate CNS using a zebrafish model in order to: (1) identify transcriptional biomarkers of exposure; and (2) examine potential pathophysiology that may occur in the absence of overt excitotoxic symptoms.

The glutathione synthesis gene Gclm modulates amphiphilic polymer-coated CdSe/ZnS quantum dot-induced lung inflammation in mice.

Quantum dots (QDs) are unique semi-conductor fluorescent nanoparticles with potential uses in a variety of biomedical applications. However, concerns exist regarding their potential toxicity, specifically their capacity to induce oxidative stress and inflammation. In this study we synthesized CdSe/ZnS core/shell QDs with a tri-n-octylphosphine oxide, poly(maleic anhydride-alt-1-tetradecene) (TOPO-PMAT) coating and assessed their effects on lung inflammation in mice.

A randomized cross-over study of inhalation of diesel exhaust, hematological indices, and endothelial markers in humans.

Background: Exposure to traffic-related air pollution (TRAP) is considered a trigger for acute cardiovascular events. Diesel Exhaust (DE) is a major contributor to TRAP in the world. We evaluated the effect of DE inhalation on circulating blood cell populations, hematological indices, and systemic inflammatory cytokines in humans using a specialized facility.

Mild passive focal cooling prevents epileptic seizures after head injury in rats.

Objective: Post-traumatic epilepsy is prevalent, often difficult to manage, and currently cannot be prevented. Although cooling is broadly neuroprotective, cooling-induced prevention of chronic spontaneous recurrent seizures has never been demonstrated. We examined the effect of mild passive focal cooling of the perilesional neocortex on the development of neocortical epileptic seizures after head injury in the rat.

Transcriptome correlation analysis identifies two unique craniosynostosis subtypes associated with IRS1 activation.

The discovery of causal mechanisms associated with nonsyndromic craniosynostosis has proven to be a difficult task due to the complex nature of the disease. In this study, differential transcriptome correlation analysis was used to identify two molecularly distinct subtypes of nonsyndromic craniosynostosis, termed subtype A and subtype B. In addition to unique correlation structure, subtype A was also associated with high IGF pathway expression, whereas subtype B was associated with high integrin expression.

A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes.

Single nucleotide polymorphisms (SNPs) in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance (AGD), anoscrotal distance (ASD) and penile width (PW). We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families.

Heterozygosity in the glutathione synthesis gene Gclm increases sensitivity to diesel exhaust particulate induced lung inflammation in mice.

Context: Inhalation of ambient fine particulate matter (PM₂.₅) is associated with adverse respiratory and cardiovascular effects. A major fraction of PM₂.

DIESEL particulate exposed macrophages alter endothelial cell expression of eNOS, iNOS, MCP1, and glutathione synthesis genes.

There is considerable debate regarding inhaled diesel exhaust particulate (DEP) causing impairments in vascular reactivity. Although there is evidence that inhaled particles can translocate from the lung into the systemic circulation, it has been suggested that inflammatory factors produced in the lung following macrophage particle engulfment also pass into the circulation. To investigate these differing hypotheses, we used in vitro systems to model each exposure.

The effect of progesterone dose on gene expression after traumatic brain injury.

Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10 mg/kg or 20 mg/kg given i.

Mammalian cytochrome CYP2E1 triggered differential gene regulation in response to trichloroethylene (TCE) in a transgenic poplar.

Trichloroethylene (TCE) is an important environmental contaminant of soil, groundwater, and air. Studies of the metabolism of TCE by poplar trees suggest that cytochrome P450 enzymes are involved. Using poplar genome microarrays, we report a number of putative genes that are differentially expressed in response to TCE.

Genetic polymorphisms in the catechol estrogen metabolism pathway and breast cancer risk.

Background: This study investigated whether single nucleotide polymorphisms (SNP) in genes within the catechol estrogen metabolism pathway altered the risk of breast cancer alone or in combination, as well as whether menopausal hormone therapy modified the effect of these SNPs on breast cancer risk.

Methods: In a population-based case-control study of breast cancer, 891 cases and 878 controls were genotyped for six functional SNPs in the COMT, CYP1B1, GSTM1, GSTP1, and GSTT1 genes.

Results: Women homozygous with the T allele in CYP1B1*2 (Ser(119); rs1056827) were at 1.

Muscarinic receptors prevent oxidative stress-mediated apoptosis induced by domoic acid in mouse cerebellar granule cells.

In mouse cerebellar granule neurons (CGNs) low concentrations of domoic acid (DomA) induce apoptotic cell death, which is mediated by oxidative stress; apoptosis is more pronounced in CGNs from Gclm (-/-) mice, which lack the modifier subunit of glutamate cysteine ligase (GCL) and have very low GSH levels. By activating M(3) muscarinic receptors, the cholinergic agonist carbachol inhibits DomA-induced apoptosis, and the anti-apoptotic action of carbachol is more pronounced in CGNs from Gclm (+/+) mice. Carbachol does not prevent DomA-induced increase in reactive oxygen species, suggesting that its anti-apoptotic effect is downstream of reactive oxygen species production.

Cervical and vulvar cancer risk in relation to the joint effects of cigarette smoking and genetic variation in interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC.

Cholecystokinin C-45T polymorphism and smoking cessation in women.

In view of the effect of cholecystokinin (CCK) on dopaminergic neurons in the mesolimbic "reward" pathway of the brain, its gene has been a focus in studies of dopamine-related conditions and behaviors, including smoking. We assessed the association between the CCK C-45T polymorphism and smoking cessation among women who participated in a randomized clinical trial of d,l-fenfluramine conducted in the Seattle area in 1993-1994. Several years later (Mdn = 3.

Association of Vitamin K epoxide reductase complex 1 (VKORC1) variants with warfarin dose in a Hong Kong Chinese patient population.

Objective: To evaluate the association of VKORC1 genetic variants with warfarin dose requirements in a Hong Kong Chinese patient population.

Methods: A retrospective study of Hong Kong Chinese patients chronically maintained on warfarin was conducted. Single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 were genotyped.

Interleukin 6 modulates c-sis gene expression in cultured human endothelial cells.

Human vascular endothelial cells secrete platelet-derived growth factor (PDGF)-like polypeptides which may mediate some of the vascular effects in the inflammatory process. We have demonstrated that IL-6 caused a significant increase in the mRNA level of the c-sis gene (PDGF B chain) in cultured human endothelial cells. IL-1 alpha and IL-1 beta also increased c-sis mRNA transcripts after an extended incubation period and both cytokines acted synergistically with IL-6 in increasing c-sis expression.

Pursuit tracking skill as a joint function of work and rest variables.

Early studies suggested that the effects of varying length of work period (TW) and duration of rest period (TR) are additive when TW and TR alternate and are constant within experimental conditions. Recent investigations indicate that the joint effect of these variables on performance depends on the ratio TW:TR. this ratio effect is not predicted by functions traditionally used to describe theoretical massing and distribution effects.