Measurement of Magnetic Cavitation Driven by Heat Flow in a Plasma.

We describe the direct measurement of the expulsion of a magnetic field from a plasma driven by heat flow. Using a laser to heat a column of gas within an applied magnetic field, we isolate Nernst advection and show how it changes the field over a nanosecond timescale. Reconstruction of the magnetic field map from proton radiographs demonstrates that the field is advected by heat flow in advance of the plasma expansion with a velocity v_{N}=(6±2)×10^{5} m/s. Kinetic and extended magnetohydrodynamic simulations agree well in this regime due to the buildup of a magnetic transport barrier.

Percentage of intrathoracic stomach predicts operative and post-operative morbidity, persistent reflux and PPI requirement following laparoscopic hiatus hernia repair and fundoplication.

PURPOSE: Large hiatus hernias are relatively common and can be associated with adverse symptoms and serious complications. Operative repair is indicated in this patient group for symptom management and the prevention of morbidity. This study aimed to identify predictors of poor outcomes following laparoscopic hiatus hernia repair and fundoplication (LHHRaF) to aid in counselling potential surgical candidates. METHODOLOGY: A retrospective analysis was performed from a prospectively maintained, multicentre database of patients who underwent LHHRaF between 2014 and 2020. Revision procedures were excluded. Hernia size was defined as the intraoperative percentage of intrathoracic stomach, estimated by the surgeon to the nearest 10%. Predictors of outcomes were determined using a prespecified multivariate logistic regression model. RESULTS: 625 patients underwent LHHRaF between 2014 and 2020 with 443 patients included. Median age was 65 years, 62.9% were female and 42.7% of patients had ≥ 50% intrathoracic stomach. In a multivariate regression model, intrathoracic stomach percentage was predictive of operative complications (P = 0.014, OR 1.05), post-operative complications (P = 0.026, OR 1.01) and higher comprehensive complication index score (P = 0.023, OR 1.04). At 12 months it was predictive of failure to improve symptomatic reflux (P = 0.008, OR 1.02) and persistent PPI requirement (P = 0.047, OR 1.02). Operative duration and blood loss were predicted by BMI (P = 0.004 and < 0.001), Type III/IV hernias (P = 0.045 and P = 0.005) and intrathoracic stomach percentage (P = 0.009 and P < 0.001). Post-operative length of stay was predicted by age (P < 0.001) and emergency presentation (P = 0.003). CONCLUSION: In a multivariate regression model, intrathoracic stomach percentage was predictive of operative and post-operative morbidity, PPI use, and failure to improve reflux symptoms at 12 months.

Observations of pressure anisotropy effects within semi-collisional magnetized plasma bubbles.

Magnetized plasma interactions are ubiquitous in astrophysical and laboratory plasmas. Various physical effects have been shown to be important within colliding plasma flows influenced by opposing magnetic fields, however, experimental verification of the mechanisms within the interaction region has remained elusive. Here we discuss a laser-plasma experiment whereby experimental results verify that Biermann battery generated magnetic fields are advected by Nernst flows and anisotropic pressure effects dominate these flows in a reconnection region. These fields are mapped using time-resolved proton probing in multiple directions. Various experimental, modelling and analytical techniques demonstrate the importance of anisotropic pressure in semi-collisional, high-ß plasmas, causing a reduction in the magnitude of the reconnecting fields when compared to resistive processes. Anisotropic pressure dynamics are crucial in collisionless plasmas, but are often neglected in collisional plasmas. We show pressure anisotropy to be essential in maintaining the interaction layer, redistributing magnetic fields even for semi-collisional, high energy density physics (HEDP) regimes.

A standardized approach for the thoracic dissection in robotic-assisted minimally invasive esophagectomy (RAMIE).

Robot-assisted minimally invasive esophagectomy (RAMIE) is increasingly being adopted as the preferred surgical treatment for esophageal cancer, as it is superior to open esophagectomy and a good alternative to conventional minimally invasive esophagectomy. This paper addresses the technical details of the thoracoscopic phase of RAMIE, including the operating room set-up, patient positioning, port placement, and surgical steps.

[Acetaminophen induced 5-oxoproline acidosis: An uncommon case of high anion gap metabolic acidosis]. / Acidose à la 5-oxoproline induite par le paracétamol : une cause rare d'acidose métabolique à trou anionique augmenté.

The most common causes of high anion gap metabolic acidosis (HAGMA) are lactic acidosis, ketoacidosis, and intoxications. Nevertheless, clinicians can be faced with unexplained HAGMA, with a need to look for less common etiologies. We describe a case of 5-oxoproline (pyroglutamate) acidosis due to chronic acetaminophen ingestion at therapeutic dose in a 79-year-old inpatient. The pathophysiology of this condition is detailed, with abnormalities in the gamma-glutamyl cycle due to acetaminophen ingestion and severe chronic morbidities, resulting in glutathione and cysteine deficiency and then accumulation of 5-oxoproline. In HAGMA, when usual causes have been excluded, 5-oxoproline acidosis should be suspected in patients with chronic morbidities and acetaminophen ingestion. This diagnosis should be kept in mind because it generally resolves quickly with cessation of acetaminophen and administration of intravenous fluids.

Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF.

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer.

Elevated PTTG and PBF predicts poor patient outcome and modulates DNA damage response genes in thyroid cancer.

The proto-oncogene PTTG and its binding partner PBF have been widely studied in multiple cancer types, particularly thyroid and colorectal, but their combined role in tumourigenesis is uncharacterised. Here, we show for the first time that together PTTG and PBF significantly modulate DNA damage response (DDR) genes, including p53 target genes, required to maintain genomic integrity in thyroid cells. Critically, DDR genes were extensively repressed in primary thyrocytes from a bitransgenic murine model (Bi-Tg) of thyroid-specific PBF and PTTG overexpression. Irradiation exposure to amplify p53 levels further induced significant repression of DDR genes in Bi-Tg thyrocytes (P=2.4 × 10-4) compared with either PBF- (P=1.5 × 10-3) or PTTG-expressing thyrocytes (P=NS). Consistent with this, genetic instability was greatest in Bi-Tg thyrocytes with a mean genetic instability (GI) index of 35.8±2.6%, as well as significant induction of gross chromosomal aberrations in thyroidal TPC-1 cells following overexpression of PBF and PTTG. We extended our findings to human thyroid cancer using TCGA data sets (n=322) and found striking correlations with PBF and PTTG expression in well-characterised DDR gene panel RNA-seq data. In addition, genetic associations and transient transfection identified PBF as a downstream target of the receptor tyrosine kinase-BRAF signalling pathway, emphasising a role for PBF as a novel component in a pathway well described to drive neoplastic growth. We also showed that overall survival (P=1.91 × 10-5) and disease-free survival (P=4.9 × 10-5) was poorer for TCGA patients with elevated tumoural PBF/PTTG expression and mutationally activated BRAF. Together our findings indicate that PBF and PTTG have a critical role in promoting thyroid cancer that is predictive of poorer patient outcome.

School breakfast and body mass index: a longitudinal observational study of middle school students.

OBJECTIVES: The objectives are to identify breakfast location patterns (frequency and place of breakfast consumption) and explore the association between breakfast patterns and weight status over time among preadolescents. METHODS: Surveys and physical measurements were completed among students from 12 randomly selected schools in a medium-sized urban school district. All students were followed from fifth (Fall, 2011) to seventh grade (Fall, 2013). Latent transition analysis and longitudinal analyses were used in the study. RESULTS: Six distinct breakfast location patterns emerged at baseline (1) frequent skippers; (2) inconsistent school eaters; (3) inconsistent home eaters; (4) regular home eaters; (5) regular school eaters and (6) double breakfast eaters. Results from the longitudinal analyses revealed that there was an increased odds of overweight/obesity among frequent skippers compared with double breakfast eaters after adjusting for school, year and students' race/ethnicity (AOR: 2.66, 95% CI: 1.67, 4.24). Weight changes from year to year were similar between double breakfast eaters and other students. CONCLUSIONS: Concerns that a second breakfast at school increases risk of excessive weight gain are unsupported. Students who regularly consumed breakfasts at school, including double breakfast eaters, were more likely to exhibit a healthy weight trajectory. Additional research is needed to understand the impact of universal school breakfast on students' overall diets.

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3.

Chitinase 3-like 1, otherwise known as YKL-40, is a secreted glycoprotein purported to have a role in extracellular matrix metabolism. The first mammalian cell type found to express YKL-40 was the human osteosarcoma-derived osteoblast, MG63. In that first study the active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25D), stimulated YKL-40 expression, thereby indicating that a vital factor for skeletal health promoted YKL-40 synthesis by bone forming cells. However, when these MG63 cells were exposed to 1,25D they were also exposed to serum, a rich source of the pleiotropic lipid mediator, lysophosphatidic acid (LPA). Given that 1,25D is now known to co-operate with selected growth factors, including LPA, to influence human osteoblast differentiation we hypothesised that 1,25D and LPA may work together to stimulate osteoblast YKL-40 expression. Herein we report that 1,25D and LPA synergistically promote YKL-40 expression by MG63 cells. Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63 cells in response to co-stimulation with 1,25D and LPA. Other ligands of the vitamin D receptor also co-operated with LPA in driving YKL-40 mobilisation. Collectively our findings highlight another important role of 1,25D and LPA in the regulation of human osteoblast function.

A review of fibropapillomatosis in Green turtles (Chelonia mydas).

Despite being identified in 1938, many aspects of the pathogenesis and epidemiology of fibropapillomatosis (FP) in marine turtles are yet to be fully uncovered. Current knowledge suggests that FP is an emerging infectious disease, with the prevalence varying both spatially and temporally, even between localities in close proximity to each other. A high prevalence of FP in marine turtles has been correlated with residency in areas of reduced water quality, indicating that there is an environmental influence on disease presentation. Chelonid herpesvirus 5 (ChHV5) has been identified as the likely aetiological agent of FP. The current taxonomic position of ChHV5 is in the family Herpesviridae, subfamily Alphaherpesvirinae, genus Scutavirus. Molecular differentiation of strains has revealed that a viral variant is typically present at specific locations, even within sympatric species of marine turtles, indicating that the disease FP originates regionally. There is uncertainty surrounding the exact path of transmission and the conditions that facilitate lesion development, although recent research has identified atypical genes within the genome of ChHV5 that may play a role in pathogenesis. This review discusses emerging areas where researchers might focus and theories behind the emergence of FP globally since the 1980s, which appear to be a multi-factorial interplay between the virus, the host and environmental factors influencing disease expression.

Atenolol offers better protection than clonidine against cardiac injury in kainic acid-induced status epilepticus.

BACKGROUND AND PURPOSE: Status epilepticus is increasingly associated with cardiac injury in both clinical and animal studies. The current study examined ECG activity for up to 48 h following kainic acid (KA) seizure induction and compared the potential of atenolol and clonidine to attenuate this cardiac pathology. EXPERIMENTAL APPROACH: Sprague-Dawley rats (male, 300-350 g) were implanted with ECG and electrocorticogram electrodes to allow simultaneous telemetric recordings of cardiac and cortical responses during and after KA-induced seizures. Animals were randomized into saline controls, and saline vehicle-, clonidine- or atenolol-pretreated KA groups. KEY RESULTS: KA administration in the saline-pretreated group produced an immediate bradycardic response (maximal decrease of 28 ± 6%), coinciding with low-level seizure activity. As high-level seizure behaviours and EEG spiking increased, tachycardia also developed, with a maximum heart rate increase of 38 ± 7% coinciding with QTc prolongation and T wave elevation. Both clonidine and atenolol pretreatment attenuated seizure activity and reduced KA-induced changes in heart rate, QTc interval and T wave amplitude observed during both bradycardic and tachycardic phases in saline-pretreated KA animals. Clonidine, however, failed to reduce the power of EEG frequencies. Atenolol and to a lesser extent clonidine attenuated the cardiac hypercontraction band necrosis, inflammatory infiltration, and oedema at 48 h after KA, relative to the saline-KA group. CONCLUSIONS AND IMPLICATIONS: Severe seizure activity in this model was clearly associated with altered ECG activity and cardiac pathology. We suggest that modulation of sympathetic activity by atenolol provides a promising cardioprotective approach in status epilepticus.

Agent-Based Modeling in Systems Pharmacology.

Modeling and simulation (M&S) techniques provide a platform for knowledge integration and hypothesis testing to gain insights into biological systems that would not be possible a priori. Agent-based modeling (ABM) is an M&S technique that focuses on describing individual components rather than homogenous populations. This tutorial introduces ABM to systems pharmacologists, using relevant case studies to highlight how ABM-specific strengths have yielded success in the area of preclinical mechanistic modeling.

International standards for neurological classification of spinal cord injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association (ASIA) regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

[Down syndrome maternal serum screening: results' comments recommended by accredited biologists]. / Dépistage de la trisomie 21 par les marqueurs sériques maternels : justification des commentaires appliqués par les biologistes.

Down syndrome maternal serum screening is largely used in France. The aim of this article is to specify and to explain the different comments applied on the reports in order to optimize the management of the patient. These comments represent the consensus of the study group of the biologist accredited for Down syndrome maternal serum screening.

Conditioning out-of-date bank-stored red blood cells using a cell-saver auto-transfusion device: effects on numbers of red cells and quality of suspension fluid.

We investigated the utility of a cell-saver device for processing out-of-date red blood cells, by washing twenty bags of red blood cells that had been stored for between 36 and 55 days. The volume of recovered cells, and the characteristics of the suspension fluid, were measured before and after treatment. The ratio of free haemoglobin to total haemoglobin was up to 0.02 before processing, and up to 0.011 afterwards, changing by between -0.013 and +0.003. This ratio met the current standard for free haemoglobin (less than 0.008 in more than 75% of samples), both before and after processing. Ninety-three percent of red blood cells survived the process. Potassium ion concentration fell from above 15 mmol.l(-1) in all cases, to a mean of 6.4 mmol.l(-1) (p < 0.001). The pH rose to a mean value of 6.44 (p = 0.001). Lactate ion concentration fell to a mean value of 14 mmol.l(-1) (p < 0.001). Sodium ion concentration rose from a mean value of 93 mmol.l(-1) to a mean value of 140 mmol.l(-1) (p < 0.001). A useful proportion of out-of-date red blood cells remained intact after conditioning using a cell-saver, and the process lowered concentrations of potentially toxic solutes in the fluid in which they were suspended.

Involvement and alteration of the Sonic Hedgehog pathway is associated with decreased cholesterol level in trisomy 18 and SLO amniocytes.

BACKGROUND: Trisomy 18 and Smith-Lemli-Opitz syndrome are two polymalformative conditions in which a cholesterol defect has been noted. When they occur prenatally, they are associated with a decreased maternal unconjugated estriol (uE(3)) level. Cholesterol plays an essential role in the Sonic Hedgehog pathway, allowing Shh protein maturation leading to its maximal activity. Many malformations in these two syndromes occur in Shh dependent tissues. We thus sought to assess whether a cholesterol defect could affect the Shh pathway and explain some of the observed malformations. MATERIALS AND METHODS: We selected 14 cases of trisomy 18 and 3 cases of SLO in which the maternal uE(3) level was decreased and reported malformations were observed after fetopathological examination. We correlated the number of malformations with maternal uE(3) level. We then carried out cholesterol concentrations in separate culture media consisting of trisomy 18, SLO and control amniocytes. Finally, we analyzed the Shh pathway by testing the gene expression of several Shh components: GLI transcription factors, BMP2, BMP4, TGFß1, COL1A1 and COL1A2. RESULTS AND DISCUSSION: There was an inverse correlation between phenotypic severity and maternal uE(3) levels in SLO and trisomy 18. The cholesterol levels in the amniocyte culture media were correlated with maternal uE3 levels and were significantly lower in T18 and SLO amniocytes, reflecting cholesterol defects. There was an alteration in the Shh pathway since expression of several genes was decreased in T18 and SLO amniocytes. However, these cholesterol defects were not solely responsible for the altered Shh pathway and the malformations observed.

International Standards for Neurological Classification of Spinal Cord Injury: cases with classification challenges.

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) is routinely used to determine the levels of injury and to classify the severity of the injury. Questions are often posed to the International Standards Committee of the American Spinal Injury Association regarding the classification. The committee felt that disseminating some of the challenging questions posed, as well as the responses, would be of benefit for professionals utilizing the ISNCSCI. Case scenarios that were submitted to the committee are presented with the responses as well as the thought processes considered by the committee members. The importance of this documentation is to clarify some points as well as update the SCI community regarding possible revisions that will be needed in the future based upon some rules that require clarification.

Manipulation of PBF/PTTG1IP phosphorylation status; a potential new therapeutic strategy for improving radioiodine uptake in thyroid and other tumors.

CONTEXT: The clinical effectiveness of ablative radioiodine treatment of thyroid tumors is limited by the availability of the sodium iodide symporter (NIS) at the plasma membrane (PM) for uptake of ¹³¹I. A significant proportion of well-differentiated thyroid tumors are unable to concentrate sufficient radioiodine for effective therapy, and in other tumor models such as breast tumors, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient. OBJECTIVE: Pituitary tumor-transforming gene-binding factor (PBF; PTTG1IP) is overexpressed in multiple cancers and significantly decreases NIS expression at the PM. The goal of this study was to identify a method by which PBF repression of NIS may be overcome in human tumors. RESULTS: Here, we identify PBF as a tyrosine phosphoprotein that specifically binds the proto-oncogene tyrosine protein kinase Src in mass spectrometry, glutathione S-transferase pulldown and coimmunoprecipitation assays. Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. The Src inhibitor PP1 inhibits PBF phosphorylation in multiple cell lines in vitro, including human primary thyroid cells. Of direct clinical importance to the treatment of thyroid cancer, PP1 stimulates iodide uptake by transfected NIS in TPC1 thyroid carcinoma cells and entirely overcomes PBF repression of iodide uptake in human primary thyroid cells. CONCLUSIONS: We propose that targeting PBF phosphorylation at residue Y174 via tyrosine kinase inhibitors may be a novel therapeutic strategy to enhance the efficacy of ablative radioiodine treatment in thyroid and other endocrine and endocrine-related tumors.