A direct wavepath-based element localization algorithm to enable flexible ultrasound array imaging.

An algorithm is developed for determining the element locations of a flexible ultrasonic array when applied to a surface of unknown geometry. The algorithm forms a dataset of traveltimes from the direct wavepaths (i.e. rays) between transmitters and receivers, which serves as the input to an optimization scheme that iterates on the array element locations until an objective function is minimized. Once, the relative array locations have been determined, they are used as an input to a phased array ultrasound imaging algorithm. In this study, the total focusing method with full matrix capture is used as a testbed code to demonstrate the benefits of the relative array element localization algorithm. The algorithm is verified by simulation and experimentation.

Low Intake of Choline Is Associated with Diminished Strength and Lean Mass Gains in Older Adults.

OBJECTIVES: Choline is an essential micronutrient for many physiological processes related to exercise training including biosynthesis of acetylcholine. Though dietary choline intake has been studied in relation to endurance training and performance, none have studied it during resistance exercise training (RET) in older adults. The objective of the study was to examine the relationship between choline intake and muscle responses to RET in older adults. METHODS: Forty-six, 60-69-year-old individuals (M=19, F=27) underwent 12 weeks of RET (3x/week, 3 sets, 8-12 reps, 75% of maximum strength [1RM], 8 exercises). Body composition (DEXA) and 1RM tests were performed before and after training. After analyzing 1,656 diet logs (3x/week, 46 participants, 12 weeks), participants' mean choline intakes were categorized into three groups: Low (2.9-5.5 mg/kg lean/d), Med-Low (5.6-8.0 mg/kg lean/d), or Adequate (8.1-10.6 mg/kg lean/d). These correspond to <50%, ~63%, and ~85% of Adequate Intake (AI) for choline, respectively. RESULTS: Gains in composite strength (leg press + chest press 1RM) were significantly lower in the Low group compared with the other groups (Low: 30.9 ± 15.1%, Med-Low: 70.3 ± 48.5%, Adequate: 81.9 ± 68.4%; p=0.004). ANCOVA with cholesterol, protein, or other nutrients did not alter this result. Reduced gains in lean mass were also observed in the Low group, compared with higher choline intake of 5.6-10.6 mg/kg lean/d (1.3 ± 0.6% vs. 3.2 ± 0.6%, p<0.05). CONCLUSION: These data suggest that this population of older adults does not consume adequate choline and lower choline intake is negatively and independently associated with muscle responses to RET.

Design elements and first data from a new Doppler backscattering system on the MAST-U spherical tokamak.

A new Doppler backscattering (DBS) system has been installed and tested on the MAST-U spherical tokamak. It utilizes eight simultaneous fixed frequency probe beams (32.5, 35, 37.5, 40, 42.5, 45, 47.5, and 50 GHz). These frequencies provide a range of radial positions from the edge plasma to the core depending on plasma conditions. The system utilizes a combination of novel features to provide remote control of the probed density wavenumber, the launched polarization (X vs O-mode), and the angle of the launched DBS to match the magnetic field pitch angle. The range of accessible density turbulence wavenumbers (kθ) is reasonably large with normalized wavenumbers kθρs ranging from ≤0.5 to 9 (ion sound gyroradius ρs = 1 cm). This wavenumber range is relevant to a variety of instabilities believed to be important in establishing plasma transport (e.g., ion temperature gradient, trapped electron, electron temperature gradient, micro-tearing, kinetic ballooning modes). The system is specifically designed to address the requirement of density fluctuation wavevector alignment which can significantly reduce the SNR if not accounted for.

Evaluation of a new DIII-D Doppler backscattering system for higher wavenumber measurement and signal enhancement.

The high density fluctuation poloidal wavenumber, kθ (kθ > 8 cm-1, kθρs > 5, ρs is the ion gyro radius using the ion sound velocity), measurement capability of a new Doppler backscattering (DBS) system at the DIII-D tokamak has been experimentally evaluated. In DBS, wavenumber (k) matching becomes more important at higher wavenumbers, owing to the exponential dependence of the measured signal loss factor on wave vector mismatch. Wave vector matching allows for the Bragg scattering condition to be satisfied, which minimizes the signal loss at higher k's. In the previous DBS system, without toroidal wave vector matching, the measured DBS signal-to-noise ratio at higher kθ (>8 cm-1) is substantially reduced, making it difficult to measure higher kθ turbulence. The new DBS system has been optimized to access higher wavenumber, kθ ≤ 20 cm-1, density turbulence measurement. The optimization hardware addresses fluctuation wave vector matching using toroidal steering of the launch mirror to produce a backscattered signal with improved intensity. The probe's sensitivity to high-k density fluctuations has been increased by approximately an order of magnitude compared to the old system that has been in use at DIII-D. Note that typical measurement locations are above or below the tokamak midplane on the low field side with normalized radial ranges of 0.5-1.0. The new DBS probe system with the toroidal matching of fluctuation wave vectors is thought to be critical to understanding high-k turbulent transport in fusion-relevant research at DIII-D.

Validating and optimizing mismatch tolerance of Doppler backscattering measurements with the beam model (invited).

We use the beam model of Doppler backscattering (DBS), which was previously derived from beam tracing and the reciprocity theorem, to shed light on mismatch attenuation. This attenuation of the backscattered signal occurs when the wavevector of the probe beam's electric field is not in the plane perpendicular to the magnetic field. Correcting for this effect is important for determining the amplitude of the actual density fluctuations. Previous preliminary comparisons between the model and Mega-Ampere Spherical Tokamak (MAST) plasmas were promising. In this work, we quantitatively account for this effect on DIII-D, a conventional tokamak. We compare the predicted and measured mismatch attenuation in various DIII-D, MAST, and MAST-U plasmas, showing that the beam model is applicable in a wide variety of situations. Finally, we performed a preliminary parameter sweep and found that the mismatch tolerance can be improved by optimizing the probe beam's width and curvature at launch. This is potentially a design consideration for new DBS systems.

In vitro activity of ceftazidime-avibactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in Malaysia: Results from the ATLAS Programme, 2013 to 2019.

INTRODUCTION: There has been a steady rise in antimicrobial resistance among common pathogens in Malaysia. This study aims to determine the in vitro antimicrobial activities of ceftazidime-avibactam and its comparators against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in Malaysia from 2013 to 2019, and to determine the rates of resistance among these isolates. MATERIALS AND METHODS: In this retrospective study, four participating study centres located in East (N = 1) and West (N = 3) Malaysia contributed to the collection of clinical isolates of Enterobacterales and P. aeruginosa from 2013 to 2019. Antimicrobial minimum inhibitory concentrations (MICs) and percentage susceptibilities were interpreted according to Clinical Laboratory Standards Institute (CLSI) breakpoints, except for tigecycline and colistin, which utilised the United States Food and Drug Administration (US FDA) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, respectively. RESULTS: A total of 1,073 isolates of Enterobacterales and 332 isolates of P. aeruginosa were collected in Malaysia from the four centres. Among Enterobacterales isolates, the highest percentages of susceptibility were seen with ceftazidimeavibactam (99.2%), meropenem (98.9%), and tigecycline (96.9%). Whereas P. aeruginosa isolates demonstrated the highest susceptibilities to colistin (95.6%), followed by ceftazidime-avibactam (93.1%) and cefepime (87.1%). All metallo-ß-lactamase (MBL)-negative isolates of Enterobacterales, including ceftazidime-nonsusceptible, meropenem-nonsusceptible, and colistin-resistant phenotypes, were susceptible to ceftazidime-avibactam. Furthermore, ceftazidime-avibactam demonstrated the highest percentage of susceptibility (97.1%) against multidrug-resistant (MDR) isolates of Enterobacterales. CONCLUSION: Ceftazidime-avibactam exhibited potent in vitro activity against clinical isolates of Enterobacterales and P. aeruginosa collected in Malaysia from 2013 to 2019. The results of this study show that ceftazidime-avibactam should be considered in the treatment of indicated infections caused by susceptible strains of aerobic Gramnegative pathogens and is a valuable alternative to carbapenems.

Colchicine inhibits ROS generation in response to glycoprotein VI stimulation.

Colchicine inhibits coronary and cerebrovascular events in patients with coronary artery disease (CAD), and although known to have anti-inflammatory properties, its mechanisms of action are incompletely understood. In this study, we investigated the effects of colchicine on platelet activation with a particular focus on its effects on activation via the collagen glycoprotein (GP)VI receptor, P2Y12 receptor, and procoagulant platelet formation. Therapeutic concentrations of colchicine in vitro (equivalent to plasma levels) significantly decreased platelet aggregation in whole blood and in platelet rich plasma in response to collagen (multiplate aggregometry) and reduced reactive oxygen species (ROS) generation (H2DCF-DA, flow cytometry) in response to GPVI stimulation with collagen related peptide-XL (CRP-XL, GPVI specific agonist). Other platelet activation pathways including P-selectin expression, GPIIb/IIIa conformational change and procoagulant platelet formation (GSAO+/CD62P+) (flow cytometry) were inhibited with higher concentrations of colchicine known to inhibit microtubule depolymerization. Pathway specific mechanisms of action of colchicine on platelets, including modulation of the GPVI receptor pathway at low concentrations, may contribute to its protective role in CAD.

Zinc Gluconate Induces Potentially Cancer Chemopreventive Activity in Barrett's Esophagus: A Phase 1 Pilot Study.

BACKGROUND: Chemopreventive effects of zinc for esophageal cancer have been well documented in animal models. This prospective study explores if a similar, potentially chemopreventive action can be seen in Barrett's esophagus (BE) in humans. AIMS: To determine if molecular evidence can be obtained potentially indicating zinc's chemopreventive action in Barrett's metaplasia. METHODS: Patients with a prior BE diagnosis were placed on oral zinc gluconate (14 days of 26.4 mg zinc BID) or a sodium gluconate placebo, prior to their surveillance endoscopy procedure. Biopsies of Barrett's mucosa were then obtained for miRNA and mRNA microarrays, or protein analyses. RESULTS: Zinc-induced mRNA changes were observed for a large number of transcripts. These included downregulation of transcripts encoding proinflammatory proteins (IL32, IL1ß, IL15, IL7R, IL2R, IL15R, IL3R), upregulation of anti-inflammatory mediators (IL1RA), downregulation of transcripts mediating epithelial-to-mesenchymal transition (EMT) (LIF, MYB, LYN, MTA1, SRC, SNAIL1, and TWIST1), and upregulation of transcripts that oppose EMT (BMP7, MTSS1, TRIB3, GRHL1). miRNA arrays showed significant upregulation of seven miRs with tumor suppressor activity (-125b-5P, -132-3P, -548z, -551a, -504, -518, and -34a-5P). Of proteins analyzed by Western blot, increased expression of the pro-apoptotic protein, BAX, and the tight junctional protein, CLAUDIN-7, along with decreased expression of BCL-2 and VEGF-R2 were noteworthy. CONCLUSIONS: When these mRNA, miRNA, and protein molecular data are considered collectively, a cancer chemopreventive action by zinc in Barrett's metaplasia may be possible for this precancerous esophageal tissue. These results and the extensive prior animal model studies argue for a future prospective clinical trial for this safe, easily-administered, and inexpensive micronutrient, that could determine if a chemopreventive action truly exists.

We need to target trauma: A prospective observational study in Eastern Cape Province, South Africa.

BACKGROUND: Emergency medicine accounts for a large proportion of medical care in many low- and middle-income countries. A better understanding of the burden of disease will guide training and resource allocation priorities, but lack of electronic medical records and standardised data collection systems makes it difficult to obtain this information. OBJECTIVES: To draw attention to the proportionally large burden of trauma in emergency centres (ECs) throughout Eastern Cape Province, South Africa (SA), in the hope of influencing resource allocation and medical provider training protocols accordingly. METHODS: A secondary data analysis was performed from information gathered in HIV testing studies in two large tertiary care centres and one regional hospital in the Eastern Cape region of SA. All patients presenting to the ECs during the 6-week study period who met the inclusion criteria were approached and requested to provide consent for point-of-care HIV testing and collection of demographic information. Information collected included patient demographics, presenting complaints and final diagnoses. Simple descriptive statistics were used to analyse the data. RESULTS: Data were collected from 4 271 patients across three study sites: Frere Hospital (n=2 391), Nelson Mandela Academic Hospital (n=622) and Mthatha Regional Hospital (n=1 258). At the two tertiary care centres, most patients were between the ages of 18 and 30 years (41.2% and 32.6%, respectively) and male (57.8% and 60.2%), and 70.4% and 41.5% had traumatic injuries. The most common complaints were stab/gunshot wounds (18.3% and 20.2%). At the district hospital, the majority of patients were female (57.2%), 40.1% were between 18 and 30 years old, and 27.3% presented with traumatic injuries. Stab/gunshot wounds were the second most common complaint (7.2%) after lower respiratory tract infections (8.7%). CONCLUSIONS: From the proportion of presenting individuals sampled, we can conclude that a large proportion of care delivered in ECs in the Eastern Cape is for trauma. Local clinical capacitation efforts must focus on trauma training.

Berberine Ameliorates Periodontal Bone Loss by Regulating Gut Microbiota.

Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro-computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency-aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

Evaluation of chromogenic factor IX assays by automated protocols.

INTRODUCTION: Chromogenic substrate assays (CSA) to measure Factor IX (FIX) have recently become commercially available. However, information on their performance characteristics and use in diagnostic haemostasis laboratories remains limited. AIM: To evaluate the Hyphen Biomed (Hyphen) and Rossix FIX CSAs on fully automated coagulation analysers and compare them to the FIX one-stage assay (OSA). This study was conducted in a tertiary referral haemostasis laboratory associated with a haemophilia treatment centre. METHODS: Automated CSA protocols were adapted to the Sysmex CS2500 (CS2500) and Diagnostica Stago STA-R (STA-R) analysers. Samples assayed were from healthy volunteers, haemophilia B patients and FIX deficient plasma spiked with either plasma derived, recombinant or extended half-life FIX products. RESULTS: Reference intervals for Hyphen and Rossix assays were 73 IU/dL to 164 IU/dL and 73 IU/dL to 168 IU/dL, respectively, on the CS2500 analyser; and 84 IU/dL to 165 IU/dL for the Rossix assay on the STA-R. Repeatability across all method/analyser combinations resulted in CVs ranging from 0.8% to 5.4%. Between run reproducibility gave CVs <6.7% for all method/analyser combinations. In spiked samples, FIX recoveries were mostly within an acceptable limit of 100 ± 25% for BeneFIX® , Rixubis® and Alprolix® with some differences between CSAs. CONCLUSION: Both commercial factor FIX CSA kits can be adapted for Stago and Sysmex automated coagulation analysers. Reagent cost and workflow practices will need to be considered. These assays are potentially more consistent than OSA in measurement of replacement FIX products in haemophilia B patients.

Novel assay demonstrates that coronary artery disease patients have heightened procoagulant platelet response.

Essentials Procoagulant platelets can be detected using GSAO in human whole blood. Stable coronary artery disease is associated with a heightened procoagulant platelet response. Agonist-induced procoagulant platelet response is not inhibited by aspirin alone. Collagen plus thrombin induced procoagulant platelet response is partially resistant to clopidogrel. SUMMARY: Background Procoagulant platelets are a subset of highly activated platelets with a critical role in thrombin generation. Evaluation of their clinical utility in thrombotic disorders, such as coronary artery disease (CAD), has been thwarted by the lack of a sensitive and specific whole blood assay. Objectives We developed a novel assay, utilizing the cell death marker, GSAO [(4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid], and the platelet activation marker, P-selectin, to identify procoagulant platelets in whole blood by flow cytometry. Patients/Methods Using this assay, we characterized the procoagulant platelet population in healthy controls and a cohort of patients undergoing elective coronary angiography. Results In patients with CAD, compared with patients without CAD, there was a heightened procoagulant platelet response to thrombin (25.2% vs. 12.2%), adenosine diphosphate (ADP) (7.8% vs. 2.7%) and thrombin plus collagen (27.2% vs. 18.3%). The heightened procoagulant platelet potential in CAD patients was not associated with other markers of platelet function, including aggregation, dense granule release and activation of α2b ß3 integrin. Although dual antiplatelet therapy (DAPT) was associated with partial suppression of procoagulant platelets, this inhibitory effect on a patient level could not be predicted by aggregation response to ADP and was not fully suppressed by clopidogrel. Conclusions We report for the first time that procoagulant platelets can be efficiently detected in a few microliters of whole blood using the cell death marker, GSAO, and the platelet activation marker, P-selectin. A heightened procoagulant platelet response may provide insight into the thrombotic risk of CAD and help identify a novel target for antiplatelet therapies in CAD.

Separation and purification using GO and r-GO membranes.

Many materials with varied characteristics have been used for water purification and separation applications. Recently discovered graphene oxide (GO), a two-dimensional derivative of graphene has been considered as a promising membrane material for water purification due to its excellent hydrophilicity, high water permeability, and excellent ionic/molecular separation properties. This review is focussed on the possible versatile applicability of GO membranes. It is also known that selective reduction of GO results in membranes with a pore size of ∼0.35 nm, ideally suited for desalination applications. This article presents the applicability of graphene-based membranes for multiple separation applications. This is indeed the first review article outlining a comparison of GO and r-GO membranes and discussing the suitability for applications based on the porosity of the membranes.

Marburg virus survivor immune responses are Th1 skewed with limited neutralizing antibody responses.

Until recently, immune responses in filovirus survivors remained poorly understood. Early studies revealed IgM and IgG responses to infection with various filoviruses, but recent outbreaks have greatly expanded our understanding of filovirus immune responses. Immune responses in survivors of Ebola virus (EBOV) and Sudan virus (SUDV) infections have provided the most insight, with T cell responses as well as detailed antibody responses having been characterized. Immune responses to Marburg virus (MARV), however, remain almost entirely uncharacterized. We report that immune responses in MARV survivors share characteristics with EBOV and SUDV infections but have some distinct differences. MARV survivors developed multivariate CD4+ T cell responses but limited CD8+ T cell responses, more in keeping with SUDV survivors than EBOV survivors. In stark contrast to SUDV survivors, rare neutralizing antibody responses in MARV survivors diminished rapidly after the outbreak. These results warrant serious consideration for any vaccine or therapeutic that seeks to be broadly protective, as different filoviruses may require different immune responses to achieve immunity.

Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis.

BACKGROUND: Ghrelin is the only orexigenic hormone known to stimulate food intake and promote obesity and insulin resistance. We recently showed that plasma ghrelin is controlled by butyrylcholinesterase (BChE), which has a strong impact on feeding and weight gain. BChE knockout (KO) mice are prone to obesity on high-fat diet, but hepatic BChE gene transfer rescues normal food intake and obesity resistance. However, these mice lack brain BChE and still develop hyperinsulinemia and insulin resistance, suggesting essential interactions between BChE and ghrelin within the brain. METHODS: To test the hypothesis we used four experimental groups: (1) untreated wild-type mice, (2) BChE KO mice with LUC delivered by adeno-associated virus (AAV) in combined intravenous (i.v.) and intracerebral (i.c.) injections, (3) KO mice given AAV for mouse BChE (i.v. only) and (4) KO mice given the same vector both i.v. and i.c. All mice ate a 45% calorie high-fat diet from the age of 1 month. Body weight, body composition, daily caloric intake and serum parameters were monitored throughout, and glucose tolerance and insulin tolerance tests were performed at intervals. RESULTS: Circulating ghrelin levels dropped substantially in the KO mice after i.v. AAV-BChE delivery, which led to normal food intake and healthy body weight. BChE KO mice that received AAV-BChE through i.v. and i.c. combined treatments not only resisted weight gain on high-fat diet but also retained normal glucose and insulin tolerance. CONCLUSIONS: These data indicate a central role for BChE in regulating both insulin and glucose homeostasis. BChE gene transfer could be a useful therapy for complications linked to diet-induced obesity and insulin resistance.

Increased thrombin generation in a mouse model of cancer cachexia is partially interleukin-6 dependent.

Essentials Cancer cachexia and cancer-associated thrombosis have not previously been mechanistically linked. We assessed thrombin generation and coagulation parameters in cachectic C26 tumor-bearing mice. C26 mice are hypercoagulable, partially corrected by blocking tumor derived interleukin-6. Coagulability and anti-inflammatory interventions may be clinically important in cancer cachexia. SUMMARY: Background Cancer cachexia and cancer-associated thrombosis are potentially fatal outcomes of advanced cancer, which have not previously been mechanistically linked. The colon 26 (C26) carcinoma is a well-established mouse model of complications of advanced cancer cachexia, partially dependent on high levels of interleukin-6 (IL-6) produced by the tumor. Objectives To assess if cancer cachexia altered the coagulation state and if this was attributable to tumor IL-6 production. Methods In male BALB/c*DBA2 (F1 hybrid) mice with a C26 tumor we used modified calibrated automated thrombogram and fibrin generation (based on overall hemostatic potential) assays to assess the functional coagulation state, and also examined fibrinogen, erythrocyte sedimentation rate (ESR), platelet count, tissue factor pathway inhibitor (TFPI) and hepatic expression of coagulation factors by microarray. C26 mice were compared with non-cachectic NC26, pair-fed and sham control mice. IL-6 expression in C26 cells was knocked down by lentiviral shRNA constructs. Results C26 mice with significant weight loss and highly elevated IL-6 had elevated thrombin generation, fibrinogen, ESR, platelets and TFPI compared with all control groups. Fibrin generation was elevated compared with pair-fed and sham controls but not compared with NC26 tumor mice. Hepatic expression of coagulation factors and fibrinolytic inhibitors was increased. Silencing IL-6 in the tumor significantly, but incompletely, attenuated the increased thrombin generation, fibrinogen and TFPI. Conclusions Cachectic C26 tumor-bearing mice are in a hypercoagulable state, which is partly attributable to IL-6 release by the tumor. The findings support the importance of the coagulation state in cancer cachexia and the clinical utility of anti-inflammatory interventions.

Overcoming structural inequalities in oral health: the role of dental curricula.

To date the role of health professional schools in addressing oral health inequalities have been minimal, as attempts have focused principally upon systemic reform and broader societal obligations. Professionalism is a broad competency that is taught throughout dental schools and encompasses a range of attributes. Professionalism as a competency draws some debate and appears to be a shifting phenomenon. We may ask if professionalism in the dental curricula may be better addressed by social accountability? Social accountability directs oral health professional curricula (education, research, and service activities) towards addressing the priority health concerns of the community, in our case oral health inequalities. Although working toward dental schools becoming more socially accountable seems like a sensible way to address oral health inequalities, it might have limitations. We will consider some of the challenges in the dental curricula by considering some of the political, structural, social and ethical factors that influence our institutions and our graduates.