Corneal Endothelium in Patients with Anterior Uveitis.
To investigate a possible effect of intraocular inflammation on corneal endothelium by describing corneal endothelial cell density (ECD) and morphologic variables in eyes with anterior uveitis, and to investigate factors that may influence these findings. Cross-sectional, observational study. Observers were not masked. Volunteers with histories of unilateral or bilateral anterior segment inflammation (anterior, intermediate, or panuveitis); included were 52 patients (84 eyes with uveitis). Endothelial cell density and morphologic variables of both eyes of all study participants were determined by specular microscopy; central corneal thickness was determined by ultrasound pachymetry. Central corneal ECD, coefficient of variability, percentage hexagonality, and central corneal thickness. Central ECD was lower among eyes that had undergone cataract or glaucoma surgery or both (n = 28; P = 0.0004). After exclusion of eyes with surgery, variables for eyes with uveitis (n = 56) were compared with 2 historical populations of normal, age-matched controls and with contralateral eyes in individuals with unilateral uveitis. Central ECD was lower in eyes with uveitis than in control eyes for all age groups (P ≤ 0.01 for four of six 10-year age intervals compared with the primary control group). Among patients with unilateral uveitis who had not undergone surgery in either eye (n = 12), central ECD was lower in eyes with uveitis (2324 cells/mm(2) [range, 1543-3289 cells/mm(2)]) than in contralateral eyes (2812.5 cells/mm(2) [range, 1887-3546 cells/mm(2)]; P = 0.0005), and percentage hexagonality was lower in eyes with uveitis (54% [range, 33%-66%]) than in contralateral eyes (58.5% [range, 52%-82%]; P = 0.004). There was no significant difference in central corneal thickness between eyes with and without uveitis (P = 0.27). No eyes had clinically apparent central corneal edema. Relationships remained unchanged after exclusion of eyes with herpetic anterior uveitis. Host and disease-related characteristics were evaluated as risk factors for variations in outcome measures. Central ECD was correlated to the duration of active uveitis (r = -0.41; P < 0.0001), maximum intraocular pressure during the course of disease (r = -0.40; P = 0.0002), and maximum laser flare photometry value (r = -0.26; P = 0.020). Observed relationships suggest that anterior segment inflammation adversely affects the corneal endothelium. Longitudinal studies are warranted to determine whether long-standing anterior uveitis increases risk of endothelial dysfunction, especially in the setting of intraocular surgery.


Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats.
Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase. Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the "mate", and has been investigated for its antioxidant action. Here, we examined the aqueous extract of IP on in vitro TBARS production and in vivo study, using two behavioral models, i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a water-maze task. In vitro, we examine different concentrations of IP against the basal, Fe(II) and sodium nitruproside-induced TBARS production in rat brain homogenate. IP extract was able to prevent the basal formation of TBARS (IC50 = 6.6 mg/ml) and TBARS induced by SNP (IC50 = 3.7 mg/ml) and Fe(II) (IC50= 4.8 mg/ml). Haloperidol administration (12 mg/kg/week, im, x4 weeks) increased VCMs (p <0.001). Rats treated with mate (50 g/l, ad libitum, 60 days) did not exhibit the increase in VCMs observed in control rats treated with haloperidol (p <0.001). In the water maze task, haloperidol treated animals displayed an impairment in memory acquisition (p <0.05) compared to rats treated with vehicle. The "mate" prevented the effects of haloperidol in this behavioral paradigm. Our results indicate that IP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit of IP is possibly related to an indirect modulation of oxidative stress.


Evaluating the photocatalytic efficiency of the BiVO4/rGO photocatalyst.
The present study reported the preparation of BiVO4 by co-precipitation method. The as-prepared BiVO4 photocatalyst were deposited on rGO sheets to form BiVO4/rGO via the hydrothermal method. The crystalline structure, morphological, optical properties, and surface properties of the synthesized pure BiVO4 compared to BiVO4/rGO composite were studied using X-ray diffraction (XRD), scanning electronmicroscopy (SEM), photoluminescence (PL) spectrophotoscopy, UV-vis spectrophotometer with an integrating sphere, and N2 adsorption-desorption isotherm based on BET theory. The photocatalytic activity of the prepared samples were evaluated by the degradation of MB dye in aqueous medium under visible light irradiation. The result showed that the BiVO4/rGO composite exhibited greater photocatalytic efficiency compared to pure BiVO4 with the photocatalytic degradation efficiency remains stable up to fifth cycle. The improved activity of the BiVO4/rGO composite might be attributed to the high surface area available to adsorb more MB molecules, and efficient charge separation of BiVO4 through π electron on the rGO structure. According to experimental results, the possible photocatalytic mechanism of the BiVO4/rGO composite were determined and the active species hydroxyl radical were reported. Based on photocatalytic activity inhibition in the presence of both h+ (VB) and O2•- (CB) scavengers over the BiVO4 photocatalyst, it can be proposed that the hydroxyl radical generated during the photocatalytic degradation mechanism is mainly responsible by the main active species of h+ and O2•- at VB and CB positions, respectively.


A Novel Combined Microstrip Resonator/Nanospray Ionization Source for Microwave-Assisted Trypsin Digestion of Proteins.
Enzymatic digestion of proteins is a critical step in bottom-up and middle-down proteomics. Here, we demonstrate a method for decreasing the time required for proteolytic digestion of proteins from multiple hours to minutes by using an in-line microstrip cavity for programmed microwave heating. When a nanospray emitter tip, containing a digestion sample, is exposed to a region of highly focused microwave field, the rate of proteolytic digestion is enhanced and the time required for digestion greatly decreased. The design is advantageous for mass spectrometry because the solution-based digestion can then be directly sprayed from a nanoelectrospray tip emitter, decreasing sample transfer loss and allowing the system to be used in a flow-through proteolytic workflow. Microwave-assisted digestion using this method is evaluated against standard overnight digestion protocols using a variety of proteins, evaluating sequence coverage and observed peptide location, digestion rate, and overall efficacy. The influence of applied microwave power is investigated, and enzymatic kinetic parameters are evaluated to estimate temperature within the microreactor. Finally, the modulation of the proteolytic digestion of proteins based upon the modulation of applied microwave power is demonstrated on a time scale of seconds in a flow-through system.


Technical report: Initial experiences with an experimental solid-state universal digital X-ray image detector.
This paper presents a brief technical evaluation and first review of clinical experiences with an experimental direct digital X-ray image detector designed to support both dynamic and snap-shot imaging. Derivatives of this type of image detector can potentially fulfil the majority of the fluoroscopic and radiographic imaging requirements of clinical radiology departments, and initial results suggest that imaging systems using the new technology will provide a high quality dose-efficient solution to the search for a universal digital X-ray image detector.


Experimental retained antrum. Diagnostic technics and histopathologic correlations.
Retained gastric antrum was evaluated in six dogs, and diagnostic methods correlated with histopathology. Secretin and calcium infusion did not significantly alter circulating gastrin levels. 99 mTc scanning was uniformly positive and did not depend on the presence of parietal cells. The failure to consistently develop hypergastrinemia and the absence of gastrin cell hyperplasia suggest that factors other than gastrin may be implicated in the recurrent ulceration seen with retained antrum.


Screening for abdominal aortic aneurysm in a geographically isolated area.
Screening for abdominal aortic aneurysm has been shown to reduce aneurysm-related mortality, but the applicability of the results to the whole of the UK has been questioned. This study examined screening in a remote and rural area. Over 3 years, men aged 65-74 years were offered screening in the community by ultrasonography, usually in general practitioner surgeries. Men with an aneurysm were rescanned at intervals or assessed for surgery. The screening and hospital costs of the programme were calculated. Some 9323 men were offered screening of whom 8355 (89.6 per cent) attended. Uptake was high in all areas. A total of 430 scans (5.1 per cent) were abnormal; 40 men had an aneurysm greater than 55 mm in diameter. Twenty further men had an aorta that enlarged to greater than 55 mm during follow-up. A total of 54 men had elective repair with one death (mortality rate 2 per cent). The cost of screening alone was 16 pound per invitation and the overall cost of the programme, including surgery, was 58 pound per invitation. Screening for abdominal aortic aneurysm can be carried out in a remote and rural area with high uptake, acceptable clinical results and at no greater cost than in more densely populated areas.


Sensors/nanosensors based on upconversion materials for the determination of pharmaceuticals and biomolecules: An overview.
Upconversion materials have been the focus of a large body of research in analytical and clinical fields in the last two decades owing to their ability to convert light between various spectral regions and their particular photophysical features. They emit efficient and sharp ultraviolet (UV) or visible luminescence after excitation with near-infrared (NIR) light. These features overcome some of the disadvantages reported for conventional fluorescent materials and provide opportunities for high sensitivity chemo-and bio-sensing. Here, we review studies that used upconversion materials as sensors for the determination of pharmaceuticals and biomolecules in the last two decades. The articles included in this review were retrieved from the SCOPUS database using the search phrases: "upconversion nanoparticles for determination of pharmaceutical compounds", and "upconversion nanoparticles for determination of biomolecules". Details of each developed upconversion nanoparticles based sensor along with their relevant analytical parameters are reported and carefully explained.


Genome-wide, high-content siRNA screening identifies the Alzheimer's genetic risk factor FERMT2 as a major modulator of APP metabolism.
Genome-wide association studies (GWASs) have identified 19 susceptibility loci for Alzheimer's disease (AD). However, understanding how these genes are involved in the pathophysiology of AD is one of the main challenges of the "post-GWAS" era. At least 123 genes are located within the 19 susceptibility loci; hence, a conventional approach (studying the genes one by one) would not be time- and cost-effective. We therefore developed a genome-wide, high-content siRNA screening approach and used it to assess the functional impact of gene under-expression on APP metabolism. We found that 832 genes modulated APP metabolism. Eight of these genes were located within AD susceptibility loci. Only FERMT2 (a β3-integrin co-activator) was also significantly associated with a variation in cerebrospinal fluid Aβ peptide levels in 2886 AD cases. Lastly, we showed that the under-expression of FERMT2 increases Aβ peptide production by raising levels of mature APP at the cell surface and facilitating its recycling. Taken as a whole, our data suggest that FERMT2 modulates the AD risk by regulating APP metabolism and Aβ peptide production.


Control of Pyragas Applied to a Coupled System with Unstable Periodic Orbits.
We apply a Pyragas-type control in order to synchronize the solutions of a glycolytic model that exhibits an aperiodic behavior. This delay control is used to stabilize the orbits of ordinary differential nonlinear equations systems. Inspired by several works that studied the chaotic behavior of diverse systems for the enzymatic reactions in the presence of feedbacks, the control to two of these models is analyzed.


Platelet ITGA2B inhibits caspase-8 and Rip3/Mlkl-dependent platelet death though PTPN6 during sepsis.
Platelets play an important role in the pathogenesis of sepsis and platelet transfusion is a therapeutic option for sepsis patients, although the exact mechanisms have not been elucidated so far. ITGA2B encodes the αIIb protein in platelets, and its upregulation in sepsis is associated with increased mortality rate. Here, we generated a Itga2b (Q887X) knockin mouse, which significantly reduced ITGA2B expression of platelet and megakaryocyte. The decrease of ITGA2B level aggravated the death of septic mice. We analyzed the transcriptomic profiles of the platelets using RNA sequencing. Our findings suggest that ITGA2B upregulates PTPN6 in megakaryocytes via the transcription factors Nfkb1 and Rel. Furthermore, PTPN6 inhibits platelet apoptosis and necroptosis during sepsis by targeting the Ripk1/Ripk3/Mlkl and caspase-8 pathways. This prevents Kupffer cells from rapidly clearing activated platelets, and eventually maintains vascular integrity during sepsis. Our findings indicate a new function of ITGA2B in the regulation of platelet death during sepsis.


The diagnostic performance of contrast-enhanced ultrasound versus contrast-enhanced computed tomography for pancreatic carcinoma: a systematic review and meta-analysis.
Pancreatic carcinoma is a highly fatal disease, and early diagnosis is of vital importance. This meta-analysis aimed to compare the diagnostic performances of contrast-enhanced ultrasonography (CEUS) against contrast-enhanced computed tomography (CECT) for pancreatic carcinoma, using pathological results or alternative imaging modality as the gold standard. A thorough search was conducted in PubMed, EMBASE, Web of Science and Cochrane Library databases. Two investigators selected the studies and extracted the data independently. A bivariate mixed-effects regression model was used to calculate the pooled data. Subgroup analysis and meta-regression were performed to explore the causes of heterogeneity. A total of 1,227 records were identified, of which 7 articles with 588 patients were assessed for eligibility. The overall sensitivity, specificity of CEUS and CECT with their 95% confidential intervals (95% CI) were 0.91 (0.85-0.94) and 0.88 (0.81-0.92), 0.83 (0.70-0.91) and 0.87 (0.73-0.94), respectively. The area under curve (AUC) of CEUS and CECT were 0.94 and 0.93. Subgroup analysis showed CEUS may be good at diagnosing lesions with diameters less than 2 cm. Tumor features, region and study type were the main causes of heterogeneity. CEUS has a satisfying diagnostic performance for pancreatic carcinoma and it has high sensitivity for small pancreatic carcinomas (≤2 cm); besides, it performs well in discriminating pancreatic cancer from chronic pancreatitis. Therefore, CEUS can be a useful supplement to CECT.


Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications.
The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme-under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness-as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking.


Usefulness of automated assessment of nuclear cardiology for prediction of major cardiac events in Japanese patients with known or suspected coronary artery disease: comparison with conventional visual assessment in a large-scale prognostic study.
There are no reports indicating that automated quantification with a total perfusion deficit (TPD) is used to predict future cardiac events in Japanese patients. We, therefore, aimed to determine the prognostic value of the automated assessment with the TPD for risk stratification of major cardiac events (MCEs) in Japanese patients with known or suspected coronary artery disease (CAD). We retrospectively investigated 2848 patients who underwent rest (201)Tl and stress (99m)Tc-tetrofosmin myocardial perfusion single photon emission computed tomography (SPECT) between October 2004 and March 2008. The follow-up period was 25.8 ± 11.0 months. The TPD was automatically derived from the SPECT image through the QPS software with the Japanese normal database. Twenty segments of SPECT images were analyzed with the 5-point visual scoring model to estimate summed scores. The endpoint of the follow-up was the occurrence of MCEs within 1 year after the SPECT, which were identified with medical records or responses to a posted questionnaire. During the first year of the follow-up, 62 patients had MCEs, which comprised cardiac death (n = 30), non-fatal myocardial infarction (n = 13), and unstable angina pectoris (n = 19). The MCE rates positively correlated with the stress TPD and the summed stress score. Sensitivity of the automated quantification with the TPD for detection of the MCEs was high and similar to that of the visual semi-quantification. Multivariate Cox regression analysis indicated that significant independent predictors for the MCEs were an estimated glomerular filtration rate and the ischemic variables both in the automated quantification and visual semi-quantification. The automated quantification with the TPD is useful for prognostic risk stratification of MCEs in Japanese patients with known or suspected CAD. Its predictive power is similar to that of the visual semi-quantification by expert interpreters.


Contemporary Outcomes of Isolated Tricuspid Valve Surgery.
Isolated tricuspid valve (TV) surgery is uncommonly performed and has historically been associated with excessive operative mortality. We previously reported improved short-term outcomes at our center. Understanding contemporary outcomes of isolated TV surgery beyond the perioperative period is essential to properly benchmark outcomes of newer transcatheter interventions. Patients who underwent isolated TV surgery from 2007 to 2021 at a single institution were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression modeling identified independent risk factors for all-cause mortality. Among 173 patients undergoing isolated TV surgery, 103 (60%) underwent TV repair and 70 (40%) underwent TV replacement. Mean age was 60.3 ± 18.9 y and 55 (32%) were male. The most common etiology of TV disease was functional (46%). In-hospital mortality was 4.1% (7/173), with no difference between TV repair and replacement (P = 0.06). Overall survival at 1 y and 5 y was 78.3% (111/142) and 64.5% (53/82), respectively. After median (interquartile range) follow-up of 2.0 (0.6-4.4) y, patients undergoing TV repair experienced a higher unadjusted survival as compared to those undergoing TV replacement (log-rank P = 0.02). However, after adjusting for covariates, TV replacement was not an independent predictor of all-cause mortality (hazard ratio 1.40; 95% confidence interval, 0.71-2.76; P = 0.33). Isolated TV surgery can be performed with lower operative mortality than historically reported. Establishing survival benchmarks from TV surgery is important in the era of developing transcatheter interventions.


The resistive ground fault of PWM voltage inverter in the EV charging station.
During the direct touch of the inverter output voltage or with the ungrounded shield of the cable connecting the inverter to the motor or other type of load, the nonsinusoidal ground currents with a basic harmonic frequency between 1.5 and 16 kHz, flow via a human's body. Here was proved that Residual Current Device (RCD) ([Formula: see text] = 30 mA) does not switch off the power supply when a ground current with a value of about some hundred milliamps occurs. Because RCDs do not disconnect the power supply, the touch on the inverter's voltage is dangerous to health and life. For the authors, the RCD usage in the Voltage Frequency Converters (VFCs) is not a good engineer practice when high-frequency common-mode distortion currents flow through it. The paper presents tests of RCD operation in the event of a resistance ground fault (via human body) during EV battery charging where the PWM voltage inverter is connected to the external rectifier to provide DC charging battery voltage. Finally, the authors propose a method of eliminating common-mode (CM) current from short protection system by using a separate circuit in which the parasitic leakage current omits an RCD.


Transmembrane protein oligomers of caprine arthritis-encephalitis lentivirus are immunodominant in goats with progressive arthritis.
To dissect mechanisms of caprine arthritis-encephalitis lentivirus-induced arthritis, an undefined immunodominant viral glycoprotein, gp90 (G. C. Johnson, A. F. Barbet, P. Klevjer-Anderson, and T. C. McGuire, Infect. Immun. 41:657-665, 1983), was characterized. Monoclonal antibody to gp90 and specific antiserum to env gene products demonstrated that gp90 was a transmembrane protein (TM) dimer. Goats with progressive arthritis had high antibody titers to oligomeric and monomeric (38-kDa) TM.


Evaluation of a Transitional Care Strategy Implemented in Adults With High-Risk and Multimorbidity in Chile.
Fragmentation of continuity of care impacts the health system's efficiency and increases inequity. It severely affects high-risk patients with multimorbidity, requiring coordinated care to avoid preventable complications. The Centro de Innovación en Salud ANCORA UC, together with the Servicio de Salud Metropolitano Sur Oriente, and the National Health Fund, implemented a transitional care strategy for high-risk adults with multimorbidity at 3 hospitals in the southeast of Santiago. The study aimed to evaluate the impact on length of hospital stay, consultations with primary care physicians and contacts after discharge, and also to describe the implementation process of the transition nurse activities. A cohort study was performed between 2017 and 2019, with 137 hospitalizations from exposed patients and 167 hospitalizations from unexposed patients. The results of the study showed a significant decrease in the length of hospital stays and an increase in consultations with physicians. The results of the implementation process showed that the transition nurse followed-up in a mean of 24 hospitalizations monthly, and 91% of the discharged patients were contacted via the telephone within 7 days. The implementation process showed that the transition nurse's tasks merged with the daily clinical activities in which training on case management, transition care, and continuous support were key aspects of success. We conclude that transitional care intervention has a strong potential in addressing fragmentation of care and is feasible to install and sustain over time in the Chilean context. Finally, this study provides a detailed description of the intervention strategy contributing to its spread and scale-up.


Sargassum horneri (Turner) inhibit urban particulate matter-induced inflammation in MH-S lung macrophages via blocking TLRs mediated NF-κB and MAPK activation.
Sargassum horneri is a nutrient rich edible brown seaweed with numerous biological properties found in shallow coastal areas of Korean peninsula. S. horneri traditionally used as a medicinal ingredient to treat several disease conditions such as hyperlipidemia, hypertension, heart disease, and inflammatory diseases (furuncle). However, to utilize S. horneri as an active ingredient for functional foods and human health applications requires to conform the bioactive properties and underlying mechanisms of those activities. Here, we investigated anti-inflammatory mechanisms of commercial grade 70% ethanol extract separated from S. horneri (SHE) on inflammatory response in particulate matter (PM)-induced MH-S lung macrophages; where PM in breathable air one of the major health concern in Korea. We compared the anti-inflammatory effects of SHE on the activity of toll-like receptors (TLR) activation, NF-κB, MAPKs, and pro-inflammatory cytokine secretion in MH-S lung macrophages exposed to PM as a lung inflammation model. According to the results, PM-stimulation, induced the levels of NO, PGE2, TNF-α, IL-1β, IL-6, iNOS, and COX2 (P < 0.05) in MH-S macrophages. In addition, phosphorylation levels of NF-κB and MAPKs were also increased with the PM stimulation through the upregulated expression of TLR. However, SHE treatment significantly repressed the secretions of inflammatory cytokines and reduced protein expression such as PGE2, TNF-α, IL-6, IL-1β, NF-κB, and MAPKs from PM-activated macrophages. Specifically, SHE inhibited the upregulated mRNA expression levels of TLR2, TLR3, TLR4, and TLR7 in PM-induced MH-S cells; known biomarkers of downstream activation of NF-κB and MAPKs. These results suggested that SHE is a potential inhibitor of PM-induced inflammatory responses in lung macrophages. Thus, SHE could inhibit PM-induced chronic inflammation in lungs via blocking TLR/NF-κB/MAPKs signal transduction. Therefore, it was concluded that SHE may be a useful substance to develop as functional product to reduce inflammation against PM-induced inflammation.


Chemosensitization by misonidazole in CCNU-treated spheroids and tumours.
Misonidazole has been demonstrated to enhance the cytotoxicity of several common antineoplastic drugs in vitro and in vivo, and its mechanism of action as a chemosensitizer, though still unknown, is thought to be dependent upon hypoxia. We have used fluorescence-activated cell sorting to evaluate chemopotentiation by misonidazole as a function of cell position in V79 spheroids and KHT tumours. CCNU toxicity was enhanced in all cell subpopulations of both tumours and spheroids, with greater consistency than might be predicted on the basis of the known variations in oxygen tension. Further, both misonidazole and CCNU as single agents were preferentially toxic in the less well oxygenated regions of each system, arguing that differential toxicity cannot be implicated in the chemopotentiation observed. In fact, increased treatment toxicity did not necessarily lead to increased chemopotentiation, nor was potentiation directly related to the metabolism/binding of the misonidazole. Chemopotentiation in multicell systems thus appears to be a complex, multi-factorial process.


Management of diabetes mellitus: is the pump mightier than the pen?
Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) compared with multiple daily insulin injections (MDI). The greatest reduction in HbA(1c) levels with CSII occurs in patients with the worst glycaemic control; therefore, the most appropriate and cost-effective use of CSII in adults with T1DM is in those who have continued, elevated HbA(1c) levels or disabling hypoglycaemic episodes with MDI (including the use of long-acting insulin analogues and structured patient education). The disadvantages of CSII include higher costs than MDI and the risk of ketosis in the event of pump failure. In children with T1DM, CSII may be used when MDI is considered impractical or inappropriate. Pumps are not generally recommended for patients with type 2 diabetes mellitus but may improve control in some subgroups. A new generation of smaller insulin infusion pumps with an integrated cannula, called patch pumps, could improve uptake of CSII in general. The important clinical question is not whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII further improves glycaemic control when this control continues to be poor with MDI, and evidence exists that in most cases it does.


Effect of blood contamination on the retention characteristics of two endodontic biomaterials in simulated furcation perforations.
The aim of the present study was to compare the effect of blood contamination on retention characteristics of white mineral trioxide aggregate (WMTA) and calcium-enriched mixture (CEM) in reconstructions of the furcation area. Furcal perforations, measuring 1.3 mm in diameter and 2 mm in height, were produced in 180 human mandibular first molars. The teeth were divided into 12 groups of 15. WMTA and CEM were used in groups 1-6 and 7-12, respectively, for perforation repair. In groups 1, 3, 5, 7, 9, and 11 the walls of the perforated area were contaminated with blood; normal saline was injected in the remaining groups. Push-out test was carried out in groups 1, 2, 7, and 8 after 24 hours, in groups 3, 4, 9, and 10 after 72 hours, and in the remaining groups 7 days after placement of the materials by using a Universal test machine. To evaluate the failure modes, the samples were sectioned at furcation floor area, divided in two in the vertical direction, and evaluated under a stereomicroscope at × 40 magnification. Data were analyzed with multivariate analysis of variance and post hoc Tukey tests. The highest (6.75 MPa) and lowest (1.77 MPa) bond strength values were recorded in groups CEM/no blood contamination at 7 days and MTA/blood contamination at 24 hours, respectively. There were no statistically significant differences in bond strength between MTA and CEM (P < .05). However, there were significant differences in bond strength between blood-contaminated and uncontaminated groups in both materials (P < .05); time had exerted a significant effect on the bond strength of the study groups (P < .05). Failure patterns were of the mixed type in all the samples. Resistance of both WMTA and CEM to displacement was similar, and elapse of time from 24 hours to 7 days and contamination resulted in an increase and decrease in bond strength of these 2 materials to dentin, respectively.


Journal standards.
Despite its many imperfections, the peer review process is a firmly established quality control system for scientific literature. It gives readers some assurance that the work and views that are reported meet standards that are acceptable to a journal. Maureen Revington's editorial in a recent issue of the Australian Veterinary Journal (Revington2002) gives a good concise warts and all overview of the process and is well worth reading. I have some concerns about several articles in the December 2002 issue of the New Zealand Veterinary Journal (Volume 50, Number 6), devoted to the health and welfare of farmed deer, that relate to extensive citing of non-peer reviewed papers. I can understand the need for information to flow from researchers to the wider community but that need is already satisfied by publications such as the proceedings of the Deer Branch of the New Zealand Veterinary Association and Proceedings of the New Zealand Society of Animal Production. Non-peer reviewed papers have been cited in the Journal in the past but never to the extent displayed in this particular issue. It degrades the peer-review process and creates an added burden for reviewers who are forced to grapple with the uncertainties of the science in non-peer reviewed citations. One of my fears is that this process allows science from non peer reviewed articles to be legitimised by its inclusion in a peer reviewed journal and perhaps go on to be accepted as dogma. This is a real danger given the difficulties associated with tracing back to original citations and the increasing volume of scientific literature. It also affords opportunities for agencies to pick up questionable and doubtful science and tout it as support for their products or particular points of view. If deer researchers choose to publish most of their work in proceedings then so be it. However this approach, which seems to becoming increasingly prevalent in the deer sector, is questionable from an established science point of view. For my part, I am increasingly reluctant to spend time reading non-peer reviewed material, despite its appeal. At present there are two distinct baskets for scientific literature, one for non-reviewed articles and another for peer reviewed information. I would sincerely hope that we are not going to need another basket as a halfway house for issues that fall in between that classification.


Partial trisomy 10p in two generations.
Two cases of partial 10p trisomy due to a t(10;20)(p12;p12) in two generations of a family are presented. Analysis of 20 known cases of such aberrations confirmed the opinion of Schleiermacher et al. (1974) that partial trisomy 10p is a distinct clinically recognizable entity. The most important diagnostic features of this syndrome are dolichocephaly, prominent forehead, wide open sutures and fontanelles, broad root of the nose, cleft lip and palate, clubfoot, and cystic changes in kidneys.


ONSTEP versus laparoscopy for inguinal hernia repair: protocol for a randomised clinical trial.
The optimal repair of inguinal hernias remains controversial. It is recommended that an inguinal hernia be repaired using a mesh, either with a laparoscopic or an open approach. In Denmark, the laparoscopic approach is used in an increasing number of cases. The laparoscopic repair has a learning curve of about 50-100 cases and decreases chronic pain, but slightly increases the risk of serious complications compared with open mesh repairs. Therefore, a simpler kind of operation is needed. The ONSTEP technique is a possible solution to this problem. The objective of the present randomised clinical trial described in this protocol is to evaluate chronic pain after inguinal hernia repair using the ONSTEP method versus the laparoscopic approach. This study is designed as a non-inferiority, two-arm, multicentre, randomised clinical trial, with a 1:1 allocation to ONSTEP or laparoscopic repair. Patients are recruited from surgical departments in Denmark and follow-up is one year. In total, 188 patients will be included. This protocol describes one of the first randomised clinical trials investigating the ONSTEP technique. To our knowledge, it is the first clinical trial comparing the ONSTEP technique with the laparoscopic technique. The results from this study are needed before it can be decided whether the ONSTEP technique should replace the laparoscopic technique in general surgical practice. This study has not received external funding. NCT01960777 (clinicaltrials.gov).


The retention and recovery of amino acids from pork longissimus muscle following cooking to either 60°C or 75°C.
Samples of pork longissimus muscle (n=16) cooked to either 60°C or 75°C in a water bath for 90 min were assessed for amino acid composition. Recovery of protein in the cooked meat plus the cooking juice was >93% and was slightly higher at 60°C (P=0.031), but retention in the meat was only 89% and 82% for the lower and higher temperatures (P<0.0001). Individual amino acids varied in recovery and retention with retention being particularly low for taurine and histidine. The balance of indispensable amino acids was less than ideal, with leucine and valine being the limiting amino acids by about 30% for both raw and cooked pork. Cooking had no detrimental effect on amino acid balance. Some examples of small effects of genotype and sex on amino acid composition of pork were shown.


Variation in tuberculosis treatment outcomes and treatment supervision practices in Uganda.
Variation in healthcare delivery is increasingly recognized as an important metric of healthcare quality. Directly observed therapy (DOT) has been the standard of care for tuberculosis (TB) treatment supervision for decades based on World Health Organization (WHO) guidelines. However, variation in implementation of DOT and associated TB treatment supervision practices remains poorly defined. We collected individual patient data from TB treatment registers at 18 TB treatment units in Uganda including District Health Centers, District Hospitals, and Regional Referral Hospitals. We also administered a survey and did observations of TB treatment supervision practices by health workers at each site. We describe variation in TB treatment outcomes and TB treatment supervision practices. Of 2767 patients treated for TB across the 18 clinical sites between January 1 and December 31, 2017, 1740 (62.9%) were men, most were of working age (median 35 years, interquartile range [IQR] 27 - 46), 2546 (92.0%) had a new TB diagnosis, and nearly half (45.9%, n = 1283) were HIV positive. The pooled treatment success proportion was 69.4% (95% confidence interval [CI] 67.8 - 71.1) but there was substantial variation across sites (range 42.6 - 87.6%, I-squared 92.7%, p < 0.001). The survey and observation of TB treatment practices revealed that the majority of sites practice community-based DOT (66.7%, n = 12) and request a family member, who receives no additional training or supervision, to serve as a treatment supporter (77.8%, n = 14). At TB medication refill visits, all sites screen for side effects and most assess adherence via self-report (83.3%, n = 15). Only 7 (38.9%) sites followed-up patients who missed appointments using either phone calls (22.2%, n = 4/7) or community health workers (16.7%, n = 3/7). All 18 sites counseled patients at treatment initiation, but none provided additional counseling at refill visits other than addressing poor adherence or missed appointments. There was substantial variation in implementation of DOT, including observation and documentation of daily dosing, training and supervision of treatment supporters, and follow-up for missed clinic visits. Identifying best practices and reducing uncontrolled variation in the delivery of TB treatment is critical to improving treatment outcomes.


Purification of murine IgG3 and IgM monoclonal antibodies by euglobulin precipitation.
We describe a simple and efficient non-chromatographic method for the purification of murine IgG3 and IgM monoclonal antibodies (MAbs) which takes advantage of their euglobulin properties. Following filtration, ascitic fluid is dialysed against demineralized water and centrifuged at 22,000 X g for 30 min. The resulting precipitate is dissolved in a high salt buffer (0.1 M Tris-HCl, 1 M NaCl, pH 8). A second cycle of dialysis and centrifugation yields a product of high purity. Nine IgG3 MAbs and eight IgM MAbs were purified by this procedure. Recovery was greater than 90% for seven of nine IgG3 MAbs. It was less reproducible for IgM MAbs and ranged from 40% to greater than 90% depending on antibody and batch. Purity was assessed by SDS-polyacrylamide gel electrophoresis. The purified immunoglobulin was essentially free of albumin, transferrin, and other mouse ascites proteins. No loss of antibody function was observed.


Genetic analysis of the capsid region of norovirus GII.4 variants isolated in South Korea.
Norovirus is one of the major causes of non-bacterial gastroenteritis in humans. The aim of this study was to analyze the amino acid variation of open reading frame 2 of GII.4 variants in South Korea during the period from November 2006 to December 2012. Sixty-nine complete nucleotide sequences of open reading frame 2 were obtained from 113 GII.4 strains. The GII.4 2006b variants were detected predominantly between 2006 and 2009; however, new GII.4 variants, which were termed the 2010 variant and the 2012 variant, emerged in 2010 and 2012, respectively. The number of GII.4 2006b variants steadily decreased until 2012, whereas the number of gastroenteritis cases caused by the new variants increased between 2010 and 2012. The amino acid sequence in the ORF2 region obtained in this study was compared with other GII.4 variants isolated in various countries. Amino acid variations were observed primarily at epitope sites and the surrounding regions. Amino acids 294, 359, 393, and 413 of the P2 subdomain were the most variable sites among the GII.4 variants. The information in this study can be useful in basic research to predict the emergence and determine the genetic functions of new GII.4 variants.


Downregulation of MACC1 facilitates the reversal effect of verapamil on the chemoresistance to active metabolite of irinotecan in human colon cancer cells.
The aim of this study is to investigate the reversal effect of verapamil (VER) on chemoresistance to irinotecan (CPT-11) in human colon cancer cells and relevant mechanisms. Cell counting kit-8 (CCK-8) test and colony-forming unit (CFU) experiment results show that VER strengthens the sensitivity of human colon cancer cell line HT29 to CPT-11 but has a small effect on SW480 cells. High-throughput transcriptome sequencing, RT-PCR, and Western blot results show that the inhibition of metastasis-associated in colon cancer-1 (MACC1) expression by VER is the key factor for reversal effect on chemoresistance to CPT-11. Transfection experiments further show that VER can reverse the resistance of human colon cancer cells to SN-38, the active metabolite of CPT-11, when MACC1 is overexpressed. The nude mouse transplantation tumor experiment provides an in vivo proof that VER can strengthen sensitivity to CPT-11 in drug-resistant human colon cancer cells, and the effect might be related to the inhibited expression of MACC1. In summary, VER might strengthen the reversal effect of VER on chemoresistance to CPT-11 in human colon cancer cells and facilitate the apoptosis of human colon cancer cells by downregulating MACC1 expression.


Induction of cytodifferentiation in C3H/10T1/2 mouse embryo cells by X-irradiation and benzo(a)pyrene.
5-Azacytidine has been reported to induce adipogenesis and myogenesis in C3H/10T1/2 mouse cells. Additionally, this agent will produce neoplastic transformation of C3H/10T1/2 cells. Very little other data is available regarding induction of differentiation by oncogenic agents. We report here that benzo(a)pyrene and X-irradiation induce a consistent frequency of adipogenesis in C3H/10T1/2 cells. The frequency of induced differentiation is similar to the frequency of the transformation event caused by these agents.


Antigenic analyses of influenza virus haemagglutinins with different receptor-binding specificities.
Monoclonal antibodies were used to compare the antigenicities of the haemagglutinins of two receptor binding mutants of X-31 (H3N2) influenza virus. The mutants which differed from each other in recognizing sialic acid in either alpha 2-6 linkage or alpha 2-3 linkage to galactose also differed exclusively at residue 226 of the HA1 polypeptides of their haemagglutinins (G. N. Rogers, J. C. Paulson, R. S. Daniels, J. J. Skehel, I. A. Wilson, and D. C. Wiley, Nature (London) 304, 76-78, 1983). The results obtained indicate that whereas the majority of antihaemagglutinin monoclonal antibodies react with both mutants equally well, a number which specifically recognize residues 193, 199, 219, and 229 of HA1 of the alpha 2-6 linkage-binding mutant fail to recognize the alpha 2-3 linkage-binding haemagglutinins. The results are discussed with reference to the three-dimensional structure of the haemagglutinin and in relation to differences in antigenicity observed in the haemagglutinins of viruses grown in cells of different types.


Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats.
Subconvulsant doses (20 mg/kg) of pilocarpine administered to a kindled rat convert a kindled seizure to status epilepticus. The hippocampus is involved in such status epilepticus. Furthermore, evidence is accumulating that GABA-mediated inhibition in the hippocampus is chronically diminished by kindling. The studies presented here compared the electrophysiologic effects of pilocarpine in vivo in the CA1 region of the hippocampus in naive and amygdala-kindled rats. A paired pulse paradigm previously shown to quantify the potency of GABAergic inhibition was employed. Stimuli were delivered in the CA3 region of urethane-anesthetized rats and population spikes were recorded in the contralateral CA1 region. In naive rats, pilocarpine (6-60 mg/kg) caused a left shift in the input-output curve measuring stimulus intensity vs population spike amplitudes, indicating an increase in neuronal excitability. In addition, paired pulse inhibition was reduced for interpulse intervals less than 70 ms. In amygdala-kindled rats, neuronal excitability was also enhanced following pilocarpine administration. The potency of baseline paired pulse inhibition was decreased in kindled rats compared to naive controls. Following pilocarpine, inhibition for interpulse intervals less than 70 ms was further reduced, but to a lesser extent than in naive rats. These findings suggest that the ability of subconvulsive doses of pilocarpine to change a discrete kindled seizure triggered by one stimulus to status epilepticus depends on the suppression of GABAergic inhibition below a critical level.


Study of lactoferrin gene expression in human and mouse adipose tissue, human preadipocytes and mouse 3T3-L1 fibroblasts. Association with adipogenic and inflammatory markers.
Lactoferrin is considered an epithelial protein present in different gland secretions. Administration of exogenous lactoferrin is also known to modulate adipogenesis and insulin action in human adipocytes. Here, we aimed to investigate lactoferrin gene expression (real-time polymerase chain reaction) and protein (enzyme-linked immunosorbent assay) levels in human (n=143) and mice adipose tissue samples, in adipose tissue fractions and during human preadipocyte and 3T3-L1 cell line differentiation, evaluating the effects of inducers (rosiglitazone) and disruptors (inflammatory factors) of adipocyte differentiation. Lactoferrin (LTF) gene and protein were detectable at relatively high levels in whole adipose tissue and isolated adipocytes in direct association with low-density lipoprotein-related protein 1 (LRP1, its putative receptor). Obese subjects with type 2 diabetes and increased triglycerides had the lowest levels of LTF gene expression in subcutaneous adipose tissue. Specifically, LTF gene expression was significantly increased in adipocytes, mainly from lean subjects, increasing during differentiation in parallel to adipogenic genes and gene markers of lipid droplets. The induction or disruption of adipogenesis led to concomitant changes (increase and decrease, respectively) of lactoferrin levels during adipocyte differentiation also in parallel to gene markers of adipogenesis and lipid droplet development. The administration of lactoferrin led to autopotentiated increased expression of the LTF gene. The decreased lactoferrin mRNA levels in association with obesity and diabetes were replicated in mice adipose tissue. In conclusion, this is the first observation, to our knowledge, of lactoferrin gene expression in whole adipose tissue and isolated adipocytes, increasing during adipogenesis and suggesting a possible contribution in adipose tissue physiology through LRP1.


Development of fluorizoline analogues as prohibitin ligands that modulate C-RAF signaling, p21 expression and melanogenesis.
Fluorizoline is a cytotoxic trifluorothiazoline that targets the scaffold proteins prohibitins-1 and -2 (PHB1/2) to inhibit the kinase C-RAF and promote the expression of the cyclin-dependent kinase inhibitor p21 to induce cancer cell death. In melanocytes, fluorizoline also induces the synthesis of melanin. Herein we report the first structural requirement of fluorizoline analogues for these activities. We identified in particular some compounds that display enhanced anti-C-RAF and anti-MEK activities, and a higher cytotoxicity in HeLa cells compared to fluorizoline. These results provide a foundation for further optimization of PHB ligands for the treatment of cancers. We also discovered an analogue of fluorizoline that displays pharmacological effects opposed to those of fluorizoline and that can be used as a chemical tool to explore PHB signaling in cancers and other diseases.


Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors.
Involvement of hormonal response (catecholamine release) to acute hypoxia induced by radioprotectors in modification of their radioprotective properties was studied in experiments on outbred mature female albino mice, female albino rats, and dogs of both sexes. The response intensity was evaluated by the reduction of radioprotective and toxic properties of indralin (a α1-adrenoceptor agonist and a radioprotector). The radioprotective effect of indralin was measured using lethal doses of whole-body γ-irradiation ((60)Co) and its acute toxicity was assessed by LD50. It was found that repeated administration of indralin with 30-60-min intervals was followed by weakening of its radioprotective effect. Similar sensitization effect of indralin was observed after pretreatment with cystamine and epinephrine. Comparison of the severity of sensitization after administration of epinephrine and cystamine in the dose providing radioprotective effect showed that the potential aminothiol-induced release of catecholamines can provide optimal long-term radioprotective effect of epinephrine.


Speech Perception in Quiet and in the Presence of Noise in Children with Autism Spectrum Disorder: A Behavioral Study.
Signal-to-noise ratio (SNR) is one of the important parameters to be considered for the effective perception of speech. Many researchers indicate that children with autism spectrum disorder (ASD) have reduced capacity to integrate sensory information across different modalities and show speech understanding difficulty in the presence of background speech or noise. So, this present study was undertaken with the aimed to evaluate and compare the speech perception ability in quiet and in the presence of noise for children with and without ASD and also to compare across different noise conditions. Speech perception in noise was measured for 15 children with ASD and 15 age-matched children without ASD in the age range of 8 to 12 years. The stimulus includes standardized bisyllabic and trisyllabic Kannada words in quiet and at different SNR conditions. The result showed that children with ASD had poor performance in all the listening conditions (quiet, speech babble, and speech noise) and the syllable conditions (bisyllables and trisyllables) compared to children without ASD. When compared across quiet and different SNR conditions for individuals with ASD, the result showed the best performance in quiet conditions followed by different SNR conditions. The performance deteriorated with a decrease in SNR for both groups. Children with ASD showed poor performance in quiet and in the presence of noise compared to children without ASD. Speech perception evaluation in the presence of noise provides a more reliable predictor of the communication difficulty faced by children with ASD than evaluating only in quiet conditions.


Mapping of a major QTL for increased robustness and detection of genome assembly errors in Asian seabass (Lates calcarifer).
For Asian seabass (Lates calcarifer, Bloch 1790) cultured at sea cages various aquatic pathogens, complex environmental and stress factors are considered as leading causes of disease, causing tens of millions of dollars of annual economic losses. Over the years, we conducted farm-based challenges by exposing Asian seabass juveniles to complex natural environmental conditions. In one of these challenges, we collected a total of 1,250 fish classified as either 'sensitive' or 'robust' individuals during the 28-day observation period. We constructed a high-resolution linkage map with 3,089 SNPs for Asian seabass using the double digest Restriction-site Associated DNA (ddRAD) technology and a performed a search for Quantitative Trait Loci (QTL) associated with robustness. The search detected a major genome-wide significant QTL for increased robustness in pathogen-infected marine environment on linkage group 11 (ASB_LG11; 88.9 cM to 93.6 cM) with phenotypic variation explained of 81.0%. The QTL was positioned within a > 800 kb genomic region located at the tip of chromosome ASB_LG11 with two Single Nucleotide Polymorphism markers, R1-38468 and R1-61252, located near to the two ends of the QTL. When the R1-61252 marker was validated experimentally in a different mass cross population, it showed a statistically significant association with increased robustness. The majority of thirty-six potential candidate genes located within the QTL have known functions related to innate immunity, stress response or disease. By utilizing this ddRAD-based map, we detected five mis-assemblies corresponding to four chromosomes, namely ASB_LG8, ASB_LG9, ASB_LG15 and ASB_LG20, in the current Asian seabass reference genome assembly. According to our knowledge, the QTL associated with increased robustness is the first such finding from a tropical fish species. Depending on further validation in other stocks and populations, it might be potentially useful for selecting robust Asian seabass lines in selection programs.


Glucagon-like peptide-1 receptor agonist administration suppresses both water and saline intake in rats.
Glucagon-like peptide-1 (GLP-1) plays an important role in energy homeostasis. Injections of GLP-1 receptor (GLP-1R) agonists suppress food intake, and endogenous GLP-1 is released when nutrients enter the gut. There is also growing evidence that the GLP-1 system is involved in the regulation of body fluid homeostasis. GLP-1R agonists suppress water intake independent of their effects on food intake. It is unknown, however, whether this suppressive effect of GLP-1R agonists extends to saline intake. Accordingly, we tested the effect of the GLP-1R agonists liraglutide (0.05 μg) and exendin-4 (0.05 μg) on water and saline intake, as stimulated either by angiotensin II (AngII) or by water deprivation with partial rehydration (WD-PR). Each agonist suppressed AngII-induced water intake; however, only exendin-4 suppressed saline intake. WD-PR-induced water and saline intakes were both attenuated by each agonist. Analysis of drinking microstructure after WD-PR found a reliable effect of the agonists on burst number. Furthermore, exendin-4 conditioned a robust taste avoidance to saccharine; however, there was no similar effect of liraglutide. To evaluate the relevance of the conditioned taste avoidance, we tested whether inducing visceral malaise by injection of lithium chloride (LiCl) suppressed fluid intake. Injection of LiCl did not suppress water or saline intakes. Overall, these results indicate that the fluid intake suppression by GLP-1R activation is not selective to water intake, is a function of post-ingestive feedback, and is not secondary to visceral malaise.


The Baccalaureate as the Minimum Entry-Level Degree in Dental Hygiene.
A growing body of evidence indicates the baccalaureate degree is needed for dental hygiene (DH) graduates to address the changes in oral health delivery and health systems, develop the societal expectations of a professional, and practice to the full extent of their education. Transitioning from the associate to the baccalaureate as the minimum entry-level degree in DH will better prepare graduates to address the increasingly complex oral health care needs of the public. The higher degree prepares the dental hygienist to serve in roles that will improve access to high-quality care and allow for interprofessional collaboration as a part of a health care team. A higher entry-level degree is also needed to advance the public perception of DH and its recognition as a unique health care profession. However, reported student barriers to the entry-level baccalaureate degree include time and funding constraints, and the belief that the associate degree education is sufficient for clinical practice coupled with a lack of perceived value/benefit of the higher-level degree. This narrative literature review examines relevant policies, standards, and survey data to assess the support for the baccalaureate degree as minimum entry-level education in DH. As the roles for dental hygienists expand to meet the needs of the changing population demographics, the health care market demands for a baccalaureate degree educated dental hygienist will follow. More research is needed to document the value of the baccalaureate-prepared dental hygienist.


Suramin inhibits tumor cell cytotoxicity mediated through natural killer cells, lymphokine-activated killer cells, monocytes, and tumor necrosis factor.
Suramin, a polysulfonated naphthylurea, is an antitrypanosomal and antifilarial drug. Because of its anti-reverse transcriptase activity and antiproliferative activity, suramin is also used for the treatment of acquired immunodeficiency syndrome and cancer. In spite of these uses, very little is known about its effects on the immune system. In this report, we investigated the effects of suramin on peripheral blood mononuclear cells. We found that natural killer (NK) cell-mediated cytotoxicity against human erythroblastoid cell line K562 was completely inhibited by suramin in a dose-dependent manner. It also completely blocked lymphokine-activated killer (LAK) cell-mediated cytotoxicity against the human B lymphoblastoid cell lines Raji and Daudi. The cytotoxicity against the human melanoma tumor cell line A-375 mediated by unstimulated and stimulated monocytes was also suppressed by suramin. Maximum inhibition of monocyte-mediated cytotoxicity was observed when suramin was present during both the activation and the effector phases of cytotoxicity. Besides its effects on cell-mediated cytotoxicity, suramin also inhibited the cytotoxic effects of tumor necrosis factor (TNF) against different tumor cell lines. Furthermore, we found that suramin interferes with the binding of TNF with its receptor. Thus our results indicate that suramin overall downregulates the immune system by inhibiting cell-mediated and TNF-mediated cytotoxicity against different tumor cells.


Development of a cold-start emission model for diesel vehicles using an artificial neural network trained with real-world driving data.
During the cold start and warm-up phase, modern vehicles emit considerable amounts of pollutants due to the incomplete combustion and deteriorated performance of aftertreatment devices. In terms of emission modeling, there have been many attempts to estimate cold start emission such as cold-hot conversion factor, regression model, and physis-based model. However, as the emission characteristic become complicated due to the adoption of aftertreatment devices and various emission control strategies for the strengthened emission regulations, the conventional cold start emission models do not always show satisfactory performances. In this study, artificial neural networks were used to predict the cold start emissions of carbon dioxide, nitrogen oxides, carbon monoxide, and total hydrocarbon of diesel passenger vehicles. We used real-world driving data to train neural networks as an emission prediction tool. Through machine leaning, numerous trainable variables of neural networks were properly adjusted to predict cold start emissions. For input variables of the ANN model, the velocity, vehicle specific power, engine speed, engine torque, and engine coolant temperature were used. The proposed ANN models accurately predicted sharp increases in carbon monoxide, hydrocarbon, and nitrogen oxides during the cold start phase. In addition to the quantitative estimations, the correlations between the operating variables and exhaust gas emissions were visually described in the form of emission maps. The emission map graphically showed the emission levels according to the vehicle and engine operating parameters.


Tread carefully: picking the right path to protecting feline welfare.
When it comes to issues such as neutering and microchipping, cats either have the advantage over their canine counterparts or are set to catch them up. But are they also at risk of following dogs down more perilous paths?


Intrapericardial fibrinolysis in purulent pericarditis-case report.
Purulent pericarditis (PP) continues to result in a very serious prognosis and high mortality. The most serious complication of pericarditis is constriction. Intrapericardial administration of fibrinolytic agents, although controversial, can prevent the development of constrictions. We present the case of a 63-year-old man with purulent inflammation of the right knee who was admitted to the intensive care unit (ICU) via emergency room orthopedic evaluation because of purulent pericarditis. Subxiphoid pericardiotomy was urgently performed, with 1200 ml of thick purulent fluid evacuated. As prevention for pericardial constriction, it was decided to administer fibrinolysis to the patient's pericardial cavity. Administration of streptokinase was complicated by the occurrence of a severe retrosternal pain and intrapericardial bleeding. Due to insufficiency of antibiotic therapy, 17 days after complicated fibrinolytic therapy with streptokinase, it was decided to administer 20 mg of r-tPA directly into the pericardium. In the following days, there remained a high drainage of purulent secretions. Fever up to 38 °C was still observed despite the use of antibiotics. Nine days after first administration of r-tPA, it was decided to apply the next dose. Daily drainage decreased from 50 to 20 ml in successive days. No fluid accumulation and symptoms and signs of constrictions were observed in clinical examinations as well as in echocardiography performed during 7 years follow-up after discharge.


Multiwavelength (0.45-10.6 µm) angle-resolved scatterometer or how to extend the optical window.
An apparatus to record scattered light in whole space over a large range of visible and infrared wavelengths (0.45-10.6 µm) is described. Parasitic light, calibration, and dynamic range are discussed to point out performances and limits of the experimental setup. Angular measurements at several wavelengths give access to bidimensional roughness spectra of polished samples in different frequency bandwidths. The results show overlap of the spectra at the intersection of the bandwidths, which provides an extended view of surface microroughness. In the midinfrared, measurements are more difficult, and specific problems such as thermal emission are analyzed.


Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study).
To determine mortality due to end-stage liver disease (ESLD) in a nationwide cohort of HIV-infected patients 5 years after the introduction of highly active antretroviral therapy (HAART) and to compare this with that observed before and during the early years of HAART. and methods: All departments of internal medicine and infectious diseases from the GERMIVIC Study Group prospectively recorded all deaths in HIV-infected patients during 2001. Sixty-five departments, following a total of 25 178 HIV-infected patients, participated in the study. Results were compared with those of previous surveys conducted using similar methodology in 1995 and 1997. Among 265 deaths observed during 2001, 129 (48.7%) were related to AIDS, 38 (14.3%) to ESLD, and 98 (36.7%) to other causes. Mortality due to ESLD represented 28% of non AIDS-related deaths; 36 of the 38 patients (95%) dying from ESLD had chronic hepatitis C virus (HCV) infection. In 2001, deaths due to ESLD (14.3%) were significantly more frequent than in 1995 (1.5%; P < 0.01) and 1997 (6.6%; P < 0.01). During this interval, the prevalence of hepatocellular carcinoma as a cause of death increased (1995, 4.7%; 1997, 11%; 2001, 25%; P < 0.05), as did alcohol consumption (P < 0.01). In the post-HAART era, ESLD due to HCV is a growing cause of mortality in HIV-infected patients. Increased longevity attributable to HAART, and a higher prevalence of alcohol consumption, are probably involved in this trend.


Transcriptional regulation and transformation by Myc proteins.
Myc genes are key regulators of cell proliferation, and their deregulation contributes to the genesis of most human tumours. Recently, a wealth of data has shed new light on the biochemical functions of Myc proteins and on the mechanisms through which they function in cellular transformation.


The Outcome of Intracranial Meningioma Surgery in Octogenarians: Matched Cohort Study.
Previous studies compared outcomes of intracranial meningioma surgery in octogenarians with outcomes in younger patients without accounting for different tumor locations and sizes. The aim of the current study was to evaluate outcomes of intracranial meningioma surgery in octogenarians taking into account patient preoperative status and comorbidities as well as tumor properties. The study cohort included all octogenarian patients who underwent elective craniotomies for intracranial meningiomas during 2008-2020 and patients <70 years old in the same time period matched for tumor size, tumor location, and preoperative Karnofsky scale score. Each group comprised 31 patients. Postoperative complications were divided into systemic, neurological, and wound related. Mortality and long-term complications were evaluated at 6-month follow-up. Mean age of patients was 82.6 ± 2.6 years for the study group and 57.9 ± 9.9 years for the control group (P < 0.0001). Two octogenarians (6.5%) died within 30 days after elective craniotomy compared with none in the younger group (P = 0.49). Mortality rates at 6 months were comparable between the 2 groups (12.9% vs. 3.2%, P = 0.35). There was no significant difference in overall postoperative complications between the octogenarian and control groups (77.4% vs. 74.2%, P = 0.77). American Society of Anesthesiologists score was the single predictor for any postoperative complications (odds ratio = 2.219, 95% confidence interval 1.024-4.811, P = 0.04). This study found no excess mortality or morbidity in octogenarians compared with younger patients. The American Society of Anesthesiologists score rather than age is a significant risk factor for overall morbidity and mortality following intracranial meningioma surgery in octogenarians.


Differential effect of FR122047, a selective cyclo-oxygenase-1 inhibitor, in rat chronic models of arthritis.
We investigated the effects of FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride), a selective cyclo-oxygenase (COX)-1 inhibitor, in rat type II collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA). Using an ex vivo rat whole blood assay, FR122047 (0.032 - 3.2 mg kg(-1)) inhibited COX-1-derived thromboxane (TX) B(2) production with ED(50) value of 0.059 mg kg(-1), indicating that it was orally active, but did not inhibit lipopolysaccharide-induced prostaglandin (PG) E(2) production derived by COX-2. Oral administration of FR122047 showed a dose-dependent anti-inflammatory effect in rat CIA with ED(50) value of 0.56 mg kg(-1). This drug also dose dependently suppressed the levels of PGE(2) and TXB(2) in CIA rat paws with ED(50) values of 0.24 and 0.13 mg kg(-1), respectively. FR122047 had no effect in rat AIA model. In contrast, indomethacin, a non-selective COX inhibitor, was anti-inflammatory and reduced the formation of PGs in AIA rat paws. Unlike indomethacin, chronic treatment of FR122047 did not damage the stomach mucosa in CIA rats. These results demonstrate that COX-1 contributes to the oedema and the formation of PGE(2) and TXB(2) in rat CIA model, but not in rat AIA model. We conclude that FR122047 has an orally active and anti-inflammatory effect mediated by inhibition of PGE(2) and TXB(2) produced by COX-1 at a site of inflammation induced by type II collagen and it may be a useful tool for studying the involvement of COX-1 in various in vivo models of inflammation.


Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss.
Serum hepatitis B virus (HBV) RNA may reflect intrahepatic HBV replication. Novel anti-viral drugs have shown potent HBV RNA decline without concomitant hepatitis B surface antigen (HBsAg) decrease. How this relates to off-treatment response is yet unclear. To study the degree of on-treatment viral antigen decline among patients with pronounced HBV RNA decrease in relation to off-treatment sustained response and HBsAg loss. HBV RNA, HBsAg and hepatitis B core-related antigen (HBcrAg) were quantified in patients with chronic hepatitis B who participated in two randomised controlled trials of peginterferon-based therapy. Sustained response (HBV DNA <2000 IU/mL) and/or HBsAg loss were assessed in patients with and without on-treatment HBV RNA response (either >2 log HBV RNA decline or >1 log decline resulting in an undetectable value at on-treatment week 24), stratified by concomitant HBsAg decline (<0.5/0.5-1/>1 log). We enrolled 279 patients; 176 were hepatitis B e antigen (HBeAg)-positive, and 103 were HBeAg-negative. Sustained response was achieved in 20.4% of patients. At on-treatment week 24, HBV RNA response was associated with higher sustained response rates (27.4% vs 13.0% in non-responders, P = 0.004). However, among patients with an HBV RNA response (n = 135), 56.4% did not experience >0.5 log HBsAg decline. Among HBV RNA responders, sustained response was achieved in 47.6% of those with >1 log HBsAg decline (n = 20/42), vs 16.0% with <0.5 log decline (n = 12/75, P = 0.001). Similar results were obtained with HBcrAg and when response was defined as HBsAg loss. In this cohort, many patients with HBV RNA response during peginterferon-based treatment did not experience HBsAg and/or HBcrAg decline. The absence of concomitant decline in these viral antigens was associated with low rates of treatment response and HBsAg loss. Future trials should therefore consider kinetics of combined biomarkers to assess anti-viral efficacy. Trial registration, ClinicalTrials.gov: NCT00114361, NCT00146705.


An investigation of the possible immunological relationship between allergen extracts from birch pollen, hazelnut, potato and apple.
In a retrospective study on selected group of patients, the coincidence of birch pollen allergy and a clinically relevant positive prick test reaction to apples and potatoes was confirmed. Immunochemical comparison using the crossed line immunoelectrophoresis technique (CLIE) confirmed partial identity between birch pollen and hazelnut. By the same method no partial immunological identity between birch pollen and extracts and fresh peel from apples and potatoes was found. However, both apples and potatoes gave rise to non-immunological affinity precipitates. On this basis it is discussed, whether the active agents from apples and potatoes were extremely labile allergens, plant lectins, or low molecular weight substances with a direct or indirect histamine release effect.


Brain and Pharyngeal Responses Associated with Pharmacological Treatments for Oropharyngeal Dysphagia in Older Patients.
Impaired pharyngo-laryngeal sensory function is a critical mechanism for oropharyngeal dysphagia (OD). Discovery of the TRP family in sensory nerves opens a window for new active treatments for OD. To summarize our experience of the action mechanism and therapeutic effects of pharyngeal sensory stimulation by TRPV1, TRPA1 and TRPM8 agonists in older patients with OD. Summary of our studies on location and expression of TRP in the human oropharynx and larynx, and clinical trials with acute and after 2 weeks of treatment with TRP agonists in older patients with OD. (1) TRP receptors are widely expressed in the human oropharynx and larynx: TRPV1 was localized in epithelial cells and TRPV1, TRPA1 and TRPM8 in sensory fibers mainly below the basal lamina. (2) Older people present a decline in pharyngeal sensory function, more severe in patients with OD associated with delayed swallow response, impaired airway protection and reduced spontaneous swallowing frequency. (3) Acute stimulation with TRP agonists improved the biomechanics and neurophysiology of swallowing in older patients with OD TRPV1 = TRPA1 > TRPM8. (4) After 2 weeks of treatment, TRPV1 agonists induced cortical changes that correlated with improvements in swallowing biomechanics. TRP agonists are well tolerated and do not induce any major adverse events. TRP receptors are widely expressed in the human oropharynx and larynx with specific patterns. Acute oropharyngeal sensory stimulation with TRP agonists improved neurophysiology, biomechanics of swallow response, and safety of swallowing. Subacute stimulation promotes brain plasticity further improving swallow function in older people with OD.


Providing high-quality care for limited English proficient patients: the importance of language concordance and interpreter use.
Provider-patient language discordance is related to worse quality care for limited English proficient (LEP) patients who speak Spanish. However, little is known about language barriers among LEP Asian-American patients. We examined the effects of language discordance on the degree of health education and the quality of interpersonal care that patients received, and examined its effect on patient satisfaction. We also evaluated how the presence/absence of a clinic interpreter affected these outcomes. Cross-sectional survey, response rate 74%. A total of 2,746 Chinese and Vietnamese patients receiving care at 11 health centers in 8 cities. Provider-patient language concordance, health education received, quality of interpersonal care, patient ratings of providers, and the presence/absence of a clinic interpreter. Regression analyses were used to adjust for potential confounding. Patients with language-discordant providers reported receiving less health education (beta = 0.17, p < 0.05) compared to those with language-concordant providers. This effect was mitigated with the use of a clinic interpreter. Patients with language-discordant providers also reported worse interpersonal care (beta = 0.28, p < 0.05), and were more likely to give low ratings to their providers (odds ratio [OR] = 1.61; CI = 0.97-2.67). Using a clinic interpreter did not mitigate these effects and in fact exacerbated disparities in patients' perceptions of their providers. Language barriers are associated with less health education, worse interpersonal care, and lower patient satisfaction. Having access to a clinic interpreter can facilitate the transmission of health education. However, in terms of patients' ratings of their providers and the quality of interpersonal care, having an interpreter present does not serve as a substitute for language concordance between patient and provider.


Occurrence and contents of trace metals and rare earth elements on plastic pellets.
We determined the occurrence of pellets (2-5 mm) and their composition in terms of trace metals and rare earth elements (REE) on nine sandy beaches of the coast of Bahia, northeastern Brazil. We compared the occurrence of pellets between oceanic and sheltered beaches and the effect of fluvial contribution on the occurrence of these microplastics. The number of pellets found was surprisingly low (i.e., max 45 pellets per m2 in an oceanic beach without fluvial river inputs). Thus, the studied beaches exhibited a very low pollution index. Concentrations of ∑REE in pellets varied between 0.36 and 1.74 mg kg-1 and were ~5-fold higher in white/transparent pellets than in brown pellets. The sum of trace metals (i.e., Fe, Cd, Cu, Ni, Pb, and Zn) was also highest in the white pellets (357 ± 12 mg kg-1). Plastic pellets are a potentially important vector of REE exposition to biota.


Possible role of atrial natriuretic hormone in pituitary-adrenocortical unresponsiveness in lactate-induced panic.
This study investigated whether lactate-induced panic attacks in patients with panic disorder would activate atrial natriuretic hormone, which could explain the missing ACTH and cortisol response found in this kind of experimentally induced panic. Sodium lactate and placebo infusions were administered to 10 patients with panic disorder and to 10 healthy comparison subjects, and the atrial natriuretic hormone responses of the two groups were compared. During lactate infusion both the seven patients who had panic attacks and the eight comparison subjects who did not responded with increased plasma concentrations of atrial natriuretic hormone, but the patients had more pronounced surges of the hormone. Because atrial natriuretic hormone suppresses both pituitary ACTH and adrenal cortisol release, the authors suggest that the immediate rise of atrial natriuretic hormone explains the reported lack of pituitary-adrenocortical activation during lactate-induced panic.


Surgical treatment of non-seminomatous germinal testes tumors.
Surgical management of germinal testis tumors other than seminoma is presented. Phase I consists of removal of the primary tumor; phase II, the surgical removal of retroperitoneal metastatic disease, and phase III, surgical management of chest metastasis. Seventy-two patients were explored with the intent of performing a simultaneous bilateral retroperitoneal lymphadenectomy. Each had a radical orchiectomy prior to exploration. Seven patients were found unresectable because of extensive disease above the renal pedicle and lymphadenectomy was not performed. The remaining 65 were found resectable and a transabdominal bilateral retroperitoneal lymphadenectomy was done. Of this number, 20, or 30%, had metastatic nodes. No other treatment was used. All had a 3-year follow-up and 53 were followed for 5 years or more. The 3-year survivals for stage I is 93%, and for stage II, 75%. Survivals of 5 or more years in stage I are 86% and in stage II, 70%. Thus, this experience with pathologic stage II cases clearly demonstrates the capability of surgery as a primary treatment to control 70% of patients with retroperitoneal lymph node metastases. This surgical technique is therfore recommended as primary therapy in stage I and II non-seminomatous geminal testis tumors.


Primary Care Clinicians' Perceived Role in Addressing Childhood Obesity in the Southern United States.
Primary care is an opportune setting to promote healthy behaviors for children and families. In 2007, an expert committee recommended that pediatric primary care clinicians assess nutrition and physical activity at wellness visits and offer recommendations; however, little is known about what pediatric primary care clinicians perceive their role as in childhood weight management. This qualitative study aimed to describe the perceived role of pediatric primary care clinicians in the prevention and treatment of childhood obesity in South Carolina, a state in the southern United States with high rates of childhood obesity. Pediatric primary care clinicians (n = 23) from South Carolina were recruited for two focus groups. Participants were asked semistructured, open-ended questions, and audio recordings were transcribed verbatim. Themes and subthemes were identified through an iterative coding and consensus-building process with two coders. Excerpts coded under the parent code of "clinician role" centered on three themes: conducting assessments, making referrals, and providing education. Pediatric primary care clinicians in South Carolina coalesced around the important role of addressing childhood obesity within primary care. Notably, clinicians primarily discussed treatment rather than prevention strategies and described changes in the scope of their practice over time as a result of the increasing numbers of pediatric patients with obesity. Addressing childhood obesity within primary care is a critical component of obesity prevention and treatment in the southern United States. Effective, sustainable prevention and treatment within primary care will depend on the involvement of pediatric clinicians, thus emphasizing the importance of understanding how they perceive their role within this setting.


Lurbinectedin in patients with pretreated endometrial cancer: results from a phase 2 basket clinical trial and exploratory translational study.
Second-line treatment of endometrial cancer is an unmet medical need. Lurbinectedin showed promising antitumor activity in a phase I study in combination with doxorubicin in advanced endometrial cancer. This phase 2 Basket trial evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 73 patients with pretreated endometrial cancer. The primary endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), safety and an exploratory translational study. Confirmed complete (CR) and partial response (PR) was reported in two and six patients, respectively (ORR = 11.3%; 95%CI, 5.0-21.0%). Median DoR was 9.2 months (95%CI, 3.4-18.0 months), median PFS was 2.6 months (95%CI, 1.4-4.0 months) and median OS was 9.3 months (95%CI, 6.1-12.8 months). Molecular subtypes showed differences in PFS rate at 6 months (p53abn 23.7% vs. "No Specific Molecular Profile" [NSMP] 42.9%) and median OS (p53abn 6.6 months vs. NSMP 16.1 months). The most common treatment-related adverse events (mostly grade 1/2) were fatigue (54.8% of patients), nausea (50.7%), vomiting (26.0%) decreased appetite (17.8%). and constipation, (19.2%). The most common grade 3/4 toxicity was neutropenia (43.8%; grade 4, 19.2%; febrile neutropenia, 4.1%). In conclusion, considering the exploratory aim of this trial and the hints of antitumor activity observed together with a predictable and manageable safety profile, further biomarker-based development of lurbinectedin is recommended in this indication in combination with other agents. Clinicaltrials.gov identifier: NCT02454972.


Gasless laparoscopic cholecystectomy is not more time-consuming.
Although abdominal wall retraction is said to be advantageous in laparoscopic cholecystectomy (LC), many surgeons have found that, when this option is chosen, more time is needed to prepare for and carry out the surgical procedure. Our aim was to determine the time required for surgical preparation and operation in patients undergoing LC with carbon dioxide (CO2) pneumoperitoneum (CO2 PP) vs abdominal wall retraction (AWR). We performed a prospective randomized study of a CO2 PP LC group (n = 19) vs an AWR LC group (n = 15). Demographic data were collected preoperatively. LC was performed with either CO2 PP (12 mmHg) or AWR (6-10 kps). Two phases were considered: (a) time employed to create the surgical field (phase 1) and (b) operating time (phase 2). The chi-square test was used to compare the medians of the two groups. The two groups were homogeneous. Phase 1 required 35 min in the CO2 PP group vs 25 min in the AWR group (p = 0.24). Phase 2 required 60 min in both groups (p = 0.76). We found no statistically significant difference between the PP CO2 and AWR groups in either time spent to create the surgical field or actual operating time.


Construction of a Range-Separated Dual-Hybrid Direct Random Phase Approximation.
Blending the good performance of the global hybrid PBE0 functional at short-range and the dual-hybrid dRPA75 functional at long range, we propose a new range-separated direct random phase approximation (dRPA75rs), which considerably improves on the accuracy of the calculated reaction energies and barrier heights compared to the parent approaches and provides a good description of noncovalent interactions without any dispersion correction. We also combine the new scheme with spin-component scaling (SCS-dRPA75rs), which enables the accurate calculation of energy differences for processes involving electron pair breaking, such as atomization. The new method scaling as the fourth power of the system size shows a balanced performance on a broad test set involving radicals, transition metal atoms, and heavy atoms, which makes it competitive with the best double-hybrid functionals based on the second-order perturbation theory. According to the results for the homogeneous electron gas, our dRPA75rs method expectedly gives errors for metallic systems similar to the dRPA approach with an additional error cancellation in the case of partial spin polarization.


Knowledge representation of motor activity of patients with Parkinson's disease.
An approach to the knowledge representation extraction from biomedical signals analysis concerning motor activity of Parkinson disease patients is proposed in this paper. This is done utilizing accelerometers attached to their body as well as exploiting video image of their hand movements. Experiments are carried out employing artificial neural networks and support vector machine to the recognition of characteristic motor activity disorders in patients. Obtained results indicate that it is possible to interpret some selected patient's body movements with a sufficiently high effectiveness.


The percentage of superantigen-reactive T cells in peripheral blood significantly decreases before massively increasing in patients with neonatal TSS-like exanthematous disease in the early acute phase.
The behavior of Vbeta2(+) T cells reactive with the pathogenic superantigen toxic shock syndrome toxin-1 (TSST-1) was examined in 12 patients with neonatal TSS-like exanthematous disease (NTED). In 8 patients, the percentage of Vbeta2(+) T cells in peripheral blood (PB) T cells had increased to three times the level in methicillin-resistant Staphylococcus aureus (MRSA)-free neonatal controls, when examined on days 4 to 7 of life. In the remaining 4 patients, however, the percentage of Vbeta2(+) T cells was significantly low, i.e., ranging from less than 10% to 30% of the control level, when they were examined on days 4 to 8 of life, and the percentage increased dramatically several days later, indicating that these patients actually had NTED. We recommend that, in patients who are suspected of having NTED, when an increase in Vbeta2(+) T cells is not observed in a comparatively early period of the illness, reassessment of the Vbeta2(+) T cells should be carried out 2 to 4 days later, to obtain a conclusive diagnosis of NTED.


Early diagenetic behavior of trace metals along with estimation of their diffusive fluxes: Ecological risk assessment in pore water and sediment of Bizerte Lagoon, Tunisia.
Bizerte Lagoon is a vital Mediterranean ecosystem subjected to intense anthropogenic pressure. The potential ecological risk caused by certain metals (Zn, Cu, Cr, Cd, Ni, Pb and Mn) is assessed from the data carried out in the sediment and pore water at two sites along with identifying the effects of diagenetic processes on the vertical distribution of these metals and their resulting diffusive fluxes. Using various ecological indices our results reveal a high ecological risk to benthic organisms from metals chiefly Cd, Pb and Ni accumulated in the sediment at both sites. Metals derived from organic matter degradation (Cu and Cd) and/or reduction of Mn-Fe-oxyhydroxydes (Pb, Ni, Zn, Cr) due to early diagenetic processes in sediment. The resulting concentration gradients between pore water and overlying water induce diffusive fluxes of metals to the water column. The estimation of the potential ecological risk caused by dissolved metals in pore waters by application of the Interstitial Water Criteria Toxic Units index indicates a slight ecological risk by Cu that was not identified in sediment. The ecological risk posed by dissolved metals is evidenced from -6 cm depth, which reduces the possibility of contamination of benthic species living above the water-sediment interface by diffusive fluxes of these metals.


The use of feedback training and a stimulus control procedure to obtain large magnitude increases in heart rate outside of the laboratory.
A series of eight single-subject experiments were performed to test the feasibility of using a stimulus control procedure to teach subjects to control heart rate in the absence of feedback and outside of the laboratory. Four of the six subjects who completed the experiments were able to demonstrate increases in heart rate of from 15 to 35 beats per minute without the assistance of feedback and outside of the laboratory. These increases were consistently produced over six daily sesssions. Through the use of a systematic replication series of experiments, it was possible tentatively to rule out age, sex, and basal heart rate of subject, as well as type of previous feedback training and number of prior training sessions, as accounting for the differential success.


Quality evaluation of low fat bologna-type meat product with a nutritional profile designed for the elderly.
The objective of this work was to evaluate the quality of a bologna-type meat product designed for the elderly. Treatments were: control, without addition of cranberries (C), prunes (P), pecan nuts (N) or flaxseed (F); NP, with 5% N+5% P; FC, with 5% F+5% C; NC, with 5% N+5% C; FP, with 5% F+5% P. These formulations resulted in a product with high protein, low SFA and high antioxidant activity. Treatments with pecan nuts had higher MUFA while those with flaxseed had higher polyunsaturated fatty acids (PUFA). Treatments with pecan nuts and flaxseed had higher PUFA/SFA ratios, but only those with flaxseed had very low n6/n3 ratios when compared to the control. Although treatments showed acceptable scores (>5.4), they were lower than the control. A combination of these non-traditional ingredients could be used to develop a meat product for older adults to provide a better nutritional profile with acceptable sensory properties.


Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we eat?
Americans consume billions of hotdogs per year resulting in more than a billion dollars in retail sales. Package labels typically list some type of meat as the primary ingredient. The purpose of this study is to assess the meat and water content of several hotdog brands to determine if the package labels are accurate. Eight brands of hotdogs were evaluated for water content by weight. A variety of routine techniques in surgical pathology including routine light microscopy with hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and electron microscopy were used to assess for meat content and for other recognizable components. Package labels indicated that the top-listed ingredient in all 8 brands was meat; the second listed ingredient was water (n = 6) and another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the total weight. Meat content determined by microscopic cross-section analysis ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42) roughly correlated with meat content. A variety of tissues were observed besides skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8), plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n = 4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not observed in any of the hotdogs. Lipid content on oil red O staining was graded as moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed recognizable skeletal muscle with evidence of degenerative changes. In conclusion, hotdog ingredient labels are misleading; most brands are more than 50% water by weight. The amount of meat (skeletal muscle) in most brands comprised less than 10% of the cross-sectional surface area. More expensive brands generally had more meat. All hotdogs contained other tissue types (bone and cartilage) not related to skeletal muscle; brain tissue was not present.


Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces actuosus leads to increased production of nosiheptide.
S-Adenosylmethionine (SAM) is synthesized via the metabolic reaction involving adenosine triphosphate and L-methionine that is catalyzed by the enzyme S-adenosyl-L-methionine synthetase (SAM-s) and encoded by the gene metK. In the present study, metK with the absence of introns from Saccharomyces cerevisiae was introduced into Streptomyces actuosus, a nosiheptide (Nsh) producer. Intracellular SAM levels were determined by high-pressure liquid chromatography. Through optimizing the nutrient content of the medium, it was shown that increased SAM production induced by the overexpression of SAM-s leads to an increase in the intracellular cysteine pool and overproduction of Nsh in S. actuosus. This investigation shows that increased SAM promotes the elevated production of the non-ribosomal thiopeptide Nsh in Streptomyces sp.


Efficacy of adjuvant laser therapy in reducing postsurgical complications after the removal of impacted mandibular third molars: A systematic review update and meta-analysis.
The authors updated a previously published systematic review to assess the effects of low-level laser therapy (LLLT) on reducing complications after the removal of impacted mandibular third molars. The authors searched for randomized clinical trials in which the investigators evaluated the efficacy of LLLT compared with that of placebo or no treatment. Two reviewers independently screened studies, extracted data, and assessed risk of bias. The authors used random effects model meta-analysis and the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of evidence. The authors included 21 studies. There was low-certainty evidence that LLLT results in less pain at 2 days after surgery (mean difference [MD], -1.42 on a 10 point scale; 95% confidence interval [CI], -2.18 to -0.67) and moderate certainty that it results in negligibly less pain at 7 days (MD, -0.59; 95% CI, -0.96 to -0.22); moderate-certainty evidence that LLLT has a negligible benefit on reducing trismus at 2 days (MD, -3.42 millimeters; 95% CI, -5.34 to -1.50) and at 7 days after surgery (MD, -2.30 mm; 95% CI, -3.96 to -0.64); lastly, there was moderate-certainty evidence that LLLT results in less postoperative swelling at 2 days (standardized MD, -0.82; 95% CI, -1.28 to -0.35) and low-certainty evidence that LLLT results in negligibly less postoperative swelling at 7 days after surgery (standardized MD, -0.17; 95% CI, -0.4 to 0.07). Low-quality evidence suggests that LLLT will not cause adverse effects. LLLT probably has negligible benefits but may not result in adverse events. Evidence does not support the use of LLLT in clinical practice to reduce complications after impacted mandibular third-molar surgical extractions.


Method for the simplistic modelling of the acoustic footprint of the vessels in the shallow marine area.
The definitions of the 11th descriptor of the EU Marine Strategy Framework Directive (MSFD) "Underwater noise and other forms of energy" outlines the standards for the continuous noise evaluation and monitoring in the European seas. Long lasting fluctuations of the continuous underwater noise at the shallow marine areas in the low frequency bands (<1 kHz) are mostly associated with the shipping noise, where these fluctuations are sensitive to changes in the spatial distribution of human activities, or changes of environmental and climatic variables. Underwater noise modelling is usually considered as a supplement to noise measurements, where models increases the utility of the measurement results. Noise mapping is considered as a form of spatial modelling, providing a convenient and accessible way to visualise models. Therefore, underwater noise models and maps can be used in management and evaluation of environmental state. There are number of freely available widely used noise source and sound propagation models. Still the simplistic logarithmic rules purposed for the sound propagation loss computations do not account for the number of factors in the marine environment, i.e. sediment type, water depth or frequency. On the other hand the sophisticated physical models purposed for the description of the footprint of noise sources such as ships are complex and their programing requires very specific knowledge. In this paper the details of the method purposed for modelling of the ship noise footprint in shallow seas is presented. Proposed method allows to compute: •depth dependent ship sound transmission losses in 1 Hz frequency bands;•sound propagation losses during different seasons (summer/winter);•acoustic footprint accounting for vessel noise directivity.