Statistically robust estimation of source bearing via minimizing the Bhattacharyya distance.
Source bearing estimation is a common technique in acoustic array processing. Many methods have been developed and most of them exploit some underlying statistical model. When applied to a practical system, the robustness to model mismatch is of major concern. Traditional adaptive methods, such as the minimum power distortionless response processor, are notoriously known for their sensitivity to model mismatch. In this paper, a parameter estimator is developed via the minimum Bhattacharyya distance estimator (MBDE), which provides a measure of the divergence between the assumed and true probability distributions and is, thus, capable of statistically matching. Under a Gaussian random signal model typical of source bearing estimation, the MBDE is derived in terms of the data-based and modeled covariance matrices without involving matrix inversion. The performance of the MBDE, regarding the robustness and resolution, is analyzed in comparison with some of the existing methods. A connection with the Weiss-Weinstein bound is also discussed, which gives the MBDE an interpretation of closely approaching a large-error performance bound. Theoretical analysis and simulations of bearing estimation using a uniform linear array show that the proposed method owns a considerable resolution comparable to an adaptive method while being robust against statistical mismatch, including covariance mismatch caused by snapshot deficiency and/or noise model mismatch.


Iron uptake, transport and storage in marine brown algae.
Iron is a vital although biologically inaccessible trace nutrient for nearly all forms of life but "free" iron can be deleterious to cells and thus iron uptake and storage must be carefully controlled. The marine environment is particularly iron poor making mechanisms for its uptake and storage even more imperative. In this brief review we explore the known and potential iron uptake and storage pathways for the biologically and economically important marine brown macroalgae (seaweeds/kelps).


Isolation and partial characterization of the amino-terminal propeptide of type II procollagen from chick embryos.
The amino-terminal propeptide from type II procollagen was isolated from organ cultures of sternal cartilages from 17-day-old chick embryos. The procedure provided the first isolation of the propeptide in amounts adequate for chemical characterization. The propeptide had an apparent molecular weight of 18000 as estimated by gel electrophoresis in sodium dodecyl sulfate. It contained a collagen-like domain as demonstrated by its amino acid composition, circular dichroism spectrum, and susceptibility to bacterial collagenase. One residue of hydroxylysine was present, the first time this amino acid has been detected in a propeptide. The peptide contained no methionine and only two residues of half-cystine. Antibodies were prepared to the propeptide and were used to establish its identity. The antibodies precipitated type II procollagen but did not precipitate type II procollagen from which the amino and carboxy propeptides were removed with pepsin. Also, they did not precipitate the carboxy propeptide of type II procollagen. The data demonstrated th at the type II amino propeptide was similar to the amino propeptides of type I and type III procollagens in that it contained a collagen-like domain. It differed, however, in that it lacked a globular domain as large as the globular domain of 77-86 residues found at the amino-terminal ends of the pro alpha 1 chains of type I and type III procollagens.


Intake of alcohol may modify the risk for non-melanoma skin cancer: results of a large Danish prospective cohort study.
Alcohol has not been linked definitively to non-melanoma skin cancer. We examined whether alcohol intake affects the risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) using data on 54,766 persons enrolled in the prospective Diet, Cancer, and Health cohort. Statistical analyses were based on the Cox proportional hazards model. All hazard ratios (HRs) were multivariate adjusted. Adjustment for exposure to UVR was not possible, but all analyses were adjusted for factors related to susceptibility to UVR, including sun sensitivity, degree of freckling, and number of nevi. A total of 2,409 BCC cases and 198 SCC cases were diagnosed within a median follow-up of 11.4 years. Total current alcohol intake was not associated with BCC risk, but beverage-specific analyses showed an increased BCC risk associated with intake of wine (HR=1.05, 95% confidence interval (CI): 1.02-1.08, current average alcohol intake, per 10 g per day) and spirits (HR=1.11, 95% CI: 1.02-1.21) and a decreased risk with beer (HR=0.97, 95% CI: 0.93-1.00). No convincing associations were found between total alcohol intake and risk for SCC, perhaps because of the limited number of cases. Our findings indicate that alcohol intake may increase the risk for BCC, but the relations seemed to depend on beverage type.


Associations of Various Nighttime Noise Exposure Indicators with Objective Sleep Efficiency and Self-Reported Sleep Quality: A Field Study.
It is unclear which noise exposure time window and noise characteristics during nighttime are most detrimental for sleep quality in real-life settings. We conducted a field study with 105 volunteers wearing a wrist actimeter to record their sleep during seven days, together with concurrent outdoor noise measurements at their bedroom window. Actimetry-recorded sleep latency increased by 5.6 min (95% confidence interval (CI): 1.6 to 9.6 min) per 10 dB(A) increase in noise exposure during the first hour after bedtime. Actimetry-assessed sleep efficiency was significantly reduced by 2%-3% per 10 dB(A) increase in measured outdoor noise (Leq, 1h) for the last three hours of sleep. For self-reported sleepiness, noise exposure during the last hour prior to wake-up was most crucial, with an increase in the sleepiness score of 0.31 units (95% CI: 0.08 to 0.54) per 10 dB(A) Leq,1h. Associations for estimated indoor noise were not more pronounced than for outdoor noise. Taking noise events into consideration in addition to equivalent sound pressure levels (Leq) only marginally improved the statistical models. Our study provides evidence that matching the nighttime noise exposure time window to the individual's diurnal sleep-wake pattern results in a better estimate of detrimental nighttime noise effects on sleep. We found that noise exposure at the beginning and the end of the sleep is most crucial for sleep quality.


Endosymbiosis and Eukaryotic Cell Evolution.
Understanding the evolution of eukaryotic cellular complexity is one of the grand challenges of modern biology. It has now been firmly established that mitochondria and plastids, the classical membrane-bound organelles of eukaryotic cells, evolved from bacteria by endosymbiosis. In the case of mitochondria, evidence points very clearly to an endosymbiont of α-proteobacterial ancestry. The precise nature of the host cell that partnered with this endosymbiont is, however, very much an open question. And while the host for the cyanobacterial progenitor of the plastid was undoubtedly a fully-fledged eukaryote, how - and how often - plastids moved from one eukaryote to another during algal diversification is vigorously debated. In this article I frame modern views on endosymbiotic theory in a historical context, highlighting the transformative role DNA sequencing played in solving early problems in eukaryotic cell evolution, and posing key unanswered questions emerging from the age of comparative genomics.


Caries decline in the primary dentition of Belgian children over 15 years.
(1) To investigate changes in caries prevalence in the primary dentition of children resident in Brussels, Belgium between 1983 and 1998, (2) to analyse associations between changes in caries and children's socioeconomic and ethnic aspects. In the Brussels region, children in the first grade at the same schools were sampled in cohort 1983 (n = 396) and cohort 1998 (n = 473). Caries experience of Belgian and non-Belgian nationals was summarized in dmf scores. The socioeconomic status of the children was established based on their parents' education and profession. The children were categorized in eight subgroups in relation to their socioeconomic status, ethnic origin and cohort (SESEC subgroups). The percentage of caries-free children increased significantly from 31.5% to 47.5%. A reduction was observed in the dmft scores from 3.9 to 2.3 (P < 0.001) and in the dmfs scores from 6.9 to 5.0 (P < 0.001). The odds ratio of being caries-free was 2.5 times higher for privileged children and 2.3 times higher for children belonging to cohort 1998. The ANCOVA analyses revealed that most of the SESEC subgroups showed significant reduction in dmft scores from 1983 to 1998 (P < 0.003). Children resident in Brussels showed caries decline in their primary dentition over 15 years. Diversity in caries decline was associated with children's socioeconomic status and ethnic origin.


ISPa46, a novel insertion sequence in the oprD porin gene of an imipenem-resistant Pseudomonas aeruginosa isolate from a cystic fibrosis patient in Marseille, France.
Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to carbapenems were recovered from a French patient with cystic fibrosis (CF) who had not received carbapenem therapy. This study was conducted to investigate the molecular mechanism conferring the carbapenem-resistant phenotype in clinical isolates of P. aeruginosa recovered from the same CF patient chronically colonised since 2005. Investigation of imipenem resistance of P. aeruginosa strain_02 isolated in May 2011 showed no carbapenemase activity. However, amplification and sequencing of the oprD porin gene revealed disruption of this gene by an insertion sequence (IS) element of 1337 bp that contained a novel transposase of 1227 bp (ISPa46) bordered by two terminal imperfect inverted repeats of 28 bp, which was associated with carbapenem resistance. Retrospective analysis of five additional strains of P. aeruginosa isolated before May 2011 from the same patient revealed that all isolates were likely to be the same clone by multilocus sequence typing analysis (ST540/551), but one of the five isolates was imipenem-susceptible. Although it was possible to demonstrate the presence of ISPa46 in all strains by PCR, this IS was transposed in the oprD gene only for imipenem-resistant isolates. Therefore, this study reports a novel IS element (ISPa46) in P. aeruginosa clinical isolates of a CF patient in Marseille, France, that was associated with carbapenem resistance and was selected in the absence of carbapenem treatment.


Natural Language Processing Accurately Identifies Dysphagia Indications for Esophagogastroduodenoscopy Procedures in a Large US Integrated Healthcare System: Implications for Classifying Overuse and Quality Measurement.
Recent evidence suggests almost half of repeat esophagogastroduodenoscopy procedures (EGDs) are overused; this prior research relied on administrative data that are often inaccurate. Our primary objective was to determine and compare the accuracy of natural language processing and administrative data to manual chart review to identify dysphagia indications for EGD procedures within the national VA healthcare system. From 396,856 EGD notes identified from 2008-2014, we classified 119,920 as "index" procedures in 2010-2012. We compared the performance of our NLP to ICD codes to correctly identify dysphagia indications in the index EGD procedures and in repeat EGD procedures. We used linked pathology data to describe esophageal biopsies performed during these EGDs. NLP performed significantly better and identified significantly more index and repeat EGD procedures with dysphagia indications than ICD codes, which has critical implications for determining appropriateness of EGD procedures.


Effect of α-Tocopherol on Lipid Peroxidation Caused by Cisplatin in Rat Kidney.
Cisplatin (CDDP) is one of the most commonly used antineoplastic agents in current clinical practice. The major toxicities of CDDP are nonhaematological as nephrotoxicity and ototoxicity. Free oxygen radicals are known to play major role in CDDP-induced acute renal failure in rats. α-tocopherol is one of the well-known antioxidant agents. This study was designed to investigate the role of α-tocopherol pretreatment against CDDP-induced lipid peroxidation in rat kidney. Male Wistar rats were divided into three groups and treated as follows: control (saline intraperitoneally), CDDP (10 kg/kg, intraperitoneally), α-tocopherol (200 kg/kg, plus CDDP, intraperitoneally). Rats were sacrificed on third day of the treatment, and kidney tissues were obtained and analyzed. CDDP-treated rats showed high malondialdehyde (MDA) levels (p< 0.05). In the CDDP plus α-tocopherol group, renal MDA levels were not significantly different from the controls. These data suggest that α-tocopherol may be used to prevent CDDP-induced lipid peroxidation.


Symmetrical Progressive Erythrokeratoderma.
A case of symmetrical progressive erythrokeratoderma in a 32 year old male patient noticed at the age of 27 years has been described.


Relation between cognitive restraint and weight: Does a content validity problem lead to a wrong axis of care?
The aim of this research is to examine the relation between weight and cognitive restraint (CR), which is the intention to control food intake in order to maintain or lose weight, in a general French population sample. Is CR more prevalent in individuals with obesity than overweight, underweight or normal-weight subjects in this cross-sectional study? Are people affected by obesity non-restrained eaters? A total of 507 French people (80.2% women and 19.8% men), aged 18-78 years, responded to an online questionnaire. It appears that the most used questionnaire measuring CR has content validity problems as it seems to measure effective control and not the intention. Therefore, a numeric scale was used to answer the questions. Even if it is not possible in this study to test a causal link with latent variable modelling, our results seem to show that people with obesity more frequently intend to eat less or to eat healthier and/or to eat less sugar and fat than other people in order to control their weight. However, people affected by obesity do not succeed in so doing. These results raise the question of treatments advocating the increase of self-control. Finally, it would be necessary to obtain a real, scientific consensus on what CR is and on how to measure it in order to study the most effective treatments for people with overweight or obesity.


Development of a Web-based event reporting system in an academic environment.
In pursuit of a strategy for patient safety and error reduction, The Ohio State University Health System developed and implemented a standardized voluntary event reporting system. The Web-based application is user friendly as well as context-sensitive and encompasses a broad range of errors, events, and near misses. A full organizational transformation was required to effectively implement the system, which involved process reengineering for event entry and for postentry automated workflows. This system serves as the foundation for efficient and consistent reporting processes, which are essential for encouraging a culture of commitment to patient safety.


Homoleptic and heteroleptic ketodiiminate zinc complexes for the ROP of cyclic l-lactide.
Homo- and heteroleptic ketodiiminate zinc complexes L12Zn2 (1, L1 = [Me2NC2H4NC(Me)CH]2CO), L2(ZnCp)2 (2, L2 = [Me2NC3H6NC(Me)CH]2CO, Cp = C5H5) and L2HZnCp* (3, Cp* = C5Me5) were synthesized and characterized by 1H and 13C NMR and IR spectroscopy as well as by elemental analysis and single crystal X-ray diffraction (sc-XRD, 2, 3). The catalytical activity of heteroleptic complexes 2 and 3 were tested in the ring-opening polymerization (ROP) of l-lactide. Homobimetallic complex 2 showed the highest activity and selectivity for the synthesis of cyclic polylactide (cPLLA; TOF = 17 460 h-1) at 100 °C in toluene solution, while linear polymers are formed with mononuclear complex 3.


Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma.
Merkel cell carcinoma (MCC) or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play a yet uncertain role in sensory transduction. Here we present the case of a 54- year old female with a basal cell carcinoma (BCC) of the skin with neuroendocrine features (positivity for chromogranin) that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphological and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy). The progression from a chromogranin positive basal cell carcinoma of the skin, to a high-grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.


Rapid modulation of GABA concentration in human sensorimotor cortex during motor learning.
Movement representations within the human primary motor and somatosensory cortices can be altered by motor learning. Decreases in local GABA concentration and its release may facilitate this plasticity. Here we use in vivo magnetic resonance spectroscopy (MRS) to noninvasively measure serial changes in GABA concentration in humans in a brain region including the primary sensorimotor cortex contralateral to the hand used for an isometric motor sequence learning task. Thirty minutes of motor sequence learning reduced the mean GABA concentration within a 2 x 2 x 2-cm3 voxel by almost 20%. This reduction was specific to motor learning: 30 min of similar, movements with an unlearnable, nonrepetitive sequence were not associated with changes in GABA concentration. No significant changes in GABA concentration were found in the primary sensorimotor cortex ipsilateral to the hand used for learning. These changes suggest remarkably rapid, regionally specific short-term presynaptic modulation of GABAergic input that should facilitate motor learning. Although apparently confined to the contralateral hemisphere, the magnitude of changes seen within a large spectroscopic voxel suggests that these changes occur over a wide local neocortical field.


[Value of brain perfusion SPECT in the follow-up of patients surgically treated for chronic adult hydrocephalus syndrome].
The aim of this study was to characterize regional cerebral blood flow in patients with Adult Hydrocephalus Syndrome (AHS) and to evaluate the changes in brain perfusion after surgical derivation treatment. 20 patients with AHS (age: 72 +/- 14, 12 men) were studied before and six months after surgery. All patients underwent a brain perfusion SPECT (99mTc-HMPAO) prior to surgery and at 6 months post-surgery. Semi-quantitative analysis was done for brain uptake: 0=Normal, 1=Mild, 2=Moderate, 3= Severe, 4=No uptake. The severity of ventricular dilatation was assessed by classifying the intensity and extension of subcortical defects: 0=Normal, 1=Mild, 2=Moderate, 3=Severe. The scores of the pre- and post-surgical studies were compared using the Student-t test. A global reduction of brain uptake was observed (mean score 12.85), mainly in frontal, parietal and temporal lobes, with a significant improvement in post surgical studies (mean score 6, p<0,001). After surgery, 16 (80%) of the 20 patients improved brain uptake. In relationship to subcortical uptake, 5 patients showed mild defects, 9 moderate defects and 6 patients presented severe uptake reduction. In post-surgical studies 15 (75%) patients improved almost one degree in the subcortical score and 65% of the patients showed a normal or mild subcortical uptake reduction. Brain perfusion SPECT is useful in patients with AHS, detecting brain perfusion defects and evaluating cerebral blood flow improvement after shunt operation.


[The impact of detecting endothelial dysfunction in atherosclerosis: Role of positron emission tomography (PET)].
The endothelium plays an important role in the regulation of the intracellular fluid, vascular permeability, and modulation of vascular focal tone and angiogenesis. Endothelial dysfunction is manifested by the loss of the endothelium ability to modulate physiology changes in its vascular bed, and actually it is considered a prognostic marker of coronary artery disease. The relevance of assessing endothelial dysfunction relies in that it has been observed in different pathologies like DM, dyslipidemia, hypertension, tabaquism and in immunologic diseases like antiphospholipid syndrome and systemic lupus. PET is a non invasive method that allows the absolute quantification of myocardial blood flow during rest, stress and adrenergic stimulation, which allows to asses endothelial function. Therefore PET is a useful diagnostic technique to identify patients with endothelial dysfunction, and in the assessment of its response to administered therapy, allowing an optimal control and prevention of secondary adverse events of these diseases.


Deflecting load of nickel titanium rotary instruments during cyclic fatigue.
The dispersion of the lifetime of NiTi instruments, and their deflecting load (DL) changes during cyclic fatigue were investigated. A total of 120 ProFile NiTi rotary instruments were tested using a specially designed cyclic fatigue testing apparatus with three pins. Using these pins, the instrument was bent and rotated at 300 rpm to fracture. DL was recorded using a load cell attached to the central pin. For each sample, the working time was converted to number of cycles to fracture (NCF) and the mean DL (DL(m)) was calculated. The averages of NCF and DL(m) of 120 samples were 584.3±180.5 cycles and 6.44±0.91 N, respectively. All samples showed a sequential decrease in DL during rotation. Based on the present study, it is impossible to estimate the lifetime of a NiTi instrument from NCF. Thus, the change in DL could be an alternative criterion to determine the remaining lifetime.


miR-25-3p promotes glioma cell proliferation and migration by targeting FBXW7 and DKK3.
MicroRNAs (miRs) serve important roles in glioma. However, the underlying molecular mechanism of miR-25 in glioma progression remains largely unknown; therefore, it was investigated in the present study. RT-qPCR analysis revealed that miR-25 expression levels were markedly increased in human glioma tissue and glioma cell lines compared with normal brain tissues and normal human astrocytes, respectively. miR-25 upregulation exhibited an association with glioma progression, and the knockdown of miR-25 significantly inhibited glioma cell proliferation and migration. F-box and WD repeat domain containing 7 (FBXW7) and dickkopf WNT signaling pathway inhibitor 3 (DKK3) were identified as target genes of miR-25. FBXW7 and DKK3 expression levels were significantly downregulated in glioma tissue samples compared with normal brain tissue, and their expression levels were negatively regulated by miR-25 expression in glioma cells. Furthermore, inhibition of FBXW7 and DKK3 expression suppressed the miR-25-induced effects on glioma cell proliferation and migration. The findings of the present study suggest that miR-25 may promote glioma cell proliferation and migration by inhibiting the expression of FBXW7 and DKK3. Therefore, miR-25 may serve as a promising molecular target for the treatment of glioma.


Stereospecific substitution of enantiomerically pure 1-(2-pyridinyl)ethyl methanesulfonate with beta-dicarbony compounds.
The alkylation of the sodium salt of the malonic acid diester with (R)-1-(2-pyridinyl)ethyl methanesulfonate (2) gave the dimethyl (R)-[1-(2-pyridinyl)ethyl]malonate (3a), stereospecifically. The alkylation reaction of methyl acetoacetate gave the methyl (2'S,2R/2S)-3-oxo-2-[1-(2-pyridinyl)ethyl]butanoate (3d) along with the methyl (S)-3-[1-(2-pyridinyl)ethoxy]-2-butenoate (4d). The acid hydrolysis and decarboxylation of 3d under acidic conditions gave (R)-4-(2-pyridinyl)pentan-2-one (6), and the alkylation of methyl (R)-[1-(2-pyridinyl)ethyl]acetoacetate with benzyl bromide gave a mixture of C-benzylated and O-benzylated products 7 and 8.


Tumor-TME Bipartite Landscape of PD-1/PD-L1 in Endometrial Cancers.
The bipartite landscape of tumor cells and stromal cells determines a tumor's response to treatment during disease management. In endometrial cancers (ECs), the mechanistic contribution of PD-L1/L2 and PD-1 signaling of the host's tumor microenvironment (TME) (CAF and immune cells) in the context of the tumor cells is elusive. To understand the tumor-stroma-immune crosstalk, we studied the compartmental pattern of PD-L1/L2 and PD-1 expression in EC tissues and their matched CAFs. Over 116 surgically resected tumors (T) and the tumor-adjacent normal tissues (N) were obtained from consented unselected consecutive patients. IHC was performed in T, N-epi-thelium, and the stromal mesenchymal environment (SME; mesenchyme) in the T and N tissues. The staining intensity and distribution patterns of PD-L1/L2 and PD-1 in the FFPE sections of T and N were evaluated by a pathologist using a standard scoring system of TPS and CPS. We tested the PD-L1/L2 and PD-1 immune landscape of tumor-TME pair and normal epithelial-stromal mesenchyme pairs from patients with different grades of disease vis-à-vis their CAF PD-L1 levels. We used qRT-PCR to determine the expressions of mRNAs, while the flow cytometry and ICC determined the level of expression of proteins. We observed higher levels of PD-L1 mRNA and protein expression in primary CAFs from the resected tumor tissue compared to the tumor-adjacent normal tissues. We also determined the expression of patients' soluble PD-L1/L2 as peripheral readouts of PD-L1/L2 and PD-1. As we evaluated the results in the context of their pathological parameters, such as grades, stages, lymphovascular invasion, percentage of myometrial invasion, and dMMR in patients, the dominance of PD-L1 expression in TME was positively correlated to the higher pathological grades of tumors, and its relationship with the dMMR. Since the neutralization of CD8-positive cytotoxic T-cells is PD-L1-dependent, our data indicate that irrespective of the PD-L1 positivity of tumor cells, the PD-L1-positive CAFs can play a critical role in bringing out an additional load of PD-L1 for an effective engagement of PD-1 within a tumor mass.


Synthesis of orthogonally protected biaryl amino acid derivatives.
The efficient and direct synthesis of protected biaryl amino acids, including dityrosine (50% overall yield over 3 steps), by Negishi cross-coupling of the serine-derived organozinc reagent 4 with iodo- and di-iodobiaryls, is reported. An improved, although still not perfect, diiodination of 2,2'-biphenol has been achieved using NMe3BnICl2-ZnCl2. Protection of phenolic hydroxyl groups as acetates, rather than benzyl ethers, is required for efficient cross-coupling, and evidence for acetyl migration has been observed during debenzylation of a substituted 2-acetoxy-2'-benzyloxybiaryl. Aromatic C-I to C-Cl conversion has been detected as a minor reaction pathway in the palladium-catalyzed coupling of aryl iodide 3b with organozinc reagent 4.


Proteomic analysis of a diabetic congenic rat identified age-dependent alteration of an acidic protein.
Proteomic analysis was performed in an attempt to identify a gene responsible for the expression of type 2 diabetes using a congenic rat, F.O-Nidd2/of, which possesses a single hyperglycemic QTL locus derived from the diabetic OLETF (Otsuka Long-Evans Tokushima Fatty) rat. Since the genetic difference between the congenic and its host strain, the F344 rat, is limited to the introgressed segment of 38 cM or ca. 2% of the rat whole genome, any discordant protein spots on two dimensional polyacrylamid gel electrophoresis (2D PAGE) will be considered strong candidate genes of this locus. Here we analyzed ca. one thousand protein spots in three different tissue types, liver, muscle and pancreas at 10, 20 and 30 weeks of age, we found that an acidic protein of 55 kD in muscle tissue shifts towards acidic end in an age dependent fashion in the congenic strain. However, the shift was not observed in the control rat, which is intriguing because the timing of the shift corresponds to the age at which hyperglycemia begins in the congenic. Future biochemical analysis should aid in elucidating the molecular mechanisms of glucose metabolism.


Non-immune human sera at higher concentrations inhibit Plasmodium falciparum growth in vitro.
Plasmodium falciparum growth in vitro related to the concentration of inactivated, non-immune human serum supplement to the RPMI medium. This study investigated the concentration of non-immune serum required to support adequate in vitro parasite growth without saturating the medium. Parasitaemia was highest with 7.5% serum concentration in suspension cultures. However, peak parasitaemia obtained under static cultures with 12.5% serum concentration did not significantly differ from the level attained with suspension cultures at the same serum concentration. Ten per cent serum-supplemented medium supported parasite growth in static and suspension cultures, and levels of parasitaemia declined with further increases in serum concentration.


Ethical dilemmas in the treatment of children with disabilities.
Issues relating to the treatment of children with disabilities, such as withholding treatment, organ donation, research, genetic screening, and prenatal diagnosis, all present ethical dilemmas. These issues always need to be reviewed to determine which ethical considerations apply. Identifying relevant principles, one can conclude which take precedence and what is ethically permissible. As with so many other medical responsibilities, this can be consulted, learned, practiced and improved upon. Pediatricians caring for children with disabilities can study and enhance their capacity for ethical reflection, so as to participate fully in these important decision-making processes.


(An)aerobic breakdown of chelating agents used in household detergents.
One of the main causes of the world-wide eutrophication of rivers and lakes is the extensive use of phosphate in both detergents and agricultural fertilizers. Partial or total substitution of phosphates in household detergents by other compounds exhibiting chelating properties has been introduced in several countries to ameliorate such problems. Various microbiological aspects of the biodegradation of the complexing agents most frequently used such as aminopolycarboxylates, phosphonates, hydroxycarboxylates and polymeric polycarboxylates, as well as tripolyphosphates, are reviewed.


Glandular-haired alfalfa resistance to potato leafhopper (Homoptera: Cicadellidae) and hopperburn: development of resistance indices.
Eight proprietary genotypes of glandular-haired alfalfa, Medicago sativa L., supplied by two different companies, were compared for the degree and types of resistance to the potato leafhopper, Ernpoasca fabae (Harris), and hopperburn. A tube cage no-choice bioassay was developed to test leafhopper mortality, feeding, settling preferences, severity of hopperburn symptoms (in this case, defined as both yellowing and stem growth reduction), and trichome density and type on feeding sites. Leafhopper mortality was both strongly and significantly associated with feeding and leaf trichome density; decreased hopperburn symptom severity was weakly, although significantly, associated with increased mortality. To quantify hopperburn in terms of both yellowing and stem growth reduction, we developed a ranking system that reduces overall hopperburn expression to a single number that considers the varying responses to both types of symptoms. Great variability in leafhopper settling, leafhopper mortality, and stem glandular trichome density was detected among alfalfa genotypes, suggesting that genotypic differences may be based on the concentration and/or chemical constituency of the trichome exudates. We postulate that, among variably resistant genotypes of glandular-haired alfalfa, differences among leafhopper responses and hopperburn severity are linked to forced movement from the stems to the leaves as refuge feeding sites. Principal component analysis was performed to reduce the 10 variables down to five biologically significant factors. Scores for these factors were then used to develop resistance indices for potato leafhopper resistance, hopperburn resistance, and an overall glandular-haired alfalfa resistance index.


Regarding the real diversity of Glyptodontidae (Mammalia, Xenarthra) in the late Pliocene (Chapadmalalan Age/Stage) of Argentina.
A large diversity of Glyptodontidae has been proposed as characterizing the Chapadmalalan Age (Pliocene). Most of these taxa were recognized on the basis of partial dorsal carapaces and/or caudal tubes, whereas the main diagnostic characteristic is a particular morphology of the exposed surface of the osteoderms. From a biostratigraphic point of view some species are biostratigraphically important. The Upper Chapadmalalan is based on the Paraglyptodon chapadmalensis biozone. Both the re-evaluation of the type and referred materials and new significant findings from the Chapadmalal and El Polvorín Formations indicate that the diversity of Pliocene Glyptodontidae is more limited than previously supposed. The particular morphology of the exposed surface of the osteoderms that characterizes some of the species actually corresponds to a taphonomic alteration, which results in a non-real ornamentation pattern. Thus, the Glyptodontinae P. chapadmalensis must be replaced as a fossil guide because neither this species nor the species included in the genera Urotherium, Trachycalyptus and Lomaphorus are well characterized. Taking into account the diversity of Glyptodontidae for this lapse, the Glyptodontinae are very scarce (a situation that contrasts with its records in the Pleistocene), whereas Eosclerocalyptus, "Plohophorini" (Plohophorus) and Doedicurinae (cf. Eleutherocercus antiquus) are among the most recorded taxa.


Analytical Methods for Pesticide Residues in the Water Environment.
A review of literature published in 2014 focusing on analytical methods for pesticides in the water environment is presented here. The review includes publications on extraction methods and on analytical methods such as biochemical assays and immunoassays, electrochemical methods, chromatographic or mass spectrometric techniques, spectrophotometric techniques, fluorescence, and chemiluminescence techniques.


Life-threatening infectious mononucleosis: is it correlated with virus-induced T cell proliferation?
Infectious mononucleosis is a well-established clinical entity characterized by the proliferation of B lymphocytes that are infected with Epstein-Barr virus (EBV). These lymphocytes give rise to an increase in specifically reacting cytotoxic T cells, which leads to self-limitation of the lympho-proliferative process. We describe the case of a 1-year-old boy who developed life-threatening EBV infection in association with liver failure, depletion of bone marrow, and severe encephalitis. The fact that clinical cure was achieved when acyclovir (50 mg/[kg.d]) and prednisolone (1 mg/[kg.d]) were administered indicates a correlation between antiviral therapy and clinical improvement. Hypogammaglobulinemia--which had not been present at the onset of disease--persisted after clinical recovery. During the acute phase of the illness, the patient's blood lymphocytes were predominantly T cells, most of which contained the EBV genome, as shown by in situ hybridization; some of these cells stained positive for EBV-specific latent membrane protein. Examination of peripheral blood mononuclear cells in vitro revealed an exceedingly high histocompatibility antigen-unrestricted cytotoxicity against the K562 cell line, which is normally not an immunogenic target of cytotoxic cells in patients infected with EBV. This anomalous natural killer cell-like T cell function suggests that EBV infection of T cells might cause auto-aggressive activity, which was probably responsible for the severity of the infection in our patient.


The residues determining differences in ion affinities among the alternative splice variants F, A, and B of the mammalian renal Na-K-Cl cotransporter (NKCC2).
Three alternatively spliced variants of the renal Na-K-Cl cotransporter (NKCC2) are found in distinct regions of the thick ascending limb of the mammalian kidney; these variants mediate Na(+)K(+)2Cl(-) transport with different ion affinities. Here, we examine the specific residues involved in the variant-specific affinity differences, utilizing a mutagenic approach to change the NKCC2B variant into the A or F variant, with functional expression in Xenopus oocytes. The splice region contains the second transmembrane domain (TM2) and the putative intracellular loop (ICL1) connecting TM2 and TM3. It is found that the B variant is functionally changed to the F variant by replacement of six residues, half of the effect brought about by three TM2 residues and half by three ICL1 residues. The involvement of the ICL1 residues strongly suggests that this region of ICL1 may actually be part of a membrane-embedded domain. Changing six residues is also sufficient to bring about the smaller functional change from the B to the A variant; three residues in TM2 appear to be primarily responsible, two of which correspond to residues involved in the B-to-F changes. A B-variant mutation reported in a mild case of Bartter disease was found to render the cotransporter inactive. These results identify the combination of amino acid variations responsible for the differences among the three splice variants of NKCC2, and they support a model in which a reentrant loop following TM2 contributes to the chloride binding and translocation domains.


Comparison of cardiorespiratory responses during aquatic and land treadmill exercise in patients with coronary artery disease.
To investigate cardiorespiratory responses during exercise stress tests using an aquatic treadmill and a land-based treadmill in patients with coronary artery disease (CAD). Twenty-one stable CAD patients were enrolled. All patients participated in 2 symptom-limited incremental exercise tests, using both an aquatic and a land treadmill. For the aquatic treadmill protocol, patients were submerged to the upper waist in 28°C water. The treadmill speed started at 2.0 km/h and increased 0.5 km/h every minute thereafter. For the land treadmill protocol, the speed and gradient were started at 2.4 km/h and 1.5%, respectively. The speed was increased by 0.3 km/h and grade by 1% every minute thereafter. Oxygen consumption ((Equation is included in full-text article.)O2), heart rate (HR), and respiratory exchange ratio were measured continuously and peak values recorded. Rating of perceived exertion, percentage of age-predicted maximal HR, and total exercise duration were also recorded. Peak cardiorespiratory responses during both protocols were compared. The peak (Equation is included in full-text article.)O2 and peak HR did not show any significant differences. The peak respiratory exchange ratio was significantly greater using the land treadmill than the aquatic treadmill protocol. Rating of perceived exertion, age-predicted maximal HR percentage, and total exercise duration were similar for both protocols. There was a significant linear relationship between HR and (Equation is included in full-text article.)O2 with both protocols. This study demonstrated that aquatic treadmill exercise elicits similar peak cardiorespiratory responses compared with land treadmill exercise, suggesting that aquatic treadmill exercise may be effective for CAD patients in cardiac rehabilitation.


Chlorogenic acid alleviates the reduction of Akt and Bad phosphorylation and of phospho-Bad and 14-3-3 binding in an animal model of stroke.
Stroke is caused by disruption of blood supply and results in permanent disabilities as well as death. Chlorogenic acid is a phenolic compound found in various fruits and coffee and exerts antioxidant, anti-inflammatory, and anti-apoptotic effects. The purpose of this study was to investigate whether chlorogenic acid regulates the PI3K-Akt-Bad signaling pathway in middle cerebral artery occlusion (MCAO)-induced damage. Chlorogenic acid (30 mg/kg) or vehicle was administered peritoneally to adult male rats 2 h after MCAO surgery, and animals were sacrificed 24 h after MCAO surgery. Neurobehavioral tests were performed, and brain tissues were isolated. The cerebral cortex was collected for Western blot and immunoprecipitation analyses. MCAO damage caused severe neurobehavioral disorders and chlorogenic acid improved the neurological disorders. Chlorogenic acid alleviated the MCAO-induced histopathological changes and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. Furthermore, MCAO-induced damage reduced the expression of phospho-PDK1, phospho-Akt, and phospho-Bad, which was alleviated with administration of chlorogenic acid. The interaction between phospho-Bad and 14-3-3 levels was reduced in MCAO animals, which was attenuated by chlorogenic acid treatment. In addition, chlorogenic acid alleviated the increase of cytochrome c and caspase-3 expression caused by MCAO damage. The results of the present study showed that chlorogenic acid activates phospho-Akt and phospho-Bad and promotes the interaction between phospho-Bad and 14-3-3 during MCAO damage. In conclusion, chlorogenic acid exerts neuroprotective effects by activating the Akt-Bad signaling pathway and maintaining the interaction between phospho-Bad and 14-3-3 in ischemic stroke model.


Dynamics of Soft and Hairy Polymer Nanoparticles in a Suspension by NMR Relaxation.
The design of surface-modified functional nanoparticles (NPs) is used to control the properties of the NPs and the NP/environment interactions. The efficient control of the final behavior of the NPs demands a comprehensive understanding of the resulting system. This is particularly challenging for systems with an architecture of the type polymer core-polymer canopy. In such systems, one of the key parameters influencing the behavior of the NPs is the local dynamics of the polymer canopy. However, because the grafting points of the canopy are experiencing their own local dynamics, predicting the final behavior of such systems is difficult. To get a deeper understanding of NPs made of a soft and swollen polymer core and a swollen polymer canopy, we prepared a library of hairy NPs made of a polystyrene (PS) core and a canopy of grafted poly(methyl acrylate) (PMA) chains. The softness of the PS core and the thickness of the PMA canopy were controlled, and the behavior and dynamics of the soft and hairy PS-PMA NPs in suspension were measured by 1H NMR relaxation and dynamic light scattering. It was observed that the rigid PS core slowed down the subsegmental dynamics of the PMA chains, while thick PMA canopies accelerated the relaxation of the PS core. The dynamics of the NPs in suspension was the result of the interplay between the PS core and the PMA canopy.


TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population.
To study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD. One hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.


[T1 bladder tumors: value of a second endoscopic resection].
To quantify the percentage of residual tumour following systematic second endoscopic resection of pT1 bladder tumours before starting treatment with intravesical instillations and to definitively exclude muscle invasion. From January 1995 to December 1999, 52 patients with a first diagnosis of pT1 bladder tumour underwent a second endoscopic resection 3 to 5 weeks later. Nine surgeons, 5 seniors and 4 juniors, managed these patients and the initial resection was considered to be complete in every case. The second resection consisted of resection of the initial tumour bed and distant biopsies either directed to zones of suspicious CIS zones or quadrant biopsies in the case of optically healthy mucosa. Of the 52 included patients, 19 (36.5%) had residual disease on the second endoscopic resection. Pathological staging was: pT0 = 63.5% (33 patients), pTa = 11.5% (6 patients), pTis = 3.85% (2 patients), pT1 = 17.3% (9 patients), > or = pT2 = 3.85% (2 patients). Residual tumour tissue was revealed at the resection site in 84.2% of cases and in another site in 15.8% of cases. Residual tumour was significantly more frequent in the case of multifocal tumour than in the case of solitary tumour (57.9% vs 24.23%), and when managed by a junior surgeon compared to a senior surgeon (53.8% vs 30.8%). This second endoscopic procedure appears to be essential to ensure the absence of residual tumour before starting conservative treatment for pT1 bladder tumours.


ABCG1 regulates pulmonary surfactant metabolism in mice and men.
Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of surfactant. Surfactant synthesis and secretion are restricted to epithelial type 2 (T2) pneumocytes (also called T2 cells). Clearance of surfactant is dependent upon T2 cells and macrophages. ABCG1 is highly expressed in both T2 cells and macrophages. ABCG1-deficient mice accumulate surfactant, lamellar body-loaded T2 cells, lipid-loaded macrophages, B-1 lymphocytes, and immunoglobulins, clearly demonstrating that ABCG1 has a critical role in pulmonary homeostasis. We identify a variant in the ABCG1 promoter in patients with PAP that results in impaired activation of ABCG1 by the liver X receptor α, suggesting that ABCG1 basal expression and/or induction in response to sterol/lipid loading is essential for normal lung function. We generated mice lacking ABCG1 specifically in either T2 cells or macrophages to determine the relative contribution of these cell types on surfactant lipid homeostasis. These results establish a critical role for T2 cell ABCG1 in controlling surfactant and overall lipid homeostasis in the lung and in the pathogenesis of human lung disease.


Famotidine-induced reversal of meperidine-related serotonin syndrome: a case report.
Serotonin syndrome is an unexpected fatal adverse event related to serotonergic medication. This case report is the first report describing the possible treatment effect of famotidine on serotonin syndrome. Furthermore, this is the first case report of serotonin syndrome induced by meperidine alone in a patient with no previous history suggesting a susceptibility to serotonin syndrome. A 70-year-old male with no recent history of serotonergic drug use presented with severe serotonin syndrome following ureteroscopy, possibly due to postoperative meperidine administration. The patient's symptoms included hypertension, tachycardia, tachypnea, hyperthermia, myoclonus, diaphoresis, retching, nausea, agitation, and semicoma mentality with no pupillary light reflex. Symptoms began to subside immediately after the administration of intravenous famotidine for prevention of aspiration pneumonia, with mental and neurological symptoms showing improvement initially, followed by autonomic symptoms. This case report suggests that the histamine type 2 receptor antagonist famotidine may be an effective emergency treatment for serotonin syndrome.


[A digital radiographic device for medical diagnosis].
The paper outlines a digital radiographic device which records radiation by scanning with a one-dimensional multiwire proportional chamber connected on-line to a computer. The device drastically reduces a dosage load on patients, improves the diagnostic potentialities of projectional radiography, yields quantitative diagnostic information, creates special diagnostic programmes, has fast-access and fire-safe archives. The device may be used for general-purpose radiographic examinations and it has advantages when used instead of conventional fluorographs.


Endoscopic treatment of recurrent tracheo-oesophageal fistulae: long-term results.
Recurrent tracheo-oesophageal fistula (RTOF) occurs in 5%-15% of patients following oesophageal atresia repair. Re-thoracotomy is technically challenging and associated with significant morbidity, including a re-fistulation rate of 10%-22%. Endoscopic occlusion of the RTOF with tissue adhesives (fibrin glue, Histoacryl) is reported to be safe and highly effective. However, long-term results of such therapy are absent from the literature. A postal survey of 13 institutions reporting the use of such treatment regimes for RTOF in the literature between 1974 and 1995 was performed, and data collected concerning the long-term outcomes of their reported patients. Eleven institutions responded to the request for data, providing 22 patients (age range 1 month to 12 years) for review. All had undergone initially successful RTOF closure by endoscopic methods and had been followed up for a median of 107 months (range 3-264 months). There was no morbidity or mortality directly related to the procedure. Overall, only 55% of these endoscopically treated fistulas remained closed long-term. Fistula recurrence invariably occurred within 12 months of successful therapy (median 46 days, range 9-335). Most patients required multiple endoscopic procedures to achieve successful RTOF closure (median 2.0, range 1-4 attempts), although significantly fewer attempts were required with fibrin glue therapy. Surgical re-exploration remains the treatment of choice in the fit child. Endoscopic therapy offers a safe and elegant alternative to high-risk surgery in the sick child, although repeated treatments may be required for successful RTOF closure.


Advance Care Planning Documentation in Electronic Health Records: Current Challenges and Recommendations for Change.
To develop a set of clinically relevant recommendations to improve the state of advance care planning (ACP) documentation in the electronic health record (EHR). Advance care planning (ACP) is a key process that supports goal-concordant care. For preferences to be honored, clinicians must be able to reliably record, find, and use ACP documentation. However, there are no standards to guide ACP documentation in the electronic health record (EHR). We interviewed 21 key informants to understand the strengths and weaknesses of EHR documentation systems for ACP and identify best practices. We analyzed these interviews using a qualitative content analysis approach and subsequently developed a preliminary set of recommendations. These recommendations were vetted and refined in a second round of input from a national panel of content experts. Informants identified six themes regarding current inadequacies in documentation and accessibility of ACP information and opportunities for improvement. We offer a set of concise, clinically relevant recommendations, informed by expert opinion, to improve the state of ACP documentation in the EHR.


"Hair-on-end" skull induced by long-term G-CSF treatment in severe congenital neutropenia.
"Hair-on-end" skull changes are typically seen in individuals suffering from thalassaemia. They are induced by widening of the diploic space due to marrow expansion that is a consequence of ineffective and excessive erythropoiesis. We present a child with severe congenital neutropenia who exhibited the typical hair-on-end sign on plain skull radiographs and MRI. In this patient the skull changes were very likely induced by the expansion of white blood cell precursors induced by long-term daily injections of recombinant human granulocyte colony stimulating factor (G-CSF) to treat his confounding disease. This case report is the first description of hair-on-end changes associated with the use of G-CSF.


Effectiveness of the Ophthalmological Training Component of the STOMP (Simulation Training for Operational Medical Providers) Curriculum.
Simulation has been used in medicine to train clinicians to manage a variety of clinical scenarios. A key adaptation of the use of simulation in military healthcare occurred in 2015 with the development of the STOMP (Simulation Training for Operational Medical Providers) curriculum, a specific curriculum designed for the intern (PGY-1) trained physicians being sent into the military to practice primary care. Despite showing the curriculum's influence on self-perceived comfort scores, no study has determined whether simulation is an effective means of improving general medical officer (GMO) physicians' skills compared to other traditional styles of education. Specifically, this study sought to determine whether simulation-based education (SBE) of ophthalmologic skills improves GMO physicians' clinical performance, as compared to traditional didactic-based instruction. The study, conducted at Naval Medical Center Portsmouth, included GMO physicians who were enrolled in the 2019 STOMP class. Following a brief overview of the study, GMO physicians who elected to participate in the study were randomized to either SBE or lecture-based training for three commonly used ophthalmological procedures: slit lamp exam, tonometry, and corneal foreign body removal. After completing the simulation and lecture-based education training sessions, participants' procedural performance was evaluated utilizing a locally developed performance checklist, and completion time for each of the three procedures was recorded. Data were analyzed using the t-test and Mann-Whitney test. A significance level of 0.05 was considered to be statistically significant. Of the 50 consented participants, 46 completed the study. The mean overall completion scores for the performance checklists were significantly higher for the SBE group (n=26) compared to the lecture group (n=20) [80% (95% CI 78-82%) vs 41% (95% CI 35-47%), respectively]. Time to completion of the individual tasks was also significantly shorter for the SBE group compared to the lecture group (with mean differences ranging from 27 to 126 seconds, all p<.05). Simulation-based training appeared to be more effective at teaching three ophthalmological procedures (slit lamp exam, tonometry, and corneal foreign body removal) to GMO physicians compared to didactic-based instruction alone.


Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: evidence for the involvement of complement and mast cell mediators.
Indicators of immune-mediated disease were studied in calves with severe natural bovine respiratory syncytial virus infection. Although antigen and antibody were detected concurrently in most calves, immune complexes were not detected by use of immunofluorescence, ELISA, and binding of the 1q component of complement. Complement component C3, however, was observed by immunofluorescence in the cranioventral, virus-infected portion of the lungs of 19 of 25 calves. Reductions in the amount of histamine and in the numbers of mast cells and mast cell granules in the virus-positive cranioventral and virus-negative caudodorsal portions of the lungs, indicated activation of mast cells and liberation of their granule contents. On the basis of these and previous findings, a model for the pathogenesis of bovine respiratory syncytial virus-induced disease was proposed.


Hepatitis C Virus p7 membrane protein quasispecies variability in chronically infected patients treated with interferon and ribavirin, with or without amantadine.
A clinical study was carried out to compare the response rate of two groups of non-responder (NR) hepatitis C virus (HCV) genotype 1 chronically infected patients treated with interferon and ribavirin, with or without amantadine. The viral load decreased more markedly in the group treated by tritherapy including amantadine, but the response rate at the end of treatment was not significantly different between bitherapy and tritherapy. As amantadine could have an antiviral effect on the ion channel activity of the p7 HCV protein, the p7 quasispecies was characterized by cloning and sequencing. Sequence data were analyzed to determine the pattern and significance of p7 genetic heterogeneity and a possible relationship with therapy. Subtype differences were confirmed between p7 HCV genotypes 1a and 1b, and quasispecies analysis showed a reduction of genetic diversity in subtype 1a, but not 1b, during tritherapy. However, the absence of changes at numerous positions, as well as the conservative changes at other positions, indicated the high conservation of the p7 structure. Residue His-17, proposed to interact with amantadine, was fully conserved in both subtypes 1a and 1b, independently of amantadine administration. In conclusion, although the analysis of the p7 sequences revealed a selective pressure during therapy, no specific residues appeared to be linked to the effect of amantadine on viral decline. These results suggest that the potential antiviral effect of amantadine might be non-specific and related to a reduction in endosomal acidification and therefore reduced viral entry of HCV via its pH-dependent pathway.


Transfer of communication teaching skills from university to the clinical workplace - does it happen? A mixed methods study.
Communication skills learned in the classroom do not transfer easily into clinical practice because they are not reinforced by teachers in the workplace setting and because lack of faculty training restricts the transfer of communication skills in real patient encounters. Trained university-based communication skills teachers often work simultaneously as doctors in clinics. This study explored if and how the skills of these teachers play a role in communication skills training in the clinical workplace. We used an exploratory sequential design: a mixed method approach that combined a survey with communication skills teachers, and qualitative individual interviews with these teachers and their educational leaders in clinical departments. The questionnaire was analysed using descriptive statistics. The interviews were analysed using content analysis. The response rate was 34 %. A majority (93 %) used their communication skills when communicating with patients and relatives. Less than half taught communication in clinical departments. Approximately half of the respondents stated that encouragement from their leaders or colleagues would inspire them to use their teaching skills in the workplace. However, only 20 % had told their leaders about their competencies in teaching communication. One third thought that they needed further teacher training to teach in the clinical workplace. Qualitative analysis showed that teaching opportunities existed but mainly consisted of random, one-off sessions that came about through the initiative of the communication skills teachers themselves. The teachers described several barriers, such as the challenge of teaching colleagues, as communication relates to identity and hierarchical structures, as well as a lack of requests from colleagues or management, and department culture prioritizing topics relating to medical expertise. None of the educational leaders made use of the teachers' specific communication skills in a structured way: some saw it as unimportant, while others saw it as a potential resource. Transfer of the teaching skills of communication skills teachers trained for university-based clinical communication training happened, but to a limited degree. Although both opportunities and barriers for transferring communication skills existed, barriers seemed to dominate, and opportunities for communication skills training in the workplace setting were not used to their full potential.


The CBL-Interacting Protein Kinase CIPK23 Regulates HAK5-Mediated High-Affinity K+ Uptake in Arabidopsis Roots.
Plant growth and development requires efficient acquisition of essential elements. Potassium (K(+)) is an important macronutrient present in the soil solution at a wide range of concentrations. Regulation of the K(+) uptake systems in the roots is essential to secure K(+) supply. It has been shown in Arabidopsis (Arabidopsis thaliana) that when the external K(+) concentration is very low (<10 µm), K(+) nutrition depends exclusively on the high-affinity K(+) transporter5 (HAK5). Low-K(+)-induced transcriptional activation of the gene encoding HAK5 has been previously reported. Here, we show the posttranscriptional regulation of HAK5 transport activity by phosphorylation. Expression in a heterologous system showed that the Ca(2+) sensors calcineurin B-like (CBL1), CBL8, CBL9, and CBL10, together with CBL-interacting protein kinase23 (CIPK23), activated HAK5 in vivo. This activation produced an increase in the affinity and the Vmax of K(+) transport. In vitro experiments show that the N terminus of HAK5 is phosphorylated by CIPK23. This supports the idea that phosphorylation of HAK5 induces a conformational change that increases its affinity for K(+). Experiments of K(+) (Rb(+)) uptake and growth measurements in low-K(+) medium with Arabidopsis single mutants hak5, akt1, and cipk23, double mutants hak5 akt1, hak5 cipk23, and akt1 cipk23, and the triple mutant hak5 akt1 cipk23 confirmed the regulatory role of CIPK23 in planta.


Supramolecular biomaterials for enhanced cancer immunotherapy.
Cancer immunotherapy has achieved promising clinical results. However, many limitations associated with current cancer immunotherapy still exist, including low response rates and severe adverse effects in patients. Engineering biomaterials for the delivery of immunotherapeutic reagents has been suggested to be an effective strategy to improve cancer immunotherapy. Among different biomaterials, supramolecular biomaterials with flexible and versatile structures and functions have exhibited unparalleled advantages in promoting cancer immunotherapy. In recent years, various supramolecular formulations have been extensively explored as immunotherapeutic delivery platforms due to their high cargo-loading capacity/feasibility, facile immunization function, and excellent biocompatibility, which make them possible candidates for modular and personalized cancer immunotherapy. These nanoarchitectures with unique topologies possess distinguishing advantages in cancer immunotherapy, incarnating a structure-property relationship. Based on extensive state-of-the-art research, this minireview highlights recent advances in supramolecular biomaterials for cancer immunotherapy and discusses the possible mechanisms underlying how supramolecular biomaterials promote the development of cancer immunotherapy together with their potential for clinical translation.


Tissue-engineered approach for the treatment of steroid-induced osteonecrosis of the femoral head: transplantation of autologous mesenchymal stem cells cultured with beta-tricalcium phosphate ceramics and free vascularized fibula.
Autologous mesenchymal stem cells (MSCs) cultured with beta-tricalcium phosphate (beta-TCP) ceramics and with a free vascularized fibula were transplanted into three patients with steroid-induced osteonecrosis of the femoral head. The average follow-up period was 34 months and the average patient age at the time of surgery was 28 years old. Fifteen milliliters of bone marrow was obtained from the patients 4 weeks before surgery, and was used for in vitro proliferation of MSCs. beta-TCP granules were immersed in the MSC suspension and the cells were further cultured for 2 weeks. Cultured MSCs/beta-TCP composite granules were implanted into the cavity that remained after curettage of necrotic bone; and finally, a free vascularized fibula was grafted. All hips showed preoperative collapse and radiographic progression was observed in two hips postoperatively. Osteonecrosis did not progress any further and early bone regeneration was observed. This tissue-engineered approach has potentials for the treatment of osteonecrosis. However, our results suggested that the present procedure could not be used for cases with severe preoperative collapse.


The interplay of plasticity and adaptation in neural circuits: a generative model.
Multiple neural and synaptic phenomena take place in the brain. They operate over a broad range of timescales, and the consequences of their interplay are still unclear. In this work, I study a computational model of a recurrent neural network in which two dynamic processes take place: sensory adaptation and synaptic plasticity. Both phenomena are ubiquitous in the brain, but their dynamic interplay has not been investigated. I show that when both processes are included, the neural circuit is able to perform a specific computation: it becomes a generative model for certain distributions of input stimuli. The neural circuit is able to generate spontaneous patterns of activity that reproduce exactly the probability distribution of experienced stimuli. In particular, the landscape of the phase space includes a large number of stable states (attractors) that sample precisely this prior distribution. This work demonstrates that the interplay between distinct dynamical processes gives rise to useful computation, and proposes a framework in which neural circuit models for Bayesian inference may be developed in the future.


Transient neurogenic urinary retention.
A patient is described who developed painless urinary retention, which resolved spontaneously within 2 weeks. At the onset of his illness neurological examination did not manifest definite abnormalities, but the cerebrospinal fluid contained excess of protein and lymphocytes. Cystonometry was normal throughout the illness.


A self-applied, Internet-based intervention for fear of public speaking.
The aim of this article is to introduce, illustrate, and present effectiveness data on a new telepsychology program for the treatment of fear of public speaking. The Talk to Me program is an Internet-based self-applied intervention that has several components, including a diagnostic assessment, a structured treatment, and an outcome protocol that evaluates treatment efficacy in a continuous manner. We describe the characteristics of the program and present a case study. Results demonstrated a significant decrease in levels of fear and avoidance related to speaking in public.


Study of long-term cultures of simian immunodeficiency virus (SIVmac 251)-infected peripheral blood lymphocytes.
A culture of rhesus monkey peripheral blood lymphocytes was divided into two parts; one was kept as an uninfected control, and the other was infected with a strain of simian immunodeficiency virus (SIVmac251) originally isolated from a rhesus monkey that died of a malignant lymphoma associated with acquired immune deficiency syndrome. Both cultures were sampled at successive intervals from 1 to 40 days postinfection. Each sample was subjected to in situ hybridization for detection of viral mRNA, immunocytochemical detection of viral core protein (p27), reverse transcriptase assay, electron microscopy, and immunophenotypic characterization of infected cells. These techniques were used to define viral growth kinetics of this novel lentivirus in peripheral blood lymphocytes. The first evidence of SIVmac251 replication was obtained by an in situ hybridization signal for viral mRNA at 2 days postinoculation. This was followed by detection of viral p27 core protein by immunocytochemistry on day 4. Reverse transcriptase activity above control values was not detected until day 8. Budding particles were not found in the infected cultures until 14 days postinfection. Results of in situ hybridization, immunocytochemistry, and reverse transcriptase assay indicated that two bursts of viral replication occurred during the course of this study. The first, at 3 weeks postinfection, was due to infection and subsequent depletion of CD4+ lymphocytes, while the second, 3 weeks later, resulted from a cycle of replication in CD8+ lymphocytes and the remaining CD4+ cells, culminating in the death of all cells on day 39 postinoculation.


[Pulsed Field Ablation shows promise - Experiences from the first 100 patients in Sweden].
Pulmonary vein isolation (PVI) of symptomatic atrial fibrillation is an effective method of maintaining sinus rhythm. Radiofrequency ablation and cryotechnology have been used for this purpose for many years. One disadvantage of these methods is the risk of serious complications such as pulmonary vein stenosis, phrenic nerve palsy and atrio-oesophageal fistula. Pulsed Field Ablation (PFA) is a promising ablation modality for treatment of atrial fibrillation. This technique employs a train of high amplitude electrical pulses with short duration that ablate myocardium with minimal effect on surrounding tissues. 100 patients underwent PFA at the Capio Arrhythmia Center Stockholm. All pulmonary veins could be identified successfully and isolation could be achieved without difficulty. No serious complication during ablation and observation time after the procedure occurred. Our experience with PFA shows that PVI with this technique in symptomatic atrial fibrillation is a safe and effective method.


Tight Regulation of Mechanotransducer Proteins Distinguishes the Response of Adult Multipotent Mesenchymal Cells on PBCE-Derivative Polymer Films with Different Hydrophilicity and Stiffness.
Mechanotransduction is a molecular process by which cells translate physical stimuli exerted by the external environment into biochemical pathways to orchestrate the cellular shape and function. Even with the advancements in the field, the molecular events leading to the signal cascade are still unclear. The current biotechnology of tissue engineering offers the opportunity to study in vitro the effect of the physical stimuli exerted by biomaterial on stem cells and the mechanotransduction pathway involved in the process. Here, we cultured multipotent human mesenchymal/stromal cells (hMSCs) isolated from bone marrow (hBM-MSCs) and adipose tissue (hASCs) on films of poly(butylene 1,4-cyclohexane dicarboxylate) (PBCE) and a PBCE-based copolymer containing 50 mol% of butylene diglycolate co-units (BDG50), to intentionally tune the surface hydrophilicity and the stiffness (PBCE = 560 Mpa; BDG50 = 94 MPa). We demonstrated the activated distinctive mechanotransduction pathways, resulting in the acquisition of an elongated shape in hBM-MSCs on the BDG50 film and in maintaining the canonical morphology on the PBCE film. Notably, hASCs acquired a new, elongated morphology on both the PBCE and BDG50 films. We found that these events were mainly due to the differences in the expression of Cofilin1, Vimentin, Filamin A, and Talin, which established highly sensitive machinery by which, rather than hASCs, hBM-MSCs distinguished PBCE from BDG50 films.


Describing Failure in a Clinical Clerkship: Implications for Identification, Assessment and Remediation for Struggling Learners.
In addition to training future members of the profession, medical schools perform the critical role of identifying students who are failing to meet minimum standards in core competencies. To better understand reasons for failure in an internal medicine clerkship. A qualitative content analysis of letters describing reasons for students' failure. Forty-three students (31 men) who failed the internal medicine clerkship at the University of Minnesota Medical School, 2002-2013. We conducted a qualitative content analysis of the 43 letters describing reasons for students' failure. We coded critical deficiencies and mapped them to the Physician Competency Reference Set (PCRS) competency domains and classified them into two categories: conduct (unprofessional behaviors) and knowledge and skills specific to the practice of medicine. We then calculated the frequency of each critical deficiency. We statistically tested for relationships between gender and critical deficiencies in each of the competency domains. We coded 50 critical deficiencies with all codes mapping to a PCRS competency domain. The most frequently cited deficiencies were "insufficient knowledge" (79 % of students) and "inadequate patient presentation skills" (74 %). Students exhibited critical deficiencies in all eight competency domains, with the highest concentrations in Knowledge for Practice (98 %) and Interpersonal and Communication Skills (91 %). All students demonstrated deficiencies in multiple competencies, with 98 % having deficiencies in three or more. All 43 students demonstrated deficits in the knowledge and skills category, and 81 % had concurrent conduct issues. There were no statistically significant relationships between gender and critical deficiencies in any competency domain. This study highlights both the diversity and commonality of reasons that students fail a clinical clerkship. Knowing the range of areas where students struggle, as well as the most likely areas of difficulty, may aid faculty in identifying students who are failing and in developing remediation strategies.


GAS, a new glutamate-rich protein, interacts differentially with SRCs and is involved in oestrogen receptor function.
Steroid receptor coactivators (SRCs) exert profound effects on animal development and physiology. Genetic ablation experiments indicate that various SRC proteins might have differential physiological roles; however, clear evidence of functional specificity has not yet been shown at the molecular level. Here we report the identification of a new SRC1 interacting protein, glutamate-rich coactivator interacting with SRC1 (GAS), which contains a central glutamate-rich region and has transactivation activity. Interestingly, GAS interacts only with SRC1, and not with glucocorticoid receptor interacting protein 1 (GRIP1) or amplified in breast cancer 1 (AIB1), the other two members of the SRC family. It interacts with oestrogen receptor-alpha (ERalpha) and participates in both oestrogen receptor-regulated gene transcription and oestrogen-stimulated G1/S cell-cycle transition. Our data thus indicate that GAS is a new transcription cofactor and that different SRCs are associated with distinct secondary cofactors.


Descent of the fetal head (station) during the first stage of labor.
High station at specific points in the first stage of labor, such as a floating head on admission, or at 4-cm dilation or when arrest of dilation occurs, is associated with higher rates of failure to deliver vaginally. Therefore it could be useful to know if station is within an expected range at a given dilation during first stage. Arrest of descent disorders have been defined thus far on criteria applicable in the second stage. Statistical modeling is an attractive methodology to characterize the relationship between station and dilation because the resulting mathematical expressions could be used as a reference for comparison in the future. In addition, they can be used to produce a finely graded assessment of descent using numerical terms such as percentile rankings. A 2-step approach to potentially improving the assessment of station could be to develop a statistical model that describes the general relationship between station and dilation in the first stage of uncomplicated births and then determine if such a model would have identified births with complications related to poor labor progress. Given the complex nature of labor data, especially the imprecision of dilation and station measurement, it is not immediately evident that such a model is identifiable or what its precision would be. We sought to characterize in mathematical terms the relationship of station to dilation during the first stage of labor for nulliparous and multiparous women with spontaneous vaginal births. This retrospective cohort study included 28,121 exams from 5555 women with singleton cephalic presentations at ≥37 weeks' gestation with electronic fetal monitoring tracings, who delivered vaginally without instrumentation and had 5-minute Apgar scores >6 at 2 academic community referral hospitals in 2012 through 2013. Women with a previous cesarean birth were excluded. We used longitudinal statistical techniques suitable to biological data that were irregularly sampled with repeated measures over time. A linear relationship was observed between station and dilation. For both nulliparous and multiparous women the final model was a linear regression with random effects for intercept and slope and a first-order autoregressive correlation structure. The 5th-95th range of station at any given dilation spanned about 3-4 cm. Our results demonstrate a general trend of increasing descent of the presenting part as dilation advances during the first stage of labor in women who delivered vaginally without instrumentation. We propose that the mathematical expressions describing this relationship may be valuable in the assessment of first-stage labor progression.


Continuity of care from the perspective of users.
Continuity of care, in addition to ensuring improvement of the quality of care, contributes to the reduction of health costs. The objective of this study was to analyse the continuity of care in health units in the municipality of Évora (south of Portugal), from the perspective of users. This is across-sectional, exploratory and descriptive study with a quantitative approach, with a sample consisting of 342 users of health units. The instrument was a questionnaire adapted from English and Spanish studies. The results show that elements of continuity were identified in the different dimensions of the continuity of care - relational, management, information and some items of flexible continuity. Longitudinal continuity has the lowest values in nursing care. In conclusion, what stands out positively, and in its different dimensions, is relational continuity, in which most users recommend their family doctor and nurse to family and friends, and flexible continuity, which translates into reduced waiting times to be attended by a doctor or nurse and access to care. What stands out negatively is the weak involvement of the user in care by health professionals, in the dimensions of relational continuity.


Evidence-Based Practice Guideline: Delirium.
Delirium is a common cause of morbidity and mortality in hospitalized older adults often superimposed on dementia. Older patients with delirium are more likely than other populations to develop hospital-acquired infections, pressure ulcers, and immobility and nutritional issues, as well as to have increased health care costs, longer hospital stays, and long-term care following discharge. Interventions that prevent or mitigate the effects of delirium while promoting recovery are essential for caring for hospitalized older patients. This article is a summary of an evidence-based guideline that includes a framework for addressing delirium that focuses on predisposing and precipitating factors for delirium. In addition, the guideline includes evidence-based assessment and intervention principles, along with a review of reliable and valid assessment instruments. The guideline also identifies measurable outcomes for managing delirium and a quality improvement approach for improving outcomes. [Journal of Gerontological Nursing, 44(2), 14-24.].


Oscillatory Behaviors in Genetic Regulatory Networks Mediated by MicroRNA With Time Delays and Reaction-Diffusion Terms.
In this paper, we investigate the oscillatory expression in Escherichia coli mediated by microRNA with time delays and reaction-diffusion terms. First of all, the integrated effects of delays and diffusions are first introduced into the genetic regulatory networks involving microRNAs, and a general model of genetic regulatory networks is then formulated. Second, two functional issues on gene regulatory networks, i.e. stability and oscillation of such model, are addressed in detail, and an explicit algorithm determining the properties of periodic oscillation is also presented. We demonstrate that the oscillatory expression of Escherichia coli is not only crucially dependent on the transcriptional and translational delays, but also heavily influenced by the diffusion coefficients. The conclusion is practically verified by a lot of biological experiments and observations. We also find that if the diffusion coefficients of miRNA, mRNA, and protein are suitably small, it can predict that inhomogeneous periodic oscillations can occur unless there only exhibits spatially homogeneous periodic oscillations. The obtained results indicate that the effects of transcriptional and translational delays are essential factors for designing or controlling genetic regulatory networks, in the meantime the functions of reaction-diffusion must beconsidered. Finally, numerical examples are presented to illustrate and visualize theoretical results.


Transient retardation in embryo growth in normal female mice made pregnant by males whose testes had been heated.
In three separate experiments, using three different strains of mice, when normal females were mated by males whose testes had been heated once to 42 degrees C for 20 min, the embryos at 10.5 days post-coitum were approximately 20% smaller than control embryos. In one experiment, the difference was still present, although proportionately less, at 15.5 and 18.5 days and, in another experiment, a difference could be seen in 11.5 and 13.5 day old embryos but not in 12.5, 14.5, 15.5 or 18.5 day old embryos. The frequency of mating and pregnancy rates were unaffected. In one experiment, the time available for mating was restricted to 4 h instead of overnight, without effect on the result. In another experiment, other males were heated for 30 min, and these showed a period of infertility from 10 to 32 days later, preceded and followed by the production of smaller than normal embryos; litter size was also reduced in the period after the return of fertility in these animals. The yolk sacs and the trophoblasts of the embryos sired by the heated males were also slightly smaller than those sired by the controls in the two experiments in which these were measured. The pattern of weight reduction is thus different from that seen in gynogenetic embryos or when the gene for insulin-like growth factor (IGF)-II is disrupted, and suggests a reduction in embryo growth at the earlier stages, with compensatory growth occurring later in pregnancy.


Chalcopyrite CuGaTe(2): a high-efficiency bulk thermoelectric material.
CuGaTe(2) with a chalcopyrite structure demonstrates promising thermoelectric properties. The maximum figure of merit ZT is 1.4 at 950 K. CuGaTe(2) and related chalcopyrites are a new class of high-efficiency bulk thermoelectric material for high-temperature applications.


HLA-DRB3 typing by restriction digestion of locus-specific amplified DNA.
Locus HLA-DRB3 codes for the serologically defined supertypic specificity DRw52 in HLA-DR3, -5 and -w6 haplotypes. Three specificities of DRw52 (DRw52a, -b and -c) can further be distinguished by cellular techniques or by DNA typing with allele-specific oligonucleotide probes. These specificities were recently reported to have significant importance in antigen presentation. To avoid a time-consuming hybridization procedure, we have developed a simple typing system using PCR and subsequent digestion by allele-specific restriction endonucleases. A system was established with locus-specific amplification of HLA-DRB3 and digestion by the enzymes KpnI, ScaI and HinfI which recognize unique restriction sites within the amplified region. This allowed HLA-DRB3 typing on agarose gel by determining whether the amplification product has been digested or not. This typing system was compared to conventional oligotyping by analyzing 145 RFLP-typed individuals for their DRw52 specificity using both methods. Agarose typing correlated well with oligotyping and was shown to be more simple and practical even in heterozygous individuals.


Performance of the NIRS fast scanning system for heavy-ion radiotherapy.
A project to construct a new treatment facility, as an extension of the existing HIMAC facility, has been initiated for the further development of carbon-ion therapy at NIRS. This new treatment facility is equipped with a 3D irradiation system with pencil-beam scanning. The challenge of this project is to realize treatment of a moving target by scanning irradiation. To achieve fast rescanning within an acceptable irradiation time, the authors developed a fast scanning system. In order to verify the validity of the design and to demonstrate the performance of the fast scanning prior to use in the new treatment facility, a new scanning-irradiation system was developed and installed into the existing HIMAC physics-experiment course. The authors made strong efforts to develop (1) the fast scanning magnet and its power supply, (2) the high-speed control system, and (3) the beam monitoring. The performance of the system including 3D dose conformation was tested by using the carbon beam from the HIMAC accelerator. The performance of the fast scanning system was verified by beam tests. Precision of the scanned beam position was less than +/-0.5 mm. By cooperating with the planning software, the authors verified the homogeneity of the delivered field within +/-3% for the 3D delivery. This system took only 20 s to deliver the physical dose of 1 Gy to a spherical target having a diameter of 60 mm with eight rescans. In this test, the average of the spot-staying time was considerably reduced to 154 micros, while the minimum staying time was 30 micros. As a result of this study, the authors verified that the new scanning delivery system can produce an accurate 3D dose distribution for the target volume in combination with the planning software.


Pressure-induced structural modifications of rare-earth hafnate pyrochlore.
Complex oxides with the pyrochlore (A2B2O7) and defect-fluorite ((A,B)4O7) structure-types undergo structural transformations under high-pressure. Rare-earth hafnates (A2Hf2O7) form the pyrochlore structure for A = La-Tb and the defect-fluorite structure for A = Dy-Lu. High-pressure transformations in A2Hf2O7 pyrochlore (A = Sm, Eu, Gd) and defect-fluorite (A = Dy, Y, Yb) were investigated up to ~50 GPa and characterized by in situ Raman spectroscopy and synchrotron x-ray diffraction (XRD). Raman spectra at ambient pressure revealed that all compositions, including the defect-fluorites, have some pyrochlore-type short-range order. In situ high-pressure synchrotron XRD showed that all of the rare earth hafnates investigated undergo a pressure-induced phase transition to a cotunnite-like (orthorhombic) structure that begins between 18 and 25 GPa. The phase transition to the cotunnite-like structure is not complete at 50 GPa, and upon release of pressure, the hafnates transform to defect-fluorite with an amorphous component. For all compositions, in situ Raman spectroscopy showed that disordering occurs gradually with increasing pressure. Pyrochlore-structured hafnates retain their short-range order to a higher pressure (30 GPa vs. <10 GPa) than defect-fluorite-structured hafnates. Rare earth hafnates quenched from 50 GPa show Raman spectra consistent with weberite-type structures, as also reported for irradiated rare-earth stannates. The second-order Birch-Murnaghan equation of state fit gives a bulk modulus of ~250 GPa for hafnates with the pyrochlore structure, and ~400 GPa for hafnates with the defect-fluorite structure. Dy2Hf2O7 is intermediate in its response, with some pyrochlore-type ordering, based on Raman spectroscopy and the equation of state, with a bulk modulus of ~300 GPa. As predicted based on the similar ionic radius of Zr4+ and Hf4+, rare-earth hafnates show similar behavior to that reported for rare earth zirconates at high pressure.


Anesthesia and Oncology: Friend or Foe?
Cancer is a leading cause of death, and surgery is an important treatment modality. Laboratory research and retrospective studies have raised the suspicion that the choice of anesthetics for cancer surgery might affect the course of cancerous disease. The aim of this review is to provide a critical overview of the current state of knowledge. Inhalational anesthesia with volatiles or total intravenous anesthesia (TIVA) with propofol are the two most commonly used anesthetic techniques. Most data comparing volatile anesthetics with TIVA is from either in vitro or retrospective studies. Although conflicting, data shows a trend towards favoring propofol. Opioids are commonly used in anesthesia. Data on potential effects of opioids on growth and recurrence of cancer are scarce and conflicting. Preclinical studies have shown that opioids stimulate cancer growth through the µ-opioid receptor. Opioids also act as immunosuppressants and, therefore, have the potential to facilitate metastatic spread. However, the finding of an adverse effect of opioids on tumor growth and cancer recurrence by some retrospective studies has not been confirmed by prospective studies. Regional anesthesia has not been found to have a beneficial effect on the outcome of surgically treated cancer patients, but prospective studies are scarce. Local anesthetics might have a beneficial effect, as observed in animal and in vitro studies. However, prospective clinical studies strongly question such an effect. Blood products, which may be needed during extensive cancer surgery suppress the immune system, and data strongly suggest a negative impact on cancer recurrence. The potential effects of other commonly used anesthetic agents on the outcome of cancer patients have not been sufficiently studied for drawing valid conclusions. In conclusion, laboratory data and most retrospective studies suggest a potential advantage of TIVA over inhalational anesthesia on the outcome of surgical cancer patients, but prospective, randomized studies are missing. Given the state of weak scientific evidence, TIVA may be used as the preferred type of anesthesia unless there is an individual contraindication against it. Studies on the effects of other drugs frequently used in anesthesia are limited in number and quality, and have found conflicting results.


The adsorption and diffusion behavior of noble metal adatoms (Pd, Pt, Cu, Ag and Au) on a MoS2 monolayer: a first-principles study.
First-principles calculations based on periodic density functional theory (DFT) have been used to investigate the geometries, electronic structures, magnetic properties and diffusion behaviors of different noble metal adatoms (Pd, Pt, Cu, Ag and Au) on MoS2 monolayers. The results demonstrate that these adatoms can chemically adsorb on MoS2 monolayers. The band gaps of MoS2 monolayers with a Pd or Pt atom adsorbed are reduced owing to impurity states that emerge simultaneously within the gap region of the pristine MoS2 monolayer. The unpaired electrons in MoS2 monolayers with a Cu, Ag or Au atom adsorbed are spin polarized, resulting in total magnetic moments of 1.0 μB per supercell, which is caused by the strong hybridization between the metal adatoms and surrounding Mo or S atoms. Long-range antiferromagnetic (AFM) coupling has been observed between group IB metal adatoms. Due to charge transfer between adatoms and the MoS2 host, the work functions were modulated upon adsorption of noble metals. In addition, the diffusion behaviors of noble metal adatoms on the MoS2 monolayer suggest that Cu, Pd and Pt atoms favor the formation of a metal nanotemplate on the MoS2 monolayer, and Ag and Au are likely to form isolated particles in the initial growth stage. These findings may provide useful guidance to extend the potential applications of MoS2 in low-dimensional nanoelectronic and spintronic devices.


Confirmation of avermectin residues in food matrices with negative-ion atmospheric pressure chemical ionization liquid chromatography/mass spectrometry.
A multi-residue LC/MS method has been developed to confirm avermectin drug residues in several food matrices. Ivermectin (IVR), doramectin (DOR), eprinomectin (EPR) and moxidectin (MOX) are confirmed using atmospheric pressure chemical ionization (APCI) with negative ion detection and selected ion monitoring of three to four ions for each compound. The drug residues are extracted from tissue or milk using previously published procedures. IVR and DOR are confirmed at 20 ppb levels in fortified salmon muscle; IVR is also confirmed in tissue from salmon dosed with the drug. Residues of DOR, IVR, and EPR are confirmed in fortified milk at the 20 ppb level and in fortified beef liver at 40 ppb. Residues of MOX can also be confirmed in these matrices, but at slightly higher levels (40-80 ppb).


Exosomes/miRNAs as mediating cell-based therapy of stroke.
Cell-based therapy, e.g., multipotent mesenchymal stromal cell (MSC) treatment, shows promise for the treatment of various diseases. The strong paracrine capacity of these cells and not their differentiation capacity, is the principal mechanism of therapeutic action. MSCs robustly release exosomes, membrane vesicles (~30-100 nm) originally derived in endosomes as intraluminal vesicles, which contain various molecular constituents including proteins and RNAs from maternal cells. Contained among these constituents, are small non-coding RNA molecules, microRNAs (miRNAs), which play a key role in mediating biological function due to their prominent role in gene regulation. The release as well as the content of the MSC generated exosomes are modified by environmental conditions. Via exosomes, MSCs transfer their therapeutic factors, especially miRNAs, to recipient cells, and therein alter gene expression and thereby promote therapeutic response. The present review focuses on the paracrine mechanism of MSC exosomes, and the regulation and transfer of exosome content, especially the packaging and transfer of miRNAs which enhance tissue repair and functional recovery. Perspectives on the developing role of MSC mediated transfer of exosomes as a therapeutic approach will also be discussed.


Avoiding "Cloudcuckooland" in ethics committee case review: matching models to issues and concerns.
... The special concerns of families, patients, and caregivers are inevitably interwoven among the difficult ethical issues that ethics committees confront when they review individual cases. Certain of these ethical issues and special concerns can be addressed more effectively by the use of one particular case review model. This means that no one model for case review is suited to address every ethically difficult patient care situation. When one case review model is used exclusively by an ethics committee, some issues and concerns will not be resolved effectively. This difficulty cannot be ameliorated by switching to another exclusive model. To do so would be to trade an Athens for a "Cloudcuckooland." The case review model selected by ethics committees must vary from case to case. The model that is chosen should be geared to resolve the ethical issues central to that situation and the special concerns of patient, family, and caregivers. An examination of the three received models [the committee as a whole, teams, and individual members or consultants] will show that each is particularly suited to resolve certain kinds of ethical issues and special concerns. Because of this, ethics committees should develop a method for choosing the most appropriate model for reviewing specific cases.


Peripheral white blood cell count as a screening tool for ventriculostomy-related infections.
One of the most common complications following external ventricular drain (EVD) placement is infection. Routine cultures of cerebrospinal fluid (CSF) are often used to screen for infection, however several days may pass before infection is discovered. In this study, we compared the predictive value of daily recorded vital sign parameters and peripheral white blood count (WBC) in identifying ventriculostomy-related infections. Patients with EVDs who had CSF cultures for microorganisms performed between January 2011 and July 2017 were assigned to either an infected and/or uninfected study group. Clinical parameters were then compared using t-test, chi squared and multiple logistic regression analyses. Patients of any age and gender were included. One hundred seventy uninfected and 10 infected subjects were included in the study. Nine of the 10 infected patients had an elevated WBC (>10.4 × 103/μL), with a significantly greater WBC (15.9 × 103/μL) than the uninfected group (10.4 × 103/μL) (p-value ≤ 0.0001). Using logistic regression, we found no association between patient vital signs and CSF infection except for WBC (p = .003). As a diagnostic marker for CSF infection, the sensitivity and specificity of WBC elevation greater than 15 × 103/μL was 70% (7/10) and 90.2% (147/163), respectively. This study serves as a 'proof of concept' that WBC could be useful as potential screening tool for early detection of CSF infection post-EVD placement. Future investigation using a large, multicenter prospective study is needed to further assess the applicability of this parameter.