Molecular marker analysis of 24- and 25-chromosome plants obtained from Solanum tuberosum L. subsp. andigena (2n = 4x = 48) pollinated with a Solanum phureja haploid inducer.
Clones with 24 or 25 chromosomes were obtained by pollinating an Andean cultivated tetraploid potato (Solanum tuberosum subsp. andigena clone 94H94, 2n = 4x = 48) with the Solanum phureja haploid-inducer clone 1.22. Their genetic composition was analyzed in an RAPD assay using 135 decamer primers and in an RFLP assay using 45 single-copy DNA probes. In total, 22 RAPD and 20 RFLP markers were found to be specific to S. phureja. None of these markers were found in the 24- and 25-chromosome clones. RFLP genotypes for the 45 RFLP loci were further determined for each clone. Genotypes of the 24-chromosome clones were characterized using two alleles randomly selected from four alleles of the parental tetraploid clone for almost all RFLP loci. Five 25-chromosome clones had extra alleles for all of the RFLP loci of chromosomes 4, 8, 10, 11, and 12, respectively, suggesting primary trisomy for one of these chromosomes. Clones with genotypes showing double reduction were also identified. Therefore, the obtained clones likely originated from random samples of female gametes, and hence are euhaploids or aneuhaploids of S. tuberosum subsp. andigena, strongly supporting parthenogenesis to be a primary mechanism for haploid induction in potato.


Readthrough acetylcholinesterase: a multifaceted inducer of stress reactions.
Stress insults induce hyperexcitation of cholinergic circuits, both peripherally in the sympathetic pathway (Tracey, 2002) and at the central nervous system (CNS) (Sapolsky, 1996). This reaction can serve to ensure survival but might also entail a risk to the hyperactivated neurons. Consequent changes in the expression of a series of proteins related to acetylcholine (ACh) metabolism might protect the organism from the potentially detrimental effects of this increase in ACh. Of particular interest among these effects is the induction by alternative splicing of the alternative, usually rare, readthrough variant of acetylcholinesterase (AChE), AChE-R. AChE-R is one of the first proteins conveying the signal that the organism has entered a state of alert. Viewing AChER as a stress signal can therefore serve to answer the question "How do we expect a stress signal to operate"? This facilitates the generation of hypotheses regarding the triggering of such signals and the effects it exerts at the molecular, cellular, and physiological levels.


8-Oxoguanine Forms Quartets with a Large Central Cavity.
Oxidation of a guanine nucleotide in DNA yields an 8-oxoguanine nucleotide (oxoG) and is a mutagenic event in the genome. Due to different arrangements of hydrogen-bond donors and acceptors, oxoG can affect the secondary structure of nucleic acids. We have investigated base pairing preferences of oxoG in the core of a tetrahelical G-quadruplex structure, adopted by analogues of d(TG4T). Using spectroscopic methods, we have shown that G-quartets can be fully substituted with oxoG nucleobases to form an oxoG-quartet with a revamped hydrogen-bonding scheme. While an oxoG-quartet can be incorporated into the G-quadruplex core without distorting the phosphodiester backbone, larger dimensions of the central cavity change the cation localization and exchange properties.


Relation between microRNA-155 and inflammatory mediators in multiple sclerosis.
Multiple sclerosis (MS) is a complex autoimmune condition affecting the central nervous system characterized by axonal damage, demyelination, and chronic inflammation. Multiple molecular and cellular components mediate neuroinflammation in MS. In human macrophages and microglia, miRNA-155 is an essential proinflammatory noncoding RNA that regulates phenotypic and functional polarization properties. This study was conducted to detect the plasma level of miRNA-155 in RRMS and assess its relationship with inflammatory and anti-inflammatory mediators. The study included 60 MS patients and 30 healthy controls. Real-time quantitative polymerase chain reaction was utilized to detect miRNA-155, iNOS, and SMAD2, whereas ELISA was used to determine TNF-α, IFN-ɣ, TGF-β, and IL-10 levels. There was no significant difference in miRNA-155, SMAD2, and iNOS expression in MS patients compared to control subjects. In addition, there was a statistically significant increase in TNF-α, INF-ɣ, and TGF-β levels. IL-10 levels did not differ significantly between MS patients and healthy controls. There was a positive correlation between miRNA-155 and TNF-α (p < 0.000, r = 0.922), INF-ɣ (p < 0.000, r = 0.81), and iNOS (p < 0.000, r = 0.916) and inverse correlation between miRNA-155 and IL-10 (p < 0.000, r = -0.928), TGF-β (p < 0.000, r = -0.904) and SMAD2 (p < 0.000, r = -0.848). We conclude that expression of miRNA-155 in MS may modulate macrophage/microglia polarization by increasing the secretion of TNF-α, IFN-ɣ & iNOS and decreasing anti-inflammatory mediators IL10 and TGF-β.


[Talus substitution using a vascular pedicled bone flap].
Authors report on the substitution of in consequence of complete talus luxation, missing talus. It succeeded with the transplantation of a free vascular pedicled bone block, gained from the crista ilei to retain the length of the extremity and to secure the gait of the patient without aid, finally to make the return to the former active life possible. The use of the method in similar cases was found to be unknown after a review of the literature. This case is an example demonstrating the growing significance of microsurgery in the traumatology.


Load independence of early diastolic filling parameters in the anesthetized canine model.
To evaluate radionuclide diastolic filling indices during acute pharmacologic changes in ventricular loading, 11 atrially paced dogs underwent simultaneous micromanometer left atrial and left ventricular pressure measurements. During phenylephrine infusion, systolic blood pressure increased from 110 +/- 16 (s.d.) to 147 +/- 19 mmHg (p < 0.01), causing the atrioventricular gradient to increase from 5 +/- 2 to 8 +/- 5 mmHg (p < 0.03) with no change in the time constant of isovolumic relaxation (Tau). Absolute peak filling rate increased from 40 +/- 21 to 59 +/- 44 kcts/sec (p < 0.05), but there was no change in first-half filling fraction. During dobutamine infusion, Tau shortened from 43 +/- 13 msec to 33 +/- 5 msec (p < 0.01) and first-half filling fraction increased from 39% +/- 19% to 56% +/- 18% (p < 0.05), with no change in atrioventricular gradient or absolute peak filling rate. Absolute changes from baseline for the first-half filling fraction were inversely proportional to absolute changes in Tau (r = -0.76, p < 0.05). We conclude that the left ventricular absolute peak filling rate is a load dependent index of diastolic function. In contrast, the radionuclide first-half filling fraction is independent of loading conditions, but is sensitive to substantial alterations in the rate of left ventricular isovolumic myocardial relaxation.


Perfluoroalkylphosphine coordination chemistry of platinum: synthesis of (C2F5)2PPh and (C2F5)PPh2 complexes of platinum(II).
A 1:1 addition of Ph2PCl to an ethereal solution of C2F5Li (formed from the reaction of BuLi with C2F5Cl) yields Ph2P(C2F5)(abbreviated pfepp) (1). The introduction of a fluoroethyl group results in a phosphine with electronic characteristics that approximate phosphites, bridging the electronic gap between traditional donor phosphine ligands and more electrophilic phosphine ligands like PhP(C2F5)2 (2). The pfepp ligand 1 is isolated as a high boiling liquid, which crystallizes upon standing at room temperature in an inert atmosphere. A series of Pt(II) complexes of the type trans-L2PtCl2 (L = pfepp 3; PhP(C2F5)2 4) have been prepared and structurally characterized by multinuclear NMR, IR and X-ray crystallography. The crystal structure of is the first example of a structurally characterized monodentate phosphine with a pentafluoroethyl pendant group.


G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells.
The effectiveness of IFN-alpha2b for human multiple myeloma has been variable. TRAIL has been proposed to mediate IFN-alpha2b apoptosis in myeloma. In this study we assessed the effects of IFN-alpha2b signaling on the apoptotic activity of TRAIL and human myeloma cell survival. While TRAIL was one of the most potently induced proapoptotic genes in myeloma cells following IFN-alpha2b treatment, less than 20% of myeloma cells underwent apoptosis. Thus, we hypothesized that an IFN-stimulated gene (ISG) with prosurvival activity might suppress TRAIL-mediated apoptosis. Consistent with this, IFN-alpha2b stabilized mitochondria and inhibited caspase-3 activation, which antagonized TRAIL-mediated apoptosis and cytotoxicity after 24 hours of cotreatment in cell lines and in fresh myeloma cells, an effect not evident after 72 hours. Induced expression of G1P3, an ISG with largely unknown function, was correlated with the antiapoptotic activity of IFN-alpha2b. Ectopically expressed G1P3 localized to mitochondria and antagonized TRAIL-mediated mitochondrial potential loss, cytochrome c release, and apoptosis, suggesting specificity of G1P3 for the intrinsic apoptosis pathway. Furthermore, RNAi-mediated downregulation of G1P3 restored IFN-alpha2b-induced apoptosis. Our data identify the direct role of a mitochondria-localized prosurvival ISG in antagonizing the effect of TRAIL. Curtailing G1P3-mediated antiapoptotic signals could improve therapies for myeloma or other malignancies.


Correlative dual-color dSTORM/AFM reveals protein clusters at the cytoplasmic side of human bronchial epithelium membranes.
The organization of a cell membrane is vital for various functions, such as receptor signaling and membrane traffic. However, the understanding of membrane organization remains insufficient, especially the localizations of specific proteins in the cell membrane. Here, we used correlative super-resolution fluorescence/atomic force microscopy to correlate the distributions of specific proteins Na+/K+-ATPase (NKA, an integral membrane protein) and ankyrin G (AnkG, a scaffolding protein) with the topography of the cytoplasmic side of human bronchial epithelium membranes. Our data showed that NKA and AnkG proteins preferred to localize in the protein islands of membranes. Interestingly, we also found that functional domains composed of specific proteins with a few hundreds of nanometers were formed by assembling protein islands with a few tens of nanometers.


Thyroid hormone metabolism and the source of plasma triiodothyronine in 2-week-old rats: effects of thyroid status.
Earlier studies have shown larger increments in serum T3 in 2-week-old congenitally hypothyroid rats than in euthyroid controls after injections of small doses of T4. Since hepatic and renal 5'-deiodination of T4 to T3 in vitro (5' D-I) is reduced during the neonatal period and in hypothyroidism, those results suggest that there may be major changes in the distribution and metabolism of T3 or that an alternative enzymatic pathway is the predominant source of extrathyroidally produced T3 in these rats. The alternative pathway, 5' D-II, is a relatively minor source of serum T3 in adult euthyroid rats, but the contribution of this pathway to the extrathyroid T3 pool during the neonatal period and in hypothyroxinemia is not known. Consequently, we studied [125I]T4 and [131I]T3 kinetics and fractional T4 to T3 conversion in 2-week-old euthyroid and hypothyroid rats and then explored the source of circulating T3 by manipulating 5' D-I activity with propylthiouracil and that of 5' D-II with thyroid hormone. The plasma clearance rate of T4 was increased in hypothyroid rats, a difference entirely accounted for by the faster fractional rate of irreversible removal in the hypothyroid pups. Plasma clearance rate of T3 was reduced in hypothyroid rats owing to the reduced volume of distribution of T3. Fractional T4 to T3 conversion was 2- to 3-fold higher in euthyroid or hypothyroid neonates than in adult rats. In euthyroid rats the serum concentration of T4 was 36 +/- 1 (SEM) ng/ml and that of T3 0.61 +/- 0.03 ng/ml, and the production rates were 432 and 159 ng day-1 30 g-1 BW for T4 and T3, respectively. About 80% of the T3 in euthyroid neonates was produced extrathyroidally . These findings are inconsistent with hepatic and renal 5' D-I being the main source of serum T3 in 2-week-old rats. In fact, liver and kidney 5' D-I activities were 40% and 65% of the corresponding adult values in euthyroid neonates, and in hypothyroid pups were further reduced to 15% and 17%. In contrast, 5' D-II, previously reported to be high in central nervous tissue and pituitary, was 7-10-fold higher in brown adipose tissue (BAT) of hypothyroid pups than in that of euthyroid ones.(ABSTRACT TRUNCATED AT 400 WORDS)


Networking Matters: A Social Network Analysis of the Association of Program Directors of Internal Medicine.
Theory: Networking has positive effects on career development; however, personal characteristics of group members such as gender or diversity may foster or hinder member connectedness. Social network analysis explores interrelationships between people in groups by measuring the strength of connection between all possible pairs in a given network. Social network analysis has rarely been used to examine network connections among members in an academic medical society. This study seeks to ascertain the strength of connection between program directors in the Association of Program Directors in Internal Medicine (APDIM) and its Education Innovations Project subgroup and to examine possible associations between connectedness and characteristics of program directors and programs. Hypotheses: We hypothesize that connectedness will be measurable within a large academic medical society and will vary significantly for program directors with certain measurable characteristics (e.g., age, gender, rank, location, burnout levels, desire to resign). Method: APDIM program directors described levels of connectedness to one another on the 2012 APDIM survey. Using social network analysis, we ascertained program director connectedness by measuring out-degree centrality, in-degree centrality, and eigenvector centrality, all common measures of connectedness. Results: Higher centrality was associated with completion of the APDIM survey, being in a university-based program, Educational Innovations Project participation, and higher academic rank. Centrality did not vary by gender; international medical graduate status; previous chief resident status; program region; or levels of reported program director burnout, callousness, or desire to resign. Conclusions: In this social network analysis of program directors within a large academic medical society, we found that connectedness was related to higher academic rank and certain program characteristics but not to other program director characteristics like gender or international medical graduate status. Further research is needed to optimize our understanding of connection in organizations such as these and to determine which strategies promote valuable connections.


Effects of non toxic doses of acyclovir on nitric oxide and cellular death responses in herpesvirus types 1 and 2 infected hep-2 cells.
Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) are among the most "successful" pathogens and code for a variety of proteins to direct the apoptosis/necrosis responses of the cells they infect. Nitric oxide (NO) is an important intracellular signaling molecule in pathological processes. Acyclovir (ACV) is a chain terminator that targets the viral DNA polymerase as an antiviral agent. In this study, NO signals, and apoptosis/necrosis responses of HEp-2 cells were compared when infected by HSV-1 and -2 for 24 hours against non toxic doses (starting from 48.8, 24.4, 12.2, 6.1, 3 to 1.5 microg/mL) of ACV. In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "upregulating effect" whereas HSV-2 had a "downregulating effect" on NO production, and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had a "down-regulating effect" whereas HSV-2 had an "upregulating effect" on NO responses (HSV-1 had a "downregulating effect" on NO production whereas HSV-2 had an "upregulating effect" on NO production without any ACV). In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "anti-apoptotic effect" whereas HSV-2 had a stimulation on "apoptotic effect", and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had an "apoptotic effect" and HSV-2 turned to "its natural viral apoptotic effect level" (HSV-1 had an "natural viral apoptotic effect" whereas HSV-2 had a "natural viral apoptotic effect" on apoptosis response without any ACV). In 48.8, and 24.4 microg/mL of ACV, HSV-1 had significant "necrotic effect" on necrotic cellular death, "necrosis" increased in 12.2, 6.1, 3 and 1.5 microg/mL of ACV (HSV-1 had a negligible "necrotic effect" on HEp-2 cells alone), and HSV-2 had a "natural viral necrotic effect" alone; and also in all non toxic ACV concentrations. These results showed that HSV-1 and -2 had different "strategies" on apoptosis/necrosis and NO with and without non toxic ACV. These differences deserve further studies in order to explain the interactions between apoptotic/anti apoptotic, necrotic genes and NO, and ACV in HSV-1 and HSV-2 infections respectively.


Effect of the microstructure of a hyperbranched polymer and nanoclay loading on the morphology and properties of novel polyurethane nanocomposites.
Novel polyurethane nanocomposites based on toluene diisocyanate, poly(propylene glycol), various hyperbranched polymers (HBPs), and layered silicate were synthesized with the aim of determining the effect of the layered silicate loading and the functionality of HBP on the structure and properties of polyurethane nanocomposites. The microstructure of the nanocomposites was investigated by X-ray diffraction analysis and high-resolution transmission electron microscopy. It was found that exfoliated morphology and good dispersion were obtained up to 8 phr clay loading for all of the nanocomposites. approximately 100% increment in tensile strength, approximately 2-fold increase in the lap shear strength, approximately 200% increment in the peel strength, and 120% increment in the storage modulus along with a dramatic improvement in thermal stability were observed with the addition of 8 phr clay, over the pristine polyurethane. The higher the level of functionality of the HBP, the higher is the property enhancement. These properties were correlated with the state of dispersion of the clay platelets in the polyurethane matrix, the structure of the matrix, and clay-polymer interaction.


Improvement of the noradrenergic symptom cluster following treatment with milnacipran.
Depression has a major impact on social functioning. Decreased concentration, mental and physical slowing, loss of energy, lassitude, tiredness, and reduced self-care are all symptoms related to reduced noradrenergic activity. Depressed mood; loss of interest or pleasure; sleep disturbances; and feelings of worthlessness, pessimism, and anxiety are related to reduced activity of both serotonergic and noradrenergic neurotransmission. The importance of noradrenergic neurotransmission in social functioning is supported by studies with the specific norepinephrine reuptake inhibitor reboxetine. In healthy volunteers, reboxetine increases cooperative social behavior and social drive. A placebo-controlled study in depressed patients comparing reboxetine with the selective serotonin reuptake inhibitor (SSRI) fluoxetine showed significantly greater improvement in social adaptation with reboxetine. Two recent studies have examined the effect of the serotonin and norepinephrine reuptake inhibitor milnacipran on social adaptation. A study in depressed patients found that at the end of 8 weeks of treatment with milnacipran, 42.2% patients were in remission on the Social Adaptation Self-evaluation Scale (SASS). Another study in depressed workers or homemakers found that mean depression scores were significantly reduced after 2 weeks, whereas the SASS scores were significantly improved after 4 weeks. A preliminary study comparing depressed patients treated with milnacipran or the SSRI paroxetine showed that milnacipran treatment resulted in a greater number of patients in social remission. The available data thus suggest that milnacipran may improve social functioning, with a possibly greater effect than the SSRI paroxetine. These preliminary data suggest further evaluation of social dysfunction and its treatment outcome in future trials of milnacipran.


Effect of combining ultralow-dose naloxone with morphine in intravenous patient-controlled analgesia: the cut-off ratio of naloxone to morphine for antiemesis after gynecologic surgery.
Admixing an ultralow dose of naloxone with intravenous morphine patient-controlled analgesia (PCA) has been shown to decrease postoperative nausea. However, the cut-off ratio of the naloxone-morphine admixture for antiemetic effects has not been investigated. The purpose of this study was to investigate the cut-off ratio of naloxone-morphine admixture in PCA for antiemesis after gynecologic surgery. This double-blind study enrolled 120 female patients who were scheduled for gynecologic surgery under general anesthesia. Patients were randomly allocated to one of three groups (n = 40 for each group). The concentration of naloxone and morphine respectively was 0 microg/mL and 1 mg/mL in group 1, 0.1 microg/mL and 1 mg/mL in group 2 (1:10,000), and 1 microg/mL and 1 mg/mL in group 3 (1:1000). Morphine consumption, verbal rating score of wound pain at rest and with exertion, and morphine-related side effects were investigated at 1, 2, 4 and 24 hours postoperatively. A total of 112 patients completed the study (37 in group 1, 36 in group 2, 39 in group 3). The incidence of nausea during the postoperative 4-24 hours was significantly lower in group 3 than in group 1 (23.1% vs. 56.8%, p < 0.05). Furthermore, the overall incidence of severe nausea was significantly lower in group 3 than in group 1 (2.6% vs. 24.3%, p < 0.05) as was the rescue antiemetic requirements (5.1% vs. 24.3%, p < 0.05). However, there were no significant differences between groups 2 and 1. The pain scores (at rest and with exertion) and 24-hour morphine consumption were not significantly different among the three groups. The antiemetic efficacy of ultralow-dose naloxone combined with PCA morphine is limited by a cut-off ratio of naloxone to morphine of 1:10,000.


Usefulness of diffusion-weighted magnetic resonance imaging-guided biopsy: pyothorax-associated lymphoma.
The relatively rare entity pyothorax-associated lymphoma (PAL) is an aggressive disease with a poor prognosis. Therefore, PAL should be diagnosed as soon as possible with minimal invasion. We herein report the case of an 81-year-old man with PAL that was successfully treated with chemotherapy. A computed tomography-guided tumor biopsy could not provide adequate specimens for pathological investigation, whereas a diffusion-weighted magnetic resonance imaging-guided tumor biopsy led to a diagnosis. Our findings suggest that diffusion-weighted image guidance for planning the biopsy of an intrathoracic mass, especially in cases of suspected PAL, is a highly accurate method because it provides information about cellularity and does not create calcification-related artifacts.


Physiological role of isocitrate lyase in dibenzo-p-dioxin and dibenzofuran metabolism by Sphingomonas wittichii RW1.
Sphingomonas wittichii RW1 is one out of three strains capable of metabolizing dioxin as a sole source for carbon and energy. Under laboratory conditions the degradation rates for these aromatics are relatively high (5 and 8 h for dibenzofuran (DBF) and dibenzo-p-dioxin (DD), respectively). However, their degradation rates are much lower in the environment due to several factors. One of these factors is the availability of other carbon sources. Acetate is a metabolized carbon source by S. wittichii RW1 and its presence in the environment would have a negative impact on DBF and DD degradation. In addition, expression of most of the genes for DBF and DD degradation were downregulated when grown on acetate compared to their growth on DBF and DD. We hypothesized that blocking the acetate utilization pathway in S. wittichii RW1 would prevent it from using acetate when present along with DD and DBF in contaminated sites. Blocking the glyoxylate shunt by deleting isocitrate lyase gene (icl) prevented the mutant strain (RW1Δicl) from using acetate as a sole carbon source thus depending on available DBF and DD in polluted sites. Our results showed that deletion of icl did not affect growth of S. wittichii RW1 on DBF and DD but blocked it from growing on acetate. Our results introduces an engineered strain that can be used as a new candidate to clean dioxin-contaminated sites which are rich with acetate.


Synthesis, antifungal activity, and QSAR study of novel trichodermin derivatives.
In an attempt to discover more potential antifungal agents, in this study, 21 novel trichodermin derivatives containing conjugated oxime ester (5a-5u) were designed and synthesized and were screened for in vitro antifungal activity. The bioassay tests showed that some of them exhibited good inhibitory activity against the tested pathogenic fungi. Compound 5a exhibited better activity against Pyricularia oryzae and Sclerotonia sclerotiorum than trichodermin, and compound 5j showed particular activity against P.oryzae and Botrytis cinerea. The quantitative structure-activity relationship (QSAR) indicated that log P and hardness were two critical parameters for the biological activities. The result suggested that these would be potential lead compounds for the development of fungicides with further structure modification.


Total and local (atom and atom type) molecular quadratic indices: significance interpretation, comparison to other molecular descriptors, and QSPR/QSAR applications.
This paper describes the significance interpretation, comparison to other molecular descriptors, and QSPR/QSAR applications of a new set of molecular descriptors: atom, atom type, and total molecular quadratic indices. The features of the kth total and local quadratic indices are illustrated by examples of various types of molecular structures, including chain lengthening, branching, heteroatoms content, and multiple bonds. The linear independence of the local (atom type) quadratic indices to others 0D, 1D, 2D, and 3D molecular descriptors is demonstrated by using principal component analysis for 42 heterogeneous molecules. It is concluded that the local quadratic indices are independent indices containing important structural information to be used in QSPR/QSAR and drug design studies. In this sense, molecular quadratic indices were used to the description and prediction of the boiling point of 28 alkyl alcohols and to the modeling of the partition coefficient (logP), specific rate constant (logk), and antibacterial activity of 2-furylethylene derivatives. These models were statistically significant and showed very good stability to data variation in leave-one-out (LOO) cross-validation experiment. The comparison with the other approaches also revealed good behaviors of our method in this QSAR study.


Active Listening Delays Attentional Disengagement and Saccadic Eye Movements.
Successful goal-directed visual behavior depends on efficient disengagement of attention. Attention must be withdrawn from its current focus before being redeployed to a new object or internal process. Previous research has demonstrated that occupying cognitive processes with a secondary cellular phone conversation impairs attentional functioning and driving behavior. For example, attentional processing is significantly impacted by concurrent cell phone use, resulting in decreased explicit memory for on-road information. Here, we examined the impact of a critical component of cell-phone use-active listening-on the effectiveness of attentional disengagement. In the gap task-a saccadic manipulation of attentional disengagement-we measured saccade latencies while participants performed a secondary active listening task. Saccadic latencies significantly increased under an active listening load only when attention needed to be disengaged, indicating that active listening delays a disengagement operation. Simple dual-task interference did not account for the observed results. Rather, active cognitive engagement is required for measurable disengagement slowing to be observed. These results have implications for investigations of attention, gaze behavior, and distracted driving. Secondary tasks such as active listening or cell-phone conversations can have wide-ranging impacts on cognitive functioning, potentially impairing relatively elementary operations of attentional function, including disengagement.


[Prevalence of diabetes, antidiabetic treatment and chronic diabetic complications reported by general practitioners].
Prevalence of type 2 diabetes has increased greatly over the past decade and focus of care for people with diabetes has shifted from specialists to general practitioners (GPs). Because of lack of the central registry, a real number of diagnosed diabetes in Poland is unknown, as unknown is the prevalence of diabetes in patients attending primary health care, provided treatment and a prevalence of chronic diabetic complications registered by GPs. Assessment of the prevalence of diabetes registered in primary health care, recommended antidiabetic treatment and prevalence of microangiopathic diabetic complications diagnosed by GPs. Study was performed in Szczecin, a city of 450 000 inhabitants, located in North-West part of Poland. Data were obtained in year 2002 from one of the primary health care centers, in which health care was provided by 12 GPs for 27 932 inhabitants (15655 females and 12277 males), aged 0-98 years (average 38.3 +/- 23.2 years). Data were extracted from medical records and provided by GP doctors. Number of diagnosed and registered diabetics was 993 (prevalence--3.56%), age 3-95 years (mean 65.4 +/- 13.6 years). The diabetic group consisted of 611 females (mean age 67.5 +/- 12.4)--prevalence--3.90% and 382 males (mean age 62.0 +/- 14.7)--prevalence--3.11% (p = 0.003). Mean duration of diabetes was 7.4 +/- 6.9 years and it was similar for males and females. Type 2 diabetes was diagnosed in 94.4%, type 1 diabetes in 4.5%, other types of diabetes in 1.1% of all patients. Prevalence of registered diabetes in the group of 0-10 years old was 0.08%, in the group 11-20 years--0.33%, 21-30 years--0.25%, 31-40 years--0.44%, 41-50 years--1.93%, 51-60 years--5.03%, 61-70 years--9.88% and in the group over 70 years old--14.37%. Prevalence of diabetes in the group over 14 years old was 4.38%, in the group over 20 years--4.86%, and in subjects older than 35 years--6.84%. Elderly patients, over 60 years account for 74% of all diabetic subjects and subjects over 70 years--for 45% of them. Reported treatment of type 2 diabetes: diet alone--9%, oral agents--68%, oral agents combined with insulin--10.5%, insulin alone--12.5%. Mean HbA1c value measured in 307 type 2 diabetic subjects was 7.25 +/- 1.28%. According to GPs' opinion chronic microangiopathic diabetes complications were present in 36.6% of type 2 diabetic subjects. Retinopathy was reported in 24.8% of patients, polyneuropathy in 2.4%, nephropathy in 1.5%, diabetic foot in 0.5%, and combination of different complications in 7.4% of them. In type 1 diabetes chronic diabetic complications were stated in 42.2% of subjects--retinopathy--in 15.6%, polyneuropathy--in 2.2%, nephropathy--in 2.2%, diabetic foot--in 2.2%, and combination of them--in 20.0%. Average number of registered diabetics was 83 per physician, however 6 doctors took care of 107-158 diabetic subjects. In the past year diabetologist consultation or hospitalisation in internal medicine unit was provided for 47% of type 2 diabetics and for 98% of type 1 diabetics. 1. The prevalence of diabetes registered in primary health care in Szczecin is higher than expected on the basis of European data. 2. Low number of type 2 diabetics is treated with diet alone and quite high number is treated with insulin. 3. Low number of chronic diabetic complications reported by GPs, despite long duration of disease, indicates the necessity of special training in delivering care for diabetic people, diagnosis of diabetic complications, increased access to secondary care and better cooperation between primary and secondary care.


Emerging outbreaks associated with conflict and failing healthcare systems in the Middle East.
The escalating conflicts in the Middle East have been associated with the rapid collapse of the existing healthcare systems in affected countries. As millions of refugees flee their countries, they become vulnerable and exposed to communicable diseases that easily grow into epidemic crises. Here, we describe infectious disease epidemics that have been associated with conflicts in the Middle East, including cholera, poliomyelitis, measles, cutaneous leishmaniasis, and diphtheria, that call for appropriate preventive measures. Local ongoing wars and failing healthcare systems have resulted in regional and global health threats that warrant international medical interventions.


The United States Armed Forces Amputee Patient Care Program.
United States military amputees are treated at either Walter Reed Army Medical Center (Washington, DC) or Brooke Army Medical Center (Fort Sam Houston, TX). At each center, a multidisciplinary team from more than a dozen specialties works together to address the psychological, social, vocational, and spiritual needs of our soldiers, marines, sailors, and airmen, as well as their physical rehabilitation. Excellent outcomes are being achieved with the current practices of the Armed Forces Amputee Care Program, but a great deal of evidence-based research must be done to determine the optimal time to close the wound, the etiology of heterotopic ossification in blast injury, the factors determining optimal socket design, and the best sequence and timing for introduction of different prosthetic technologies in the rehabilitation process.


Hadronic density of states from string theory.
We present an exact calculation of the finite temperature partition function for the hadronic states corresponding to a Penrose-Güven limit of the Maldacena-Nùñez embedding of the N=1 super Yang-Mills (SYM) into string theory. It is established that the theory exhibits a Hagedorn density of states. We propose a semiclassical string approximation to the finite temperature partition function for confining gauge theories admitting a supergravity dual, by performing an expansion around classical solutions characterized by temporal windings. This semiclassical approximation reveals a hadronic energy density of states of a Hagedorn type, with the coefficient determined by the gauge theory string tension as expected for confining theories. We argue that our proposal captures primarily information about states of pure N=1 SYM theory, given that this semiclassical approximation does not entail a projection onto states of large U(1) charge.


Genetic diversity and structure of Neotyphodium species and their host Achnatherum sibiricum in a natural grass-endophyte system.
Achnatherum sibiricum (Poaceae) is a perennial bunchgrass native to the Inner Mongolia Steppe of China. This grass is commonly infected by epichloë endophytes with high-infection frequencies. Previously, we identified two predominant Neotyphodium spp., N. sibiricum and N. gansuense. In the present study, genetic diversity and structure were analyzed for the two predominant Neotyphodium spp. as well as the host grass. We obtained 103 fungal isolates from five populations; 33 were identified as N. sibiricum and 61 as N. gansuense. All populations hosted both endophytic species, but genetic variation was much higher for N. gansuense than for N. sibiricum. The majority of fungal isolates were haploid, and 13% of them were heterozygous at one SSR locus, suggesting hybrid origins of those isolates. Significant linkage disequilibrium of fungal SSR loci suggested that both fungal species primarily propagate by clonal growth through plant seeds, whereas variation in genetic diversity and the presence of hybrids in both endophytic species revealed that although clonal propagation was prevalent, occasional recombination might also occur. By comparing genetic differentiation among populations, we found around 4-7-fold greater differentiation of endophyte populations than host populations, implying more restricted gene flow of endophytes than hosts. We proposed that endophyte infection of A. sibiricum might confer the host some selective advantages under certain conditions, which could help to maintain high-endophyte-infection frequencies in host populations, even when their gene flows do not match each other. Furthermore, we suggested that the same genotype of endophyte as well as host should be confirmed if the objective of the study is to know the influence of endophyte or host genotype on their symbiotic relationship, instead of just considering whether the plant is infected by an endophyte or not, since endophytes from the same host species could exhibit high levels of genetic diversity, which is likely to influence the outcome of their symbiotic relationship.


FITC-dextran as a probe for endosome function and localization in kidney.
Fluorescein isothiocyanate (FITC)-labeled endosomes were localized in kidney epithelial cells after tissue fixation and sectioning, and specific membrane transport properties of isolated endocytic vesicles were measured using the same probe. Rats were infused intravenously with 10 kDa FITC-dextran, and kidneys were fixed with paraformaldehyde lysine periodate. FITC-labeled vesicles were visualized in semithin (1 micron) frozen sections of excised tissue by epifluorescent microscopy and by electron microscopy after a photoconversion reaction. Most FITC-labeled endosomes were apically located in epithelial cells lining the urinary tubules. By immunocytochemistry the anti-lysosomal glycoprotein LGP 120 was absent from most of the FITC-labeled vesicles, although some colocalization was noted. The limiting membrane of FITC-labeled endosomes contained a vacuolar proton pump (pHmin = 6.23 +/- 0.033) and a water channel (osmotic water permeability coefficient, Pf = 0.052 +/- 0.005 cm/s) and was highly permeable to ethylene glycol and urea but relatively impermeable to glucose. Methods allowing the attribution of specific membrane functions to vesicles that can be visualized in the apical endocytic pathway of epithelial cells should be of general use for the study of endocytic pathways in a variety of systems.


Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease.
A growing body of evidence suggests a role for platelets in sickle cell disease (SCD). Despite the proinflammatory, occlusive nature of platelets, a role for platelets in acute chest syndrome (ACS), however, remains understudied. To provide evidence and potentially describe contributory factors for a putative link between ACS and platelets, we performed an autopsy study of 20 SCD cases-10 of whom died from ACS and 10 whose deaths were not ACS-related. Pulmonary histopathology and case history were collected. We discovered that disseminated pulmonary platelet thrombi were present in 3 out of 10 of cases with ACS, but none of the matched cases without ACS. Those cases with detected thrombi were associated with significant deposition of endothelial vWF and detection of large vWF aggregates adhered to endothelium. Potential clinical risk factors were younger age and higher platelet count at presentation. However, we also noted a sharp and significant decline in platelet count prior to death in each case with platelet thrombi in the lungs. In this study, neither hydroxyurea use nor perimortem transfusion was associated with platelet thrombi. Surprisingly, in all cases, there was profound pulmonary artery remodeling with both thrombotic and proliferative pulmonary plexiform lesions. The severity of remodeling was not associated with a severe history of ACS, or hydroxyurea use, but was inversely correlated with age. We thus provide evidence of undocumented presence of platelet thrombi in cases of fatal ACS and describe clinical correlates. We also provide novel correlates of pulmonary remodeling in SCD.


Examining the association of eating psychopathology with suicidality: Comparing cross-sectional and longitudinal tests of interpersonal-psychological mediators.
Eating disorders (EDs) are associated with high mortality rates from suicide. Empirical tests of the Interpersonal-Psychological Theory of Suicide (IPTS) have provided preliminary cross-sectional support for its application to individuals with EDs. Because IPTS seeks to predict development and changes in suicidal ideation (SI), longitudinal investigations are ideal. The purpose of this study was to conduct cross-sectional and longitudinal mediational tests of the effect of ED psychopathology on SI as explained by perceived burdensomeness, thwarted belongingness, and hopelessness. Participants were undergraduate students (N = 738) who completed self-report measures of ED symptoms and IPTS variables at up to three time points across 10 weeks. Multiple mediation analyses were conducted on cross-sectional and longitudinal data. Cross-sectional analyses indicate mostly consistent findings with existing literature; however, results from the longitudinal analyses failed to identify any mediational effects of ED psychopathology on SI. These differences emphasize the importance of empirical tests in both cross-sectional and longitudinal data. Given the inconsistent results, the utility of IPTS features in explaining the association between ED psychopathology and SI is unclear. Future studies should seek to replicate these findings using other methods of measurement across time (e.g., ecological momentary assessment) and within clinical ED samples.


Morphological distribution of μ chains and cd15 receptors in colorectal polyp and adenocarcinoma specimens.
We have recently investigated the localisation of immunoglobulin-producing cells (IPCs) in inflamed intestinal tissue samples from patients with inflammatory bowel disease (IBD), and identified two main patterns of B lymphocyte infiltration: one characterised by the moderate strong stromal localisation of small B1 cell-like IgM+/CD79+/CD20-/CD21-/CD23-/CD5 ± IPCs, and the other by the peri-glandular localisation of IPCs with irregular nuclei that had surface markers specific for a B cell subset (IgM and CD79), but quantitative differences in their λ and κ chains. The same patients were also tested for CD15+ receptors, which were localised on inflammatory cell surfaces or in the crypts of the intestinal epithelium. CD15+ receptor distribution in inflamed tissues was limited to the cell structures. The aim of the study was to analyse variations in IPCs and CD15+ cell morphology or distribution in bowel biopsy specimens taken from patients with pre-malignant polyps or adenocarcinomas. IPCs were analysed by means of immunofluorescence using polyclonal goat anti-human μ chains. The pre-malignant polyp specimens were tested for B cell surface phenotype λ and κ chains, CD79, CD20, CD21 and CD23 using an immunoperoxidase method. CD15+ cells were evaluated using the immunoperoxidase method and monoclonal anti-CD15 IgM. The study involved 14 patients (four with pre-malignant polyps and 10 with colorectal adenocarcinomas). The distribution of μ chains and CD15 markers varied in all of the biopsies, but delineated normal cell structures in the pre-malignant polyp specimens. B cell surface phenotype analysis of μ chain-positive cells identified a subset of CD79+/CD20-/CD21-/CD23- IPCs. The IPCs in certain areas showed the sporadic disintegration of inflammatory cell membranes or the accumulation of fluorescence in individual cells. IPC membrane disintegration was particularly marked in all of the adenocarcinoma samples, in which the CD15 markers also showed epithelial cell involvement. Furthermore, six of the ten adenocarcinoma samples had atypical and reorganised membranes that expressed an excess of both receptors and isolated small portions of tissue within the tumour. The findings of this preliminary morphological study suggest the presence of membrane disintegration and remodelling mechanisms in the tumours. The newly-formed membranes expressed high concentrations of inflammatory cell receptors that can confer adhesive properties.


The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.
Post-transcriptional modifications of miRNAs with 3' non-templated nucleotide additions (NTA) are a common phenomenon, and for a handful of miRNAs the additions have been demonstrated to modulate miRNA stability. However, it is unknown for the vast majority of miRNAs whether nucleotide additions are associated with changes in miRNA expression levels. We previously showed that miRNA 3' additions are regulated by multiple nucleotidyl transferase enzymes. Here we examine the changes in abundance of miRNAs that exhibit altered 3' NTA following the suppression of a panel of nucleotidyl transferases in cancer cell lines. Among the miRNAs examined, those with increased 3' additions showed a significant decrease in abundance. More specifically, miRNAs that gained a 3' uridine were associated with the greatest decrease in expression, consistent with a model in which 3' uridylation influences miRNA stability. We also observed that suppression of one nucleotidyl transferase, TUT1, resulted in a global decrease in miRNA levels of approximately 40% as measured by qRT-PCR-based miRNA profiling. The mechanism of this global miRNA suppression appears to be indirect, as it occurred irrespective of changes in 3' nucleotide addition. Also, expression of miRNA primary transcripts did not decrease following TUT1 knockdown, indicating that the mechanism is post-transcriptional. In conclusion, our results suggest that TUT1 affects miRNAs through both a direct effect on 3' nucleotide additions to specific miRNAs and a separate, indirect effect on miRNA abundance more globally.


Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue.
Mast cells and basophils have been known to play a central role in allergic inflammation through the release of chemical mediators by cross-linkage of IgE receptors. The IgE receptor triggering and calcium ionophore A23187 have also been shown to induce gene expression and production of tumor necrosis factor (TNF) by rat basophilic leukemia cells. In the present study, we examined whether IgE receptor triggering could induce gene expression and production of TNF in rat lung tissue. The lung tissue released not only histamine but also cytotoxic activity on L929 cells 2 and 4 h after incubation with dinitrophenyl conjugated to ovalbumin (DNP-OVA) following passive sensitization with anti-DNP monoclonal rat IgE antibody, whereas neither DNP-OVA nor anti-DNP IgE antibody could induce the cytotoxic activity when used solely. Calcium ionophore A23187 also could induce both histamine release and cytotoxic activity. These activities induced by IgE receptor triggering, A23187, and lipopolysaccharide were completely neutralized by preincubation with anti-mouse TNF-rabbit serum, but not with normal rabbit serum. Northern blot analysis using cDNA probe of mouse TNF demonstrated expression of TNF gene as early as 2 h after IgE receptor triggering. These data demonstrating that IgE receptor triggering induced gene expression and production of TNF in lung tissue suggest the participation of TNF in the pathogenesis of late asthmatic response through its biologic activities such as the attraction and activation of neutrophils and eosinophils.


Not in my treatment center: Leadership's perception of barriers to MOUD adoption.
Despite their well-established effectiveness, medications for opioid use disorder (MOUD) are widely underutilized across the United States. In the context of a large publicly funded behavioral health system, we examined the relationship between a range of implementation barriers and a substance use disorder treatment agency's level of adoption of MOUD. We surveyed leadership of publicly funded substance use disorder treatment centers in Philadelphia about the significance of barriers to implementing MOUD related to their workforce, organization, funding, regulations, and beliefs about MOUD's efficacy and safety. We queried leaders on the percentage of their patients with opioid use disorder who receive MOUD and examined associations between implementation barriers and MOUD adoption. Ratings of regulatory, organizational, or funding barriers of respondents who led high MOUD adopting agencies (N = 20) were indistinguishable from those who led agencies that were low adopting of MOUD (N = 23). In contrast, agency leaders who denied MOUD-belief or workforce barriers were significantly more likely to lead high-MOUD-adopting organizations. These findings suggest that leadership beliefs about MOUD may be a key factor of the organizational decision to adopt and should be a target of implementation efforts to increase direct provision of these medications.


A pathway and genetic factors contributing to elevated gene expression noise in stationary phase.
Previous studies have identified factors associated with transcription and translation efficiency, such as promoter strength and mRNA sequences, that can affect stochasticity in gene expression. Here we present evidence for a pathway and associated genetic factors (namely, the ribosome modulation factor RMF and ppGpp) in Escherichia coli that contribute to heightened levels of gene expression noise during stationary phase. Endogenous cellular mechanisms that globally affect gene expression noise, such as those identified in this study, could provide phenotypic diversity under adverse conditions such as stationary phase.


RBANS memory percentage retention: No evidence of incremental validity beyond RBANS scores for diagnostic classification of mild cognitive impairment and dementia and for prediction of daily function.
RBANS percentage retention scores may be useful for diagnosis, but their incremental validity is unclear. Percentage retention versus RBANS immediate and delayed memory subtests and delayed index scores were compared for diagnostic classification and for prediction of function. Data from 173 memory clinic patients with an interdisciplinary diagnosis (no cognitive impairment, amnestic mild cognitive impairment [aMCI], and dementia due to Alzheimer's disease [AD]) and complete RBANS data were analyzed. Across diagnostic contrasts, list percentage retention classification accuracy was similar to List Learning delayed recall, but below the Delayed Memory Index (DMI). Similarly, for classifying no cognitive impairment versus aMCI or dementia due to AD, story percentage retention was similar to Story Memory subtests and below the DMI. For classifying aMCI versus AD; however, Story Memory exceeded the DMI, but was similar to Story Memory subtest scores. Similarly, for prediction of function percentage retention measures did not predict variance beyond that predicted by the RBANS subtest or index scores. In sum, there is no evidence that calculation of percentage retention for RBANS adds clinical utility beyond those provided by the standard RBANS scores.


Effects of naloxone administration on endocrine abnormalities in chronic renal failure.
In 72 patients with end-stage renal failure and 70 healthy subjects, the influence of blockade of opioid receptors by naloxone on secretion of prolactin, lutropin (LH), follitropin (FSH), adrenocorticotropin (ACTH), somatotropin (HGH), insulin (IRI), glucagon (IR-G), parathyroid hormone (PTH) and calcitonin (CT) was studied. Administration of naloxone stimulated luliberin-induced LH and FSH secretion quantitatively equally in patients and controls. Blockade of opioid receptors was followed by a less marked suppression of chlorpromazine-induced prolactin secretion but by a higher response of hypoglycemia-induced ACTH secretion in uremic patients than in controls. In addition, a less marked suppressive effect of naloxone was noted on hypoglycemia-induced HGH secretion in chronic renal failure as compared with controls. Blockade of opioid receptors improved significantly glucose tolerance and glucose-induced insulin secretion in uremic patients and suppressed nearly completely glucagon secretion response during the second phase of a glucose tolerance test. Finally, administration of naloxone was followed by a blunted response of Ca-induced CT secretion and suppression of PTH. Data presented in this paper suggest the existence of hyperendorphinism in end-stage renal failure.


Lymphogranuloma venereum in a pregnant woman.
Lymphogranuloma venereum was diagnosed postpartum in a young black woman, who was a drug abuser. Chlamydia trachomatis was isolated from aspirate of a left inguinal mass, and the patient was also seropositive for human immunodeficiency virus. During hospitalization she was treated with ampicillin, gentamicin, and doxycycline. Her twin infant girls had no evidence of C. trachomatis infection. The mother was discharged from the hospital after partial resolution of the left inguinal mass and was lost to follow-up.


The predictive value of clonogenic stem cell assays for the diagnosis of polycythaemia vera.
Spontaneous growth of erythroid progenitor cells is one of the hallmarks of polycythaemia vera (PV). In vitro clonogenic assays can be used to support the diagnosis of PV. However, clonogenic assays are difficult to standardize, and their diagnostic value is accepted as a minor criteria for PV only in the case of positive results. Clonogenic assays need to be validated and normal ranges established carefully before they can be used for diagnostic purposes. In a retrospective study, we analysed the results of 146 consecutive clonogenic assays performed in patients with erythrocytosis between January 1992 and December 2000. Normal ranges were established on the basis of the results from 81 controls. The charts of the 146 patients were reviewed and the patients were allocated to the following diagnostic groups: PV (n = 38) and non-primary erythrocytosis (NPE, n = 65) according to the criteria of Pearson & Messinezy. In total, 43 patients were excluded from the study because of missing data. The clonogenic assay results were correlated with the final clinical diagnosis of the patients. At a cut-off value of 5 erythroid colony-forming unit colonies per well, 29 out of 38 patients with PV showed positive results, and 9 out of 38 patients showed false-negative results. In the NPE group, there were 64 out of 65 real-negative results and 1 out of 65 false-positive result. Thus the positive predictive value of the clonogenic assay for the diagnosis of PV was 97%. We conclude that clonogenic assays, in the case of positive results, and if carefully validated, are very useful and reliable tools for the diagnosis of PV.


Avoidance of neonicotinoid-treated seeds and cotyledons by captive eared doves (Zenaida auriculata, Columbidae).
Farmland birds can be exposed to neonicotinoids through the ingestion of treated unburied seeds and cotyledons. The aim of this study was to evaluate the avoidance of sorghum with imidacloprid, clothianidin or thiamethoxam, soybean with imidacloprid, and soybean cotyledons with imidacloprid or thiamethoxam on eared doves (Zenaida auriculata). Doves were fed with test food (untreated and neonicotinoid-treated sorghum, soybean or soybean cotyledons) and maintenance food (seed mix) for 3-5 days to study the repellency (primary repellency and conditioned aversion) and anorexia caused by neonicotinoid-treated food, followed by a 7-day period on maintenance food to study the persistence of the anorexic effect after neonicotinoid exposure. Immediately afterward, the same doves were exposed to treated test food during a second period of 3-5 days to study the potential reinforcement of food avoidance. Finally, doves were fed with untreated test food to test the capacity of the pesticide to induce conditioned food aversion against untreated food in subsequent encounters. Intoxication signs and differences of body weight were determined. With sorghum, the three neonicotinoids produced a decrease in the consumption of treated seeds by >97% compared to control birds. However, this was not enough to prevent the death of 3/8 and 1/8 of the doves exposed to imidacloprid and clothianidin, respectively. Anorexia was clearly observed with neonicotinoid-treated sorghum. The birds did not avoid the untreated sorghum after exposure to the treated sorghum, indicating that avoidance is not generalized to the type of food without an associated sensory cue. The results obtained with soybean seeds and cotyledons were less conclusive because captive doves hardly consumed these foods, even without neonicotinoid treatment. The avoidance of sorghum seeds treated with neonicotinoids was insufficient to prevent poisoning and death of eared doves.


Overexpression of OsHAK5 potassium transporter enhances virus resistance in rice (Oryza sativa).
Intracellular potassium (K+ ) transported by plants under the action of a number of transport proteins is crucial for plant survival under distinct abiotic and biotic stresses. A correlation between K+ status and disease incidence has been found in many studies, but the roles of K+ in regulating disease resistance to viral diseases remain elusive. Here, we report that HIGH-AFFINITY K+ TRANSPORTER 5 (OsHAK5) regulates the infection of rice grassy stunt virus (RGSV), a negative-sense single-stranded bunyavirus, in rice (Oryza sativa). We found the K+ content in rice plants was significantly inhibited on RGSV infection. Meanwhile, a dramatic induction of OsHAK5 transcripts was observed in RGSV-infected rice plants and in rice plants with K+ deficiency. Genetic analysis indicated that disruption of OsHAK5 facilitated viral pathogenicity. In contrast, overexpression of OsHAK5 enhanced resistance to RGSV infection. Our analysis of reactive oxygen species (ROS) including H2 O2 and O2- , by DAB and NBT staining, respectively, indicated that RGSV infection as well as OsHAK5 overexpression increased ROS accumulation in rice leaves. The accumulation of ROS is perhaps involved in the induction of host resistance against RGSV infection in OsHAK5 transgenic overexpression rice plants. Furthermore, RGSV-encoded P3 induced OsHAK5 promoter activity, suggesting that RGSV P3 is probably an elicitor for the induction of OsHAK5 transcripts during RGSV infection. These findings indicate the crucial role of OsHAK5 in host resistance to virus infection. Our results may be exploited in the future to increase crop yield as well as improve host resistance via genetic manipulations.


Comparison of enoxaparin and unfractionated heparin in coronary angioplasty.
Recent studies have shown that enoxaparin may be equally as safe and effective as unfractionated heparin during a coronary angioplasty procedure. The aim of this study was to investigate whether enoxaparin can be used effectively and safely in place of unfractionated heparin in patients undergoing emergency or programmed coronary angioplasty, regardless of the use of platelet glycoprotein IIb/IIIa inhibitors. We compared two series of consecutive patients, who received unfractionated heparin (n = 217) or enoxaparin (n = 116) during emergency or programmed angioplasty, regardless of age, weight, renal function and the coadministration of platelet glycoprotein IIb/IIIa inhibitors. In the patients who received enoxaparin the arterial sheaths were removed immediately after the procedure. There were no significant differences between the two groups as regards clinical characteristics or risk factors for coronary artery disease. During a 30-day follow up no major adverse cardiac events were observed (death, myocardial infarction, target vessel revascularisation). Multivariate logistic regression analysis showed no correlation between the anticoagulant used and the occurrence of major cardiac events in the two groups of patients (log odds ratio = -9.46, p = 0.89), after controlling for age, sex, administration of platelet glycoprotein IIb/IIIa inhibitors, number of coronary lesions, number of stents used, clinical picture and risk factors for coronary artery disease. As regards the development of haematoma in the groin, the only significant independent predictive factor for this was the coadministration of platelet glycoprotein IIb/IIIa inhibitors. The use of enoxaparin in coronary angioplasty is safe, effective and allows faster removal of sheaths and mobilisation of the patient.


Polymorphisms of the DNA repair gene XRCC1 and the frequency of somatic mutations at the glycophorin A locus in newborns.
Two DNA polymorphisms in the XRCC1 gene, a microsatellite repeat region in the 3' un-translated region (3'UTR) of the gene and a G-->A substitution resulting in an Arg to Gln amino acid change in codon 399, were examined in 189 newborns who had previously been studied for glycophorin A (GPA) N0 and NN variant frequencies (Vfs) in cord blood erythrocytes. The GPA analysis had revealed that 14 of the 189 had extreme NN Vfs ranging from 40 x 10(-6) to 1787 x 10(-6). Mean Vfs for the remaining 175 were N0=(4.8+/-2.80)x10(-6) and NN=(2.62+/-2.01)x10(-6). Seven alleles of a polymorphic tandem [AC](n) region of the XRCC1 gene were identified. No association between [AC](n) genotype and either N0 or NN Vfs was found amongst the group of 175 nor was the distribution of genotypes unusual for the group of 14 with extreme NN Vfs. Analysis of the 399Gln polymorphism revealed that for the group of 175, 36.0% were Arg/Arg, 49.7% Arg/Gln and 14.3% Gln/Gln and genotype had no influence on N0 and NN Vfs. However, the distribution of genotypes was significantly different in the group of 14 with extreme NN Vfs, 14.3% being Arg/Arg, 42.8% Arg/Gln and 42.8% Gln/Gln. The 14 newborns with extreme NN Vfs may represent a sub-group with an unidentified genotoxic exposure and/or predisposition to gene-duplication mutations or alternatively the high values could have arisen by increased clonal expansion of haemopoietic precursor cells carrying NN mutations. Our results suggest that carriers of the Gln/Gln genotype are over represented in this group but the role that the genotype has in the derivation of high NN Vfs remains to be resolved.


Variation in test ordering behaviour of GPs: professional or context-related factors?
The aim of this study was to describe GPs' test ordering behaviour, and to establish professional and context-related determinants of GPs' inclination to order tests. A cross-sectional analysis was carried out of 229 GPs in 40 local GP groups from five regions in The Netherlands of the combined number of 19 laboratory and eight imaging tests ordered by GPs, collected from five regional diagnostic centres. In a multivariable multilevel regression analysis, these data were linked with survey data on professional characteristics such as knowledge about and attitude towards test ordering, and with data on context-related factors such as practice type or experience with feedback on test ordering data. The main outcome measure was the percentage point differences associated with professional and context-related factors. The total median number of tests per GP per year was 998 (interquartile range 663-1500), with significant differences between the regions. The response to the survey was 97%. At the professional level, 'individual involvement in developing guidelines' (yes versus no), and at the context-related level 'group practice' (versus single-handed and two-person practices) and 'more than 1 year of experience working with a problem-oriented laboratory order form' (yes versus no) were associated with 27, 18 and 41% lower numbers of tests ordered, respectively. In addition to professional determinants, context-related factors appeared to be strongly associated with the numbers of tests ordered. Further studies on GPs' test ordering behaviour should include local and regional factors.


Deafness due to haemorrhagic labyrinthitis and a review of relapses in Streptococcus suis meningitis.
Deafness is a common and often permanent neurological sequel of Streptococcus (S.) suis meningitis. Suppurative labyrinthitis, rather than direct auditory nerve infection, has been found to be the site responsible for deafness. Neuroimaging is important to localise the site involved in hearing loss and to assess the feasibility of a cochlear implantation. S. suis is very sensitive to penicillin. Although a relapse of S. suis meningitis is uncommon, it can occur despite an adequate duration of appropriate antibiotic therapy. We describe a patient with S. suis meningitis, who developed permanent deafness from haemorrhagic labyrinthitis, as shown on magnetic resonance imaging. She suffered a relapse despite a seven-week course of intravenous antibiotics. A review on six cases of relapse reported in the literature shows that relapses occurred despite two to four weeks of antibiotics being administered to the patients. The clinical implications and treatment of relapse are discussed.


Microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic dynein.
Bone marrow megakaryocytes produce platelets by extending long cytoplasmic protrusions, designated proplatelets, into sinusoidal blood vessels. Although microtubules are known to regulate platelet production, the underlying mechanism of proplatelet elongation has yet to be resolved. Here we report that proplatelet formation is a process that can be divided into repetitive phases (extension, pause, and retraction), as revealed by differential interference contrast and fluorescence loss after photoconversion time-lapse microscopy. Furthermore, we show that microtubule sliding drives proplatelet elongation and is dependent on cytoplasmic dynein under static and physiological shear stress by using fluorescence recovery after photobleaching in proplatelets with fluorescence-tagged β1-tubulin. A refined understanding of the specific mechanisms regulating platelet production will yield strategies to treat patients with thrombocythemia or thrombocytopenia.


Cell-surface translational dynamics of nicotinic acetylcholine receptors.
Synapse efficacy heavily relies on the number of neurotransmitter receptors available at a given time. In addition to the equilibrium between the biosynthetic production, exocytic delivery and recycling of receptors on the one hand, and the endocytic internalization on the other, lateral diffusion and clustering of receptors at the cell membrane play key roles in determining the amount of active receptors at the synapse. Mobile receptors traffic between reservoir compartments and the synapse by thermally driven Brownian motion, and become immobilized at the peri-synaptic region or the synapse by: (a) clustering mediated by homotropic inter-molecular receptor-receptor associations; (b) heterotropic associations with non-receptor scaffolding proteins or the subjacent cytoskeletal meshwork, leading to diffusional "trapping," and (c) protein-lipid interactions, particularly with the neutral lipid cholesterol. This review assesses the contribution of some of these mechanisms to the supramolecular organization and dynamics of the paradigm neurotransmitter receptor of muscle and neuronal cells -the nicotinic acetylcholine receptor (nAChR). Currently available information stemming from various complementary biophysical techniques commonly used to interrogate the dynamics of cell-surface components is critically discussed. The translational mobility of nAChRs at the cell surface differs between muscle and neuronal receptors in terms of diffusion coefficients and residence intervals at the synapse, which cover an ample range of time regimes. A peculiar feature of brain α7 nAChR is its ability to spend much of its time confined peri-synaptically, vicinal to glutamatergic (excitatory) and GABAergic (inhibitory) synapses. An important function of the α7 nAChR may thus be visiting the territories of other neurotransmitter receptors, differentially regulating the dynamic equilibrium between excitation and inhibition, depending on its residence time in each domain.


Intravascular ultrasound-supported percutaneous angioplasty of post-kidney transplant renal artery bifurcation stenosis.
Transplant renal artery stenosis (TRAS) is an uncommon complication following renal transplantation. Its usual clinical presentation includes worsening hypertension and/or renal function, without any evidence of graft rejection. Bifurcation renal artery stenosis of the transplanted renal artery is rarely encountered. Percutaneous transluminal renal angioplasty (PTRA) with or without stenting is the procedure of choice to treat TRAS. We hereby describe a patient, who presented with impaired renal functions, four months following the renal transplantation. He underwent intravascular ultrasound-guided PTRA of the bifurcation lesion of TRAS.Results and conclusion: Superior renal artery had coronary drug-eluting stent implantation, while inferior renal artery and side branch of the superior renal artery had balloon angioplasty, alone. Post-intervention, the raised serum creatinine level decreased from 2.9 mg% to 1.7 mg%. The index case described the successful PTRA and stenting of the bifurcation lesion of TRAS, the technical results of which was optimized with the use of intravascular ultrasound.


T cell-monocyte interactions in the production of humoral factors regulating human granulopoiesis in vitro.
A variety of monocyte functions are modulated by the T cell lymphokine interferon-gamma (IFN-gamma). We assessed the capacity of IFN-gamma to induce release of granulocyte-monocyte stimulating factors (CSF-GM) from highly purified monocyte preparations. Whereas secretion of CSF-GM by monocytes is negligible in the absence of T cells, CSF-GM secretion is inducible when concentrations of IFN-gamma as low as 10 U/ml are present. This effect could be abrogated by specific neutralizing monoclonal antibody to IFN-gamma and was restricted to monocytes, as resting T cells failed to secrete detectable CSF-GM in response to IFN-gamma. The response of monocyte preparations to IFN-gamma was biphasic in that concentrations greater than 250 U/ml did not induce detectable CSF-GM activity. However, this was shown to be due to the release of a humoral inhibitor of G/M-progenitor cells, and not necessarily due to a lack of CSF-GM secretion.


Practical considerations in the development of a human cancer vaccine.
Factors involved in the development of a human oncornavirus vaccine are discussed. The isolation and purification of subviral gp69/71 antigenic components enhance the feasibility of developing safe vaccine. The recent isolation of a C-type virus (the HL-23) from a human leukemic patient and its similarity to the simian sarcoma virus presents us with a unique opportunity to test the safety and potency of a vaccine in nonhuman primates.


l-Isoleucine-Schiff Base Copper(II) Coordination Polymers: Crystal Structure, Spectroscopic, Hirshfeld Surface, and DFT Analyses.
A new copper(II) coordination polymer was synthesized from the l-isoleucine-Schiff base and characterized by elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy, single-crystal X-ray diffraction (XRD) analysis, electronic paramagnetic resonance, and thermogravimetric analysis. XRD analysis confirmed the square planar coordination geometry of metallic centers and a zipper-like polymer structure. Vibrational, electronic, and paramagnetic spectroscopies and thermal analysis were consistent with the crystal structure. A Hirshfeld surface (HS) and density functional theory (DFT) analyses were employed to gain additional insight into interactions responsible for complex packing. The quantitative examination of two-dimensional (2D) fingerprint plots revealed, among other van der Waals forces, the dominating participation of H···H and H···Cl interactions in the molecular packing. The use of computational methods provided great help in detailing the supramolecular interactions occurring in the crystal, which were mainly van der Waals attractions. The electronic transition analysis helped corroborate the electronic transitions observed experimentally in the absorption spectrum. The frequency and vibrational mode analysis gave a deeper insight into the characterization of the CuLCL complex.


Urea and protein metabolism in burned children: effect of dietary protein intake.
The response of urea metabolic kinetics, the rate of whole-body protein breakdown, and muscle and skin protein synthesis rates to dietary protein intake (1.15 to 2.92 g/kg/d) was assessed in children with 20% to 40% total body surface area burn injury using a primed continuous infusion of 15N2-urea and L-13C6-phenylalanine. Plasma urea concentration, production, and excretion rates increased with dietary protein intake without evidence of approaching maximum plateau values. There was no consistent evidence of urea recycling in these subjects (urea production = excretion) at any level of protein intake. The rate of appearance (Ra) of phenylalanine (an index of whole-body protein breakdown) and rate of muscle protein synthesis were independent of dietary protein, whereas there was a significant increase in skin protein synthesis with higher protein intake. We conclude that there seems to be little benefit of high protein intake on whole-body protein breakdown and muscle protein synthesis rates in these burn patients, although high-protein diets may enhance wound healing.


Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.
Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.


Recurrent ameloblastoma of the infratemporal fossa: diagnostic implications and a review of the literature.
It is unusual for odontogenic tumours such as ameloblastoma to occur in the infratemporal fossa. Although these odontogenic tumours usually arise in jaws, they can infiltrate into the infratemporal region, pterygomaxillary space or fissure, invading soft tissues by way of extension. A case of recurrent ameloblastoma in the infratemporal fossa region arising from an extension of the lesion from the site of previous occurrence in the right mandibular body is reported.


Formation of iodinated trihalomethanes and noniodinated disinfection byproducts during chloramination of algal organic matter extracted from Microcystis aeruginosa.
The increasing occurrence of harmful algal blooms in surface waters may increase the input of algal organic matter (AOM) to the dissolved organic matter pool. The formation of iodinated trihalomethanes (I-THMs) and noniodinated disinfection byproducts (DBPs) in synthetic waters containing AOM extracted from Microcystis aeruginosa was investigated in chloramination (preformed and in-situ formed chloramine, NH2Cl and Cl2-NH2Cl, respectively) and chlorination (Cl2) processes. AOM is much more favorable for iodine incorporation than natural organic matter (NOM). For example, the formation of I-THM from AOM is much higher than NOM isolate extracted from treated water (e.g., 3.5 times higher in the NH2Cl process), and thus higher iodine utilization and substitution factors from AOM were observed. Short contact time (2 min) chlorination in Cl2-NH2Cl process leading to the formation of halogenated intermediates favored I-THM formation, compared with NH2Cl process. However, further increasing chlorine contact time from 5 min to 24 h facilitated the conversion from iodide to iodate and thus I-THM formation decreased. Meanwhile, the formation of noniodinated THM4, haloacetonitriles (HANs), and haloacetaldehydes (HALs) increased. Factors including concentrations of AOM and bromide, pH, and chlorine/nitrogen ratios influenced the formation of I-THMs and noniodinated DBPs. To evaluate the benefit of mitigating I-THM formation over the risk of noniodinated DBP formation, measured DBPs were weighed against their mammalian cell toxicity indexes. Increasing the chlorine exposure increased the calculated cytotoxicity based on concentrations of measured I-THMs and noniodinated DBPs since unregulated HANs and HALs were the controlling agents.


Dispersive Raman spectroscopy and multivariate data analysis to detect offal adulteration of thawed beefburgers.
Beef offal (i.e., kidney, liver, heart, lung) adulteration of beefburgers was studied using dispersive Raman spectroscopy and multivariate data analysis to explore the potential of these analytical tools for detection of adulterations in comminuted meat products with complex formulations. Adulterated (n = 46) and authentic (n = 36) beefburger samples were produced based on formulations derived using market knowledge and an experimental design. Raman spectral data in the fingerprint range (900-1800 cm(-1)) were examined using both a classification (partial least-squares discriminant analysis, PLS-DA) and class-modeling (soft independent modeling of class analogy, SIMCA) approach to identify offal-adulterated and authentic beefburgers. PLS-DA models correctly classified 89-100% of authentic and 90-100% of adulterated samples. SIMCA models were developed using either PCA or PLS scores as input data. For authentic beefburgers, they exhibited sensitivity, specificity, and efficiency values of 0.94-1, 0.64-1, and 0.80-0.97, respectively. PLS regression quantitative models were also developed in an attempt to quantify total offal and added fat in these samples. The performance of PLS regression quantitative models for prediction of added fat may be acceptable for screening purposes, with the most accurate model producing a coefficient of determination in prediction of 0.85 and a root-mean-square error of prediction equal to 3.8% w/w.


The performance of culture-based methods and microscopy for quantification of noninfectious airborne microorganisms in epidemiological studies of highly contaminated work environments.
Airborne levels of microorganisms traditionally have been measured by culture-based methods. Culture-based methods are suitable for the detection of infectious agents, but their suitability for the detection of microorganisms with toxic and allergic effects is less clear, because these effects do not depend on viability of the organisms. During the last 15 years several noncultural methods have been developed for the quantification of airborne microorganisms, including microscopic methods. Microscopy may be expected to provide more valid exposure estimates of microorganisms than culture-based methods, because live and dead microorganisms can be detected. However, their validity may also depend on the ability to differentiate between species. The literature was searched for epidemiological studies in which exposure-response analyses were carried out using culture-based methods and/or microscopy. The influence of several factors on exposure-response associations were considered: design; population size; analytical method; sampling method; exposure levels; outcome; and confounder adjustment. Thirteen studies were found, including a total of 49 exposure-response analyses, and 45% of the analyses showed associations. It was found that the potential of microscopic methods to uncover exposure-response associations was only marginally better than that of culture-based methods (47 and 44%, respectively). Exposure-response associations were more often found with fungi (70%) than with gram-negative bacteria (50%) or total bacteria (22%), perhaps because fungal exposure is more strongly associated to respiratory outcomes than exposure to bacteria. But the shortcomings of the measurement methods may also be important. Further development of measurement methods for bacteria is therefore needed. The complex composition of bioaerosols in many work environments necessitate the assessment of exposure to multiple agents and multivariate statistical analysis of exposure-response associations.


Ultrasonographic interpretation of physiological changes in the female pelvis.
Ultrasonographic assessment of the pelvis of women of child bearing age requires an appreciation of the physiologic changes that occur during the menstrual cycle. A prospective study on 15 women was done between July and December 1981. Pre-ovulatory (late proliferative phase), post-ovulatory (early secretory phase), and premenstrual (late secretory phase) scans were performed during each menstrual cycle. Basal body temperatures were used to determine the time of ovulation. The appearance of the ovaries, uterus, and pouch of Douglas was documented. The purpose of this study was to assess if the developmental stage of a follicle can be determined by observing the presence or absence of ovarian cysts and noting their change with time, to determine if free fluid is an indicator of follicle rupture, and to assess changes in the endometrium. We concluded that one or more small or large ovarian cysts on a single scan is an unreliable predictor of the stage of follicular development; that serial scanning is the preferred method for following physiologic follicular change; that free fluid is associated with ovulation and is commonly seen on post-ovulatory scans; and that while a thick and echogenic endometrium is normal in the premenstrual phase, in most people a more subtle progressive thickening and increased reflectivity is observed.


[Measurement of cutaneous blood flow by laser Doppler velocimetry. Importance of probe effect and solvent effect after topical application].
A comparative methodological study of the probe and/or vehicle effects was performed in Human volunteers with two laser Doppler velocimeters (L.D.V.): Laserflo BPM 403, T.S.I., U.S.A. and Periflux PF2B, Perimed, Sweden. Individual variations of skin blood flow are great (up to 1,400%); this could be related to spontaneous variations and/or to the occlusive effect of the probe. Skin blood flow was significantly increased in 35% of the subjects after the application of the probe alone, and in 70 to 90% of the cases after topical application of water or ethanol (20 to 50 microliters). Lag times before vasodilatation measured only when the probe was applied on the skin were between 7.4 and 27 minutes, they were reduced between 5.2 and 8.3 minutes when the vehicles were applied. These data suggest that in any protocol for L.D.V. determination an absolute control and a vehicle control should be included to evaluate objectively topical vasoactive drugs.


Spontaneous reossification of the sella in transsphenoidal reoperation associated with strontium ranelate.
Spontaneous reossification of the sellar floor after transsphenoidal surgery has been rarely reported. Strontium ranelate, a divalent strontium salt, has been shown to increase bone formation, increasing osteoblast activity. We describe an unusual case of a young patient with Cushing's disease who was treated with strontium ranelate for low bone mass who experienced spontaneous sellar reossification after transsphenoidal surgery. A 21-year-old male presented with Cushing's features. His past medical history included delayed puberty diagnosed at 16 years, treated with testosterone for 3 years without further work-up. He was diagnosed with Cushing's disease initially treated with transsphenoidal surgery, which was not curative. The patient did not come to follow-up visits for more than 1 year. He was prescribed strontium ranelate 2 g orally once daily for low bone mass by an outside endocrinologist, which he received for more than 1 year. Two years after first surgery he was reevaluated and persisted with active Cushing's disease. Magnetic resonance image revealed a left 4 mm hypointense mass, with sphenoid sinus occupation by a hyperintense material. At repeated transsphenoidal surgery, sellar bone had a very hard consistency; surgery was complicated and the patient died. Sellar reossification negatively impacted surgery outcomes in this patient. While this entity is possible after transsphenoidal surgery, it remains unclear whether strontium ranelate could have affected sellar ossification. Delayed puberty can be a manifestation of Cushing's syndrome. A complete history, physical examination and appropriate work-up should be performed before initiating any treatment.Sellar reossification should always be taken into account when considering repeated transsphenoidal surgery. Detailed preoperative evaluation of bony structures by computed tomography ought to be performed in all cases of reoperation.We speculate if strontium ranelate may have affected bone mineralization at the sellar floor. We strongly recommend that indications for prescribing this drug should be carefully followed.


Distal Duodenal Varices: First Presentation of Upper Gastrointestinal Bleeding.
Varices are abnormal dilated veins which result from increased pressure in the portal circulation. Although the oesophagus and stomach are the most common sites for varices to develop, they may also occur as ectopic varices in the duodenum, rectum, and retroperitoneal areas. Isolated duodenal varices involving distal duodenum, particularly the fourth part of the duodenum, are extremely rare. However, such ectopic varices are associated with an increased risk of bleeding and mortality. Not only are they a diagnostic challenge, particularly if they present as a first manifestation of portal hypertension, they are also very difficult to treat due to their location. We present an interesting case of upper gastrointestinal bleeding where ectopic varices in the fourth part of the duodenum presented as a first manifestation of upper gastrointestinal bleeding. Gastroscopy did not reveal the source of bleeding and thus CT angiogram was performed in order to confirm the diagnosis. Radiological intervention by embolisation resulted in successful treatment.


Increased iodine uptake in the Nabothian cyst.
A 31-year-old female patient with papillary thyroid cancer, status post-total thyroidectomy and radioablation with (131)I underwent posttherapy whole-body scan with SPECT, which revealed increased iodine activity in the cervix. The subsequent ultrasound examination demonstrated that the site of elevated iodine activity was caused by cervical Nabothian cyst.


Defibrillation in children: why a range in energy dosing?
Infants and children have historically received a weight-based escalating defibrillation dose, commencing at 2J/kg. Researchers are increasingly suggesting that 2J/kg maybe an ineffective initial defibrillation dose. However without a definitive study there has been hesitancy to modify this initial dose. The International Liaison Committee on Resuscitation made a recommendation in 2010 of an initial dose of 2-4 J/Kg, increased from 2 J/Kg. The American Heart Association and the European Resuscitation Councils now have different initial dosing recommendations for children. The ERC advocates 4J/kg as the initial dose without escalation for subsequent shocks, while the AHA recommends 2-4 J/Kg, increasing to ≥ 4 J/Kg with subsequent shocks up to adult dose. The difficulty of finding a dose based on robust evidence continues to provide a stimulus for research to better define the best defibrillation energy dose for children.


[How I treat...a patient presenting with mycosis fungoides].
Primary lymphomas of the skin exhibit singular clinical, histological and prognostic features that are not shared by lymphomas originating from the lymphoid tissues. This review is an update of the current concepts about the diagnosis and treatment of mycosis fungoides, the most frequent entity among the primary cutaneous lymphomas.


In vitro evaluation of the antibacterial activity of five sealers used in root canal therapy.
Antibacterial activity is one of the important characteristics of an ideal root canal sealer. The aim of this study was to investigate the antibacterial activity of five different sealers against Enterococcus faecalis using two different methods. The mineral trioxide aggregate (MTA) Fillapex, Tg-sealer, Endomethasone, AH-26, and RoekoSeal sealers were placed into the brain heart infusion (BHI) culture medium containing E. faecalis (PTCC1393). The diameter of the bacterial zone of inhibition was measured. In the direct contact test, a suspension containing grinded set sealers and E. faecalis bacteria was cultured in BHI after 6, 15, and 60 min. The number of colonies in milliliter was calculated. Data were subjected to one-way ANOVA and Tukey's multiple comparisons test (P < 0.05). In the agar diffusion test, Endomethasone had the highest antibacterial activity against E. faecalis compared to other sealers (P < 0.001). In the direct test, the antibacterial effect of MTA Fillapex was significantly higher than that of all other sealers (P < 0.001). The technique and components of the tested sealers affect the antibacterial activity results. This study showed that all of sealers had antimicrobial effect.


Protein/polysaccharide interactions and their impact on haze formation in white wines.
Proteins in white wines may aggregate and form hazes at room temperature. This was previously shown to be related to pH-induced conformational changes and to occur for pH <3.5. The aim of the present work was to study the impact of wine polysaccharides on pH-induced haze formation by proteins but also the consequences of their interactions with these proteins on the colloidal stability of white wines. To this end, model systems and purified global pools of wine proteins and polysaccharides were used first. Kinetics of aggregation, proteins involved, and turbidities related to final hazes were monitored. To further identify the impact of each polysaccharide, fractions purified to homogeneity were used in a second phase. These included two neutral (mannoprotein and arabinogalactan) and two negatively charged (rhamnogalacturonan II dimer (RG-II) and arabinogalactan) polysaccharides. The impact of major wine polysaccharides on wine protein aggregation at room temperature was clearly less marked than those of the pH and the ionic strength. Polysaccharides modulated the aggregation kinetics and final haziness, indicating that they interfere with the aggregation process, but could not prevent it.


Analysis of the 1982 ARA lupus criteria data set by recursive partitioning methodology: new insights into the relative merit of individual criteria.
The 339 cases of systemic lupus erythematosus (SLE) and controls used in 1982 to develop the current ARA rules for classifying this disease were further analyzed using recursive partitioning methodology. The method identified 9 subgroups of cases and controls. It allowed correct classification of 97% of cases and 95% of controls while using only 6 criteria instead of 11. Antibodies to DNA were found to be the overall best discriminator. The largest subgroup (116 cases/4 controls) was made up of patients with both anti-DNA and fluorescent antinuclear antibody (FANA). Presence of malar rash was helpful in distinguishing SLE cases among patients who were anti-DNA negative. Low and high FANA values, in combination with other variables, helped to identify 3 SLE subgroups. Unlike the 1982 criteria, which did not include serum complement, the classification tree also identified subgroups of patients in which complement was either the best or the 2nd best discriminator. Recursive partitioning methodology thus gives important insights into how the criteria interact and the relative importance of specific variables for classification purposes.


Toll-like receptors 3, 7, 8, and 9 in gastric cancer.
Toll-like receptors (TLRs) have been shown to have anti-tumor, pro-tumor, or even dual effects in cancer, and are thus potential prognostic biomarkers and immunotherapeutic targets. The present study aimed to evaluate associations between endosomal TLRs, namely TLR3, TLR7, TLR8, and TLR9, expression and clinicopathological variables and survival in gastric cancer. A total of 564 gastric adenocarcinoma patients were included in this retrospective cohort study. Samples and clinicopathological data were retrieved and organized into tissue microarray blocks. Protein expressions were detected by immunohistochemical staining. The patients were divided into low expression and high expression groups by median values of expression. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for confounders. Patients with high nuclear TLR3 expression had significantly poorer 5-year survival than the low nuclear TLR3 expression group in the univariable analysis (crude HR 1.31, 95% CI 1.07-1.60). With radically resected patients, poor prognosis was also seen in the multivariable analysis (adjusted HR 1.38, 95% CI 1.08-1.77). Cytoplasmic TLR3, TLR7, TLR8, and TLR9 were not associated with 5-year survival. In conclusion, high nuclear TLR3 expression seems to have prognostic impact in gastric cancer, while TLR7, TLR8, and TLR9 do not.


Consumer Preferences of Topical Vitamin C Products: A Comparative Study.
Hyperpigmentation disorders greatly impact the quality of life of many patients. Vitamin C and ascorbic acid derivatives are commonly used as topical agents to reduce the effect of facial dyschromia. The market for vitamin C topicals has greatly increased, but with little oversight, resulting in a wide variety of products with regard to purity and efficacy. In this study, we conducted an analysis of the most highly rated vitamin C-containing compounds on Amazon and Sephora. It was found that consumers for both retailers prioritized efficacy and cosmetic elegance in their rating of products. Additionally, consumers displayed no preference among vitamin C derivatives in the products available to them. This study highlights the diverse vitamin C formulations currently available as well as consumer preferences, emphasizing the importance of fully reviewing all products patients are utilizing to better counsel on treatment regimens.


Integrating the 3Ds--social determinants, health disparities, and health-care workforce diversity.
The established relationships among social determinants of health (SDH), health disparities, and race/ethnicity highlight the need for health-care professionals to adequately address SDH in their encounters with patients. The ethnic demographic transition slated to occur during the next several decades in the United States will have numerous effects on the health-care sector, particularly as it pertains to the need for a more diverse and culturally aware workforce. In recent years, a substantial body of literature has developed, exploring the extent to which diversity in the health-care workforce may be used as a tool to eliminate racial/ethnic disparities in health and health care in the U.S. We explore existing literature on this topic, propose a conceptual framework, and identify next steps in health-care policy for reducing and eliminating health disparities by addressing SDH and diversification of the health-care workforce.


A novel approach to evaluate the pharmacodynamics of a selective dopamine D1/D5 receptor partial agonist (PF-06412562) in patients with stable schizophrenia.
PF-06412562 is an orally bioavailable, selective dopamine D1/D5 receptor partial agonist with a non-catechol structure under evaluation for treatment of cognitive impairment in schizophrenia. This randomized, double-blind, placebo-controlled, parallel-group, Phase 1b study examined the pharmacokinetics and pharmacodynamics of three doses of PF-06412562 (3 mg, 9 mg, and 45 mg twice daily) over 15 days in patients with schizophrenia receiving antipsychotics. Primary endpoints included adjunctive safety/tolerability and effects on MATRICS Consensus Cognitive Battery Working Memory domain and reward processing (Monetary Incentive Delay) tasks. Exploratory endpoints included other behavioral/neurophysiological tasks, including the N-back task. Among 95 subjects (78% male; mean age 34.8 years), baseline characteristics were similar across groups. The MATRICS Consensus Cognitive Battery Working Memory composite change from baseline on Day 13 improved in all groups, the smallest improvement was observed in the 45 mg group and was significantly smaller than that in the placebo group (two-sided p=0.038). For the Monetary Incentive Delay task (change from baseline in blood-oxygen-level-dependent functional magnetic resonance imaging activation in anterior ventral striatum for the contrast of cue gain>cue no gain on Day 15), no PF-06412562 dose was significantly different from placebo. No doses of PF-06412562 showed a significant difference on two-back task accuracy versus placebo. Adjunctive treatment with PF-06412562 was safe and well tolerated in patients with schizophrenia. PF-06412562 failed to show clinical benefit relative to placebo on assessments of cognition or reward processing in symptomatically stable patients over a 15-day treatment period. Numerous limitations due to the safety study design warrant further efficacy evaluation for this drug mechanism.