Oscillation of ion fluxes in mammalian erythrocytes. Mechanism of oscillation.
The dependence of ionophore-induced oscillations in rat erythrocytes on various concentrations of A23187, FCCP and Ca2+ was analysed using ion-selective electrodes. The oscillations were shown to be independent of the extracellular concentration of carbonylcyanide p-trifluoromethoxyphenylhydrazone and Ca2+. The dependence of oscillations on the concentration A23187 was shown to be a threshold characteristic and represented by a bell-shaped curve. In the course of oscillations the redistribution of A23187 between cells and the incubation medium was demonstrated using high-speed centrifugation. A hypothesis for oscillatory-state generation in erythrocytes was suggested on the basis of pH-dependent changes of the Ca2+ ionophore A23187 content in cells. According to this hypothesis the H+ concentration within the external membrane-adjacent layer serves as a causative factor for induction of cyclic desorption of A23187 molecules from the cell membrane.


Collection of triatomines from sylvatic habitats by a Trypanosoma cruzi-infected scent detection dog in Texas, USA.
Triatomine insects, vectors of the etiologic agent of Chagas disease (Trypanosoma cruzi), are challenging to locate in sylvatic habitats. Collection techniques used in the United States often rely on methods to intercept seasonally dispersing adults or on community scientists' encounters. Neither method is suited for detecting nest habitats likely to harbor triatomines, which is important for vector surveillance and control. Furthermore, manual inspection of suspected harborages is difficult and unlikely to reveal novel locations and host associations. Similar to a team that used a trained dog to detect sylvatic triatomines in Paraguay, we worked with a trained scent detection dog to detect triatomines in sylvatic locations across Texas. Ziza, a 3-year-old German Shorthaired Pointer previously naturally infected with T. cruzi, was trained to detect triatomines. Over the course of 6 weeks in the fall of 2017, the dog and her handler searched at 17 sites across Texas. The dog detected 60 triatomines at 6 sites; an additional 50 triatomines were contemporaneously collected at 1 of these sites and 2 additional sites without the assistance of the dog. Approximately 0.98 triatomines per hour were found when only humans were conducting searches; when working with the dog, approximately 1.71 triatomines per hour were found. In total, 3 adults and 107 nymphs of four species (Triatoma gerstaeckeri, Triatoma protracta, Triatoma sanguisuga, and Triatoma indictiva) were collected. PCR testing of a subset revealed T. cruzi infection, including DTUs TcI and TcIV, in 27% of nymphs (n = 103) and 66% of adults (n = 3). Bloodmeal analysis of a subset of triatomines (n = 5) revealed feeding on Virginia opossum (Didelphis virginiana), Southern plains woodrat (Neotoma micropus), and eastern cottontail (Sylvilagus floridanus). A trained scent detection dog enhanced triatomine detections in sylvatic habitats. This approach is effective at detecting nidicolous triatomines. Control of sylvatic sources of triatomines is challenging, but this new knowledge of specific sylvatic habitats and key hosts may reveal opportunities for novel vector control methods to block the transmission of T. cruzi to humans and domestic animals.


Analytic solution during an infusion test of the linear unsteady poroelastic equations in a spherically symmetric model of the brain.
This work determines the spatial and temporal distribution of cerebrospinal fluid (CSF) pressure and brain displacement during an infusion test in a spherically symmetric model of the brain. The response of CSF pressure and parenchymal displacement to blood pressure pulsations is determined in the solution. We use a spherically symmetric, three-component poroelastic model of the brain, differentiating between the solid elastic matrix, the CSF and the arterial blood compartments. The governing equations are linearized with quasi-constant poroelastic parameters. The solution does reproduce the average intracranial pressure increase during the test as well as the rise in CSF pressure pulsation amplitude due to transmission of blood pressure oscillations. In addition, the CSF flux into and out of the parenchyma is shown over time.


Mouse dead end 1-β interacts with c-Jun and stimulates activator protein 1 transactivation.
Dead end 1 (DND1), important for maintaining the viability of primordial germ cells, is the first protein containing an RNA recognition motif that has been directly implicated as a heritable cause of spontaneous tumorigenesis. In the present study, c-Jun was identified through yeast two-hybrid screening of a 10.5-day old mouse embryo cDNA library as one of the proteins which interact with DND1-β. The interaction between DND1-β and c-Jun was demonstrated to occur by glutathione S‑transferase pull‑down and co-immunoprecipitation. Using confocal microscopy, DND1-β was found to be specifically expressed in GC-1 spermatogonia cells, mainly in the nuclei. When transfected into GC-1 cells, DND1-β and c-Jun were demonstrated to be co-localized principally in the nuclei. Furthermore, in a dual luciferase reporter assay, the transcriptional activity of activator protein 1 was demonstrated to be significantly increased by co-transfection with DND1-β and c-Jun plasmids in GC-1 cells. The identification and confirmation of an additional protein interacting with DND1-β facilitates the investigation of the functions and molecular mechanisms of DND1.


Towards kinetic modeling of genome-scale metabolic networks without sacrificing stoichiometric, thermodynamic and physiological constraints.
Mathematical modeling is an essential tool for the comprehensive understanding of cell metabolism and its interactions with the environmental and process conditions. Recent developments in the construction and analysis of stoichiometric models made it possible to define limits on steady-state metabolic behavior using flux balance analysis. However, detailed information on enzyme kinetics and enzyme regulation is needed to formulate kinetic models that can accurately capture the dynamic metabolic responses. The use of mechanistic enzyme kinetics is a difficult task due to uncertainty in the kinetic properties of enzymes. Therefore, the majority of recent works considered only mass action kinetics for reactions in metabolic networks. Herein, we applied the optimization and risk analysis of complex living entities (ORACLE) framework and constructed a large-scale mechanistic kinetic model of optimally grown Escherichia coli. We investigated the complex interplay between stoichiometry, thermodynamics, and kinetics in determining the flexibility and capabilities of metabolism. Our results indicate that enzyme saturation is a necessary consideration in modeling metabolic networks and it extends the feasible ranges of metabolic fluxes and metabolite concentrations. Our results further suggest that enzymes in metabolic networks have evolved to function at different saturation states to ensure greater flexibility and robustness of cellular metabolism.


Intracellular activation of human adamalysin 19/disintegrin and metalloproteinase 19 by furin occurs via one of the two consecutive recognition sites.
Adamalysin 19 (a disintegrin and metalloproteinase 19, ADAM19, or meltrin beta) is a plasma membrane metalloproteinase. Human ADAM19 zymogen contains two potential furin recognition sites (RX(K/R)R), (196)KRPR(200)R and (199)RRMK(203)R, between its pro- and catalytic domains. Protein N-terminal sequencing revealed that the cellular mature forms of hADAM19 started at (204)EDLNSMK, demonstrating that the preferred furin cleavage site was the (200)RMK(203)R downward arrow(204)EDLN. Those mature forms were catalytically active. Both Pittsburgh mutant of alpha(1)-proteinase inhibitor and dec-Arg-Val-Lys-Arg-chloromethyl ketone, two specific furin inhibitors, blocked the activation of hADAM19. Activation of hADAM19 was also blocked by brefeldin A, which inhibits protein trafficking from the endoplasmic reticulum to the Golgi, or, a calcium ionophore known to inhibit the autoactivation of furin. When (202)KR were mutated to AA, the proenzyme was also activated, suggesting that (197)RPRR is an alternative activation site. Furthermore, only pro-forms of hADAM19 were detected in the (199)RR to AA mutant, which abolished both furin recognition sites. Moreover, the zymogens were not converted into their active forms in two furin-deficient mammalian cell lines; co-expression of hADAM19 and furin in these two cell lines restored zymogen activation. Finally, co-localization between furin and hADAM19 was identified in the endoplasmic reticulum-Golgi complex and/or the trans-Golgi network. This report is the first thorough investigation of the intracellular activation of adamalysin 19, demonstrating that furin activated pro-hADAM19 in the secretory pathway via one of the two consecutive furin recognition sites.


Non-covalent interactions in biomacromolecules.
Non-covalent interactions play an important role in chemistry, physics and especially in biodisciplines. They determine the structure of biomacromolecules such as DNA and proteins and are responsible for the molecular recognition process. Theoretical evaluation of interaction energies is difficult; however, perturbation as well as variation (supermolecular) methods are briefly described. Accurate interaction energies can be obtained by complete basis set limit calculations providing a large portion of correlation energy is covered (e.g. by performing CCSD(T) calculations). The role of H-bonding and stacking interactions in the stabilisation of DNA, oligopeptides and proteins is described, and the importance of London dispersion energy is shown.


Review of cytomegalovirus infection findings with mammalian target of rapamycin inhibitor-based immunosuppressive therapy in de novo renal transplant recipients.
Cytomegalovirus (CMV) infection and disease are major complications in the renal transplant recipient. The occurrence of CMV is associated with acute rejection, allograft dysfunction, significant end-organ disease, and mortality. Several clinical studies have indicated that the use of certain immunosuppressive drugs can delay the reconstitution of CMV-specific cell-mediated immune responses, thereby leading to uncontrolled CMV replication. Accumulating evidence indicates, however, that the use of the mammalian target of rapamycin (mTOR) inhibitors, sirolimus, and everolimus, may decrease the incidence and severity of CMV infection in renal transplant recipients. The purpose of this article is to review CMV infection data from randomized clinical trials that investigated the use of sirolimus- and everolimus-based treatment regimens in de novo renal transplantation. The mTOR inhibitor clinical trials included were primarily identified using biomedical literature database searches, with additional studies added at the authors' discretion. This review will summarize these studies to discuss whether mTOR inhibitor-based immunosuppressive therapy can reduce the magnitude of CMV-related complications in the de novo renal transplantation setting.


Hyperamylasemia due to poorly differentiated adenosquamous carcinoma of the ovary.
In a patient with poorly differentiated ovarian carcinoma, the symptomatology was mistaken for acute pancreatitis. A review of the pertinent literature argues in favor of the early use of amylase isoenzymes in patients whose history, objective signs, and routine diagnostic studies fail to disclose pancreatic disease.


Use of mechanical ventilation in adults with severe asthma.
Asthma severe enough to require intubation and mechanical ventilation is associated with a mortality rate of about 10%. Therapeutic modalities are ever-changing and at times controversial. This paper provides an update on such modalities and presents, in a step-wise fashion, those most appropriate for practical patient care. The timing of intubation and the methods used to control airway patency, arterial pH and gas levels, and hemodynamic status are crucial to the success of therapy. Finally, conventional and disputed methods of bronchodilation are outlined.


Advances in optical molecular imaging for neural visualization.
Iatrogenic nerve injury is a significant complication in surgery, which can negatively impact patients' quality of life. Currently, the main clinical neuroimaging methods, such as computed tomography, magnetic resonance imaging, and high-resolution ultrasonography, do not offer precise real-time positioning images for doctors during surgery. The clinical application of optical molecular imaging technology has led to the emergence of new concepts such as optical molecular imaging surgery, targeted surgery, and molecular-guided surgery. These advancements have made it possible to directly visualize surgical target areas, thereby providing a novel method for real-time identification of nerves during surgery planning. Unlike traditional white light imaging, optical molecular imaging technology enables precise positioning and identifies the cation of intraoperative nerves through the presentation of color images. Although a large number of experiments and data support its development, there are few reports on its actual clinical application. This paper summarizes the research results of optical molecular imaging technology and its ability to realize neural visualization. Additionally, it discusses the challenges neural visualization recognition faces and future development opportunities.


The Caenorhabditis elegans CUB-like-domain containing protein RBT-1 functions as a receptor for Bacillus thuringiensis Cry6Aa toxin.
Plant-parasitic nematodes cause huge agricultural economic losses. Two major families of Bacillus thuringiensis crystal proteins, Cry5 and Cry6, show nematicidal activity. Previous work showed that binding to midgut receptors is a limiting step in Cry toxin mode of action. In the case of Cry5Ba, certain Caenorhabditis elegans glycolipids were identified as receptors of this toxin. However, the receptors for Cry6 toxin remain unknown. In this study, the C. elegans CUB-like-domain containing protein RBT-1, released by phosphatidylinositol-specific phospholipase C (PI-PLC), was identified as a Cry6Aa binding protein by affinity chromatography. RBT-1 contained a predicted glycosylphosphatidylinositol (GPI) anchor site and was shown to locate in lipid rafts in the surface of the midgut cells. Western ligand blot assays and ELISA binding analysis confirmed the binding interaction between Cry6Aa and RBT-1 showing high affinity and specificity. In addition, the mutation of rbt-1 gene decreased the susceptibility of C. elegans to Cry6Aa but not that of Cry5Ba. Furthermore, RBT-1 mediated the uptake of Cry6Aa into C. elegans gut cells, and was shown to be involved in triggering pore-formation activity, indicating that RBT-1 is required for the interaction of Cry6Aa with the nematode midgut cells. These results support that RBT-1 is a functional receptor for Cry6Aa.


Sexual selection drives asymmetric introgression in wall lizards.
Hybridisation is increasingly recognised as an important cause of diversification and adaptation. Here, we show how divergence in male secondary sexual characters between two lineages of the common wall lizard (Podarcis muralis) gives rise to strong asymmetries in male competitive ability and mating success, resulting in asymmetric hybridisation upon secondary contact. Combined with no negative effects of hybridisation on survival or reproductive characters in F1-hybrids, these results suggest that introgression should be asymmetric, resulting in the displacement of sexual characters of the sub-dominant lineage. This prediction was confirmed in two types of secondary contact, across a natural contact zone and in two introduced populations. Our study illustrates how divergence in sexually selected traits via male competition can determine the direction and extent of introgression, contributing to geographic patterns of genetic and phenotypic diversity.


Electroconvulsive Therapy in Elderly Patients With Cerebral Aneurysms: A Systematic Review With Clinical Recommendations.
Electroconvulsive therapy (ECT) is commonly used in the elderly due to its proven efficacy and safety profile. However, presence of cardiovascular comorbidities such as cerebral aneurysms may complicate the course of treatment. Our knowledge about the possible risk factors and precautionary measures remains limited. We performed a systematic review of published case reports of elderly patients with cerebral aneurysms treated with ECT. A total of 11 cases were included for the review. One patient died because of subarachnoid hemorrhage (SAH) secondary to ictal hypertensive surge during treatment with ECT. Risk factors such as history of hypertension, age of the patient, extent of the ictal surge in blood pressure, efficacy of prophylactic treatment to control surge in blood pressure and characteristics of cerebral aneurysm each elevated the risk of complication in these cases. We reviewed safety measures based on the evidence from the current literature available. ECT is safe in elderly patients with cerebral aneurysms provided appropriate safety measures are employed. Screening for cerebral aneurysms in high risk patients, effective prevention and management of blood pressure elevation acutely during ECT is the best practice to avoid adverse outcomes.


An Overview of Investigational and Experimental Drug Treatment Strategies for Marfan Syndrome.
Marfan syndrome (MFS) is a heritable connective tissue disorder caused by pathogenic variants in the gene coding for the extracellular matrix protein fibrillin-1. While the disease affects multiple organ systems, the most life-threatening manifestations are aortic aneurysms leading to dissection and rupture. Other cardiovascular complications, including mitral valve prolapse, primary cardiomyopathy, and arrhythmia, also occur more frequently in patients with MFS. The standard medical care relies on cardiovascular imaging at regular intervals, along with pharmacological treatment with β-adrenergic receptor blockers aimed at reducing the aortic growth rate. When aortic dilatation reaches a threshold associated with increased risk of dissection, prophylactic surgical aortic replacement is performed. Although current clinical management has significantly improved the life expectancy of patients with MFS, no cure is available and fatal complications still occur, underscoring the need for new treatment options. In recent years, preclinical studies have identified a number of potentially promising therapeutic targets. Nevertheless, the translation of these results into clinical practice has remained challenging. In this review, we present an overview of the currently available knowledge regarding the underlying pathophysiological processes associated with MFS cardiovascular pathology. We then summarize the treatment options that have been developed based on this knowledge and are currently in different stages of preclinical or clinical development, provide a critical review of the limitations of current studies and highlight potential opportunities for future research.


Brachydactyly, a possible inherited anomaly at prehistoric Prince Rupert Harbour.
Disproportionately short metacarpals or metatarsals in eight burial skeletons and three unusually short metapodials recovered as disturbed bones were identified in a 1500 B.C. to A.D. 500 skeletal series from eight archeological sites of the north mainland coast of British Columbia, Canada. At least ten people were affected from four sites for a minimum series frequency of 5.2%. Various factors clinically implicated in the occurrence of brachymetapody were investigated to account for the anomaly. Context-sensitive information suggested that trauma, infarction or infection, and individual or family-related malformation syndromes were unlikely possibilities. Some modern population data suggest that the series frequency was unusually high, particularly for fourth metatarsal involvement, the most commonly affected bone. Modern pedigree interpretations, ethnohistoric inferences, and the archeological contexts of the affected burial skeletons and site samples provide a framework for concluding that brachymetapody in the series was more likely due to the inheritance of an essentially isolated anomaly.


Population analysis of Streptococcus pneumoniae serotype 19A by whole genome sequencing in the Czech Republic and in Europe after serotype 19A inclusion in pneumococcal conjugate vaccine.
To present the results of whole genome sequencing (WGS) analysis of Streptococcus pneumoniae serotype 19A and to compare them with the respective data from Europe. The vaccine serotype 19A is widely distributed in the Czech Republic. WGS was used in this study as the most powerful available method for detailed characterization of S. pneumoniae. Nineteen Czech isolates of S. pneumoniae 19A were analysed and compared with 415 European isolates included in the PubMLST database. S. pneumoniae serotype 19A causes all types of pathogen - host interaction, from carriage to noninvasive and invasive pneumococcal disease (IPD). In 2010 - 2019, 3872 cases of IPD were reported within the surveillance programme in the Czech Republic, with 323 of these caused by serotype 19A. WGS data of the Czech serotype 19A isolates show a numerous and genetically related subpopulation of three sequencing types: ST-199, ST-416, and ST-3017. Within this subpopulation, the largest is the cluster of nine ST-199 isolates. High relatedness of ST-199 isolates is also confirmed by the fact that all but one isolate, 117/2019 (novel rST- -137805), share the same ribosome sequencing profile - rST-11365. Outside the above-mentioned subpopulation, there are only four isolates that form three separate genetic lines of serotype 19A. A highly similar situation is observed across European countries, where about half of all serotype 19A isolates form a genetically closely related subpopulation (ST-199, ST-416, ST-450, ST-667, ST-3017, and ST-10360) while isolates which are not part of this subpopulation represent a large number of unrelated genetic lines. The study has shown a mostly homogeneous population of S. pneumoniae serotype 19A to circulate in the post-vaccination era in both the Czech Republic and Europe, with some unrelated isolates located outside this population.


Capsular Block Syndrome Following Combined Cataract and Vitrectomy Surgery in a Patient With Intraocular Gas.
The aim of this report is to describe the diagnosis, treatment, and prevention of the rare complication of capsular block syndrome following combined cataract and vitrectomy surgery in a patient with intraocular gas.


[Use of josamycin in the eradication of meningococcus].
Because of their in vitro and in vivo activity on Neisseria meningitidis, good salivary and tonsillar tissue levels, high safety and non-penetration through the meningeal barrier, macrolides are agents of choice for treating Meningococcus carriers. To assess the value of josamycin for eliminating Meningococci in carriers, we carried out a 14-month study with bacteriological control. 27 carriers identified (throat specimens) among contacts of 28 children with meningococcal meningitis hospitalized in Pediatrics at the Amiens and Toulouse CHU (teaching hospitals) were treated. Josamycin was given in a dosage of 50 mg/kg/day in children and 2 g/day in adults, in two divided doses daily, for six days. Bacteriologic control at the end of treatment showed that every study patient was free of Meningococci. In vitro, strains recovered from carriers were inhibited by josamycin at concentrations of 0.25 to 1 microgram/l. Given its safety and efficacy, josamycin is well suited to prophylaxis of meningococcal infections.


Genetic compatibility and hatching success in the sea lamprey (Petromyzon marinus).
Recent discussion of genetic benefits of polyandry and female mate choice has distinguished between two potential factors influencing offspring quality: (i) some males carry higher quality genes and (ii) males and females differ in their degree of genetic compatibility. We examined evidence for effects of good genes and genetic compatibility on embryonic survival of sea lamprey (Petromyzon marinus), a fish species with external fertilization that spawns in North Atlantic rivers. Using in vitro fertilization, we made all possible crosses among 10 males and 5 females collected in the spawning grounds. Male identity did not have any significant effect on hatching success. However, female identity and male x female interactions had a highly significant effect on hatching success. Our results suggest that genetic compatibility between male and female genomes plays an important role in embryo survival during the early stages of development in the sea lamprey.


Tumor-to-tumor metastases: papillary thyroid carcinoma into a clear cell renal cell carcinoma.
Thyroid metastases to distant sites are uncommon incidents, most often metastasizing to the lungs and bones. Rates of metastasis to the kidney are particularly low, ranging from 2.8-3.8% for papillary and 6-20% for follicular variants of well-differentiated thyroid cancers (WDTCs). In rare instances, tumor-to-tumor metastasis between two true primary neoplasms can occurs. This medical phenomenon has previously occurred as a clear cell renal cell carcinoma (CCRCC) spreading to a WDTC. To our knowledge, this is the first report of a tumor-to-tumor metastasis of a thyroid cancer metastasizing to a primary renal neoplasm. A 72 year old male presented to the urology clinic with complaints of flank pain. Computed tomography (CT) imaging of the abdomen and pelvis revealed a 5.7 cm solid enhancing mass from the lateral aspect of the right kidney, suspicious for renal cell carcinoma (RCC). The patient subsequently underwent a right laparoscopic radical nephrectomy, and immunohistochemical staining of the 5.5 cm lesion revealed a positive RCC marker to establish a diagnosis of a pT1b ISUP Grade 2 CCRCC. The tumor contained a 3 mm focus of a lesion staining positive for TTF1 and Thyroglobulin, and negative for RCC marker. This finding established a diagnosis of a tumor-to-tumor metastasis of PTC to CCRCC. Subsequent ultrasound and CT of the head and neck revealed a heterogeneously hypodense 3.3 cm mass in the right thyroid lobe, prompting a total thyroidectomy and level VI neck dissection. Pathology revealed a classic variant multifocal PTC and two ipsilateral lymph nodes positive for metastatic PTC. Ultimately, the thyroid specimen was positive for lymphatic vascular invasion, extrathyroidal extension with invasion of the tracheal cartilage, staging as T4aN1aM1. On follow up examination the patient was recovering well, without signs of dysphagia or dysphonia, and showed bilateral mobile vocal cords on laryngoscope examination. Tumor-to-tumor metastasis between the thyroid and kidney is an extremely rare occurrence, reports of RCC metastases from a WDTC has not yet been reported in the literature. Corroboration of diagnostic imaging findings with immunohistochemistry staining can consolidate a diagnosis of thyroid neoplasm tumor-to-tumor metastasis to a RCC, thereby prompting surgical excision.


Smooth and accurate predictions of joint contact force time-series in gait using over parameterised deep neural networks.
Alterations in joint contact forces (JCFs) are thought to be important mechanisms for the onset and progression of many musculoskeletal and orthopaedic pain disorders. Computational approaches to JCFs assessment represent the only non-invasive means of estimating in-vivo forces; but this cannot be undertaken in free-living environments. Here, we used deep neural networks to train models to predict JCFs, using only joint angles as predictors. Our neural network models were generally able to predict JCFs with errors within published minimal detectable change values. The errors ranged from the lowest value of 0.03 bodyweight (BW) (ankle medial-lateral JCF in walking) to a maximum of 0.65BW (knee VT JCF in running). Interestingly, we also found that over parametrised neural networks by training on longer epochs (>100) resulted in better and smoother waveform predictions. Our methods for predicting JCFs using only joint kinematics hold a lot of promise in allowing clinicians and coaches to continuously monitor tissue loading in free-living environments.


A long isoform of the epithelial sodium channel alpha subunit forms a highly active channel.
A long isoform of the human Epithelial Sodium Channel (ENaC) α subunit has been identified, but little data exist regarding the properties or regulation of channels formed by α728. The baseline whole cell conductance of oocytes expressing trimeric α728βγ channels was 898.1±277.2 and 49.59±13.2 µS in low and high sodium solutions, respectively, and was 11 and 2 fold higher than the conductances of α669βγ in same solutions. α728βγ channels were also 2 to 5 fold less sensitive to activation by the serine proteases subtilisin and trypsin than α669βγ in low and high Na+ conditions. The long isoform exhibited lower levels of full length and cleaved protein at the plasma membrane and a rightward shifted sensitivity to inhibition by increases of [Na+]i. Both channels displayed similar single channel conductances of 4 pS, and both were activated to a similar extent by reducing temperature, altogether indicating that activation of baseline conductance of α728βγ was likely mediated by enhanced channel activity or open probability. Expression of α728 in native kidneys was validated in human urinary exosomes. These data demonstrate that the long isoform of αENaC forms the structural basis of a channel with different activity and regulation, which may not be easily distinguishable in native tissue, but may underlie sodium hyperabsorption and salt sensitive differences in humans.


Application of nested polymerase chain reaction to detection of Salmonella in poultry environment.
Isolation of Salmonella from environmental and processing-plant poultry samples requires the sampling of large numbers of areas within the poultry house or plant. Subsequently, the required number of samples necessitates a large volume of work for a microbiology laboratory, especially when the protocol requires the inclusion of a delayed secondary enrichment for the isolation of Salmonella. This study examined the use of the polymerase chain reaction (PCR) to identify those secondary enrichments containing Salmonella. The unique Salmonella virulence gene invA was chosen as the target for the development of a nested PCR because of its uniform distribution among Salmonella serotypes. The use of nested PCR primers increased the sensitivity of detection 100-fold, resulting in the detection of as few as four cells. There was a strong, statistically significant positive correlation between PCR and culture results as determined by chi-square (P < 0.001) and kappa (kappa = 0.915; excellent agreement) tests. Using PCR to screen primary enrichments for presumptive Salmonella contamination, we improved our efficiency at isolating Salmonella upon secondary enrichment by 20%, and no false negatives were observed. This method will not only validate the use of secondary enrichment procedures but also reduce costs and manpower required for the surveillance of Salmonella.


Teaching practical skills: a guide for preceptors.
Concern has been expressed that recently qualified nurses may be deficient in clinical skills. In this article the authors explore psychomotor skills learning and suggest strategies to support preceptors who have responsibility for developing such skills in students. The advice should prove helpful to clinical staff who are involved in teaching clinical skills to nursing students.


Evaluation of Hematocrit Influence on Self-Monitoring of Blood Glucose Based on ISO 15197:2013: Comparison of a Novel System With Five Systems With Different Hematocrit Ranges.
ISO 15197:2013 recommends testing procedures and acceptance criteria for the evaluation of influence quantities such as hematocrit on measurement results with systems for self-monitoring of blood glucose (SMBG). In this study, hematocrit influence was evaluated for a novel SMBG system (system A) and five other systems with different hematocrit ranges based on ISO 15197:2013. Test procedures were performed with one test strip lot for each system. Each system was tested within the hematocrit range indicated in the manufacturer's labeling (system A: 10-65%, B: 15-65%, C: 20-60%, D: 35-60%, E: 30-60%, F: 30-55%). According to ISO 15197:2013, clause 6.4.2, venous blood samples were used for the evaluation of hematocrit influence. The evaluation was performed for three glucose concentration categories (30-50 mg/dL, 96-144 mg/dL, and 280-420 mg/dL). For each glucose concentration category, at least five different hematocrit levels were investigated. The novel system A and systems B, E, and F complied with the tested lot with the defined criteria and showed ≤10 mg/dL and ≤10% difference between the test sample and the respective control sample with a hematocrit value of 42% ± 2% for BG concentrations <100 mg/dL and ≥100 mg/dL, respectively. Two systems showed >10% difference at glucose concentrations ≥100 mg/dL. Remarkable hematocrit influence within the labeled hematocrit range was obtained in two systems with the tested reagent system lot. Adequate SMBG systems should be carefully chosen by patients and their health care professionals, particularly for patients with increased and decreased hematocrit values.


PKD1 alleviates oxidative stress-inhibited osteogenesis of rat bone marrow-derived mesenchymal stem cells through TAZ activation.
Oxidative stress is known to inhibit osteogenesis and PKD1 is implicated in bone remodeling and skeletogenesis. In the present study, we explored the role of PKD1 in osteogenesis under oxidative stress. H2 O2 was used to induce oxidative stress in rat bone marrow (BM)-mesenchymal stem cells (MSCs) during osteoblast differentiation. Alkaline phosphatase (ALP) activity, calcium deposits, and the RUNX2 marker were assayed to determine osteogenic differentiation. The correlation of PKD1, Sirt1, c-MYC, and TAZ was further confirmed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. We found that H2 O2 induced the downregulation of PKD1 expression and the upregulation of c-MYC, and Sirt1 was accompanied by decreasing cell viability in BM-MSCs. During osteogenic differentiation, the expression of PKD1 was upregulated significantly whereas Sirt1 tended to be upregulated mildly under normal conditions. Both PKD1 and Sirt1 were upregulated upon oxidative stress. The positive correlation of PKD1 expression with osteogenic differentiation under normal conditions might be hindered by oxidative stress and PKD1 could interact with TAZ under oxidative stress to regulate osteogenic differentiation. Our results suggest that PKD1 may alleviate oxidative stress-inhibited osteogenesis of rat BM-MSCs through TAZ activation.


Third person singular -s in typical development and specific language impairment: Input and neighbourhood density.
The purpose of this study was to examine factors promoting the use of third person singular -s by 23 children with specific language impairment (SLI) and 21 children with typical development (TD). Relative proportions of third person singular -s forms in the input (input proportion) were calculated for 25 verbs based on data from an American English corpus of child-directed speech. Neighbourhood density values were also collected for these verbs. With previously collected probes of third person singular -s use for each of these verbs, we found with logistic regression that input proportion was positively associated with the likelihood of third person singular -s use for both groups. For neighbourhood density, we found that children with SLI were more likely to inflect sparse verbs than dense verbs; density was not significantly related to inflection use for TD children. We argue that as a result of their verbs' poorly encoded phonological representations, children with SLI were less able to inflect dense verbs than sparse verbs. We recommend that clinicians be aware of the effects of input proportion and neighbourhood density to ensure that assessments are representative and that treatment success is optimal.


Thought disorder in schizophrenic and control adoptees and their relatives.
Previous research showed significantly elevated levels of thought disorder in the relatives of persons with schizophrenia, as well as in the persons with schizophrenia themselves. Comparisons of schizophrenic and control adoptees and their respective relatives provide a method for minimizing the confounding of genetic and environmental sources of familial resemblance and for elucidating whether the elevated levels of thought disorder in persons with schizophrenia and their relatives reflect the influence of shared genetic factors, shared environmental factors, or both. The present study provides the first such adoption-sample data on an operationally defined measure of thought disorder. Speech samples elicited by standard interview questions from schizophrenic and control adoptees and their respective biological and adoptive relatives were tape-recorded. Verbatim transcripts of these speech samples were scored, while unaware of the personal or family diagnoses of the subjects, using the Thought Disorder Index (TDI). The mean TDI scores were significantly higher in schizophrenic than in control adoptees and in biological relatives of the schizophrenic adoptees than in the biological relatives of the control adoptees, whereas the respective groups of adoptive relatives did not differ significantly. The differences were most marked for the samples of biological sibs and half sibs, which were larger and more representative than the samples of parents. Results suggest that the elevated TDI scores in the relatives of persons with schizophrenia that have been found in other studies reflect the operation of genes increasing the liability for schizophrenia, rather than the rearing experiences that were shared in common with schizophrenic probands.


Methyl-β-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue.
This study was designed to determine whether methyl-β-cyclodextrin (MCD) can substitute for albumin in incubation medium for neonatal swine adipose tissue explants, or whether MCD affects metabolism and cytokine expression. Subcutaneous adipose tissue explants (100 ± 10 mg) were prepared from 21-day-old pigs. Explants were incubated in medium 199 supplemented with 25 mM HEPES, 1.0 nM insulin at 37°C. The medium also contained bovine serum albumin (BSA) or MCD at 0%, 0.05%, 0.1%, 0.2% or 0.3%. Tissue explants were treated with these media for 1 h and then switched to the same basal incubation medium containing 0.05% BSA. Explants were removed from basal medium at 2 or 8 h of incubation, and real-time PCR was performed to assess expression of tumor necrosis α (TNF) and interleukin 6 (IL6), acetyl CoA carboxylase (ACAC) and fatty acid synthase (FASN). Alternatively, rates of 14C-glucose oxidation and lipogenesis were monitored ± insulin (100 nM), following MCD treatment. Incubation with BSA had minimal effects on gene expression or adipose tissue metabolism, only producing a doubling in TNF mRNA abundance (P < 0.01). Treatment with MCD increased TNF mRNA abundance by eightfold (P < 0.009), whereas IL6 gene expression increased a 100-fold (P < 0.001) with a suppression in ACAC and FASN expression (P < 0.01). This was paralleled by MCD inhibition of insulin-stimulated glucose oxidation and lipogenesis (P < 0.001). Addition of a TNF antibody to the incubation medium alleviated this inhibition of insulin-stimulated glucose metabolism by ~30% (P < 0.05).


Analyzing Gaps to Design Educational Interventions.
This article addresses how nursing professional development practitioners can meet educational design criterion 1 in the American Nurses Credentialing Center Primary Accreditation process and standards 1 and 2 in the Association for Nursing Professional Development Scope and Standards of Practice. J Contin Educ Nurs. 2018;49(1):4-6.


Immunohistochemical detection of StarD6 in the rat nervous system.
Steroidogenic acute regulatory (StAR)-related lipid transfer (START) domain 6 (StarD6) is known to be exclusively expressed in germ cells of testis. As little is known about StarD6 expression in the nervous system, we investigated the distribution of StarD6 in rat neural tissues. Immunoreactivity of StarD6 was detected in the brain, spinal cord and dorsal root ganglia; particularly cerebral cortex (layer V and VI), hippocampus, substantia gelatinosa of the spinal cord. We provided compelling evidence that multiple neuronal and glial populations were immunolabelled with anti-StarD6 antibody throughout the nervous system. We postulate that StarD6 might play an important role in lipid sensing of the nervous system based on its immunolocalization in this study.


A meta-analysis of adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility.
Several studies have investigated the correlation between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk. However, the results were not conclusive with each other. Therefore, to overcome this obstacle, we performed this meta-analysis to further explicate the adiponectin gene rs22411766 T>G polymorphism and ischemic stroke susceptibility. Case-control or cohort studies focused on adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk were electronic searched in the databases of Medline, Pubmed, Cochrane library, Excerpta Medica database(EMBASE) and China National Knowledge Infrastructure (CNKI). All the potentially relevant studies were included in this meta-analysis. The association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke was expressed by odds ratio with its confidence interval. Publication bias has been assessed by begg's funnel plot. All the analyses have been performed by Revman 5.1 statistical software. Finally, a total of six studies with 1,345 cases and 1,421 controls were included in this meta-analysis. Our results demonstrated that there was a significant association between adiponectin gene rs22411766 T>G polymorphism and ischemic stroke risk (p<0.05). People with G single nucleotide of adiponectin gene have the increased risk of developing ischemic stroke compared to T single nucleotide.


A High-Resolution SAR Focusing Experiment Based on GF-3 Staring Data.
Spotlight synthetic aperture radar (SAR) is a proven technique, which can provide high-resolution images as compared to those produced by traditional stripmap SAR. This paper addresses a high-resolution SAR focusing experiment based on Gaofen-3 satellite (GF-3) staring data with about 55 cm azimuth resolution and 240 MHz range bandwidth. In staring spotlight (ST) mode, the antenna always illuminates the same scene on the ground, which can extend the synthetic aperture. Based on a two-step processing algorithm, some special aspects such as curved-orbit model error correction, stop-and-go correction, and antenna pattern demodulation must be considered in image focusing. We provide detailed descriptions of all these aspects and put forward corresponding solutions. Using these suggested methods directly in an imaging module without any modification for other data processing software can make the most of the existing ground data processor. Finally, actual data acquired in GF-3 ST mode is used to validate these methodologies, and a well-focused, high-resolution image is obtained as a result of this focusing experiment.


[Magnetic resonance perfusion weighted imaging manifestation of late radiation-induced encephalopathy at temporal lobe].
The imaging appearances of radiation-induced encephalopathy (REP) of nasopharyngeal carcinoma (NPC) patients were widely reported. As a new technique, magnetic resonance perfusion weighted imaging (MR PWI) is gradually applied to clinical study of REP. This study was designed to observe the characteristics of REP of NPC patients on MR PWI, and investigate its diagnostic value. The MRI and MR PWI records of 26 volunteers and 19 NPC patients with 37 lesions of MRI-diagnosed temporal lobe REP were retrospectively analyzed. The MRI was performed 30 months to 9 years after radiation therapy for NPC. The imaging sequences included T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), MR PWI, and Gd-DTPA-contrasted T1WI. Unilateral temporal lobe was involved in 1 case of REP, and bilateral temporal lobes in 18 cases of REP. MR PWI revealed that in edema areas of REP, relative cerebral blood volume (rCBV) and relative cerebral blood flood (rCBF) were decreased, mean transit time (MTT), time to peak (TTP), and time of arrival (TO) were delayed simultaneously; in demolished blood-brain barrier areas of REP, rCBV and rCBF were normal, but MTT, TTP, and TO were delayed; no blood perfusion was observed in myelinopathy areas of REP. MR PWI can clearly reveal brain blood perfusion changes in various lesions of REP, and indicate that obvious malfunction of brain blood perfusion is occurred in REP.


Network representation of protein interactions: Theory of graph description and analysis.
A methodological framework is presented for the graph theoretical interpretation of NMR data of protein interactions. The proposed analysis generalizes the idea of network representations of protein structures by expanding it to protein interactions. This approach is based on regularization of residue-resolved NMR relaxation times and chemical shift data and subsequent construction of an adjacency matrix that represents the underlying protein interaction as a graph or network. The network nodes represent protein residues. Two nodes are connected if two residues are functionally correlated during the protein interaction event. The analysis of the resulting network enables the quantification of the importance of each amino acid of a protein for its interactions. Furthermore, the determination of the pattern of correlations between residues yields insights into the functional architecture of an interaction. This is of special interest for intrinsically disordered proteins, since the structural (three-dimensional) architecture of these proteins and their complexes is difficult to determine. The power of the proposed methodology is demonstrated at the example of the interaction between the intrinsically disordered protein osteopontin and its natural ligand heparin.


HIV dementia persists, but now it's a chronic disease.
Highly active antiretroviral therapy has not eliminated HIV dementia, but it has changed the problem from one that strikes with severity and quickly leads to death to a process of slow, chronic cognitive decline, according to new research. 'What's been observed is there appears to be less of the old AIDS dementia, at least among patients with access to the new antiretroviral therapies,' says Dawn McGuire, MD, medical director of the Western NeuroAIDS Program at the HIV Institute for Treatment and Research in San Francisco.


Assessment of Northern Jordanian adolescents' knowledge and attitudes towards asthma.
Background Asthma is a chronic illness of the airways that can cause a persistent cough. The illness affects a significant population of young people worldwide and can affect their ongoing quality of life. Aim To explore Jordanian adolescents' knowledge and attitudes to asthma. Method A cross-sectional research design was used with a convenience sample of 302 adolescents from six schools in northern Jordan, who completed a self-reported knowledge and attitude survey. Results Although the adolescents had an adequate knowledge level about asthma, several areas of knowledge deficit were identified and some negative attitudes were demonstrated. No significant association was found between adolescents' level of knowledge and their attitudes to adolescents with asthma. Conclusion Jordanian adolescents need more educational programmes about living with life-changing chronic illnesses such as asthma, and about how the knowledge and positive attitudes of peer groups can normalise the illness for the affected person, enhancing their quality of life.


A theoretical model of job retention for home health care nurses.
Predicted severe nursing shortages and an increasing demand for home health care services have made the retention of experienced, qualified nursing staff a priority for health care organizations. The purpose of this paper is to describe a theoretical model of job retention for home health care nurses. The theoretical model is an integration of the findings of empirical research related to intent to stay and retention, components of Neal's theory of home health care nursing practice and findings from earlier work to develop an instrument to measure home health care nurses' job satisfaction. The theoretical model identifies antecedents to job satisfaction of home health care nurses. The antecedents are intrinsic and extrinsic job characteristics. The model also proposes that job satisfaction is directly related to retention and indirectly related to retention though intent to stay. Individual nurse characteristics are indirectly related to retention through intent to stay. The individual characteristic of tenure is indirectly related to retention through autonomy, as an intrinsic characteristic of job satisfaction, and intent to stay. The proposed model can be used to guide research that explores gaps in knowledge about intent to stay and retention among home health care nurses.


Transferring two grades I cleavage-stage embryo might not be a good protocol.
The aim of this study was to explore whether transferring two grades I cleavage-stage embryo was suitable for the patients in the first fresh transfer. This study included 202 single grades I cleavage-stage, 229 single grades III cleavage-stage, 743 single excellent blastocyst, 522 double grades I cleavage-stage, and 596 double grades III cleavage-stage embryo transfers. Main clinical outcomes: clinical pregnancy and twin-pregnancy rate. Among single excellent blastocyst, single grades I and single grades III group, the clinical pregnancy rate was significantly higher in single excellent blastocyst group than single grades I and grades III group (67.16% versus 42.08% versus 23.97%; p < 0.001). When transferred double grades I cleavage-stage embryos, the clinical pregnancy rate reached 68.20% which was no significant difference compared with the single excellent blastocyst group (67.16%). However, the twin-pregnancy rate was significantly higher in double grades I group than double grades III and single excellent blastocyst group (43.26% versus 26.70% versus 0.60%; p < 0.001). Because of higher twin-pregnancy incidence rate, transferring two grades I cleavage-stage embryo might not be a good protocol. Extended culture to blastocyst-stage could be considered for the patient with only two grades I cleavage-stage embryos.


[Three cases of recurrent gastric cancer responding to TS-1 therapy following combination therapy with 5-fluorouracil, mitomycin C and cisplatin].
We report three patients with recurrent gastric cancer responding to TS-1 therapy after combination chemotherapy with 5-fluorouracil, mitomycin C and cisplatin. All 3 cases had undergone total gastrectomy with lymphadenectomy for advanced gastric cancer. Postoperative follow-up computed tomography (CT) showed liver metastases (cases 1 and 3), peritoneal dissemination (case 2) and enlargement of paraaortic lymph nodes (case 1) due to cancer recurrence. After 2 to 4 courses of combined treatment with 5-fluorouracil (500-750 mg/body/day, days 1-5, civ), mitomycin C (6-8 mg/body, day 6) and cisplatin (60-80 mg/body, day 7), CT revealed considerable reduction of the metastatic tumors. Subsequently oral administration of TS-1 (80-100 mg/body/day) for 4 weeks was performed. All 3 patients are well without any signs of increase in tumor size.


Deep-Sequencing Analysis of the Dynamics of HIV-1 Quasiespecies in Naive Patients during a Short Exposure to Maraviroc.
In this study, we have characterized quasispecies dynamics and the evolution of viral tropism in naive HIV-1-infected patients treated with a short course of maraviroc monotherapy (ClinicalTrials.gov registration no. NCT01060618) independently of the tropism of the infecting virus. We randomly selected 20 patients infected with viruses displaying different basal tropisms-10 carrying R5 and 10 carrying dual/mixed X4 (DM/X4) viruses-at recruitment as determined by phenotypic assay (Trofile). Evolution of viral quasiespecies at the end of treatment was determined by ultradeep sequencing of the V3 region using a 454 Life Sciences Platform and geno2pheno (g2p) algorithm for viral tropism prediction. The false-positive rate (FPR) that defines the probability of classifying an R5 virus falsely as X4 was set at 10%. X4-specific HIV-1 viral load (VL) was calculated from sequences with an FPR of <3.75%. Virological response as defined as >1-log10 copies/ml reduction in VL was detected in 70% of patients independently of the basal tropism of the infecting virus. Viral tropism remained stable, and nonsignificant differences in FPR values before and after treatment were found for the majority of patients in both tropism groups. Only three patients (one with R5 and two with DM/X4 viruses) showed an increased (>1 log) X4 VL, and one patient harboring a DM/X4-tropic virus displayed a significant reduction in FPR values at the end of treatment. Fast changes in the composition of viral populations were observed in all patients after 10 days of maraviroc (MVC) monotherapy treatment, and a complete replacement of viral quasiespecies was found in 3/10 patients carrying R5-using viruses and 4/10 patients carrying DM/X4-using viruses.IMPORTANCE Initiation of treatment with maraviroc requires previous determination of viral tropism by genotypic or phenotypic methods because of the risk of treatment failure and selection of DM/X4-tropic variants. In this study, we confirm previous work showing that the virologic response to maraviroc is independent of basal tropism. By deep-sequencing analysis, we determined that fast changes in viral populations were due to the emergence of minority variants in some patients whereas in others generation of new strains was detected. The risk of DM/X4 selection was very low as FPR values remained stable, and only one patient showed a detrimental switch to DM/X4 variants. Our data show that some DM/X4 viruses are sensitive to maraviroc treatment probably because only a low proportion of DM/X4 viruses use preferentially the X4 receptor and contain authentically maraviroc-resistant viruses that are not accurately detected by current assays.


Peptide-mediated targeting of liposomes to tumor cells.
One of the biggest obstacles for efficient drug delivery is specific cellular targeting. Liposomes have long been used for drug delivery, but do not possess targeting capabilities. This limitation may be circumvented by surface coating of colloidal delivery systems with peptides, proteins, carbohydrates, vitamins, or antibodies that target cell surface receptors or other biomolecules. Each of these coatings has significant drawbacks. One idealized system for drug delivery combines stabilized "protein module" ligands with a colloidal delivery vehicle. Prior studies have shown that peptide-amphiphiles, whereby both a peptide "head group" and a lipid-like "tail" are present in the same molecule, can be used to engineer collagen-like triple-helical or alpha-helical miniproteins. The tails serve to stabilize the head group structural elements. These peptide-amphiphiles can be designed to bind to specific cell surface receptors with high affinity. Structural stabilization of the integrated targeting ligand in the peptide-amphiphile system equates to prolonged in vivo stability through resistance to proteolytic degradation. Liposomes have been prepared incorporating a melanoma targeting peptide-amphiphile ligand, and shown to be stable with retention of peptide-amphiphile triple-helical structure. Encapsulated fluorescent dyes are selectively delivered to cells. In this chapter we describe the methods and techniques employed in the preparation and characterization of peptide-amphiphiles and peptide-amphiphile-targeted large and small unilamellar vesicles (LUVs and SUVs). Fluorescence microscopy is subsequently utilized to examine the targeting capabilities of peptide-amphiphile LUVs, which should allow for improved drug selectivity towards melanoma vs normal cells based on differences in the relative abundance of the targeted cell surface receptors.


Protection of HepG2 cells against acrolein toxicity by 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide via glutathione-mediated mechanism.
Acrolein is an environmental toxicant, mainly found in smoke released from incomplete combustion of organic matter. Several studies showed that exposure to acrolein can lead to liver damage. The mechanisms involved in acrolein-induced hepatocellular toxicity, however, are not completely understood. This study examined the cytotoxic mechanisms of acrolein on HepG2 cells. Acrolein at pathophysiological concentrations was shown to cause apoptotic cell death and an increase in levels of protein carbonyl and thiobarbituric acid reactive acid substances. Acrolein also rapidly depleted intracellular glutathione (GSH), GSH-linked glutathione-S-transferases, and aldose reductase, three critical cellular defenses that detoxify reactive aldehydes. Results further showed that depletion of cellular GSH by acrolein preceded the loss of cell viability. To further determine the role of cellular GSH in acrolein-mediated cytotoxicity, buthionine sulfoximine (BSO) was used to inhibit cellular GSH biosynthesis. It was observed that depletion of cellular GSH by BSO led to a marked potentiation of acrolein-mediated cytotoxicity in HepG2 cells. To further assess the contribution of these events to acrolein-induced cytotoxicity, triterpenoid compound 2-cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) was used for induction of GSH. Induction of GSH by CDDO-Im afforded cytoprotection against acrolein toxicity in HepG2 cells. Furthermore, BSO significantly inhibited CDDO-Im-mediated induction in cellular GSH levels and also reversed cytoprotective effects of CDDO-Im in HepG2 cells. These results suggest that GSH is a predominant mechanism underlying acrolein-induced cytotoxicity as well as CDDO-Im-mediated cytoprotection. This study may provide understanding on the molecular action of acrolein which may be important to develop novel strategies for the prevention of acrolein-mediated toxicity.


Macronutrient Composition of the Australian Population's Diet; Trends from Three National Nutrition Surveys 1983, 1995 and 2012.
Although the role of individual macronutrients in the development of obesity remains controversial, changes in macronutrient composition of the diet may have played a causal role in the obesity epidemic. The aim of this analysis was to determine the percentage energy (%E) for protein, carbohydrate and fat of Australian adults' diets over time. Cross-sectional, national nutrition surveys from 1983, 1995 and 2012 assessed diet using one 24 h recall. The prevalence of obesity increased between each survey, from 9.6% to 19.7% and 27.7%. Protein (%E) differed between each survey and contributed 17.7%, 16.8% and 18.3% energy in 1983, 1995 and 2012, respectively (p < 0.001). Carbohydrate (%E) increased from 40.0% in 1983 to 44.9% in 1995 (p < 0.001), with no change in dietary fibre but declined in 2012 to 43.1%. Fat (%E) declined between each survey from 35.3%, 31.9%, to 30.9%, respectively (p < 0.001). Alcohol (%E) has declined for younger adults and men but intake increased for women aged >45 years. Prospective cohort studies with comprehensive assessment of foods consumed, together with measurements of weight and height, will advance the understanding of the relationship between macronutrients and changes in body weight and obesity.


Improving Synthetic Biology Communication: Recommended Practices for Visual Depiction and Digital Submission of Genetic Designs.
Research is communicated more effectively and reproducibly when articles depict genetic designs consistently and fully disclose the complete sequences of all reported constructs. ACS Synthetic Biology is now providing authors with updated guidance and piloting a new tool and publication workflow that facilitate compliance with these recommended practices and standards for visual representation and data exchange.


Bifunctional Paramagnetic and Luminescent Clays Obtained by Incorporation of Gd3+ and Eu3+ Ions in the Saponite Framework.
A novel bifunctional saponite clay incorporating gadolinium (Gd3+) and europium (Eu3+) in the inorganic framework was prepared by one-pot hydrothermal synthesis. The material exhibited interesting luminescent and paramagnetic features derived from the co-presence of the lanthanide ions in equivalent structural positions. Relaxometry and photoluminescence spectroscopy shed light on the chemical environment surrounding the metal sites, the emission properties of Eu3+, and the dynamics of interactions between Gd3+ and the inner-sphere water placed in the saponite gallery. The optical and paramagnetic properties of this solid make it an attractive nanoplatform for bimodal diagnostic applications.


Pain patterns in the rheumatic disorders.
Pain patterns vary greatly in the different types of arthritis, from the localized agony without mental overtones in acute gout to the diffuse disorder we call rheumatoid arthritis, where inflammation of many joints, systemic illness, anaemia, anxiety, and depression are usually all present in some degree. Each pain pattern calls for a different therapeutic approach, physical, psychological, and pharmacological. Few patients suffer as much pain and suffering over many years as do chronic arthritics. It is all the more important to instruct them in the essentials of their own treatment. A patient with an occupied and instructed mind usually suffers less than an ignorant and depressed one, fearful of her disease and its complications and of the dark uncertain future that lies ahead.


New glycyl radical enzymes catalysing key metabolic steps in anaerobic bacteria.
During the last decade, an increasing number of new enzymes containing glycyl radicals in their active sites have been identified and biochemically characterised. These include benzylsuccinate synthase (Bss), 4-hydroxyphenylacetate decarboxylase (Hpd) and the coenzyme B12-independent glycerol dehydratase (Gdh). These are involved in metabolic pathways as different as anaerobic toluene metabolism, fermentative production of p-cresol and glycerol fermentation. Some features of these newly discovered enzymes are described and compared with those of the previously known glycyl radical enzymes pyruvate formate-lyase (Pfl) and anaerobic ribonucleotide reductase (Nrd). Among the new enzymes, Bss and Hpd share the presence of small subunits, the function of which in the catalytic mechanisms is still enigmatic, and both enzymes contain metal centres in addition to the glycyl radical prosthetic group. The activating enzymes of the novel systems also deviate from the standard type, containing at least one additional Fe-S cluster. Finally, the available whole-genome sequences of an increasing number of strictly or facultative anaerobic bacteria revealed the presence of many more hitherto unknown glycyl radical enzyme (GRE) systems. Recent studies suggest that the particular types of these enzymes represent the ends of different evolutionary lines, which emerged early in evolution and diversified to yield remarkably versatile biocatalysts for chemical reactions that are otherwise difficult to perform in anoxic environments.


Voltammetric heparin-selective electrode based on thin liquid membrane with conducting polymer-modified solid support.
A novel, solid-supported voltammetric ion-selective electrode to detect anticoagulant/antithrombotic heparin at polarizable poly(vinyl chloride) (PVC) membrane/water interfaces was developed. An approximately 3-4.5-microm-thick PVC membrane plasticized with 2-nitrophenyl octyl ether was supported on a gold electrode modified with a poly(3-octylthiophene) (POT) film as an ion-to-electron transducer. Charge transport through the PVC-covered POT film is electrochemically reversible, as demonstrated by cyclic voltammetry with nonpolarizable membrane/water interfaces. In addition to the fast charge transport, adequate redox capacity of the POT film and a small ohmic potential drop in the thin PVC membrane enable ion transfer voltammetry at polarizable macroscopic membrane/water interfaces in a standard three-electrode cell. Reversible ClO4- transfer at the interfaces coupled with oxidation of a neutral POT film was examined by cyclic voltammetry to determine the distribution of the applied potential to the two polarizable interfaces by convolution technique. Interfacial adsorption and desorption of heparin facilitated by octadecyltrimethylammonium were studied also by cyclic voltammetry and convolution technique to demonstrate that the processes are electrochemically irreversible. Stripping voltammetry based on the interfacial processes gives a low detection limit of 0.005 unit/mL heparin in a saline solution, which is slightly lower than the detection limit of most sensitive heparin sensors reported so far (0.01 unit/mL).


Enhancing and priming of macrophages for superoxide anion production by taxol.
Taxol, an anticancer drug, has been known not only to block cell division by stabilizing microtubules but also to activate murine macrophages to express TNF-alpha, interleukin-1, and to produce nitric oxide (NO). We therefore reasoned that taxol could activate murine macrophages to generate reactive oxygen intermediates, such as superoxide anion (O2-), which are responsible for intracellular killing of pathogenic microbes. Treatment of RAW264.7 cells, murine macrophage cell line, with taxol increased phorbol ester-induced O2- production in a dose dependent manner (approximately 2 fold). In addition, taxol rapidly (< 1 hr) primed RAW264.7 cells to enhance O2- release stimulated with PMA. Taxol also enhanced stimulation of O2- production by FMLP, but not by Con A. This effect was abolished by prior treatment with both superoxide dismutase (SOD) and N-acetyl-L-cystein, a free radical scavenger. To investigate the mechanism of taxol-induced macrophage stimulation, we evaluated the ability of colchicine, a drug that inhibit tubulin polymerization, and cAMP analogues, which is known to depolymerize microtubule. Taxol-induced O2- production was inhibited by the treatment with both colchicine and DB-cAMP. Taken together, these results demonstrated that taxol provides two signals, "priming" and "enhancing", to generate superoxide anion via the stabilization of microtubules in murine RAW264.7 cells


Bean Type Modifies Larval Competition in Zabrotes subfasciatus (Chrysomelidae: Bruchinae).
Larval competition is particularly prevalent among grain beetles that remain within their mother-selected grain throughout development, and the behavioral process of competition is usually inferred by the competition outcome. The Mexican bean weevil Zabrotes subfasciatus (Boheman) is subjected to resource availability variation because of the diversity of common bean types and sizes, from small (e.g., kidney beans) to large (e.g., cranberry beans). The competition process was identified in the Mexican bean weevil reared on kidney and cranberry beans by inference from the competition outcome and by direct observation through digital X-ray imaging. Increased larval density negatively affected adult emergence in kidney beans and reduced adult body mass in both kidney and cranberry beans. Developmental time was faster in cranberry beans. The results allowed for increased larval fitness (i.e., higher larval biomass produced per grain), with larval density reaching a maximum plateau >5 hatched larvae per kidney bean, whereas in cranberry beans, larval fitness linearly increased with density to 13 hatched larvae per bean. These results, together with X-ray imaging without evidence of direct aggressive interaction among larvae, indicate scramble competition, with multiple larvae emerging per grain. However, higher reproductive output was detected for adults from lower density competition with better performance on cranberry beans. Larger populations and fitter adults are expected in intermediate larval densities primarily in cranberry beans where grain losses should be greater.


Human microdialysis.
Microdialysis has been used extensively in animal studies for decades and in human pharmacokinetic studies for about 10 years. Microdialysis is based on the passive diffusion of a compound along its concentration gradient from the tissue through the membrane into the dialysate. Microdialysis samples from the interstitial space which is a defined, anatomical compartment; there is no net loss of body fluid; the sample is "purified" and no enzymatic degradation takes place because proteins do not pass through the probe membrane into the dialysate; microdialysis data relate to the intact molecule; time resolution is high compared to biopsy and skin blister techniques; radioabelling or induction of a magnetic response is not needed; microdialysis is also an alternative method to determine protein binding of a compound in vivo; microdialysis can readily be set up in clinical research units without expensive infrastructure. Microdialysis has been used to measure tissue concentrations of endogenous compounds and to investigate the tissue penetration of drugs in a variety of tissues in humans in vivo in both healthy volunteers and patients. Microdialysis data have also been used in PK-PD modelling and to obtain concentration-response relationships locally in tissues in vivo. There are also studies combining microdialysis with imaging techniques, e.g. PET. Microdialysis data may be used in early studies to select the appropriate compound, to optimise dosing regimens and to investigate the kinetic and dynamic consequences in the tissues of drug-drug and drug-disease interactions. Microdialysis can also be used in late phase studies to provide tissue concentration data in support of therapeutic efficacy trials or to create a niche for an already marketed drug. FDA and CPMP documents emphasise the value and importance of human tissue drug concentration data and support the use of microdialysis in humans to obtain such information. Microdialysis can satisfy regulatory requirements by providing data on drug concentrations in a well-defined anatomical tissue compartment at or close to the effect target site. Microdialysis is a versatile technique because of its multifaceted utility, low cost, ease of use, adaptability to different types of compounds and its feasibility for a number of organs and tissues. Equipment and probes for use in various organs have been commercially available for years.


Assessment of the Efficacy of TMJ Arthroscopy-Assisted Masseter Nerve Avulsion on Hemimasticatory Spasm: An Original Research.
The goal of this study is to find a cure for the masticatory muscle disease known as hemimasticatory spasm (HMS). This retrospective investigation intends to find a more efficient therapeutic approach for HMS patients by examining the clinical effectiveness of masseteric nerve avulsion performed on HMS using a temporomandibular arthroscope. A clinical study was piloted where the subjects were treated for masseter nerve avulsion by TMJ arthroscopy. The follow-up was done till 2 years, and the subjects were evaluated for the various characteristics like difficulties, masticatory abilities, and various sounds at the joint for the various functions of the joint. The diagnosis was done using the electrophysiological electromyogram (EMG) at the designated time intervals. There was a complete remission in all the subjects. The masseter nerve avulsion was effective since the scores lowered. Within 3 years of the operation, electrophysiological EMG depicted no discharge potential with a high frequency, and the total efficiency when paired with the clinical effectiveness was deemed acceptable. The maximal masseter power between the treated and nontreated sides was comparable. The mastication, on comparing, was also as effective as the normal side; however, lower mastication was noted in the first year. The avulsed nerve tissues lacked any apparent demyelination. Masseteric nerve avulsion with temporomandibular arthroscope assistance provided acceptable and stable total effectiveness for the intervention of the hemimasticatory spasm. While the strength of the muscle of the afflicted side was only marginally reduced, its masticatory effectiveness was optimally preserved.


Application of the WHO surgical safety checklist outside the operating theatre: medicine can learn from surgery.
Safety checklists in medicine are designed to identify a potential error before it results in harm to a patient. The World Health Organization (WHO) safety checklist was widely implemented in surgical practice in the UK after significant reductions in death, and peri-operative complications were achieved in eight countries worldwide in the 'Safe Surgery Saves Lives' campaign of 2008. Nevertheless, use of the checklist for invasive medical procedures is not yet routine. Such procedures are becoming ever more complex, necessitating multidisciplinary team management and involving higher-risk patients, with the need for general anaesthesia on occasion. As a result, the potential for error increases and the need for a safety checklist has become more apparent. Such a checklist can be modified to provide a framework for specialty-specific safety checks, enhanced team-working and communication for invasive medical procedures. Following an audit of use of the WHO checklist in 20 cases under general anaesthesia in our quaternary referral cardiac catheterisation laboratory, we discovered use of this safety tool was poor (performed/documented: sign in 30%/40%, time out 10%/15%, sign out 10%/15%) and we identified two 'near miss' incidents within the audit period. We then developed and implemented a modified WHO checklist for the specific challenges faced in the cardiac catheterisation laboratory. Following a staff education programme, a subsequent audit of 34 cases demonstrated improvement in all sections (performed/documented: sign in 91.2%/82.4%, time out 85.3%/76.5%, sign out 73.5%/64.7%) with no patient safety incidents during the post-intervention audit period. Well-designed, procedural checklists may well prove to be of benefit in other areas of interventional medicine.


New genus and species of fish blood fluke (Digenea: Aporocotylidae Odhner, 1912) from stoplight parrotfish, Sparisoma viride (Bonnaterre, 1788), (Labridae: Scarinae) in the Caribbean Sea.
Primisanguis caribbeanensis n. gen., n. sp. (Digenea: Aporocotylidae) infects the stoplight parrotfish, Sparisoma viride (Bonnaterre, 1788), (Labridae: Scarinae) in the Caribbean Sea off La Parguera (17°58'26" N, 67°02'47"W), Puerto Rico. It is most easily distinguished from other nominal aporocotylids by the combination of having an adult body that is approximately 5-10 times longer than wide, a sinistral posterolateral body protuberance, tegumental body spines that are straight (lacking recurved tip) and wrap dorsoventrally around the body margin, posterior ceca that are 2-5 times the anterior ceca length, a single testis that extends lateral to both the ceca and nerve cords, an ovary abutting the posterior margin of the testis, a symmetrical vitellarium and medial primary vitelline duct, a post-cecal and post-gonadal ootype, and a proximal uterus that is extensively convoluted posterior to the ootype and which functions as a uterine seminal receptacle. The new genus lacks a spinous anterior sucker, pharynx, auxiliary external seminal vesicle, cirrus stylet, oviducal seminal receptacle, and Laurer's canal. The new species is morphologically most similar to the other aporocotylids that have a posterolateral body protuberance, including species of Psettarium Goto and Ozaki, 1930, Aporocotyle Odhner, 1900, Ankistromeces Nolan and Cribb, 2004 , Phthinomita Nolan and Cribb, 2006, and Littorellicola Bullard, 2010, but it can be differentiated from them, at the least, by lack of a spinous anterior sucker in the adult and by the combination of having dorsoventral rows of tegumental spines, a testis dorsal to the posterior ceca, and a uterine seminal receptacle posterior to the ootype. The new species is the first aporocotylid reported from the Caribbean Sea or from a parrotfish of Sparisoma.


It's like standing in front of a prison fence - Dying during the SARS-CoV2 pandemic: A qualitative study of bereaved relatives' experiences.
Since the onset of the SARS CoV2 pandemic, protective and isolation measures had a strong impact on the care and support provided to seriously ill and dying people at the end-of-life. Exploring bereaved relatives' experiences of end-of-life care during the SARS-CoV2 pandemic. Qualitative interview study with bereaved relatives. Thirty-two relatives of patients who died during the pandemic, regardless of infection with SARS-CoV2. Three core categories were identified: needs, burden and best practice. Relatives wished for a contact person responsible for providing information on the medical and mental condition of their family members. The lack of information, of support by others and physical closeness due to the visiting restrictions, as well as not being able to say goodbye, were felt as burdens and led to emotional distress. However, case-by-case decisions were made and creative ways of staying in touch were experienced positively. Our results indicate that the strong need for closeness when a family member was dying could not be met due to the pandemic. This led to suffering that can be prevented. Visits need to be facilitated by making considered decisions on a case-by-case basis. For easy communication with relatives, approaches should be made by healthcare professionals and support for virtual communication should be offered. Furthermore, the results of the study can help to implement or develop ideas to enable dignified farewells even during pandemics.


The hemolytic equivalence of human, guinea pig and canine complement proteins.
The ability of functionally pure human, guinea pig and canine complement proteins to fulfill the hemolytic function of a substituted analagous component in an otherwise totally homogeneous complement sequence was investigated by means of conventional hemolytic assays. A striking feature was the observation that for hemolysis to occur, differing requirements for enzyme-substrate homology were exhibited by each of the three species of C3 and C5 convertases (C3 and C5 CVA). The results suggest that different strategies of molecular interaction evolved in complement systems of different species.


Outcome of 200 patients after an extracardiac Fontan procedure.
Despite the known advantages of the extracardiac conduit Fontan procedure, the long-term outcomes related to the longevity of the conduit and anticoagulation therapy have not been determined. The purpose of this study was to evaluate the outcome of hospital survivors with an extracardiac Fontan circulation. Between 1996 and 2006, 200 patients had the extracardiac conduit Fontan operation. The median age at operation was 3.4 years. Most patients (89.5%) underwent a bidirectional cavopulmonary shunt. Fenestration was required in 85 patients. Overall, the 10-year survival was 92.4% +/- 2.1%. Multivariate analysis identified severe infection during the early postoperative period and a high pulmonary arterial pressure during the preoperative period as independent risk factors for patient mortality. The Kaplan-Meier estimate for freedom from reoperation was 82.4% +/- 4.1% at 10 years. Arrhythmia occurred in 32 patients after the Fontan operation; freedom from arrhythmia was 85.1% +/- 4.4% at 10 years. The risk factors for arrhythmia were the heterotaxy syndrome, follow-up duration, and age at Fontan operation. Freedom from thromboembolism at 10 years was 92.9% +/- 1.9%. Among all of the patients, 95.2% were classified in New York Heart Association class I. The results of this study showed that during 10 years of follow-up, the overall survival and the functional status of the survivors after an extracardiac Fontan procedure were satisfactory. We might infer that fenestration provided benefit inasmuch as the high-risk Fontan patients fenestrated had similar outcomes to those not fenestrated, who were presumably low risk. The incidence of late death, reoperation, obstruction of the cavopulmonary pathway, arrhythmias, and thromboembolism was low.


The nurse-patient trajectory framework.
The development of nursing knowledge should give structure and form to the practice of nursing. The development of Nursing Process Theory resulted from early nursing observations and inferences from nursing practice that resulted in formal data accumulation processes, mutual correspondence between nurses and patients, and exchange of information. The development of the nursing process discipline helped to substantiate the need for professional nursing services. The shifts towards examining the links between processes and outcomes, professional accountability, and classification of distinct nursing functions have influenced the development of information systems. The Nurse-Patient Trajectory Framework described in this paper may be used to show the relationships between the virtual information system and the real world that it affects. The framework is visualized along two separate and distinct nurse and patient trajectories.


Self-harm behaviors across the life cycle: a pilot study of inpatients with borderline personality disorder.
The purpose of this study was to explore, throughout the life cycle, the prevalence of self-harm behaviors among psychiatric inpatients with and without borderline personality disorder (BPD). Psychiatric inpatients with BPD (n = 43) were compared to those without BPD (n = 40) with regard to self-reported self-harm behaviors during their lifetime. The mean number of self-harm behaviors, including high-lethal behaviors (i.e., suicide attempts, cutting oneself, overdosing), among those with BPD dramatically increased between the ages of 18 and 24 years and was sustained through ages 50 to 59 years. Non-BPD patients showed a similar pattern, but the means were notably less. These data suggest that the behavioral "burn out" theory of personality disorders does not necessarily occur among inpatients with BPD.


Experimental colonization of pigs with methicillin-resistant Staphylococcus aureus (MRSA): insights into the colonization and transmission of livestock-associated MRSA.
Two models were used for colonizing pigs under experimental conditions. In the first model, six 5-week old piglets were challenged by nasal and gastrointestinal inoculation with a mixture of four strains representing the most prevalent methicillin-resistant Staphylococcus aureus (MRSA) sequence types (ST398, ST9) and spa types (t08, t011, t034, t899) associated with pig farming. In the second model, the vagina of a pregnant sow was inoculated with the same MRSA mixture shortly before farrowing. While MRSA carriage was unstable following nasal-gastrointestinal inoculation of piglets, vaginal inoculation of the sow resulted in persistent carriage of t011-ST398 and t899-ST9 in all newborn piglets. The results from the two models provide evidence that livestock-associated MRSA can efficiently spread by vertical perinatal transmission and that direct colonization of weaned piglets is hampered by unknown host, bacterial or environmental factors. The vaginal inoculation model described in this study represents a useful tool for studying MRSA-host interactions in pigs having the same genetic background.


RNA recognition mechanism of the minimal active domain of the human immunodeficiency virus type-2 nucleocapsid protein.
NCp8 of HIV-2 contains two CCHC-type zinc fingers connected by a linker, and is involved in many critical steps of the virus life cycle. It was previously shown that the first zinc finger flanked by the linker is the minimal active domain for specific binding to viral RNA. In our previous study, we determined the three-dimensional structure of NCp8-f1, including the minimal active domain, and found that a hydrogen bond between Asn(11) N(delta)H and Arg(27) O stabilized the conformation of the linker in the vicinity of the zinc finger [Kodera et al. (1998) Biochemistry 37, 17704-17713]. In this study, RNA binding activities of NCp8-f1 and three types of its mutant peptides were analysed by native PAGE assay. The activity and three-dimensional structure of NCp8-f1/N11A, in which alanine is substituted for Asn(11) thereby affecting the conformation of the linker, was analyzed and compared with those of NCp8-f1. We demonstrated that the existence of Arg(4) and/or Lys(5) and Arg(26) and/or Arg(27) were necessary for binding RNA. Furthermore, the linker's flexible orientation, which is controlled by the hydrogen bond between Asn(11) N(delta)H and Arg(27) O, appears to be a structural basis for NCp8 existing as a multi-functional protein.


Do patients like psychometric testing by computer?
Programmed a micro-computer to administer and score the Crown-Crisp Experiential Index (CCEI) (Crown & Crisp, 1979) for a study of the psychological state of 59 newly delivered mothers. This publication reports the findings of a separate paper-and-pencil questionnaire assessment of the patients' attitudes to the computer itself. The 59 patients were almost unanimous in finding the computer acceptable and easy to use; only 1 S minded using it. None found the instructions difficult to understand, and only 1 had difficulty in reading them. Only 2 would object to using the computer again.


Analysis of the early immune response to infection by infectious bursal disease virus in chickens differing in their resistance to the disease.
Chicken whole-genome gene expression arrays were used to analyze the host response to infection by infectious bursal disease virus (IBDV). Spleen and bursal tissue were examined from control and infected birds at 2, 3, and 4 days postinfection from two lines that differ in their resistance to IBDV infection. The host response was evaluated over this period, and differences between susceptible and resistant chicken lines were examined. Antiviral genes, including IFNA, IFNG, MX1, IFITM1, IFITM3, and IFITM5, were upregulated in response to infection. Evaluation of this gene expression data allowed us to predict several genes as candidates for involvement in resistance to IBDV. Infectious bursal disease (IBD) is of economic importance to the poultry industry and thus is also important for food security. Vaccines are available, but field strains of the virus are of increasing virulence. There is thus an urgent need to explore new control solutions, one of which would be to breed birds with greater resistance to IBD. This goal is perhaps uniquely achievable with poultry, of all farm animal species, since the genetics of 85% of the 60 billion chickens produced worldwide each year is under the control of essentially two breeding companies. In a comprehensive study, we attempt here to identify global transcriptomic differences in the target organ of the virus between chicken lines that differ in resistance and to predict candidate resistance genes.


Bioethics and political ideology: the case of active voluntary euthanasia.
In different countries responses to important bioethical issues are different, as exemplified by the attitudes towards the voluntary and active forms of medical euthanasia. But why is this the case? My suggestion is that the roots of the variety are, to be considerable degree, ideological. The most important present-day political ideologies all have their roots in the prevailing doctrines of moral and social philosophy. In the paper these doctrines are outlined and the predicted response towards active voluntary euthanasia within each model is sketched. The conclusion reached is that while it would in some countries be dangerous to allow euthanasia in the prevailing circumstances, the solution is not to hinder the legalization process but to alter the circumstances.


Finger ridge-count asymmetry and diversity in Andean Indians and interpopulation comparisons.
A separate analysis of ulnar and radial finger ridge-counts, obtained from 115 Aymara Indians (55 males and 60 females) of northern Chile, was performed. From these variables, directional asymmetry, fluctuating asymmetry, indices of bilateral asymmetry (square root of A2), and intraindividual diversity (s/square root of 5) were calculated for each sex. The results show that most bimanual differences for the ridge-counts are not statistically significant in the Aymara, except for radial counts in female first and second fingers (right hand means are larger), while most ulnar-radial differences are highly significant in both sexes (radial values exceed ulnar ones). Most sex differences do not reach statistical significance, although males have more ridge-counts, lower directional asymmetry, somewhat lower fluctuating asymmetry, and lower indices of asymmetry and diversity than females. As fluctuating asymmetry is not larger in males, the dermatoglyphic findings do not indicate support for the hypothesis that males are less canalized than females. In accordance with the findings of other authors, interpopulation comparisons in the indices of asymmetry and diversity show ethnic differences. Both indices tend to be low in samples of African ancestry, high in samples of European origin, and intermediate in the Aymara, while Indian groups are characterized by high asymmetry and low diversity values. Moreover, the data reveal a geographical trend in that asymmetry and diversity values tend to decrease from the northern to the southern hemisphere in populations of Europe, the Middle East, and Africa, thus indicating greater ridge-count variability and heterogeneity among fingers in northern populations. It is assumed that this gradient primarily reflects different degrees of miscegenation and heterozygosity.


Stimulus dependence of the action of small-molecule inhibitors in the CD3/CD28 signalling network.
Cells in the body are exposed simultaneously to a multitude of various signals. Inside a cell, molecular signalling networks integrate this information into a physiologically meaningful response. Interestingly, in the cellular testing of drug candidates, this complexity is largely ignored. Compounds are tested for cells that are challenged with one stimulus only. The activation of T lymphocytes through engagement of the T cell receptor (TCR)-CD3 complex and CD28 coreceptor is a prominent example for a cellular response that depends on the integration of signals. We investigated the cellular response characteristics of this network at different strengths of receptor and coreceptor activation. A novel cellular microarray-based approach, in which various combinations of antibodies directed against the CD3 complex and CD28 were spotted, was employed for analysing the stimulus dependence of activation of the transcription factor NFAT and actin reorganisation. For both responses, quantitative differences in inhibitor activity were observed. Remarkably, for IL-2 expression, which was detected by standard ELISA, low doses of the Src-family kinase inhibitor PP2 strongly potentiated IL-2 expression at high-level, but not at low-level, CD28 co-engagement. Therefore, for a physiologically highly relevant signalling network, the cellular response might vary qualitatively with only quantitative variations of a stimulus. This level of complexity should be considered in early cellular drug testing.


Tuberculosis of the colon in a kidney transplant patient.
A 58-year-old woman experienced recurrent fever episodes after kidney transplantation. She was treated with antibiotics because of suspicion of staphylococcus infection. Abdominal pain combined with haemorrhagic diarrhoea occurred eight months after transplantation. A barium enema revealed a stenotic process in the middle part of the ascending colon mimicking carcinoma, and hemicolectomy was consequently performed. Histological examination revealed tuberculosis with little granuloma formation and abundant acid-fast tubercle bacilli in the mucosa and submucosa, and only slight perigranulomatous reactions. The patient was successfully treated with triple antituberculous chemotherapy without deterioration of allograft function. Tuberculosis should be suspected in immunosuppressed patients suffering from pyrexia of unknown origin, even when chest X-ray is normal.


[Prolonged postoperative thromboprophylaxis--current state of knowledge].
By "prolonged thromboprophylaxis" is usually meant around 30 days postoperatively. This modality using low molecular heparin in patients undergoing total hip replacement has been shown to be effective as regards incidence of both phlebographically detected deep vein thrombosis and--in meta-analysis--clinical venous thromboembolism. It is important to identify further risk groups who may be in need of prolonged thromboprophylaxis. Recent data suggest that patients undergoing abdominal/pelvic surgery for malignant diseases belong to such a group.


Phylogenetic relationships of Vepris (Rutaceae) inferred from chloroplast, nuclear, and morphological data.
The tribe Toddalieae Hook. F. (Rutaceae) has been controversial since its inception by Bentham and Hooker. The nine taxa examined, Acronychia J.R. & G.Foster, Diphasia Pierre, Diphasiopsis Mendonca, Fagaropsis Mildbr.ex. Siebenl., Oricia Pierre, Teclea Delile, Toddaliopsis Engl., Toddalia Juss. and Vepris Comm. ex. A. Juss, have been recognized under the tribe Toddalieae or Tribes Acronychia, Phellodendron and Toddalia. More recently Araliopsis Engl., Diphasia, Diphasiopsis, Oricia, Teclea, and Toddaliopsis have been incorporated into the genus Vepris, while Toddalia and Fagaropsis have continued to be recognized as closely related. For this study, sequence data of one non-coding chloroplast region (trnL-F) and one nuclear region (ITS) and various morphological characters, based on Mziray's taxonomic studies were examined to try to elucidate these relationships. This study found that the taxa Diphasia, Diphasiopsis, Oricia, Teclea, Toddaliopsis, Vepris, Toddalia eugeniifolia Engl. and Toddalia glomerata F. Hoffm. form a monophyletic group. Due to the amount of intrageneric and intraspecific variation, species delimitations were difficult to determine; however, these genera should be united into Vepris. The analyses also confirmed that Toddalia asiatica (L.) Lam., Zanthoxylon sp. and Fagaropsis angolensis (Engl.) H.M. Gardner are the closest relatives to this group.


Effect of Lactobacillus inoculants and forage dry matter on the fermentation and aerobic stability of ensiled mixed-crop tall fescue and meadow fescue.
This study evaluated the effects of Lactobacillus plantarum with or without Lactobacillus buchneri on the fermentation and aerobic stability of mixed tall fescue (Festuca arundinacea Schreb) and meadow fescue (Festuca pratensis Huds.) silage ensiled at different dry matter (DM) contents. The first cut was harvested at boot stage and second-cut grasses were harvested when 30- to 35-cm tall. Four DM content treatments of the first cut were 17.9, 24.9, 34.6, and 48.7%; and of the second cut were 29.1, 36.3, 44.1, and 49.2%. Chopped grasses at each DM content were treated with (1) deionized water (control), (2) Lb. plantarum MTD-1 (LP), or (3) a combination of Lb. plantarum MTD-1 and Lb. buchneri 40788 (LP+LB). The application amount of each inoculant to the fresh forage was 1 × 10(6) cfu/g. Grasses were ensiled in vacuum-sealed polyethylene bags containing 150 g of DM for 60 d, with 4 replicates for each treatment. Silages inoculated with LP+LB had greater pH compared with untreated or LP-treated silages. Lactate was greater in LP silage than control or LP+LB silages. As silage DM increased, lactate in untreated and LP-treated silages decreased, but increased in LP+LB-treated silage. Acetate concentration decreased with increased DM in all silages. The LP+LB-treated silage had the longest and control silage the shortest aerobic stability for both harvests. The greatest values in aerobic stability were observed in silages with highest DM content. In this study, aerobic stability of grass mixes ensiled between 18 and 44% DM content increased as the percentage of DM increased. The LP and LP+LB inoculants improved aerobic stability of silages harvested between 18 and 44% DM content.


Rapid changes in poly (A) tail length of vasopressin and oxytocin mRNAs form a common early component of neurohypophyseal peptide gene activation following physiological stimulation.
The time course of acute changes in vasopressin (VP) and oxytocin (OT) mRNA size and level during dehydration has been studied in rats. Total RNA was extracted from samples of the supraoptic nucleus at various intervals after water deprivation, subjected to northern blotting, and probed with oligonucleotides specific for VP and OT mRNA. The VP and OT mRNA size, shown previously to reflect 3'-poly (A) tail length, was consistently increased 2 h after dehydration, prior to significant changes in plasma osmolality or haematocrit. Intraperitoneal administration of hypertonic saline resulted in a similarly rapid VP and OT mRNA size response, in some cases within 1 h of treatment. The effect of a discrete hypovolaemic stimulus was investigated with intraperitoneal injections of polyethylene glycol; again, the VP and OT mRNA size was rapidly increased. No significant changes in mRNA level were observed in any of the experimental groups. The results show that an increase in VP and OT mRNA poly(A) tail length forms an acute and general response to activation of the hypothalamo-neurohypophyseal system. The rapidity of the poly (A) tail response, which appears to be independent of physiological signalling mechanisms associated with increases in mRNA accumulation (observed after 2 days of dehydration), provides a paradigm for the investigation of novel modes of neuronal gene regulation.