Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for alpha 5-containing GABAA receptors.
The synthesis and pharmacological properties of imidazobenzodiazepines with both high affinity and selectivity for alpha 5-containing GABAA receptors are described. Four of these compounds (5, 6, 8, and 9) inhibited [3H]flunitrazepam binding to recombinant alpha 5 beta 2 gamma 2 GABAA receptors with IC50 values between approximately 0.4 and 5 nM. These compounds were > or = 24-75-fold more selective for recombinant receptors containing alpha 5 subunits compared to other, "diazepam-sensitive" GABAA receptors containing either alpha 1, alpha 2, or alpha 3 subunits. Imidazobenzodiazepine 9 (used as the prototypical alpha 5 selective ligand) inhibited [3H]flunitrazepam binding to hippocampal membranes with high- and low-affinity components (IC50 0.6 +/- 0.2 and 85.6 +/- 13.1 nM, respectively), representing approximately 16% and approximately 84% of the receptor pool. Inhibition of [3H]flunitrazepam binding to cerebellar membranes with imidazobenzodiazepine 9 was best fitted to a single population of sites with an IC50 of 79.8 +/- 18.3 nM. These imidazobenzodiazepines behaved as GABA negative ligands in recombinant GABAA receptors expressed in Xenopus oocytes and were convulsant in mice after parenteral administration. The relative potencies of flumazenil and zolpidem in blocking convulsions induced by 9 and DMCM, respectively, indicated that occupation of alpha 5-containing GABAA receptors substantially contributed to the convulsant properties of acetylene analog 9. These 8-substituted imidazobenzodiazepines (5, 6, 8 and 9) should prove useful in examining the physiological roles of GABAA receptors bearing an alpha 5 subunit and may also lead to the development of novel, subtype selective therapeutic agents.


Rice Exo70 interacts with a fungal effector, AVR-Pii, and is required for AVR-Pii-triggered immunity.
Vesicle trafficking including the exocytosis pathway is intimately associated with host immunity against pathogens. However, we still have insufficient knowledge about how it contributes to immunity, and how pathogen factors affect it. In this study, we explore host factors that interact with the Magnaporthe oryzae effector AVR-Pii. Gel filtration chromatography and co-immunoprecipitation assays identified a 150 kDa complex of proteins in the soluble fraction comprising AVR-Pii and OsExo70-F2 and OsExo70-F3, two rice Exo70 proteins presumably involved in exocytosis. Simultaneous knockdown of OsExo70-F2 and F3 totally abrogated Pii immune receptor-dependent resistance, but had no effect on Pia- and Pik-dependent resistance. Knockdown levels of OsExo70-F3 but not OsExo70-F2 correlated with reduction of Pii function, suggesting that OsExo70-F3 is specifically involved in Pii-dependent resistance. Under our current experimental conditions, over-expression of AVR-Pii or knockdown of OsExo70-F2 and -F3 genes in rice did not affect the virulence of compatible isolates of M. oryzae. AVR-Pii interaction with OsExo70-F3 appears to play a crucial role in immunity triggered by Pii, suggesting a role for OsExo70 as a decoy or helper in Pii/AVR-Pii interactions.


Neurophysiology of Spatial Cognition.
Understanding of the neurophysiology of cognition is advancing through the study of how animals navigate and understand space. Manipulating various classes of spatial information and recording from hippocampal neurons provides a robust model for understanding how the brain stores and constructs the spatial memories that are critical for organizing daily experience.


Passive immunity to pandemic H1N1 2009 by swine flu parties.
The general population is concerned about the probable devastating effects of pandemic H1N1 2009. Based upon the 1918 Spanish flu pandemic, scientific publications and theories, the idea of swine flu parties to achieve passive immunity against pandemic H1N1 2009 has been proposed. Public health officials have asked the general public not to resort to this method. However, no concrete evidence of the reasoning behind the recommendation has been given. In this paper, we have dynamically modeled the effect of swine flu parties on the immunity achieved and associated mortality for a period of two years. The simulations show that the public should not organize or participate in swine flu parties as they will likely increase swine flu-associated mortality.


Planar rainbow refractometry.
Rainbow refractometry has been used in the past to measure size and refractive index of spherical particles, typically droplets in a spray. In the present study, conventional optical configurations for point measurements or line measurements have been extended to allow also the particle position in a plane to be determined, and hence, the designation planar rainbow refractometry. However, this extension introduces challenges in accurately calibrating the 2D scattering angles with the image coordinates. This challenge has been met using a novel calibration method, employing a monodispersed droplet stream traversed through the measurement plane. Experiments confirm achievable horizontal and vertical position accuracies of 0.42 mm and 0.36 mm, respectively, and a refractive index uncertainty of 2×10-4.


Effects of substance P and somatostatin on taurocholate-stabilized and CCK- or secretin-induced choleresis in the anesthetized dog.
Eleven anesthetized dogs were provided with a common bile duct fistula, and the gallbladder was excluded. After stabilization of the bile flow by intravenous infusions of taurocholate, various peptides were administered intravenously. Substance P (SP) decreased the output of hepatic bile, bile acids, sodium, potassium, and bicarbonate by about 50%. When SP was superimposed on cholecystokinin (CCK)- or secretin-induced choleresis, all CCK-induced effects were abolished, whereas SP had a less pronounced anticholeretic effect when choleresis was induced by secretin. Somatostatin (SST) decreased the output of hepatic bile, bile acids, sodium, potassium, and bicarbonate by about 25%. SST had no inhibitory effect on CCK- or secretin-induced choleresis. It is suggested that the principal mode of action of SST on bile flow is indirect by inhibiting the release of choleretic hormones, whereas SP is suggested to act directly on the hepatocytes.


Modification of M1 cells by exogenous introduction of IL6 gene: a model for gene therapy of acute and chronic myeloid leukemia in mice.
A number of recent studies has shown that animals immunized with cytokine secreting primary tumors show resistance against an unmodified tumor cell challenge. In the present study we have evaluated the potential role of IL6, a myeloid differentiation inducing factor, in modifying myeloid leukemia cells, a tumor so far not challenged by this approach. M1 cells transduced with N2 based retrovirus carrying the murine IL6 gene exhibit morphological and functional alterations. Genetically modified M1 cells show significant reduction in the growth constant coefficient and in the ability to form hematopoietic colonies. Flow cytometry analysis demonstrate increased expression of CD11b, CD18, F4/80, FcR and MHC class II, suggesting driven differentiation towards commitment. Transduced cells secrete high level of autocrine IL6 and, upon activation with LPS, high levels of TNF further indicating a functional alteration and differentiation. The insertion of IL6 gene coding for signals of cell activation and improved expression of MHC antigens into myeloid leukemia cells may enable more effective tumor recognition in vivo, and boost the local as well as the systemic immune-mediated anti-leukemia response.


HIV-related metabolic abnormalities in the brain: depiction with proton MR spectroscopy with short echo times.
To analyze brain metabolite changes in human immunodeficiency virus (HIV)-positive neurologically asymptomatic patients and patients with acquired immunodeficiency syndrome (AIDS) dementia complex (ADC). Twelve ADC patients, 11 HIV-positive asymptomatic patients, and 10 healthy control subjects underwent magnetic resonance (MR) imaging and proton MR spectroscopy with short echo times. Changes in N-acetyl aspartate (NAA), choline (Cho), myoinositol (MI), and creatine (Cr) were presented as ratios with Cr as the reference. Statistically significant (P < .05) differences were noted. In ADC patients, all with MR findings of brain atrophy and diffuse white matter disease, NA/Cr decreased (white matter, -31.8%; gray matter, -22.3%), MI/Cr increased (white matter, +42.5%; gray matter, +51.8%), and Cho/Cr increased (white matter, +20.6%; gray matter, +51.7%) compared with healthy control subjects. In HIV-positive asymptomatic patients, NA/Cr decreased slightly (white matter, -6.9%; gray matter, -5.1%), MI/Cr increased slightly (white matter, +13.7%; gray matter, +10.7%), and Cho/Cr did not change. ADC has a uniform pathologic metabolic pattern that affects NAA, MI, and Cho. Proton MR spectroscopy with short echo times helps detect early abnormalities in clinically asymptomatic patients.


Mobile X-ray service for nursing homes.
Transport to a radiology department can be a strain on nursing home patients, leading to less use of diagnostic imaging. The purpose of this study was to examine the use and benefit of a mobile X-ray service that enables imaging at nursing homes. In connection with 300 of a total of 326 referrals to a mobile X-ray service in Vestfold County in the period March to September 2015, 66 doctors at 33 nursing homes completed a questionnaire on the options patients would have had in the absence of the mobile service. A hundred of these referrals were followed up one to two weeks later with a further questionnaire on the implications of the X-ray scan for diagnosis, treatment and nursing. Eighty-seven questionnaires were completed. In 219 cases (73 %), the patients would have been sent to a hospital radiology department if the mobile X-ray service had not been available. In 60 cases (20 %) the patients would not have had an X-ray examination. In the follow-up, doctors answered that the X-rays had yielded new diagnostic information in 81 cases (95 %), that 71 (83 %) of the X-ray results had had implications for further treatment and that 29 (34 %) had helped patients avoid hospitalisation. In 77 cases (89 %), the X-rays enabled important information to be given to patients and their families. A mobile X-ray service makes it possible to avoid transports that place a strain on patients and to provide necessary diagnoses for patients who would not otherwise have been examined.


Crafting interactivity for stakeholder engagement: transforming assumptions about communication in science and policy.
The International Radiation Protection Association's guiding principles for stakeholder engagement focus on fostering, facilitating, and enabling interaction among stakeholders that is inclusive and fosters competent decision making. Implicit in these standards is a call to cultivate knowledge and competence in designing communication for stakeholder engagement among radiation protection professionals. Communication as design is an approach to risk communication in science and policy that differs from, yet complements, the more well-known communication practices of informing and persuading. Design focuses on the recurring practical problem faced by professionals in making communication possible among stakeholders where it has otherwise been difficult, impossible, or even unimagined. The knowledge and competence associated with design involves principles for crafting interactivity across a variety of mediated and non-mediated encounters among stakeholders. Risk communication can be improved by cultivating expertise in scalable communication design that embraces the demands of involvement without abandoning the need for competence in science and policy communication.


Preanalytical errors in medical laboratories: a review of the available methodologies of data collection and analysis.
Preanalytical errors have previously been shown to contribute a significant proportion of errors in laboratory processes and contribute to a number of patient safety risks. Accreditation against ISO 15189:2012 requires that laboratory Quality Management Systems consider the impact of preanalytical processes in areas such as the identification and control of non-conformances, continual improvement, internal audit and quality indicators. Previous studies have shown that there is a wide variation in the definition, repertoire and collection methods for preanalytical quality indicators. The International Federation of Clinical Chemistry Working Group on Laboratory Errors and Patient Safety has defined a number of quality indicators for the preanalytical stage, and the adoption of harmonized definitions will support interlaboratory comparisons and continual improvement. There are a variety of data collection methods, including audit, manual recording processes, incident reporting mechanisms and laboratory information systems. Quality management processes such as benchmarking, statistical process control, Pareto analysis and failure mode and effect analysis can be used to review data and should be incorporated into clinical governance mechanisms. In this paper, The Association for Clinical Biochemistry and Laboratory Medicine PreAnalytical Specialist Interest Group review the various data collection methods available. Our recommendation is the use of the laboratory information management systems as a recording mechanism for preanalytical errors as this provides the easiest and most standardized mechanism of data capture.


[Effect of Electroacupuncture Stimulation of Heart Meridian on Autonomic Nervous Activities in Acute Myocardial Ischemia Rats].
To observe the effect of electroacupuncture (EA) stimulation of the Heart Meridian on electrical activities of neck sympathetic and vagal nerves in acute myocardial ischemia (AMI) rats. Thirty SD rats were randomly divided into 3 groups, sham operation (sham), model and EA(n=10 rats in each group). The left anterior descending branch (LADB) of the coronary artery was occluded to make an acute myocardial ischemia (AMI) model.For rats of the sham group, a surgical suture was simply threaded beneath the LADB without ligation. EA stimulation (2 Hz, 1 mA)was applied to bilateral "Shenmen" (HT 7), "Tongli" (HT 5) and the middle-point between HT 7 and HT 5 for 20 min. The electrical activities of the left cervical sympathetic and vagal nerves were recorded using a bipolar platinum wire electrodes and a BIOPAC MPl 50 system, and the electrocardiogram (ECG) of the standard limb lead Ⅱ was recorded simultaneously. The AMI severity was evaluated by using J-spot height of ECG. After AMI, the heart rate (HR), J-spot of ECG, and the discharge frequency of the cervical sympathetic nerve were significantly increased in the model group compared with the sham group (P<0.01), while the discharge frequency of vagal nerve was obviously decreased (P<0.01). Following EA stimulation, the increased levels of HR, J-spot height and discharge frequency of sympathetic nerve, and the decreased discharge frequency of vagus were significantly suppressed at time-points of 1, 3, 5 and 15 min after EA (P<0.01). In addition, the ratio of discharge frequencies of vagal/sympathetic nerves was notably down-regulated after AMI (P<0.01). After EA stimulation, the ratios of vagal/sympathetic discharge at the time-points of 1, 3, 5 and 15 min following EA were significantly increased (P<0.01). EA stimulation of the Heart Meridian may improve AMI by inhibiting sympathetic discharges and elevating vagal discharges in AMI rats, i.e., coordinating activities of the autonomic nerve systems.


Impact of Bacterial Injury and Repair in Food Microbiology: its Past, Present and Future.
Studies done during the past 25 years revealed that microorganisms present in semipreserved foods can be injured by sublethal treatments. The injured cells, irrespective of differences in sublethal treatments, have similarities in their manifestation of injury and their repair. A simple resuscitation step incorporated into currently recommended isolation procedures would enable detection of these cells. In the future, microbial cell injury studies should be directed to include not only effective detection of index and pathogenic bacteria from foods, but also growth inhibition of spoilage microorganisms and preservation of lactic cultures.


T-lymphocyte immunophenotyping in polymyositis and dermatomyositis.
The objective was to elucidate the immunological abnormalities underlying polymyositis (PM) and dermatomyositis (DM). The phenotype of peripheral blood mononuclear cell (PBMNC) subsets and cell surface expression of activation (CD25 and HLA-DR) and adhesion (LFA-1) molecules was studied in 12 patients with PM and in 10 patients with DM. PBMNC subsets and expression of T-cell activation molecules were evaluated by cytofluorography. Double immunofluorescence and indirect immunoperoxidase techniques were applied to muscle biopsies to define T-cell phenotype and LFA-1/ICAM-1 expression. In PM, the absolute number of circulating cytotoxic (CD8+CD28+) T cells was selectively reduced. T cells showed increased expression of activation molecules, CD25 and HLA-DR, and increased adhesion capacity as the absolute numbers of CD3+CD25+, CD8+HLA-DR+, CD3+LFA-1+('bright') and CD8+ CD8+LFA-1+('bright') cells were higher than in healthy donors and DM patients. In PM muscle biopsies, T cells were mainly CD3+CD8+ and LFA-1+; additionally, endothelial cells and myofibres surrounded by T cells showed positive staining for ICAM-1. In DM, there was a general lymphopenia that led to a decreased absolute number of all T-lymphocyte subsets. It is proposed that in PM, in contrast to DM, LFA-1/ICAM-1 interactions enable activated CD8+ T cells to migrate selectively into the inflamed muscle and to adhere to myofibres, leading to tissue injury.


Spatial stochastic models of cancer: fitness, migration, invasion.
Cancer progression is driven by genetic and epigenetic events giving rise to heterogeneity of cell phenotypes, and by selection forces that shape the changing composition of tumors. The selection forces are dynamic and depend on many factors. The cells favored by selection are said to be more 'fit'than others. They tend to leave more viable offspring and spread through the population. What cellular characteristics make certain cells more fit than others? What combinations of the mutant characteristics and 'background' characteristics make the mutant cells win the evolutionary competition? In this review we concentrate on two phenotypic characteristics of cells: their reproductive potential and their motility. We show that migration has a direct positive impact on the ability of a single mutant cell to invade a pre-existing colony. Thus, a decrease in the reproductive potential can be compensated by an increase in cell migration. We further demonstrate that the neutral ridges (the set of all types with the invasion probability equal to that of the host cells) remain invariant under the increase of system size (for large system sizes), thus making the invasion probability a universal characteristic of the cells' selection status. We list very general conditions under which the optimal phenotype is just one single strategy (thus leading to a nearly-homogeneous type invading the colony), or a large set of strategies that differ by their reproductive potentials and migration characteristics, but have a nearly-equal fitness. In the latter case the evolutionary competition will result in a highly heterogeneous population.


Effects of sodium butyrate on proliferation-dependent insulin gene expression and insulin release in glucose-sensitive RIN-5AH cells.
A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the presence of amino acids, these cells showed a dose-dependent insulin response to glucose with a half-maximal and maximal 6.5-fold stimulation by 0.8 and 5.6 mmol/liter D-glucose, respectively. However, as the control cells approached growth arrest, insulin gene expression subsided to below detectability, an occurrence that is associated with decreased insulin release and accumulation of cells in the G1 phase of the cell cycle. In contrast, NaB-arrested cells showed continuous insulin gene expression throughout the experiment. Despite this, insulin release in response to glucose was lost. NaB revealed a biphasic effect on the cell-cycle: after an initial leaky G1 arrest during the first 24 h, the 5AH-B cells were arrested in G2 during the following 3 days. These data suggest that insulin gene expression and glucose-stimulated insulin release are affected by the cell cycle. These glucose-sensitive RIN-5AH-T2-B cells may be useful in studies of insulin secretion and gene regulation.


Climate change and the possible health effects on older Australians.
Climate change is an important issue for Australia. Climate change research forecasts that Australia will experience accelerated warming due to anthrogenic activities. Australia's aging society will face special challenges that demand current attention. This paper discusses two issues in relation to climate change and older Australians: first, pharmacology and autoregulation; and second, mental health among older Australians.


The MicroRNA397a-LACCASE17 module regulates lignin biosynthesis in Medicago ruthenica (L.).
Mechanical strength is essential for the upright growth habit, which is one of the most important characteristics of terrestrial plants. Lignin, a phenylpropanoid-derived polymer mainly present in secondary cell walls plays critical role in providing mechanical support. Here, we report that the prostrate-stem cultivar of the legume forage Medicago ruthenica cultivar 'Mengnong No. 1' shows compromised mechanical strength compared with the erect-stem cultivar 'Zhilixing'. The erect-stem cultivar, 'Zhilixing' has significantly higher lignin content, leading to higher mechanical strength than the prostrate-stem cultivar. The low abundance of miRNA397a in the Zhiixing cultivar causes reduced cleavage of MrLAC17 transcript, which results in enhanced expression level of MrLAC17 compared to that in the prostrate-stem cultivar Mengnong No. 1. Complementation of the Arabidopsis lac4 lac17 double mutants with MrLAC17 restored the lignin content to wild-type levels, confirming that MrLAC17 perform an exchangeable role with Arabidopsis laccases. LAC17-mediated lignin polymerization is therefore increased in the 'Zhilixing', causing the erect stem phenotype. Our data reveal the importance of the miR397a in the lignin biosynthesis and suggest a strategy for molecular breeding targeting plant architecture in legume forage.


Histopathology and the lethal effect of Cry proteins and strains of Bacillus thuringiensis Berliner in Spodoptera frugiperda J.E. Smith Caterpillars (Lepidoptera, Noctuidae).
Among the phytophagous insects which attack crops, the fall armyworm, Spodoptera frugiperda (J.E. Smith, 1797) (Lepidoptera, Noctuidae) is particularly harmful in the initial growth phase of rice plants. As a potential means of controlling this pest, and considering that the entomopathogen Bacillus thuringiensis Berliner demonstrates toxicity due to synthesis of the Cry protein, the present study was undertaken to evaluate this toxic effect of B. thuringiensis thuringiensis 407 (pH 408) and B. thuringiensis kurstaki HD-73 on S. frugiperda. The following method was used. Both bacterial strains were evaluated in vitro in 1st instar S. frugiperda caterpillars, by means of histopathological assays. The Cry1Ab and Cry1Ac proteins, codified by the respective strains of B. thuringiensis, were evaluated in vivo by bioassays of 1st instar S. frugiperda caterpillars in order to determine the Mean Lethal Concentration (LC50). The results of the histopathological analysis of the midget of S. frugiperda caterpillars demonstrate that treatment with the B. thuringiensis thuringiensis strain was more efficient, because the degradations of the microvilosities started 9 hours after treatment application (HAT), while in the B. thuringiensis kurstaki the same effect was noticed only after 12 HAT. Toxicity data of the Cry1Ab and Cry1Ac proteins presented for the target-species LC50 levels of 9.29 and 1.79 microgxcm-2 respectively. The strains and proteins synthesised by B. thuringiensis thuringiensis and B. thuringiensis kurstaki are effective in controlling S. frugiperda, and may be used to produce new biopesticides or the genes may be utilised in the genetic transformation of Oryza sativa L.


An antiapoptotic role of sorting nexin 7 is required for liver development in zebrafish.
Sorting nexin (SNX) family proteins are best characterized for their abilities to regulate protein trafficking during processes such as endocytosis of membrane receptors, endosomal sorting, and protein degradation, but their in vivo functions remain largely unknown. We started to investigate the biological functions of SNXs using the zebrafish model. In this study, we demonstrated that SNX7 was essential for embryonic liver development. Hepatoblasts were specified normally, and the proliferation of these cells was not affected when SNX7 was knocked down by gene-specific morpholinos; however, they underwent massive apoptosis during the early budding stage. SNX7 mainly regulated the survival of cells in the embryonic liver and did not affect the viability of cells in other endoderm-derived organs. We further demonstrated that down-regulation of SNX7 by short interfering RNAs induced apoptosis in cell culture. At the molecular level, the cellular FLICE-like inhibitory protein (c-FLIP)/caspase 8 pathway was activated when SNX7 was down-regulated. Furthermore, overexpression of c-FLIP(S) was able to rescue the SNX7 knockdown-induced liver defect. SNX7 is a liver-enriched antiapoptotic protein that is indispensable for the survival of hepatoblasts during zebrafish early embryogenesis.


Life-threatening ventricular arrhythmias in septicemia.
Sixteen episodes of ventricular tachycardia and/or fibrillation, 12 of which occurred during shaking chills, were recorded in six patients with septicemia. All patients were greater than 60 years of age and had suffered a previous myocardial infarction. Patients who survived the condition sustained no further arrhythmias during a follow-up period of 1 to 4 years, despite the fact that no antiarrhythmic medication was administered. It is suggested that patients greater than 60 years of age who had suffered a previous myocardial infarction should be carefully monitored during septic episodes and especially during shaking chills, since these may represent vulnerable periods facilitating the precipitation of potentially lethal arrhythmias.


Rural Public Health Workforce Training and Development: The Performance of an Undergraduate Internship Programme in a Rural Hospital and Healthcare Centre.
Workforce shortages in the field of public health and healthcare are significant. Due to the limitations of career opportunities and compensation, rural hospitals and healthcare centres usually have on-going career openings for all departments. As a result, university departments of public health and healthcare management, and rural hospitals and health centres may need to establish internship and training programmes for undergraduate senior-year students in order to provide opportunities and human resource opportunities for both students and public health professions. The research examined the performance, feedback, and opinions of a university-based one-year-long on-site internship training programme between a university public health and healthcare undergraduate department and a regional hospital and healthcare centre in a rural region in the United States. Individual interview data were collected from management trainees and focus group activities data were collected from hospital departmental supervisors who have completed this one-year-long on-site internship training programme. The results offered an assessment of performance and evaluation of how a one-year-long internship programme could be beneficial to hospitals and health centres in the areas of human resources, manpower management, and skill training to prospective professionals in rural and regional communities. Also, the study provided a blueprint and alternative for universities and partnered sites to redesign and improve their current internship programmes which may better fit their needs for their actual situations.


Fixation of rotationally unstable extracapsular proximal femoral fractures.
It was thought that the AO types A1.2 and A1.3 fractures are rotationally stable; however, it revealed instability when fixed using the dynamic hip screw. Therefore, we hypothesized that these fractures should be treated as rotationally unstable. A series of 83 fractures of the AO types A1, A2, and B2.1 were treated using dynamic hip screw with derotation screw (DHS/DRS) composite and then prospectively followed for 24 months. Adequacy of reduction and fixation were immediately assessed after surgery, and fracture collapse was assessed at six months or when fractures healed. To investigate the feasibility of our hypothesis, fractures were classified into two groups: 1) the inevitably unstable group (IUG) included the AO types A1.1, A2.1, A2.2, A2.3, and B2.1 fractures and 2) the potentially unstable group (PUG) included the AO types A1.2 and A1.3 fractures. The results were statistically analyzed. Adequate reduction was achieved in 77 and adequate fixation in 71 fractures. All fractures healed in a mean time of 13.5 weeks, and the amount of the fracture collapse averaged 5.8 mm. Equalization of the lower limbs was achieved in 66 patients, and hip motion range equalized the healthy contralateral in 80 patients. Re-operation was performed in one case with AO type A1.2. Comparison of IUG and PUG using the outcomes revealed insignificant differences. Using the DHS/DRS composite, anatomical features of the proximal femoral end were restored and maintained during the follow-up period. Insignificant differences between outcomes of IGU and PGU render the addition of the AO types A1.2 and A1.3 to the rotationally unstable fractures reasonable.


4-Aminobenzimidazole-1-methylthymine: a model for investigating Hoogsteen base-pairing between adenine and thymine.
We report the infrared spectrum of the 4-aminobenzimidazole-1-methylthymine (4ABI:1MT) heterodimer, detected by femtosecond multiphoton ionization. Based on calculations of both the harmonic and the anharmonic frequencies, the observed vibrational spectrum is assigned to a structure that mimics the Hoogsteen base pairing of adenine and thymine. A notable observation made in the course of this study is that there is a significant imbalance in the observed strengths of the H-bonds. While the N···H-N bond reveals a large red shift of >700 cm(-1) for the NH stretch frequency, the N-H···O bond is characterized by only a 50 cm(-1) shift. The importance of this observation in the formation of Hoogsteen duplexes by thymine-based oligonucleotides is discussed.


The relationship of heart rate and lactate to cumulative muscle fatigue during recreational alpine skiing.
Common indices of fatigue may not respond similarly between downhill skiing and other activities because of the influence of factors such as snow conditions, changing terrain, and skiing style. The purpose of this study was to investigate the relationship and predictors of common fatigue indices during downhill skiing. Ten healthy female recreational skiers skied for 3 hours under standardized conditions. Feedback on heart rate (HR) and finishing time were given to each skier at the end of each run to maintain a relatively stable load. A chronic stress score (Cstress) was calculated from creatine kinase (CK), cortisol, and isometric endurance. Finishing times and HR from runs 2, 12, and 24 were similar. Heart rate averaged 82% of HRmax. Heart rate was an insignificant predictor (p = .65) and was poorly correlated (r = 0.16) to Cstress. Blood lactate (LA) was a significant predictor of the Cstress (p = 0.05; r = 0.62). Pre- to postskiing peak forces were not different (p = 0.62), but skiers experienced a significant decrease in isometric endurance from 106.1 +/- 29.6 to 93.2 +/- 24.0 seconds. Endurance decreased by 13%, whereas cortisol and CK increased by 16 and 42%, respectively. Isometric contraction endurance and blood LA were significant predictors of overall stress. Individual compensation mechanisms and skiing style contributed to highly variable responses during skiing. Whereas HR may indicate stress within a given run, it is not a significant indicator of Cstress and fatigue during recreational alpine skiing. However, the cumulative stress variables and LA can be used in field testing of skiers. It is suggested that LA is a practical on-hill marker of chronic stress.


The action and mode of binding of thiazolidinedione ligands at free fatty acid receptor 1.
The endogenous ligands for free fatty acid receptor 1 (FFA1) are medium and longer chain free fatty acids. However, a range of selective, small molecule ligands have recently been developed as tool compounds to explore the therapeutic potential of this receptor, whereas clinically employed thiazolidinedione "glitazone" drugs are also agonists at FFA1. Each of these classes of agonist was able to promote phosphorylation of the ERK1/2 mitogen-activated protein (MAP) kinases in cells able to express human FFA1 on demand. However, although both lauric acid and the synthetic agonist GW9508X produced rapid and transient ERK1/2 MAP kinase phosphorylation, the thiazolidinedione rosiglitazone produced responses that were sustained for a substantially longer period. Despite this difference, the effects of each ligand required FFA1 and were transduced in each case predominantly via G proteins of the Galphaq/Galpha11 family. Different glitazone drugs also displayed markedly different efficacy and kinetics of sustainability of ERK1/2 MAP kinase phosphorylation. A number of orthosteric binding site mutants of FFA1 were generated, and despite variations in the changes of potency and efficacy of the three ligand classes in different functional end point assays, these were consistent with rosiglitazone also binding at the orthosteric site. Four distinct polymorphic variants of human FFA1 have been described. Despite previous indications that these display differences in function and pharmacology, they all responded in entirely equivalent ways to lauric acid, rosiglitazone, and GW9508X in measures of ERK1/2 MAP kinase phosphorylation, enhancement of binding of [35S]GTPgammaS (guanosine 5'-O-(3-[35S]thio)triphosphate) to Galphaq, and elevation of intracellular [Ca2+], suggesting that individuals expressing each variant are likely to respond equivalently to orthosteric agonists of FFA1.


Structure, bonding, and solvation of dilithiodiamines.
Computational methods were used to determine the structure of dilithiodiamines and the effects of solvation by ethereal solvents. Solvation was examined by the use of microsolvation with explicit dimethyl ether or THF ligands and by the combined use of microsolvation and the IEFPCM continuum solvent model. It was determined that each of the compounds studied exists exclusively as a bridged intramolecular dimer, both in the gas phase and in solution. Thermodynamic properties were calculated at 200 and 298 K to estimate the effect of temperature on the cyclization energies. Infrared spectroscopy was used to confirm the proposed intramolecular dimer structures.


Rapid response: a quality improvement conundrum.
Many in-hospital cardiac arrests and other adverse events are heralded by warning signs that are evident in the preceding 6 to 8 hours. By promptly intervening before further deterioration occurs, rapid response teams (RRTs) are designed to decrease unexpected intensive care unit (ICU) transfers, cardiac arrests, and inpatient mortality. While implementing RRTs is 1 of the 6 initiatives recommended by the Institute for Healthcare Improvement, data supporting their effectiveness is equivocal. Before implementing an RRT in our institution, we reviewed cases of failure to rescue and found that (1) poor outcomes were often associated with attempts to manage early decompensations without a bedside evaluation, and (2) the common causes of decompensation for floor patients (early sepsis, aspiration, pulmonary embolism) were within the scope of our primary teams' practice. Therefore, we felt that prompt, mandatory bedside evaluations by the primary team would decrease untoward outcomes.


Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit.
Currents through the inward rectifier K channel (iK X rec) and the ACh-operated K channel (iK X ACh) were recorded in isolated heart cells of rabbit using the patch clamp technique with electrodes having 0.5-1 micron tip inner diameter. The maximum number of overlaps of open iK X rec channels per patch was measured over 347 experiments. An average of 2.3 was found in ventricular cells and 0.03-0.06 in sinoatrial (S-A) and atrioventricular (A-V) node cells. The estimated total number of the iK X rec channels for each ventricular cell was great enough to supply the resting K conductance of the cell. The iK X ACh channel was present in S-A and A-V node cells, but was never observed in the ventricular cells. The resting conductance of the nodal cells measured with whole cell clamp recordings was about 16 times smaller than that of the ventricular cells, and was hardly decreased at all by the removal of K+ from the bath solution. Thus, the lower membrane potential of the nodal cells compared with that of the ventricular cells was attributed to the smaller K conductance of the resting membrane, which is due to the very low density of the iK X rec channel. On the other hand, the iK X ACh channel, when activated by neural regulation, may play a major role in generating the resting K conductance of the nodal cells.


Parallels between research in mental health in Brazil and in the field of Global Mental Health: an integrative literature review.
Global Mental Health is a field of teaching, research, and practice whose goal is to improve access to mental health and reduce inequalities in mental health outcomes for all people worldwide, especially proposing action in low- and middle-income countries like Brazil. Given this global scenario and Brazil's progress in health and psychiatric reforms, it is important to investigate the current status of the Brazilian mental health literature and its relationship to Global Mental Health, describing how Brazilian research deals with key topics in the Global Mental Health field. The authors performed an integrative literature review using a qualitative and descriptive approach. The article search was performed for the years 2014 and 2015 in Portuguese and English, using the terms "mental health" and "Brazil", combined with key words corresponding to the principal themes addressed by authors in Global Mental Health. The search yielded 88 articles, which were analyzed according to authorship, periodicals and regions, and the analytical categories of access, primary care, community mental health services, social determinants of health, human rights, and equity. Brazil's mental health research revealed a rich and diverse body of studies, showing parallels with the literature on global mental health, but with limited systematization. Although the review revealed efforts to generate knowledge in this field within Brazil, some barriers may be limiting Brazil's participation in the international debate on Global Mental Health.


Comprehensive Characterization of Biotherapeutics by Selective Capturing of Highly Acidic Glycans Using Stepwise PGC-SPE and LC/MS/MS.
The glycosylation of biologics is an important factor in pharmacological functions such as efficacy, safety, and biological activity and is easily affected by subtle changes in the cellular environment. Hence, comprehensive and in-depth glycomic characterization of biological products should be performed to ensure product quality and process consistency prior to regulatory approval, but it is still highly challenging due to glycan microheterogeneity produced by enzymatic machinery. In this study, we have developed a systematic methodology for the separation and characterization of various glycans of biotherapeutics using the combination of solid-phase extraction (SPE) and high resolution LC/MS. Neutral and multiple-acidic glycans were selectively fractionated by SPE with a porous graphitized carbon (PGC) cartridge according to their molecule size and polarity (acidity, p Ka). Subsequent LC-MS and -MS/MS analyses enabled us to obtain glycan compositions, structures, and quantitative information. Indeed, we have successfully performed glycomic characterization of agalsidase-beta, a representative therapeutic enzyme containing both phosphorylated and sialylated glycans. In addition, a comparative analysis of functional glycans released from different batches of enzymes was performed to verify our method. These results suggest that stepwise PGC-SPE and LC/MS/MS pairwise assays can be used as an efficient tool to detect glycosylation changes of therapeutic glycoproteins including abundant acidic species in biologics or biosimilar development.


Outcomes of cholera and measles outbreak alerts in the Democratic Republic of Congo.
In 1995, a rapid response project for humanitarian and medical emergencies, including outbreak responses, named 'Pool d'Urgence Congo' (PUC), was implemented in the Democratic Republic of Congo by Médecins Sans Frontières. To assess the outcomes of cholera and measles outbreak alerts that were received in the PUC surveillance system between 2016 and 2018. This was a retrospective cross-sectional study. Overall, 459 outbreak alerts were detected, respectively 69% and 31% for cholera and measles. Of these, 32% were actively detected and 68% passively detected. Most alerts (90%) required no intervention and 10% of alerts had an intervention. There were 25% investigations that were not carried out despite thresholds being met; 17% interventions were not performed, the main reported reason being PUC operational capacity was exceeded. Confirmed cholera and measles outbreaks that met an investigation threshold comprised respectively 90% and 76% of alerts; 59% of measles investigations were followed by a delayed outbreak response of ⩾14 days (n = 10 outbreaks). Some alerts for cholera and measles outbreaks that were detected in the PUC system did not lead to a response even when required; the main reported reason was limited operational capacity to respond to all of them.


[Chemical constituents from Punica granatum flowers].
To investigate the chemical constituents in the flowers of Punica granatum. The chemical constituents were separated by silica gel column chromatography and their structures were determined by spectroscopic experiments. As a result, twelve compounds were isolated and identified as oleanolic acid (1), ursolic acid (2), palmitic acid (3), tricin (4), catechin (5), rutin (6), apigenin (7), apigenin-7-O-glucoside (8), 2S, 3S, 4S-trihydroxypentanoic acid (9), gallic acid (10), beta-stitosterol (11), and daucosterol (12). Compounds 3, 4, 7, 8 and 9 are separated from this plant for the first time, and compounds 3, 4 and 9 are isolated from this genus for the first time.


Autistic Siblings with Novel Mutations in Two Different Genes: Insight for Genetic Workups of Autistic Siblings and Connection to Mitochondrial Dysfunction.
The prevalence of autism spectrum disorder (ASD) is high, yet the etiology of this disorder is still uncertain. Advancements in genetic analysis have provided the ability to identify potential genetic changes that may contribute to ASD. Interestingly, several genetic syndromes have been linked to metabolic dysfunction, suggesting an avenue for treatment. In this case study, we report siblings with ASD who had similar initial phenotypic presentations. Whole exome sequencing (WES) revealed a novel c.795delT mutation in the WDR45 gene affecting the girl, which was consistent with her eventual progression to a Rett-like syndrome phenotype including seizures along with a stereotypical cyclic breathing pattern. Interestingly, WES identified that the brother harbored a novel heterozygous Y1546H variant in the DEP domain-containing protein 5 (DEPDC5) gene, consistent with his presentation. Both siblings underwent a metabolic workup that demonstrated different patterns of mitochondrial dysfunction. The girl demonstrated statistically significant elevations in mitochondrial activity of complex I + III in both muscle and fibroblasts and increased respiration in peripheral blood mononuclear cells (PBMCs) on Seahorse Extracellular Flux analysis. The boy demonstrates a statistically significant decrease in complex IV activity in buccal epithelium and decreased respiration in PBMCs. These cases highlight the differences in genetic abnormalities even in siblings with ASD phenotypes as well as highlights the individual role of novel mutations in the WDR45 and DEPDC5 genes. These cases demonstrate the importance of advanced genetic testing combined with metabolic evaluations in the workup of children with ASD.


Inhomogeneous cortical synchronization and partial epileptic seizures.
Interictal synchronization clusters have recently been described in several publications using diverse techniques, including neurophysiological recordings and fMRI, in patients suffering from epilepsy. However, little is known about the role of these hyper-synchronous areas during seizures. In this work, we report an analysis of synchronization clusters jointly with several network measures during seizure activity; we then discuss our findings in the context of prior literature. Subdural activity was recorded by electrocorticography (with 60 electrodes placed at temporal and parietal lobe locations) in a patient with temporal lobe epilepsy with partial seizures with and without secondary generalization (SG). Both interictal and ictal activities (during four seizures) were investigated and characterized using local synchronization and complex network methodology. The modularity, density of links, average clustering coefficient, and average path lengths were calculated to obtain information about the dynamics of the global network. Functional connectivity changes during the seizures were compared with the time evolution of highly synchronized areas. Our findings reveal temporal changes in local synchronization areas during seizures and a tight relationship between the cortical locations of these areas and the patterns of their evolution over time. Seizure evolution and SG appear to be driven by two different underlying mechanisms.


A young man who could not walk.
Infections affecting the central nervous system caused by Blastomyces dermatitidis are rare but curable. We describe a case of a 24-year-old man who presented to the emergency department with progressive bilateral lower extremity weakness over 1 month. On the day of admission, he had minimal muscle strength and was hyperreflexic in the lower extremities. Sensation, however, was intact. Skin examination revealed annular, raised, crusted lesions on his face and legs. A magnetic resonance imaging (MRI) scan showed marrow replacement of the T7 and T8 vertebral bodies and an epidural mass with cord compression. A chest radiograph showed an infiltrate, and a subsequent needle biopsy revealed yeast resembling B. dermatitidis. A skin biopsy was then obtained, and the culture grew out B. dermatitidis. He received 4 weeks of amphotericin B lipid complex (total of 6 grams), followed by oral itraconazole. After 1 week on antifungals, he was able to walk with a walker and the skin lesions virtually resolved. At 5 months he was ambulatory and riding a bicycle daily. Blastomycosis should be included in the differential diagnosis of epidural masses.


Premortality Effects of Zoophthora radicans Infection in Plutella xylostella
The effect of Zoophthora radicans infection on food consumption and utilization by Plutella xylostella larvae and oviposition by adults was investigated. Larval food consumption and weight gain were not affected by Z. radicans until the third day after infection, 1 day prior to death from mycosis. No food was eaten on the day on which larvae died. Overall, infected larvae ate 44% less leaf tissue than control larvae. Of the leaf tissue consumed by infected larvae 87.5% was eaten on the first 2 days after infection and after this time infected larvae gained little weight. The efficiency with which ingested food was converted into body weight did not change as infection progressed. Infected female moths laid significantly fewer eggs than control moths. This difference was not only due to differential mortality between the infected and control treatments as the egg production by infected females, until the point of death (Day 4 after infection), was significantly less than that of control females over the same period. Incubating females for 24 hr after eclosion (to allow further egg maturation), prior to infection, did not result in greater overall egg production when compared with moths infected on the day of eclosion. The possible causes for these reductions in larval feeding and adult oviposition rates are discussed. Copyright 1997 Academic Press. Copyright 1997 Academic Press


Managed care spillover effects.
In addition to influencing care for patients enrolled in managed care plans, growth in managed care could lead to broad changes in the structure and functioning of the health care system that could ultimately influence care for all patients, even those not covered by managed care plans. This paper summarizes the mechanisms by which these effects could arise, including shifts in the types of services available in markets and changes in physician practice patterns. The paper summarizes available empirical evidence on broad-level effects of managed care, concluding that the literature supports the view that managed care can have generalized effects on health care spending, utilization patterns, and infrastructure, although existing literature has not clearly identified effects on health outcomes.


Rectal cancer staging.
Rectal cancer staging provides critical information concerning the extent of the disease. The information gained from staging is used to determine prognosis, to guide management, and to assess response to therapy. Accurate staging is essential for directing the multidisciplinary approach to therapy. This article focuses on the evolution of staging systems, the rational for staging, and current methods used to stage rectal cancer.


Human spermatozoa: revelations on the road to conception.
Human spermatozoa are highly complex specialized cells designed to survive a long and perilous journey from the site of insemination to the upper reaches of the female reproductive tract where fertilization occurs. During this journey, these cells have to run the gauntlet laid down by the female immune system and time their physiological maturation so that as soon as an egg appears in the Fallopian tube, they are equipped to recognize this cell and participate in a remarkable cascade of cellular interactions culminating in fertilization. Despite their high level of specialization, human spermatozoa are notoriously inadequate and appear to be major contributors to the poor fertility that characterizes our species. Defective spermatozoa are also known to have a major impact on the progress of pregnancy and the health trajectory of the offspring, resulting in paternally mediated increases in miscarriage rate and a range of diseases in the progeny, including dominant genetic diseases and cancer. The causes of defective sperm function are complex and involve both genetic and environmental impacts, as well as paternal age. Where genetic factors are involved, there is a concern that the widespread use of assisted conception technologies will serve to enhance the retention of poor fertility genes in the population such that the more we use assisted reproductive technologies in one generation the more we shall need them in the next. These observations may have important implications for the health and well-being of children and for the provision of reproductive healthcare services for future generations.


Pd nanoparticles deposited on Co(OH)2 nanoplatelets as a bifunctional electrocatalyst and their application in Zn-air and Li-O2 batteries.
The development of affordable electrocatalysts for both oxygen reduction and evolution reactions (ORR/OER) has received great interest due to their importance in metal-air batteries and regenerative fuel cells. We developed a high-performance bifunctional oxygen electrocatalyst based on Pd nanoparticles supported on cobalt hydroxide nanoplatelets (Pd/Co(OH)2) as an air cathode for metal-air batteries. The Pd/Co(OH)2 shows remarkably higher electrocatalytic activity in comparison with commercial catalysts (Pt/C, IrO2), including an ORR half-wave potential (E1/2) of 0.87 V vs. RHE and an OER overpotential of 0.39 V at 10 mA cm-2 in aqueous alkaline medium. The Zn-air battery constructed with Pd/Co(OH)2 presents stable charge/discharge voltage (ΔEOER-ORR = 0.69 V), along with durable cycling stability for over 30 h. Also, this cathode exhibits a maximum discharge capacity of 17 698 mA h g-1, and stable battery operation over 50 cycles at a fixed capacity of 1000 mA h g-1, as an efficient air electrode for Li-O2 batteries, indicating that Pd/Co(OH)2 can be a potential candidate for both aqueous and non-aqueous metal-air batteries.


Target-initiated autonomous synthesis of metal-ion dependent DNAzymes for label-free and amplified fluorescence detection of kanamycin in milk samples.
Accurate and sensitive monitoring of the abused antibiotics is vital because excessive antibiotics in human body can cause toxicity to kidney or lead to potential loss of hearing. In this work, we described a label-free and highly sensitive fluorescent aptasensing platform for detecting kanamycin in milk samples based on the synchronization signal amplification of primer exchange reaction (PER) and metal-ion dependent DNAzyme. The target kanamycin binds the aptamer sequence hybridized on a hairpin template and initiates PER for autonomous synthesis of Mg2+-dependent DNAzyme sequences with aid of Bst-DNA polymerase at isothermal conditions. Such a synthesis process can be repeated many times to produce lots of DNAzymes to cyclically cleave the rA site in the signal hairpin substrates under the assistance of Mg2+ cofactor to liberate numerous free G-quadruplex fragments. The organic dye thioflavin T (ThT) further associates with these G-quadruplex fragments to yield substantially intensified fluorescence for sensitive detection of kanamycin with a low detection limit of 0.36 nM. In addition, the developed aptamer sensing method also shows a good selectivity for kanamycin against other interfering antibiotics, and can realize the monitoring of kanamycin added in milk samples, highlighting its potential for sensitive monitoring of trace amount of kanamycin for food safety applications.


New synthetic ways for the preparation of high-performance liquid chromatography supports.
The latest developments and in particular important synthetic aspects for the preparation of modern HPLC supports are reviewed. In this context, the chemistry of inorganic supports based on silica, zirconia, titania or aluminum oxide as well as of organic supports based on poly(styrene-divinylbenzene), acrylates, methacrylates and other, more specialized polymers is covered. Special consideration is given to modern approaches such as sol-gel technology, molecular imprinting, perfusion chromatography, the preparation of monolithic separation media as well as to organic HPLC supports prepared by new polymer technologies such as ring-opening metathesis polymerization. Synthetic particularities relevant for the corresponding applications are outlined.


Clock-drawing test and unilateral spatial neglect.
We investigated the ability of 25 patients with left unilateral spatial neglect to make a clock face by putting numbers inside a printed circle. Impairment seen in this clock-drawing test did not parallel neglect severity as judged by results of the line-cancellation and line-bisection tests, as well as the copying of a daisy. The score for clock drawing correlated highly with the verbal WAIS score. Most neglect patients with a verbal IQ of 87 or more could draw a clock face fairly well and used planning in placing the numbers 12, 3, 6, and 9 before the others. In clock drawing, verbal intelligence may compensate for left unilateral spatial neglect. We therefore recommend use of the line-cancellation and line-bisection tests, as well as the copying test, but do not recommend use of the clock-drawing test in the diagnosis of left unilateral spatial neglect.


Current Perspectives on rosuvastatin.
Rosuvastatin is one of the most potent statins available for reducing circulating low-density lipoprotein cholesterol (LDL-C) levels, which enables more high-risk patients to achieve their lipid goals. Its favorable balance of effects on atherogenic and protective lipoproteins and its pleiotropic effects, including anti-inflammatory and antioxidant effects and improvement in endothelial dysfunction, are associated with slowing of progression of atherosclerosis within the artery wall and have been translated into clinical benefits for cardiovascular outcomes. This review provides an update on the safety and the efficacy of rosuvastatin in recent large clinical trials. It appears that rosuvastatin has a beneficial effect on the progression of atherosclerosis across the clinical dosage range of 2.5-40 mg. It reduced cardiovascular events in relatively low-risk subjects with elevated high-sensitivity C-reactive protein and normal low-density lipoprotein cholesterol. As with other statins, rosuvastatin did not show overall benefit in terms of survival in patients with heart failure, but certain clinical or biochemical markers reflecting underlying disease characteristics may help to identify subgroups of patients that benefit from statin therapy. In patients with end-stage renal disease undergoing chronic hemodialysis, rosuvastatin had no effect on reducing cardiovascular events. Although there is a slightly increased risk of incident diabetes with this class of agents, the absolute benefits of statin therapy on cardiovascular events overweigh the risk in patients with moderate or high cardiovascular risk or with documented cardiovascular disease. As with other statins, rosuvastatin is an appropriate therapy in addition to antihypertensive treatment to reduce cardiovascular risk in hypertensive patients.


Reduced lymphoid response to skin allotransplants in cows with hepatic lipidosis.
The immune responsiveness of cows with hepatic lipidosis (fatty liver) in comparison to control cows with a normal liver fat content was tested by applying skin allotransplants to the skin of the back of cows on day 3 after parturition. Immunoreactivity was determined by semiquantitative counting of the number of infiltrating lymphocytes in the recipient skin adjacent to the allotransplants during a period of 21 days. There were more invading lymphocytes in samples from control cows than there were in samples from cows with hepatic lipidosis. It was concluded that cows with hepatic lipidosis have a reduced lymphoid response to skin allotransplants.


Abrupt withdrawal from intrathecal baclofen: recognition and management of a potentially life-threatening syndrome.
To suggest guidelines for the prevention, recognition, and management of a life-threatening syndrome (high fever, altered mental status, profound muscular rigidity that sometimes progressed to fatal rhabdomyolysis) in patients who experience the abrupt withdrawal of intrathecal baclofen (ITB) therapy. Retrospective literature and safety-file review. Expert panel drawn from physiatry, neurology, and neurosurgery. Experienced users of ITB therapy in the pediatric and adult populations in the United States. Not applicable. We reviewed literature reports, MedWatch reports to the US Food and Drug Administration, and our own experiences. We critically analyzed patient management and drug therapy in the context of the pharmacology of baclofen and other antispastic agents. An abrupt reduction in gamma-aminobutyric acid(B) (GABA) agonist activity in the central nervous system can cause the ITB withdrawal syndrome, which is clinically and pathophysiologically distinct from autonomic dysreflexia, malignant hyperthermia, and neuroleptic-malignant syndrome. ITB withdrawal evolves over 1 to 3 days, but may become fulminant if not recognized and treated early. The syndrome can be interrupted by the restoration of ITB therapy. However, supportive measures and high-dose benzodiazepine infusion may be life saving in the interval before ITB therapy is resumed. Dantrolene infusion may relieve muscle rigidity but does not reverse the other manifestations of GABAergic agonist withdrawal. Most episodes of severe ITB withdrawal were preventable. Patients at risk can be identified and educated prospectively and given medication for emergency use. Treatment with GABAergic agonist drugs may prevent potentially fatal sequelae.


Effective phage cocktail to combat the rising incidence of extensively drug-resistant Klebsiella pneumoniae sequence type 16.
Bacteriophages are the most abundant organisms on Earth. As there are few effective treatment options against some pathogens, the interest in the bacteriophage control of multi-drug-resistant bacterial pathogens is escalating, especially for Klebsiella pneumoniae. This study aimed to develop a phage-based solution to the rising incidence of extensively drug-resistant clinical Klebsiella pneumoniae sequence type (ST16) infections starting from a set of phages recently characterized against this lineage. A phage-cocktail (Katrice-16) composed of eight lytic phages was characterized for potential use in humans. In vitro and in vivo broth inhibition and Galleria mellonella rescue assays were used to demonstrate the efficacy of this approach using a collection of 56 strains of K. pneumoniae ST16, with distinct genetic backgrounds that were collected from clinical infections from four disparate nations. Additionally, Katrice-16 anti-biofilm activity, synergism with meropenem, and activity in human body fluids were also assessed. Katrice-16 was highly active in vitro against our K. pneumoniae ST16 collection (AUC% median = 86.48%; Q1 = 83.8%; Q2 = 96.85%; Q3 = 98.85%). It additionally demonstrated excellent in vivo activity in G. mellonella rescue assays, even with larvae infected by isolates that exhibited moderate in vitro inhibition. We measured significant anti-biofilm activity over 12 h (p = .0113) and synergic activity with meropenem. In addition, we also demonstrate that Katrice-16 maintained high activity in human body fluids. Our results indicate that our cocktail will likely be an effective solution for human infections with this increasingly prevalent and often highly resistant bacterial clone.


Incidence of dengue virus infection among Japanese travellers, 2006 to 2010.
Dengue continues to be a global public health concern. In Japan, although dengue cases are currently seen only among travellers returning from endemic areas, the number of reported cases is rising according to the national case-based surveillance system. We evaluated the characteristics of dengue cases imported into Japan and the relationship between the incidence of infection and season of travel to popular destinations. Dengue cases reported to the national surveillance system were retrospectively examined. The number of reported cases per number of Japanese travellers to a dengue-endemic country was calculated to estimate the country-specific incidence of imported dengue virus infection. The incidence of dengue infection among Japanese travellers was compared between dengue high season and low season in each country using relative risk (RR) and associated 95% confidence intervals (CI). Among 540 Japanese residents who were reported as dengue cases from 2006 to 2010, the majority had travelled to Indonesia, India, the Philippines and Thailand. The RR of dengue infection among Japanese travellers during dengue high season versus low season was 4.92 (95% CI: 3.01-8.04) for the Philippines, 2.76 (95% CI: 1.67-4.54) for Thailand and 0.37 (95% CI: 0.15-0.92) for Indonesia. Overall, higher incidence of imported cases appeared to be related to historic dengue high seasons. Travellers planning to visit dengue-endemic countries should be aware of historic dengue seasonality and the current dengue situation.


Reliability of maternal reporting in identifying major congenital malformations.
We compared maternal reports of major congenital malformations with physicians' reports in a teratology counseling service. The reports of women followed during gestation were matched to those submitted by physicians caring for the infants. In 153/165 cases neither the mother nor the physician described major malformations. There were 12 cases where both mother and physician described similar major malformations. In several of them the mother used non-medical terms (eg "hole in the heart"). Maternal reports of major anomalies were in close agreement with physicians' reports. This lends credibility to research based on pregnancy follow-up with maternal reports that are corroborated by physicians' reports.


[Importance of the sporotrichosis asteroid body for the rapid diagnosis of sporotrichosis].
Eighty patients with cutaneous sporotrichosis were studied between 1985 and 1996. The investigation of asteroid bodies (AB) was done by direct microscopic slides examination of pus obtained from the lesions. Patients were divided into two groups: 32 consulting before 1989, and 48 consulting after 1990. In the first group, material was obtained as usual by simple digital pressure of the most productive lesion, and then wet preparation microscopic examination was performed. Fourteen patients with AB were found in this group (43.75%). In the second group the initial pus was discarded and new samples were taken more deeply, and examined up to five slides for each patient. The slides were carefully examined at light microscope. Fourty five patients with AB were detected in this group (93.75%). All eighty samples were cultured and all of them were positive for Sporothrix schenckii. The change of methodology to obtain the samples and the exhaustive observations, increased the possibility of AB detection. ABs are of great diagnostic value and might be of importance to initiate treatment before reporting culture.


An unusually large aggressive adenomatoid odontogenic tumor of maxilla involving the third molar: A clinical case report.
Adenomatoid odontogenic tumor (AOT) is a rare tumor comprising only 3% of all odontogenic tumors. It is a benign, encapsulated, noninvasive, nonaggressive, slowly growing odontogenic lesion associated with an impacted tooth. These lesions may go unnoticed for years. The usual treatment is enucleation and curettage, and the lesion does not recur. Here, we present a rare case of an unusually large aggressive AOT of maxilla associated with impacted third molar. The authors also discuss clinical, radiographic, histopathologic, and therapeutic features of the case. Subtotal maxillectomy with simultaneous reconstruction of the surgical defect with temporalis myofascial flap was planned and carried out.


Does care consultation affect use of VHA versus non-VHA care?
The Partners in Dementia Care (PDC) intervention has shown improved psychosocial outcomes while reducing overall inpatient and emergency department (ED) utilization among veterans with cognitive impairment and behavioral symptoms. However, veterans who use the Veterans Health Administration (VHA) also seek care from non-VHA sources, potentially reducing the effectiveness of care coordination. We evaluated whether PDC affected VHA and non-VHA inpatient and ED use by veterans with dementia. PDC is a telephone-based care coordination and support service program implemented in 2 VHA intervention sites that were compared with 3 VHA control sites. Veterans with a dementia diagnosis and their caregivers participated. Data came from administrative records and structured interviews with caregivers. We modeled the likelihood of site of care across 3 periods: preintervention (baseline), baseline to 6 months, and 6 months to 12 months. Compared with veterans at control sites, veterans at intervention sites who lived closer to VHA medical centers showed an increase over time (P ≤.01) in the likelihood of seeking VHA inpatient care as opposed to non-VHA care, whereas the likelihood of seeking non-VHA relative to VHA inpatient care increased for veterans living further away. ED visits did not show a comparable intervention effect. PDC intervention affected the choice of VHA versus non-VHA inpatient care, with its impact differing by distance from VHA medical centers. Site of ED care was not affected. Accountable care organizations share some of the VHA's vulnerabilities to out-of-system use; thus, the implications of our findings extend beyond the VHA system.


d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice.
d-Allulose, a rare sugar, improves glucose metabolism and has been proposed as a candidate calorie restriction mimetic. This study aimed to investigate the effects of d-allulose on aerobic performance and recovery from exhaustion and compared them with the effects of exercise training. Male C57BL/6J mice were subjected to exercise and allowed to run freely on a wheel. Aerobic performance was evaluated using a treadmill. Glucose metabolism was analyzed by an intraperitoneal glucose tolerance test (ipGTT). Skeletal muscle intracellular signaling was analyzed by Western blotting. Four weeks of daily oral administration of 3% d-allulose increased running distance and shortened recovery time as assessed by an endurance test. d-Allulose administration also increased the maximal aerobic speed (MAS), which was observed following treatment for >3 or 7 days. The improved performance was associated with lower blood lactate levels and increased liver glycogen levels. Although d-allulose did not change the overall glucose levels as determined by ipGTT, it decreased plasma insulin levels, indicating enhanced insulin sensitivity. Finally, d-allulose enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase and the expression of peroxisome proliferator-activated receptor γ coactivator 1α. Our results indicate that d-allulose administration enhances endurance ability, reduces fatigue, and improves insulin sensitivity similarly to exercise training. d-Allulose administration may be a potential treatment option to alleviate obesity and enhance aerobic exercise performance.


[Abdominal and pelvic segmented T1-weighted echo-planar imaging and MRI. Comparison with T1-TSE and T2-UTSE sequences].
To assess, quantitatively and qualitatively, the diagnostic value of a segmented EPI T1W sequence compared to T1W and T2W TSE sequences. A prospective analysis of abdominal and pelvic MRI examinations of 70 patients (44 women, 26 men, mean age of 61 years), was performed on a 0.5 T supraconductive magnet with 15 mT/m gradients. The sequences were randomized and compared in a blinded fashion by 3 independent reviewers: TSE T1W (TR/TE = 500/12 ms, NSA = 6, turbo factor 5, 3:49 min), EPI T1W (TR/TE = 500/30 ms, NSA = 6, EPI factor = 7, 2:13 min) and UTSE T2W (TR/TE = 1600-2500/100, NSA = 6, turbo factor = 31, 2:20 min). Quantitatively, no significant difference was found between T1W sequences for signal to noise ratio. The EPI T1W sequence had lower signal but stronger enhancement after gadolinium injection. Qualitatively, EPI T1W had significantly less flow artefacts (p < 0.001, wilcoxon test), and more chemical shift artifact (p < 0.01). For lesion detection, differences were not statistically significant between T1W sequences or between paired T1W and T2W sequences (sensitivity and specificity 84 and 86% for TSE T1W 76 and 86% for EPI T1W, 78 and 79% for UTSE T2W, 90 and 65% for TSE T1W-UTSE T2W, 88 and 65% for EPI T1W-UTSE T2W). Kappa concordance test (0.686) and Mac Nemar symmetry test (3.55) were high between T1W sequences. The segmented EPI T1W sequence used had equivalent results compared to the TSE T1W sequence, it allows a 40% reduction in acquisition time and this without difference in the diagnostic performances of the reviewers.


Long-term outcome of epilepsy in patients with Prader-Willi syndrome.
Prader-Willi syndrome is a multisystemic genetic disorder that can be associated with epilepsy. There is insufficient information concerning the clinical and electroencephalographic characteristics of epilepsy and the long-term outcome of these patients. The aim of this study is to describe seizure types, electroencephalographic patterns and long-term seizure outcome in Prader-Willi syndrome patients suffering from epilepsy. We retrospectively studied 38 patients with Prader-Willi syndrome and seizures. Results of neuroimaging studies were obtained for 35 individuals. We subdivided these patients into two groups: group A, 24 patients, without brain lesions; and group B, 11 patients, with brain abnormalities. All patients were re-evaluated after a period of at least 10 years. Twenty-one patients (55.2 %) were affected by generalized epilepsy and 17 patients (44.8 %) presented focal epilepsy. The most common seizure type was generalized tonic-clonic seizure. The mean age at seizure onset was 4.5 years (ranged from 1 month to 14 years). In the follow-up period, seizure freedom was achieved in 32 patients (84.2 %). Seizure freedom was associated with electroencephalographic normalization, while the six children presenting drug-resistant epilepsy showed persistence of electroencephalographic abnormalities. Group B patients showed a higher prevalence of drug-resistant epilepsy. Patients with Prader-Willi syndrome were frequently affected by generalized seizures. Most of the patients had a favorable evolution, although, patients with brain abnormalities presented a worse outcome, suggesting that the presence of these lesions can influence the response to antiepileptic therapy.


College counselors' use of informal language online: student perceptions of expertness, trustworthiness, and attractiveness.
The purpose of this study was to examine language formality and informality in online counseling sessions. Specifically, the author compared undergraduate student (n = 224) perceptions of college counselors' use of informal language and mirroring of client's formality in four mock online counseling scenarios. A multivariate analysis of covariance found significant differences between conditions. Pairwise analyses revealed that counselors who used informal language following their client's formal expressions were perceived as having less expertise. However, language mirroring seemed to moderate perceptions of expertise when counselors followed their client's informal language use.


Effects of partial substitution of nitrites with purple-fleshed sweet potato powder on physicochemical characteristics of sausages.
Synthetic nitrite imparts a reddish-pink color to meat and a distinct flavor to meat products, delays lipid oxidation, and inhibits microbial growth and pathogens. However, excessive intake of nitrite might result in the production of carcinogenic nitrosamine, which might increase the risk of cancer in humans. Therefore, we aimed to find an alternative natural colorant for pork sausages. Pork sausages were mixed with 0.014% sodium nitrite (NaNO2) alone (CON), without either NaNO2 or purple-fleshed sweet potato powder (PP; CON1), 0.5% PP alone (PP1), 1% PP (PP2) alone, 0.011% NaNO2 and 0.5% PP (SP1), and 0.011% NaNO2 and 1% PP (SP2). The sausages were then cooked and stored for physicochemical analysis on days 0, 5, 10, 15, and 20. The a* and W* values were the greatest and lowest in the SP2 and CON1 treatments, respectively (p < 0.05). The concentrations of residual nitrite in the sausages at 20 days decreased in the order of CON > SP1, SP2 > PP2 > PP1, CON1. The fatty acid content was higher, and flavorous amino acids were more in PP2 (p < 0.05). The fatty acid composition was comparable between the SP2 and CON groups, but the contents of glutamic acid and alanine were greater in the SP2 group. In conclusion, SP2 (0.011% NaNO2 with 1% PP) could be added as a natural colorant for pork sausage production, and NaNO2 could be substituted with up to 20% PP without detrimental effects on sausage appearance and/or quality.


Long-duration freewheel running and submandibular lymphocyte response to forced exercise in older mice.
Submandibular lymph nodes (SLN) are crucial for immune surveillance of the anterior ocular chamber and upper respiratory tract; little is known about how training and exercise affect SLN lymphocytes. The intent of this study was to describe the impact of long term freewheel running followed by acute strenuous exercise on SLN lymphocytes in mice. Female C57BL/6 mice were assigned to running wheels or remained sedentary for 8 months, and further randomized to treadmill exercise and sacrifice immediately, treadmill exercise and sacrifice 24 h after exercise cessation, or no treadmill exposure. SLN lymphocytes were isolated and analyzed for CD3, CD4, CD8, and CD19 cell surface markers, phosphatidylserine externalization as a marker of apoptosis, and intracellular glutathione as a marker of oxidative stress. Compared with running wheel mice, older sedentary mice had a lower percent of T cells and higher percent of B cells (p < 0.05). Although intracellular glutathione did not differ between groups, running mice had a lower percent of Annexin V(+) SLN lymphocytes 24 h after treadmill exercise. Further research will be needed to determine if voluntary exercise translates into improved anterior ocular and upper respiratory tract health.


Epinephelus moara: a valid species of the family Epinephelidae (Pisces: Perciformes).
This study documents the major external and internal morphological differences between Epinephelus bruneus and Epinephelus moara, and analyses the complete mitogenomes of both species. The partial cytochrome oxidase subunit I (coI) sequence divergence between E. bruneus and E. moara is significantly higher than specimens within the same species (P < 0·05). Analyses of gene flow (Nm = 0·02) and genetic differentiation (ϕst = 0·92995, P > 0·05) reveal reproductive isolation between E. bruneus and E. moara. These results support the hypothesis that E. moara is a valid species. Further molecular comparisons between E. bruneus and E. moara obtained in this study and a specimen identified in GenBank as E. bruneus from South Korea reveal that the latter is identical to E. moara rather than to E. bruneus.


Prochymosin polymorphism in calves of black-and-white cattle and their crosses with Simental bulls.
Polymorphism of prochymosin was observed in individual calf abomasa, using agarose gel electrophoresis followed by detection of proteolytic activity. Abomasum samples were randomly collected during slaughtering from 239 and 146 calves (3-5 weeks old) of Black-and-White cattle and their crosses with Simental bulls, respectively. Four distinct prochymosins were found and, according to their decreasing electrophoretic mobility in alkaline agarose gel, termed as prochymosin A, D, B and C which occurred singly and in pairs (then with equal proteolytic activities of both components). Prochymosin A, B and C (designation according to FOLTMANN, 1966) activated at pH 4.7 was transformed into electrophoretically distinct chymosin. When prochymosin D was activated at this pH, chymosin D showed similar mobility as chymosin B both at alkaline and acidic pHs. Prochymosin variants occurred at genetical equilibrium in nine and ten phenotypes in the first and second genetic group. The distribution of phenotypes in the two groups differed significantly (P < 0.05). The gene frequencies of prochymosin A, D, B and C were 0.35, 0.11, 0.52 and 0.02 in Black-and-White calves, and 0.39, 0.08, 0.47 and 0.06 in crosses, respectively. These prochymosins were controlled by four pairs of codominant alleles. A possible correlation of the results obtained by FOLTMANN (1966) with ours and those of ASATO and RAND (1972, 1977) was discussed.


Lipogranulomas and gold in the liver in rheumatoid arthritis.
Liver biopsies have been performed routinely as part of a protocol to evaluate methotrexate therapy in severe rheumatoid arthritis. All patients in the study had failed standard medical therapy, including gold treatment. Twenty-three of 41 patients (56%) had well-formed lipogranulomas (LGs) in the lobules, compared with an incidence of approximately 5% in our general biopsy population. Twenty-seven of 41 patients (66%) had a unique pigment in their livers. In 20 of these, the pigment was in LGs; in the seven patients with pigment not associated with lobular LG, it was found in lipid droplets in portal triads. The pigment varied from irregular pale brown granules slightly larger than those of hemosiderin, to smaller black round granules. Lipogranuloma-associated pigment of this type is an unusual finding, reminiscent of argyria. There was a variable appearance upon polarization, the black granules at times being strikingly refractile. There was a positive correlation between the prominence of LG and the quantity of pigment. The pigment resembled that described with gold deposition in other tissues. Radiographic microanalysis of both brown and black granules was performed in three cases. Characteristic spectra (energy-dispersive spectroscopy) demonstrated the presence of gold in each case. Silver was not identified. The high incidence of LG may reflect the frequent administration of gold in an oily vehicle. Gold may remain trapped in the liver for a prolonged time. Thus far, we have not detected any adverse effect from the presence of LG-associated gold.


Change of external urethral sphincter function in prostatic patients.
External urethral function was urodynamically examined in 13 patients with benign prostatic hypertrophy (BPH) associated with chronic urinary retention and in 5 volunteers. Prevoiding drop in external urethral sphincter pressure was noted in all the volunteers, whereas it was not found in 6 of the 13 cases of BPH. Bladder neck opening pressure was higher in these 6 cases (p less than 0.05). After administration of phentolamine, prevoiding drop was noted in 5 of these 6 cases, and bladder neck opening pressure decreased so much that there was no significant intergroup difference. The above results mean that the increase in alpha-adrenergic receptors makes the prostate, which has been already hypertrophied, less elastic, inhibiting external urinary sphincter function.


Synthesis of complex optical wavefronts.
For any coding scheme designed for the synthesis of an optical wavefront by a computer-generated, amplitude-transmittance hologram, two types of synthetic holograms may be defined: the first is the encoded form of the optical wavefront itself; the second is the encoded form of the Fourier transform of the wavefront. The extent of the optical wavefront produced by the first type varies inversely, while that of the second type varies directly, with resolution. Five coding schemes are characterized by two important quantities: the first is the minimum number of samples that must be numerically evaluated and drawn; the second is the product of the minimum resolution (lines/unit length) and length (per dimension) required for the drawing. These quantities are a measure of the required computer and drawing device capabilities, respectively, and knowledge of them permits comparison of the coding schemes.


Effects of Solvent Debinding on the Microstructure and Properties of 3D-Printed Alumina Ceramics.
Solvents assist in the debinding of stereolithography-based 3D-printed alumina green bodies. The green bodies subsequently undergo thermal debinding and sintering to obtain alumina ceramics. In this study, several solvents were tested, including polyethylene glycol, oxalic acid, ammonium hydroxide, ethyl alcohol, methyl methacrylate, butyl acetate, dimethyl carbonate, methanol, ethyl acetate, and sec-butyl alcohol. The tested solvents during the debinding process showed different effects on microstructure and properties of 3D-printed alumina ceramics due to the variable aspects of their solubility toward the binders. The microstructure of the samples changed significantly after green bodies underwent solvent debinding, thermal debinding, and sintering, leading to loose spongy structures, porous aggregates, and compact structures, respectively. Shrinkage, bulk density, and open porosity changed slightly due to the debinding function of different solvents. Polyethylene glycol-impregnated samples displayed the minimum shrinkage in length direction (5.3%). Ethyl alcohol-impregnated sample showed minimum shrinkage in width (4.8%) and height (11.5%) directions. Ammonium hydroxide-impregnated samples exhibited minimum bulk density (2.8 g/cm3) and maximum open porosity (28.3%). Dimethyl carbonate-impregnated samples presented minimum flexural strength (32.6 MPa), and oxalic acid-impregnated samples revealed maximum flexural strength (63.4 MPa). In sum, the as-obtained ceramics would be used as ceramic cores for hollow blades in aircraft engines due to their high open porosity and moderate flexural strength.


Pneumatized spaces, sinuses and spongy bones in the skulls of primates.
The earliest attempts to understand the "pneumatized spaces" in the skulls of primates in general were focussed on the hollow spaces and the epithelium which covers their surfaces. More recent approaches consider the sinuses as a means to optimise skull architecture. Still, many attempts to get hold of the meaning of the intriguing pneumatized spaces circle around the air filled volumes they enclose. Here, we would like to reverse the approach and focus our biomechanic interpretation on the walls surrounding the big, empty, or at least not mechanically resistant spaces, and their mechanical properties. As a working hypothesis, we consider not only the walls of the more or less closed cavities, or sinuses, but also the braincase, the orbits, and the nasal channel as thin-walled shells of which we know that they can carry surprisingly large loads with a minimum of material. Details of the wall's profiles fit with this approach. From the same viewpoint, the bubble-like, air-filled cavernous systems in the ethmoid or temporal bones, and the marrow-filled spongy substance in the upper jaw are looked at as honeycomb-structures, which provide mechanical properties that are biologically advantageous and allow the saving of weight.


Evaluation of Amyloid Polypeptide Aggregation Inhibition and Disaggregation Activity of A-Type Procyanidins.
The number of people worldwide suffering from Alzheimer's disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins 1-7 and their substructures 8 and 9, by conducting structure-activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds 1-6 exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound 7, without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases.


[The place of radiography in endodontic treatment carried out in general practice in Dakar].
An investigation conducted over dental surgeons of 52 dental offices in Dakar and it's near suburb (40 from private sector and 12 from public and quasi-public) has shown that the use of retro-alveolar radiography during endodontic treatment was not systematic, due to the price of retro-alveolar film, waste of time and relative facility of the endodontic treatment of monoradicular teeth. The preparatory negative is favored (32.70%) particularly by private dental surgeons, who use two retro-alveolar films for endodontic treatment: pre and post operative radiography (30%). The immediate post operator control is executed only in case of post-operator pains by public and quasi-public dental surgeons (16.67%) with one retro-alveolar film on average for the endodontic treatment; at term any radiographic control is done. Three retro-alveolar films per endodontic treatment were exceptionally used (9.61%) and offset incidences (15%) are not much used as well as support-films (angulators). The retro-alveolar radiography is still a reliable guide for a clinical success in endodontic treatment with a minimum of three retro-alveolar films and offset incidences.


The effect of fish oil supplements on blood pressure.
We conducted a double-blind, placebo-controlled crossover study to determine the effects of fish oil supplementation on blood pressure in middle-aged men. Subjects were randomly assigned to consume either 20 g of fish oil or safflower oil for 12 weeks and then consume the other oil for an additional 12 weeks after a 4-week washout period. We found no significant changes from the pretreatment value in systolic or diastolic blood pressure with the use of fish oil supplements. In addition, there were no significant differences in the posttreatment blood pressures comparing the fish and safflower oil phases of the study.


Amino Acid Transport into Cultured Tobacco Cells: I. LYSINE TRANSPORT.
Lysine transport into suspension-cultured Wisconsin-38 tobacco cells was observed. Uptake was linear (up to 90 minutes) with respect to time and amount of tissue only after 4 to 6 hours preincubation in calcium-containing medium. The observed cellular accumulation of lysine was against a concentration gradient and not due to exchange diffusion. Transport was stimulated by low pH and characterized by a biphasic uptake isotherm with two K(m) values for lysine. System I (K(m) approximately 5 x 10(-6) molar; V(max) approximately 180 nanomoles per gram fresh weight per hour) and system II (K(m) approximately 10(-4) molar; V(max) approximately 1900 nanomoles per gram fresh weight per hour) were inhibited by N-ethylmaleimide and a variety of respiratory inhibitors. This inhibition was not due to increased efflux. In antagonism experiments, system I was inhibited most effectively by basic amino acids, followed by the sulfur amino acids. System I was only slightly inhibited by the neutral and aromatic amino acids and was not inhibited by the acidic amino acids aspartic and glutamic acids. Transport by system II was inhibited by all of the tested amino acids (including aspartic and glutamic acids) and analogs; however, this system was not inhibited by d-arginine. Neither system was strongly inhibited by d-lysine or the lysine analog S-2-aminoethyl-l-cysteine. Arginine was shown to be a competitive inhibitor of both systems with values for K(i) similar to the respective K(m) values.These studies suggest the presence of at least two amino acid permeases in W-38 tobacco cells.


Characteristics of liver injury in drug-induced systemic hypersensitivity reactions.
The liver is the most commonly involved internal organ in drug-induced systemic hypersensitivity. However, data obtained from these patients have yet to be analyzed in depth with respect to liver injury. The medical records of 136 patients who developed delayed-type drug hypersensitivity were reviewed at a tertiary referral hospital. Culprit drugs, the pattern and degree of liver injury, and the effect of systemic corticosteroids were evaluated in the group of patients with drug-induced systemic hypersensitivity and liver dysfunction (aspartate aminotransferase or alanine aminotransferase ≥80 IU/L). Clinical characteristics of patients with drug-induced systemic hypersensitivity and liver injury were analyzed. Among the 61 patients with drug-induced systemic hypersensitivity and liver dysfunction, the clinical phenotypes were drug reaction with eosinophilia and systemic symptoms (n = 29, 48%), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 11, 18%), and maculopapular rash (n = 17, 28%). Antibiotics (n = 27, 44%) were the most common cause of drug-induced systemic hypersensitivity with liver dysfunction. Whereas patients with Stevens-Johnson syndrome/toxic epidermal necrolysis had mild hepatocellular-type liver injury of relatively brief duration, those with drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome had more severe and prolonged hepatocellular injury in addition to moderate to severe cholestatic-type liver injury. The use of systemic corticosteroids did not significantly affect either recovery from liver injury or mortality. This study was retrospective and the number of subjects was small. The results suggest that the severity, pattern, and duration of liver injury differ according to the drug-hypersensitivity phenotype. Further studies are needed to evaluate the role of systemic corticosteroids in drug-induced systemic hypersensitivity and liver injury.


[Bronchogenic cysts and their atypical localizations. A case of pleuro-diaphragmatic cyst].
Bronchogenic cysts represent about 10 p. 100 of all surgical tumours of the mediastinum. They can never be diagnosed with absolute certainty prior to the operation, but when they arise in their typical sites, they can be suspected with a high probability. However, they can occur in very atypical sites, in which case the diagnosis remains very hypothetical until the operation. The authors report a case of a cyst which developed under the diaphragmatic pleura, in direct contact with the dome of the diaphragm and attached to the mediastinum by a fine vascular pedicle which inserted in the root of the triangular ligament.


A Comprehensive Review of Natural Products against Liver Fibrosis: Flavonoids, Quinones, Lignans, Phenols, and Acids.
Liver fibrosis resulting from continuous long-term hepatic damage represents a heavy burden worldwide. Liver fibrosis is recognized as a complicated pathogenic mechanism with extracellular matrix (ECM) accumulation and hepatic stellate cell (HSC) activation. A series of drugs demonstrate significant antifibrotic activity in vitro and in vivo. No specific agents with ideally clinical efficacy for liver fibrosis treatment have been developed. In this review, we summarized the antifibrotic effects and molecular mechanisms of 29 kinds of common natural products. The mechanism of these compounds is correlated with anti-inflammatory, antiapoptotic, and antifibrotic activities. Moreover, parenchymal hepatic cell survival, HSC deactivation, and ECM degradation by interfering with multiple targets and signaling pathways are also involved in the antifibrotic effects of these compounds. However, there remain two bottlenecks for clinical breakthroughs. The low bioavailability of natural products should be improved, and the combined application of two or more compounds should be investigated for more prominent pharmacological effects. In summary, exploration on natural products against liver fibrosis is becoming increasingly extensive. Therefore, natural products are potential resources for the development of agents to treat liver fibrosis.


Prenatal diagnosis of thrombosed aneurysm of vein of Galen.
Aneurysm of the vein of Galen in the fetus is a rare malformation that has been described in a small number of case reports. Thrombosis of aneurysm of the vein of Galen is a rare occurrence reported in postnatal cases. We report a case of thrombosis of vein of Galen aneurysm occurring in a fetus of 21 weeks' gestation. The fetus showed an echogenic mass posterior and superior to the thalamus. It also showed dilated dural venous sinuses, dilated neck vessels, cardiomegaly and minimal ascites. The pregnancy was terminated and autopsy confirmed the diagnosis. The present case is the first report of the prenatal sonographic features of this condition in the literature.