Shoaling preference and evidence for maintenance of sibling groups by juvenile black perch Embiotoca jacksoni.
Group sizes in free-living juvenile black perch Embiotoca jacksoni were quantified and predictions of the hypothesis that such groups comprise sibling brood-mates were tested. Group sizes in the field were within the range of female brood sizes and often occurred close to each other but did not merge. In captivity, juveniles formed groups immediately after birth. In laboratory experiments, they also associated significantly more with chambers containing familiar members of their own brood than empty chambers but did not associate more with chambers containing similar-sized juveniles from a different brood. Juvenile E. jacksoni also associated significantly more with chambers containing familiar brood-mates than with chambers containing unfamiliar members of a different brood. The strength of this preference increased with the number of days fish had been together since birth. When two broods were placed in a large outdoor tank, all individuals from both broods directed significantly more aggressive acts towards members of the other brood than towards members of their own brood. While the relative effects of familiarity and relatedness cannot be completely separated in this viviparous species, associating with familiar individuals would facilitate the maintenance of sibling groups in the field.


Detection of immunoglobulin M antibodies to hepatitis E virus by class capture enzyme immunoassay.
The measurement of antibodies to hepatitis E virus (anti-HEV) has been essential for understanding the epidemiology of hepatitis E. Studies to determine the prevalence of HEV infections require a reliable serologic assay that is sensitive and specific. It is also important to distinguish the acute from the convalescent phase of an infection; this usually requires the detection of the immunoglobulin M (IgM) class of antibody. Few enzyme immunoassays (EIAs) that measure IgM anti-HEV have been described, and most have utilized the sandwich method. The present study describes an EIA that detects IgM anti-HEV by antibody class capture methodology. The assay was validated by using serum and/or plasma panels from experimentally infected nonhuman primates. It was used to demonstrate an anamnestic response and the reappearance of IgM anti-HEV in a chimpanzee experimentally challenged with HEV at two different times 45 months apart. The class capture method was more sensitive than the sandwich EIA when used to test clinical samples from two hepatitis E epidemics in Pakistan; it also had the advantage of distinguishing IgM anti-HEV in the presence of high titers of IgG anti-HEV.


Evidence of central and peripheral vestibular pathology in blast-related traumatic brain injury.
To prospectively assay the vestibular and oculomotor systems of blast-exposed service members with traumatic brain injury (TBI). Prospective, nonblinded, nonrandomized descriptive study. Tertiary care facility (Department of Defense Medical Center). Twenty-four service members recovering from blast-related TBI sustained in Iraq or Afghanistan. Focused history and physical, videonystagmography (VNG), rotational chair, cervical vestibular-evoked myogenic potentials, computerized dynamic posturography, and self-report measures. Vestibular testing confirms a greater incidence of vestibular and oculomotor dysfunction in symptomatic (vestibular-like dizziness) personnel with blast-related TBI relative to asymptomatic group members. VNG in the symptomatic group revealed abnormal nystagmus or oculomotor findings in 6 of 12 subjects tested. Similarly, rotational chair testing in this group revealed evidence of both peripheral (4/12) and central (2/12) vestibular pathology. By contrast, the asymptomatic group revealed less vestibular impairment with 1 of 10 rotational chair abnormalities. The asymptomatic group was further characterized by fewer aberrant nystagmus findings (4/12 abnormal VNGs). Computerized dynamic posturography testing revealed no significant differences between groups. Self-report measures demonstrated differences between groups. Vestibular function testing confirms a greater incidence of peripheral vestibular hypofunction in dizzy service members with blast-related TBI relative to those who are asymptomatic. Additionally, oculomotor abnormalities and/or nystagmus consistent with central involvement were present in 10 of the 24 study participants tested. The precise cause of these findings remains unknown.


Single Cell Genetics and Epigenetics in Early Embryo: From Oocyte to Blastocyst.
Single cell technology has enormously changed the landscape of biomedical science, including single cell omics, gene editing, single cell imaging, single cell (embryo) manipulate, or non-invasive micro-test. Single cell technology also leads the research area of early embryo from basic research to reproductive medical application. We got the knowledge of programming/reprogramming and the epigenetics dynamics in the cell lineage differentiation. In the reproductive medicine, the genomic sequencing of embryo or polar body and the preimplantation genetic diagnosis rely on the single cell techniques. Those discoveries will improve the assisted reproductive technologies, human health, and livestock husbandry. In the future, the comprehensive atlas of cell state and lineage information can be generated for cellular systems by single-cell multi-omics approaches.


Use of proton pump inhibitors and the risk of cholangitis: a nationwide cohort study.
Proton pump inhibitor (PPI) use may alter the gut microbiome and increase the risk of cholangitis. However, the association of PPI use with the risk of incident cholangitis has not been evaluated. To evaluate whether PPI use was associated with a higher risk of cholangitis. This cohort study included a nationwide representative sample of the Korean general population followed up for 10 years (1 January 2003 to 31 December 2013). PPI use was identified from treatment claims and considered as a time-varying variable. Incident cholangitis was identified from hospitalisation and out-patient visit claims. During 4 212 003 person-years of follow-up, 58,863 participants had at least one PPI prescription and 1 834 participants developed cholangitis. The age-, sex-, residential area- and income-adjusted hazard ratio (HR) for incident cholangitis comparing PPI use with non-use was 6.06 (95% CI, 4.64-7.91). The association was essentially unchanged in fully adjusted models (HR 5.75; 95% CI, 4.39-7.54). The risk was highest during PPI treatment and decreased gradually after PPI discontinuation (Ptrend <.001). In this large cohort, PPI use was associated with an increased risk of cholangitis. Physicians prescribing PPIs should consider cholangitis as a potential complication of PPI use.


Optimizing the design of a bioabsorbable metal stent using computer simulation methods.
Computer simulation is used extensively in the design of permanent stents. In order to address new challenges that arise in the design of absorbable metal stents (AMSs), such as corrosion and the limited mechanical properties of bioabsorbable alloys, new simulation and design techniques are needed. In this study a new method for simulating AMS corrosion is developed to study the effects of corrosion on the mechanical performance of a range of stent designs. The corrosion model is combined with an optimization strategy to identify AMS features that give optimal corrosion performance in the body. It is found that strut width is the predominant geometrical factor in determining long-term AMS scaffolding performance. An AMS with superior scaffolding performance to a commercial design is identified, based on deployment and corrosion simulations in stenosed vessels. These simulation and design techniques give new insights into in-vivo AMS performance and the role of device geometry in determining long-term scaffolding performance.


Computational Characterization of Antibody-Excipient Interactions for Rational Excipient Selection Using the Site Identification by Ligand Competitive Saturation-Biologics Approach.
Protein therapeutics typically require a concentrated protein formulation, which can lead to self-association and/or high viscosity due to protein-protein interaction (PPI). Excipients are often added to improve stability, bioavailability, and manufacturability of the protein therapeutics, but the selection of excipients often relies on trial and error. Therefore, understanding the excipient-protein interaction and its effect on non-specific PPI is important for rational selection of formulation development. In this study, we validate a general workflow based on the site identification by ligand competitive saturation (SILCS) technology, termed SILCS-Biologics, that can be applied to protein therapeutics for rational excipient selection. The National Institute of Standards and Technology monoclonal antibody (NISTmAb) reference along with the CNTO607 mAb is used as model antibody proteins to examine PPIs, and NISTmAb was used to further examine excipient-protein interactions, in silico. Metrics from SILCS include the distribution and predicted affinity of excipients, buffer interactions with the NISTmAb Fab, and the relation of the interactions to predicted PPI. Comparison with a range of experimental data showed multiple SILCS metrics to be predictive. Specifically, the number of favorable sites to which an excipient binds and the number of sites to which an excipient binds that are involved in predicted PPIs correlate with the experimentally determined viscosity. In addition, a combination of the number of binding sites and the predicted binding affinity is indicated to be predictive of relative protein stability. Comparison of arginine, trehalose, and sucrose, all of which give the highest viscosity in combination with analysis of B22 and kD and the SILCS metrics, indicates that higher viscosities are associated with a low number of predicted binding sites, with lower binding affinity of arginine leading to its anomalously high impact on viscosity. The present study indicates the potential for the SILCS-Biologics approach to be of utility in the rational design of excipients during biologics formulation.


Validating a Termite-Inspired Construction Coordination Mechanism Using an Autonomous Robot.
Many species of termites build large, structurally complex mounds, and the mechanisms behind this coordinated construction have been a longstanding topic of investigation. Recent work has suggested that humidity may play a key role in the mound expansion of savannah-dwelling Macrotermes species: termites preferentially deposit soil on the mound surface at the boundary of the high-humidity region characteristic of the mound interior, implying a coordination mechanism through environmental feedback where addition of wet soil influences the humidity profile and vice versa. Here we test this potential mechanism physically using a robotic system. Local humidity measurements provide a cue for material deposition. As the analogue of the termite's deposition of wet soil and corresponding local increase in humidity, the robot drips water onto an absorbent substrate as it moves. Results show that the robot extends a semi-enclosed area outward when air is undisturbed, but closes it off when air is disturbed by an external fan, consistent with termite building activity in still vs. windy conditions. This result demonstrates an example of adaptive construction patterns arising from the proposed coordination mechanism, and supports the hypothesis that such a mechanism operates in termites.


[A scale for the assessment of psychiatrically disordered children and adolescents].
A global assessment scale for children and adolescents is presented. The reliability and validity of the scale were documented in previous studies. In the present study the instrument was used to assess a group of children and adolescents seen consecutively at an outpatient psychiatric clinic. Again the scale was found to differentiate well among patients with a variety of problems. Both mental retardation and low socioeconomic status are associated with low scores on the scale. With a cutoff score of 70 most subjects with problems or impairments can be differentiated from normal subjects. The scale also reflects the need for treatment and gives an indication of the type of therapy needed. Furthermore, it can be used to assess changes during therapy.


Human spermatogenesis in vitro: respective effects of follicle-stimulating hormone and testosterone on meiosis, spermiogenesis, and Sertoli cell apoptosis.
In spite of the availability of abundant data about in vitro spermatogenesis in laboratory animals, studies on human in vitro spermatogenesis are scarce. This study employed a relatively simple culture system, involving all cell types of seminiferous tubules, to analyze the effects of FSH and testosterone (T) on different characteristics of human germ and Sertoli cells in culture. By using fluorescence in-situ hybridization, we show that in vitro reduction of germ cell ploidy can be stimulated by FSH but not by T. FSH, but not T, also induced unexpectedly rapid (24-48 h) morphological changes resembling spermiogenesis, although individual changes (spermatid nucleus condensation and protrusion, cell body elongation, and flagellar growth) proceeded in an uncoordinated way and mostly resulted in the development of abnormal forms of elongated spermatids. Though ineffective alone, T potentiated the effects of FSH on meiosis and spermiogenesis. These effects of T were probably caused by the prevention of Sertoli cell apoptosis, an effect that could not be mimicked by FSH. These data show that, in the presence of high concentrations of FSH and T, human spermatogenesis can proceed in vitro with an unusual speed, but the resulting gametes are morphologically abnormal. The potential practical relevance of these findings to assisted reproduction remains to be assessed.


Baseline Impedance Measured During High-resolution Esophageal Impedance Manometry in Patients With Rumination Syndrome is as Abnormal as in Patients With GERD.
Baseline impedance measured during high-resolution impedance manometry (HRIM) can distinguish patients with gastroesophageal reflux disease (GERD) from controls, presumably due to differences in esophageal acid exposure. The characteristics of regurgitation and reflux in rumination syndrome and GERD are very different, and thus we investigated whether baseline esophageal impedance would differ in these 2 patient groups compared with controls. We compared 20 patients with rumination syndrome with 20 patients who had GERD and 40 controls. Baseline impedance was measured over 15 seconds during the landmark period of HRIM in all 18 impedance sensors on a HRIM catheter. The mean distal baseline impedance measured in ohms during HRIM was 1336 Ω [95% confidence interval (CI)=799, 1873) in patients with GERD, 1536 Ω in rumination syndrome (95% CI=1012, 2061), and 3379 Ω in controls (95% CI=2999, 3759) (P<0.0001). Proximal impedance was significantly lower in the GERD and rumination groups compared with controls; rumination syndrome (2026; 95% CI=1493, 2559 Ω), GERD (2572; 95% CI=2027, 3118 Ω), and controls (3412; 95% CI=3026, 3798 Ω) (P<0.001). Baseline impedance measured during HRIM in patients with rumination syndrome is significantly lower than controls and appears similar to patients with GERD both in the proximal and distal esophagus. These findings suggest that the postprandial regurgitation in rumination syndrome alters both the distal and proximal esophageal mucosal barrier.


Electrocatalytic water oxidation by a dinuclear copper complex in a neutral aqueous solution.
Electrocatalytic water oxidation using the oxidatively robust 2,7-[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyridine ligand (BPMAN)-based dinuclear copper(II) complex, [Cu2(BPMAN)(μ-OH)](3+), has been investigated. This catalyst exhibits high reactivity and stability towards water oxidation in neutral aqueous solutions. DFT calculations suggest that the O-O bond formation takes place by an intramolecular direct coupling mechanism rather than by a nucleophilic attack of water on the high-oxidation-state Cu(IV)=O moiety.


What happens with airway resistance (RAW) in asthma and COPD exacerbation.
To show that during the exarcerbration of asthma and COPD, increased airway resistance is accompanied with decreased spirometry values (FVC, FEV1, FEF50, and PEF) also comes increasing of airway resistance (RAW). This research included 74 patients, in exacerbation phase of disease. All the patients got spirometry and plethysmography measurements, including adequate therapy, and after at least one month on control examination they repeated spirometry and plethysmography and answered a short life questionnaire. The mean value of RAW after therapy in asthma is decreased for -17.68% and in COPD for -15.44%. The mean value of RAW in all levels of obstruction is higher in COPD than in asthma, before and after therapy. After therapy spirometry values (FVC, FEV1, FEF50, and PEF) were significantly increased in asthma than in COPD. From questionnaire analyses 78.37% (58) of patients felt well, 17.57% (13) felt the same like before therapy and 4.05% (3) of them felt worst. All the patients who felt worst were in COPD group of patients. All of them had increased RAW, almost all felt better (96.43%) had decreased RAW. In asthma nobody felt worst. In most of the patients (76.67%) who felt better RAW was decreased. Adequate therapy during exacerbation of asthma and COPD decreases value of RAW and increases spirometry values. Increase in spirometry values in asthma is much higher than in COPD. Mean values of resistance in COPD are higher before and after therapy than in asthma. There is a negative relationship between subjective experience of illness and the level of resistance. Measuring of RAW can be a good parameter for monitoring COPD and asthma control.


Obstructive Hypertrophic Cardiomyopathy and Takotsubo Syndrome: How to Deal With Left Ventricular Ballooning?
Currently, there are 2 proposed causes of acute left ventricular ballooning. The first is the most cited hypothesis that ballooning is caused by direct catecholamine toxicity on cardiomyocytes or by microvascular ischemia. We refer to this pathogenesis as Takotsubo syndrome. More recently, a second cause has emerged: that in some patients with underlying hypertrophic cardiomyopathy, left ventricular ballooning is caused by the sudden onset of latent left ventricular outflow tract obstruction. When it becomes severe and unrelenting, severe afterload mismatch and acute supply-demand ischemia appear and result in ballooning. In the context of 2 causes, presentations might overlap and cause confusion. Knowing the pathophysiology of each mechanism and how to determine a correct diagnosis might guide treatment.


Angiotensin II type 2 receptor signaling significantly attenuates growth of murine pancreatic carcinoma grafts in syngeneic mice.
Pancreatic cancer is one of the most aggressive human malignancies, with a very poor prognosis. To evaluate the effect of angiotensin II (Ang II) type 2 receptor (AT2) expression in the host's body on the growth of pancreatic carcinoma, we have investigated the growth of mouse pancreatic ductal carcinoma grafts in syngeneic wild type and AT2 receptor-deficient (AT2-KO) mice. The role of AT2 receptor-signaling in stromal cells on the growth of murine pancreatic carcinoma cells (PAN02) was studied using various in vitro and in vivo assays. In vivo cell proliferation, apoptosis, and vasculature in tumors were monitored by Ki-67 immunostaining, TUNEL assay, and von Willebrand factor immunostaining, respectively. In the co-culture study, cell proliferation was measured by MTT cell viability assay. All the data were analyzed using t-test and data were treated as significant when p < 0.05. Our results show that the growth of subcutaneously transplanted syngeneic xenografts of PAN02 cells, mouse pancreatic ductal carcinoma cells derived from the C57/BL6 strain, was significantly faster in AT2-KO mice compared to control wild type mice. Immunohistochemical analysis of tumor tissue revealed significantly more Ki-67 positive cells in xenografts grown in AT2-KO mice than in wild type mice. The index of apoptosis is slightly higher in wild type mice than in AT2-KO mice as evaluated by TUNEL assay. Tumor vasculature number was significantly higher in AT2-KO mice than in wild type mice. In vitro co-culture studies revealed that the growth of PAN02 cells was significantly decreased when grown with AT2 receptor gene transfected wild type and AT2-KO mouse-derived fibroblasts. Faster tumor growth in AT2-KO mice may be associated with higher VEGF production in stromal cells. These results suggest that Ang II regulates the growth of pancreatic carcinoma cells through modulating functions of host stromal cells; Moreover, Ang II AT2 receptor signaling is a negative regulator in the growth of pancreatic carcinoma cells. These findings indicate that the AT2 receptor in stromal fibroblasts is a potentially important target for chemotherapy for pancreatic cancer.


Adolescent presentations to an adult hospital emergency department.
Age-related policies allow adolescents to access paediatric and adult EDs. Anecdotally, paediatric and adult EDs report challenges when caring for older and younger adolescents, respectively. Our aim was to describe the characteristics of an adolescent population attending an adult ED, co-located with a tertiary paediatric ED. The Westmead Hospital ED database was accessed for 14.5-17.9 years old presentations between January 2010 and December 2012. Patient diagnosis coding (SNOMED) was converted to ICD-10. De-identified data were transferred into Microsoft Excel with analysis performed using spss V22. There were 5718 presentations made to the Westmead Hospital, Sydney, Australia ED by 4450 patients, representing 3.3% (95% CI 3.2-3.4) of total visits from all patients 14.5 years and above. The mean age of the sample was 16.6 years (male 51.8%). Presentations triaged as level 4 or 5 represented 61.0% (95% CI 58.7-61.3) of visits. The proportion of patients who did not wait to receive care was 13.8% (95% CI 12.9-14.7), which was significantly higher than adult rates (P < 0.01). There were 279 unscheduled return visits (visits made <72 h of discharge) representing 4.9% (95% CI 4.4-5.8) of all presentations. Injury was the most common diagnosis (30.2%, 95% CI 28.8-31.6). Chronic physical illness and alcohol-related visits comprised 2.1% (95% CI 1.7-2.5) and 0.8% (95% CI 0.6-1.0) of adolescent presentations, respectively. Contrary to reported staff perceptions, adolescent chronic physical illness presentations were not a major burden. Alcohol was likely under-recorded as a contributing factor to presentations.


Xenopus Xlmo4 is a GATA cofactor during ventral mesoderm formation and regulates Ldb1 availability at the dorsal mesoderm and the neural plate.
We have identified and functionally characterized the Xenopus Xlmo4 gene, which encodes a member of the LIM-domain-only protein family. Xlmo4 is activated at gastrula stages in the mesodermal marginal zone probably in response to BMP4 signaling. Soon after, Xlmo4 is downregulated in the dorsal region of the mesoderm. This repression seems to be mediated by organizer-expressed repressors, such as Gsc. Xlmo4 downregulation is necessary for the proper formation of this territory. Increasing Xlmo4 function in this region downregulates Spemman Organizer genes and suppresses dorsal-anterior structures. By binding to Ldb1, Xlmo4 may restrict the availability of this cofactor for transcription factors expressed at the Spemman Organizer. In the ventral mesoderm, Xlmo4 is required to establish the identity of this territory by acting as a positive cofactor of GATA factors. In the neural ectoderm, Xlmo4 expression depends on Xiro homeoprotein activity. In this region, Xlmo4 suppresses differentiation of primary neurons and interferes with gene expression at the Isthmic Organizer, most likely by displacing Ldb1 from active transcription factor complexes required for these processes. Together, our data suggest that Xlmo4 uses distinct mechanisms to participate in different processes during development.


Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.
Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited. The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment. For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents. A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%). The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient.


Hypocretin-1 modulates rapid eye movement sleep through activation of locus coeruleus neurons.
The hypocretins (hcrts), also known as orexins, are two recently identified excitatory neuropeptides that in rat are produced by approximately 1200 neurons whose cell bodies are located in the lateral hypothalamus. The hypocretins/orexins have been implicated in the regulation of rapid eye movement (REM) sleep and the pathophysiology of narcolepsy. In the present study, we investigated whether the locus coeruleus (LC), a structure receiving dense hcrtergic innervation, which is quiescent during REM sleep, might be a target for hcrt to regulate REM sleep. Local administration of hcrt1 but not hcrt2 in the LC suppressed REM sleep in a dose-dependent manner and increased wakefulness at the expense of deep, slow-wave sleep. These effects were blocked with an antibody that neutralizes hcrt binding to hcrt receptor 1. In situ hybridization and immunocytochemistry showed the presence of hcrt receptor 1 but not the presence of hcrt receptor 2 in the LC. Iontophoretic application of hcrt1 enhanced the firing rate of LC neurons in vivo, and local injection of hcrt1 into the LC induced the expression of c-fos in the LC area. We propose that hcrt receptor 1 in the LC is a key target for REM sleep regulation and might be involved in the pathophysiological mechanisms of narcolepsy.


Cloning and structural analysis of the cDNA and the gene encoding the murine type 1 sigma receptor.
We have isolated a mouse cDNA which codes for a functional type 1 sigma receptor. The functional identity of the cDNA was established by expressing the cDNA in mammalian cells and measuring the cDNA-induced binding of haloperidol. Using this cDNA as the probe, we have isolated a murine genomic clone which contains the type 1 sigma receptor gene in its entirety. We have sequenced the gene completely, deduced the exon-intron organization and analyzed the promoter region sequence for transcription factor binding sites. The gene (approximately 7 kbp) is TATA-less but contains CCAATC and GC boxes immediately upstream of the transcription start site. The gene consists of 4 exons and 3 introns. The 5'-flanking region contains putative binding sites for AP-1, AP-2, GATA-1 and steroid receptors.


Identification of Lactobacillus plantarum genes that are induced in the gastrointestinal tract of mice.
Lactobacillus plantarum is a flexible and versatile microorganism that inhabits a variety of environmental niches, including the human gastrointestinal (GI) tract. Moreover, this lactic acid bacterium can survive passage through the human or mouse stomach in an active form. To investigate the genetic background of this persistence, resolvase-based in vivo expression technology (R-IVET) was performed in L. plantarum WCFS1 by using the mouse GI tract as a model system. This approach identified 72 L. plantarum genes whose expression was induced during passage through the GI tract as compared to laboratory media. Nine of these genes encode sugar-related functions, including ribose, cellobiose, sucrose, and sorbitol transporter genes. Another nine genes encode functions involved in acquisition and synthesis of amino acids, nucleotides, cofactors, and vitamins, indicating their limited availability in the GI tract. Four genes involved in stress-related functions were identified, reflecting the harsh conditions that L. plantarum encounters in the GI tract. The four extracellular protein encoding genes identified could potentially be involved in interaction with host specific factors. The rest of the genes are part of several functionally unrelated pathways or encode (conserved) hypothetical proteins. Remarkably, a large number of the functions or pathways identified here have previously been identified in pathogens as being important in vivo during infection, strongly suggesting that survival rather than virulence is the explanation for the importance of these genes during host residence.


Unusual massive neurinoma in the suboccipital region--case report.
An 8-year-old boy with no evidence of von Recklinghausen's disease presented with an unusual neurinoma manifesting as a gradually progressive swelling in the suboccipital region over 2 years. The lesion was massive and had widely eroded the posterior aspects of the atlas, axis, and suboccipital bone. The tumor had involved the dura of the sigmoid and transverse sinuses, was highly vascular, and had encased the ipsilateral vertebral artery. The tumor was almost completely resected although with considerable loss of blood through a large rent in the right sigmoid sinus. This unusual benign neurinoma most probably arose from the second cervical ganglion.


Obstetric complications in grand and great grand multiparous women.
To investigate pregnancy and labour outcomes in grand and great grand multiparous women. A retrospective population-based study was conducted between the years 1988 and 2007. Parturients were classified into three groups: multiparous; 2-5 deliveries, grand multiparous; 6-9 deliveries, and great grand multiparous; 10+ deliveries. Stratified analyses included multiple logistic regression models. A significant linear association was found between parity and adverse maternal and perinatal outcomes such as malpresentation, labour dystocia, caesarean delivery, postpartum haemorrhage, maternal anaemia (HB<10), congenital malformations and perinatal mortality. Using multivariable logistic regression models, grand multiparity was found an independent risk factor for labour dystocia, first stage (OR=1.5, P<0.001), and perinatal mortality (OR=2.0, P<0.001). Great grand multiparity was found an independent risk factor for labour dystocia, first stage (OR=2.6, P<0.001), labour dystocia, second stage (OR=2.1, P<0.001), and perinatal mortality (OR=2.5, P<0.001). Women with high birth order are at increased risk for adverse obstetric outcomes. The risk is higher for great grand multiparous women compared to grand multiparous women. Grand and great grand multiparity are independent risk factors for labour dystocia and perinatal mortality.


Dorsal Augmentation with AlloDerm.
The augmentation-reduction principle is becoming pervasive in nasal surgery. Rhinoplasty surgeons have discovered that nasal skin does not consistently contract. Therefore, nasal augmentation is an increasingly accepted technique, and grafts are required. Autogenous cartilage is the grafting material of choice. There are drawbacks to autogenous material, especially in secondary rhinoplasty patients who are often graft-depleted. Cartilage grafts may cause unsightly irregularities over time. Therefore, an interest in alternative soft tissue substitutes has developed. AlloDerm is freeze-dried acellular cadaver dermis. AlloDerm acts as a filler to expand portions of the nasal skin envelope to balance the overresected nose and adhere to the augmentation-reduction principle. AlloDerm facilitates touch-ups, especially in the author's own personal patients. It is soft, thin, and pliable and can be placed under very thin skin. AlloDerm obviates the necessity for graft harvest. It is safe in that it can eliminate the risk of donor-site problems for dorsal onlays such as cranial bone or rib grafts. It is natural and acts as an excellent camouflage graft when used as padding over a cartilage graft. It is incorporated into the surrounding tissue and does not develop unsightly irregularities over time. Extrusion is rare. It does not shift over time. It is especially useful in donor-site-depleted patients. Overcorrection is absolutely necessary because a portion of the implanted AlloDerm is always absorbed. Resorption is most common over the bony dorsum with about 20 to 30% of the graft absorbing. Resorption is disappointing for the patient and frustrating for the surgeon. Absorption does not seem to relate to the number of layers used. No graft absorption has been noted after 1 year. Therefore, it is safe to assume that the patient has a stable result from the AlloDerm graft after 1 year, and no further change should be anticipated. It is easy to use. The advantages and caveats should be kept in mind when evaluating a patient for a dorsal graft.


The effect of preoperative arteriography on vascular endothelium and replant survival in rabbit ears.
Although contrast media injected during arteriography is known to decrease microcirculatory blood flow and alter oxygen delivery capacity of the red blood cell, its effect on the vascular endothelium is unknown. This experiment was designed to determine if there were any alterations in arterial or venous endothelial anatomy by scanning electron microscopy and whether replant survival was decreased following arteriography. Our results suggest that when the injection pressure of arteriography is carefully controlled, the contrast media used in this experiment has no effect on vascular endothelium in rabbit ears examined 30 minutes and 24 hours after arteriography. Furthermore, the survival rate of replanted rabbit ears is not affected by arteriography 24 hours prior to replantation. We conclude that preoperative arteriography remains a valuable tool in the planning of free composite tissue transfer but, based on this study, cannot rule out mechanical complications of arteriography that may be deleterious to free tissue transfer.


Chronologic and geographic variability of neurovascular structures in the human mandible.
To compare the dimensions of mandibular anatomical landmarks of human mandibles of three different chronological periods and seven different geographic regions. Cone beam computed tomography (CBCT) images were acquired from human mandibles of three different chronological periods (Neolithic, Medieval and 19-20th Century). The 19-20th Century consisted of seven human mandibular samples from different geographic locations. Image analysis consisted of comparing anatomic variability and dimensions of the mandibular, lingual and incisive canals, mental foramen and their relationship to specific reference teeth as such to determine geographic region and historic period variabilities. There were statistically significant differences between the 19-20th Century group and the Medieval and Neolithic groups. The 19-20th Century group differed significantly in mandibular canal diameter, tooth root length, length of the lateral lingual canal. In addition, the group also differed from the Medieval sample for the lateral lingual foramen diameter and the midline lingual canal length. Furthermore, the prevalence of anatomic variations was significantly different for the geographic samples tested, with double mental foramina significantly more present in the Congolese sample, and significantly more lateral lingual canals noted in Indonesian and Greenland Eskimo samples. This study suggests that mandibular neurovascularisation may show some geographic as well as historic variation. Further studies on larger data samples are needed to verify this statement, as such that it can be potentially used in anthropology and forensic dentistry. More research is also needed to address whether the geographic and historic variations are linked, as well to investigate evolutionary trends in these structures.


Abundant carbon substrates drive extremely high sulfate reduction rates and methane fluxes in Prairie Pothole Wetlands.
Inland waters are increasingly recognized as critical sites of methane emissions to the atmosphere, but the biogeochemical reactions driving such fluxes are less well understood. The Prairie Pothole Region (PPR) of North America is one of the largest wetland complexes in the world, containing millions of small, shallow wetlands. The sediment pore waters of PPR wetlands contain some of the highest concentrations of dissolved organic carbon (DOC) and sulfur species ever recorded in terrestrial aquatic environments. Using a suite of geochemical and microbiological analyses, we measured the impact of sedimentary carbon and sulfur transformations in these wetlands on methane fluxes to the atmosphere. This research represents the first study of coupled geochemistry and microbiology within the PPR and demonstrates how the conversion of abundant labile DOC pools into methane results in some of the highest fluxes of this greenhouse gas to the atmosphere ever reported. Abundant DOC and sulfate additionally supported some of the highest sulfate reduction rates ever measured in terrestrial aquatic environments, which we infer to account for a large fraction of carbon mineralization in this system. Methane accumulations in zones of active sulfate reduction may be due to either the transport of free methane gas from deeper locations or the co-occurrence of methanogenesis and sulfate reduction. If both respiratory processes are concurrent, any competitive inhibition of methanogenesis by sulfate-reducing bacteria may be lessened by the presence of large labile DOC pools that yield noncompetitive substrates such as methanol. Our results reveal some of the underlying mechanisms that make PPR wetlands biogeochemical hotspots, which ultimately leads to their critical, but poorly recognized role in regional greenhouse gas emissions.


Specific Expert Learning: Enriching Ensemble Diversity via Knowledge Distillation.
In recent years, ensemble methods have shown sterling performance and gained popularity in visual tasks. However, the performance of an ensemble is limited by the paucity of diversity among the models. Thus, to enrich the diversity of the ensemble, we present the distillation approach-learning from experts (LFEs). Such method involves a novel knowledge distillation (KD) method that we present, specific expert learning (SEL), which can reduce class selectivity and improve the performance on specific weaker classes and overall accuracy. Through SEL, models can acquire different knowledge from distinct networks with various areas of expertise, and a highly diverse ensemble can be obtained afterward. Our experimental results demonstrate that, on CIFAR-10, the accuracy of the ResNet-32 increases 0.91% with SEL, and that the ensemble trained by SEL increases accuracy by 1.13%. Compared to state-of-the-art approaches, for example, DML only improves accuracy by 0.3% and 1.02% on single ResNet-32 and the ensemble, respectively. Furthermore, our proposed architecture also can be applied to ensemble distillation (ED), which applies KD on the ensemble model. In conclusion, our experimental results show that our proposed SEL not only improves the accuracy of a single classifier but also boosts the diversity of the ensemble model.


Evaluation of A-ring fused pyridine d-modified androstane derivatives for antiproliferative and aldo-keto reductase 1C3 inhibitory activity.
New A-ring pyridine fused androstanes in 17a-homo-17-oxa (d-homo lactone), 17α-picolyl or 17(E)-picolinylidene series were synthesized and validated by X-ray crystallography, HRMS, IR and NMR spectroscopy. Novel compounds 3, 5, 8 and 12 were prepared by treatment of 4-en-3-one or 4-ene-3,6-dione d-modified androstane derivatives with propargylamine catalyzed by Cu(ii), and evaluated for potential anticancer activity in vitro using human cancer cell lines and recombinant targets of steroidal anti-cancer drugs. Pyridine fusion to position 3,4 of the A-ring may dramatically enhance affinity of 17α-picolyl compounds for CYP17 while conferring selective antiproliferative activity against PC-3 cells. Similarly, pyridine fusion to the A-ring of steroidal d-homo lactones led to identification of new inhibitors of aldo-keto reductase 1C3, an enzyme targeted in acute myeloid leukemia, breast and prostate cancers. One A-pyridine d-lactone steroid 5 also has selective submicromolar antiproliferative activity against HT-29 colon cancer cells. None of the new derivatives have affinity for estrogen or androgen receptors in a yeast screen, suggesting negligible estrogenicity and androgenicity. Combined, our results suggest that A-ring pyridine fusions have potential in modulating the anticancer activity of steroidal compounds.


Symbiont-Derived Antimicrobials Contribute to the Control of the Lepidopteran Gut Microbiota.
Insects develop efficient antimicrobial strategies to flourish in a bacterial world. It has long been proposed that native gut microbiota is an important component of host defense; however, the responsible species have rarely been isolated to elucidate the mechanism of action. Here we show that the dominant symbiotic bacterium Enterococcus mundtii associated with the generalist herbivore Spodoptera littoralis actively secretes a stable class IIa bacteriocin (mundticin KS) against invading bacteria, but not against other gut residents, facilitating the normal development of host gut microbiota. A mundticin-defective strain lost inhibitory activity. Furthermore, purified mundticin cures infected larvae. Thus, the constitutively produced antimicrobials by native extracellular symbionts create a significant chemical barrier inside limiting invader expansion. This unique property also benefits E. mundtii itself by providing a competitive advantage, contributing to its dominance within complex microbial settings and its prevalence across Lepidoptera, and probably promotes the long-term cooperative symbiosis between both parties.


[Method of study of epidemiology of diabetic angiopathies].
The authors present a method of a perspective study of the epidemiology of diabetic angiopathies with the use of standardized methods of examination of the cardiovascular system, including the assessment of microangiopathies and also glycemia and lipid metabolism indices in accordance with the WHO recommendations. This method can be used by endocrinologists, therapeutists and physicians of other specialties in studying the factors influencing the development of vascular affections in patients with diabetes mellitus.


Developing Nano-size carrier systems for Amphotericin-B: A review on the biomedical application of nanoparticles for the treatment of leishmaniasis and fungal infections.
New formulations of Amphotericin-B (Am-B), the most popular therapeutic drug for many human infections such as parasitic and fungal pathogens, are safe, economical, and effective in the world. Several newly designed carrier systems for Am-B can also be considered orally with sufficient gastrointestinal permeability and good solubility. However, the clinical application of several new formulations of Am-B with organ cytotoxicity, low bioavailability, high costs, and technical problems have caused some issues. Therefore, more attention and scientific design are required to progress safe and effective drug delivery systems. Currently, the application of Nano-based technology and Nano-materials in the advancement of drug delivery systems exhibits promising outcomes to cure many human systemic infections. Designing novel drug delivery systems including solid lipid nanostructured materials, lipo polymersomes, drug conjugates and microneedles, liposomes, polymer and protein-based nanostructured materials, dendrimers, emulsions, mixed micelles, polymeric micelles, cyclodextrins, Nano-capsules, and Nano-cochleate for Am-B has many advantages to reducing several related issues. The unique properties of Nano-structured particles such as proper morphology, small size, surface coatings, and, electrical charge, permit scientists to design new Nano-composite materials against microorganisms for application in various human diseases. These features have made these nanoparticles an ideal candidate for drug delivery systems in clinical approaches to cure a number of human disorders and currently, several therapeutic nanostructured material formulations are under different stages of clinical tests. Hence, this scientific paper mainly discussed the advances in new formulations of Am-B for the treatment of human systemic infections and related clinical tests. This article is protected by copyright. All rights reserved.


Primary prophylaxis in severe haemophilia should be started at an early age but can be individualized.
The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.


The reference strain Aeromonas hydrophicla CIP 57.50 should be reclassified as Aeromonas salmonicida CIP 57.50.
The use of reference strains is a critical element for the quality control of different assays, from the development of molecular methods to the evaluation of antimicrobial activities. Most of the strains used in these assays are not type strains and some of them are cited erroneously because of subsequent reclassifications and descriptions of novel species. In this study, we propose that the reference strain Aeromonas hydrophila CIP 57.50 be reclassified as Aeromonas salmonicida CIP 57.50 based on phenotypic characterization and sequence analyses of the cpn60, dnaJ, gyrB and rpoD genes.


Quantifying the speech-gesture relation with massive multimodal datasets: Informativity in time expressions.
The development of large-scale corpora has led to a quantum leap in our understanding of speech in recent years. By contrast, the analysis of massive datasets has so far had a limited impact on the study of gesture and other visual communicative behaviors. We utilized the UCLA-Red Hen Lab multi-billion-word repository of video recordings, all of them showing communicative behavior that was not elicited in a lab, to quantify speech-gesture co-occurrence frequency for a subset of linguistic expressions in American English. First, we objectively establish a systematic relationship in the high degree of co-occurrence between gesture and speech in our subset of expressions, which consists of temporal phrases. Second, we show that there is a systematic alignment between the informativity of co-speech gestures and that of the verbal expressions with which they co-occur. By exposing deep, systematic relations between the modalities of gesture and speech, our results pave the way for the data-driven integration of multimodal behavior into our understanding of human communication.


Electroporation and EGFP labeling of gastrulating quail embryos.
Labeling embryonic cells to trace their motion is a classical experimental approach with a host of techniques being used to mark live cells and tissues. Genetically engineered fluorescent protein vectors (DNA plasmids) are a recent technology well suited to time-resolved studies of cellular motion in live embryos. DNA plasmids encoding fluorescent proteins can be introduced into cells using several methods, including electroporation, a technique used widely for analysis of tissue culture and embryonic cells. Here we describe a technique designed to introduce DNA plasmids into early gastrulation stage quail embryos, ex ovo. The method is effective, and with practice enables an investigator to direct the vectors to relatively confined regions of gastrulating embryos. The required electroporation chamber can be fabricated from common laboratory materials. We anticipate that using this method of labeling cells in a warm-blooded embryo, during gastrulation, will be a fruitful means of studying subsequent embryogenesis.


[Isolation of carotenoid-containing subcellular structures from mollusk nerve tissue].
A subcellular fraction with a high share of carotenoids (about 150 mkg/mg of protein) was obtained from the nerve tissue of Lymnaea stagnalis, the fractionation being made by sucrose density gradient centrifugation. The quantity of carotenoids extracted from fractions was estimated spectrophotometrically. The electron microscope observations demonstrated the presence of structures analogous to fraction components in the mollusc neurones and similar to some kinds of plant chromplasts (carotenoidplasts).


KTt-45, a T-type calcium channel blocker, acts as an anticancer agent by inducing apoptosis on HeLa cervical cancer cell line.
The abnormal expression in the T-type calcium channels is involved in various cancer types, thus inhibiting T-type calcium channels is one of approaches in cancer treatment. The fact that KTt-45 acted as a T-type calcium channel inhibitor as well as a pain-relief agent prompts us to address if KTt-45 plays any role against cancer cells. The results showed that KTt-45 caused cytotoxic effects towards HeLa cervical, Raji lymphoma, MCF-7 breast cancer, and A549 lung cancer cell lines with IC50 values less than 100 μM, in which highly selective toxicity was against HeLa cells (IC50 = 37.4 μM, SI > 3.2). Strikingly, the KTt-45 induced an accumulation of cytoplasmic vacuoles after 48 h treatment and mitochondrial-dependent apoptosis activation as evidenced by morphological features, chromatin condensation, nuclear fragmentation, and significant activation of caspase-9 as well as caspase-3. In conclusion, KTt-45 could inhibit cell growth and trigger mitochondrial-dependent apoptosis in HeLa cervical cancer cells. The results, taken together, strongly demonstrated that KTt-45 is a potential agent for further study on anticancer drug development which not only targets cancer cells but also helps to relieve neuropathic pain in cancer patients.


Autophagy and caspases: a new cell death program.
Autophagy is used to degrade components of the cytoplasm and functions as a cell survival mechanism during nutrient deprivation. Autophagic structures have also been observed in many types of dying cells, but experimental evidence for autophagy playing a role in the regulation of programmed cell death is limited. We have recently shown that the autophagy genes Atg7 and Beclin1 are required for the death of certain cells, thus demonstrating that this mechanism of proteolysis is involved in both survival and death. The factors that enable autophagy to regulate distinct cell survival and death responses are not clear, and future work is needed to determine the mechanism(s) that regulate autophagic cell death.


Methylation analysis of MLH1 improves the selection of patients for genetic testing in Lynch syndrome.
Inactivation of MLH1 due to promoter hypermethylation strongly suggests a sporadic origin, providing exclusion criteria for Lynch syndrome. The aim of this study is to compare the utility of methylation analysis of MLH1 and BRAF V600E mutations for the selection of patients with MLH1 negative colorectal cancer for genetic testing. MLH1 methylation status was evaluated by MethyLight and methylation-specific MLPA (MS-MLPA) in tumor DNA from 73 colorectal cancer patients with loss of MLH1 protein expression. These tumors were analyzed for BRAF V600E mutations, and genetic testing for germline MLH1 mutations was performed in all corresponding patients. Ten patients had germline mutations in MLH1 and none of their tumors showed significant MLH1 methylation or BRAF V600E mutation. MLH1 genetic testing excluded patients by MethyLight in 47 patients (64%), by MS-MLPA in 49 (67%), and BRAF V600E mutation in only 25 patients (34%) (chi(2) P = 0.00001). Specificity was 75% for MethyLight, 78% for MS-MLPA and 40% for BRAF V600E mutation. The use of MethyLight or MS-MLPA instead of BRAF mutation resulted in a cost reduction of 41% and 45%, respectively, per every MLH1 mutation detected. Taken together, methylation analysis of MLH1 shows better performance characteristics than BRAF V600E mutation in the selection of patients for genetic testing of MLH1, especially when using MS-MLPA.


Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity.
Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte-derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, "anhedonia," and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.


Low physical activity is associated with two hypokinetic motor abnormalities in psychosis.
Individuals with schizophrenia engage in more sedentary behavior than healthy controls, which is thought to contribute to multiple health adversities. Age, medication side effects and environment are critical determinants of physical activity in psychosis. While motor abnormalities are frequently observed in psychosis, their association with low physical activity has received little interest. Here, we aimed to explore the association of actigraphy as an objective measure of physical activity with clinician assessed hypokinetic movement disorders such as parkinsonism and catatonia. Furthermore, we studied whether patients with current catatonia would differ on motor rating scales and actigraphy from patients without catatonia. In 52 patients with schizophrenia spectrum disorders, we cross-sectionally assessed physical activity using wrist actigraphy and ratings of catatonia, parkinsonism, and negative syndrome. The sample was enriched with subjects with severe psychomotor slowing. Lower activity levels correlated with increased age and severity of catatonia and parkinsonism. The 22 patients with catatonia had lower activity as well as higher scores on parkinsonism, involuntary movements, and negative symptoms compared to the 30 patients without catatonia. Collectively, these results suggest that various hypokinetic motor abnormalities are linked to lower physical activity. Therefore, future research should determine the direction of the associations between hypokinetic motor abnormalities and physical activity using longitudinal assessments and interventional trials.


Perceptions of nurses' roles in end-of-life care and organ donation - imposition or obligation?
South Africa has a rich organ-transplant history, and studies suggest that the SA public supports organ donation. In spite of this, persistently low donor numbers are a significant challenge. This may be due to a lack of contextually appropriate awareness and education, or to barriers to referring patients and families in clinical settings. It may also be due to ad hoc regulations that are not uniformly endorsed or implemented. In this article we present the findings of a study in Johannesburg that explored the attitudes and roles of nurses in end-of-life care and organ donation. A total of 273 nurses participated. Most were female and <50 years old. The majority expressed positive attitudes towards both end-of-life care and organ donation, but there was ambiguity as to whether referring patients and families for these services was within nursing scope of practice. The vast majority of participants noted that they would refer patients themselves if there was a mandatory, nationally endorsed referral policy. These findings have implications for clinical practice and policy, and suggest that the formulation and implementation of robust national guidelines should be a priority. Because nurses would follow such guidelines, this might lead to an increase in donor rates and circumvent some uncertainty regarding referral.


Tissue regeneration in dentistry: Can salamanders provide insight?
The ability to regenerate damaged tissues would be of tremendous benefit for medicine and dentistry. Unfortunately, humans are unable to regenerate tissues such as teeth and fingers or to repair injured spinal cord. With an aging population, health problems are more prominent and dentistry is no exception as loss of bone tissue in the orofacial sphere from periodontal disease is on the rise. Humans can repair oral soft tissues exceptionally well; however, hard tissues, such as bone and teeth, are devoid of the ability to repair well or at all. Fortunately, Mother Nature has solved nearly every problem that we would like to solve for our own benefit and tissue regeneration is no exception. By studying animals that can regenerate, like Axolotls (Mexican salamander), we hope to find ways to stimulate regeneration in humans. We will discuss the role of the transforming growth factor beta cytokines as they are central to wound healing in humans and regeneration in Axolotls. We will also compare wound healing in humans (skin and oral mucosa) to Axolotl skin wound healing and limb regeneration. Finally, we will address the problem of bone regeneration and present results in salamanders which indicate that in order to regenerate bone you need to recruit non-bone cells. Fundamental research, such as the work being performed in animals that can regenerate, offers insight to help understand why some treatments are successful while others fail when it comes to specific tissues such as bones.


[Differentiation of concomitant glaucomatous optic neuropathy in optic disc drusen].
Characteristics of ocular blood flow (OBF) in primary open-angle glaucoma (POAG) in eyes with optic disc drusen have been investigated. The study enrolled 21 patient (35 eyes) with optic disc drusen, of which 7 (8 eyes) were diagnosed with POAG. Besides the standard tests, the ophthalmological assessment included evaluation of OBF (flowmetry) and an individual normal range of intraocular pressure (IOP). The results showed that optic disc drusen are not associated with OBF changes. Concomitant POAG might be suspected in a patient with optic disc drusen whose OBF is significantly decreased and IOP is above the individual normal range. Differentiation of morphofunctional changes in chronic optic neuropathy, which might be due to either glaucomatous optic neuropathy or optic disc drusen, is complicated when actual IOP lies within the average normal range. Ocular blood flow evaluation by means of flowmetry with calculation of an individual normal range of IOP has been demonstrated as a highly effective predictor of concomitant POAG in patients with optic disc drusen.


Suppression of melanoma cell tyrosinase activity and tumorigenicity after incorporation of bromouracil for one or two cell divisions.
We have studied the kinetics of suppression of tyrosinase activity and tumorigenicity in unsynchronized B16 mouse melanoma cells (clone B559) exposed to 5-bromodeoxyuridine (BrdU, 3 mug/ml) for one or two cell divisions, then cultured in BrdU-free medium (RM) for five or six days. Bromouracil replaced about 23% of thymine residues after 24 hours (1 cell division) and almost 40% after 48 hours (2 cell divisions) in the presence of BrdU. Upon subsequent growth in RM the extent of replacement declined in a manner consistent with dilution by new DNA synthesis, reaching 5-10% substitution by day 7 of these experiments. Tyrosinase activity was significantly reduced after treatment with BrdU for 24 or 48 hours but continued to decline after the cultures were changed to RM, approaching undetectable levels on day 7. The time course of reduction was similar to that previously determined in cells grown continuously for seven days in the presence of BrdU. Therefore, suppression of tyrosinase activity can result from incorporation of BrdU during a single cell cycle, but requires about seven days for full manifestation of the effect. Tumorigenicity decreased to 55% after 24 hours and to 15% after 48 hours with BrdU but rapidly reversed to approach that of untreated melanoma cells when subsequently grown in RM for 5-6 days. The effects of BrdU on total RNA or protein synthesis, or on plating efficiency appeared insufficient to account for the degree of suppression observed. Our results indicate that substitution by bromouracil into either strand of DNA loci controlling tyrosinase activity or tumorigenic potential may be sufficient for suppression. In addition, they demonstrate that such brief treatment with BrdU may be used to probe the regulation of differentiated function and tumorigenicity in these melanoma cells.


[Implication of lead poisoning in psychopathology of Vincent van Gogh].
The authors, by means of documental research, study the possibility that the physical and psychic symptoms of Vincent van Gogh may have been due to chronic lead poisoning. The technique and materials used by Van Gogh are analysed as the cause of repeated exposure to lead as well as the possible means of penetration of the metal. Through historical-biographical analysis, the progressive symptoms of the illness are compared with those of lead poisoning. The authors conclude that the excessive and continuous use by Van Gogh of pigments which were highly toxic due to their high lead content, such as white lead (lead carbonate) and yellow chrome (lead chromium), could have penetrated his organism by digestive system (primarily) in minimal daily amounts, giving rise to a clinical condition of chronic lead poisoning. This type of poisoning coincides with the clinical symptoms Van Gogh describes in his autographed letters: initial debilitation, stomatitis with loss of teeth, recurring abdominal pains, anaemia (with a "plumbic" skin tone), neuropathy of the radial and saturnine encephalopathy including epileptic crises, progressive character changes and periods of delirium. The clinical symptoms shown by Van Gogh meet present criteria for diagnosis of Organic Mental Disorder due to cerebral lesion or somatic illness (F.06; CIE-10) (DSM-IV-R), and Organic Character Disorder (F.07; CIE-10) (DSM-IV-R).


Single-step PCR for detection of Brucella spp. from blood and milk of infected animals.
A versatile method for the extraction of Brucella DNA and PCR are presented as reliable tools for the detection of Brucella spp. from body fluids of infected animals. Two oligonucleotides homologous to regions of the gene encoding for an outer membrane protein (omp-2) were designed to detect the pathogen from milk and/or blood of infected goats, bovines, and human patients. The sensitivity of our test and its ability to detect the pathogen in samples from the field reveal a promising advance in the diagnosis of brucellosis in animals and humans.


Mobile Health Physical Activity Intervention Preferences in Cancer Survivors: A Qualitative Study.
Cancer survivors are at an elevated risk for several negative health outcomes, but physical activity (PA) can decrease those risks. Unfortunately, adherence to PA recommendations among survivors is low. Fitness mobile apps have been shown to facilitate the adoption of PA in the general population, but there are limited apps specifically designed for cancer survivors. This population has unique needs and barriers to PA, and most existing PA apps do not address these issues. Moreover, incorporating user preferences has been identified as an important priority for technology-based PA interventions, but at present there is limited literature that serves to establish these preferences in cancer survivors. This is especially problematic given the high cost of app development and because the majority of downloaded apps fail to engage users over the long term. The aim of this study was to take a qualitative approach to provide practical insight regarding this population's preferences for the features and messages of an app to increase PA. A total of 35 cancer survivors each attended 2 focus groups; a moderator presented slide shows on potential app features and messages and asked open-ended questions to elicit participant preferences. All sessions were audio recorded and transcribed verbatim. Three reviewers independently conducted thematic content analysis on all transcripts, then organized and consolidated findings to identify salient themes. Participants (mean age 63.7, SD 10.8, years) were mostly female (24/35, 69%) and mostly white (25/35, 71%). Participants generally had access to technology and were receptive to engaging with an app to increase PA. Themes identified included preferences for (1) a casual, concise, and positive tone, (2) tools for personal goal attainment, (3) a prescription for PA, and (4) an experience that is tailored to the user. Participants reported wanting extensive background data collection with low data entry burden and to have a trustworthy source translate their personal data into individualized PA recommendations. They expressed a desire for app functions that could facilitate goal achievement and articulated a preference for a more private social experience. Finally, results indicated that PA goals might be best established in the context of personally held priorities and values. Many of the desired features identified are compatible with both empirically supported methods of behavior change and the relative strengths of an app as a delivery vehicle for behavioral intervention. Participating cancer survivors' preferences contrasted with many current standard practices for mobile app development, including value-based rather than numeric goals, private socialization in small groups rather than sharing with broader social networks, and interpretation of PA data rather than merely providing numerical data. Taken together, these insights may help increase the acceptability of theory-based mHealth PA interventions in cancer survivors.


Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial.
Tenofovir alafenamide is a novel prodrug formulated to deliver the active metabolite to target cells more efficiently than tenofovir disoproxil fumarate at a lower dose, thereby reducing systemic exposure. In patients with HIV, tenofovir alafenamide was as efficacious as tenofovir disoproxil fumarate, with reduced bone and renal toxic effects. We compared the efficacy and safety of the two drugs in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection in a non-inferiority study. We did this ongoing double-blind, non-inferiority study in 161 outpatient centres in 19 countries. Patients with chronic HBV infection who were positive for the hepatitis B e antigen (HBeAg) were randomly assigned (2:1) to receive either 25 mg tenofovir alafenamide or 300 mg tenofovir disoproxil fumarate with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size six) stratified by plasma HBV DNA concentration and previous treatment experience. The primary efficacy endpoint was the proportion of patients with HBV DNA less than 29 IU/mL at week 48 in all patients who were randomly assigned and received at least one dose of study drug using a missing-equals-failed approach. The pre-specified non-inferiority margin was 10%. Key prespecified safety endpoints were bone and renal parameters at week 48. This study is registered with ClinicalTrials.gov, number NCT01940471. Of the 1473 patients screened from Sept 11, 2013, to Dec 20, 2014, 875 eligible patients were randomly assigned and 873 received treatment (581 with tenofovir alafenamide and 292 with tenofovir disoproxil fumarate). 371 (64%) patients receiving tenofovir alafenamide had HBV DNA less than 29 IU/mL at week 48, which was non-inferior to the 195 (67%) of patients receiving tenofovir disoproxil fumarate who had HBV DNA less than 29 IU/mL (adjusted difference -3·6% [95% CI -9·8 to 2·6]; p=0·25). Patients given tenofovir alafenamide had a significantly smaller decrease in bone mineral density at hip (mean change -0·10% [95% CI -0·29 to 0·09] vs -1·72% [-2·02 to -1·41]; adjusted difference 1·62 [1·27 to 1·96]; p<0·0001) and at spine (mean change -0·42% [-0·66 to -0·17] vs -2·29% [-2·67 to -1·92]; adjusted difference 1·88 [1·44 to 2·31]; p<0·0001) as well as smaller mean increases in serum creatinine at week 48 (0·01 mg/dL [0·00-0·02] vs 0·03 mg/dL [0·02-0·04]; p=0·02). The most common adverse events overall were upper respiratory tract infection (51 [9%] of 581 patients receiving tenofovir alafenamide vs 22 [8%] of 292 patients receiving tenofovir disoproxil fumarate), nasopharyngitis (56 [10%] vs 16 [5%]), and headache (42 [7%] vs 22 [8%]). 22 (4%) patients receiving tenofovir alafenamide and 12 (4%) patients receiving tenofovir disoproxil fumarate experienced serious adverse events, none of which was deemed by the investigator to be related to study treatment. 187 (32%) of 581 patients in the tenofovir alafenamide group and 96 (33%) of 292 patients in the tenofovir disoproxil fumarate group had grade 3 or 4 laboratory abnormalities, the most common of which were elevations in ALT (62 [11%] of 577 patients receiving tenofovir alafenamide and 36 [13%] of 288 patients receiving tenofovir disoproxil fumarate) and AST (20 [3%] of 577 patients receiving tenofovir alafenamide and 19 [7%] of 288 patients receiving tenofovir disoproxil fumarate). In patients with HBeAg-positive HBV infection, tenofovir alafenamide was non-inferior to tenofovir disoproxil fumarate, and had improved bone and renal effects. Longer term follow-up is needed to better understand the clinical impact of these changes. Gilead Sciences.


Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura.
Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient.


[Management of chronic hepatitis B in treatment-naive patients].
Chronic hepatitis B (CHB) is a serious health problem in Korea. The natural history of chronic HBV infection has been divided into 4 phases: immune tolerance, immune clearance, inactive HBsAg carrier state and reactivation. During the phases of immune tolerance and inactive HBsAg carrier state, no treatment is required. Patients in the immune clearance or reactivation phases are candidates for therapy. In the last years, treatment effects of CHB have considerably improved. Several agents are currently approved for the treatment of CHB: interferon alpha, pegylated interferon alpha, lamivudine, adefovir, entecavir, telbivudine and clevudine in Korea. The treatment recommendations from the 2004 Korean Association for the Study of the Liver guideline on the management of CHB have been updated to incorporate new therapeutic options. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Issues for consideration include efficacy, safety and incidences of resistance, and method of administration of antiviral therapy in treatment-naive patients.


Fast quantitation of 5-hydroxymethylfurfural in honey using planar chromatography.
An approach for rapid quantitation of 5-hydroxymethylfurfural (HMF) in honey using planar chromatography is suggested for the first time. In high-performance thin-layer chromatography (HPTLC) the migration time is approximately 5 min. Detection is performed by absorbance measurement at 290 nm. Polynomial calibration in the matrix over a range of 1:80 showed correlation coefficients, r, of ≥ 0.9997 for peak areas and ≥ 0.9996 for peak heights. Repeatability in the matrix confirmed the suitability of HPTLC-UV for quantitation of HMF in honey. The relative standard deviation (RSD, %, n = 6) of HMF at 10 ng/band was 2.9% (peak height) and 5.2% (peak area); it was 0.6% and 1.0%, respectively, at 100 ng/band. Other possible detection modes, for example fluorescence measurement after post-chromatographic derivatization and mass spectrometric detection, were also evaluated and can coupling can be used as an additional tool when it is necessary to confirm the results of prior quantitation by HPTLC-UV. The confirmation is provided by monitoring the HMF sodium adduct [M + Na](+) at m/z 149 followed by quantitation in TIC or SIM mode. Detection limits for HPTLC-UV, HPTLC-MS (TIC), and HPTLC-MS (SIM) were 0.8 ng/band, 4 ng/band, and 0.9 ng/band, respectively. If 12 μL honey solution was applied to an HPTLC plate, the respective detection limits for HMF in honey corresponded to 0.6 mg kg(-1). Thus, the developed method was highly suitable for quantitation of HMF in honey at the strictest regulated level of 15 mg kg(-1). Comparison of HPTLC-UV detection with HPTLC-MS showed findings were comparable, with a mean deviation of 5.1 mg kg(-1) for quantitation in SIM mode and 6.1 mg kg(-1) for quantitation in TIC mode. The mean deviation of the HPTLC method compared with the HPLC method was 0.9 mg kg(-1) HMF in honey. Re-evaluation of the same HPTLC plate after one month showed a deviation of 0.5 mg kg(-1) HMF in honey. It was demonstrated that the proposed HPTLC method is an effective method for HMF quantitation in honey. Figure Fast quantitation of 5-hydroxymethylfurfural in honey.


Overexpression of Prdx6 reduces H2O2 but does not prevent diet-induced atherosclerosis in the aortic root.
The mammalian 1-Cys peroxiredoxin (Prdx6) is a unique member of the peroxiredoxin family of proteins capable of protecting cells from metal-catalyzed oxidative damage. We recently identified Prdx6 as a candidate for the quantitative trait locus Ath1, a gene responsible for a difference in diet-induced atherosclerosis susceptibility in mice. To investigate the role of Prdx6 in atherosclerosis, we generated transgenic mice that overexpress the Prdx6 allele from the Ath1-resistant 129/SvJ strain on an Ath1-susceptible C57BL/6J background. These mice expressed significantly elevated levels of Prdx6 mRNA and protein in multiple tissues including liver, aorta, and peritoneal macrophages, which accumulated significantly lower levels of hydrogen peroxide, revealing an enhanced antioxidant activity in these mice. However, overexpression of Prdx6 had no protective effect on LDL oxidation in vitro, and transgenic mice fed an atherogenic diet for 10 weeks did not possess an increased resistance to atherosclerosis nor did they maintain the high prediet plasma HDL levels consistent with the Ath1-resistant phenotype. In addition, the Prdx6 allele from the susceptible strain was shown to have a higher antioxidant activity than that of the resistant strains. These data suggest that the increased peroxidase activity attributable to Prdx6 overexpression in transgenic mice is not sufficient to protect mice from atherosclerosis, and that Prdx6 is not likely to be the gene underlying Ath1.


Genome-Scale Modeling of NADPH-Driven β-Lapachone Sensitization in Head and Neck Squamous Cell Carcinoma.
The purpose of this study was to investigate differential nicotinamide adenine dinucleotide phosphate, reduced (NADPH) production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β-lapachone. We have developed a novel human genome-scale metabolic modeling platform that combines transcriptomic, kinetic, thermodynamic, and metabolite concentration data. Upon incorporation of this information into cell line-specific models, we observed that the radiation-resistant HNSCC model redistributed flux through several major NADPH-producing reactions. Upon RNA interference of canonical NADPH-producing genes, the metabolic network can further reroute flux through alternate NADPH biosynthesis pathways in a cell line-specific manner. Model predictions of perturbations in cellular NADPH production after gene knockdown match well with experimentally verified effects of β-lapachone treatment on NADPH/NADP+ ratio and cell viability. This computational approach accurately predicts HNSCC-specific oxidoreductase genes that differentially affect cell viability between radiation-responsive and radiation-resistant cancer cells upon β-lapachone treatment. Quantitative genome-scale metabolic models that incorporate multiple levels of biological data are applied to provide accurate predictions of responses to a NADPH-dependent redox cycling chemotherapeutic drug under a variety of perturbations. Our modeling approach suggests differences in metabolism and β-lapachone redox cycling that underlie phenotypic differences in radiation-sensitive and -resistant cancer cells. This approach can be extended to investigate the synergistic action of NAD(P)H: quinone oxidoreductase 1 bioactivatable drugs and radiation therapy. Antioxid. Redox Signal. 29, 937-952.


The prognostic value of the hamstring outcome score to predict the risk of hamstring injuries.
Hamstring injuries are common among soccer players. The hamstring outcome score (HaOS) might be useful to identify amateur players at risk of hamstring injury. Therefore the aims of this study were: To determine the association between the HaOS and prior and new hamstring injuries in amateur soccer players, and to determine the prognostic value of the HaOS for identifying players with or without previous hamstring injuries at risk of future injury. Cohort study. HaOS scores and information about previous injuries were collected at baseline and new injuries were prospectively registered during a cluster-randomized controlled trial involving 400 amateur soccer players. Analysis of variance and t-tests were used to determine the association between the HaOS and previous and new hamstring injury, respectively. Logistic regression analysis indicated the prognostic value of the HaOS for predicting new hamstring injuries. Analysis of data of 356 players indicated that lower HaOS scores were associated with more previous hamstring injuries (F=17.4; p=0.000) and that players with lower HaOS scores sustained more new hamstring injuries (T=3.59, df=67.23, p=0.001). With a conventional HaOS score cut-off of 80%, logistic regression models yielded a probability of hamstring injuries of 11%, 18%, and 28% for players with 0,1, or 2 hamstring injuries in the previous season, respectively. The HaOS is associated with previous and future hamstring injury and might be a useful tool to provide players with insight into their risk of sustaining a new hamstring injury risk when used in combination with previous injuries.


CAN: chain of nodes approach to direct rule induction.
CAN is a heuristic algorithm that employs an information theoretic measure to learn rules. CAN approach distinguishes itself from other approaches by being direct, meaning that there are no intermediate representations, an induced rule is never altered in later stages and only tests that appear in the final solution are generated. In the selection of rule conditions (tests) existing rule induction algorithms do not provide a satisfactory answer to the partitioning of the feature space of discrete feature variables with nonordered qualitative values (i.e., categorical attributes) for multiclass problems. Existing algorithms have exponential complexity in N, where N is the number of feature values. Therefore, heuristic algorithms are employed at this step. An important contribution of this paper is to show that in test selection within CAN framework optimal partitions are achieved in linear time in N for the multiclass case.


[Rare malignant tumors and pseudotumors of the prostate].
The authors presents an updated review of rare malignant tumours of the prostate other than adenocarcinoma, as well as of some diagnostic problems caused by inflammatory pseudotumours. Sarcomas, particularly rhabdomyosarcoma (in childhood) and leiomyosarcoma, represent 0.1 to 0.2% of all prostatic malignant neoplasms. Sarcomas show early local extension and vascular invasion. Treatment consists of combined surgery, chemotherapy and radiotherapy. Other types of even rarer tumours, either primary or metastatic, have also been described in the prostate (carcinoid, malignant melanoma, malignant lymphoma). Finally, some inflammatory and pseudotumours of the prostate (different forms of prostatitis, abcess, infarction) can mimick carcinoma.


[Coflex interspinous dynamic internal fixation for the treatment of degenerative lumbar spinal stenosis].
To assess the clinical outcomes of Coflex interspinous dynamic internal fixation and the imaging changes for degenerative lumbar spinal stenosis. From October 2007 to February 2009, 30 patients with degenerative lumbar spinal stenosis were treated with Coflex interspinous dynamic internal fixation, including 17 males and 13 females with an average age of 45 years (range, 39 to 65 years). The operation level at L4,5 were 20 cases, L5S1 9 cases and 1 case was in both the two levels. The ODI scores and JOA questionnaires were assessed before and after operation. The radiological measurement included ventral and dorsal intervertebral space height, segmental intervertebral angles formed by lines drawn on the upper and lower endplates of the instrumented and adjacent levels on flexion-extension radiographs; the area of spinal canal, dural sac, the sagittal and transverse diameter of the spinal canal and dural sac on CT scan. All the patients were treated with limited laminectomy and were implanted with Coflex device. All the patients were followed up for 5 to 19 months. There were significant differences in the ODI scores and the JOA questionnaires by paired t-test (P<0.01). All the patients were satisfied with surgical outcomes except 3 patients whose pain were not obviously relieved and need drugs or block therapy; 3 patient complaining of progressive hypoesthesia. There were no complications associated with the Coflex device. The height of dorso-intervertebral disc was increased obviously while the range of motion in adjacent levels was not increased on flexion-extension radiographs; the area of spinal canal and dural sac were significantly increased. It shows a good clinical result to release the degenerative lumbar spinal stenosis symptoms and decrease short-term complications by using Coflex device. It is available for patients with increasing the intervertebral space, area of spinal canal and preventing the adjacent segment degeneration.


Activation of factor VII-activating protease in human inflammation: a sensor for cell death.
Cell death is a central event in the pathogenesis of sepsis and is reflected by circulating nucleosomes. Circulating nucleosomes were suggested to play an important role in inflammation and were demonstrated to correlate with severity and outcome in sepsis patients. We recently showed that plasma can release nucleosomes from late apoptotic cells. Factor VII-activating protease (FSAP) was identified to be the plasma serine protease responsible for nucleosome release. The aim of this study was to investigate FSAP activation in patients suffering from various inflammatory diseases of increasing severity. We developed ELISAs to measure FSAP-C1-inhibitor and FSAP-α2-antiplasmin complexes in plasma. FSAP-inhibitor complexes were measured in the plasma of 20 adult patients undergoing transhiatal esophagectomy, 32 adult patients suffering from severe sepsis and 8 from septic shock and 38 children suffering from meningococcal sepsis. We demonstrate plasma FSAP to be activated upon contact with apoptotic and necrotic cells by an assay detecting complexes between FSAP and its target serpins α2-antiplasmin and C1-inhibitor, respectively. By means of that assay we demonstrate FSAP activation in post-surgery patients, patients suffering from severe sepsis, septic shock and meningococcal sepsis. Levels of FSAP-inhibitor complexes correlate with nucleosome levels and correlate with severity and mortality in these patients. These results suggest FSAP activation to be a sensor for cell death in the circulation and that FSAP activation in sepsis might be involved in nucleosome release, thereby contributing to lethality.


The role of teaching and research hospitals in improving global health (in a globalized world).
Globalization is impacting on Hong Kong and Australia in different ways, but the experience of the public healthcare systems in both jurisdictions suggests a need for teaching and research hospitals to refocus from the management of international patients to better meet the needs for global health. Traditional globalization suggests a stockpiling of capital--a focus on improving global health suggests dismantling the stockpiles and sharing access to the necessary data, information, knowledge and discoveries to further develop local health expertise. Consistent with its position as a leading healthcare provider, the University Health Network (UHN) has been reflecting on the impact of increasing globalization on hospitals. The goals of the UHN paper on globalization are threefold--to suggest how the external and internal environments of hospitals will change as a result of globalization; to suggest a role for hospitals in a globalized world; and to stimulate discussion and debate. Given our perspective, from the other side of the world, we are pleased to contribute to the discussion and debate but will limit our comments to the future role of teaching and research hospitals based on some of the experiences of Australia and Hong Kong. The citizens of Hong Kong have been acutely aware of the issue of globalization--the excellent deep-water harbour has ensured the position of Hong Kong as a major trading hub. Hong Kong has also had a continually evolving role as a financial centre and gateway to China, and with China's accession to the World Trade Organization the impact of globalization will be even greater. On the other hand, the citizens of Australia have lived with geographic isolation, relatively limited natural resources and a small population, all of which have limited their role in global trade and financial markets. However, both Hong Kong and Australia have seen recent benefits from the increasing speed of communication and information transfer and exchange. While it may still take close to a month for Australian practitioners to receive the hard copy of the journal in the mail, a electronic transfer is instantaneous. The globalization of knowledge and practice is one of the largest impacts of the Internet. With one of the most connected populations in the world, Hong Kong is very active in the sharing of knowledge with international experts.


Health effects and metabolism of dietary eicosapentaenoic acid.
Eicosapentaenoic acid (EPA), a long chain fatty acid of the n-3 series, is found in marine foods. Beneficial effects of these foods containing EPA on factors associated with cardiovascular disease risk and arterial thrombosis have been demonstrated. More recently, studies have suggested that EPA may also have a favourable effect on other human diseases such as arthritis, renal disorders, psoriasis and possibly also cancer. EPA is metabolized in a manner generally similar to that of arachidonic acid (AA) although some significant differences between the two are apparent. The metabolic fate of dietary EPA in human subjects is reviewed herein with inclusion of information from animal studies where human data is not available. The metabolism of EPA in the phospholipids of human platelets is emphasized to some extent. Effects of EPA on AA metabolism are also described.


Participation in group-based physical activity programmes for adults in Germany and associated factors: data from a nationwide cohort study.
Characteristics of different participation groups can provide important information to increase participation in group-based physical activity programmes (GPAPs). This study examined four types of participation in GPAPs and the factors that characterised these participant groups. The present sample comprised 3219 participants. The analyses were based on data from the 'German Health Interview and Examination Survey for Adults' (t1) conducted in 2009-2011, which included 3959 people who had participated in the 'German National Health Interview and Examination Survey 1998' (t0). The outcome variable was participation in GPAPs, classified in four groups: 'once at t1' (participation only at t1), 'twice' (participation at t0 and t1), 'once at t0' (participation only at t0) and 'no' (no participation). Predictor variables were sex, age, educational level, income, sports activity, self-rated health and counselling for physical activity, measured at t0 and t1. Frequencies with 95% confidence intervals (CI) for each group were calculated. Four stepwise logistic regression models with estimated odds ratios (OR) were used to determine group differences. The largest participant group was 'no' (80.8%). Among those who participated in GPAPs, the 'once at t1' group was the largest (13.1%), followed by the 'once at t0' (4.0%) and 'twice' (2.1%) groups. 'Once at t1' participation was associated with female sex (OR 2.58), being active in sports (OR 6.59), a high level of education (OR 1.88). If additionally health status and the physician's counselling are included into the models, then having fair/poor/very poor health (OR 1.71) and having had physician counselling on physical activity (OR 2.50) are relevant factors. For 'twice' participation, being female (OR 5.19) and practising sports (OR 4.51) were predictors. GPAPs should be tailored to build on previous experience of sports activities and to reach men as well as people with low education, groups that have been the least reached. To reach more people and encourage participation in GPAPs, providing opportunity for physician counselling for physical activity may be promising, especially with groups of poorer health.


Ejaculation does not contribute to the stress response to electroejaculation in sheep.
Electroejaculation procedures (EEPs) provoke stress; nevertheless, ejaculation produces physiological changes similar as those usually used to measure stress responses. The application of EEP to animals that cannot ejaculate-as ewes-may be useful to discriminate the responses induced by ejaculation from those provoked by EEP. The aim was to determine the stress response to EEP in rams and ewes. The EEPs were applied to 10 rams and 10 ewes during the non-breeding season, and the number of vocalizations, the heart rate, rectal temperature, serum cortisol concentration, biochemical and haematological parameters were measured. Overall, EEP provoked increases in cortisol concentration, glycaemia, rectal temperature and concentration of creatine kinase (all them: p < .0001) as well as relative concentration of granulocytes (p = .003) and absolute granulocyte concentration (p = .0002) in both, rams and ewes. Heart rate, relative concentration of lymphocytes (p = .001), haematocrit (p = .02) and haemoglobin (p = .045) decreased in animals from both genders after EEP. Besides, cortisol (p < .0001), rectal temperature (p = .002) and glycaemia (p = .001) were greater in ewes than rams, and creatine kinase also tended to be greater in ewes than rams (p = .054). On the other hand, the number of animals that vocalized (p = .006), white blood cells (p = .02) and absolute lymphocytes (p = .02) were greater in rams than ewes. The general trends show a similar pattern of stress responses in animals from both genders. Therefore, we concluded that ejaculation does not contribute to the stress response provoked by the EEP. This procedure also provokes muscular damage and probably pain.


Influence of pH on ketoconazole activity against Candida parapsilosis and Candida albicans.
Experiments involving viable count determinations during incubation of yeasts in a synthetic liquid medium showed that ketoconazole was significantly more active at pH 7.0 than it was at pH 5.5 against strains of Candida parapsilosis and Candida albicans.


Function and regulation mechanism of Chk1 during meiotic maturation in porcine oocytes.
Checkpoint 1 (Chk1), as an important member of DNA replication checkpoint and DNA damage response, has an important role during the G2/M stage of mitosis. In this study, we used porcine oocyte as a model to investigate the function of Chk1 during porcine oocyte maturation. Chk1 was expressed from germinal vesicle (GV) to metaphase II (MII) stages, mainly localized in the cytoplasm at GV stage and moved to the spindle after germinal vesicle breakdown (GVBD). Chk1 depletion not only induced oocytes to be arrested at MI stage with abnormal chromosomes arrangement, but also inhibited the degradation of Cyclin B1 and decreased the expression of Mitotic Arrest Deficient 2-Like 1 (Mad2L1), one of spindle assembly checkpoint (SAC) proteins, and cadherin 1 (Cdh1), one of coactivation for anaphase-promoting complex/cyclosome (APC/C). Moreover, Chk1 overexpression delayed GVBD. These results demonstrated that Chk1 facilitated the timely degradation of Cyclin B1 at anaphase I (AI) and maintained the expression of Mad2L1 and Cdh1, which ensured that all chromosomes were accurately located in a line, and then oocytes passed metaphase I (MI) and AI and exited from the first meiotic division successfully. In addition, we proved that Chk1 had not function on GVBD of porcine oocytes, which suggested that maturation of porcine oocytes did not need the DNA damage checkpoint, which was different from the mouse oocyte maturation.