Integration of linkage and chromosome maps of red clover (Trifolium pratense L.).
Red clover (Trifolium pratense L.) is a forage legume and an allogamous diploid plant (2n = 14; 440 Mb). Here, we examine the 7 prometaphase chromosomes of red clover using fluorescence in situ hybridization (FISH) with ribosomal RNA sequences, pericentromeric and telomeric repeats, as well as bacterial artificial chromosome (BAC) clones. Position of hybridization signals and chromosome condensation patterns were quantified by the help of the chromosome image analysis system ver. 4.0 (CHIAS IV). Fourteen BAC clones belonging to linkage groups (LG) 1-7 hybridized to individual chromosomes 4, 2, 6, 5, 1, 7, and 3, respectively. Quantitative analysis of FISH mapping and chromosome analysis using CHIAS IV allowed us to construct a quantitative idiogram that constitutes the comprehensive chromosome map of red clover. Chromosomal positions of the 26S rDNA locus were detected at a heterozygous locus on chromosome 6 in the variety HR, and polymorphisms of rDNA loci were observed in other varieties, although chromosomal positions of some BAC clones did not vary among HR and other varieties. These results demonstrate chromosomal collinearity among allogamous red clover varieties. This integration of genetic linkage and quantitative chromosome maps should provide valuable insight into allogamous legume genetics.


Higher mortality rate in patients hospitalised for acute pulmonary embolism during weekends.
The management of acute pulmonary embolism (PE) is often challenging and requires specific medical expertise, diagnostic techniques and therapeutic options that may not be available in all hospitals throughout the entire week. The aim of our study was to evaluate whether or not an association exists between weekday or weekend admission and mortality for patients hospitalised with acute PE. Using routinely collected hospital administrative data, we examined patients discharged with a diagnosis of PE from the hospitals of the Emilia- Romagna Region in Italy (January 1999-December 2009). The risk of in-hospital death was calculated for admissions at the weekend and compared to weekday admissions. Of a total of 26,560 PEs, 6,788 (25.6%) had been admitted during weekends. PE admissions were most frequent on Mondays (15.8%) and less frequent on Saturdays and Sundays/holidays (12.8%) (p<0.001). Weekend admissions were associated with significantly higher rates of in-hospital mortality than weekday admissions (28% vs. 24.8%) (p<0.001). The risk of weekend admission and in-hospital mortality was higher after adjusting for sender, hospital characteristics, and the Charlson co-morbidity index. In conclusion, hospitalisation for PE on weekends seems to be associated with a significantly higher mortality rate than on weekdays. Further research is needed to investigate the reasons for this observed difference in mortality in order to try and implement future strategies that ensure an adequate level of care throughout the entire week.


Canadian respiratory therapists who considered leaving their clinical position experienced elevated moral distress and adverse psychological and functional outcomes during the COVID-19 pandemic.
Respiratory therapists (RTs) faced morally distressing situations throughout the COVID-19 pandemic, including working with limited resources and facilitating video calls for families of dying patients. Moral distress is associated with a host of adverse psychological and functional outcomes (e.g. depression, anxiety, symptoms of posttraumatic stress disorder [PTSD] and functional impairment) and consideration of position departure. The purpose of this study was to understand the impact of moral distress and its associated psychological and functional outcomes on consideration to leave a clinical position among Canadian RTs during the COVID-19 pandemic. Canadian RTs (N = 213) completed an online survey between February and June 2021. Basic demographic information (e.g. age, sex, gender) and psychometrically validated measures of moral distress, depression, anxiety, stress, PTSD, dissociation, functional impairment, resilience and adverse childhood experiences were collected. One in four RTs reported considering leaving their position. RTs considering leaving reported elevated levels of moral distress and adverse psychological and functional outcomes compared to RTs not considering leaving. Over half (54.5%) of those considering leaving scored above the cut-off for potential diagnosis of PTSD. Previous consideration to leave a position and having left a position in the past each significantly increased the odds of currently considering leaving, along with system-related moral distress and symptoms of PTSD, but the contribution of these latter factors was small. Canadian RTs considering leaving their position reported elevated levels of distress and adverse psychological and functional outcomes, yet these individual-level factors appear unlikely to be the primary factors underlying RTs' consideration to leave, because their effects were small. Further research is required to identify broader, organizational factors that may contribute to consideration of position departure among Canadian RTs.


Subclass discriminant analysis.
Over the years, many Discriminant Analysis (DA) algorithms have been proposed for the study of high-dimensional data in a large variety of problems. Each of these algorithms is tuned to a specific type of data distribution (that which best models the problem at hand). Unfortunately, in most problems the form of each class pdf is a priori unknown, and the selection of the DA algorithm that best fits our data is done over trial-and-error. Ideally, one would like to have a single formulation which can be used for most distribution types. This can be achieved by approximating the underlying distribution of each class with a mixture of Gaussians. In this approach, the major problem to be addressed is that of determining the optimal number of Gaussians per class, i.e., the number of subclasses. In this paper, two criteria able to find the most convenient division of each class into a set of subclasses are derived. Extensive experimental results are shown using five databases. Comparisons are given against Linear Discriminant Analysis (LDA), Direct LDA (DLDA), Heteroscedastic LDA (HLDA), Nonparametric DA (NDA), and Kernel-Based LDA (K-LDA). We show that our method is always the best or comparable to the best.


Optimizing real time fMRI neurofeedback for therapeutic discovery and development.
While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain-behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders.


[Simultaneous quantitative determination of amprenavir and indinavir in human plasma by high-performance liquid chromatography].
A reversed-phase high-performance liquid chromatographic assay for the determination of the HIV protease inhibitors amprenavir (Agenerase) and indinavir (Crixivan) in human plasma is described, using a mobile phase consisting of 0.50 M phosphate buffer (adjusted to pH 5,5) - Milli-Q water - acetonitrile (120: 1,080: 800, v/v/v). A solid-phase extraction using C18 extraction columns (Discovery columns 100 mg, 1 ml Supelco) and a liquid-liquid extraction with 0.5 ml hydrogenocarbonate/carbonate buffer (adjusted to pH 10.6) and 6 ml methyl ter-butyl ether have been compared. The liquid-liquid extraction has been chosen to be easier and cheaper. The method has been validated over the range of 60 to 3,000 ng/ml for amprenavir and 20 to 3,000 ng/ml for indinavir using a 0.5 ml sample volume. The specificity, linearity, accuracy and precision have been studied. The limit of detection was respectively for amprenavir and indinavir 15 and 4 ng, and the limit of quantification was 60 and 20 ng/ml. Stability tests under various conditions were performed. This assay can readily be used in a hospital laboratory for the routine monitoring of plasma concentrations of amprenavir in HIV-infected patients. The trough plasma concentrations average has been determined in patients treated by amprenavir and indinavir for seven months.


[Similar prognosis for transplanted and non-transplanted patients with hematological malignancy admitted to the intensive care unit].
There is scarce information on the influence of stem cell transplantation (SCT) on the prognosis of patients with hematological malignancies admitted to an intensive care unit (ICU). The mortality during ICU admission, long-term survival and the prognostic factors for survival were analyzed and compared in transplanted vs. non-transplanted patients. 116 critically-ill patients with a hematological malignancy transferred to the ICU in a single institution were analyzed. Thirty patients had received SCT prior to ICU admission. Transplanted and non-transplanted patients were comparable for demographic variables (except age and disease status) and reasons for ICU admission. No differences were found in overall survival or survival after discharge from ICU between transplanted and non-transplanted patients. Thirty-nine out of 85 non-transplanted patients (46%) and 11 out of 31 transplanted patients (35%) could be discharged from the ICU. The prognostic factors for survival in non-transplanted patients were need of mechanical ventilation or cardiovascular vasoactive drugs. However, only the liver function impairment predicted the outcome in the transplanted patients through the multivariate analysis. A significant proportion of patients admitted to ICU were discharged despite previous SCT. These patients did not have a worse prognosis than those transferred to the ICU with a hematologic malignancy, although the prognostic factors for survival were different in the 2 groups of patients.


Guanabenz Sensitizes Glioblastoma Cells to Sunitinib by Inhibiting GADD34-Mediated Autophagic Signaling.
Limited therapeutic efficacy of temozolomide (TMZ) against glioblastomas highlights the importance of exploring new drugs for clinical therapy. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is currently being tested as therapy for glioblastomas. Unfortunately, sunitinib still has insufficient activity to cure glioblastomas. Our aim was to determine the molecular mechanisms counteracting sunitinib drug sensitivity and find potential adjuvant drugs for glioblastoma therapy. Through in vitro experiments, transcriptome screening by RNA sequencing, and in silico analyses, we found that sunitinib induced glioma apoptotic death, and downregulated genes were enriched in oncogenic genes of glioblastoma. Meanwhile, sunitinib-upregulated genes were highly associated with the protective autophagy process. Blockade of autophagy significantly enhanced sunitinib's cytotoxicity. Growth arrest and DNA damage-inducible protein (GADD) 34 was identified as a candidate involved in sunitinib-promoted autophagy through activating p38-mitogen-activated protein kinase (MAPK) signaling. Higher GADD34 levels predicted poor survival of glioblastoma patients and induced autophagy formation in desensitizing sunitinib cytotoxicity. Guanabenz, an alpha2-selective adrenergic agonist and GADD34 functional inhibitor, was identified to enhance the efficacy of sunitinib by targeting GADD34-induced protective autophagy in glioblastoma cells, TMZ-resistant cells, hypoxic cultured cells, sphere-forming cells, and colony formation abilities. A better combined treatment effect with sunitinib and guanabenz was also observed by using xenograft mice. Taken together, the sunitinib therapy combined with guanabenz in the inhibition of GADD34-enhanced protective autophagy may provide a new therapeutic strategy for glioblastoma.


[Surveillance of viral hepatitis in Lower Saxony for investigating risk factors: results and experiences from a regional public health project 1999-2001].
In Lower Saxony, a regional public health project for an enlarged surveillance of viral hepatitis was carried out from 1999 to 2001. Five district public health authorities collected additional information on notified viral hepatitis cases in a standardised way, particularly regarding risk factors. In the survey, 270 hepatitis (hep.) cases were investigated, among them hep. A 51 (18.9%), hep. B 87 (32.2%) and hep. C 132 (48.9%). The proportion of chronic cases and healthy carriers was as follows: hep. A 0%, hep. B 47.1% and hep. C 79.5%. In approximately 50% of the cases of all three forms risk factors could be identified. The most frequent risk factors were in hep. A visits to foreign countries (29.4%), contacts to infected individuals (17.6%) and attendance at public institutions or care facilities (13.7%), in hep. B visits to foreign countries (24.1%), contacts to infected individuals (19.5%; sexual contacts 16.1%) and medical treatments (19.5%) and in hep. C injecting drug use (31.1%) and medical treatments (18.2%; 9.8% blood transfusion in the past in combination with chronic hep. C). The results are in accordance with current data under the new infection protection law, where reporting of chronic cases was mostly abolished. In the survey, the well-known risk factors were confirmed, but some risks were reported more frequently than in other surveys, e. g. sexual behaviour for hep. B or injecting drugs for hep. C.


Hands-On Experiences in Deploying Cost-Effective Ambient-Assisted Living Systems.
Older adults' preferences to remain independent in their own homes along with the high costs of nursing home care have motivated the development of Ambient Assisted Living (AAL) technologies which aim at improving the safety, health conditions and wellness of the elderly. This paper reports hands-on experiences in designing, implementing and operating UbiCare, an AAL based prototype system for elderly home care monitoring. The monitoring is based on the recording of environmental parameters like temperature and light intensity as well as micro-level incidents which allows one to infer daily activities like moving, sitting, sleeping, usage of electrical appliances and plumbing components. The prototype is built upon inexpensive, off-the-shelf hardware (e.g., various sensors, Arduino microcontrollers, ZigBee-compatible wireless communication modules) and license-free software, thereby ensuring low system deployment costs. The network comprises nodes placed in a house's main rooms or mounted on furniture, one wearable node, one actuator node and a centralized processing element (coordinator). Upon detecting significant deviations from the ordinary activity patterns of individuals and/or sudden falls, the system issues automated alarms which may be forwarded to authorized caregivers via a variety of communication channels. Furthermore, measured environmental parameters and activity incidents may be monitored through standard web interfaces.


Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: A case report.
Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4). This translocation is believed to involve the fusion of NSD3 or FGFR1 with NUP98; however, apart from targeted mRNA quantitative PCR analysis, no molecular approaches have been utilized to define the chimeric fusions present in these rare cases. Here we present the case of a 51-year-old female with AML with myelodysplastic-related morphologic changes, 13q deletion and t(8;11), where initial fluorescence in situ hybridization (FISH) assays were consistent with the presence of NUP98 and FGFR1 rearrangements, and suggestive of NUP98/FGFR1 fusion. Using a streamlined clinical whole-genome sequencing approach, we resolved the breakpoints of this translocation to intron 4 of NSD3 and intron 12 of NUP98, indicating NUP98/NSD3 rearrangement as the likely underlying aberration. Furthermore, our approach identified small variants in WT1 and STAG2, as well as an interstitial deletion on the short arm of chromosome 12, which were cryptic in G-banded chromosomes. NUP98 fusions in acute leukemia are predictive of poor prognosis. The associated fusion partner and the presence of co-occurring mutations, such as WT1, further refine this prognosis with potential clinical implications. Using a clinical whole-genome sequencing analysis, we resolved t(8;11) breakpoints to NSD3 and NUP98, ruling out the involvement of FGFR1 suggested by FISH while also identifying multiple chromosomal and sequence level aberrations.


Computational modeling of healing: an application of the material force method.
The basic aim of the present contribution is the qualitative simulation of healing phenomena typically encountered in hard and soft tissue mechanics. The mechanical framework is provided by the theory of open system thermodynamics, which will be formulated in the spatial as well as in the material motion context. While the former typically aims at deriving the density and the spatial motion deformation field in response to given spatial forces, the latter will be applied to determine the material forces in response to a given density and material deformation field. We derive a general computational framework within the finite element context that will serve to evaluate both the spatial and the material motion problem. However, once the spatial motion problem has been solved, the solution of the material motion problem represents a mere post-processing step and is thus extremely cheap from a computational point of view. The underlying algorithm will be elaborated systematically by means of two prototype geometries subjected to three different representative loading scenarios, tension, torsion, and bending. Particular focus will be dedicated to the discussion of the additional information provided by the material force method. Since the discrete material node point forces typically point in the direction of potential material deposition, they can be interpreted as a driving force for the healing mechanism.


[Location of an insulinoma by transhepatic phlebography with staged insulin assays (author's transl)].
Insulinoma was easily diagnosed in a 73-year-old woman who had organic hypoglycaemia associated with hyperinsulinism, but the tumour could not be located by echotomography and computerized tomography. The state of the patient's arteries precluded arteriography. Pancreatic phlebography was carried out by the portal transhepatic route and blood was collected at different levels for plasma insulin assays. A very high gradient at the pancreatic isthmus indicated the site of the tumour, which was found on surgery to be precisely there and could be enucleated. This technique cannot be used systematically to locate insulinomas, but it is unquestionably helpful when the tumour cannot be located by other methods or when these are contra-indicated.


Autonomic cardiac regulation, blood pressure and cardiorespiratory fitness responses to different training doses over a 12 week group program in the elderly.
The study assessed the effects of different weekly training frequencies performed over a 12 week exercise programme (strength, endurance, balance) on autonomic cardiac activity, blood pressure and cardiorespiratory fitness (CRF) in elderly individuals. Fifty-eight individuals participated in the study: 2TG (N=24, 71.1±6.4 yrs; 19 females, 5 males) performing two, 60min sessions/week; and 3TG (N=34, 72.3±7.9 yrs; 25 females, 9 males) performing three, 60min sessions/week. Time domain and spectral analysis of heart rate variability (HRV) quantified autonomic cardiac regulation. Natural logarithm (Ln) transformation was applied to all HRV parameters. There were significant reductions in total power (Ln TP) (p=0.006), low frequency (Ln LF) (p=0.013), high frequency (Ln HF) (p=0.013) and root mean square of successive differences (Ln rMSSD) (p=0.014) post training in 3TG after intervention. Diastolic BP (DBP) decreased significantly in both groups (2TG: P<0.001; 3TG: P<0.001). Both groups showed significant improvements in six-minute walk distance (2TG: P=0.003, 3TG: P=0.001). However, there were significant HRV differences between 2TG and 3TG for Ln TP (P=0.018), Ln LF (P=0.049), Ln HF (P=0.039) and Ln rMSSD (P=0.049). A combined exercise programme resulted in improved DBP and CRF irrespective of training two or three 60min sessions/week. However, training three, sessions/week induced negative health-related changes in autonomic cardiac activity through reducing HRV parasympathetic function, while HRV was maintained in the group training twice a week.


[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats].
Spironolactone, a diuretic antagonist of aldosterone has an unexplained side effect of amenorrhea which could be due to an angiogenesis inhibition. In this study we compared the effects of spironolactone, canrenone an active metabolite of spironolactone and eplerenone a more selective mineralocorticoid antagonist in rats implanted with a fibrin gel chamber. Perforated plexiglass chambers filled with rat fibrin, spironolactone (50 microM), canrenone (100 microM), eplerenone (500 microM), DMSO (0.05%) and control were implanted into the dorsal subcutaneous space of wistar rats. After 14 days of implantation, an invasion of the fibrin gel chamber by neovascularised buds had occurred through the holes. The number of vessels in the central field and in two or three peripheral fields covering the surface of the bud, were measured for each drug tested and compared to the control. In spironolactone treated chambers, the numbers of peripheral and central vessels were significantly reduced compared to control (p < 0.001). Canrenone, eplerenone and DMSO did not reduce the number of vessels (m +/- ESM, ANOVA followed by Newman-Keuls test). Spironolactone but not canrenone, nor eplerenone inhibited vessels formation in vivo. This antiangiogenic activity appeared to be not related to the antimineralocorticoid effect of spironolactone.


Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production.
Forkhead box P3 (FOXP3) is currently thought to be the most specific marker for naturally occurring CD4(+)CD25(+) T regulatory cells (nTregs). In mice, expression of FoxP3 is strictly correlated with regulatory activity, whereas increasing evidence suggests that in humans, activated T effector cells (Teffs) may also express FOXP3. In order to better define the role of FOXP3 in human Teff cells, we investigated the intensity and kinetics of expression in ex vivo Teff cells, suppressed Teff cells and Teff cell lines. We found that all dividing Teff cells expressed FOXP3, but only transiently, and at levels that were significantly lower than those in suppressive nTregs. This temporary expression in Teff cells was insufficient to suppress expression of reported targets of FOXP3 repressor activity, including CD127, IL-2 and IFN-gamma, and was not correlated with induction of a nTreg phenotype. Thus expression of FOXP3 is a normal consequence of CD4(+) T cell activation and, in humans, it can no longer be used as an exclusive marker of nTregs. These data indicate that our current understanding of how FOXP3 contributes to immune tolerance in humans needs to be re-evaluated.


Stem cell homeostasis by integral feedback through the niche.
Hematopoiesis is a paradigm for tissue development and renewal from stem cells. Experiments show that the maintenance of hematopoietic stem cells (HSCs) relies on signals from niche cells. However, it is not known how the size of the HSC compartment is set. Competition by HSCs for niche access has been suggested, yet niche cells in the bone marrow outnumber HSCs. Here we propose a cooperative model of HSC homeostasis in which stem and niche cells mutually interact such that niche cells function as negative feedback regulators of HSC proliferation. This model explains puzzling experimental findings, including homeostatic recovery of the HSC compartment after irradiation versus apparent lack of recovery after HSC ablation. We show that bidirectional niche-stem cell regulation has properties of a proportional-integral feedback controller. Moreover, we predict that the outflux of differentiated cells from HSCs can be regulated by the affinity of HSCs for niche cells. Much effort has been devoted to elucidating niche cell signaling to stem cells; our theoretical insights indicate that studying the effect of stem cells on the niche may be equally important for understanding stem cell homeostasis.


A distributed chemosensory circuit for oxygen preference in C. elegans.
The nematode Caenorhabditis elegans has complex, naturally variable behavioral responses to environmental oxygen, food, and other animals. C. elegans detects oxygen through soluble guanylate cyclase homologs (sGCs) and responds to it differently depending on the activity of the neuropeptide receptor NPR-1: npr-1(lf) and naturally isolated npr-1(215F) animals avoid high oxygen and aggregate in the presence of food; npr-1(215V) animals do not. We show here that hyperoxia avoidance integrates food with npr-1 activity through neuromodulation of a distributed oxygen-sensing network. Hyperoxia avoidance is stimulated by sGC-expressing oxygen-sensing neurons, nociceptive neurons, and ADF sensory neurons. In npr-1(215V) animals, the switch from weak aerotaxis on food to strong aerotaxis in its absence requires close regulation of the neurotransmitter serotonin in the ADF neurons; high levels of ADF serotonin promote hyperoxia avoidance. In npr-1(lf) animals, food regulation is masked by increased activity of the oxygen-sensing neurons. Hyperoxia avoidance is also regulated by the neuronal TGF-beta homolog DAF-7, a secreted mediator of crowding and stress responses. DAF-7 inhibits serotonin synthesis in ADF, suggesting that ADF serotonin is a convergence point for regulation of hyperoxia avoidance. Coalitions of neurons that promote and repress hyperoxia avoidance generate a subtle and flexible response to environmental oxygen.


TRPV3: a 'more than skinny' channel.
The skin is our largest organ serving different tasks from barrier formation through somatosensing to hair development. Recently, members of the large trp (Transient Receptor Potential, TRP) gene family encoding proteins that form cation selective ion channel have been identified to play a crucial role in skin functions. Within the 28 different mammalian TRP channels, TRPV3 might be the most important member in the skin. This review gives an overview on functional properties of TRPV3 in skin physiology and in certain skin diseases.


Both maturation and survival of human dendritic cells are impaired in the presence of anergic/suppressor T cells.
T cell suppression is a well established phenomenon, but the mechanisms involved are still a matter of debate. Mouse anergic T cells were shown to suppress responder T cell activation by inhibiting the antigen presenting function of DC. In the present work we studied the effects of co-culturing human anergic CD4+ T cells with autologous dendritic cells (DC) at different stages of maturation. Either DC maturation or survival, depending on whether immature or mature DC where used as APC, was impaired in the presence of anergic cells. Indeed, MHC and costimulatory molecule up-regulation was inhibited in immature DC, whereas apoptotic phenomena were favored in mature DC and consequently in responder T cells. Defective ligation of CD40 by CD40L (CD154) was responsible for CD95-mediated and spontaneous apoptosis of DC as well as for a failure of their maturation process. These findings indicate that lack of activation of CD40 on DC by CD40L-defective anergic cells might be the primary event involved in T cell suppression and support the role of CD40 signaling in regulating both activation and survival of DC.


Respiratory syncytial virus infection. Rapid diagnosis in children by use of indirect immunofluorescence.
Specimens of 387 nasopharyngeal suction smears obtained from 354 children hospitalized with acute respiratory infections during an eight-month period were examined for the presence of respiratory syncytial (RS) virus by the indirect immunofluorescence antibody technique (IFAT) and by conventional tissue culture infectivity techniques. Respiratory syncytial virus was identified in nasopharyngeal suction smear specimens from 123 of these specimens (32%) with the use of both techniques. Of the specimens positive on tissue culture 92% were also positive for RS virus by IFAT. However, eight specimens positive for RS virus by tissue culture were negative by IFAT, although three of the specimens were technically unsuitable. Six percent of the specimens negative for RS virus by tissue culture were positive for RS virus antigen when tested by IFAT. Using IFAT, identification of RS virus could be accomplished within four to six hours, whereas isolation by tissue culture took an average period of ten days. These data suggest that IFAT is a reliable means for the rapid diagnosis of RS virus infection in infants and children.


[Polypectomy of the digestive tract].
Endoscopic polypectomy was one of the first therapeutic procedures, as it was done even before the appearance of colonoscopy through rigid endoscopies. Immediately after the use of monopolar current in endoscopy, polyp resection in the digestive tract has been a elective treatment, and is reserved only for surgeries which are very extensive, or those which cannot be surrounded with a wire loop. The impact of the polypectomy in colonic adenomas has been notable because of the possibility of the diagnosis of the entire surgical piece, and for the treatment of lesions with premalignant potential. The success of the complete resection of a colonic polyp is directly proportional to its size and shape, given that pendicular polyps guarantee the complete extirpation of the tumor, in that sessile polyps require additional techniques to elevate the lesion. Among the precautions in prepolypectomy are found the following: Anti-inflammatory non-steroidal (AINS) suspension; anticoagulant suspension, and adequate intestinal preparation. Hemorrhage and perforation occur in 0.1% of each. Postcoagulation syndrome is a secondary effect which only requires vigilance. The inherent complications in the use of secondary current are minimal when its technical principles are known. The success of endoscopic polypectomy depends on the refinement of the procedure, which is achieved through experience.


Highly ordered mesoporous cobalt oxide nanostructures: synthesis, characterisation, magnetic properties, and applications for electrochemical energy devices.
Highly ordered mesoporous Co(3)O(4) nanostructures were prepared using KIT-6 and SBA-15 silica as hard templates. The structures were confirmed by small angle X-ray diffraction, high resolution transmission electron microscopy, and N(2) adsorption-desorption isotherm analysis. Both KIT-6 cubic and SBA-15 hexagonal mesoporous Co(3)O(4) samples exhibited a low Néel temperature and bulk antiferromagnetic coupling due to geometric confinement of antiferromagnetic order within the nanoparticles. Mesoporous Co(3)O(4) electrode materials have demonstrated the high lithium storage capacity of more than 1200 mAh g(-1) with an excellent cycle life. They also exhibited a high specific capacitance of 370 F g(-1) as electrodes in supercapacitors.


Sequential signaling through Notch1 and erbB receptors mediates radial glia differentiation.
Radial glia cells both generate neurons and physically guide nascent neurons to their target destination in the cortex, and as such they are essential for CNS development. It has been proposed that in the developing cerebellum, neuronal contact induces radial glia formation, however, the mechanisms involved in this process are not well understood. Here we demonstrate that neuronal induction of radial glia formation is the result of sequential signaling through Notch1 and erbB receptors. First, Notch1 activation by neuronal contact induces the glial expression of the brain lipid binding protein (BLBP) and erbB2 genes. Interestingly, two different signaling pathways mediate these effects of Notch1 on transcription, BLBP expression being dependent on Su(H), whereas erbB2 is regulated by a yet unidentified Notch1 pathway. The subsequent increase in erbB2 receptor expression makes the glia more responsive to neuronal NRG, which then induces the morphological transformation into radial glia. Thus, these results unveil some of the mechanisms underlying radial glia formation.


A connection between MAPK pathways and circadian clocks.
Circadian clocks and mitogen-activated protein kinase (MAPK) signaling pathways are fundamental features of eukaryotic cells. Both pathways provide mechanisms for cells to respond to environmental stimuli, and links between them are known. We recently reported that the circadian clock in Neurospora crassa regulates daily rhythms in accumulation of phosphorylated, and thus active, OS-2 MAPK, a relative of mammalian p38 MAPK, when cells are grown in constant conditions. In the absence of acute stress, rhythmically activated MAPK then signals to downstream effector molecules to regulate rhythmic expression of target genes of the pathway. Clock regulation of MAPK signaling pathways provides a mechanism to coordinately control major groups of genes such that they peak at the appropriate times of day to provide a growth and survival advantage to the organism by anticipating stresses. MAPK pathways are well known for their role in cell proliferation and tumor suppression. New evidence reveals that some mammalian clock components also function as tumor suppressors and rhythms in phospho-MAPK have been observed in higher eukaryotes. Thus, the role of the clock in regulation of the activity of MAPK pathways provides important clues into the function of the circadian clock as a tumor suppressor.


Haplotype Counting for Sensitive Chimerism Testing: Potential for Early Leukemia Relapse Detection.
Fields of forensics, transplantation, and paternity rely on human identity testing. Currently, this is accomplished through amplification of microsatellites followed by capillary electrophoresis. An alternative and theoretically better approach uses multiple single-nucleotide polymorphisms located within a small region of DNA, a method we initially developed using HLA-A and called haplotype counting. Herein, we validated seven additional polymorphic loci, sequenced a total of 45 individuals from three of the 1000 Genomes populations (15 from each), and determined the number of haplotypes, heterozygosity, and polymorphic information content for each locus. In addition, we developed a multiplex PCR that amplifies five of these loci simultaneously. Using this strategy with a small cohort of leukemic patients who underwent allogeneic bone marrow transplantation, we first attempted to define a threshold (0.26% recipient) by examining seven patients who tested all donor and did not relapse. Although this initial threshold will need to be confirmed in a larger cohort, we detected increased recipient DNA above this threshold 90 to 145 days earlier than microsatellite positivity, and 127 to 142 days before clinical relapse in four of eight patients (50%). Haplotype counting using these novel loci may be useful for ultrasensitive detection in fields such as bone marrow transplantation, solid organ transplant rejection, patient identification, and forensics.


A nanoporous interferometric micro-sensor for biomedical detection of volatile sulphur compounds.
This work presents the use of nanoporous anodic aluminium oxide [AAO] for reflective interferometric sensing of volatile sulphur compounds and hydrogen sulphide [H2S] gas. Detection is based on changes of the interference signal from AAO porous layer as a result of specific adsorption of gas molecules with sulphur functional groups on a gold-coated surface. A nanoporous AAO sensing platform with optimised pore diameters (30 nm) and length (4 µm) was fabricated using a two-step anodization process in 0.3 M oxalic, followed by coating with a thin gold film (8 nm). The AAO is assembled in a specially designed microfluidic chip supported with a miniature fibre optic system that is able to measure changes of reflective interference signal (Fabry-Perrot fringes). When the sensor is exposed to a small concentration of H2S gas, the interference signal showed a concentration-dependent wavelength shifting of the Fabry-Perot interference fringe spectrum, as a result of the adsorption of H2S molecules on the Au surface and changes in the refractive index of the AAO. A practical biomedical application of reflectometric interference spectroscopy [RIfS] Au-AAO sensor for malodour measurement was successfully shown. The RIfS method based on a nanoporous AAO platform is simple, easy to miniaturise, inexpensive and has great potential for development of gas sensing devices for a range of medical and environmental applications.


Time-resolved fluorescence spectroscopy study of excited state dynamics of alkyl- and benzo-substituted triphyrin(2.1.1).
We have investigated the photophysical properties of alkyl-substituted triphyrin(2.1.1) (ATp) and benzotriphyrin(2.1.1) (BTp) by steady-state and time-resolved fluorescence spectroscopy. We focused on the effect of NH proton tautomerization, planarity of the macrocycles, and substituents on these properties. The fluorescence quantum yields (Φy) of ATp did not depend on solvent viscosity, whereas those of BTp increased with solvent viscosity, reaching a maximum value of 0.17 in paraffin. Interestingly, analyzing Φy showed that the non-radiative rate constant of BTp decreased sharply as the solvent viscosity increased. These results suggest that the substituted phenyl groups play a crucial role in suppressing molecular distortion, thus leading to decreased non-radiative relaxation in triphyrin(2.1.1). The hydrogen bond formed in the inner cavity potentially contributes to the suppression of the structural distortion, whereas the pyrrole rings in the macrocycle are close, as in porphycene.


Antipyrine metabolism in patients with diabetes mellitus.
1. A pharmacokinetic study of antipyrine was performed in healthy volunteers and diabetic subjects, ten in each group. After a single oral dose of antipyrine (18 mg/kg) multiple samples of saliva were collected for the determination of antipyrine concentration and a pharmacokinetic analysis was carried out. 2. The mean salivary half-life of antipyrine was found to be significantly higher in patients with uncontrolled diabetes as compared to the healthy subjects. However, there was no significant difference in volume of distribution and metabolic clearance rates. 3. After 15 days of insulin therapy, there was a significant reduction in the mean half-life of antipyrine in the diabetic patients. The mean half-life of antipyrine in the patients with controlled diabetes was not significantly different from that of the normal healthy subjects. 4. There was no significant correlation between the salivary half-life of antipyrine and a 2 hour postprandial blood sugar level in the diabetic patients. 5. Our data suggest impaired hepatic microsomal enzyme activity in patients with uncontrolled diabetes which was corrected after 15 days of insulin therapy.


The distribution and origin of the calretinin-containing innervation of the nucleus accumbens of the rat.
The nucleus accumbens of the rat consists of several subregions that can be distinguished on the basis of histochemical markers. For example, the calcium-binding protein calbindin D28k is a useful marker of the core compartment of the nucleus accumbens. Calretinin, another calcium-binding protein, is found in a dense fibre plexus in the accumbal shell and septal pole regions. The source of the accumbal calretinin innervation is not known. We examined the distribution of calretinin in the nucleus accumbens and used tract-tracing and lesion methods to determine the source of this calretinin innervation. Intense calretinin immunoreactivity was present in the medial shell, but the density of calretinin axons diminished sharply in the ventrolateral shell. Regions of dense calretinin immunostaining and those areas with calbindin-like immunoreactive cell bodies were generally segregated in the nucleus accumbens, although some overlap in the transition region between the core and shell was seen. Small clusters of calretinin-immunoreactive fibres were seen in the core, where they were restricted to calbindin-negative patches. Injections of the anterograde tracer biotinylated dextran amine into the paraventricular thalamic nucleus labelled fibres in calretinin-rich regions of the accumbens. Conversely, injections of Fluoro-gold into the accumbal shell retrogradely labelled numerous cells in the paraventricular thalamic nucleus that were calretinin-immunoreactive. Electrolytic lesions of the paraventricular thalamic nucleus reduced calretinin levels in the shell by approximately 80%. These data indicate that the calretinin innervation of the nucleus accumbens is derived primarily from the thalamic paraventricular nucleus, and marks accumbal territories that are largely complementary to those defined by calbindin.


Minimal effective weight-based dosing of ondansetron to reduce hypotension in cesarean section under spinal anesthesia: a randomized controlled superiority trial.
The weight-based dosing of ondansetron to reduce hypotension has never been investigated. The aim of this study is to determine the optimal dose of ondansetron required based on the patient's weight to reduce hypotension following spinal anesthesia for cesarean section. In this prospective, triple-blinded, parallel group, randomized controlled trial, a total of 228 pregnant women were randomized to receive either normal saline (group NS) or ondansetron 0.05 mg/kg (group O1) or ondansetron 0.1 mg/kg (group O2) intravenously 5 min before induction of spinal anesthesia. The incidence of hypotension, mean arterial pressure, heart rate, vasopressor requirements, and blood loss between the three groups were compared. Maternal and neonatal complications were also assessed. Changes in blood pressure and heart rate were compared using the generalized estimating equations method. Thirteen patients were excluded from the analysis because of no intervention (n = 12) and protocol violation (n = 1). Two hundred and fifteen patients remained for the intention-to-treat analysis. The incidence of hypotension in groups NS (n = 72), O1 (n = 71), and O2 (n = 72) were 81.9%, 84.5%, and 73.6%, respectively (P = 0.23). The episodes of hypotension before delivery (first 14 min after spinal anesthesia) were significantly higher in group O1 compared to NS (5 vs 2, P = 0.02). The overall heart rates throughout the operations were not different among the three groups. The ephedrine requirements and amount of blood loss were also similar among the three groups. The metoclopramide requirement was significantly lower in group O2 compared to group NS (2.8% vs 16.7%, P = 0.01). There were no serious adverse events in terms of maternal or neonatal complications. Ondansetron 0.05 mg/kg or 0.1 mg/kg administered before spinal anesthesia did not reduce the incidence of hypotension in this study. Thai Clinical Trials Registry, TCTR 20160323001 , 22 March 2016.


The influence of acidity on microbial fuel cells containing Shewanella oneidensis.
Microbial fuel cells (MFCs) traditionally operate at pH values between 6 and 8. However, the effect of pH on the growth and electron transfer abilities of Shewanella oneidensis MR-1 (wild-type) and DSP10 (spontaneous mutant), bacteria commonly used in MFCs, to electrodes has not been examined. Miniature MFCs using bare graphite felt electrodes and nanoporous polycarbonate membranes with MR-1 or DSP10 cultures generated >8W/m(3) and approximately 400muA between pH 6-7. The DSP10 strain significantly outperformed MR-1 at neutral pH but underperformed at pH 5. Higher concentrations of DSP10 were sustained at pH 7 relative to that of MR-1, whereas at pH 5 this trend was reversed indicating that cell count was not solely responsible for the observed differences in current. S. oneidensis MR-1 was determined to be more suitable than DSP10 for MFCs with elevated acidity levels. The concentration of riboflavin in the bacterial cultures was reduced significantly at pH 5 for DSP10, as determined by high performance liquid chromatography (HPLC) of the filter sterilized growth media. In addition, these results suggest that mediator biosynthesis and not solely bacterial concentration plays a significant role in current output from S. oneidensis containing MFCs.


Measuring lipoprotein(a) for cardiovascular disease prevention - in whom and when?
The aim of this study is to summarize major cardiovascular guideline recommendations on lipoprotein(a) and highlighting recent findings that emphasize how measuring lipoprotein(a) once in all adults is meaningful regardless of age, sex, comorbidities, or ethnicity. Many international guidelines now recommend once in a lifetime measurement of lipoprotein(a) in all adult individuals to facilitate accurate risk prediction. Lipoprotein(a)-lowering therapy to reduce cardiovascular disease is on the horizon, with results from the first phase 3 trial expected in 2025. Elevated lipoprotein(a) is an independent causal risk factor for atherosclerotic cardiovascular disease and aortic valve stenosis and measuring lipoprotein(a) once in all individuals regardless of age, sex, comorbidities, or ethnicity is meaningful to aid in risk stratification.


Axon guidance cues in auditory development.
The innervation of the cochlear sensory epithelium is intricately organized, allowing the tonotopy established by the auditory hair cells to be maintained along the ascending auditory pathways. These auditory projections are patterned by several gene families that regulate neurite attraction and repulsion, known as axon guidance cues. In this review, the roles of various axon guidance molecules, including fibroblast growth factor, ephs, semaphorins, netrins and slits, are examined in light of their known contribution to auditory development. Additionally, morphogens are discussed in the context of their recently described influence on axonal pathfinding in other sensory systems. The elucidation of these various mechanisms may guide the development of therapies aimed at maximizing the connectivity of auditory neurons in the context of congenital or acquired sensorineural hearing loss, especially as pertains to cochlear implants. Further afield, improved understanding of the molecular processes which regulate innervation of the organ of Corti during normal development may prove useful in connecting regenerated hair cells to the central nervous system.


Negative experiences on Ecstasy: the role of drug, set and setting.
Similar to other sociological studies of Ecstasy use, the authors' research suggests that Ecstasy users tend to report positive effects of the drug. However, we also observed that most users experienced at least one adverse psychological outcome while using Ecstasy. The present study examines those negative experiences within the context of drug, set and setting. Data were collected through in-depth interviews with 98 current or former users of Ecstasy. The results indicate that, in general, negative experiences with Ecstasy did not deter people from using the drug again. The findings suggest that most negative experiences with Ecstasy can be attributed to the interaction between two or more factors, nearly always involving set or setting. Although various analyses have shown that the same "brand" of Ecstasy can contain varying degrees of MDMA, other drugs and adulterants, results from the present study suggest that users' expectations of the drug's effects appear to be related to the brand or label of Ecstasy that is consumed. The role of individual disposition in producing negative drug experiences is less clear; it is possible that this factor might interact with user set or friends' set in contributing to the overall drug experience.


Cobalt-60: the heart of gamma-radiation sterilization.
Currently, more than three million cubic metres of single-use medical devices are sterilized by gamma radiation each year. The wide use of this method of sterilization is a result of the lethal effects of ionizing radiation on microbial populations and the penetrative powers of cobalt-60. This article describes how cobalt-60 is produced and used in gamma-radiation sterilization, and how it is disposed of once it has reached the end of its useful life. Cobalt-60 sources typically have a life of 20 years, at which point they are returned to the suppliers for re-encapsulation, reprocessing, recycling, or disposal.


Resistance of Mycobacterium tuberculosis to antibiotics in Lao PDR: first multicentric study conducted in 3 hospitals.
It is estimated that Lao People's Democratic Republic (Lao PDR) ranks fifth among the seven countries most affected by TB in the WHO Western Pacific Region. However, because of late implementation of mycobacterial culture, no study on resistance to anti-TB drugs had been performed yet. The objective of this study was to document drug resistance rate among patients hospitalized for pulmonary TB in threeprovinces of Lao PDR. A cross-sectional study was conducted in three sites, one central and two regional hospitals, from April to November 2010. For each TB suspected patient sputum smear microscopy and culture on Lowenstein-Jensen media were performed. GenoType® MTBDRplus assay was used to test the susceptibility to isoniazid (INH) and rifampicin (RMP), GenoType® MTBDRsl for second-line drugs and GenoType® Mycobacterium CMAS for non-tuberculous mycobacteria (NTM). Out of 104 positive culture on Lowenstein-Jensen, 87 (83.6%) were M. tuberculosis and 17 (16.4%) were NTM. Of 73 new TB cases, 5 isolates (6.8%) were resistant to INH. Of 14 previously treated cases, 2 isolates (14.3%) were resistant to INH and one isolate was XDR. Despite an overall rate of resistance still moderate, the frequency of mutations conferring INH monoresistance and identification of the first strain of XDR require strengthening surveillance of drug resistant tuberculosis in Lao PDR.


Case report: Blindness associated with Learedius learedi trematode infection in a green sea turtle, Chelonia mydas, of the northern Red Sea.
Spirorchiid blood flukes are widespread in sea turtles, causing disease and mortality in their populations, with high prevalence in several ocean basins. Besides being leading parasitic causes of sea turtle strandings in several parts of the world, these infectious agents can cause endocarditis, vasculitis, thrombosis, miliary egg granulomas, and aneurysms, which ultimately may compromise the survival of green sea turtles. More severe cases may also result in multifocal granulomatous meningitis or pneumonia, both of which can be fatal. Herein, we report the first case of severe trematode infection, Caused by Learedius learedi, in a green sea turtle in the northern Red Sea; this infection is associated with bilateral blindness. Necropsy revealed multiple granulomas with intralesional trematode eggs in the optic nerve, eyes, spleen, heart, and lungs. The parasite was identified as Learedius learedi through specific primers of the ribosomal genome and COI sequences obtained from GenBank. Altogether, these findings emphasize the importance of recognizing the systemic nature of this particular fluke infection to ultimately protect the lives of these marine animals and ensure the sustainability of these species in the wild.


Management of digestive tract fistulas. A review.
Digestive tract fistulas are a complex subject in terms both of classification and management. There is still a lack of firm epidemiological data regarding the their incidence, though the prognostic factors conditioning the prognosis of these patients are now well known. They are related mainly to the nutritional status of the patients and to the presence or otherwise of sepsis. Instrumental investigations should be aimed not merely at identifying the complication, but also at guiding clinicians in their choice of therapeutic management. According to the various situations arising, the treatment will be surgical, endoscopic or conservative medical. In the latter case, the clinician should establish first of all whether, as a result of the site of the fistula or the nutritional status, the patient requires total parenteral or enteral artificial nutrition, whenever possible. In those cases in which parenteral nutrition is indicated, the ideal drug with the best proven ability to shorten healing times and reduce the number of complications when used in combination with parenteral nutrition is naturally occurring somatostatin at the dose of 250 micrograms/h over 24 h. In all other cases, if the fistula is clinically important, its synthetic analogue, octreotide, should be the drug of choice and can be administered subcutaneously. The amount of octreotide administered ranges from 300 to 600 micrograms/day in 3 or 4 daily doses.


[Differential diagnosis and therapy of gigantopapillary conjunctivitis].
If wearers of contact lenses present with secretion and incompatibility of the contact lens, simple ectropionation of the upper eyelids often is sufficient to diagnose a giant papillary conjunctivitis as the cause. This form of papillary hypertrophy affecting wearers of both hard and soft contact lenses is morphologically similar to vernal conjunctivitis, which should be considered in cases of corneal ulceration resistant to therapy. The histological difference between the two forms of papillary hypertrophy is that contact lens-induced giant papillary conjunctivitis shows remarkably less eosinophilic infiltration of the papillary stroma. Both forms of papillary hypertrophy seem to be based on a complex immunologic reaction.


Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort.
Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, previous studies are limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS measured by the hyperinsulinaemic euglycaemic clamp in a healthy population on no medications. We performed oral glucose tolerance test (OGTT) and measured % body fat (DEXA), BMI, blood pressure and M-value (hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males). The majority of the study population (n = 89, 85.6%) were classified on their BMI as overweight/obese. eGFR was related to age, BMI, M-value (IS), 2-hour glucose levels post OGTT and white blood cell count (WBC) (all p < 0.05); but not to SBP (p = 0.1) or fasting glucose levels (p = 0.2). After adjustment for gender, BMI, SBP and WBC, the inverse association between eGFR and M-value (p = 0.001), and 2-hour glucose post OGTT (p = 0.02) persisted. In conclusion, although eGFR has been associated with BMI and blood pressure in previous studies, in our healthy population, eGFR was more closely related to markers of glucose metabolism (IS and 2-hour glucose post OGTT) than to BMI and blood pressure.


High intracellular calcium levels during and after electrical discharges in molluscan peptidergic neurons.
Intracellular calcium levels ([Ca2+]i) during and following electrical activity of the neuroendocrine caudodorsal cells of the pond snail (Lymnaea stagnalis) were measured in situ and in dissociated cells by combining electrical recordings and Fura-2 measurements. Caudodorsal cells are typical neuroendocrine cells that control egg laying via the release of a set of peptides during a stereotyped discharge of action potentials. Single action potentials or short trains of spikes in dissociated caudodorsal cells induced only small but consistent increases in [Ca2+]i. With longer or repeated spike trains, larger [Ca2+]i transients were measured, indicating accumulation of calcium. The calcium channel blocker Ni2+ suppressed the calcium elevation, suggesting that calcium influx occurred through voltage-activated calcium channels. Calcium levels in caudodorsal cells in situ were measured before, during and after the stereotyped firing pattern, a approximately 35-min discharge of regular spiking. Basal calcium levels in caudodorsal cells in situ were about 125 nM. During the initial phase of the discharge, the intracellular calcium level increased to approximately 250 nM. Maximal calcium levels (300-600 nM) were only reached at the final phase of the discharge or several minutes after the cessation of firing. Calcium levels remained elevated for up to 1 h after the end of the discharge. During this time, caudodorsal cells were characterized by very low excitability. We suggest that the prolonged, elevated level of calcium following the discharge need not be directly dependent on action potentials. The long-lasting [Ca2+]i elevation may cause the release of neuropeptides to outlast the duration of electrical activity, thus uncoupling release from spiking. In addition, it may cause reduced excitability of neuroendocrine cells following a period of spiking, thereby inducing a refractory period.


POCN Ni(ii) pincer complexes: synthesis, characterization and evaluation of catalytic hydrosilylation and hydroboration activities.
A series of iminophosphinite POCN pincer Ni(ii) complexes, (POCN)NiMe and (POCN)NiLn(BX4) (L = CH3CN, n = 0, 1; X = F, Ph, C6F5), have been developed and subjected to catalytic hydrosilylation of alkenes, aldehydes and ketones and hydroboration of carbonyl compounds. The stoichiometric reactivity of (POCN)NiMe and (POCN)Ni(BF4) with PhSiH3 and HBPin suggests that catalytic reactions proceed via the hydride intermediate (POCN)NiH. With regard to reactions with HBPin, efficient and mild hydroboration of a variety of carbonyl compounds, including highly chemoselective hydroboration of benzaldehyde in the presence of other common potent reductive functional groups, such as alkenes, alkynes, esters, amides, nitriles, nitro compounds and even ketones, and the first example of base metal catalyzed hydroboration of amides, including mild direct hydroborative reduction of primary and secondary amides to borylated amines were demonstrated for (POCN)NiMe.


Estimating risk propagation between interacting firms on inter-firm complex network.
We derive a stochastic function of risk propagation empirically from comprehensive data of chain-reaction bankruptcy events in Japan from 2006 to 2015 over 5,000 pairs of firms. The probability is formulated by firm interaction between the pair of firms; it is proportional to the product of α-th power of the size of the first bankrupt firm and β-th power of that of the chain-reaction bankrupt firm. We confirm that α is positive and β is negative throughout the observing period, meaning that the probability of cascading failure is higher between a larger first bankrupt firm and smaller trading firm. We additionally introduce a numerical model simulating the whole ecosystem of firms and show that the interaction kernel is a key factor to express complexities of spreading bankruptcy risks on real ecosystems.


The role of drug delivery systems in cancer chemotherapy.
One approach to effective cancer chemotherapy is to maximize the exposure of tumor cells to cytotoxic drugs while minimizing the exposure of sensitive normal cells to such agents. This implies the need for control of the pharmacodynamics of anti-tumor drugs in terms of blood clearance kinetics, disposition in tissues, passage across membrane barriers, and interaction with metabolic pathways. A promising approach to pharmacodynamic control is the microencapsulation of drugs within liposomes. The clearance kinetics and tissue disposition of the drug is then dictated by the pharmacokinetic behavior of the liposomal carrier. The blood clearance rates and tissue uptake of liposomes themselves depend upon physical characteristics such as particle size and surface charge. It is also possible to promote specific interaction between cells and liposomes in vitro by preparing liposomes containing biological macromolecules such as lectin receptors. The potentialities of microencapsulation as an adjunct to chemotherapy are discussed.


Muscular dystrophy modeling in zebrafish.
Skeletal muscle performs an essential function in human physiology with defects in genes encoding a variety of cellular components resulting in various types of inherited muscle disorders. Muscular dystrophies (MDs) are a severe and heterogeneous type of human muscle disease, manifested by progressive muscle wasting and degeneration. The disease pathogenesis and therapeutic options for MDs have been investigated for decades using rodent models, and considerable knowledge has been accumulated on the cause and pathogenetic mechanisms of this group of human disorders. However, due to some differences between disease severity and progression, what is learned in mammalian models does not always transfer to humans, prompting the desire for additional and alternative models. More recently, zebrafish have emerged as a novel and robust animal model for the study of human muscle disease. Zebrafish MD models possess a number of distinct advantages for modeling human muscle disorders, including the availability and ease of generating mutations in homologous disease-causing genes, the ability to image living muscle tissue in an intact animal, and the suitability of zebrafish larvae for large-scale chemical screens. In this chapter, we review the current understanding of molecular and cellular mechanisms involved in MDs, the process of myogenesis in zebrafish, and the structural and functional characteristics of zebrafish larval muscles. We further discuss the insights gained from the key zebrafish MD models that have been so far generated, and we summarize the attempts that have been made to screen for small molecules inhibitors of the dystrophic phenotypes using these models. Overall, these studies demonstrate that zebrafish is a useful in vivo system for modeling aspects of human skeletal muscle disorders. Studies using these models have contributed both to the understanding of the pathogenesis of muscle wasting disorders and demonstrated their utility as highly relevant models to implement therapeutic screening regimens.


Strategies for detecting toxoplasma immunity.
A strategy for identifying toxoplasma immunity in pregnancy must provide good evidence of immunity but not falsely reassure; that for immunocompromised patients should identify immunity and also the risk of reactivated toxoplasmosis. Using sera from both of these patient groups, the performance of an in-house IgG EIA and two commonly used commercial assays (Abbott AxSYM Toxo-G and Eiken latex test) were compared with the dye test. False-positive results were obtained using the IgG enzyme immunoassay (EIA) and AxSYM Toxo-G, and false negatives using all three screen tests. During pregnancy, positive results may falsely reassure, and patients should be tested for toxoplasma-specific IgM to differentiate between current infection and immunity. In immunocompromised patients, positive results indicate immunity but negative results do not exclude it; these should be tested by dye test. Despite these reservations, we have demonstrated that immunity screening can be performed within a district general hospital.


The loving support breastfeeding campaign: awareness and practices of health care providers in Mississippi.
To evaluate the impact of the national breastfeeding promotion campaign, Loving Support Makes Breastfeeding Work, on health care providers in Mississippi. Cross-sectional study. The Mississippi WIC (Women, Infants, and Children) program implemented the national Loving Support project for the state. Questionnaires were mailed to all hospitals with obstetric services and WIC clinics and to a random sample of one half of the practicing pediatricians and one third of the practicing family physicians in the state. Two hundred and two health care providers, including 104 nurses and 98 physicians, responded to the questionnaire. Health care providers' (a) awareness of the breastfeeding promotion activities in the state; (b) changes in practice in providing breastfeeding advice and referrals to lactation specialists and for breast pumps; and (c) changes in the management of breastfeeding-related problems. A significantly higher proportion of nurses than physicians mentioned breastfeeding benefits to mothers, provided breastfeeding management advice, and referred mothers for breast pumps and to lactation specialists after the campaign. This study showed the positive impact of the campaign on nurses' breastfeeding awareness and practices. More efforts are needed to continue breastfeeding outreach activities for health care providers.


Targeted Molecular Strategies for Genetic Neurodevelopmental Disorders: Emerging Lessons from Dravet Syndrome.
Dravet syndrome is a severe developmental and epileptic encephalopathy mostly caused by heterozygous mutation of the SCN1A gene encoding the voltage-gated sodium channel α subunit Nav1.1. Multiple seizure types, cognitive deterioration, behavioral disturbances, ataxia, and sudden unexpected death associated with epilepsy are a hallmark of the disease. Recently approved antiseizure medications such as fenfluramine and cannabidiol have been shown to reduce seizure burden. However, patients with Dravet syndrome are still medically refractory in the majority of cases, and there is a high demand for new therapies aiming to improve behavioral and cognitive outcome. Drug-repurposing approaches for SCN1A-related Dravet syndrome are currently under investigation (i.e., lorcaserin, clemizole, and ataluren). New therapeutic concepts also arise from the field of precision medicine by upregulating functional SCN1A or by activating Nav1.1. These include antisense nucleotides directed against the nonproductive transcript of SCN1A with the poison exon 20N and against an inhibitory noncoding antisense RNA of SCN1A. Gene therapy approaches such as adeno-associated virus-based upregulation of SCN1A using a transcriptional activator (ETX101) or CRISPR/dCas technologies show promising results in preclinical studies. Although these new treatment concepts still need further clinical research, they offer great potential for precise and disease modifying treatment of Dravet syndrome.


Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss.
Given evidence for age-related differences in the effects of drugs of abuse, surprisingly few preclinical studies have explored effects of opioids in adolescents (versus adults). This study compared the motor stimulating and ataxic effects of repeatedly administered morphine in adolescent, late adolescent, and adult mice. Mice were treated with saline or morphine (10-100 mg/kg, i.p.) once per day for 4 days, and morphine (3.2-56 mg/kg)-induced locomotion was assessed 3 days or 5 weeks later. Different mice were treated repeatedly with morphine and ataxia was measured. Acute administration of morphine increased locomotion more in adolescents than in adults. Repeated morphine enhanced morphine-induced locomotion, assessed 3 days later, to a similar extent in each age group (minimum effective dose 17.8 mg/kg). This sensitization was still evident 5 weeks later when the adolescents had become adult, but was smaller and occurred at a higher dose (56 mg/kg). In animals treated repeatedly with morphine as adults, sensitization was no longer apparent 5 weeks later. Intermittent morphine was at least 10-fold less potent to produce body weight loss in adolescents than in adults. Repeated morphine did not alter morphine-induced ataxia at any age. Compared with adults, adolescents were more sensitive to the acute locomotor stimulating effects of morphine and to its long-lasting locomotor sensitizing effects, consistent with overactivity of dopamine systems during adolescence. In contrast, adolescents were less sensitive than adults to body weight loss induced by intermittent morphine, an effect indicative of morphine withdrawal in adult rodents.


Prevention of soya-induced enteritis in Atlantic salmon (Salmo salar) by bacteria grown on natural gas is dose dependent and related to epithelial MHC II reactivity and CD8α+ intraepithelial lymphocytes.
An experiment was carried out to study the preventive effect of bacterial meal (BM) produced from natural gas against plant-induced enteropathy in Atlantic salmon (Salmo salar). Salmon were fed a diet based on fish meal (FM) or seven diets with 200 g/kg solvent-extracted soyabean meal (SBM) to induce enteritis in combination with increasing levels of BM from 0 to 300 g/kg. Salmon fed a SBM-containing diet without BM developed typical SBM-induced enteritis. The enteritis gradually disappeared with increasing inclusion of BM. By morphometry, no significant (P>0.05) differences in the size of stretches stained for proliferating cell nuclear antigen were found with 150 g/kg BM compared with the FM diet. Increasing BM inclusion caused a gradual decline in the number of cluster of differentiation 8 α positive (CD8α+) intraepithelial lymphocytes, and fish fed BM at 200 g/kg or higher revealed no significant difference from the FM diet. Histological sections stained with antibody for MHC class II (MHC II) showed that fish with intestinal inflammation had more MHC II-reactive cells in the lamina propria and submucosa, but less in the epithelium and brush border, compared with fish without inflammation. There were no significant (P>0.05) differences in growth among the diets, but the highest levels of BM slightly reduced protein digestibility and increased the weight of the distal intestine. In conclusion, the prevention of SBM-induced enteritis by BM is dose dependent and related to intestinal levels of MHC II- and CD8α-reactive cells.


Novel inhibitors of leukocyte transendothelial migration.
Leukocyte transendothelial migration is one of the most important step in launching an inflammatory immune response and chronic inflammation can lead to devastating diseases. Leukocyte migration inhibitors are considered as promising and potentially effective therapeutic agents to treat inflammatory and auto-immune disorders. In this study, based on previous trioxotetrahydropyrimidin based integrin inhibitors that suboptimally blocked leukocyte adhesion, twelve molecules with a modified scaffold were designed, synthesized, and tested in vitro for their capacity to block the transendothelial migration of immune cells. One of the molecules, namely, methyl 4-((2-(tert-butyl)-6-((2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) methyl) phenoxy) methyl) benzoate, (compound 12), completely blocked leukocyte transendothelial migration, without any toxic effects on immune or endothelial cells (IC50 = 2.4 µM). In vivo, compound 12 exhibited significant therapeutic effects in inflammatory bowel disease (IBD)/Crohn's disease, multiple sclerosis, fatty liver disease, and rheumatoid arthritis models. A detailed acute and chronic toxicity profile of the lead compound in vivo did not reveal any toxic effects. Such a type of molecule might therefore provide a unique starting point for designing a novel class of leukocyte transmigration blocking agents with broad therapeutic applications in inflammatory and auto-immune pathologies.


Complementary and alternative medicine use by Canadian patients with inflammatory bowel disease: results from a national survey.
Previous studies of complementary and alternative medicine (CAM) use by patients with inflammatory bowel disease (IBD) have relied on samples from specialty clinics. The aim of this study was to determine the prevalence of use and perceived outcomes of CAM in a large, diverse IBD population. A postal survey of the members of the Crohn's and Colitis Foundation of Canada gathered data on demographic, disease, and conventional IBD treatment characteristics, and on the use and perceived effects of CAM. Respondents were characterized as not using CAM, as past or present users of CAM for their IBD, or as present users of CAM for other reasons. Comparisons between groups were made with the chi(2) test. The final sample included 2847 IBD patients. Current or past use of CAM for IBD was reported by 1332 patients, of whom 666 continued their use of CAM. Use was lowest in the eastern provinces and highest in the west. Only 15% had used CAM before their IBD diagnosis. Herbal therapies were the most commonly used (41% of CAM users). Improvements in sense of well-being, IBD symptoms, and sense of control over the disease were the most commonly reported benefits. Only 16% of prior CAM users reported any adverse effect of CAM use. A complementary practitioner was consulted by 34%. During the previous year, 46% had spend more than $250 on CAM. Use of CAM by IBD patients is very common. Most of these patients attribute significant benefits to their CAM use. Few report significant adverse events.


Comparing Plan Recognition Algorithms Through Standard Plan Libraries.
Plan recognition deals with reasoning about the goals and execution process of an actor, given observations of its actions. It is one of the fundamental problems of AI, applicable to many domains, from user interfaces to cyber-security. Despite the prevalence of these approaches, they lack a standard representation, and have not been compared using a common testbed. This paper provides a first step towards bridging this gap by providing a standard plan library representation that can be used by hierarchical, discrete-space plan recognition and evaluation criteria to consider when comparing plan recognition algorithms. This representation is comprehensive enough to describe a variety of known plan recognition problems and can be easily used by existing algorithms in this class. We use this common representation to thoroughly compare two known approaches, represented by two algorithms, SBR and Probabilistic Hostile Agent Task Tracker (PHATT). We provide meaningful insights about the differences and abilities of these algorithms, and evaluate these insights both theoretically and empirically. We show a tradeoff between expressiveness and efficiency: SBR is usually superior to PHATT in terms of computation time and space, but at the expense of functionality and representational compactness. We also show how different properties of the plan library affect the complexity of the recognition process, regardless of the concrete algorithm used. Lastly, we show how these insights can be used to form a new algorithm that outperforms existing approaches both in terms of expressiveness and efficiency.


Leveraging family history in population-based case-control association studies.
Population-based epidemiologic studies often gather information from study participants on disease history among their family members. Although investigators widely recognize that family history will be associated with genotypes of the participants at disease susceptibility loci, they commonly ignore such information in primary genetic association analyses. In this report, we propose a simple approach to association testing by incorporating family history information as a "phenotype." We account for the expected attenuation in strength of association of the genotype of study participants with family history under Mendelian transmission. The proposed analysis can be performed using standard statistical software adopting either a meta- or pooled-analysis framework. Re-analysis of a total of 115 known susceptibility single-nucleotide polymorphisms, discovered through genome-wide association studies for several disease traits, indicates that incorporation of family history information can increase efficiency by as much as 40%. Efficiency gain depends on the type of design used for conducting the primary study, extent of family history, and accuracy and completeness of reporting.


Outcome and prognostic factors of childhood diffuse brainstem glioma.
The outcome and prognostic factors of brainstem glioma were evaluated following radiotherapy methods. Between 1986 and 2001, 45 childhood patients with diffuse brainstem glioma were treated. There were 26 boys and 19 girls, with a median age of 7 years (range 3 approximately 18). The histopathological diagnoses were confirmed in 13 patients, which revealed a low-grade glioma in four patients, and high-grade glioma in the other nine. Before 1993, radiation therapy using a regime of 1.8 to 2.0 Gy once a day was performed in 16 cases; thereafter, a regimes of 1.1 or 1.5 Gy twice a day was given in 15 and 14 cases, respectively. Nine patients were treated with adjuvant chemotherapy. The response to the treatment was evaluated by the MRI findings 4 weeks after radiotherapy. After radiotherapy, the neurological deficit improved in 42 of the 45 patients (93%). The MRI responses were as follows; partial response 22/39 (56%), minimal to no response in 16/39 (41%) and tumor progression in 1/39 (3%). The median time to disease progression was 7 months, and the median survival was 12 months; the overall survival rate at 1 year was 41%. There was no significant prognostic factor for overall survival. The progression-free survival was influenced by the tumor histology (low grade vs. high grade, p=0.05) in those patients whose pathology was confirmed. The radiation therapy fractionation schedule did not influence the survival. Low grade histology was a possible favorable prognostic factor of progression-free survival in pediatric brainstem glioma patients.


Emergency unscheduled returns: can we do better?
This study serves to identify the reasons for unscheduled return visits to the emergency department (ED), paying particular attention to system, physician and patient factors. Its purpose is to highlight inadequacies and plan strategies to reduce re-attendance. All patients returning to the ED within 72 hours of initial visit were identified between January 2005 and June 2005. 842 cases were reviewed to identify reasons for unscheduled returns. Unscheduled return visits accounted for two percent of patient encounters with the younger mobile group of patients contributing the largest number. Patients presenting with abdominal pain constituted a quarter of unscheduled returns, where more than half were admitted. Possible causes were lack of rehydration and lack of proper discharge advice to these patients. The assessment and disposition of abdominal pain patients with uncertain aetiology was a major category and 68.7 percent of missed diagnosis came from this group. There was a significant difference in the unscheduled return rates between the senior and junior doctors. There was minimal morbidity and no mortality among patients who returned to the ED for the second time. A proposed strategy to reduce the number of unscheduled returns would be to target patients with abdominal pain with more liberal hydration strategies. Discharge advice with information about expected prognosis and specific signs and symptoms to look out for should be included. Educational sessions and better supervision of junior staff emphasising acute abdominal conditions should be actively incorporated to avoid associated morbidities with a missed diagnosis.


Photoplethysmography-based derivation of physiological information using the BioPoint.
The BioPoint is a new wireless and wearable device, targeting both the ambulatory and on-site monitoring of biosignals. It is described as being capable of streaming and recording the i) electromyography, ii) electrocardiography, iii) electrodermal activity, iv) photoplethysmography, v) skin temperature and vi) actigraphy simultaneously, while making the raw signals recorded by the sensors readily available. However, an in-depth assessment of the biophysical signals recorded by this device, as well as its ability to derive vital signs and other health metrics, remains to be carried out. Consequently, this work proposes a preliminary study to evaluate the quality of the signals that can be acquired by this wearable with a focus on the derivation of heart rate and peripheral blood oxygenation via photoplethysmography. The device is quantitatively compared to the medical-grade pulse oximeter NoninConnect 3245, by Nonin inc. This study was performed with participants wearing the BioPoint at different positions on the body (finger, wrist, forearm, biceps and plantar arch), while the NoninConnect was worn on the fingertip and used as the ground truth. The results show that the BioPoint can accurately determine both heart rate and oxygen saturation from various locations on the body. However, as the BioPoint's photoplethysmograph is not calibrated it cannot be used for medical purposes (non-medical-grade).


Calculation of vibrationally resolved absorption spectra of acenes and pyrene.
The absorption spectra of naphthalene, anthracene, pentacene and pyrene in the ultraviolet-visible (UV-Vis) range have been simulated by using an efficient real-time generating function method that combines calculated adiabatic electronic excitation energies with vibrational energies of the excited states. The vertical electronic excitation energies have been calculated at the density functional theory level using the PBE0 functional and at the second-order approximate coupled-cluster level (CC2). The absorption spectra have been calculated at the PBE0 level for the studied molecules and at the CC2 level for naphthalene. The transition probabilities between vibrationally resolved states were calculated by using the real-time generating function method employing the full Duschinsky formalism. The absorption spectrum for naphthalene calculated at the PBE0 and CC2 levels agrees well with the experimental one after the simulated spectra have been blue-shifted by 0.48 eV and 0.12 eV at the PBE0 and CC2 level, respectively. The absorption spectra for anthracene, pentacene and pyrene simulated at the PBE0 level agree well with the experimental ones when they are shifted by 0.49 eV, 0.57 eV and 0.46 eV, respectively. The strongest transitions of the main vibrational bands have been assigned.


Seasonal variation of birthweight in Bangladesh.
Analysis of birthweights of 1772 singleton babies born alive at Kumudini Hospital in rural Bangladesh over 2 consecutive years, 1983 and 1984, showed a consistent seasonal variation. The highest birthweights occurred in the period March to May (summer) and the lowest in the September to November period (autumn). This could not be correlated with differences in maternal age or parity, but was correlated with seasonal availability of food and changes in children's nutritional status as recorded in the hospital under-5s clinic. It is concluded that poor maternal nutrition in the last trimester of pregnancies in mothers delivered in the September to November period is the main factor, and recommendations for health education are made accordingly.


Primary care physician communication at hospital discharge reduces medication discrepancies.
Medication discrepancies are common as patients transition from hospital to home. Errors with post-discharge medication regimens may play a role in hospital readmissions. To determine whether primary care physician (PCP) contact with patients at hospital discharge impacts the frequency of medication discrepancies at 24 hours post-discharge. With the PCP-Enhanced Discharge Communication Intervention, PCPs were asked to speak with treating hospitalists and contact patients within 24 hours of hospital discharge (either in person or by phone) to discuss any hospital medication changes. Research staff enrolled subjects during their hospitalization and telephoned subjects 48 hours post-discharge to determine medication discrepancies and PCP contact. One hundred fourteen community-dwelling adults, admitted to acute medicine services >24 hours on ≥ 5 medications. Of the 114 subjects enrolled in the hospital, 75 subjects completed 48 hours postdischarge phone interviews. Of the 75 study patients, 39 patients (50.6%) experienced a total of 84 medication discrepancies (mean, 2.1 discrepancies/patient). Subjects who were contacted by their PCP at discharge were 70% less likely to have a discrepancy when compared with those not contacted (P = 0.04). Males were 4.34 times more likely to have a discrepancy (P = 0.02). PCP communication with patients within 24 hours of discharge was associated with decreased medication discrepancies. Our results further demonstrate the importance of PCP involvement in the hospital discharge process.


Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring.
Intrauterine growth restriction caused by uteroplacental insufficiency increases the risk of cardiovascular disease in adulthood. Vascular mechanisms in female offspring are poorly understood. The aim of this study was to investigate the effects of uteroplacental insufficiency on blood pressure, vascular reactivity and arterial stiffness in four vascular beds in female offspring born growth restricted. Uteroplacental insufficiency was induced on day 18 of gestation in Wistar Kyoto rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Controls). Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of 18-month-old female offspring. Collagen and elastin fibres were quantified using circular crossed-polarized light microscopy and quantitative real time polymerase chain reaction. Restricted female offspring were born 10-15% smaller. Restricted females were normotensive, had plasma triglycerides 2-fold elevated and had uterine endothelial dysfunction, attributed to a 23% reduction in the maximal relaxation produced by endothelium-derived hyperpolarizing factor. Uterine artery stiffness was increased, with an augmented proportion of thick and decreased proportion of thin collagen fibres. Vascular reactivity and mechanical wall properties were preserved in mesenteric, renal and femoral arteries in growth restricted females. Female offspring born growth restricted have selective uterine artery endothelial dysfunction and increased wall stiffness. The preserved vascular function in other arteries may explain the lack of hypertension in these females. The uterine artery specific dysfunction has potential implications for impaired pregnancy adaptations and a compromised intrauterine environment of the next generation.


Job satisfaction, personality traits, and its impact on motivation among mental health workers.
Working in a resource setting that caters to people's poor mental health is associated with increased vulnerability to physical, psychological, and social stressors that make motivation to work a difficult goal to attain. One way of viewing physical and social stressors in the workplace is to evaluate job satisfaction which has both intrinsic and extrinsic components. The personality of workers is a component of psychological wellbeing and this determines the way events and situations are perceived. Thus, the achievement of the mission and vision of an organisation will be dependent on the level of motivation of the employees which will be influenced by their predominant personality traits and the level of satisfaction at work. My study aimed to sought to highlight the relationship between motivation, job satisfaction and personality dimensions. The Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria. Our study involved a cross-sectional study of staff showing the relationship between motivation, job satisfaction and personality traits among mental health workers. A total of 146 participants using systematic proportional sampling were analysed with a response rate of 67.3%. A Socio-demographic Questionnaire, Minnesota Satisfaction Questionnaire (Short Version), Big Five Inventory and the Multidimensional Work-Motivation Scale were administered to the participants. In the analysis, linear correlation and linear regression were used to determine the relationship between continuous variables (Normality was determined using kurtosis and skewness) while t-test was used to determine the relationship between categorical independent variables and continuous dependent variables. The level of significance was set at < 0.05 while higher scores using the Multidimensional Work-Motivation Scale represented motivated participants and vis-a-vis. The socio-demographic variable was explored using descriptive statistics; the relationship between personality, job satisfaction and motivation were explored using t-test. Most of the participants were married (80.8%), female (60.3%), with at least tertiary education (63%) and with an occupational status of class I (76%). The mean age of the participants was 40.29 ± 8.27 with a mean length of service of 13.63 ± 8.49. The most dominant personality traits were agreeableness (97.3%) and conscientiousness (97.3%), and the least was neuroticism (55.5). High agreeableness (0.01), high conscientiousness (0.03), and high openness (0.01) were significant and positively correlated with motivation. The relationship between motivation and gender (t = 4.26; p ≤ 0.001) and occupational status were statistically significant (t = -3.59; p ≤ 0.001). To proffer a solution to poor motivation in the workplace, human resource department should give more focus to individuals with high scores in agreeableness, conscientiousness, and openness. This is because it appears that they are more likely to be motivated at work and likely to move the organisation to a greater height. Besides, those with high neurotic scores who have already been employed will require some form of psychological remodelling (therapy), so they can contribute meaningfully to the institution.


Predictive Prognostic Value of Tissue-Based MicroRNA Expression in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.
Oral squamous cell carcinoma (OSCC) is a common type of cancer characterized by a low survival rate, mostly due to local recurrence and metastasis. In view of the importance of predicting tumor behavior in the choice of treatment strategies for OSCC, several studies have attempted to investigate the prognostic value of tissue biomarkers, including microRNA (miRNA). The purpose of this study was to perform a systematic review and meta-analysis to evaluate the relationship between miRNA expression and survival of OSCC patients. Studies were identified by searching on MEDLINE/PubMed, SCOPUS, Web of Science, and Google Scholar. Quality assessment of studies was performed with the Newcastle-Ottawa Scale. Data were collected from cohort studies comparing disease-free survival and overall survival in patients with high miRNA expression compared to those with low expression. A total of 15 studies featuring 1,200 OSCC samples, predominantly from Asia, met the inclusion criteria and were included in the meta-analysis. Poor prognosis correlated with upregulation of 9 miRNAs (miR-21, miR-455-5p, miiR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181) and downregulation of 7 miRNAs (miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b). The pooled hazard ratio values (95% confidence interval) related to different miRNA expression for overall survival and disease-free survival were 2.65 (2.07-3.39) and 1.95 (1.28-2.98), respectively. The results of this meta-analysis revealed that the expression levels of specific miRNAs can robustly predict prognosis of OSCC patients.


Neisseria gonorrhoeae induces focal polymerization of actin in primary human urethral epithelium.
The pathogenic Neisseria species induce cytoskeletal reorganization in immortalized cell lines. In Chang conjunctival epithelium and T84 intestinal epithelium, focal cytoskeletal rearrangements in which bacteria contacted the epithelial surface were observed. We show that actin footprints are induced in gonococcus-challenged primary urethral epithelium. Moreover, the microbes induced microvillus extension from the epithelial cell surface. Our results indicate that formation of actin footprints is not an artifact of commonly used immortalized cell lines.


Elucidation of the Synthetic Mechanism of Acylceramide, an Essential Lipid for Skin Barrier Function.
The primary function of the skin is to act as a permeability barrier that prevents water loss from inside the body and external invasion such as by pathogens, harmful substances, and allergens. Lipids play a critical role in skin barrier formation by forming multi-lamellar structures in the stratum corneum, the outermost cell layer of the epidermis. Ceramide, the backbone of sphingolipids, accounts for more than 50% of the stratum corneum lipids. Acylceramides are epidermis-specific ceramide species essential for skin barrier formation. Decreases in acylceramide levels and changes in ceramide composition and chain-length are associated with such cutaneous disorders as ichthyosis, atopic dermatitis, and psoriasis. Acylceramide consists of a long-chain base and an amide-linked ultra-long-chain fatty acid (ULCFA, 28-36 carbon chain), which is ω-hydroxylated and esterified with linoleic acid. Although the molecular mechanism by which acylceramide is generated has not been fully understood for decades, we recently identified two genes, CYP4F22 and PNPLA1, involved in acylceramide synthesis and elucidated the entire biosynthetic pathway of acylceramide: the synthesis of ULCFA by ELOVL1 and ELOVL4, ω-hydroxylation of the ULCFA by CYP4F22, amide-bond formation with a long-chain base by CERS3, and transacylation of linoleic acid from triacylglycerol to ω-hydroxyceramide by PNPLA1 to generate acylceramide. CYP4F22 and PNPLA1 are the causative genes of ichthyosis. We demonstrated that mutations of CYP4F22 or PNPLA1 markedly reduced acylceramide production. Our recent findings provide important insights into the molecular mechanisms of skin barrier formation and of ichthyosis pathogenesis.


[Development of a new soybean variety with null trypsin inhibitor and lipoxygenase 2.3 genes--zhonghuang 16 and its cultivation practices].
Soybean protein is a kind of high-quality protein composed of balanced amino acids, which contains all kinds of amino acid, especially 8 amino acids necessary for human, but also contains some components that are not good for human and affect food quality, such as Trypsin inhibitor and Lipoxygenase. Nutritional value and processing quality of soybean can be improved by means of development of new variety with null Lox and Ti. In this paper, a new soybean variety Zhonghuang 16 (originally name as Zhongzuo 96-952) was developed by Institute of Crop Breeding and Cultivation Chinese Academy of Agricultural Sciences through years of biochemical marker assistant selection for null trypsin inhibitor by Native-polyacrylamid gel electrophoresis (Native-PAGE) and null lipoxygenase by means of isoelectric focusing-polyacrylamid gel electrophoresis (IEF-PAGE) in the hybrid progenies of "ti15176" (Female parent)--a high-yielding, mosaic virus resistant and null trypsin inhibitor line and "Century-2.3" (Male parent)--a null lipoxygenase near isogene line of an elite American variety "Century". This variety was subjected to Beijing regional trial for summer-sowing soybean during 1999-2000, and to Beijing demonstration test in 2001. In 2002, it was passed the examination and approval by the Beijing Committee of Crop Variety Examination and Approval because of its outstanding characteristics such as high and stable yielding, good quality (high protein and fat content, high protein content and good protein quality-null Ti and Lox2.3), disease resistant and good general character. It is the first new soybean variety with null Ti and Lox2.3 genes in our country. In this paper, the development process and cultivation of Zhonghuang 16 were described.