Oligomerization mediated by a helix-loop-helix-like domain of baculovirus IE1 is required for early promoter transactivation.
IE1 is a principal transcriptional regulator of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Transactivation by IE1 is stimulated when early viral promoters are cis linked to homologous-region (hr) enhancer sequences of AcMNPV. This transcriptional enhancement is correlated with the binding of IE1 as a dimer to the 28-bp palindromic repeats comprising the hr enhancer. To define the role of homophilic interactions in IE1 transactivation, we have mapped the IE1 domains required for oligomerization. We report here that IE1 oligomerizes by a mechanism independent of enhancer binding, as demonstrated by in vitro pull-down assays using fusions of IE1 (582 residues) to the C terminus of glutathione S-transferase. In vivo oligomerization of IE1 was verified by immunoprecipitation of IE1 complexes from extracts of plasmid-transfected SF21 cells. Analyses of a series of site-directed IE1 insertion mutations indicated that a helix-loop-helix (HLH)-like domain extending from residue 543 to residue 568 is the primary determinant of oligomerization. Replacement of residues within the hydrophobic face of the putative dimerization domain disrupted IE1 homophilic interactions and caused loss of IE1 transactivation of hr-dependent promoters in plasmid transfection assays. Thus, oligomerization is required for IE1 transcriptional stimulation. HLH mutations also reduced IE1 stability and abrogated transactivation of non-hr-dependent promoters. These data support a model wherein IE1 oligomerizes prior to DNA binding to facilitate proper interaction with the symmetrical recognition sites within the hr enhancer and thereby promote the transcription of early viral genes.


Rapid generation of a human monoclonal antibody to combat Middle East respiratory syndrome.
The last century has witnessed the emergence of several previously unknown viruses as life-threatening human pathogens. Several examples include HIV, Ebola, Lujo, and, most recently, the Middle East respiratory syndrome (MERS) and Ebola. In this study, we describe a method for the swift generation of a human-derived monoclonal antibody, known as LCA60, as a treatment for MERS infections. LCA60 antibody was generated using the Cellclone Technology from the immortalized B cells of a human donor recovering from MERS. Only four months were required from the initial screening of B cells to the development of a stable CHO cell line suitable for the production of clinical grade antibody, thereby delineating a rapid pathway for the development of antiviral therapies against emerging viruses. Currently, the LCA60 antibody is being considered for clinical development, which includes prophylaxis in individuals at risk and a treatment for severe MERS-CoV infections.


Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?
Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011-2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.


Dynamic testicular adhesion junctions are immunologically unique. I. Localization of p120 catenin in rat testis.
In the seminiferous epithelium, morphologically diverse junctions mediate inter-Sertoli and Sertoli-germ cell adhesive contact, but the molecular composition of such junctions is not well known. At prototypical adherens junctions, proteins termed catenins bind to the intracellular domain of classic cadherins and regulate the strength of adhesion. Using a panel of monoclonal antibodies (5A7, 8D11, and 15D2), p120 catenin (p120) was localized in postnatal and adult rat testis cryosections and touch preparations by immunofluorescence. Immunoprecipitation of testis homogenates showed that at least four p120 isoforms were expressed from Postnatal Day 7 through adulthood. Both inter-Sertoli and Sertoli-germ cell junctions were p120-positive, however, individual p120 monoclonals were localized to specific junctions. The 5A7 and 8D11 antibodies colocalized with beta-catenin and plectin at inter-Sertoli and Sertoli-spermatocyte junctions. At inter-Sertoli junctions, p120 was juxtaposed to but did not colocalize with f-actin. Thus, p120 is likely a component of inter-Sertoli desmosome-like junctions. In contrast, the 15D2 monoclonal antibody specifically immunostained Sertoli-round spermatid and inter-Sertoli cell junctions in a dynamic pattern. From the time that round spermatids form to their differentiation into elongate spermatids, Sertoli-round spermatid 15D2 immunostaining cycled from a single mass to a curvilinear pattern, and finally to punctate structures scattered throughout the epithelium. This localization and stage-specific immunostaining pattern indicated that 15D2 recognized Sertoli-round spermatid desmosome-like junctions. Between Sertoli cells, 15D2 immunostained newly formed junctions (at Postnatal Days 21 through 43), but not mature junctions in the adult. From these data, we conclude that p120 is a component of most, if not all, desmosome-like junctions, and that desmosome-like junctions between different cell types contain a unique molecular composition.


Magnetic resonance diffractive imaging.
Magnetic resonance (MR) diffractive imaging is proposed as a new approach to MR angiography. The expression of the nuclear MR signal is similar to the equation for the Fresnel diffraction of a three-dimensional (3-D) object in light or sound waves. The proposed technique offers the possibility of fast angiographic imaging and the on-line reconstruction of 3-D volumetric images using the holographic technique. Static imaging experiments using an ultra-low-field MRI system are performed to verify the feasibility of the technique. It is shown that the images focused on an arbitrary plane can be reconstructed from data scanned in two dimensions, even though blurred image data is superimposed on the image. Moreover, the 3-D image can be observed in a coherent optical imaging system. This study demonstrates the possibility of the proposed method as a fast imaging technique for MR angiography.


Women's opinions about routine HIV testing during pregnancy: implications for the opt-out approach.
The 1995 United States Public Health Service (USPHS) recommendation regarding HIV testing for pregnant women was revised in 2003 calling for routine HIV testing for pregnant women with patient notification. Routine testing (opt-out screening) offers women the opportunity to decline HIV testing but eliminates the requirement of pretest counseling and separate written consent. To assess women's opinions about the opt-out approach to HIV testing during pregnancy, a cross-sectional survey was conducted in May-June 2004 at 14 geographically diverse clinics funded by Ryan White CARE Act (RWCA) Part C and Part D agreements. Of 853 women respondents to the one-page, self-completed survey questionnaire, 90% agreed with routine HIV testing and 91% reported being comfortable with testing, demonstrating that the large majority of women agree with and support HIV testing as a part of routine prenatal care. Women's opinions were associated with HIV testing status, e.g., 76% of women who had never been tested for HIV thought HIV testing should be part of a routine pregnancy check-up as compared with women who were HIV-negative (93%) or HIV-positive (90%) (chi(2) = 31.3943, p < 0.0001). Comfort with HIV testing was associated with higher HIV knowledge. Approximately half of the respondents indicated that HIV tests are different from other tests and that women need more information prior to testing. Results demonstrated clear consensus in support of routine testing. Increased efforts to disseminate resources to providers coupled with providers' effective communication of information to pregnant women can build on the support that women have conveyed for HIV testing during pregnancy.


Deficient crisis-probing practices and taken-for-granted assumptions in health organisations.
The practice of crisis-probing in proactive organisations involves meticulous and sustained investigation into operational processes and management structures for potential weaknesses and flaws before they become difficult to resolve. In health organisations, crisis probing is a necessary part of preparing to manage emerging health threats. This study examined the degree of pre-emptive probing in health organisations and the type of crisis training provided to determine whether or not they are prepared in this area. This evidence-based study draws on cross-sectional responses provided by executives from chiropractic, physiotherapy, and podiatry practices; dental and medical clinics; pharmacies; aged care facilities; and hospitals. The data show a marked lack of mandatory probing and a generalised failure to reward crisis reporting. Crisis prevention training is poor in all organisations except hospitals and aged care facilities where it occurs at an adequate frequency. However this training focuses primarily on natural disasters, fails to address most other crisis types, is mostly reactive and not designed to probe for and uncover key taken-for-granted assumptions. Crisis-probing in health organisations is inadequate, and improvements in this area may well translate into measurable improvements in preparedness and response outcomes.


Personal and family history of cancer and the risk of Barrett's esophagus in men.
The association between Barrett's esophagus (BE) and a personal or family history of cancer other than gastroesophageal remains unknown. To evaluate the effect of personal and family history of certain cancers and cancer treatments on the risk of BE, we analyzed data from a Veterans Affairs case-control study that included 264 men with definitive BE (cases) and 1486 men without BE (controls). Patients with history of esophageal or gastric cancer were excluded. Patients underwent elective esophagogastroduodenoscopy or a study esophagogastroduodenoscopy concurrently with screening colonoscopy to determine BE status. Personal and family history of several types of cancer was obtained from self-reported questionnaires, supplemented and verified by electronic medical-record reviews. We estimated the association between personal and family history of cancer or radiation/chemotherapy, and BE. Personal history of oropharyngeal cancer (1.5% vs. 0.4%) or prostate cancer (7.2% vs. 4.4%) was more frequently present in cases than controls. The association between BE and prostate cancer persisted in multivariable analyses (adjusted odds ratio 1.90; 95% confidence interval 1.07-3.38, P = 0.028) while that with oropharyngeal cancer (adjusted odds ratio 3.63; 95% confidence interval 0.92-14.29, P = 0.066) was attenuated after adjusting for retained covariates of age, race, gastroesophageal reflux disease, hiatal hernia, and proton pump inhibitor use. Within the subset of patients with cancer, prior treatment with radiation or chemotherapy was not associated with BE. There were no significant differences between cases and controls in the proportions of subjects with several specific malignancies in first- or second-degree relatives. In conclusion, the risk of BE in men may be elevated with prior personal history of oropharyngeal or prostate cancer. However, prior cancer treatments and family history of cancer were not associated with increased risk of BE. Further studies are needed to elucidate if there is a causative relationship or shared risk factors between prostate cancer and BE.


Phylogenetic and functional clustering illustrate the roles of adaptive radiation and dispersal filtering in jointly shaping late-Quaternary mammal assemblages on oceanic islands.
Islands frequently harbour unique assemblages of species, yet their ecological roles and differences are largely ignored in island biogeography studies. Here, we examine eco-evolutionary processes structuring mammal assemblages on oceanic islands worldwide, including all extant and extinct late-Quaternary mammal species. We find island mammal assemblages tend to be phylogenetically clustered (share more recent evolutionary histories), with clustering increasing with island area and isolation. We also observe that mammal assemblages often tend to be functionally clustered (share similar traits), but the strength of clustering is weak and generally independent from island area or isolation. These findings indicate the important roles of in situ speciation and dispersal filtering in shaping island mammal assemblages under pre-anthropogenic conditions, notably through adaptive radiation of a few clades (e.g. bats, with generally high dispersal abilities). Our study demonstrates that considering the functional and phylogenetic axes of diversity can better reveal the eco-evolutionary processes of island community assembly.


Nucleoside diphosphate kinase Nm23-H1 regulates chromosomal stability by activating the GTPase dynamin during cytokinesis.
Chromosomal instability and the subsequent genetic mutations are considered to be critical factors in the development of the majority of solid tumors. Here, we describe how the nucleoside diphosphate kinase Nm23-H1, a protein with a known link to cancer progression, regulates a critical step during cytokinesis. Nm23-H1 acts to provide a local source of GTP for the GTPase dynamin. Loss of Nm23-H1 in diploid cells leads to cytokinetic furrow regression, followed by cytokinesis failure and generation of tetraploid cells. Loss of dynamin phenocopies loss of Nm23-H1, and ectopic overexpression of WT dynamin complements the loss of Nm23-H1. In the absence of p53 signaling, the tetraploid cells resulting from loss of Nm23-H1 continue cycling and develop classic hallmarks of tumor cells. We thus provide evidence that the loss of Nm23-H1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability.


The natural head position. Different techniques of head positioning in the study of craniocervical posture.
The aim of this paper was to describe the most important definitions of head posture and the most important methodology to get an natural head posture. After a careful analysis of the literature with no limitations of language or time period, 31 papers were selected. Relevant information was also derived from reference lists of the publications retrieved. The key words used in the search were head posture, cranio-cervical posture, cephalometric analysis, natural head position, lateral cephalometric radiographs, cephalostat, self balance position, mirror position. The definitions of natural head position are various. An accurate head posture registration is time consuming and not particularly feasible on a clinical field. Nevertheless it is possible to apply a craniostat to the patient before the execution of the radiograph without modifying the NHP. The execution of radiographs of the craniocervical zone is connected to the correct position of the head. The NHP is a reproducible positions, and can be useful for making comparisons at any time in the case of the same patient or in comparing different patients cephalometrically.


Effect of Drawing Parameters on the Properties of Polypropylene/Inorganic Particles Composites by Solid-State Die Drawing.
Die drawing is an effective method for improving the properties of polymer. In this work, polypropylene (PP)/inorganic particle composites were fabricated by a solid-state die drawing process to investigate the effects of drawing parameters, such as inorganic particles types, drawing temperature, and drawing speed, on the thermal properties, microstructure, and mechanical behavior of the drawn composites. The mechanical properties of the material were significantly improved through this processing method. For the drawn PP/inorganic particle composites with 45 wt% CaCO3, when the drawing speed was 2.0 m/min and the drawing temperature was 110 °C, the density of the drawn composites reached the lowest at 1.00 g/cm3. At this time, the tensile strength, flexural strength, and impact strength of the drawn composites were 128.32 MPa, 77.12 MPa, and 170.42 KJ/m2, respectively. This work provides a new strategy for the preparation of lightweight and high-strength PP-based composites, which have broad application prospects in the field of engineering and structural materials.


Laryngeal pathology in the acquired immunodeficiency syndrome: diagnostic and therapeutic dilemmas.
The acquired immunodeficiency syndrome has produced a growing population of patients who, because of their associated immune system compromise, are prone to opportunistic infections and neoplastic diseases. The larynx, with its relatively inaccessible yet critical anatomic location, is a site in which these processes can produce clinical dilemmas, with respect to diagnosis as well as to therapy. By presenting 4 cases involving unusual laryngeal problems in patients infected with the human immunodeficiency virus (HIV), we emphasize these inherent diagnostic and therapeutic problems. Otolaryngologists must be familiar with the many diagnostic possibilities and therapeutic alternatives when HIV-infected patients present with laryngeal complaints.


Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats.
Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184mg phorate/kg bw for 14days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G(2)/M arrest and appearance of a distinctive SubG(1) peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats.


Synaptic density, convergence, and dendritic complexity of prevertebral sympathetic neurons.
Prevertebral sympathetic ganglia contain a unique population of final motor neurons receiving convergent synaptic inputs not only from spinal preganglionic neurons, but also from peripheral intestinofugal neurons projecting from the gut. We used quantitative confocal and ultrastructural immunohistochemistry to determine how this increased synaptic convergence is accommodated by sympathetic final motor neurons in the celiac ganglion of guinea pigs. Terminals of intestinofugal neurons were identified by their immunoreactivity to vasoactive intestinal peptide. Stereologic analyses were based on transects and point counts at confocal and ultrastructural levels. The relative amount of dendritic neuropil in the medial regions of the ganglion was approximately 2.5 times greater than in the lateral regions of the ganglion, consistent with the 2 to 3 times difference in average dendritic field size of neurons in these regions. The total numbers of boutons and synaptic profiles showed significant positive correlations with the relative amount of neuropil in a region. However, the overall density of synaptic boutons was twice as high in the medial region of the ganglion compared with the lateral regions. Because the relative density of preganglionic synapses was similar in each region, this difference was due to the selective projection of intestinofugal inputs to neurons in the medial celiac ganglion, where they provided 45% of synaptic contacts. These results show that, compared with vasoconstrictor neurons, sympathetic neurons regulating gastrointestinal activity support a higher number of convergent inputs in two ways: in addition to having larger dendritic fields, they also have a twofold higher density of synapses.


Early Exclusion of Major Adverse Cardiac Events in Emergency Department Chest Pain Patients: A Prospective Observational Study.
The current evaluation of patients with chest pain presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) is a lengthy process involving serial measurements of troponin. We aimed to validate the diagnostic accuracy of a Thrombolysis in Myocardial Infarction (TIMI) score with single high-sensitive cardiac troponin T (hs-cTnT) for early rule out of 30-day major adverse cardiac events (MACE), and to compare the TIMI score with combinations of heart-type fatty acid binding protein (H-FABP) and a modified HEART (history, electrocardiogram, age, risk factors, troponin) score. We recruited 602 consecutive adult patients with chest pain and suspected ACS in the ED. Each patient had TIMI and HEART scores, and a point-of-care H-FABP test. MACE occurred in 42 (7.0%) patients within 30 days. A low risk for 30-day MACE was identified by a modified TIMI score of 0 in 65 (11%) patients, and by a HEART score ≤ 2 in 96 (16%) patients. No MACE occurred in these groups, giving both scores a sensitivity of 100% (95% confidence interval [CI] 91.6-100%), and specificity of 11.6% (95% CI 9.2-14.5%) and 17.1% (95% CI 14.2-20.5%), respectively. Use of combined TIMI and HEART scores improved the specificity further to 22.0% (95% CI 18.7-25.6%) without lowering sensitivity. Early H-FABP measurement > 7 μg/L had a sensitivity of 41.5% (95% CI 27.8-56.6%) and a specificity of 91.1% (95% CI 88.4-93.2%) for predicting 30-day MACE. A modified TIMI score of 0 or a HEART score of ≤ 2, incorporating a single hs-cTnT level, will identify patients with low risk of 30-day MACE for early discharge within 2 h of ED arrival.


Adenoma of the endolymphatic sac.
A woman, who presented with symptoms of unilateral Ménière's disease, was found to have an adenoma of the endolymphatic sac, when an endolymphatic sac decompression was performed. Such a finding has not previously been reported. The possible role of the tumor in causing endolymphatic hydrops is discussed.


Large twisted ovarian fibroma in menopausal women: a case report.
Ovarian fibroma is the most common benign solid tumors of the ovary, commonly misdiagnosed as uterine fibromaor as malignant ovarian tumors. It occurs generally in older perimenopausal and postmenopausal women. Occasionally large fibromas may undergo torsion causing acute abdominal pain. Doppler Ultrasonographyimaging is the choice study. CT and MRI are often needed for further characterization and differentiation from other solid ovarian masses. The choice treatment is surgical removal with intraoperative frozensection. Immunohistochemicalanalysis is recommended to rule out the differential diagnosis. Here we present a case of a postmenopausal woman with a large twisted ovarian fibroma reflecting diagnostic and management difficulties including potential misdiagnosis of the tumor as a malignant ovarian neoplasm that may influence the surgical approach.


Giant encephalocele.
A 37-year-old man who presented with difficulty breathing and nasal obstruction was found to have a large encephalocele, along with other, associated congenital anomalies. The etiology, epidemiology, classification, clinical presentation, imaging, and surgical approaches used for encephaloceles are discussed.


CD11d integrin blockade reduces the systemic inflammatory response syndrome after traumatic brain injury in rats.
Traumatic CNS injury triggers a systemic inflammatory response syndrome (SIRS), in which circulating inflammatory cells invade body organs causing local inflammation and tissue damage. We have shown that the SIRS caused by spinal cord injury is greatly reduced by acute intravenous treatment with an antibody against the CD11d subunit of the CD11d/CD18 integrin expressed by neutrophils and monocyte/macrophages, a treatment that reduces their efflux from the circulation. Traumatic brain injury (TBI) is a frequently occurring injury after motor vehicle accidents, sporting and military injuries, and falls. Our studies have shown that the anti-CD11d treatment diminishes brain inflammation and oxidative injury after moderate or mild TBI, improving neurological outcomes. Accordingly, we examined the impact of this treatment on the SIRS triggered by TBI. The anti-CD11d treatment was given at 2h after a single moderate (2.5-3.0 atm) or 2 and 24h after each of three consecutive mild (1.0-1.5 atm) fluid percussion TBIs. Sham-injured, saline-treated rats served as controls. At 24h, 72 h, and 4 or 8 weeks after the single TBI and after the third of three TBIs, lungs of rats were examined histochemically, immunocytochemically and biochemically for downstream effects of SIRS including inflammation, tissue damage and expression of oxidative enzymes. Lung sections revealed that both the single moderate and repeated mild TBI caused alveolar disruption, thickening of inter-alveolar tissue, hemorrhage into the parenchyma and increased density of intra-and peri-alveolar macrophages. The anti-CD11d treatment decreased the intrapulmonary influx of neutrophils and the density of activated macrophages and the activity of myeloperoxidase after these TBIs. Moreover, Western blotting studies showed that the treatment decreased lung protein levels of oxidative enzymes gp91(phox), inducible nitric oxide synthase and cyclooxygenase-2, as well as the apoptotic pathway enzyme caspase-3 and levels of 4-hydroxynonenal-bound proteins (an indicator of lipid peroxidation). Decreased expression of the cytoprotective transcription factor Nrf2 reflected decreased lung oxidative stress. Anti-CD11d treatment also diminished the lung concentration of free radicals and tissue aldehydes. In conclusion, the substantial lung component of the SIRS after single or repeated TBIs is significantly decreased by a simple, minimally invasive and short-lasting anti-inflammatory treatment.


The Linxian trials: mortality rates by vitamin-mineral intervention group.
Two randomized nutrition intervention trials were conducted in Linxian, an area of north central China with some of the world's highest rates of esophageal and stomach cancer and a population with a chronically low intake of several nutrients. One trial used a factorial design that allowed us to assess the effects in nearly 30,000 participants of daily supplementation with four nutrient combinations: retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta-carotene, alpha-tocopherol, and selenium. The second trial provided daily multiple vitamin-mineral supplementation or placebo in 3318 persons with esophageal dysplasia, a precursor to esophageal cancer. After supplements were given for 5.25 y in the general population trial, small but significant reductions in total [relative risk (RR) = 0.91] and cancer (RR = 0.87) mortality were observed in subjects receiving beta-carotene, alpha-tocopherol, and selenium but not the other nutrients. The reductions were greater in women than men, and in those under compared with over the age of 55; however, differences by sex or age were not significant. After multiple vitamin and mineral supplements were given for 6 y in the smaller dysplasia trial, reductions in total (RR = 0.93) and cancer (RR = 0.96) mortality were observed but these were not significant. The largest reductions were for cerebrovascular disease mortality, but the effects differed by sex: a significant reduction was observed in men (RR = 0.45) but not women (RR = 0.90). Restoring adequate intake of certain nutrients may help to lower the risk of cancer and other diseases in this high-risk population.


Communication: Unusual dynamics of hybrid nanoparticles and their binary mixtures.
We present the results on the evolution of microscopic dynamics of hybrid nanoparticles and their binary mixtures as a function of temperature and wave vector. We find unexpectedly a nonmonotonic dependence of the structural relaxation time of the nanoparticles as a function of the morphology. In binary mixtures of two of the largest nanoparticles studied, we observe re-entrant vitrification as a function of the volume fraction of the smaller nanoparticle, which is unusual for such high diameter ratio. Possible explanation for the observed behavior is provided.


Molecular and morphological characterization of Echinococcus in cervids from North America.
Many issues concerning the taxonomy of Echinococcus have been resolved in recent years with the application of molecular tools. However, the status of Echinococcus maintained in transmission cycles involving cervid intermediate hosts remains to be determined. The recent characterization of the parasite from cervids in Finland has highlighted the paucity of data available, particularly that from North America. In this study, we have characterized a large number of Echinococcus isolates from cervids from Western Canada on the basis of morphology and molecular genetic techniques. Our results support earlier studies suggesting that Echinococcus of cervid origin is phenotypically and genetically distinct to Echinococcus maintained in domestic host assemblages, and also confirms that Echinococcus of cervid origin does not constitute a genetically homogeneous group. However, our data do not support the existence of 2 distinct genotypes (strains/subspecies) with separate geographical distributions. Our data appear to support the existence of only 1 species in cervids, but additional isolates from cervids and wolves in other endemic regions should be characterized before a final decision is made on the taxonomic status of Echinococcus in cervids.


Both the helix-loop-helix and the leucine zipper motifs of c-Myc contribute to its dimerization specificity with Max.
The oncoprotein c-Myc contains two dimerization motifs- the helix-loop-helix (HLH) and the leucine zipper (LZ) - through which c-Myc specifically dimerizes with Max. We substituted regions of the c-Myc HLH and LZ motifs with the corresponding regions of structurally related proteins that do not interact with Max. Specific association of c-Myc with Max was dictated by helices 1 and 2 of the HLH motif and by the LZ. Within helix 2, residues 6 and 7 were important determinants of dimerization specificity. c-Myc and Max proteins with three amino acids inserted between their HLH and LZ motifs interacted efficiently, suggesting that the spacing between the motifs can be varied. Furthermore, alignment of the motifs at the primary sequence level was not obligatory, since Max with the three amino acid insertion could interact with wild-type c-Myc. These findings are consistent with our recently proposed model for the architecture of HLH/LZ domains.


Comparison of stroke work between repaired tetralogy of Fallot and normal right ventricular physiologies.
Adult patients who underwent tetralogy of Fallot repair surgery (rTOF) confront life-threatening ailments due to right ventricular (RV) myocardial dysfunction. Pulmonary valve replacement (PVR) needs to be performed to restore the deteriorating RV function. Determination of correct timing to perform PVR in an rTOF patient remains subjective, due to the unavailability of quantifiable clinical diagnostic parameters. The objective of this study is to evaluate the possibility of using RV body surface area (BSA)-indexed stroke work (SW(I)) to quantify RV inefficiency in TOF patients. We hypothesized that RV SW(I) required to push blood to the lungs in rTOF patients is significantly higher than that of normal subjects. Seven patients with rTOF pathophysiology and eight controls with normal RV physiology were registered for this study. Right ventricular volume and pressure were measured using cardiac magnetic resonance imaging and catheterization, respectively. Statistical analysis was performed to quantify the difference in SW(I) between the RV of the rTOF and control groups. Right ventricular SW(I) in rTOF patients (0.176 ± 0.055 J/m(2)) was significantly higher by 93.4% (P = 0.0026) than that of controls (0.091 ± 0.030 J/m(2)). Further, rTOF patients were found to have significantly higher (P < 0.05) BSA normalized RV end-systolic volume, end-systolic pressure, and regurgitation fraction than control subjects. Ejection fraction and peak ejection rate of rTOF patients were significantly lower (P < 0.05) than those of controls. Patients with rTOF pathophysiology had significantly higher RV SW(I) compared with subjects with normal RV physiology. Therefore, RV SW(I) may be useful to quantify RV inefficiency in rTOF patients along with currently used clinical end points such as RV volume, pressure, regurgitation fraction, and ejection fraction.


PACAP enhances stimulation-induced norepinephrine release in canine pancreas in vivo.
The present study was to investigate whether pituitary adenylate cyclase activating polypeptide (PACAP) can modify norepinephrine (NE) release in response to pancreatic nerve stimulation in anesthetized dogs. Plasma catecholamine concentrations in aortic and superior pancreaticoduodenal (SPD) venous blood were determined by a high performance liquid chromatography method. SPD venous blood flow was measured with an electromagnetic flowmeter. Pancreatic nerves were directly stimulated for 1 min (2 ms, 12 V) at various frequencies at the level of the SPD artery. Various doses of PACAP1-27 (PACAP27) were locally infused into the pancreas through the SPD artery. Nerve stimulation significantly increased both SPD venous NE concentration and its output from the pancreas in a frequency-dependent manner. With PACAP27 alone, neither SPD venous NE concentration nor its output changed significantly following the local administration of PACAP27 at any dose tested. In the presence of PACAP27, however, the net increases in NE concentration and its output in response to nerve stimulation at 2 Hz were significantly enhanced in a dose-dependent manner. The enhanced NE responses to nerve stimulation by PACAP27 were thus significantly greater than those obtained from the group receiving either PACAP27 or stimulation alone. Increases in NE concentration and its output induced by local administration of tyramine were virtually abolished by desipramine, a neural amine uptake inhibitor. However, the NE response to tyramine was not diminished by PACAP27. The results indicate that PACAP27 enhances the stimulation-induced NE release in the pancreas, and that this facilitatory effect of PACAP27 does not result from an inhibition of the neural amine uptake mechanism. The study suggests that PACAP receptor-mediated mechanisms may be involved either directly or indirectly in the local modulation of neural NE release in the canine pancreas in vivo.


Behavior and Three-Dimensional Finite Element Modeling of Circular Concrete Columns Partially Wrapped with FRP Strips.
Fiber-reinforced polymer (FRP) jacketing/wrapping has become an attractive strengthening technique for concrete columns. Wrapping an existing concrete column with continuous FRP jackets with the fiber in the jacket being oriented in the hoop direction is referred to as FRP full wrapping strengthening technique. In practice, however, strengthening concrete columns with vertically discontinuous FRP strips is also favored and this technique is referred to as FRP partial wrapping strengthening technique. Existing research has demonstrated that FRP partial wrapping strengthening technique is a promising and economical alternative to the FRP full wrapping strengthening technique. Although extensive experimental investigations have hitherto been conducted on partially FRP-confined concrete columns, the confinement mechanics of confined concrete in partially FRP-confined circular columns remains unclear. In this paper, an experimental program consisting of fifteen column specimens was conducted and the test results were presented. A reliable three-dimensional (3D) finite element (FE) approach for modeling of partially FRP-confined circular columns was established. In the proposed FE approach, an accurate plastic-damage model for concrete under multiaxial compression is employed. The accuracy of the proposed FE approach was verified by comparisons between the numerical results and the test results. Numerical results from the verified FE approach were then presented to gain an improved understanding of the behavior of confined concrete in partially FRP-confined concrete columns.


A case of fatal respiratory failure after surgery for advanced supraglottic laryngeal carcinoma.
Pulmonary lymphangitic carcinomatosis (PLC) is an uncommon type of pulmonary metastasis from laryngeal carcinoma. We encountered a case of fatal respiratory failure after surgery for supraglottic laryngeal carcinoma with multiple cervical lymph node metastases. On day 25 postoperatively, the patient suddenly developed fever and noted slowly progressive difficulty in breathing. Laboratory data, radiological findings, and the clinical course of this patient were strongly suggestive of PLC. The patient refused fiberoptic bronchoscopy and glucocorticoid therapy, leading to rapid deterioration due to increasing respiratory distress, and died of respiratory failure on postoperative day 32. PLC should be considered a possible presentation of pulmonary metastasis associated with head and neck carcinoma. Chest CT may be needed to detect subclinical PLC, especially in cases of advanced head and neck carcinomas.


The miR165/166 Mediated Regulatory Module Plays Critical Roles in ABA Homeostasis and Response in Arabidopsis thaliana.
The function of miR165/166 in plant growth and development has been extensively studied, however, its roles in abiotic stress responses remain largely unknown. Here, we report that reduction in the expression of miR165/166 conferred a drought and cold resistance phenotype and hypersensitivity to ABA during seed germination and post-germination seedling development. We further show that the ABA hypersensitive phenotype is associated with a changed transcript abundance of ABA-responsive genes and a higher expression level of ABI4, which can be directly regulated by a miR165/166 target. Additionally, we found that reduction in miR165/166 expression leads to elevated ABA levels, which occurs at least partially through the increased expression of BG1, a gene that is directly regulated by a miR165/166 target. Taken together, our results uncover a novel role for miR165/166 in the regulation of ABA and abiotic stress responses and control of ABA homeostasis.


Germinoma with syncytiotrophoblastic giant cells arising in the corpus callosum.
A previously healthy 31-year-old Japanese man presented with a very rare germinoma of the corpus callosum without other intracranial lesions manifesting as transitory speech disturbance. Magnetic resonance (MR) imaging revealed a heterogeneously enhanced mass in the corpus callosum extending into the cavity of the septum pellucidum. A tumor specimen obtained by stereotactic biopsy revealed a two-cell pattern germinoma containing human chorionic gonadotropin (HCG)-beta-positive giant cells. The cerebrospinal fluid and serum levels of HCG and HCG-beta subunit were measurable. The diagnosis was germinoma with syncytiotrophoblastic giant cells. Three cycles of chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by radiation therapy achieved complete remission, and 5 cycles of chemotherapy with carboplatin and etoposide were added. MR imaging performed 40 months after the diagnosis showed a cicatricial cyst in the body of the corpus callosum, the original tumor site. All 11 previously reported cases of germinoma in the corpus callosum were associated with synchronous or metachronous intracranial lesions. These patients tended to be older than patients with general intracranial germinoma. Germinoma should be included in the differential diagnosis of corpus callosum tumors, especially in young adult males.


The effect of phloretin on the hydration of egg phosphatidylcholine multilayers.
The effect of phloretin on the hydration, structure and interactive properties of supported phospholipid bilayers has been studied by a combination of direct water adsorption measurements and X-ray diffraction. Adsorption isotherms show that over a wide range of relative vapor pressures (from 0 to approximately 1.0) the addition of 20 or 40 mol% phloretin significantly alters the amount of water adsorbed by egg phosphatidylcholine (EPC) multilayers. X-ray diffraction analysis shows that the incorporation of phloretin decreases the width of the EPC bilayer, thereby increasing the area per lipid molecule from approximately 64 A2 for EPC to about 78 A2 for EPC:Ph, 3:2, M:M. Phloretin also decreases the distance between apposing EPC bilayers, most likely because it causes a reduction in repulsive hydration/steric pressure between apposing bilayers. Because phloretin decreases the fluid layer between bilayers by a larger amount than it increases the area per EPC molecule, phloretin has the effect of decreasing the water volume in the multilayers.


Conical intersections, charge localization, and photoisomerization pathway selection in a minimal model of a degenerate monomethine dye.
We propose a minimal model Hamiltonian for the electronic structure of a monomethine dye, in order to describe the photoisomerization of such dyes. The model describes interactions between three diabatic electronic states, each of which can be associated with a valence bond structure. Monomethine dyes are characterized by a charge-transfer resonance; the indeterminacy of the single-double bonding structure dictated by the resonance is reflected in a duality of photoisomerization pathways corresponding to the different methine bonds. The possible multiplicity of decay channels complicates mechanistic models of the effect of the environment on fluorescent quantum yields, as well as coherent control strategies. We examine the extent and topology of intersection seams between the electronic states of the dye and how they relate to charge localization and selection between different decay pathways. We find that intersections between the S(1) and S(0) surfaces only occur for large twist angles. In contrast, S(2)/S(1) intersections can occur near the Franck-Condon region. When the molecule has left-right symmetry, all intersections are associated with con- or disrotations and never with single bond twists. For asymmetric molecules (i.e., where the bridge couples more strongly to one end) the S(2) and S(1) surfaces bias torsion about different bonds. Charge localization and torsion pathway biasing are correlated. We relate our observations with several recent experimental and theoretical results, which have been obtained for dyes with similar structure.


Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues.
Ambient ionization methods for MS enable direct, high-throughput measurements of samples in the open air. Here, we report on one such method, desorption electrospray ionization (DESI), which is coupled to a linear ion trap mass spectrometer and used to record the spatial intensity distribution of a drug directly from histological sections of brain, lung, kidney, and testis without prior chemical treatment. DESI imaging provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measuring the abundance of the intact ion at m/z 327.1, and ii) monitoring the dissociation of the protonated drug compound at m/z 327.1 to its dominant product ion at m/z 270.1. In lung tissues, DESI imaging was performed in the full-scan mode over an m/z range of 200-1100, providing an opportunity for relative quantitation by using an endogenous lipid to normalize the signal response of clozapine. The presence of clozapine was detected in all tissue types, whereas the presence of the N-desmethyl metabolite was detected only in the lung sections. Quantitation of clozapine from the brain, lung, kidney, and testis, by using LC-MS/MS, revealed concentrations ranging from 0.05 microg/g (brain) to a high of 10.6 microg/g (lung). Comparisons of the results recorded by DESI with those by LC-MS/MS show good agreement and are favorable for the use of DESI imaging in drug and metabolite detection directly from biological tissues.


Theoretical study on the alkaline hydrolysis of methyl thioacetate in aqueous solution.
A base-catalyzed hydrolysis reaction of thiolester has been studied in both gas and solution phases using two ab initio quantum mechanics calculations such as Gaussian09 and CPMD. The free-energy surface along the reaction path is also constructed using a configuration sampling technique, namely, the metadynamics method. While there are two different reaction paths obtained for the potential profile of the base-catalyzed hydrolysis reaction for thiolester in the gas phase, a triple-well reaction path is computed for the reaction in the solution phase by two quantum mechanics calculations. Unlike the S(N)2 mechanism (a concerted mechanism) found for the gas-phase reaction, a nucleophilic attack from the hydroxide ion on the carbonyl carbon to yield a tetrahedral intermediate (a stepwise mechanism) is observed for the solution-phase reaction. Moreover, the energy profiles computed by these two theoretical calculations are found to be very comparable with those determined experimentally.


Skin adnexal neoplasms--part 2: an approach to tumours of cutaneous sweat glands.
Tumours of cutaneous sweat glands are uncommon, with a wide histological spectrum, complex classification and many different terms often used to describe the same tumour. Furthermore, many eccrine/apocrine lesions coexist within hamartomas or within lesions with composite/mixed differentiation. In addition to the eccrine and apocrine glands, two other skin sweat glands have recently been described: the apoeccrine and the mammary-like glands of the anogenital area. In this review (the second of two articles on skin adnexal neoplasms), common as well as important benign and malignant lesions of cutaneous sweat glands are described, and a summary for differentiating primary adnexal neoplasms from metastatic carcinoma is outlined, striving to maintain a common and acceptable terminology in this complex subject. Composite/mixed adnexal tumours are also discussed briefly.


Nasolacrimal canal morphology with or without idiopathic obstruction in Caucasian adults: a multidetector CT study.
To compare the morphological features of the bony nasolacrimal canal (NLC) in Caucasian adults with and without primary acquired nasolacrimal duct obstruction (PANDO). The study included one eye each from 38 patients with PANDO and 38 age- and gender-matched controls without PANDO, all of whom underwent multidetector computed tomography. In tomographic images, length, and orientation angles of the NLC, transverse canal diameters at the duct entrance and lower end, and minimum (narrowest) transverse and anterior-posterior canal diameters were measured. The two groups were similar for NLC length and angulations. The transverse entrance diameter was significantly narrower in the PANDO group (mean, 4.6 mm vs. 5.1 mm) (p = 0.09). The narrowest site was most frequently in the middle duct or slightly above the middle in both groups (p > 0.05). The minimum canal diameters were significantly smaller in the PANDO group (p = 0.010 and p = 0.003). When gender subgroups were compared, the significant differences continued for the transverse entrance and minimum diameters in females with PANDO (p = 0.006) and for the minimum anterior-posterior diameter in males with PANDO (p = 0.02). Narrowness of the upper and/or middle part of the bony nasolacrimal duct may play a role in the development of PANDO in the adult Caucasian population.


Challenging FRET-based E-Cadherin force measurements in Drosophila.
Mechanical forces play a critical role during embryonic development. Cellular and tissue wide forces direct cell migration, drive tissue morphogenesis and regulate organ growth. Despite the relevance of mechanics for these processes, our knowledge of the dynamics of mechanical forces in living tissues remains scarce. Recent studies have tried to address this problem with the development of tension sensors based on Förster resonance energy transfer (FRET). These sensors are integrated into force bearing proteins and allow the measurement of mechanical tensions on subcellular structures. Here, we developed such a FRET-based sensor to measure E-Cadherin tensions in different Drosophila tissues in and ex vivo. Similar to previous studies, we integrated the sensor module into E-cadherin. We assessed the sensitivity of the sensor by measuring dynamic, developmental processes and mechanical modifications in three Drosophila tissues: the wing imaginal disc, the amnioserosa cells and the migrating border cells. However, these assays revealed that the sensor is not functional to measure the magnitude of tensions occurring in any of the three tissues. Moreover, we encountered technical problems with the measurement of FRET, which might represent more general pitfalls with FRET sensors in living tissues. These insights will help future studies to better design and control mechano-sensing experiments.


Monitoring of pesticide residues in dairy cattle farms from NW Spain.
The consequences of the use of pesticides in agricultural activities for food and feed product safety are subjects of major concern. In the present work, simple and environmentally friendly methodologies were applied to the analysis of soil and cattle feed samples collected in dairy cattle farms from Galicia (NW Spain). This forms part of an integrated study aiming to investigate the global impact of the use of pesticides in such farms. The target compounds were 36 plant protection products belonging to different families. Organochlorine and organophosphorus pesticides were the most commonly detected compounds in the analyzed samples; pyrethroid and chloroacetanilide pesticides were also found in some of them, but not so frequently. Detected levels were rarely above the established legal limits.


Changes in Abscisic Acid and Indoleacetic Acid before and after Anthesis Relative to Changes in Abscission Rates of Cotton Fruiting Forms.
Cotton (Gossypium hirsutum L.) fruiting forms exhibit pronounced changes, with age, in their probability of abscission. Large floral buds rarely abscise, but after anthesis the young fruits (bolls) have a high probability of abscising. Abscission rate reaches a peak about 5 to 6 days after anthesis and then gradually decreases. An experiment was conducted to try to determine the reason for the rapid and pronounced increase in probability of abscission just after anthesis. Cotton was grown in the field and fruiting forms of various ages from 9 days before to 9 days after anthesis were all harvested the same day and subsequently analyzed for ABA and IAA. The concentration of ABA decreased slightly at anthesis and increased gradually thereafter. In contrast, the concentration of IAA was high before anthesis and then decreased at anthesis to about one-fifth the previous concentration. IAA remained low for at least 4 days after anthesis and then increased rapidly between 7 and 9 days after anthesis. The high concentration of IAA in floral buds before anthesis is probably a major factor in their resistance to abscission. Likewise, the low concentration of IAA at anthesis and for about 4 days thereafter may promote fruit abscission during the young boll stage.


Are recent statin recommendations to employ fixed doses and abandon targets effective for treatment of hypercholesterolaemia? Investigation based on number needed to treat.
Assessed by number needed to treat (NNT) to prevent one event, it was previously shown that for those at similar atherosclerotic cardiovascular disease (CVD) risk, the benefit accruing from treating people with higher cholesterol levels with statins is greater than for those with lower levels. By estimating NNT from both the absolute atherosclerotic cardiovascular risk and the pre-treatment low density lipoprotein cholesterol (LDL-C) concentration, recent recommendations for fixed dose high and moderate intensity statin treatment in the primary and secondary prevention of CVD were compared with cholesterol-lowering therapy aimed at a target LDL-C. We report that the USA and UK recommendations to employ a fixed dose of atorvastatin 20 mg daily for primary prevention will produce good results in people with low cholesterol levels, but are a disadvantage for those with higher levels who benefit more from a therapeutic target and statin dose titration and, where necessary, adjunctive cholesterol-lowering therapy to achieve this target. The higher dose of atorvastatin 80 mg daily with no target recommended for secondary prevention is generally more effective than aiming for a LDL-C goal except in people with particularly high cholesterol. For optimum clinical effectiveness, initial LDL-C concentration must be considered in deciding whether a target will allow a greater decrease in LDL-C and thus a lower NNT than a fixed dose regimen. Individual variation in the LDL-C response to statins also makes post-treatment cholesterol measurement essential.


Adjustments to the segment center of mass proportions of Clauser et al. (1969).
One of the most commonly-referenced studies on body segment masses and centers of mass is by Clauser et al. (AMRL Technical Report 69-70, Wright Patterson Air Force Base, 1969). The Clauser et al. data, however, are difficult to use, because the investigators used certain bony landmarks rather than joint centers as reference points for the center of mass proportions. The purpose of this study was to make adjustments to those proportions so that they could be applied directly to segments having joint centers as endpoints. The segments affected by these adjustments were the trunk, upper arm, forearm, thigh, and calf. These new proportions are markedly different than those originally reported by Clauser et al., especially for the trunk segment. Readers are cautioned against using the original proportions when using joint centers as segment endpoints.


pKa of fentanyl varies with temperature: implications for acid-base management during extremes of body temperature.
The pKa of fentanyl has not been measured previously at varying extremes of body temperature. The goal of this laboratory investigation was to test the hypothesis that the pKa of fentanyl changes with temperature. The investigation involved measuring the pKa values of aqueous fentanyl at varying temperatures. The investigation was conducted in a controlled laboratory environment. No human or animal subjects were involved. Because no live subjects were involved in the investigation, no interventions were necessary. This paper reports the effect of temperature on the pKa of fentanyl. The pKa of aqueous fentanyl was measured at 15 degrees C, 25 degrees C, 37 degrees C, 42 degrees C, and 47.5 degrees C by potentiometric titration in 0.01 mmol/L of potassium chloride after extensive degassing. Data were analyzed using the least squares method with an appropriately fitting equation. The pKa of fentanyl was found to change in a similar manner to the neutral point of water at varying temperatures. This finding has implications for the bioavailability of fentanyl at extremes of body temperature in association with the clinical acid-base management of the patient. Clinical implications for differing methods of intraoperative acid-base management at varying temperatures are discussed.


Blood glucose level on postoperative day 1 is predictive of adverse outcomes after cardiovascular surgery.
Hyperglycaemia is now a recognized predictive factor of morbidity and mortality after coronary artery bypass grafting (CABG). For this reason, we aimed to evaluate the postoperative management of glucose control in patients undergoing cardiovascular surgery, and to assess the impact of glucose levels on in-hospital mortality and morbidity. This was a retrospective study investigating the association between postoperative blood glucose and outcomes, including death, post-surgical complications, and length of stay in the intensive care unit (ICU) and in hospital. A total of 642 consecutive patients were enrolled into the study after cardiovascular surgery (CABG, carotid endarterectomy and bypass in the lower limbs). Patients' mean age was 68+/-10 years, and 74% were male. In-hospital mortality was 5% in diabetic patients vs 2% in non-diabetic patients (OR: 1.66, P=0.076). Having blood glucose levels in the upper quartile range (> or =8.8 mmol/L) on postoperative day 1 was independently associated with death (OR: 10.16, P=0.0002), infectious complications (OR: 1.76, P=0.04) and prolonged ICU stay (OR: 3.10, P<0.0001). Patients presenting with three or more hypoglycaemic episodes (<4.1 mmol/L) had increased rates of mortality (OR: 9.08, P<0.0001) and complications (OR: 8.57, P<0.0001). Glucose levels greater than 8.8 mmol/L on postoperative day 1 and having three or more hypoglycaemic episodes in the postoperative period were predictive of mortality and morbidity among patients undergoing cardiovascular surgery. This suggests that a multidisciplinary approach may be able to achieve better postoperative blood glucose control.


Fate of fructo-oligosaccharides in the human intestine.
There is a need for studies on colonic fermentation in order to learn more about health and diseases of the colon. The aim of the present study was to evaluate the fate of two different doses of fructo-oligosaccharides (5 and 15 g/d) v. glucose in the intestine of healthy men. Twenty-four volunteers participated in a 5-week study. The study was a completely balanced multiple crossover trial using an orthogonal Latin-square design for three periods, with supplement periods of 7 d and two 7 d wash-out periods. Breath samples and faecal samples were collected. There was a clear gaseous response to the consumption of fructo-oligosaccharides. The highest dose significantly increased 24 h integrated excretion of breath H2 (P < 0.05). Breath H2 excretion after ingestion of 5 g fructo-oligosaccharides was higher than control, but did not reach significance. No effects on the total concentration of short-chain fatty acids in faeces were observed, no modification of the molar proportions of the various short-chain fatty acids was observed. The faecal pH did not change. No changes in faecal weight were observed. No fructo-oligosaccharides were recovered in faeces. We conclude that fructo-oligosaccharides added to the diet of young Western subjects are fully metabolized in the large intestine. The level of fermentation seem to be dose-dependent.


Antigen-specific CD8+ T cells switch the immune response induced by antigen from an IgG to a cell-mediated mode.
We have developed an in vivo/in vitro immunization procedure with xenogeneic RBC as Ag that results in the generation of a lymphoid population that expresses potent delayed-type hypersensitivity (DTH) and produces little, if any, antibody. This lymphoid population contains Ag-specific CD8+ T cells that can inhibit the induction of a strong IgG response. These CD8+ T cells are shown to not only inhibit the antibody response in an Ag-specific manner but allow the Ag to induce cells of the target population to express DTH. Furthermore, the Ag-specific inhibition of the antibody response and the Ag-specific enhancement of the induction of DTH appear to be coordinately regulated, as the same number of CD8+ T cells cells is required to achieve both effects. Thus these CD8+ T cells are shown to switch the response induced by Ag from a humoral to a cell-mediated mode. These regulatory characteristics are consistent with a physiologic role for these cells of ensuring the absence of antibody production during a strong, cell-mediated response.


Pulmonary Hypertension and Pregnancy Outcomes: Insights From the National Inpatient Sample.
Pregnant women with pulmonary hypertension (PH) are at risk for adverse cardiac outcomes, particularly at the time of labor and delivery. The purpose of this study is to define the impact of PH on pregnancy outcomes and the risk of major adverse cardiac events (MACE). The National Inpatient Sample was screened for hospital admissions of women delivering during the years 2003 to 2012. The primary outcome was MACE, a composite of death, cardiac arrest, cardiogenic shock, myocardial infarction, respiratory failure, arrhythmia, stroke, and embolic event. Data on 1519 patients with PH and 6 757 582 without heart disease or PH were available. There were 59.6% with isolated PH; 10.7% with PH and congenital heart disease; 18.1% with PH and valvular heart disease; 3% with PH and valvular heart disease and congenital heart disease; 6.6% PH and cardiomyopathy; and 1.9% with PH and cardiomyopathy and valvular heart disease. Compared with women without heart disease or PH, women with PH experienced significantly higher MACE (24.8 versus 0.4%, P<0.0001). Among the subsets of women with PH, the highest MACE was noted in women with the combination of PH and cardiomyopathy and valvular heart disease, and PH and cardiomyopathy, primarily because of heart failure and arrhythmia. Women with PH were significantly more likely to experience eclampsia syndromes, preterm delivery, and intrauterine fetal demise (P<0.0001 for all). PH subtype was significantly associated with MACE in multivariable analysis (P<0.001). In a contemporary data set of pregnant women in the United States, PH was associated with an increase in MACE during the hospitalization for delivery, with an exceptionally elevated risk among women with associated cardiomyopathy.


In Vivo Measurement of Indole-3-acetic Acid Decarboxylation in Aging Coleus Petiole Sections.
The concentration of indoleacetic acid (IAA) in plant tissues is regulated, in part, by its rate of decarboxylation. However, the commonly used in vitro assays for IAA oxidase may not accurately reflect total in vivo decarboxylation rates. A method for measuring in vivo decarboxylation was utilized in which (14)CO(2) is collected following uptake of [1-(14)C]IAA by excised tissue sections. After a 30-minute equilibration period, the evolution of (14)CO(2) was found to follow an approximately linear course with respect to both time and tissue weight.Decarboxylation rates were measured by this method in petiole sections of the Princeton clone of Coleus blumei Benth. Both the (14)CO(2) evolved per milligram tissue and the percent of [1-(14)C]IAA uptake decarboxylated were highest in sections from the youngest petioles tested, and declined in the older tissue. Thin layer chromatography of acetonitrile extracts from the [1-(14)C]IAA-treated petioles showed a decreasing amount of free IAA and an increase at the retardation factor of indoleacetylaspartate in the older sections. The decreased decarboxylation rates in the older petioles may be attributable to a generally lower metabolic rate and increased protection of the IAA by conjugation.


Immunohistochemical progesterone receptor assay. Measurement by image analysis.
To determine the efficiency of image analysis in immunohistochemical progesterone receptor (PgR) measurement, 94 primary breast carcinoma tissue samples were evaluated for PgR by biochemical dextran-coated charcoal assay (DCC) and an immunohistochemical method. Frozen sections immunostained for PgR with a monoclonal antibody (Abbott PgR-ICA, Chicago, IL) and the peroxidase-antiperoxidase technique were scored semiquantitatively histologic score by microscopy and quantitatively (percentage nuclear area immunopositivity [PNA] using the CAS 200 image analyzer (Cell Analysis Systems, Elmhurst, IL). There was a positive correlation between dextran-coated charcoal assay and both histologic score (r = 0.82) and PNA (r = 0.69). Selected cutoff points of 60 histologic score and 6.5% PNA based on sensitivity/specificity calculations yielded a predictive value of a negative test of 73% and 80%, respectively, and a positive predictive value of 100% for both; ranges of fmol/mg protein PgR correspond to ranges of histologic score and PNA. The use of an image analyzer to measure PNA in PgR-immunostained sections is a viable alternative to dextran-coated charcoal assay, especially when insufficient fresh tissue is available.


Comprehensive drug-use evaluation program in a health maintenance organization.
Development and use of a drug-use evaluation (DUE) program for hospital and outpatient facilities of a health-maintenance organization (HMO) are described. A full-time pharmacist coordinates the DUE program. Primary components of the DUE program are (1) establishment and use of drug therapy management protocols, (2) periodic review and evaluation of drug-use statistics by the pharmacy and therapeutics (P&T) committee, (3) monitoring of pharmacist interventions, and (4) evaluation of specific drug use within individual medical staff departments. Information from all DUE activities is channeled through the P&T committee and linked to the HMO's overall quality assurance program. The DUE program has the support of the HMO physicians. It has enhanced the quality of drug use and identified opportunities to further improve the quality of patient care. In surveys by the Joint Commission on Accreditation of Healthcare Organizations, the HMO facilities have received no recommendations. Pharmacists and physicians have cooperated to develop a comprehensive DUE program for an HMO.


Update on survival in thalassemia major.
Long-term follow-up of cohorts of patients treated in high-income countries has shown a progressive improvement in life expectancy. Myocardial toxicity from iron overload has been the major cause of mortality; however, there has been a substantial decline in cardiac deaths in recent years, related to switching high-risk patients from subcutaneous desferrioxamine to chelation regimes which include the oral chelator deferiprone. The role of deferasirox in enhancing life expectancy is yet to be determined, but it is reasonable to expect an improvement compared with past experience with desferrioxamine. Other causes of mortality will become an increasingly important issue for older thalassemic patients: Surveillance, prophylaxis, and prompt treatment of infection remains essential, and chronic hepatitis virus infection should be managed with best available current therapies. More data on follow-up of thalassemic patients in middle income countries are needed to demonstrate a similar trend in improved survival. The life expectancy for those in low-income countries is similar to the situation 50 years ago in Europe and the United States. The global thalassemia and public health community should consider how to respond to this disparity.


EMDR beyond PTSD: A Systematic Literature Review.
Background: Eye Movement Desensitization and Reprocessing (EMDR) is a psychotherapeutic approach that has demonstrated efficacy in the treatment of Post-traumatic Stress Disorder (PTSD) through several randomized controlled trials (RCT). Solid evidence shows that traumatic events can contribute to the onset of severe mental disorders and can worsen their prognosis. The aim of this systematic review is to summarize the most important findings from RCT conducted in the treatment of comorbid traumatic events in psychosis, bipolar disorder, unipolar depression, anxiety disorders, substance use disorders, and chronic back pain. Methods: Using PubMed, ScienceDirect, and Scopus, we conducted a systematic literature search of RCT studies published up to December 2016 that used EMDR therapy in the mentioned psychiatric conditions. Results: RCT are still scarce in these comorbid conditions but the available evidence suggests that EMDR therapy improves trauma-associated symptoms and has a minor effect on the primary disorders by reaching partial symptomatic improvement. Conclusions: EMDR therapy could be a useful psychotherapy to treat trauma-associated symptoms in patients with comorbid psychiatric disorders. Preliminary evidence also suggests that EMDR therapy might be useful to improve psychotic or affective symptoms and could be an add-on treatment in chronic pain conditions.


Compression of the medulla oblongata and acute respiratory failure caused by rupture of a thrombosed large aneurysm of the anterior inferior cerebellar artery.
A 65-year-old female presented with an extremely rare case of a ruptured thrombosed large aneurysm of the anterior inferior cerebellar artery (AICA) in which a local hematoma compressed the medulla oblongata and caused acute respiratory failure. She first presented with dizziness, general fatigue, and nausea 2 months before admission. She was hospitalized for intense general fatigue, nausea, and occipitalgia. Computed tomography and T(1)-weighted magnetic resonance imaging showed a heterogeneous lesion around the right cerebello-medullary cistern. Angiography revealed a fusiform aneurysm of the right AICA. Asphyxia occurred 4 days after admission and the patient underwent an emergency operation. No subarachnoid hematoma was present, but a hematoma around the ruptured portion markedly compressed the medulla oblongata. The medulla oblongata was adequately decompressed after subtotal removal of the aneurysm. The patient's respiratory status and consciousness level recovered after the operation.


Identification of a placental enhancer for the human leptin gene.
Leptin is a hormone that regulates metabolic efficiency, energy expenditure, and food intake. Leptin is produced chiefly in adipose cells, but in humans, mRNA encoding leptin is also present in the placenta. Here we elucidate the basis for placental leptin production. The same promoter is used for adipose and placental transcription. An upstream enhancer functions in the JEG-3 and JAR choriocarcinoma cell lines but not in adipocytes or HeLa cells. The minimal positive acting region is 60 base pairs in length. This region is within a MER11 repetitive element, suggesting that human placental expression of leptin is the result of insertion of this element. Binding analyses demonstrated three protein binding sites, designated placental leptin enhancer elements (PLE)1, PLE2, and PLE3. PLE2 binds Sp1. Enhancer activity was reduced by mutation of the PLE1 or PLE3 sites but was unaffected by alteration of PLE2. Proteins binding to PLE3 were present in JEG-3 and human placental nuclear extracts but not in extracts from non-placental sources. Upon triplication, the PLE3 element was a strong enhancer in choriocarcinoma cells but not in HeLa cells. The protein binding to the PLE3 motif appears to be a novel, placenta-specific transcription factor.


Effect of cardiopulmonary bypass on plasma levels of nifedipine.
Blood levels of many medications are acutely lowered by cardiopulmonary bypass (CPB). Because nifedipine is often used to provide protection from coronary ischemia, a determination of the effect of CPB on plasma nifedipine levels might help to determine the potential clinical benefit of nifedipine during and after bypass. Four samples of blood were drawn from each of eight patients undergoing cardiac surgery: one before, two during, and one after CPB. Although plasma levels of nifedipine declined during and after bypass (P less than 0.05, analysis of variance), the time-course and slope of the decline indicate that this was an effect of normal metabolism of the drug rather than an effect of physiologic changes occurring during CPB. An important additional finding was that the majority of patients had subtherapeutic levels of nifedipine before bypass, suggesting that additional nifedipine given during and after surgery might be of benefit. The effect of the CPB circuit itself was also examined in vitro by mixing nifedipine into a pump prime solution that was then recirculated with 2 U of outdated blood while levels of nifedipine were measured for 3 h. Plasma levels did not change in either a CPB circuit exposed to light or kept in a darkened room.


[GIS and scenario analysis aid to water pollution control planning of river basin].
The forward and backward algorithms for watershed water pollution control planning were summarized in this paper as well as their advantages and shortages. The spatial databases of water environmental function region, pollution sources, monitoring sections and sewer outlets were built with ARCGIS8.1 as the platform in the case study of Ganjiang valley, Jiangxi province. Based on the principles of the forward algorithm, four scenarios were designed for the watershed pollution control. Under these scenarios, ten sets of planning schemes were generated to implement cascade pollution source control. The investment costs of sewage treatment for these schemes were estimated by means of a series of cost-effective functions; with pollution source prediction, the water quality was modeled with CSTR model for each planning scheme. The modeled results of different planning schemes were visualized through GIS to aid decision-making. With the results of investment cost and water quality attainment as decision-making accords and based on the analysis of the economic endurable capacity for water pollution control in Ganjiang river basin, two optimized schemes were proposed. The research shows that GIS technology and scenario analysis can provide a good guidance to the synthesis, integrity and sustainability aspects for river basin water quality planning.


The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization.
The Ecm1 gene encodes an 85-kDa protein of unknown function that was originally identified as a secretory protein of the murine osteogenic stromal cell line MN7. This paper describes the isolation of a genomic clone containing the human ECM1 gene from a chromosome 1 cosmid library and the characterization of its exon-intron structure. The protein coding region comprises 10 exons. The ECM1 gene maps at chromosome 1q21 outside the epidermal differentiation complex region. The ECM1 gene appears to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils. The full-length human ECM1 transcript contains 1838 bp and has an overall homology of 79.6% with the mouse Ecm1 cDNA. This transcript codes for a protein of 540 amino acids that is 69.4% identical and 81.3% similar to the corresponding mouse protein. The alternatively spliced variant, 1450 bp long, encodes a protein of 415 amino acids.


Interaction of lipid vesicle with silver nanoparticle-serum albumin protein corona.
The physical interaction between a lipid vesicle and a silver nanoparticle (AgNP)-human serum albumin (HSA) protein "corona" has been examined. Specifically, the binding of AgNPs and HSA was analyzed by spectrophotometry, and the induced conformational changes of the HSA were inferred from circular dichroism spectroscopy. The fluidity of the vesicle, a model system for mimicking cell membrane, was found to increase with the increased exposure to AgNP-HSA corona, though less pronounced compared to that induced by AgNPs alone. This study offers additional information for understanding the role of physical forces in nanoparticle-cell interaction and has implications for nanomedicine and nanotoxicology.


Selective contributions of the medial preoptic nucleus to testosterone-dependant regulation of the paraventricular nucleus of the hypothalamus and the HPA axis.
Previous data have consistently demonstrated an inhibitory effect of androgens on stress-induced hypothalamic-pituitary-adrenal (HPA) responses. Several brain regions may influence androgen-mediated inhibition of the HPA axis, including the medial preoptic area. To test the role of the medial preoptic nucleus (MPN) specifically, we examined in high- and low-testosterone-replaced gonadectomized rats bearing discrete bilateral lesions of the MPN basal and stress-induced indexes of HPA function, and the relative levels of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the amygdala. High testosterone replacement decreased plasma adrenocorticotropin hormone (ACTH) and paraventricular nucleus (PVN) Fos responses to restraint exposure in sham- but not in MPN-lesioned animals. AVP-, but not CRH-immunoreactivity staining in the external zone of the median eminence was increased by testosterone in sham animals, and MPN lesions blocked this increment in AVP. A similar interaction between MPN lesions and testosterone occurred on AVP mRNA levels in the medial nucleus of the amygdala. These findings support an involvement of MPN projections in mediating the AVP response to testosterone in both the medial parvocellular PVN and medial amygdala. We conclude that the MPN forms part of an integral circuit that mediates the central effects of gonadal status on neuroendocrine and central stress responses.


Predicting the stimulation effectiveness using pre-stimulation neural states via optogenetic activation of the medial septum glutamatergic neurons modulating the hippocampal neural activity.
In this study, we explored the role of pre-stimulation neural states on the effectiveness of optogenetic stimulation. Optogenetic stimulation was applied to the medial septum glutamatergic neurons to modulate the hippocampal neural activity in a rat tetanus toxin seizure model. The hippocampal local field potential was recorded using a multi electrode array in an awake and behaving rat. Optical stimulation with a 465nm light source was applied at 35Hz in a 20 seconds off / 20 seconds on pattern with simultaneous recording from the hippocampus. Both the baseline and the stimulation period recordings were divided into 2 second segments and used for the further analysis. In the first experiment, a support vector machine (SVM) model classified the neural states by using spectral features between 0 and 50Hz. 447 out of 545 segments (82.02%) were correctly labeled as `Baseline' while only 326 out of 544 (59.93%) segments from the stimulation period were correctly labeled as `Stimulation.' As the ratio of mislabels is significantly higher for the stimulation period (chi-squared, p<;0.01), we concluded that the stimulation was not always effective. In the second experiment, an SVM model predicted the stimulation effectiveness using the spectral features of the pre-stimulation segments. The classification result shows that 63.7% of the pre-stimulation segments correctly predicted the stimulation effectiveness. These findings suggest that the prediction of the stimulation effectiveness may improve the stimulation efficacy by implementing a state-based stimulation protocol.


The Oryx Antelope (Oryx gazella): An Unexpected Host for Porcine Circovirus-2 (PCV-2).
For several years after its discovery, Porcine circovirus 2 (PCV-2) represented a major threat to the swine industry through economic losses due to the associated clinical syndromes, decreased production performances in both symptomatic and asymptomatic animals and disease management costs. Widespread vaccination administration has largely reduced the impact of this infection and represents the most effective control measure. The efficacy of vaccination is threatened by the emergence of novel (or uncommon) PCV-2 genotypes. In addition to domestic pigs, PCV-2 has been detected in several other species, a fact which could have an impact on new variant emergence and maintenance. Considering this, the present study assessed the distribution of the minor PCV-2c genotype in non-Suidae ungulates in Namibia. Red hartebeests (Alcelaphus buselaphus caama) (n = 44), kudus (Tragelaphus strepsiceros) (n = 10) and oryxes (Oryx gazella) (n = 54), whose mediastinal lymph nodes were sampled after slaughtering during the period 2019-2021, were included in the study. Two oryxes (3.7%; 95% CI = 0.45-12.75%) were PCV-2-positive by PCR. Complete genome sequence was obtained for the two samples identifying them as PCV-2c genotype. The sequences were identical and shared a high percentage of identity (~99.9%) with those recently obtained from warthogs living in the same area. The present study confirms the presence of the PCV-2c genotype (previously considered extinct) in Namibian wild animal populations and demonstrates greater than expected PCV-2 host plasticity. Because of the role these niches can have in the maintenance and evolution of minor PCV-2 genotypes, more extensive and dedicated studies should be performed to prepare authorities to promptly react to potential emerging threats from these viruses.


Vulnerable child syndrome in the neonatal intensive care unit: A review and a new preventative intervention with feasibility and parental satisfaction data.
Vulnerable Child Syndrome (VCS) occurs in the setting in which a child recovers from a life-threatening illness, as result of which the parent develops heightened parental perceptions of child vulnerability (PPCV). This leads to a pattern of overprotective parenting which may result in adverse neurodevelopmental and behavioral outcomes in the child over time. Parents of premature infants have been shown to be at increased risk of developing raised PPCV while their infants may develop symptoms of VCS. The PreVNT trial is a randomized controlled trial designed to test the efficacy of a 5-session manualized Cognitive Behavioral Therapy (CBT) intervention to reduce PPCV. Results of a pilot study of parents of premature infants (n = 41) demonstrate that the intervention can be delivered with high ratings of treatment fidelity and with a completion rate of 100% during the NICU admission, and 78% at 6 months post term. Ratings of parental satisfaction ranged between 4.9 and 5 out of 5 demonstrating high satisfaction with the intervention. Pilot feasibility and maternal satisfaction data are presented for a group of 22 intervention families, which suggest a CBT model for understanding VCS is feasible and deemed helpful by parents. This review is gauged to summarize risk of VCS development, diagnosis of VCS, and effective treatments for VCS through Cognitive Behavioral Therapy. We also present a paradigm shift in a therapeutic approach by introducing the PreVNT Trial. Given that VCS can interfere with the long-term outcomes of both infant and family, it is important to understand VCS and address its involvement in NICU and post NICU discharge care. Further research is needed in this area.


Topology of electronic charge density and energetics of planar faults in fcc metals.
Using ab initio calculations we have studied the energetics and the evolution of the electronic charge density with shear in three fcc metals exhibiting different deformation properties, aluminum, silver, and iridium. The charge redistribution described by the change in character of specific charge density critical points (cps), is ascertained from the values of the charge density, rho(0), and its three principal curvatures, rho( parallel parallel), rho(hh), and rho(vv), respectively. The change in character of cps correlates with the energetics. For all three metals, rho(hh) vanishes near the unstable stacking configuration. The symmetry or asymmetry of the charge redistribution, measured by rho(hh)/rho(vv), may be an important factor determining stacking fault energies.


Enhancing pharmacy practice doctoral research with patient and public involvement.
Evidence shows that patient and public involvement (PPI) can have a positive effect on the quality and relevance of health services research. This article describes the experiences of PPI contributors within a pharmacy practice doctoral research project. This includes practical examples of how PPI contributed to the project and the impact this made. In addition, the PPI contributors and doctoral candidates' reflections are presented along with learning points to support other doctoral researchers planning PPI in their research.


Metvix (PhotoCure).
Metvix is a photosensitive cream containing the methyl ester of 5-aminolevulinic acid, which has been developed and launched by PhotoCure in Sweden for the treatment of high-risk basal cell carcinoma and actinic keratosis.


Echo-shifted multislice EPI for high-speed fMRI.
The advantages of event-related functional Magnetic Resonance Imaging (fMRI) and the increasing use of fMRI in cognitive experiments are both driving the development of techniques that allow images sensitive to the blood oxygen level-dependent effect to be acquired at ever-higher temporal resolution. Here, we present a technique based on the use of echo shifting (ES) in conjunction with a multislice (MS) echo planar imaging (EPI) readout, which allows T2*-weighted images to be generated with a repetition time per slice that is less than the echo time (TE). Using this ES-MS-EPI approach, it is shown that images with a TE of 40 ms can be acquired with an acquisition time per slice of only 27 ms. The utility of the MS-ES-EPI sequence is demonstrated in a visual-motor, event-related fMRI study in which nine-slice image volumes are acquired continuously at a rate of 4.1 Hz. The sequence is shown to produce reliable activation associated with both visual stimuli and motor actions.


Dexmedetomidine combined with ropivacaine for erector spinae plane block after posterior lumbar spine surgery: a randomized controlled trial.
Due to lumbar spinal surgery is frequently accompanied with moderate-to-severe postoperative pain, it is necessary to find an effective postoperative analgesia for patients with this surgery. This study aimed to observe the analgesic effect of dexmedetomidine combined with ropivacaine erector spinae plane block (ESPB) used in posterior lumbar spine surgery. In this clinical trial, patients undergoing posterior lumbar spine surgery were recruited and randomly divided into two groups: intervention and control. The intervention group (Group E) received 0.375% ropivacaine with 1 µg/kg dexmedetomidine in a total of 20 ml for ESPB; the control group (Group C) received 20 ml ropivacaine 0.375% for ESPB. US-guided ESPB was performed preoperatively in all patients. Demographics, anesthesia time, surgery time, and ASA grade from the participants were recorded at baseline. The primary clinical outcome measures were 2-, 4-, 8-, 12-, 24-and 48-h visual analog scale (VAS) pain scores after surgery at rest and movement state. Other end points included opioid consumption, number of PCIA presses, flurbiprofen-axetil consumption, quality of recovery and pain management after surgery. One hundred twenty patients were enrolled in the study (mean [SD] ages: Group E, 54.77 [8.61] years old; Group C,56.40 [7.87] years old; P = 0.280). The mean anesthesia time was 152.55 (15.37) min in Group E and 152.60 (16.47) min in Group C (P = 0.986). Additionally, the surgery time was 141.70 (15.71) min in Group E compared to 141.48 (17.13) min in Group C (P = 0.943). In addition, we found that the VAS pain scores in the resting state during the postoperative period at 8-48 h were lower in Group E than in Group C. However, the VAS pain scores in the active state were lower in Group E at 12-48 h (P < 0.05). More importantly, the consumption of opioids and flurbiprofen-axetil after surgery was also lower in Group E (P < 0.05). Subsequently, we administered questionnaires on the quality of recovery and pain management after surgery that were positively correlated with the postoperative analgesic effect. It was worth affirming that the QoR-15 scores and APS-POQ-R questionnaire results were different between the two groups, further confirming that the combination of drugs not only could obtain an ideal analgesic effect but also had no obvious adverse reactions (P < 0.05). All the findings suggested that dexmedetomidine could significantly relieve postoperative pain and reduce the consumption of opioids in patients undergoing posterior lumbar spine surgery without obvious adverse reactions as a local anesthetic adjuvant. Further studies with larger sample sizes and different drug dosages may be useful in understanding the potential clinical benefits of dexmedetomidine.


Experimental and numerical study of nonsmooth maximum bounce height changes in a bouncing ball system.
The bouncing ball system is a simple mechanical collision system that has been extensively studied for several decades. In this study, we investigate the bouncing ball's dynamics both numerically and experimentally. We implement the system using a table tennis ball and paddle vibrated by a shaker. We focus on the relationship between the ball's maximum bounce height in the long time interval and the paddle's vibration frequency, observing several stepwise height changes for frequencies of 25-50 Hz, noting this significant characteristic in both our experiments and numerical simulations. We concentrate on this paddle frequency interval because the phenomenon is easy to handle in numerical simulations. Because the observed phenomenon has a simple order, it can be universal and appear in a large class of collision dynamics. Possibly, some researchers have investigated the bouncing ball system in which the nonsmooth maximum bounce height changes occur. However, they may have failed to notice the changes because the maximal height of the ball was not considered.


Possible role of endothelin in the pathogenesis of cerebral vasospasm.
Since the discovery of endothelin-1 (ET-1), its involvement in cerebral vasospasm after subarachnoid hemorrhage (SAH) has been suspected. We performed various experiments, first to demonstrate the presence of ET in both patients and dogs with SAH, and second to examine the effects of ET synthesis inhibition in experimental vasospasm. Here we report that ET was present in both plasma and cerebrospinal fluid (CSF) in SAH, but did not correlate with vasospasm. However, ET was locally expressed in the vascular endothelium in vasospasm. Several therapeutic approaches causing the inhibition of ET synthesis were effective in preventing the development of vasospasm. Such approaches utilized drugs that inhibited RNA and DNA synthesis. Among them, actinomycin D treatment was most effective. We also utilized phosphoramidon, a recently found conversion inhibitor of big ET to ET. However, this product failed to ameliorate the development of vasospasm. Therefore, although we cannot yet conclude that ET is the main cause of cerebral vasospasm, it may, at least, act as one of the modifying factors in cerebral vasospasm.


Masters of adaptation: learning in late life adjustments.
The purpose of this research is to understand the relationship between human development in older adults and personal learning. Personal or self-directed learning (SDL) refers to a style of learning where the individual directs, controls, and evaluates what is learned. It may occur with formal classes, but most often takes place in non-formal situations. This study employed a descriptive qualitative design incorporating in-depth, semistructured interviews for data collection. The sample of 10 purposefully selected older adults from a rural area reflected diversity in gender, race, education, and employment. Data analysis was guided by the constant comparative method. The primary late life adjustments of these older adults were in response to having extra time, changes in family, and social and physical loss. This research also indicated that late life adjustments are a primary incentive for self-directed learning. The results of this study indicated that older adults become masters of adaptation through the use of self-directed learning activities.


MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats.
As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO). MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.


Analysis of betaS and betaA genes in a Mexican population with African roots.
To investigate the origin of the beta(A) and beta(S) genes in a Mexican population with African roots and a high frequency of hemoglobin S, we analyzed 467 individuals (288 unrelated) from different towns in the states of Guerrero and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was 12.8%, which may represent a public health problem. The frequencies of the beta-haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37 beta(S)). We observed 15 different beta(A) haplotypes, the most common of which were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise distributions and Nei's genetic distance analysis using 32 worldwide populations showed that the beta(A) genes are more closely related to those of Mexican Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%, respectively. Comparison of these haplotypes with 17 other populations revealed a high similitude with the population of the Central African Republic. These data suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals from the Costa Chica region.


[Brain metastases from hepatocellular carcinoma: clinical features and prognostic factors in 31 cases].
Brain metastases (BM) from hepatocellular carcinoma (HCC) are rare and are associated with a poor prognosis. The aim of this study was to analyze the clinical features and evaluate the prognostic factors of brain metastases from hepatocellular carcinoma. The clinical data of thirty-one patients with HCC and BM treated in the First Affiliated Hospital of Xinjiang Medical University between January 1998 and December 2013 were retrospectively reviewed. Univariate and multivariate survival analyses were performed to identify possible prognostic factors. Thrity-one patients were diagnosed with BM from HCC, an incidence rate of 0.61%. The median age at diagnosis of brain metastases was 48.5 years. Twenty-six patients were male. The median interval from diagnosis of hepatocellular carcinoma to brain metastases was 14 months. The median survival after the diagnosis of BM was 10 weeks. Univariate analysis showed that treatment modality, number of brain lesions, Karnofsky performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on the survival. The multivariate analysis showed that the low RPA class and aggressive brain radiotherapy were positively associated with improved survival. BM from HCC is rare and associated with an extremely poor prognosis. However, patients with a low RPA class may benefit from aggressive brain radiotherapy.