Autotaxin--an LPA producing enzyme with diverse functions.
Autotaxin (ATX) is an ecto-enzyme responsible for lysophosphatidic acid (LPA) production in blood. ATX is present in various biological fluids such as cerebrospinal and seminal fluids and accounts for bulk LPA production in these fluids. ATX is a member of the nucleotide pyrophosphatase/phosphodiesterase (NPP) family and was originally isolated from conditioned medium of melanoma cells as an autocrine motility stimulating factor. LPA, a second-generation lipid mediator, binds to its cognate G protein-coupled receptors through which it exerts a number of biological functions including influencing cell motility and proliferation stimulating activity. Some of the biological roles of LPA can be mediated by ATX. However, there are other LPA-producing pathways independent of ATX. The accumulating evidences for physiological and pathological functions of ATX strongly support that ATX is an important therapeutic target. This review summarizes the historical aspects, structural basis, pathophysiological functions identified in mice studies and clinical relevance discovered by measuring the blood ATX level in human. The general features and functions of each NPP family member will be also briefly reviewed. The presence of the ATX gene in other model organisms and recently developed ATX inhibitors, both of which will be definitely useful for further functional analysis of ATX, will also be mentioned.


Association of nasomaxillary asymmetry in children with unilateral cleft lip and palate and their parents.
It has been suggested previously that increased width of midfacial structures is associated with the development of palatal clefting. The aim of this study was to evaluate the association of transverse craniofacial asymmetry between children with unilateral cleft lip and palate (UCLP) and their parents. Specifically, we hypothesized that parental transverse craniofacial asymmetry is a risk factor associated with the development of asymmetry in children with UCLP. Retrospective cross-sectional investigation including affected children and their noncleft parents. A total of 64 children-parent sets of data (32 child-biological mother + 32 child-biological father) were included. Subject records included posteroanterior cephalometric radiographs obtained from 29 Costa Rican families with UCLP. The side of parental nasal asymmetry was significantly associated with the side of cleft in their children. For the majority of parents with children suffering from a left cleft, nasal width was larger on the left, compared with the right side. Similarly, in the majority of parents with children suffering from a right cleft, nasal width was larger on the right, compared with the left side. The results suggest that unilaterally increased nasomaxillary width in parents may play a key role in the development of ipsilateral palatal clefting in their offspring, therefore underscoring the importance of craniofacial form as a genetic etiologic factor in the genesis of clefting. Better understanding of the role of craniofacial form in cleft development will ultimately allow for the assessment of risk for cleft lip and palate.


Difference in enzymatic properties between "staphylothrombin" and free alpha-thrombin.
Bacterial protein, staphylocoagulase, binds stoichiometrically to human prothrombin resulting in a coagulant complex, staphylothrombin. The enzymatic properties of staphylothrombin differ from those of alpha-thrombin in their substrate specificities toward natural and synthetic substrates, in addition to their interaction with protease inhibitors. In order to obtain information about the region of staphylocoagulase that interacts with human prothrombin, staphylocoagulase was cleaved by alpha-chymotrypsin. This limited alpha-chymotryptic cleavage of staphylocoagulase yielded three large fragments, fragments of 43, 30, and 20 kDa. The 43-kDa fragment exhibited a high affinity for human prothrombin (Kd = 1.7 nM), which is comparable to the affinity observed using intact staphylocoagulase (Kd = 0.46 nM). A complex of the 43-kDa fragment and prothrombin possessed both clotting and amidase activities essentially identical to those observed in a complex of intact staphylocoagulase and prothrombin. The 30-kDa fragment exhibited weaker affinity for prothrombin (Kd = 120 nM). While a complex of this fragment and prothrombin did not exhibit clotting activity, it nonetheless possessed a weak amidase activity. The 20-kDa fragment was found only to bind to prothrombin. The NH2-terminal sequence analyses of these fragments revealed that the 43-kDa fragment constitutes the NH2-terminal portion of staphylocoagulase, and contains the 30-kDa and 20-kDa fragments. It is therefore concluded that the functional region of staphylocoagulase for binding and activation of prothrombin is localized in the NH2-terminal region of the intact protein. The 43-kDa fragment contains 324 amino acids with a molecular weight of 38,098. The 43-kDa fragment has an unusual amino acid composition based on the sequence, in which the sum of Asp (28 residues), Asn (22), Glu (35), Gln (9), and Lys (52) residues accounts for more than 45% of the total residues. A comparison of the amino acid sequence of the 43-kDa fragment with that of streptokinase did not reveal any obvious sequence homology. There was also no sequence homology with those of trypsin, alpha-chymotrypsin, and elastase.


Differential expression of interleukin-35 receptor distinguishes different subsets of granulocyte-macrophage-colony-stimulating factor-producing T helper cells in a mouse endometriosis model.
The immune system contributes to the pathophysiology of endometriosis. The role of ThGM cells, which produce granulocyte macrophage-colony-stimulating factor (GM-CSF), in the pathogenesis of endometriosis remains unknown. To analyze the features of ThGM cells in endometriosis, a mouse endometriosis model was established. ThGM cells in the spleen, peritoneal fluid (PF), and endometriotic lesions (EL) were measured by flow cytometry, based on the expression of surface markers and intracellular proteins. Live ThGM cells were sorted according to chemokine receptor expression profiles and their effects on other CD4+ T cell subsets were determined by co-culture assays. An adoptive transfer assay was performed to characterize the effect of ThGM cells on endometriosis. We found that ThGM cells were present in endometriotic PF and EL. Live EL ThGM cells were enriched in CD4+CXCR3-CCR8-CCR4+CCR10+ T cells. EL ThGM cells differentially express interleukin-35 receptor (IL-35R), consisting of an IL-35R+ subset and an IL-35R- subset. The IL-35R+ subset expressed less GM-CSF, interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α) and proliferated slower than the IL-35R- subset. Meanwhile, the IL-35R+ subset was weaker than the IL-35R- subset in promoting the functions of Th1 and Th17 cells. ThGM cell transfer did not influence EL development but significantly alleviated pro-inflammatory cytokines in PF and ELs. Interleukin-35 (IL-35), the ligand of IL-35R, suppressed ThGM cell function and proliferation in an IL-35R-dependent manner. In summary, ThGM cells in the PF and ELs might exacerbate endometriotic inflammation. IL-35 might suppress the function of ThGM cells via IL-35R.


Regression comparisons of Tetrahymena pyriformis and Poecilia reticulata toxicity.
The toxicity data of chemicals common to both the Poecilia reticulata mortality assay and the Tetrahymena pyriformis growth impairment assay were evaluated. Two chemicals were not toxic at saturation in the T. pyriformis assay. In addition, due to abiotic transformation, a third chemical was removed from further consideration. Each chemical was a priori assigned a mode of toxic action: neutral non-covalent, polar non-covalent, or electrophilic covalent toxicity. To further investigate comparisons between endpoints, polar and electrophilic chemicals were separated into class-based groups. The polar non-covalent chemicals were separated into phenols and anilines, while the electrophilic chemicals were separated into those reacting via Schiff-base formation (i.e., aldehydes) and those reacting via bimolecular substitution to a nucleophile (i.e., selected nitroaromatics). A comparison of toxic potency as a collective set was statistically described by the relationship; log(LC50(-1)) = 1.05(log(IGC50(-1))) + 0.56, n = 124; r2 = 0.85; s = 0.42; F = 682; Pr > F = 0.0001. The relationship between endpoints was inversely proportional to reactivity associated with the mode of action. While the comparative toxicity for neutral narcotics exhibited an excellent fit (r2 = 0.94), the fits for polar narcotics and electrophiles were poorer, r2 = 0.69 and 0.62, respectively. Investigations into class-based groupings indicated fit of toxic potency data for aldehydes (r2 = 0.85) and phenols (r2 = 0.81) were quite good. However, fits for anilines (r2 = 0.43) and nitroaromatics (r2 = 0.68) revealed that toxicity was not as well related between endpoints for these chemicals.


Molecular Characterization of Low-Density Polyethene (LDPE) Degrading Bacteria and Fungi from Dandora Dumpsite, Nairobi, Kenya.
This study aimed at molecular and biochemical characterization of low-density polyethene (LDPE) degrading fungi and bacteria from Dandora dumpsite, Nairobi. Twenty bacterial and 10 fungal isolates were identified using 16S rDNA and 18S rDNA sequences for bacteria and fungi, respectively. The highest fungal degradation was attributed to Aspergillus oryzae strain A5,1 while the highest bacterial degradation was attributed to Bacillus cereus strain A5,a and Brevibacillus borstelensis strain B2,2, respectively. Isolates were screened for their ability to produce extracellular laccase and esterase; Aspergillus fumigatus strain B2,2 exhibited the highest presence of laccase (15.67 mm) while Aspergillus oryzae strain A5,1 exhibited the highest presence of esterase (14.33 mm). Alkane hydroxylase-encoding genes were screened for using primer AlkB 1 which amplified the fragment of size 870 bp. Four bacterial samples were positive for the gene. Optimum growth temperature of the fungal isolates was 30°C. The possession of laccase, esterase, and alkane hydroxylase activities is suggested as key molecular basis for LDPE degrading capacity. Knowledge of optimum growth conditions will serve to better utilize microbes in the bioremediation of LDPE. The application of Aspergillus oryzae strain A5,1 and Bacillus cereus strain A5,a in polyethene degradation is a promising option in this kind of bioremediation as they exhibited significantly high levels of biodegradation. Further investigation of more alkane degrading genes in biodegrading microbes will inform the choice of the right microbial consortia for bioaugmentation strategies.


Clonal variation in paramecium. I. Persistent unstable clones.
Clones of Paramecium of identical serotype when cultured in test tubes may differ in their ability to give rise to subclones of this serotype. Characteristically, stable clones yield progeny indistinguishable from their parents, while from unstable clones diverse subclones with new serotypes can be isolated repeatedly. Stable lines are resistant to changes in culture medium and also are unaffected by most sera. In contrast, the numbers and kinds of serotypes displayed among subclones derived from unstable lines are often affected by these same agents. Stable and unstable clones are interconvertible when the medium from individual cultures is repeatedly and frequently replaced by fresh culture fluid. This effect is very likely a result of the removal of the initial exhausted medium with any cell products rather than the addition of fresh nutrient.


BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity.
L-Glutamate (Glu) activates at least eight different G protein-coupled receptors known as metabotropic glutamate (mGlu) receptors, which mostly act as regulators of synaptic transmission. These receptors consist of two domains: an extracellular domain in which agonists bind and a transmembrane heptahelix region involved in G protein activation. Although new mGlu receptor agonists and antagonists have been described, few are selective for a single mGlu subtype. Here, we have examined the effects of a novel compound, BAY36-7620 [(3aS,6aS)- 6a-Naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on], on mGlu receptors (mGlu1-8), transiently expressed in human embryonic kidney 293 cells. BAY36-7620 is a potent (IC(50) = 0.16 microM) and selective antagonist at mGlu1 receptors and inhibits >60% of mGlu1a receptor constitutive activity (IC(50) = 0.38 microM). BAY36-7620 is therefore the first described mGlu1 receptor inverse agonist. To address the mechanism of action of BAY36-7620, Glu dose-response curves were performed in the presence of increasing concentrations of BAY36-7620. The results show that BAY36-7620 largely decreases the maximal effect of Glu. Moreover, BAY36-7620 did not displace the [(3)H]quisqualate binding from the Glu-binding pocket, further indicating that BAY36-7620 is a noncompetitive mGlu1 antagonist. Studies of chimeric receptors containing regions of mGlu1 and regions of DmGluA, mGlu2, or mGlu5, revealed that the transmembrane region of mGlu1 is necessary for activity of BAY36-7620. Transmembrane helices 4 to 7 are shown to play a critical role in the selectivity of BAY36-7620. This specific site of action of BAY36-7620 differs from that of competitive antagonists and indicates that the transmembrane region plays a pivotal role in the agonist-independent activity of this receptor. BAY36-7620 will be useful to further delineate the functional importance of the mGlu1 receptor, including its putative agonist-independent activity.


The problem of camouflaging via mirror reflections.
This work is related to billiards and their applications in geometric optics. It is known that perfectly invisible bodies with mirror surface do not exist. It is, therefore, natural to search for bodies that are, in a sense, close to invisible. We introduce a visibility index of a body measuring the mean angle of deviation of incident light rays, and derive a lower estimate for this index. This estimate is a function of the body's volume and of the minimal radius of a ball containing the body. This result is far from being final and opens a possibility for further research.


Iodmetric and spectrophotometric assays for cephradine after its hydrolysis with a beta-lactamase.
Iodmetric and spectrophotometric methods were developed for the analysis of the new antibiotic cephradine. The procedures are modifications of known methods but are novel in employing a specific beta-lactamase for hydrolysis of the beta-lactam ring of the cephalosporin molecule. The iodometric method is rapid, precise, and accurate, but it requires fairly large amounts of cephradine. The spectrophotometric method, using differential UV absorption at 260 nm, is more rapid and more sensitive than the iodometric method but somewhat less accurate. Both methods proved useful for the routine assay of cephradine in certain formulations.


Giant hiatal hernia.
A giant hiatal hernia (HH) is a hernia that includes at least 30% of the stomach in the chest, although a uniform definition does not exist; most commonly, a giant HH is a type III hernia with a sliding and paraesophageal component. The etiology of giant HH is not entirely clear, and two potential mechanisms exist: (1) gastroesophageal reflux disease (GERD) leads to esophageal scarring and shortening with resulting traction on the gastroesophageal junction and gastric herniation; and (2) chronic positive pressure on the diaphragmatic hiatus combined with a propensity to herniation leads to gastric displacement into the chest, resulting in GERD. The short esophagus and GERD are key concepts to understanding the pathophysiology of giant HH, and these concepts are critical to address this problem appropriately. A successful repair of giant HH requires adherence to basic hernia repair principles (ie, hernia sac excision, tension-free repair), recognition and correction of a short esophagus, and a well-performed antireflux procedure. Recurrence rates for open giant HH repairs in expert hands range between 2% and 12%; large series have demonstrated that meticulous laparoscopic surgical technique can emulate the results of open giant HH repair.


Car driving in schizophrenia: can visual memory and organization make a difference?
Driving is a meaningful occupation which is ascribed to functional independence in schizophrenia. Although it is estimated that individuals with schizophrenia have two times more traffic accidents, little research has been done in this field. Present research explores differences in mental status, visual working memory and visual organization between drivers and non-drivers with schizophrenia in comparison to healthy drivers. There were three groups in the study: 20 drivers with schizophrenia, 20 non-driving individuals with schizophrenia and 20 drivers without schizophrenia (DWS). Visual perception was measured with Rey-Osterrieth Complex Figure test and a general cognitive status with Mini-Mental State Examination. The general cognitive status predicted actual driving situation in people with schizophrenia. No statistically significant differences were found between driving and non-driving persons with schizophrenia on any of the visual parameters tested, although these abilities were significantly lower than those of DWS. The research demonstrates that impairment of visual abilities does not prevent people with schizophrenia from driving and emphasizes the importance of general cognitive status for complex and multidimensional everyday tasks. The findings support the need for further investigation in the field of car driving for this population - a move that will considerably contribute to the participation and well-being. Implication for Rehabilitation Unique approach for driving evaluation in schizophrenia should be designed since direct applications of knowledge and practice acquired from other populations are not reliable. This research demonstrates that visual perception deficits in schizophrenia do not prevent clients from driving, and general cognitive status appeared to be a valid determinant for actual driving. We recommended usage of a general test of cognition such as Mini-Mental State Examination, or conjunction number of cognitive factors such as executive functions (e.g., Trail Making Test) and attention (e.g., Continuous Performance Test) in addition to spatial-visual ability tests (e.g., Rey-Osterrieth Complex Figure test) for considering driving status in schizophrenia.


The socioecological psychology of upward social mobility.
Intergenerational upward economic mobility-the opportunity for children from poorer households to pull themselves up the economic ladder in adulthood-is a hallmark of a just society. In the United States, there are large regional differences in upward social mobility. The present research examined why it is easier to get ahead in some cities and harder in others. We identified the "walkability" of a city, how easy it is to get things done without a car, as a key factor in determining the upward social mobility of its residents. We 1st identified the relationship between walkability and upward mobility using tax data from approximately 10 million Americans born between 1980 and 1982. We found that this relationship is linked to both economic and psychological factors. Using data from the American Community Survey from over 3.66 million Americans, we showed that residents of walkable cities are less reliant on car ownership for employment and wages, significantly reducing 1 barrier to upward mobility. Additionally, in 2 studies, including 1 preregistered study (1,827 Americans; 1,466 Koreans), we found that people living in more walkable neighborhoods felt a greater sense of belonging to their communities, which is associated with actual changes in individual social class. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Health care management of children with cognitive and physical disabilities: to treat or not to treat.
Advanced medical technology has provided life support and maintenance for high risk infants. In dramatically increasing numbers, children surviving aggressive intervention as neonates and infants suffer from varying degrees of physical and mental disability. Once these children are stable and grow older difficult medical intervention decisions need to be made. As nurses, we are often in situations involving difficult treatment decisions made by the family and health care team. We need to be aware of our personal beliefs and ethical principles to effectively support family members and participate in decision making. Ethical principles serve as a guide to the decision making process.


Integrating Linguistics, Social Structure, and Geography to Model Genetic Diversity within India.
India represents an intricate tapestry of population substructure shaped by geography, language, culture, and social stratification. Although geography closely correlates with genetic structure in other parts of the world, the strict endogamy imposed by the Indian caste system and the large number of spoken languages add further levels of complexity to understand Indian population structure. To date, no study has attempted to model and evaluate how these factors have interacted to shape the patterns of genetic diversity within India. We merged all publicly available data from the Indian subcontinent into a data set of 891 individuals from 90 well-defined groups. Bringing together geography, genetics, and demographic factors, we developed Correlation Optimization of Genetics and Geodemographics to build a model that explains the observed population genetic substructure. We show that shared language along with social structure have been the most powerful forces in creating paths of gene flow in the subcontinent. Furthermore, we discover the ethnic groups that best capture the diverse genetic substructure using a ridge leverage score statistic. Integrating data from India with a data set of additional 1,323 individuals from 50 Eurasian populations, we find that Indo-European and Dravidian speakers of India show shared genetic drift with Europeans, whereas the Tibeto-Burman speaking tribal groups have maximum shared genetic drift with East Asians.


Efficacy and safety of patient-controlled thoracic epidural analgesia alone versus patient-controlled intravenous analgesia with acetaminophen after laparoscopic distal gastrectomy for gastric cancer: a propensity score-matched analysis.
Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control. We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration. Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups. PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG.


New strategies for the management of no-reflow after primary percutaneous coronary intervention.
The myocardial no-reflow phenomenon is characterized by a reduced antegrade myocardial blood flow despite an open infarct-related artery in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Importantly, no-reflow is known to be associated with unfavorable clinical outcome and prognosis. It is a complex phenomenon and is caused by the variable combination of four pathogenetic components: distal atherothrombotic embolization, ischemic injury, reperfusion injury and susceptibility of coronary microcirculation to injury. As a consequence, appropriate strategies to prevent or treat each of these components are expected to reduce the occurrence of no-reflow. Mechanical and pharmacological approaches performed before, during and after performing myocardial revascularization have been investigated in recent studies, in order to reduce the rate of no-reflow. In this article, we concentrate on the major preventive and therapeutic approaches currently available for the management of the no-reflow phenomenon.


Adiponectin and its association with bone mass accrual in childhood.
Circulating adiponectin levels are inversely related to bone mineral density (BMD) in humans and animal models. Previous studies in humans have been confined largely to adult populations, and whether adiponectin influences bone mass accrual in childhood is unclear. We examined this question using the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort by investigating relationships between circulating adiponectin levels at a mean age of 9.9 years, indices of bone mass as measured by total-body dual-energy X-ray absorptiometry (DXA) at ages 9.9 and 15.5 years, and cortical bone parameters as measured by peripheral quantitative computed tomography (pQCT) of the midtibia at age 15.5 years. A total of 4927 children were included at age 9.9 years, of whom 97% and 90% of boys and girls, respectively, were in prepuberty or early puberty, as defined by Tanner stage 1-2. A total of 2754 children were included at age 15.5 years, of whom 95% and 97% of boys and girls, respectively, were in late puberty, as defined by Tanner stage 4-5. Circulating adiponectin was found to be related to fat mass, lean mass, and, to a lesser extent, height, so analyses were adjusted for these three variables to identify possible independent effects of adiponectin on bone development. Adiponectin was inversely related to total-body-less-head bone mineral content (BMC; -3.0%), bone area (BA; -1.8%), BMC divided by BA (BMD; -4.8%), and BMC adjusted for BA by linear regression (aBMC; -5.6%), as measured at age 9.9 years (coefficients show change per doubling in adiponectin concentration, p < .001). Consistent with these results, inverse associations also were seen between adiponectin and cortical BMC (-4.8%) and cortical bone area (-4.7%), as measured by tibial pQCT at age 15.5 years (p < .001). Further pQCT results suggested that this inverse association of adiponectin with skeletal development predominantly involved a negative association with endosteal relative to periosteal expansion, as reflected by cortical thickness (-6.0%, p < .001). We conclude that, independent of fat mass, lean mass, and height, adiponectin is associated with lower bone mass in childhood predominantly owing to an influence on relative endosteal expansion. Since these associations were observed before and after puberty, this suggests that setting of adiponectin levels in midchildhood has the potential to exert long-term effects on bone strength and fracture risk.


Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases.
In 67 patients (mean age 51 years, range 26-79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation greater than 80% in 75%, serum ferritin greater than 1000 micrograms/l in 84%, and overt diabetes in 48%. Alcohol intake was greater than 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA-A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p less than 0.01) and 9% (p less than 0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty-three patients were followed for 1-260 months (median 24); 43 received regular iron-depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.


Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury.
Spinal cord injury (SCI) results in loss of oligodendrocytes demyelination of surviving axons and severe functional impairment. Spontaneous remyelination is limited. Thus, cell replacement therapy is an attractive approach for myelin repair. In this study, we transplanted adult brain-derived neural precursor cells (NPCs) isolated from yellow fluorescent protein-expressing transgenic mice into the injured spinal cord of adult rats at 2 and 8 weeks after injury, which represents the subacute and chronic phases of SCI. A combination of growth factors, the anti-inflammatory drug minocycline, and cyclosporine A immunosuppression was used to enhance the survival of transplanted adult NPCs. Our results show the presence of a substantial number of surviving NPCs in the injured spinal cord up to 10 weeks after transplantation at the subacute stage of SCI. In contrast, cell survival was poor after transplantation into chronic lesions. After subacute transplantation, grafted cells migrated >5 mm rostrally and caudally. The surviving NPCs integrated principally along white-matter tracts and displayed close contact with the host axons and glial cells. Approximately 50% of grafted cells formed either oligodendroglial precursor cells or mature oligodendrocytes. NPC-derived oligodendrocytes expressed myelin basic protein and ensheathed the axons. We also observed that injured rats receiving NPC transplants had improved functional recovery as assessed by the Basso, Beattie, and Bresnahan Locomotor Rating Scale and grid-walk and footprint analyses. Our data provide strong evidence in support of the feasibility of adult NPCs for cell-based remyelination after SCI.


State programs for universal newborn hearing screening.
Published reports of several statewide and hospital-based systems for universal newborn hearing screening demonstrate that successful large-scale programs that appropriately identify infants with hearing loss in the earliest months of life can be developed. These programs are characterized by nursery-based screening rates of 95% or higher, referral rates of 6% or less, and reasonable per-infant costs. Less data are available regarding the outcome of these screening programs in ensuring confirmation of hearing loss by 3 months of age and initiation of intervention by 6 months of age. The results of the MDNC survey provide important information on the status of newborn hearing screening, audiologic assessment, and intervention services in 16 states. The survey reveals that hospitals have initiated universal newborn hearing screening programs using appropriate technology but that confirmation of hearing loss, fitting of amplification, and enrollment in early intervention are often delayed beyond the JCIH recommendations. Several factors might contribute to late confirmation of hearing loss and delayed amplification and intervention. First, as shown in the Colorado report, lack of a mandatory statewide system for tracking and reporting may delay transition of infants and families from screening to diagnosis, and diagnosis to intervention. In addition, many states lack a centralized system for reporting confirmed hearing loss. Successful statewide programs for universal newborn hearing screening, audiologic diagnosis, and early intervention depend on data-reporting strategies that facilitate transition of infants and families through a system of care. Second, lack of understanding about the urgent need for intervention in the earliest months of life may hinder referral to early intervention programs. Recent data from Colorado's universal newborn hearing screening program reveals that infants who are deaf or who have hearing losses achieve significantly better language development outcomes if intervention begins before age 6 months than infants whose intervention begins after 6 months of age. Hopefully, as these data become more widely available, the compelling need for early intervention will facilitate transition into these services. Although universal newborn hearing screening programs are increasing rapidly, states have not yet developed the coordinated systems for linking universal newborn hearing screening programs to audiologic diagnostic services and audiologic diagnostic services to early intervention programs. Key issues impeding development of these systems may be lack of tracking and reporting systems, lack of standardized guidelines for screening, diagnostic audiologic assessment, hearing aid fitting for very young infants, and lack of understanding about the compelling need for intervention in the earliest months of life. Development of complete systems of care must become a priority for universal newborn hearing screening to provide its ultimate benefit.


Permanent ileostomy without external appliance: Kock internal reservoir (pouch) operation.
Employing a surgical technique described by Dr. Nils Kock of Göteborg, Sweden one can create a continent ileostomy beyond an internal reservoir of ileum for patients who have had total proctocolectomy. This operation is designed to obviate the necessity for wearing an external appliance. Instead, the patient introduces a catheter through the ileostomy into the reservoir of ileum three or four times daily and evacuates it in a convenient manner. Our experience with seven patients, as well as a useful opertive variation of our own, is described. In six patients the procedure was carried out at the time of proctocolectomy. Currently six of the seven patients function without an appliance. Two of the seven had serious postoperative complications which were associated with the pouch. While a number of physical and emotional advantages are ascribed to the procedure, the specific hazards of the complex surgery, the extra time consumed daily in emptying the reservoir, and the necessity for further surgery if the pouch fails to function in a satisfactory manner must be balanced against them. Over the short term, the experience of our patients with this operation has been favorable. Larger series have been reported by Dr. Kock and by Dr. Beahrs at the Mayo Clinic. While 80% of their patients have had satisfactory eventual outcomes, a larger number of secondary operations and an ultimate 20% incidence of unsatisfactory results dictate the necessity for a guarded approach to this procedure.


Regulation of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA contents in human hepatoma cell line Hep G2 by distinct classes of mevalonate-derived metabolites.
Hep G2 cells were incubated under conditions known to influence the HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity, e.g. in the presence of compactin (a competitive inhibitor of HMG-CoA reductase itself) and U18666A (a squalene-2,3-epoxide cyclase inhibitor). We studied the effects of these conditions both on the HMG-CoA reductase activity and on the reductase mRNA content. In the presence of compactin the mRNA content increased, but less than the enzyme activity, as determined after removal of the inhibitor. The increase in mRNA could be prevented by addition of mevalonate or by a combination of low-density lipoprotein (LDL) plus a low concentration of mevalonate. LDL alone prevented the compactin-induced increases in mRNA and activity only partially. The effect of U18666A on reductase mRNA content and activity was biphasic, i.e. a slight decrease at low (0.3-0.5 microM) concentrations, with a concomitant formation of polar sterols [Boogaard, Griffioen & Cohen (1987) Biochem. J. 241, 345-351], and an increase at high (20-30 microM) concentrations, with complete blockage of sterol formation. At these high concentrations of U18666A, additional compactin (2 microM) increased the reductase activity, but not the mRNA content. We conclude that non-sterol metabolites of mevalonate regulate exclusively at the enzyme level, whereas sterol metabolites regulate at the reductase mRNA level. In the latter group of regulators we distinguish mevalonate metabolites which can, and metabolites which cannot, be replaced by exogenous LDL.


CHARACTERIZATION OF CELL WALL POLYSACCHARIDES OF THE COENCOCYTIC GREEN SEAWEED BRYOPSIS PLUMOSA (BRYOPSIDACEAE, CHLOROPHYTA) FROM THE ARGENTINE COAST(1).
Bryopsis sp. from a restricted area of the rocky shore of Mar del Plata (Argentina) on the Atlantic coast was identified as Bryopsis plumosa (Hudson) C. Agardh (Bryopsidales, Chlorophyta) based on morphological characters and rbcL and tufA DNA barcodes. To analyze the cell wall polysaccharides of this seaweed, the major room temperature (B1) and 90°C (X1) water extracts were studied. By linkage analysis and NMR spectroscopy, the structure of a sulfated galactan was determined, and putative sulfated rhamnan structures and furanosidic nonsulfated arabinan structures were also found. By anion exchange chromatography of X1, a fraction (F4), comprising a sulfated galactan as major structure was isolated. Structural analysis showed a linear backbone constituted of 3-linked β-d-galactose units, partially sulfated on C-6 and partially substituted with pyruvic acid forming an acetal linked to O-4 and O-6. This galactan has common structural features with those of green seaweeds of the genus Codium (Bryopsidales, Chlorophyta), but some important differences were also found. This is the first report about the structure of the water-soluble polysaccharides biosynthesized by seaweeds of the genus Bryopsis. These sulfated galactans and rhamnans were in situ localized mostly in two layers, one close to the plasma membrane and the other close to the apoplast, leaving a middle amorphous, unstained cell wall zone. In addition, fibrillar polysaccharides, comprising (1→3)-β-d-xylans and cellulose, were obtained by treatment of the residue from the water extractions with an LiCl/DMSO solution at high temperature. These polymers were also localized in a bilayer arrangement.


A flattening filter for brachytherapy skin irradiation.
Radioactive sources in close contact offer an alternative to superficial radiation in the treatment of skin lesions. A flattening filter was designed for a lead surface applicator to improve the skin dose distribution of a high dose rate (HDR) brachytherapy unit (Nucletron). At three heights from the opening (10, 15 and 25 mm) of the cylindrical applicator, the 192Ir source can be driven into the centre of the applicator. Thin sheets of lead foil (0.2 mm) were cut into circular shapes and placed in the opening to build a cylindrical cone that acts as a flattening filter. The shape of the cone was optimized in an iterative process using a spreadsheet and the resulting dose distribution under the applicator was determined using radiosensitive film. The use of the filter improved the dose distribution in a plane perpendicular to the beam axis to be within +/- 5% of the central axis dose. The present applicator and flattening filter together with an HDR brachytherapy unit offer an alternative for skin irradiation where a superficial unit is not available or will be replaced with a more flexible device. As the depth dose characteristics can be modified using different source-to-surface distances, the dose throughout the patient's skin can be shaped as desired by the radiation oncologist using a compensator design type approach.


Community and nosocomial transmission of Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus: implications for healthcare.
In the UK, infections due to Panton-Valentine leucocidin-positive community-associated meticillin-resistant Staphylococcus aureus (PVL-MRSA) have been reported sporadically. In September 2006, a fatal PVL-MRSA infection occurred in a Filipino healthcare worker (HCW) after she underwent caesarean section. Throat and nasal swabs were obtained from contacts of cases in community and hospital. MRSA with an antibiogram similar to the PVL-MRSA strain were characterised including toxin gene profiling, polymerase chain reaction- and sequence-based typing. Carriers underwent decolonisation treatment, and HCWs were restricted from patient care until they and their household members were considered negative for PVL-MRSA. The PVL-MRSA belonged to ST30, was protein A gene (spa) type t019, SCCmec IVc, agr 3, and resistant only to beta-lactam antibiotics. Representatives of the same lineage were identified among a further 16 individuals in community and hospital. Infections likely to be caused by PVL-MRSA had occurred in 12 cases, and were likely to be hospital-acquired in two patients (one fatal) and occupationally acquired in one HCW. Nine cases worked as nursing staff in the hospital. Eight of these had emigrated from the Philippines in the previous five years and were linked socially. Thus, PVL-MRSA-ST30 was detected in a HCW community in the UK. This is the first report of nosocomial transmission of this pandemic clone in the UK associated with a fatality. Increased vigilance in healthcare and community is needed in response to this emerging threat.


A specific primer pair for the diagnosis and identification of Acanthamoeba astronyxis by random amplified polymorphic DNA-polymerase chain reaction.
Random amplified polymorphic DNA (RAPD) is a useful tool for species identification. The obtained band patterns can be used for specific primer pair design that is useful for species identification. In this study, a distinctive 485-bp band in Acanthamoeba astronyxis band patterns was found, using the OPC20 primer (ACTTCGCCAC). The band specificity was confirmed by hybridization, using it as a probe, against all OPC20 amplifications from different Acanthamoeba species. Once the fragment was sequenced, we used it to design a specific primer pair that was useful for the identification of different isolates as A. astronyxis species.


Delta-like 1 homolog (DLK1) as a possible therapeutic target and its application to radioimmunotherapy using 125I-labelled anti-DLK1 antibody in lung cancer models (HOT1801 and FIGHT004).
Delta-like 1 homolog (DLK1) is a non-canonical Notch ligand known to be expressed in several cancers but whose role in lung cancer is not yet fully understood. We sought to confirm DLK1 expression in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), and to examine DLK1's clinical significance. Furthermore, we examined the possible utility of DLK1 as a novel target in radioimmunotherapy (RIT). We retrospectively assessed the correlation between clinical features and DLK1 expression by immunohistochemistry in resected specimens from 112 patients with SCLC and 101 patients with NSCLC. Moreover, we performed cell and animal experiments, and examined the possibility of RIT targeting DLK1 in SCLC using iodine-125 (125I) -labeled anti-DLK1 antibody, knowing that 125I can be replaced with the alpha-particle-emitter astatine-211 (211At). In SCLC and NSCLC, 20.5 % (23/112) and 16.8 % (17/101) of patients (respectively) had DLK1-positive tumors. In NSCLC, DLK1 expression was associated with recurrence-free survival (P < 0.01) but not with overall survival. In SCLC, there was no association between DLK1 expression and survival. In addition, 125I-labeled anti-DLK1 antibody specifically targeted DLK1 on human SCLC tumor cell lines. Furthermore, 125I-labeled anti-DLK1 antibody was incorporated into tumor tissue in a mouse model. A proportion of SCLC and NSCLC exhibits DLK1 expression. As a clinical feature, DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could serve as a new therapeutic target, including RIT, as suggested by our pilot study using a radiolabeled anti-DLK1 antibody in SCLC.


HIV prevention services and testing utilization behaviors among men who have sex with men at elevated risk for HIV in Chongqing, China.
To investigate barriers and correlates of the use of HIV prevention services and HIV testing behaviors among men who have sex with men in Chongqing. Three consecutive cross-sectional surveys provided demographic, sexual behavior, HIV/syphilis infection, HIV prevention service, and testing behavior data. Of 1239 participants, 15.4% were infected with HIV, incidence was 12.3 per 100 persons/year (95% CI: 9.2-15.3), 38% of the participants reported ever having unprotected insertive anal sex, 40% ever received free condom/lubricants in the past year, and 27.7% ever obtained free sexually transmitted infection examination/treatment in the past year. Multivariable logistic regression revealed that lower levels of HIV/AIDS related stigmatizing/discriminatory attitudes, full-time jobs, and sex debut with men at a younger age were independently associated with use of free condom/lubricants. Large social networks, higher incomes, and sexual debut with men at a younger age were associated with use of any HIV prevention and HIV testing services. Lower levels of stigmatizing/discriminatory attitudes were also associated with HIV testing. Fearing needles and being unaware of the venues for testing were top barriers for testing service utilization. It is imperative to address HIV/AIDS related stigmatizing/discriminatory attitudes and other barriers while delivering intervention and testing services.


Elastosis perforans serpiginosa: causes and associated disorders.
Elastosis perforans serpiginosa (EPS) is an uncommon cutaneous disorder classified under perforating diseases (PD); a group of dermatoses with transepidermal extrusion of collagen or elastic tissue. Three EPS subtypes have been reported that differ according to aetiology, associated diseases, and histopathological features. Herein, we report a systematic review of the literature, as well as a case of a 41-year-old woman with Wilson disease treated with penicillamine (PCM), who developed EPS after 11 years of drug intake. To analyse and characterise EPS subtypes based on an evaluation of potential different histological patterns. A systematic literature search in Pubmed was performed to identify articles describing EPS. A peculiar histological pattern was identified in EPS PCM-related patients, either in affected or unaffected skin samples. Using specific elastic fibre stains (Verhoeff-van Gieson, Weigert, and Orcein), fibres appeared with an irregular surface with thorn-like protrusion, probably due to weaker fibre cross-links, making them unable to re-expand after contraction along their long axis. Interestingly, similar histological patterns have also been reported in elastic tissues of vessel walls of the lungs and upper respiratory tract, joints, visceral adventitia, and kidney. A distinctive histological pattern of PCM-related EPS is observed in affected and normal-appearing skin, as well as extracutaneous elastic tissue, suggesting serious potential widespread drug-induced systemic elastolytic damage.


Inhibition of prolyl-4-hydroxylase ameliorates chronic rejection of mouse kidney allografts.
Interstitial fibrosis, glomerulosclerosis and arteriosclerosis are the major components of chronic allograft nephropathy (CAN), the leading cause of late graft failure after transplantation. To investigate the mechanism of collagen deposition in CAN, we studied the effects of prolyl-hydroxylase inhibitor (PHI), an enzyme essential for collagen formation, using a mouse model of kidney transplantation. Kidneys from H-2b mice were transplanted into MHC-incompatible H-2d recipients (allografts) and at 3 weeks post-transplant, received either PHI or vehicle treatment daily for 3 weeks. At 6 weeks post-transplant, GFR was significantly improved in the allografts receiving PHI (3.3 +/- 0.5 mL/min/kg) compared with those receiving vehicle (1.8 +/- 0.5 mL/min/kg, p < 0.05), while renal function was relatively unimpaired in the nonrejecting isografts (6.45 +/- 0.53 mL/min/kg). Allografts had histologic changes of CAN but the severity was significantly reduced with PHI treatment compared with vehicle, with reductions in interstitial inflammation and fibrosis. Furthermore, TGFâ and connective tissue growth factor mRNA expression was enhanced in both allograft groups compared with the isografts. In conclusion, PHI-treated allografts had improved renal function and reduced the severity of renal injury as a result of CAN. Inhibition of matrix synthesis may be a useful adjunct in ameliorating the development of CAN in humans.


Live eyeworm (Oxyspirura petrowi) extraction, in vitro culture, and transfer for experimental studies.
Northern bobwhite ( Colinus virginianus ) have experienced a dramatic decline in West Texas over the last 3 yr, and investigations are underway to evaluate the role of parasites in this decline. One of the key parasites being investigated is the eyeworm (Oxyspirura petrowi). Live eyeworms were extracted from both live and dead northern bobwhites, and in vitro survival was tested using 10 liquid media. Eyeworms placed in an egg white and physiological saline solution lived for at least 36 days. Live O. petrowi placed into the eyes of uninfected pen-raised bobwhites were monitored for 21 days to demonstrate successful transfer. Eyeworm behavior during feeding, mating, and development were monitored. This study is important to research that requires "banking" of live O. petrowi from wild-captured definitive hosts for life history studies and assessing the impact of O. petrowi on host individuals.


Severe morbidity after coronary artery surgery.
When operations become safer, attention inevitably shifts from mortality to morbidity. Unfortunately, morbidity is more difficult to measure than death, but it is arguably of greater interest to the patient and to those from public or private institutions that have the responsibility for balancing a health care budget. Studies that focus on morbidity are currently few, and specific risk models are being developed. It is already evident that risk factors associated with hospital death are qualitatively different from risk factors associated with prolonged hospital stay. The study of morbidity after coronary artery surgery is important to surgeons and physicians, to assess quality of care and the impact of new treatments and procedures.


What is the appropriate "dress code" for the cardiac catheterization laboratory?
In order to determine the effect of the manner of dress by personnel and observers on cardiac catheterization-related infections, a retrospective survey was undertaken of 107,203 catheterization procedures done during the calendar year prior to this survey. An analysis of 55,976 cutdowns and 53,578 percutaneous procedures was performed (some subjects had both procedures performed). A total of 379 infections in 109,554 entrance sites were reported for an overall incidence of infection of 0.35%. There were 33 infections at the percutaneous site (incidence = 0.06%) and 346 at the cutdown site (incidence = 0.62%). The manner of dress of personnel not involved with catheter manipulation and of the observers had no relationship to the incidence of infection when the percutaneous technique was used. When cutdowns were performed, there was a lower incidence of infection in those laboratories where all personnel and observers were required to wear a mask, cap, and gown (17,311 cutdowns, 83 infections, 0.48% infection rate) than in those laboratories where none of these was required (15,170 cutdowns, 109 infections, 0.72% infection rate) (P less than 0.025). Laboratories which did 150 or less cutdowns/year had more infections than those laboratories performing more than 150/year (P less than 0.0001). Our data suggest that the risk of infection from cardiac catheterization is more closely correlated with the volume of studies done in the laboratory than in the manner of dress of the laboratory personnel and visitors in the laboratory. However, the wearing of full "sanitary clothing" will help decrease the infection rate in cutdowns.


MEF2C, a transcription factor that facilitates learning and memory by negative regulation of synapse numbers and function.
Learning and memory depend on the activity-dependent structural plasticity of synapses and changes in neuronal gene expression. We show that deletion of the MEF2C transcription factor in the CNS of mice impairs hippocampal-dependent learning and memory. Unexpectedly, these behavioral changes were accompanied by a marked increase in the number of excitatory synapses and potentiation of basal and evoked synaptic transmission. Conversely, neuronal expression of a superactivating form of MEF2C results in a reduction of excitatory postsynaptic sites without affecting learning and memory performance. We conclude that MEF2C limits excessive synapse formation during activity-dependent refinement of synaptic connectivity and thus facilitates hippocampal-dependent learning and memory.


Relative sea-level change regulates organic carbon accumulation in coastal habitats.
Because coastal habitats store large amounts of organic carbon (Corg ), the conservation and restoration of these habitats are considered to be important measures for mitigating global climate change. Although future sea-level rise is predicted to change the characteristics of these habitats, its impact on their rate of Corg sequestration is highly uncertain. Here we used historical depositional records to show that relative sea-level (RSL) changes regulated Corg accumulation rates in boreal contiguous seagrass-saltmarsh habitats. Age-depth modeling and geological and biogeochemical approaches indicated that Corg accumulation rates varied as a function of changes in depositional environments and habitat relocations. In particular, Corg accumulation rates were enhanced in subtidal seagrass meadows during times of RSL rise, which were caused by postseismic land subsidence and climate change. Our findings identify historical analogs for the future impact of RSL rise driven by global climate change on rates of Corg sequestration in coastal habitats.


Use Via Early Access to Ixazomib (UVEA-IXA) Study: Effectiveness and Safety of Ixazomib-based Therapy in Relapsed/Refractory Multiple Myeloma Outside of the Clinical Trial Setting.
In multiple myeloma (MM), improving our understanding of routine clinical practice and the effectiveness of agents outside of clinical trials is important. TOURMALINE-MM1 data resulted in approval of ixazomib for MM patients who have received ≥ 1 prior therapy. UVEA-IXA comprised a retrospective chart review in the early access program, and a prospective 1-year follow-up period. Eligible patients had had a biochemical and/or symptomatic relapse after 1-3 prior lines of therapy; no anti-MM therapy for > 3 cycles at the start of ixazomib therapy; and an Eastern Cooperative Oncology Group performance score of 0-2. Lenalidomide- or proteasome inhibitor (PI)-refractory patients were ineligible. Primary endpoints were response and progression-free survival (PFS). Of 357 enrolled patients, 309 were evaluable; most patients received ixazomib alongside lenalidomide (98%) and dexamethasone (97%); 61% had received 2-3 prior lines of therapy. Median PFS was 15.6 months (95% confidence interval [CI]: 12.0-20.6) in all evaluable patients, and 19.6 (95% CI: 12.1-27.0) and 13.9 (95% CI: 10.1-18.1) months in patients who received 1 and ≥ 2 prior lines of therapy, respectively. The overall response rate was 67% in all evaluable patients, and 72% and 63%, respectively, in patients who received 1 and ≥ 2 prior lines of therapy. Median overall survival was 35.5 months. The ixazomib safety profile was consistent with previous reports. This study supports ixazomib-based therapy as an effective and tolerable treatment in the real-world. Outcomes were favorable in patients with 1 or ≥ 2 prior lines of therapy who were not lenalidomide- or PI-refractory.


Evaluation of serum procalcitonin, serum interleukin-6, and interleukin-8 as predictors of serious infection in children with febrile neutropenia and cancer.
Early diagnosis of sepsis in children with febrile neutropenia remains difficult owing to non-specific clinical and laboratory signs of infection. There is a need to assess the utility of inflammatory markers in clinical risk assessment for their ability to discriminate between low-risk and high-risk neutropenic patients since presently there is insufficient data to recommend their routine use. This is a prospective study of children on therapy admitted with febrile neutropenia and sampled for serum procalcitonin (PCT), interleukin-6 (IL-6), and interleukin-8 (IL-8) at admission. The febrile neutropenia episodes were categorized into two groups - Group I: no focus of infection and Group II: clinically/microbiologically documented infection. Statistical analyses for comparison were performed using Z-test and receiver operating curves at various cut-off levels. A total of 46 episodes of febrile neutropenia in 33 children were analyzed. In total, 76% were categorized as group I and 24% as group II. The mean value of PCT in group II was higher (28.07 ng/mL) than group I (1.03 ng/mL) though there was no significant statistical difference. At a cut-off level of 2 ng/mL for PCT, sensitivity of 63%, specificity of 91%, positive predictive values (PPV) of 70%, and negative predictive value (NPV) of 88% were observed. There was no significant difference in the IL-6 and IL-8 levels between both the groups. However, at an optimal cut-off value of 50 pg/mL, IL-6 had an NPV of 80% and at a cut-off level of 130 pg/mL, IL-8 had an NPV of 73%, however, with low sensitivity and specificity. IL-6, IL-8, and PCT can be utilized to define a group of patients with a low risk of sepsis in view of their favorable NPV. The use of these biomarkers together can facilitate early discharge from the hospital, and the use of oral antimicrobial therapy, in turn, reducing the cost of supportive therapy in a developing country.


MRP2 Inhibition by HIV Protease Inhibitors in Rat and Human Hepatocytes: A Quantitative Confocal Microscopy Study.
Hepatic drug transporters play a pivotal role in the excretion of drugs from the body, in drug-drug interactions, as well as in drug-induced liver toxicity. Hepatocytes cultured in sandwich configuration are an advantageous model to investigate the interactions of drug candidates with apical efflux transporters in a biorelevant manner. However, the commonly used "offline" assays (i.e., that rely on measuring intracellular accumulated amounts after cell lysis) are time- and resource-consuming, and the data output is often highly variable. In the present study, we used confocal microscopy to investigate the inhibitory effect of all marketed HIV protease inhibitors (10 μM) on the apical efflux transporter multidrug resistance-associated protein 2 (MRP2; ABCC2) by visualizing the biliary accumulation of the fluorescent substrate 5(6)-carboxy-2',7'-dichlorofluorescein (CDF). This method was applied with sandwich-cultured human and rat hepatocytes. Alterations in the biliary excretion index of CDF were calculated on the basis of quantitative analysis of fluorescence intensities in the confocal images. In human hepatocytes, lopinavir followed by tipranavir, saquinavir, atazanavir, and darunavir were the most potent inhibitors of MRP2-mediated efflux of CDF. In rat hepatocytes, tipranavir inhibited Mrp2-mediated CDF efflux most potently, followed by lopinavir and nelfinavir. In conclusion, a comparison of these findings with previously published data generated in offline transporter inhibition assays indicates that this microscopy-based approach enables investigation of the inhibitory effect of drugs on efflux transporters in a very sensitive but nondestructive manner.


Probiotics in the Treatment of Diverticular Disease. A Systematic Review.
Diverticular disease is a common gastrointestinal condition. Low-grade inflammation and altered intestinal microbiota have been identified as factors contributing to abdominal symptoms. Probiotics may lead to symptoms improvement by modifying the gut microbiota and are promising treatments for diverticular disease. The aim of this study was to systematically review the efficacy of probiotics in diverticular disease in terms of remission of abdominal symptoms and prevention of acute diverticulitis. According to PRISMA, we identified studies on diverticular disease patients treated with probiotics (Pubmed, Embase, Cochrane). The quality of these studies was evaluated by the Jadad scale. Main outcomes measures were remission of abdominal symptoms and prevention of acute diverticulitis. 11 studies (2 double-blind randomized placebo-controlled, 5 open randomized, 4 non-randomized open studies) were eligible. Overall, diverticular disease patients were 764 (55.1% females, age 58-75 years). Three studies included patients with symptomatic uncomplicated diverticular disease, 4 studies with symptomatic uncomplicated diverticular disease in remission, 4 studies with complicated or acute diverticulitis. Mainly (72.7%) single probiotic strains had been used, most frequently Lactobacilli. Follow-up ranged from 1 to 24 months. Interventions were variable: in 8 studies the probiotic was administered together with antibiotic or anti-inflammatory agents and compared with the efficacy of the drug alone; in 3 studies the probiotic was compared with a high-fibre diet or used together with phytoextracts. As an outcome measure, 4 studies evaluated the occurrence rate of acute diverticulitis, 6 studies the reduction of abdominal symptoms, and 6 studies the recurrence of abdominal symptoms. Meta-analysis on the efficacy of probiotics in diverticular disease could not be performed due to the poor quality of retrieved studies. This systematic review showed that high-quality data on the efficacy of probiotics in diverticular disease are scant: the available data do not permit conclusions. Further investigation is required to understand how probiotics can be employed in this condition.


Intracellular factors determining the deposition of glycogen. The role of gluconeogenesis.
The interrelationship between glycogen biosynthesis and do novo glucose formation in rats was studied by determining the oxaloacetic acid, ATP, and glycogen levels in the tissues of healthy starved rats and during the growth of transplantable hepatomas with different rates of growth. From the results obtained it was proposed that glycogen biosynthesis and de novo glucose formation are mutually enhanced and coupled processes. The validity of this conclusion was confirmed by in vitro model experiments involving the use of isolated-liver perfusion. Results of a multiple regression analysis indicated that the efficiency of gluconeogenesis and glycogen deposition is determined by the supply of oxygen to the liver, by the oxaloacetic acid content of this organ, and also by the degree of reduction of the glucose precursor. It was also shown that the ability of glucocorticoids and glucagon to enhance gluconeogenesis is dependent on the supply of oxygen to the liver. From the results of this in vivo and in vitro comparative study it is concluded that deposition of glycogen in the liver and possibly also in the brain is determined by the efficiency of gluconeogenesis.


Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis.
Mannose-binding lectin (MBL) and ficolin-2 (FCN) are activators of the lectin pathway of complement and act as primary defences against infection. Single-nucleotide polymorphisms (SNPs) in the MBL2 and FCN2 genes influence the functionality of the proteins. Both proteins are capable of binding staphylococci, which are pathogens that frequently cause peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We studied the role of polymorphisms in the MBL2 and FCN2 genes as a risk factor for developing CAPD peritonitis caused by staphylococci. We analysed SNPs in the MBL2 and FCN2 genes in 40 CAPD patients with staphylococcal peritonitis and in 65 CAPD patients without any history of peritonitis. Additionally, we analysed the prevalence of exit site infections and nasal Staphylococcus aureus carriage in both groups. The + 6359C > T SNP leading to the Thr236Met amino acid alteration in the FCN2 gene, associated with decreased substrate binding, was significantly more prevalent in CAPD patients with a history of staphylococcal peritonitis compared with patients on CAPD without a history of peritonitis (P = 0.037). No difference was found in MBL2 genotypes between the two groups. In CAPD patients with a history of staphylococcal peritonitis, exit site infection with S. aureus was also more prevalent (P < 0.01), while S. aureus carriage was not (P = 0.073). In addition to known risk factors such as exit site infection, the + 6359C > T SNP in the FCN2 gene might be a risk factor for staphylococcal peritonitis in CAPD patients due to decreased binding of FCN to staphylococci.


Diagnostic Accuracy of Indocyanine Green Clearance Test for Different Stages of Liver Fibrosis and Cirrhosis.
(1) Background: This study aimed to correlate the indocyanine green clearance (ICG) test with histopathological grades of liver fibrosis and liver cirrhosis to assess its diagnostic accuracy in differentiating normal liver parenchyma from liver fibrosis and liver cirrhosis. (2) Methods: A total of 82 patients who received a histopathological liver examination, imaging, and ICG test within three months were included in this retrospective study. The histopathological level of fibrosis was graded using the Ishak scoring system, and the patients were divided into five categories: no liver fibrosis (NLF), mild liver fibrosis (MLF), advanced liver fibrosis (ALF), severe liver fibrosis (SLF), and liver cirrhosis (LC). The non-parametric Kruskal-Wallis test with post hoc pairwise comparison utilizing Mann-Whitney U tests and Bonferroni adjustment was used to analyze differences in the ICG test results between the patient groups. Cross correlation between the individual fibrosis/cirrhosis stages and the score of the ICG test was performed, and the sensitivity, specificity, and positive and negative predictive values were calculated for each model predicting liver fibrosis/cirrhosis. (3) Results: A significant difference (p ≤ 0.001) between stages of NLF, LF, and LC was found for the ICG parameters (ICG plasma disappearance rate (ICG-PDR) and ICG retention percentage at 15 min (ICG-R15)). The post hoc analysis revealed that NLF significantly differed from SLF (ICG-PDR: p = 0.001; ICG-R15: p = 0.001) and LC (ICG-PDR: p = 0.001; ICG-R15: p = 0.001). ALF also significantly differed from SLF (ICG-PDR: p = 0.033; ICG-R15: p = 0.034) and LC (ICG-PDR: p = 0.014; ICG-R15: p = 0.014). The sensitivity for detection of an initial stage of liver fibrosis compared to no liver fibrosis (Ishak ≥ 1) was 0.40; the corresponding specificity was 0.80. The differentiation of advanced liver fibrosis or cirrhosis (Ishak ≥ 4) compared to other stages of liver fibrosis was 0.75, with a specificity of 0.81. (4) Conclusions: This study shows that the ICG test, as a non-invasive diagnostic test, is able to differentiate patients with no liver fibrosis from patients with advanced liver fibrosis and liver cirrhosis. The ICG test seems to be helpful in monitoring patients with liver fibrosis regarding compensation levels, thus potentially enabling physicians to both detect progression from compensated liver fibrosis to advanced liver fibrosis and cirrhosis and to initiate antifibrotic treatment at an earlier stage.


IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammation.
Inflammation and innate immunity involve signalling pathways leading to the production of inflammatory mediators. Usually such responses are self-limiting, but aberrant resolution of inflammation results in chronic diseases. Much attention has focused on pro-inflammatory signalling but little is known about the mechanisms that resolve inflammation. The IkappaB kinase (IKK) complex contains two catalytic subunits, IKKalpha and IKKbeta, and controls the activation of NF-kappaB transcription factors, which play a pivotal role in inflammation. Ample evidence indicates that IKKbeta mediates NF-kappaB activation in response to pro-inflammatory cytokines and microbial products. IKKalpha regulates an alternative pathway important for lymphoid organogenesis, but the role of IKKalpha in inflammation is unknown. Here we describe a new role for IKKalpha in the negative regulation of macrophage activation and inflammation. IKKalpha contributes to suppression of NF-kappaB activity by accelerating both the turnover of the NF-kappaB subunits RelA and c-Rel, and their removal from pro-inflammatory gene promoters. Inactivation of IKKalpha in mice enhances inflammation and bacterial clearance. Hence, the two IKK catalytic subunits have evolved opposing but complimentary roles needed for the intricate control of inflammation and innate immunity.


Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy.
Nuclear-cytoplasmic shuttling is a highly regulated and complex process, which involves both proteins and nucleic acids. Changes in cellular compartmentalization of various proteins, including oncogenes and tumor suppressors, affect cellular behavior, promoting or inhibiting proliferation, apoptosis and sensitivity to therapies. In this review, we will recapitulate the role of various shuttling components in Chronic Myeloid Leukemia and we will provide insights on the potential role of shuttling proteins as therapeutic targets.


The Omaha System as a Structured Instrument for Bridging Nursing Informatics With Public Health Nursing Education: A Feasibility Study.
Advancements in healthcare systems include adoption of health information technology to ensure healthcare quality. Educators are challenged to determine strategies to integrate health information technology into nursing curricula for building a nursing workforce competent with electronic health records, standardized terminology, evidence-based practice, and evaluation. Nursing informatics, a growing specialty field, comprises health information technology relative to the profession of nursing. It is essential to integrate nursing informatics across nursing curricula to effectively position competent graduates in technology-laden healthcare environments. Nurse scholars developed and evaluated a nursing informatics case study assignment used in undergraduate level public health nursing courses. The assignment included an unfolding scenario followed by electronic health record charting using standardized terminology to guide the nursing process. The assignment was delivered either online or in class. Seventy-two undergraduate students completed the assignment and a posttest. Fifty-one students completed a satisfaction survey. Results indicated that students who completed the assignment online demonstrated a higher level of content mastery than those who completed the assignment in class. Content mastery was based on posttest results, which evaluated students' electronic health record charting for the nursing assessment, evidence-based interventions, and evaluations. This innovative approach may be valuable to educators in response to the National Academy of Sciences recommendations for healthcare education reform.


Congenital Lobar Emphysema with Pulmonary Extramedullary Hematopoiesis.
Congenital lobar emphysema is a one of the rare variety of congenital abnormality of the lung causing respiratory distress in newborns and infants. Herein, we report a case of congenital lobar emphysema in a 3-week-old female admitted to the pediatric intensive care unit with severe respiratory distress. CT scan revealed a hyperinflated, hyperlucent left upper lobe, collapse of the ipsilateral lung and marked mediastinal shift to the right. The patient underwent emergency left upper lobectomy with improvement of her condition in the postoperative period. Histopathological findings confirmed the clinical diagnosis of congenital lobar emphysema with an unusual finding of pulmonary extramedullary hematopoiesis. Congenital lobar emphysema often presents a diagnostic and therapeutic dilemma and therefore requires a high index of suspicion in neonates presenting with respiratory distress to avoid morbidity and mortality.


Short-term fumigation of honey bee (Hymenoptera: Apidae) colonies with formic and acetic acids for the control of Varroa destructor (Acari: Varroidae).
Controlling populations of varroa mites is crucial for the survival of the beekeeping industry. Many treatments exist, and all are designed to kill mites on adult bees. Because the majority of mites are found under capped brood, most treatments are designed to deliver active ingredients over an extended period to control mites on adult bees, as developing bees and mites emerge. In this study, a 17-h application of 50% formic acid effectively killed mites in capped worker brood and on adult bees without harming queens or uncapped brood. Neither acetic acid nor a combined treatment of formic and acetic acids applied to the West Virginia formic acid fumigator was as effective as formic acid alone in controlling varroa mites. In addition, none of the treatments tested in late summer had an effect on the late-season prevalence of deformed wing virus. The short-term formic acid treatment killed > 60% of varroa mites in capped worker brood; thus, it is a promising tool for beekeepers, especially when such treatments are necessary during the nectar flow.


Comparative studies of the quantification of genetically modified organisms in foods processed from maize and soy using trial producing.
Seven types of processed foods, namely, cornstarch, cornmeal, corn puffs, corn chips, tofu, soy milk, and boiled beans, were trial produced from 1 and 5% (w/w) genetically modified (GM) mixed raw materials. In this report, insect resistant maize (MON810) and herbicide tolerant soy (Roundup Ready soy, 40-3-2) were used as representatives of GM maize and soy, respectively. Deoxyribonucleic acid (DNA) was extracted from the raw materials and the trial-produced processed food using two types of methods, i.e., the silica membrane method and the anion exchange method. The GM% values of these samples were quantified, and the significant differences between the raw materials and the trial-produced processed foods were statistically confirmed. There were some significant differences in the comparisons of all processed foods. However, our quantitative methods could be applied as a screening assay to tofu and soy milk because the differences in GM% between the trial-produced processed foods and their raw materials were lower than 13 and 23%, respectively. In addition, when quantitating with two primer pairs (SSIIb 3, 114 bp; SSIIb 4, 83 bp for maize and Le1n02, 118 bp; Le1n03, 89 bp for soy), which were targeted within the same taxon specific DNA sequence with different amplicon sizes, the ratios of the copy numbers of the two primer pairs (SSIIb 3/4 and Le1n02/03) decreased with time in a heat-treated processing model using an autoclave. In this report, we suggest that the degradation level of DNA in processed foods could be estimated from these ratios, and the probability of GM quantification could be experimentally predicted from the results of the trial producing.


Statistical multimodal integration for audio-visual speech processing.
Sensory information is indispensable for living things. It is also important for living things to integrate multiple types of senses to understand their surroundings. In human communications, human beings must further integrate the multimodal senses of audition and vision to understand intention. In this paper, we describe speech related modalities since speech is the most important media to transmit human intention. To date, there have been a lot of studies concerning technologies in speech communications, but performance levels still have room for improvement. For instance, although speech recognition has achieved remarkable progress, the speech recognition performance still seriously degrades in acoustically adverse environments. On the other hand, perceptual research has proved the existence of the complementary integration of audio speech and visual face movements in human perception mechanisms. Such research has stimulated attempts to apply visual face information to speech recognition and synthesis. This paper introduces works on audio-visual speech recognition, speech to lip movement mapping for audio-visual speech synthesis, and audio-visual speech translation.


Noninvasive and Multicancer Biomarkers: The Promise of LINE-1 Retrotransposons.
LINE-1 retrotransposons are frequently active in epithelial tumors. In a new study, Taylor, Wu and colleagues now describe that one of the proteins encoded by LINE-1 elements, ORF1p, is detected in the bloodstream of patients with cancer, and can be used as a noninvasive and multicancer biomarker for diagnosis or treatment monitoring. See related article by Taylor, Wu et al., p. 2532 (7).


Transverse rectus sheath plication in abdominoplasty.
The standard abdominoplasty technique uses a wide, vertically oriented plication of the rectus sheath to narrow the waistline. This reduces the contribution of the rectus sheath to the anterior abdominal wall from more than 50 percent to 25 percent or less and creates an unnaturally flat appearance. No amount of exercise can restore the native form of the rectus sheath. For the past 3 years, the authors have performed a transverse plication of the rectus sheath, to address vertical laxity, complemented by a bilateral crescent-shaped plication of the external oblique fascia, to address waistline contour. Six consecutive patients who underwent the transverse rectus plication technique were compared with a similar group of patients who underwent vertical rectus plication. Comparison was made via preoperative and postoperative photographic analysis by two impartial judges. Although the overall result was excellent in both groups, the global score was significantly higher in the transverse plication group (4.5 versus 3.9, p = 0.044). Scores for anterior abdominal contour (4.7 versus 4.2, p = 0.029) and definition of the linea semilunaris (4.6 versus 3.7, p = 0.008) were also significantly higher for the transverse plication group. The difference for waistline contour (4.5 versus 3.8, p = 0.067), definition of the linea alba (4.4 versus 3.9, p = 0.067), and hip-waist transition (4.4 versus 3.7, p = 0.067) did not reach statistical significance. The outline of the rectus sheath is a significant portion of what is perceived as an aesthetic abdomen. Transverse plication of the rectus sheath with bilateral crescent-shaped plications of the external oblique fascia retains this native form. The result is improved anterior abdominal contour and definition of the rectus sheath with a comparable or better improvement in waistline contour and transition from the hips to the waist when compared with wide, vertical rectus plication.


Glycan Complexity and Heterogeneity of Glycoproteins in Somatic Extracts and Secretome of the Infective Stage of the Helminth Fasciola hepatica.
Fasciola hepatica is a global helminth parasite of humans and their livestock. The invasive stage of the parasite, the newly excysted juvenile (NEJs), relies on glycosylated excreted-secreted (ES) products and surface/somatic molecules to interact with host cells and tissues and to evade the host's immune responses, such as disarming complement and shedding bound antibody. While -omics technologies have generated extensive databases of NEJs' proteins and their expression, detailed knowledge of the glycosylation of proteins is still lacking. Here, we employed glycan, glycopeptide, and proteomic analyses to determine the glycan profile of proteins within the NEJs' somatic (Som) and ES extracts. These analyses characterized 123 NEJ glycoproteins, 71 of which are secreted proteins, and allowed us to map 356 glycopeptides and their associated 1690 N-glycan and 37 O-glycan forms to their respective proteins. We discovered abundant micro-heterogeneity in the glycosylation of individual glycosites and between different sites of multi-glycosylated proteins. The global heterogeneity across NEJs' glycoproteome was refined to 53 N-glycan and 16 O-glycan structures, ranging from highly truncated paucimannosidic structures to complex glycans carrying multiple phosphorylcholine (PC) residues, and included various unassigned structures due to unique linkages, particularly in pentosylated O-glycans. Such exclusive glycans decorate some well-known secreted molecules involved in host invasion, including cathepsin B and L peptidases, and a variety of membrane-bound glycoproteins, suggesting that they participate in host interactions. Our findings show that F. hepatica NEJs generate exceptional protein variability via glycosylation, suggesting that their molecular portfolio that communicates with the host is far more complex than previously anticipated by transcriptomic and proteomic analyses. This study opens many avenues to understand the glycan biology of F. hepatica throughout its life-stages, as well as other helminth parasites, and allows us to probe the glycosylation of individual NEJs proteins in the search for innovative diagnostics and vaccines against fascioliasis.


Utilization of peripherin and S-100 immunohistochemistry in the diagnosis of Hirschsprung disease.
Evaluation of rectal biopsies for ganglion cells is performed for patients suspected of having Hirschsprung disease. At times, identification of ganglion cells can be difficult, especially in newborns. To assist in diagnosis, frozen tissue can be collected for acetylcholinesterase histochemical staining. At our institution, we developed a protocol using peripherin and S-100 immunostaining as an adjunct to hematoxylin and eosin (H&E) for the identification of ganglion cells. Further, at the time of frozen section, we performed Diff Quik staining to highlight ganglion cells. One hundred and thirty eight rectal biopsies submitted for evaluation of Hirschsprung disease were compiled from the archives of the Medical College of Georgia from 2002 to 2009. Initial evaluation consisted of eight levels of H&E-stained slides and two unstained slides each for immunostaining with peripherin and S-100. If on initial evaluation, ganglion cells were not identified, additional H&E and peripherin immunostains were performed. Peripherin immunostaining was unequivocally identified in the cytoplasm of ganglion cells of patients at all ages. Of the 136 patients with diagnostic biopsies, 80% had ganglion cells. Of these, 93% of cases were diagnosed on the original eight levels. Twenty-seven cases were devoid of ganglion cells, and of these, 81% showed submucosal neural hypertrophy on S-100 staining. Twenty-six patients had confirmed aganglionic segments at the time of colonic resection. One patient had colostomy only. A total of 54 frozen sections were performed on 25 patients over this same period of time. Diff Quick staining was found to be very useful. In this study, our protocol proved to be very sensitive, specific, and efficient for the diagnosis of Hirschsprung disease.


Avulsion fracture of the anterior inferior iliac spine.
A 14-year-old was admitted with right groin pain which has started after kicking ball in a football game one week before. He had limited active and passive hip extension. A plain AP radiograph of the pelvis revealed a bone fragment displaced inferiorly about 1 cm from the right anterior inferior iliac spine. The patient was treated conservatively with analgesics and limited weight bearing. Four weeks later, range of motion was normal without pain and at eighth week the hip flexors regained full strength.


Global myocardial function is compromised in infants with pulmonary hypertension.
Persistent pulmonary hypertension of the newborn is a serious clinical entity with significant mortality and long-term morbidity. The objective was to study the profile of myocardial function, especially diastolic function, in term infants with pulmonary hypertension treated with nitric oxide. Unit electronic database was accessed to identify infants ≥34 weeks gestation who were administered nitric oxide for pulmonary hypertension over the last 6 years. Medical records and archived echocardiographic images were retrieved. Those with no echocardiogram on the day of administration of nitric oxide, concomitant congenital heart disease or ≥2 weeks of age at the time of nitric administration were excluded. Low biventricular outputs were noted in >2/3rd infants. Tricuspid regurgitation was noted in 20/25 (80%) infants, and ductal shunt was bidirectional in the majority of cases. Right ventricular diastolic function was assessed by systolic to diastolic duration ratio; dysfunction was widely prevalent. A large percentage of infants were haemodynamically severely compromised. This is the first study to detail right ventricular diastolic dysfunction in infants with pulmonary hypertension and highlights the therapeutic role of milrinone, a lusitropic drug with myocardial relaxation properties. Comprehensive evaluation of cardiovascular haemodynamics can optimize clinical care.


IPX066 , a mixed immediate/sustained-release levodopa preparation for Parkinson's disease.
L-DOPA has long been the 'gold standard' treatment for Parkinson's disease (PD), but suffers from poor oral bioavailability and rapid pharmacokinetic elimination. A longer acting preparation has long been sought. We conducted PubMed search for IPX066 and reviewed abstracts from meetings that included the topic of PD. IPX066 is a novel mixed immediate release (IR) and sustained-release levodopa preparation designed to prolong the clinical effect of a single dose. Pharmacokinetic studies demonstrate similar time to peak dose as regular IR L-DOPA, but a longer duration of time with > 50% of peak dose. This contrasts with available controlled release preparations that have a delay to onset. Clinic trials in fluctuating PD patients show that IPX066 provided more 'on' time despite fewer daily doses, compared to IR L-DOPA. As expected, it was also superior to placebo in early PD. However, it is not known whether it can achieve l-DOPA levels that are continuous enough to delay the onset of fluctuations when given early in the disease. Although not a radical advance in L-DOPA therapy, the drug will clearly have a role in more advanced patients taking multiple L-DOPA doses and may have a role as first-line therapy when starting l-DOPA.


Molecular cloning and polymorphism of the porcine H2AFZ gene.
H2A histone family, member Z (H2A.Z) is required for early mammalian development. In the present study, the 932 bp of full-length cDNA encoding a 128 amino-acid protein and the sequences of intron 2 to 4 of the porcine H2A histone family, member Z (pH2AFZ) gene were obtained. By comparative sequencing of pH2AFZ gene in Large White and Meishan pigs, a 4 bp deletion/insertion in intron 2 was detected and a PCR-Bsu15I-RFLP was established to detect this variation. In DIV (4th Dam line of Chinese lean-type new lines) pigs, the first-parity females with AA genotype had fewer piglets born alive (-2.64 and -1.83 piglets per litter) than those with AB (P < 0.01) and BB (P < 0.05) genotype. The additive allelic and dominance effect were estimated to be 0.92 (P < 0.05) and -0.87 piglets per litter (P < 0.01) for number of piglets born alive, respectively. This result suggests that the pH2AFZ gene might be a good candidate gene of litter-size trait and provides some marker information for marker-assisted selection.


From global change to a butterfly flapping: biophysics and behaviour affect tropical climate change impacts.
Difficulty in characterizing the relationship between climatic variability and climate change vulnerability arises when we consider the multiple scales at which this variation occurs, be it temporal (from minute to annual) or spatial (from centimetres to kilometres). We studied populations of a single widely distributed butterfly species, Chlosyne lacinia, to examine the physiological, morphological, thermoregulatory and biophysical underpinnings of adaptation to tropical and temperate climates. Microclimatic and morphological data along with a biophysical model documented the importance of solar radiation in predicting butterfly body temperature. We also integrated the biophysics with a physiologically based insect fitness model to quantify the influence of solar radiation, morphology and behaviour on warming impact projections. While warming is projected to have some detrimental impacts on tropical ectotherms, fitness impacts in this study are not as negative as models that assume body and air temperature equivalence would suggest. We additionally show that behavioural thermoregulation can diminish direct warming impacts, though indirect thermoregulatory consequences could further complicate predictions. With these results, at multiple spatial and temporal scales, we show the importance of biophysics and behaviour for studying biodiversity consequences of global climate change, and stress that tropical climate change impacts are likely to be context-dependent.


Investigation of the association between the outcomes of sperm chromatin condensation and decondensation tests, and assisted reproduction techniques.
The main purpose of this prospective study is to examine possible influences of abnormalities of sperm nuclear condensation and chromatin decondensation with sodium dodecyl sulphate (SDS)-EDTA on outcomes of intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI) cycles. Semen samples from 122 IUI and 236 ICSI cycles were evaluated. Before semen preparation for IUI or ICSI, basic semen analysis was performed and a small portion from each sample was spared for fixation. The condensation of sperm nuclear chromatin was evaluated with acidic aniline blue, followed by sperm chromatin decondensation by SDS-EDTA and evaluation under light microscope. Ongoing pregnancy rate was 24% and 26.2% in the IUI and ICSI groups respectively. The chromatin condensation rate was significantly higher in the ongoing pregnancy-positive group compared to the negative group, both in IUI (P = 0.042) and ICSI groups (P = 0.027), and it was positively correlated with ongoing pregnancy rate in both IUI and ICSI groups (P = 0.015, r = 0.214 and P = 0.014, r = 0.312 respectively). Chromatin decondensation rates were not significantly different in neither of the groups. These results indicate that IUI and ICSI outcome is influenced by the rate of spermatozoa with abnormal chromatin condensation. Sperm chromatin condensation with aniline blue is useful for selecting assisted reproduction techniques (ART) patients.


Enhanced reliability and accuracy for field deployable bioforensic detection and discrimination of Xylella fastidiosa subsp. pauca, causal agent of citrus variegated chlorosis using razor ex technology and TaqMan quantitative PCR.
A reliable, accurate and rapid multigene-based assay combining real time quantitative PCR (qPCR) and a Razor Ex BioDetection System (Razor Ex) was validated for detection of Xylella fastidiosa subsp. pauca (Xfp, a xylem-limited bacterium that causes citrus variegated chlorosis [CVC]). CVC, which is exotic to the United States, has spread through South and Central America and could significantly impact U.S. citrus if it arrives. A method for early, accurate and sensitive detection of Xfp in plant tissues is needed by plant health officials for inspection of products from quarantined locations, and by extension specialists for detection, identification and management of disease outbreaks and reservoir hosts. Two sets of specific PCR primers and probes, targeting Xfp genes for fimbrillin and the periplasmic iron-binding protein were designed. A third pair of primers targeting the conserved cobalamin synthesis protein gene was designed to detect all possible X. fastidiosa (Xf) strains. All three primer sets detected as little as 1 fg of plasmid DNA carrying X. fastidiosa target sequences and genomic DNA of Xfp at as little as 1 - 10 fg. The use of Razor Ex facilitates a rapid (about 30 min) in-field assay capability for detection of all Xf strains, and for specific detection of Xfp. Combined use of three primer sets targeting different genes increased the assay accuracy and broadened the range of detection. To our knowledge, this is the first report of a field-deployable rapid and reliable bioforensic detection and discrimination method for a bacterial phytopathogen based on multigene targets.


Homotransplant renal artery stenosis.
Transplant renal artery stenosis occurred in 12 of 101 consecutive kidney transplants. Stenoses were all located in the renal artery distal to the anastomosis. Two separate forms of stenosis are recognized: angulation and segmental. All transplant patients with severe diastolic hypertension, refractory to medical management, and an audible abdominal bruit should undergo angiography. Surgical correction of the stenosis was accomplished in nine of 12 patients with cure of their hypertension.


RNA aptamer-mediated gene therapy of prostate cancer: lessons from the past and future directions.
Prostate cancer (PCa) is one of the most prevalent cancers in the world, and the fifth cause of death from cancer in men. Among the non-surgical treatments for PCa, gene therapy strategies are in the early stages of development and recent clinical trials have provided new insights suggesting promising future. Recently, the creation of targeted gene delivery systems, based on specific PCa cell surface markers, has been viewed as a viable therapeutic approach. Prostate-specific membrane antigen (PSMA) is vastly expressed in nearly all prostate malignancies, and the intensity of expression increases with tumor aggressiveness, androgen independence, and metastasis. RNA aptamers are short and single-stranded oligonucleotides, which selectively bind to a specific ligand on the surface of the cells, which makes them fascinating small molecules for target delivery of therapeutics. PSMA-selective RNA aptamers represent great potential for developing targeted-gene delivery tools for PCa. This review provides a thorough horizon for the researchers interested in developing targeted gene delivery systems for PCa via PSMA RNA aptamers. In addition, we provided general information about different prospects of RNA aptamers including discovery approaches, stability, safety, and pharmacokinetics.


Improved distribution of antigenic site specificity of poliovirus-neutralizing antibodies induced by a protease-cleaved immunogen in mice.
Previous studies showed that the distribution of antigenic site specificity of neutralizing antibodies to type 3 poliovirus obtained with the inactivated poliovirus vaccine can be deficient as compared with that obtained following poliovirus infection. This observation was shown by the relatively low capacity of sera from inactivated-poliovirus-vaccine-immunized persons to neutralize poliovirus cleaved at antigenic site 1. We investigated possibilities for improving the situation in a mouse model. Balb/c mice were immunized with intact or trypsin-cleaved type 3 poliovirus (Saukett strain). Sera from mice immunized with the intact virus readily neutralized the intact virus but neutralized the cleaved virus only rarely. In contrast, cleaved-virus-immunized mice produced antibodies that were able to neutralize the cleaved virus as well as the intact one. Mice immunized with a 100-fold-higher dose of the intact virus produced significant levels of antibodies to the cleaved virus, too. Somewhat surprisingly, mice immunized with high doses of the cleaved virus produced antibodies specific for the intact loop between beta sheets B and C of VP1 (virion protein 1), which should be cleaved in the immunogen. This was shown by a higher titer of antibodies to intact Saukett virus than to the corresponding cleaved virus, as well as to a type 1/type 3 hybrid poliovirus in which only the BC loop amino acids were derived from type 3 poliovirus. The cleavage-induced enhanced availability of antigenic determinants residing outside the BC loop was also shown by increased neutralization titers of monoclonal antibodies specific for some of these other determinants. These results indicate that by using a trypsin-cleaved type 3 poliovirus as a parenteral immunogen, it is possible to change the distribution of antigenic site specificities of neutralizing antibodies to resemble that following poliovirus infection.