TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.
The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.


[Effect of fluorine on enzyme activity in the small intestine mucosa during absorption of sodium, potassium, monosaccharides and amino acids].
Effect of NaF on ATP-ase, creatine kinase, acid and basic phosphatases activity of small intestine mucosa in white rats during enteral administration of NaCl, KCl solutions has been studied under conditions of acute experiment. Inhibition of the Mg2+-ATP-ase activity by 13%, general ATP-ase activity by 25%, creatine kinase by 22% and a 2.2-3 fold inhibition of Na, K+-ATP-ase activity is observed. Acid and basic phosphatase activity does not change, swelling of mucosa is observed. The acid phosphatase activity in the intestinal contents increases 1.5 times, basic phosphatase activity--1.7 times, creatine amount--1.7 times, Pi amount 1.8 times. In experiments in vitro F- produces 20% activation of the basic phosphatase of mucosa and a 2.6-fold inhibition of the acid phosphatase. Rate of fructose absorption falls by 34%, that of methionine--by 29%, glucose--by 24%, glutaminic acid--by 10%. Activity of general ATP-ase in this case decreases by 22, 15, 27, 20% respectively. It is supposed that the F- effect results in destabilization of the membrane structures of the intestine mucosa.


alpha-Glucosidase inhibitory action of natural acylated anthocyanins. 2. alpha-Glucosidase inhibition by isolated acylated anthocyanins.
Four diacylated pelargonidin (Pg: SOA-4 and SOA-6), cyanidin (Cy: YGM-3), and peonidin (Pn: YGM-6) 3-sophoroside-5-glucosides isolated from the red flowers of the morning glory, Pharbitis nil cv. Scarlett O'Hara (SOA), and the storage roots of purple sweet potato, Ipomoea batatas cv. Ayamurasaki (YGM), were subjected to an alpha-glucosidase (AGH) inhibitory assay, in which the assay was performed with the immobilized AGH (iAGH) system to mimic the membrane-bound AGH at the small intestine. As a result, the acylated anthocyanins showed strong maltase inhibitory activities with IC(50) values of <200 microM, whereas no sucrase inhibition was observed. Of these, SOA-4 [Pg 3-O-(2-O-(6-O-(E-3-O-(beta-D-glucopyranosyl)caffeyl)-beta-D-glucopyranosyl)-6-O-E-caffeyl-beta-D-glucopyranoside)-5-O-beta-D-glucopyranoside] possessed the most potent maltase inhibitory activity (IC(50) = 60 microM). As a result of a marked reduction of iAGH inhibitory activity by deacylating the anthocyanins, that is, Pg (or Cy or Pn) sophoroside-5-glucoside, acylation of anthocyanin with caffeic (Caf) or ferulic (Fer) acid was found to be important in the expression of iAGH (maltase) inhibition. In addition, the result that Pg-based anthocyanins showed the most potent maltase inhibition, with an IC(50) value of 4.6 mM, and the effect being in the descending order of potency of Pg > Pn/Cy strongly suggested that no replacement at the 3'(5')-position of the aglycon B-ring may be essential for inhibiting iAGH action.


Phenolic constituents and anticancer properties of Morus alba (white mulberry) leaves.
Flavonoids are by far the most dominant class of phenolic compounds isolated from Morus alba leaves (MAL). Other classes of compounds are benzofurans, phenolic acids, alkaloids, coumarins, chalcones and stilbenes. Major flavonoids are kuwanons, moracinflavans, moragrols and morkotins. Other major compounds include moracins (benzofurans), caffeoylquinic acids (phenolic acids) and morachalcones (chalcones). Research on the anticancer properties of MAL entailed in vitro and in vivo cytotoxicity of extracts or isolated compounds. Flavonoids, benzofurans, chalcones and alkaloids are classes of compounds from MAL that have been found to be cytotoxic towards human cancer cell lines. Further studies on the phytochemistry and anticancer of MAL are suggested. Sources of information were PubMed, PubMed Central, ScienceDirect, Google, Google Scholar, J-Stage, PubChem and China National Knowledge Infrastructure.


Bacillus acidiceler sp. nov., isolated from a forensic specimen, containing Bacillus anthracis pX02 genes.
Research at the Center for Biological Defense identified plasmid-borne forms of Bacillus anthracis pXO2 genes in a Gram-positive, endospore-forming rod, isolated from a forensic specimen considered a credible threat of harbouring anthrax. Conventional, commercial and molecular-based methods indicated that the isolate (CBD 119(T)) was not B. anthracis and considered not to be a member of the Bacillus cereus group. Based on the 16S rRNA gene sequence similarities, strain CBD 119(T) was most closely related to Bacillus luciferensis LMG 18422(T) (99.3 %). Phenotyping and fatty acid methyl ester analysis of the isolate were conducted alongside B. luciferensis JCM 12212(T). The major cellular fatty acids (anteiso-C(15 : 0), iso-C(15 : 0), and >7 iso or anteiso forms) supported inclusion of the isolate in the genus Bacillus. Strain CBD 119(T) was inconsistent with B. luciferensis JCM 12212(T) for 18 of 96 traits evaluated including motility, degree of endospore-driven swelling and pH optimum; the two were linked by fatty acid methyl ester analysis as separate but closely related species. DNA-DNA relatedness between strain CBD 119(T) and B. luciferensis JCM 12212(T) resulted in less than 20 % hybridization. The results of biochemical and physiological characterization, chemotaxonomic analysis and DNA-DNA hybridization differentiated strain CBD 119(T) both phenotypically and genotypically from the only species with validly published name with greater than 97 % 16S rRNA gene sequence similarity. The isolate has an accelerated doubling time when grown in aerated broth at pH 5.9 relative to that at pH 7.1. Therefore, it is proposed that strain CBD 119(T) represents a novel species, Bacillus acidiceler sp. nov. The type strain is strain CBD 119(T) (=NRRL B-41736(T)=DSM 18954(T)).


Impact of temporal changes and host factors on the genetic structure of a population of Opisthorchis viverrini sensu lato in Khon Kaen Province (Thailand).
The population genetics of 317 individual Opisthorchis viverrini from Khon Kaen Province Thailand, from 4 different years and 4 cyprinid fish species was examined using multilocus enzyme electrophoresis of enolase (Enol), phosphoglucomutase (Pgm) and triose phosphate isomerase (Tpi). Allele and genotype frequencies for Enol and Pgm were consistent irrespective of year or host species. No heterozygote deficiency was detected for Enol. Significant heterozygote deficiencies were detected in 3 of 4 years for Pgm. For Tpi, allele frequencies of the most common allele and genotype frequency varied between years and among individuals from different host species. Heterozygote deficiencies for Tpi were detected in 2 years. No significant heterozygous deficiencies were detected among O. virerrini from different fish species in 2005, except at Pgm and Tpi from Puntioplites protozsron. There was no statistical significance in pairwise FST values between O. viverrini from Cyclocheilichthys armatus in different years or different host species in 2005. Significant departures from Hardy-Weinberg expectations and a high rate of gene flow in a population of O. viverrini are discussed in terms of self- and cross-fertilisation, natural selection, non-random mating, the Wahlund effect, presence of null alleles, intensity of infection, biology and ecology of their intermediate cyprinid hosts.


Determinants of diabetic retinopathy in Southwest Ethiopia: a facility-based case-control study.
Diabetic Retinopathy is one of the serious complications patients' diabetic patients suffer from. Little is known about which risk factors are associated with this complication. The aim of this study was therefore to identify determinants of Diabetic Retinopathy in Jimma University Medical Center. A facility-based case-control study was conducted. Cases were Diabetic patients with diabetic retinopathy and who were on follow up at the Jimma University Medical Center while controls were Diabetic patients but free of diabetic retinopathy and who were on follow up at the Jimma University Medical Center. Cases and controls were identified and 311 of them were recruited using systematic random sampling. Data were entered into the Epi-Data version 4.1 and analyzed using SPSS Version 20. Binary Logistic regression analysis was conducted to identify determinants of diabetic retinopathy. A total of 106 cases and 205 controls diabetic participated in the study. Being ≥60 years of age (AOR = 5.04,95%CI: 1.83,13.87),being illiterate (AOR = 7.17, 95% CI: 2.61,19.7), poor adherence to medication (AOR =3: 95% CI: 1.29,6.95),having high systolic blood pressure (AOR = 3.38:95% CI: 1.26,9.05), having family history of Diabetes Mellitus (AOR = 3.95: 95% CI: 1.64,9.54), having other micro vascular complications (AOR = 3.76,95% CI: 1.33,10.66), poor glycemic control (AOR = 9.08, 95%CI: 3.7,22.29), poor cholesterol control (AOR = 0.21, 95%CI: 0.08,0.51) and being anaemic (AOR = 2.8, 95%CI: 1.05,7.47) were the independent determinants of diabetic retinopathy. This study found that poor adherence to medication, being at the age of 60 years and above, being illiterate patients, having high systolic blood pressure, having a family history of Diabetes Mellitus, having other micro vascular complication, poor glycemic control, poor cholesterol control and being anemic patient were the independent determinants of diabetic retinopathy. Therefore, more attention should be given to older age and illiterate patients. Giving more emphasis for patients poorly adhered to anti-diabetic medications and giving advice for diabetic patients with high systolic blood pressure to follow their blood pressure regularly are also vital. Diabetic patients should also control their Blood sugar and blood cholesterol levels to prevent diabetic retinopathy or reduce its further complications.


Extrusion of cells with inappropriate Dpp signaling from Drosophila wing disc epithelia.
Decapentaplegic (Dpp) is a signaling molecule that controls growth and patterning of the developing Drosophila wing. Mutant cells lacking Dpp signal transduction have been shown to activate c-Jun amino-terminal kinase (JNK)-dependent apoptosis and to be lost from the wing disc epithelium. These observations have led to the hypothesis that Dpp promotes cell survival by preventing apoptosis. Here, we show that in the absence of JNK-dependent apoptosis, mutant cells lacking Dpp signal transduction can survive; however, they are still lost from the wing disc epithelium. This loss correlates with extensive cytoskeletal changes followed by basal epithelial extrusion. We propose that Dpp promotes cell survival within disc epithelia by affecting cytoskeletal organization.


Medication adherence and persistence in type 2 diabetes mellitus: perspectives of patients, physicians and pharmacists on the Spanish health care system.
A good relationship between diabetes patients and their health care team is crucial to ensure patients' medication adherence and self-management. To this end, we aimed to identify and compare the views of type 2 diabetes mellitus (T2DM) patients, physicians and pharmacists concerning the factors and strategies that may be associated with, or could improve, medication adherence and persistence. An observational, cross-sectional study was conducted using an electronic self-administered questionnaire comprising 11 questions (5-point Likert scale) concerning factors and strategies related to medication adherence. The survey was designed for T2DM patients and Spanish National Health System professionals. A total of 963 T2DM patients, 998 physicians and 419 pharmacists participated in the study. Overall, a lower proportion of pharmacists considered the proposed factors associated with medication adherence important as compared to patients and physicians. It should be noted that a higher percentage of physicians in comparison to pharmacists perceived that "complexity of medication" (97% vs 76.6%, respectively) and "adverse events" (97.5% vs 72.2%, respectively) were important medication-related factors affecting adherence. In addition, both patients (80.8%) and physicians (80.8%) agreed on the importance of "cost and co-payment" for adherence, whereas only 48.6% of pharmacists considered this factor important. It is also noteworthy that nearly half of patients (43%) agreed that "to adjust medication to activities of daily living" was the best strategy to reduce therapeutic complexity, whereas physicians believed that "reducing the frequency of administration" (47.9%) followed by "reducing the number of tablets" (28.5%) was the most effective strategy to improve patients' adherence. Our results highlight the need for pharmacists to build a stronger relationship with physicians in order to improve patients monitoring and adherence rates. Additionally, these findings may help to incorporate greater patient-centeredness when developing management strategies, focusing on adjusting medication regimens to patients' daily lives.


[The assessment of factor VIII-related antigen in endothelial cells of pulmonary blood vessels in multiple organ failure].
Twenty-five rabbits were randomized into test group (n = 20) and control group (n = 5). Test group animals were fed E coli [(0.4-0.6) x 10(11)/kg] by gastro-lavage and followed by hemorrhagic shock (MBP 40 mmHg for an hour) plus rapid reinfusion with the shed blood. The control group served as operation control. Twelve animals in test group developed MOF (60%). The application of the PAP method in assaying the amount of F VIIIR: Ag in endothelial cells of pulmonary blood vessels. The result showed that the scores of test group was 0.66 +/- 0.24 and the control group 3.01 +/- 0.22. The difference between two groups was statistically significant (P less than 0.05). The PaO2 in MOF animals was 63.1 +/- 9.6 mmHg and the control group 93.6 +/- 4.6 mmHg. The decrease of PaO2 and value scores of FVIIIR: Ag was closely related (r = 0.72, P less than 0.01). The result suggests that a large amount of F VIIIR: Ag was released into blood due to the endothelial injury of pulmonary blood vessels in MOF. The injury of endothelial cells in pulmonary blood vessels was an important factor in pathogenesis of MOF.


Low birth weight across generations: the effect of economic environment.
To determine whether economic environment across generations underlies the association of maternal low birth weight (<2,500 g, LBW) and infant LBW including its preterm (<37 weeks) and intrauterine growth retardation (IUGR) components. Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational dataset of White and African-American infants (1989-1991) and their mothers (1956-1976) with appended US census income data. Population Attributable Risk percentages were calculated to estimate the percentage of LBW births attributable to maternal LBW. Among Whites, former LBW mothers (N = 651) had an infant LBW rate of 7.1% versus 3.9% for former non-LBW mothers (N = 11,505); RR = 1.8 (1.4-2.5). In multilevel logistic regression models that controlled for economic environment and individual maternal risk factors, the adjusted OR of infant LBW, preterm birth, and intrauterine growth retardation for maternal LBW (compared to non-LBW) equaled 1.8 (1.3-2.5), 1.3 (1.0-1.8), and 1.8 (1.5-2.3), respectively. Among African-Americans, former LBW mothers (N = 3,087) had an infant LBW rate of 19.5% versus 13.3% for former non-LBW mothers (N = 18,558);RR = 1.5 (1.3-1.6). In multilevel logistic models of African-Americans, the adjusted OR of infant LBW, preterm birth, and IUGR for maternal LBW (compared to non-LBW) were 1.6 (1.4-1.8), 1.3 (1.2-1.5), and 1.6 (1.5-1.8), respectively. In both races, approximately five percent of LBW infants with mothers and maternal grandmother who resided in high-income neighborhoods were attributable to maternal LBW. A similar generational transmission of LBW including its component pathways of preterm birth and intrauterine growth retardation occurs in both races independent of economic environment across generations.


Quantum Monte Carlo simulation of a particular class of non-stoquastic Hamiltonians in quantum annealing.
Quantum annealing is a generic solver of the optimization problem that uses fictitious quantum fluctuation. Its simulation in classical computing is often performed using the quantum Monte Carlo simulation via the Suzuki-Trotter decomposition. However, the negative sign problem sometimes emerges in the simulation of quantum annealing with an elaborate driver Hamiltonian, since it belongs to a class of non-stoquastic Hamiltonians. In the present study, we propose an alternative way to avoid the negative sign problem involved in a particular class of the non-stoquastic Hamiltonians. To check the validity of the method, we demonstrate our method by applying it to a simple problem that includes the anti-ferromagnetic XX interaction, which is a typical instance of the non-stoquastic Hamiltonians.


Unveiling contextual realities by microscopically entangling a neutron.
The development of qualitatively new measurement capabilities is often a prerequisite for critical scientific and technological advances. Here we introduce an unconventional quantum probe, an entangled neutron beam, where individual neutrons can be entangled in spin, trajectory and energy. The spatial separation of trajectories from nanometers to microns and energy differences from peV to neV will enable investigations of microscopic magnetic correlations in systems with strongly entangled phases, such as those believed to emerge in unconventional superconductors. We develop an interferometer to prove entanglement of these distinguishable properties of the neutron beam by observing clear violations of both Clauser-Horne-Shimony-Holt and Mermin contextuality inequalities in the same experimental setup. Our work opens a pathway to a future of entangled neutron scattering in matter.


SPP1 and AGER as potential prognostic biomarkers for lung adenocarcinoma.
Overdue treatment and prognostic evaluation lead to low survival rates in patients with lung adenocarcinoma (LUAD). To date, effective biomarkers for prognosis are still required. The aim of the present study was to screen differentially expressed genes (DEGs) as biomarkers for prognostic evaluation of LUAD. DEGs in tumor and normal samples were identified and analyzed for Kyoto Encyclopedia of Genes and Genomes/Gene Ontology functional enrichments. The common genes that are up and downregulated were selected for prognostic analysis using RNAseq data in The Cancer Genome Atlas. Differential expression analysis was performed with 164 samples in GSE10072 and GSE7670 datasets. A total of 484 DEGs that were present in GSE10072 and GSE7670 datasets were screened, including secreted phosphoprotein 1 (SPP1) that was highly expressed and DEGs ficolin 3, advanced glycosylation end-product specific receptor (AGER), transmembrane protein 100 that were lowly expressed in tumor tissues. These four key genes were subsequently verified using an independent dataset, GSE19804. The gene expression model was consistent with GSE10072 and GSE7670 datasets. The dysregulation of highly expressed SPP1 and lowly expressed AGER significantly reduced the median survival time of patients with LUAD. These findings suggest that SPP1 and AGER are risk factors for LUAD, and these two genes may be utilized in the prognostic evaluation of patients with LUAD. Additionally, the key genes and functional enrichments may provide a reference for investigating the molecular expression mechanisms underlying LUAD.


[Calcification of the meniscus].
Degenerative-dystrophic changes in resected damaged menisci are noted with frequency, their calcification is a rare event. The authors in their orthopedic practice observed three patients with meniscus calcification. There is given a communication of one observation. The authors believe that meniscus calcification is an indication for its removal.


Anion order in perovskite oxynitrides.
Transition-metal oxynitrides with perovskite-type structures are an emerging class of materials with optical, photocatalytic, dielectric and magnetoresistive properties that may be sensitive to oxide-nitride order, but the anion-ordering principles were unclear. Here we report an investigation of the representative compounds SrMO(2)N (M = Nb, Ta) using neutron and electron diffraction. This revealed a robust 1O/2(O(0.5)N(0.5)) partial anion order (up to at least 750 °C in the apparently cubic high-temperature phases) that directs the rotations of MO(4)N(2) octahedra in the room-temperature superstructure. The anion distribution is consistent with local cis-ordering of the two nitrides in each octahedron driven by covalency, which results in disordered zigzag M-N chains in planes within the perovskite lattice. Local structures for the full range of oxynitride perovskites are predicted and a future challenge is to tune properties by controlling the order and dimensionality of the anion chains and networks.


Status of tuberculosis infection control programs at United States hospitals, 1989 to 1992. APIC. Association for Professionals in Infection Control and Epidemiology.
Recent nosocomial outbreaks have raised concern about the risk of Mycobacterium tuberculosis transmission in United States hospitals. To determine current tuberculosis (TB) infection control practices, we surveyed a sample of approximately 3000 acute care facilities about the number of patients with drug-susceptible or multidrug-resistant TB (MDR-TB), health care worker (HCW) tuberculin skin test (TST) results, and compliance with the 1990 Centers for Disease Control and Prevention (CDC) TB guidelines. Analyses were restricted to one response per hospital. Personnel at 1494 (49.8%) hospitals returned a completed survey. Respondent hospitals had a mean of 881 HCWs (range 8 to 10,000) and 196 (range 6 to 2450) beds; 62% percent were community nonteaching hospitals. Of respondent hospitals providing data for 1989 through 1992, the proportion that cared for patients with TB or MDR-TB increased from 46.4% to 56.6% and 0.8% to 4.5%, respectively. The pooled mean HCW TST positivity rate at hire rose from 0.95% to 1.14%, and the pooled mean HCW TST conversion rate increased from 0.40% to 0.51%. In 1992, when we compared hospitals with zero, one to five, or six or greater patients with TB, the risk of a positive HCW TST result at hire or at routine testing significantly increased with increasing number of patients with TB. From 1989 through 1992, the number of hospitals reporting the use of surgical masks for HCW respiratory protection decreased from 96.8% to 66.8%. In 1992, 66% of the hospitals reported compliance with four or more of the AFB isolation room criteria specified in the 1990 CDC TB guidelines. Contrary to prior surveys, this study shows that many U.S. community hospitals admit patients with TB less frequently than do teaching hospitals, and infrequently admit patients with MDR-TB. Because the risk of HCW TST conversion varies with hospital characteristics, these data show the importance of performing a risk assessment, as recommended in the CDC TB guidelines, for each ward and hospital so that TB control measures can be individualized.


Objective technique for evaluating painful heel syndrome and its treatment.
The biomechanical evaluation of patients with painful heels has received only limited attention although the potential morbidity and disability associated with such an ailment can be severe. An objective analysis of the patient's foot function during gait can produce useful information to assess the underlying pathology. This method can also help to evaluate the efficacy of various existing treatment protocols. The impulse distribution based on foot-floor vertical reaction force and time under the hind-, mid-, and forefoot was determined in 32 normal subjects while walking in their usual street shoes. Variations related to shoe types were noted, with high heeled shoes causing the most significant deviations from normal. The same technique was applied to 13 painful heel syndrome patients. Characteristic deviations from the normal impulse distribution were noted in these patients which provided the basis for differentiating the pathological condition between the patients with painful heel pads and those with plantar fasciitis. The effectiveness of using heel cups as a therapeutic device was also assessed. Although significant gait changes were not associated with the insertion of heel cups, they did seem to shift the foot-floor impulse forward from the heel region, which made them effective in patients afflicted with localized heel pain, but not in those with plantar fasciitis.


Actin dynamics modulate mechanosensitive immobilization of E-cadherin at adherens junctions.
Mechanical stress is increasingly being shown to be a potent modulator of cell-cell junctional morphologies in developmental and homeostatic processes. Intercellular force sensing is thus expected to be an important regulator of cell signalling and tissue integrity. In particular, the interplay between myosin contractility, actin dynamics and E-cadherin recruitment largely remains to be uncovered. We devised a suspended cell doublet assay to quantitatively assess the correlation between myosin II activity and local E-cadherin recruitment. The single junction of the doublet exhibited a stereotypical morphology, with E-cadherin accumulating into clusters of varied concentrations at the rim of the circular contact. This local recruitment into clusters derived from the sequestration of E-cadherin through a myosin-II-driven modulation of actin turnover. We exemplify how the regulation of actin dynamics provides a mechanism for the mechanosensitive response of cell contacts.


Dientamoeba fragilis--a protozoal infection which may cause severe bowel distress.
A retrospective study of 87 patients diagnosed with the protozoan Dientamoeba fragilis was performed due to a recent increase in the number of patients diagnosed with this organism at the Unit of Clinical Parasitology, Huddinge University Hospital, Stockholm, Sweden. Medical records were reviewed. The highest incidence was found in pre-school boys, who also had the longest duration of symptoms, with a range of 1-630 weeks. A majority of the patients had symptoms of diarrhea, abdominal pain and flatus. The diarrhea varied from watery to loose, blood being reported only sporadically. Most patients had traveled outside Europe and had no other parasites in their stools. This study indicates potential pathologic properties in D. fragilis, and prospective studies are recommended.


GH elevates serum IGF-I levels but does not alter mucosal atrophy in parenterally fed rats.
Growth hormone (GH) action is primarily mediated by insulin-like growth factor I (IGF-I), although both growth factors show tissue-selective effects. We investigated the effects of GH, IGF-I, and GH plus IGF-I on jejunal growth and function in rats maintained with total parenteral nutrition (TPN) and given recombinant human GH (rhGH) (400 micrograms/day sc, twice daily) and/or rhIGF-I (800 micrograms/day in TPN solution) for 5 days. Administration of GH or IGF-I alone produced similar increases in serum IGF-I levels and body weight; GH plus IGF-I further increased these parameters. TPN reduced mucosal mass, protein and DNA content, villus height, crypt depth, and enterocyte migration rate. IGF-I or GH plus IGF-I produced equivalent increases in all intestinal growth parameters; GH alone had no effect. GH, IGF-I, or GH plus IGF-I reduced TPN-induced increases in sucrase-specific activity. IGF-I, but not GH, attenuated TPN-induced increases in tissue conductance and carbachol-stimulated ion secretion. In contrast to IGF-I, GH does not stimulate intestinal growth during TPN and has less effect on normalizing TPN-induced changes in epithelial function.


Update in paediatric asthma management: where is evidence challenging current practice?
Extrapolation of management strategies based on results from predominantly adult asthma studies frequently occurs in paediatric asthma despite increasing evidence that paediatric asthma and, in particular, pre-school recurrent wheeze are very different disease entities. Response to medications in paediatric subjects is often different from that seen in their older adolescent and adult counterparts. In this update, we discussed recent studies that have had important implications for future paediatric asthma management. The overuse of combination inhaled steroid and long-acting beta2 agonist inhalers in paediatric asthma despite ongoing safety concerns is an increasing trend in paediatric asthma, and recent evidence has helped clarify how they should be used in children. Other aspects discussed include the role of oral corticosteroids in pre-school viral-induced wheeze and the utility of leukotriene receptor antagonists in exercise-induced asthma.


Identification of noncoding transcripts from within CENP-A chromatin at fission yeast centromeres.
The histone H3 variant CENP-A is the most favored candidate for an epigenetic mark that specifies the centromere. In fission yeast, adjacent heterochromatin can direct CENP-A(Cnp1) chromatin establishment, but the underlying features governing where CENP-A(Cnp1) chromatin assembles are unknown. We show that, in addition to centromeric regions, a low level of CENP-A(Cnp1) associates with gene promoters where histone H3 is depleted by the activity of the Hrp1(Chd1) chromatin-remodeling factor. Moreover, we demonstrate that noncoding RNAs are transcribed by RNA polymerase II (RNAPII) from CENP-A(Cnp1) chromatin at centromeres. These analyses reveal a similarity between centromeres and a subset of RNAPII genes and suggest a role for remodeling at RNAPII promoters within centromeres that influences the replacement of histone H3 with CENP-A(Cnp1).


Intestinal parasitic infections among prison inmates and tobacco farm workers in Shewa Robit, north-central Ethiopia.
Intestinal parasitic infections (IPIs) particularly soil-transmitted helminthiasis (STH) and schistosomiasis are among neglected tropical diseases (NTDs) globally. Apart from being associated with anemia, malabsorption and retarded cognitive development these diseases are complicating the clinical picture of more serious infections like HIV, TB and malaria. Renewed and up-to-date information on the epidemiology of IPIs in more vulnerable groups such as irrigated-farm workers and prisoners would significantly contribute towards improving the health condition of such at-risk groups. A cross-sectional survey was conducted to determine the prevalence of IPIs among prison inmates and tobacco farm workers in Shewa-Robit, north-central Ethiopia in November 2008. A total of 236 fecal samples were examined microscopically to detect helminths and/or protozoa using direct-smear and formol-ether concentration methods. Overall, 8 intestinal parasite species have been recovered singly or in combinations from 146 (61.8 %) samples. The prevalence in prison population (88/121 = 72.7%) was significantly higher than that in tobacco farm (58/115 = 50.4%). There were no significant differences in the prevalence of IPI by most socio-demographics. Except for hookworm there was no significant difference in parasite prevalence between different age-groups though the frequency of individual parasites slightly varied between the age-groups. Multivariate logistic regression analysis showed that inmates were more likely to acquire IPIs than tobacco-farm workers (Odds Ratio (OR) = 2.62, 95% confidence interval (CI) = 1.52-4.5). In addition, participants who did not report past treatment for IPIs were more likely to acquire IPIs than participants who self-reported treatment for IPIs in the past twelve months (OR = 3.25, 95% CI = 1.75-6.06). All other socio-demographics were not significantly associated with IPIs in univariate analysis. Entamoeba histolytica/dispar/moshkovskii was the most frequently encountered species in both study sites accounting for 48.8 and 51.7 percent of the positives in prison and tobacco farm population respectively. Other intestinal parasites detected, with slight variation in prevalence in the two study areas, were hookworm, Ascaris lumbricoides, Trichuris trichiura, Schistosoma mansoni, Strongyloides stercolaris, Hymenolepis nana and Taenia sp. 35.5 and 33.0 percent of the total positive cases were mixed infections in Shewa Robit prison and tobacco farm, respectively. The results show that IPIs are common health problems in the studied populations.


Cluster of methicillin-resistant Staphylococcus aureus colonization in a small animal intensive care unit.
Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the tracheostomy tube of an 18-month-old castrated male Golden Retriever in the intensive care unit (ICU) of the Ontario Veterinary College. This prompted an investigation of MRSA colonization in other animals in the ICU. On day 1 of the investigation, MRSA was isolated from nasal swabs obtained from 2 of 10 animals (2/7 dogs and 0/3 cats), including the index case. Subsequently, MRSA was isolated from 3 of 12 animals on day 9; 3 of 9 animals on day 13; and none of 14, 5, and 6 animals on day 20, 27, and 78, respectively. Overall, MRSA was isolated from 6 of 26 (23%) animals during the outbreak period (4/22 dogs and 2/4 cats). The apparent incidence of MRSA acquisition in the ICU from days 1 through 13 was 20% (5/25 animals). No clinical signs of MRSA infections developed. All isolates were indistinguishable from one another. Infection-control measures including active surveillance of all animals in the ICU, barrier precautions, and hand hygiene were used to control the apparent outbreak. Methicillin-resistant S aureus is an emerging problem in veterinary medicine. Intensive care units may be at particular risk for periodic outbreaks of colonization and disease. The outbreak of this report highlights the potential for clinically inapparent transmission of MRSA within a facility; infection-control measures that might facilitate MRSA eradication should be considered in ICU settings.


End-organ damage in urbanized Africans with low plasma renin levels: the SABPA study.
The purpose of this study was to evaluate whether active renin concentration is associated with markers of end-organ damage in urbanized Africans. This study forms part of the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. For this study, 81 men and 74 women were divided into low- and high-renin groups. Ambulatory blood pressure measurements were conducted. A resting 12-lead ECG was determined in order to determine the gender-specific Cornell voltage. Cardiovascular variables were continuously recorded with the Finometer. Carotid-dorsalis pedis pulse wave velocity was obtained with the Complior acquisition system. The carotid intima-media thickness (CIMT) was obtained with the SonoSite MicroMaxx. Blood samples were collected; serum and plasma were stored at -80 °C for analysis. Anthropometric measurements were taken using standard methods. A general health questionnaire was also completed. The urinary creatinine was determined with a calorimetric method and albumin with a turbidimetric method. The serum sodium and potassium were determined by making use of the Konelab TM 20i Sequential Multiple Analyzer Computer (SMAC). The concentration of active renin in the plasma was analyzed by making use of a high-sensitivity radio-immunometric assay. A negative association (r=-0.29, p<0.01) exists between renal function (ACR) and plasma renin in the low-renin group (<6.18 pg/mL), which was not observed in Africans with high-renin levels. It seems evident that low renin in black South Africans may result in sub-clinical renal damage and impaired vascular function in a group of urbanized black South Africans.


Glucose-mediated de novo lipogenesis in photoreceptors drives early diabetic retinopathy.
Diabetic retinopathy (DR) is an increasingly frequent cause of blindness across populations; however, the events that initiate pathophysiology of DR remain elusive. Strong preclinical and clinical evidence suggests that abnormalities in retinal lipid metabolism caused by diabetes may account for the origin of this disease. A major arm of lipid metabolism, de novo biosynthesis, is driven by elevation in available glucose, a common thread binding all forms of vision loss in diabetes. Therefore, we hypothesized that aberrant retinal lipid biogenesis is an important promoter of early DR. In murine models, we observed elevations of diabetes-associated retinal de novo lipogenesis ∼70% over control levels. This shift was primarily because of activation of fatty acid synthase (FAS), a rate-limiting enzyme in the biogenic pathway. Activation of FAS was driven by canonical glucose-mediated disinhibition of acetyl-CoA carboxylase, a major upstream regulatory enzyme. Mutant mice expressing gain-of-function FAS demonstrated increased vulnerability to DR, whereas those with FAS deletion in rod photoreceptors maintained preserved visual responses upon induction of diabetes. Excess retinal de novo lipogenesis-either because of diabetes or because of FAS gain of function-was associated with modestly increased levels of palmitate-containing phosphatidylcholine species in synaptic membranes, a finding with as yet uncertain significance. These findings implicate glucose-dependent increases in photoreceptor de novo lipogenesis in the early pathogenesis of DR, although the mechanism of deleterious action of this pathway remains unclear.


Transcriptome profiles of the skeletal muscle of mature cows during feed restriction and realimentation.
Realimentation can compensate for weight loss from poor-quality feedstuffs or drought. Mature cows fluctuate in body weight throughout the year due to nutrient availability. The objective of this study was to determine whether cows that differ in weight gain during realimentation also differ in the abundance of transcripts for enzymes associated with energy utilization in skeletal muscle. Mature cows were subjected to feed restriction followed by ad libitum feed. Skeletal muscle transcriptome expression differences during the two feeding periods were determined from cows with greater (n = 6) and less (n = 6) weight gain during the ad libitum feeding period. A total of 567 differentially expressed genes (408 up- and 159 down-regulated) were identified for the comparison of restriction and ad libitum periods (PBonferroni < 0.05). These genes were over-represented in lysosome, aminoacyl-tRNA biosynthesis, and glutathione metabolism pathways. Validation of the expression of five of the genes was performed and four were confirmed. These data suggest that realimentation weight gain for all cows is partially controlled by protein turnover, but oxidative stress and cellular signaling pathways are also involved in the muscle tissue. This dataset provides insight into molecular mechanisms utilized by mature cows during realimentation after a period of low abundance feed.


Fecal microbial communities of healthy adult dogs fed raw meat-based diets with or without inulin or yeast cell wall extracts as assessed by 454 pyrosequencing.
Our objective was to determine the effects of feeding raw meat-based diets with or without inulin or yeast cell wall extract (YCW) on fecal microbial communities of dogs using 454 pyrosequencing. Six healthy female adult beagles (5.5 ± 0.5 years; 8.5 ± 0.5 kg) were randomly assigned to six test diets using a Latin square design: (1) beef control; (2) beef + 1.4% inulin; (3) beef + 1.4% YCW; (4) chicken control; (5) chicken + 1.4% inulin; and (6) chicken + 1.4% YCW. Following 14 days of adaptation, fresh fecal samples were collected on day 15 or day 16 of each period. Fecal genomic DNA was extracted and used to create 16S rRNA gene amplicons, which were subjected to 454 pyrosequencing and qPCR. Predominant fecal bacterial phyla included Fusobacteria, Firmicutes, Bacteroidetes, and Proteobacteria. Beef-based diets increased (P < 0.05) Escherichia, but decreased (P < 0.05) Anaerobiospirillum vs. chicken-based diets. Inulin decreased (P < 0.05) Enterobacteriaceae. Inulin increased (P < 0.05) Megamonas vs. control. Inulin also decreased (P < 0.05) Escherichia vs. YCW. qPCR data showed that YCW increased (P < 0.05) Bifidobacterium vs. inulin and control and inulin increased (P < 0.05) Lactobacillus vs. YCW. Although a few changes in fecal microbiota were observed with inulin or YCW consumption, a strong prebiotic effect was not observed.


[Cervical schwannoma presenting with trauma-induced neurological symptoms].
A 37-year-old man was admitted with neurological complaints after a traffic accident. Physical examination showed no signs of injury due to the accident. Magnetic resonance imaging of the neck revealed a well-demarcated lesion showing homogeneous contrast enhancement at the level of C(1-2). The patient underwent elective surgery, and histopathological diagnosis of the surgical specimen was made as cervical schwannoma. His neurological complaints disappeared on the second postoperative day. No neurological deficit was observed at six-month follow-up. To our knowledge, there has been no literature report in which the diagnosis of cervical schwannoma was made during investigation of trauma-induced neurological symptoms.


Factors affecting survival following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma.
To assess factors associated with better overall survival (OS) and progression-free survival (PFS) following chemoembolization with doxorubicin-eluting microspheres for inoperable hepatocellular carcinoma (HCC) MATERIALS AND METHODS: Data of 130 patients (104 men; median age, 62 y) with inoperable HCC who underwent successful DEB chemoembolization with 100-300 -μm LC Bead particles loaded with 50 mg doxorubicin per vial were reviewed following human research committee approval. Effects of various clinical, imaging, and response factors on OS and PFS were assessed by univariate Kaplan-Meier survival analysis. Multiple Cox regression with backward elimination was performed for terms found significant (P ≤ .05) on univariate analysis. The number of DEB chemoembolization procedures per patient ranged from one to four (mean, 2 ± 1). The median PFS and OS were 5.7 months (95% confidence interval, 4.6-7.6 mo) and 14.7 months (95% confidence interval, 12.3-19.7 mo), respectively. On multivariate Cox regression, Cancer of the Liver Italian Program (CLIP) score of 1 or lower, necrosis of more than 50%, and response or stable disease per Response Evaluation Criteria In Solid Tumors after DEB chemoembolization were associated with better PFS. CLIP score of 1 or lower, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 1 or lower, absence of portal vein (PV) thrombosis, and necrosis greater than 50% following DEB chemoembolization were associated with better OS. CLIP score of 1 or lower and necrosis of more than 50% are independent variables affecting PFS and OS after DEB chemoembolization, whereas absence of PV thrombosis and ECOG PS of 1 or lower affected OS but not PFS.


Subjective Fatigue in Children With Hearing Loss Assessed Using Self- and Parent-Proxy Report.
The primary purposes of this study were to examine the effects of hearing loss and respondent type (self- vs. parent-proxy report) on subjective fatigue in children. We also examined associations between child-specific factors and fatigue ratings. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS; Varni, Burwinkle, Katz, Meeske, & Dickinson, 2002). We compared self- and parent-proxy ratings from 60 children with hearing loss (CHL) and 43 children with normal hearing (CNH). The children ranged in age from 6 to 12 years. School-age CHL experienced more overall and cognitive fatigue than CNH, although the differences were smaller than previously reported. Parent-proxy report was not strongly associated with child self-report, and parents tended to underestimate their child's fatigue, particularly sleep/rest fatigue. Language ability was also associated with subjective fatigue. For CHL and CNH, as language abilities increased, cognitive fatigue decreased. School-age CHL experience more subjective fatigue than CNH. The poor association between parent-proxy and child reports suggests that the parent-proxy version of the PedsQL-MFS should not be used in isolation when assessing fatigue in school-age children. Future research should examine how language abilities may modulate fatigue and its potential academic consequences in CHL.


Renal tubular function in patients with beta-thalassaemia major in Zahedan, southeast Iran.
In patients with beta-thalassaemia major, impaired biosynthesis of the beta-globin leads to accumulation of unpaired alpha-globin chain. Shortened red cell lifespan and iron overload cause functional and physiological abnormalities in various organ systems. Thus, in patients with beta-thalassaemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron. The aim of this study is to investigate renal tubular and glomerular functions in patients with beta-thalassaemia major. 166 subjects with beta-thalassaemia major (96 male, 70 female) were enrolled in the study. Fasting blood and 24-hour urine samples were obtained for haematological and biochemical analyses. Patients with beta-thalassaemia major showed significant signs of renal tubulopathy, such as hypercalciuria (12.9 percent), proteinuria (8.6 percent), phosphaturia (9.2 percent), magnesiumuria (8.6 percent), hyperuricosuria (38 percent) and excretion of beta-2 microglobin (13.5 percent). We found that 95.1 percent of patients had iron overload (ferritin more than 1,000 ng/ml). The determination of biochemical indices of renal function might help prevention of serious kidney damage before any clinical symptom is observed. Beta-thalassaemia patients present multiple renal abnormalities which may be due to iron overload. We suggest the appropriate chelation therapy and regular monitoring of the status of iron overload.


Stromal invasion and micropapillary pattern in 212 consecutive surgically resected stage I lung adenocarcinomas: histopathological categories for prognosis prediction.
It is of importance to search for prognostic indicators supplementing the tumour-node-metastasis stage for surgically resected early-stage lung adenocarcinomas. The roles of stromal invasion and micropapillary pattern in categorising histopathology and predicting the prognosis of stage I lung adenocarcinomas are explored. We retrospectively examined 212 consecutive surgically resected stage I lung adenocarcinomas to propose a new histopathology-based categorical classification. Category A tumours have pure lepidic growth pattern without stromal invasion (ie, adenocarcinoma in situ). Stromal invasion in the form of central fibrotic focus is absent in category B tumours and present in category C tumours. Category B is subclassified into B1, which has areas of lepidic growth, and B2, which does not. Category C is subclassified into C1, which has invasive tumour cells in the periphery of central fibrotic focus, and C2, which has invasive tumour cells in the centre of central fibrotic focus. Based on the absence or presence of micropapillary pattern, the C2 tumours are further subclassified into C2a and C2b, respectively. The 5-year recurrence-free probabilities for categories B1 (17 cases), B2 (10 cases), C1 (nine cases), C2a (114 cases) and C2b (62 cases) are 100%, 78.8%, 100%, 67.5% and 53.1%, respectively (p<0.001). Based on stromal invasion and micropapillary pattern, the histopathological categorical classification proposed here provides a concise and precise scheme for outcome prediction in early-stage lung adenocarcinomas.


Serotypes of Campylobacter jejuni isolated from patients attending a diarrhoeal disease hospital in urban Bangladesh.
The serotypes of strains of Campylobacter jejuni isolated from patients attending the International Center for Diarrhoeal Disease Research, Bangladesh (ICDDR, B), Dhaka, and from animals were ascertained by Penner and Hennessy's (1980) serotyping scheme. Of 102 isolates from man, 74% were typable and serotypes 53, 15 and 22 predominated. Of 26 isolates from animals, 65% were typable and serotypes 15 and 53 occurred frequently. The diarrhoeal illnesses associated with different serotypes were similar. In one-third of cases other enteropathogens were present. C. jejuni was isolated from 7% of patients tested in a 4% sampling system during 1983, and the prevalent serotypes appeared in most months. It is concluded that C. jejuni is a common enteropathogen in Bangladesh, that a few serotypes predominate among isolates from both man and animals, and that serotype does not determine clinical symptoms.


Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial.
Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to μmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4-8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. Between Sept 17, 2013, and April 14, 2014, 23,664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0-18·4) in the alert group and 0·6% (0·0-17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90-1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81-1·68]; p=0·40). An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. Penn Center for Healthcare Improvement and Patient Safety.


[Steroid hormone receptors and cellular proliferative activity following the short-term use of tamoxifen and chlorotrianisene in breast cancer].
The content of estrogen receptors (ER), progesterone receptors (PR), the proliferative pool level in the tumour tissue were investigated in 6 patients with the disseminated breast tumour before and after 9-day treatment with tamoxifen and chlorotrianisene for intensification of the effect of cytostatic preparations. A significant increase of the DNA synthesis intensity and proliferative pool value is observed in ER+ tumours of 2 patients. An increase of the PR level in tumour biopsies was registered in 2 patients. A decrease of the ER+ level was detected in ER+ tumours in all three patients.


Just-in-time adaptive intervention to promote fluid consumption in patients with kidney stones.
Kidney stones are painful and costly. Prevention guidelines emphasize a simple behavior change: increasing fluid intake and urine output. Unfortunately, adherence to those prevention guidelines is limited, and patients report forgetting or not being thirsty enough. This study evaluated the acceptability of using semiautomated tracking of fluid consumption to trigger just-in-time reminders to drink and increase the experienced automaticity of fluid intake. In a single-group trial, participants with a history of kidney stones (n = 31) used the sipIT digital tools (H2OPal connected water bottle, H2OPal mobile app for self-tracking, Fitbit smartwatch app for gesture detection) for 3 months. The semiautomated monitoring system detected 46,654 drinking events. From baseline to 1-month follow-up, the experienced automaticity of fluid intake increased significantly (d = 0.50) and remained elevated at 3-month follow-up (d = 0.64). A major barrier to adherence (lack of thirst) decreased from baseline to follow-ups. Retention rates and participant feedback indicated that this digital tool was acceptable to patients. Semiautomated tracking of fluid consumption can be used to trigger just-in-time reminders. Based on this demonstration, the sipIT tools are ready for testing in a rigorous Phase II trial to evaluate efficacy for increasing fluid consumption and urine output as recommended for preventing the recurrence of kidney stones. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Lymphocyte reactivity contributes to protection conferred by specific antibody passively transferred to herpes simplex virus-infected mice.
Passively acquired immunity to herpes simplex virus (HSV) was studied in antithymocyte serum (ATS)-treated mice and athymic nude mice to determine whether immunocompetent lymphocytes contribute to the protection observed after transfer of HSV-specific antibody to infected animals. Mice were given three intraperitoneal injections of 0.1 ml of ATS at 24-h intervals. This treatment reduced concanavalin A and lipopolysaccharide stimulation of lymphocytes harvested from these animals by 90% when compared with the stimulation of lymphocytes harvested from untreated animals. It was found that intraperitoneal injection of 0.5 ml of specific antibody 8 h after corneal HSV type 1 infection or subcutaneous HSV type 2 infection did not protect ATS-treated animals from virus infection. Specific antibody passively transferred to ATS-treated animals 8 and 120 h postinfection also failed to protect lymphocyte-depleted animals from HSV. However, ATS-treated animals were protected from HSV infection by passively acquired antibody when lymphocytes harvested from these animals regained 80% of their ability to be stimulated with concanavalin A and lipopolysaccharide. It was also found that specific antibody conferred protection to nude mice infected with HSV only if they were first reconstituted with syngeneic thymus cells 48 h before infection. The results suggest that both antiviral antibody and thymus-derived lymphocytes contribute to the recovery of HSV-infected hosts after passive immunization.


Psychometric Properties of the Preschool Age Psychiatric Assessment (PAPA) in Farsi: Based on DSM-5.
The first onset of many psychiatric disorders usually occurs in childhood or adolescence. The structured interview of Preschool Age Psychiatric Assessment (PAPA) was developed in response to the need for a standardized and reliable method to assess psychiatric disorders in preschool-age children. This study aimed to translate DSM-5-based PAPA into Farsi and evaluate its face and content validity and reliability. The procedure was a forward translation of PAPA to Farsi, evaluation for face and content validity, finalization of items within the expert panel, backward translation to English, matching the original PAPA with randomly selected items from the backward translation version, and revision as needed, and finally evaluation for the validity of the changes for localization and cultural considerations. The interviews based on the final Farsi version were performed on thirty parents of children from two to five years old (chosen from Tabriz health centers) to determine the reliability and were repeated at an interval of two weeks. The mean of CVI=0.91 and Modified Kappa=0.90 were obtained, and reliability with Cronbach's alpha was 0.89. The Farsi version of the DSM-5-based PAPA diagnostic interview has good face and content validity and reliability.


Graphene nanomesh photodetector with effective charge tunnelling from quantum dots.
Graphene nanomesh (GNM)-based optoelectronics integrated with quantum dots (QDs) are investigated in this article. The charge transfer mechanism in the QDs/GNM interface is probed in four terminal gated FET-type photodetectors. The insulating ligand is used to make the GNM/ligand/QDs vertically behave like a metal/insulate/semiconductor (MIS) structure to facilitate the charge tunnelling. With the current constraint effect of the GNM and the effective charge tunnelling, a high-performance photodetector is fabricated with higher responsivity, higher on/off ratio and shorter response time. The results of our analysis and experimental approach can be extended to future graphene-based photodetectors, as long as suitable ligands and an effective architecture are chosen for this type of device.


Personal outcomes as measures of quality.
The Council on Quality and Leadership in Supports for People With Disabilities (The Council), formerly known as The Accreditation Council, altered its definition of quality from "compliance with organizational process" to "responsiveness to people." Council representatives conducted focus group and individual meetings with people who have disabilities to identify priority outcomes they expect from services and supports. The 1993 Outcome Based Performance Measures was used in 447 interviews as part of 54 accreditation reviews. Staff analysis and factor analysis of the outcome interviews using a principle components extraction and varimax rotation resulted in 24 variables loading onto seven major factors (Identity, Autonomy, Affiliation, Attainment, Rights, Health, and Safeguards), which form the basis of The Council 1997 Personal Outcome Measures.


The magnetism of surgery: small bowel obstruction in an 8-year-old boy.
An 8-year-old boy with Asperger's syndrome presented with right-sided abdominal pain, which was consistent with a probable appendicitis, but revisiting the history with a high index of suspicion confirmed multiple foreign body ingestion to be the cause of his symptoms. An emergency laparotomy was performed. Multiple toy magnets and other metal objects were found, which were causing small bowel obstruction with interloop fistulation. Following removal and repair, the patient made an excellent recovery.


Gene duplication in the diversification of secondary metabolism: tandem 2-oxoglutarate-dependent dioxygenases control glucosinolate biosynthesis in Arabidopsis.
Secondary metabolites are a diverse set of plant compounds believed to have numerous functions in plant-environment interactions. The large chemical diversity of secondary metabolites undoubtedly arises from an equally diverse set of enzymes responsible for their biosynthesis. However, little is known about the evolution of enzymes involved in secondary metabolism. We are studying the biosynthesis of glucosinolates, a large group of secondary metabolites, in Arabidopsis to investigate the evolution of enzymes involved in secondary metabolism. Arabidopsis contains natural variations in the presence of methylsulfinylalkyl, alkenyl, and hydroxyalkyl glucosinolates. In this article, we report the identification of genes encoding two 2-oxoglutarate--dependent dioxygenases that are responsible for this variation. These genes, AOP2 and AOP3, which map to the same position on chromosome IV, result from an apparent gene duplication and control the conversion of methylsulfinylalkyl glucosinolate to either the alkenyl or the hydroxyalkyl form. By heterologous expression in Escherichia and the correlation of gene expression patterns to the glucosinolate phenotype, we show that AOP2 catalyzes the conversion of methylsulfinylalkyl glucosinolates to alkenyl glucosinolates. Conversely, AOP3 directs the formation of hydroxyalkyl glucosinolates from methylsulfinylalkyl glucosinolates. No ecotype coexpressed both genes. Furthermore, the absence of functional AOP2 and AOP3 leads to the accumulation of the precursor methylsulfinylalkyl glucosinolates. A third member of this gene family, AOP1, is present in at least two forms and found in all ecotypes examined. However, its catalytic role is still uncertain.


Impact of respiratory care training and family support using telemedicine on tracheostomized children admitted with respiratory infection after discharge.
Children with tracheostomies usually require a long hospital stay, high healthcare costs and caregiver burden. With the help of telemedicine, this study attempted to determine how home respiratory care training and family support affected admission days, admission costs, ICU admission rates, and caregivers' confidence. We enrolled children with tracheostomies who were admitted between 2020 and 2022 with respiratory infections. Before discharge, we evaluated the knowledge and skills of the caregivers and gave them practice in home respiratory care while providing them with structured feedback using a checklist, a peer-to-peer mentor assignment, a virtual home visit, teleeducation, and teleconsultation via a mobile application. We compared the admission days, admission costs, and ICU admission rates one year following the program with the historical control one year earlier. Forty-eight children with tracheostomies were enrolled. Thirteen percent of those had a 1-year readmission. The median [IQR] number of admission days decreased from 55 [15-140] to 6 [4-17] days (p value < 0.001). The median [IQR] admission costs decreased from 300,759 [97,032 - 1,132,323] to 33,367 [17,898-164,951] baht (p value < 0.001). The ICU admission rates decreased from 43.8% to 2.1% (p value < 0.001). Immediately after the program, caregivers' confidence increased from 47.9% to 85.5% (p value < 0.001). This respiratory care training and telehealth program decreased admission days, admission costs, and ICU admission rates for children with tracheostomies admitted with respiratory infections. The confidence of caregivers was also increased immediately after the program.


Transmembrane channel-formation by five complement proteins.
Five serum proteins act in concert to form the membrane attack complex (MAC) of complement. The precursor proteins, C5, C6, C7, C8 and C9, are hydrophilic glycoproteins with molecular weights ranging from 70,000 to 180,000. When C5 is cleaved by the serine protease C5 convertase, nascent C5b is produced which forms together with C6 a soluble and stable bimolecular complex (C5b,6). Upon binding of C5b,6 to C7 a trimolecular complex (C5b-7) is formed, which expresses a metastable membrane binding site. Membrane-bound C5b-7 constitutes the receptor for C8 and the tetramolecular C5b-8 complex binds and polymerizes C9. During the assembly process the proteins undergo hydrophilic-amphiphilic transition and the end product consists of C5b-8 (Mr approx. 550,000) and of tubular poly C9 (Mr approx. 1,100,000). The functional channel size varies but its maximal diameter is approximately 10 nm. C9 polymerization appears to involve initial reversible associations of several C9 molecules, which leads to temperature dependent, constrained unfolding. Unfolded C9 monomers then associate laterally with each other and polymerization terminates with closure of the circular structure, which consists of 12-18 C9 monomers. Amino acid composition and sequence indicate that the N-terminal half of the single chain C9 molecule is hydrophilic and the C-terminal half rather hydrophobic. Phospholipid binding and insertion into membranes are functions of the C-terminal portion of the molecule.


The generation and function of moral emotions in teams: An integrative review.
By considering moral emotions in light of a team context, we offer a new way of thinking about the socially embedded nature of moral emotions and how they influence various types of ethical behaviors in teams. To achieve this goal, we review the key literature on moral emotions within teams. We integrate this literature with Bandura's (1991, 2002, 2008) theory of moral thought and action, coupled with the social functional account of emotions (Keltner & Haidt, 1999) to examine how team norms are connected, through their influence on individual team members' moral emotions, to ethical behavior within team contexts. This review and integration highlights how team norms regarding moral approbation and moral perspective taking influence members' proscriptive (e.g., fear, guilt, shame, embarrassment) and prescriptive (e.g., sympathy/compassion, pride) moral emotions. In turn, each of these moral emotions has unique action tendencies linked to 1 or more of 3 different types of ethical behaviors witnessed in teams: compliance behaviors, humanistic behaviors, and supererogatory behaviors. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


JAMIE: joint analysis of multiple ChIP-chip experiments.
Chromatin immunoprecipitation followed by genome tiling array hybridization (ChIP-chip) is a powerful approach to identify transcription factor binding sites (TFBSs) in target genomes. When multiple related ChIP-chip datasets are available, analyzing them jointly allows one to borrow information across datasets to improve peak detection. This is particularly useful for analyzing noisy datasets. We propose a hierarchical mixture model and develop an R package JAMIE to perform the joint analysis. The genome is assumed to consist of background and potential binding regions (PBRs). PBRs have context-dependent probabilities to become bona fide binding sites in individual datasets. This model captures the correlation among datasets, which provides basis for sharing information across experiments. Real data tests illustrate the advantage of JAMIE over a strategy that analyzes individual datasets separately. JAMIE is freely available from http://www.biostat.jhsph.edu/~hji/jamie


Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden.
In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice. This was a non-interventional, observational, multicenter Swedish study. We included adult KTPs with stable graft function, remaining on IR-T or converting from IR-T to PR-T. Data were collected at baseline, and months 3, 6, and 12 post-baseline. The primary endpoint was adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©). Secondary assessments included tacrolimus dose and trough levels, clinical laboratory parameters (eg, estimated glomerular filtration rate), and adverse drug reactions (ADRs). Overall, data from 233 KTPs were analyzed (PR-T, n = 175; IR-T, n = 58). Mean change in PR-T dose from baseline (4.8 mg/d) to month 12 was -0.2 mg/d, and for IR-T (4.2 mg/d) was -0.4 mg/d; tacrolimus trough levels remained similar. Overall adherence was similar between baseline and month 12 in both groups (PR-T: 54.4% vs 57.0%, respectively; IR-T: 65.5% vs 69.4%); timing adherence followed a similar pattern. The probability of taking adherence improved between baseline and month 12 (odds ratio, 1.97; P = .0092) in the PR-T group only. Mean BAASIS visual analog scale score at baseline was 94.3 ± 11.1% (PR-T) and 95.3 ± 7.6% (IR-T), and >95% at subsequent visits. Laboratory parameters remained stable. Eight (4.6%) patients receiving PR-T (none receiving IR-T) had ADRs considered probably/possibly treatment-related. Disparity existed between high, patient-perceived and low, actual adherence. Overall adherence to the immunosuppressive regimen (measured by BAASIS) did not improve significantly over 12 months in stable KTPs converting to PR-T or remaining on IR-T; renal function remained stable.


Chasing Mendel: five questions for personalized medicine.
Ideas about personalized medicine are underpinned in part by evolutionary biology's Modern Synthesis. In this essay we link personalized medicine to the efforts of the early statistical investigators who quantified the heritability of human phenotype and then attempted to reconcile their observations with Mendelian genetics. As information about the heritability of common diseases was obtained, similar efforts were directed at understanding the genetic basis of disease phenotypes. These ideas were part of the rationale driving the Human Genome Project and subsequently the personalized medicine movement. In this context, we discuss: (1) the current state of the genotype-phenotype relationship in humans, (2) the common-disease-common-variant hypothesis, (3) the current ability of 'omic' information to inform clinical decision making, (4) emerging ideas about the therapeutic insight available from rare genetic variants, and (5) the social and behavioural barriers to the wider potential success of personalized medicine. There are significant gaps in knowledge as well as conceptual, intellectual, and philosophical limitations in each of these five areas. We then provide specific recommendations to mitigate these limitations and close by asking if it is time for the biomedical research community to 'stop chasing Mendel?'


The aminoacylation of transfer ribonucleic acid. Inhibitory effects of some amino acid analogues with altered side chains.
Several amino acid analogues that are able to replace amino acid residues in binding positions of the biologically active C-terminal tetrapeptide amide sequence, Trp-Met-Asp-PheNH2, of the gastrins were examined for their ability to inhibit the aminoacylation of tRNA in an Escherichia coli and rat liver system. Although in both systems the amino acid side chains are involved in the recognition process, the structural requirements of the side chain in the two systems are not comparable. Analogues of methionine and phenylalanine behaved similarly in the E. coli and rat liver systems, whereas analogues of tryptophan behaved differently. From the results it is possible to suggest structural features of the amino acid side chains which are required for recognition by the aminoacyl-tRNA synthetases.


A comparative wordlist for the languages of The Gran Chaco, South America.
Home to more than twenty indigenous languages belonging to six linguistic families, the Gran Chaco has raised the interest of many linguists from different backgrounds. While some have focused on finding deeper genetic relations between different language groups, others have looked into similarities from the perspective of areal linguistics. In order to contribute to further research of areal and genetic features among these languages, we have compiled a comparative wordlist consisting of translational equivalents for 326 concepts - representing basic and ethnobiological vocabulary - for 26 language varieties. Since the data were standardized in various ways, they can be analyzed both quantitatively and qualitatively. In order to illustrate this in detail, we have carried out an initial computer-assisted analysis of parts of the data by searching for shared lexicosemantic patterns resulting from structural rather than direct borrowings.


Light-triggered multifunctionality at surfaces mediated by photolabile protecting groups.
Photoremovable protecting groups (PRPGs) are applied to organic surfaces, thin polymer films, and hydrogels to achieve light-based remote control of their (bio)chemical and physical properties. These can be localized (i.e. patterned), tunable by exposure dose, and generated on-demand. Using PRPGs with independent response to different wavelengths, multifunctional materials with a number of individually addressable functional states can be generated. Light-triggered polymerization, crosslinking, and degradation processes as well as release of attached molecules can be realized. Light-responsive surfaces and materials based on PRPGs open interesting possibilities for the next generation of instructive materials for cell culture and tissue regeneration.


Evaluation of neurotoxic and immunotoxic effects of trichloroacetic acid on rats.
This study was carried out to investigate the neurotoxic and immunotoxic effects of trichloroacetic acid (TCA) on rats at subchronic exposure. The neurotoxic effects of TCA were evaluated by measuring the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Biomarkers selected for immunotoxic monitoring were the activities of adenosine deaminase (ADA) and myeloperoxidase (MPO) in various tissues of rats exposed to 2000 parts per million (ppm) dosage of TCA for 52 days. Results showed that the administrations of TCA decreased BChE activities in heart and lungs tissue of the rats treated with TCA. With regard to the immunotoxic effects, ADA activity significantly decreased in the heart, lungs and spleen whereas MPO activity increased after subchronic exposure with 2000 ppm dosage in all of the tissues except for heart tissue of rats compared with controls. The observations presented led us to conclude that the administration of TCA at subchronic was decreased BChE and ADA activities whereas increased MPO activity in various tissues of rats. This may reflect the potential role of these parameters as useful biomarkers for toxicity of TCA.


Excess Mortality Related to Chikungunya Epidemics in the Context of Co-circulation of Other Arboviruses in Brazil.
Chikungunya is an emerging arbovirus that reached the Western Hemisphere at the end of 2013. Studies in the Indian Ocean and India suggest that passive surveillance systems cannot recognize many of deaths associated with chikungunya, which can be inferred by an increase in the overall mortality observed during chikungunya epidemics. We assess the mortality associated with chikungunya epidemics in the most affected states in Brazil, from 2015 and 2016. We studied the monthly mortality by age group, comparing a period without epidemics to a chikungunya epidemic period, which we defined arbitrarily as consecutive months with incidences of more than 50 cases/100,000 persons. We obtained official data from the National System of Reported Diseases (SINAN) and the Mortality Information System (SIM), both maintained by the Ministry of Health. We identified a significant increase in the all-cause mortality rate during chikungunya epidemics, while there was no similar mortality in the previous years, even during dengue epidemics. We estimated an excess of 4,505 deaths in Pernambuco during the chikungunya epidemics (47.9 per 100,000 persons).The most affected age groups were the elderly and those under 1 year of age, and the same pattern occurred in all the states. Further studies at other sites are needed to confirm the association between increased mortality and chikungunya epidemics indifferent age groups. If these findings are confirmed, it will be necessary to revise the guidelines to recognize the actual mortality associated with chikungunya and to improve therapeutic approaches and protective measures in the most vulnerable groups.


Liver transplantation for alcoholic liver disease: evaluation of a selection protocol.
We have used a formal transplant protocol to select patients with alcoholic liver disease (ALD) for transplantation. We retrospectively analyzed all the patients with ALD who were referred specifically for transplantation to our Liver Unit between 1987 and 1994. Patients were selected for liver transplantation if they had end-stage liver disease and had remained abstinent from the time they were medically advised to stop alcohol intake. Of the 180 patients referred for transplantation, 43 (none of whom were transplanted) had case records insufficiently complete for full analysis; this may bias the analysis. Of the remaining 137 patients, 39 were transplanted and 4 were awaiting transplantation at the time of analysis. Of the patients who were not accepted for transplantation, 13 died during the assessment, 7 were considered to be unlikely to survive the procedure, 29 were found to be medically unsuitable, 16 psychologically unsuitable, 7 patients refused the offer of transplantation, and an additional 19 either showed clinical improvement or were considered too well for transplantation. Special investigations, such as brain computerized tomography (CT) scan and echocardiograph, changed the clinical decision to transplant in only a small number of cases (4% and 5%, respectively). Nine of the transplanted patients died and the remaining were followed up for a median of 25 (range, 7-63) months. One year actuarial survival for the transplanted patients was 79%, for those considered too sick was 0%, for medically unsuitable patients was 44%, for psychologically unsuitable patients was 65% and for those considered too well was 94%. Only 5 of the transplanted patients (13%) reverted to drinking. The observed actuarial survival of nontransplanted patients was compared with the expected survival calculated by 'the Beclere model.' The observed actuarial survival in the nontransplanted groups was much better than anticipated from the Beclere model, which therefore, is not applicable to our patients. The proportional hazards regression analysis of our nontransplanted patients identified serum bilirubin, serum albumin, blood urea, ascites, and spontaneous bacterial peritonitis as factors significantly predictive of their probability of survival. Using a model based on these parameters, the expected survival of our transplanted patients was calculated. Although we applied the model to a different population, the observed actuarial survival in the transplanted patients was found to be better than their expected survival (P < or = .001). Our protocol was useful in selecting suitable patients with ALD for liver transplantation, which resulted in significant survival advantage with low recidivism rate.


Arginine vasopressin promoter regulation is mediated by a neuron-restrictive silencer element in small cell lung cancer.
Arginine vasopressin (AVP) is often expressed in small cell lung cancer (SCLC), and a 65-bp AVP minimal promoter fragment is sufficient to restrict activity to SCLC in vitro. We now describe a motif with homology to the neuron-restrictive silencer element (NRSE) within this fragment. Electrophoretic mobility shift analysis demonstrated that multiple specific complexes are bound by this motif. These complexes are cross-competed with a characterized SCG10 NRSE probe and do not bind to the AVP probe with a specific mutation in the NRSE. The complexes vary in mobility between lung tumor cell lines, showing different levels of AVP expression, and some are differentially bound in SCLC. Overexpression of a neuron-restrictive silencer factor expression construct can silence reporter gene expression supported by the AVP promoter in SCLC, although this was dependent on both the level of endogenous AVP expression in the cells and putative enhancer elements in larger promoter constructs. Activation of the proximal AVP promoter in SCLC is therefore proposed to, at least partially, rely on modulation of normal repressor activity at the NRSE.


[The effects of the short-term regular exercise-diet program on lipid profile in sedentary subjects].
Regular aerobic exercise leads to changes in plasma lipids, lipoprotein and apoprotein levels. The aim of this study was to examine the training effects of the intervention program consisted of regular exercise and low fat diet on plasma lipid profile. The effects of the four weeks intervention programme which consisted of walking and dietary restriction on lipid profile in sedentary subjects were investigated. Subjects, who had dyslipidemia or obesity, were instructed to walk (consecutive 60 minutes, one times daily) and to consume no more than 20% total fat and 300 mg/d of cholesterol for four weeks. At the end of fourth week, 41 subjects who had implemented exercise-diet programme, were assigned to study (intervention) group; 21 subjects who had remained sedentary, nondieting, were included into the control group. Total-C, triglycerides, LDL-C, HDL-C, Lp (a), apo A1 and apo B100 were measured in fasting blood samples before and after 4 weeks of intervention programme. At the end of four weeks, subjects in the exercise-diet group, as compared with the control group, showed a significant reduction in body weight (respectively 1.67 +/- 2.36 kg versus -0.21 +/- 1.36 kg, p = 0.001), total cholesterol (35 +/- 37 mg/dl vs -20 +/- 25 mg/dl, p < 0.001), triglycerides (30 +/- 68 mg/dl vs -10 +/- 52 mg/dl, p = 0.024) and LDL-C (29 +/- 41 mg/dl vs -18 +/- 25 mg/dl, p < 0.001) levels. However, at the end of programme, in the exercise-diet group, as compared with the control group, the changes in HDL-C (respectively -0.85 +/- 7.30 mg/dl vs 1.05 +/- 5.64 mg/dl, p = 0.302), Lp (a) (1.59 +/- 3.06 mg/dl vs -0.09 +/- 3.96 mg/dl, p = 0.069), apo A1 (0.61 +/- 22.69 mg/dl vs -0.66 +/- 17.27 mg/dl, p = 0.822) and apo B100 (5.41 +/- 19.33 mg/dl vs -4.00 +/- 20.51 mg/dl, p = 0.080) were not significant. The data of this study demonstrate that the four weeks programme based on regular daily aerobic exercise and low fat diet is capable of decreasing total cholesterol, triglycerides and LDL-C levels and that this short-term intervention is insufficient in increasing HDL-C, in decreasing Lp (a) and improving apoprotein levels.


The preliminary study on the effects of growth hormone and insulin-like growth factor-I on κ-casein synthesis in bovine mammary epithelial cells in vitro.
The effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) on protein synthesis and gene expression of κ-casein in bovine mammary epithelial cell in vitro were studied. The treatments were designed as follows: the growth medium without serum was set as the control group, while the treatments were medium supplemented with GH (100 ng/ml), IGF-I (100 ng/ml), and GH (100 ng/ml) + IGF-I (100 ng/ml). The quantity of κ-casein protein was measured by ELISA, and the κ-casein gene (CSN3) expression was examined by real-time quantitative PCR (RT-qPCR). Compared with the control group, all the experimental groups had greater (p < 0.05) expression of CSN3. The concentration of κ-casein followed a similar response as CSN3, but the difference between the treatments and the control was not statistically significant (p > 0.05). Furthermore, no synergistic effect of GH and IGF-I was observed for both the κ-casein concentration and CSN3 expression. It is therefore concluded that GH or IGF-I can independently promote the expression of CSN3 in bovine mammary epithelial cells in vitro.


Nodal expression in triple-negative breast cancer: Cellular effects of its inhibition following doxorubicin treatment.
Triple-negative breast cancer (TNBC) represents an aggressive cancer subtype characterized by the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The independence of TNBC from these growth promoting factors eliminates the efficacy of therapies which specifically target them, and limits TNBC patients to traditional systemic neo/adjuvant chemotherapy. To better understand the growth advantage of TNBC - in the absence of ER, PR and HER2, we focused on the embryonic morphogen Nodal (associated with the cancer stem cell phenotype), which is re-expressed in aggressive breast cancers. Most notably, our previous data demonstrated that inhibition of Nodal signaling in breast cancer cells reduces their tumorigenic capacity. Furthermore, inhibiting Nodal in other cancers has resulted in improved effects of chemotherapy, although the mechanisms for this remain unknown. Thus, we hypothesized that targeting Nodal in TNBC cells in combination with conventional chemotherapy may improve efficacy and represent a potential new strategy. Our preliminary data demonstrate that Nodal is highly expressed in TNBC when compared to invasive hormone receptor positive samples. Treatment of Nodal expressing TNBC cell lines with a neutralizing anti-Nodal antibody reduces the viability of cells that had previously survived treatment with the anthracycline doxorubicin. We show that inhibiting Nodal may alter response mechanisms employed by cancer cells undergoing DNA damage. These data suggest that development of therapies which target Nodal in TNBC may lead to additional treatment options in conjunction with chemotherapy regimens - by altering signaling pathways critical to cellular survival.


Novel Hg2+-induced nephropathy in rats and mice lacking Mrp2: evidence of axial heterogeneity in the handling of Hg2+ along the proximal tubule.
The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg(2+)) was studied in rats (TR(-)) and mice (Mrp2(-/-)), which lack functional Mrp2, and control animals. Animals were exposed to nephrotoxic doses of HgCl2. Forty-eight or 24 hours after exposure, tissues were harvested and analyzed for Hg content and markers of injury. Histological analyses revealed that the proximal tubular segments affected pathologically by Hg(2+) were significantly different between Mrp2-deficient animals and controls. In the absence of Mrp2, cellular injury localized almost exclusively in proximal tubular segments in the subcapsular (S1) to midcortical regions (early S2) of the kidney. In control animals, cellular death occurred mainly in the proximal tubular segments in the inner cortex (late S2) and outer stripe of the outer medulla (S3). These differences in renal pathology indicate that axial heterogeneity exists along the proximal tubule with respect to how mercuric ions are handled. Total renal and hepatic accumulation of mercury was also greater in animals lacking Mrp2 than in controls, indicating that Mrp2 normally plays a significant role in eliminating mercuric ions from within proximal tubular cells and hepatocytes. Analyses of plasma creatinine, BUN, and renal expression of Kim-1 and Ngal tend to support the severity of the nephropathies detected histologically. Collectively, our findings indicate that a fraction of mercuric ions is normally secreted by Mrp2 in early portions of proximal tubules into the lumen and then is absorbed downstream in straight portions, where mercuric species typically induce toxic effects.


Novel amiloride-sensitive sodium-dependent proton secretion in the mouse proximal convoluted tubule.
The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na(+)/H(+) exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known to be present on the apical membrane of the PCT. Here we examined apical membrane PCT sodium-dependent proton secretion of wild-type (NHE3(+/+)/NHE2(+/+)), NHE3(-/-), NHE2(-/-), and double-knockout NHE3(-/-)/NHE2(-/-) mice to determine their relative contribution to luminal proton secretion. NHE2(-/-) and wild-type mice had comparable rates of sodium-dependent proton secretion. Sodium-dependent proton secretion in NHE3(-/-) mice was approximately 50% that of wild-type mice. The residual sodium-dependent proton secretion was inhibited by 100 microM 5-(N-ethyl-N-isopropyl) amiloride (EIPA). Luminal sodium-dependent proton secretion was the same in NHE3(-/-)/NHE2(-/-) as in NHE3(-/-) mice. These data point to a previously unrecognized Na(+)-dependent EIPA-sensitive proton secretory mechanism in the proximal tubule that may play an important role in acid-base homeostasis.


Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells.
Cigarette smoke augments asbestos-induced bronchogenic carcinoma in a synergistic manner by mechanisms that are not established. One important mechanism may involve alveolar epithelial cell (AEC) injury resulting from oxidant-induced DNA damage that subsequently activates poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair that can deplete cellular energy stores. We previously showed that whole aqueous cigarette smoke extracts (CSE) augment amosite asbestos-induced DNA damage and cytotoxicity to cultured AEC in part by generating iron-induced free radicals. We hypothesized that CSE increase asbestos-induced AEC injury by triggering PARP activation resulting from DNA damage caused by iron-induced free radicals. Aqueous CSE were prepared fresh on the day of each experiment. PARP activity in WI-26 (a type I-like cell line) and A549 (a type II-like cell line) cells was assessed by the uptake of labeled NAD over 4 hours and confirmed on the basis of the reduction of PARP levels in the presence of a PARP inhibitor, 3-aminobenzamide (3-ABA). Cell survival was assessed by trypan blue dye exclusion. Hydrogen peroxide (H2O2; 1-250 microM), CSE (0.4-10 vol%), and amosite asbestos (5-250 micrograms/cm2) each caused PARP activation in WI-26 and A549 cells. The combination of asbestos (5 micrograms/cm2) and CSE (0.04-10%) induced WI-26 and A549 cell PARP activation without evidence of synergism. 3-ABA significantly attenuated WI-26 and A549 cell PARP activity and cell death after exposure to H2O2, CSE, and asbestos. Phytic acid, an iron chelator, catalase, and superoxide dismutase each decreased WI-26 cell PARP activation caused by asbestos and CSE. CSE and asbestos induced PARP activation in cultured AEC in a nonsynergistic manner. These data provide further support that asbestos and cigarette smoke are genotoxic to relevant lung target cells and that iron-induced free radicals in part cause these effects.


Anxiety, depression, and quality of life in Parkinson's disease: the implications of multidisciplinary treatment.
Anxiety and depression in Parkinson's disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi "Bonino-Pulejo" Ethical Committee (approval No. 6/2016) in June 2016.


N(4)C-alkyl-N(4)C cross-linked DNA: bending deformations in duplexes that contain a -CNG- interstrand cross-link.
Short DNA duplexes containing a 1,3-N(4)C-alkyl-N(4)C interstrand cross-link that joins the two C residues of a -CNG- sequence were prepared using either a phosphoramidite or convertible nucleoside approach. The alkyl cross-link consists of 2, 4, or 7 methylene groups. The duplexes, which contain a seven-base-pair core and A(3)/T(3) complementary 3'-overhanging ends, were characterized by enzymatic digestion and MALDI-TOF mass spectrometry. Ultraviolet thermal denaturation studies showed that the duplexes denature in a cooperative manner and that the length of the cross-link affects the thermal stability. Thus, the transition temperature of the ethyl cross-linked duplex, 42 degrees C, is 16 degrees C higher than the melting temperature of the corresponding non-cross-linked control, whereas the transition temperatures of the butyl and heptyl cross-linked duplexes, 73 and 72 degrees C, respectively, are 46-47 degrees C higher. The reduced molecularity of denaturation of the cross-linked duplexes versus melting of the non-cross-linked duplex most likely accounts for these differences. Examination of molecular models suggests that the ethyl cross-link is too short to span the distance between the two C residues at the site of the cross-link in B-form DNA without causing distortion of the helix, whereas less and no distortion would be expected for the butyl and heptyl cross-links, respectively. The circular dichroism spectra, which show greatest deviation in the ethyl cross-linked duplex from B-form DNA, are consistent with this expectation. Anomalous mobilities on native polyacrylamide gels of multimers produced by self-ligation of each of the cross-linked duplexes suggest that the ethyl and butyl cross-linked duplexes undergo bending deformations, whereas multimers derived from the heptyl cross-linked duplex migrated normally. The bending angle was estimated to be 20 degrees, 13 degrees, and 0 degrees for the ethyl, butyl, and heptyl cross-linked duplexes, respectively. Thus, it appears that the degree of bending in these N(4)C-alkyl-N(4)C cross-linked duplexes is controlled by the length of the cross-link.


Long-term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses.
Mucopolysaccharidoses (MPS) are devastating inherited diseases treated with hematopoietic cell transplantation (HCT). However, disease progression, especially skeletal, still occurs in all patients. Secondary inflammation has been hypothesized to be a cause. To investigate whether systemic inflammation is present in untreated patients and to evaluate the effect of HCT on systemic inflammation, dried blood spots (n = 66) of patients with MPS (n = 33) treated with HCT between 2003 and 2019 were included. Time points consisted of pre-HCT and, for patients with MPS type I (MPS I), also at 1, 3, and 10 years of follow-up. Ninety-two markers of the OLINK inflammation panel were measured and compared with those of age-matched control subjects (n = 31) by using principal component analysis and Wilcoxon rank sum tests with correction. Median age at transplantation was 1.3 years (range, 0.2-4.8 years), and median time of pre-HCT sample to transplantation was 0.1 year. Normal leukocyte enzyme activity levels were achieved in 93% of patients post-HCT. Pretransplant samples showed clear separation of patients and control subjects. Markers that differentiated pre-HCT between control subjects and patients were mainly pro-inflammatory (50%) or related to bone homeostasis and extracellular matrix degradation (33%). After 10 years' follow-up, only 5 markers (receptor activator of nuclear factor kappa-Β ligand, osteoprotegerin, axis inhibition protein 1 [AXIN1], stem cell factor, and Fms-related tyrosine kinase 3 ligand) remained significantly increased, with a large fold change difference between patients with MPS I and control subjects. In conclusion, systemic inflammation is present in untreated MPS patients and is reduced upon treatment with HCT. Markers related to bone homeostasis remain elevated up to 10 years after HCT and possibly reflect the ongoing skeletal disease, making them potential biomarkers for the evaluation of new therapies.


Marital Aspirations, Sexual Behaviors, and HIV/AIDS in Rural Malawi.
We explore how marital aspirations are related to the sexual behaviors of adolescents and young adults in Malawi, where HIV/AIDS prevalence among adults exceeds 10%. We also consider whether the specter of AIDS is shaping ideals about marriage. By combining survey data (N = 1,087) and in-depth interviews (N = 133) with young Malawians from the Malawi Diffusion and Ideational Change Project, we show that looking for and finding a suitable spouse are linked to sexual behaviors and, thus, HIV risks. Moreover, concerns about contracting HIV are closely tied to the ideal characteristics of a future spouse. Our findings draw long-overdue attention to the importance of marital aspirations in understanding adolescent sexual behaviors and risks in the era of AIDS.