Shallow Heavily Doped n++ Germanium by Organo-Antimony Monolayer Doping.
Functionalization of Ge surfaces with the aim of incorporating specific dopant atoms to form high-quality junctions is of particular importance for the development of solid-state devices. In this study, we report the shallow doping of Ge wafers with a monolayer doping strategy that is based on the controlled grafting of Sb precursors and the subsequent diffusion of Sb into the wafer upon annealing. We also highlight the key role of citric acid in passivating the surface before its reaction with the Sb precursors and the benefit of a protective SiO2 overlayer that enables an efficient incorporation of Sb dopants with a concentration higher than 1020 cm-3. Microscopic four-point probe measurements and photoconductivity experiments show the full electrical activation of the Sb dopants, giving rise to the formation of an n++ Sb-doped layer and an enhanced local field-effect passivation at the surface of the Ge wafer.


Influence of different ceramics on resin cement Knoop Hardness Number.
This study evaluated: (1) the effect of different ceramics on light attenuation that could affect microhardness, measured as the Knoop Hardness Number (KHN), of a resin cement immediately and 24 hours after polymerization and (2) the effect of different activation modes (direct light-activation, light activation through ceramics and chemical activation) on the KHN of a resin cement. Resin cement Rely XARC (3M ESPE) specimens 5.0 mm in diameter and 1.0 mm thickwere made in a Teflon mold covered with a polyester film. The cement was directly light activated for 40 seconds with an XL 2500 curing unit (3M ESPE) with 650 mW/cm2, light activated through ceramic discs of Duceram Plus (DeguDent), Cergogold (DeguDent), IPS Empress (Ivoclar), IPS Empress 2 (Ivoclar), Procera (NobelBiocare), In Ceram Alumina (Vita) and Cercon (DeguDent), having a 1.2 mm thickness or chemically activatedwith-out light application. The resin cement specimens were flattened, and KHN wasobtained using an HMV 2 microhardnesstester (Shimadzu) with a load of 50 g applied for 15 seconds 100 microm from the irradiated surface immediately and after storage at 37 degrees C for 24 hours. Ten measurements were made for each specimen, with three specimens for each group at each time. The data were submitted to ANOVA and Tukey's test (p = 0.05). The KHN of the resin cement was not only affected by the mode of activation, but also by the post-activation testing time. The mean KHN of the resin cementfor chemical activation and through all ceramics showed statistically significant lower values compared to direct activation immediately and at 24 hours. The KHN for 24 hourspost-activation was always superior to the immediate post-activation test except with direct activation. The most opaque ceramics resulted in the lowest KHN values.


[Pathogen spectrum of non-gonorrhea urethritis].
By cultural investigations in 333 males with non-gonorrhoical urethritis (NGU) and 158 control probands it was demonstrated that Chlamydia trachomatis is the main germ of this disease also in the GDR with a frequency of 40% of the cases. A chlamydia-negative NGU was caused in 15% by Ureaplasma urealyticum in a number of greater than or equal to 10(4) germs/ml urine and in 5% by Trichomonas vaginalis, respectively. Candida albicans occurred significant more frequently in the patient group (21%) than in the control group (4%). Other optional pathogenic bacterias were the cause of NGU in single cases. The diagnosis and therapy of NGU should be considered this germ spectrum and the sexual partner also.


A Simple Method to Improve Detection of Femoral Nail Abutment in the Distal Femur: A Computer Modeling Study.
Proximal femur fractures are more frequently treated with long femoral nails. Lateral radiographs are used to assess the nail position in the distal femur. However, because of the asymmetric shape of the distal femur, standard lateral radiographs alone are suboptimal for assessing anteriorly positioned nails in the distal femur. Consequently, instances of nail abutment or even perforation might be missed intraoperatively. Using a three-dimensional (3D) modelling approach, we asked: When the nail is in the anterior fifth of the canal, will rotating the femur to align the simulated x-ray beam with the anterior femoral condyles instead of the posterior femoral condyles increase the diagnostic accuracy of detecting nail perforation of the anterior cortex? 3D models of 42 unilateral femora from a population sample representative of patients with hip fractures (mean age of 76 ± 7 years, 10 males and 32 females, and 16 left and 26 right femora) were used. The patients had a mean height of 158 ± 9 cm; 27 femora were from Asians and 15 were from Caucasians. Clinically appropriately sized nails had already been virtually implanted previously as part of a quantitative nail fit assessment study. In a preliminary step, the mean angles of inclination of the distal anterior supracondylar region were quantified using four axial sections of the distal femur. For the femora with the nail tip in the anterior fifth of the canal, projections representing a lateral radiograph were generated along with rotated projections at mean angle (5°, 8°) rotations, with the anterior femoral condyles aligned, and anterior femoral condyle alignment followed by internal and external rotation to detect maximum nail perforation. The distance from the nail to the distal anterior cortex was measured for each rotational projection and used to detect anterior nail perforation. The accuracy of detection was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) analysis. Rotating the 3D models by aligning the x-ray beam with the anterior femoral condyles improves the diagnostic ability of detecting anterior nail perforation compared with standard lateral radiographs. The AUC increased with rotation from 0.50 (95% confidence interval 0.50 to 0.50) on the lateral projection to 0.73 (95% CI 0.57 to 0.88, difference = -0.23; p = 0.004) at 5° of rotation, 0.77 (95% CI 0.62 to 0.93, difference = -0.27; p = 0.001) at both 8° of rotation and with the anterior femoral condyles aligned, and to 0.82 (95% CI 0.67 to 0.97, difference = -0.32; p < 0.001) with internal/external rotations past the anterior femoral condyles. There were no differences in accuracy between the four methods of rotation. This study shows that rotating the femur to align the anterior femoral condyles on a lateral radiograph and then internally/externally rotating it, improves the accuracy assessed via the AUC of detecting anterior perforation when long nails are positioned in the anterior fifth of the distal femur. This approach can easily be used in a clinical setting. Intraoperatively, the image intensifier can be rotated around the leg to produce an image with the anterior femoral condyle aligned, providing surgeons with an opportunity to identify and improve the nail's position or exchange the nail while the patient is still under anesthesia.


Mutagenicity of nitroaromatic degradation compounds.
The mutagenicity of 2,4-dinitrotoluene (24DNT), and 2,6-dinitrotoluene (26DNT), and their related transformation products such as hydroxylamine and amine derivatives, which are formed by Clostridium acetobutylicum, were tested in crude cell extracts using Salmonella typhimurium TA100. A previous publication already reported the mutagenic activities of 2,4,6-trinitrotoluene (TNT) and its related hydroxylamine derivatives in this test system. A time course of the mutagenicity during the anaerobic transformation of TNT, 24DNT, and 26DNT was also investigated under the same conditions to compare with the results from the pure compounds. The monohydroxylamino intermediates 2-hydroxylamino-4-nitrotoluene (2HA4NT), 4-hydroxylamino-2-nitrotoluene (4HA2NT) and 2-hydroxylamino-6-nitrotoluene (2HA6NT) formed during anaerobic transformation of dinitrotoluenes were proven to be mutagenic in the Ames test using Salmonella typhimurium TA100. This study reports that 4HA2NT is the most stable derivative, whereas 2HA4NT and 2HA6NT are less stable and these intermediates are mutagenic in the Ames test. Both 24DNT and 26DNT and their final metabolites 2,4-diaminotoluene (24DAT) and 2,6-aminotoluene (26DAT) appeared nonmutagenic. In a time-course study of TNT degradation, the temporal sample containing 85% of 2,4-dihydroxylamino-6-nitrotoluene (24HA6NT) is most mutagenic. These observations suggest that the bioremediation approach for treatment of 24DNT and 26DNT should be carried past the hydroxylamino intermediate.


A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria.
To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations, pegvaliase injection. Searches of MEDLINE (1946-September 1, 2018) were conducted using the terms pegvaliase and phenylalanine ammonia lyase (PAL). Additional data were obtained from the prescribing information, the product dossier obtained from the manufacturer, and Clinicaltrials.gov. All English language articles related to pharmacology, pharmacokinetics, efficacy, or safety of the combination therapy in human subjects were reviewed. Pegvaliase is a pegylated PAL enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. Blood phenylalanine levels were reduced by approximately 50% to 70% in patients receiving therapeutic doses of pegvaliase. However, most patients experienced adverse events. The mainstay of therapy in phenylketonuria (PKU) has historically consisted of dietary restriction of phenylalanine. Pegvaliase injection is the first Food and Drug Administration (FDA)-approved enzyme substitution therapy for patients with PKU. The therapy may be a viable option for patients with documented blood phenylalanine >600 µmol/L who have failed existing management strategies.


[Clinical pharmacology of propafenone].
Aim of our study is to examine some aspects of the relationship between pharmacokinetics and pharmacodynamics of Propafenon that are important as far as its current use is concerned. Orally administered Propafenon is largely absorbed and easily metabolized by the liver. Bioavailability is on the average 50%. Ninety per cent of the administered dose is eliminated in the feces and in the urine in about 60 hours. Because of the lack of a good correlation between chronically administered doses and plasmatic concentration, we tried to see whether the peak concentration after administration of a single dose could predict in some way the response of the patients arrhythmia. So far we do not have a clear cut answer to this question, which probably requires a different, more complex approach to the relations between pharmacokinetics, plasmatic levels and therapeutic range of an antiarrhythmic drug.


Probiotic sepsis in preterm neonates-a systematic review.
Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks' gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment. Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised. • Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants. • Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants. • This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants. • All except one case where the diagnosis was uncertain recovered after antimicrobial therapy.


Influence of preconstructed effector loop location using a barbed unidirectional suture on leakage pressures following canine enterotomy closure.
To evaluate the influence of preconstructed effector loop location using a barbed unidirectional suture on leakage pressures following canine enterotomy closure. Randomized, experimental, cadaveric. Grossly normal jejunal segments from three canine cadavers. Jejunal segments were harvested and randomly assigned based upon effector loop location from the beginning of the incisional line. Groups (n = 12/group) included 0 mm, 5 mm, 10 mm, 15 mm, and intact controls (n = 6/group), repaired using a 3-0 unidirectional barbed suture in a simple continuous pattern. Initial leakage pressure (ILP), maximum intraluminal pressure (MIP), repair time, and leakage location were recorded. Mean ILP for 0 mm group (24.42 ± 8.43 mmHg) was lower (p ≤ .001) compared to all experimental groups with ILP ~40% lower. There was no difference in MIP among experimental groups (p = .239). Repair time increased (p < .0001) as the distance of the effector loop increased ≥5 mm from the beginning of the incisional line. Leakage location differed among groups (p < .001) with leakage in the 0 mm group from the incisional line (75%), compared to leakage from predominantly from the suture holes in other groups, respectively. Effector loop location influenced ILP and leakage location. Effector loops placed at the beginning of the incisional line (0 mm) decreased ILP compared to loops placed at 5, 10, and 15 mm. Effector loop location using a unidirectional barbed suture should be placed ≥5 mm from beginning of the incisional line for enterotomy closure. Further in vivo studies are necessary to determine the clinical significance of these findings.


Infectious diseases presentations of Munchausen syndrome by proxy: case report and review of the literature.
Munchausen syndrome by proxy is a form of abuse, usually of a child by a parent, in which a factitious illness is reported or produced in the child, resulting in unnecessary medical evaluations and treatments. A dramatic case of a 17-month-old infant with recurrent polymicrobial bacteremia prompted a review of cases diagnosed by the Pediatric Infectious Diseases consultation service at our referral children's hospital and a review of the infectious diseases presentations in the medical literature. The infectious diseases presentations of the syndrome as well as criteria for the diagnosis are reviewed and discussed.


Characterization of ligand-functionalized microcantilevers for metal ion sensing.
A sensor for metal cations is demonstrated using single and binary mixtures of different thiolated ligands as self-assembled monolayers (SAMs) functionalized on silicon microcantilevers (MCs) with gold nanostructured surfaces. Binding of charged metal ions to the active surface of a cantilever induces an apparent surface stress, thereby causing static bending of the MC that is detected in this work by a beam-bending technique. A MC response mechanism based on changes in surface charge is discussed. The monodentated ligands arranged as SAMs on the MC surface are not expected to fully satisfy the coordination sphere of the detected metals. This leads to lower binding constants than would be expected for chelating ligands, but reversible responses. The modest binding constants are compensated in terms of the magnitudes of responses by the inherent higher sensitivity of the nanostructured approach as opposed to more traditional smooth surface MCs. Response characteristics are optimized in terms of SAM formation time, concentration of ligand solution, and pH of working buffer solution. Limits of detection for the tested mono-, di-, and trivalent metal ions are in low to submicromolar range. The results indicated that shapes and magnitudes of response profiles are characteristics of the metal ions and type of SAM. The response factors for a given SAM with the tested metal ions, or for a given metal with the tested SAMs, varied by roughly 1 order of magnitude. While the observed selectivity is not large, it is anticipated that sufficient ionic recognition contrast is available for selective metal ion identification when differentially functionalized arrays of MCs (different ligands on different cantilevers in the array) are used in conjunction with pattern recognition techniques.


Comparative investigation of the solution species [U(CO3)5]6- and the crystal structure of Na6[U(CO3)5].12H2O.
The limiting U(IV) carbonate species in aqueous solution was investigated by comparing its structure parameters with those of the complex preserved in a crystal structure. The solution species prevails in aqueous solution of 0.05 M U(IV) and 1 M NaHCO(3) at pH 8.3. Single crystals of Na(6)[U(CO(3))(5)].12H(2)O were obtained directly from this mother solution. The U(IV) carbonate complex in the crystal structure was identified as a monomeric [U(CO(3))(5)](6-) anionic complex. The interatomic distances around the U(IV) coordination polyhedron show average distances of U-O = 2.461(8) A, U-C = 2.912(4) A and U-O(dist) = 4.164(6) A. U L(3)-edge EXAFS spectra were collected from the solid Na(6)[U(CO(3))(5)].12H(2)O and the corresponding solution. The first shell of the Fourier transforms (FTs) revealed, in both samples, a coordination of ten oxygen atoms at an average U-O distance of 2.45 +/- 0.02 A, the second shell originates from five carbon atoms with a U-C distance of 2.91 +/- 0.02 A, and the third shell was fit with single and multiple scattering paths of the distal oxygen at 4.17 +/- 0.02 A. These data indicate the identity of the [U(CO(3))(5)](6-) complex in solid and solution state. The high negative charge of the [U(CO(3))(5)](6-) anion is compensated by Na(+) cations. In solid state the Na(+) cations form a bridging network between the [U(CO(3))(5)](6-) units, while in liquid state the Na(+) cations seem to be located close to the anionic complex. The average metal-oxygen distances of the coordination polyhedron show a linear correlation to the radius contraction of the neighbouring actinide(IV) ions and indicate the equivalence of the [An(CO(3))(5)](6-) coordination within the series of thorium, uranium, neptunium and plutonium.


Unveiling the mechanistic role of the Aryl hydrocarbon receptor in environmentally induced Breast cancer.
The aryl hydrocarbon receptor (AhR) is a crucial cytosolic evolutionary conserved ligand-activated transcription factor and a pleiotropic signal transducer. The biosensor activity of the AhR is attributed to the promiscuity of its ligand-binding domain. Evidence suggests exposure to environmental toxins such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls and halogenated aromatic hydrocarbons activates the AhR signaling pathway. The constitutive activation of the receptor signaling system leads to multiple health adversities and enhances the risk of several cancers, including breast cancer (BC). This review evaluates several mechanisms that integrate the tumor-inducing property of such environmental contaminants with the AhR pathway assisting in BC tumorigenesis, progress and metastasis. Intriguingly, immune evasion is identified as a prominent hallmark in BC. Several emerging pieces of evidence have identified AhR as a potent immunosuppressive effector in several cancers. Through AhR signaling pathways, some tumors can avoid immune detection. Thus the relevance of AhR in the immunomodulation of breast tumors and its putative mode of action in the breast tumor microenvironment are discussed in this review. Additionally, the work also explores BC stemness and its associated inflammation in response to several environmental cues. The review elucidates the context-dependent ambiguous behavior of AhR either as an oncogene or a tumor suppressor with respect to its ligand. Conclusively, this holistic piece of literature attempts to potentiate AhR as a promising pharmacological target in BC and updates on the therapeutic manipulation of its various exogenous and endogenous ligands.


Up-regulation of MBD1 promotes pancreatic cancer cell epithelial-mesenchymal transition and invasion by epigenetic down-regulation of E-cadherin.
Methyl-CpG binding domain protein 1 (MBD1) has been implicated in transcriptional regulation, heterochromatin formation, genomic stability, cell-cycle progression and development. It is also predicted that MBD1 might be involved in tumor development and progression. However, whether and how MBD1 is involved in tumorigenesis, especially in pancreatic cancer (PC), is currently unknown. We found that MBD1 was significantly up-regulated in PC tissues compared with the surrounding normal tissues according to RT-PCR data. Tissue microarray (TMA) based immunohistochemical study from 58 surgically resected PC specimens indicated that higher MBD1 expression correlated with lymph node metastasis and poor survival in PC patients. Gain- and loss-of-function studies in vitro validated MBD1 as a potent oncogene promoting PC cell invasion as well as epithelial-mesenchymal transition (EMT). Mechanistically, MBD1 is associated with Twist and NAD-dependent deacetylase sirtuin-1 (SIRT1), thereby forming the Twist-MBD1-SIRT1 complex on the CDH1 promoter, which resulted in reduced E-cadherin transcription activity and increased cell EMT ability. Significantly, targeting MBD1 reversed the EMT phenotype of PC and restored sensitivity to chemotherapy. Taken together, the results of our study revealed a novel function of MBD1 in PC invasion and metastasis by providing a molecular mechanism underlying MBD1-promoted EMT. Thus MBD1 may serve as a potential therapeutic target for PC.


Structural studies of the vacuolar membrane ATPase from Neurospora crassa and comparison with the tonoplast membrane ATPase from Zea mays.
The H+-translocating ATPase located on vacuolar membranes of Neurospora crassa was partially purified by solubilization in two detergents, Triton X-100 and N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, followed by centrifugation on sucrose density gradients. Two polypeptides of Mr approximately equal to 70,000 and approximately equal to 62,000 consistently migrated with activity, along with several minor bands of lower molecular weight. Radioactively labeled inhibitors of ATPase activity, N-[14C]ethylmaleimide and 7-chloro-4-nitro[14C]benzo-2-oxa-1,3-diazole, labeled the Mr approximately equal to 70,000 polypeptide; this labeling was reduced in the presence of ATP. N,N'-[14C]dicyclohexylcarbodiimide labeled a polypeptide of Mr approximately equal to 15,000. Estimation of the functional size of the vacuolar membrane ATPase by radiation inactivation gave a value of Mr 5.2 X 10(5), 10-15% larger than the mitochondrial ATPase. The Neurospora vacuolar ATPase showed no crossreactivity with antiserum to plasma membrane or mitochondrial ATPase but strongly crossreacted with antiserum against a polypeptide of Mr approximately equal to 70,000 associated with the tonoplast ATPase of corn coleoptiles. These results suggest that fungal and plant vacuolar ATPases may be large multisubunit complexes, somewhat similar to, but immunologically distinct from, known F0F1 ATPases.


A bicistronic vector with destabilized mRNA secondary structure yields scalable higher titer expression of human neurturin in E. coli.
Human neurturin (NTN) is a cystine knot growth factor with potential therapeutic use in diseases such as Parkinson's and diabetes. Scalable high titer production of native NTN is particularly challenging because of the cystine knot structure which consists of an embedded ring comprised of at least three disulfide bonds. We sought to pursue enhanced scalable production of NTN in Escherichia coli. Our initial efforts focused on codon optimization of the first two codons following AUG, but these studies resulted in only a marginal increase in NTN expression. Therefore, we pursued an alternative strategy of using a bicistronic vector for NTN expression designed to reduce mRNA secondary structure to achieve increased ribosome binding and re-initiation. The first cistron was designed to prevent sequestration of the translation initiation region in a secondary conformation. The second cistron, which contained the NTN coding sequence itself, was engineered to disrupt double bonded base pairs and destabilize the secondary structure for ribosome re-initiation. The ensemble approach of reducing NTN's mRNA secondary structure and using the bicistronic vector had an additive effect resulting in significantly increased NTN expression. Our strain selection studies were conducted in a miniaturized bioreactor. An optimized strain was selected and scaled up to a 100 L fermentor, which yielded an inclusion body titer of 2 g/L. The inclusion bodies were refolded to yield active NTN. We believe that our strategy is applicable to other candidate proteins that are difficult-to-express due to stable mRNA secondary structures. Biotechnol. Bioeng. 2017;114: 1753-1761. © 2017 Wiley Periodicals, Inc.


[Effects of lactoferrin on vascular endothelial growth factor and basic fibroblast growth factor expression in human Tca8113 cell line].
To investigate the effect of lactoferrin on vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression. Lactoferrin at concentration of 0.006, 0.013, 0.025, 0.050 g/L and blank control groups were included in this study. The gene and protein expression of VEGF, bFGF were examined by RT-PCR and Western blotting. The RT-PCR and Western blotting assay showed that VEGF mRNA(0.31 +/- 0.08) and protein (0.68 +/- 0.11) in lactoferrin (0.050 g/L) group were significantly lower than in the control group (P < 0.05), and the bFGFmRNA (0.27 +/- 0.10) and protein (0.68 +/- 0.07) in lactoferrin (0.050 g/L) group were also significantly lower than in the control group (P < 0.05). Lactoferrin could inhibit the expression of VEGF, bFGFmRNA and protein in Tca8113 cells. This effect might be one of the mechanisms for anticancer function of lactoferrin.


Acute and sublethal effects of organophosphate insecticide chlorpyrifos on freshwater fish Oreochromis niloticus.
Chlorpyrifos is a widely used organosphosphate insecticide in India. Residue of the insecticide is frequently detected in trace to moderate concentration in food grains and in surface water of different freshwater ecosystems of the country. In this study, 96 h LC50 of the technical grade (94% a.i.) and commercial formulation (20% EC) of chlorpyrifos to freshwater fish Oreochromis niloticus were determined as 90.0 and 42.0 µg/L based on 2 h actual concentration of chlorpyrifos in water. About 96 h exposure to sublethal concentrations (0, 12.0 and 25.0 μg/L) of the commercial formulation (20% EC) of chlorpyrifos reduced the level of hepatic glycogen, activities of alkaline phosphatase, acetylcholinesterase, and catalase in liver and elevated the level of plasma glucose and activities of hepatic acid phosphatase, aspartate aminotransferase, and alanine aminotransferase in O. niloticus. About 28-day exposure to these sub-lethal concentrations caused anemia in fish, while 90 days exposure reduced growth of the fish and carcass concentration of crude protein and crude lipid as compared to control. It was concluded from this study that commercial formulation of chlorpyrifos (20% EC) was highly toxic to O. niloticus. Exposure to sub-lethal concentrations of the insecticide could induce oxidative stress and anemia resulting in reduced growth of the fish.


Genotypic diversity of complement component C4 does not predict kidney transplant outcome.
Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effector in transplant rejection, we hypothesized that C4 genetic diversity may partially explain the variation in allograft outcomes. This retrospective study included 1969 deceased-donor kidney transplants randomly selected from the Collaborative Transplant Study DNA bank. We determined recipient and donor gene copy number of total C4, C4 isotypes (C4A and C4B), and C4 gene length variants (C4L and C4S) by quantitative real-time PCR analysis. Groups defined according to recipient C4 gene copy number (low, intermediate, and high) had similar 10-year allograft survival. Genotypic groups showed comparable rates of graft dysfunction, treatment for rejection, immunological graft loss, hospitalization for infection, malignant disease, and death. Similarly, separate analyses of C4A, C4B, C4L, and C4S; combined evaluation of donor and recipient C4 genotype; or analysis of recipients with higher risk for rejection did not reveal considerable outcome effects. In conclusion, we did not demonstrate that C4 gene copy number associates with transplant outcome, and we found no evidence that the resulting variation in the strength of classical complement activation influences susceptibility to rejection.


Adult blood lead epidemiology and surveillance--United States, Fourth Quarter, 1996.
CDC's National Institute for Occupational Safety and Health Adult Blood Lead Epidemiology and Surveillance program (ABLES) monitors laboratory-reported elevated blood lead levels (BLLs) among adults in 25 states. This report presents ABLES data through the fourth quarter of 1996, compares these data with that from the same period in 1995, and describes cases of severe lead poisoning in adults in New York during 1996.


Regenerating nucleus pulposus of the intervertebral disc using biodegradable nanofibrous polymer scaffolds.
Low back pain is a leading health problem in the United States, which is most often resulted from nucleus pulposus (NP) degeneration. To date, the replacement of degenerated NP relies entirely on mechanical devices. However, a biological NP replacement implant is more desirable. Here, we report the regeneration of NP tissue using a biodegradable nanofibrous (NF) scaffold. Rabbit NP cells were seeded on the NF scaffolds to regenerate NP-like tissue both in vitro and in a subcutaneous implantation model. The NP cells on the NF scaffolds proliferated faster than those on control solid-walled (SW) scaffolds in vitro. Significantly more extracellular matrix (ECM) production (glycosaminoglycan and type II collagen) was found on the NF scaffolds than on the control SW scaffolds. The constructs were then implanted in the caudal spine of athymic rats for up to 12 weeks. The tissue-engineered NP could survive, produce functional ECM, remain in place, and maintain the disc height, which is similar to the native NP tissue.


Neonatal infection with the Daniels strain of Theiler's murine encephalomyelitis virus.
The clinical and pathologic manifestation of Theiler's murine encephalomyelitis are age related. Animals infected during the first week of life die of a fulminant encephalitis analogous to human poliomyelitis. By contrast, animals infected within 2 and 4 weeks of age survive but develop chronic relapsing demyelination and persistent infection of the central nervous system. The neonatal infection results in widespread necrosis beginning with neuronal vacuolar degeneration followed by inflammatory infiltrates. Electron microscopy reveals paracrystalline arrays of 27-nm viral particles characteristic of picornaviruses within neurons and macrophages. In addition, oligodendrocytes show reactive changes and intracytoplasmic vacuoles. Immunoperoxidase studies show viral antigen primarily localized within neurons of the cerebral cortex, basal ganglia, hippocampus, and anterior horn cells. Viral antigen is found within the apical dendrites and axonal projections of hippocampal pyramidal cells suggesting that Theiler's murine encephalomyelitis may travel intraaxonally.


Redirecting the humoral immune response against Streptococcus mutans antigen P1 with monoclonal antibodies.
The adhesin P1 of Streptococcus mutans has been studied as an anticaries vaccine antigen. An anti-P1 monoclonal antibody (MAb) bound to S. mutans prior to mucosal immunization of mice was shown previously to alter the amount, specificity, isotype, and biological activity of anti-P1 antibodies. The present study was undertaken to screen this and four additional anti-P1 MAbs for immunomodulatory activity when complexed with S. mutans and administered by a systemic route and to evaluate sera from immunized mice for the ability to inhibit adherence of S. mutans to immobilized human salivary agglutinin. All five MAbs tested influenced murine anti-P1 serum antibody responses in terms of subclass distribution and/or specificity. The effects varied depending on which MAb was used and its coating concentration. Two MAbs promoted a more effective, and two others a less effective, adherence inhibition response. An inverse relationship was observed between the ability of the MAbs themselves to inhibit adherence and the ability of antibodies elicited following immunization with immune complexes to inhibit adherence. Statistically significant correlations were demonstrated between the levels of anti-P1 serum immunoglobulin G2a (IgG2a) and IgG2b, but not of IgG1 or IgG3, and the ability of sera from immunized animals to inhibit bacterial adherence. These results indicate that multiple anti-P1 MAbs can mediate changes in the immune response and that certain alterations are potentially more biologically relevant than others. Immunomodulation by anti-P1 MAbs represents a useful strategy to improve the beneficial immune response against S. mutans.


Catalytic mechanism and molecular recognition of E. coli UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase probed by mutagenesis.
UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a metal-dependent deacetylase that catalyzes the hydrolysis of UDP-3-O-myristoyl-N-acetyl-glucosamine to form UDP-3-O-myristoyl-glucosamine and acetate. This is the committed step in the biosynthesis of lipid A, and therefore, LpxC is a target for the development of antimicrobial agents in the treatment of Gram-negative infections. To facilitate the development of potent and specific inhibitors of LpxC, the molecular determinants of binding and specificity and the catalytic mechanism for this enzyme have been probed. The functions of active site residues have been classified on the basis of changes in steady-state turnover (kcat, KM, and kcat/KM) and product binding affinity (KDProduct). We have identified side chains that enhance product affinity and reactivity (F192, K239, D246, and H265), destabilize product affinity (E78 and D197), and preferentially enhance catalytic efficiency (H19, T19, K143, and N162). In addition, the affinity of LpxC for myrUDP-GlcNH2 is dependent on two ionizations, one deprotonation and one protonation, with apparent pKa values of 6.5 +/- 0.1 and 7.4 +/- 0.1, respectively. The UDP moiety of the product contributes significantly to recognition by LpxC, suggesting that this region can be targeted in drug development. These data provide a map of the active site features essential for catalysis and molecular recognition by LpxC that can be used for developing more potent LpxC inhibitors.


Characteristics of blood tests in patients with acute cerebral infarction who developed symptomatic intracranial hemorrhage after intravenous administration of recombinant tissue plasminogen activator.
Patients suspected as having acute ischemic stroke usually undergo blood tests, including coagulation-related indexes, because thrombocytopenia and coagulopathy are contraindications for recombinant tissue plasminogen activator (rtPA) administration. We aimed to identify blood test indexes associated with symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke who received intravenous rtPA. This retrospective observational study included patients diagnosed with acute ischemic stroke who were treated with intravenous rtPA at the emergency department of a tertiary hospital in Seoul between February 2008 and January 2018. Blood test indexes were compared between the sICH and non-sICH groups. Logistic regression and receiver-operating characteristic curve analyses were performed. In this study, 375 patients were finally included. Of 375 patients, 42 (11.2%) showed new intracranial hemorrhage on follow-up brain computed tomography, of whom 14 (3.73%) had sICH. Platelet count, aspartate aminotransferase and lactate dehydrogenase levels were significantly different between the sICH and non-sICH groups, and platelet count showed statistical significance in the regression analysis. Significantly lower platelet counts were observed in the sICH group than in the non-sICH group (174,500 vs. 228,000/mm3, P=0.020). The best cutoff platelet count was 195,000/mm3, and patients with platelet counts of <195,000/mm3 had a 5.4- times higher risk of developing sICH than those with platelet counts of ≥195,000/mm3. Platelet count was the only independent parameter associated with sICH among the blood test indexes. Mild thrombocytopenia may increase the risk of sICH after intravenous administration of rtPA.


Bidirectional Cardio-Respiratory Interactions in Heart Failure.
We investigated cardio-respiratory coupling in patients with heart failure by quantification of bidirectional interactions between cardiac (RR intervals) and respiratory signals with complementary measures of time series analysis. Heart failure patients were divided into three groups of twenty, age and gender matched, subjects: with sinus rhythm (HF-Sin), with sinus rhythm and ventricular extrasystoles (HF-VES), and with permanent atrial fibrillation (HF-AF). We included patients with indication for implantation of implantable cardioverter defibrillator or cardiac resynchronization therapy device. ECG and respiratory signals were simultaneously acquired during 20 min in supine position at spontaneous breathing frequency in 20 healthy control subjects and in patients before device implantation. We used coherence, Granger causality and cross-sample entropy analysis as complementary measures of bidirectional interactions between RR intervals and respiratory rhythm. In heart failure patients with arrhythmias (HF-VES and HF-AF) there is no coherence between signals (p < 0.01), while in HF-Sin it is reduced (p < 0.05), compared with control subjects. In all heart failure groups causality between signals is diminished, but with significantly stronger causality of RR signal in respiratory signal in HF-VES. Cross-sample entropy analysis revealed the strongest synchrony between respiratory and RR signal in HF-VES group. Beside respiratory sinus arrhythmia there is another type of cardio-respiratory interaction based on the synchrony between cardiac and respiratory rhythm. Both of them are altered in heart failure patients. Respiratory sinus arrhythmia is reduced in HF-Sin patients and vanished in heart failure patients with arrhythmias. Contrary, in HF-Sin and HF-VES groups, synchrony increased, probably as consequence of some dominant neural compensatory mechanisms. The coupling of cardiac and respiratory rhythm in heart failure patients varies depending on the presence of atrial/ventricular arrhythmias and it could be revealed by complementary methods of time series analysis.


[Genetic background and treatment of pediatric ALL].
Molecular genomic studies for acute lymphoblastic leukemia (ALL) have been focused on genetic alterations in leukemic cells, while germline cells are mainly used as a control to identify the somatic mutation. However, recent studies demonstrate that germline mutations may contribute to the pathogenesis of ALL, and currently, the genetic background has been found to play an essential role in the development of pediatric ALL. An association between polymorphism and adverse events has already been reported, and recent genomic analyses of familial ALL cases identified inherited causative genes for ALL. Moreover, non-syndromic/familial ALL cases may present pathogenic germline variants in cancer predisposition genes. These variants could not only contribute to poor response to treatment but also lead to an increased risk of secondary neoplasms. Comprehensive understanding of the biology in both ALL cells and germline cells is required.


Interleukin-11 levels in healthy and thrombocytopenic neonates.
Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.


Automation of the cytokinesis-block micronucleus cytome assay by laser scanning cytometry and its potential application in radiation biodosimetry.
Here we describe the adaptation of laser scanning cytometry (LSC) to measure micronuclei (MN) automatically in lymphocytes. MN frequencies were determined in irradiated human lymphocytes using the cytokinesis-block technique, and the results from LSC were compared with visual scoring results obtained from slides of cells stained using Fast Green and 4',6-diamidino-2-phenylindole (DAPI). This fluorescent approach allowed clear identification of binucleated cells and detection of MN. The dose responses measured visually and by LSC showed similar trends and correlated positively (r = 0.9689; P < 0.0001). High-content analysis was developed to further automatically score MN within mono-, tri- and tetra-nucleated cells and to determine the nuclear division index and nuclear circularity values. The high-throughput nature of LSC can provide unique advantages in future DNA damage diagnostics in experimental and epidemiological studies. Importantly, it allows for co-detection of other biomarkers of interest within a single lymphocyte, and further development of this capability is anticipated.


[Relationship between lipids and cutaneous immunity: example of the gangliosides].
Gangliosides are glycosphingolipids made of hydrophobic ceramides coupled to hydrophilic sialylated oligosaccharides. They belong to lipid rafts located on the outer leaflet of the plasma membrane and their oligosaccharide moieties are exposed on the cell surface. Gangliosides are shed as monomeric molecules from the plasma membrane by a largely unknown mechanism into the extracellular medium and they are synthesized de novo by the cells. The shed gangliosides bind to lipoproteins from which they are taken up by erythrocytes and leukocytes. The ganglioside enrichment of leukocytes results in an alteration in the transduction of activation signals, leading to an impaired cellular immunity.


Practical operationalizations of risk factors for fracture in older women: results from two longitudinal studies.
Several guidelines on osteoporosis have proposed algorithms to identify persons at high risk of fractures. Although these algorithms include well-known risk factors, it is not clear how they can best be operationalized for use in general practice. The aim of this study was to compare the predictive performance of different operationalizations of four categories of risk factors for fractures that can be used in general practice. This study included 4157 women of > or =60 yr of age (mean +/- SD: 74.1 +/- 9.1 yr) with a median follow-up of 8.9 yr of the Rotterdam Study and 762 women of > or =65 yr of age (mean +/- SD: 76.0 +/- 6.7.yr) with a median follow-up of 6.0 yr of the Longitudinal Aging Study Amsterdam (LASA). At baseline, information on four categories of risk factors was obtained, including (1) family history of hip fractures, (2) type of prior fractures, (3) low body weight/body mass index (BMI), and (4) mobility impairment. The occurrence of fragility fractures, including hip, pelvic, humerus, and wrist fractures, was used as outcome measure. We quantified the predictive performance of each risk factor by a chi(2) statistic, calculated as the difference in -2 Log likelihood attributable to the risk factor, with adjustment for age and other risk factors. In the Rotterdam Study, 399 fragility fractures occurred during 31,472 person-years (PY) of follow-up. In this study, any prior fracture in the past 5 yr (chi(2) = 6; p = 0.02), body weight < 64 kg (versus > or =64 kg; chi(2) = 6.7; p = 0.01), BMI < 22 kg/m(2) (versus > or =22 kg/m(2); chi(2) = 8.7; p = 0.003), and use of a walking aid (chi(2) = 7.5; p = 0.004) were the most practical operationalizations of the risk factor categories, after adjustment for age and other risk factors. In LASA, 52 fragility fractures occurred during 3935 PY of follow-up. Associations were similar as in the Rotterdam Study, except that low body weight and BMI were not associated with fragility fracture. None of the usual operationalizations of family history of hip fractures was independently associated with fragility fracture in either study. Prior osteoporotic fracture, body weight <64 kg, a BMI <22 kg/m(2), and the use of a walking aid are practical operationalizations of risk factors for fragility fractures. On the basis of the results of this study, a simple, practical algorithm can be developed for use in general practice.


Childhood diabetes in China. Enormous variation by place and ethnic group.
To investigate the incidence rate of IDDM in China. The Chinese IDDM registry was established in 1991 as part of the World Health Organization's Multinational Project for Childhood Diabetes (DiaMond) project. Twenty-two centers were developed to monitor the incidence of IDDM in children < 15 years of age. The population under investigation includes > 20 million individuals, representing approximately 7% of the children in China. Capture-recapture methods were used to estimate the ascertainment. The overall ascertainment-corrected IDDM incidence rate in China was 0.51 per 100,000, the lowest rate ever reported. There was a 12-fold geographic variation (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north and the east. There was a sixfold difference among ethnic groups (highest: Mongol group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). China has an extremely low overall IDDM incidence rate. China also has the greatest geographic and ethnic variation seen for any country.


Medication as object.
People experience and treat medication as though it were a person: in other words, as an object. Among the many symbolic meanings attributed to medication, this sort of personification, or object representation, is a meaning that medication is uniquely positioned to contain and convey: imbued with intentionality and influence, medication moves beyond the sphere of static, iconic representation and enters the changeable, dynamic object world of action, aim, and agency. Unlike more generic or stereotypic meanings, object representations attributed to medication may reflect the patient's specific dynamics and object relations. These representations are many and mutable, and take on shifting and overlapping forms that evolve with the analytic process. Medication may represent a third person within the framework of an analytic treatment, expanding the analytic dyad into a triad and offering new transference paradigms to explore. The defensive displacement of transferential qualities and attitudes, or split-off parts thereof, from the analyst onto medication can serve as a powerful resistance to the awareness of the transference to the analyst. Clinical examples illustrate the utility and importance of the analysis of medication as object, for both patient and analyst, with particular attention to the transference.


The diagnostic yield and characteristics of bronchoalveolar lavage in suspected nontuberculous mycobacterial pulmonary disease.
Bronchoalveolar lavage (BAL) has widely been used to manage respiratory diseases including respiratory infections. The aim of this study was to evaluate the diagnostic yield of BAL for detecting nontuberculous Mycobacterium (NTM). We retrospectively reviewed the records of 54 patients who underwent bronchoscopy due to suspected NTM pulmonary disease. Positive culture results of respiratory specimens were defined as NTM pulmonary disease. For BAL, two or three aliquots of 50 mL (total 100 or 150 mL) of sterile normal saline were instilled through bronchoscope. NTM was detected in 31 of 54 (57.4%) patients. The detection rates were not different between the patients who underwent bronchoscopy with BAL (24 of 39, 61.5%) and those without (7 of 15, 46.7%) (P = 0.437). BAL fluid was mostly neutrophil dominant in both positive and negative NTM culture groups. In the subgroup analysis of 33 patients who underwent both the BAL and anti- glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody measurements, 12 of 19 (63.2%) positive Mycobacterium avium complex (MAC) culture patients and 8 of 14 (57.1%) negative MAC culture patients were positive for anti-GPL-core IgA antibody (seropositive) (P = 0.991). There was no severe complication related to BAL. The diagnostic yield of BAL with ≥100 mL sterile saline was not superior to that of bronchial wash or sputum aspiration in patients with suspected NTM pulmonary disease. Patients with seropositive but negative culture results for MAC suggest pseudonegative for pulmonary MAC disease.


[The serum pepsinogen analysis and its relation to bovine ostertagiasis (author's transl)].
An outline of literature on the pepsinogen analysis and its application, especially within the veterinary parasitology, is given. The pepsinogen content of the blood in experimental infection with Ostertagia larvae is mentioned. The authors state their own experiences with the analysis. Testing of 100 parasite-free calves kept indoors gave a mean value of 0.5 units tyrosin/litre. 95 of the calves were within the range 0.3-0.7 units. Flutuations of serum pepsinogen in the course of a subclinical infection in 6 calves during their first grazing season are described and compared to pasture contamination and egg excretion of the calves. In a second experiment the authors give a critical evaluation of the correlation between pasture contamination, weight gain, pepsinogen, and eggs in faeces. The correlation between pepsinogen and weight gain was found to be considerably higher than the correlation between e.p.g. and weight gain. A highly significant correlation between pasture contamination and serum pepsinogen (r=0.60-0.75) was found. The correlation between pasture contamination and e.p.g. was considerably lower (r=0.10-0.43) and only significant in a single case. The value of pepsinogen determinations in epidemiological experiments and weight gain experiments with calves is emphasized and the authors indicate possibilities of their application in practice.


Response of mice connective tissue to three different endodontic materials.
The aim of this study was to evaluate the biocompatibility of mineral trioxide aggregate (MTA) Bio and Portland cement (PC) and compare with those of ProRoot MTA. Polyethylene tubes were filled with materials and placed into dorsal subcutaneous connective tissue of Wistar albino rats. After 7, 30, and 60 days after the surgical procedure, the implants with the surrounding tissue were removed. Tissue samples were subjected to histological processing, and sections were stained with hematoxylin and eosin. Sections were evaluated for the intensity of inflammation, predominant cell type, presence of fibrous capsule and granulation tissue. Data were submitted to Kruskal-Wallis test at a significant level of P ≤ 0.05. No statistical differences were observed at any evaluated condition among tested materials (P > 0.05). Statistically significant differences were observed between mean inflammatory scores, cell types and granulation tissue of the same material in different experimental periods (P < 0.05). Can be concluded that biocompatibility of MTA bio and PC were comparable with that of ProRoot MTA.


Synthesis and Conformational Analyses of Cyclonucleoside Having 13-Membered Ring Bridging Nucleobase and 5'-Position via a Linker Containing Sulfonamide.
A cyclic nucleoside has been designed and synthesized to serve as a conformationally fixed building block for the development of functional oligonucleotides. The bridge was introduced between the nucleobase and the 5'-position to fix the rotation around the C4'-C5' bond, the base orientation, and the sugar puckering all at once. The 13-membered cyclic structure was introduced using a sulfonamide linkage, which retains an N-H group that can be used to attach an additional nucleoside moiety. The sulfonamide linkage was formed through the end-to-end cyclization of an intermediate that contained both a sulfonyltriazole and amino groups. Both 1H NMR and computational studies revealed that the sugar conformation, base orientation, and γ torsion angle were S-type, anti, and trans, respectively. As such, cyclic nucleosides show promise for introducing these specific distorted conformations into functional nucleic acids.


The emergence of homegrown stereotypes.
Homegrown stereotypes are generalizations that groups develop about their own typical characteristics. They are a distinct class of in-group stereotypes in the contexts and processes that give rise to them, as well as in their consequences for individual group members. The authors develop the concept of homegrown stereotypes and locate the origins of these stereotypes in self-presentation processes. They discuss the accuracy of these stereotypes and consider their similarities to and differences from a number of related phenomena. An examination of homegrown stereotypes highlights the importance of taking into account the impact of in-group, as well as intergroup, dynamics on the production of stereotypes.


Streptococcus bovis infectious endocarditis and occult gastrointestinal neoplasia: experience with 25 consecutive patients treated surgically.
To assess the prevalence of gastrointestinal neoplasia in patients with Streptococcus bovis infectious endocarditis we performed a retrospective cohort analysis of all episodes of S. bovis infectious endocarditis treated at our institution between January 2000 through December 2014. Twenty-five patients were identified for this purpose. 12/25 patients received colonoscopy and 1/25 of the patients was assessed with CT colonography. Of the 13 who underwent colonic assessment, 11 were diagnosed with colonic neoplasms at different stages of development. In the absence of any strong contraindication, gastroenteroscopic evaluation in all patients diagnosed with S. bovis infectious endocarditis should be pursued.


A GENETIC AND BEHAVIORAL ANALYSIS OF MATE CHOICE AND SONG NEIGHBORHOODS IN INDIGO BUNTINGS.
Neighboring males of indigo buntings (Passerina cyanea) share songs in southern Michigan. We sampled polymorphic enzymes to compare the genetic variation between mates and the variation among contiguous song neighborhoods. Mate choice was independent of the genetic and morphometric similarity of female and male, and these measures were independent of each other. The incidence of extrapair copulations and fertilizations was independent of the song of cuckolding males. Breeding success of the mated pairs was independent of their genetic or morphological similarity. Males characterized by different song dialects did not differ in mean lifetime reproductive success. We found no significant genetic differences among the neighborhoods. Most birds that bred in one song neighborhood were born in another, and neighborhoods were not isolated demes. Bunting songs may provide no information to a female about genetic quality of males. The results are consistent with a neutral model of no mate choice for genes.


Audit of nuclear medicine scientific and technical standards.
The British Nuclear Medicine Society has developed a process for the service-specific organizational audit of nuclear medicine departments. This process identified the need for a scheme suitable for the audit of the scientific and technical standards of a department providing such a service. This document has evolved following audit visits of a number of UK departments. It is intended to be used as a written document to facilitate the audit procedure and may be used for both external and self-audit purposes. Scientific and technical standards have been derived from a number of sources, including regulatory documents, notes for guidance and peer-reviewed publications. The audit scheme is presented as a series of questions with responses graded according to legal and safety obligations (A), good practice (B) and desirable aspects of service delivery (C). This document should be regarded as part of an audit framework and should be kept under review as the process evolves to meet the future demands of this high-technology-based clinical service.


[SEVERE INFANTILE HYPOPHOSPHATASIA].
Hypophosphatasia is the inborn error of metabolism that is characterized by low serum alkaline-phosphatase activity, due to loss-of-function mutations within the gene for tissuenonspecific isoenzyme of alkaline phosphatase [TNSALP]. The manifestations of hypophosphatasia range from neonatal death with almost no skeletal mineralization to dental problems in adults without any bone symptoms. There are no case reports of infantile hypophosphatasia in Israel. The existence of enzymatic replacement treatment for this disease makes it important to diagnose this problem as soon as possible. We describe a 5 month old infant who presented with bulging fontanel, neonatal pyridoxine responsive seizures, respiratory distress, hypercalcemia and very low blood levels of alkaline phosphatase. The baby was found to have a homozygote mutation in the TNSAP gene.


Yeast beta-alanine synthase shares a structural scaffold and origin with dizinc-dependent exopeptidases.
beta-Alanine synthase (beta AS) is the final enzyme of the reductive pyrimidine catabolic pathway, which is responsible for the breakdown of pyrimidine bases, including several anticancer drugs. In eukaryotes, beta ASs belong to two subfamilies, which exhibit a low degree of sequence similarity. We determined the structure of beta AS from Saccharomyces kluyveri to a resolution of 2.7 A. The subunit of the homodimeric enzyme consists of two domains: a larger catalytic domain with a dizinc metal center, which represents the active site of beta AS, and a smaller domain mediating the majority of the intersubunit contacts. Both domains exhibit a mixed alpha/beta-topology. Surprisingly, the observed high structural homology to a family of dizinc-dependent exopeptidases suggests that these two enzyme groups have a common origin. Alterations in the ligand composition of the metal-binding site can be explained as adjustments to the catalysis of a different reaction, the hydrolysis of an N-carbamyl bond by beta AS compared with the hydrolysis of a peptide bond by exopeptidases. In contrast, there is no resemblance to the three-dimensional structure of the functionally closely related N-carbamyl-d-amino acid amidohydrolases. Based on comparative structural analysis and observed deviations in the backbone conformations of the eight copies of the subunit in the asymmetric unit, we suggest that conformational changes occur during each catalytic cycle.


Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis.
Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients. A total 667 dengue patients (2008-2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods. There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001],rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction OR (95% CI):17.9 (9.14–35.12), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR(95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3days) was also observed among AKI patients (OR = 1.3, P = 0.044) [corrected].Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI. The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians' alertness to this highly morbid and potentially fatal complication for optimal prevention and management.


Characterization of charge isomers of yeast phosphoglycerate kinase. Evidence for intracellular differences.
Three electrophoretic components of phosphoglycerate kinase have been isolated from baker's yeast. The isoionic point of the major component is 7.18 at 10 degrees C. Corresponding values for the minor ones are 6.91 and 7.48, respectively. There is a difference of one charge-unit between the isomers 1 and 2, and between the isomers 2 and 3. The release of component 3 from the yeast cells appears in contrast to the isomers 1 and 2 to be promoted by an organic solvent, thus suggesting this component to be bound to the cell-membrane. The amino-terminal amino acid residue appears to be N-acetylated serine in each of the three cases. The carboxyl-terminal ends seem to be identical also with -(Ala, Leu, Val, Lys)- Ala-Lys as the ultimate sequence. From the circular dichroism spectra the contents of alpha-helix and beta-structure were estimated to 15 and 40-50%, respectively. Factors have been determined for transformation and comparison of the specific activities as determined under the various conditions used at different laboratories.


Reduction of CD68+ macrophages and decreased IL-17 expression in intestinal mucosa of patients with inflammatory bowel disease strongly correlate with endoscopic response and mucosal healing following infliximab therapy.
Antibodies against tumor necrosis factor represent an effective therapy for patients with inflammatory bowel disease. Despite their successful results, the exact mechanism by which infliximab suppresses intestinal inflammation is still a matter of debate. In this study, we used a translational approach to identify the key mechanisms associated with resolution of mucosal inflammation induced by infliximab. A total of 16 patients with active inflammatory bowel disease (9 with Crohn's disease and 7 with ulcerative colitis) and 16 controls were enrolled in the study. Patients received infliximab infusions at 0, 2, and 6 weeks. At enrollment and at week 6, patients underwent flexible sigmoidoscopy, and biopsies were taken from the sigmoid colon. RNA was extracted, and mucosal expression of 96 immune-related genes was evaluated by qRT-PCR and confirmed by immunofluorescence microscopy on tissue. Correlation between infliximab-induced gene expression modulation and endoscopic response to therapy was calculated. Lamina propria mononuclear cell apoptosis induced by infliximab was evaluated on tissue sections by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. We found that infliximab-induced downregulation of macrophage and Th17 pathway genes was significantly associated with both endoscopic response to the therapy and achievement of mucosal healing. Importantly, the observed reduction of lamina propria CD68 macrophages was associated with an increased rate of macrophage apoptosis. The 2 mechanisms associated with infliximab-induced resolution of intestinal inflammation are the reduction of lamina propria infiltrating CD68 macrophages and the downregulation of interleukin 17A. Moreover, the data suggest that infliximab-induced macrophage apoptosis may represent a key mechanism for the therapeutic success of anti-tumor necrosis factor antibodies.


Prevalence and Predictors of Metabolic Syndrome in People With Schizophrenia in Inpatient Rehabilitation Wards.
Atypical antipsychotic medications increase the risk of developing metabolic syndrome (MetS) and cardiovascular diseases in people with schizophrenia. To explore the prevalence of MetS and the predictors associated with the number of MetS components in people with chronic schizophrenia. We recruited 357 participants from 10 rehabilitation wards in northern Taiwan. The Beck Anxiety Inventory, Beck Depression Inventory-II, Health-Promoting Lifestyle Profile (HPLP), and modified Baecke physical activity questionnaire were used to evaluate the participants. MetS prevalence was calculated using the modified Adult Treatment Panel III criteria for Asians. The prevalence of MetS in this sample was 37.8%. Multinomial logistic regression revealed that the HPLP-exercise score (odds ratio [OR] = 0.411, p = .002) and depressive symptoms (OR = 0.949, p = .040) were protective factors for ≥4 MetS components. The leisure physical activity level (OR = .536, p = .024) was a protective factor for three MetS components. Body mass index ≥24 kg/m(2) was the strongest risk factor for two MetS components (OR = 8.057, p < .001), three MetS components (OR = 11.287, p < .001), and ≥four MetS components (OR = 15.621, p < .001). Additionally, participants' age >40 (OR = 3.638, p = .012) was a risk factor for ≥four MetS components. In this study, the prevalence of MetS was higher than that reported for patients utilizing community-based services in Taiwan. The important risk factors for MetS were being overweight and older than 40. The protective factors for MetS were a high HPLP-exercise score and leisure-based physical activities.


Risk Factors Associated With Seroreactivity Against Leptospira sp. in Horses From Brazilian Amazon.
This study investigated the risk factors associated with seroreactivity to Leptospira sp. in horses from Brazilian Amazon. Blood samples were collected and microscopic agglutination test was performed, and univariate and multivariate analyses were conducted for association with risk factors. General seroprevalence was 32.7% and the most prevalent serogroup observed was Sejroe (5.9%). Seroreactivity was associated with age, sex, activity (work, leisure, or both), feed supplementation, trash accumulation, and presence of felines. Epidemiology of leptospirosis remains poorly understood in Amazon region, particularly in livestock, requiring more studies to improve control and prevention measures.


Hand, Foot, and Mouth Disease in Children: Clinical Characteristics of an Outbreak in Novi Sad, Serbia.
Hand, foot, and mouth disease (HFMD) is a relatively common mild viral infection that usually affects young children, mainly occurring during the late spring, early summer, and fall months. It is most commonly caused by members of the human enterovirus (HEV) genus. Recently, HFMD has received renewed attention because of evidence that this disease could have clinical, epidemiological, and etiological characteristics different from those initially associated with it. HFMD may be associated with neurologic or cardiopulmonary complications and can, rarely, lead to death. Our study was a retrospective analysis on 83 children (<18 years of age) who were clinically diagnosed with HFMD at the Department of Dermatology of the Institute for Child and Youth Health Care of Vojvodina, in a single, tertiary-care university hospital in Novi Sad, Vojvodina province, Serbia, for the time period from January 2016 to December 2017. During the study period, HFMD was diagnosed in 83 children. Our results suggest that the outbreak of HFMD occurred in younger children (average age 3.10 years), who seem to be the most susceptible age group for HFMD infection. Taking into account that the diagnosis of HFMD is usually clinical, we believe that it is important for health professionals to be well-informed about the clinical features and the course of the disease. Good personal hygiene and the implementation of a surveillance system can help stop the spread of the disease and prevent outbreaks.


The colorimetry and smartphone determination of perfluorooctane sulfonate based on cytidine 5'-monophosphate-capped gold nanoclusters with peroxidase-like activity.
Besides being a luminescent material, cytidine 5'-monophosphate-capped gold nanoclusters (AuNCs@CMP) also show superior peroxidase-like activity which can promote TMB oxidation in the presence of H2O2, causing the solution to turn efficiently from pale to blue. However, the presence of perfluorooctane sulfonate (PFOS) in the above system inhibited TMB oxidation and bluing of the solution, consequently establishing a colorimetric platform of AuNCs/H2O2/TMB for PFOS determination. The results showed that it responded to PFOS over a wide range of 2.0-50 μM, with a limit of detection (LOD) as low as 150 nM. Furthermore, in-depth mechanism investigation revealed that, rather than the active site of the catalyst being occupied by PFOS, such a hypochromatic effect originated from depletion of the reactive oxygen species (ROS) by PFOS degradation, thereby also offering a unique strategy to scavenge the lethal toxicity of PFOS. In addition, the colorimetric response of AuNCs/H2O2/TMB to PFOS was extended to smartphone determination conveniently based on RGB values. Finally, the established platform was applied to PFOS determination both in soil extracts and in tap water with good recovery, which supplies a novel colorimetric platform for visual determination of PFOS in practice. The method has the advantages of being rapid, sensitive and highly selective, which highlight the design and construction of more systems for determination and elimination of lethal pollutants in environmental water.


Prospective study of posttraumatic stress disorder symptoms and coronary heart disease in the Normative Aging Study.
Various correlates of posttraumatic stress disorder (PTSD), such as high levels of sympathetic activation and hypothalamic-pituitary-adrenal axis dysregulation, have been linked to arterial damage and coronary heart disease (CHD) risk. While psychological disturbance is frequently found among patients with cardiac disease, whether psychological problems precede or occur as a result of having a potentially fatal disease is not clear. To our knowledge, no prospective studies to date have evaluated whether PTSD is associated with increased risk of CHD. To test the hypothesis that high levels of PTSD symptoms may increase CHD risk, using 2 different measures of PTSD. Prospective cohort study. Community-dwelling men from the Greater Boston, Mass, area who served in the military. Data are from the Veterans Affairs Normative Aging Study. Men who completed either the Mississippi Scale for Combat-Related PTSD in 1990 (n = 1002) or the Keane PTSD scale in 1986 (n = 944) were included in the study. Incident CHD occurring during follow-up through May 2001. Levels of PTSD symptoms in this cohort were low to moderate. Men with preexisting CHD at baseline were excluded, and PTSD was measured with the Mississippi Scale for Combat-Related PTSD. For each SD increase in symptom level, men had age-adjusted relative risks of 1.26 (95% confidence interval, 1.05-1.51) for nonfatal myocardial infarction and fatal CHD combined and 1.21 (95% confidence interval, 1.05-1.41) for all of the CHD outcomes combined (nonfatal myocardial infarction, fatal CHD, and angina). Findings were replicated using the Keane PTSD scale and somewhat strengthened after controlling for levels of depressive symptoms. To our knowledge, this is the first study to demonstrate a prospective association between PTSD symptoms and CHD even after controlling for depressive symptoms. These results suggest that a higher level of PTSD symptoms may increase the risk of incident CHD in older men.


Preventing ARDS: progress, promise, and pitfalls.
Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality.


Integrating Lung Physiology, Immunology, and Tuberculosis.
Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several 'interaction points' (IPs) which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence.


Time scales and pathways of vibrational energy relaxation in liquid CHBr3 and CDBr3.
Molecular dynamics simulations are used in conjunction with Landau-Teller, fluctuating Landau-Teller, and time-dependent perturbation theories to investigate energy flow out of various vibrational states of liquid CHBr3 and CDBr3. The CH stretch overtone is found to relax with a time scale of about 1 ps compared to the 50 ps rate for the fundamental. The relaxation pathways and rates for the CD stretch decay in CDBr3 are computed in order to understand the changes arising from deuteration. While the computed relaxation rate agrees well with experiments, the pathway is found to be more complex than anticipated. In addition to the above channels for CH(D) stretch relaxation that involve only the hindered translations and rotations of the solvent, routes involving off-resonant and resonant excitations of solvent vibrational modes are also examined. Finally, the decay of energy from low frequency states to near-lying solute states and solvent vibrations are studied.


Counts of axons in electron microscopic sections of ventral roots in lampreys.
The number of motoneurons in the lamprey spinal cord was estimated by counting axons in electron microscopic sections of ventral roots. Physiologically identified and marked motoneurons had one axon each in an ipsilateral ventral root. The corresponding axons in sections were unmyelinated, individually ensheathed, and 2-20 micron in diameter. Lampreys lack an organized sympathetic nervous system, but a minor and variable population of small axons with dense-cored vesicles was also present in ventral and dorsal roots. The estimated numbers of motor axons per ventral root in adult Ichthyomyzon unicupis and I. castaneus were 70.6 +/- 9.3 (mean +/- SD), in adult landlocked Petromyzon marinus 100.1 +/- 15.0, and in large ammocoetes of anadromous Petromyzon marinus 106.8 +/- 14.3. The total estimated numbers of myotomal and fin motoneurons were as many as 13,000 in the spinal cord of adult Ichthymyzon and 24,000 in adult Petromyzon.


Integration of primary care into the substance use disorder outpatient treatment setting.
Americans experiencing substance use disorder (SUD) carry a significant chronic disease burden, yet only half use primary care. Patients in treatment for SUD who are connected with primary care typically have better overall health outcomes. The identified intensive outpatient program (IOP) had no protocol in place to engage patients with primary care. This project piloted the development and implementation of an original, evidence-based primary care integration program. It consisted of a psychoeducation group, a referral by case management, and establishment of an internal referral process to affiliated primary care providers (PCPs). Following the psychoeducation group, pre and posttests of patient-reported knowledge and attitudes regarding primary care were compared. Participants were contacted to collect further data after IOP discharge. An education and feedback session was held with affiliated PCPs, and an internal referral process was devised by leadership. Mean scores measuring patient knowledge and attitudes regarding primary care increased after participation in the structured psychoeducation group. By time of IOP discharge, 100% (n = 12) of participants had either a referral or scheduled appointment with a PCP in place. At time of follow-up, 90% (n = 9) reported that they had attended or planned to attend their scheduled PCP appointment. A comprehensive integration program in the IOP setting can improve patient engagement with primary care. Quality improvement implementation will require consideration of challenges faced during the pilot involving scheduling, staff buy-in, changes in patient acuity, the electronic medical record, and insurance.


How older adults regulate lateral stepping on narrowing walking paths.
Walking humans often navigate complex, varying walking paths. To reduce falls, we must first determine how older adults purposefully vary their steps in contexts that challenge balance. Here, 20 young (21.7±2.6 yrs) and 18 older (71.6±6.0 yrs) healthy adults walked on virtual paths that slowly narrowed (from 45 cm to as narrow as 5 cm). Participants could switch onto an "easier" path whenever they chose. We applied our Goal Equivalent Manifold framework to quantify how participants adjusted their lateral stepping variability and step-to-step corrections of step width and lateral position as these paths narrowed. We also extracted these characteristics at the locations where participants switched paths. As paths narrowed, all participants reduced their lateral stepping variability, but older adults less so. To stay on the narrowing paths, young adults increasingly corrected step-to-step deviations in lateral position more, by correcting step-to-step deviations in step width less. Conversely, as older adults also increasingly corrected lateral position deviations, they did so without sacrificing correcting step-to-step deviations in step width, presumably to preserve balance. While older adults left the narrowing paths sooner, several of their lateral stepping characteristics remained similar to those of younger adults. Older adults largely maintained overall walking performance per se, but they did so by changing how they balanced the competing stepping regulation requirements intrinsic to the task: maintaining position vs. step width. Thus, balancing how to achieve multiple concurrent stepping goals while walking provides older adults the flexibility they need to appropriately adapt their stepping on continuously narrowing walking paths.


Screening for depression with the Edinburgh Postnatal Depression Scale and finding borderline personality disorder.
The aim of the study was to explore the range of psychiatric diagnoses seen in pregnant women who score above the 'cut-off' on the Edinburgh Postnatal Depression Scale when this is used as a routine screening instrument in the antenatal period. Subjects were all pregnant women referred to and seen by the Perinatal Consultation-Liaison Psychiatry Team of a tertiary public hospital over a 14-month period. Edinburgh Postnatal Depression Scale score at maternity 'booking-in' visit, demographic and clinical data were recorded and diagnoses were made according to Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria following clinical interview(s) and review of documented past history. Data were analysed using descriptive statistics. A total of 200 patients who had completed the Edinburgh Postnatal Depression Scale were seen for assessment; 86 (43%) scored ⩾13 on Edinburgh Postnatal Depression Scale. Of those scoring 13 or more on Edinburgh Postnatal Depression Scale, 22 (25.6%) had a depressive disorder. In total, 12 patients (14%) had an anxiety disorder, 14 (16.3%) had borderline personality disorder and 13 (15.1%) had a substance use disorder. An additional 23 women (26.7%) had two or more borderline personality traits. Psychiatric assessment of women who scored 13 or more on the Edinburgh Postnatal Depression Scale at routine antenatal screening identified a significant number with borderline personality disorder or borderline personality traits rather than depressive or anxiety disorders. Clinical Practice Guidelines note the importance of further assessment for all women who score 13 or more on the Edinburgh Postnatal Depression Scale. The findings here suggest that this assessment should be made by a clinician able to identify personality pathology and organise appropriate and timely interventions.


PTENP1 acts as a ceRNA to regulate PTEN by sponging miR-19b and explores the biological role of PTENP1 in breast cancer.
This study aimed to investigate role of long noncoding RNA PTENP1 regulating PTEN expression via miR-19b to affect breast cancer (BC) progression. We measured expressions of PTENP1, miR-19b and PTEN in 65 matched BC cancerous and noncancerous tissues by quantitative real-time fluorescence PCR (qRT-PCR) and investigated the biological effects of PTENP1 in BC MDA-MB-231 cells by several in vitro experiments including CCK8, wound healing, transwell and Annexin V-FITC/PI analysis. Besides, the competing endogenous RNA (ceRNA) activity of PTENP1 on miR-19b was detected by luciferase reporter assay, and the expressions of related genes and proteins were determined by western blot assay and qRT-PCR. Increased PTENP1 and PTEN and decreased miR-19b were observed in BC tissues and cell lines. Further, PTENP1 and PTEN are direct targets of miR-19b, and overexpressed PTENP1 in MDA-MB-231 cells could supress cell proliferation, migration and invasion and promote cell apoptosis. Moreover, PTENP1 could upregulate PTEN via its ceRNA interaction on miR-19b, as well as induced the upregulation of p53 and downregulation of p-AKT. Enhanced PTENP1 could inhibit BC cell growth, metastasis and tumourigenicity by inhibiting miR-19b and facilitating PTEN in BC, thereby may represent a novel target for diagnosis and treatment of BC.


The influence of low-level laser on orthodontic relapse in rats.
This study evaluated the effect of low-level laser therapy (LLLT) on the tendency of rat molars to relapse following orthodontic tooth movement (OTM). Maxillary rat molars were moved mesially for 10 days. Animals were randomly assigned to group I (non-irradiated) or II (irradiation with LLLT). Appliances were removed, and the molars allowed to relapse for 1, 3, 5, 7, 14, or 21 days; rats in group II received LLLT according to a protocol. Bone density of periapical alveolar bone was measured using radiographs and Digora software. Dental supporting structures were examined histologically with haematoxylin and eosin and tartrate-resistant acid phosphatase. In both groups, first molar relapse was rapid 1 day after the end of active treatment; by 21 days percentage relapse was measured as 86.11 per cent in group I, and 72.22 per cent in group II. Osteoclast number was highest at the end of active OTM, and thereafter successively decreased during the relapse phase in both groups. Decrease in number, and redistribution of osteoclasts occurred more rapidly in the non-irradiated than the LLLT group. Whilst molar relapse was generally less and osteoclast numbers generally higher in group II compared to group I, the differences were not significant. There was no significant difference in bone density between the two groups. These results indicate that LLLT may reduce the relapse tendency, possibly due in part to bone formation in previous tension areas, and to redistribution of osteoclasts following removal of orthodontic force. The role of LLLT in the prevention of orthodontic relapse requires further study.


Neuroprotective effects of nimodipine and nifedipine in the NGF-differentiated PC12 cells exposed to oxygen-glucose deprivation or trophic withdrawal.
The goal of this study was to compare the neuroprotective properties of the L-type Ca²⁺ channel blockers, nimodipine and nifedipine, using nerve growth factor (NGF)-differentiated PC12 neuronal cultures exposed to oxygen-glucose deprivation (OGD) and trophic withdrawal-induced cell death. Nimodipine (1-100 μM) conferred 65±13% neuroprotection upon exposure to OGD and 35±6% neuroprotection towards different trophic withdrawal-induced cell death measured by lactate dehydrogenase and caspase 3 activities. The time window of nimodipine conferred neuroprotection was detected during the first 5h but not at longer OGD exposures. Nifedipine (1-100 μM), to a lower potency than nimodipine, conferred 30-55±8% neuroprotection towards OGD in PC12 cells and 29±5% in rat hypocampal slices, and 10±3% neuroprotection at 100 μM towards trophic withdrawal-induced PC12 cell death. The ability to demonstrate that nimodipine conferred neuroprotection in a narrow therapeutic time-window indicates that the OGD PC12 model mimics the in vivo models and therefore suitable for neuroprotective drug discovery and development.


Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses.
Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric condition that affects approximately 5.3% of children worldwide. This disorder is defined by a combination of symptoms of inattention and hyperactivity/impulsivity. Diagnosis is based on impairment in these two domains determining several problems in personal and academic life. Although it is known that genetic and environmental factors are important in ADHD etiology, how these factors influence the brain and consequently behavior is still under debate. There seems to be a consensus in the literature that a fronto-subcortical dysfunction is responsible, at least in part, for the ADHD spectrum. Considering that these brain regions are rich in dopamine (DA), the DA hypothesis has an important role to understand ADHD pathophysiology. The main goal of the present review is to show evidence from different areas that support the idea that dysregulation in the DA system underlies ADHD. We discuss here evidences from animal models, pharmacology, brain imaging and genetics studies.


Persistence of chromosomal aberrations in blood lymphocytes of testicular cancer patients. I. The effect of vinblastine, cisplatin and bleomycin adjuvant therapy.
Chromosomal aberrations and sister chromatid exchanges were examined in 45 patients with nonseminomatous testicular cancer at different times after the termination of vinblastine, cisplatin and bleomycin (VPB) therapy and in 22 age-matched healthy men and untreated testicular cancer patients. After 36 months, the frequency of unstable aberrations markedly decreased in peripheral blood lymphocytes of VPB-treated patients, however the persistence of aberrant cells even 75 months after the termination of treatment underlines the necessity of longer follow-up of VPB-treated patients in order to evaluate the relationship between their carcinogen sensitivity and the risk of second malignancies.


Perceptions and experiences of lifestyle interventions in women with polycystic ovary syndrome (PCOS), as a management strategy for symptoms of PCOS.
The international clinical practice guidelines for PCOS emphasize diet and exercise as first-line management of clinical signs and symptoms. This study aimed to describe the patterns, perceptions and experiences of lifestyle interventions for women in the community with PCOS. An electronic survey of 493 members of two PCOS consumer support groups, collected by cloud-based Survey Monkey, described women's types and patterns of diet and exercise, experiences and perceptions of effectiveness. Women were recruited from the Polycystic Ovary Association of Australia (POSAA) and from the Facebook group, PCOS University Research Group. Associations between participants perceptions of effectiveness, and diet types and exercise patterns were assessed using logistic regression. Response bias for the POSAA group was assessed with a continuum of resistance model. 91% of POSAA members and 311 Facebook group members aged 16-50 years responded to the survey. Nearly all women reported adjusting their dietary and exercise practices with the aim to improve their health and/or PCOS (82% and 73% respectively), however less than 13% reported achievement of health goals (12.2% and 8.1% respectively). Low carbohydrate, high protein diets, and vigorous activity were associated with self-perceived effectiveness (r.0.16, p < 0.01; r.0.15 p < 0.01 and r.0.2 p < 0.01 respectively). Barriers for lifestyle interventions included psychosocial factors. Response bias was not assessed for the Facebook group, however self-reported PCOS aligned with prevalence of clinical phenotypes and suggests results are generalizable to clinical populations of women with PCOS, who are responsible for self-directing and administering lifestyle interventions to manage their PCOS. Perceptions of effectiveness for lifestyle interventions by women with PCOS may be complicated by a lack of rigorous evidence. The strength of recommendations in clinical practice guidelines may be enhanced by clinical trials investigating flexible and feasible lifestyle interventions for women in the community with PCOS.


A Strategic Plan for Strengthening America's Families: A Brief from the Coalition of Behavioral Science Organizations.
Despite significant progress in research on the treatment and prevention of psychological, behavioral, and health problems, the translation of this knowledge into population-wide benefit remains limited. This paper reviews the state of America's children and families, highlighting the influence of stressful contextual and social conditions on child and family well-being and the concentration of disadvantage in numerous neighborhoods and communities throughout the nation. It then briefly reviews the progress that has been made in pinpointing policies that can reduce stressful contextual conditions such as poverty, discrimination, and the marketing of unhealthful foods and substances. It also describes numerous family and school interventions that have proven benefit in preventing psychological and behavioral problems as diverse as tobacco, alcohol, and other drug use; depression; antisocial behavior; academic failure; obesity prevention; and early childbearing. We argue that progress in translating existing knowledge into widespread benefit will require a nationwide effort to intervene comprehensively in neighborhoods and communities of concentrated disadvantage. We present a strategic plan for how such an effort could be organized. The first step in this organizing would be the creation of a broad and diverse coalition of organizations concerned with advancing public health and well-being. Such a coalition could increase public support both for the policies needed to focus on these disadvantaged areas and the research needed to incrementally improve our ability to help these areas.


Hyperthermia inhibits the repair of DNA double-strand breaks induced by ionizing radiation as determined by pulsed-field gel electrophoresis.
Hyperthermia is known to synergistically interact with X-rays to kill cells. We have used pulsed-field gel electrophoresis to investigate the effects of hyperthermia on cell survival and on repair of radiation-induced DNA double-strand breaks (dsbs). Combining hyperthermia (43 degrees C, 45 min) with radiation (7.5 Gy) resulted in a complete inhibition of dsb repair and a surviving fraction of 0.9%. Cells treated with hyperthermia alone resulted in a 55% cell survival with no increase in dsb levels over background. Cells treated with 7.5 Gy alone demonstrated 11% survival and exponential dsb repair. Dsb repair was equally inhibited by hyperthermia whether administered immediately before or after the radiation. We compared the rejoining of dsbs resulting from 7.5 Gy at 37 and 43 degrees C to determine whether dsbs were being repaired during hyperthermia. While repair occurred at 37 degrees C, no dsbs were repaired at 43 degrees C. Our results indicate that hyperthermia completely inhibits dsb repair.


Modelling tumour biology-progression relationships in screening trials.
There has been some recent work in the statistical literature for modelling the relationship between tumour biology properties and tumour progression in screening trials. While non-parametric methods have been proposed for estimation of the tumour size distribution at which metastatic transition occurs, their asymptotic properties have not been studied. In addition, no testing or regression methods are available so that potential confounders and prognostic factors can be adjusted for. We develop a unified approach to non-parametric and semi-parametric analysis of modelling tumour size-metastasis data in this article. An association between the models considered by previous authors with survival data structures is discussed. Based on this relationship, we develop non-parametric testing procedures and semi-parametric regression methodology of modelling the effect of size of tumour on the probability at which metastatic transitions occur in two situations. Asymptotic properties of these estimators are provided. The proposed methodology is applied to data from a screening study in lung cancer.


Site-dependent activity of atomic Ti catalysts in Al-based hydrogen storage materials.
Doping catalytically inactive materials with dispersed atoms of an active species is a promising route toward realizing ultradilute binary catalyst systems. Beyond catalysis, strategically placed metal atoms can accelerate a wide range of solid-state reactions, particularly in hydrogen storage processes. Here we analyze the role of atomic Ti catalysts in the hydrogenation of Al-based hydrogen storage materials. We show that Ti atoms near the Al surface activate gas-phase H(2), a key step toward hydrogenation. By controlling the placement of Ti, we have found that the overall reaction, comprising H(2) dissociation and H spillover onto the Al surface, is governed by a pronounced trade-off between lowering of the H(2) dissociation barrier and trapping of the products near the active site, with a sharp maximum in the overall activity for Ti in the subsurface layer. Our findings demonstrate the importance of controlling the placement of the active species in optimizing the activity of dilute binary systems.