Sagittal Alignment With Downward Slope of the Lower Lumbar Motion Segment Influences Its Modes of Failure in Direct Compression: A Mechanical and Microstructural Investigation.
Microstructural investigation of compression-induced herniation of ovine lumbar discs with and without added component of anterior-inferior slope. Does increased shear arising from a simulated component of motion segment slope imitating sacral slope weaken the lateral annulus and increase risk of overt herniation at this same region. An increase in sacral slope secondary to lordosis and pelvic incidence increases shear stresses at the lumbosacral junction and has been associated with an increase in spondylolisthetic disorders and back injury. The small component of forward shear induced when a segment is compressed in flexion is suggested to cause differential recruitment of the lateral annular fibers leading to its early disruption followed by intra-annular nuclear tracking to the posterolateral/posterior regions. However, the influence of even greater forward shear arising from the added component of slope seen where pelvic incidence and lumbar lordosis are increased in the lower lumbar spine is less understood. Ovine motion segments were compressed at 40 mm/min up to failure; 9 with a horizontal disc alignment and 26 with a segment slope of 15° and then analyzed structurally. All the horizontal discs failed (11.8 ± 2.4 kN) via vertebral fracture without any evidence of soft tissue failure even in the lateral aspects of the discs. The increased forward shear resulting from the slope decreased the failure load (6.4 ± 1.6 kN). The sloping discs mostly suffered mid-span, noncontinuous disruption of the lateral annulus with some extruding nuclear material directly from these same lateral regions. The increased level of forward shear generated in moderately sloping lumbar segments when compressed was abnormally damaging to the lateral regions of the disc annulus. This is consistent with the view that shear differentially loads the oblique-counter oblique fiber sets in the lateral annulus, increasing its vulnerability to early disruption and overt herniation. N/A.


Modeling of S mutans and A naeslundii acid production in vitro with caries incidence of low- and high-risk children.
Nowadays, the extended ecological plaque hypothesis equates dental health with the occurrence of acidogenic generalists in the plaque flora and explains disease?the irreversible demineralization of the dental hard tissue?by an ecologic shift in plaque composition, favoring acidogenic and aciduric specialists, following repeated conditions of high sugar. In the present study, aspects of the extended ecological plaque hypothesis were examined in retrospect. Serving as a basis were data on (1) the caries incidence of children, classified according to their DMFT as having low or high caries risk; (2) the qualitative plaque composition of the children with the prevalence of mutans streptococci and actinomyces; (3) the amounts of acid and acid tolerance, determined by pH state titration (glucose), of representatively isolated strains of mutans streptococci and actinomyces; (4) the extrapolation of the acid amount to the occurrence of mutans streptococci and actinomyces in the plaque of children; and (5) the relationship between the extrapolated acid amount in plaque and caries incidence and the respective classification of the children into low and high caries risk. The synoptic consideration of the numbers of A naeslundii and S mutans in plaque of children, with their capacity for acid production in vitro, reflected the caries risk classification. The analysis of the clinical, microbiologic, and in vitro findings concerning the virulence of the plaque isolates supports the extended ecological plaque hypothesis. Children with low caries risk had developed one new decayed surface within 4 years; children with high caries risk developed four within the same time period.


Physical Activity, Aerobic Capacity, and Total Antioxidant Capacity in Healthy Men and in Men with Coronary Heart Disease.
The purpose of the study was to assess total antioxidant capacity (TAC) of blood serum in relation with habitual leisure time physical activity (LTPA) and aerobic capacity in a group of 90 men with coronary heart disease (CHD) aged 34.8-77.0 years and in 90 age-matched peers without CHD. Two spectrophotometric methods were applied to assess TAC: Ferric Reducing Ability of Serum (TAC-FRAS) and 2.2-diphenyl-1-picryl-hydrazyl (TAC-DPPH) tests. Aerobic capacity was expressed as physical working capacity at 85% of the maximal heart rate (PWC(85%HRmax)). CHD patients had higher values of TACFRAS (1.37 ± 0.28 versus 1.27 ± 0.23 mmol FeCl2·L(-1); P < 0.05) but there were no group differences for TAC-DPPH and for uric acid (UA). Negative correlation was found between LTPA (also when calculated per kg of body mass) and TAC-DPPH in CHD patients. In CHD patients, TAC-FRAS and UA were lower in subjects with higher aerobic capacity expressed as PWC(85%HRmax/kg). Those associations were not found in healthy men. We conclude that TAC of blood serum is moderately adversely related to LTPA and aerobic capacity in patients with CHD. UA, as the main determinant of serum TAC, may be partially responsible for those associations.


Initial experience of a novel method for electrical isolation of the superior vena cava using cryoballoon in patients with atrial fibrillation.
Damage to the sinus node (SN) has been described as a potential complication of superior vena cava (SVC) isolation. There have been reports of permanent SN injury requiring pacemaker implantation during isolation of the SVC. It is safe and effective to isolate SVC with the second-generation 28-mm cryoballoon by using a novel method. Forty-three patients (including six redo cases) with SVC-related atrial fibrillation (AF) from a consecutive series of 650 patients who underwent cryoballoon ablation were included. After pulmonary vein isolation was achieved, if the SVC trigger was identified, the SVC was electrically isolated using the cryoballoon. First, the cryoballoon was inflated in the right atrium (RA) and advanced towards the SVC-RA junction. After total occlusion was confirmed by dye injection with total retention of contrast in the SVC, the SVC-RA junction was determined. Next, the cryoballoon was deflated, advanced into SVC, then reinflated, and pulled back gently. The equatorial band of the cryoballoon was then set slightly (4.32 ± 0.71 mm) above the SVC-RA junction for isolation of the SVC. Real-time SVC potential was observed in all patients during ablation. The mean time to isolation was 24.5 ± 10.7 s. The SVC was successfully isolated in all patients. The mean number of freeze cycles was 2.5 ± 1.4 per patient, and the mean ablation time was 99.8 ± 22.7 s. A transient phrenic nerve (PN) injury occurred in one patient (2.33%). There were no SN injuries. Freedom from AF rates at 6 and 12 months was 97.7% and 93.0%, respectively. This novel method for SVC isolation using the cryoballoon is safe and feasible when the SVC driver during AF is determined and could avoid SN injury. PN function should still be carefully monitored during an SVC isolation procedure.


EEG signal varies with different outcomes in comatose patients: A quantitative method of electroencephalography reactivity.
Electroencephalographic reactivity (EEG-R) is a major predictor of outcome in comatose patients; however, the inter-rater reliability is limited due to the lack of homogeneous stimuli and quantitative interpretation. EEG-R testing was employed in comatose patients by quantifiable electrical stimulation. Reactivity at different frequency bands was computed as the difference between pre- and post-stimulations in power spectra and connectivity function (including magnitude squared coherence and transfer entropy). The clinical outcomes were dichotomized as good and poor according to the recovery of consciousness. Signal discrimination of EEG-R was compared between the two groups. A total of 18 patients (43%) regained consciousness at a 3-month follow-up. In the patients who regained consciousness, the EEG power increased significantly (P < 0.05) at the Alpha and Beta frequency bands after stimulation as compared to those with no behavioral awakening. Also, connectivity enhancement (including linear and nonlinear analysis) in the Beta and Gamma bands and connectivity decrease (nonlinear transfer entropy analysis) in the Delta band after stimulus were observed in the good outcome group. In this study, the combined use of quantifiable stimulation and quantitative analysis shed new light on differentiating brain responses in comatose patients with good and poor outcomes as well as exploring the nature of EEG changes concerning the recovery of consciousness. The combination of quantifiable electrical stimulation and quantitative analysis with spectral power and connectivity for the EEG-R may be a promising method to predict the outcome of comatose patients.


Gene surfing in expanding populations.
Large scale genomic surveys are partly motivated by the idea that the neutral genetic variation of a population may be used to reconstruct its migration history. However, our ability to trace back the colonization pathways of a species from their genetic footprints is limited by our understanding of the genetic consequences of a range expansion. Here, we study, by means of simulations and analytical methods, the neutral dynamics of gene frequencies in an asexual population undergoing a continual range expansion in one dimension. During such a colonization period, lineages can fix at the wave front by means of a "surfing" mechanism [Edmonds, C.A., Lillie, A.S., Cavalli-Sforza, L.L., 2004. Mutations arising in the wave front of an expanding population. Proc. Natl. Acad. Sci. 101, 975-979]. We quantify this phenomenon in terms of (i) the spatial distribution of lineages that reach fixation and, closely related, (ii) the continual loss of genetic diversity (heterozygosity) at the wave front, characterizing the approach to fixation. Our stochastic simulations show that an effective population size can be assigned to the wave that controls the (observable) gradient in heterozygosity left behind the colonization process. This effective population size is markedly higher in the presence of cooperation between individuals ("pushed waves") than when individuals proliferate independently ("pulled waves"), and increases only sub-linearly with deme size. To explain these and other findings, we develop a versatile analytical approach, based on the physics of reaction-diffusion systems, that yields simple predictions for any deterministic population dynamics. Our analytical theory compares well with the simulation results for pushed waves, but is less accurate in the case of pulled waves when stochastic fluctuations in the tip of the wave are important.


Tracing nitrogenous byproducts during ozonation in the presence of bromide and ammonia using stable isotope labeling and high resolution mass spectrometry.
Ammonia has been widely used to inhibit bromate formation during ozonation. However, our recent study found that during ozonation in the presence of bromide and ammonia, toxicity increased under certain conditions that might be attributed to the formation of nitrogenous byproducts. Herein, a typical structural moiety of natural organic matter (NOM), hydroquinone, was evaluated for its potential to form nitrogenous byproducts. During ozonation of the hydroquinone solution containing bromide and ammonia, toxicity of organic byproducts increased significantly. As organic bromine was hardly detected, organic nitrogen was responsible for the increased toxicity. An effective method combining ultra-performance liquid chromatography in tandem with high resolution mass spectrometry (UPLC-HRMS) with an isotope labeling strategy was used to trace nitrogenous byproducts. Four newly formed nitrogenous byproducts were detected, two of which were also detected in Suwannee River natural organic matter (SRNOM) solution treated under the same ozonation condition. Furthermore, the molecular structures and formation pathways of these nitrogenous byproducts were proposed. This study highlights that, despite the widespread use, adding ammonia to inhibit bromate formation during ozonation might increase the toxicity posed by nitrogenous byproducts. During ozonation in the presence of bromide and ammonia, particular attention should be paid to nitrogenous byproducts.


Dopamine-containing neurons in the mammalian central nervous system: electrophysiology and pharmacology.
A decade of research culminated in the late 1950's with the demonstration that dopamine was a chemical neurotransmitter within the mammalian brain. Since this time, dopaminergic neuronal systems have been extensively studied using numerous techniques. This paper will review the last 14 years of electrophysiological investigation on neurochemically identified dopamine-containing neurons in the central nervous system. This will include an examination of both the electrophysiological and pharmacological characteristics in these cells, as well as the resulting insights into the regulation of dopamine cell electrical activity which is derived from this work.


Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction.
Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR.


Vaginal opening in the Mongolian gerbil, Meriones unguiculatus: normal data and the influence of social factors.
Mean age at vaginal opening was 41 days, range 33-53 days. Bodyweight at weaning and age at vaginal opening were negatively correlated, but there was no relationship between bodyweight and age at vaginal opening. The presence of a male before vaginal opening did not accelerate either the time of its occurrence or first conception. The vaginas of females caged singly from weaning opened earlier than in those kept in groups of 2 or 3.


Recombinant invasive Lactobacillus plantarum expressing the J subgroup avian leukosis virus Gp85 protein induces protection against avian leukosis in chickens.
Avian leukosis, caused by avian leukosis virus (ALV), is an infectious tumor disease and severely hinders the development of the poultry industry. The use of Lactobacillus plantarum (L. plantarum) could effectively alleviate viremia in the early period of J subgroup ALV (ALV-J) infection. In this study, an invasive L. plantarum NC8 expressing Gp85 protein of ALV-J was constructed. After chickens were orally administered the recombinant invasive NC8, the levels of expression of CD4+ and CD8+ T lymphocytes in peripheral blood and spleen by flow cytometry and the proliferation ability of splenocytes by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were examined, and the contents of cytokines, the anti-ALV-J antibody in serum, and mucosal antibody sIgA in intestinal lavage fluid were detected by enzyme-linked immunosorbent assay (ELISA). The immunoprotective efficiency was evaluated by monitoring the infection rate, the percent of cloacal swabs and survival, body weight gain, the organ indexes, and relative virus loads after challenge with ALV-J. The results showed that the recombinant invasive strain (FnBPA-gp85) could promote the expression levels of the CD8+T cells in peripheral blood and spleen, the proliferation of splenocytes, the secretions of cytokines interleukin 2 (IL-2) and γ-interferon (IFN-γ), and the production of IgG and sIgA compared with the PBS and FnBPA control groups in chickens. The FnBPA-gp85 group was exhibited the highest immune protection against ALV-J infection. The above results indicated that the recombinant invasive NC8 could promote the cellular immunity, humoral immunity, and mucosal immunity responses in chicken and provide a new method for exploring the live vaccine against ALV-J.Key points• The FnBPA-gp85 strain could enhance cellular immunity response.• The FnBPA-gp85 strain could improve the immune protection against ALV-J infection.


Some effects of chronic antidepressant treatments on rat brain monoaminergic systems.
A range of established and putative antidepressant therapies were studied for the effect of their long-term administration on two facets of presynaptic monoaminergic functioning in rat brain, namely NE, DA, and 5-HT turnover and alpha 2-adrenoceptor sensitivity. Unless stated otherwise drugs (10 mg/kg) were injected i.p. twice daily for 14 days. ECT (100 mA for 1 s) was applied once daily for 10 days. Changes in turnover were indirectly assessed by measuring levels of metabolites. Brain levels of MHPG-SO4 were unchanged by chronic amitriptyline, imipramine, nisoxetine (20 mg/kg), nortriptyline, salbutamol (5 mg/kg), and ECT. Amitriptyline elicited a slight, but significant, increase in brain DOPAC content. Brain levels of 5-HIAA were increased by amitriptyline, imipramine, salbutamol, and ECT. An overall view of the results indicates that no common pattern of change was elicited by the range of antidepressant therapies studied. Central alpha 2-adrenoceptor sensitivity was assessed by investigating the effect of various therapies on the ability of clonidine (25 mg/kg i.p.) to decrease rat brain MHPG-SO4 content. The clonidine-induced fall was attenuated by desipramine, imipramine, and ECT. Amitriptyline, iprindole, mianserin, nisoxetine, nortriptyline, Org 6582 (10 mg/kg once daily), pargyline (25 mg/kg once daily), salbutamol, and trazodone were ineffective. The following chronic antidepressant therapies were investigated for their effect on rat frontal cortex 3H-clonidine binding: amitriptyline, desipramine, imipramine, iprindole, mianserin, nisoxetine, nortriptyline, pargyline, salbutamol, and ECT. CHronic, but not acute, pargyline decreased 3H-clonidine binding and this was due to a diminished number of binding sites. The induction of subsensitive presynaptic alpha 2-adrenoceptors in rat brain is not a property common to all forms of antidepressant therapies. Hence it cannot be the fundamental mode of action of antidepressants. No correlation exists between the changes in rat cortical 3H-clonidine binding and the observed changes in the sensitivity of central presynaptic alpha 2-adrenoceptors.


The ubiquitin-proteasome system as a critical regulator of synaptic plasticity and long-term memory formation.
Numerous studies have supported the idea that de novo protein synthesis is critical for synaptic plasticity and normal long-term memory formation. This requirement for protein synthesis has been shown for several different types of fear memories, exists in multiple brain regions and circuits, and is necessary for different stages of memory creation and storage. However, evidence has recently begun to accumulate suggesting that protein degradation through the ubiquitin-proteasome system is an equally important regulator of memory formation. Here we review those recent findings on protein degradation and memory formation and stability and propose a model explaining how protein degradation may be contributing to various aspects of memory and synaptic plasticity. We conclude that protein degradation may be the major factor regulating many of the molecular processes that we know are important for fear memory formation and stability in the mammalian brain.


Dendritic cell-specific antigen delivery by coronavirus vaccine vectors induces long-lasting protective antiviral and antitumor immunity.
Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo. Vaccine vectors based on heavily attenuated murine coronavirus genomes were generated to express epitopes from the lymphocytic choriomeningitis virus glycoprotein, or human Melan-A, in combination with the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. Single application of only low vector doses elicited strong and long-lasting cytotoxic T-cell responses, providing protective antiviral and antitumor immunity. Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8(+) T cells. Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity.


Comparative inhibitory effects of niflumic acid and novel synthetic derivatives on the rat isolated stomach fundus.
Novel derivatives of 2-[3-(trifluoromethyl)-analino]nicotinic acid (niflumic acid) were synthesized. The compounds were compared for their inhibitory effects on 5-hydroxytryptamine (5-HT)- and KCI-induced contraction of the rat fundus. The aim was to assess structure-activity relationships regarding the selectivity and potency of these compounds. Niflumic acid (1-100 microM) concentration-dependently inhibited 5-HT-induced tonic contractions with an IC50 value (concentration reducing the control contractile response by 50%, calculated from semi-log graphs) of 0.24 x 10(4) M (n = 9). In contrast, it was significantly less potent at inhibiting KCl-induced responses (IC50 = 1.49 x 10(4) M, n = 9). The methyl ester (NFAme) and amido (NFAm) analogues showed no selectivity between 5-HT- and KCl-induced contractions with IC50 values of 1.64 x 10(-4) M (n = 8) and 1.87 x 10(-4) M (n = 9) for 5-HT responses, and 2.61 x 10(-4) M (n = 8) and 2.55 x 10(-4) M (n = 7) for KCl-induced responses, respectively. Our results suggest that alteration of the carboxylic acid moiety of niflumic acid reduces the selectivity and potency of its inhibitory action on 5-HT-induced contractile responses of the rat fundus, possibly via a reduced interaction with calcium-activated chloride channels.


Midterm Outcome after Mega-Prosthesis Implanted in Patients with Bony Defects in Cases of Revision Compared to Patients with Malignant Tumors.
Use of mega-prostheses is a common option for the treatment of patients with malignant tumors as well as in patients with large osseous defects at the time of revision surgery. No studies have compared the two groups to determine whether there is a relative difference in clinical outcomes. We performed a midterm-outcome-study to evaluate our results in these two patient populations. Deep infection was found more often in our revision group (29.5% vs. 9.1%), however no significant differences in WOMAC-results could be found between the two groups. Surgeons should recognize the high complication rate as well as the differences in results using mega-prostheses in these two distinct groups of patients.


Water relations of the root hemiparasite Olax phyllanthi (Labill) R.Br. (Olacaceae) and its multiple hosts.
Water relations of the root hemiparasite Olax phyllanthi were compared with those of its major species of hosts in natural habitat in coastal heath near Denmark, SW Australia. Leaf water potentials of Olax during winter were 0.4 to 1.4 MPa lower (more negative) than those of all (29) non parasitic host species examined. During the dry summer months (January to March), shallow-rooted hosts developed water potentials up to 3 MPa lower than those of Olax, and were accordingly rated as no longer accessible as a source of water to the hemiparasite. By contrast, deep-rooted hosts, with access to the water table, showed water potentials less negative than Olax, and haustorial contacts retained with these apparently enabled continued extraction of water and nutrients throughout the summer. Three other species of root hemiparasites parasitized by Olax, but not themselves parasitizing Olax, showed leaf water potentials throughout the year very close to, and mostly slightly more negative than those of Olax. Nocturnal measurements of leaf water potential in winter (July and August) in soil at field capacity (water potential -0.006 MPa) showed maintenance of a 0.5-0.8 MPa potential difference between Olax and a range of common host species. By dawn most hosts had equilibrated with the water potential of the soil, whereas both exposed and bagged Olax plants recorded potentials of -0.8 MPa. Daytime rates of transpiration and photosynthesis of Olax were less than those of a range of common hosts, but water use efficiencies were not consistently different between hemiparasite and hosts. This was reflected in almost identical mean values for carbon isotope ratio (13C/12C) between Olax (mean δ value -27.0) and thirteen frequently exploited hosts (δ value -27.1). The results are discussed in relation to published information on other angiosperm hemiparasites.


Gravity prior in human behaviour: a perceptual or semantic phenomenon?
Humans show a gravitational advantage in perception: we are more precise at judging the speed of downwards-moving than upwards-moving objects, indicating that gravitational acceleration is an internalised prior. However, it is unclear whether this gravity prior is based on purely perceptual cues or whether it can incorporate semantic knowledge. Previous research has used only objects which are known to comply with gravity, possibly confounding semantic and perceptual cues. Here we have addressed this question by asking participants to judge the speed of objects that typically move coherently with gravity (ball) or against it (rocket). Our results showed a perceptual advantage for falling stimuli, irrespective of object identity, suggesting the gravity prior is based on perceptual cues.


[Role of double-stranded RNA in eukaryotic gene silencing].
Data on RNA interference, that is, posttranscriptional gene silencing by homologous double-stranded (ds) RNA, are reviewed. Gene silencing caused by exogenous dsRNA in artificial systems and observed in transgenic organisms carrying additional gene copies is considered. Data are summarized on the mechanism that arose during evolution of the Drosophila melanogaster genome to suppress repetitive genes with the use of dsRNA and thereby to prevent male sterility. The role of dsRNA in inhibiting expression and transposition of mobile elements is discussed on the basis of authors own and published findings.


Molecular and phenotypic responses of Japanese medaka (Oryzias latipes) early life stages to environmental concentrations of cadmium in sediment.
Japanese medaka embryos were exposed to environmental concentrations of cadmium (Cd) to investigate adverse and adaptive responses in fish early life stages. Embryos were exposed during their whole development by static sediment-contact to environmental Cd concentrations (2 and 20 μg/g dry weight). Cd bioaccumulation, developmental defects, biochemical and biomolecular (qRT-PCR) responses were analyzed in embryos and hatchlings. A dose-dependent increase of Cd bioaccumulation and developmental defects was observed at hatching. Cd had clear impacts on heartbeat and cardiac morphogenesis and also induced to spinal deformities. The profile and the level of gene transcription were differentially modulated according to the Cd concentration, the duration of exposure and/or the developmental stage of fish. Pro-apoptotic bax and DNA repair rad51 transcripts were significantly repressed in embryos exposed to the highest Cd concentration. Repression of these genes was correlated to the increase of heart rate in 6-day-old embryos. NADH-dehydrogenase nd5 gene transcription was inhibited in larvae at the lowest concentration suggesting mitochondrial respiratory chain impairment, in association with Cd-induced teratogenicity. Finally, wnt1 gene was overexpressed indicating putative deregulation of Wnt signaling pathway, and suggested to be implied in the occurrence of some spinal and cardiac deformities. Results of this study permitted to propose some promising markers at the transcriptional and phenotypical level, responding to environmental concentrations of Cd. The present work also highlights the usefulness of the modified version of the medaka embryo-larval assay with sediment-contact exposure (MELAc) to investigate the toxicity and the modes of action of sediment-bound pollutants.


Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells.
Melatonin is a neurohormone and has high potent of antioxidant that is widely reported to be active against methamphetamine (METH)-induced toxicity to neuron, glial cells, and brain endothelial cells. However, the role of melatonin on the inflammatory responses which are mostly caused by blood-brain barrier (BBB) impairment by METH administration has not been investigated. This study used the primary rat brain microvascular endothelial cells (BMVECs) to determine the protective mechanism of melatonin on METH-induced inflammatory responses in the BBB via nuclear factor-ĸB (NF-κB) and nuclear factor erythroid 2-related factor-2 (Nrf2) signaling. Herein, we demonstrated that melatonin reduced the level of the inflammatory mediators, including intercellular adhesion molecules (ICAM)-1, vascular cell adhesion molecules (VCAM)-1, matrix metallopeptidase (MMP)-9, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) caused by METH. These responses were related to the decrease of the expression and translocation of the NF-κB p65 subunit and the activity of NADPH oxidase (NOX)-2. In addition, melatonin promoted the antioxidant processes, modulated the expression and translocation of Nrf2, and also increased the level of heme oxygenase (HO)-1, NAD (P) H: quinone oxidoreductase (NQO)-1, γ-glutamylcysteine synthase (γ-GCLC), and the activity of superoxide dismutase (SOD) through NOX2 mechanism. In addition, we found that the protective role of melatonin in METH-induced inflammatory responses in the BBB was mediated through melatonin receptors (MT1/2). We concluded that the interaction of melatonin with its receptor prevented METH-induced inflammatory responses by suppressing the NF-κB signaling and promoting the Nrf2 signaling before BBB impairment.


Chromosome losses in tumorigenic revertants of EJ/ras-expressing somatic cell hybrids.
Tumorigenic transformation of SV40-immortalized human uroepithelial cells (SV-HUC) after transfection with EJ/ras was previously reported to be a rare event. To test the hypothesis that ras transformation requires loss of suppressor genes, somatic cell hybrids were generated between a rare tumorigenic transformant and an isogeneic nontumorigenic EJ/ras transfectant obtained in the same experiment. Both parental cell lines, as well as all hybrid progeny, expressed mutant p21 ras protein, but injections of three such independent hybrids into athymic nude mice at passage (P) 4 demonstrated that tumorigenicity was suppressed at 20 of 22 sites. Two tumors developed, after a relatively long 17-week latent period, as compared with a 4-week latent period for the tumorigenic parent. All three hybrids produced tumors at P8, but these showed different latent periods (3-14 weeks). Revertant hybrid tumors were high-grade carcinomas. Cell lines derived from these tumors expressed mutant p21 ras and retained at least 1 EJ/ras integration site. Karyotypic analysis of six independent hybrid tumor revertants showed that each had a unique clonal karyotype. Losses of two or more homologues of 1p, 3p, 4, 8, 10p, 11p, 13q, and 18 were identified in one or more tumorigenic revertants. Losses of all these chromosomes were previously associated with transformation of SV-HUC by EJ/ras, but were also associated with chemical transformation of SV-HUC in tumors that did not express mutant ras. Genetic losses involving most of these chromosomes have also been identified in clinical bladder cancers (i.e., 1p, 3p, 8, 11p, 13 and 18q). These data show that expression of EJ/ras does not negate or significantly alter requirements for multiple genetic losses in HUC tumorigenesis.


Health and wellbeing in refugee families from Syria resettled in Denmark.
The aim was to evaluate self-reported health status and wellbeing in a well-defined group of refugee families from Syria 2-4 years after resettlement in Denmark, and, where possible, compare it with a Danish reference population. The purpose was to determine the need for specialized health care to resettled refugees. This cross-sectional study involved 90 individuals from Syria aged 13-56 years. We used questionnaire survey to assess the general health and wellbeing in the study population in relation to a Danish reference population. Objective measurements of selected health indicators like overweight, hypertension and levels of cholesterol and blood glucose (HbA1c) were also determined for the study population. Mean wellbeing scores and the proportion of study participants rating their health as good were lower among the study participants compared with the Danish population for all age groups. The proportion of participants who reported often being alone against their will was significantly higher than among Danes, as was the proportion who had nobody to talk to when having problems. A significantly higher proportion of participants experienced various forms of pain or discomfort than in the Danish population. Overall, 23.6% and 3.4% of participants had elevated cholesterol and HbA1c levels, respectively, and the prevalence of overweight (BMI ≥ 25) was 70%. Hypertension was more frequent (16.2%) than in another refugee population in Denmark (9%). The study demonstrated various mental and physical health challenges among the Syrian refugee families, and their health and wellbeing appeared to be substantially poorer as compared to the Danish reference population. The findings emphasize the need for systematic and specialized health care services at a municipality level to resettling refugees as a prerequisite for the refugees to become contributing citizens.


Reversed-phase high-performance liquid chromatographic separation of saccharin, caffeine and benzoic acid using non-linear programming.
A method is described which allows a chromatographic assay to be optimized with respect to the time needed to complete an analysis, while maintaining good resolution. The method introduces an operational research technique called linear programming. It was used to optimize the eluent composition for the assay of saccharin, caffeine and benzoic acid and resulted in a significant reduction in the analysis time.


Co-exposure effects of lead and TiO2 nanoparticles in primary kidney cell culture from the freshwater fish Hoplias malabaricus.
This study evaluated the effects of Lead (Pb) and titanium dioxide nanoparticles (TiO2 NPs) alone or in combination in anterior kidney macrophages of the freshwater fish Hoplias malabaricus, naïve or stimulated with 1 ng.mL-1 lipopolysaccharide (LPS). Pb (1 ×10-5 to 1 ×10-1 mg.mL-1) or TiO2 NPs (1.5 ×10-6 to 1.5 ×10-2 mg.mL-1) reduced cell viability despite LPS stimulation, especially Pb 10-1 mg.mL-1. In combination, lower concentrations of NPs intensified Pb-induced cell viability reduction while higher concentrations restored the cell viability independently of LPS stimulation. Basal and LPS- induced NO production was reduced by both TiO2 NPs and Pb isolated. The combination of both xenobiotics avoided this reduction of NO production by the isolated compounds at lower concentrations but the protective effect was lost as the concentrations increased. None xenobiotic increase DNA fragmentation. Therefore, at specific conditions, TiO2 NPs may have a protective effect over Pb toxicity, may also provide additional toxicity at higher concentrations.


Limb-salvage surgery versus extremity amputation for early-stage bone cancer in the extremities: a population-based study.
Many attempts have been made to induce limb salvage as an alternative to amputation for primary bone cancer in the extremities, but efforts to establish its benefits over amputation yielded inconsistent results with regard to outcomes and functional recovery. This study aimed to investigate the prevalence and therapeutic efficiency of limb-salvage tumor resection in patients with primary bone cancer in the extremities, and to compare it with extremity amputation. Patients diagnosed with T1-T2/N0/M0 primary bone cancer in the extremities between 2004 and 2019 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between overall survival (OS) and disease-specific survival (DSS). The cumulative mortality rates (CMRs) for non-cancer comorbidities were also estimated. The evidence level in this study was Level IV. A total of 2,852 patients with primary bone cancer in the extremities were included in this study, among which 707 died during the study period. Of the patients, 72.6% and 20.4% underwent limb-salvage resection and extremity amputation, respectively. In patients with T1/T2-stage bone tumors in the extremities, limb-salvage resection was associated with significantly better OS and DSS than extremity amputation (OS: adjusted HR, 0.63; 95% confidence interval [CI], 0.55-0.77; p < 0.001; DSS: adjusted HR, 0.70; 95% CI, 0.58-0.84; p < 0.001). Limb-salvage resection was associated with significantly better OS and DSS than extremity amputation for patients with limb osteosarcoma (OS: adjusted HR, 0.69; 95% CI, 0.55-0.87; p = 0.001; DSS: adjusted HR, 0.73; 95% CI, 0.57-0.94; p = 0.01). Mortality from cardiovascular diseases and external injuries was remarkably declined in primary bone cancer in the extremities patients who underwent limb-salvage resection (cardiovascular diseases, p = 0.005; external injuries, p = 0.009). Limb-salvage resection exhibited excellent oncological superiority for T1/2-stage primary bone tumors in the extremities. We recommend that patients with resectable primary bone tumors in the extremities undergo limb-salvage surgery as the first choice of treatment.


Effects of stone-made wind shelter structures over an arid nebkha foredune.
Beach users often use a range of strategies to shelter from the wind and blown sand. This involves building structures made of stacking stones. Different from other portable wind blockers, stone-made wind shelters can remain in the landscape for a long time. The process of stone removal from their original place and stone-stacking at another location has well-known effects on rock-dwelling wildlife. Less known are the impacts of stone wind shelters on biogeomorphological processes of beach-dune systems, especially those in arid coastlines, where foredunes formed by nebkhas are naturally discontinuous. This is the case of Playa del Inglés beach (Gran Canaria, Spain), the main sediment input to the Maspalomas dunefield, where the presence of stone wind shelters (goros) made by users has increased in recent decades following an increase of visitors. This research aims to investigate the effects of stone wind shelters on the dynamics of an arid beach-dune system at various spatiotemporal scales. The methodology includes the use of aerial photography to study the appearance and evolution of stone shelters in Playa del Inglés and some of their long-term effects on the foredune. Field data was also collected to investigate the effects that stone shelters have over a representative foredune nebkha in detail, by monitoring the changes (topography, airflow, and vegetation) of an individual landform as we progressively remove pebbles from a previously built stone shelter. Results show that stone stacking has an impact on airflow and sediment transport dynamics around landforms, limiting sediment accumulation inside nebkhas and therefore arid foredune growth. Stone stacking also constrict vegetation growth and its ability to retain sediment. The impacts of these artificial structures can be reverted following their removal but that the process of dismantling stones must be carefully planned. We elaborate some recommendations here to do it avoid damaging foredune vegetation.


Pericardial reconstruction using a pedicle flap of the diaphragmatic central tendon.
A 46-year-old woman was referred to our hospital for further evaluation of an abnormal shadow on a chest X-ray. Chest computed tomography and magnetic resonance imaging revealed a lobulated tumor arising from the left lower lobe. At operation, the tumor tissue was found to have invaded the lingula and pericardium, involving the left phrenic nerve. Resection of the left lower lobe, lingula and pericardium including the phrenic nerve was performed for extended pulmonary malignancy. A pedicle flap of the diaphragmatic central tendon was used as a pericardial patch for pericardial reconstruction with satisfactory results. The patient's postoperative course was uneventful. The postoperative histological diagnosis was pulmonary adenocarcinoma with sarcomatous elements [pT3N2M0]. At present, 43 months after the operation, the patient is receiving chemotherapy after having undergone cyberknife radiotherapy for brain metastasis of the tumor. The use of a pedicle diaphragmatic flap was effective in repairing a pericardial defect after extensive resection of pulmonary malignancy.


Injectable platelet rich fibrin facilitates hair follicle regeneration by promoting human dermal papilla cell proliferation, migration, and trichogenic inductivity.
Hair follicle regeneration has been successful in mice but failed in human being for years. Dermal papilla cells, a specialized mesenchymal stem cell derived from dermal papilla within hair follicles, is considered the key cells for hair follicle regeneration function as both regeneration initiator and regulator. Injectable platelet rich fibrin (i-PRF), a novel biomaterial rich in a variety of growth factors and three-dimensional scaffolds, has shown promising effects on tissue regeneration. In this study, we aimed to evaluate the application of i-PRF in human hair follicle regeneration by examining the biological effects of i-PRF on human dermal papilla cells (hDPCs). Biomaterial compatibility, cell viability, proliferation, migration, alkaline phosphatase activity and trichogenic inductivity were assessed after exposing hDPCs to different concentrations of i-PRF extracts. In addition, we investigated the ultrastructure of i-PRF with all cell components filtered. The results revealed that i-PRF possessing excellent biocompatibility and could significantly promote hDPCs proliferation, migration, and trichogenic inductivity. Furthermore, the concentration of i-PRF is able to remarkably influence hDPCs behavior in a dose-dependent pattern. Different concentrations exhibited differential effects on hDPCs behavior. In general, lower concentration promotes cell proliferation better than higher concentration, while higher concentration promotes cell function better reversely. Best concentration for hDPCs in vitro expending is 1% concentration. 20% concentration is optimal for hair follicle regeneration. In summary, our findings concluded that i-PRF facilitates hair follicle regeneration by promoting human dermal papilla cell proliferation, migration, and trichogenic inductivity.


A serologic marker for the Ars-C family of anti-arsonate antibodies.
Attempts are being made to define, at the serologic, structural and genetic levels, the anti-arsonate repertoire. We previously identified three families of anti-arsonate antibodies based on the amino acid sequence of the heavy chain V regions. The present report establishes the serologic correlates of one of these families, the Ars-C family. The determinants defining this family are expressed by anti-Ar molecules displaying the A/J minor idiotype or the BALB/c major idiotype; these determinants are also expressed on molecules of different specificity, notably by the DNP-binding myelomas, MOPC-460 and MOPC-315. All strains tested employed the Ars-C family in the response to arsonate.


Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats.
The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats. The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant.


Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients.
The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS.


Estimated rates of influenza-associated outpatient visits during 2001-2010 in 6 US integrated healthcare delivery organizations.
Population-based estimates of influenza-associated outpatient visits including both pandemic and interpandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare. To estimate influenza-associated outpatient visits in 6 US integrated healthcare delivery organizations enrolling ~7.7 million persons. Using negative binomial regression methods, we modeled rates of influenza-associated visits with ICD-9-CM-coded pneumonia or acute respiratory outpatient visits during 2001-10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in 2 contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits. Outpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30-70) and 203 (95% CI, 180-240) per 10 000 person-years, respectively, for interpandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161-255) and 542 (95% CI, 441-823) per 10 000 person-years. During the pandemic, children aged 2-17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50-121] to 381 [95% CI, 366-481]). Rates estimated with pneumonia visits were consistent with rates of RT-PCR-confirmed influenza visits during 4 of 5 seasons in 1 comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude. Estimated rates of influenza-associated outpatient visits were higher in children than adults during pre-pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza-coded visits were similar to rates from studies using RT-PCR-confirmed influenza.


Evidence of reorganization in the hippocampal mossy fiber synapses of adult rats rehabilitated after prolonged undernutrition.
We have previously demonstrated that prolonged low-protein diet leads to irreversible cell loss in the hippocampal formation for the adult rat. Because the extent of the resulting hippocampal synaptic alterations is not well characterized, we studied the contacts between mossy fibers and the dendritic excrescences of CA3 pyramidal cells (MF-CA3 synapses) using quantitative methods. Moreover, we investigated whether rehabilitation from undernutrition would influence the morphology of hippocampal synapses. To address these issues, three groups of adult rats were compared: (a) rats fed with a normal diet for 12 months (control rats); (b) rats treated during the same period with low-protein diet (undernourished rats); and (c) rats undernourished for 6 months and then switched to normal diet for 6 months (recovery rats). Timm staining and electron microscopy were employed to estimate the volume of the mossy fiber system and the number and related quantitative features of MF-CA3 synapses. The volume of the suprapyramidal bundle of the mossy fiber system and its total number of synapses were smaller in undernourished rats than in control and recovery animals. These parameters did not differ between the latter two groups. The size of mossy fiber terminals and dendritic excrescences and the surface area of synapses were smaller in undernourished than in control and recovery groups. Conversely, in recovery animals, the volume of the suprapyramidal bundle of the mossy fiber system, the size of mossy fiber terminals and dendritic excrescences, and the total number and surface area of synapses were similar to those of controls. These findings indicate that, following rehabilitation, the pre- and postsynaptic compartments of MF-CA3 synapses undergo structural alterations which compensate for the neuronal loss induced by undernutrition.


2-Azido-N-(4-methyl-phen-yl)acetamide.
The asymmetric unit of the title compound, C9H10N4O, comprises three independent mol-ecules, two pairs of which differ significantly in the rotational orientation of the azido group and one pair having very similar conformations; the N-N-C-C torsion angles are -173.9 (2), -102.7 (2) and -173.6 (2)°. In the crystal, each independent mol-ecule forms N-H⋯O hydrogen bonds with its glide-plane-related counterparts, forming zigzag chains extending along the c-axis direction.


The cofactor challenge in synthetic methylotrophy: bioengineering and industrial applications.
Methanol is a promising feedstock for industrial bioproduction: it can be produced renewably and has high solubility and limited microbial toxicity. One of the key challenges for its bio-industrial application is the first enzymatic oxidation step to formaldehyde. This reaction is catalysed by methanol dehydrogenases (MDH) that can use NAD+, O2 or pyrroloquinoline quinone (PQQ) as an electron acceptor. While NAD-dependent MDH are simple to express and have the highest energetic efficiency, they exhibit mediocre kinetics and poor thermodynamics at ambient temperatures. O2-dependent methanol oxidases require high oxygen concentrations, do not conserve energy and thus produce excessive heat as well as toxic H2O2. PQQ-dependent MDH provide a good compromise between energy efficiency and good kinetics that support fast growth rates without any drawbacks for process engineering. Therefore, we argue that this enzyme class represents a promising solution for industry and outline engineering strategies for the implementation of these complex systems in heterologous hosts.


The role of computed tomography scans in diaphyseal femur fractures following gunshot injuries: A survey of orthopaedic traumatologists.
The objective of this study was to analyze if the addition of CT changed the management of femoral shaft fractures caused by gunshot wounds when compared to those managed with plain radiography alone. A multiple-choice, single-answer electronic survey was created to compare utility of advanced imaging when treating femur fractures resulting from gunshot injury. A total of ten femoral shaft fracture cause by gunshot injuries were selected for an online survey to be administered to orthopeaedic traumatologists. The survey compared the use the of fixation device and surgical planning before and after the CT scan. A total of 99 surveys were initiated, of which 82 were completed. For proximal shaft fractures, 37% of experts reported that a CT scan should be ordered based on the radiograph alone, prior to reviewing the CT. After reviewing the CT, 5% of experts reported that they would have performed a "major" change, and 10% reported that they would have performed a "minor" change. 4% of surveyors would have changed their decision regarding ordering a CT. For distal femoral shaft fractures, 42% of experts selected that a CT scan would have been ordered prior to reviewing the CT. After reviewing the CT, 2% would have performed a "major" change, and 8% would have performed a "minor" change in management. 5% of surveyors would have changed their decision regarding ordering a CT. Our study demonstrated that CT scans are relatively unlikely to cause major changes in fracture management of gunshot-induced fractures of femoral shaft.


Psychological well-being and death anxiety among breast cancer survivors during the Covid-19 pandemic: the mediating role of self-compassion.
Despite the abundance of clinical data available for Coronavirus Disease 2019 (COVID-19), little research on the psychological well-being of breast cancer survivors has been published. We investigate the extent to which self-compassion accounted for the association between psychological well-being (depression, anxiety) and death anxiety in breast cancer survivors. A cross-sectional study design was applied. Participants were recruited from three departments of oncology in Zanjan, Iran. Data were collected from 210 breast cancer patients. Participants completed self-report measures. Pearson correlation coefficient was used to assess the relationship among the study variables. Bootstrapping analyses were used to test the significance of indirect effects. Correlational analyses revealed that depression and anxiety were significantly and positively related to death anxiety (r = 0.77, p < 0.01; r = 0.85, p < 0.01, respectively) and negatively to self-compassion (r = - 0.48, p < 0.01; r = - 0.53, p < 0.01, respectively). Bootstrapping analyses revealed significant indirect effects of depression (β = 0.065, SE = 0.35, p < 0.03, 95% CI [LL = - 0.0083, UL: - 0.1654]) and anxiety (β = 0.089, SE = 0.09, p < 0.04, 95% CI [LL = - 0.0247, UL: - 0.1987]) on death anxiety through self-compassion. Findings from this study indicate that self-compassion may be considered as one treatment strategy to improve psychological well-being of cancer patients in the new context of the COVID-19 pandemic.


Does mental health mediate the effect of deviant peer affiliation on school adaptation in migrant children: evidence from a nationally representative survey in China.
This study aimed to examine the impact of deviant peer affiliation on migrant children's school adaptation in China and explore the mediating role of mental health in the relationship between deviant peer affiliation and school adaptation among migrant children. This was a cross-sectional study based on secondary data. This study was based on the nationally representative China Education Panel Survey. Multiple linear regression models were used to quantify the relationship between deviant peer affiliation and school adaptation among 1,012 migrant children aged 12-17 years. Bootstrap test was used to evaluate the mediating effect of children's mental health. Deviant peer affiliation showed a significant negative impact on the school adaptation of migrant children (β = -0.41, 95% confidence interval = -0.56 to -0.26). The relationship between deviant peer affiliation and school adaptation was partially mediated by children's mental health, resulting in an indirect effect of deviant peer affiliation on their school adaptation through their mental health (β = -0.05, 95% confidence interval = -0.09 to -0.03). The mediating role of mental health could explain 11.4% of the relationship between deviant peer affiliation and school adaptation. Among migrant children, deviant peer affiliation showed unique effects on their school adaptation. Taking care of their mental health might help improve their school adaptation.


Sulfated proteoglycans in Bruch's membrane of the human eye: localization and characterization using cupromeronic blue.
The distribution of sulfated proteoglycans in Bruch's membrane of the human eye was evaluated histochemically using Cupromeronic Blue in combination with specific enzyme digestions and nitrous acid treatment. Five distinct categories of filament-shaped profiles were present following staining with this dye. Type 1 (90 +/- 13 nm long and 7 +/- 1 nm in diameter) (mean +/- S.D.) and type 2 (43 +/- 7 nm long and 5 +/- 1 nm in diameter) filaments were associated with collagen fibrils in the inner and outer collagenous zones. Type 3 profiles (70 +/- 18 nm long and 8 +/- 1 nm in diameter) were present in two locations--along the cortical border of the central elastic zone and within the basal infoldings of the pigment epithelium. Type 4 (60 +/- 11 nm long and 6 +/- 1 nm in diameter) and type 5 (200 +/- 100 nm long and 100 +/- 50 nm in diameter) filaments were associated with the basal laminae of the retinal pigment epithelium and choriocapillaris. Chondroitinase AC treatment eliminated the staining of type 1 filaments. Chondroitinase ABC treatment eliminated the staining of both type 1 and type 2 filaments. Nitrous acid eliminated the staining of type 4 and type 5 filaments. Incubations with keratanase or hyaluronidase did not alter the staining of any filament type. Type 3 filaments were resistant to all enzyme digestions and nitrous acid treatment. These results are consistent with an interpretation that Bruch's membrane contains chondroitin sulfate, dermatan sulfate and heparan sulfate-type proteoglycans. Proteoglycans containing chondroitin sulfate (type 1) and dermatan sulfate (type 2) are associated uniquely with collagen fibrils. Heparan sulfate type proteoglycans (types 4 and 5) are associated with the basal lamina of the pigment epithelium and choriocapillaris. The identity of type 3 profiles, which were resistant to all enzyme and nitrous acid digestions employed, could not be established at this time.


Myrtenal inhibits acetylcholinesterase, a known Alzheimer target.
Inhibition of acetylcholinesterase (AChE) is a common treatment for early stages of the most general form of dementia, Alzheimer's disease. In this study selected components of essential oils, which carry a variety of important functional groups, were tested for their in-vitro anti-acetylcholinesterase activity. In-vitro anti-acetylcholinesterase activity was measured by an adapted version of Ellman's colorimetric assay. 1,8-cineole, carvacrol, myrtenal and verbenone apparently inhibited AChE; the highest inhibitory activity was observed for myrtenal (IC50 = 0.17 mm). This is the first study showing the AChE inhibitory activity of myrtenal. Our investigations provided evidence for the efficacy of monoterpenes as inhibitors of AChE.


Factors predicting fear of falling avoidance behavior in parkinsonisms.
Fear of falling avoidance behavior (FFAB) is common in parkinsonisms and results in potentially mitigable downstream consequences. Determine the characteristics of individuals with parkinsonisms most associated with FFAB. A retrospective, cross-sectional study was conducted from medical records data of 142 patients with parkinsonisms. These data included: demographics (age, sex), disease severity (Movement Disorders Society -Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III), years since diagnosis), fall history (number of fall injuries in previous year), and gait and balance function (five times sit to stand, MiniBESTest, Timed Up and Go (TUG), dual-task TUG, ten-meter walk test (10MWT), observed freezing of gait (FOG) (MDS-UPDRS III item 11)). 10MWT (p < .001) and MDS-UPDRS III item 11 (p < .014) were significantly associated with FFAB above and beyond disease severity, which also contributed significantly to the overall model (ps < .046). Fall history was not associated with FFAB. Our findings suggest that the largest portion of variability in FFAB is explained by gait velocity and FOG; however, disease severity also explains a significant portion of the variability of FFAB. Further investigation into factors predictive of FFAB and mitigation of downstream consequences, using more robust designs, is warranted.


Application of MALDI-TOF MS for identification of environmental bacteria: A review.
Bacteria play a variety of roles in the environment. They maintain the balance in the ecosystem and provide different ecosystem services such as in biogeochemical cycling of nutrients, biodegradation of toxic pollutants, and others. Therefore, isolation and identification of different environmental bacteria are important to most environmental research. Due to the high cost and time associated with the conventional molecular techniques, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has gained considerable attention for routine identification of bacteria. This review aims to provide an overview of the application of MALDI-TOF MS in various environmental studies through bibliometric analysis and literature review. The bibliometric analysis helped to understand the time-variable application of MALDI-TOF MS in various environmental studies. The categorical literature review covers various environmental studies comprising areas like ecology, food microbiology, environmental biotechnology, agriculture, and plant sciences, which show the application of the technique for identification and characterization of pollutant-degrading, plant-associated, disease-causing, soil-beneficial, and other environmental bacteria. Further research should focus on bridging the gap between the phylogenetic identity of bacteria and their specific environmental functions or metabolic traits that can help in rapid advancements in environmental research, thereby, improving time and cost savings.


Synthesis and biological activity of adenophostin derivatives as IP3 receptor ligands.
The three derivatives of adenophostin A, which were the C-glycosidic analogs 3a and 3b, and the 5'-phenyl analog 4, were designed and synthesized as efficient IP3 receptor ligands.


Changes in the Total Lipid, Neutral Lipid, Phospholipid and Fatty Acid Composition of Phospholipid Fractions during Pastırma Processing, a Dry-Cured Meat Product.
Pastırma is a dry-cured meat product, produced from whole beef or water buffalo muscles. This study was carried out to investigate the effect of production stages (raw meat, after curing, after 2nd drying and pastırma) on the total lipid, neutral lipid, phospholipid and fatty acid composition of phospholipid fraction of pastırma produced from beef M. Longissimus dorsi muscles. The pH and colour (L*, a* and b*) analyses were also performed in raw meat and pastırma. It was found that pastırma production stages had significant effects (p<0.01) on the total amounts of lipid, neutral lipid and phospholipid, and the highest amounts of lipid, neutral lipid and phospholipid were detected in pastırma. In pastırma, neutral lipid ratio was determined as 79.33±2.06% and phospholipid ratio as 20.67±2.06%. Phospholipids was proportionately lower in pastırma than raw meat. Pastırma production stages affected pentadecanoic acid (15:1) (p<0.01), linoleic acid (18:2n-6) (p<0.05), γ-linoleic acid (18:3n-6) (p<0.05), erucic acid (22:1n-9) (p<0.05), docosapentaenoic acid (22:5n-6) (p<0.05), total unsaturated fatty acid (ΣUSFA) (p<0.05) and total saturated fatty acid (ΣSFA) (p<0.05) ratios of phospholipid fraction and also the moisture content (p<0.01). Pastırma process also affected pH and colour (L*, a* and b*) values (p<0.01), and these values were higher in pastırma than raw meat.


Nonparametric chemical descriptors for the calculation of ligand-biopolymer affinities with machine-learning scoring functions.
The computational prediction of ligand-biopolymer affinities is a crucial endeavor in modern drug discovery and one that still poses major challenges. The choice of the appropriate computational method often reveals itself as a trade-off between accuracy and speed, with mathematical devices referred to as scoring functions being the fastest. Among the many shortcomings of scoring functions there is the lack of universal applicability to every molecular system. This is so largely due to their reliance on atom type perception and/or parametrization. This article proposes the use of nonparametric Model of Effective Radii of Atoms descriptors that can be readily computed for the entire Periodic Table and demonstrate that, in combination with machine learning algorithms, they can yield competitive performances and chemically meaningful insights.


Acyclovir in herpes simplex keratitis.
Herpes simplex keratitis is the most frequent cause of loss of vision from corneal disease in the industrialised world. This has led to the widespread use of a variety of antiviral drugs in treatment and these are reviewed, with particular attention to their clinical value. Study of the reports concerning the use of acyclovir (ACV) in this condition suggests that this antiviral may be more effective than others, not only in acute infections but possibly in herpetic iridocyclitis and also as a prophylactic antiviral cover following corneal grafting.


Effects of a novel amiodarone-like compound SAR114646A on the pig atrium and susceptibility to ventricular fibrillation in dogs and pigs.
Amiodarone is one of the most effective antiarrhythmic drugs. However, poor solubility of this compound has limited its intravenous application. SAR11464A is a water-soluble amiodarone-like drug that lacks iodine and inhibits multiple cardiac ion channels in vitro. This study evaluated the antiarrhythmic efficacy of this drug in vivo. In porcine studies, atrial effective refractory period (AERP) was measured in pentobarbital-anesthetized thoracotomized pigs and atrial fibrillation (AF) was induced by a premature beat. Ventricular fibrillation (VF) was induced via either burst pacing or programmed electrical stimulation (a series of progressively shorter beats, S1-S5). In canine studies, VF was induced by a 2-min occlusion of the left circumflex coronary artery during the last minute of exercise in dogs with healed myocardial infarctions (n = 8). One week later, this test was repeated after pretreatment with SAR114646A (3.0 mg/kg, i.v., slow bolus). SAR114646A produced a significant dose-dependent prolongation of AERP, inhibited AF induced by a premature stimulus, and electrically induced VF in anesthetized pigs. At 1.0 and 3.0 mg/kg, i.v., it was superior to amiodarone, dofetilide, and flecainide. In dogs, SAR114646A did not alter any ECG parameter including QTc (control, 236.9 ± 8.5 ms vs. SAR, 237.2 ± 3.5 ms) but significantly reduced the incidence of VF, protecting six of eight animals (Fisher's exact test, P = 0.01). SAR114646A was effective against both atrial and ventricular arrhythmias without altering ventricular repolarization. These data suggest that the amiodarone-like drug SAR114646A may be an effective antiarrhythmic intervention that does not adversely prolong ventricular repolarization.


New insights into testing for density dependence.
The reasons why tests for density dependence often differ in their results for a particular time-series were investigated using modelled time-series of 20 generations in lenght. The test of Pollard et al. (1987) is the most reliable; it had the greatest power with the three forms of density dependent data investigated (mean detection rates of 50.8-61.1%) and was least influenced by the form of the density dependence in time-series. Bulmer's first test (Bulmer 1975) had slightly lower power (mean detection rates of 27.4-56.8%) and was more affected by the form of density dependence present in the data. The mean power of the other tests was lower and detection rates were more variable. Rates were 24.6-46.2% for regression of k-value on abundance, 6.4-32.6% for regression of k-value on logarithmic abundance and 0.2-13.7% for Bulmer's second test (Bulmer 1975). Bulmer's second test is not useful because of low power. For one method, regression of k-value on abundance. density dependence was detected in 19.9% of timeseries generated using a random-walk model. For regression of k-value on logarithmically-transformed abundance the equivalent figure was 18.3% of series. These rates of spurious detection were significantly (P<0.001) greater than the generally accepted 5% level of type 1 errors and so these methods are not suitable for the analysis of time-series data for density dependence. Levels of spurious detection (from random-walk data) were around the 5% level and hence were acceptable for Bulmer's first test, Bulmer's second test, and the tests of Pollard et al. (1987), Reddinguis and den Boer (1989) and Crowley (1992). For all tests, except Bulmer's second test, the rate of detection and the amount of autocorrelation in time-series were negatively correlated. The degree of autocorrelation accounted for as much as 59.5-77.9% of the deviance in logit proportion detection for regression of k-value on abundance, Bulmer's first test, and the tests of Pollard et al. and Reddingius and den Boer. For regression of k-value on abundance this relationship accounted for less of the deviance (29.4%). Independent effects of density dependence were largely absent. It is concluded that these are tests of autocorrelation, not density dependence (or limitation). Autocorrelation was found to become positive (which is similar to values from random-walk data) as the intrinsic growth rate became either small or large. As the strength of density dependence (in the discrete exponential logistic equation) is dependent on the product of the intrinsic growth rate and the density dependent parameter α it is unclear whether this is because of variation in the strength of density dependent mortality or reproduction per se. However, small values of the intrinsic grwoth rate cause the amount of variation in the data to become small, which might hinder detection of density dependence, and large values of the intrinsic growth rate are coincident with determinstic chaos which hinders detection. The user of these tests for density dependence should be aware of their potential weakness when variation within time-series is small (which itself is difficult to judge) or if the intrinsic growth rate is large so that chaotic dynamics might result. Power and levels of variability in rates of detection using Reddingius and den Boer's test were intermediate between those of the test of Pollard et al. and Bulmer's first test. This, combined with the strong relationship between rates of detection of limitation and the value of the autocorrelation coefficient, make testing for limitation similar to testing for density dependence. Crowley's test of attraction gave the widest range of mean detection rates from density dependent data of all the tests (20.4-60.6%). The relative rates of detection for the three forms of density dependent data were opposite to those found for Bulmer's first test and the test of Pollard et al. I conclude that testing for attraction is a complementary concept to testing for density dependence. As dynamics represented in time-series generated using a stochastic form of the exponential logistic equation became chaotic, Bulmer's first test, the test of Pollard et al. and regression of k on abundance failed to detect density dependence reliably. Conversely, Crowley's test was capable of detecting attraction with a power between 96 and 100% with time-series containing both stochastically and deterministically chaotic dynamics. This difference from other tests is in agreement with the lower influence of autocorrelation.


Digital image reconstruction for the study of brain structure and function.
Functional activity of brain can be defined as the change in physiological activity that accompanies change in behavior. Although the precise relationship between such coupled activity is still being explored, autoradiographic methods for measuring brain blood flow, metabolism and receptor ligand densities have advanced to the point where it is possible to survey the entire brain of an animal for such changes. These developments offer the opportunity for studying brain as a whole--that is, for surveying the entire brain to identify the sites where changes in blood flow, metabolism or receptor chemistry occur with a particular behavior. The development of computer-based image analysis systems offer the possibility for visualizing such holistic brain function. We identified 4 steps which must be accomplished in developing a three-dimensional (3D) display for studying brain function. This paper describes the development and implementation of procedures for these 4 steps. Sectioning and digitizing representative tissue (e.g. autoradiograms, histology, histochemistry) with an adequate sampling frequency. Alignment and reconstruction of the components which make up the whole brain so that the original shape and orientation prior to sectioning is maintained. Projection and surface generation of a 3D model where the shading of the surface is mathematically dependent on the location of light source(s) and the viewer. Localization and quantification of planar cuts through the 3D model. Density data which reference the original autoradiograms are displayed along the exposed surface of the designated plane. The final presentation of data once these 4 steps are completed allows for the identification and visualization of changes in functional activity within the whole brain.


Beijing's diagnosis-related group payment reform pilot: Impact on quality of acute myocardial infarction care.
In 2012, China's first diagnosis-related group (DRG) payment system was piloted in Beijing. This study explored whether this payment pilot improved quality and reduced costs of acute myocardial infarction (AMI) care in hospitals implementing DRG payment as compared to control hospitals. A difference-in-difference study design was used with regression and considered several quality indicators including aspirin at arrival, aspirin at discharge, β-blocker at arrival, β-blocker at discharge, statin at discharge, in-hospital mortality, and 30-day readmission rates. DRG payment mechanisms without specific mechanisms to promote care quality did not improve quality of AMI care. Future studies should study the impact of cost control mechanisms together with quality improvement efforts to assess how quality of care may be improved within the Chinese healthcare system. These lessons would be helpful to share with lower-middle-income countries undergoing rapid development that are transitioning to a significantly higher burden of non-communicable diseases.


Lymphocytes which differentiate in an allogeneic thymus. II. Evidence for both central and peripheral mechanisms in tolerance to donor strain tissues.
Nude mice which have been grafted with an allogeneic H-2-incompatible thymus are frequently specifically tolerant to skin grafts from the thymus donor strain. The evidence presented here indicates that both clonal deletion and peripheral suppressor cells play a part in maintaining this tolerance.


Influence of pH on the inhibitory effects of local anesthetics on histamine release induced from rat mast cells by concanavalin A and compound 48/80.
The study concerned the effects of lidocaine and mepivacaine on rat mast cell histamine release. At low concentrations these drugs inhibited the histamine release induced by concanavalin A and compound 48/80 although, at high concentrations, they caused cell lysis. The mechanism of their inhibition of histamine release was studied by examining the pH dependence of the inhibitory action. In the absence of drugs, the release of histamine was not affected by the pH of the medium, but the inhibitory effects of the drugs increased with increase in pH. The percent inhibition of histamine release by these drugs at each pH was plotted against the calculated concentration of the nonionized form of the drug, according to the Henderson-Hasselbalch equation. The inhibitory action was correlated with the concentration of nonionized molecules, which readily penetrate the cell membrane. From the interaction of lidocaine with the phospholipid bilayer, it was concluded that this drug penetrates the lipid bilayer and that this effect increases with increasing pH of the medium. Thus, it seems that it is the nonionized form of local anesthetics that inhibits histamine release and that it is nonionized molecules that penetrate the mast cell membrane.


Rapid Resource Change and Visitor-Use Management: Social-ecological Connections at the Bonneville Salt Flats.
Parks and protected areas are complex, and managers often need integrated social-ecological science-based information that illuminates the dynamic interactions between the biophysical and social processes. However, modeling and determining social-ecological connections are difficult due to disciplinary paradigms, divergent research questions, and data sets representing different scales. During this investigation, researchers sought to evaluate social-ecological linkages at a large salt pan (Bonneville Salt Flats) in western Utah (US). Specifically, the investigation evaluated how the changing level and location of salt-crust moisture and ponding water influenced visitors' spatial distribution of use and important elements of their experience. The findings indicate that visitors travel more distance, spend more time recreating, and use the Salt Flats in higher densities during dry conditions. However, the results also highlight that importance levels ascribed to specific aspects of the visitor experience remained relatively stable regardless of changes in salt-crust moisture and ponding water. Illuminating such linkages is important because most natural resource issues in society, including resources at the Bonneville Salt Flats, are not solely ecological or social in nature but characterized by deeper enmeshment between the two.


Baseline levels in muscle relaxation training.
Variations in the baseline levels of physiological measures, a familiar problem in psychophysiological research, can affect the results of clinical applications and research in the self-control of bodily processes. In this presentation, the problem is illustrated within the context of skeletal muscle relaxation training using continuous biofeedback (BF) based on surface electromyographic (EMG) activity. In terms of the Law of Initial Values (LIV), higher EMG levels are expected to be associated with greater decreases during training. The combined results of two studies documented an LIV-like effect for pretraining baseline levels with greater EMG decreases after training for subjects with the higher pretraining baselines. Left uncorrected, such baseline differences were shown to lead to discrepant results between two identical studies, and therefore to conflicting conclusions about the effectiveness of these procedures. The available methods suggested to correct for the biasing effect of baseline differences in research are described, with particular emphasis on the analysis of covariance.


Mapping elasticity in human lenses using bubble-based acoustic radiation force.
This study uses acoustic radiation pressure to displace a femtosecond laser-produced bubble in human lens tissue. Bubble displacement is monitored with low-amplitude, high-resolution ultrasound. Displacements are compensated by bubble size determined from ultrasonic backscatter. The Young's modulus is proportional to the inverse of the compensated displacement with the constant of proportionality determined from similar measurements in a controlled gelatin sample. Multiple measurements were obtained on 12 human lens specimens grouped into two age categories, middle-age (about 40 years old) and old-age (63-70 years old). There were 3 lenses from 2 donors in the middle-age group and 9 lenses from 5 donors in the old-age group. At each radial position, the median value was computed for all measurements within each group. For middle-age lenses, Young's modulus ranged from 5.2kPa in the center to 1.1kPa on the periphery. For old-age lenses, Young's modulus ranged from 10.6kPa in the center to 1.4kPa on the periphery. These values are the same order of magnitude as previous measurements using other techniques. The age related change in elasticity distribution is also similar to a previous study. Radially varying elasticity may provide insight into the mechanics of accommodation.


Prospective Associations Between Preschool Exposure to Violent Televiewing and Psychosocial and Academic Risks in Early Adolescent Boys and Girls.
Risks of early exposure to media violence remain unclear. This study examines typical early childhood violent media exposure and subsequent psychosocial and academic risks. Our longitudinal birth cohort comprised 978 girls and 998 boys. Child-reported and teacher-reported measures of adjustment at age 12 years were linearly regressed on parent-reported televised violence exposure at ages 3.5 and 4.5 years while adjusting for individual/family confounders. For girls, preschool violent televiewing was associated with increases in emotional distress (b = 0.31; 95% confidence interval [CI], 0.13-0.49) and decreases in classroom engagement (b = -0.97; 95% CI, -1.55 to -0.40), academic achievement (b = -2.60; 95% CI, -3.48 to -1.72), and academic motivation (b = -0.58; 95% CI, -1.09 to -0.07) at age 12 years. For boys, preschool violent televiewing was associated with increases in emotionally distressed (b = 0.33; 95% CI, 0.13-0.53), inattentive (b = 0.25; 95% CI, 0.06-0.45), conduct disordered (b = 0.11; 95% CI, 0.00-0.21), and socially withdrawn behavior (b = 0.23; 95% CI, 0.05-0.40), as well as decreases in classroom engagement (b = -0.84; 95% CI, -1.57 to -0.12), academic achievement (b = -1.19; 95% CI, -2.15 to -0.23), and academic motivation (b = -0.58; 95% CI, -1.13 to -0.03) at age 12 years. Compared with no preschool exposure, violent televiewing is associated with distinct and enduring psychosocial risks by early adolescence. Acknowledging such risks remains a pertinent health literacy target for pediatric professionals, parents, and communities.


Full Metal Species Quantification of Supported Catalysts: Beyond Metal Dispersion.
Metal dispersion is a key concept in heterogeneous catalysis. The conventional approaches for its estimation strongly rely on chemisorption with different probe molecules. Albeit they can generally provide an 'averaged' value in a cost-effective manner, the inhomogeneity of the metal species and the complicated metal-support interactions pose formidable challenges for the accurate determination. Full metal species quantification (FMSQ) is introduced as an advanced method to depict the whole distribution of the metal species, ranging from single atoms to clusters and nanoparticles, in a practical solid catalyst. In this approach, automated analysis of massive high-angle annular dark field scanning transmission electron microscopic images is realized through algorithms specialized in combining the electron microscopy-based atom recognition statistics and deep learning-driven nanoparticle segmentation. In this Concept article, different techniques for determining the metal dispersion are discussed with their pros and cons. FMSQ is highlighted for it can circumvent the drawbacks of conventional approaches, allowing more reliable structure-performance relationships beyond the metal size.


Intracerebroventricular administration of bacterial lipopolysaccharide prevents the development of acute experimental pancreatitis in the rat.
Lipopolysaccharides (LPS) are responsible for septic shock but low doses of LPS reduce pancreatic damage produced by caerulein-induced pancreatitis (CIP) in rats. Leptin, produced by adipocytes attenuates the severity of CIP. The aim of this study was to evaluate the effect of intracerebroventricular (i.c.v.) administration of LPS on CIP and plasma leptin level and to investigate the involvement of sensory nerves (SN) in the effects of LPS on CIP. CIP was produced by subcutaneous (s.c.) infusion of caerulein (25 Kg/kg) to conscious rats. SN were deactivated with capsaicin (100 mg/kg s.c.). LPS (0.2, 2, or 20 Kg/rat) were applied to the right cerebral ventricle 30 min prior to CIP. CIP was manifested by an increase in plasma levels of amylase, lipase, leptin and an anti-inflammatory interleukin 10 (IL-10), (by 400%, 1000%, 700% and 50%, respectively), confirmed by histological examination and accompanied by 40% reduction in pancreatic blood flow. Pretreatment of CIP rats with i.c.v. LPS resulted in significant reduction of CIP accompanied by dose-dependent increase in plasma levels of leptin and IL-10. Deactivation of SN, which by itself failed to affect CIP, completely reversed the beneficial effects of i.c.v. administration of LPS on CIP and reduced plasma leptin and IL-10 concentrations. Pretreatment with LPS given i.c.v. prevents the development of caerulein-induced pancreatitis through the activation of SN and though the release of leptin.


An Exploration of the Anatomy of the Forehead of Asians and Its Relationship With Forehead Lines Based on Ultrasound Imaging.
A profound understanding of the various frontal tissues' morphology and their relationship with forehead lines can efficiently guide clinical treatment. The authors explored the relationship between frontal anatomy and frontal lines. We measured the thickness and shape of tissues in different regions of the forehead of 241 Asians. Then, we analyzed the relationship between the types of frontalis muscle and frontal lines, as well as the relationship between the frontal anatomical structures and the production of frontal lines. We classified the types of frontalis muscle into 3 categories comprising 10 subtypes. The skin (0.78 mm vs 0.90 mm, P < .05), superficial subcutaneous tissue (0.66 mm vs 0.75 mm, P < .05), and frontalis muscle thickness (0.29 mm vs 0.37 mm, P < .05) of people with obvious dynamic forehead lines were significantly thicker than those of people without significant dynamic forehead lines. However, no significant difference in the deep subcutaneous tissue thickness was found between people with and without static forehead lines (1.36 mm vs 1.34 mm, P < .05). This study shows the relationship between the frontal structure and frontal lines. Therefore, these results can provide references for treating frontal lines, to a certain extent.


Phosphatidylserine administration during postnatal development improves memory in adult mice.
Postnatal administration of an aqueous suspension of phosphatidylserine (BC-PS) to C57BL/6 mice resulted in improvement of memory processes in adulthood, as assessed in a passive avoidance task. These findings are discussed in terms of the effects of BC-PS on cholinergic mechanisms and of cholinergic patterns of this inbred strain.


GATA3 haplo-insufficiency causes human HDR syndrome.
Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations. Studies in patients with 10p deletions have defined two non-overlapping regions that contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which is located more telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR patients, and here we define a critical 200-kilobase region which contains the GATA3 gene. This gene belongs to a family of zinc-finger transcription factors that are involved in vertebrate embryonic development. Investigation for GATA3 mutations in three other HDR probands identified one nonsense mutation and two intragenic deletions that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations.


Direct determination of lignin peroxidase released from Phanerochaete chrysosporium by in-capillary enzyme assay using micellar electrokinetic chromatography.
Here we describe the application of an in-capillary enzyme assay using micellar electrokinetic chromatography (MEKC) in the determination of enzyme activity in a crude culture medium containing lignin peroxidase released from Phanerochaete chrysosporium (P. chrysosporium). The method consists of a plug-plug reaction between lignin peroxidase and its substrate, veratryl alcohol, the separation of the product, veratraldehyde, from the other components including the enzyme and the culture medium, and the determination of the enzyme activity from the peak area of veratraldehyde produced by the plug-plug reaction. This method is more sensitive than conventional spectrophotometry since the background originates from the enzyme and the culture medium can be removed via MEKC separation. Veratraldehyde was separated at -10kV in a background electrolyte containing 50mM tartrate buffer (pH 2.5) and 50mM sodium dodecyl sulfate (SDS) after a plug-plug reaction in the capillary for 5min. The calibration curve of veratraldehyde was linear up to 4pmol (500μM) with a limit to quantification of 0.026pmol (3.2μM) (SN=10). The activity of lignin peroxidase was directly measured from the peak area of veratraldehyde. The activity of lignin peroxidase released from P. chrysosporium into the medium for 7 days was successfully determined to be 3.40UL(-1).


A comparative analysis of three habitat suitability models for commercial yield estimation of Tapes philippinarum in a North Adriatic coastal lagoon (Sacca di Goro, Italy).
Habitat Suitability (HS) models have been extensively used by conservation planners to estimate the spatial distribution of threatened species and of species of commercial interest. In this work we compare three HS models for the estimation of commercial yield potential and the identification of suitable sites for Tapes philippinarum rearing in the Sacca di Goro lagoon (Italy) on the basis of six environmental factors. The habitat suitability index (HSI) is based on expert opinion while the habitat suitability conditional (HSC) is calibrated on observational data. The habitat suitability mixed (HSM) model is a two-part model combining expert knowledge and regression analysis: the first component of the model uses logistic regression to identify the areas in which clams are likely to be present; the second part applies the same parameter-specific suitability functions of the HSI model only in the areas previously identified as productive by the logistic component. The HS models were validated on an independent data set and estimates of potential yield of the Goro lagoon were compared. The effectiveness of the three approaches is then discussed in terms of predicted yield and identification of suitable sites for farming.


[Nailing of metaphyseal fractures].
Nailing of metaphyseal fractures demands thorough preoperative planning. The trauma surgeon has to take the specific morphology of the fracture, the individual anatomy of the broken bone, and the design and characteristics of the selected implant into consideration. The fracture has to be precisely reduced and the reduction controlled during nail insertion. The reduction technique and reduction aids must be chosen preoperatively. The nail has to be introduced with care and brought to its correct and ideal position. Only after successful proximal and distal interlocking can the nail become the central weight bearing implant, which holds the fracture stable and reduced. In the following contribution, the specific problems of reduction and nail fixation of metaphyseal fractures of the proximal humerus, proximal and distal femur, and proximal and distal tibia together with the needed reduction and fixation aids are presented.


Structure, function and regulation of the tricarboxylate transport protein from rat liver mitochondria.
Recent progress is summarized on the structure, function, and regulation of the tricarboxylate (i.e., citrate) transport protein (CTP) from the rat liver mitochondrial inner membrane. The transporter has been purified and its reconstituted function characterized. A cDNA clone encoding the CTP has been isolated and sequenced, thus enabling a deduction of the complete amino acid sequence of this 32.6 kDa transport protein. Dot matrix analysis and sequence alignment indicate that based on structural considerations the CTP can be assigned to the mitochondrial carrier family. Hydropathy analysis of the transporter sequence indicates six putative membrane-spanning alpha-helices and has permitted the development of an initial model for the topography of the CTP within the inner membrane. The questions as to whether more than one gene encodes the CTP and whether more than one isoform is expressed remain unanswered at this time. Studies documenting a diabetes-induced alteration in the function of several mitochondrial anion transporters, which can be reversed by treatment with insulin, provide a physiologically/pathologically relevant experimental system for studying the molecular mechanism(s) by which mitochondrial transporters are regulated. Potential future research directions are discussed.