Your Performance Is My Concern: A Perspective-Taking Competition Task Affects ERPs to Opponent's Outcomes.
Previous research has shown that people have more empathic responses to in-group members and more schadenfreude to out-group members. As a dimension of cognitive empathy, perspective-taking has been considered to be related to the enhancement of empathy. We tried to combine these effects through manipulation of a competitive task with opponents and an in-group partner and investigated the potential effect of in-group bias or the perspective-taking effect on outcome evaluation. We hypothesized that the neural activities would provide evidence of in-group bias. We tested it with a simple gambling observation task and recorded subjects' electroencephalographic (EEG) signals. Our results showed that the opponent's loss evoked larger feedback-related negativity (FRN) and smaller P300 activity than the partner's loss condition, and there was a win vs. loss differential effect in P300 for the opponent only. The principal component analysis (PCA) replicated the loss vs. win P300 effect to opponent's performance. Moreover, the correlation between the inclusion of the other in the self (IOS) scores and FRN suggests perspective-taking may induce greater monitoring to opponent's performance, which increases the win vs. loss differentiation brain response to the out-group agent. Our results thus provide evidence for the enhanced attention toward out-group individuals after competition manipulation, as well as the motivation significance account of FRN.


Comparison of the PTS1- and Rab8b-binding properties of Pex5p and Pex5Rp/TRIP8b.
Tetratricopeptide (TPR)-domain proteins are involved in various cellular processes. The TPR domain is known to be responsible for interaction with other proteins commonly recognizing sequence motifs at the C-termini. One such TPR-protein, TRIP8b, was originally identified in rat as an interaction partner of Rab8b, and its human orthologue as a protein related to the peroxisomal targeting signal 1 (PTS1) receptor Pex5p (Pex5Rp). Somewhat later, the mouse orthologue was reported to bind the hyperpolarization-activated, cyclic nucleotide-regulated HCN channels, and, very recently, the rat orthologue was shown to interact with latrophilin 1, the calcium-independent receptor of alpha-latrotoxin. Here we employed various methodological approaches to investigate and compare the binding specificities of the human PTS1 receptor Pex5p and the related protein Pex5Rp/TRIP8b towards a subset of targets, including Rab8b and various C-termini resembling PTS1. The results show that the TPR domains of Pex5p and Pex5Rp/TRIP8b have distinct but overlapping substrate specificities. This suggests that selectivity in the recognition of substrates by the TPR domains of Pex5p and Pex5Rp/TRIP8b is a matter of considerable complexity, and that no single determinant appears to be sufficient in unambiguously defining a binding target for either protein. This idea is further corroborated by our observations that changes in the surrounding residues or the conformational state of one of the binding partners can profoundly alter their binding activities. The implications of these findings for the possible peroxisome-related functions of Pex5Rp/TRIP8b are discussed.


Cranial ultrasound and clinical studies in preterm infants.
Serial ultrasound imaging of the brain was used to determine the ventricular index (VI), and the ratio (VR) of the VI to the cranial hemidiameter during the nursery course and first year post-term in preterm infants of less than 33 weeks gestation. Twenty-nine of the infant survivors with no intracranial hemorrhage or major medical complication during their nursery course composed group 1. Twenty-two survivors with intracranial hemorrhage unassociated with early ventricular dilation composed group 2. Group 3 was comprised of 10 other survivors who had neonatal intraventricular hemorrhage with early ventriculomegaly; all 10 infants had at least one major medical complication during their neonatal course. In groups 1 and 2 the VR decreased and the VI increased significantly with age post-conception. Infants in group 3, compared with those in groups 1 or 2, had decreased occipitofrontal growth during the early postnatal period and increased VR and VI during the neonatal period and first year post-term. These results suggest that the ventriculomegaly associated with neonatal intracranial hemorrhage cannot be explained by posthemorrhagic hydrocephalus alone and may also be related to cerebral atrophy or decreased brain growth or both. Neurodevelopmental assessments at 20 to 30 months of age disclosed significantly lower Bayley Motor Development scores in group 3 compared with groups 1 or 2. Four infants in group 3, but none in groups 1 or 2, had cerebral palsy. The neurodevelopmental deficits in group 3 infants may reflect the complex pathogenesis of the ventriculomegaly as well as the effects of the intraventricular hemorrhage and posthemorrhagic hydrocephalus.


The short chain fatty acid sodium butyrate regulates the induction of CD1a in developing dendritic cells.
Dendritic cells (DCs) are professional antigen-presenting cells with attributes for priming/activating T cells and mediating immune responses. Considering the importance of DCs in the initiation of immune responses, it will be of interest to study their mechanisms of regulation. Histone-modifying enzymes, such as histone deacetylases (HDACs), are critical in controlling chromatin organization. The aim of our study was to investigate DC differentiation under the influence of sodium butyrate (NaB), a short chain fatty acid that is a histone deacetylase inhibitor. Monocytes from healthy individuals were differentiated into immature DCs with IL-4 and GM-CSF in the presence or absence of NaB. DC differentiation was evaluated by CD14 and CD1a expression by flow cytometry. We observed that monocytes stimulated to differentiate in the presence of NaB displayed colony formation and dendritic cell morphology, lost CD14 and showed decreased secretion of IL-1β. The acquisition of CD1a, however, was impaired. Being a natural short chain fatty acid, NaB may regulate CD1a acquisition independently of its HDAC inhibitory activity. We observed that the addition of peroxisome proliferator-activated receptor γ (PPAR-γ) antagonist (GW9662) did not reverse NaB effect, suggesting this was not the pathway involved. On the other hand, CD1a can also be induced by toll like receptors 2 (TLR 2) agonists, such as Pam3Cys, and NaB inhibited this effect. Our data suggest that the histone deacetylase inhibitor NaB instead of impairing DC differentiation inhibits the acquisition of CD1a induced both by cytokines and by TLR 2 agonist stimulus. Furthermore, this occurs at the transcriptional level as NaB led to a decrease in mRNA levels of CD1a and upregulation of CD1d.


15N abundance of soils and plants along an experimentally induced forest nitrogen supply gradient.
15N abundances of soils and a grass species (Deschampsia flexuosa (L.) Trin.) were analysed in a forest fertilization experiment 10 years after the last fertilization. Nitrogen had been given as urea, at seven doses, ranging from 0 to 2400 kg N ha-1. Previously, we have shown that plants in systems experiencing large losses of N become enriched with 15N. This was explained by the fact that processes leading to loss of N, e.g. ammonia volatilization, nitrification followed by leaching or denitrification and denitrification itself, tend to fractionate against 15N. In this experiment, 15N abundance increased with dose of N applied in both grass and soil total-N, but more so in the grass. This was interpreted to be due to the grass sampling small but active pools of N subject to losses. In contrast, soil total-N largely consists of inactive N that does not immediately exchange with pools of N from which fractionating losses occur. Hence, soil total-N shows a large pretreatment 15N memory effect, and is, therefore, and integrator of the long-term N balance. When short-term changes (years, decades) in N balances are monitored using variations in 15N abundance, plants are more suitable indicators of such change than is soil total-N.


Seeing the child in context: Supporting gender diverse children and their families in multiple ways - An introduction to this special edition.
This Special Issue of Clinical Child Psychology and Psychiatry includes a group of papers that originated in the work of the Gender Identity Development Service (GIDS), which is the nationally designated National Health Service (NHS) in the United Kingdom to work with children and adolescents experiencing significant concern and distress about their gender. This short introduction to those papers aims to set the context and explain why certain areas have been given a focus.


Termination of paroxysmal supraventricular tachycardia by intranasal swab insertion.
Paroxysmal supraventricular tachycardia (SVT) is a common emergency department presentation. Vagal maneuvers are commonly tried to terminate SVT but are often unsuccessful in terminating the dysrhythmia. The use of adenosine, while often successful, is associated with a number of side effects and is often disliked by patients with recurrent episodes of SVT. We report on a 44-year-old woman with a past medical history of SVT who presented to the emergency department (ED) due to a recurrence of her SVT. The patient had no intravenous access and preferred not to receive adenosine. The patient received intranasal stimulation with a nasopharyngeal swab used for COVID-19 testing for 5-10 s. After less than 10 s, the patient converted to a sinus rhythm. She was successfully discharged from the ED after 1 h of observation and no recurrence of her SVT.


The effect of earthworms and snails in a simple plant community.
Snails and earthworms affected the dynamics of a simple, three-species plant community, in the Ecotron controlled environment facility. Earthworms enhanced the establishment, growth and cover of the legume Trifolium dubium, both via the soil and interactions with other plant species. Worms increased soil phosphates, increased root nodulation in T. dubium, and enabled T. dubium seedlings to establish in the presence of grass (Poa annua) litter, by increasing soil heterogeneity. Worms also buried the seeds of Poa annua and Senecio vulgaris, reducing the germination of new seedlings. Snails reduced nitrogen-fixing Trifolium dubium and increased cover of plant litter, thereby reducing ammonia-nitrogen concentrations in the soil. These effects and their interactions demonstrate that the detritivore food chain, and earthworms in particular, cannot be ignored if we are to understand the spatial and temporal dynamics of plant communities.


A longitudinal assessment of chronic periodontitis in Australian adults.
The study aimed to estimate the incidence/progression and reversal of chronic periodontitis and to identify factors associated with chronic periodontitis in Australian adults over a 12-year period. Data were obtained from the longitudinal component of the National Study of Adult Oral Health (NSAOH) in 2004-2006, and repeated data, among the same adults, in 2017-2018. NSAOH 2004-2006 was a population-based study of Australian adults aged 15+ years. The American Academy of Periodontology/European Federation of Periodontology case definitions were used, and then compared with two other case definitions. Multivariable Poisson regression models were used to estimate incidence rate ratios (IRRs) and reversal rate ratio (RRRs) of periodontitis. A total of 775 dentate Australian adults had dental examinations at both times. The proportion of incidence/progression and reversal among Australian adults was 56.4% and 11.0%, respectively. Tobacco smokers presented with more than three times higher incidence (IRR: 3.32, 95% CI: 1.50-7.60) and lower reversals (RRR: 0.94, 95% CI: 0.39-0.98) than those who had never smoked. Cessation of smoking was positively associated with periodontitis reversal. The total incidence/progression was 471.7/10,000 person-years, with reversal being 107.5/10,000 person-years. The average number of teeth lost due to periodontal disease was 1.9 in 2017-2018. Being male and not having periodontal treatment were significant risk markers for the incidence/progression of periodontitis. Smoking is a risk factor for periodontitis. Cessation of smoking is an effective means of reducing the incidence and progression of chronic periodontitis, to reduce the risk of tooth loss, and to improve overall periodontal health.


Interferon-alpha enhances sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis.
To determine whether interferon-alpha(IFNalpha) can enhance doxorubicin sensitivity in osteosarcoma cells and its molecular mechanism. Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was studied using Flow cytometry analysis, Hoechst33258 staining, DNA fragmentation assay, as well as the activation of caspase-3 and poly (ADP-ribose) polymerase. Protein expression was detected by Western blotting. The dependence of p53 was determined using p53-siRNA transfection. IFNalpha increased doxorubicin-induced cytotoxicity to a much greater degree through apoptosis in human osteosarcoma p53-wild U2OS cells, but not p53-mutant MG63 cells. IFNalpha markedly upregulated p53, Bax, Mdm2, and p21, downregulated Bcl-2, and activated caspase-3 and PARP cleavage in response to doxorubicin in U2OS cells. Moreover, the siRNA-mediated silencing of p53 significantly reduced the IFNalpha/doxorubicin combination-induced cytotoxicity and PARP cleavage. IFNalpha enhances the sensitivity of human osteosarcoma U2OS cells to doxorubicin by p53-dependent apoptosis. The proper combination with IFNalpha and conventional chemotherapeutic agents may be a rational strategy for improving the treatment of osteosarcoma with functional p53.


Dissatisfaction of people with type 2 diabetes with the care received at a diabetes clinic in Ningbo, China: A cross-sectional study.
The study aimed to assess the dissatisfaction of people with type 2 diabetes mellitus (T2DM) with the care that they received at a diabetes outpatient clinic in Ningbo, China and to determine the associated factors. A cross-sectional study was conducted among 406 adults with T2DM in 2020-2021. Those who were treated at the diabetes outpatient clinic for at least six consecutive months before the survey date were eligible. The Short Assessment of Patient Satisfaction scale was used to assess participants' dissatisfaction with the care that they received. Of the participants, 25.1% were not satisfied with the care that they received at the diabetes outpatient clinic in Ningbo. The odds of dissatisfaction were higher in physically active people compared to those who were not (odds ratio [OR]: 3.41; 95% confidence interval [CI]: 1.56-7.45) and those with >1-5 years of T2DM compared to ≤1 year (OR: 2.18; 95% CI: 1.05-4.53). A quarter of people with T2DM were dissatisfied with the care that they received at the diabetes outpatient clinic in Ningbo, China, and the factors associated with dissatisfaction were identified.


Opportunity for pharmacogenomic testing in patients with cystic fibrosis.
Patients with cystic fibrosis (CF) are exposed to many drugs in their lifetime and many of these drugs have Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines that are available to guide dosing. Contemporary CF treatments are targeted to specific mutations in the CF transmembrane conductance regulator (CFTR) gene, and thus, require patients to have genetic testing before initiation of modulator therapy. However, aside from CFTR genetic testing, pharmacogenomic testing is not standard of care for CF patients. The aim of this study is to determine the number of non-CFTR modulator medications with CPIC guidelines that are prescribed to patients with CF. We identified all patients with a diagnosis of CF and queried our hospital electronic medical records (EMR) for all orders, including inpatient and prescriptions, for all drugs or drug classes that have CPIC actionable guidelines for drug-gene pairs that can be used to guide therapy. We identified 576 patients with a diagnosis of CF that were treated at our institution during this 16-year period between June 2005 and May 2021. Of these patients, 504 patients (87.5%) received at least one drug that could have been dosed according to CPIC guidelines if pharmacogenomic results would have been available. Patients with CF have high utilization of drugs with CPIC guidelines, therefore preemptive pharmacogenomic testing should be considered in CF patients at the time of CFTR genetic testing.


Increase in liver antioxidant enzyme activities in non-alcoholic fatty liver disease.
Steatosis may increase oxidative stress, which is counteracted by cellular enzymatic (cytosolic and mitochondrial superoxide dismutases (Cu/Zn-SOD and Mn-SOD), glutathione peroxidase (GPx), catalase) and non-enzymatic antioxidant systems. We aimed to determine, in patients with non-alcoholic fatty liver disease (NAFLD), the level of antioxidant defenses (1) in liver biopsies, to demonstrate the existence of oxidative stress; (2) in erythrocytes and plasma, to determine whether their antioxidant defenses reflect liver oxidative stress. Erythrocyte and plasma antioxidant defenses were prospectively studied in two groups of 16 patients: patients with NAFLD and controls. Liver biopsies were performed in eight NAFLD patients; liver antioxidant enzyme activities were measured and compared with those in 12 control livers used for transplantation. Cu/Zn-SOD, GPx and catalase activities were significantly higher in NAFLD livers than in controls whereas no significant differences were observed in Mn-SOD activity, and thiobarbituric acid-reactive substance (TBARS) concentration. No differences were observed in erythrocyte antioxidant enzyme activities (GPx, catalase, Cu/Zn-SOD), erythrocyte TBARS concentration, and plasma alpha-tocopherol concentration. Liver antioxidant enzyme activities were high in patients with NAFLD, reflecting an oxidative stress possibly involved in inflammation and fibrogenesis. However, erythrocyte and plasma antioxidant defenses did not reflect intrahepatic peroxidation.


Regulation of sex hormone-binding globulin secretion and gene expression by cycloheximide in vitro.
The role of protein synthesis in sex hormone-binding globulin (SHBG) secretion and gene expression was studied in HepG2 cell cultures. Inhibition of protein synthesis by cycloheximide suppressed SHBG levels. Triiodothyronine and estradiol increased SHBG production, and cycloheximide reduced their effects to an extent which correlated with the degree of suppression obtained with the drug alone. Insulin decreased SHBG production, and the effect of the treatment with insulin and cycloheximide together did not differ from that with cycloheximide alone. Cycloheximide did not, alone or with the hormones, decrease SHBG levels more markedly extra- than intracellularly. Therefore, cycloheximide does not impair the secretion of SHBG which is synthesized in the presence of the drug. In contrast to SHBG protein levels, cycloheximide increased SHBG mRNA levels. When the effect of cycloheximide on the rate of SHBG mRNA decay was tested, the drug was found to extend the half-life of SHBG mRNA. Of the hormones, insulin decreased and triiodothyronine modestly increased SHBG mRNA levels, whereas estradiol had no clear effect. Treatment with cycloheximide together with any of the hormones resulted in an increase in SHBG mRNA levels. We conclude that protein synthesis inhibition does not impair the secretion of SHBG produced under such conditions, but stabilizes SHBG mRNA by removing some hepatic protein species involved in the regulation of its degradation.


Neurotrophic effects of leptin on cerebellar Purkinje but not granule neurons in vitro.
As recent evidence has revealed a pro-survival role for the anti-obesity hormone leptin in the nervous system, we investigated the generality of this finding on cerebellar Purkinje and granule neurons in vitro. We found that whilst leptin promoted cerebellar Purkinje neuron survival, it had no affect on cerebellar granule cells. In addition, we discovered that leptin promoted both the outgrowth of neurites from cerebellar Purkinje neurons and increased the complexity of the neurite arbor. Thus, leptin has different effects on two neighbouring populations of neurons within the cerebellum implying specificity of its actions in the central nervous system.


Intensification of pharmacological decongestion but not the actual daily loop diuretic dose predicts worse chronic heart failure outcome: insights from TIME-CHF.
Both loop diuretics (LDs) and congestion have been related to worse heart failure (HF) outcome. The relationship between the cause and effect is unknown. The aim of this study was to investigate the interaction between congestion, diuretic use and HF outcome. Six hundred and twenty-two chronic HF patients from TIME-CHF were studied. Congestion was measured by means of a clinical congestion index (CCI). Loop diuretic dose was considered at baseline and month 6. Treatment intensification was defined as the increase in LD dose over 6 months or loop diuretic and thiazide or thiazide-like diuretic co-administration. The end-points were survival and HF hospitalisation-free survival. High-LD dose at baseline and month 6 (≥ 80 mg of furosemide per day) was not identified as an independent predictor of outcome. CCI at baseline remained independently associated with impaired survival [hazard ratio (HR) 1.34, (95% confidence interval) (95% CI) (1.20-1.50), p < 0.001] and HF hospitalisation-free survival [HR 1.09, 95% CI (1.02-1.17), p = 0.015]. CCI at month 6 was independently associated with HF hospitalisation-free survival [HR 1.24, 95% CI (1.11-1.38), p < 0.001]. Treatment intensification was independently associated with survival [HR 1.75, 95% CI (1.19-1.38), p = 0.004] and HF hospitalisation-free survival [HR 1.69, 95% CI (1.22-2.35), p = 0.002]. Patients undergoing treatment intensification resulting in decongestion had better outcome than patients with persistent (worsening) congestion despite LD dose up-titration (p < 0.001). Intensification of pharmacological decongestion but not the actual LD dose was related to poor outcome in chronic HF. If treatment intensification translated into clinical decongestion, outcome was better than in case of persistent or worsening congestion.


Complex karyotypic aberrations, including i(12p), in malignant mixed mullerian tumor of uterus.
We report the cytogenetic findings in a malignant mixed mullerian tumor of the uterus in a 59-year-old woman. Karyotypic analysis of short-term cultures revealed two abnormal clones of cells characterized by extensive structural and numerical rearrangements. An i(12p) maker chromosome was present in addition to other changes in both clones. This marker, characteristically associated with testicular germ cell tumors in males, has recently been reported in ovarian germ cell tumors, a mediastinal germ cell tumor and in a mixed mullerian tumor of the ovary.


Spying on parahydrogen-induced polarization transfer using a half-tesla benchtop MRI and hyperpolarized imaging enabled by automation.
Nuclear spin hyperpolarization is a quantum effect that enhances the nuclear magnetic resonance signal by several orders of magnitude and has enabled real-time metabolic imaging in humans. However, the translation of hyperpolarization technology into routine use in laboratories and medical centers is hampered by the lack of portable, cost-effective polarizers that are not commercially available. Here, we present a portable, automated polarizer based on parahydrogen-induced hyperpolarization (PHIP) at an intermediate magnetic field of 0.5 T (achieved by permanent magnets). With a footprint of 1 m2, we demonstrate semi-continuous, fully automated 1H hyperpolarization of ethyl acetate-d6 and ethyl pyruvate-d6 to P = 14.4% and 16.2%, respectively, and a 13C polarization of 1-13C-ethyl pyruvate-d6 of P = 7%. The duty cycle for preparing a dose is no more than 1 min. To reveal the full potential of 1H hyperpolarization in an inhomogeneous magnetic field, we convert the anti-phase PHIP signals into in-phase peaks, thereby increasing the SNR by a factor of 5. Using a spin-echo approach allowed us to observe the evolution of spin order distribution in real time while conserving the expensive reagents for reaction monitoring, imaging and potential in vivo usage. This compact polarizer will allow us to pursue the translation of hyperpolarized MRI towards in vivo applications further.


Safety and efficiency of oocyte vitrification.
As the oocyte is the starting point for a new life, artificial reproductive technology (ART) techniques should not affect the (ultra) structural and functional integrity, or the developmental competence. Oocyte vitrification -one of the most significant achievements in human ART during the past decade- should therefore be a safe and efficient technique. This review discusses the principles and developments of the existing and future techniques, applications possibilities and safety concerns. The broad range of vitrification media and devices that are currently available, show differences in their effects on the oocyte ultrastructure and preimplantation development. It is not yet fully decided whether this has an influence on the obstetric and neonatal outcome, since only limited information is available with different media and devices. For autologous oocytes, the obstetric and neonatal outcomes appear promising and comparable to pregnancies obtained with fresh oocytes. This however, is not the case for heterologous fresh or vitrified oocytes, where the immunological foreign foetus induces adverse obstetric and neonatal outcomes. Besides the oocyte vitrification process itself, the effect of multiple stimulations (for oocyte banking or for oocyte donors), seems to influence the possibility to develop gynaecological cancers further in life. Automated vitrification/warming should offer a consistent, cross-contamination free process that offers the highest safety level for the users. They should also produce more consistent results in survival, development and clinical pregnancies between different IVF clinics.


[Study on morphology of Blastocystis hominis in culture and from diarrhea patients].
To study morphology of different stage Blastocystis hominis (B. h) for establishing a base in the research of life cycle and pathogenicity of B. h and providing information for clinical laboratory. B. h from diarrheal patients was continuously cultured in LES medium, and morphology of B. h was studied with iodine and iron hematoxylin staining under light microscope. The vacuolar, granular, amoeboid and cyst forms of B. h and transformation among the forms were observed microscopically. Among different forms, the vacuolar and granular forms were often seen clinically and the vacuolar form can transform to cysts.


Radiosensitization of human glioma cells in vitro and in vivo with acyclovir and mutant HSV-TK75 expressed from adenovirus.
We recently reported that an adenovirus-expressing mutant HSV-TK75 (AdCMV-TK75) radiosensitized rat syngeneic gliomas in combination with low concentrations of acyclovir (ACV) much more effectively than a virus expressing wild-type herpes simplex virus thymidine kinase (HSV-TK). In this report we have examined whether similar radiosensitizing effects are also seen with human glioma cells in vitro and in vivo. Human U87 MG glioma cells were transduced with AdCMV-TK75 and exposed to ACV followed by single-dose irradiation and colony-forming survival assays. Similarly, U87 MG xenografts were infused with AdCMV-TK75 or Adbetagal control virus, followed by ACV administration and fractionated irradiation. Therapeutic efficacy was monitored by tumor growth. U87 MG cells transduced with AdCMV-TK75 were significantly more sensitive to ACV (3 microM) than cells transduced with either wild-type HSV-TK or control virus. To determine whether human cells also demonstrate improved radiosensitization similar to that seen with rat glioma cells and tumors, we transduced U87 MG cells with either AdCMV-TK75, AdCMV-TK, expressing wild-type HSV-TK, or Adbetagal and then treated the cells with 3 microM of ACV. Cells transduced with AdCMV-TK75 were significantly more radiosensitive (dose enhancement ratio [D(37)]: 2.6) by colony-forming survival assay than cells transduced with either AdCMV-TK or Adbetagal. Furthermore, we found that U87 MG xenografts infused with AdCMV-TK75 by slow positive pressure infusion were more radiosensitive after administration of ACV than tumors infused with Adbetagal. A more dramatic result was achieved when fractionated irradiation was carried out concurrently with ACV administration, in which case AdCMV-TK75-treated tumors did not grow at all. These results demonstrate that transduction of human glioma cells in vitro and infusion of xenografts in vivo with AdCMV-TK75 and treatment with concentrations of ACV that can be achieved in vivo produce similar radiosensitization, as previously reported with rat glioma cells and intracerebral syngeneic tumors. In addition, concurrent treatment with ACV and radiation therapy is more efficient than when ACV is administered before radiation therapy.


The phosphorus budget of the Thame catchment, Oxfordshire, UK: 1. Mass balance.
The relative magnitudes of annual diffuse and point source loads of phosphorus (P) to the River Thame were estimated from daily and monthly measurements of discharge and concentration. Existing data from gauging and monitoring sites on the river network and at point sources were supplemented by survey data at a range of spatial scales. Results showed that during low flow periods most of the P could be attributed to point sources, while at high flows the figure was less than 10%. The introduction of P stripping at Aylesbury, a major sewage treatment works in the catchment, was estimated to have reduced the annual load of P from the sewage treatment works by approximately 45 t, with a similar reduction in loss from the catchment. This gave a reduction in low flow concentrations of soluble reactive phosphorus (SRP) from 2.5 to 1.7 mg l(-1). Concentrations of SRP in river water remain above eutrophication thresholds because of the influence of other STWs in the catchment and insufficient natural discharge to dilute this.


Real-World LEAP Implementation.
In 2015, findings from the Learning Early About Peanut allergy (LEAP) trial provided the first convincing evidence that peanut allergy may be preventable through early peanut introduction into the infant diet. Here we discuss implementation of the LEAP study findings around the world and emerging evidence of the impacts on infant feeding and food allergy. The LEAP findings led to rapid changes in allergy prevention guidelines internationally to recommend early peanut introduction. There is now emerging evidence that this has been followed by a substantial increase in early peanut introduction to infants. Studies investigating the impact of these changes in infant feeding practices on the prevalence of peanut allergy are underway. The LEAP trial represented a significant step forwards in food allergy prevention and new research over the past 5 years has provided insights into how best to implement this intervention in the real world.


Characterization of water-soluble hemicelluloses from spruce and aspen employing SEC/MALDI mass spectroscopy.
Partly depolymerized hemicelluloses isolated from wood chips of spruce and aspen employing microwave treatment were resolved using size-exclusion chromatography (SEC) into oligo- and polysaccharide fractions containing components with a narrow range of sizes, as determined by MALDI mass spectroscopy. The degree of substitution with acetyl moieties (DS) was also calculated on the basis of the MALDI-MS spectra obtained prior to and following deacetylation. For spruce hemicelluloses, the low molecular mass fraction contained small arabino-4-O-methylglucuronoxylan oligosaccharides, with DP values ranging from 4 to approximately 20, separated primarily on the basis of their charge density. The fraction eluted last consisted of an O-acetyl-(galacto)glucomannan polysaccharide of peak-average DP value (DP(p)) 14. The degree of substitution with acetyl groups (DS) decreased with decreasing DP, a value DS of 0.39 being obtained for the fraction with DP(p) 12. For the aspen hemicelluloses, the SEC fractions eluted first contained an acidic O-acetyl-4-O-methylglucuronoxylan polysaccharide with DP ranging from 10 to approximately 28 and an average DS of approximately 0.75. The fractions eluted last consisted of oligosaccharide mixtures composed primarily of small neutral O-acetyl-xylooligosaccharides (DP(p) 6, DS 0.41), together with minor quantities of an O-acetyl-glucomannan.


Ultrasound-guided peripheral nerve blocks: what are the benefits?
Use of ultrasound by anaesthesiologists performing regional blocks is rapidly gaining popularity. The aims of this review were to summarize and update accumulating evidence on ultrasound-guided nerve blocks, with an emphasis on the clinical relevance of the results and to critically appraise changing standards in regional anaesthesia. A search of MEDLINE and EMBASE (1966 to 31 December 2007) was conducted using the following free terms: 'ultrasound and regional anesthesia', 'ultrasound and peripheral block' and 'ultrasound and nerve and block'. These were combined with the MESH terms 'nerve block' and 'ultrasonography'. The following limits were applied: studies with abstracts, only in humans, published in core clinical journals. Trial type: meta-analysis, randomized-controlled trial and clinical trial. When peripheral nerves are adequately imaged by ultrasound, the concomitant use of nerve stimulation offers no further advantage. However, several studies reported problems with obtaining satisfactory images in some patients. Ultrasound guidance significantly shortened the block performance time and/or reduced the number of needle passes to reach the target in all comparative studies. The occurrence of paraesthesia during block performance was also reduced, but not the incidence of short-lasting post-operative neuropraxia. The frequency of accidental vascular punctures may be lower, but the data are contradictory. Block onset time was significantly shortened. Block duration was longer in children, but not in adults. Ultrasound also allowed dose reduction of the local anaesthetic (LA). Ultrasound guidance shortens the block performance time, reduces the number of needle passes and shortens the block onset time. Blocks may be performed using lower LA doses.


Biologics for allergy: therapeutic potential for ocular allergic diseases and adverse effects on the eye.
Biologics applying antibodies against IgE, IL-5, IL-5 receptor α, IL-4 receptor α, and IL-13 have dramatically improved recent treatment outcomes in allergic diseases including asthma, rhinitis, and atopic dermatitis. However, these drugs have not been approved for ocular allergic diseases such as allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. Although the putative mechanisms suggest that these drugs should have beneficial effects in patients with ocular allergies and some studies have reported such beneficial effects, various adverse ocular symptoms have also been observed in clinical trials and off-label use studies. Since ocular allergic diseases have distinct pathogeneses, each biologic drug must be examined regarding specific effects on each ocular allergy. For example, IgE-mediated type 1 hypersensitivity plays a critical role in allergic conjunctivitis. By contrast, T cells and eosinophilic and non-IgE-mediated type 2 inflammation play important roles in vernal keratoconjunctivitis. Allergists must fully understand the effects of each drug on the eye. This review outlines both potential therapeutic and adverse effects of various biologics on allergic diseases of the eye.


Host genes and dental caries.
With the attention now being given to molecular genetic analysis of cariogenic microorganisms, the role of host genes in influencing susceptibility to caries should not be forgotten. Increasing knowledge in this field will lead to identification of individuals at particular risk of dental decay and will help in planning rational strategies for management and prevention.


Erythrocyte superoxide dismutase in different racial groups in Malaysia. A variant in a Filipino.
A rare electrophoretic variant of superoxide dismutase (SOD) was found in one Filipino of 146 Filipinos, 1382 Malaysians and 816 Indonesians examined. The variant consists of two usual bands and two slower migrating bands similar to those reported earlier. Superoxide dismutase variants are common among people of certain localized regions in Europe, however, this is the first report of such a variant occurring in people of non-European origin.


Down regulation of Peroxiredoxin-3 in 3T3-L1 adipocytes leads to oxidation of Rictor in the mammalian-target of rapamycin complex 2 (mTORC2).
Mitochondrially-derived oxidative stress has been implicated in the development of obesity-induced insulin resistance and is correlated with down regulation of Peroxiredoxin-3 (Prdx3). Prdx3 knockout mice exhibit whole-body insulin resistance, while Prdx3 transgenic animals remain insulin sensitive when placed on a high fat diet. To define the molecular events linking mitochondrial oxidative stress to insulin action, Prdx3 was silenced in 3T3-L1 adipocytes (Prdx3 KD) and the resultant cells evaluated for mitochondrial function, endoplasmic reticulum stress (ER stress), mitochondrial unfolded protein response (mtUPR) and insulin signaling. Prdx3 KD cells exhibit a two-fold increase in H2O2, reduced insulin-stimulated glucose transport and attenuated S473 phosphorylation of the mTORC2 substrate, Akt. Importantly, the decrease in glucose uptake can be rescued by pre-treatment with the antioxidant N-acetyl-cysteine (NAC). The changes in insulin sensitivity occur independently from activation of the ER stress or mtUPR pathways. Analysis of mTORC2, the complex responsible for phosphorylating Akt at S473, reveals increased cysteine oxidation of Rictor in Prdx3 KD cells that can be rescued with NAC. Taken together, these data suggest mitochondrial dysfunction in adipocytes may attenuate insulin signaling via oxidation of the mammalian-target of rapamycin complex 2 (mTORC2).


Semisynthetic oleanane triterpenoids inhibit migration and invasion of human breast cancer cells through downregulated expression of the ITGB1/PTK2/PXN pathway.
This paper reports a study on the role of two synthetic derivatives of oleanolic acid (OA), HIMOXOL and Br-HIMOLID, in the regulation of cell migration and invasion and the underlying molecular mechanisms of breast cancer cells. The effect of the compounds on four breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-468, and T-47D) and also on noncancerous breast cells, MCF-12A, was reported. The compounds had no effect on the migration of MCF-12A cells. However, both the derivatives revealed a higher cytotoxicity than the maternal compound OA, and in sub-cytotoxic concentrations, they decreased the migration of MCF7, MDA-MB-231, and MDA-MB-468 breast cancer cells and also the invasion of MCF7 and MDA-MB-231 cells; although, the derivatives had no effect on the migration and invasion of T-47D cells. Both the derivatives of OA inhibited the cell migratory and invasive abilities of breast cancer cells by downregulating the expressions of ITGB1, PTK2, and PXN genes and by decreasing the phosphorylation status and the level of its respective proteins (integrin β1, FAK, and paxillin, respectively). This study is the first to report the antimigratory and anti-invasive activities of HIMOXOL and Br-HIMOLID in breast cancer cells.


[Characteristics of pain in oncologic disease of the knee].
10% of > 55-year-old adults suffer some kind of non-neoplastic knee pain and 75% of the musculoskeletal neoplastic disease develops in the knee. to identify clinical characteristics of knee pain in neoplastic knee pathology. after appropriate authorization of the Local Committee of Investigation and under informed consent, we made a crosssectional and a risk analysis study. We included 160 patients who were seeking medical help due to knee pain. They answered a standardized questionnaire relating to the characteristics of their pain symptomatology. Data were integrated into two groups with knee pain; a) neoplasic (cases, n = 65), b) non-neoplasic (controls, n = 95) and analyzed (SPSS v.15™). We used homogeneity tests between groups (p > 0.05); inferential analysis (Student t test, χ(2)) and risk assessment (OR), p ≤ 0.05, (CI 95%), Statistical power was > 0.80. female gender predominated (55%); age was 40.3 ± 19.6 years. The most prevalent diagnoses were knee osteoarthritis 37% for non-neoplasic group; giant cell tumor 10% for benign neoplasic group and osteosarcoma 6.1% for neoplasic malignant group. Knee pain lasting < 4 months (OR 7.6; CI 95% 3.48-16.5) and severe intensity (OR 5.7; CI 95% 2.82-11.64), constant pain (OR 2.9; CI 95% 1.37-6.36), rapidly progressive fluctuation (OR 31; CI 95% 7.01-137) and nocturnal predominance (OR 7.72; CI 95% 3.2-18.5) were characteristics of neoplasic knee pain. the neoplasic knee pain was characterized for a rapid onset, severe and constant pain, progressive, fluctuation and predominantly by night-time.


Serum- and protein-free media formulations for the Chinese hamster ovary cell line DUKXB11.
The production of therapeutic proteins in mammalian cell lines is of outstanding importance. The maintenance of most mammalian cell lines in culture requires the addition of serum to the culture medium. The elimination of serum from mammalian cell culture is desirable since serum is expensive and a source of contaminants, e.g. viruses, mycoplasma or prions. Here we describe the composition of serum- and protein-free media for the Chinese hamster ovary (CHO) cell line DUKXB11. The serum-free formulation supports excellent growth of CHO DUKXB11 cells at low (23cells/cm2) and high (2 x 10(4) cells/cm2) seeding densities characterized by a generation time of 10-12h, and, after addition of 0.2% pluronic F-68, the growth of a recombinant suspension cell line derived from DUKXB11. In addition, this formulation also allowed us to adapt recombinant cell lines expressing various amounts of human antithrombin ATIII (ATIII) to serum-free conditions. Secretion of ATIII was readily observed in the serum-free medium. Minor changes to the serum-free formulation resulted in a protein free formulation that supported growth of CHO DUKXB11 cells, growth of recombinant CHO cells expressing ATIII, and production of ATIII.


Fusidic acid in infections of the external eye.
A newly developed 1% eye preparation of the potent antistaphylococcal antibiotic fusidic acid, showed an excellent clinical effect in 206 Egyptian children with external eye infections. The 248 patients included in the study were randomized, in the ratio 5:1, to either fusidic acid or chloramphenicol 0.5% eye drops. Both preparations were given four to six times daily for one week. Bacterial conjunctivitis was diagnosed in 56% of the children. Offending eye pathogens were mainly Staphylococcus aureus (60%), Haemophilus aegyptius (10%), Streptococcus pneumoniae (13%) and Neisseria gonorrhoeae (6%). The overall clinical success rate in children with bacterial conjunctivitis was 85% with fusidic acid, compared to 48% with chloramphenicol (p less than 0.001). The better effect of fusidic acid could be ascribed to a lower frequency of in vitro resistance (16%) in comparison to chloramphenicol (55%). Both drugs were apparently well tolerated and no side-effects were observed.


The Meaning of the Child Interview: A new procedure for assessing and understanding parent-child relationships of 'at-risk' families.
Reder and Duncan's well-known studies of the 1990s on fatal child abuse drew attention to how parental scripts regarding their children could dangerously distort relationships in ways that were sometimes fatal to children. This article reports on a new system for assessing the 'meaning of the child to the parent', called the Meaning of the Child Interview (MotC). Parents are interviewed using the established Parent Development Interview, or equivalent, and the transcript of the interview is then analysed according to parental sensitivity and likely risk to the child. The MotC constructs were developed from those used in observed parent-child interaction (specifically, the CARE-Index) and the form of discourse analysis used in the Dynamic Maturational Model - Adult Attachment Interview, allowing a more systemic and inter-subjective understanding of parenting representations than often put forward. This article discusses the theoretical background to the MotC, gives a brief review of similar measures and then introduces the coding system and patterns of caregiving. The validity of the MotC is addressed elsewhere.


High Performance Organic-Nanostructured Silicon Hybrid Solar Cell with Modified Surface Structure.
Silicon nanowires (SiNWs) with excellent light trapping properties have been widely applied in photovoltaic devices, which provide opportunities for boosting the photons harvested by Si. However, the photoexcited carriers are easily trapped and recombined by high-density surface defects due to higher surface area prolonging to depth of nanowire. In this work, in order to reduce the surface defects and recombination rate of SiNWs, a simple solution process is used to modify the surface structure. Applying the tetramethyl ammonium hydroxide (TMAH) treatment leads to smooth and taper Si NW surface, which improves the open-circuit voltage (Voc) and fill factor (FF) obviously. Thus, a champion PCE of 14.08% is achieved for the nanostructured Si/PEDOT:PSS hybrid device by 60-s TMAH treatment. It also indicates that TMAH treatment promises a simple and effective method for enhancing Si NW-based devices.


Intraoperative superior hypogastric plexus block for pain relief after a cesarean section: a case-control study.
To investigate the efficacy of intraoperative superior hypogastric plexus (SHP) block for postoperative pain relief in patients undergoing a cesarean section. One hundred and fifteen pregnant women scheduled for an elective cesarean under general anesthesia were randomly divided into an SHP block (n=65) and a control group (n=50). SHP block was administered with bupivacaine injection. The controls received saline injection in the SHP area. Postoperative pain was assessed by the 10-cm visual analog scale (VAS). The presence of side effects and complications, including opioid or non-steroidal anti-inflammatory drugs (NSAID) requirement, gastrointestinal function, nausea, and vomiting were evaluated. The SHP block group had significantly lower VAS scores 2, 6, 24, and 48 hours postoperatively (P<0.001) and required a significantly lower rescue dose of NSAID or opioids (P=0.003, P<0.05, respectively). SHP block may be an effective and safe pain relief treatment after a cesarean section.


The alternative sigma factor sigma B of Staphylococcus aureus modulates virulence in experimental central venous catheter-related infections.
The impact of the alternative sigma factor sigma B (SigB) on pathogenesis of Staphylococcus aureus is not conclusively clarified. In this study, a central venous catheter (CVC) related model of multiorgan infection was used to investigate the role of SigB for the pathogenesis of S. aureus infections and biofilm formation in vivo. Analysis of two SigB-positive wild-type strains and their isogenic mutants revealed uniformly that the wild-type was significantly more virulent than the SigB-deficient mutant. The observed difference in virulence was apparently not linked to the capability of the strains to form biofilms in vivo since wild-type and mutant strains were able to produce biofilm layers inside of the catheter. The data strongly indicate that the alternative sigma factor SigB plays a role in CVC-associated infections caused by S. aureus.


Time to pregnancy and perinatal outcomes in a cohort of spontaneous pregnancies.
Obstetric and perinatal outcomes depend not only on care during pregnancy, as there is an increasing evidence of their relationship with preexisting conditions. Woman's age and time to pregnancy (TTP) have been related to the prognosis in reproductive success, but TTP could influence fetal well-being and newborn. According to the World Health Organization, 48 million couples have subfertility globally. We analyzed the relationship between TTP and obstetric (premature labor, preeclampsia…), labor (type of delivery, postpartum hemorrhage…), and neonatal outcomes (low birth weight…) in a cohort of 190 spontaneous gestations. Subfertility is a disease defined by the failure to achieve a pregnancy after 12 months of regular unprotected sexual intercourse. TTP was >12 months in 23.1 % (95 % CI = 17.57-29.55), however, no correlation was found with the perinatal outcomes (p = 0.24). We observed that 45.2 % of subfertile women had obstetric complications, 13.2 % labor complications, and 34.2 % neonatal complications, whereas non-subfertile women had 29.4 %, 21.0 %, and 21.0 %, respectively. Half of pregnancies have at least one adverse outcome, and obstetric complications were the most frequent. Subfertility condition may appear in up to a fifth of our couples. Subfertility may behave as a mild risk factor for adverse perinatal outcomes. Obstetric or perinatal complication may be expected in up to half of the cases. Subfertile women ≥ 35 years of age have a 3-fold increase in their risk of having an obstetric complication when compared to non-subfertile women of the same age.


Treatments and outcomes in Chinese patients with serologically active clinically quiescent systemic lupus erythematosus: a retrospective observational study.
To clarify the frequency and outcome of patients with systemic lupus erythematosus (SLE) who achieved the clinical state as serologically active clinically quiescent (SACQ) and to identify factors associated with the flare of disease. Clinical data of patients diagnosed as SLE and followed in Peking University First Hospital from 2009 to 2015 were retrospectively reviewed. Six hundred eighty-two patients who were followed up for more than 6 months were analyzed. SACQ was defined as an at least a 6-month period with persistent serologic activity and without clinical activity and daily dose of prednisone or equivalent were less than 7.5 mg. Serologically quiescent clinically quiescent (SQCQ) patients served as control groups. Data including demographics, initial symptoms, duration to SACQ, treatments before and after SACQ, and characteristics of the patients suffered from flare were analyzed. Among the 682 patients, 170 patients were SACQ (24.9%) and 187 patients were SQCQ. SQCQ patients (38.61 ± 15.08 years old) were older at baseline than SACQ patients (38.61 ± 15.08 years vs. 32.09 ± 14.35 years, p < 0.001). Of 170 SACQ patients, 32.9% experienced flare that was significantly higher than 15.5% of SQCQ patients (29/187). Corticosteroids (OR 1.323, 95% CI 1.129 to 1.550; p = 0.001) was an independent risk factor for flare, while antimalarials (OR 0.045, 95% CI 0.004 to 0.474; p = 0.010) and immunosuppressants (OR 0.332, 95% CI 0.156 to 0.706; p = 0.004) were protective factors in SACQ patients; however, only antimalarials was protective factors in SQCQ patients (OR 0.028, 95% CI 0.001 to 0.743; p = 0.033). About one third of SLE patients with SACQ experience flare, significantly more frequent than that of patients with SQCQ. Thus, approach to prevent flare in SACQ patient is required. Maintenance therapy of hydroxychloroquine and immunosuppressant agents may be protective and beneficial treatment strategy in these patients.


Clinical challenges in a patient with dabigatran-induced fatal hemorrhage.
To report clinical challenges in managing dabigatran-induced bleeding. A 78-year-old woman came to the hospital with severe coagulopathy, respiratory failure, hypotension, and bleeding secondary to dabigatran therapy. At admission, creatinine clearance was 15 mL/min; prothrombin time, 147.5 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 12.42. Medications taken at home included dabigatran, 150 mg BID. During the hospitalization, multiple blood product transfusions were given, vitamin K and prothrombin complex concentrate were administered, and dialysis was initiated in an attempt to achieve hemostasis. Despite multiple interventions, coagulopathy persisted (prothrombin time, 70.8 seconds; activated partial thromboplastin time, >200 seconds; and international normalized ratio, 6.05), with continued bleeding. On hospital day 5, the patient died. According to the Naranjo probability scale, bleeding associated with dabigatran revealed a probable relationship. This fatal case illustrates our concern about the usefulness of currently recommended anticoagulation laboratory tests and of the efficacy of blood transfusion, dialysis, and prothrombin complex concentrate in managing life-threatening bleeding secondary to dabigatran. In addition, clinicians should be cognizant of the renal recommendations for the newer oral anticoagulant agents to prevent potentially catastrophic results.


MicroRNAs as regulators and mediators of c-MYC function.
In the past ten years microRNAs (miRNAs) have been widely implicated as components of tumor suppressive and oncogenic pathways. Also the proto-typic oncogene c-MYC has been connected to miRNAs. The c-MYC gene is activated in approximately half of all tumors, and its product, the c-MYC transcription factor, regulates numerous processes e.g. cell cycle progression, metabolism, epithelial-mesenchymal transition (EMT), metastasis, stemness, and angiogenesis, thereby facilitating tumor initiation and progression. c-MYC target-genes, which mediate these functions of c-MYC, represent a complex network of protein- and non-coding RNAs, including numerous miRNAs. For example, c-MYC directly regulates expression of the miR-17-92 cluster, miR-34a, miR-15a/16-1 and miR-9. Moreover, the expression and activity of c-MYC itself are under the control of miRNAs. Here, we survey how these networks mediate and regulate c-MYC functions. In the future, miRNAs connected to c-MYC may be used for diagnostic and therapeutic approaches. This article is part of a Special Issue entitled: Myc proteins in cell biology and pathology.


Anti-IgE-induced histamine release from rat tissues passively sensitized in vivo with myeloma IgE differs with strain and mast cell source.
Four different strains of rats, BDII, E3, LE, and OM/N, each with a low basal serum level of IgE, were examined with respect to anti-IgE- and ConA-induced release of histamine from serosal mast cells and chopped lung tissue. Tests were performed before and three days after i.p. injection of a graded dose of myeloma IgE (IR 162)-containing ascitic fluid. There was a clearcut strain difference in response capacity with respect to ConA- and anti-IgE-induced release of histamine from serosal mast cells before myeloma IgE-injection. Response capacity increased in some but not all strains after myeloma IgE injection; increase in response capacity of serosal mast cells did not correlate to that of chopped lung tissue. Analogous findings were observed when two of the strains, LE and E3, were passively sensitized by i.p. injection with serum containing another myeloma IgE (IR2). These results indicate that differences exist between mast cells of different rat strains, and within strain between mast cells of various tissues in capacity to become sensitized to myeloma IgE.


Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine.
The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that results from the combination of trastuzumab and DM1, a derivative of the antimicrotubule agent maytansine. This molecule has the ability to enhance cytotoxic drug delivery to specifically targeted cells that overexpress HER2, therefore, maximizing efficacy while sparing toxicity. In recent years, T-DM1 has shown to improve outcomes in metastatic HER2-positive breast cancer that is resistant to trastuzumab. In addition, T-DM1 is currently being tested in the neoadjuvant and adjuvant settings to identify patients who may benefit from this therapy. This review focuses on the mechanism of action, early and late-phase clinical trials, and ongoing studies of T-DM1 in HER2-positive breast cancer.


Evolutionarily conserved A-to-I editing increases protein stability of the alternative splicing factor Nova1.
The structural complexity of the vertebrate brain is mirrored by its unparalleled transcriptome complexity. In particular, two post-transcriptional processes, alternative splicing and RNA editing, greatly diversify brain transcriptomes. Here we report a close connection between these two processes: we show A-to-I RNA editing in Nova1, a key brain-specific regulator of alternative splicing. Nova1 editing levels increase during embryonic development in mouse and chicken brains and show significant variation across postnatal brain regions. Evolutionary conservation of both editing and editing-associated RNA secondary structure of the Nova1 mRNA for 300 million years attests to the functional importance of Nova1 editing. Using a combination of different assays in human HEK293T cell lines, we report a novel post-translational role for this RNA editing. Whereas functional assays showed no effect of RNA editing on the regulatory splicing activity of the encoded proteins, we found evidence that edited forms exhibit reduced proteasome targeting and increased protein half-life. In addition, we found evidence for similar regulation of protein half-life by an evolutionarily conserved alternative splicing event in Nova1. These results open new venues of research on the multi-level integration of gene expression by: (1) revealing the novel role of RNA editing in regulating protein stability, and (2) establishing protein stability as a new target of multifaceted regulation.


Biodemographic perspectives for epidemiologists.
A new scientific discipline arose in the late 20th century known as biodemography. When applied to aging, biodemography is the scientific study of common age patterns and causes of death observed among humans and other sexually reproducing species and the biological forces that contribute to them. Biodemography is interdisciplinary, involving a combination of the population sciences and such fields as molecular and evolutionary biology. Researchers in this emerging field have discovered attributes of aging and death in humans that may very well change the way epidemiologists view and study the causes and expression of disease. In this paper, the biodemography of aging is introduced in light of traditional epidemiologic models of disease causation and death.


The analysis of blood pressure profiles and their severity in relation to diabetic cardiovascular autonomic neuropathy in the Chinese population: preliminary analysis.
The study sought to investigate the associations of blood pressure profiles and its severity with diabetic cardiovascular autonomic neuropathy (DCAN) in a Chinese population. We conducted a community-based, cross-sectional study for risk factor analysis of DCAN in 455 individuals recruited from a Chinese population. Blood pressure profile risk score (BPRS) was calculated for associations between severity of blood pressure profile and DCAN. Multivariable logistic regression (MLR) was carried out to analyze the associations of blood pressure profiles and its severity with DCAN. In category variable models, participants with high SBP have significantly higher DCAN prevalence as compared to participants with low SBP (25.66 vs. 31.69 %, P = 0.011). MLR demonstrated that there was significant associations between SBP and DCAN controlling for potential confounding factors (P = 0.016). Moreover, MLR assessed significant associations of BPRS-0 or BPRS-2 with DCAN (P value = 0.014 for BPRS-0 and P value = 0.031 for BPRS-2). Our findings indicated that SBP and severity of BP profiles were significantly and independently associated with DCAN, respectively. These suggested BP profile may influence the progression of DCAN and also provided insight into biological functions. ClinicalTrials.gov Identifier NCT02461472.


Metabolic activity of bacteria isolated from soil, rhizosphere and mycorrhizosphere of pine (Pinus silvestris L.).
Casamino acids were found to be the best substrate for bacteria isolated from soil, rhizosphere and mycorrhizosphere of pine. Most active with this substrate were however the root zone bacteria. Glucose was oxidized similarly by the bacteria isolated from the three sources.


Membrane-damaging action of staphylococcal alpha-toxin on phospholipid-cholesterol liposomes.
The mechanism of membrane damage by staphylococcal alpha-toxin was studied using carboxyfluorescein (internal marker)-loaded multilamellar liposomes prepared from various phospholipids and cholesterol. Liposomes composed of phosphatidylcholine or sphingomyelin and cholesterol bound alpha-toxin and released carboxyfluorescein in a dose dependent manner, when they were exposed to alpha-toxin of concentrations higher than 1 or 8 micrograms/ml, respectively. In contrast, the other liposomes composed of phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol or phosphatidylinositol plus cholesterol were not susceptible to the toxin even at high concentrations up to 870 micrograms/ml. The insensitive liposomes containing either phosphatidylserine or phosphatidylglycerol were made sensitive to alpha-toxin by inserting phosphatidylcholine into the liposomal membranes. In addition, phosphorylcholine inhibited the toxin-induced marker release from liposomes. These results indicated that the choline-containing phospholipids are required for the interaction between alpha-toxin and liposomal membranes. Susceptibility of liposomes containing phosphatidylcholine or sphingomyelin increased with the increase in cholesterol contents of the liposomes. Based on these results, we propose that the choline-containing phospholipids are possible membrane components or structures responsible for the toxin-membrane interaction, which leads to damage of membranes. Furthermore, cholesterol may facilitate the interaction between alpha-toxin and membrane as a structural component of the membrane.


Pneumothorax during positive-pressure mechanical ventilation.
The hemodynamic and respiratory effects of unilateral pneumothorax were studied during positive-pressure mechanical ventilation in five sheep. The sheep were anesthetized, intubated, and placed on mechanical ventilation with positive end-expiratory pressure (5 cm H2O). After baseline studies, including chest roentgenograms, were taken, increments of air were injected into the right pleural cavity. Measurements were repeated at pneumothoraces of 500, 1,000, and 1,500 ml. There was a steady fall in cardiac output (p less than 0.02) at pneumothoraces of 1,000 and 1,500 ml. The decrease in cardiac stroke volume paralleled that of cardiac output. Heart rate rose (p less than 0.05) at a pneumothorax of 1,500 ml. There appeared to be a linear relationship between the percent increase in pneumothorax as estimated by roentgenogram and the percent fall in cardiac output (r = 0.991). There was a steady rise in mean pulmonary arterial, pulmonary arterial capillary wedge, superior vena caval, and inferior vena caval pressures, although the changes in inferior vena caval pressure were not statistically different from baseline. Peak airway pressure increased from baseline at pneumothoraces of 1,000 and 1,500 ml. Both right and left end-expiratory intrapleural pressures increased and were statistically different (p less than 0.01) from baseline. However, there was a substantially greater rise in right intrapleural pressure than left. Arterial oxygen tension remained physiological throughout the study. This study indicates that cardiac output decreases as the amount of pneumothorax increases in sheep during mechanical ventilation. This study also demonstrates that, during positive-pressure mechanical ventilation, a relatively benign-appearing pneumothorax by chest roentgenogram may be associated with a significantly depressed cardiac output. In addition, arterial oxygen tension may not be useful in predicting the onset of pneumothorax during mechanical ventilation.


Biogenic preparation of copper oxide nanoparticles using table olive: Catalytic reduction, cytotoxicity, and burn wound healing activities.
Green strategy for the preparation of copper oxide nanoparticles (CuO NPs) using table olive has been researched in the present work. Some characterization assays viz., transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) was used for evaluation of the crystal structure, size and morphology of the manufactured NPs. As a catalyst, the prepared material demonstrated remarkable catalytic capability (>99% in 4 min) for the reduction of rhodamine B using sodium borohydride. In addition, the treated cells with the CuO NPs were examined by regarding the cytotoxicity properties on normal (HUVEC) cell line. The results showed that the prepared CuO NPs did not have any cytotoxicity effects on HUVEC (up to 500 μg/mL). Furthermore, in vivo experiments on burn wounds in rats show that the synthesized CuO NPs ointment significantly diminished (p ≤ 0.01) the wound area. On the other hand, the wound contracture factor was increased in comparison with the control groups. Collectively, the CuO NPs prepared by biological method have potential applications in organic pollutants reduction and wound care applications. In this viewpoint, CuO NPs may be considered as an effective for treatment of different wounds including burn wounds or injuries from surgeries such as plastic surgery.


Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model.
Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between -13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. Strong correlations were observed between posture and: mean carotid/femoral arterial (r = - 0.97, r = - 0.87), intracranial, intrathecal (r = - 0.98, r = 0.94), jugular (r = - 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = - 0.83, r = 0.84, r = - 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of - 15.9 ± 6.0 dB/decade. Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.


The MCV MC159 protein inhibits late, but not early, events of TNF-α-induced NF-κB activation.
Tumor necrosis factor (TNF-alpha) triggers biphasic activation of the NF-kappaB transcriptional regulator. This process consists of an initial, IkappaBalpha-mediated transient phase and a later, persistent phase dependent on IkappaBbeta degradation. To presumably interfere with the fulfillment of this immunity-associated event in cells infected with the molluscum contagiosum virus (MCV), this pathogen produces the intracellular MC159 protein. To define the mode of action of MC159, the impact of TNF-alpha on HEK 293T cells ectopically expressing the MC159 protein was examined. In this regard, TNF-alpha-induced expression of an NF-kappaB-regulated luciferase reporter gene was partially inhibited by the MC159 protein. This ability was attributed to blockage of the persistent phase of TNF-alpha-induced NF-kappaB activation for the following reasons: (1) the initial phase of NF-kappaB transcriptional activation was not affected by the MC159 protein; (2) the MC159 protein inhibited TNF-alpha-directed degradation of IkappaBbeta, but not IkappaBalpha; and (3) expression of the late NF-kappaB-regulated cell genes, TNF-alpha and CCL2, was decreased in the presence of the MC159 protein while transcription of the early NF-kappaB-regulated cell gene, CXCL1, was not altered. Previously reported MC159-RIP interactions appear to be irrelevant for the MC159 inhibitory function. In contrast, MC159-TRAF2 associations are more relevant for inhibitory function since mutant MC159 proteins unable to bind TRAF2 also cannot inhibit TNF-mediated NF-kappaB activation. In vivo, the MC159 protein may act to prolong virus survival by preventing the infected cell from responding to TNF-alpha, ultimately preventing the cellular production of proinflammatory and immunoattractant molecules.


Urocanic acid-modified chitosan-mediated p53 gene delivery inducing apoptosis of human hepatocellular carcinoma cell line HepG2 is involved in its antitumor effect in vitro and in vivo.
The p53 tumor suppressor gene is the most frequently mutated gene identified in many tumors, including hepatocellular carcinoma (HCC). Gene therapy using the p53 gene has been proposed and performed with inactivation of p53 function. However, there have been few reports of nonviral vector-mediated p53 gene delivery in HCC. In this study, the wild-type p53 (wt-p53) gene was transfected into human hepatocellular carcinoma cell line HepG(2) using the urocanic acid-modified chitosan (UAC) as a nonviral vector, and transfection efficiency was determined by FACS analysis. UAC-mediated p53 transfection in HepG(2) cells resulted in high expression levels of wt-p53 mRNA and protein and significant cellular growth inhibition. DAPI staining and Annexin V/PI double-staining assay revealed apoptosis occurrence in HepG(2) cells after treatment with UAC/pEGFP-p53 complexes. In in vivo studies, intratumoral injection of UAC/pEGFP-p53 complexes into BALB/c nude mice bearing HepG(2) cells clearly suppressed tumor growth, and significantly induced apoptosis. These results demonstrated that UAC-mediated efficient p53 gene transfer could induce apoptosis thereby significantly inhibiting the growth of HepG(2) cells in vitro and in vivo, and suggested that UAC-mediated p53 gene delivery might be a promising approach for HCC gene therapy.


Effect of chitooligosaccharides on human gut microbiota and antiglycation.
Chitooligosaccharides (COS) have garnered great attention in the field of human healthcare. The prebiotic activities and antiglycation of COS were investigated using a combination of in vitro and in vivo studies. COS supplementation dramatically increased the levels of acetic acid, while reducing the concentrations of propionic and butyric acids. It also decreased the total bacterial population; however, it did not affect diversity and richness of the gut microbiota. In addition, COS modulated the gut microbiota composition by increasing Bacteroidetes, decreasing Proteobacteria and Actinobacteria, and lowering the Firmicutes/Bacteroidetes ratio. COS promoted the generation of beneficial Bacteroides and Faecalibacterium genera, while suppressing the pathogenic Klebsiella genus. The antiglycation activity of COS and acetic acid was dose-dependent. Furthermore, COS prevented the decrease of serum Nε-(carboxymethyl) lysine (CML) level caused by CML ingestion in a mouse model of diet-induced obesity. To improve host health, COS could be potential prebiotics in food products.


Lipoatrophic diabetes in familial partial lipodystrophy type 2: From insulin resistance to diabetes.
Subjects with Familial Partial Lipodystrophy type 2 (FPLD2) are at high risk to develop diabetes. To better understand the natural history and variability of this disease, we studied glucose tolerance, insulin response to an oral glucose load, and metabolic markers in the largest cohort to date of subjects with FPLD2 due to the same LMNA variant. A total of 102 patients aged > 18 years, with FPLD2 due to the LMNA 'Reunionese' variant p.(Thr655Asnfs*49) and 22 unaffected adult relatives with normal glucose tolerance (NGT) were enrolled. Oral Glucose Tolerance Tests (OGTT) with calculation of derived insulin sensitivity and secretion markers, and measurements of HbA1c, C-reactive protein, leptin, adiponectin and lipid profile were performed. In patients with FPLD2: 65% had either diabetes (41%) or prediabetes (24%) despite their young age (median: 39.5 years IQR 29.0-50.8) and close-to-normal BMI (median: 25.5 kg/m2 IQR 23.1-29.4). Post-load OGTT values revealed insulin resistance and increased insulin secretion in patients with FPLD2 and NGT, whereas patients with diabetes were characterized by decreased insulin secretion. Impaired glucose tolerance with normal fasting glucose was present in 86% of patients with prediabetes. Adiponectin levels were decreased in all subjects with FPLD2 and correlated with insulin sensitivity markers. OGTT reveals early alterations of glucose and insulin metabolism in patients with FPLD2, and should be systematically performed before excluding a diagnosis of prediabetes or diabetes to adapt medical care. Decreased adiponectin is an early marker of the disease. Adiponectin replacement therapy warrants further study in FPLD2.


Synthesis of trimetallic oxide (Fe2O3-MgO-CuO) nanocomposites and evaluation of their structural and optical properties.
In this paper, tri-phase Fe2O3-MgO-CuO nanocomposites (NCs) and pure CuO, Fe2O3 and MgO nanoparticles (NPs) were prepared using sol-gel technique. The physical properties of the prepared products were examined using SEM, XRD, and UV-visible. The XRD data indicated the formation of pure CuO, Fe2O3 and MgO NPs, as well as nanocomposite formation with Fe2O3 (cubic), MgO (cubic), and CuO (monoclinic). The crystallite size of all the prepared samples was calculated via Scherrer's formula. The energy bandgap of CuO, Fe2O3 and MgO and Fe2O3-MgO-CuO NCs were computed from UV-visible spectroscopy as following 2.13, 2.29, 5.43 and 2.96 eV, respectively. The results showed that Fe2O3-MgO-CuO NCs is an alternative material for a wide range of applications as optoelectronics devices due to their outstanding properties.


Influence of leaf traits on the spatial distribution of insect herbivores associated with an overstorey rainforest tree.
The spatial distribution of insect herbivores associated with the Australian rainforest treeArgyrodendron actinophyllum (Sterculiaceae) was investigated by restricted canopy fogging. The foliage of this species was low in nitrogen and water content, and high in fibre content. Herbivore abundance was positively correlated with the amount of young foliage present within the samples and in adjacent samples, and with the nitrogen content of young leaves. In particular, the occurrence of phloem-feeders was correlated with the magnitude of translocation within the samples. The influence of leaf water content upon herbivore distribution was marginal, presumably because this factor is not limiting in rain-forest environments during the wet season, which usually coincides with the season of leaf-flush. Specific leaf weight, leaf size and foliage compactness had little or no apparent effect on herbivore distribution. Since the magnitude of leaf turnover affected both the quantity and the quality, as exemplified by translocation effects, of young foliage available, this factor may be critical to herbivores associated with evergreen rainforest trees which are particularly low in foliar nutrients, such asA. actinophyllum.


A dye sensitized solar cell using natural counter electrode and natural dye derived from mangosteen peel waste.
Mangosteen peel is an inedible portion of a fruit. We are interested in using these residues as components of a dye sensitized solar cell (DSSC). Carbonized mangosteen peel was used with mangosteen peel dye as a natural counter electrode and a natural photosensitizer, respectively. A distinctive mesoporous honeycomb-like carbon structure with a rough nanoscale surface was found in carbonized mangosteen peels. The efficiency of a dye sensitized solar cell using carbonized mangosteen peel was compared to that of DSSCs with Pt and PEDOT-PSS counter electrodes. The highest solar conversion efficiency (2.63%) was obtained when using carbonized mangosteen peel and an organic disulfide/thiolate (T2/T(-)) electrolyte.


Erratum to: Short-Term Exposure to Enriched Environment in Adult Rats Restores MK-801-Induced Cognitive Deficits and GABAergic Interneuron Immunoreactivity Loss.
The original version of this article unfortunately contained a mistake. The name of author was changed from "Pascual Gargiulo" to "Pascual Ángel Gargiulo.


CT coronary angiography: quantitative assessment of myocardial perfusion using test bolus data-initial experience.
The aim of this study is to quantify myocardial perfusion during coronary CT angiography using data from a modified timing test-bolus acquisition. Institutional review board approval and informed consent were obtained. Nineteen patients with suspected coronary artery disease underwent combined coronary CT angiography and cardiac (82)Rubidium-PET perfusion. Prior to the CT angiogram a retrospectively ECG-gated dynamic test bolus was obtained following 25 mls of IV contrast medium injected at 5 ml/s. Images were acquired every 1.5 s for 30 s using 4 x 1.25-mm slices at 120 kV, 35 mAs. Regions of interest were drawn to delineate the myocardium and aorta on the resulting transaxial images. Time density curves were created and perfusion calculated using two simple approaches: maximum-slope method and peak method. In patients with normal PET myocardial perfusion, the mean (SD) resting myocardial perfusion estimated by CT using the maximum-slope method was 0.89 (+/-0.27) ml/min/g and 0.93 (+/-0.21) ml/min/g at end-systole and end-diastole, respectively, and 0.69 (+/-0.11) ml/min/g and 0.79 (+/-0.19) at end-systole and end-diastole, respectively, for the peak method. Thus quantification of myocardial perfusion from a routine coronary CT angiography test bolus is possible. CT-derived myocardial perfusion values are consistent with published values derived from other techniques.


Monoclonal antibodies for the rapid diagnosis of respiratory syncytial virus infection by immunofluorescence.
Eight separate monoclonal antibodies to the Long strain of respiratory syncytial virus (RSV) were tested for their utility as rapid diagnostic reagents in immunofluorescence. Preliminary screening indicated that all 8 reacted with 11 field strains from three previous local RSV outbreaks and with 4 of 5 additional strains chosen because of their antigenic diversity by neutralization. Two monoclonal antibodies, one each directed against a surface glycoprotein and the nucleocapsid protein, were then compared, singly and combined, with a polyclonal antiserum as diagnostic reagents in 209 consecutive samples submitted to our diagnostic laboratory. Agreement between the two monoclonal antibodies was 100% and between them and the polyclonal serum was 98%. Sensitivity in relation to culture was 96-98%. Monoclonal antibodies are excellent immunofluorescent diagnostic reagents; antigenic diversity among RSV strains was not an impediment to their use in this study.


Inactivated pep27 mutant as an effective mucosal vaccine against a secondary lethal pneumococcal challenge in mice.
A pep27 mutant may be able to elicit mucosal immunity against pneumococcal diseases, and could be employed as an inexpensive attenuated vaccine. However, this particular mutant contains an erythromycin-resistance marker. The purpose of the current study is to develop a markerless pep27 mutant and assess whether this inactivated mutant is able to induce mucosal immunity. Mice were vaccinated intranasally with the inactivated markerless pep27 mutant every 2 weeks for a total of three times, after which time serum samples were analyzed for antibody titers. The mice were then challenged with a lethal D39 strain and their survival time was measured. The cross-reactivity of the antisera against pep27 was also compared to other mutant serotypes. Intranasal immunization of mice with the inactivated markerless pep27 mutant provides effective protection and rapidly cleared bacterial colonization in vivo. Moreover, antisera raised against the pep27 mutant may cross-react with several other serotype strains. Intranasal immunization with the inactivated pep27 mutant may be able to provide mucosal immunity, and could represent an efficient mucosal vaccine.


Evaluation of the vestibular system with video head impulse test in pregnant women with hyperemesis gravidarum.
We aimed to evaluate the semicircular canal functions of the vestibular system in pregnant women with hyperemesis gravidarum. This is a prospective case-control study. Among pregnant women in their first trimester (<14. gestational weeks) who presented to our outpatient clinic, 36 patients diagnosed with hyperemesis gravidarum defined as persistent nausea and vomiting requiring intravenous hydration or loss of at least 5% of prepregnancy weight and 34 healthy pregnant without nausea and vomiting were included. Otorhinolaryngologic examination and video head impulse test (vHIT) was performed to all patients. Vestibular-ocular reflex (VOR) gain and gain asymmetry were assessed between groups. The VOR gains in each semicircular canal did not differ between hyperemesis and control groups. Using a VOR gain cut-off value of 0.8, the groups were compared in terms of the frequency of low values. In the hyperemesis group, abnormally low gain values of left anterior canal were more frequently observed than in the control group (32 [88.9%], 22 [64.7%], respectively, P = 0.01). In left anterior-right posterior (LARP) plane VOR gain asymmetry was higher in hyperemesis group (13.5 [1.0-71.0], 6.0 [0.0-35.0], P = 0.001). No significant gain asymmetry was detected between the groups in the other planes. Semicircular canal functions were not abnormal globally in women with hyperemesis gravidarum. However, higher LARP plane asymmetry and low LA gain in women with hyperemesis suggests need for further research to clarify functional role of vestibular system on hyperemesis gravidarum.


Alveolar bone changes after tooth-borne surgically assisted rapid maxillary expansion: A three-dimensional study.
Surgically assisted rapid maxillary expansion (SARME) with a dental-anchorage appliance can induce dental and skeletal complications adjacent to the teeth supporting the device. The purpose of this study was to quantify the dentoskeletal changes observed after SARME using a tooth-borne device. Cone beam CT images from 39 patients were compared between the preoperative (T1) and the postoperative period (T2). The mean time to complete the second imaging was 13.8 ± 6.9 months after the SARME. Dental and bone parameters were assessed: the vestibular bone height (BH), the bone thickness (BT), the existence of fenestrations, and the root resorption at the level of first upper premolar (P1) and the first upper molar (M1). The maxillary expansion parameters were also collected. Both vertical and horizontal vestibular bone loss were observed mainly in the first upper molar sectors: The BT decreased from 0.93 ± 0.50 mm to 0.53 ± 0.51 mm (p < 0.0001) and the BH decreased from 1.84 ± 1.05 mm to 0.93 ± 1.02 mm (p < 0.0001) for tooth #16. The bone loss also affected the first upper premolars but in a more limited manner. Significant fenestrations were observed at the apex of the mesio-vestibular root of teeth #16 and #26. We noted significant root resorption affecting the mesio-, disto-vestibular and palatal roots of tooth #16 (mean reductions of 0.32, 0.35, and 0.55 mm, respectively; p < 0.05), and the palatal root of tooth # 26 (loss of 0.58 mm; p = 0.004). The mean bone expansion was 3.76 mm and 1.41 mm at the premolar and molar levels, respectively (p < 0.0001), while a mean 6.24 mm and 4.23 mm inter-cuspid expansion was noted at the P1 and M1 levels (p < 0.0001). Our results document the vestibular bone changes and low root resorption, mostly in the molar sectors, associated with SARME using dental-anchorage devices.


Modified Functional Walking Categories and participation in people with multiple sclerosis.
Gait velocity influences the ability of a person to move in different outdoor or indoor contexts and has accordingly been classified through the Modified Functional Walking Categories (MFWC). Community ambulation in persons with multiple sclerosis (PwMS) may give information on their social and productive participation, as well as independence in household activities. To investigate factors associated with walking and mobility restrictions as classified by the Modified Functional Walking Categories (MFWC) and analyze the influence of disease characteristics, demographical and walking factors on participation in PwMS. 155 PwMS attending two rehabilitation center were evaluated. Community ambulation was classified with the MFWC; participation was measured with the Community Integration Questionnaire (CIQ). MFWC and statistically significant variables associated with CIQ score were entered in a multivariate logistic model to assess the multiple relationships. PwMS with a secondary progressive type of disease, longer disease duration and using walking aids were classified in the worse MFWC. Participation restrictions were more frequent in Limited Household (72.3%) and in Physiological Walkers (93.7%). The final multivariate model (p < 0.0001) showed that the use of a walking aid (OR = 2.59), being male (OR = 2.94) and older (OR = 1.06) increased the likelihood of having participation restrictions. The same variables predicted home participation; MFWC and age predicted productive participation while only age influenced social participation. Modified Functional Walking Categories were associated with type of disease, disease duration, disability level and type of walking aid. The best clinical predictor of participation restriction was walking aid while walking categories only predicted productive participation.


Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest.
Therapeutic hypothermia improves survival and neurological outcome in patients successfully resuscitated after cardiac arrest. Accurate temperature control during cooling is essential to prevent cooling-related side effects. Prospective observational study of 12 patients assessed during therapeutic hypothermia (32-34°C) achieved by intravascular cooling following cardiac arrest. Simultaneous temperature measurements were taken using a Swan-Ganz catheter (blood temperature BLT), nasopharyngeal probe (nasopharyngeal temperature NPT) and the urinary bladder catheter (urinary bladder temperature UBT). A total of 1728 measurements (144 measurements per patient) were recorded over a 48-h period and analyzed. Blood temperature was considered as the reference measurement. Temperature profiles obtained from BLT, NPT and UBT compared with the use of analysis of variance did not differ significantly. Pearson correlation revealed that the correlation between BLT and NPT as well as BLT and UBT was statistically significant (r=0.96, p<0.001 and r=0.95, p<0.001, respectively). Bland-Altman analysis proved that the agreement between all measurements was satisfactory and the differences were not clinically important. In 12 post-cardiac arrest patients undergoing intravascular cooling, both nasopharyngeal and urinary bladder temperature measurements were similar to blood temperatures measured using a pulmonary artery catheter.


The Hsp70-Hsp90 co-chaperone Hop/Stip1 shifts the proteostatic balance from folding towards degradation.
Hop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70-Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures the proteostatic equilibrium. Thus, cells may act on the level and/or activity of Hop to shift the proteostatic balance between folding and degradation.


Long Paths in First Passage Percolation on the Complete Graph II. Global Branching Dynamics.
We study the random geometry of first passage percolation on the complete graph equipped with independent and identically distributed positive edge weights. We consider the case where the lower extreme values of the edge weights are highly separated. This model exhibits strong disorder and a crossover between local and global scales. Local neighborhoods are related to invasion percolation that display self-organised criticality. Globally, the edges with relevant edge weights form a barely supercritical Erdős-Rényi random graph that can be described by branching processes. This near-critical behaviour gives rise to optimal paths that are considerably longer than logarithmic in the number of vertices, interpolating between random graph and minimal spanning tree path lengths. Crucial to our approach is the quantification of the extreme-value behavior of small edge weights in terms of a sequence of parameters ( s n ) n ≥ 1 that characterises the different universality classes for first passage percolation on the complete graph. We investigate the case where s n → ∞ with s n = o ( n 1 / 3 ) , which corresponds to the barely supercritical setting. We identify the scaling limit of the weight of the optimal path between two vertices, and we prove that the number of edges in this path obeys a central limit theorem with mean approximately s n log ( n / s n 3 ) and variance s n 2 log ( n / s n 3 ) . Remarkably, our proof also applies to n-dependent edge weights of the form E s n , where E is an exponential random variable with mean 1, thus settling a conjecture of Bhamidi et al. (Weak disorder asymptotics in the stochastic meanfield model of distance. Ann Appl Probab 22(1):29-69, 2012). The proof relies on a decomposition of the smallest-weight tree into an initial part following invasion percolation dynamics, and a main part following branching process dynamics. The initial part has been studied in Eckhoff et al. (Long paths in first passage percolation on the complete graph I. Local PWIT dynamics. Electron. J. Probab. 25:1-45, 2020. 10.1214/20-EJP484); the current paper focuses on the global branching dynamics.


The impact of occluding pairs on the chewing patterns among the elderly.
This study aims to investigate the impact of occluding pairs (OPs) on chewing strokes, chewing time, mealtime duration, and bite force in an aging population. The 100 participants included 52 women and 48 men with average age of 71.2 years. The subjects were restricted to those who can eat what they wanted and had no temporomandibular joint disorder (TMD) and dysphagia history; their OPs were counted in the posterior occlusal support zone in accordance with the Eichner classification. Free habitual mastication of a cornstarch cookie was analyzed by recording the number of chewing strokes and the amount of time needed for complete mastication. Strokes were counted by considering the opening and closing mandibular movements. Mealtime was defined as the time spent to finish a lunchbox and accomplish swallowing. Bite force was estimated with a T-Scan III®. A linear regression analysis was used to evaluate the impact of the OPs on the chewing strokes, chewing time, mealtime duration, and bite force. In this study, 76% of the participants had 4 OPs and 12% participants had 3 OPs. Increasing the OPs significantly shortened the chewing time and mealtime duration (P = 0.02). The mealtime duration did not notably affect the chewing time (P = 0.237). There was significant association between OPs and bite force (P < 0.0001). In elderly, increasing OPs significantly raised the bite force and shortened the chewing time and strokes. More OPs might be the key to maintain good chewing function. Among the elderly, increasing OPs significantly raised the bite force and shortened the chewing time and mealtime duration. To provide better chewing function, good oral hygiene is important to maintain as many OPs as possible; how to gain more OPs is essential concern in the prosthodontic treatment plan making.


CORC's Survey of Routine Outcome Monitoring and National CAMHS Dataset Developments: A Response to Johnston and Gower.
The CAMHS Outcome Research Consortium has 44 members across Great Britain who are collaborating to introduce routine outcome monitoring into clinical practice. Members were surveyed in 2004, in order to establish a baseline against which we could measure progress. Like Johnston and Gowers, we discovered a wide range of measures were being used, while a third of CORC members were sharing information with clinicians and commissioners, and were using it to develop clinical practice or services. We discuss the constraints brought up by our members and by Johnston and Gowers, as well as recent work in relation to the development of a national CAMHS dataset.


Construction of stable microbial consortia for effective biochemical synthesis.
Microbial consortia can complete otherwise arduous tasks through the cooperation of multiple microbial species. This concept has been applied to produce commodity chemicals, natural products, and biofuels. However, metabolite incompatibility and growth competition can make the microbial composition unstable, and fluctuating microbial populations reduce the efficiency of chemical production. Thus, controlling the populations and regulating the complex interactions between different strains are challenges in constructing stable microbial consortia. This Review discusses advances in synthetic biology and metabolic engineering to control social interactions within microbial cocultures, including substrate separation, byproduct elimination, crossfeeding, and quorum-sensing circuit design. Additionally, this Review addresses interdisciplinary strategies to improve the stability of microbial consortia and provides design principles for microbial consortia to enhance chemical production.


Purification and characterisation of recombinant Bacteroides fragilis toxin-2.
Fragilysin (BFT) is metalloprotease that is secreted by enterotoxigenic Bacteroides fragilis. Studying the mechanism of BFT interaction with intestinal epithelial cells requires a pure protein sample. In this study, we cloned DNA-fragments coding for the catalytic domain of fragilysin-2 and profragilysin-2 into an E. coli expression vector. Purification methods for the recombinant fragilysin-2 catalytic domain and profragilysin-2 were developed. In addition, we obtained mature active fragilysin-2 from recombinant proprotein by limited tryptic digestion. We tested the biological activity of the recombinant protein samples and revealed that E-cadherin was cleaved when HT-29 cells were treated with mature fragilysin-2 but not with profragilysin-2. Azocoll, azocasein and gelatin were not proteolytically cleaved by mature fragilysin-2. Proteins released in culture medium after HT-29 cells treatment with mature active BFT-2 were identified.


Studies of enuresis. VIII. Detrusor and sphincter instability caused by overactivity of integral voiding reflexes.
Ninety-one children with nocturnal enuresis or enuresis plus daytime urgency incontinence were studied by cystometry. Seventy-two per cent of the girls and 62 per cent of the boys had evidence of bladder instability. Sixty-eight children in whom abnormalities were found on preliminary voiding urodynamics or voiding cystourethrography also underwent calibration and endoscopic examination under anesthesia. An atropine-suppression test was also performed preoperatively in some children with a markedly unstable bladder demonstrated on preoperative cystometry. In the majority of children tested suppression of bladder instability with atropine was demonstrable. Voluntary detrusor sphincter dyssynergia was demonstrated in a majority of the children with daytime urgency incontinence. Sixty-five per cent of the boys and 81 per cent of the girls were treated for urethral obstructive lesions suspected to be of functional urodynamic significance. Postoperative cystometry showed marked improvement in bladder stability in 57 per cent of the girls and 63 per cent of the boys treated for suspected urethral obstructive pathology. The anticholinergic suppression test was found to have no significant predictive value relative to the cause or surgical curability of bladder instability. The pathophysiologic significance of overactivity of integral voiding reflexes 6 through 11 is described.