The cellular pathway of CD1e in immature and maturing dendritic cells.
Dendritic cells (DCs) present antigens to T cells via CD1, HLA class I or class II molecules. During maturation, HLA class II-restricted presentation is optimized. The relocalization of CD1e from Golgi to endosomal compartments during DC maturation suggests also an optimization of the antigen-presentation pathway via CD1 molecules. We here detail the biosynthesis and cellular pathway of CD1e in immature and maturing DCs. Unlike the other CD1 molecules, CD1e was found to reach late endosomes through sorting endosomes, without passing through the plasma membrane in either immature or maturing cells. After induction of DC maturation, CD1e disappeared rapidly from the Golgi and was transiently localized in HLA-DR+ vesicles, while the number of CD1e+/CD1b+ compartments increased for at least 20 h. High-resolution light microscopy showed that, in immature DCs, CD1e+ vesicles were often in close apposition to EEA1+ or HLA-DR+ compartments, while CD1e displayed a nearly exclusive distribution in the lysosomes of mature DCs, a finding corroborated by immunoelectron microscopy. During maturation, CD1e synthesis progressively declined, while the endosomal cleavage of CD1e still occurred. Thus, CD1e displays peculiar properties, suggesting an unexpected role among the family of CD1 antigen-presenting molecules.


The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA.
Previous work by our laboratory has described the presence and widespread distribution of a PRL-like immunoreactive protein in brain. The persistence of this PRL in brain after hypophysectomy provided substantial evidence that brain PRL represented the product of a synthetic pool separate from that of the anterior pituitary PRL. To pursue this concept of independent synthesis further, we sought to determine whether brain tissue expressed PRL mRNA. Although we were easily able to detect a single species of PRL mRNA in pituitary by Northern hybridization, we could not visualize message in hypothalamus or extrahypothalamic brain by this technique. Therefore, we performed the polymerase chain reaction on cDNAs from anterior pituitary, hypothalamus, discrete extrahypothalamic brain regions, and other tissues. Hypothalamus and extrahypothalamic brain parts, including the cerebellum, caudate, brain stem, amygdala, thalamus, cortex, and hippocampus, were all positive to varying degrees. Lung and liver were negative, and anterior pituitary was consistently positive. All positive tissues, including anterior pituitary, expressed two hybridization signals: the expected amplified product and another smaller one. The smaller amplified product is presumably the result of an alternatively spliced transcript that is missing part of the PRL gene. Hypophysectomized animals did not express PRL message in brain, but expression was restored in hypophysectomized animals treated with testosterone. Transcripts for Pit-1 (GHF-1), a transcription factor important in regulation of pituitary PRL, were not detected in hypothalamus or any of the extrahypothalamic brain parts. The finding of testosterone stimulation of brain PRL message and undetectable levels of Pit-1 (GHF-1) in hypothalamic and extrahypothalamic brain regions indicates that the transcriptional regulation of PRL in the brain is different from that in the anterior pituitary.


Truncation of monocyte chemoattractant protein 1 by plasmin promotes blood-brain barrier disruption.
Previous studies have shown that plasmin cleaves monocyte chemoattractant protein 1 (MCP1; officially known as C-C motif chemokine 2, CCL2) at K104, and this cleavage enhances its chemotactic potency significantly. Accumulating evidence reveals that MCP1 also disrupts the integrity of the blood-brain barrier (BBB). Here, we show that K104Stop-MCP1, truncated at the K104 where plasmin would normally cleave, is more efficient than the full-length protein (FL-MCP1) in compromising the integrity of the BBB in in vitro and in vivo models. K104Stop-MCP1 increases the permeability of BBB in both wild-type mice and mice deficient for tissue plasminogen activator (tPA), which converts plasminogen into active plasmin, suggesting that plasmin-mediated truncation of MCP1 plays an important role in BBB compromise. Furthermore, we show that the mechanisms underlying MCP1-induced BBB disruption involve redistribution of tight junction proteins (occludin and ZO-1) and reorganization of the actin cytoskeleton. Finally, we show that the redistribution of ZO-1 is mediated by phosphorylation of ezrin-radixin-moesin (ERM) proteins. These findings identify plasmin as a key signaling molecule in the regulation of BBB integrity and suggest that plasmin inhibitors might be used to modulate diseases accompanied by BBB compromise.


[Split tibialis posterior tendon transfer on peroneus brevis for equinovarus foot in CP children].
Equinovarus deformity of the foot is a result of the muscles imbalance in which inventors of the foot, mostly posterior and anterior tibialis muscle, overpower evertors. In children with cerebral palsy untreated spastic equinovarus deformity may cause severe fixed foot deformity and painful callosities under metatarsal heads and on the lateral side of the foot. The gait pattern becomes less effective and needs more energy. The study group consisted of 154 children with cerebral palsy treated in our Clinic by the multilevel soft tissue surgery. For foot problems 136 children needed surgical intervention. In 19 ambulatory patients, with hemiplegia or diplegia, split tibialis posterior tendon transfer together with tendo Achilles lengthening and plantar aponeurectomy were performed. The study was based on clinical examination, parents' questionnaire, radiology and gait analysis at least one year after surgery. The mean follow up was 4.6 years. The functional improvement was observed in 17 (89%) children with tendon transfer. At the last follow up those patients were brace free, with plantigrade foot while walking (without DAFO orthesis) and normal shoes were used. All painful callosities disappeared. On a standing AP X-ray adequate correction of the hindfoot-forefoot relation was achieved in 14 (74%) cases. Persistent equinovarus deformity over 10 degrees was observed in 2 cases. Those patients underwent additional bone surgery. With a properly planned approach the split tibialis posterior tendon transfer can bring good clinical and functional results in CP children with equinovarus deformation. We recommend this procedure in early stage of the deformity what can eliminate more harmful triple arthrodesis in severe deformities.


Quantitative trait loci associated with the humoral innate immune response in chickens were confirmed in a cross between Green-Legged Partridgelike and White Leghorn.
Natural antibodies (NA) create a crucial barrier at the initial steps of the innate humoral immune response. The main role of NA in the defense system is to bind the pathogens at early stages of infection. Different pathogens are recognized by the presence of highly conserved antigen determinant [e.g., lipopolysaccharide (LPS) in gram-negative bacteria or lipoteichoic acid (LTA) in gram-positive bacteria]. In chickens, a different genetic background of NA binds LPS and LTA antigens, encoded by different QTL. The main objective of this work was to confirm known QTL associated with LPS and LTA NA. For this purpose a chicken reference population was created by crossing 2 breeds: a commercial layer, White Leghorn, and a Polish indigenous chicken, Green-Legged Partridgelike. The chromosomal regions analyzed harbored to GGA3, GGA5, GGA6, GGA8, GGA9, GGA10, GGA14, GGA15, GGA18, and GGAZ. The data collected consisted of the NA titers binding LPS and LTA (determined by ELISA at 12 wk of age) as well as the genotypes (30 short tandem repeat markers; average of 3 markers/chromosome, collected for generations F(0), F(1), and F(2)). The analyses were performed with 3 statistical models (paternal and maternal half-sib, line cross, and linkage analysis and linkage disequilibrium) implemented in GridQTL software (http://www.gridqtl.org.uk/). The QTL study of humoral innate immune response traits resulted in the confirmation of 3 QTL associated with NA titers binding LPS (located on GGA9, GGA18, and GGAZ) and 2 QTL associated with NA titers binding LTA (located on GGA5 and GGA14). A set of candidate genes within the regions of the validated QTL has been proposed.


MOF (UiO-66-NH2)@COF (TFP-TABQ) hybrids via on-surface condensation reactions for sustainable energy storage.
Core-shell MOF@COF hybrids were synthesized via subsequent modification of MOF UiO-66-NH2 with 1,3,5-triformylphloroglucinol (TFP) and 2,3,5,6-tetraaminobenzoquinone (TABQ). The hybrids exhibited significant surface area (236 m2 g-1) and outstanding electrochemical performance (103 F g-1 at 0.5 A g-1), surpassing both COFs and MOFs, thereby showcasing the potential of on-surface condensation reactions for developing high-performance energy storage devices.


[Multiple antibiotic resistance mediated by R plasmid in Shigella flexneri strains isolated in the northeast of Brazil].
In Shigella strains were studied the molecular mechanism that mediated the multiply antibiotic-resistance. Twenty-six strains of Shigella flexneri were utilised in this investigation. These strains were submitted to disk diffusion test, mating experiments and plasmid isolation. In relation to antibiotics resistance standard it was observed that all Shigella flexneri strains were resistant to at least, three antibiotics tested. From twenty-six Shigella flexneri strains donors submitted to conjugation process, 34.6% (nine strains) resulted in variable frequency of transconjugants. From strains that conjugated, 100%, transferred the resistance factor acquainted with ampicillin. Being that, in all transconjugants which were observed, just one plasmid with 23.1 Kb was evidenced. This plasmid found in all strains was characterised as the cause of resistance to ampicillin.


Optical scanning of laser line sensors for 3D imaging.
In scanning laser triangulation sensors for 3D imaging, the achievable throughput is strongly limited by the moving mass. By realizing an optical scanning approach rather than repositioning the entire sensor, this limitation could be reduced, leading to a reduced measurement time. This work presents sensor system geometries in which only the optical path of a line triangulation sensor is manipulated by a tip-tilt mirror. In the proposed rotational scanning systems, either the illumination path or both the illumination and the reflection path are manipulated. By using ray-tracing simulation, the performance of the scanning systems are optimized and possible disadvantages can be determined up front. Using geometric relations, the surface profile can be reconstructed from the measured sensor data, the mirror position, and the model parameters. Experimental results show that the image quality of the proposed rotational scanning systems is comparable to systems based on classical translational scanning motion.


Reovirus antibodies among animals in Taiwan.
Serum specimens for reovirus antibody survey were collected from 60 pigs, 50 buffalos, 30 rabbits, 30 guinea pigs, 20 albino rats, 60 Swiss mice, 15 Taiwan monkeys, 14 goats and 12 dogs. Serum antibodies were measured by the hemagglutination inhibition (HI) test. HI antibodies to reovirus were found in a high percentage of pigs, albino rats, Swiss mice, dogs and goats, and less frequently in rabbits, guinea pigs, Taiwan monkeys and buffalos.


Patterns of physiological decline due to age and selection in Drosophila melanogaster.
In outbred sexually reproducing populations, age-specific mortality rates reach a plateau in late life following the exponential increase in mortality rates that marks aging. Little is known about what happens to physiology when cohorts transition from aging to late life. We measured age-specific values for starvation resistance, desiccation resistance, time-in-motion, and geotaxis in ten Drosophila melanogaster populations: five populations selected for rapid development and five control populations. Adulthood was divided into two stages, the aging phase and the late-life phase according to demographic data. Consistent with previous studies, we found that populations selected for rapid development entered the late-life phase at an earlier age than the controls. Age-specific rates of change for all physiological phenotypes showed differences between the aging phase and the late-life phase. This result suggests that late life is physiologically distinct from aging. The ages of transitions in physiological characteristics from aging to late life statistically match the age at which the demographic transition from aging to late life occurs, in all cases but one. These experimental results support evolutionary theories of late life that depend on patterns of decline and stabilization in the forces of natural selection.


PET imaging of medulloblastoma with an 18F-labeled tryptophan analogue in a transgenic mouse model.
In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application. Using a transgenic mouse model for the sonic hedgehog (Shh) subgroup of medulloblastoma, here we evaluated the potential of the newly developed 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[18F]FETrp was synthesized on a PETCHEM automatic synthesizer with good chemical and radiochemical purities and enantiomeric excess values. Imaging was performed in tumor-bearing Smo/Smo medulloblastoma mice with constitutive actvation of the Smoothened (Smo) receptor using a PerkinElmer G4 PET-X-Ray scanner. Medulloblastoma showed significant and specific accumulation of 1-L-[18F]FETrp. 1-L-[18F]FETrp also showed significantly higher tumor uptake than its D-enantiomer, 1-D-[18F]FETrp. The uptake of 1-L-[18F]FETrp in the normal brain tissue was low, suggesting that 1-L-[18F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors.


Covalent Group IV Atomic Clusters.
Atomic clusters containing from two to several hundred atoms offer the possibility of studying the transition from molecules to crystalline solids. The covalent group IV elements carbon, silicon, and germanium are now being examined with this long-range objective. These elements are particularly interesting because of the very different character of their crystalline solids and because they are intermediate between metals and insulators in the nature of their bonding. Small mass-selected atom cluster ions are formed by pulsed laser techniques and identified by time-of-flight methods. Laser photoexcitation is used to study the relative stability of these clusters and their modes of fragmentation. These modes for C(n)(+) clusters, which tend to fragment with a characteristic loss of a neutral C(3), are found to be different from the modes for Si(n)(+) and Ge(n)(+) clusters, which tend to fragment to "magic" clusters such as Si(4)(+), Si(6)(+) and Si(10)(+). These experimental results can be accounted for by recent theoretical calculations of the ground-state structure and stability of small silicon and carbon clusters. Several theoretical approaches give consistent results, showing that small silicon clusters are compact and different from small fragments of the bulk crystal. Calculations show that carbon clusters change from linear structures toward cyclic structures as the cluster size increases, but with significant odd-even differences.


Microarray Analysis of Gene Expression in the Uterine Endometrium during the Implantation Period in Pigs.
During embryo implantation in pigs, the uterine endometrium undergoes dramatic morphological and functional changes accompanied with dynamic gene expression. Since the greatest amount of embryonic losses occur during this period, it is essential to understand the expression and function of genes in the uterine endometrium. Although many reports have studied gene expression in the uterine endometrium during the estrous cycle and pregnancy, the pattern of global gene expression in the uterine endometrium in response to the presence of a conceptus (embryo/fetus and associated extraembryonic membranes) has not been completely determined. To better understand the expression of pregnancy-specific genes in the endometrium during the implantation period, we analyzed global gene expression in the endometrium on day (D) 12 and D15 of pregnancy and the estrous cycle using a microarray technique in order to identify differentially expressed endometrial genes between D12 of pregnancy and D12 of the estrous cycle and between D15 of pregnancy and D15 of the estrous cycle. Results showed that the global pattern of gene expression varied with pregnancy status. Among 23,937 genes analyzed, 99 and 213 up-regulated genes and 92 and 231 down-regulated genes were identified as differentially expressed genes (DEGs) in the uterine endometrium on D12 and D15 of pregnancy compared to D12 and D15 of the estrous cycle, respectively. Functional annotation clustering analysis showed that those DEGs included genes involved in immunity, steroidogenesis, cell-to-cell interaction, and tissue remodeling. These findings suggest that the implantation process regulates differential endometrial gene expression to support the establishment of pregnancy in pigs. Further analysis of the genes identified in this study will provide insight into the cellular and molecular bases of the implantation process in pigs.


Infant hearing loss: from diagnosis to therapy Official Report of XXI Conference of Italian Society of Pediatric Otorhinolaryngology.
Hearing loss is one of the most common disabilities and has lifelong consequences for affected children and their families. Both conductive and sensorineural hearing loss (SNHL) may be caused by a wide variety of congenital and acquired factors. Its early detection, together with appropriate intervention, is critical to speech, language and cognitive development in hearing-impaired children. In the last two decades, the application of universal neonatal hearing screening has improved identification of hearing loss early in life and facilitates early intervention. Developments in molecular medicine, genetics and neuroscience have improved the aetiological classification of hearing loss. Once deafness is established, a systematic approach to determining the cause is best undertaken within a dedicated multidisciplinary setting. This review addresses the innovative evidences on aetiology and management of deafness in children, including universal neonatal screening, advances in genetic diagnosis and the contribution of neuroimaging. Finally, therapy remains a major challenge in management of paediatric SNHL. Current approaches are represented by hearing aids and cochlear implants. However, recent advances in basic medicine which are identifying the mechanisms of cochlear damage and defective genes causing deafness, may represent the basis for novel therapeutic targets including implantable devices, auditory brainstem implants and cell therapy.


Prevalence of albuminuria in Australia: the AusDiab Kidney Study.
Albuminuria is an important predictor of risk of progressive renal disease, cardiovascular disease, and mortality; however, the prevalence in the general population is not well defined. We determined estimates of the population prevalence and associations of microalbuminuria and macroalbuminuria in Australian adults; 11,247 Australians aged > or = 25 years living in 42 randomly selected population clusters were tested for albuminuria (spot urine albumin:creatinine (mg/mmol): normal < 3.4, microalbuminuria 3.4 to 34, macroalbuminuria > 34). Prevalence of micro- and macroalbuminuria were assessed with age, sex, obesity, smoking, hypertension (> or = 140/90 mm Hg or known diagnosis on treatment), glucose metabolism status (WHO criteria according to fasting glucose and oral glucose tolerance test), ischemic heart and cerebrovascular disease, and low glomerular filtration rate (calculated glomerular filtration rate < 60 mL/min/1.73m2). Microalbuminuria and macroalbuminuria proteinuria were present in 6.0% and 0.6% of the population, respectively. The majority of subjects with microalbuminuria (64%) and macroalbuminuria (76%) had hypertension, and approximately half of those with albuminuria had abnormal glucose metabolism. Of all participants with microalbuminuria, 25.9% had normal blood pressure and glucose metabolism, and in this group, alternative associations of microalbuminuria included obesity (13.5%), smoking (20.7%), and low glomerular filtration rate (12.3%). Albuminuria is present in a small percentage of the general adult population, but is highly prevalent in subjects with hypertension and/or abnormal glucose metabolism. The majority of cases of microalbuminuria and macroalbuminuria in the general population are among those with hypertension.


Interleukin-6 induces microglial CX3CR1 expression in the spinal cord after peripheral nerve injury through the activation of p38 MAPK.
Peripheral nerve injury leading to neuropathic pain induces the upregulation of interleukin (IL)-6 and microglial CX3CR1 expression, and activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord. Here, we investigated whether IL-6 regulates CX3CR1 expression through p38 MAPK activation in the spinal cord in rats with chronic constriction injury (CCI) of the sciatic nerve. Similar temporal changes in the expression of IL-6, phosphorylated p38 MAPK and CX3CR1 were observed following CCI. The increases in CX3CR1 expression, p38 MAPK activation and pain behavior after CCI were suppressed by blocking IL-6 action with a neutralizing antibody, while they were enhanced by supplying exogenous recombinant rat IL-6 (rrIL-6). rrIL-6 also induced increases in spinal CX3CR1 expression, p38 MAPK activation and pain behavior in naive rats without nerve injury. Furthermore, treatment with the p38 MAPK-specific inhibitor, SB203580, suppressed the increase in CX3CR1 expression induced by CCI or rrIL-6 treatment. Finally, blocking CX3CR1 or p38 MAPK activation prevented the development of mechanical allodynia and thermal hyperalgesia induced by CCI or rrIL-6 treatment. These results suggest a new mechanism of neuropathic pain, in which IL-6 induces microglial CX3CR1 expression in the spinal cord through p38 MAPK activation, enhancing the responsiveness of microglia to fractalkine in the spinal cord, thus playing an important role in neuropathic pain after peripheral nerve injury.


RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia.
We developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery-based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced CNS leukemia in NOD-SCID mice. Targeting RAC2 significantly inhibited in vitro invasion and delayed disease onset in mice. Induced expression of RAC2 in cell lines with low/absent expression of AEP and ICAM1 did not result in an invasive phenotype or murine CNS disease. Flow cytometric analysis identified an enriched population of blast cells expressing ICAM1/lymphocyte function associated antigen-1 (LFA-1)/CD70 in the CD10(+)/CD19(+) fraction of bone marrow aspirates obtained from relapsed compared with normal controls and those with primary disease. CD10(+)/CD19(+) fractions obtained from relapsed patients also express RAC2 and give rise to CNS disease in mice. Our data suggest that combinations of processes are involved in the pathogenesis of CNS disease in pre-B-cell ALL, support a model in which CNS disease occurs as a result of external invasion, and suggest that targeting the processes of adhesion and invasion unique to pre-B cells may prevent recurrences within the CNS.


Devices for Autonomic Regulation Therapy in Heart Failure With Reduced Ejection Fraction.
Heart failure (HF) is associated with significant morbidity and mortality and an increasing economic burden. The persistence of HF's risk factors, coupled with an aging population, also leads to an increase in its incidence and prevalence. It is well established that sympathetic hyperactivity and parasympathetic withdrawal are instrumental in the development and worsening of HF. Therefore, restoring autonomic balance to the cardiovascular system is an attractive therapeutic approach. The following is a review of current clinical trials of device-based autonomic regulation therapy in the management of HF with a reduced ejection fraction.


Ag nanorod@PEI-Ag nanohybrid as an excellent signal label for sensitive and rapid detection of serum HER2.
The accurate detection of Human epidermal growth factor receptor-2 (HER2) as a critical breast cancer biomarker can be essential for the early selection of therapeutic approaches. HER2 is a prominent component of a signaling network. Overexpression of the HER2 protein due to amplification of its gene leads to the development of an aggressive subtype of breast cancer. Patients with tumors that overexpress HER2 are eligible for treatment that significantly reduces mortality rates. Herein, we present a fast and simple method for detecting serum HER2. A new electrochemical label has been developed using charged Ag nanorod@ polyethylenimine-Ag (Ag NR@ PEI-Ag) nanohybrid. The synthesized Ag NR@PEI-Ag nanohybrid simultaneously has the electroactive property of silver and the large surface area of the PEI, which results in the enhancement of the detection signal. So, using Ag NR@PEI-Ag nanohybrid as the electrochemical label, a simple, fast, and sensitive electrochemical biosensor was designed to detect HER2. This way, after immobilizing HER2 aptamer on the Au electrode surface, HER2 or human serum was exposed to the aptamer. Then, the positively charged Ag NR@PEI-Ag nanohybrid was adsorbed onto the negatively charged aptamer-HER2 complex, and the current that was produced due to the Ag/AgCl reaction was measured as the electrochemical signal. The aptasensor shows a broad linear response from 10-12 to 10-7 g, a low detection limit (LOD) of 10 pg, and a total assay time of ~ 30 min.


Adhesive luting of all-ceramic restorations--the impact of cementation variables and short-term water storage on the strength of a feldspathic dental ceramic.
To investigate the impact of resin cement luting variables and short-term water storage on the strength of an adhesively luted all-ceramic restorative material. An understanding of the strengthening mechanisms will result in optimisation of operative techniques and materials selection criteria. The "fit" surfaces of 480 disk-shaped feldspathic porcelain specimens were alumina air abraded to introduce a clinically relevant surface texture and consistent surface defect population. Thirty specimens randomly allocated to each of 16 groups were coated with silane, unfilled resin or filled resin cement, or a combination. Eight groups were stored either dry or wet for 24 h prior to bi-axial flexure testing (ball-on-ring). Statistical analysis of the flexure strength data involved a three-factor general linear model (p < 0.05) prior to a Weibull analysis. Resin coating the porcelain surface resulted in a significant increase in the characteristic stress (sigma(o)), and strengthening was dependent on coating type (p < 0.001). Silane priming resulted in additional strengthening when preceding filled resin cement coating. Water immersion for 24 h resulted in a strength degradation of both the uncoated control and coated specimens, whereby the magnitude of strength degradation was dependent on coating type (p < 0.001). Resin luting of dental ceramics results in significant strengthening likely to impact on clinical performance. The strengthening is dependent on the creation of a resin-ceramic hybrid layer sensitive to cementation variables and clinical placement technique. Short-term water immersion results in a significant degradation of strengthening sensitive to the characteristics of the resin-ceramic hybrid layer.


Influence of the Sequence Motive Repeating Number on Protein Folding in Spider Silk Protein Films.
Like multiblock copolymers, spider silk proteins are built of repetitive sequence motives. One prominent repetitive motif is based on the consensus sequence of spidroin 4 of the spider Araneus diadematus ADF4. The number x of the repeating sequence motives (C) determines the molecular weight of the recombinant ADF4-based, engineered spider silk protein denoted as eADF4(Cx). eADF4(Cx) can be used as a model for intrinsically disordered proteins (IDP) and to elucidate their folding. Herein, the influence of the variation of the sequence motive repeating number x (x = 1, 2, 4, 8, 16) on the protein folding within eADF4(Cx) films was investigated. eADF4(Cx) films were cast from 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) solutions onto planar silicon model substrates, revealing mainly helical or random coil structure. Upon treatment with methanol vapor (ptm), the formation of crystalline β-sheets was triggered. Dichroic Fourier-transform infrared (FTIR) spectroscopy, circular dichroism, spectroscopic ellipsometry, atomic force microscopy, grazing-incidence small-angle X-ray scattering (GISAXS), grazing-incidence wide-angle X-ray scattering (GIWAXS), and electrokinetic and contact angle measurements were used to get information concerning the secondary structure and folding kinetics, orientation of β-sheets, the ratio of parallel/antiparallel β-sheets, domain sizes and distributions, surface topography, surface potential, hydrophobicity and the film integrity under water. Significant differences in the final β-sheet content, the share of antiparallel β-sheet structures, film integrity, surface potential, and isoelectric points between eADF4(Cx) with x = 1, 2 and eADF4(Cx) with x = 4, 8, 16 gave new insights in the molecular weight-dependent structure formation and film properties of IDP systems. GISAXS and kinetic measurements confirmed a relation between β-sheet crystal growth rate and final β-sheet crystal size. Further, competing effects of reduced diffusibility hindering accelerated crystal growth and enhanced backfolding promoting accelerated crystal growth with increasing molecular weight were discussed.


Staphylococcus epidermidis graft infection is associated with locally suppressed major histocompatibility complex class II and elevated MAC-1 expression.
To determine the local cellular immune response in a series of human patients with Staphylococcus epidermidis prosthetic graft infection and to use a murine model to investigate the response in polytef (PTFE) and in a nonslime-producing S epidermidis variant. Externally supported Dacron and PTFE grafts, either sterile or colonized with slime (RP-62A)- or nonslime (RP-62NA)-producing S epidermidis (10(7) colony forming units/cm2) were implanted in a dorsal subcutaneous pocket of Swiss Webster mice (Taconic, Germantown, NY). The grafts were harvested at 7, 10, 14, and 28 days with local bacterial and leukocyte counts obtained. Perigraft and blood monocyte major histocompatibility complex class II (MHC-II) (immune antigen) and membrane attack complex type 1 (MAC-1) (glycoprotein) expression were analyzed by flow cytometry in the murine model and in 3 patients representing 4 Dacron graft infections. The human infected Dacron perigraft monocytes revealed a suppressed MHC-II and elevated MAC-1 expression, and early correlation with the murine model was seen. No notable perigraft monocyte MHC-II suppression occurred in the infected PTFE graft. The reciprocal relationship in Dacron between monocyte MAC-1 and MHC-II expression was exaggerated with the lack of slime production. Bacterial clearance was variable. Supranormal expression was observed at 1 month in sterile Dacron but not in PTFE grafts. Staphylococcus epidermidis infection is associated with local cellular immune suppression in Dacron but not PTFE grafts. Slime-producing S epidermidis induced a lesser cytotoxic-phagocytic response than the nonslime variant. The reduced immunologic response to slime-producing S epidermidis may explain, in part, its indolent nature and resistance to eradication.


Diagnostic Utility of GATA3 and ISL1 in Differentiating Neuroblastoma From Other Pediatric Malignant Small Round Blue Cell Tumors.
Accurate diagnosis of neuroblastoma may be challenging, especially with limited or inadequate specimen and at the metastatic sites due to overlapping imaging, histopathologic, and immunohistochemical (immunohistochemistry [IHC]; infidelity among various lineage-associated transcription factors eg FLI1, transducin-like enhancer 1, etc) features. GATA3 and ISL1 have recently been described as markers of neuroblastic differentiation. This study aims at determining the diagnostic utility of GATA3 and ISL1 in differentiating neuroblastoma from other pediatric malignant small round blue cell tumors. We evaluated GATA3 and ISL1 expression in 74 pediatric small round blue cell tumors that included 23 NMYC-amplified neuroblastomas, 11 EWSR1-rearranged round cell sarcomas, 7 SYT::SSX1-rearranged synovial sarcomas, 5 embryonal rhabdomyosarcomas, 10 Wilms tumors (nephroblastomas), 7 lymphoblastic lymphoma, 7 medulloblastoma, and 4 desmoplastic small round cell tumor. All 23 neuroblastomas (moderate to strong staining in >50% of the tumor cells), 5 T-lymphoblastic lymphomas (moderate to strong staining in 40%-90% of the tumor cells), and 2 desmoplastic small round cell tumors (weak to moderate staining in 20%-30% of the tumor cells) expressed GATA3, while other tumors were negative. ISL1 immunoreactivity was observed in 22 (96%) neuroblastomas (strong staining in in >50% of the tumor cells, n = 17; moderate to strong staining in 26%-50% of the tumor cells, n = 5), 3 embryonal rhabdomyosarcoma (moderate to strong staining in 30%-85% of the tumor cells), 1 synovial sarcoma (weak staining in 20% of the tumor cells), and 7 medulloblastoma (strong staining in 60%-90% of the tumor cells). Other tumors were negative. Overall, GATA3 showed 86% specificity, 100% sensitivity, and 90% accuracy for neuroblastoma, with a positive predictive value (PPV) and negative predictive value (NPV) of 77% and 100%, respectively. ISLI showed 72% specificity, 96% sensitivity, and 81% accuracy for neuroblastoma, with a PPV and NPV of 67% and 97%, respectively. After the exclusion of T-lymphoblastic lymphoma and desmoplastic small round cell tumors, GATA3 had 100% specificity, sensitivity, accuracy, and PPV and NPV for neuroblastoma. Similarly, in pediatric small round blue cell tumors, ISL1 had 100% specificity, sensitivity, accuracy, PPV, and NPV for neuroblastoma, after embryonal rhabdomyosarcoma, synovial sarcoma, and medulloblastoma were excluded. GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up.


[Effect of cannabis use on health].
Impairment in short-term memory and lingering deficit in psychomotor performance are but two of the acute cannabis intoxication components that may have long-term consequences. The former because it affects learning and the latter because it interferes with proper handling of motor vehicles. The most frequently observed complication of cannabis inebriation, however, is a short-lasting acute psychological disturbance with symptoms of panic, paranoid apprehension and personality disorganization. This type of reaction is often not dose-related, and could appropriately be termed "pathological intoxication". In addition to the acute effects of cannabis on mental performance and behaviour, this paper reviews the psychiatric consequences of chronic use and the accumulated evidence on organic toxicity associated with it: residual cognitive deficit, lethargic symptoms, cannabis psychosis, respiratory, gastro-intestinal and cardiovascular complications, as well as effects on immune response and gonadal functions, are discussed. Also included are reviews on the pharmacology and therapeutic potential of cannabinoids.


Somatosensory-Auditory Processing of the Fifth Cervical Nerve in Tinnitus.
Cervical spinal nerve projections influence auditory responses and play a role in the pathology of tinnitus. The intention of our research was to lay down the amenity of treatment of the fifth (C5) cervical nerve to lessen tinnitus and to obtain specifications associated with a long-term effect of this method. Subjects were 54 tinnitus patients who were treated with infiltration of the fifth cervical nerve. Clinical data form these patients were reviewed retrospectively. An independent perceiver evaluated the long-term effect of the therapy by telephone interview. Treating the C5 is beneficial for 30% of the tinnitus patients. The majority of patients with a beneficial result rated the tinnitus reduction of 50% or more. At 9 months, half of the patients still had benefit. Less hearing at 1 kHz together with a large spur in front of the fifth cervical vertebrae forecasted a beneficial effect of the C5 therapy on tinnitus at 7 weeks. Treating cervical spine complaints can lessen tinnitus. Therapy of C5 resulted in less tinnitus for 30% of the tinnitus patients. However, selection of tinnitus patients with an evident spur in front of the fifth cervical vertebrae together with a less hearing at 1 kHz will improve the success rate of C5 therapy.


Anthropometric measures in relation to basal cell carcinoma: a longitudinal study.
The relationship between anthropometric indices and risk of basal cell carcinoma (BCC) is largely unknown. We aimed to examine the association between anthropometric measures and development of BCC and to demonstrate whether adherence to World Health Organisation guidelines for body mass index, waist circumference, and waist/hip ratio was associated with risk of BCC, independent of sun exposure. Study participants were participants in a community-based skin cancer prevention trial in Nambour, a town in southeast Queensland (latitude 26 degrees S). In 1992, height, weight, and waist and hip circumferences were measured for all 1621 participants and weight was remeasured at the end of the trial in 1996. Prevalence proportion ratios were calculated using a log-binomial model to estimate the risk of BCC prior to or prevalent in 1992, while Poisson regression with robust error variances was used to estimate the relative risk of BCC during the follow-up period. At baseline, 94 participants had a current BCC, and 202 had a history of BCC. During the 5-year follow-up period, 179 participants developed one or more new BCCs. We found no significant association between any of the anthropometric measures or indices and risk of BCC after controlling for potential confounding factors including sun exposure. There was a suggestion that short-term weight gain may increase the risk of developing BCC for women only. Adherence to World Health Organisation guidelines for body mass index, waist circumference and waist/hip ratio is not significantly associated with occurrence of basal cell carcinomas of the skin.


Differences in psychosocial constructs among elementary school staff that implement physical activity programs: a step in designing implementation strategies.
Multiple types of school staff members (e.g., classroom teachers, principals) are involved in implementing physical activity programs (e.g., classroom-based, gym), but factors specific to their job responsibilities may inhibit their ability to implement programming effectively. Thus, implementation strategies tailored by job type may be needed. We compare perceptions of behavioral constructs related to implementation of school-based physical activity programs, by job type, among school staff. School staff (n = 139), including principals/assistant principals (n = 21), physical education teachers (n = 41), and classroom teachers (n = 77), from elementary schools (n = 25), completed a cross-sectional survey measuring perceptions of attitudes, barriers, knowledge, and outcome expectations related to the implementation of physical activity programs. We compared constructs between job types using complex samples general linear models. Classroom teachers reported more perceived implementation barriers, lower physical activity knowledge, and lower outcome expectations than physical education teachers. Principals reported more perceived implementation barriers than physical education teachers. Classroom teachers reported lower physical activity knowledge than principals. Attitudes towards physical activity were not different by job type. Each job type has a unique constellation of factors affecting their capacity to implement physical activity programs. Understanding these differences enables tailoring of implementation strategies by job type.


Night-time heart rate nondipping: clinical and prognostic significance in the general population.
Studies addressing the association between a reduced drop of heart rate (HR) at night with subclinical organ damage and cardiovascular events in the general population are scanty. We evaluated this issue in individuals enrolled in the Pressioni Monitorate E Loro Associazioni study. At entry, 2021 individuals underwent diagnostic tests including laboratory investigations, 24-h ambulatory blood pressure (BP) monitoring and echocardiography. Participants were followed from the initial medical visit for a time interval of 148 ± 27 months. To explore the association of circadian HR rhythm and outcomes, participants were classified in the primary analysis according to quartiles of nocturnal HR decrease. In secondary analyses, the population was also classified according nondipping nocturnal HR (defined as a drop in average HR at night lower than 10% compared with day-time values) and next in four categories: first, BP/HR dipper, second, BP/HR nondipper, third, HR dipper/BP nondipper, fourth, HR nondipper/BP dipper). A flattened circadian HR rhythm (i.e. lowest quartile of night-time HR dip) was independently associated with left atrial enlargement, but not to left ventricular hypertrophy; moreover, it was predictive of fatal and nonfatal cardiovascular events, independently of several confounders (hazard ratio 1.8, confidence interval: 1.13-2.86, P < 0.01 vs. highest quartile). A blunted dipping of nocturnal HR is associated with preclinical cardiac damage in terms of left atrial enlargement and is predictive cardiovascular morbidity and mortality in the general population.


A systematic review of modelling approaches in economic evaluations of health interventions for drug and alcohol problems.
The overarching goal of health policies is to maximize health and societal benefits. Economic evaluations can play a vital role in assessing whether or not such benefits occur. This paper reviews the application of modelling techniques in economic evaluations of drug and alcohol interventions with regard to (i) modelling paradigms themselves; (ii) perspectives of costs and benefits and (iii) time frame. Papers that use modelling approaches for economic evaluations of drug and alcohol interventions were identified by carrying out searches of major databases. Thirty eight papers met the inclusion criteria. Overall, the cohort Markov models remain the most popular approach, followed by decision trees, Individual based model and System dynamics model (SD). Most of the papers adopted a long term time frame to reflect the long term costs and benefits of health interventions. However, it was fairly common among the reviewed papers to adopt a narrow perspective that only takes into account costs and benefits borne by the health care sector. This review paper informs policy makers about the availability of modelling techniques that can be used to enhance the quality of economic evaluations for drug and alcohol treatment interventions.


Evaluation of certain food additives and contaminants.
This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives and a food contaminant with a view to concluding as to safety concerns and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation of and assessment of dietary exposure to food additives. A summary follows of the Committee's evaluations of technical, toxicological and dietary exposure data for seven food additives (advantame; glucoamylase from Trichoderma reesei expressed in Trichoderma reesei; glycerol ester of gum rosin; glycerol ester of tall oil rosin; glycerol ester of wood rosin; nisin; and octenyl succinic acid modified gum arabic) and an assessment of dietary exposure to cadmium from cocoa and cocoa products. Specifications for the following food additives were revised: annatto extracts (solvent-extracted bixin and solvent-extracted norbixin); Benzoe tonkinensis; food additives containing aluminium and/or silicon; mineral oil (medium viscosity); modified starches; paprika extract; phosphates (analytical methods for the determination of phosphorus and revision of specifications); 3-phytase from Aspergillus niger expressed in Aspergillus niger; potassium aluminium silicate; and potassium aluminium silicate-based pearlescent pigments. Annexed to the report are tables summarizing the Committee's recommendations for dietary exposures to and toxicological evaluations of the food additives and contaminant considered.


A nonhemolytic phospholipase C from Burkholderia cepacia.
Burkholderia cepacia is an opportunistic pathogen that causes serious pulmonary infections in cystic fibrosis patients. Although several potential virulence factors-a protease, lipase, and two phospholipases C (one hemolytic and one nonhemolytic)-have been identified, only two, the protease and the lipase, have been described in detail. The goal of this study was to purify and characterize a nonhemolytic phospholipase C secreted by B. cepacia strain Pc224c. The enzyme was concentrated from culture supernatants and purified by polyacrylamide gel electrophoresis. The 54-kDa protein was stable in the presence of sodium dodecyl sulfate (up to 10%) and at 4 degrees, 22 degrees, and 37 degrees C; it was, however, inactivated at 100 degrees C. The enzyme bound to glass, chromatography matrices, and polyvinylidene difluoride and cellulose membranes, suggesting that it is hydrophobic. In a genetic approach, primers based on conserved sequences of a B. cepacia Pc69 hemolytic phospholipase C and both the Pseudomonas aeruginosa hemolytic and nonhemolytic proteins were designed to identify the Pc224c nonhemolytic phospholipase C gene. One polymerase chain reaction product was identified; it was sequenced and the sequence compared with sequences in the BLAST database. The best match was the Pseudomonas aeruginosa hemolytic phospholipase C. Ten additional B. cepacia strains were screened for the gene by Southern hybridization; five had the 4-kb band, suggesting that these strains have a similar form of the PLC gene. Nine of the ten strains reacted with the probe, suggesting that similar sequences were present, but in another form.


Use of health care services by people with mental illness: secondary data from three statutory health insurers and the German Statutory Pension Insurance Scheme.
A discipline- and sector-specific analysis of health-care utilization by persons with mental illness in Germany is an indispensable aid to planning for the provision of adequate basic care. Secondary data from three statutory health insurers and the German Statutory Pension Insurance Scheme for the period 2005-2007 were evaluated to identify insurees with mental illness (ICD-10 diagnosis groups F0-F5). In the period 2005-2007, 3.28 million (33%) of 9.92 million insurees had at least one contact with the health-care system in which a mental disorder was diagnosed. 50.4% (1,651,367) of these insurees had at least two mental disorders. Nearly all (98.8%) of the insurees with a psychiatric index diagnosis had at least one somatic diagnosis coded as well. 95.7% of treatments were provided in the outpatient setting. Somatic medical specialties provided the majority of treatments both in ambulatory care and in the hospital. For example, 77.5% of persons with severe depression were treated with five kinds of treatment that were provided exclusively by primary care physicians and other specialists in somatic medicine in private practice, sometimes in combination with psychiatric treatment or psychotherapy. There was a high degree of comorbidity of mental and somatic illness. The fact that the vast majority of treatment was provided in the outpatient setting implies that cooperation across health-care sectors and disciplines should be reinforced, and that measures should be taken to ensure the adequate delivery of basic psychiatric care by primary care physicians.


Disentangling categorical relationships through a graph of co-occurrences.
The mesoscopic structure of complex networks has proven a powerful level of description to understand the linchpins of the system represented by the network. Nevertheless, the mapping of a series of relationships between elements, in terms of a graph, is sometimes not straightforward. Given that all the information we would extract using complex network tools depend on this initial graph, it is mandatory to preprocess the data to build it on in the most accurate manner. Here we propose a procedure to build a network, attending only to statistically significant relations between constituents. We use a paradigmatic example of word associations to show the development of our approach. Analyzing the modular structure of the obtained network we are able to disentangle categorical relations, disambiguating words with success that is comparable to the best algorithms designed to the same end.


Acute and chronic effects of pentobarbital in relation to postsynaptic GABA receptors: a study with muscimol.
Muscimol, a GABA agonist, enhanced pentobarbital sleeping time in a dose-dependent manner. The GABA antagonists such as bicuculline and picrotoxin, and the CNS stimulant such as pentylenetetrazol, inhibited pentobarbital sleeping time; however, all except picrotoxin produced less than 35% maximum inhibition. Picrotoxin, and agent which blocks the chloride ionophore of GABA-receptor complex, exhibited a parallel dose-response curve with respect to muscimol. Chronic administration of pentobarbital by pellet implantation induced tolerance as evidenced by decreased sleeping time; the tolerance receded gradually upon abrupt withdrawal. Muscimol enhanced pentobarbital sleeping time both in tolerant and withdrawal mice. Na+-independent GABA-receptor binding, using [3H]muscimol as a ligand, was increased after acute and chronic pentobarbital administration; withdrawal of the pentobarbital reversed the increase in receptor population. None of the treatments altered the affinity of [3H]muscimol binding. These results support the contention that pentobarbital (a) directly acts on the postsynaptic chloride ionophore and (b) augments GABA-mediated postsynaptic effects. The functional significance of the increase in GABA receptor population after pentobarbital treatment is unclear.


[Effectiveness of a training course on the measure of uterine height for nurses and nursing students].
A prospective, longitudinal study sought to quantify the intra and inter-observer variability of the uterine height (UH) measurement and verify the contribution of a training course for nurses and nursing students in measurement bias. We selected two participants who performed two measurements in 20 pregnant women before and after the course. We calculated the intra and inter-observer variability, the coefficient of intraclass correlation, the absolute and relative technical error of measurement and the measure reliability. The paired t test showed a statistically significant reduce (p = 0.0396) in the measurement bias. We conclude that the training of nurses and nursing students in the technical measurement of UH significantly reduces intra and inter-observer variability.


Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.
MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR) inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI) and a slight decrease in the water apparent diffusion coefficient (ADC) were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV), relative microvascular blood volume (rMBV), transverse relaxation time (T2), blood vessel permeability (K(trans)), and extravascular-extracellular space (ν(e)). The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.


Proteomic and genetics insights on the response of the bacteriocinogenic Lactobacillus sakei CRL1862 during biofilm formation on stainless steel surface at 10°C.
Some lactic acid bacteria have the ability to form biofilms on food-industry surfaces and this property could be used to control food pathogens colonization. Lactobacillus sakei CR1862 was selected considering its bacteriocinogenic nature and ability to adhere to abiotic surfaces at low temperatures. In this study, the proteome of L. sakei CRL1862 grown either under biofilm on stainless steel surface and planktonic modes of growth at 10°C, was investigated. Using two-dimensional gel electrophoresis, 29 out of 43 statistically significant spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Ten proteins resulted up-regulated whereas 16 were down-regulated during biofilm formation. Differentially expressed proteins were found to belong to carbohydrate, nucleotide, aminoacid and lipid metabolisms as well as translation, peptide hydrolysis, cell envelope/cell wall biosynthesis, adaption to atypical conditions and protein secretion. Some proteins related to carbohydrate and nucleotide metabolisms, translation and peptide degradation were overexpressed whereas those associated to stress conditions were synthesized in lower amounts. It seems that conditions for biofilm development would not imply a stressful environment for L. sakei CRL1862 cells, directing its growth strategy towards glycolytic flux regulation and reinforcing protein synthesis. In addition, L. sakei CRL1862 showed to harbor nine out of ten assayed genes involved in biofilm formation and protein anchoring. By applying qRT-PCR analysis, four of these genes showed to be up regulated, srtA2 being the most remarkable. The results of this study contribute to the knowledge of the physiology of L. sakei CRL1862 growing in biofilm on a characteristic food contact surface. The use of this strain as green biocide preventing L. monocytogenes post-processing contamination on industrial surfaces may be considered.


Identification and genetic characterization of a novel CRF22_01A1 recombinant form of HIV type 1 in Cameroon.
Cameroon is a country in West Central Africa in which all four groups of HIV-1 (M, N, O, and P), some circulating recombinant forms (CRFs) and unique recombinant forms (URFs) are prevalent. The CRF22 was initially identified through a novel URF strain, 01CM53122, and later defined from two additional sequences; however, the genomic properties of CRF22 have never been demonstrated in detail. In this study, we describe the characterization of five CRF22_01A1 strains, 02CMLT72, 01CM1867LE, 01CM001BBY, 02CM3097MN, and 02CM1917LE, identified in Cameroon without apparent epidemiological links. A typical CRF22_01A1 strain contains five fragments that can be assigned to the CRF01_AE and subsubtype A1 radiations. Forty-eight percent of the genome is classified as CRF01_AE, spanning the entire region of the gag gene, part of the pol gene, and accessory genes as well as the beginning and the end of the env gene and nef gene. Fifty-two percent of the genome is subsubtype A1 including regions mostly in the pol, vif, and env genes. The five CRF22_01A1 viruses formed a deep branch outside the groups of CRF01_AE and displayed similar mosaic structure but were moderately different from the original strain of CRF22_01A1, 01CM53122. Further analysis of the 01CM53122 genome showed that this virus represents a diverse set of mosaic genomes from CRF22_01A1, including a 446-nt segment of 01CM53122 in the env region, but unlike other CRF22 strains, clustered with CRF01_AE rather than the A1 sequence, suggesting that the 01CM53122 strain is a recombinant of CRF22_01A1 and CRF01_AE.


Early Detection of Pre-Cancerous and Cancerous Cells Using Raman Spectroscopy-Based Machine Learning.
Cancer is the most common and fatal disease around the globe, with an estimated 19 million newly diagnosed patients and approximately 10 million deaths annually. Patients with cancer struggle daily due to difficult treatments, pain, and financial and social difficulties. Detecting the disease in its early stages is critical in increasing the likelihood of recovery and reducing the financial burden on the patient and society. Currently used methods for the diagnosis of cancer are time-consuming, producing discomfort and anxiety for patients and significant medical waste. The main goal of this study is to evaluate the potential of Raman spectroscopy-based machine learning for the identification and characterization of precancerous and cancerous cells. As a representative model, normal mouse primary fibroblast cells (NFC) as healthy cells; a mouse fibroblast cell line (NIH/3T3), as precancerous cells; and fully malignant mouse fibroblasts (MBM-T) as cancerous cells were used. Raman spectra were measured from three different sites of each of the 457 investigated cells and analyzed by principal component analysis (PCA) and linear discriminant analysis (LDA). Our results showed that it was possible to distinguish between the normal and abnormal (precancerous and cancerous) cells with a success rate of 93.1%; this value was 93.7% when distinguishing between normal and precancerous cells and 80.2% between precancerous and cancerous cells. Moreover, there was no influence of the measurement site on the differentiation between the different examined biological systems.


Evaluation of maxillary anterior teeth proportion with Chu's Gauge in a population of Central India: an in vivo study.
To evaluate the width/height proportions in maxillary anterior natural dentition and its correlation with Chu's esthetic proportion Gauge. Observational cross-sectional study with the inclusion criteria of well aligned maxillary anterior teeth. The present study attempts to perceive the application of Chu's Esthetic Proportion Gauge in a group of the central Indian population. A total number of 150 participants within the age group 18-30 years were screened, out of which 80 participants were selected, who fulfilled the inclusion criteria of well aligned maxillary anterior teeth with pleasing smile, unrestored, periodontally sound, no fracture, no missing, absence of diastema teeth and no H/O orthodontic treatment. The selected participants were seated on the dental chair with the Frankforts horizontal plane parallel to the floor. The participants were observed for height and width proportions using the Chu's esthetic proportion gauge and measured using digital vernier calliper. The proportion and measured height and width ratios were then compared. The recorded data was compiled and entered in a spreadsheet computer program (Microsoft Excel 2007) and then exported to data editor page of SPSS version 20.0 (SPSS Inc., Chicago, Illinois, USA). Intergroup comparison between gauge and vernier caliper was done using Chi-square test for proportions percentages (Qualitative data) and Mann-Whitney U test of width and height and then categorized into esthetic and unesthetic anterior teeth. Level of significance was set at 0.05. Within the limitations of the study, it was concluded that maxillary anterior teeth did show similarity with Chu's esthetic proportion scale.


2014 European Guideline on HIV testing.
Testing for HIV is one of the cornerstones in the fight against HIV spread. The 2014 European Guideline on HIV Testing provides advice on testing for HIV infection in individuals aged 16 years and older who present to sexually transmitted infection, genito-urinary or dermato-venereology clinics across Europe. It may also be applied in other clinical settings where HIV testing is required, particularly in primary care settings. The aim of the guideline is to provide practical guidance to clinicians and laboratories that within these settings undertake HIV testing, and to indicate standards for best practice.


Antiglobulin antibody in the sera of contacts of children with leukaemia.
Healthy adults (parents, neighbours, and hospital staff) in close contact with children with leukaemia were found to have a high incidence of positive latex agglutination antiglobulin tests (probably an IgM antiglobulin antibody). This may explain a previous report of a high incidence of IgM anti-EB virus antibodies in parents of leukaemic children, which our results did not confirm (IgM antiglobulin, reacting with IgG anti-EB virus, could have been misinterpreted as IgM anti-EB virus). The antiglobulin antibody probably represents a nonspecific response to an infective agent. Other hospital staff, including those exposed to nonleukaemic children with infections, had a much lower incidence of the antibody, and it may represent a response to the leukaemic process itself, rather than to the infections to which such children are prone. Some leukaemic children have a similar antibody.


Systematic review of the cost effectiveness of prophylactic treatments in the prevention of gastropathy in patients with rheumatoid arthritis or osteoarthritis taking non-steroidal anti-inflammatory drugs.
A systematic review on the cost effectiveness of prophylactic treatments of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy in patients with osteoarthritis or rheumatoid arthritis was conducted. Two reviewers conducted the literature search and the review. Both full and partial economic evaluations published in English, Dutch, or German were included. The criteria list published in the textbook of Drummond was used to determine the quality of the economic evaluations. The methodological quality of three randomised controlled trials (RCTs) in which the economic evaluations obtained probability estimates of NSAID induced gastropathy and adverse events was assessed by a list of internal validity criteria. The conclusions were based on a rating system consisting of four levels of evidence. Ten economic evaluations were included; three were based on RCTs. All evaluations studied misoprostol as prophylactic treatment: in one evaluation misoprostol was studied as a fixed component in a combination with diclofenac (Arthrotec). All economic evaluations comprised analytical studies containing a decision tree. The three trials were of high methodological quality. Nine economic evaluations were considered high quality and one economic evaluation was considered of low methodological quality. There is strong evidence (level "A") that the use of misoprostol for the prevention of NSAID induced gastropathy is cost effective, and limited evidence (level "C") that the use of Arthrotec is cost effective. Although the levels of evidence used in this review are arbitrary, it is believed that a qualitative analysis is useful: quantitative analyses in this field are hampered by the heterogeneity of economic evaluations. Existing criteria to evaluate the methodological quality of economic evaluations may need refinement for use in systematic reviews.


The handling of the mechanistic probe 5-fluorouridine by the pseudouridine synthase TruA and its consistency with the handling of the same probe by the pseudouridine synthases TruB and RluA.
RNA containing 5-fluorouridine (F(5)U) had previously been used to examine the mechanism of the pseudouridine synthase TruA, formerly known as pseudouridine synthase I [Gu et al. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 14270-14275]. From that work, it was reasonably concluded that the pseudouridine synthases proceed via a mechanism involving a Michael addition by an active site aspartic acid residue to the pyrimidine ring of uridine or F(5)U. Those conclusions rested on the assumption that the hydrate of F(5)U was obtained after digestion of the product RNA and that hydration resulted from hydrolysis of the ester intermediate between the aspartic acid residue and F(5)U. As reported here, (18)O labeling definitively demonstrates that ester hydrolysis does not give rise to the observed hydrated product and that digestion generates not the expected mononucleoside product but rather a dinucleotide between a hydrated isomer of F(5)U and the following nucleoside in RNA. The discovery that digestion products are dinucleotides accounts for the previously puzzling differences in the isolated products obtained following the action of the pseudouridine synthases TruB and RluA on F(5)U in RNA.


Developmental toxicity of e-cigarette aerosols.
Maternal smoking during pregnancy represents a major public health concern increasing the risk for low birth weight, congenital anomalies, preterm birth, fetal mortality, and morbidity. In an effort to diminish adverse developmental effects of exposure to cigarette smoking, pregnant women, and women of reproductive age, are increasingly turning to electronic nicotine delivery systems (ENDS), such as e-cigarettes, as an alternative. Given that health risks associated with ENDS use during pregnancy are largely unknown, there is an acute need to determine risks vs. benefits of e-cigarette use by pregnant women. While the most recent Surgeon General's Report on the "Health Consequences of Smoking" states that "the evidence is sufficient to infer that nicotine adversely affects maternal and fetal health during pregnancy, contributing to multiple adverse outcomes," it remains unclear whether use of ENDS represents a "safer alternative" to tobacco smoking during pregnancy. This is due, in part, to the lack of sufficient and conclusive evidence concerning whether or not maternal e-cigarette use adversely affects embryonic/fetal development. While several recent developmental studies have challenged the safety of nicotine inhalation via ENDS, the true risks of smoking e-cigarettes during the first trimester of pregnancy-the period of organogenesis-are largely unknown. Moreover, evidence is emerging that even nicotine-free e-cigarette aerosols may harm the developing conceptus, suggesting that components of e-cigarette liquid, including flavorings, may be developmentally toxicity. Focused human epidemiological analyses, and carefully designed animal studies are critically needed to address the question of the safety of ENDS use during pregnancy.


Between-trial inhibition and facilitation in goal-directed aiming: manual and spatial asymmetries.
Three experiments were conducted with right-handed participants to examine between-trial inhibition and facilitation effects in goal-directed aiming. Participants were required to execute rapid left-hand or right-hand aiming movements upon illumination of a target light in left or right space. Thus, from trial to trial, participants executed movements to either the same target location or a different target location with the either same hand or the other hand. Our reaction time results indicated that participants were particularly slow in initiating their movements when they were required to return to the same target location with the other hand. This was especially the case when the right hand was required to move to a target just occupied by the left hand. For both reaction time and movement time the right hand but not the left hand exhibited an advantage when it was required to perform the same movement two times in a row. Taken together these results suggest that inhibition of return, in a target-target paradigm, is more associated with the particular spatial location of the target than the organization of a specific movement to that location. Moreover, the between-trial facilitation observed for the right hand may reflect the ability of the left cerebral hemisphere to maintain an already parameterized motor program over a short intertrial interval.


Papillary thyroid microcarcinomas: a comparative study of the characteristics and risk factors at presentation in two cancer registries.
Papillary thyroid microcarcinoma (PTMC) is an indolent neoplasia, often asymptomatic and discovered incidentally. Some PTMCs, however, exhibit a more aggressive behavior, frequently recur, and can even cause cancer-related death. The aim of this study was to evaluate the prevalence of PTMCs and the associated risk factors at presentation in 2 thyroid cancer registries from areas with different genetic and environmental characteristics. We conducted a retrospective, observational study of all incident cases of PTMCs recorded over a 5-year period in the Sicilian Regional Registry for Thyroid Cancer (SRRTC) and in the Surveillance Epidemiology and End Results (SEER) US registry. The study took place at an academic hospital. The incidence of PTMCs was much higher in Sicily (1777 PTMC diagnosed in 2002-2006; age-standardized incidence rate for the world population [ASRw] = 5.8 per 100 000) than in the United States (14 423 PTMC in the period 2004-2008; ASRw = 2.9 per 100 000). Within the SRRTC, a significantly higher incidence was observed in the volcanic area (ASRw = 10.4 vs 4.6 in the rest of Sicily). In Sicily, the female to male ratio was higher, and PTMC patients were younger. In both registries, a significant inverse correlation was observed between age and tumor size. Young patients (≤45 y) exhibited a higher frequency of nodal metastases. PTMC incidence is twice as high in Sicily compared with the United States, and within Sicily, the incidence is twice as high in the volcanic area. In young patients, PTMCs are larger at presentation and exhibit more risk factors. In both registries, more than 35% of PTMCs exhibited 2 or more risk factors, suggesting that they may require surgery and follow-up similar to that of larger carcinomas.


Cordyceps cicadae induces G2/M cell cycle arrest in MHCC97H human hepatocellular carcinoma cells: a proteomic study.
Cordyceps cicadae is a medicinal fungus that is often used for treating cancer. However, the anticancer mechanisms of C. cicadae are largely unknown. This study aims to investigate the anticancer mechanisms of C. cicadae against hepatocellular carcinoma cells in vitro using a proteomic approach. Human hepatocellular carcinoma MHCC97H cells were treated with a water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) for 48 h and harvested for cell viability assays. The significant differences in protein expression between control and C. cicadae-treated cells were analyzed by two-dimensional gel-based proteomics coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry. Flow cytometry analysis was employed to investigate the cell cycle and cell death. The anticancer molecular mechanism was analyzed by whole proteome mapping. The water extract of C. cicadae (0, 100, 250, 500, and 1000 μg/mL) inhibited the growth of MHCC97H cells in a dose-dependent manner via G2/M phase cell cycle arrest with no evidence of apoptosis. Among the identified proteins with upregulated expression were dynactin subunit 2, N-myc downstream-regulated gene 1, heat shock protein beta-1, alpha-enolase isoform 1, phosphatidylinositol transfer protein, and WD repeat-containing protein 1. Meanwhile, the proteins with downregulated expression were 14-3-3 gamma, BUB3, microtubule-associated protein RP/EB family member 1, thioredoxin-like protein, chloride intracellular channel protein 1, ectonucleoside triphosphate diphosphohydrolase 5, xaa-Pro dipeptidase, enoyl-CoA delta isomerase 1, protein-disulfide isomerase-related chaperone Erp29, hnRNP 2H9B, peroxiredoxin 1, WD-40 repeat protein, and serine/threonine kinase receptor-associated protein. The water extract of C. cicadae reduced the growth of human hepatocellular carcinoma MHCC97H cells via G2/M cell cycle arrest.


Evaluating the immunogenicity of chemically-synthesised peptides derived from foot-and-mouth disease VP1, VP2 and VP3 proteins as vaccine candidates.
Foot-and-mouth disease (FMD) is one of the most contagious veterinary viral diseases known, having economic, social and potentially devastating environmental impacts. The vaccines currently being marketed/sold around the world for disease control and prevention in bovines do not stimulate the production of antibodies having crossed reactions to different serotypes. This means that if an animal becomes infected by a serotype which has not been included in a vaccine then it will develop the disease. Synthetic peptide vaccines represent a safer option and (depending on the design) can stimulate antibodies protecting against different variants. Based on the forgoing, this work was aimed at evaluating FMDV VP1, VP2 and VP3 protein-derived, modified and chemically-synthesised peptides' ability to induce an immune response for developing a vaccine contributing towards controlling the disease. VP1, VP2 and VP3 proteins' conserved regions were selected for this. Peptides from these regions were chemically synthesised; binding assays were then carried out for ascertaining whether they were involved in BHK-21 cell binding. Selected peptides' structure and location were studied. Peptides which did bind were modified and formulated with Montanide ISA 70 adjuvant; 17 animals were immunised twice with the formulation. The animals were genotyped by amplifying the BoLA-DRB3.2 gene. Blood samples were taken from 17 cattle on day 43 post-first immunisation for studying the formulation's immunogenicity. The sera were used in ELISA, immunofluorescence, flow cytometry, immunoadsorption and seroneutralisation assays. The A24 Cruzeiro and O1 Campos virus serotypes were used for these assays. The results revealed that even though protein exposure and 3D structure might be different amongst serotypes, the antibodies so produced could inhibit virus entry to cells, thereby showing the selected peptides' in vitro protection-inducing ability.


Prevalence and nature of early glaucomatous defects in the central 10° of the visual field.
The macula is essential for visual functioning and is known to be affected even in early glaucoma. However, little is currently understood about the prevalence and nature of central vision loss in early glaucoma. To determine the prevalence and characteristics of visual field (VF) defects in the central 10° in glaucoma suspects and patients with mild glaucoma using a prospective design. This prospective observational cohort study was conducted at an outpatient glaucoma specialty clinic. One hundred eyes from 74 patients with glaucomatous optic neuropathy and a 24-2 VF with mean deviation better than -6 dB were prospectively studied and tested with a 10-2 test. Reliable: VF hemifields were classified as abnormal based on a cluster criterion, and abnormal 10-2 VFs were categorized based on the pattern of abnormal points: arcuatelike, widespread, or other. In addition, at each point of the 10-2 VF, the total deviation values were averaged across eyes and the number of abnormal points with total deviation values below a specific criterion level were calculated. RESULTS There appeared to be as many abnormal 10-2 hemifields (53%) as abnormal 24-2 hemifields (59%). Of the eyes with normal 24-2 hemifields, 16% were classified as abnormal when the 10-2 test was used. Of the abnormal 10-2 hemifields, 68%, 8%, and 25% were arcuatelike, widespread, and other, respectively. The average total deviation values and number of abnormal points plots revealed superior VF defects that were deeper and closer to fixation than those in the inferior VF. The 10-2 VF was abnormal in nearly as many hemifields as was the 24-2 VF, including some with normal 24-2 VF, suggesting that the 24-2 test is not optimal for detecting early damage of the macula. The pattern of the defects was in agreement with a recent model of macular damage.


Closing the gap: A novel metric of change in performance.
Interventions to improve performance of global programs in the HIV cascade of care are widespread and increasing the focus of implementation science. At present, however, there is no clear consensus on how to conceptualize their improvement at the program level. The commonly used measures of association, based on ratios of probabilities (or odds), have well-known defects in public health applications. They yield large effect sizes even when the absolute effects, and therefore the public health impact, are small. On the other hand, risk differences create problems because settings with higher baseline values are penalized. We aim to examine ways of quantifying improvement in each health center of a cluster-randomized trial in Uganda to accelerate antiretroviral therapy initiation among HIV-infected adults. We formalize the concept of the 'improvement index,' defined as the fraction of gaps closed as a metric of improvement, and suggest that it has unique features and strengths when compared to risk ratios and risk differences. Overall agreement between the different indices was not high, especially among health centers that were among the top 5 or 10. However, all ranking showed broad similarities at the far ends of the spectrum. On scatter plots, there was a positive linear relationship between the metrics, and the Bland Altman (B-A) plots were in agreement. The improvement index can be used as an alternative measure of association in implementation science interventions. It can be useful for public health purposes as it demonstrates how much can be covered from the baseline.


Epidemiology of gastric cancer in the gangetic areas of west bengal.
There is marked geographical variation in the distribution and incidence of stomach cancer. We tried here to describe the pattern of relationships of age, sex, religion distribution, symptom profile, histological subtypes and Helicobacter pylori (H. pylori) infection with gastric cancer in Gangetic West Bengal. This study was done over a period of five years (2006-2010). The patients residing in the Gangetic areas of West Bengal presenting with upper gastrointestinal symptoms underwent UGI endoscopy. Among gastric cancer patients, demographic characteristics, symptomatology, macroscopic and histologic lesions and H. pylori status were analyzed. At confidence level 95%, "Z" and "P" value were calculated to find significance. Among 23851 patients underwent UGI endoscopy, 14106 were males, 9745 females, 17889 Hindus and 5962 Muslims. Among 462 gastric cancer patients, Male : Female 2.7 : 1, Hindus : Muslim 3 : 1, abdominal pain, indigestion, and weight-loss were commonest presentations. Antrum was the commonest site whereas ulceroproliferative type was commonest type. H. pylori positivity was 80.89% in adenocarcinoma with statistically significant relation with intestinal type. In future, our target will be to modify risk factors; it will need further demographic studies and analysis, so that we can detect it earliest.


Relative effects of inhaled corticosteroids on immunopathology and physiology in asthma: a controlled study.
Although corticosteroids are recognised as the most efficacious treatment for bronchial asthma, their mode of action remains unclear. A placebo controlled trial was undertaken of the effect of inhaled corticosteroids on physiological and immmunopathological parameters in asthmatic patients in whom the correlations between these indices were tested after treatment. Sixteen patients (two women) with asthma entered a double blind, placebo controlled, parallel study during which they inhaled either budesonide 800 micrograms twice daily or matching placebo for six weeks. Spirometric parameters and bronchial reactivity to histamine and terbutaline were measured and endobronchial biopsy samples were taken before and after treatment. Patients recorded morning and evening flow rates during the treatment period. The biopsy samples were subjected to immunohistological analysis to determine the disposition of inflammatory cells within the bronchial wall. Treatment with budesonide resulted in a significant improvement in the 25-75% forced expiratory flow (FEF25-75) from a mean of 133 l/min before treatment to 169 l/min after treatment, and in the morning peak expiratory flow rate (PEFR) from a mean of 384 l/min before treatment to 415 l/min after treatment. No changes were seen in the placebo group. Comparison between the changes in the immunopathological indices after six weeks of treatment with placebo or budesonide showed a significant reduction in the numbers of mast cells (0.5/unit area to 0.2/ unit area), activated eosinophils, and the expression of HLA-DR antigens (relative density -1.9 before to 1.02 after treatment) on inflammatory cells in response to treatment with budesonide. Although reductions in the numbers of other inflammatory cells within the bronchial wall were recorded using immunohistological analysis, these changes were not statistically significant. Significant correlations were found between changing immunological indices and lung physiology. This controlled study shows that inhaled corticosteroids cause improvement in physiological and immunopathological parameters in patients with stable asthma that are not seen with placebo, and that cause and effect relationships may exist between these two measures of disease status.


Effects of dietary polyenylphosphatidylcholine on metabolism of cholesterol and triglycerides in hypertriglyceridemic patients.
This study was carried out primarily to determine whether the feeding of lecithin (polyenylphosphatidylcholine) has systemic effects on metabolism of cholesterol and triglycerides in patients with endogenous hypertriglyceridemia (type 4 hyperlipoproteinemia). Ten patients were studied during control periods and lecithin feeding. In the former period, 7 g of safflower oil were added to the diet to balance the addition of 10 g of lecithin in the latter period. Lecithin feeding had no influence on levels of plasma cholesterol and triglycerides, or lipoprotein-cholesterol, transport of VLDL-triglycerides, or total steroid balance. However, lecithin feeding did significantly increase the molar percent of bile acids and decrease the molar percent lecithin in gallbladder bile suggesting that it has a systemic effect. In addition, it had a small but significant inhibitory effect on intestinal absorption of cholesterol.


Multigene phylogeny of choanozoa and the origin of animals.
Animals are evolutionarily related to fungi and to the predominantly unicellular protozoan phylum Choanozoa, together known as opisthokonts. To establish the sequence of events when animals evolved from unicellular ancestors, and understand those key evolutionary transitions, we need to establish which choanozoans are most closely related to animals and also the evolutionary position of each choanozoan group within the opisthokont phylogenetic tree. Here we focus on Ministeria vibrans, a minute bacteria-eating cell with slender radiating tentacles. Single-gene trees suggested that it is either the closest unicellular relative of animals or else sister to choanoflagellates, traditionally considered likely animal ancestors. Sequencing thousands of Ministeria protein genes now reveals about 14 with domains of key significance for animal cell biology, including several previously unknown from deeply diverging Choanozoa, e.g. domains involved in hedgehog, Notch and tyrosine kinase signaling or cell adhesion (cadherin). Phylogenetic trees using 78 proteins show that Ministeria is not sister to animals or choanoflagellates (themselves sisters to animals), but to Capsaspora, another protozoan with thread-like (filose) tentacles. The Ministeria/Capsaspora clade (new class Filasterea) is sister to animals and choanoflagellates, these three groups forming a novel clade (filozoa) whose ancestor presumably evolved filose tentacles well before they aggregated as a periciliary collar in the choanoflagellate/sponge common ancestor. Our trees show ichthyosporean choanozoans as sisters to filozoa; a fusion between ubiquitin and ribosomal small subunit S30 protein genes unifies all holozoa (filozoa plus Ichthyosporea), being absent in earlier branching eukaryotes. Thus, several successive evolutionary innovations occurred among their unicellular closest relatives prior to the origin of the multicellular body-plan of animals.


African swine fever virus infection in Classical swine fever subclinically infected wild boars.
Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a+) and a decrease in CD4+ T cells in the PBMCs from CSFV PI animals after ASFV infection. Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice versa. ASFV infection could be a trigger factor for the disease progression in CSFV PI animals, as their survival after ASFV was similar to that of the pestivirus-free ASFV-infected group. This fact suggests a high resistance in CSFV PI animals even against a virus like ASFV; this may mean that there are relevant implications for CSF control in endemic countries. The diagnosis of ASFV and CSFV co-infection in endemic countries cannot be ruled out and need to be studied in greater depth.


[Clinical study on the abutment periodontal condition with extracoronal attachment denture].
To evaluate the abutment periodontium condition after restored with the distal-extension extracoronal attachment dentures. 20 mandibular distal-extension cases were followed up, to measure the gingival index (GI) and plaque index (PLI) of the distant-abutments before restored with attachment dentures and after restored for one month, six months and one year; to compare the length of distant alveolar bone before restored with that after restored one year by taking digital stomatology tomogram photos. There were not significantly different in the PLI of distant-abutment between before repaired and after repaired one month, six months, one year (P > 0.05). There were not significantly different in the GI of distant-abutment between before repaired and after repaired one month, six months (P > 0.05), but the GI of distant-abutment after repaired one year was significantly higher than that before repaired (P < 0.05). There were no significant differences on the length of distant alveolar bone in distant-abutment before repaired and after repaired one year(P > 0.05). It is important to protect the periodontal health of the abutment when restored with distal-extension extracoronal attachment dentures. It is necessary to examine periodically after restored in order to keep the periodontal health of the abutment.


Atomically resolved single-molecule triplet quenching.
The nonequilibrium triplet state of molecules plays an important role in photocatalysis, organic photovoltaics, and photodynamic therapy. We report the direct measurement of the triplet lifetime of an individual pentacene molecule on an insulating surface with atomic resolution by introducing an electronic pump-probe method in atomic force microscopy. Strong quenching of the triplet lifetime is observed if oxygen molecules are coadsorbed in close proximity. By means of single-molecule manipulation techniques, different arrangements with oxygen molecules were created and characterized with atomic precision, allowing for the direct correlation of molecular arrangements with the lifetime of the quenched triplet. Such electrical addressing of long-lived triplets of single molecules, combined with atomic-scale manipulation, offers previously unexplored routes to control and study local spin-spin interactions.


Human eating behaviour in an evolutionary ecological context.
Present-day human eating behaviour in industrialised society is characterised by the consumption of high-energy-density diets and often unstructured feeding patterns, largely uncoupled from seasonal cycles of food availability. Broadly similar patterns of feeding are found among advantaged groups in economically-emerging and developing nations. Such patterns of feeding are consistent with the evolutionary ecological understanding of feeding behaviour of hominids ancestral to humans, in that human feeding adaptations are likely to have arisen in the context of resource seasonality in which diet choice for energy-dense and palatable foods would have been selected by way of foraging strategies for the maximisation of energy intake. One hallmark trait of human feeding behaviour, complex control of food availability, emerged with Homo erectus (1.9 x 10(6)-200000 years ago), who carried out this process by either increased meat eating or by cooking, or both. Another key trait of human eating behaviour is the symbolic use of food, which emerged with modern Homo sapiens (100000 years ago to the present) between 25000 and 12000 years ago. From this and subsequent social and economic transformations, including the origins of agriculture, humans have come to use food in increasingly elaborate symbolic ways, such that human eating has become increasingly structured socially and culturally in many different ways.


Glucose intolerance and cardiovascular risk factors in Hong Kong: data from two occupation-based cross-sectional surveys.
To examine the distribution of plasma glucose and related cardiovascular risk factors in two occupation-based cross-sectional surveys in a Chinese ethnic population. Two cross-sectional surveys in a Hong Kong working population. In 1990, 1496 participants aged 18-66 years underwent an OGTT, anthropometric, and other biochemical measures. Identical measures were collected from 534 participants aged 20-72 years in 2001-2003. Data were direct age-standardised to compare CVD risk factor prevalence. Linear regression modelling was used to examine the distribution of continuous CVD risk factors. Mean (SD) 2-h plasma glucose values were 5.6mmol/l (2.1) in 1990 and 6.5mmol/l (2.5) in 2001-2003, an apparent increase of 0.5mmol/l (95% CI 0.3 to 0.7, p<0.001) after age and sex adjustment. However, there was no significant difference in the age-standardised prevalence of glucose intolerance, overweight or obesity. There were significantly smaller proportions of women with hypertension and hyperlipidaemia and male smokers in the second compared to the first survey. We observed a relatively adverse glycaemia profile, which may have worsened over time, in two healthy populations of survey respondents, with comparatively low rates of most CVD risk factors. This has implications for the future burden of disease associated with hyperglycaemia in this population.


Mechanical Mapping of Spinal Cord Growth and Repair in Living Zebrafish Larvae by Brillouin Imaging.
The mechanical properties of biological tissues are increasingly recognized as important factors in developmental and pathological processes. Most existing mechanical measurement techniques either necessitate destruction of the tissue for access or provide insufficient spatial resolution. Here, we show for the first time to our knowledge a systematic application of confocal Brillouin microscopy to quantitatively map the mechanical properties of spinal cord tissues during biologically relevant processes in a contact-free and nondestructive manner. Living zebrafish larvae were mechanically imaged in all anatomical planes during development and after spinal cord injury. These experiments revealed that Brillouin microscopy is capable of detecting the mechanical properties of distinct anatomical structures without interfering with the animal's natural development. The Brillouin shift within the spinal cord remained comparable during development and transiently decreased during the repair processes after spinal cord transection. By taking into account the refractive index distribution, we explicitly determined the apparent longitudinal modulus and viscosity of different larval zebrafish tissues. Importantly, mechanical properties differed between tissues in situ and in excised slices. The presented work constitutes the first step toward an in vivo assessment of spinal cord tissue mechanics during regeneration, provides a methodical basis to identify key determinants of mechanical tissue properties, and allows us to test their relative importance in combination with biochemical and genetic factors during developmental and regenerative processes.


Orthodontic considerations for gingival health during pregnancy: a review.
Gingivitis is caused by several known systemic and local factors. Among systemic factors, the role of hormonal changes during pregnancy is well established. While presence of fixed orthodontic appliances alone may not cause gingivitis, factors such as pregnancy and poor oral hygiene combined together could precipitate acute gingival inflammation that may progress to a periodontal condition in a patient receiving orthodontic therapy. There has been an increase in the number of adult patients who are receiving orthodontic treatment. Orthodontic appliances could act as a potential plaque retentive source and aggravate inflammatory reactions that are seen during pregnancy. There is a lack of awareness regarding oral healthcare issues among patients who are pregnant and choose to seek orthodontic treatment. In addition, there is a need in the literature to outline management guidelines for patients who want to receive orthodontic treatment during pregnancy, with or without pre-existing gingival conditions. This review focuses on the aetiology of pregnancy gingivitis and the management of orthodontic patients during pregnancy. Our emphasis is on patient education, oral hygiene maintenance, preventive and treatment strategies for the management of gingival health in orthodontic patients during pregnancy. We also highlight some of the possible complications of initiating orthodontic treatment during pregnancy.