bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of a primary preventive dental programme in non‐fluoridated areas of Victoria, Australia
Authors: Morgan M. V. , Campain A. C. , Crowley S. J. , Wright F. A. C.
Published: October 2010

A primary preventive dental programme targeting adolescents living in non‐fluoridated areas of Victoria, Australia was evaluated for a three‐year period. The programme comprised annual placement or replacement/repair of fissure sealants combined with a weekly 0.2 per cent sodium fluoride mouthrinse and was evaluated in terms of acceptance by the providers and the community to which it was directed. Acceptance was measured using accessibility, availability, continuity, quality of care, role responsibility, provider and consumer satisfaction, and cost‐effectiveness. In general, the programme was considered to represent an acceptable model for future preventive interventions, although there were areas of its design that were found to require improvement. In particular, deficiencies in the manner in which the fluoride mouthrinsing component was delivered indicate that further investigation would be required before a recommendation to adopt its use could be made.
Florid cemento‐osseous dysplasia in a young Chinese man. Case report
Authors: Ong Siew‐Tin , Siar Chong‐Huat
Published: October 2010

Florid cemento‐osseous dysplasia refers to a group of fibro‐osseous lesions which are exuberant, multi‐quadrant and arise from the tooth‐bearing area of the jaws. It is classically described as a condition occurring almost exclusively in middle‐aged black women. A case of florid cemento‐osseous dysplasia occurring in a young Chinese male is reported which was rare in regard to race and sex.

This 20 year old Chinese man presented with huge symmetrical bony lesions in all four quadrants of the jaws. Clinical presentation, radiological findings and histological features of the excised specimens are described. Treatment of the lesions was unusual. Curettage was first done with minimal benefit and it was followed by mandibular recontouring to improve facial appearance. The outcome of these procedures will be discussed.
Mechanism of diabetic neuropathy: Where are we now and where to go?
Authors: Yagihashi Soroku , Mizukami Hiroki , Sugimoto Kazuhiro
Published: October 2010

Neuropathy is the most common complication of diabetes. As a consequence of longstanding hyperglycemia, a downstream metabolic cascade leads to peripheral nerve injury through an increased flux of the polyol pathway, enhanced advanced glycation end‐products formation, excessive release of cytokines, activation of protein kinase C and exaggerated oxidative stress, as well as other confounding factors. Although these metabolic aberrations are deemed as the main stream for the pathogenesis of diabetic microvascular complications, organ‐specific histological and biochemical characteristics constitute distinct mechanistic processes of neuropathy different from retinopathy or nephropathy. Extremely long axons originating in the small neuronal body are vulnerable on the most distal side as a result of malnutritional axonal support or environmental insults. Sparse vascular supply with impaired autoregulation is likely to cause hypoxic damage in the nerve. Such dual influences exerted by long‐term hyperglycemia are critical for peripheral nerve damage, resulting in distal‐predominant nerve fiber degeneration. More recently, cellular factors derived from the bone marrow also appear to have a strong impact on the development of peripheral nerve pathology. As evident from such complicated processes, inhibition of single metabolic factors might not be sufficient for the treatment of neuropathy, but a combination of several inhibitors might be a promising approach to overcome this serious disorder. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00070.x, 2010)
PGC-1
α, A Potential Therapeutic Target for Early Intervention in Parkinson’s Disease
Authors: Zheng Bin , Liao Zhixiang , Locascio Joseph J. , Lesniak Kristen A. , Roderick Sarah S. , Watt Marla L. , Eklund Aron C. , Zhang-James Yanli , Kim Peter D. , Hauser Michael A. , Grünblatt Edna , Moran Linda B. , Mandel Silvia A. , Riederer Peter , Miller Renee M. , Federoff Howard J. , Wüllner Ullrich , Papapetropoulos Spyridon , Youdim Moussa B. , Cantuti-Castelvetri Ippolita , Young Anne B. , Vance Jeffery M. , Davis Richard L. , Hedreen John C. , Adler Charles H. , Beach Thomas G. , Graeber Manuel B. , Middleton Frank A. , Rochet Jean-Christophe , Scherzer Clemens R. ,   the Global PD Gene Expression (GPEX) Consortium
Published: October 2010

Abnormal expression of genes for energy regulation in Parkinson’s disease patients identifies a master regulator as a possible therapeutic target for early intervention.
The Bayh-Dole Act Turns 30
Authors: Loise Vicki , Stevens Ashley J.
Published: October 2010

The act that gave U.S. institutions the right to claim title to inventions resulting from federally funded work dramatically increased public benefits from research.
Induction of Toll-Like Receptor 3-Mediated Immunity during Gestation Inhibits Cortical Neurogenesis and Causes Behavioral Disturbances
Authors: De Miranda Joari , Yaddanapudi Kavitha , Hornig Mady , Villar Gabriel , Serge Robert , Lipkin W. Ian
Published: October 2010

Maternal infection during pregnancy with a wide range of RNA and DNA viruses is associated with increased risk for schizophrenia and autism in their offspring. A common feature in these exposures is that virus replication induces innate immunity through interaction with Toll-like receptors (TLRs). We employed a mouse model wherein pregnant mice were exposed to polyinosinic-polycytidylic acid [poly(I  ⋅  C)], a synthetic, double-stranded RNA molecular mimic of replicating virus. Poly(I ⋅ C) inhibited embryonic neuronal stem cell replication and population of the superficial layers of the neocortex by neurons. Poly(I ⋅ C) also led to impaired neonatal locomotor development and abnormal sensorimotor gating responses in adult offspring. Using Toll-like receptor 3 (TLR3)-deficient mice, we established that these effects were dependent on TLR3. Inhibition of stem cell proliferation was also abrogated by pretreatment with the nonsteroidal anti-inflammatory drug (NSAID) carprofen, a cyclooxygenase (COX) inhibitor. Our findings provide insights into mechanisms by which maternal infection can induce subtle neuropathology and behavioral dysfunction, and they may suggest strategies for reducing the risk of neuropsychiatric disorders subsequent to prenatal exposures to pathogens and other triggers of innate immunity.

IMPORTANCE
Maternal infection during gestation increases the risk of neuropsychiatric disorders in their offspring. Furthermore, work in animal models indicates that pre- or neonatal infections with a wide range of viruses results in similar neurodevelopmental outcomes. These observations are consistent with a mechanism whereby damage is mediated through common pathways. Exposure of pregnant mice to polyinosinic-polycytidylic acid [poly(I ⋅ C)], a synthetic, double-stranded RNA (dsRNA) molecular mimic of replicating virus, inhibited embryonic neuronal stem cell replication and led to behavioral abnormalities in their offspring. These effects were mediated through TLR3 and abrogated by pretreatment with the nonsteroidal anti-inflammatory drug (NSAID) carprofen. Our findings provide insights into mechanisms by which maternal infection can induce subtle neuropathology and may suggest strategies for reducing the risk of neuropsychiatric diseases following exposures to infectious agents and other triggers of innate immunity during gestation.
p16INK4aimmunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions
Authors: Dijkstra Maaike G , Heideman Daniëlle A M , de Roy Sabine C , Rozendaal Lawrence , Berkhof Johannes , van Krimpen Kees , van Groningen Krijn , Snijders Peter J F , Meijer Chris J L M , van Kemenade Folkert J
Published: October 2010

Background

Histomorphological grading of cervical intraepithelial neoplasia (CIN) is crucial for clinical management. CIN grading is however subjective and affected by substantial rates of discordance among pathologists, which may lead to overtreatment. To minimise this problem, a histology review of CIN lesions by a consensus panel of pathologists is often used. Diffuse strong p16INK4aimmunostaining has been proposed to aid the identification of true high-grade cervical lesions (ie, CIN2/3).

Aim

To assess the value of additional interpretation of p16INK4aimmunostains for making a more reproducible diagnosis of CIN2/3 lesions.

Methods

The authors used a series of 406 biopsies of cervical lesions, with known HPV status, stained for both H&E- and p16INK4a. First, in a randomly selected set of 49 biopsies, we examined the effect of additional interpretation of p16INK4aimmunostained slides, on the agreement of CIN diagnosis among three pathologists. Second, the full series of samples was used to assess the accuracy of p16INK4a-supported lesion grading by a single pathologist, by evaluating the degree of diagnostic agreement with the consensus diagnosis of expert pathologists based on H&E-stained sections only.

Results

The study shows that the interobserver agreement between three pathologists for the routine H&E-based diagnosis ranged from fair (weighted kappa 0.44 (95% CI 0.19 to 0.64)) to moderate (weighted kappa 0.66 (95% CI 0.47 to 0.79)). The concordance increased substantially for p16INK4a-supported grading (mean weighted kappa 0.80 (95% CI 0.66 to 0.89)). Furthermore, an almost perfect agreement was found between the p16INK4a-supported diagnosis of a single pathologist and the consensus diagnosis of an expert pathology panel (kappa 0.88 (95% CI 0.85 to 0.89)).

Conclusions

These data demonstrate that additive use of p16INK4aimmunohistochemistry significantly improves the accuracy of grading CIN lesions by a single pathologist, equalling an expert consensus diagnosis. Hence, the authors advocate the combined use of p16INK4a-stained slides and conventional H&E sections in routine histopathology to improve accuracy of diagnosis.
Xerostomia, hyposalivation and sialadenitis in patients with chronic hepatitis C are not associated with the detection of HCV RNA in saliva or salivary glands
Authors: Grossmann Soraya de Mattos Camargo , Teixeira Rosângela , Oliveira Guilherme Corrêa de , Gleber-Netto Frederico Omar , Araújo Flávio Marcos Gomes , Araújo Filipe Maia , Carmo Maria Auxiliadora Vieira do
Published: October 2010

Objective

Salivary gland disorders in patients with chronic hepatitis C (CHC) have been considered oral extrahepatic manifestations, reinforcing the hepatitis C virus (HCV) as a sialotropic virus. Hence, the authors investigated the prevalence of HCV RNA in saliva and salivary glands and its possible association with xerostomia, hyposalivation and sialadenitis in patients with CHC.

Patients and methods

In 65 patients with confirmed CHC, the HCV RNA was investigated by nested RT-PCR in saliva samples and minor salivary glands. Xerostomia, hyposalivation, clinical and histopathological evidence of sialadenitis were also evaluated. Univariate and multivariate analyses were employed to verify associations.

Results

HCV RNA was detected in the saliva of 26/65 (40.0%) patients and in 12/65 (18.5%) salivary glands. Xerostomia was reported by 23/65 (35.4%) patients, and hyposalivation was diagnosed in 13/65 (20.0%) patients. Sialadenitis was confirmed by histopathological features in 31/65 (47.7%) patients. Twelve (38.7%) of the 31 patients with sialadenitis presented HCV RNA in saliva and 2/31 (6.5%) in salivary glands. No associations were found between xerostomia, hyposalivation or sialadenitis and the detection of HCV RNA in saliva or in salivary glands.

Conclusions

Although xerostomia, hyposalivation and sialadenitis are frequent findings in CHC patients, our study did not confirm the association between the detection of HCV RNA in saliva or salivary glands with these salivary gland disorders. However, an indirect role of HCV by immune-mediated virus mechanisms in the pathogenesis of salivary gland disorders in this group of patients cannot be ruled out.
Absence ofNPM1promoter hypermethylation in human myelodysplastic syndrome
Authors: Cheng Yuen-Yee , Chau David , Chan Thomas , Gill Harinder , Liang Raymond , Kwong Yok-Lam , Tse Eric
Published: October 2010

Npm1+/−heterozygous mice develop a haematological disorder with features resembling human myelodysplastic syndrome (MDS). Promoter hypermethylation of theNPM1gene may lead to suppressed gene transcription and hence functional haploinsufficiency, which contributes to the development of MDS. Thirty-one patients with MDS and eight normal individuals were studied for promoter methylation and mRNA expression ofNPM1. Methylation-specific PCR (MSP), COBRA and bisulfite sequencing were used to examine theNPM1methylation status. Quantitative PCR was used to assess the expression ofNPM1.NPM1DNA methylation was rare, occurring in one of 31 cases as determined by MSP. There was no significant difference inNPM1mRNA expression between MDS and normal blood samples. In conclusion, the finding suggests thatNPM1methylation is rare in MDS and does not play a major role in its pathogenesis.
Colorectal duplication in adults: report of seven cases and review of the literature
Authors: Mourra Najat , Chafai Najim , Bessoud Bertrand , Reveri Valeria , Werbrouck Anabelle , Tiret Emmanuel
Published: October 2010

Background

Gastrointestinal duplications are uncommon congenital abnormalities, usually recognised before the age of 2 (80%). Colorectal duplications (CDDs) occur in only 6.8% of cases, rarely in adults, and are revealed by abdominal pain and intestinal obstruction. Malignant changes are uncommon, but are most often found in the colon.

Methods and results

During the last 7 years, the authors have observed seven cases of CDD (three men) with mean age 50.7 years (range 32–73). Four cases were revealed by abdominal pain, and three by intestinal obstruction. Five duplications were located in the caecum, one in the transverse colon, and one in the sigmoid colon. All CDDs were of the cystic type (4.42 cm, range 2–7.5), and three had a communication with the intestinal lumen. All patients except one underwent ‘en bloc’ resection of the cyst with the adjacent colon. On microscopic examination, CDDs contained multiple layers of the bowel wall, including colonic or small intestinal mucosa. Heterotopic gastric mucosa was observed in only one case, high-grade dysplasia in one case, and low-grade dysplasia in another. No invasive carcinoma was found.

Conclusion

Although uncommon, CDDs should be included in the differential diagnosis of all abdominal masses. The treatment approach is excision, in order to avoid any complication. En bloc resection of the colon with CDD may be necessary, because of the intimate attachments of the common wall. Thorough sampling of the specimen is mandatory in order to detect any malignant changes.
The role of Central Asia in dinosaurian biogeography
Authors: Russell Dale A.
Published: October 2010

Dinosaurian biogeography may have been largely controlled by the Mesozoic fragmentation of Pangea and the reassembly of its fragments into a new, boreal supercontinent (Laurasia). Although Late Triassic and Early Jurassic dinosaurs were globally distributed, Chinese assemblages were dominated by endemic forms from Middle Jurassic into Early Cretaceous time. The affinities of Aptian – Albian immigrants to Asia were strongest with North America and Europe rather than Gondwana, indicating that the northern and southern hemispheres had by then attained their biogeographic identity. This distinctiveness was maintained through Cretaceous time. Europe seems to have been a buffer area between Paleolaurasia and Gondwana; of the northern continents it was the most strongly influenced by Gondwana dispersants. Late Jurassic dinosaur assemblages in North America exhibited Gondwana affinities, but by Late Cretaceous time they were dominated by forms of Asian ancestry.
New material of Xinjiangchelys (Reptilia: Testudines) from the Late Jurassic Qigu Formation (Shishugou Group) of the Pingfengshan locality, Junggar Basin, Xinjiang
Authors: Peng Jiang-Hua , Brinkman Donald B.
Published: October 2010

The Late Jurassic Qigu Formation of the Shishugou Group in the Pingfengshan locality contains a vertebrate fauna dominated by two taxa of turtles, both members of the genus Xinjiangchelys. One of these, Xinjiangchelys latimarginalis (Young and Chow, 1953), is well represented by a series of specimens. The second is specifically indeterminate and is represented by only a single fragmentary specimen but is distinctive in having a long narrow plastral lobe.Derived features of Xinjiangchelys that separate it from Plesiochelys include the presence of a loose connection between the plastron and carapace, with pegs on the plastron fitting in sockets on the peripherals; the extension of the pleural–marginal sulcus onto costals one to five; the dorsal thickening of the lateral edges of peripherals two to seven; the highly expanded seventh to eleventh peripherals; the extension of the anal scute to the hypoplastron–xiphiplastron suture or onto the hypoplastron; a reduction in length of the first dorsal rib; and the presence of a sinusoidal midline sulcus. The first five of these features are shared with Early Cretaceous turtles from Asia generally referred to the "Macrobaenidae," indicating that Xinjiangchelys is more closely related to this group than is Plesiochelys.
A large mamenchisaurid from the Junggar Basin, Xinjiang, People's Republic of China
Authors: Russell Dale A. , Zheng Zhong
Published: October 2010

An articulated neck of a large, mature sauropod, with enormously elongated cervical ribs, was discovered in strata of Late Jurassic age in the eastern Junggar Basin, Xinjiang, People's Republic of China. The animal is estimated to have originally measured 26 m in length, but was lightly proportioned relative to Brachiosaurus and Apatosaurus. Rudimentary spines on the anteriormost cervical vertebrae diagnose a previously undescribed species of Mamenchisaurus. Cranial parts associated with the neck do not support a close relationship with diplodocids. Mamenchisaurs apparently belong to an endemic Jurassic radiation of Asian sauropods.
The affinities of a new theropod from the Alxa Desert, Inner Mongolia, People's Republic of China
Authors: Russell Dale A. , Dong Zhi-Ming
Published: October 2010

Remains of bipedal saurischians from lacustrine strata of Albian age in the Alxa ("Alashan") Desert of Inner Mongolia represent a new taxon and the most complete remains of an Early Cretaceous theropod so far discovered in Asia. A skeletal reconstruction generally resembles that of a moderately large prosauropod with long arms and a short tail. However, in its detailed morphology the reptile appears to be close to the ancestry of the Therizinosauridae Maleev, 1954 (for which Segno-sauridae Perle, 1979 is probably a junior synonym). These theropods are best referred to the Tetanurae of Gauthier, 1986. However, a provisional analysis of the distribution of therizinosauroid characters within tetanurans suggests the existence of two subordinate groups: the Carnosauria (Allosaurus, dromaeosaurids, and tyrannosaurids) and the Oviraptorosauria (including therizinosauroids, ornithomimids, troodontids, and oviraptorids).
Chirotherium
, the Liverpool footprint hunters and their interpretation of the Middle Trias environment
Authors: Bowden A. J. , Tresise G. R. , Simkiss W.
Published: October 2010

The footprints called ‘
Chirotherium
’, because of their resemblance to human hands, were found in Triassic sandstones from Germany in 1834 and Cheshire in 1838. As no bones or other fossil remains were found at either locality, the trackmaker's identity was a mystery. Marsupial mammals were first suggested but in 1842 Richard Owen confidently identified the prints as those of labyrinthodont amphibians. Later discoveries in Cheshire and elsewhere indicated that the trackmakers were more likely to have been pseudosuchian reptiles. In 1965 strong confirmation of this view came from the discovery in Switzerland of the skeleton of
Ticinosuchus ferox.

The absence of fossil remains associated with the footprints has always been ascribed to the arid climate of Triassic times – a view reinforced by Henry Charles
Beasley in 1907
. A more moderate viewpoint was put forward by George Highfield Morton in 1898, who took note of the traces of flora found in the local Triassic strata. Pictorial representations of the Anisian through the late nineteenth and twentieth centuries indicate varying interpretations of the degree of aridity from sparsely vegetated landscapes to sand sea desert. Recent work shows that the environment in a local context was more richly vegetated and humid than had previously been supposed and that the historical interpretation of aridity has probably been overstated. A modern context may, perhaps, be seen in the river valleys of the Atacama Desert in northern Chile. Here, permanent fertile fluvial systems support a mixed indigenous flora of giant horsetails and conifers. The flora displays an adaptation to high groundwater salinity, which may have lessons in interpretation of the Anisian environment.
Pneumaticity, the early years: Wealden Supergroup dinosaurs and the hypothesis of saurischian pneumaticity
Authors: Naish Darren
Published: October 2010

Saurischian dinosaurs were pneumatic animals. The presence of invasive skeletal foramina leading to large internal chambers within the skeleton strongly indicate the presence of avian-style skeletal pneumaticity of the skeleton in sauropodomorphs and non-avian theropods. While the hypothesis of skeletal pneumaticity has undergone a renaissance in recent years, it was initially promoted during the late 1800s after dinosaur fossils from the English Lower Cretaceous Wealden Supergroup led Richard Owen and Harry Seeley to note the pneumatic, bird-like features of the vertebrae they described (Hermann von Meyer had also briefly alluded to skeletal pneumaticity in dinosaurs during the 1830s). In describing the theropod
Becklespinax altispinax
from the Hastings Beds Group (at the time referred to
Megalosaurus
), Richard Owen proposed that the laminae on the neural arch served to house ‘parts of the lungs’. He evidently imagined
Becklespinax
to exhibit avian-style post-cranial skeletal pneumaticity. In 1870 Harry Seeley described two sauropod vertebrae from the Wealden Supergroup, naming them
Ornithopsis hulkei
. Contrary to what is often stated, Seeley did not identify
Ornithopsis
as a pterosaur, but as an animal that might ‘bridge over’ the gap between birds and pterosaurs, while at the same time having some affinity with dinosaurs. The lateral foramina and internal bony cavities of one of these specimens were regarded by Seeley as allowing ‘the prolongation of the peculiarly avian respiratory system into the bones’, and he emphasized ‘the lightest and airiest plan’ of the specimen. In 1876 Owen described the Wessex Formation sauropod
Chondrosteosaurus gigas
. While regarding the lateral fossae as probably having ‘lodged a saccular process of the lung’, Owen now took the opportunity to attack Seeley's claims of pneumaticity in
Ornithopsis
, arguing that the internal cavities in
Chondrosteosaurus
‘were occupied in the living reptile by unossified cartilage, or chondrine’. The name
Chondrosteosaurus gigas
(‘giant cartilage and bone lizard’) also looks like a direct assault on Seeley's proposal of a pneumatic vertebral interior. Owen's actions seem odd given that he was familiar with the internal morphology of avian vertebrae (which are often strikingly similar to those of sauropods). However, both authors have proved insighful in correctly identifying skeletal pneumaticity during this early phase of dinosaur research. A thorough historical review of early ideas on dinosaurian pneumaticity is still required.
The history of Late Jurassic pterosaurs housed in Hungarian collections and the revision of the holotype of
Pterodactylus micronyx
Meyer 1856 (a ‘Pester Exemplar’)
Authors: Ősi Attila , Prondvai Edina , Géczy Barnabás
Published: October 2010

The history and scientific significance of three Late Jurassic pterosaur specimens housed in different Hungarian palaeontological collections are described. One of these is the holotype of
Pterodactylus micronyx
Meyer 1856 that was thought to be lost, but with its rediscovery in the 1980s the ‘Pester Exemplar’ becomes the name-bearing type again. The second specimen is an articulated, partially three-dimensional skeleton of a
Rhamphorhynchus muensteri
; and the third is an articulated right hindlimb of a
Pterodactylus
sp. – both donated by Andor Semsey to the Hungarian Geological Institute. The anatomical revision of the holotype of
P. micronyx
indicated the osteological immaturity of the specimen; however, there is insufficient data on this taxon to assess its taxonomic validity.
The early history of pterosaur discovery in Great Britain
Authors: Martill David M.
Published: October 2010

The first pterosaur fossil was described by Cosimo Alessandro Collini in 1784, but the epithet
ptero dactyle
was not applied until Georges Cuvier recognized the fossil as that of a volant animal in 1801. In eighteenth-century Britain, pterosaur bones had been discovered in Jurassic strata at Stonesfield, Oxfordshire but were considered to be bird bones, and largely went unnoticed. Bones of pterosaurs considerably larger than those of the first pterosaurs were discovered in the early nineteenth century by Gideon Mantell, but because of their comparatively large size were considered by Cuvier to also be the bones of birds. This perception by early nineteenth-century palaeontologists, including William Buckland and Gideon Mantell, that pterosaurs were relatively small animals was probably the reason their remains went unrecognized in British Jurassic and Cretaceous strata for several decades. Furthermore, the eighteenth- and early nineteenth-century dogmatic acceptance that fossil birds
were
present in the Jurassic Stonesfield ‘slate’ of Oxfordshire delayed the identification of medium-sized pterosaurs until the late 1820s, when Dean William Buckland described the Liassic
Pterodactylus
(=
Dimorphodon
)
macronyx
in 1829. Even after that date many fragmentary, but large, pterosaur bones were misidentified as avian, despite there being no convincing evidence for Mesozoic birds until the discovery of
Archaeopteryx
in the 1860s. Truly gigantic pterosaurs were first discovered in Great Britain some 20 years before
Pteranodon
was found in the Late Cretaceous of Kansas. However, the British material was so fragmentary that it was easily eclipsed by the spectacular, near-complete skeletons of
Pteranodon
found by O. C. Marsh and others from the 1870s onwards.
Loss of stearoyl-CoA desaturase activity leads to free cholesterol synthesis through increased Xbp-1 splicing
Authors: Paton Chad M. , Ntambi James M.
Published: October 2010

Stearoyl-CoA desaturase-1 (SCD-1) is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids (MUFA), which are required for efficient neutral lipid esterification. In the present investigation, we demonstrate that loss of SCD-1 activity increases free cholesterol (FC) content and induces Xbp-1 splicing. We assessed the small molecule SCD-1 inhibitor A939572 on [14C]stearate incorporation into neutral lipids and found its incorporation into triglyceride was unaffected, whereas labeled cholesteryl ester (CE) content was notably diminished. Using either A939572 or liver knockout mice (LKO), we show that loss of SCD-1 activity increases FC levels and activates the liver X receptor (LXR) pathway. Using adenoviral delivery of an active form of X-box binding protein-1 (Xbp-1; Xbp-1s), we show increased sterol synthesis only when cells lack the ability to generate MUFA. The results of the cell-based model were confirmed in LKO mice where fasting-refeeding decreased CE, increased FC, and increased Xbp-1s. On the basis of the present data, we conclude that SCD-1 activity is required for efficient cholesterol esterification to MUFA and that loss of its activity increases Xbp-1s-mediated FC synthesis. It is likely that the accumulation of FC enhances Xbp-1 splicing, induces LXR transcriptional activity, and increases ABCA1 (ATP-binding cassette transporter A1) expression to maintain cholesterol homeostasis.
Computational fluid dynamic analysis of flow velocity waveform notching in umbilical arteries
Authors: Tejada-Martínez Andrés E. , Borberg Christian J. , Venugopal Resmi , Carballo Carlos , Moreno Wilfrido A. , Quintero Rubén A.
Published: October 2010

Umbilical artery Doppler velocimetry waveform notching has long been associated with umbilical cord abnormalities, such as distortion, torsion, and/or compression (i.e., constriction). The physical mechanism by which the notching occurs has not been elucidated. Flow velocity waveforms (FVWs) from two-dimensional pulsatile flows in a constricted channel approximating a compressed umbilical cord are analyzed, leading to a clear relationship between the notching and the constriction. Two flows with an asymmetric, semi-elliptical constriction are computed using a stabilized finite-element method. In one case, the constriction blocks 75% of the flow passage, and in the other the constriction blocks 85%. Channel width and prescribed flow rates at the channel inflow are consistent with typical cord diameters and flow rates reported in the literature. Computational results indicate that waveform notching is caused by flow separation induced by the constriction, giving rise to a vortex (core) wave and associated eddies. Notching in FVWs based on centerline velocity (centerline FVW) is directly related to the passage of an eddy over the point of measurement on the centerline. Notching in FVWs based on maximum cross-sectional velocity (envelope FVW) is directly related to acceleration and deceleration of the fluid along the vortex wave. Results show that notching in envelope FVW is not present in flows with less than a 75% constriction. Furthermore, notching disappears as the vortex wave is attenuated at distances downstream of the constriction. In the flows with 75 and 85% constriction, notching of the envelope FVW disappears at ∼3.8 and ∼4.3 cm (respectively) downstream of the constriction. These results are of significant medical importance, given that envelope FVW is typically measured by commercial Doppler systems.
The Episodic Nature of Spike Trains in the Early Visual Pathway
Authors: Butts Daniel A. , Desbordes Gaëlle , Weng Chong , Jin Jianzhong , Alonso Jose-Manuel , Stanley Garrett B.
Published: October 2010

An understanding of the neural code in a given visual area is often confounded by the immense complexity of visual stimuli combined with the number of possible meaningful patterns that comprise the response spike train. In the lateral geniculate nucleus (LGN), visual stimulation generates spike trains comprised of short spiking episodes (“events”) separated by relatively long intervals of silence, which establishes a basis for in-depth analysis of the neural code. By studying this event structure in both artificial and natural visual stimulus contexts and at different contrasts, we are able to describe the dependence of event structure on stimulus class and discern which aspects generalize. We find that the event structure on coarse time scales is robust across stimulus and contrast and can be explained by receptive field processing. However, the relationship between the stimulus and fine-time-scale features of events is less straightforward, partially due to a significant amount of trial-to-trial variability. A new measure called “label information” identifies structural elements of events that can contain ≤30% more information in the context of natural movies compared with what is available from the overall event timing. The first interspike interval of an event most robustly conveys additional information about the stimulus and is somewhat more informative than the event spike count and much more informative than the presence of bursts. Nearly every event is preserved across contrast despite changes in their fine-time-scale features, suggesting that—at least on a coarse level—the stimulus selectivity of LGN neurons is contrast invariant. Event-based analysis thus casts previously studied elements of LGN coding such as contrast adaptation and receptive field processing in a new light and leads to broad conclusions about the composition of the LGN neuronal code.
Voice Activity and Participation Profile Presenting Coordinates for Readjustment of Preventive Action of Educators
Authors: Dragone Maria Lúcia Suzigan
Published: October 2010

Purpose: To investigate the perception of voice impairment in professional and social contexts, to correlate these data with existing data in the literature, and to explore the perception of voice problems and the adherence to vocal health programs. Method: 502 Brazilian educators working in municipal public schools responded to the Voice Activity and Participation Profile (VAPP) questionnaire. Then a correlation was made with previous results in the literature dealing with a dysphonic and a nondysphonic group. Results: The VAPP data showed that self-perception of voice problems had a higher vocal impact on daily communication and lower scores for activity limitation and participation restriction. The educators’ scores were closer to those of the nondysphonic group with regard to daily and social communication, and emotional and activity limitation, but perception of the voice problem was closest to that of the dysphonic group. Nevertheless, the opposite was the case for participation restriction. Conclusions: The educators perceive vocal problems but do not perceive participation restriction to the same extent. This may explain the decreasing participation in the Vocal Health Program. It probably occurs because adults voluntarily apply for training when they feel that their work performance needs to improve so that they can carry out their job properly.
A Novel Target of Mizoribine Inhibiting Mesangial Cell Proliferation: S Phase Kinase-Associated Protein 2
Authors: Liu Shuxin , Xie Yuansheng , Lv Yang , Qin Fufang , Fu Bo , Shi Suozhu , Yin Zhong , Hong Quan , Zhang Xueguang , Wang Jianzhong , Chang Ming , Chen Xiangmei
Published: October 2010

Background/Aims: Mizoribine (MZR) can inhibit mesangial cell (MC) proliferation, but the mechanism remains unknown. In this study, we investigated the inhibitory effect of MZR on MC proliferation via a cell cycle regulatory protein-dependent mechanism. Methods: We investigated the effect of MZR on MC proliferation and expression of cell cycle regulatory proteins such as cyclin D1, cyclin-dependent kinase 2 and p27kip1 in primary cultured rat MCs. We further focused on analyzing the effects of MZR on S phase kinase-associated protein 2 (Skp2), which played a crucial role in p27kip1 degradation. Results: MZR effectively inhibited MC proliferation in primary cultured rat MCs, reduced the expression of cyclin D1 and cyclin-dependent kinase 2, while it dramatically increased the protein level of p27kip1, maintained the nucleus location of p27kip1 and induced G1/S arrest. In contrast to the protein level, MZR produced no changes in p27kip1 mRNA abundance. MZR impaired p27kip1 degradation through downregulating the expression of Skp2 and this effect was not dependent on its inhibition on DNA synthesis. Skp2 overexpression abolished MZR-induced p27kip1 accumulation. Conclusion: These results suggested that MZR-induced p27kip1 accumulation was at least partly mediated by Skp2, and that Skp2 might be a novel target of MZR inhibiting MC proliferation.
Systematic Removal of Outliers to Reduce Heterogeneity in Case-Control Association Studies
Authors: Shen Yuanyuan , Liu Zhe , Ott Jurg
Published: October 2010

Background/Aims: In human case-control association studies, population heterogeneity is often present and can lead to increased false-positive results. Various methods have been proposed and are in current use to remedy this situation. Methods: We assume that heterogeneity is due to a relatively small number of individuals whose allele frequencies differ from those of the remainder of the sample. For this situation, we propose a new method of handling heterogeneity by removing outliers in a controlled manner. In a coordinate system of the c largest principal components in multidimensional scaling (MDS), we systematically remove one after another of the most extreme outlying individuals and each time recompute the largest association test statistic. The smallest p value obtained within M removals serves as our test statistic whose significance level is assessed in randomization samples. Results: In power simulations of our method and three methods in current use, averaged over several different scenarios, the best method turned out to be logistic regression analysis (based on all individuals) with MDS components as covariates. Conclusion: Our proposed method ranked closely behind logistic regression analysis with MDS components but ahead of other commonly used approaches. In analyses of real datasets our method performed best.
Water Conservation: An Emerging but Vital Issue in Hemodialysis Therapy
Authors: Tarrass Faissal , Benjelloun Meryem , Benjelloun Omar , Bensaha Tarik
Published: October 2010

Water conservation refers to reducing the usage of water and recycling of wastewater for different purposes such as irrigation, laundry and sanitation. As water scarcity increases worldwide, dialysis facilities should be focused on salvaging water. However, most of them still ignorantly discard to the sewer huge volumes of this reusable resource. This article reviews the current water conservation techniques in hemodialysis and the potential benefits drawn when using this technology.
Principles of Antibacterial Dosing in Continuous Renal Replacement Therapy
Authors: Choi Gordon , Gomersall Charles D. , Tian Qi , Joynt Gavin M. , Li Alexander M.M.Y. , Lipman Jeffrey
Published: October 2010

Background: Appropriate antibacterial therapy is important to maximize patient survival in sepsis. Acute renal failure complicates optimal antibiotic administration. Methods: MEDLINE search from 1986 to 2010 using the terms ‘acute renal failure’, ‘pharmacokinetics’, ‘clearance’, ‘dosage’, ‘h(a)emofiltration’, ‘h(a)emodialysis’, ‘h(a)emodiafiltration’, ‘continuous renal replacement therapy’, ‘antibiotics’, ‘intensive care’ and ‘critically ill’. Results: Maximal bacterial killing and minimization of side effects depend on achieving pharmacokinetic targets appropriate to the selected antibacterial agent. Volume of distribution and clearance may be altered by critical illness and/or acute kidney injury. Clearance is determined by nonrenal clearance, residual renal clearance and continuous renal replacement therapy dose. Sieving and saturation coefficients are membrane specific, but may be altered by changes in protein binding induced by critical illness. A significant proportion of studies failed to report the essential dataset required for adequate antibacterial dosage calculation. Conclusions: Individualized dosing based on first principles may be the most appropriate method of dosing, particularly when enhanced by therapeutic drug monitoring.
High Efficiency of a Sequential Recombinase-Mediated Cassette Exchange Reaction in Escherichia coli
Authors: Malchin Natalia , Molotsky Tatiana , Borovok Ilya , Voziyanov Yuri , Kotlyar Alexander B. , Yagil Ezra , Kolot Mikhail
Published: October 2010

A comparison between the efficiency of recombinase-mediated cassette exchange (RMCE) reactions catalyzed in Escherichia coli by the site-specific recombinases Flp of yeast and Int of coliphage HK022 has revealed that an Flp-catalyzed RMCE reaction is more efficient than an Int-HK022 catalyzed reaction. In contrast, an RMCE reaction with 1 pair of frt sites and 1 pair of att sites catalyzed in the presence of both recombinases is very inefficient. However, the same reaction catalyzed by each recombinase individually supplied in a sequential order is very efficient, regardless of the order. Atomic force microscopy images of Flp with its DNA substrates show that only 1 pair of recombination sites forms a synaptic complex with the recombinase. The results suggest that the RMCE reaction is sequential.
Enoxaparin Versus Dabigatran or Rivaroxaban for Thromboprophylaxis After Hip or Knee Arthroplasty
Authors: Huisman Menno V. , Quinlan Daniel J. , Dahl Ola E. , Schulman Sam
Published: October 2010

Background—

Dabigatran and rivaroxaban are novel oral anticoagulants approved for prevention of venous thromboembolism after hip or knee arthroplasty. However, information assessing clinically important efficacy and bleeding outcomes of these 2 new agents versus low-molecular-weight heparin (enoxaparin) is lacking.

Methods and Results—

We separately pooled efficacy and safety data from 6 phase III randomized trials (18 405 participants) comparing equivalent durations of treatment with enoxaparin (40 mg once daily [od] or 30 mg twice daily) versus dabigatran (220 mg od) or versus rivaroxaban (10 mg od) after hip or knee arthroplasty. Odds ratios (OR) for individual outcomes were calculated for each trial and were pooled using the Mantel-Haenszel method. Compared with dabigatran, enoxaparin had a similar risk of symptomatic venous thromboembolism plus all-cause mortality (0.9% versus 1.1%; OR, 0.76; 95% confidence interval [CI], 0.44 to 1.31; I
2
=76%) and bleeding (5.0% versus 5.6%; OR, 0.90; 95% CI, 0.71 to 1.15; I
2
=0%). Compared with rivaroxaban, enoxaparin had a 2-fold higher risk of symptomatic venous thromboembolism plus all-cause mortality (1.2% versus 0.6%; OR, 2.04; 95% CI, 1.32 to 3.17;
P
<0.001; number needed to treat, 167; I
2
=0%) but demonstrated a significant lower risk of bleeding (2.5% versus 3.1%; OR, 0.79; 95% CI, 0.62 to 0.99;
P
=0.049; number needed to harm, 167; I
2
=0%).

Conclusions—

In patients undergoing hip or knee arthroplasty, enoxaparin and dabigatran showed similar rates of efficacy and bleeding. Enoxaparin was less effective than rivaroxaban but had a lower risk of bleeding. These results may have important implications for the choice of prophylactic agent in major joint arthroplasty.
Metabolomics of Supragingival Plaque and Oral Bacteria
Authors: Takahashi N. , Washio J. , Mayanagi G.
Published: October 2010

Dental caries is initiated by demineralization of the tooth surface through acid production by sugar metabolism of supragingival plaque microflora. To elucidate the sugar metabolic system, we used CE-MS to perform metabolomics of the central carbon metabolism, the EMP pathway, the pentose-phosphate pathway, and the TCA cycle in supra- gingival plaque and representative oral bacteria, Streptococcus and Actinomyces. Supragingival plaque contained all the targeted metabolites in the central carbon metabolism, except erythrose 4-phosphate in the pentose-phosphate pathway. After glucose rinse, glucose 6-phosphate, fructose 6-phosphate, fructose 1,6-bisphosphate, dihydroxyacetone phosphate, and pyruvate in the EMP pathway and 6-phosphogluconate, ribulose 5-phosphate, and sedoheptulose 7-phosphate in the pentose-phosphate pathway, and acetyl CoA were increased. Meanwhile, 3-phosphoglycerate and phosphoenolpyruvate in the EMP pathway and succinate, fumarate, and malate in the TCA cycle were decreased. These pathways and changes in metabolites observed in supragingival plaque were similar to the integration of metabolite profiles in Streptococcus and Actinomyces.
Genetic Etiology and Dental Pulp Cell Deficiency of Hypophosphatasia
Authors: Liu H. , Li J. , Lei H. , Zhu T. , Gan Y. , Ge L.
Published: October 2010

Hypophosphatasia is caused by mutations of the tissue-non-specific alkaline phosphatase ( TNSALP) gene with deficiency of dentin structure. The aim of this study was to examine whether TNSALP mutation in dental pulp cells contributes to dentin dysplasia in hypophosphatasia. Mutation analysis showed that compound heterozygous mutations of TNSALP were identified in three hypophosphatasia patients, including 3 novel mutation sites. Exfoliated teeth from the patients showed abnormal dentin mineralization and loss of cementum, as assessed by ground sections and scanning electron microscope analysis. Dental pulp cells isolated from one of the patients showed a significantly reduced TNSALP activity and mineralization capacity when compared with those in dental pulp cells from the unaffected individuals. Our results suggested that dentin dysplasia in hypophosphatasia may be associated with the decreased mineralization ability of dental pulp cells.
ALK5 Inhibition Blocks TGFβ-induced CCN2 Expression in Gingival Fibroblasts
Authors: Thompson K. , Hamilton D.W. , Leask A.
Published: October 2010

Connective tissue growth factor (CCN2/CTGF) is not normally expressed in gingival fibroblasts, but is induced by the potent profibrotic cytokine TGFβ and is overexpressed in gingival fibrosis. Since CCN2 is a marker and mediator of fibrosis, targeting CCN2 expression in gingival fibroblasts may provide new insights into the future development of novel therapeutic opportunities to treat oral fibrosis. Herein we used real-time polymerase chain-reaction, Western blot, and indirect immunofluorescence analysis to evaluate whether SB-431542, a specific pharmacological inhibitor of TGFβ type I receptor (ALK5), blocks the ability of TGFβ to induce CCN2 mRNA and protein expression in human gingival fibroblasts. Our results indicate that CCN2 mRNA and protein are induced by TGFβ in gingival fibroblasts in a SB-431542-sensitive fashion. These results suggest that blocking ALK5 may be useful in blocking the profibrotic effects of TGFβ in gingival fibroblasts.
Transfer Function Analysis of Cerebral Autoregulation Dynamics during Jaw Movements
Authors: Sakagami J. , Ono T. , Hasegawa Y. , Hori K. , Zhang M. , Maeda Y.
Published: October 2010

Mastication as a mild but life-long exercise has been examined as a possibility for maintaining brain function in the elderly. Little is known, however, about the cerebral circulatory response during masticatory movement. The aim of this study was to develop a monitoring system for circulation dynamics during masticatory movement and to apply this system to the study of cerebral autoregulation. Cerebral blood flow, heart rate, and arterial blood pressure were simultaneously recorded, and changes in these circulatory systems were quantitatively evaluated in 38 young healthy volunteers. Transfer function analysis was also performed on blood pressure and cerebral blood flow for investigation of cerebral autoregulation during gum chewing. Although increases in cerebral blood flow, mean blood pressure, and heart rate suggested the activation of cerebral and systemic circulation during gum chewing, increased cerebral circulation was independent of systemic circulation. Our results suggest that cerebral autoregulation is well maintained during jaw movements.
Loaded Microplasma-sprayed CaP-coated Implants in vivo
Authors: Junker R. , Manders P.J.D. , Wolke J. , Borisov Y. , Braceras I. , Jansen J.A.
Published: October 2010

Microplasma spray equipment to deposit calcium phosphate ceramic (CaP) coatings has been developed. Fifty-six titanium implants were inserted into the mandibles of 7 adult beagle dogs. The implants were either acid-etched (NC), conventionally plasma-sprayed (PS), micro-plasma-sprayed (MPS), or micro-plasma-sprayed (aMPS) only at the apical part. After 6 weeks, implants in one half of the mandible were subjected to load. Fifty-two weeks thereafter, the animals were killed. Regardless of load, bone healing was comparable for all surfaces tested. It was concluded that loading of MPS CaP-coated implants evokes a favorable bone response, and that the bone response does not differ from that of PS CaP-coated implants. However, functional loading of PS as well as MPS CaP-coated implants might be associated with increased crestal bone maintenance as compared with non-coated implants.