bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐term outcome of a third anti‐TNF monoclonal antibody after the failure of two prior anti‐TNFs in inflammatory bowel disease
Authors: de Silva P. S. A. , Nguyen D. D. , Sauk J. , Korzenik J. , Yajnik V. , Ananthakrishnan A. N.
Published: July 2012

Background

A significant proportion of patients with IBD lose response to anti‐TNF therapies. There is limited knowledge of the long‐term outcomes of those who have failed two anti‐TNF agents and commenced a third.

Aim

To examine the safety and efficacy of third anti‐TNF treatment after failure of two prior anti‐TNF agents in patients with inflammatory bowel disease.

Methods

This was a retrospective study of all IBD patients [Crohn's disease (CD), ulcerative colitis (UC)] treated with a third anti‐TNF agent after loss of response or intolerance to two prior anti‐TNF agents at a single tertiary North American centre. Disease activity, drug therapy and Montreal phenotypes were noted at disease onset and commencement of the third anti‐TNF agent. Kaplan–Meier estimates were used to calculate the probability of remaining on the third anti‐TNF agent and to identify predictors of long‐term clinical response.

Results

A total of 63 patients (64% women, 57 CD and 6 UC) were included in the analysis. The mean disease duration at initiation of third anti‐TNF was 12 years. Thirty‐five (55.6%) patients discontinued the third anti‐TNF after a mean of 13.2 months. Probability of remaining on the third anti‐TNF was 0.69, 0.55, 0.37 and 0.25 at 6, 12, 24 and 36 months respectively. Prior primary nonresponders to the first anti‐TNF agent [hazard ratio (HR) 6.4, 95% CI 2.5–16.1] and persistent disease activity at 3 months after commencement of a third anti‐TNF (HR 3.2, 95% CI 1.3–7.8) predicted poorer response.

Conclusions

Over half of patients with inflammatory bowel disease, initiated on a third anti‐TNF agent after failure of two prior anti‐TNF drugs, are able to remain on the third anti‐TNF at 1 year.
Anti‐tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients
Authors: Mohabbat A. B. , Sandborn W. J. , Loftus E. V. , Wiesner R. H. , Bruining D. H.
Published: July 2012

Background

Ulcerative colitis (UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation (OLT) despite post‐transplantation immunosuppressive therapy.

Aim

To evaluate the efficacy and safety of anti‐tumour necrosis factor (anti‐TNF) agents for the management of IBD following OLT.

Methods

We reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti‐TNF therapy post‐OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti‐TNF usage, and mucosal healing was defined as the absence of ulcerations on follow‐up endoscopy.

Results

The median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT (UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis (PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis,
Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein–Barr virus‐positive post‐transplant lympho‐proliferative disorder. One death occurred due to complications from recurrent PSC.

Conclusions

Starting Anti‐TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy.
Disease and pollution alter Daphnia taxonomic and clonal structure in experimental assemblages
Authors: BUSER CLAUDIA C. , SPAAK PIET , WOLINSKA JUSTYNA
Published: July 2012

1. Environmental stressors can influence population and community structure. However, the majority of experimental work on multiple environmental stressors has been done at the individual level only.

2. In this work, we followed changes in experimental assemblages of Daphnia (waterfleas; consisting of two taxa and three clones per taxon) after exposure to the fungal parasite Metschnikowia sp. and/or the pesticide diazinon.

3. We found a significant shift in taxonomic and clonal composition under both stressors. Strikingly, in the parasite and parasite + pesticide treatments, one taxon went extinct. While the pesticide had no effect on total parasite prevalence, the taxon that was more susceptible to extinction was, at the same time, more infected when additionally exposed to the pesticide. Furthermore, the density of all adult females was significantly reduced in the parasite treatment, but not in the pesticide treatment.

4. Our results demonstrate that the dynamics of Daphnia assemblages are altered by parasites and pesticide exposure. Given the key role of Daphnia in aquatic food webs in transferring primary production into fish food, this could be of wide significance in aquatic ecosystems.
Cardiovascular diseases and the health‐related quality of life after total hip replacement
Authors: Király Edit , Gondos Tibor
Published: July 2012

Aims and objectives.  To evaluate to what degree total hip replacement, or co‐morbidities or their progression, influence the health‐related quality of life of patients after the operation. We have looked for an objective method to reflect the severity of cardiovascular diseases and to better characterise the health‐related quality of life of patients with total hip replacement.

Background.  The main weakness of the different health‐related quality of life methods that are applied to the analysis is the lack of information regarding the contributory role of co‐morbidities, especially cardiovascular diseases.

Design.  Retrospective longitudinal study.

Methods.  This study involved 109 patients who had had total hip replacement. The patients’ health status – objective and subjective functional performance at the time of operation and five years later – was evaluated using questionnaires (including EQ‐5D and Western Ontario and McMaster Universities’ Ostoearthritis Index scores) and the hospital database. An Objective Cardiovascular Classification grouping was developed to evaluate the deterioration of cardiovascular diseases.

Results.  The subjective assessment of the patients’ health status at Year 5 revealed highly significant differences between healthy and sick patients in respect of EQ‐5D and Objective Cardiovascular Classification but not in the case of the Western Ontario and McMaster Universities’ Ostoearthritis Index scores. Evaluating postoperative subjective health awareness, a higher sensitivity and specificity and a significantly better individual‐discriminating role was demonstrated in Objective Cardiovascular Classification vs. EQ‐5D.

Conclusion.  After successful total hip replacement postoperative health awareness is influenced mainly by existing and developing cardiovascular diseases. It seems to be the case that for patients with significant hypertension, ischaemic heart disease or chronic heart failure, even successful surgery will not improve the patients’ overall feeling of health.

Relevance to clinical practice.  Nursing care of patients with total hip replacement, in respect of cardiovascular diseases, can contribute a better health‐related quality of life.
Mice overexpressing wild‐type human alpha‐synuclein display alterations in colonic myenteric ganglia and defecation
Authors: Wang L. , Magen I. , Yuan P.‐Q. , Subramaniam S. R. , Richter F. , Chesselet M.‐F. , Taché Y.
Published: July 2012

Background  Prevalent non‐motor symptoms of Parkinson’s disease (PD) include gastrointestinal motor impairments and advanced stage PD displays pathological aggregates of α‐synuclein in colonic enteric neurons. We previously showed that 12 months old mice overexpressing human wild type (WT) α‐synuclein under the Thy1 promoter (Thy1‐aSyn) displayed colonic motor dysfunction. We investigated functional gut alterations at earlier ages and histological correlates.

Methods  Defecation, gastric emptying (GE), and immunostaining for α‐synuclein, peripheral choline acetyltransferase (pChAT), tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), and vasoactive intestinal peptide (VIP) in distal colon myenteric plexuses were assessed in male Thy1‐aSyn compared to littermate WT mice.

Key Results  Thy1‐aSyn mice aged 2.5–3 or 7–8 months old had 81% and 55% reduction in fecal pellet output, respectively, in the first 15 min of exposure to a novel environment. The reduction remained significant in the older group for 2‐h, and subsequent refeeding resulted also in a 60% and 69% reduction of defecation in the first hour, respectively. Thy1‐aSyn mice (8–10 months) displayed increased α‐synuclein in the myenteric plexuses with abundant varicose terminals surrounding pChAT‐immunoreactive (ir) neurons, and only a few, nNOS‐ir neurons. There were no conspicuous changes in pChAT‐ and nNOS‐ir neurons, or TH‐ and VIP‐ir nerve fibers. Thy1‐aSyn mice aged 4–18 months had normal GE.

Conclusions & Inferences  The occurrence of over‐production of pre‐synaptic α‐synuclein in colonic myenteric ganglia several months before the loss of striatal dopamine may provide an anatomical basis for interference with cholinergic neuronal activation, causing an early impairment in defecation to stimuli.
NrCAM‐regulating neural systems and addiction‐related behaviors
Authors: Ishiguro Hiroki , Hall Frank S. , Horiuchi Yasue , Sakurai Takeshi , Hishimoto Akitoyo , Grumet Martin , Uhl George R. , Onaivi Emmanuel S. , Arinami Tadao
Published: July 2012

We have previously shown that a haplotype associated with decreased NrCAM expression in brain is protective against addiction vulnerability for polysubstance abuse in humans and that Nrcam knockout mice do not develop conditioned place preferences for morphine, cocaine or amphetamine. In order to gain insight into NrCAM involvement in addiction vulnerability, which may involve specific neural circuits underlying behavioral characteristics relevant to addiction, we evaluated several behavioral phenotypes in Nrcam knockout mice. Consistent with a potential general reduction in motivational function, Nrcam knockout mice demonstrated less curiosity for novel objects and for an unfamiliar conspecific, showed also less anxiety in the zero maze. Nrcam heterozygote knockout mice reduced alcohol preference and buried fewer marbles in home cage. These observations provide further support for a role of NrCAM in substance abuse including alcoholism vulnerability, possibly through its effects on behavioral traits that may affect addiction vulnerability, including novelty seeking, obsessive compulsion and responses to aversive or anxiety‐provoking stimuli. Additionally, in order to prove glutamate homeostasis hypothesis of addiction, we analyzed glutamatergic molecules regulated by NRCAM expression. Glutaminase appears to be involved in NrCAM‐related molecular pathway in two different tissues from human and mouse. An inhibitor of the enzyme, prolyl‐leucyl‐glycinamide, treatment produced, at least, some of the phenotypes of mice shown in alcohol preference and in anxiety‐like behavior. Thus, NrCAM could affect addiction‐related behaviors via at least partially modulation of some glutamatergic pathways and neural function in brain.
Variation in OPRM1 moderates the effect of desire to drink on subsequent drinking and its attenuation by naltrexone treatment
Authors: Kranzler Henry R. , Armeli Stephen , Covault Jonathan , Tennen Howard
Published: July 2012

To evaluate the role of the functional Asn40Asp polymorphism in the mu‐opioid receptor gene on drinking behavior and naltrexone's ability to attenuate drinking, we used a daily diary method in a 12‐week, randomized clinical trial of naltrexone to reduce drinking. Participants (n = 158 problem drinkers) were assigned to receive either daily or targeted naltrexone 50 mg (n = 81) or matching placebo (n = 77). Patients reported by telephone each evening their current desire to drink and their drinking during the previous night and during the reporting day. We examined genotype, medication, desire to drink and their interactions as predictors of nighttime drinks consumed, controlling for drinking earlier in the day. Asp40 carriers showed a stronger positive association between evening desire (deviations from their mean levels) and later night drinking levels than Asn40 homozygotes (P = 0.019). The desire × genotype × medication condition interaction was also significant (P = 0.009), with a significant desire × genotype interaction for the placebo group (
P = 0.001) but not for the naltrexone group (P = 0.74). In summary, when the evening level of desire to drink was relatively high, Asp40 allele carriers were at greater risk than Asn40 homozygotes to drink more, which was attenuated by naltrexone. Although average measures across the study were not informative, daily reports helped to demonstrate the moderating effects of genetic variation on the relation between desire to drink and alcohol consumption and the effects of naltrexone on that phenotype.
X‐linked CHARGE‐like Abruzzo–Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations
Authors: Pauws E , Peskett E , Boissin C , Hoshino A , Mengrelis K , Carta E , Abruzzo MA , Lees M , Moore GE , Erickson RP , Stanier P
Published: July 2012

X‐linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X‐linked, CHARGE‐like Abruzzo–Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the Tbx22 developmental expression pattern but not previously associated in CPX patients. A novel TBX22 splice acceptor mutation (c.593−5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both in silico and in vitro splicing studies. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that TBX22 is the gene underlying Abruzzo–Erickson syndrome, expanding the phenotypic spectrum of TBX22 mutations.
Expression of Mn‐SOD, iNOS and eNOS mRNAs in Osteoblasts from the Maxilla of Osteopetrotic Mice
Authors: Kuwana M. , Watanabe H. , Abe S. , Yanagisawa T. , Sasaki J.
Published: July 2012

Active oxygens and free radicals are involved in the metabolism and clinical conditions of tissues; however, little is known about the localisation and expression levels of associated enzymes. The expressions of active oxygens, free radicals and associated enzymes are reported to be site‐specific; therefore, the expression states of free radical enzymes differ between sites, even within the same cell. In particular, there has been no report concerning the catabolic enzymes of active oxygens in osteoblasts of the maxilla, other than normal osteoblasts that were weakly positive by immunohistochemical staining. We conducted this study to elucidate the relationship between osteodystrophy and radical‐associated enzymes by investigating mRNAs of enzymes associated with active oxygens and free radicals using osteoblasts from the maxilla of normal and osteopetrotic model (op/op) mice. In op/op mouse maxilla osteoblasts, mRNAs of Mn‐SOD, i‐NOS and e‐NOS were strongly positive. Mn‐SOD and iNOS enzymes were considered to be highly expressed in osteoblasts of the narrowed medullary cavity of this bone.
Relationship between litters per sow per year sire breeding values and sire progeny means for farrowing rate, removal parity and lifetime born alive
Authors: Abell C.E. , Mabry J.W. , Dekkers J.C.M. , Stalder K.J.
Published: July 2012

The objective of this study was to determine the relationship between individual sire estimated breeding values (EBV) for litters/sow/year (LSY) and sire progeny means for farrowing rate (FR), removal parity and lifetime born alive (LTBA). Genetic parameters and breeding values were estimated using ASREML. The heritability estimate for LSY was 0.11. When all sires with 10 or more daughters with records were included in the analysis, Spearman rank correlations between the sire's LSY EBV and the sires' daughter means for FR, removal parity and LTBA were 0.49, 0.23 and 0.25 (p < 0.01). The sire EBV for LSY was favourably correlated with sires' daughter means for all three traits. This provides evidence that selecting sires with high EBV for LSY could improve herd FR, removal parity and LTBA. By including LSY as part of the selection criterion, the LTBA may be indirectly improved. The positive genetic correlation between LTBA and LSY may be a result of the improved longevity of sows with greater LSY compared with sows with lower LSY. The relationships between LSY and FR, removal parity and LTBA are strongly supported by the correlations between the sire progeny means for each trait and the sire LSY EBV.
A possible chemopreventive role for photodynamic therapy in Gorlin syndrome: a report of basal cell carcinoma reduction and review of literature
Authors: Wolfe Christopher M. , Green W. Harris , Cognetta Armand B. , Hatfield H. Keith
Published: July 2012

Multiple basal cell carcinomas (BCC) are a significant cause of morbidity and disfigurement in patients with naevoid basal cell carcinoma syndrome (NBCCS). Chemopreventive strategies are needed to reduce the formation of new BCC in these patients. Appropriate evidence‐based guidelines for photodynamic therapy chemoprevention in NBCCS do not exist. We herein report one patient treated with methyl aminolevulinate PDT with red light (630 nm) activation to continue sustained chemoprevention following other BCC chemopreventive modalities and a relevant literature review.
Movement and phenology of bees in a subtropical Australian agricultural landscape
Authors: CUNNINGHAM SAUL A. , SCHELLHORN NANCY A. , MARCORA ANNA , BATLEY MICHAEL
Published: July 2012

Bees are mobile organisms that seek food and nesting opportunities from a range of habitats. It is important to understand the way they move in agricultural landscapes if we are to conserve them and benefit from their activity as pollinators. We surveyed bees using directional flight interception (Malaise) traps over a 1‐year period in two agricultural landscapes in south‐east Queensland, Australia. We placed traps at the ecotone between crops and remnant vegetation to establish the pattern of movement between these habitats. Species richness in these landscapes (70) was high relative to that in comparable studies. Some bees were active year round, but most were caught in the period September to March. Across the whole assemblage there was a significant pattern where more species were detected leaving rather than entering remnant vegetation. The same bias was true for the number of individuals of the two most abundant species (Homalictus urbanus and Apis mellifera). Species exclusively found in crops were smaller on average (and therefore have smaller foraging range) than their non‐crop counterparts. Together, these patterns indicate that while bees are abundant in crop habitat, the remnant vegetation is important as the point of origin for bee movements, and the riparian remnant in particular is richer than the dry native remnant. Compositional similarity among samples was significantly explained by landscape but also movement direction (i.e. to or from the riparian remnant) because different species showed different patterns of response. The landscape with greater native vegetation cover supported more species in and around crops than the landscape with less native vegetation.
Communication before coherence
Authors: Rolls Edmund T. , Webb Tristan J. , Deco Gustavo
Published: July 2012

The hypothesis of communication through coherence proposes that coherent or synchronous oscillations in connected neural systems can promote communication. It has been applied mainly to how oscillations interact in connected networks. We tested by simulations whether information transmission about an external stimulus from one network to a second network is influenced by gamma oscillations, by whether the oscillations are coherent, and by their phase. Gamma oscillations were induced by increasing the relative conductance of AMPA to NMDA excitatory synapses. It was found that small associative connection strengths between the networks were sufficient to produce information transmission (measured by Shannon mutual information) such that the second attractor network took the correct decision based on the state of the first network. Although gamma oscillations were present in both networks, the synaptic connections sufficient for perfect information transmission about the stimulus presented to the network (100% correct, 1 bit of information) were insufficiently strong to produce coherence, or phase‐locking, between the two networks; this only occurred when the synaptic strengths between the networks were increased by > 10 ×. Further, the phase of the oscillations between the networks did not influence the information transmission or its speed at these connection strengths. Moreover, information transmission was as good when the AMPA‐to‐NMDA ratio was reduced to its normal value, and oscillations were not present. Similar results were found when the second network was not an attractor decision‐making network. Thus information transmission can occur before synapses have been made sufficiently strong to produce coherence.
Functional characterization of ether‐à‐go‐go‐related gene potassium channels in midbrain dopamine neurons – implications for a role in depolarization block
Authors: Ji Huifang , Tucker Kristal R. , Putzier Ilva , Huertas Marco A. , Horn John P. , Canavier Carmen C. , Levitan Edwin S. , Shepard Paul D.
Published: July 2012

Bursting activity by midbrain dopamine neurons reflects the complex interplay between their intrinsic pacemaker activity and synaptic inputs. Although the precise mechanism responsible for the generation and modulation of bursting in vivo has yet to be established, several ion channels have been implicated in the process. Previous studies with nonselective blockers suggested that ether‐à‐go‐go‐related gene (ERG) K+ channels are functionally significant. Here, electrophysiology with selective chemical and peptide ERG channel blockers (E‐4031 and rBeKm‐1) and computational methods were used to define the contribution made by ERG channels to the firing properties of midbrain dopamine neurons in vivo and in vitro. Selective ERG channel blockade increased the frequency of spontaneous activity as well as the response to depolarizing current pulses without altering spike frequency adaptation. ERG channel block also accelerated entry into depolarization inactivation during bursts elicited by virtual NMDA receptors generated with the dynamic clamp, and significantly prolonged the duration of the sustained depolarization inactivation that followed pharmacologically evoked bursts. In vivo, somatic ERG blockade was associated with an increase in bursting activity attributed to a reduction in doublet firing. Taken together, these results show that dopamine neuron ERG K+ channels play a prominent role in limiting excitability and in minimizing depolarization inactivation. As the therapeutic actions of antipsychotic drugs are associated with depolarization inactivation of dopamine neurons and blockade of cardiac ERG channels is a prominent side effect of these drugs, ERG channels in the central nervous system may represent a novel target for antipsychotic drug development.
Cenozoic evolution of Muricidae (Mollusca, Neogastropoda) in the Southern Ocean, with the description of a new subfamily
Authors: Barco Andrea , Schiaparelli Stefano , Houart Roland , Oliverio Marco
Published: July 2012

Barco, A., Schiaparelli, S., Houart, R. & Oliverio, M. (2012). Cenozoic evolution of Muricidae (Mollusca, Neogastropoda) in the Southern Ocean, with the description of a new subfamily. —Zoologica Scripta, 41, 596–616.

Gastropods are among the most studied group in Antarctica, and taxa with an advanced status of systematic knowledge can be used as a model to study how oceanographic and climatic patterns shaped Recent faunal assemblages. Within the ongoing study of the muricid phylogeny, we have analysed molecular and morphological data from species traditionally ascribed to the muricid subfamily Trophoninae. Particularly, the availability of specimens collected in the Southern Ocean and surrounding basins allowed to demonstrate as the genera Pagodula, Xymenopsis, Xymene and Trophonella, which are traditionally classified in the Trophoninae, actually belong to a distinct lineage, for which the new subfamily Pagodulinae is herein introduced. We propose and discuss a possible framework for the origin and radiation of Antarctic muricids.
Impact of postprandial glycaemia on health and prevention of disease
Authors: Blaak E. E. , Antoine J.‐M. , Benton D. , Björck I. , Bozzetto L. , Brouns F. , Diamant M. , Dye L. , Hulshof T. , Holst J. J. , Lamport D. J. , Laville M. , Lawton C. L. , Meheust A. , Nilson A. , Normand S. , Rivellese A. A. , Theis S. , Torekov S. S. , Vinoy S.
Published: July 2012

Postprandial glucose, together with related hyperinsulinemia and lipidaemia, has been implicated in the development of chronic metabolic diseases like obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). In this review, available evidence is discussed on postprandial glucose in relation to body weight control, the development of oxidative stress, T2DM, and CVD and in maintaining optimal exercise and cognitive performance. There is mechanistic evidence linking postprandial glycaemia or glycaemic variability to the development of these conditions or in the impairment in cognitive and exercise performance. Nevertheless, postprandial glycaemia is interrelated with many other (risk) factors as well as to fasting glucose. In many studies, meal‐related glycaemic response is not sufficiently characterized, or the methodology with respect to the description of food or meal composition, or the duration of the measurement of postprandial glycaemia is limited. It is evident that more randomized controlled dietary intervention trials using effective low vs. high glucose response diets are necessary in order to draw more definite conclusions on the role of postprandial glycaemia in relation to health and disease. Also of importance is the evaluation of the potential role of the time course of postprandial glycaemia.
Effects of Input Properties, Vocabulary Size, and L1 on the Development of Third Person Singular –s in Child L2 English
Authors: Blom Elma , Paradis Johanne , Duncan Tamara Sorenson
Published: July 2012

This study was designed to investigate the development of third‐person singular (3SG) –s in children who learn English as a second language (L2). Adopting the usage‐based perspective on the learning of inflection, we analyzed spontaneous speech samples collected from 15 English L2 children who were followed over a 2‐year period. Assessing the contribution of a wide range of predictors, we show that word frequency, allomorph, lexicon size, inflectional properties of the first language (L1), and months of exposure to English all have impact on English L2 children's use of 3SG –s in obligatory contexts. This study enhances both our understanding of the development of 3SG –s and of child L2 acquisition. The outcomes support a usage‐based approach to learning inflection and emphasize the importance of a multifactorial analysis of language development.
Contract enforcement in Russian serf society, 1750–18601
Authors: Dennison Tracy
Published: July 2012

This article examines questions about contract enforcement in the absence of formal legal institutions, using archival evidence for one particular rural society in pre‐emancipation Russia. The evidence presented indicates that enforcement services provided by the local landlord made it possible for Russians from different socioeconomic and legal strata to engage in a wide variety of contractual transactions. However, this system had significant drawbacks in that the poorest serfs could not afford these services and no serf had recourse beyond his local estate.
Vitamin D for the prevention of stroke incidence and disability: promising but too early for prime time
Authors: Michos E. D. , Gottesman R. F.
Published: July 2012

Click here to view the accompanying paper in this issue.
Missed epidemics and missing links: international birth cohort trends in multiple sclerosis
Authors: Ajdacic‐Gross V. , Tschopp A. , Schmid M. , Bopp M. , Gutzwiller F.
Published: July 2012

Background and purpose

Many hypotheses on the etiopathogenesis of multiple sclerosis (MS) focus on risk factors occurring early in life. This study examined the variability of birth cohort trends in international MS data by means of age‐period‐cohort (APC) analysis.

Methods

The data from 25 countries were taken from the WHO mortality database. Data were encoded according to the International Classification of Diseases and covered slightly varying periods between 1951 and 2009. The APC analyses were based on logit models applied to cohort tables with 5‐year age‐ and period intervals.

Results

In most countries, the birth cohort estimates peaked in those born in the first half of the 20th century. In countries from Central and Western Europe, the peak concerned those born before and around 1920. A second group of countries (Denmark, Sweden, Italy, Ireland, Scotland) shared a later peak amongst cohorts born in the 1920s and 1930s. Group 3 included Commonwealth countries, the USA and Norway, with a double or extended peak starting in the 1910s or 1920s, and ending by the 1950s. The fourth group, consisting of Mediterranean countries and Finland, was characterized by a steady increase in the birth cohort estimates until the 1950s. The fifth group with countries from Eastern Europe and Japan showed no particular pattern.

Conclusions

Birth cohort trends have influenced the change in MS risk across the 20th century in many Western countries. This silent epidemic points to a most important but unknown latent risk factor in MS.
First evidence of bacterial biofilms in the anaerobe part of scalp hair follicles: a pilot comparative study in folliculitis decalvans
Authors: Matard B. , Meylheuc T. , Briandet R. , Casin I. , Assouly P. , Cavelier–balloy B. , Reygagne P.
Published: July 2012

Background  The cause of folliculitis decalvans (FD) remains unknown. We hypothesized that a bacterial biofilm could be involved in its pathogenesis.

Objective  To assess the presence or not of a bacterial biofilm in the hair roots of the scalp in FD.

Patients and methods  Hairs plucked from four patients and three controls were examined by field emission scanning electron microscopy (FESEM) and confocal laser scanning microscopy (CLSM).

Results  Bacterial communities organized as biofilms were observed both by FESEM and CLSM in the under infundibular part of hair follicles in all patients and in two of the three controls. In patients and controls, these biofilms were formed exclusively of bacilli of comparable shapes.

Conclusion  This pilot study provides the first evidence of the presence of bacterial biofilms in the infra infundibular part of human scalp hair follicles. These biofilms were detected both in FD patients and controls, suggesting their ubiquity as a commensal biofilm with a possible pathogenic shift in FD.
Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta
Authors: Zahradnicek Oldrich , Horacek Ivan , Tucker Abigail S.
Published: July 2012

This paper describes tooth development in a basal squamate, Paroedura picta. Due to its reproductive strategy, mode of development and position within the reptiles, this gecko represents an excellent model organism for the study of reptile development. Here we document the dental pattern and development of non‐functional (null generation) and functional generations of teeth during embryonic development. Tooth development is followed from initiation to cytodifferentiation and ankylosis, as the tooth germs develop from bud, through cap to bell stages. The fate of the single generation of non‐functional (null generation) teeth is shown to be variable, with some teeth being expelled from the oral cavity, while others are incorporated into the functional bone and teeth, or are absorbed. Fate appears to depend on the initiation site within the oral cavity, with the first null generation teeth forming before formation of the dental lamina. We show evidence for a stratum intermedium layer in the enamel epithelium of functional teeth and show that the bicuspid shape of the teeth is created by asymmetrical deposition of enamel, and not by folding of the inner dental epithelium as observed in mammals.
Army ant defensive behaviour and chimpanzee predation success: field experiments in Nigeria
Authors: Allon O. , Pascual‐Garrido A. , Sommer V.
Published: July 2012

Across Africa, chimpanzees prey on army ants, typically using stick tools. Population differences in predation patterns reflect environmental as well as sociocultural factors. However, as for ecological constraints, we lack information about how the ants' defensive response unfolds over the course of a predatory attempt and how this influences chimpanzee reward. We studied these aspects of insectivory in the habitat of Nigerian chimpanzees through field experiments with previously used tools. The speed with which ants run up a tool decreased continuously during experimental dips into nests. This suggests that soldiers with long legs run up the tools first, before fanning out to deter the intruder. Workers attacking later on were increasingly smaller, thus running less fast. Yet, because more and more insects join the defence, harvesting yield (g dry weight) steadily increased for the first 17 min, to then drop markedly. We hypothesize that the length of dipping sessions by wild chimpanzees is limited by either diminishing return or discomfort caused by being continually bitten. Actual harvesting success cannot be reconstructed from ant remains in chimpanzee faeces without knowing what proportion of consumed insects is detectable in excreta. Through human self‐experiments, we found that only 10% of ingested ants are found in a subsequent excretion. Based on counts of ant heads in chimpanzee faeces, this translates into 12.9 g dry weight ingested per dipping session, which is far more than elsewhere. Although prey availability and harvesting technique varies across sites, our data still suggest a much greater yield for Nigeria. One reason for this may be a particular aggressiveness of Dorylus rubellus. While this is the only army ant species preyed upon in Nigeria, it is not regularly eaten elsewhere. Standardized experiments and faecal analyses across study sites will be necessary to better understand how ecological constraints influence chimpanzee myrmecophagy.
Parent‐reported participation in children with cerebral palsy: the contribution of recurrent musculoskeletal pain and child mental health problems
Authors: RAMSTAD KJERSTI , JAHNSEN REIDUN , SKJELDAL OLA H , DISETH TROND H
Published: July 2012

Aim  The aim of the study was to explore the contribution of recurrent musculoskeletal pain and mental health to aspects of participation in children with cerebral palsy (CP).

Method  A total of 105 participants (54 males, 51 females); mean age 14y (SD 3) were assessed by clinical examination, interview, and parental questionnaires. CP type distribution was as follows: spastic unilateral, 37%; spastic bilateral, 56%; and dyskinetic, 7%. Motor function assessed using the Gross Motor Function Classification System was level I, 33%; level II, 40%; level III, 15%; and level IV/V, 11%. Parents reported child participation using the Assessment of Life Habits, child mental health problems using the Strengths and Difficulties Questionnaire, their own mental health using the General Health Questionnaire, and their socioeconomic status.

Results  Recurrent musculoskeletal pain was associated with reduced accomplishment of daily activities (B=−1.22, p=0.02) and social roles (B=−1.17, p=0.03), and with reduced parental satisfaction with the accomplishment of daily activities (B=−1.14, p=0.03) and social roles (B=−1.48, p<0.01). Increasing levels of child mental health problems was associated with reduced accomplishment of daily activities (B=−0.10, p=0.02) and social roles (B=−0.11, p<0.01), and with reduced parental satisfaction with the accomplishment of social roles (B=−0.21, p<0.01).

Interpretation  Pain and child mental health should be considered in most participation models in CP. Regarding participation as an objective outcome measure is questionable.
The conceptualization of participation
Authors: VARGUS‐ADAMS JILDA N
Published: July 2012

This commentary is on the original article by Ramstad et al. on pages 829‐835 of this issue.
Assessing the Possible Antipoverty Effects of Recent Rises in Age‐Specific Minimum Wages in New Zealand
Authors: Maloney Tim , Pacheco Gail
Published: July 2012

Real minimum wages increased by nearly 33 percent for adults and 123 percent for teenagers in New Zealand between 1999 and 2008. Where fewer than 2 percent of workers were being paid a minimum wage at the outset of this sample period, more than 8 percent of adult workers and 60 percent of teenage workers were receiving hourly earnings close to the minimum wage by the end of this period. These policy changes provide a unique opportunity to estimate the effects of the minimum wage on poverty. Although minimum wage workers are more likely to live in the poorest households, they are relatively widely dispersed throughout the income distribution. This is particularly true of teenage minimum wage workers. Furthermore, low‐income households often do not contain any working members. We estimate that a 10 percent increase in minimum wages, even without a loss in employment or hours of work, would lower the relative poverty rate by less than one‐tenth of a percentage point.
Optimal Biopsy Site for Helicobacter pylori Detection during Endoscopic Mucosectomy in Patients with Extensive Gastric Atrophy
Authors: Lee Jeong Hoon , Park Young Soo , Choi Kwi‐Sook , Kim Do Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Jang Se Jin , Jung Hwoon‐Yong , Kim Jin‐Ho
Published: July 2012

Background

Helicobacter pylori eradication is essential for metachronous gastric cancer prevention in patients undergoing endoscopic mucosectomy (EMR). This study was aimed to determine the optimal biopsy site for
H. pylori detection in the atrophic remnant mucosa of EMR patients.

Material and Methods

Data were analyzed from 91 EMR patients. Three paired biopsies for histology were taken at antrum, corpus lesser (CLC), and greater curve (CGC). Additional specimens were obtained at antrum and CGC for rapid urease test (RUT).
H. pylori infection was defined as at least two positive specimens on histology and/or RUT. Serologic atrophy was determined by pepsinogen levels.

Results

Overall
H. pylori infection rate was 72.5%. The proportions of moderate‐to‐marked atrophy/intestinal metaplasia at CGC (5.6/6.6%) were significantly lower than those at antrum (58.6/75.8%) and CLC (60.7/70.0%). Sensitivity of histology in detecting
H. pylori was significantly higher at CGC than at antrum and CLC (84.8 vs 30.3 and 47.0%, respectively; p < .001). On RUT, detection at CGC also showed higher sensitivity than at antrum (77.3 vs 33.3%, p < .001). Specificities of all three biopsy sites were more than 90%. Regardless of serologic atrophy, CGC showed consistently higher sensitivities on histology and RUT. In patients with serologic atrophy, antral sensitivities were much lower than those of nonatrophic patients, 9.5 versus 40.0% on histology (p = .012) and 14.3 versus 42.2% on RUT (p = .025).

Conclusions

CGC is the optimal biopsy site for
H. pylori diagnosis in EMR patients with extensive atrophy. Antral biopsy should be avoided, especially in serologically atrophic patients.
Dermatofibrosarcoma Protuberans in Children: an Update on the Diagnosis and Treatment
Authors: Kornik Rachel I. , Muchard Lisa K. , Teng Joyce M.
Published: July 2012

Abstract:  Dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor of low grade malignant potential. Although rare, pediatric cases pose a particular challenge in diagnosis and management. In children, the clinical appearance may be heterogeneous and a high index of suspicion is necessary to avoid delays in diagnosis which can lead to further morbidity. Histologic examination, often with the use of appropriate immunostains, is necessary for diagnosis. Advances in the understanding of the molecular genetics of DFSP have led to further diagnostic and therapeutic modalities. DFSP is thought to result from a translocation between platelet‐derived growth factor beta (PDGFB, 22q13.1) and type 1 collagen (COL1A1, 17q21∼22) leading to a fusion protein (PDGFB) which stimulates the PDGF receptor. Detection of this translocation in tissue via PCR or fluorescence in situ hybridization (FISH) can be helpful in difficult cases. While surgery with wide local excision or Mohs micrographic surgery is the mainstay of treatment, the use of targeted therapy with imatanib mesylate shows promise in large or unresectable tumors. Knowledge of the clinical features, histology, genetics, and treatment options is important for successful management of these tumors.
Presurgical Nasoalveolar Molding (PNAM) for a Unilateral Cleft Lip and Palate: A Clinical Report
Authors: Kamble Vaibhav D. , Parkhedkar Rambhau D. , Sarin Soumil P. , Patil Pravinkumar G.
Published: July 2012

Cleft lip and palate deformity is a congenital defect of the middle third of the face. Incidence varies from 1:500 to 1:2500 live births. Etiology depends upon hereditary and environmental factors. Restoration of these defects is important not only for functional and esthetic reasons, but also because there may be a positive psychological impact for the patient and parents. The goal of primary closure of the lip for unilateral cleft lip is to ensure a normal and symmetrical lip and nose. Presurgical infant orthopedics has been employed since the 1950s as an adjunctive neonatal therapy for the correction of cleft lip and palate. Presurgical nasoalveolar molding (PNAM) represents a paradigm shift from the traditional methods of presurgical infant orthopedics. PNAM consists of active molding of the alveolar segments as well as the surrounding soft tissues. This clinical report describes a new approach of PNAM therapy for an infant with complete unilateral cleft lip and palate showing significant reduction in cleft defect size and improved contour and topography of deformed surrounding soft tissues.
Periodontal pathogen load and increased antibody response to heat shock protein 60 in patients with cardiovascular disease
Authors: Leishman Shaneen J. , Ford Pauline J. , Do Hong Lien , Palmer Janet E. , Heng Nicholas C.K. , West Malcolm J. , Seymour Gregory J. , Cullinan Mary P.
Published: July 2012

Aim

To determine the relationship between periodontal pathogen load and anti‐human heat shock protein 60 (hHSP60) antibodies in patients with established cardiovascular disease (CVD).

Materials and Methods

Participants were cardiovascular patients (n = 74) with a previous hospital admission for myocardial infarction. Concurrent periodontal pathogen load of Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia and Aggregatibacter actinomycetemcomitans was determined using quantitative real‐time PCR. Serum antibodies to these pathogens, GroEL and hHSP60 were determined using an ELISA.

Results

There was a trend for increasing anti‐hHSP60 antibody as the number of bacterial species increased. The strongest positive correlations were found between anti‐hHSP60 levels and numbers of T. forsythia (r = 0.43; p < 0.001) and between anti‐hHSP60 and anti‐GroEL levels (r = 0.39; p = 0.001). Patients with extensive periodontal pocketing (≥4 mm) had higher numbers of P. gingivalis and T. forsythia (p < 0.05) and a higher subgingival pathogen load (p < 0.05) than patients with minimal pocketing (≤1 site ≥ 4 mm). They also had significantly elevated anti‐hHSP60 levels (p < 0.05). Overall, the highest anti‐hHSP60 levels were seen in patients with extensive periodontal pocketing and all four bacterial species.

Conclusions

In cardiovascular patients, a greater burden of subgingival infection with increased levels of P. gingivalis and T. forsythia is associated with modestly higher anti‐hHSP60 levels.
An Analysis of C‐Reactive Protein, Procalcitonin, and D‐Dimer in Pre‐Eclamptic Patients
Authors: Kucukgoz Gulec Umran , Tuncay Ozgunen Fatma , Baris Guzel Ahmet , Buyukkurt Selim , Seydaoglu Gulsah , Ferhat Urunsak Ibrahim , Cuneyt Evruke Ismail
Published: July 2012

Problem

The aim of this study was to evaluate serum procalcitonin (PCT), C‐reactive protein (CRP), and plasma D‐Dimer levels in mild and severe pre‐eclampsia.

Method of study

Serum PCT, CRP, and D‐Dimer levels were analyzed in 64 cases with pre‐eclampsia as the study group and 33 healthy pregnant women in the third trimester as the control group. Pre‐eclamptic group consisted of mild (n = 31) and severe pre‐eclamptic subgroup (n = 33). Laboratory results were compared between the groups and diagnostic usefulness of these parameters were evaluated.

Results

PCT, CRP, and D‐Dimer levels were significantly higher in study group than the control group (P = 0.001). PCT, CRP, and D‐Dimer were significantly higher in the patients with severe pre‐eclampsia than mild pre‐eclampsia. There were significant positive correlations between these markers and mean arterial pressure (MAP). Logistic regression analysis using the control and pre‐eclampsia group showed that higher PCT (OR, 15.68; 95%‐CI, 3.15–78.10), CRP (OR, 14.29; 95%‐CI, 3.08–66.34), and D‐Dimer levels (OR, 4.97; 95%‐CI, 1.22–20.29) were found to be risk factors significantly associated with pre‐eclampsia.

Conclusions

This study results confirm that evidence of a possible exaggerated systemic inflammatory response in pre‐eclampsia especially in severe pre‐eclampsia.
IFN‐γ Inhibits Osteopontin Expression in Human Decidual Stromal Cells and can be Attenuated by 1α,25‐Dihydroxyvitamin D3
Authors: Hu Bin , Zhou Hao , Gao Hui , Liu Yan , Yan Ting , Zou Li , Chen Lijuan
Published: July 2012

Problem

The effect of IFN‐γ on the expression of osteopontin (OPN), in the presence or absence of 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D3), in decidual stromal cells (DSC).

Method of study

Decidual stromal cells were isolated from women undergoing elective termination of pregnancy (gestational age, 6–9 weeks). After characterization, they were treated with IFN‐γ in the presence or absence of 1,25(OH)2D3. The uterus of pregnancy IFN‐γ knockout mice were collected on gestation day (gd) 7.5, and the expression of OPN were examined.

Results

IFN‐γ drastically decreased the expression of OPN in DSC, which was reverted by the addition of 1,25(OH)2D3 to the IFN‐γ‐treated decidual cells. Moreover, the OPN expression in uterus of IFN‐γ knockout mice was higher than that of wild‐type counterparts.

Conclusions

We demonstrated OPN was expressed in DSC in human first‐trimester decidua and in the uterus in mice at 7.5 gd. The OPN expression was closely correlated with regulation of IFN‐γ and 1,25(OH)2D3 in human early pregnancy. OPN expression in DSC was significantly decreased with the treatment of IFN‐γ. 1,25(OH)2D3 played an opposite role in IFN‐γ‐mediated inhibition of OPN expression in human DSC.