bluuebunny/crossref_metadata_2025 huggingface dataset:
How should we manage patients with mildly increased serum thyrotrophin concentrations?
Authors: Vanderpump Mark P. J.
Published: September 2009

A mildly increased serum thyrotrophin (TSH) is usually because of mild thyroid failure, and the most common aetiology in iodine‐replete communities is chronic autoimmune thyroiditis. It is more common in women, and the prevalence increases with age in both men and women and is associated with the presence of antithyroid antibodies. The majority will have serum TSH levels between 5–10 mIU/l, normal free thyroxine (T4) levels and relatively few symptoms. In 2004, US evidence‐based consensus guidelines concluded that there were no adverse outcomes of a mildly increased serum TSH other than a risk of progression to overt hypothyroidism and few data to justify levothyroxine therapy. There is still debate as to what constitutes an increased serum TSH, particularly in older subjects. Although some subjects will progress to overt hypothyroidism, recent data suggest a significant proportion revert to a serum TSH within the reference range without treatment. Two recent meta‐analyses have suggested that the possible cardiovascular risks may be more significant in younger adults. Other data suggest that mild thyroid failure may be the only reversible cause of left ventricular diastolic dysfunction. No appropriately powered prospective, randomized, controlled, double‐blinded interventional trial of levothyroxine therapy for a mildly increased serum TSH exists. However, treatment in subjects who are symptomatic, pregnant or preconception, aged less than 65 years and older subjects with evidence of heart failure appear justified.
Nitrogen uptake and the importance of internal nitrogen loading in Lake Balaton
Authors: Présing Mátyás , Herodek Sándor , Preston Tom , Vörös Lajos
Published: September 2009

1. The importance of various forms of nitrogen to the nitrogen supply of phytoplankton has been investigated in the mesotrophic eastern and eutrophic western basin of Lake Balaton.  2. Uptake rates of ammonium, urea, nitrate and carbon were measured simultaneously. The uptake rates were determined using N and
C methodologies, and N2‐fixation was measured using the acetylene‐reduction method. The light dependence of uptake was described with an exponential saturation equation and used to calculate surface‐related (areal) daily uptake.  3. The contribution of ammonium, urea and nitrate to the daily nitrogen supply of phytoplankton varied between 11 and 80%, 17 and 73% and 1 and 15%, respectively. N2‐fixation was negligible in the eastern basin and varied between 5 and 30% in the western region of the lake. The annual external nitrogen load was only 10% of that utilized by algae.  4. The predominant process supplying nitrogen to the phytoplankton in the lake is the rapid recycling of ammonium and urea in the water column. The importance of the internal nutrient loading is emphasized.
Spatial and temporal patterns of invertebrate drift in streams draining a Neotropical landscape
Authors: Ramírez Alonso , Pringle Catherine M.
Published: September 2009

1. Invertebrate drift in streams draining a tropical landscape in Costa Rica was studied to assess differences in assemblage composition above and below a major gradient break in geomorphic landform and to assess temporal patterns of drift in lowland reaches below the gradient break. The gradient break (∼50 m a.s.l.) is the point at which the foothills of the Costa Rican Cordillera Central (piedmont) merge with the Caribbean coastal plain (lowlands).  2. Spatial patterns were assessed along two streams by sampling drift over 24 h once a month for 3 months in both the piedmont (90 m a.s.l.) and lowlands (30 m a.s.l.). Temporal patterns of drift were assessed through monthly diel sampling of three lowland sites over 8–10 months, encompassing both ‘dry’ (<400 mm precipitation per month, November to May) and wet (July to October) seasons.  3. Drift composition was insect dominated in piedmont sites and larval shrimp dominated in the lowlands. Percent similarity of assemblages between piedmont and lowland sites was low (range 26–43%) because of high larval shrimp densities in lowland versus piedmont sites.  4. Drift densities were higher during night than day, with peaks at sunset on all dates and at all sites. Diel patterns in drift agree with previous observations for the study area and support the ‘risk of predation’ hypothesis.  5. Analysis of monthly patterns in lowland sites showed high variability in drift densities; however, all major taxa were found every month. Overall, there was a trend for high invertebrate densities during the ‘dry’ season, but these trends were not significant.  6. Observed changes in drift composition support the concept of river zonation, which predicts a change in community composition along the stream continuum due to geomorphic features. Drift at lowland sites below the gradient break was dominated by shrimps, which are linked to marine environments via their migratory behaviour.
Long‐term impact of an invertebrate predator, Heterocope septentrionalis, on an arctic pond zooplankton community
Authors: O'Brien W. John
Published: September 2009

1. A long‐term field experiment to determine what forces structure and maintain the large‐bodied zooplankton assemblages in ponds which lack visual predators was undertaken at the Toolik Lake Research Station in arctic Alaska. Predatory copepods, Heterocope septentrionalis, were introduced to a pond that lacked both fish and invertebrate predators, but contained small‐ to medium‐sized zooplankton, Bosmina longirostris, Daphnia pulex, and Diaptomus pribilofensis. A second pond, which also lacked any predators but had a population of B. longirostris, but no other abundant species, served as a reference population for B. longirostris. 2. The introduction of H. septentrionalis caused the extinction of D. pulex within 1 year and drove B. longirostris to extremely low densities within 4 years. The population of B. longirostris in the reference pond fluctuated throughout the study period, but remained above five individuals per litre. This experiment demonstrates that H. septentrionalis, under natural conditions, made a numerical response to abundant prey and had the capacity to eliminate or reduce vulnerable prey populations of small‐ to medium‐sized zooplankton.
Responses of fungal root colonization, plant cover and leaf nutrients to long‐term exposure to elevated atmospheric CO2 and warming in a subarctic birch forest understory
Authors: OLSRUD MARIA , CARLSSON BENGT Å. , SVENSSON BRITA M. , MICHELSEN ANDERS , MELILLO JERRY M.
Published: September 2009

Responses of the mycorrhizal fungal community in terrestrial ecosystems to global change factors are not well understood. However, virtually all land plants form symbiotic associations with mycorrhizal fungi, with approximately 20% of the plants' net primary production transported down to the fungal symbionts. In this study, we investigated how ericoid mycorrhiza (ErM), fine endophytes (FE) and dark septate endophytes (DSE) in roots responded to elevated atmospheric CO2 concentrations and warming in the dwarf shrub understory of a birch forest in the subarctic region of northern Sweden. To place the belowground results into an ecosystem context we also investigated how plant cover and nutrient concentrations in leaves responded to elevated atmospheric CO2 concentrations and warming. The ErM colonization in ericaceous dwarf shrubs increased under elevated atmospheric CO2 concentrations, but did not respond to warming following 6 years of treatment. This suggests that the higher ErM colonization under elevated CO2 might be due to increased transport of carbon belowground to acquire limiting resources such as N, which was diluted in leaves of ericaceous plants under enhanced CO2. The elevated CO2 did not affect total plant cover but the plant cover was increased under warming, which might be due to increased N availability in soil. FE colonization in grass roots decreased under enhanced CO2 and under warming, which might be due to increased root growth, to which the FE fungi could not keep up, resulting in proportionally lower colonization. However, no responses in aboveground cover of Deschampsia flexuosa were seen. DSE hyphal colonization in grass roots significantly increased under warmer conditions, but did not respond to elevated CO2. This complex set of responses by mycorrhizal and other root‐associated fungi to global change factors of all the fungal types studied could have broad implications for plant community structure and biogeochemistry of subarctic ecosystems.
A hierarchical classification of freshwater mussel diversity in North America
Authors: Haag Wendell R.
Published: September 2009

Aim  North America harbours the most diverse freshwater mussel fauna on Earth. This fauna has high endemism at the continental scale and within individual river systems. Previous faunal classifications for North America were based on intuitive, subjective assessments of species distributions, primarily the occurrence of endemic species, and do not portray continent‐wide patterns of faunal similarity. The aim of this study is to provide an analytical portrayal of patterns of mussel diversity in a hierarchical framework that informs the biogeographical history of the fauna.

Location  The study considered the mussel fauna of North America from the Rio Grande system northwards.

Methods  Patterns of mussel faunal similarity in 126 river systems or lake watersheds across North America were examined. The dataset was developed from the literature and consisted of recent species presence/absence (282 species) in each drainage unit; subspecies were not included. Patterns of mussel diversity were examined with hierarchical cluster analysis, based on a pairwise distance matrix between all drainage units.

Results  Cluster analysis revealed 17 faunal provinces within four major faunal regions: Mississippian, Atlantic, Eastern Gulf and Pacific. The Mississippian Region dominates the North American fauna with 11 provinces, including five not recognized by previous classifications: Mississippi Embayment, Upper Mississippi, Great Plains, Ohioan and Pontchartrain–Pearl–Pascagoula. Within the Eastern Gulf Region (containing three provinces), the Escambia–Choctawhatchee Province is distinctive from the Apalachicolan Province, under which it was previously subsumed. Patterns of diversity in the Atlantic Region (two provinces) and Pacific Region (one province) were similar to previous classifications.

Main conclusions  The classification proposed in this study largely corroborates earlier schemes based on the occurrence of endemic species but identifies additional heterogeneity that reflects unique assemblages of widely distributed species. The study proposes a hierarchical structure that illustrates relationships among these provinces. Although some provinces in the Mississippian Region have high endemism, all Mississippian provinces share a group of widely distributed species. The Atlantic and Eastern Gulf regions have distinctive, endemic faunas suggesting limited past connectivity with the Mississippian Region. The Pacific Region is the most distinct fauna in North America and bears close affinity to the Eurasian mussel fauna.
Mycorrhizal community resilience in response to experimental plant functional type removals in a woody ecosystem
Authors: Urcelay Carlos , Díaz Sandra , Gurvich Diego E. , Chapin III F. Stuart , Cuevas Elvira , Domínguez Laura S.
Published: September 2009

1. Dominant plant functional types (PFTs) are expected to be primary determinants of communities of other above‐ and below‐ground organisms. Here, we report the effects of the experimental removal of different PFTs on arbuscular mycorrhizal fungi (AMF) communities in a shrubland ecosystem in central Argentina.

2. On the basis of the biomass‐ratio hypothesis and plant resource use strategy theory, we expected the effect of removal of PFTs on AMF colonization and spores to be proportional to the biomass removed and to be stronger when more conservative PFTs were removed. The treatments applied were: undisturbed control (no plant removed), disturbed control (mechanical disturbance),no shrub(removal of deciduous shrubs),no perennial forb(removal of perennial forbs),no graminoid(removal of graminoids) andno annual forb(removal of annual forbs). AMF colonization was assessed after 5, 17 and 29 months. Total density of AMF spores, richness and evenness of morphotaxa, and AMF functional groups were quantified after 5, 17, 29, 36 and 39 months.

3. Five months after the initial removal we found a significant reduction in total AMF colonization in all plots subjected to PFT removals and in the disturbed control plots, as compared with the undisturbed controls. This effect disappeared afterwards and no subsequent effect on total colonization and colonization by arbuscules was observed. In contrast, a significant increase in colonization by vesicles was observed in months 17 and 29, mainly inno graminoidplots. In general, treatments did not significantly affect AMF spores in the soil. On the other hand,no annual forbpromoted transient (12–18 months) higher ammonia availability, andno shrubpromoted lower nitrate availability in the longer term (24–28 months).

4. Synthesis.Our experiment, the first to investigate the effects of the removal of different PFTs on AMF communities in natural ecosystems, indicates that AMF communities are resilient to changes in the soil and in the functional composition of vegetation. Furthermore, it does not provide consistent evidence in support of the biomass‐ratio hypothesis or differential trait‐based direct or indirect effects of different PFTs on AMF in this particular system.
Do pathways lead to better organized care processes?
Authors: Vanhaecht Kris , De Witte Karel , Panella Massimiliano , Sermeus Walter
Published: September 2009

Aim  Clinical pathways are used worldwide to (re)organize care processes. They are used by multidisciplinary teams in their search towards excellence. The goal of this study is (1) to assess differences in the perception of health professionals in their evaluation of care processes; (2) to assess whether care processes supported by clinical pathways perform better than those not supported by clinical pathways; and (3) to assess the sensitivity and specificity of clinical pathways in predicting well‐organized care processes.

Methods  A cross‐sectional, multi‐centre study was performed comprising 309 healthcare workers, 103 care processes and 49 hospitals. The Care Process Self Evaluation Tool (CPSET) was used to score care processes according to their organization. Processes were also scored according to the level of pathway implementation.

Results  (1) Significant differences between healthcare professionals were found on two of five CPSET subscales. No significant differences were found among the overall CPSET scores. (2) Care processes supported by pathways had the highest CPSET scores. Nonetheless, continuous follow‐up is necessary. (3) Clinical pathways have significant impact on the coordination of care (odds ratio: 8.92), follow‐up (odds ratio: 6.65) and overall CPSET score (odds ratio: 4.26). Clinical pathways have a positive impact on the organization of care processes. Not all pathways have high CPSET scores, and care processes without pathways can also be well organized. Continuous evaluation is essential. This is the first study to analyse how healthcare teams perceive the organization of care processes with respect to clinical pathways. Our findings are important for other quality improvement methods.
First‐trimester Down syndrome screening in women younger than 35 years old and cost‐effectiveness analysis in Taiwan population
Authors: Chou Ching‐Yu , Hsieh Fon‐Jou , Cheong Mei‐Leng , Lee Fa‐Kung , She Bo‐Quing , Tsai Ming‐Song
Published: September 2009

Objectives  Outcome of the first‐trimester Down syndrome screening in younger population was less reported before. We present the outcome of this screening in Taiwanese women younger than 35 years old. We also test whether or not the first‐trimester Down syndrome screening of women <35 years of age and women >35 years old routinely receiving amniocentesis is cost‐effective compared with all pregnant women screened with this test in the setting of increased maternal age.

Methods  From 1999 to 2007, the first‐trimester Down syndrome screening including nuchal thickness, pregnancy‐associated plasma protein A and free β‐hCG are provided to 10 811 singleton women <35 years of age with the cut‐off of 1/270. A cost‐effectiveness analysis of young women receiving this screening and older women undergo amniocentesis versus all women undergo this screening was performed in Taiwan population from 1987 to 2006, in which advanced age pregnancies increased from 2.8% to 11.6% of total pregnancies.

Results  Detection rates of trisomy 21, trisomy 18, Turner syndrome and other chromosome anormalies in women <35 years of age are 87.5% (14/16), 50% (2/4), 80% (8/10) and 63% (12/19), respectively, with a false‐positive rate of 5.5% (590/10 811). As advanced age pregnancies reached 11.6%, the average cost per one case averted for all women screened ranged from $77 204 to $98 421, while the cost ranged from $99 647 to $116 433 for only women <35 years of age receiving this screening.

Conclusions  In an aging population, the first‐trimester Down syndrome screening should be implemented for all pregnant women when it is available.
Health promotion as a systems science and practice
Authors: Norman Cameron D.
Published: September 2009

Rationale  Health promotion is where clinical practice and prevention science intersect to address complex or ‘wicked’ problems that have multiple sources and require a broad perspective to address. This means focusing on the social determinants of health and the complex individual, community and environmental interactions that influence health and wellbeing. Health promotion research and practice recognizes that social change is not linear and involves multiple communities of interest working together in a coordinated manner in order to address health problems. An approach that acknowledges this non‐linear system of interaction in its data gathering, strategic planning, and program implementation is necessary to addressing this complexity in practice.

Methods  Concepts such as chaos theory, self‐organization, social emergence can inform how health promotion is practiced at multiple levels. Evaluation approaches such as social network analysis, system dynamics modeling combined with social organizing strategies like communities of practice and unconferences provide opportunities to leverage social capital effectively to promote health in complex environments with diverse populations.

Conclusion  Health promotion's focus on the multi‐layered, complex interactions that create or limit health and wellbeing require knowledge and action that match this complexity. Approaches to engagement and evaluation that are based on systems theories and methodologies provide the means of addressing this complexity, while framing health promotion as a systems science and practice.
Levels of Dendritic Cell Populations and Regulatory T Cells Vary Significantly Between Two Commonly Used Mouse Strains
Authors: Vogelsang Petra , Hovden Arnt‐Ove , Jonsson Roland , Appel Silke
Published: September 2009

Dendritic cells (DC) are a heterogeneous group of professional antigen‐presenting cells (APC) involved in both initiating immune responses and maintaining tolerance. Roughly, DC can be divided into plasmacytoid DC (pDC) and conventional DC (cDC). By controlling regulatory T cells (Treg), DC can influence the outcome of both immunity and autoimmunity. Since the use of mice as in vivo models became a practical tool for researchers studying pathological events in all kind of human diseases, we decided to compare levels of cDC, pDC and Treg in both spleen and blood between two inbred mouse strains. Here we show that two commonly used mouse strains, BALB/c and C57BL/10J mice, have significantly different levels of distinct CD11c+/CD4–/CD8a+, CD11c+/CD4+/CD8a– and CD11c+/CD4–/CD8a– cDC populations, pDC and Treg. Therefore, we emphasize the importance of considering the proper model when comparing data sets from different mouse strains.
Genotype–phenotype studies in infantile spinal muscular atrophy (SMA) type I in Germany: implications for clinical trials and genetic counselling
Authors: Rudnik‐Schöneborn S , Berg C , Zerres K , Betzler C , Grimm T , Eggermann T , Eggermann K , Wirth R , Wirth B , Heller R
Published: September 2009

We reviewed the natural history and assessed the SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 and 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion in the first 6 months of life. After excluding patients who had received valproic acid, the median/mean age at disease endpoint was 6.1/7.3 months (range 0.0–34.0). Four (6.1%) patients with one SMN2 copy had severe SMA type ‘0’ with joint contractures and respiratory distress from birth. Median/mean age at onset (months) in 57 (86.3%) patients with two SMN2 copies was 1.2/1.3, and 3.5/3.4 in 5 (7.6%) patients with three SMN2 copies. Median/mean age at disease endpoint was 6.5/7.8 months (range 0.5–30) in patients with two SMN2 copies. All patients with three SMN2 copies were still alive at 10–55 months, two of them under permanent ventilation. Our data are relevant for prognostication and genetic counselling. The observed clinical variability, especially in the group with two SMN2 copies, might be important for clinical trials in SMA I where a possible control group could be defined as follows: age at onset within 4–5 months, age at genetic diagnosis <6 months, two SMN2 copies present, head control in less than 10%, no respiratory distress from birth, disease endpoint either age at death or age at permanent ventilation.
Development and disease of the photoreceptor cilium
Authors: Ramamurthy V , Cayouette M
Published: September 2009

Primary cilia are microtubule‐rich hair‐like extensions protruding from the surface of most post‐mitotic cells. They act as sensory organelles that help interpret various environmental cues. Mutations in genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia lead to a wide variety of diseases commonly referred to as ciliopathies, which include primary ciliary dyskinesia, situs invertus, hydrocephalus, kidney diseases, respiratory diseases, and retinal degenerations. In the retina, the photoreceptor cells have a highly specialized primary cilium called the outer segment (OS), which is essential for photosensation. Development of the photoreceptor OS shares key regulatory mechanisms with ciliogenesis in other cell types. Accumulating evidence indicates that mutations that affect OS development and/or protein transport to the OS generally lead to photoreceptor degeneration, which can be accompanied by a range of other clinical manifestations due to the dysfunction of primary cilia in different cell types. Here, we review the general mechanisms regulating ciliogenesis, and present different examples of mutations affecting OS ciliogenesis and protein transport that lead to photoreceptor degeneration. Overall, we conclude that the genetic and molecular evidence accumulated in recent years suggest a clear link between the development and function of the primary cilium and various clinical conditions. Future studies aimed at uncovering the cellular and molecular mechanisms implicated in ciliogenesis in a wide variety of animal models should greatly increase our understanding of the pathophysiology of many human diseases, including retinal degenerations.
High resolution definition of HLA‐DRB haplotypes by a simplified microsatellite typing technique
Authors: Doxiadis G. G. M. , De Groot N. , Dauber E. ‐M. , Van Eede P. H. , Fae I. , Faner R. , Fischer G. , Grubic Z. , Lardy N. M. , Mayr W. , Palou E. , Swelsen W. , Stingl K. , Doxiadis I. I. N. , Bontrop R. E.
Published: September 2009

In humans, the region configurations DR1, DR8, DR51, DR52 and DR53 are known to display copy number as well as allelic variation, rendering high resolution typing of HLA‐DRB haplotypes cumbersome. Advantage was taken of microsatellite D6S2878, present in all DRB genes/pseudogenes with an intact exon 2‐intron 2 segment. This DRB‐STR is highly polymorphic in composition and length. Recently, it was proven that all exon 2 sequences could be linked to a certain DRB‐STR that segregates with the respective DRB allele. Because haplotypes show differential copy numbers and compositions of exon 2‐positive DRB genes/pseudogenes, unique DRB‐STR patterns could be described that appear to be specific for a particular DRB haplotype. The aim of this workshop project was to approve and to qualify this simple typing protocol in a larger panel covering different European populations. All participants succeeded in correctly defining the DRB‐STR amplicons varying from 135 to 222 base pair (bp) lengths. The panel of 101 samples covered 50 DRB alleles distributed over 37 different haplotypes as defined by exon 2 sequence‐based typing. These haplotypes could be refined into 105 haplotypes by DRB‐STR typing. Thus, discrimination of exon 2‐identical DRB alleles was feasible, as well as the exact description of three different crossing‐over events that resulted in the generation of hybrid DR region configurations. This typing procedure appears to be a quick and highly robust technique that can easily be performed by different laboratories, even without experience in microsatellite typing; thus, it is suitable for a variety of researchers in diverse research areas.
Prevalence of rhinitis‐related symptoms in Latin American children – Results of the International Study of Asthma and Allergies in Childhood (ISAAC) phase three
Authors: Solé Dirceu , Mallol Javier , Camelo‐Nunes Inês C , Wandalsen Gustavo F ,   Latin American ISAAC Study Group
Published: September 2009

Solé D, Mallol J, Camelo‐Nunes IC, Wandalsen GF, Latin American ISAAC Study Group. Prevalence of rhinitis‐related symptoms in Latin American children – Results of the International Study of Asthma and Allergies in Childhood (ISAAC) phase three. Pediatr Allergy Immunol 2010: 21: e127–e136. © 2009 John Wiley & Sons A/S

The aim of this study was to evaluate the prevalence of rhinitis‐related symptoms among children living in different parts of Latin America (LA) considering all centers involved in ISAAC Phase Three (Ph3). 93,851 children (6–7 yr‐old) from 35 centers in 14 LA countries and 165,917 adolescents (13–14 yr‐old) from 56 centers in 17 LA countries were enrolled. The mean prevalence rate of current rhinoconjunctivitis was 12.7% and ranged from 5.5% in Rosario City (Argentina) to 21.2% in Caracas (Venezuela) for the schoolchildren. The mean prevalence rate of current rhinoconjunctivitis was 18.5% and ranged from 7.1% in Cuernavaca (México) to 45.1% in Asunción (Paraguay) for the adolescents. These indexes were among the higher observed during ISAAC Ph3. In general the prevalence of rhinitis‐related symptoms was higher among the Spanish speaking centers. Environmental risk factors must be evaluated in order to explain the differences observed even in centers from the same country.
Storage of buffy‐coat‐derived platelets in additive solutions: in vitro effects on platelets stored in reformulated PAS supplied by a 20% plasma carry‐over
Authors: Sandgren P. , Mayaudon V. , Payrat J.‐M. , Sjödin A. , Gulliksson H.
Published: September 2009

Background and Objectives  Platelet additive solutions (PAS) have been shown to be suitable for extended platelet (PLT) storage. Depending on the PAS formulation, the percentage of plasma carry‐over contributes to success. Improving PLT quality by optimizing the composition of PAS may allow a reduction to be made in the amount of plasma carried over to the final unit. Reducing the proportion of plasma carried over would probably decrease transfusion of unwanted antibodies and make greater amounts of plasma available for other needs.

Study Design and Methods  Platelets from eight pools of 25 buffy coats were aliquoted and prepared for storage in plasma and different PAS units: InterSol and three alternate PAS named PSM1, PSM2 and PSM3. All PAS units were supplied with a 20% plasma carry‐over and stored at room temperature with agitation for 9 days with in vitro testing for metabolic, cellular and activation parameters.

Results  During storage, PLTs stored in InterSol displayed significantly lower glucose concentration (P < 0·01), lower adenosine triphosphate levels (P < 0·01), a higher mean PLT volume (P < 0·01), a lower response to hypotonic shock response activity (P < 0·01) and a higher CD62P expression (P < 0·01) when compared with PLTs stored in plasma and PSM1–3 solutions. pH was maintained at > 6·8 (day 9) and swirling remained at the highest level (score = 2) for all units throughout storage.

Conclusion  Our results suggest that PLTs stored in PAS with addition of magnesium, potassium and glucose (PSM2 and PSM3) and 20% plasma carry‐over maintained metabolic and cellular characteristics, equivalent to PLTs stored in 100% plasma during 9 days of storage. Our results also suggest that presence of potassium in addition to magnesium or alternatively the concentration of phosphate as well as the supply of additional glucose to normal plasma levels improve in vitro data of PLTs stored in PAS.
Spatial scale and habitat‐dependent diversity patterns in nematode communities in three seepage related sites along the Norwegian Sea margin
Authors: Van Gaever Saskia , Raes Maarten , Pasotti Francesca , Vanreusel Ann
Published: September 2009

Assessing the relative contribution of local diversity to regional biodiversity may be the key to understanding large‐scale and even global patterns in species diversity. Here, the contribution of habitat heterogeneity of cold seeps at three spatial scales [micro‐scale (ms), macro‐scale (10 to 100s of ms), and mega‐scale (10 to 100s of km)] to the total nematode biodiversity (genus level) along the Norwegian continental margin is evaluated. Due to the development of higher resolution bathymetry and increased bottom sampling in recent years, continental margins, once regarded as monotonous landscapes, are now acknowledged to have a high degree of habitat complexity and diversity. By calculating the additive partitioning of gamma diversity in alpha and beta fractions, we examined to what extent habitat diversity of seep sites significantly increases the nematode genus composition and diversity at different spatial scales. Siboglinidae patches and control sediments yielded comparably high levels of nematode genus richness. They exhibited low turnover rates within and across the different seep sites. In contrast, the bacterial mats at Håkon Mosby Mud Volcano (HMMV) and the reduced sediments at the Nyegga pockmarks harboured genus‐poor nematode communities with an equally high dominance of one or two species, which were different for each seep. Different habitats, in particular at the HMMV, contributed significantly to the seep nematode richness. This study demonstrates that the presence of distinct habitat types within multiple seep sites contributes to the high diversity of nematode communities inhabiting the seeps in the Norwegian deep sea.
Thyroid dysfunction in patients with chronic hepatitis C receiving a combined therapy of interferon and ribavirin: Incidence, associated factors and prognosis
Authors: Kee Kwong‐Ming , Lee Chuan‐Mo , Wang Jing‐Houng , Tung Hung‐Da , Changchien Chi‐Sin , Lu Sheng‐Nan , Wang Pei‐Wen
Published: September 2009

Abstract Background and Aims:  Interferon (IFN) plus ribavirin therapy for chronic hepatitis C (CHC) virus infection has been associated with thyroid dysfunction. The goal of our current study was to elucidate predictive factors of: (i) thyroid dysfunction associated with combination therapy; and (ii) long‐term reversibility of thyroid dysfunction.

Methods:  In total, 461 patients with CHC and normal baseline thyroid functions were enrolled. All patients received IFN‐α‐2b, 3 or 5 million units thrice weekly, or pegylated (PEG)‐IFN‐α‐2b 80 or 100 µg weekly combined with ribavirin 1–1.2 g daily for 24–48 weeks. Assays for serum thyroid stimulating hormone (TSH) and free thyroxine were performed.

Results: By the end of the treatment, thyroid dysfunction (TSH <0.1 or >5 mU/L) had developed in 58 patients (12.6%). Female gender was significantly associated with thyroid dysfunction (P < 0.001 odds ratio (OR) = 2.85; 95% confidence interval (CI) = 1.6–5.1). The incidence of thyroid dysfunction was similar for standard IFN and PEG‐IFN‐treated patients (49/391 vs 9/70; P = 1.00). Under a nested case‐control design, detailed laboratory assessment was carried out on frozen serum samples from patients and age‐ (± 5 years) and sex‐matched controls (n = 58). Multivariate analysis revealed significant association between higher positive rates of pretreatment TMA and patients who developed thyroid dysfunction (OR = 5.8, 95% CI = 1.2–27.9). Ten patients (∼2%) remained thyroid dysfunctional at the end of follow up (median, 26.5 months). For these patients, no risk factor can predict the reversibility of thyroid function.

Conclusions:  Female gender and pretreatment TMA positivity are associated with thyroid dysfunction. Long‐term thyroid dysfunction may persist in a small group of patients (∼2%).
Identification of high‐risk dementia cohorts in a community sample of Japanese elderly
Authors: Shinagawa Shunichiro , Nakamura Shiori , Iwamoto Makoto , Tsuno Norifumi , Shigeta Masahiro
Published: September 2009

Aim:  The aim of this study was to develop a simple diagnostic procedure for subjects at high risk of developing dementia using the Clinical Dementia Rating (CDR), which is applicable to community‐based activities.

Methods:  This study divided 252 community‐dwelling elderly with a CDR score of 0.5 into two groups based on the presence or absence of cognitive decline within the previous one year of the baseline, as assessed by a semi‐structured interview. One hundred subjects were in the ‘previously progressive group’ (PP group) and 152 subjects were in the ‘previously stable group’ (PS group). After 6 years of observation, a total of 111 subjects were assessed in the follow‐up investigation.

Results:  Among the 39 subjects from the PP group (82.9 ± 6.8 years old, 11 male, 28 female), 34 developed dementia (87%). Among the 72 subjects from the PS group (84.4 ± 6.0 years old, 22 male, 50 female), 44 developed dementia (61%). The relative risk of developing dementia for the PP group versus the PS group was 1.43. The rate of conversion to dementia was 12.9% per 100 person‐years in the PP group, and 9.8% in the PS group. In the PP group, the Mini‐Mental State Examination score was significantly lower and the CDR score was significantly higher than in the PS group.

Conclusion:  Although there have been many attempts to identify subjects with high risk of dementia, this preliminary study suggests that information about temporal changes in cognitive function is useful when performing community‐based surveys.
Characterization of endoglin and Ki‐67 expression in endothelial cells from benign and malignant lesions of the uterine cervix
Authors: Cimpean Anca M. , Saptefrati Lilian , Ceausu Raluca , Raica Marius
Published: September 2009

Activation of endothelial cells is often associated with the cellular proliferation in vitro. CD105 is a more specific marker of activated endothelial cells from tumor vessels and Ki‐67 is used to assess the proliferation status of both tumor and endothelial cells. The aim of the present study was to evaluate the status of endothelial cells using CD105 and Ki‐67 immunohistochemistry in benign and malignant lesions of the uterine cervix. Double stain for CD105/Ki‐67 in benign and malignant lesions of the uterine cervix showed that these two markers had divergent expression on endothelial cells from associated tumor blood vessels dependent on lesion type and proliferation status of tumor cells. Absence of CD105/Ki‐67 coexpression in endothelial cells was correlated with histopathology of the uterine cervix lesions and tumor proliferative status. The present findings suggest that CD105 expression is an early event, specific for premalignant lesions of the uterine cervix, while endothelial proliferation assessed on Ki‐67 combined with the lack of CD105 expression is often associated with invasive cervical carcinoma.
Diagnostic findings of ultrasound‐guided fine‐needle aspiration cytology for gastrointestinal stromal tumors: Proposal of a combined cytology with newly defined features and histology diagnosis
Authors: Yoshida Satoko , Yamashita Kazuya , Yokozawa Masashi , Kida Mitsuhiro , Takezawa Miyoko , Mikami Tetuo , Okayasu Isao
Published: September 2009

Recently, endoscopic ultrasonography‐guided fine needle aspiration (EUS‐FNA) has been applied for diagnosis of gastrointestinal submucosal tumors. There have been no definite criteria, however, for the adequate cytological diagnosis of gastrointestinal stromal tumor (GIST) in practice. To facilitate this a novel method is proposed that combines cytology and histology. For 49 cases of submucosal tumor of gastrointestinal tract, EUS‐FNA was performed. The aspirated materials were processed for cytology and histology. Both cytological and histological findings were examined on immunocytochemical and immunohistochemical staining of c‐kit. Of 49 cases, 40 (81.6%) proved adequate for cytological and/or histological examination. On cytology, cluster types were classified into type A (piled clusters with high cellularity showing a fascicular pattern), type B (thin layered clusters with high cellularity showing a fascicular pattern), and type C (mono‐layered clusters or scattered cells). Types A and B were strongly associated with histological diagnosis of GIST. Type C clusters needed confirmation on c‐kit positivity and histology. Thus, the combined cytology with newly defined features, and classification and histological diagnostic method for EUS‐FNA materials can contribute to improved routine diagnosis for GIST.
Decreased protein and gene expression of hepatic cholesterol 7a‐hydroxylase associated with dilated endoplasmic reticulum in chronic hypothyroid rats
Authors: Zhou Xinli , Han Yong , Liu Jia , Gao Ling , Zhao Jiajun
Published: September 2009

Chronic hypothyroidism is associated with an increased risk for cardiovascular disease attributed, in part, to increased serum cholesterol and atherosclerosis. Decreased hepatic activity of cholesterol 7a‐hydroxylase (CYP7A1) is thought to contribute to hypercholesterolemia in hypothyroidism. The endoplasmic reticulum (ER) has been shown to be a central organelle, and it is the location of CYP7A1 in hepatocyte. The aim of the present study was to determine whether the expression of CYP7A1 mRNA and protein could be decreased and whether ER could undergo morphological changes in a rodent model of chronic hypothyroidism induced by methimazole (MMI). Male Wistar rats were treated with MMI (0.04% wt/vol) or regular water for 14 weeks. Hepatic CYP7A1 mRNA was analyzed on quantitative real‐time polymerase chain reaction (PCR). Hepatic CYP7A1 protein expression was assessed on western blot. In conjunction with these molecular biological assessments the morphology of ER was evaluated on transmission electron microscopy (TEM). Serum total cholesterol increased significantly compared to controls and was associated with decreased CYP7A1 mRNA and protein, and TEM indicated remarkable dilation of ER in hepatocytes in the chronic hypothyroid rats. These findings suggest that a relationship between the decreased expression of hepatic CYP7A1 mRNA and protein and dilated ER could exist, which may contribute to hypercholesterolemia in chronic hypothyroidism.
Atypical cell clusters expressing both neuronal and oligodendrocytic markers: Novel histological pattern of glioneuronal tumors?
Authors: Phi Ji Hoon , Park Sung‐Hye , Chung Chun Kee , Wang Kyu‐Chang , Cho Byung‐Kyu , Kim Seung‐Ki
Published: September 2009

Glioneuronal tumors are a group of brain tumors that consist of both neuronal and glial cells. The spectrum of glioneuronal tumors is currently expanding, and many atypical glioneuronal tumors require further characterization. Two patients are described who had an atypical glioneuronal tumor with peculiar pathological features. One patient was a 7‐year‐old girl with a tumor in the right cerebellar hemisphere. This patient had no recurrence after total resection. The other was a 37‐year‐old man with a tumor in the spinal cord. He suffered incessant recurrence and received operative treatment four times. Although the clinical features (age at diagnosis, tumor location, and recurrence) were very different in these patients, the tumors had a characteristic common feature of atypical cell clusters. Intriguingly, the tumor cells in the clusters expressed both neuronal and oligodendroglial markers, indicating aberrant differentiation. Furthermore, the cluster‐forming cells had modest proliferative indices and CD133 expression, indicating their role in the growth of the tumor. It is believed that these atypical cell clusters are a novel pattern of differentiation of glioneuronal tumors and that they need further investigation.
Small invasive ductal adenocarcinoma of the pancreas associated with lymphoplasmacytic sclerosing pancreatitis
Authors: Motosugi Utaroh , Ichikawa Tomoaki , Yamaguchi Hiroshi , Nakazawa Tadao , Katoh Ryohei , Itakura Jun , Fujii Hideki , Sato Tadashi , Araki Tsutomu , Shimizu Michio
Published: September 2009

An asymptomatic 59‐year‐old man underwent pancreatoduodenectomy for a pancreatic mass that was discovered during a health check‐up. Histopathology indicated typical features of lymphoplasmacytic sclerosing pancreatitis (LPSP) or autoimmune pancreatitis along with the presence of abundant IgG4‐positive plasma cells throughout the mass. A small invasive ductal adenocarcinoma was observed in the center of the area affected by LPSP. The present case suggests that LPSP may be closely related to carcinogenesis of the pancreas.
Osteopontin expression in pulmonary tumor thrombotic microangiopathy caused by gastric carcinoma
Authors: Takahashi Fumiyuki , Kumasaka Toshio , Nagaoka Tetsutaro , Wakiya Midori , Fujii Hiroaki , Shimizu Kazue , Uchida Koji , Morio Yoshiteru , Seyama Kuniaki , Hino Okio , Takahashi Kazuhisa , Fukuchi Yoshinosuke
Published: September 2009

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by fibrocellular intimal proliferation and thrombus formation in small pulmonary arteries and arterioles in patients with metastatic carcinoma. Osteopontin (OPN) is a multifunctional cytokine and adhesive protein, and has been demonstrated to be implicated in fibrosis, neointima formation, arterial occlusion by thrombus, and tumor metastases in cooperation with platelet‐derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Herein is described an autopsy case of gastric adenocarcinoma with severe pulmonary hypertension due to PTTM. Histologically, tumor cell emboli markedly induced both fibromuscular intimal thickening and thrombosis, resulting in luminal stenosis and occlusion of small pulmonary arteries and arterioles. Tumor cells, both in the PTTM lesions and primary gastric carcinoma, had positive immunoreactivity for OPN, PDGF, and VEGF. In addition, proliferating fibromuscular intimal cells also showed expression of OPN, PDGF, and VEGF. These findings suggest that OPN may be involved in fibrocellular intimal proliferation and thrombus formation in PTTM together with PDGF and VEGF. To the best of the authors' knowledge this is the first report to demonstrate the possible involvement of OPN in PTTM. It is postulated that OPN is one of the candidate molecules for the development of PTTM.
Heparin‐induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long‐term follow up
Authors: Ichinoe Masaaki , Mikami Tetuo , Ujiie Sachiko , Suzuki Kosuke , Okayasu Isao
Published: September 2009

Heparin‐induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68‐year‐old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long‐term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.
Mucinous cystadenoma of the pancreas with huge mural hematoma
Authors: Hisa Takeshi , Ohkubo Hiroki , Shiozawa Satoshi , Ishigame Hiroki , Ueda Mizuho , Takamatsu Masato , Furutake Masayuki
Published: September 2009

A 60‐year‐old woman was referred for evaluation of a cystic mass in the pancreatic body that extended to the tail. Transabdominal ultrasonography demonstrated an oval cystic mass 24 cm in diameter, filled with debris. On the cyst wall there was a wide‐based, smooth‐surfaced, heterogeneous high‐echoic protrusion that was 5 cm in diameter. On CT the protrusion showed internal enhancement. Endoscopic pancreatography showed no intraductal mucin or communication with the cyst. A distal pancreatectomy was performed under the diagnosis of mucinous cystadenocarcinoma. Grossly there was a brownish, hemispherical protrusion into the thin monolocular cyst. The cut surface of the protrusion showed a peripheral yellow‐brownish area and an internal wine‐colored area. Histopathologically the cyst wall consisted of tall columnar cells without atypical nuclei, ovarian‐type stroma beneath the epithelium, and fibrotic tissue with abundant capillary vessels, suggestive of a mucinous cystadenoma. The protrusion was composed of peripheral organized hematoma without a covering epithelium, and internal hemorrhage and many capillary vessels, with no evidence of tumor cell necrosis. These histopathological findings appear to be similar to those of chronic expanding hematoma. The formation of a huge mural hematoma in a mucinous cystic neoplasm can occur as a repair process after the breaking of intrawall vessels.