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Background: The etiology of congenital solitary functioning kidney (CSFK) is largely unknown but likely includes various risk factors. We performed a case–control study to compare exposure to environmental and parental risk factors during embryonic kidney development between children with CSFK and healthy controls. Methods: We included 434 children with CSFK and 1302 healthy controls from the AGORA data- and biobank matched on year of birth. Exposure to potential risk factors was investigated using parental questionnaire data. Crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were estimated for each potential risk factor. Multiple imputation was used to deal with missing values. Confounders for each potential risk factor were selected using directed acyclic graphs. Results: Maternal stress was newly identified as a risk factor for CSFK (aOR 2.1, 95% CI 1.2–3.5). Known associations with conception using in vitro fertilization/intracytoplasmic sperm injection (aOR 1.8, 95% CI 1.0–3.2), maternal infections during pregnancy (aOR 2.5, 95% CI 1.4–4.7), smoking during pregnancy (aOR 1.4, 95% CI 1.0–2.0), and parental CAKUT (aOR 6.6, 95% CI 2.9–15.1) were confirmed, but previous associations with diabetes and obesity could not be replicated. Folic acid supplement use and younger maternal age seemed to reduce the risk of CSFK (aORs 0.7, 95% CI 0.5–1.0, and 0.8, 95% CI 0.6–1.0, respectively). Conclusions: Environmental and parental risk factors are likely to be involved in the development of CSFK and future studies should combine genetic, environmental, and gene-environment interaction analyses. Women wanting to become pregnant should consider optimizing their health and lifestyle. [ABSTRACT FROM AUTHOR]

The invention of scanning probe microscopy revolutionized the way electronic phenomena are visualized1. Whereas present-day probes can access a variety of electronic properties at a single location in space2, a scanning microscope that can directly probe the quantum mechanical existence of an electron at several locations would provide direct access to key quantum properties of electronic systems, so far unreachable. Here, we demonstrate a conceptually new type of scanning probe microscope—the quantum twisting microscope (QTM)—capable of performing local interference experiments at its tip. The QTM is based on a unique van der Waals tip, allowing the creation of pristine two-dimensional junctions, which provide a multitude of coherently interfering paths for an electron to tunnel into a sample. With the addition of a continuously scanned twist angle between the tip and sample, this microscope probes electrons along a line in momentum space similar to how a scanning tunnelling microscope probes electrons along a line in real space. Through a series of experiments, we demonstrate room-temperature quantum coherence at the tip, study the twist angle evolution of twisted bilayer graphene, directly image the energy bands of monolayer and twisted bilayer graphene and, finally, apply large local pressures while visualizing the gradual flattening of the low-energy band of twisted bilayer graphene. The QTM opens the way for new classes of experiments on quantum materials.A quantum twisting microscope based on a unique van der Waals tip and capable of performing local interference experiments opens the way for new classes of experiments on quantum materials. [ABSTRACT FROM AUTHOR]

In cerebral small vessel disease (cSVD), whole brain MRI markers of cSVD-related brain injury explain limited variance to support individualized prediction. Here, we investigate whether considering abnormalities in brain tracts by integrating multimodal metrics from diffusion MRI (dMRI) and structural MRI (sMRI), can better capture cognitive performance in cSVD patients than established approaches based on whole brain markers. We selected 102 patients (73.7 ± 10.2 years old, 59 males) with MRI-visible SVD lesions and both sMRI and dMRI. Conventional linear models using demographics and established whole brain markers were used as benchmark of predicting individual cognitive scores. Multi-modal metrics of 73 major brain tracts were derived from dMRI and sMRI, and used together with established markers as input of a feed-forward artificial neural network (ANN) to predict individual cognitive scores. A feature selection strategy was implemented to reduce the risk of overfitting. Prediction was performed with leave-one-out cross-validation and evaluated with the R2 of the correlation between measured and predicted cognitive scores. Linear models predicted memory and processing speed with R2 = 0.26 and R2 = 0.38, respectively. With ANN, feature selection resulted in 13 tract-specific metrics and 5 whole brain markers for predicting processing speed, and 28 tract-specific metrics and 4 whole brain markers for predicting memory. Leave-one-out ANN prediction with the selected features achieved R2 = 0.49 and R2 = 0.40 for processing speed and memory, respectively. Our results show proof-of-concept that combining tract-specific multimodal MRI metrics can improve the prediction of cognitive performance in cSVD by leveraging tract-specific multi-modal metrics. [ABSTRACT FROM AUTHOR]

The cerebellum is increasingly recognised for its role in modulation of cognition, behaviour, and affect. The present study examined the relation between structural cerebellar damage (grey matter volume (GMV), white matter hyperintensities (WMHs), lacunar infarcts (LIs) and microbleeds (MBs)) and measures of cognitive, psychological (i.e. symptoms of depression and apathy) and general daily functioning in a population of community-dwelling older persons with mild cognitive deficits, but without dementia. In 194 participants of the Discontinuation of Antihypertensive Treatment in Elderly People (DANTE) Study Leiden, the association between cerebellar GMV, WMHs, LIs and MBs and measures of cognitive, psychological and general daily functioning was analysed with linear regression analysis, adjusted for age, sex, education and cerebral volume. Cerebellar GMV was associated with the overall cognition score (standardised beta 0.20 [95% CI, 0.06–0.33]). Specifically, posterior cerebellar GMV was associated with executive function (standardised beta 0.18 [95% CI, 0.03–0.16]). No relation was found between vascular pathology and cognition. Also, no consistent associations were found on the cerebellar GMV and vascular pathology measures and psychological and general daily functioning. In this population of community-dwelling elderly, less posterior cerebellar GMV but not vascular pathology was associated with worse cognitive function, specifically with poorer executive function. No relation was found between cerebellar pathology and psychological and general daily functioning. [ABSTRACT FROM AUTHOR]

Introduction: The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). Methods: This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. Results: Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p < 0.001). High expression of Claudin 18.2 was neither associated with histomorphogical subtype, or tumor state, nor with overall survival. Conclusion: In Caucasian AEG/S patients, 17.1% appeared to be eligible for an anti-Claudin 18.2 therapy. Claudin 18.2 expression itself has no impact on prognosis and is not related to any tumor subtype. [ABSTRACT FROM AUTHOR]

T-cell receptor gene beta (TCRβ) gene rearrangement represents a complex, tightly regulated molecular mechanism involving excision, deletion and recombination of DNA during T-cell development. RUNX1, a well-known transcription factor for T-cell differentiation, has recently been described to act in addition as a recombinase cofactor for TCRδ gene rearrangements. In this work we employed a RUNX1 knock-out mouse model and demonstrate by deep TCRβ sequencing, immunostaining and chromatin immunoprecipitation that RUNX1 binds to the initiation site of TCRβ rearrangement and its homozygous inactivation induces severe structural changes of the rearranged TCRβ gene, whereas heterozygous inactivation has almost no impact. To compare the mouse model results to the situation in Acute Lymphoblastic Leukemia (ALL) we analyzed TCRβ gene rearrangements in T-ALL samples harboring heterozygous Runx1 mutations. Comparable to the Runx1+/− mouse model, heterozygous Runx1 mutations in T-ALL patients displayed no detectable impact on TCRβ rearrangements. Furthermore, we reanalyzed published sequence data from recurrent deletion borders of ALL patients carrying an ETV6-RUNX1 translocation. RUNX1 motifs were significantly overrepresented at the deletion ends arguing for a role of RUNX1 in the deletion mechanism. Collectively, our data imply a role of RUNX1 as recombinase cofactor for both physiological and aberrant deletions. [ABSTRACT FROM AUTHOR]

Twisted bilayer graphene near the magic angle1–4 exhibits rich electron-correlation physics, displaying insulating3–6, magnetic7,8 and superconducting phases4–6. The electronic bands of this system were predicted1,2 to narrow markedly9,10 near the magic angle, leading to a variety of possible symmetry-breaking ground states11–17. Here, using measurements of the local electronic compressibility, we show that these correlated phases originate from a high-energy state with an unusual sequence of band population. As carriers are added to the system, the four electronic ‘flavours’, which correspond to the spin and valley degrees of freedom, are not filled equally. Rather, they are populated through a sequence of sharp phase transitions, which appear as strong asymmetric jumps of the electronic compressibility near integer fillings of the moiré lattice. At each transition, a single spin/valley flavour takes all the carriers from its partially filled peers, ‘resetting’ them to the vicinity of the charge neutrality point. As a result, the Dirac-like character observed near charge neutrality reappears after each integer filling. Measurement of the in-plane magnetic field dependence of the chemical potential near filling factor one reveals a large spontaneous magnetization, further substantiating this picture of a cascade of symmetry breaking. The sequence of phase transitions and Dirac revivals is observed at temperatures well above the onset of the superconducting and correlated insulating states. This indicates that the state that we report here, with its strongly broken electronic flavour symmetry and revived Dirac-like electronic character, is important in the physics of magic-angle graphene, forming the parent state out of which the more fragile superconducting and correlated insulating ground states emerge.Local electronic compressibility measurements of magic-angle twisted bilayer graphene show that the insulating and superconducting phases of this system are both derived from a high-energy symmetry-broken state. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Trials to test disease-modifying treatments for frontotemporal dementia are eagerly awaited and sensitive instruments to assess potential treatment effects are increasingly urgent, yet lacking thus far. We aimed to identify gene-specific instruments assessing clinical onset and disease progression by comparing cognitive functioning between bvFTD patients across genetic mutations. Methods: We examined differences in 7 cognitive domains between bvFTD patients with GRN (n = 20), MAPT (n = 29) or C9orf72 (n = 31) mutations, and non-carriers (n = 24), and described longitudinal (M = 22.6 months, SD = 16.6) data in a subsample (n = 27). Results: Patients showed overall cognitive impairment, except memory recall, working memory and visuoconstruction. GRN patients performed lower on executive function (mean difference − 2.1; 95%CI − 4.1 to − 0.5) compared to MAPT and lower on attention compared to MAPT (mean difference − 2.5; 95%CI − 4.7 to − 0.3) and C9orf72 (mean difference − 2.4; 95%CI − 4.5 to − 0.3). Only MAPT patients were impaired on delayed recall (mean difference − 1.4; 95%CI − 2.1 to − 0.7). GRN patients declined rapidly on attention and memory, MAPT declined in confrontation naming, whereas C9orf72 patients were globally impaired but remained relatively stable over time on all cognitive domains. Discussion: This study shows gene-specific cognitive profiles in bvFTD, which underlines the value of neuropsychological tests as outcome measures in upcoming trials for genetic bvFTD. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Root lesion nematodes (Pratylenchus spp.) are the most common plant-parasitic nematodes present in apple orchards in South Africa. During a survey conducted in 2017 and 2018 in the main apple production regions in South Africa, P. hippeastri was detected in 85% of samples that contained root lesion nematodes. Morphological and morphometric characters as well as DNA sequencing of the D2–D3 expansion segments of 28S rRNA confirmed the identity of the nematodes extracted from apple roots. Apple rootstocks supported reproduction of these nematodes with an average reproduction factor of 14, measured 90 days after inoculation. This study confirms the host status of apple (Malus domestica Borkh.) for P. hippeastri and is the first record of P. hippeastri in South Africa. [ABSTRACT FROM AUTHOR]

The article focuses on the first-line treatment of patients with Idiopathic aplastic anemia (AA). Topics discussed include effectiveness of of antithymocyte globul in the treatment of aplastic anemia and mentions treatment options for AA by allogeneic hematopoietic cell transplantation and immunosuppressive therapy with cyclosporin A.

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The aim of this prospective study was to determine the efficiency of the Gore Bio-A synthetic plug in the treatment of anal fistulas. Methods: A synthetic bioabsorbable anal fistula plug was implanted in 60 patients. All fistulas were transsphincteric and cryptoglandular in origin. Results: The healing rate after 1 year of follow-up was 52 % (31 out of 60 patients). No patient was lost to follow-up. The treatment had no effect on the incontinence score. The plug dislodgement rate was 10 % (6 out of 60 patients). Thirty-four per cent of the patients (16 out of 47) required reoperation. The average operating time was 32 ± 10.2 min, and the average length of hospital stay was 3.3 ± 1.8 days. Conclusions: Synthetic plugs may be an alternative to bioprosthetic fistula plugs in the treatment of transsphincteric anal fistulas. This method might have better success rates than treatment with bioprosthetic fistula plugs. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This latest study on in vivo transdermal drug delivery by using opto-thermal radiometry and a capacitance-based fingerprint sensor is presented. A small amount of solvent was applied on the test sites of a volar forearm for a few minutes; opto-thermal measurements and fingerprint sensor measurements were performed both before the solvent application and periodically after. The results showed that, by selecting different detection wavelengths, opto-thermal radiometry could give the information either on the water concentration within skin or the solvent concentration within skin. The capacitance-based fingerprint sensor could clearly visualize solvent penetration through in vivo human skin, as it generated dynamic two-dimensional (2D) images of solvent distribution within skin, and combining with tape stripping, it was also possible to get solvent 3D depth profiles within skin. The correlation between opto-thermal transient emission radiometry and fingerprint sensor measurements was also evaluated. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In order to identify acute myeloid leukemia (AML) CD34+-specific gene expression profiles, mononuclear cells from AML patients (n=46) were sorted into CD34+ and CD34− subfractions, and genome-wide expression analysis was performed using Illumina BeadChip Arrays. AML CD34+ and CD34− gene expression was compared with a large group of normal CD34+ bone marrow (BM) cells (n=31). Unsupervised hierarchical clustering analysis showed that CD34+ AML samples belonged to a distinct cluster compared with normal BM and that in 61% of the cases the AML CD34+ transcriptome did not cluster together with the paired CD34− transcriptome. The top 50 of AML CD34+-specific genes was selected by comparing the AML CD34+ transcriptome with the AML CD34− and CD34+ normal BM transcriptomes. Interestingly, for three of these genes, that is, ankyrin repeat domain 28 (ANKRD28), guanine nucleotide binding protein, alpha 15 (GNA15) and UDP-glucose pyrophosphorylase 2 (UGP2), a high transcript level was associated with a significant poorer overall survival (OS) in two independent cohorts (n=163 and n=218) of normal karyotype AML. Importantly, the prognostic value of the continuous transcript levels of ANKRD28 (OS hazard ratio (HR): 1.32, P=0.008), GNA15 (OS HR: 1.22, P=0.033) and UGP2 (OS HR: 1.86, P=0.009) was shown to be independent from the well-known risk factors FLT3-ITD, NPM1c+ and CEBPA mutation status. [ABSTRACT FROM AUTHOR]

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chronic periaortitis is thought to result from an autoallergic reaction to oxidized low-density lipoprotein (OxLDL). No data exist on lipid profile and atherosclerotic biomarkers. We investigated circulating levels of OxLDL and of anti-OxLDL (aOxLDL) antibodies in patients with chronic periaortitis using the cross-sectional case-control study on 20 patients with chronic periaortitis. Patients were compared to 20 age- and sex-matched controls. aOxLDL antibodies were measured by ELISA and expressed as mean optical density values at 450 nm from duplicate measurements (OD). aOxLDL antibody titers (median [interquartile range]) did not differ significantly between patients and controls (aOxLDL-IgM: 0.70 [0.24-1.08] vs. 0.54 [0.25-0.73] OD; aOxLDL-IgG: 0.59 [0.38-0.75] vs. 0.41[0.33-0.63]OD). Female patients had higher aOxLDL-IgM levels than male patients (1.02 [0.46-1.38] vs. 0.29 [0.22-0.84] OD; P = 0.05). aOxLDL-IgM titers were lower in patients with cardiovascular disease (CVD) than in patients without CVD (0.22 [0.16-0.37] vs. 0.92 [0.70-1.30] OD; P = 0.003) and correlated positively with HDL-cholesterol ( r = 0.47, 95% CI 0.02-0.69; P = 0.03) and inversely with diastolic blood pressure ( r = −0.46, 95% CI −0.75 to −0.01; P = 0.03) and OxLDL/apoB ratio ( r = −0.41, 95% CI −0.73 to 0.04; P = 0.06). No differences or associations were found between aOxLDL-IgG titers and other variables between or within patients and/or controls. In patients OxLDL levels correlated with smoking pack-years ( r = 0.58, 95% CI 0.17-0.81; P = 0.007). Data suggest a differing innate immune response to OxLDL in patients with chronic periaortitis compared to controls. Whether this response is causally related to chronic periaortitis development remains to be clarified. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is associated with moderate decrements in cognitive functioning, mainly in verbal memory, information-processing speed and executive functions. How this cognitive profile evolves over time is uncertain. The present study aims to provide detailed information on the evolution of cognitive decrements in type 2 diabetes over time. Sixty-eight patients with type 2 diabetes and 38 controls matched for age, sex and estimated IQ performed an elaborate neuropsychological examination in 2002–2004 and again in 2006–2008, including 11 tasks covering five cognitive domains. Vascular and metabolic determinants were recorded. Data were analysed with repeated measures analysis of variance, including main effects for group, time and the group × time interaction. Patients with type 2 diabetes showed moderate decrements in information-processing speed (mean difference in z scores [95% CI] −0.37 [−0.69, −0.05]) and attention and executive functions (−0.25 [−0.49, −0.01]) compared with controls at both the baseline and the 4 year follow-up examination. After 4 years both groups showed a decline in abstract reasoning (−0.16 [−0.30, −0.02]) and attention and executive functioning (−0.29 [−0.40, −0.17]), but there was no evidence for accelerated cognitive decline in the patients with type 2 diabetes as compared with controls (all p > 0.05). In non-demented patients with type 2 diabetes, cognitive decrements are moderate in size and cognitive decline over 4 years is largely within the range of what can be viewed in normal ageing. Apparently, diabetes-related cognitive changes develop slowly over a prolonged period of time. [ABSTRACT FROM AUTHOR]

A laboratory test and several geophysical tests conducted in the last decades of the 20th century suggested deviations from the inverse square distance dependence of Newton’s law of gravity. While further work has failed to substantiate these results, renewed interest in inverse square law tests of increased sensitivity has been stimulated by a wide range of new theoretical ideas. Of particular interest are tests at submillimeter ranges, which could reveal the existence of compact new dimensions accessible only to gravity. This paper reviews the current status of inverse square law tests, with emphasis on present and proposed experimental techniques. [ABSTRACT FROM AUTHOR]

The present work involved the preparation and characterization of SiC–Al composites containing kaolin concentrations varying from 10 to 50% in substitution of the major SiC phase. Ceramic preforms were produced, controlling the granulometric fraction of SiC/kaolin. After sintering at 1100 °C, these preforms were highly porous. XRD analyses revealed the existence of quartz and SiC phase. During the infiltration process, the molten aluminum reacted preferentially with the quartz and with other aluminosilicates in the preforms, reducing them and precipitating alumina and silica in the microstructure, which also showed excess aluminum that did not react in the process. The silica and silicates of the preform, by reacting preferentially with the aluminum, preventing the formation of Al4C3 phase. The SiC–kaolin–Al composites developed here can be used in applications that require high flexural strength (240–300 MPa), low density, and surface hardness of 180–380 kgf/mm2. [ABSTRACT FROM AUTHOR]

Underlying mechanisms for decreased cognitive functioning in patients with type 2 diabetes are unclear. In the general population, cerebral hypoperfusion is a risk factor for cognitive dysfunction and dementia. Reduced cerebral perfusion may account for cognitive impairments in diabetic patients relative to controls. A total of 98 patients with type 2 diabetes and 47 control participants underwent neuropsychological evaluation. Total cerebral blood flow (CBF) was assessed non-invasively by measuring the volume flow in the internal carotid arteries and basilar artery with two-dimensional phase–contrast magnetic resonance angiography. Relative total CBF, a measure of mean total cerebral perfusion, was obtained by expressing total CBF per 100 ml brain parenchyma volume. Patients with type 2 diabetes performed worse on neuropsychological tests ( p < 0.05). Total CBF per 100 ml brain parenchyma volume did not differ between participants with and without diabetes (difference −2.3 ml min−1 100 ml−1; 95% CI −6.0, 1.3). In the entire group, total CBF per 100 ml brain parenchyma volume was positively associated with cognitive functioning (0.09 SD increase in composite z score per 10 ml min−1 100 ml−1 increase in relative total CBF). This association was not affected by type 2 diabetes. Although total CBF per 100 ml brain parenchyma volume was associated with cognitive functioning, it did not explain cognitive impairments in patients with type 2 diabetes relative to controls. [ABSTRACT FROM AUTHOR]

This study is related to research on informative physicochemical indicators for zoning of contaminated territories. The digital field of the radioactive 137Cs contamination in the southern branch of the eastern Chernobyl radioactive trace is studied. The use of fractal analysis based on a technique developed earlier by the authors is proposed for zoning this territory. A brief geomorphologic characterization of the surveyed territory is presented and the requirements for an aerial gamma radiation survey, the processing of data, and the calculation of the fractal dimension are described. Special studies are devoted to the sensitivity of fractal dimension values to the use of different data processing methods. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. [ABSTRACT FROM AUTHOR]

Aims/hypothesis Diabetes mellitus is a risk factor for the development of cognitive impairment and dementia in the general population up to 75 years of age. As part of the Leiden 85-plus Study we studied the effects of diabetes on cognition in the oldest old. Subjects and methods The Leiden 85-plus Study is a prospective population-based study of 599 persons from age 85 onward. Cognitive function was assessed each year from ages 85 to 90 by means of four neuropsychological tests. The presence of diabetes and vascular disease was recorded at baseline, HbA1c was assessed by means of a blood sample at ages 85 and 90. The cross-sectional and prospective associations between diabetes and cognitive function were analysed with linear mixed models, adjusted for sex and level of education. Results At age 85, diabetes was associated with a lower level of cognitive functioning on the Letter Digit Coding test and the Stroop Test. Diabetes was not associated with accelerated cognitive decline during follow-up. Within the group of diabetic patients, macrovascular disease was the most important determinant of cognitive dysfunction. Conclusions/interpretation The association between diabetes and accelerated cognitive decline, which has been documented previously in patients up to 75 years of age, may be less evident after age 85. This suggests that the damage occurs in previous years and that therapies aimed at preventing cognitive decline and dementia should focus on the younger old. [ABSTRACT FROM AUTHOR]

The estimation of probability densities of variables described by stochastic differential equations has long been done using forward time estimators, which rely on the generation of forward in time realizations of the model. Recently, an estimator based on the combination of forward and reverse time estimators has been developed. This estimator has a higher order of convergence than the classical one. In this article, we explore the new estimator and compare the forward and forward–reverse estimators by applying them to a biochemical oxygen demand model. Finally, we show that the computational efficiency of the forward–reverse estimator is superior to the classical one, and discuss the algorithmic aspects of the estimator. [ABSTRACT FROM AUTHOR]

Chromosomal rearrangements involving 3q26 either due to inversion or translocation with various partner chromosomes are a recurrent finding in malignant myeloid disorders. Typically, these chromosome aberrations contribute to ectopic expression of or to the formation of fusion genes involving the EVI1 proto-oncogene. Chromosomal translocations involving the short arm of chromosome 2 (p15-p23) and the distal part of the long arm of chromosome 3 (q26-q27) are a rare but recurrent finding in patients with myeloid malignancies, and are assumed to be part of this spectrum of disorders. Thus far, however, these translocations have been poorly studied. Here, we present 21 new cases with myelodysplasia, acute myeloid leukemia or CML in blast crisis, which upon karyotyping showed the presence of a t(2;3). Furthermore, an extensive literature review disclosed 29 additional cases. Morphological, clinical and cytogenetic assessment revealed the typical hallmarks of 3q26/EVI1 rearrangements, that is, trilineage dysplasia and dysmegakaryopoiesis, poor prognosis and additional monosomy 7. Molecular cytogenetic analysis and PCR in selected samples indicated that in most cases the translocation indeed targets the EVI1 locus. Mapping of the chromosome 2 breakpoints confirmed the initially suspected cytogenetic breakpoint heterogeneity at the 2p arm.Leukemia (2004) 18, 1108-1114. doi:10.1038/sj.leu.2403346 Published online 15 April 2004 [ABSTRACT FROM AUTHOR]

Reports on the results of the Berlin-Franfurt-Munster (BFM)-oriented treatment of children with acute lymphoblastic leukemia without cranial irradiation and treatmetn reduction for standard risk patients. Prognostic factor analysis; Learning effect.

The multidrug resistance proteins (MRPs) MRP1, MRP2, MRP3, MRP5 and P-glycoprotein (P-gp) act in concert with each other to give a net resultant pump function in acute myeloid leukemia (AML). The aim of the present study was to analyze the activity of these proteins, which might be upregulated at relapse as compared with de novo AML due to clonal selection. The mRNA expression and activity of P-gp and the MRPs were determined with RT-PCR and flow cytometry, in conjunction with phenotype, as measured with the monoclonal antibodies CD34, CD38 and CD33, in 30 paired samples of de novo and relapsed AML. P-gp and MRP activity varied strongly between the cases (rhodamine 123 efflux-blocking by PSC833: 5.4+/-7.7, and carboxyfluorescein efflux-blocking by MK-571: 4.3+/-6.7, n = 60). P-gp and MRP activity were increased in 23% and 40% of the relapse samples, and decreased in 30% and 20% of the relapse samples, respectively (as defined by a difference of >2 x standard deviation of the assays). Up- or downregulation of mRNA expression was observed for MDR1 (40%), MRP1 (20%), MRP2 (15%), MRP3 (30%), and MRP5 (5%). Phenotyping demonstrated a more mature phenotype in 23% of the relapsed AML cases, and a more immature phenotype in 23% of the relapses, which was independent of the karyotypic changes that were observed in 50% of the studied cases. P-gp and MRP activity correlated with the phenotypic changes, with higher P-gp and MRP activities in less mature cells (r = -0.66, P < 0.001 and r = -0.31, P = 0.02, n = 58). In conclusion, this study shows that P-gp and MRP activity are not consistently upregulated in relapsed AML. However, P-gp and MRP activities were correlated with the maturation stage as defined by immune phenotype, which was observed to be different in 46% of the relapses. [ABSTRACT FROM AUTHOR]

Our retrospective karyotype review revealed two rare recurrent translocations affecting ETV6 (TEL): t(7;12)(q36;p13) and t(7;12)(q32;p13). Five patients with a t(7;12) were from a group of 125 successfully karyotyped pediatric patients enrolled in consecutive clinical AML trials of the Dutch Childhood Leukemia Study Group over a period of 7 years. During a search of available cytogenetic databases, we found 7q and 12p abnormalities in two additional Dutch patients and in three participants in Pediatric Oncology Group trials. A del(12p) had been initially identified in four of these patients and re-examination of the original karyograms revealed a t(7;12)(q36;p13) in two instances and a probable t(7;12) in the other two. FISH confirmed the presence of a t(7;12)(q36;p13) in the latter. Most (n = 7) also had trisomy 19. The t(7;12)(q36;p13) (n = 9) was more common than the t(7;12)(q32;p13) (n = 1). These subtle translocations were found only in children 18 months of age or younger. A literature search revealed that the t(7;12) with break-points at 7q31-q36 and 12p12-p13 had been reported in six children with myeloid disorders and in two with acute lymphoblastic leukemia; all were 12 months of age or younger. Only two of the 17 for whom survival data were available, were alive after at least 22 months of continuous complete remission. Our findings suggest that ETV6 rearrangements due to a t(7;12) may play an adverse role in myeloid disorders in children 18 months of age or younger. Therefore, children in this age group with myeloid disorders should be screened for both MLL and ETV6 rearrangements. [ABSTRACT FROM AUTHOR]

We collected peripheral blood stem cells (PBSC) in 19 early chronic phase CML patients following each of two consecutive cycles of intensive chemotherapy (CT) to evaluate whether an additional cycle of CT would increase Philadelphia (Ph)-negativity of the PBSC harvest. Autologous SCT (autoSCT) was performed if a major cytogenetic response (MCR) of the PBSC harvest was obtained. CT consisted of cytarabine 200 mg/ m2/day (days 1–7)/idarubicin 12 mg/m2/day (days 1–2) (cycle one) and cytarabine 2000 mg/m2/day (days 1–6)/amsacrine 120 mg/m2/day (days 1–3) (cycle two). One patient died of fungal pneumonia after the first cycle. Stem cells were harvested in 18 patients after cycle one and in 16 patients after cycle two. After the first cycle, all patients showed a cytogenetic response of their graft (MCR in eight patients: three complete, five partial), after cycle two, seven patients obtained an MCR (one complete, six partial). Seven patients became eligible for autoSCT. All patients proceeded with IFNα maintenance. Currently, 16 patients are alive. At the latest cytogenetic examination of bone marrow, four patients showed an MCR and four a minor response. In conclusion, although a second cycle of CT may contribute to elimination of leukemia residing in the patient, it appeared to be ineffective in improving the Ph-negativity of the PBSC graft. Bone Marrow Transplantation (2000) 25, 1147–1155. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the presence of inhibitors in urine specimens causing false-negative results in a commercial Chlamydia trachomatis gap-filling ligase chain reaction (Gap-LCR) assay. On testing of urine samples by the Gap-LCR assay and urethral swab specimens by cell culture, 73 (19%) Chlamydia trachomatis positive subjects were detected among 382 men attending a clinic for sexually transmitted diseases. In 56 subjects, the agent was detected in both the urine and the urethral samples, while 309 subjects were negative in both tests. In seven subjects urine samples were Gap-LCR positive (confirmed by a different Gap-LCR assay), but the corresponding urethral swab samples were cell culture-negative. In another ten subjects the urethral swab samples were cell culture positive, but their urine samples were Gap-LCR negative. Subsequent re-analysis of the urine samples including the addition of external Chlamydia trachomatis DNA indicated full or partial inhibition in nine of the cell culture-positive Gap-LCR negative subjects. When urine preparations were freeze-thawed and diluted prior to testing, Chlamydia trachomatis was detected in six of the ten initially Gap-LCR-negative samples. Gap-LCR inhibitors were present in at least nine (12%) of the 73 urine preparations from the Chlamydia trachomatis positive individuals. Identification of samples containing Gap-LCR inhibitors and subsequent processing to reduce the inhibition increased the sensitivity of the test from 86% to 95%. [ABSTRACT FROM AUTHOR]

The current classification of renal-cell adenomas (RCAs) and carcinomas (RCCs) is based on eight basic cell and tumor types (entities) with characteristic morphologic features: (1) RCCs of clear-cell type, (2) RCAs/RCCs of chromophilic-cell type, (3) RCAs/RCCs of chromophobic-cell type, (4) RCCs of duct Bellini type, (5) RCCs of transitional-cell type, (6) RCCs of neuroendocrine type, (7) RCAs of oncocytic type, and (8) RCAs of metanephroid type. Tumors with a proposed histogenesis from the proximal tubule (clear-cell and chromophilic tumors) amount to 85% of renal cancers, whereas tumors with a proposed histogenesis from the connecting tubule/collecting duct (chromophobic-, oncocytic-, and duct Bellini-type tumors) amount to only 11%. The remaining tumor types represent rare entities (less than 1% each). Tumor cytogenetics data confirm the proposed eight morphologic subtypes and give further indications for type-specific tumor development and progression. [ABSTRACT FROM AUTHOR]

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Dissolution profiles of choline theophyllinate tablets as obtained from twelve manufacturers (or distributors) and two choline theophyllinate containing trade mark products (Cholegyl and Dilasmyl) have been studied, using the apparatus for the disintegration test as described in Ph. Eur. ed 1. Tablets have been tested both according to the monograph of 'plain coated tablets' and that of 'enteric coated tablets'. Cholegyl proved to meet the specifications of enteric coated tablets, but several of the generic products did not and (although chemically equivalent) consequently cannot be considered as being biopharmaceutic equivalents to the trade mark product. Large differences were found between the dissolution characteristics of the various generic products. Prescribing is dissuaded. Oplosprofielen van cholinetheofyllinaattabletten (farmaceutische preparaten) zoals deze werden verkregen van twaalf fabrikanten (of leveranciers) en van twee cholinetheofyllinaat bevattende spécialités (Cholegyl en Dilasmyl) werden bestudeerd met behulp van het apparaat voor de desintegratietest ( Ph. Eur. ed. i). De tabletten werden getest volgens de monografie voor 'omhulde tabletten' en die voor 'maagsapresistente tabletten'. Cholegyl bleek te voldoen aan de eisen gesteld aan maagsapresistente tabletten, maar verscheidene van de farmaceutische preparaten ('loco's') voldeden niet aan de gestelde eisen. Deze farmaceutische preparaten (hoewel chemisch equivalent) kunnen derhalve niet worden beschouwd als farmaceutische equivalenten van het genoemde spécialité. Er werden grote verschillen gevonden tussen de oplosprofielen van de diverse farmaceutische preparaten. Het voorschrijven van deze preparaten wordt afgeraden. [ABSTRACT FROM AUTHOR]