Ultrastructural analysis of human proximal tubules and cortical interstitium in chronic renal disease (Hydronephrosis)

Summary A systematic ultrastructural analysis of proximal tubule atrophy and cortical interstitial changes was carried out in human chronic nephropathy. The investigation was based on human hydronephrotic kidneys, which had been surgically removed and subsequently perfusion-fixed for light and electron microscopy. Normal kidney tissue, which was derived from nephrectomy specimens with pathological changes confined to part of the kidney or to the renal pelvis, was used for control material. A slight degree of proximal tubule atrophy was characterized by reduction of mitochondria and basolateral membranes, enlargement of large endocytic vacuoles and increased numbers of lysosomes containing lamellar material. In moderate atrophy these changes were further accentuated, and in addition there was an increasing loss of microvilli and a reduction of endocytic invaginations and small endocytic vacuoles. In severe atrophy all types of organelles were sparse and the architecture of the tubule cells greatly simplified. A distinctive feature of atrophic tubules was the presence in the tubule cells of large bundles of actin-like filaments, which were often associated with outpouchings of basal cell parts and basement membrane. The reduction of mitochondria and basolateral cell membranes and the changes of endocytic vacuoles and lysosomes indicate that proximal tubule atrophy also in early stages may be associated with impairment of tubular transport processes. Comparisons with previous observations in various types of experimentally induced tubule cell degeneration and with the ultrastructure of regenerating proximal tubule cells provide some evidence that degenerative changes as well as imperfect regeneration of tubule cells may contribute to the alterations of ultrastructure in tubular atrophy. It is suggested that changes of the cortical interstitium may be of pathogenic importance for the progression of tubular atrophy by altering the spatial relationships between tubules and capillaries.This work was supported by grants from the Danish Medical Research Council (no 12-0528) and from the Research Foundation at the University of Aarhus.     

On the relationship between Lp(a) Iipoprotein, "sinking pre-β-lipoprotein" and inherited hyper-β-lipoproteinaemia

The presence of extra pre-β-lipoprotein bands on lipoprotein electrophoretograms has recently been implicated by different workers as a major risk factor in coronary heart disease. We observed such "sinking pre-β-lipoprotein" in members of three kindreds which were being studied because of hyper-β-lipoproteinaemia with xanthomatosis and coronary heart disease (type IIa hyperlipoproteinaemia). The hyper-β-lipoproteinaemia, Lp(a) antigen and extra lipoprotein band segregated in an autosomal dominant fashion in these families. Electrophoretic and immunologic studies confirmed the identity of "sinking pre-β-lipoprotein" with the Lp(a) lipoprotein. Presence of "sinking pre-β-lipoprotein" reflects high concentration of the Lp(a) lipoprotein. Close genetic linkage between hyper-β-lipoproteinaemia and the Lp trait was excluded.
Thus, the present data speak against linkage as well as association between hyper-β-lipoproteinaemia as it occurs in the three kindreds and the Lp trait. If the possilble association of Lp(d) lipoprotein with coronary heart diease, as suggested by studies of other workers, is confirmed, the data from the present family study may suggest that the majority of cases of coronary heart disease are genetically distinct from hyper-β-lipoproteinaemia of type IIa.     

A Critical Look at Entropy‐Based Gene‐Gene Interaction Measures

Several entropy‐based measures for detecting gene‐gene interaction have been proposed recently. It has been argued that the entropy‐based measures are preferred because entropy can better capture the nonlinear relationships between genotypes and traits, so they can be useful to detect gene‐gene interactions for complex diseases. These suggested measures look reasonable at intuitive level, but so far there has been no detailed characterization of the interactions captured by them. Here we study analytically the properties of some entropy‐based measures for detecting gene‐gene interactions in detail. The relationship between interactions captured by the entropy‐based measures and those of logistic regression models is clarified. In general we find that the entropy‐based measures can suffer from a lack of specificity in terms of target parameters, i.e., they can detect uninteresting signals as interactions. Numerical studies are carried out to confirm theoretical findings.     

Model-based estimation of the attributable fraction for cross-sectional,case–control and cohort studies using the <Emphasis FontCategory="NonProportional">R</Emphasis> package <Emphasis FontCategory="NonProportional">AF</Emphasis>

The attributable fraction (or attributable risk) is a widely used measure that quantifies the public health impact of an exposure on an outcome. Even though the theory for AF estimation is well developed, there has been a lack of up-to-date software implementations. The aim of this article is to present a new R package for AF estimation with binary exposures. The package AF allows for confounder-adjusted estimation of the AF for the three major study designs: cross-sectional, (possibly matched) case–control and cohort. The article is divided into theoretical sections and applied sections. In the theoretical sections we describe how the confounder-adjusted AF is estimated for each specific study design. These sections serve as a brief but self-consistent tutorial in AF estimation. In the applied sections we use real data examples to illustrate how the AF package is used. All datasets in these examples are publicly available and included in the AF package, so readers can easily replicate all analyses.     

Changes in cognitive functioning in sick-listed participants in occupational rehabilitation: A feasibility study

Background: Individuals on long-term sick leave attending occupational rehabilitation often complain about impairments in cognitive functions such as memory and attention. Knowledge of cognitive functioning in these individuals is limited. Such knowledge is clinically relevant for improving occupational rehabilitation programmes.

Objective: The aims of this feasibility study were to assess the methodological design and to investigate changes in memory and attention on participants during occupational rehabilitation.

Methods: Individuals attending occupational rehabilitation (n?=?28) and individuals working full time (n?=?25) matched for age, gender, and education participated. The two groups were administered cognitive tests targeting memory and attention and self-reported questionnaires at pre-test and post-test. Outcome measures were speed and accuracy of responses on the cognitive tests and self-reported work ability, subjective health complaints, and symptoms of depression and anxiety.

Results: In total, 35% of all invited participants agreed to take part and 93% of these also completed the second test. The mean gain scores in the intervention group were significantly higher than in the control group in response latency on simple and choice reaction time and errors in spatial working memory.

Conclusion: The results of this study indicate that the motivation of participants to complete testing was high. Improvements in memory and attention were evident in rehabilitation participants indicating that rehabilitation may have an effect on cognitive functions.     

New Reactive Block Copolymers as Stabilizers in Emulsion Polymerization

The synthesis and application of partly sulfonated polybutadiene‐block‐poly(ethylene glycol) copolymers as a new class of stabilizers for emulsion polymerizations is reported. These stabilizers combine all known stabilization mechanisms – electrostatic, steric, and electrosteric – together with the ability to participate in radical polymerization in a single molecule. It was found that the kind of initiator has a strong influence on the latex properties. Due to the polyelectrolyte nature of the new stabilizers, nonionic water‐soluble poly(ethylene glycol)‐azo‐initiators lead to smaller particles and less coagulum compared to water‐soluble ionic initiators. The investigations surprisingly revealed that the poly(ethylene glycol)‐azo‐initiators accumulate in the small‐particle‐size fraction due to side reactions leading to their incorporation. The efficiency of the new stabilizers in a radical emulsion polymerization of styrene is highest if the degree of sulfonation is between 20 and 40%. Compared to low molecular weight stabilizers like sodium dodecylsulfate, the reactive block copolymer stabilizers are much more efficient especially at stabilizer concentrations below 0.1% relative to the mass of monomer. The almost complete covalent binding of the reactive polymeric stabilizers to the particles is proved by a combination of ultrafiltration, elemental analysis, GPC, and FT‐IR investigations.     

Identification of Post-Traumatic Stress Disorder in Individuals with Autism Spectrum Disorder and Intellectual Disability: A Systematic Review

Introduction: autism spectrum disorder (ASD) and intellectual disability (ID) seem to influence the risk of and vulnerability to exposure to trauma and adverse events. While assessment of a psychiatric disorder in ASD and ID generally is challenging, identification of post-traumatic stress disorder (PTSD) seems particularly so, and knowledge does not seem easily accessible. Methods: This article provides a systematic review of studies describing trauma reactions in individuals with both ASD and ID, including studies involving any single case with the combination of ASD, ID, and PTSD. To systematically explore PTSD symptom presentation in the group, all reported symptoms from studies were assigned by DSM-5 criteria. Results: Eighteen studies met the inclusion criteria, eight group studies and 10 case studies. Assessment methodology in studies varied, as did the format of symptom report. DSM-5 criteria provided a useful framework for integrating findings across studies, indicating that PTSD may be identified in individuals with ASD and ID. However, symptoms involving alterations in arousal and negative alterations in thought and behavior seem more easily identified than symptoms of reexperiencing and avoidance. Conclusions: There is an urgent need to identify behavioral equivalents to PTSD symptoms in this group, making it possible to identify warning signs of trauma and abuse even if such incidents are not known to family or professional carers.     

A duplication in 1q21.3 in a family with early onset and childhood absence epilepsy

Early onset absence epilepsy (EOAE) starting before the age of 4 years constitutes a rare subgroup of the idiopathic generalized epilepsies (IGEs). A strong genetic component in IGE has been suggested by twin and family studies. We describe a boy with absence seizures starting at the age of 9 months whose parents both had childhood absence epilepsy. A 192-kb duplication in 1q21.3 was identified in the proband and his father, encompassing the gene CHRNB2 coding for the β-2 subunit of the nicotinic acetylcholine receptor and the gene ADAR coding for adenosine deaminase, an enzyme responsible for RNA editing. Both are candidate genes for seizure disorders. The duplication was not identified in 191 independent IGE patients (93 EOAE; 98 classical IGE) or in 1,157 population controls.