Encoding and retrieval of landmark‐related spatial cues during navigation: An fMRI study

To successfully navigate, humans can use different cues from their surroundings. Learning locations in an environment can be supported by parallel subsystems in the hippocampus and the striatum. We used fMRI to look at differences in the use of object‐related spatial cues while 47 participants actively navigated in an open‐field virtual environment. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the removed target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. Participants were informed in blocks about which type of retrieval trial was most likely to occur, thereby modulating expectations of having to rely on a single landmark or on a configuration of landmarks. How the spatial learning systems in the hippocampus and caudate nucleus were involved in these landmark‐based encoding and retrieval processes were investigated. Landmark configurations can create a geometry similar to boundaries in an environment. It was found that the hippocampus was involved in encoding when relying on configurations of landmarks, whereas the caudate nucleus was involved in encoding when relying on single landmarks. This might suggest that the observed hippocampal activation for configurations of objects is linked to a spatial representation observed with environmental boundaries. Retrieval based on configurations of landmarks activated regions associated with the spatial updation of object locations for reorientation. When only a single landmark was available during retrieval, regions associated with updating the location of oneself were activated. There was also evidence that good between‐participant performance was predicted by right hippocampal activation. This study therefore sheds light on how the brain deals with changing demands on spatial processing related purely to landmarks. © 2014 Wiley Periodicals, Inc.     

Diagnostic accuracy of range of motion measurements in early symptomatic hip and/or knee osteoarthritis

Objective

To examine the diagnostic accuracy of hip internal rotation, hip flexion, and knee flexion measurements for the presence of osteophytosis and joint space narrowing (JSN) in early symptomatic osteoarthritis (OA).

Methods

The baseline data for 598 participants of the Cohort Hip & Cohort Knee study were used. Participants underwent a standardized physical and radiographic examination. The active range of motion (ROM) was assessed using a goniometer. The ROM cutoff with the highest discriminative ability for radiographic features of OA was defined by maximizing the sum of the sensitivity and specificity. Several diagnostic measures were calculated to establish the diagnostic accuracy of ROM measurements for the presence of radiographic features.

Results

In patients with hip symptoms, hip internal rotation <24° and flexion <114° were found to be the cutoffs with the highest discriminative ability to distinguish between patients with and without radiographic features. In patients with knee symptoms, knee flexion <132° was the cutoff with the highest discriminative ability. The American College of Rheumatology (ACR) criterion of hip internal rotation <15° increased the probability of the presence of osteophytosis or JSN from 25% to 58%. The diagnostic accuracy of hip and knee flexion measurements was low.

Conclusion

To reduce the number of patients that are not identified by the ACR criterion of hip internal rotation <15°, it is recommended to change the cutoff to internal rotation <24° in patients with early symptomatic OA. Individual hip and knee flexion measurements seem to be of little diagnostic value in early symptomatic OA.     

Activities of several classes of acyclic nucleoside phosphonates against camelpox virus replication in different cell culture models

Camelpox virus (CMLV) is the closest known virus to variola virus. Here we report on the anti-CMLV activities of several acyclic nucleoside phosphonates (ANPs) related to cidofovir [(S)-1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (HPMPC; Vistide)] against two CMLV strains, CML1 and CML14. Cytopathic effect (CPE) reduction assays performed with human embryonic lung fibroblast monolayers revealed the selectivities of the first two classes of ANPs (cHPMPA, HPMPDAP, and HPMPO-DAPy) and of the hexadecyloxyethyl ester of 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine (HDE-cHPMP-5-azaC), belonging to the newly synthesized ANPs, which are HPMP derivatives containing a 5-azacytosine moiety. The inhibitory activities of ANPs against both strains were also confirmed with primary human keratinocyte (PHK) monolayers, despite the higher toxicity of those molecules on growing PHKs. Virus yield assays confirmed the anti-CML1 and anti-CML14 efficacies of the compounds selected for the highest potencies in CPE reduction experiments. Ex vivo studies were performed with a 3-dimensional model of human skin, i.e., organotypic epithelial raft cultures of PHKs. It was ascertained by histological evaluation, as well as by virus yield assays, that CMLV replicated in the human skin equivalent. HPMPC and the newly synthesized ANPs proved to be effective at protecting the epithelial cells against CMLV-induced CPE. Moreover, in contrast to the toxicity on PHK monolayers, signs of toxicity in the differentiated epithelium were seen only at high ANP concentrations. Our results demonstrate that compounds belonging to the newly synthesized ANPs, in addition to cidofovir, represent promising candidates for the treatment of poxvirus infections.     

Psoriasis risk genes of the late cornified envelope-3 group are distinctly expressed compared with genes of other LCE groups

Deletion of the late cornified envelope (LCE) genes LCE3B and LCE3C has recently been identified as a risk factor for psoriasis. Expression of 16 LCE genes of LCE groups 1, 2, 3, 5, and 6 was examined in vivo and in vitro. Quantitative PCR demonstrated that moderate to high LCE expression was largely confined to skin and a few oropharyngeal tissues. Genes of the LCE3 group demonstrated increased expression in lesional psoriatic epidermis and were induced after superficial injury of normal skin, whereas expression of members of other LCE groups was down-regulated under these conditions. Immunohistochemistry and immunoelectron microscopy demonstrated that LCE2 protein expression was restricted to the uppermost granular layer and the stratum corneum. Stimulation of in vitro reconstructed skin by several psoriasis-associated cytokines resulted in induction of LCE3 members. The data suggest that LCE proteins of groups 1, 2, 5, and 6 are involved in normal skin barrier function, whereas LCE3 genes encode proteins involved in barrier repair after injury or inflammation. These findings may provide clues to the mechanistic role of LCE3B/C deletion in psoriasis.     

Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration

In bone tissue regeneration, certain polymer and calcium-phosphate-based composites have been reported to enhance some biological surface phenomena, facilitating osteoinduction. Although the crucial role of inorganic fillers in heterotopic bone formation by such materials has been shown, no reports have been published on the potential effects the polymer phase may have. The present work starts from the assumption that the polymer molecular weight regulates the fluid uptake, which determines the hydrolysis rate and the occurrence of biological surface processes. Here, two composites were prepared by extruding two different molecular weight l/d,l-lactide copolymers with calcium phosphate apatite. The lower molecular weight copolymer allowed larger fluid uptake in the composite thereof, which was correlated with a higher capacity to adsorb proteins in vitro. Further, the large fluid absorption led to a quicker composite degradation that generated rougher surfaces and enhanced ion release. Following intramuscular implantation in sheep, only the composite with the lower molecular weight polymer could induce heterotopic bone formation. Besides influencing the biological potential of composites, the molecular weight also regulated their viscoelastic behaviour under cyclic stresses. The results lead to the conclusion that designing biomaterials with appropriate physico-chemical characteristics is crucial for bone tissue regeneration in mechanical load-bearing sites.     

Pericardial Effusions in Adolescent Girls With Anorexia Nervosa: Clinical Course and Risk Factors

The aim of this study was to evaluate cardiac, biochemical and endocrine differences between female adolescents with anorexia nervosa (AN) with and without pericardial effusions. We studied 128 female adolescents (9.8–17.7 years) with anorexia nervosa (AN) diagnosed according to DSM-IV (American Psychiatric Association, 1994 American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th, Washington, DC: Author.  [Google Scholar]) criteria. They all underwent an echocardiographic evaluation. In 29 patients (22.2 %) a pericardial effusion (ranging between ≥ 0.35–2.5 cm) was noted. None of the patients were clinically symptomatic. After 3 months of refeeding, the effusions disappeared in 18/29 patients while in 7/29 patients a pericardial effusion > 0.3 cm persisted. Risk factors for development of effusions were a BMI ≤ 13,5 kg/m², weight loss ≥ 25% and IGF-1-level ≤100 ng/ml. Pericardial effusions are common in adolescent AN patients. They are mostly asymptomatic not requiring any intervention and spontaneously regress with refeeding. They are more common in the patients with the most significant weight loss.