Prevalence of dental alterations in patients under bisphosphonates therapy: a systematic review

Oral and Maxillofacial Surgery - This systematic review aimed to estimate the prevalence and describe dentoalveolar lesions associated with bisphosphonates therapy. A systematic review of the...     

Association of biallelic RFC1 expansion with early-onset Parkinson's disease

Background and Purpose

The biallelic repeat expansion (AAGGG)_exp in the replication factor C subunit 1 gene (RFC1) is a frequent cause of cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) as well as late-onset ataxia. The clinical spectrum of RFC1 disease has expanded since the first identification of biallelic (AAGGG)_exp and includes now various nonclassical phenotypes. Biallelic (AAGGG)_exp in RFC1 in patients with clinically confirmed Parkinson's disease (PD) has recently been found.

Methods

A nationwide cohort of 273 Finnish patients with early-onset PD was examined for the biallelic intronic expansion in RFC1. The expansion (AAGGG)_exp was first screened using extra long polymerase chain reactions (Extra Large-PCRs) and flanking multiplex PCR. The presence of biallelic (AAGGG)_exp was then confirmed by repeat-primed PCR and, finally, the repeat length was determined by long-read sequencing.

Results

Three patients were found with the biallelic (AAGGG)_exp in RFC1 giving a frequency of 1.10% (0.23%–3.18%; 95% confidence interval). The three patients fulfilled the diagnostic criteria of PD, none of them had ataxia or neuropathy, and only one patient had a mild vestibular dysfunction. The age at onset of PD symptoms was 40–48 years and their disease course had been unremarkable apart from the early onset.

Conclusions

Our results suggest that (AAGGG)_exp in RFC1 is a rare cause of early-onset PD. Other populations should be examined in order to determine whether our findings are specific to the Finnish population.     

Brain activity associated with illusory correlations in animal phobia

Anxiety disorder patients were repeatedly found to overestimate the association between disorder-relevant stimuli and aversive outcomes despite random contingencies. Such an illusory correlation (IC) might play an important role in the return of fear after extinction learning; yet, little is known about how this cognitive bias emerges in the brain. In a functional magnetic resonance imaging study, 18 female patients with spider phobia and 18 healthy controls were exposed to pictures of spiders, mushrooms and puppies followed randomly by either a painful electrical shock or nothing. In advance, both patients and healthy controls expected more shocks after spider pictures. Importantly, only patients with spider phobia continued to overestimate this association after the experiment. The strength of this IC was predicted by increased outcome aversiveness ratings and primary sensory motor cortex activity in response to the shock after spider pictures. Moreover, increased activation of the left dorsolateral prefrontal cortex (dlPFC) to spider pictures predicted the IC. These results support the theory that phobia-relevant stimuli amplify unpleasantness and sensory motor representations of aversive stimuli, which in turn may promote their overestimation. Hyper-activity in dlPFC possibly reflects a pre-occupation of executive resources with phobia-relevant stimuli, thus complicating the accurate monitoring of objective contingencies and the unlearning of fear.     

Arachidonic acid release mediated by OX1 orexin receptors

Background and purpose:

We have previously shown that lipid mediators, produced by phospholipase D and C, are generated in OX₁ orexin receptor signalling with high potency, and presumably mediate some of the physiological responses to orexin. In this study, we investigated whether the ubiquitous phospholipase A₂ (PLA₂) signalling system is also involved in orexin receptor signalling.

Experimental approach:

Recombinant Chinese hamster ovary-K1 cells, expressing human OX₁ receptors, were used as a model system. Arachidonic acid (AA) release was measured from ³H-AA-labelled cells. Ca²⁺ signalling was assessed using single-cell imaging.

Key results:

Orexins strongly stimulated [³H]-AA release (maximally 4.4-fold). Orexin-A was somewhat more potent than orexin-B (pEC₅₀= 8.90 and 8.38 respectively). The concentration–response curves appeared biphasic. The release was fully inhibited by the potent cPLA₂ and iPLA₂ inhibitor, methyl arachidonyl fluorophosphonate, whereas the iPLA₂ inhibitors, R- and S-bromoenol lactone, caused only a partial inhibition. The response was also fully dependent on Ca²⁺ influx, and the inhibitor studies suggested involvement of the receptor-operated influx pathway. The receptor-operated pathway, on the other hand, was partially dependent on PLA₂ activity. The extracellular signal-regulated kinase, but not protein kinase C, were involved in the PLA₂ activation at low orexin concentrations.

Conclusions and implications:

Activation of OX₁ orexin receptors induced a strong, high-potency AA release, possibly via multiple PLA₂ species, and this response may be important for the receptor-operated Ca²⁺ influx. The response coincided with other high-potency lipid messenger responses, and may interact with these signals.     

Kinematische Untersuchungen des muskuloskelettalen Systems

Image-based preoperative planning has become a routine component in surgery on the musculoskeletal system. In joint arthroplasty it is obligatory. Surgeons are increasingly considering new approaches with additional computer-based kinematic examinations that also generate dynamic image analyses. This article describes several of these new examination techniques and discusses their clinical relevance.     

Retrorectus mesh reinforcement of ileostomy site fascial closure: stoma closure and reinforcement (SCAR) trial phase I/II results

Hernia - Loop ileostomy (LI) is commonly employed during colorectal surgeries to reduce the consequences of anastomotic leak. Unfortunately, LI is associated with a 10–30% incisional hernia...