Designing an implementation strategy to improve interprofessional shared decision making in sciatica: study protocol of the DISC study

ABSTRACT: BACKGROUND: Sciatica is a common condition worldwide that is characterized by radiating leg pain and regularly caused by a herniated disc with nerve root compression. Sciatica patients with persisting leg pain after six to eight weeks were found to have similar clinical outcomes and associated costs after prolonged conservative treatment or surgery at one year follow-up. Guidelines recommend that the team of professionals involved in sciatica care and patients jointly decide about treatment options, so-called interprofessional shared decision making (SDM). However, there are strong indications that SDM for sciatica patients is not integrated in daily practice. We designed a study aiming to explore the barriers and facilitators associated with the everyday embedding of SDM for sciatica patients. All related relevant professionals and patients are involved to develop a tailored strategy to implement SDM for sciatica patients. METHODS: The study consists of two phases: identification of barriers and facilitators and development of an implementation strategy. First, barriers and facilitators are explored using semi-structured interviews among eight professionals of each (para)medical discipline involved in sciatica care (general practitioners, physical therapists, neurologists, neurosurgeons, and orthopedic surgeons). In addition, three focus groups will be conducted among patients. Second, the identified barriers and facilitators will be ranked using a questionnaire among a representative Dutch sample of 200 GPs, 200 physical therapists, 200 neurologists, all 124 neurosurgeons, 200 orthopedic surgeons, and 100 patients. A tailored team-based implementation strategy will be developed based on the results of the first phase using the principles of intervention mapping and an expert panel. DISCUSSION: Little is known about effective strategies to increase the uptake of SDM. Most implementation strategies only target a single discipline, whereas multiple disciplines are involved in SDM among sciatica patients. The results of this study can be used as an example for implementing SDM in other patient groups receiving multidisciplinary complex care (e.g., elderly) and can be generalized to other countries with similar context, thereby contributing to a worldwide increase SDM in preference sensitive choices.     

In Vivo Measurement of Hippocampal GABAA/cBZR Density with [18F]-Flumazenil PET for the Study of Disease Progression in an Animal Model of Temporal Lobe Epilepsy

Purpose

Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [¹⁸F]-flumazenil ([¹⁸F]-FMZ) PET could be used to non-invasively characterise GABA_A/central benzodiazepine receptor (GABA_A/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE.

Methods

Dynamic [¹⁸F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5–25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [¹⁸F]-FMZ PET scan (3.6–4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [¹⁸F]-FMZ PET data.

Key Findings

The PSM was found to adequately model [¹⁸F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [¹⁸F]-FMZ binding.

Significance

Alterations to hippocampal GABA_A/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [¹⁸F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [¹⁸F]-FMZ PET is useful for investigating the role that changes GABA_A/cBZR density and binding affinity play in the pathogenesis of TLE.     

Recording of focal direct current (DC) changes in the human cerebral cortex using refined non-invasive DC-EEG methodology.

A non-invasive DC electroencephalographic (DC-EEG) method was developed to record and analyze focal low-frequency (<0.1 Hz) DC changes in the human cerebral cortex. A simple repetitive finger-movement task was used as a physiological activation paradigm. DC-EEG amplitudes were recorded using a custom-made DC amplifier with automatic offset correction. A total of 16 standard Ag/AgCl electrodes covered the left primary motor cortex. In three of six subjects, reliable focal motor-related DC-EEG shifts over the hand cortex were monitored. This study demonstrates that refined DC-EEG recording and data analysis procedures allow non-invasive recording of low-frequency and low-amplitude focal cortical changes in humans. An important clinical perspective of this technology is the detection of stroke-associated cortical DC activity.     

Marine, intertidal, freshwater and terrestrial biodiversity of an isolated polar archipelago

Aim We ask how biodiverse is a polar archipelago; how this faunal richness is spread across marine, intertidal, freshwater, terrestrial and parasitic realms; and how fast species are accumulated with increased sampling effort. Location The South Orkney Islands (SOI), Scotia Arc, Southern Ocean. Methods We sampled mega‐ and macro‐benthos at the SOI using scuba in the shallows (0–10 m), a rough bottom otter trawl at 150–250 m and an Agassiz trawl and epibenthic sledge, both at depths of 200, 500, 1000 and 1500 m. We also collated species occurrence at the SOI in each realm from a century of literature and modern databases to investigate patterns in species accumulation, endemism, faunistic affinities and bathymetric ranges in three model taxa. Results Our 11 benthic samples showed that point biodiversity at the SOI is high, yielding 19 classes and 158 species. Nearly a third were new to the area, whilst five species and one genus were new to science. The shallowest samples were richest but had fewest new records of species. Known richness at the SOI is dominated by marine species (1026), of which 821 (83.3%) were benthic. Across all realms, 1224 species (50 classes, 24 phyla) were recorded, of which 43 were intertidal, 64 freshwater, 100 terrestrial, 60 parasitic and 40 birds. Species accumulation curves for model taxa showed new sampling yields about 0.75% per sample of known benthic richness, so by Antarctic standards we know the SOI quite well. Most species are Southern Ocean endemics, but very few occur only at the SOI. Main conclusions This first estimate of faunal biodiversity of a polar locality demonstrates both high richness and high levels of knowledge at the SOI. As suspected but never quantified, the benthos dominates polar biodiversity, at least at the SOI. Marine species there constitute 20% of those recently listed for the entire Southern Ocean, whilst > 60% of terrestrial species are known from Antarctica. The SOI, being one of the better‐studied polar locations, of known age and with a discrete shelf, represent an important source of comparison for biodiversity studies. Our data clearly show that richness and our knowledge of the polar fauna differ across environments.     

Pain Processing after Social Exclusion and Its Relation to Rejection Sensitivity in Borderline Personality Disorder

Objective

There is a general agreement that physical pain serves as an alarm signal for the prevention of and reaction to physical harm. It has recently been hypothesized that “social pain,” as induced by social rejection or abandonment, may rely on comparable, phylogenetically old brain structures. As plausible as this theory may sound, scientific evidence for this idea is sparse. This study therefore attempts to link both types of pain directly. We studied patients with borderline personality disorder (BPD) because BPD is characterized by opposing alterations in physical and social pain; hyposensitivity to physical pain is associated with hypersensitivity to social pain, as indicated by an enhanced rejection sensitivity.

Method

Twenty unmedicated female BPD patients and 20 healthy participants (HC, matched for age and education) played a virtual ball-tossing game (cyberball), with the conditions for exclusion, inclusion, and a control condition with predefined game rules. Each cyberball block was followed by a temperature stimulus (with a subjective pain intensity of 60% in half the cases). The cerebral responses were measured by functional magnetic resonance imaging. The Adult Rejection Sensitivity Questionnaire was used to assess rejection sensitivity.

Results

Higher temperature heat stimuli had to be applied to BPD patients relative to HCs to reach a comparable subjective experience of painfulness in both groups, which suggested a general hyposensitivity to pain in BPD patients. Social exclusion led to a subjectively reported hypersensitivity to physical pain in both groups that was accompanied by an enhanced activation in the anterior insula and the thalamus. In BPD, physical pain processing after exclusion was additionally linked to enhanced posterior insula activation. After inclusion, BPD patients showed reduced amygdala activation during pain in comparison with HC. In BPD patients, higher rejection sensitivity was associated with lower activation differences during pain processing following social exclusion and inclusion in the insula and in the amygdala.

Discussion

Despite the similar behavioral effects in both groups, BPD patients differed from HC in their neural processing of physical pain depending on the preceding social situation. Rejection sensitivity further modulated the impact of social exclusion on neural pain processing in BPD, but not in healthy controls.     

Similar Intracellular Location and Stimulus Reactivity,but Differential Mobility of Tailless (Vicia faba) and Tailed Forisomes (Phaseolus vulgaris) in Intact Sieve Tubes

Sieve elements of legumes contain forisomes—fusiform protein bodies that are responsible for sieve-tube occlusion in response to damage or wound signals. Earlier work described the existence of tailless and tailed forisomes. This study intended to quantify and compare location and position of tailless (in Vicia faba) and tailed (in Phaseolus vulgaris) forisomes inside sieve elements and to assess their reactivity and potential mobility in response to a remote stimulus. Location (distribution within sieve elements) and position (forisome tip contacts) of more than altogether 2000 forisomes were screened in 500 intact plants by laser scanning confocal microscopy in the transmission mode. Furthermore, we studied the dispersion of forisomes at different locations in different positions and their positional behaviour in response to distant heat shocks. Forisome distribution turned out to be species-specific, whereas forisome positions at various locations were largely similar in bushbean (Phaseolus) and broadbean (Vicia). In general, the tailless forisomes had higher dispersion rates in response to heat shocks than the tailed forisomes and forisomes at the downstream (basal) end dispersed more frequently than those at the upstream end (apical). In contrast to the tailless forisomes that only oscillate in response to heat shocks, downstream-located tailed forisomes can cover considerable distances within sieve elements. This displacement was prevented by gentle rubbing of the leaf (priming) before the heat shock. Movement of these forisomes was also prohibited by Latrunculin A, an inhibitor of actin polymerization. The apparently active mobility of tailed forisomes gives credence to the idea that at least the latter forisomes are not free-floating, but connected to other sieve-element structures.     

Reporters for Single-Cell Analysis of Colicin Ib Expression in Salmonella enterica Serovar Typhimurium

Colicins are toxins that mediate interference competition in microbial ecosystems. They serve as a “common good” for the entire producer population but are synthesized by only few members which pay the costs of colicin production. We have previously shown that production of colicin Ib (cib), a group B colicin, confers a competitive advantage to Salmonella enterica serovar Typhimurium (S. Tm) over commensal E. coli strains. Here, we studied regulation of S. Tm cib expression at the single cell level. Comparative analysis of a single- and a multicopy gfp-reporter for the colicin Ib promoter (Pcib) revealed that the latter yielded optimal signal intensity for a diverse range of applications. We further validated this reporter and showed that gfp expression correlated well with colicin Ib (ColIb) protein levels in individual cells. Pcib is negatively controlled by two repressors, LexA and Fur. Only a small fraction of S. Tm expressed cib under non-inducing conditions. We studied Pcib activity in response to mitomycin C mediated DNA damage and iron limitation. Both conditions, if applied individually, lead to an increase in the fraction of GFP⁺ S. Tm, albeit an overall low fluorescence intensity. When both conditions were applied simultaneously, the majority of S. Tm turned GFP⁺ and displayed high fluorescence intensity. Thus, both repressors individually confine cib expression to a subset of the population. Taken together, we provide the first thorough characterization of a conventional gfp-reporter to study regulation of a group B colicin at the single cell level. This reporter will be useful to further investigate the costs and benefits of ColIb production in human pathogenic S. Tm and analyze cib expression under environmental conditions encountered in the mammalian gut.     

Relationships between Religion and Two Forms of Homonegativity in Europe—A Multilevel Analysis of Effects of Believing,Belonging and Religious Practice

This paper examines relationships between religion and two forms of homonegativity across 43 European countries using a bivariate response binary logistic multilevel model. The model analyzes effects of religious believing, belonging and practice on two response variables: a) a moral rejection of homosexuality as a practice and b) intolerance toward homosexuals as a group. The findings indicate that both forms of homonegativity are prevalent in Europe. Traditional doctrinal religious believing (belief in a personal God) is positively related to a moral rejection of homosexuality but to a much lesser extent associated with intolerance toward homosexuals as a group. Members of religious denominations are more likely than non-members to reject homosexuality as morally wrong and to reject homosexuals as neighbors. The analysis found significant differences between denominations that are likely context-dependent. Attendance at religious services is positively related to homonegativity in a majority of countries. The findings vary considerably across countries: Religion is more strongly related to homonegativity in Western than in Eastern Europe. In the post-soviet countries homonegativity appears to be largely a secular phenomenon. National contexts of high religiosity, high perceived government corruption, high income inequality and shortcomings in the implementation of gay rights in the countries’ legislations are statistically related to higher levels of both moralistic homonegativity and intolerance toward homosexuals as a group.     

A Comparison of Some Organizational Characteristics of the Mouse Central Retina and the Human Macula

Mouse models have greatly assisted our understanding of retinal degenerations. However, the mouse retina does not have a macula, leading to the question of whether the mouse is a relevant model for macular degeneration. In the present study, a quantitative comparison between the organization of the central mouse retina and the human macula was made, focusing on some structural characteristics that have been suggested to be important in predisposing the macula to stresses leading to degeneration: photoreceptor density, phagocytic load on the RPE, and the relative thinness of Bruch’s membrane. Light and electron microscopy measurements from retinas of two strains of mice, together with published data on human retinas, were used for calculations and subsequent comparisons. As in the human retina, the central region of the mouse retina possesses a higher photoreceptor cell density and a thinner Bruch’s membrane than in the periphery; however, the magnitudes of these periphery to center gradients are larger in the human. Of potentially greater relevance is the actual photoreceptor cell density, which is much greater in the mouse central retina than in the human macula, underlying a higher phagocytic load for the mouse RPE. Moreover, at eccentricities that correspond to the peripheral half of the human macula, the rod to cone ratio is similar between mouse and human. Hence, with respect to photoreceptor density and phagocytic load of the RPE, the central mouse retina models at least the more peripheral part of the macula, where macular degeneration is often first evident.