The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders.

BACKGROUND: Psychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M1 receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M1/4 receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M1 receptor signaling in psychotic disorders. METHODS: Twenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M1 antagonist biperiden, while performing the paired associated learning task. M1 binding potentials (BPND) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using 123I-IDEX single photon emission computed tomography. RESULTS: In the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M1 antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M1 receptor binding during learning, with no association found with M1 receptor binding in the DLPFC. M1 receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase. CONCLUSION: The current study is the first to show differences in M1 receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M1 receptor reserve in temporal-limbic areas

An orbital fistula complicating anaerobic frontal sinusitis and osteomyelitis

A patient is described with an orbital fistula complicating frontal sinusitis and osteomyelitis of the frontal bone. The fistula was excised, but a fortnight later an acute exacerbation occurred. From the discharging pus a Staphylococcus aureus was cultured and from mucosa obtained during surgery a microaerophilic Streptococcus. These findings led to the diagnosis: synergistic bacterial inflammation of the frontal sinus, with osteomyelitis and orbital cellulitis

Empowerment or Engagement? Digital Health Technologies for Mental Healthcare

We argue that while digital health technologies (e.g. artificial intelligence, smartphones, and virtual reality) present significant opportunities for improving the delivery of healthcare, key concepts that are used to evaluate and understand their impact can obscure significant ethical issues related to patient engagement and experience. Specifically, we focus on the concept of empowerment and ask whether it is adequate for addressing some significant ethical concerns that relate to digital health technologies for mental healthcare. We frame these concerns using five key ethical principles for AI ethics (i.e. autonomy, beneficence, non-maleficence, justice, and explicability), which have their roots in the bioethical literature, in order to critically evaluate the role that digital health technologies will have in the future of digital healthcare

Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells

Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it is difficult to study the role of specific cells or matrix elements in an in vivo setting. The aim of this study is to develop an automated technique that can be employed to obtain and analyze local collagen matrix remodeling by single smooth muscle cells. We combined a motorized microscopic setup and time-lapse video microscopy with a new cross-correlation based image analysis algorithm to enable automated recording of cell-induced matrix reorganization. This method rendered 60–90 single cell studies per experiment, for which collagen deformation over time could be automatically derived. Thus, the current setup offers a tool to systematically study different components active in matrix remodeling

BRCA1/2 mutation testing in breast cancer patients: a prospective study of the long-term psychological impact of approach during adjuvant radiotherapy

This study assessed psychological distress during the first year after diagnosis in breast cancer patients approached for genetic counseling at the start of adjuvant radiotherapy and identified those vulnerable to long-term high distress. Of the approached patients some chose to receive a DNA test result (n = 58), some were approached but did not fulfill criteria for referral (n = 118) and some declined counseling and/or testing (n = 44). The comparative group consisted of patients not eligible for genetic counseling (n = 182) and was therefore not approached. Patients actively approached for genetic counseling showed no more long-term distress than patients not eligible for such counseling. There were no differences between the subgroups of approached patients. Predictors for long-term high distress or an increase in distress over time were pre-existing high distress and a low quality of life, having children, and having no family members with breast cancer. It is concluded that breast cancer patients can be systematically screened and approached for genetic counseling during adjuvant radiotherapy without imposing extra psychological burden. Patients vulnerable to long-term high distress already displayed high distress shortly after diagnosis with no influence of their medical treatment on their level of distress at long-term

Detection of emphysema progression in alpha 1-antitrypsin deficiency using CT densitometry; Methodological advances

<p>Abstract</p> <p>Background</p> <p>Computer tomography (CT) densitometry is a potential tool for detecting the progression of emphysema but the optimum methodology is uncertain. The level of inspiration affects reproducibility but the ability to adjust for this variable is facilitated by whole lung scanning methods. However, emphysema is frequently localised to sub-regions of the lung and targeted densitometric sampling may be more informative than whole lung assessment.</p> <p>Methods</p> <p>Emphysema progression over a 2-year interval was assessed in 71 patients (alpha 1-antitrypsin deficiency with PiZ phenotype) with CT densitometry, using the 15^thpercentile point (Perc15) and voxel index (VI) -950 Hounsfield Units (HU) and -910 HU (VI -950 and -910) on whole lung, limited single slices, and apical, central and basal thirds. The relationship between whole lung densitometric progression (ΔCT) and change in CT-derived lung volume (ΔCT_Vol) was characterised, and adjustment for lung volume using statistical modelling was evaluated.</p> <p>Results</p> <p>CT densitometric progression was statistically significant for all methods. ΔCT correlated with ΔCT_Voland linear regression indicated that nearly one half of lung density loss was secondary to apparent hyperinflation. The most accurate measure was obtained using a random coefficient model to adjust for lung volume and the greatest progression was detected by targeted sampling of the middle third of the lung.</p> <p>Conclusion</p> <p>Progressive hyperinflation may contribute significantly to loss of lung density, but volume effects and absolute tissue loss can be identified by statistical modelling. Targeted sampling of the middle lung region using Perc15 appears to be the most robust measure of emphysema progression.</p

Feasibility of MRI-guided large-core-needle biopsy of suspiscious breast lesions at 3 T

The feasibility of large-core-needle magnetic resonance imaging (MRI)-guided breast biopsy at 3 T was assessed. Thirty-one suspicious breast lesions shown only by MRI were detected in 30 patients. Biopsy procedures were performed in a closed-bore 3-T clinical MR system on a dedicated phased-array breast coil with a commercially available add-on stereotactic biopsy device. Tissue sampling was technically successful in 29/31 (94%) lesions. Median lesion size (n = 29) was 9 mm. Histopathological analysis showed 19 benign lesions (66%) and one inconclusive biopsy result (3%). At follow-up of these lesions, 15 lesions showed no malignancy, no information was available in three patients and two lesions turned out to be malignant (one lesion at surgical excision 1 month after biopsy and one lesion at a second biopsy because of a more malignant enhancement curve at 12-months follow-up MRI). Nine biopsy results showed a malignant lesion (31%) which were all surgically removed. No complications occurred. MRI-guided biopsy at 3 T is a safe and effective method for breast biopsy in lesions that are occult on mammography and ultrasound. Follow-up MRI at 6 months after the biopsy should be performed in case of a benign biopsy result

Fine-root turnover rates of European forests revisited: an analysis of data from sequential coring and ingrowth cores

Background and Aims Forest trees directly contribute to carbon cycling in forest soils through the turnover of their fine roots. In this study we aimed to calculate root turnover rates of common European forest tree species and to compare them with most frequently published values. Methods We compiled available European data and applied various turnover rate calculation methods to the resulting database. We used Decision Matrix and Maximum-Minimum formula as suggested in the literature. Results Mean turnover rates obtained by the combination of sequential coring and Decision Matrix were 0.86 yr−1 for Fagus sylvatica and 0.88 yr−1 for Picea abies when maximum biomass data were used for the calculation, and 1.11 yr−1 for both species when mean biomass data were used. Using mean biomass rather than maximum resulted in about 30 % higher values of root turnover. Using the Decision Matrix to calculate turnover rate doubled the rates when compared to the Maximum-Minimum formula. The Decision Matrix, however, makes use of more input information than the Maximum-Minimum formula. Conclusions We propose that calculations using the Decision Matrix with mean biomass give the most reliable estimates of root turnover rates in European forests and should preferentially be used in models and C reporting