Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation to cognitive functioning

BACKGROUND: Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear. AIMS: To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques. METHODS: A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. RESULTS: Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder ( n  = 16, age = 33, 4 females) were lower compared to healthy controls ( n  = 23, age = 24, 7 females; p  = 0.005, d  = 1.06). Stratified analyses showed lower glutamate levels in the caudate ( p  = 0.046, d  = 0.76) and putamen p  = 0.013, d  = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed ( r(30) = 0.49, p  = 0.028), but not with other cognitive domains. CONCLUSIONS: We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Environmental Outlook Overijssel: Air quality, noise load and health

Het gezondheidsrisico van luchtvervuiling en het geluidniveau waar inwoners van de provincie Overijssel aan worden blootgesteld, is gemiddeld genomen lager dan het gemiddelde in Nederland. Dat komt omdat de luchtkwaliteit in de provincie beter is en de geluidbelasting lager dan het Nederlandse gemiddelde. Fijn stof zorgt voor het grootste gezondheidsrisico in de provincie. Als het voorgenomen beleid voor luchtkwaliteit wordt uitgevoerd, zal de luchtkwaliteit in de provincie naar verwachting in de toekomst verbeteren. Dit is in lijn met de ontwikkelingen in de rest van Nederland. Het is niet bekend hoe de geluidbelasting zich ontwikkelt. Dit blijkt uit onderzoek van het RIVM naar de milieukwaliteit in relatie tot gezondheid in de provincie Overijssel. Door de milieukwaliteit in de provincie en het bijbehorende gezondheidsrisico inzichtelijk te maken, wordt duidelijk in welke gebieden mensen wonen met een hoger gezondheidsrisico als gevolg van luchtverontreiniging en geluidbelasting. Dit is belangrijk omdat milieugerelateerde gezondheidsrisico's ook onder de huidige wettelijke grenswaarden voor luchtverontreiniging en geluid optreden. Verder is het van belang om ook naar andere milieufactoren te blijven kijken die gezondheidswinst opleveren, zoals een gezonde leefomgeving. Bronnen in de provincie, zoals provinciaal verkeer en lokale industrie, dragen ongeveer 10 procent bij aan de fijnstofconcentratie. Aan de concentraties roet- en stikstofdioxide, onder andere afkomstig van houtstook en verkeer, dragen de bronnen in de provincie ongeveer een kwart bij. Buitenlandse bronnen, waaronder landbouw en industrie, leveren de grootste bijdrage aan de luchtverontreiniging in Overijssel. De belangrijkste bron van geluidbelasting is het gemeentelijk wegverkeer. Voor de verkenning is berekend wat de concentraties van fijnstof (PM10 en PM2.5), stikstofdioxide en roet in 2016 en 2030 zijn. Ook is de huidige geluidbelasting in de provincie in kaart gebracht. Op basis van de concentratie van PM10 en stikstofdioxide, en de geluidbelasting is het milieugezondheidsrisico berekend.The health risk of air pollution and noise pollution to which residents of the province of Overijssel are exposed is lower than the average for The Netherlands. This is because the air quality is better than average and the yearly noise load lower. Exposure to particulate matter represents the biggest environmental health risk in the province. Air quality is expected to improve in the future, in line with the overall trend in The Netherlands. It is unclear how the yearly noise load will develop. These are the results of RIVM research into the environmental quality and its associated health risk in the province of Overijssel. Determining the environmental quality in the province and its associated health risk shows where people with a higher health risk related to air pollution and yearly noise load live. This is important because environmental health risks also occur below current environmental standards for air pollution and noise. In addition, it is also important to focus on other environmental factors that might benefit health, such as a healthy living environment. Emission sources in the province, such as provincial road traffic and local industry, contribute about 10 percent to the particulate matter concentration. Emission sources in the province contribute about a quarter to the concentrations of elemental carbon and nitrogen dioxide, primarily caused by road traffic and wood burning. Foreign emission sources, such as agriculture and industry, are the main sources of air pollution in Overijssel. The main source of the yearly noise load is municipal road traffic. For this outlook, concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide and elementaral carbon in 2016 and 2030 have been calculated. The yearly noise load in the province has been determined for the year 2016. The environmental health risk was calculated based on the concentration of PM10 and nitrogen dioxide, and the yearly noise load.Provincie Overijsse

Intramedullary nailing of humeral shaft fractures: failure analysis of a single centre series

Intramedullary nailing (IMN) is an accepted technique for the treatment of humeral shaft fractures. Previous studies published concerns over whether this technique had higher complication rates such as nonunion and technical failures compared to plate osteosynthesis. We, therefore, conducted a single centre failure analysis to critically evaluate our results regarding IMN of humeral shaft fractures.status: publishe

MRI and (31)P magnetic resonance spectroscopy hardware for axillary lymph node investigation at 7T

\u3cp\u3ePURPOSE: Neoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high-field (7T) (31) P magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes.\u3c/p\u3e\u3cp\u3eMETHOD: A dual-tuned quadrature coil that is a (31) P (120 MHz) transceiver and a (1) H (300 MHz) receiver was designed using a novel detune circuit. The transceiver/receiver coil in the axilla is used with a fractionated dipole antenna on the back of the subject and the conventional breast coil for transmit.\u3c/p\u3e\u3cp\u3eRESULTS: The novel circuit detuned the (1) H resonance without disturbing the (31) P resonance. In vivo demonstrations included: >80% homogeneous B1 (+) for (1) H over the axilla, identification of a small (3-mm diameter) lymph node, and (31) P MR spectra from a single healthy lymph node. The setup can detect <2 millimolar concentrations of metabolites from a 2-mL voxel.\u3c/p\u3e\u3cp\u3eCONCLUSIONS: The first (31) P MR spectrum from an in vivo lymph node indicates that the presented design may be sufficiently sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of the lymph nodes at 7T is possible through combining lightweight antenna elements with dual-tuned transceiver/receive-only coils.\u3c/p\u3

MRI and (31)P magnetic resonance spectroscopy hardware for axillary lymph node investigation at 7T

\u3cp\u3ePURPOSE: Neoadjuvant treatment response in lymph nodes predicts patient outcome, but existing methods do not track response during therapy accurately. In this study, specialized hardware was used to adapt high-field (7T) (31) P magnetic resonance spectroscopy (MRS), which has been shown to track treatment response in small breast tumors, to monitor axillary lymph nodes.\u3c/p\u3e\u3cp\u3eMETHOD: A dual-tuned quadrature coil that is a (31) P (120 MHz) transceiver and a (1) H (300 MHz) receiver was designed using a novel detune circuit. The transceiver/receiver coil in the axilla is used with a fractionated dipole antenna on the back of the subject and the conventional breast coil for transmit.\u3c/p\u3e\u3cp\u3eRESULTS: The novel circuit detuned the (1) H resonance without disturbing the (31) P resonance. In vivo demonstrations included: >80% homogeneous B1 (+) for (1) H over the axilla, identification of a small (3-mm diameter) lymph node, and (31) P MR spectra from a single healthy lymph node. The setup can detect <2 millimolar concentrations of metabolites from a 2-mL voxel.\u3c/p\u3e\u3cp\u3eCONCLUSIONS: The first (31) P MR spectrum from an in vivo lymph node indicates that the presented design may be sufficiently sensitive to detect metabolic response to neoadjuvant therapy. Multinuclei MRS of the lymph nodes at 7T is possible through combining lightweight antenna elements with dual-tuned transceiver/receive-only coils.\u3c/p\u3

Homogeneous B\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array

\u3cp\u3eTo explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B\u3csub\u3e1\u3c/sub\u3e field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B\u3csub\u3e1\u3c/sub\u3e map, a T\u3csub\u3e1\u3c/sub\u3e-weighted image, and a T\u3csub\u3e2\u3c/sub\u3e-weighted image were acquired to assess B\u3csub\u3e1\u3c/sub\u3e efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR\u3csub\u3e10g\u3c/sub\u3e value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of −11.8 dB, and a maximum inter-element coupling of −14.2 dB. The maximum coupling between the antennas and the receive loops was −18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T\u3csub\u3e1\u3c/sub\u3e-weighted images with a high spatial resolution of 0.7 mm\u3csup\u3e3\u3c/sup\u3e isotropic and T\u3csub\u3e2\u3c/sub\u3e-weighted spin echo images with uniformly weighted contrast.\u3c/p\u3