Grey matter volume alterations in CADASIL: a voxel-based morphometry study

CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized

The deep-subsurface sulfate reducer Desulfotomaculum kuznetsovii employs two methanol-degrading pathways

Methanol is generally metabolized through a pathway initiated by a cobalamine-containing methanol methyltransferase by anaerobic methylotrophs (such as methanogens and acetogens), or through oxidation to formaldehyde using a methanol dehydrogenase by aerobes. Methanol is an important substrate in deep-subsurface environments, where thermophilic sulfate-reducing bacteria of the genus Desulfotomaculum have key roles. Here, we study the methanol metabolism of Desulfotomaculum kuznetsovii strain 17T, isolated from a 3000-m deep geothermal water reservoir. We use proteomics to analyze cells grown with methanol and sulfate in the presence and absence of cobalt and vitamin B12. The results indicate the presence of two methanol-degrading pathways in D. kuznetsovii, a cobalt-dependent methanol methyltransferase and a cobalt-independent methanol dehydrogenase, which is further confirmed by stable isotope fractionation. This is the first report of a microorganism utilizing two distinct methanol conversion pathways. We hypothesize that this gives D. kuznetsovii a competitive advantage in its natural environment.Research was funded by grants of the Division of Chemical Sciences (CW-TOP 700.55.343) and Earth and Life Sciences (ALW 819.02.014) of The Netherlands Organisation for Scientific Research (NWO), the European Research Council (ERC grant 323009), and the Gravitation grant (024.002.002) of the Netherlands Ministry of Education, Culture and Scienceinfo:eu-repo/semantics/publishedVersio

Low back pain beliefs are associated to age, location of work, education and pain-related disability in Chinese healthcare, professionals working in China: a cross sectinal survey

Background: Low back pain (LBP) is the leading cause of disability worldwide. Evidence pointing towards a more efficacious model of care using a biopsychosocial approach for LBP management highlights the need to understand the pain-related beliefs of patients and those who treat them. The beliefs held by healthcare professionals (HCPs) are known to influence the treatment advice given to patients and consequently management outcomes. Back pain beliefs are known to be influenced by factors such as culture, education, health literacy, place of work, personal experience of LBP and the sequelae of LBP such as disability. There is currently a knowledge gap among these relationships in non-western countries. The aim of this study was to examine the associations between LBP-related beliefs among Chinese HCPs and characteristics of these HCPs. Methods: A convenience sample of 432 HCPs working in various health settings in Shanghai, China, completed a series of questionnaires assessing their demographic characteristics, LBP status, pain-related disability and their beliefs about their own LBP experience, using the Back beliefs Questionnaire (BBQ) and the Fear Avoidance Beliefs Questionnaire (FABQ).Results: Younger Chinese HCPs (20–29 years) held more negative beliefs and attitudes related to LBP compared to older HCPs (>40years; BBQ mean difference [95% CI]: 2.4 [0.9 - 3.9], p = 0.001). HCPs working outside tertiary hospitals had poorer beliefs concerning the inevitable consequences of LBP (BBQ mean difference [95% CI]: -2.4 [-3.8 - -1.0], p = 0.001). HCPs who experienced LBP had higher level of fear avoidance beliefs when experiencing high LBP-related disability (FABQ-physical mean difference [95% CI]: 2.8 [1.5 - 4.1], p < 0.001; FABQ-work mean difference [95% CI]: 6.2 [4.0 - 8.4], p < 0.001)) and had lower level of fear avoidance beliefs if they had completed postgraduate study(FABQ-physical mean difference [95% CI]: 2.9 [-5.8 - 0.0], p = 0.049).Conclusion: This study suggests that LBP-related beliefs and attitudes among Chinese HCPs are influenced by age, location of work, level of LBP-related disability and education level. Understanding back pain beliefs of Chinese HCPs forms an important foundation for future studies into the condition and its management in China

An extreme magneto-ionic environment associated with the fast radio burst source FRB 121102

Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin(1-3). The only known repeating fast radio burst source(4-6)-FRB 121102-has been localized to a star-forming region in a dwarf galaxy(7-9) at redshift 0.193 and is spatially coincident with a compact, persistent radio source(7,10). The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from + 1.46 x 10(5) radians per square metre to + 1.33 x 10(5) radians per square metre at epochs separated by seven months) and narrow (below 30 microseconds) temporal structure. The large and variable rotation measure demonstrates that FRB 121102 is in an extreme and dynamic magneto-ionic environment, and the short durations of the bursts suggest a neutron star origin. Such large rotation measures have hitherto been observed(11,12) only in the vicinities of massive black holes (larger than about 10,000 solar masses). Indeed, the properties of the persistent radio source are compatible with those of a low-luminosity, accreting massive black hole(10). The bursts may therefore come from a neutron star in such an environment or could be explained by other models, such as a highly magnetized wind nebula(13) or supernova remnant(14) surrounding a young neutron star.</p

Aptamers for pharmaceuticals and their application in environmental analytics

Aptamers are single-stranded DNA or RNA oligonucleotides, which are able to bind with high affinity and specificity to their target. This property is used for a multitude of applications, for instance as molecular recognition elements in biosensors and other assays. Biosensor application of aptamers offers the possibility for fast and easy detection of environmental relevant substances. Pharmaceutical residues, deriving from human or animal medical treatment, are found in surface, ground, and drinking water. At least the whole range of frequently administered drugs can be detected in noticeable concentrations. Biosensors and assays based on aptamers as specific recognition elements are very convenient for this application because aptamer development is possible for toxic targets. Commonly used biological receptors for biosensors like enzymes or antibodies are mostly unavailable for the detection of pharmaceuticals. This review describes the research activities of aptamer and sensor developments for pharmaceutical detection, with focus on environmental applications

Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial

BACKGROUND: Local treatment of the prostate might not only improve local control, but also slow the progression of metastatic disease. We hypothesised that radiotherapy (RT) to the prostate would improve overall survival in men presenting with metastatic prostate cancer (PCa) and that the survival benefit would be greater in men with a lower metastatic burden. METHOD: STAMPEDE is a multi-arm multi-stage platform protocol that included a randomised phase III comparison to test the above hypotheses. Standard-of-care (SOC) was lifelong ADT, with up-front docetaxel permitted from Dec-2015. Stratified randomisation within 12 weeks on ADT allocated pts 1:1 to SOC or SOC+RT. Men allocated to RT received daily (55Gy/20f over 4 weeks) or weekly (36Gy/6f over 6 weeks) RT, started ≤8 weeks after randomisation or completion of docetaxel. The RT schedule was nominated before randomisation. The primary outcome measure was death from any cause; secondary outcome measures included failure-free survival (FFS). Comparison of SOC vs SOC+RT for survival had 90% power at 2.5% 1-sided alpha for hazard ratio (HR) of 0.75, requiring approximately 267 control arm deaths. Analyses used Cox proportional hazards & flexible parametric models, adjusted for stratification factors. A pre-specified subgroup analysis tested the effects of prostate RT by baseline metastatic burden. RESULTS: 2061 men with newly-diagnosed M1 PCa were randomised from Jan 2013 to Sep 2016. Randomised groups were well balanced: median age 68yrs; median PSA 97ng/ml; 18% early docetaxel; metastatic burden: 40% lower metastatic burden, 54% higher metastatic burden, 6% unknown in the group as a whole. Prostate RT improved FFS (HR=0.76, 95%CI 0.68, 0.84; p=3.36x10-7 60 ) but not overall survival (HR=0.92, 95%CI 0.80, 1.06; p=0.266). Pre-specified subgroup analysis showed 62 improved overall survival for prostate RT in 819 men with a lower metastatic burden 63 (HR=0.68, 95%CI 0.52, 0.90; p=0.007) but not in 1120 men with a higher metastatic burden (HR=1.07, 95%CI 0.90, 1.28; p=0.300). RT was well-tolerated during (G3-4 5% SOC+RT) and after treatment (G3-4 <1% SOC, 4% SOC+RT). CONCLUSIONS: Radiotherapy to the prostate did not improve survival for unselected patients with newly-diagnosed metastatic prostate cancer, but, in a pre-specified subgroup analysis, did improve survival in men with a lower metastatic burden. Therefore, prostate radiotherapy should be a standard treatment option for men with oligometastatic disease