Ethnic Differences in Carotid Intima-Media Thickness Between UK Children of Black African-Caribbean and White European Origin.

BACKGROUND AND PURPOSE: UK black African-Caribbean adults have higher risks of stroke than white Europeans and have been shown to have increased carotid intima-media thickness (cIMT). We examined whether corresponding ethnic differences in cIMT were apparent in childhood and, if so, whether these could be explained by ethnic differences in cardiovascular risk markers. METHODS: We conducted a 2-stage survey of 939 children (208 white European, 240 black African-Caribbean, 258 South Asian, 63 other Asian, 170 other ethnicity), who had a cardiovascular risk assessment and measurements of cIMT at mean ages of 9.8 and 10.8 years, respectively. RESULTS: Black African-Caribbean children had a higher cIMT than white Europeans (mean difference, 0.014 mm; 95% CI, 0.008-0.021 mm; P<0.0001). cIMT levels in South Asian and other Asian children were however similar to those of white Europeans. Among all children, cIMT was positively associated with age, systolic and diastolic blood pressure and inversely with combined skinfold thickness and serum triglyceride. Mean triglyceride was lower among black African-Caribbeans than white Europeans; blood pressure and skinfold thickness did not differ appreciably. However, adjustment for these risk factors had little effect on the cIMT difference between black African-Caribbeans and white Europeans. CONCLUSIONS: UK black African-Caribbean children have higher cIMT levels in childhood; the difference is not explained by conventional cardiovascular risk markers. There may be important opportunities for early cardiovascular prevention, particularly in black African-Caribbean children

The Pathway to Detangle a Scrambled Gene

Programmed DNA elimination and reorganization frequently occur during cellular differentiation. Development of the somatic macronucleus in some ciliates presents an extreme case, involving excision of internal eliminated sequences (IESs) that interrupt coding DNA segments (macronuclear destined sequences, MDSs), as well as removal of transposon-like elements and extensive genome fragmentation, leading to 98% genome reduction in Stylonychia lemnae. Approximately 20-30% of the genes are estimated to be scrambled in the germline micronucleus, with coding segment order permuted and present in either orientation on micronuclear chromosomes. Massive genome rearrangements are therefore critical for development.To understand the process of DNA deletion and reorganization during macronuclear development, we examined the population of DNA molecules during assembly of different scrambled genes in two related organisms in a developmental time-course by PCR. The data suggest that removal of conventional IESs usually occurs first, accompanied by a surprising level of error at this step. The complex events of inversion and translocation seem to occur after repair and excision of all conventional IESs and via multiple pathways.This study reveals a temporal order of DNA rearrangements during the processing of a scrambled gene, with simpler events usually preceding more complex ones. The surprising observation of a hidden layer of errors, absent from the mature macronucleus but present during development, also underscores the need for repair or screening of incorrectly-assembled DNA molecules

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Inhibition of IL-34 Unveils Tissue-Selectivity and Is Sufficient to Reduce Microglial Proliferation in a Model of Chronic Neurodegeneration

The proliferation and activation of microglia, the resident macrophages in the brain, is a hallmark of many neurodegenerative diseases such as Alzheimer’s disease (AD) and prion disease. Colony stimulating factor 1 receptor (CSF1R) is critically involved in regulating microglial proliferation, and CSF1R blocking strategies have been recently used to modulate microglia in neurodegenerative diseases. However, CSF1R is broadly expressed by many cell types and the impact of its inhibition on the innate immune system is still unclear. CSF1R can be activated by two independent ligands, CSF-1 and interleukin 34 (IL-34). Recently, it has been reported that microglia development and maintenance depend on IL-34 signaling. In this study, we evaluate the inhibition of IL-34 as a novel strategy to reduce microglial proliferation in the ME7 model of prion disease. Selective inhibition of IL-34 showed no effects on peripheral macrophage populations in healthy mice, avoiding the side effects observed after CSF1R inhibition on the systemic compartment. However, we observed a reduction in microglial proliferation after IL-34 inhibition in prion-diseased mice, indicating that microglia could be more specifically targeted by reducing IL-34. Overall, our results highlight the challenges of targeting the CSF1R/IL34 axis in the systemic and central compartments, important for framing any therapeutic effort to tackle microglia/macrophage numbers during brain disease

Identification of Molecular Pathologies Sufficient to Cause Neuropathic Excitability in Primary Somatosensory Afferents Using Dynamical Systems Theory

Pain caused by nerve injury (i.e. neuropathic pain) is associated with development of neuronal hyperexcitability at several points along the pain pathway. Within primary afferents, numerous injury-induced changes have been identified but it remains unclear which molecular changes are necessary and sufficient to explain cellular hyperexcitability. To investigate this, we built computational models that reproduce the switch from a normal spiking pattern characterized by a single spike at the onset of depolarization to a neuropathic one characterized by repetitive spiking throughout depolarization. Parameter changes that were sufficient to switch the spiking pattern also enabled membrane potential oscillations and bursting, suggesting that all three pathological changes are mechanistically linked. Dynamical analysis confirmed this prediction by showing that excitability changes co-develop when the nonlinear mechanism responsible for spike initiation switches from a quasi-separatrix-crossing to a subcritical Hopf bifurcation. This switch stems from biophysical changes that bias competition between oppositely directed fast- and slow-activating conductances operating at subthreshold potentials. Competition between activation and inactivation of a single conductance can be similarly biased with equivalent consequences for excitability. “Bias” can arise from a multitude of molecular changes occurring alone or in combination; in the latter case, changes can add or offset one another. Thus, our results identify pathological change in the nonlinear interaction between processes affecting spike initiation as the critical determinant of how simple injury-induced changes at the molecular level manifest complex excitability changes at the cellular level. We demonstrate that multiple distinct molecular changes are sufficient to produce neuropathic changes in excitability; however, given that nerve injury elicits numerous molecular changes that may be individually sufficient to alter spike initiation, our results argue that no single molecular change is necessary to produce neuropathic excitability. This deeper understanding of degenerate causal relationships has important implications for how we understand and treat neuropathic pain

Urinary tract infections and antibiotic use in pregnancy - qualitative analysis of online forum content

Background Antibiotics are standard treatment for asymptomatic and symptomatic urinary tract infections (UTIs) in pregnancy. Their overuse, however, can contribute to antimicrobial resistance (AMR) and expose the foetus to drugs that might affect its development. Preventative behaviours are currently the best option to reduce incidences of UTIs and to avoid the use of antibiotics in pregnancy. The aim of this study was to explore women’s experiences of UTIs in pregnancy to develop an understanding of their concerns and to optimise and encourage behaviours that facilitate appropriate use of antibiotics. Methods An online pregnancy forum in the United Kingdom (UK) was used to collect data on women’s discussions of UTIs. A total of 202 individual threads generated by 675 different usernames were selected for analysis. The data was organised using NVivo 11® software and then analysed qualitatively using inductive thematic analysis. Results Women’s perceptions of UTIs and antibiotic use in pregnancy were driven by their pre-natal attachment to the foetus. UTIs were thought to be common and high risk in pregnancy, which meant that antibiotics were viewed as essential in the presence of suspected symptoms. The dominant view about antibiotics was that their use was safe and of little concern in pregnancy. Women reported an emotional reaction to developing a UTI. They coped by seeking information about behaviour change strategies to assist with recovery and through emotional support from the online forum. Conclusions Women face dual risks when they experience UTIs; the risk from the infection and the risk from antibiotic treatment. Pre-natal attachment to the foetus is highlighted in the decision making process. The focus is on the shorter term risk from UTIs while undermining the longer term risks from antibiotic use, especially the risk of AMR. A balanced view needs to be presented, and evidence-based infection prevention strategies should be promoted, to women to ensure appropriate antibiotic use in pregnancy, to address the global challenge of AMR

Galaxy And Mass Assembly (GAMA): stellar mass functions by Hubble type

We present an estimate of the galaxy stellar mass function and its division by morphological type in the local (0.025 < z < 0.06) Universe. Adopting robust morphological classifications as previously presented (Kelvin et al.) for a sample of 3, 727 galaxies taken from the Galaxy And Mass Assembly survey, we define a local volume and stellar mass limited sub-sample of 2, 711 galaxies to a lower stellar mass limit of M = 109.0M_. We confirm that the galaxy stellar mass function is well described by a double Schechter function given by M_ = 1010.64M_, _1 = −0.43, __1 = 4.18 dex−1Mpc−3, _2 = −1.50 and __2 = 0.74 dex−1Mpc−3. The constituent morphological-type stellar mass functions are well sampled above our lower stellar mass limit, excepting the faint little blue spheroid population of galaxies. We find approximately 71+3−4% of the stellar mass in the local Universe is found within spheroid dominated galaxies; ellipticals and S0-Sas. The remaining 29+4−3% falls predominantly within late type disk dominated systems, Sab-Scds and Sd-Irrs. Adopting reasonable bulge-to-total ratios implies that approximately half the stellar mass today resides in spheroidal structures, and half in disk structures. Within this local sample, we find approximate stellar mass proportions for E : S0 Sa : Sab-Scd : Sd-Irr of 34 : 37 : 24 : 5

An assessment of the quality of randomised controlled trials conducted in China

Background: Despite the rapid increase in research in China, little is known about the quality of clinical trials conducted there.Methods: A systematic review and critical appraisal of randomised controlled trials (RCTs) conducted in China and published in 2004 was undertaken to describe their characteristics, assess the quality of their reporting, and where possible, the quality of their conduct. Randomised controlled trials in all disease areas and types of interventions, which took place in China and included Chinese citizens were identified using PubMed and hand searching the Journal Series of the Chinese Medical Association. Quality was assessed against a subset of criteria adapted from the CONSORT statement.Results: Three hundred and seven RCTs were included. One hundred and ninety-nine (64.8%) failed to report methods of randomization and 254 (82.4%) did not mention blinding of either participants or investigators. Reporting of baseline characteristics, primary outcome and length of follow-up was inadequate in a substantial proportion of studies. Fewer than 11% of RCTs mentioned ethical approval and only 18.0% adequately discussed informed consent. However, dropout rates were very favourable with nearly 44% of trials reporting a zero dropout rate.Conclusion: Reporting of RCTs in China requires substantial improvement to meet the targets of the CONSORT statement. The conduct of Chinese RCTs cannot be directly inferred from the standard of reporting; however without good reporting the methods of the trials cannot be clearly ascertained

Galaxy And Mass Assembly (GAMA): stellar mass functions by Hubble type

We present an estimate of the galaxy stellar mass function and its division by morphological type in the local (0.025 < z < 0.06) Universe. Adopting robust morphological classifications as previously presented (Kelvin et al.) for a sample of 3, 727 galaxies taken from the Galaxy And Mass Assembly survey, we define a local volume and stellar mass limited sub-sample of 2, 711 galaxies to a lower stellar mass limit of M = 109.0M_. We confirm that the galaxy stellar mass function is well described by a double Schechter function given by M_ = 1010.64M_, _1 = −0.43, __1 = 4.18 dex−1Mpc−3, _2 = −1.50 and __2 = 0.74 dex−1Mpc−3. The constituent morphological-type stellar mass functions are well sampled above our lower stellar mass limit, excepting the faint little blue spheroid population of galaxies. We find approximately 71+3−4% of the stellar mass in the local Universe is found within spheroid dominated galaxies; ellipticals and S0-Sas. The remaining 29+4−3% falls predominantly within late type disk dominated systems, Sab-Scds and Sd-Irrs. Adopting reasonable bulge-to-total ratios implies that approximately half the stellar mass today resides in spheroidal structures, and half in disk structures. Within this local sample, we find approximate stellar mass proportions for E : S0 Sa : Sab-Scd : Sd-Irr of 34 : 37 : 24 : 5

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region