Hierarchical microchanneled scaffolds modulate multiple tissue-regenerative processes of immune-responses, angiogenesis, and stem cell homing

Recapitulating the in vivo microenvironments of damaged tissues through modulation of the physicochemical properties of scaffolds can boost endogenous regenerative capacity. A series of critical events in tissue healing including immune-responses, angiogenesis, and stem cell homing and differentiation orchestrate to relay the regeneration process. Herein, we report hierarchically structured (‘microchanneled’) 3D printed scaffolds (named ‘μCh’), in contrast to conventional 3D printed scaffolds, induce such cellular responses in a unique way that contributes to accelerated tissue repair and remodeling. The μCh reduced the extracellular trap formation of anchored neutrophils at the very beginning (24 h) of implantation while increasing the number of live cells. Among the macrophages covered the surface of μCh over 7 days a major population polarized toward alternativelly activated phase (M2) which contrasted with control scaffolds where classically activated phase (M1) being dominant. The mesenchymal stem cells (MSCs) recruited to the μCh were significantly more than those to the control, and the event was correlated with the increased level of stem cell homing cytokine, stromal derived factor 1 (SDF1) sequestered to the μCh. Furthermore, the neo-blood vessel formation was more pronounced in the μCh, which was in line with the piling up of angiogenic factor, vascular endothelial growth factor (VEGF) in the μCh. Further assays on the protein sequestration to the μCh revealed that a set of chemokines involved in early pro-inflammatory responses were less found whereas representative adhesive proteins engaged in the cell-matrix interactions were significantly more captured. Ultimately, the fibrous capsule formation on the μCh was reduced with respect to the control, when assessed for up to 21 days, indicating less severe foreign body reaction. The tissue healing and regenerative capacity of the μCh was then confirmed in a critically sized bone model, where those series of events observed are essential to relay bone regeneration. The results over 6 weeks showed that the μCh significantly enhanced the early bone matrix deposition and accelerated bone regeneration. While more in-depth studies remain as to elucidate the underlying mechanisms for each biological event, the molecular, cellular and tissue reactions to the μCh were coherently favorable for the regeneration process of tissues, supporting the engineered scaffolds as potential therapeutic 3D platforms

Declined frontal white matter integrity in Alzheimer’s disease: a diffusion tensor imaging study

INTRODUCTION: Previous studies on structural changes of Alzheimer’s disease (AD) have been focused on grey matter atrophy. There is a resurgence of interests on white matter integrity in this prominently increasing patient population. Diffusion tensor imaging (DTI) provides key information on the microstructural changes beyond macroscopic anatomical imaging by in-vivo tracing molecular diffusion in the brain, and the measured fractional anisotrophy (FA) value may represent axonal integrity of neuronal networks. Data of DTI from AD patients are limited, and the literature is controversial regarding whether the AD process has a greater impact on anterior versus posterior cerebral white matter. METHODS: Eighteen patients with mild AD and 16 age-matched healthy adults were recruited into the study. Demographic features of the two groups were comparable. Data of DTI were collected using a Philips 3.0T MRI scanner. Scan parameters were as follows: B0=800 s/mm2, FOV=224*224*140 mm, resolution=1.75*1.75*2 mm, non-collinear 15 directions was acquired. 3D T1 anatomy was also collected. We processed DTI data with DTI toolbox, and anatomical T1 data with VBM5 toolbox in SPM. Voxel-by-voxel analysis was applied to compare the difference in FA value, and volume of white matter of the normalised brain between the elderly and AD groups. RESULTS: Voxel-based analysis showed no significant difference in white matter volume between the two groups, but FA value was reduced greatly in the left anterior cingulate (−10,37,−3), right anterior cingulate (12,0,28), and left medial frontal lobe (−18,32,−12). Minor reduction was found in other brain regions such as body of the corpus callosum, right midbrain (12,−12,−6), right posterior corpus callosum (8,−44,2), and bilateral, especially right temporal lobe (36,−8,−20), upon right hippocampus. Coordinates (x,y,z) were labelled according to Talairach atlas. CONCLUSION: DTI could be valid and more sensitive than traditional T1 anatomy in detecting microscopic white matter lesions. Our data showed a greater decrement in FA value over the anterior than posterior brain regions, and this decrement was not due to white matter atrophy. Our findings are in line with the retrogenesis hypothesis which predicts reversed demyelination during the process of AD, as the frontal lobe fibres are myelinated relatively late during brain development. These results also support previous findings of our behavioural study that frontal lobe abnormality might be the neural basis for cognitive deficit in AD patients.published_or_final_versionThe 15th Medical Research Conference; Department of Medicine, The University of Hong Kong, Hong Kong, 16 January 2010. In Hong Kong Medical Journal, 2010, v. 16 suppl 1, p. 21, abstract no. 2

Successful outcome of a pregnancy in a woman with advanced cirrhosis due to hepatitis B surface antigenemia, delta super-infection and hepatitis C co-infection: a case report

Pregnancy in women with advanced liver disease is rare. In this paper we described the case of a successful pregnancy in a young woman with advanced cirrhosis due to hepatitis B surface antigenemia, hepatitis delta super-infection and Hepatitis C co-infection. A brief review of the medical literature on pregnancy in women with cirrhosis is also presented

The SPX domain of the yeast low-affinity phosphate transporter Pho90 regulates transport activity

Yeast has two phosphate-uptake systems that complement each other: the high-affinity transporters (Pho84 and Pho89) are active under phosphate starvation, whereas Pho87 and Pho90 are low-affinity transporters that function when phosphate is abundant. Here, we report new regulatory functions of the amino-terminal SPX domain of Pho87 and Pho90. By studying truncated versions of Pho87 and Pho90, we show that the SPX domain limits the phosphate-uptake velocity, suppresses phosphate efflux and affects the regulation of the phosphate signal transduction pathway. Furthermore, split-ubiquitin assays and co-immunoprecipitation suggest that the SPX domain of both Pho90 and Pho87 interacts physically with the regulatory protein Spl2. This work suggests that the SPX domain inhibits low-affinity phosphate transport through a physical interaction with Spl2

Early clinical and laboratory risk factors of intensive care unit requirement during 2004–2008 dengue epidemics in Singapore: a matched case–control study

Background: Dengue infection can result in severe clinical manifestations requiring intensive care. Effective triage is critical for early clinical management to reduce morbidity and mortality. However, there is limited knowledge on early risk factors of intensive care unit (ICU) requirement. This study aims to identify early clinical and laboratory risk factors of ICU requirement at first presentation in hospital and 24 hours prior to ICU requirement. Method: A retrospective 1:4 matched case–control study was performed with 27 dengue patients who required ICU, and 108 dengue patients who did not require ICU from year 2004–2008, matched by year of dengue presentation. Univariate and multivariate conditional logistic regression were performed. Optimal predictive models were generated with statistically significant risk factors identified using stepwise forward and backward elimination method. Results: ICU dengue patients were significantly older (P=0.003) and had diabetes (P=0.031), compared with non-ICU dengue patients. There were seven deaths among ICU patients at median seven days post fever. At first presentation, the WHO 2009 classification of dengue severity was significantly associated (P<0.001) with ICU, but not the WHO 1997 classification. Early clinical risk factors at presentation associated with ICU requirement were hematocrit change ≥20% concurrent with platelet <50 K [95% confidence-interval (CI)=2.46-30.53], hypoproteinemia (95% CI=1.09-19.74), hypotension (95% CI=1.83-31.79) and severe organ involvement (95% CI=3.30-331). Early laboratory risk factors at presentation were neutrophil proportion (95% CI=1.04-1.17), serum urea (95% CI=1.02-1.56) and alanine aminotransferase level (95% CI=1.001-1.06). This predictive model has sensitivity and specificity up to 88%. Early laboratory risk factors at 24 hours prior to ICU were lymphocyte (95% CI=1.03-1.38) and monocyte proportions (95% CI=1.02-1.78), pulse rate (95% CI=1.002-1.14) and blood pressure (95% CI=0.92-0.996). This predictive model has sensitivity and specificity up to 88.9% and 78%, respectively. Conclusions: This is the first matched case–control study, to our best knowledge, that identified early clinical and laboratory risk factors of ICU requirement during hospitalization. These factors suggested differential pathophysiological background of dengue patients as early as first presentation prior to ICU requirement, which may reflect the pathogenesis of dengue severity. These risk models may facilitate clinicians in triage of patients, after validating in larger independent studies.Published versio

The expected performance of stellar parametrization with Gaia spectrophotometry

Gaia will obtain astrometry and spectrophotometry for essentially all sources in the sky down to a broad band magnitude limit of G=20, an expected yield of 10^9 stars. Its main scientific objective is to reveal the formation and evolution of our Galaxy through chemo-dynamical analysis. In addition to inferring positions, parallaxes and proper motions from the astrometry, we must also infer the astrophysical parameters of the stars from the spectrophotometry, the BP/RP spectrum. Here we investigate the performance of three different algorithms (SVM, ILIUM, Aeneas) for estimating the effective temperature, line-of-sight interstellar extinction, metallicity and surface gravity of A-M stars over a wide range of these parameters and over the full magnitude range Gaia will observe (G=6-20mag). One of the algorithms, Aeneas, infers the posterior probability density function over all parameters, and can optionally take into account the parallax and the Hertzsprung-Russell diagram to improve the estimates. For all algorithms the accuracy of estimation depends on G and on the value of the parameters themselves, so a broad summary of performance is only approximate. For stars at G=15 with less than two magnitudes extinction, we expect to be able to estimate Teff to within 1%, logg to 0.1-0.2dex, and [Fe/H] (for FGKM stars) to 0.1-0.2dex, just using the BP/RP spectrum (mean absolute error statistics are quoted). Performance degrades at larger extinctions, but not always by a large amount. Extinction can be estimated to an accuracy of 0.05-0.2mag for stars across the full parameter range with a priori unknown extinction between 0 and 10mag. Performance degrades at fainter magnitudes, but even at G=19 we can estimate logg to better than 0.2dex for all spectral types, and [Fe/H] to within 0.35dex for FGKM stars, for extinctions below 1mag.Comment: MNRAS, in press. Minor corrections made in v

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

Non-conformal Hydrodynamics in Einstein-dilaton Theory

In the Einestein-dilaton theory with a Liouville potential parameterized by $\eta$, we find a Schwarzschild-type black hole solution. This black hole solution, whose asymptotic geometry is described by the warped metric, is thermodynamically stable only for $0 \le \eta < 2$. Applying the gauge/gravity duality, we find that the dual gauge theory represents a non-conformal thermal system with the equation of state depending on $\eta$. After turning on the bulk vector fluctuations with and without a dilaton coupling, we calculate the charge diffusion constant, which indicates that the life time of the quasi normal mode decreases with $\eta$. Interestingly, the vector fluctuation with the dilaton coupling shows that the DC conductivity increases with temperature, a feature commonly found in electrolytes.Comment: 27 pages and 2 figures, published in JHE

Synergistic effects of longitudinal amyloid and vascular changes on lobar microbleeds

OBJECTIVE: To determine whether amyloid and hypertensive cerebral small vessel disease (hCSVD) changes synergistically affect the progression of lobar microbleeds in patients with subcortical vascular mild cognitive impairment (svMCI). METHODS: Among 72 patients with svMCI who underwent brain MRI and [11C] Pittsburgh compound B (PiB)–PET, 52 (72.2%) completed the third year of follow-up. These patients were evaluated by annual neuropsychological testing, brain MRI, and follow-up PiB-PET. RESULTS: Over 3 years, 31 of 52 patients (59.6%) had incident cerebral microbleeds (CMBs) in the lobar and deep regions. Both baseline and longitudinal changes in lacune numbers were associated with increased numbers of lobar and deep microbleeds, while baseline and longitudinal changes in PiB uptake ratio were associated only with the progression of lobar microbleeds, especially in the temporal, parietal, and occipital areas. Regional white matter hyperintensity severity was also associated with regional lobar CMBs in the parietal and occipital regions. There were interactive effects between baseline and longitudinal lacune number and PiB retention on lobar microbleed progression. Increased lobar, but not deep, CMBs were associated with decreased scores in the digit span backward task and Rey-Osterrieth Complex Figure Test. CONCLUSIONS: Our findings suggest that amyloid-related pathology and hCSVD have synergistic effects on the progression of lobar microbleeds, providing new clinical insight into the interaction between amyloid burden and hCSVD on CMB progression and cognitive decline with implications for developing effective prevention strategies

Antiferromagnetic Order Induced by an Applied Magnetic Field in a High-Temperature Superconductor

One view of the cuprate high-transition temperature (high-Tc) superconductors is that they are conventional superconductors where the pairing occurs between weakly interacting quasiparticles, which stand in one-to-one correspondence with the electrons in ordinary metals - although the theory has to be pushed to its limit. An alternative view is that the electrons organize into collective textures (e.g. charge and spin stripes) which cannot be mapped onto the electrons in ordinary metals. The phase diagram, a complex function of various parameters (temperature, doping and magnetic field), should then be approached using quantum field theories of objects such as textures and strings, rather than point-like electrons. In an external magnetic field, magnetic flux penetrates type-II superconductors via vortices, each carrying one flux quantum. The vortices form lattices of resistive material embedded in the non-resistive superconductor and can reveal the nature of the ground state - e.g. a conventional metal or an ordered, striped phase - which would have appeared had superconductivity not intervened. Knowledge of this ground state clearly provides the most appropriate starting point for a pairing theory. Here we report that for one high-Tc superconductor, the applied field which imposes the vortex lattice, also induces antiferromagnetic order. Ordinary quasiparticle pictures cannot account for the nearly field-independent antiferromagnetic transition temperature revealed by our measurements