Melasma has a complex pathophysiology with different cell types and signalling pathways involved. Paracrine factors secreted by keratinocytes, fibroblasts and endothelial cells act on melanocytes and ...stimulate melanogenesis. These paracrine factors are involved in the oxidative stress, inflammatory, vascular and hormonal pathways, among others. Damage of the dermoepidermal barrier also occurs and facilitates melanin deposition in the dermis, also known as dermal or mixed melasma. We used artificial intelligence tools to define the best combination of compounds for skin pigmentation inhibition. Mathematical models suggested the combination of retinol, diosmin and ferulic acid to be the most effective one. In vitro cellular tyrosinase activity assay proved that this combination had a synergistic depigmenting effect. Further assays proved that the combination could inhibit key pathways involved in melasma by downregulating ET‐1 and COX‐2 gene expression and IBMX‐induced dendricity in human melanocytes, and upregulated the gene expression of IL‐1b, TIMP3 and several endogenous antioxidant enzymes. The combination also reduced melanin levels in a phototype VI 3D epidermis model. These results indicate that the combination of retinol, diosmin and ferulic acid is an effective synergistic complex for the treatment of melasma by regulating the key molecular pathways involved in skin hyperpigmentation pathophysiology.
The ubiquitous Internet of Things (IoT) devices nowadays are generating various and numerous data from everywhere at any time. Since it is not always necessary to centralize and analyze IoT data ...cumulatively (e.g., the Monte Carlo analytics and Convergence analytics demonstrated in this article), the traditional implementations of big data analytics (BDA) will suffer from unnecessary and expensive data transmissions as a result of the tight coupling between computing resource management and data processing logics. Inspired by software-defined infrastructure (SDI), we propose the "microservice-oriented platform" to break the environmental monolith and further decouple data processing logics from their underlying resource management in order to facilitate BDA implementations in the IoT environment (which we name "IoBDA"). Given predesigned standard microservices with respect to specific data processing logics, the proposed platform is expected to largely reduce the complexity in and relieve inexperienced practices of IoBDA implementations. The potential contributions to the relevant communities include (1) new theories of a microservice-oriented platform on top of SDI and (2) a functional microservice-oriented platform for IoBDA with a group of predesigned microservices.
ARCIMBOLDO_LITE: single-workstation implementation and use Sammito, Massimo; Millán, Claudia; Frieske, Dawid ...
Acta crystallographica. Section D, Biological crystallography.,
September 2015, Letnik:
71, Številka:
9
Journal Article
Recenzirano
ARCIMBOLDO solves the phase problem at resolutions of around 2 Å or better through massive combination of small fragments and density modification. For complex structures, this imposes a need for a ...powerful grid where calculations can be distributed, but for structures with up to 200 amino acids in the asymmetric unit a single workstation may suffice. The use and performance of the single‐workstation implementation, ARCIMBOLDO_LITE, on a pool of test structures with 40–120 amino acids and resolutions between 0.54 and 2.2 Å is described. Inbuilt polyalanine helices and iron cofactors are used as search fragments. ARCIMBOLDO_BORGES can also run on a single workstation to solve structures in this test set using precomputed libraries of local folds. The results of this study have been incorporated into an automated, resolution‐ and hardware‐dependent parameterization. ARCIMBOLDO has been thoroughly rewritten and three binaries are now available: ARCIMBOLDO_LITE, ARCIMBOLDO_SHREDDER and ARCIMBOLDO_BORGES. The programs and libraries can be downloaded from http://chango.ibmb.csic.es/ARCIMBOLDO_LITE.
Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should ...be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.
The objective of this study was to investigate and compare optic nerve and retinal layers in eyes of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) with paired control ...eyes using optical coherence tomography.
Sixty-three eyes of 34 subjects, 12 eyes with AD and 51 eyes with MCI, positive to 11C-labeled Pittsburgh Compound-B with positron emission tomography (11C-PiB PET/CT), and the same number of sex- and age-paired control eyes underwent optical coherence tomography scanning analyzing retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), Bruch's membrane opening–minimum rim width (BMO-MRW), inner plexiform layer (IPL), outer nuclear layer, and lamina cribrosa (LC).
Compared with healthy controls, eyes of patients with positive 11C-PiB PET/CT showed a significant thinning of RNFL (P < .028) and GCL (P < .014). IPL and outer nuclear layer also showed significant thinning in two (P < .025) and one location (P < .010), respectively. No significant differences were found when optic nerve measurements BMO-MRW and LC were compared (P > .131 and P > .721, respectively). Temporal sector GCL, average RNFL, and temporal sector RNFL also exhibited significant thinning when MCI and control eyes were compared (P = .015, P = .005 and P = .050, respectively), and also the greatest area under the curve values (0.689, 0.647, and 0.659, respectively). GCL, IPL, and RNFL tend to be thinner in the AD group compared with healthy controls.
Our study suggests that RNFL and GCL are useful for potential screening in the early diagnosis of AD. LC and BMO-MRW appear not to be affected by AD.
There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep ...parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the
APOE ε
4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the
APOE
ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that
APOE
modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.
Subcutaneous granuloma annulare is a benign inflammatory disorder that primarily affects healthy children and manifests as a rapidly growing, painless, nonmobile mass, most commonly located in the ...leg. The current case highlights the sonographic appearance of subcutaneous granuloma annulare. Ultrasound color Doppler is a helpful noninvasive imaging test that may allow physicians to confirm the diagnosis of subcutaneous granuloma annulare and avoid unnecessary medical procedures.
Abstract
Background
The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With ...tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform.
Methods
Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of
ApoE
4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A − / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors.
Results
Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / − , AD + / − , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89.
Conclusions
Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects.
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