The preparation of solution-processable graphene from graphite oxide typically involves a hydrazine reduction step, but the use of such a reagent in the large-scale implementation of this approach is ...not desirable due to its high toxicity. Here, we compare the deoxygenation efficiency of graphene oxide suspensions by different reductants (sodium borohydride, pyrogallol, and vitamin C, in addition to hydrazine), as well as by heating the suspensions under alkaline conditions. In almost all cases, the degree of reduction attainable and the subsequent restoration of relevant properties (e.g., electrical conductivity) lag significantly behind those achieved with hydrazine. Only vitamin C is found to yield highly reduced suspensions in a way comparable to those provided by hydrazine. Stable suspensions of vitamin C-reduced graphene oxide can be prepared not only in water but also in common organic solvents, such as N,N-dimethylformamide (DMF) or N-methyl-2-pyrrolidone (NMP). These results open the perspective of replacing hydrazine in the reduction of graphene oxide suspensions by an innocuous and safe reductant of similar efficacy, thus facilitating the use of graphene-based materials for large-scale applications.
Alzheimer's disease (AD) is the leading cause of dementia in elderly people. The etiology of this disease remains a matter of intensive research in many laboratories. We have advanced the idea that ...disseminated fungal infection contributes to the etiology of AD. Thus, we have demonstrated that fungal proteins and DNA are present in nervous tissue from AD patients. More recently, we have reported that bacterial infections can accompany these mycoses, suggesting that polymicrobial infections exist in AD brains. In the present study, we have examined fungal and bacterial infection in brain tissue from AD patients and control subjects by immunohistochemistry. In addition, we have documented the fungal and bacterial species in brain regions from AD patients and control subjects by next-generation sequencing (NGS). Our results from the analysis of ten AD patients reveal a variety of fungal and bacterial species, although some were more prominent than others. The fungal genera more prevalent in AD patients were
,
,
, and
. We also compared these genera with those found in elderly and younger subjects. One of the most prominent genera in control subjects was
. Principal component analysis clearly indicated that fungi from frontal cortex samples of AD brains clustered together and differed from those of equivalent control subjects. Regarding bacterial infection, the phylum
was the most prominent in both AD patients and controls, followed by
,
, and
. At the family level,
and
exhibited higher percentages in AD brains than in control brains. These findings could be of interest to guide targeted antimicrobial therapy for AD patients. Moreover, the variety of microbial species in each patient may constitute a basis for a better understanding of the evolution and severity of clinical symptoms in each patient.
Background and Aims
Patients with hepatitis C virus (HCV) and advanced fibrosis remain at risk of hepatocellular carcinoma (HCC) after sustained viral response (SVR) and need lifelong surveillance. ...Because HCC risk is not homogenous and may decrease with fibrosis regression, we aimed to identify patients with low HCC risk based on the prediction of noninvasive markers and its changes after SVR.
Approach and Results
This is a multicenter cohort study, including patients with HCV and compensated advanced fibrosis that achieved SVR after direct antivirals. Clinical and transient elastography (TE) data were registered at baseline, 1 year, and 3 years after the end of treatment (EOT). All patients underwent liver ultrasound scan every 6 months. Patients with clinical evaluation 1 year after EOT were eligible. Univariate and multivariate Cox regression analysis were performed, and predictive models were constructed. HCC occurrence rates were evaluated by Kaplan‐Meier. Nine hundred and ninety‐three patients were eligible (56% male; 44% female; median age 62 years), 35 developed HCC (3.9%), and the median follow‐up was 45 months (range 13‐53). Baseline liver stiffness measurement (LSM) (HR 1.040; 95% CI 1.017‐1.064), serum albumin (HR 0.400; 95% CI 0.174‐0.923), 1‐year DeltaLSM (HR 0.993; 95% CI 0.987‐0.998), and 1‐year FIB‐4 score (HR 1.095; 95% CI 1.046‐1.146) were independent factors associated with HCC. The TE‐based HCC risk model predicted 0% of HCC occurrence at 3 years in patients with score 0 (baseline LSM ≤ 17.3 kPa, albumin >4.2 g/dL, and 1‐year DeltaLSM > 25.5%) versus 5.2% in patients with score 1‐3 (Harrell’s C 0.779; log‐rank 0.002). An alternative model with FIB‐4 similarly predicted HCC risk.
Conclusions
A combination of baseline and dynamic changes in noninvasive markers may help to identify patients with a very low risk of HCC development after SVR.
Multiple sclerosis (MS) is the prototypical inflammatory disease of the central nervous system (CNS), leading to multifocal demyelination and neurodegeneration. The etiology of this incurable disease ...is unknown and remains a matter of intensive research. The possibility that microbial infections, such as viruses or bacteria, can trigger an autoimmune reaction in CNS tissue has been suggested. However, the recent demonstration that bacteria are present in CNS tissue points to a direct involvement of microbial infections in the etiology of MS. In the present study, we provide the first evidence of fungal infection in CNS tissue of MS patients, and demonstrate that fungal DNA from different species can be detected in the CNS. We used, nested PCR assays together with next-generation sequencing to identify the fungal species in the nervous tissue of 10 patients with MS. Strikingly, Trichosporon mucoides was found in the majority of MS patients, and particularly high levels of this fungus were found in two patients. Importantly, T. mucoides was not detected in the CNS of control subjects. We were also able to visualize fungal structures in CNS tissue sections by immunohistochemistry using specific antifungal antibodies, which also revealed the accumulation of a number of microbial cells in microfoci. Again, microbial structures were not observed in CNS sections from controls. In addition to fungi, neural tissue from MS patients was also positive for bacteria. In conclusion, our present observations point to the novel concept that MS could be caused by polymicrobial infections. Thus, mycosis of the CNS may be accompanied by opportunistic bacterial infection, promoting neuroinflammation and directly causing focal lesions, followed by demyelination and axonal injury.
•Multiple sclerosis (MS) is the prototypical inflammatory disease of unknown etiology.•The possibility that MS is caused by microbial infections has been suggested.•We provide the first evidence that fungal infections can be detected in MS brains.•Both, fungal DNA and the direct visualization of fungal structures, can be detected.•In addition, bacteria can be identified in neural tissue from MS patients.
We present a mechanochemical procedure, with solvent-free, green-chemistry credentials, to grow all-inorganic CsPbBr3 perovskite. The crystal structure of this perovskite and its correlations with ...the physicochemical properties have been studied. Synchrotron X-ray diffraction (SXRD) and neutron powder diffraction (NPD) allowed us to follow the crystallographic behavior from 4 to 773 K. Unreported features like the observed negative thermal expansion of the b unit-cell parameter stem from octahedral distortions in the 4–100 K temperature range. The mechanochemical synthesis was designed to reduce the impact energy during the milling process, leading to a defect-free, well-crystallized sample characterized by a minimum unit-cell volume and octahedral tilting angles in the low-temperature orthorhombic perovskite framework, defined in the Pbnm space group. The UV–vis diffuse reflectance spectrum shows a reduced band gap of 2.22(3) eV, and the photocurrent characterization in a photodetector reveals excellent properties with potential applications of this material in optoelectronic devices.
Cells continually sample their mechanical environment using exquisite force sensors such as talin, whose folding status triggers mechanotransduction pathways by recruiting binding partners. ...Mechanical signals in biology change quickly over time and are often embedded in noise; however, the mechanics of force-sensing proteins have only been tested using simple force protocols, such as constant or ramped forces. Here, using our magnetic tape head tweezers design, we measure the folding dynamics of single talin proteins in response to external mechanical noise and cyclic force perturbations. Our experiments demonstrate that talin filters out external mechanical noise but detects periodic force signals over a finely tuned frequency range. Hence, talin operates as a mechanical band-pass filter, able to read and interpret frequency-dependent mechanical information through its folding dynamics. We describe our observations in the context of stochastic resonance, which we propose as a mechanism by which mechanosensing proteins could respond accurately to force signals in the naturally noisy biological environment.
Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of ...sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein. Randomized, double-blind, placebo-controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG₄ to Pru p 3. Tolerance was assessed with a careful recording of adverse events. After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG₄ to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter-group differences were only observed in the SPT and IgG₄ responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity. In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance.
We present a new catalog of TeV gamma-ray sources using 1523 days of data from the High-Altitude Water Cherenkov (HAWC) Observatory. The catalog represents the most sensitive survey of the northern ...gamma-ray sky at energies above several TeV, with three times the exposure compared to the previous HAWC catalog, 2HWC. We report 65 sources detected at ≥5 significance, along with the positions and spectral fits for each source. The catalog contains eight sources that have no counterpart in the 2HWC catalog, but are within 1° of previously detected TeV emitters, and 20 sources that are more than 1° away from any previously detected TeV source. Of these 20 new sources, 14 have a potential counterpart in the fourth Fermi Large Area Telescope catalog of gamma-ray sources. We also explore potential associations of 3HWC sources with pulsars in the Australia Telescope National Facility (ATNF) pulsar catalog and supernova remnants in the Galactic supernova remnant catalog.
A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy ...of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI.
A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas.
One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001.
For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of delayed and 94.8% of late cases are diagnosed. The conjunction of histopathology and sonicate fluid culture yields a sensitivity of 100% for all types of infection.
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