Plasma glycine level is low in patients with obesity or diabetes and the improvement of insulin resistance increases plasma glycine concentration. In prospective studies, hypoglycinemia at baseline ...predicts the risk of developing type 2 diabetes and higher serum glycine level is associated with decreased risk of incident type 2 diabetes. Consistently, plasma glycine concentration is lower in the lean offspring of parents with type 2 diabetes compared to healthy subjects. Among patients with type 2 diabetes, hypoglycinemia occurs before clinical manifestations of the disease, but the pathophysiological mechanisms underlying glycine deficit and its potential clinical repercussions are unclear. Glycine participates in several metabolic pathways, being required for relevant human physiological processes. Humans synthesize glycine from glyoxylate, glucose (via serine), betaine and likely from threonine and during the endogenous synthesis of L-carnitine. Glycine conjugates bile acids and other acyl moieties producing acyl-glycine derivatives. The glycine cleavage system catalyzes glycine degradation to carbon dioxide and ammonium while tetrahydrofolate is converted into 5,10-methylene-tetrahydrofolate. Glycine is utilized to synthesize serine, sarcosine, purines, creatine, heme group, glutathione, and collagen. Glycine is a major quantitative component of collagen. In addition, the role of glycine maintaining collagen structure is critical, as glycine residues are required to stabilize the triple helix of the collagen molecule. This quality of glycine likely contributes to explain the occurrence of medial arterial calcification and the elevated cardiovascular risk associated with diabetes and chronic kidney disease, as emerging evidence links normal collagen content with the initiation and progression of vascular calcification in humans.
Merlin (Moesin-ezrin-radixin-like protein, also known as schwannomin) is a tumor suppressor protein encoded by the neurofibromatosis type 2 gene NF2. Loss of function mutations or deletions in NF2 ...cause neurofibromatosis type 2 (NF2), a multiple tumor forming disease of the nervous system. NF2 is characterized by the development of bilateral vestibular schwannomas. Patients with NF2 can also develop schwannomas on other cranial and peripheral nerves, as well as meningiomas and ependymomas. The only potential treatment is surgery/radiosurgery, which often results in loss of function of the involved nerve. There is an urgent need for chemotherapies that slow or eliminate tumors and prevent their formation in NF2 patients. Interestingly NF2 mutations and merlin inactivation also occur in spontaneous schwannomas and meningiomas, as well as other types of cancer including mesothelioma, glioma multiforme, breast, colorectal, skin, clear cell renal cell carcinoma, hepatic and prostate cancer. Except for malignant mesotheliomas, the role of NF2 mutation or inactivation has not received much attention in cancer, and NF2 might be relevant for prognosis and future chemotherapeutic approaches. This review discusses the influence of merlin loss of function in NF2-related tumors and common human cancers. We also discuss the NF2 gene status and merlin signaling pathways affected in the different tumor types and the molecular mechanisms that lead to tumorigenesis, progression and pharmacological resistance.
Diffusion MRI tractography has emerged as a useful and popular tool for mapping connections between brain regions. In this study, we examined the performance of quantitative anisotropy (QA) in ...facilitating deterministic fiber tracking. Two phantom studies were conducted. The first phantom study examined the susceptibility of fractional anisotropy (FA), generalized factional anisotropy (GFA), and QA to various partial volume effects. The second phantom study examined the spatial resolution of the FA-aided, GFA-aided, and QA-aided tractographies. An in vivo study was conducted to track the arcuate fasciculus, and two neurosurgeons blind to the acquisition and analysis settings were invited to identify false tracks. The performance of QA in assisting fiber tracking was compared with FA, GFA, and anatomical information from T1-weighted images. Our first phantom study showed that QA is less sensitive to the partial volume effects of crossing fibers and free water, suggesting that it is a robust index. The second phantom study showed that the QA-aided tractography has better resolution than the FA-aided and GFA-aided tractography. Our in vivo study further showed that the QA-aided tractography outperforms the FA-aided, GFA-aided, and anatomy-aided tractographies. In the shell scheme (HARDI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 30.7%, 32.6%, and 24.45% of the false tracks, respectively, while the QA-aided tractography has 16.2%. In the grid scheme (DSI), the FA-aided, GFA-aided, and anatomy-aided tractographies have 12.3%, 9.0%, and 10.93% of the false tracks, respectively, while the QA-aided tractography has 4.43%. The QA-aided deterministic fiber tracking may assist fiber tracking studies and facilitate the advancement of human connectomics.
ABSTRACT Based on new near-infrared spectroscopic data from the instrument Espectrógrafo Multiobjeto Infra-Rojo (EMIR) on the 10.4 m Gran Telescopio Canarias, we report the presence of an ionized and ...warm molecular outflow in the luminous type-2 quasar J150904.22+043441.8 (z = 0.1118). The ionized outflow is faster than its molecular counterpart, although the outflow sizes that we derive for them are consistent within the errors (1.34 ± 0.18 and 1.46 ± 0.20 kpc, respectively). We use these radii, the broad emission-line luminosities and in the case of the ionized outflow, the density calculated from the trans-auroral O ii and S ii lines, to derive mass outflow rates and kinetic coupling efficiencies. While the ionized and warm molecular outflows represent a small fraction of the AGN power (≤0.033 and 0.0001 per cent of Lbol, respectively), the total molecular outflow, whose mass is estimated from an assumed warm-to-cold gas mass ratio of 6 × 10−5, has a kinetic coupling efficiency of ∼1.7 per cent Lbol. Despite the large uncertainty, this molecular outflow represents a significant fraction ofLbol and it could potentially have a significant impact on the host galaxy. In addition, the quasar spectrum reveals bright and patchy narrow Paα emission extending out to 4 arcsec (8 kpc) south-east and north-west from the active nucleus.
Environmental niche modeling (ENM) is commonly used to develop probabilistic maps of species distribution. Among available ENM techniques, MaxEnt has become one of the most popular tools for modeling ...species distribution, with hundreds of peer-reviewed articles published each year. MaxEnt's popularity is mainly due to the use of a graphical interface and automatic parameter configuration capabilities. However, recent studies have shown that using the default automatic configuration may not be always appropriate because it can produce non-optimal models; particularly when dealing with a small number of species presence points. Thus, the recommendation is to evaluate the best potential combination of parameters (feature classes and regularization multiplier) to select the most appropriate model. In this work we reviewed 244 articles published between 2013 and 2015 to assess whether researchers are following recommendations to avoid using the default parameter configuration when dealing with small sample sizes, or if they are using MaxEnt as a "black box tool." Our results show that in only 16% of analyzed articles authors evaluated best feature classes, in 6.9% evaluated best regularization multipliers, and in a meager 3.7% evaluated simultaneously both parameters before producing the definitive distribution model. We analyzed 20 articles to quantify the potential differences in resulting outputs when using software default parameters instead of the alternative best model. Results from our analysis reveal important differences between the use of default parameters and the best model approach, especially in the total area identified as suitable for the assessed species and the specific areas that are identified as suitable by both modelling approaches. These results are worrying, because publications are potentially reporting over-complex or over-simplistic models that can undermine the applicability of their results. Of particular importance are studies used to inform policy making. Therefore, researchers, practitioners, reviewers and editors need to be very judicious when dealing with MaxEnt, particularly when the modelling process is based on small sample sizes.
It has been reported that neural tube defects (NTD) can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for ...the prevention of other birth defects and maternal and infant outcomes are unclear.
This review aims to examine whether periconceptional folate supplementation reduces the risk of neural tube and other congenital anomalies (including cleft palate) without causing adverse outcomes in mothers or babies. This is an update of a previously published Cochrane review on this topic.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2015). Additionally, we searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (31 August 2015) and contacted relevant organisations to identify ongoing and unpublished studies.
We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies. We assessed the quality of the body of evidence using the GRADE approach.
Five trials involving 7391 women (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs) were included. Four comparisons were made: 1) supplementation with any folate versus no intervention, placebo or other micronutrients without folate (five trials); 2) supplementation with folic acid alone versus no treatment or placebo (one trial); 3) supplementation with folate plus other micronutrients versus other micronutrients without folate (four trials); and 4) supplementation with folate plus other micronutrients versus the same other micronutrients without folate (two trials). The risk of bias of the trials was variable. Only one trial was considered to be at low risk of bias. The remaining studies lacked clarity regarding the randomisation method or whether the allocation to the intervention was concealed. All the participants were blinded to the intervention, though blinding was unclear for outcome assessors in the five trials.The results of the first comparison involving 6708 births with information on NTDs and other infant outcomes, show a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.17 to 0.58); five studies; 6708 births; high quality evidence). Only one study assessed the incidence of NTDs and showed no evidence of an effect (RR 0.07, 95% CI 0.00 to 1.32; 4862 births) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.34, 95% CI 0.18 to 0.64); four studies; 1846 births). Subgroup analyses suggest that the positive effect of folic acid on NTD incidence and recurrence is not affected by the explored daily folic acid dosage (400 µg (0.4 mg) or higher) or whether folic acid is given alone or with other vitamins and minerals. These results are consistent across all four review comparisons.There is no evidence of any preventive or negative effects on cleft palate (RR 0.73, 95% CI 0.05 to 10.89; three studies; 5612 births; low quality evidence), cleft lip ((RR 0.79, 95% CI 0.14 to 4.36; three studies; 5612 births; low quality evidence), congenital cardiovascular defects (RR 0.57, 95% CI 0.24 to 1.33; three studies; 5612 births; low quality evidence), miscarriages (RR 1.10, 95% CI 0.94 to 1.28; five studies; 7391 pregnancies; moderate quality evidence) or any other birth defects (RR 0.94, 95% CI 0.53 to 1.66; three studies; 5612 births; low quality evidence). There were no included trials assessing the effects of this intervention on neonatal death, maternal blood folate or anaemia at term.
Folic acid, alone or in combination with vitamins and minerals, prevents NTDs, but does not have a clear effect on other birth defects.
Abstract
In this paper, we describe the routine photometric calibration of data taken with the VISTA infrared camera (VIRCAM) instrument on the ESO Visible and Infrared Survey Telescope for Astronomy ...(VISTA) telescope. The broad-band ZYJHKs data are directly calibrated from Two Micron all Sky Survey (2MASS) point sources visible in every VISTA image. We present the empirical transformations between the 2MASS and VISTA, and Wide-Field Camera and VISTA, photometric systems for regions of low reddening. We investigate the long-term performance of VISTA+VIRCAM. An investigation of the dependence of the photometric calibration on interstellar reddening leads to these conclusions: (1) For all broad-band filters, a linear colour-dependent correction compensates the gross effects of reddening where E(B − V) < 5.0. (2) For Z and Y, there is a significantly larger scatter above E(B − V) = 5.0, and insufficient measurements to adequately constrain the relation beyond this value. (3) The JHKs filters can be corrected to a few per cent up to E(B − V) = 10.0. We analyse spatial systematics over month-long time-scales, both inter- and intradetector and show that these are present only at very low levels in VISTA. We monitor and remove residual detector-to-detector offsets. We compare the calibration of the main pipeline products: pawprints and tiles. We show how variable seeing and transparency affect the final calibration accuracy of VISTA tiles, and discuss a technique, grouting, for mitigating these effects. Comparison between repeated reference fields is used to demonstrate that the VISTA photometry is precise to better than ≃ 2 per cent for the YJHKs bands and 3 per cent for the Z bands. Finally, we present empirically determined offsets to transform VISTA magnitudes into a true Vega system.
The dental profession has experienced a dramatic acceleration in the use of communication systems and information-based technologies over recent years, originating new paradigms for the prevention ...and promotion of oral health. The purpose of this systematic review was to determine the effect of teledentistry-based (telematic) strategies, reported in randomized controlled trials and quasi-randomized trials, with a focus on oral health prevention and promotion–related outcomes in patients of all ages. We searched Medline via PubMed, SCOPUS, and Web of Science from inception until August 2020, regardless of the language of publication. We selected studies for inclusion and conducted data extraction, assessed risk of bias (Cochrane tool), and evaluated the certainty of the evidence (GRADE approach) in duplicate and independently. Out of 898 potentially eligible references, we selected 43 for full-text screening, of which 19 studies proved eligible: 18 randomized controlled trials and 1 quasi-randomized study. Virtual interventions were mostly asynchronous via apps (n = 9), text messages (n = 9), or computer-aided learning (n = 1). The use of teledentistry as compared with conventional strategies may result in a large reduction in the plaque index (standardized mean difference, −1.18; 95% CI, −1.54 to −0.82; I2 = 92%; low certainty) and will likely result in a large reduction in the gingival index (standardized mean difference, −2.17; 95% CI, −3.15 to −1.19; I2 = 97%; moderate certainty) and in the incidence of white spot lesions (risk ratio, 0.48; 95% CI, 0.35 to 0.66; I2 = 0%; moderate certainty), with an increased effect over time. Evidence suggests that teledentistry, particularly mHealth (messages and apps), is a promising clinical tool for preventing and promoting oral health, especially under the accelerated virtualization of dentistry. Future studies should include a broader spectrum of the population, including adults and elders, to better inform policy and implementation of teledentistry (PROSPERO: CRD42020192685).
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