Tag: pubmed

Seizure. 2021 Jun 29;91:213-227. doi: 10.1016/j.seizure.2021.06.028. Online ahead of print.

ABSTRACT

An imbalance between excitation and inhibition has been a longstanding proposed mechanism regarding ictogenesis and epileptogenesis. This imbalance is related to increased extracellular glutamate in the brain and/or reduction in GABA concentrations, leading to excitotoxicity, seizures, and cell death. This review aims to summarize the microdialysis and magnetic resonance spectroscopy (MRS) literature investigating glutamate and GABA concentrations in epilepsy patients, present limitations, and suggest future directions to help direct the search for novel epilepsy treatments. The majority of microdialysis studies demonstrated increased glutamate in epileptic regions either compared to control regions or to baseline levels; however, sample sizes were small, with some statistical comparisons missing. For the MRS research, two of six studies reported significant changes in glutamate levels compared to controls, though the results were mixed, with one reporting increased and the other reporting decreased glutamate levels. Eleven of 20 studies reported significant changes in Glx (glutamate + glutamine) or Glx ratios, with most reporting increased levels, except for a few epilepsy syndromes where reduced levels were reported. Few studies investigated GABA concentrations, with one microdialysis and four spectroscopy studies reporting increased GABA levels, and one study reporting decreased GABA in a different brain region. Based on this review, future research should account for medication use; include measurements of GABA, glutamate, and glutamine; use high-tesla strength MRI; and further evaluate the timing of microdialysis. Understanding the importance of brain glutamate and GABA levels in epilepsy may provide direction for future therapies and treatments.

PMID:34233236 | DOI:10.1016/j.seizure.2021.06.028

Water Res. 2021 Jun 26;202:117384. doi: 10.1016/j.watres.2021.117384. Online ahead of print.

ABSTRACT

While the microbiome of activated sludge (AS) in wastewater treatment plants (WWTPs) plays a vital role in shaping the resistome, identifying the potential bacterial hosts of antibiotic resistance genes (ARGs) in WWTPs remains challenging. The objective of this study is to explore the feasibility of using a machine learning approach, random forests (RF’s), to identify the strength of associations between ARGs and bacterial taxa in metagenomic datasets from the activated sludge of WWTPs. Our results show that the abundance of select ARGs can be predicted by RF’s using abundant genera (Candidatus Accumulibacter, Dechloromonas, Pesudomonas, and Thauera, etc.), (opportunistic) pathogens and indicators (Bacteroides, Clostridium, and Streptococcus, etc.), and nitrifiers (Nitrosomonas and Nitrospira, etc.) as explanatory variables. The correlations between predicted and observed abundance of ARGs (erm(B), tet(O), tet(Q), etc.) ranged from medium (0.400 < R² < 0.600) to strong (R² > 0.600) when validated on testing datasets. Compared to those belonging to the other two groups, individual genera in the group of (opportunistic) pathogens and indicator bacteria had more positive functional relationships with select ARGs, suggesting genera in this group (e.g., Bacteroides, Clostridium, and Streptococcus) may be hosts of select ARGs. Furthermore, RF’s with (opportunistic) pathogens and indicators as explanatory variables were used to predict the abundance of select ARGs in a full-scale WWTP successfully. Machine learning approaches such as RF’s can potentially identify bacterial hosts of ARGs and reveal possible functional relationships between the ARGs and microbial community in the AS of WWTPs.

PMID:34233249 | DOI:10.1016/j.watres.2021.117384

J Dent. 2021 Jul 4:103740. doi: 10.1016/j.jdent.2021.103740. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to clinically evaluate the 5-years clinical performance of indirect resin composite inlays luted with three different resin cement strategies in MOD Class II restorations.

MATERIALS AND METHODS: A randomized clinical trial was conducted following CONSORT guidelines. Forty patients with three large cavities indicated for indirect MOD Class II restorations were enrolled in the current study. Then, 120 indirect resin composite inlay restorations (SR Nexco) were placed and luted with three different resin cement strategies (n=40); an etch-and-rinse (Variolink N), self-etch (Panavia F2.0) and self-adhesive (RelyX Unicem. These restorations were evaluated to the periods of 1 week (baseline), 1, 3 and 5 years using modified USPHS criteria. Statistical analyses were performed with Wilcoxon and Friedman tests with level of significance set at 0.05.

RESULTS: The outcome of the clinical trial showed that, there was neither loss of restorations nor recurrent caries after 5 years for all luting cements groups. Both self-etch Panavia F2.0 and self-adhesive RelyX Unicem resin cements exhibited significant differences between the evaluation periods regarding to marginal discoloration and marginal adaptation (p=0.03). At baseline, only 8 cases of etch-and-rinse (Variolink N) resin cement group exhibited post-operative sensitivity which were relieved after short time (p=0.04).

CONCLUSION: All the three resin cement strategies tested, showed acceptable clinical performance after 5-years recall period. In time, etch-and-rinse resin cement group showed better clinical performance regarding marginal discoloration and marginal adaptation at 5-years recall period. Clinical Relevance statement:In vitro and in vivo studies reveal contradictory evidence of the clinical performance of indirect resin composite inlays luted with different resin cement strategies. Thus, this study revealed that etch-and-rinse resin cement still has the best prognosis for adhesive luting of indirect resin composite inlays.

PMID:34233204 | DOI:10.1016/j.jdent.2021.103740

J Biomech. 2021 Jun 24;125:110585. doi: 10.1016/j.jbiomech.2021.110585. Online ahead of print.

ABSTRACT

Wind influences the jump length in ski jumping, which raises questions about the fairness. To counteract the wind problem, the International Ski Federation has introduced a wind compensation system in 2009: time-averaged wind velocity components tangential to the landing slope are obtained from several sites along the landing slope, and these data are used in a linear statistical model for estimating the jump length effect of wind. This is considered in the total score of the ski jump. However, it has been shown that the jump length effect estimates can be inaccurate and misleading. The present article introduces an alternative mathematical wind compensation approach that is based on an accurate mechanistic model of the flight phase. This estimates the jump length effect as difference between the jump length of the real ski jump at the given wind condition and the computed jump length of the simulated ski jump at calm wind. Inputs for the computer simulation are the initial flight velocity and aerodynamic coefficients of the real ski jump that can be obtained from kinematic and wind velocity data collected during the flight. The initial flight velocity is readily available from the kinematic data and inverse dynamics can be used to compute the aerodynamic coefficients. The accuracy of the estimated jump length effect of the mechanistic model-based approach depends only on the measurement errors in the kinematic and wind velocity data, but not on inaccuracies of an approach that is based on a linear statistical model.

PMID:34233216 | DOI:10.1016/j.jbiomech.2021.110585

Exp Eye Res. 2021 Jul 4:108697. doi: 10.1016/j.exer.2021.108697. Online ahead of print.

ABSTRACT

Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related αA-crystallin truncation in the lens nucleus. The truncation sites in αA-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract.

PMID:34233175 | DOI:10.1016/j.exer.2021.108697

Acta Ophthalmol. 2021 Jul 7. doi: 10.1111/aos.14973. Online ahead of print.

ABSTRACT

PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets.

METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups.

RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2% when all three risk factors were present versus 4.4% when none were present (c-index = 0.737, 95% CI: 0.608, 0.865; p < 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475).

CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.

PMID:34233090 | DOI:10.1111/aos.14973

J Small Anim Pract. 2021 Jul 7. doi: 10.1111/jsap.13379. Online ahead of print.

ABSTRACT

OBJECTIVES: Activity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6′-methylresorufin) ester (DGGR) lipase is considered to be more pancreas specific than traditional lipase assays. The aim of this study was to evaluate the diagnostic performance of DGGR lipase activity for suspected acute pancreatitis in dogs and to assess its prognostic usefulness.

METHODS: Retrospective study of case records for suspected acute pancreatitis based on clinician-stated diagnosis, point-of-care and quantitative canine pancreas-specific lipase (cPL) results and consistent ultrasonographic features. Diagnostic performance of DGGR lipase was assessed by receiver-operating characteristic curve analysis, agreement by Cohen’s kappa (κ) and prognostic value by multiple regression analysis.

RESULTS: Median DGGR lipase activity was significantly (P < 0.001) higher in dogs with suspected acute pancreatitis [93.7 (range, 11.0-2853.0) U/L (n = 158)] compared to those with no evidence of pancreatitis [range, 20.9 (6.7-89.0) U/L (n = 356)]. A DGGR lipase activity >42.15 U/L had the best combined diagnostic sensitivity (81.0%) and specificity (92.1%). Previously established cut-offs (>130 and >80 U/L) had sensitivities of 40.5 and 43.0%, and specificities of 100 and 99.7%, respectively. There was near perfect (κ = 0.821) and substantial (κ = 0.751) agreement between DGGR lipase activity >42.15 U/L and quantitative cPL concentrations ≥200 and ≥400 μg/L, respectively. DGGR lipase activity but not quantitative cPL concentration was statistically (P = 0.043, odds ratio = 0.999) predictive of discharge but clinical utility is questionable.

CLINICAL SIGNIFICANCE: Using DGGR lipase at the lower cut-off could provide an additional test for supporting a diagnosis of acute pancreatitis in dogs particularly if cPL results are not available. Larger studies are required to more fully assess its value in prognostication.

PMID:34233038 | DOI:10.1111/jsap.13379

J Evol Biol. 2021 Jul 7. doi: 10.1111/jeb.13900. Online ahead of print.

ABSTRACT

Both assortment and plasticity can facilitate social evolution, as each may generate heritable associations between the phenotypes and fitness of individuals and their social partners. However, it currently remains difficult to empirically disentangle these distinct mechanisms in the wild, particularly for complex and environmentally responsive phenotypes subject to measurement error. To address this challenge, we extend the widely used animal model to facilitate unbiased estimation of plasticity, assortment, and selection on social traits, for both phenotypic and quantitative genetic analysis. Our social animal models (SAMs) estimate key evolutionary parameters for the latent reaction norms underlying repeatable patterns of phenotypic interaction across social environments. As a consequence of this approach, SAMs avoid inferential biases caused by various forms of measurement error in the raw phenotypic associations between social partners. We conducted a simulation study to demonstrate the application of SAMs and investigate their performance for both phenotypic and quantitative genetic analyses. With sufficient repeated measurements, we found desirably high power, low bias, and low uncertainty across model parameters using modest sample and effect sizes, leading to robust predictions of selection and adaptation. Our results suggest that SAMs will readily enhance social evolutionary research on a variety of phenotypes in the wild. We provide detailed coding tutorials and worked examples for implementing SAMs in the Stan statistical programming language.

PMID:34233047 | DOI:10.1111/jeb.13900

Bioelectromagnetics. 2021 Jul 7. doi: 10.1002/bem.22359. Online ahead of print.

ABSTRACT

In magnetobiology, it is difficult to reproduce the nonspecific (not associated with specialized receptors) biological effects of weak magnetic fields. This means that some important characteristic of the data may be missed in standard statistical processing, where the set of measurements to be averaged belongs to the same population so that the contribution of fluctuations decreases according to the Central Limit Theorem. It has been shown that a series of measurements of a nonspecific magnetic effect contains not only the usual scatter of data around the mean but also a significant random component in the mean itself. This random component indicates that measurements belong to different statistical populations, which requires special processing. This component, otherwise called heterogeneity, is an additional characteristic that is typically overlooked, and which reduces reproducibility. The current method for studying and summarizing highly heterogeneous data is the random-effect meta-analysis of absolute values, i.e., of magnitudes, rather than the values themselves. However, this estimator-the average of absolute values-has a significant positive bias when it comes to the small effects that are characteristic of magnetobiology. To solve this problem, an improved estimator based on the folded normal distribution that gives several times less bias is proposed. We used this improved estimator to analyze the nonspecific effect of the hypomagnetic field in the Stroop test in 40 subjects and found a statistically significant meta-effect with a standardized average of magnitudes of about 0.1. It has been shown that the proposed approach can also be applied to a single study. © 2021 Bioelectromagnetics Society.

PMID:34233018 | DOI:10.1002/bem.22359

Acta Paediatr. 2021 Jul 7. doi: 10.1111/apa.16025. Online ahead of print.

ABSTRACT

AIM: Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used.

METHODS: All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012-2016 were included. Vancomycin trough levels were registered. Student t-test, Wilcoxon test and regression models were used for statistical analysis.

RESULTS: A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p=0.09).

CONCLUSIONS: In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.

PMID:34233034 | DOI:10.1111/apa.16025