Christensengregory5258

Vervets dosed with BMAA + l-serine displayed reduced neuropathological changes. This study demonstrates that chronic dietary exposure to BMAA causes ALS/MND-type pathological changes in the vervet and coadministration of l-serine reduces the amount of reactive gliosis and the number of protein inclusions in motor neurons. © 2020 American Association of Neuropathologists, Inc.CONTEXT The actions of both endogenous incretin hormones during a meal have not previously been characterized. EKI-785 nmr OBJECTIVE Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility. DESIGN Randomized, double-blinded, placebo-controlled, crossover design. SETTING On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min). PATIENTS OR OTHER PARTICIPANTS Twelve healthy male volunteers. INTERVENTIONS Infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (0-20 min 1000 pmol/kg/min; 20-270 min 450 pmol/kg/min), GIP(3-30)NH2+exendin(9-39)NH2, or placebo/saline. MAIN OUTCOME MEASURE Baseline-subtracted area under the curve (bsAUC) of C-peptide. RESULTS Infusion of GIP(3-30)NH2+exendin(9-39)NH2 significantly increahy men. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.In 2011, Florida established a Prescription Drug Monitoring Program and adopted new regulations for independent pain-management clinics. This paper examines the association of those reforms with drug overdose deaths and other injury fatalities. Florida's post-reform monthly mortality rates - for drug-involved deaths, motor vehicle crashes, and suicides by means other than poisoning - were compared to a counterfactual estimate of what those rates would have been absent reform. The counterfactual was estimated using a Bayesian structural time-series model based on mortality trends in similar states. By December 2013, drug overdose deaths were down -17% (95% CI, -21% to -12%), motor vehicle crash deaths were down -9% (-14%, to -4%), and suicide deaths were unchanged compared to what would be expected in the absence of reform. Florida's opioid psrescribing reform substantially reduced drug overdose deaths. Reforms may also have reduced motor vehicle crash deaths but were not associated with a change in suicides; more research is needed to understand these patterns. Bayesian structural time-series modeling is a promising new approach to interrupted time-series studies. © The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The oxygen uptake (V˙O2) kinetics during onset of and recovery from exercise have been shown to provide valuable parameters regarding functional capacity of both chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) patients. To investigate the influence of comorbidity of COPD in patients with CHF with reduced ejection fraction on recovery from submaximal exercise, 9 CHF-COPD male patients and 10 age-, gender-, and left ventricle ejection fraction (LVEF)-matched CHF patients underwent constant-load exercise tests (CLET) at moderate and high loads. The V˙O2, heart rate (HR), and cardiac output (CO) recovery kinetics were determined for the monoexponential relationship between these variables and time. Within-group analysis showed that the recovery time constant of HR (P0.05 in group vs load analysis). The ventilatory efficiency was related to MRT of V˙O2 during high CLET (r=0.71). Our results suggested that the combination of CHF and COPD may further impair the recovery kinetics compared to CHF alone.The objective of this study was to evaluate changes in sexual function after total laparoscopic hysterectomy (TLH) or transabdominal hysterectomy (TAH). This retrospective cohort study included patients with benign uterine tumors that were divided into TLH group and TAH group based on the hysterectomy technique used. Baseline, intraoperative, and postoperative characteristics were compared between groups. Postoperative sexual function was assessed using the Brief Index of Sexual Functioning for Women. The TLH and TAH groups contained 119 patients (age, 51.5±6.1 years) and 126 patients (age, 50.0±4.7 years), respectively. Baseline characteristics were comparable between groups, although uterine size was larger in the TAH group (P0.05). Both TLH and TAH had comparable negative effects on sexual function in women treated for benign uterine tumors in China, with a decreased frequency of sexual activity, reduced libido, orgasm dysfunction, and increased dyspareunia.We previously reported that both the high-carbohydrate diet (HCD) and high-fat diet (HFD) given for two months promote lipid deposition and inflammation in the liver and brain of mice. The results obtained indicate a tissue-specific response to both diets. Herein, we compared the effects of HCD and HFD on fatty acid (FA) composition and inflammation in the gastrocnemius muscle. Male Swiss mice were fed with HCD or HFD for 1 or 2 months. Saturated FA (SFA), monounsaturated FA (MUFA), n-3 polyunsaturated FA (n-3 PUFA), and n-6 PUFA were quantified. The activities of stearoyl-CoA desaturase 1 (SCD-1), Δ-6 desaturase (D6D), elongase 6, and de novo lipogenesis (DNL) were estimated. As for indicators of the inflammatory tissue state, we measured myeloperoxidase (MPO) activity and gene expression of F4/80, tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, and IL-10. The HCD led to a lower deposition of SFA, MUFA, n-3 PUFA, and n-6 PUFA compared to HFD. However, the HCD increased arachidonic acid levels, SFA/n-3 PUFA ratio, DNL, SCD-1, D6D, and MPO activities, and expression of IL-6, contrasting with the general idea that increased lipid deposition is associated with more intense inflammation. The HCD was more potent to induce skeletal muscle inflammation than the HFD, regardless of the lower lipid accumulation.The mosaic 45,X/46,XY karyotype is a common sex chromosomal abnormality in infertile men. Males with this mosaic karyotype can benefit from assisted reproductive therapies, but the transmitted abnormalities contain 45,X aneuploidy as well as Y chromosome microdeletions. The aim of this study was to investigate the clinical and genetic characteristics of infertile men diagnosed with 45,X/46,XY mosaicism in China. Of the 734 infertile men found to carry chromosomal abnormalities, 14 patients were carriers of 45,X/46,XY mosaicism or its variants, giving a prevalence of 0.27% (14/5269) and accounting for 1.91% (14/734) of patients with a chromosomal abnormality. There were ten cases (71.43%, 10/14) of 45,X mosaicism exhibiting AZF microdeletions. Case 1 and Case 4 had AZFc deletions, and the other eight cases had AZFb+c deletions. A high frequency of Y chromosome microdeletions were detected in male patients with 45,X/46,XY mosaicism. Preimplantation genetic diagnosis should be offered to men having intracytoplasmic sperm injection for hypospermatogenesis caused by 45,X/46,XY mosaicism, to avoid the risk of transfering AZF microdeletions in addition to X monosomy in male offspring.The immune stimulatory and anti-neoplastic functions of type I interferon have long been applied for the treatment of melanoma. However, the systemic application of high levels of this recombinant protein is often met with toxicity. An approach that provides localized, yet transient, production of type I interferon may overcome this limitation. We propose that the use of mesenchymal stem cells (MSCs) as delivery vehicles for the production of interferon-β (IFNβ) may be beneficial when applied together with our cancer gene therapy approach. In our previous studies, we have shown that adenovirus-mediated gene therapy with IFNβ was especially effective in combination with p19Arf gene transfer, resulting in immunogenic cell death. Here we showed that MSCs derived from mouse adipose tissue were susceptible to transduction with adenovirus, expressed the transgene reliably, and yet were not especially sensitive to IFNβ production. MSCs used to produce IFNβ inhibited B16 mouse melanoma cells in a co-culture assay. Moreover, the presence of p19Arf in the B16 cells sensitizes them to the IFNβ produced by the MSCs. These data represent a critical demonstration of the use of MSCs as carriers of adenovirus encoding IFNβ and applied as an anti-cancer strategy in combination with p19Arf gene therapy.This letter comments on two examples of numerical results of kinetic parameters which are inconsistent with the experimental data given in the same articles. Since this seems to be a trend in inorganic chemistry articles dealing with the catalytic oxidation of 3,5 di tert- butylcatechol and ortho-aminophenol, we call the attention of editors, reviewers and readers about grossly overestimated catalytic parameters in the literature.Anionic states of benzonitrile are investigated by high-level electronic structure methods. The calculations using equation-of-motion coupled-cluster theory for electron-attached states confirm earlier conclusions drawn from the photodetachment experiments wherein the ground state of the anion is the valence 2B1 state, while the dipole bound state lies adiabatically ∼0.1 eV above. Inclusion of triple excitations and zero-point vibrational energies is important for recovering relative state correct ordering. The computed Franck-Condon factors and photodetachment cross-sections further confirm that the observed photodetachment spectrum originates from the valence anion. The valence anion is electronically bound at its equilibrium geometry, but it is metastable at the equilibrium geometry of the neutral. The dipole-bound state, which is the only bound anionic state at the neutral equilibrium geometry, may serve as a gateway state for capturing the electron. Thus, the emerging mechanistic picture entails electron capture via a dipole bound state, followed by non-adiabatic relaxation forming valence anions.The absorption spectra of molecular organic chromophores in aqueous media are of considerable importance in environmental chemistry. In this work, the UV-vis spectra of benzoic acid (BA), the simplest aromatic carboxylic acid, in aqueous solutions at varying pH and in the presence of salts are measured experimentally. The solutions of different pH provide insights into the contributions from both the non-dissociated acid molecule and the deprotonated anionic species. The microscopic interpretation of these spectra is then provided by quantum chemical calculations for small cluster models of benzoic species (benzoic acid and benzoate anion) with water molecules. Calculations of the UV-vis absorbance spectra are then carried out for different clusters such as C6H5COOH·(H2O)n and C6H5COO-·(H2O)n, where n = 0-8. The following main conclusions from these calculations and the comparison to experimental results can be made (i) the small water cluster yields good quantitative agreement with observed solution experiments; (ii) the main peak position is found to be very similar at different levels of theory and is in excellent agreement with the experimental value, however, a weaker feature about 1 eV to lower energy (red shift) of the main peak is correctly reproduced only by using high level of theory, such as Algebraic Diagrammatic Construction (ADC); (iii) dissociation of the BA into ions is found to occur with a minimum of water molecules of n = 8; (iv) the deprotonation of BA has an influence on the computed spectrum and the energetics of the lowest energy electronic transitions; (v) the effect of the water on the spectra is much larger for the deprotonated species than for the non-dissociated acid.