Application to nonlinear optical properties of the RSX-QIDH double-hybrid range-separated functional.

The effective calculation of static nonlinear optical properties requires a considerably high accuracy at a reasonable computational cost, to tackle challenging organic and inorganic systems acting as precursors and/or active layers of materials in (nano-)devices. That trade-off implies to obtain very accurate electronic energies in the presence of externally applied electric fields to consequently obtain static polarizabilities ( α i j ) and hyper-polarizabilities ( ß i j k and γ i j k l ). Density functional theory is known to provide an excellent compromise between accuracy and computational cost, which is however largely impeded for these properties without introducing range-separation techniques. We thus explore here the ability of a modern (double-hybrid and range-separated) Range-Separated eXchange Quadratic Integrand Double-Hybrid exchange-correlation functional to compete in accuracy with more costly and/or tuned methods, thanks to its robust and parameter-free nature.

Assessment of the nonempirical r2SCAN-QIDH double-hybrid density functional against large and diverse datasets.

We update the Quadratic Integrand Double-Hybrid (QIDH) model [J. Chem. Phys. 141, 031101 (2014)] by incorporating the nonempirical restored-regularized Strongly Constrained and Appropriately Normed (r2SCAN) meta-generalized gradient approximation exchange-correlation functional, thus devising a robust density functional approximation free of any empirical parameter and incorporating all the constraints so far known for the exchange-correlation kernel. We assessed the new r2SCAN-QIDH expression on the GMTKN55 database and further extend its application to various types of non-covalent interactions (e.g., S66 × 8, O24 × 5). The assessment done shows that the model becomes very competitive in accuracy with respect to parent exchange-correlation functionals of any type, but without relying on any fitted parameter or numerical training.

Relativistic effects on electronic pair densities: A perspective from the radial intracule and extracule probability densities.

While the effect of relativity in the electronic density has been widely studied, the effect on the pair probability, intracule, and extracule densities has not been studied before. Thus, in this work, we unveil new insights related to changes in the electronic structure caused by relativistic effects. Our numerical results suggest that the mean inter-electronic distance is reduced (mostly) due to scalar-relativistic effects. As a consequence, an increase in the electron-electron repulsion energy is observed. Preliminary results suggest that this observation is also valid when electronic correlation effects are considered.

Effect of marker dosage frequency and spot fecal sampling frequency in the prediction accuracy of fecal output using chromic oxide and titanium dioxide in grazing BON steers.

This study aimed to evaluate the effect of two marker dosage frequencies and two spot fecal sampling frequencies on the variability of fecal output estimation and fecal recovery rate in grazing Blanco Orejinegro (BON) steers with chromium (Cr) or titanium (Ti) as external markers. Four steers (230.5 ± 14.4 kg BW) were used in a 4 × 4 Latin square design in a split-plot arrangement with two markers: Cr or Ti, two marker dosage frequencies: 10.0 g Cr2O3 or TiO2/steer once daily (DF1) or 5.0 g Cr2O3 or TiO2/steer twice daily (DF2), and two fecal sampling frequencies: spot sampling once daily (SF1) or spot sampling twice daily (SF2). Steers were equipped with fecal collection bags to evaluate the actual fecal output (FOR). Fecal marker concentration (FMC) was affected by marker dosage frequency × fecal sampling frequency interaction (P = 0.032): SF1DF1 allowed higher FMC (2.26 g/kg DM) than SF2DF1 (1.95 g/kg DM). Chromium marker allowed higher estimated fecal output (FOe) values when compared to FOR (P < 0.001). Both Ti mean and SD bias (+ 0.074 ± 0.160 kg) were lower than Cr mean and SD bias (+ 0.312 ± 0.272 kg). The Ti fecal output prediction showed lower both RSR (0.586 vs 1.401) and MSPE (0.029 vs 0.167) than Cr prediction. The titanium external marker allowed fecal output estimation with more accuracy in grazing beef cattle trials. A protocol including a once-daily marker dosage associated with a once-daily fecal sampling is plausible, allowing good fecal recovery rates and accurate fecal output estimation.

Lipid changes and tolerability in a cohort of adult HIV-infected patients who switched to rilpivirine/emtricitabine/tenofovir due to intolerance to previous combination ART: the PRO-STR study.

Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5 ±âŸ38.4 mg/dL; week 48: 171.0 ±âŸ35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2 ±âŸ1.2; week 48: 4.0 ±âŸ1.2), HDL (baseline: 49.1 ±âŸ12.0 mg/dL; week 48: 49.2 ±âŸ45.8 mg/dL), LDL (baseline: 119.2 ±âŸ30.2 mg/dL; week 48: 114.2 ±âŸ110.7 mg/dL), and triglycerides (baseline: 136.6 ±âŸ86.8 mg/dL; week 48: 113.4 ±âŸ67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2 ±âŸ48.8 mg/dL; week 48: 173.4 ±âŸ36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7 ±âŸ1.6; week 48: 4.0 ±âŸ1.2), HDL (baseline: 46.4 ±âŸ12.5 mg/dL; week 48: 52.1 ±âŸ54.4 mg/dL), LDL (baseline: 127.0 ±âŸ36.3 mg/dL; week 48: 111.4 ±âŸ35.8 mg/dL), and triglycerides (baseline: 167.6 ±âŸ107.7 mg/dL; week 48: 122.7 ±âŸ72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.

Electron-Pair Distribution in Chemical Bond Formation.

The chemical formation process has been studied from relaxation holes, Δh(u), resulting from the difference between the radial intracule density and the nonrelaxed counterpart, which is obtained from atomic radial intracule densities and the pair density constructed from the overlap of the atomic densities. Δh(u) plots show that the internal reorganization of electron pairs prior to bond formation and the covalent bond formation from electrons in separate atoms are completely recognizable processes from the shape of the relaxation hole, Δh(u). The magnitude of Δh(u), the shape of Δh(u) ∀ u < Req, and the distance between the minimum and the maximum in Δh(u) provide further information about the nature of the chemical bond formed. A computational affordable approach to calculate the radial intracule density from approximate pair densities has been also suggested, paving the way to study electron-pair distributions in larger systems.

Efficacy and safety of switching to abacavir/lamivudine (ABC/3TC) plus rilpivirine (RPV) in virologically suppressed HIV-infected patients on HAART.

We analysed the efficacy and safety of switching from a regimen based on nonnucleoside reverse transcriptase inhibitors (NNRTI) or integrase inhibitors (INI) to ABC/3TC + RPV in virologically suppressed HIV-infected patients. This multicentre, retrospective study comprised asymptomatic HIV-infected patients who switched from 2 NRTI + NNRTI or 2 NRTI + INI to ABC/3TC + RPV between February 2013 and December 2013; all had undetectable HIV viral load prior to switching. Efficacy and safety, and changes in lipids and cardiovascular risk (CVR) were analysed at 48 weeks. Of 85 patients (74.1 % men, mean age 49.5 years), 83 (97.6 %) switched from a regimen based on NNRTI (EFV 74, RPV 5, ETV 2, NVP 2), and 45 (53 %) switched from TDF/FTC to ABC/3TC. The main reasons for switching were toxicity (58.8 %) and convenience (29.4 %). At 48 weeks, 78 (91.8 %) patients continued taking the same regimen; efficacy was 88 % by intention to treat, and 96 % by per protocol. Two patients were lost to follow-up and five ceased the new regimen (4 due to adverse effects and 1 virologic failure). Mean CD4 cell counts increased (744 vs. 885 cells/µL; p = 0.0001), and there were mean decreases in fasting total cholesterol (-15.9 mg/dL; p < 0.0001) and LDL-cholesterol (-11.0 mg/dL; p < 0.004), with no changes in HDL-cholesterol, triglycerides, total cholesterol:HDL-cholesterol ratio, and CVR. ABC/3TC + RPV is effective and safe in virologically-suppressed patients on antiretroviral therapy (ART). Forty-eight weeks after switching the lipid profile improved with decreases in total and LDL cholesterol.

Impact of maternal diabetes on birthweight is greater in non-Hispanic blacks than in non-Hispanic whites.

AIMS/HYPOTHESIS: To determine the impact of maternal diabetes during pregnancy on racial disparities in fetal growth. METHODS: Using linked birth certificate, inpatient hospital and prenatal claims data we examined live singleton births of mothers resident in South Carolina who self-reported their race as non-Hispanic white (NHW; n = 140,128) or non-Hispanic black (NHB; n = 82,492) and delivered at 28-42 weeks' gestation between 2004 and 2008. RESULTS: Prepregnancy diabetes prevalence was higher in NHB (3.0%) than in NHW (1.7%), while the prevalence of gestational diabetes mellitus (GDM) was similar in NHB (6.1%) and NHW (6.3%). At a delivery BMI of 35 kg/m(2), GDM exposure was associated with an average birthweight only 17 g (95% CI 4, 30) higher in NHW, but 78 g (95% CI 61, 95) higher in NHB (controlling for gestational age, maternal age, infant sex and availability of information on prenatal care). Figures for prepregnancy diabetes were 58 g (95% CI 34, 81) in NHW and 60 g (95% CI 37, 84) in NHB. GDM had a greater impact on birthweight in NHB than in NHW (60 g racial difference [95% CI 39, 82]), while prepregnancy diabetes had a large but similar impact. Similarly, the RR for GDM of having a large- relative to a normal-weight-for-gestational-age infant was lower in NHW (RR 1.41 [95% CI 1.34, 1.49]) than in NHB (RR 2.24 [95% CI 2.05, 2.46]). CONCLUSIONS/INTERPRETATION: These data suggest that the negative effects of GDM combined with obesity during pregnancy may be greater in NHB than in NHW individuals.

[Welcome to reading]. / Bienvenida la lectura.

No Abstract available.

We all want to know.

No Abstract available.

Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation.

Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.

Non-cellulosic polysaccharide content in feed ingredients and ileal and total tract non-cellulosic polysaccharide digestibility in 21- and 42-day-old broilers fed diets with and without added composite enzymes.

An initial study profiled non-cellulosic polysaccharide (NCP) levels in feed ingredient samples-corn, soybean meal (SBM), whole soybean, and distillers dried grains with solubles (DDGS). A separate NCP digestibility assay was performed in broilers at day 21 (grower phase) and day 42 (finisher phase) fed corn-soy based diets with and without composite enzymes (phytases, multi-carbohydrases, and proteases). Negative control (NC), NC + composite enzymes (NC+E), and positive control (PC) diets were tested. Negative control and NC + E diets were isocaloric, 3,020 kcal/kg ME at grower phase and 3,026 kcal/kg ME at finisher phase. Positive control diet was formulated to meet the Cobb standard nutrient specifications. Diets, pooled digesta, and excreta samples from all treatment diets were collected from 21- and 42-day-old birds and NCP content analyzed as soluble NCP (S-NCP) and insoluble NCP (I-NCP) fractions. Digestibility coefficient (DC) values were determined for all dietary treatments for both the feeding periods. Results from the ingredient analysis showed NCP levels of ∼7 to 10% in corn samples, ∼8 to 11% in SBM samples, ∼11 to 14% (including pectin level) in whole soybean, and ∼12 to 17% in DDGS samples, suggesting variation (P < 0.05) in NCP levels existed within ingredient samples. Digestibility assays showed that enzyme treated (NC + E) diet improved DC values at day 21 from 6 to 10 units and 6 to 9 units for ileal and total tract collection, respectively, for I-NCP fraction (P < 0.05) compared to DC values for NC or PC diets. The ileal DC values at day 42 were not different between treatment diets (∼0.6) but total tract DC values improved 9 to 11 units for broilers fed NC + E diet compared to NC or PC diets. Higher DC values for S-NCP were observed for all treatments for both feeding periods (∼0.7-ileal and ∼0.8-total tract) compared to DC values for I-NCP. Overall, the use of supplemental enzymes in corn-soy-based diets showed improvement in total NCP digestion.

Role of the water-drinking test in medically treated primary open angle glaucoma patients.

PURPOSE: The water-drinking test (WDT) has recently re-emerged as a possible way to determine the competency of the trabecular meshwork. We performed a prospective interventional study to test the hypothesis that the WDT could be useful in assessing fluctuations in patients undergoing treatment for primary open angle glaucoma (POAG). METHODS: We included 122 patients; 62 on medical treatment for POAG (n=123 eyes) and 60 controls (n=120 eyes). The study group had been on intraocular pressures (IOP) lowering treatment continuously for at least 3months with stable IOP. The WDT was performed during fasting and was considered positive if it fluctuated ≥6mmHg. RESULTS: The patients on medical treatment had a mean age of 50.56±18.45 years vs. 51.35±11.22 for the controls (P=0.34); with 71% being female in the study group and 77% in the control group. In the study group; 52% were on beta blockers (n=64), 27% combination of two or more medications (n=33), 19% prostaglandin analogues (n=24) and 2% alpha agonists (n=2). The WDT was positive in 17.07% (n=21) in the study group and 2.5% (n=3) in the control group (P=0.0001). The mean fluctuation was 7.14±2.15mmHg in the study group and 6.00±0mmHg in the controls (P=0.33). A positive WDT was found in 33.33% (n=11) of those on combination therapy; 12.5% (n=3) prostaglandin analogues and 10.94% (n=7) beta blockers (P=0.03). Combination therapy had the highest positive WDT fluctuation (7.54±2.87) followed by prostaglandin analogues (7.00±1.00) and beta blockers (6.57±0.78) with a P value of 0.44. CONCLUSIONS: The WDT can identify significant fluctuations in eyes with POAG that are medically treated.

Safety and Efficacy of Dolutegravir Plus Rilpivirine in Treatment-Experienced HIV-Infected Patients: The DORIVIR Study.

OBJECTIVES: To analyze the efficacy and safety of dolutegravir/rilpivirine (DTG/RPV) in HIV-infected patients who switched from any other antiretroviral therapy (ART). METHODS: Open-label, multicenter study including patients who switched to DTG/RPV between February 2015 and February 2016. Efficacy (HIV RNA <50 copies/mL), adverse events, and metabolic changes at 24 weeks were analyzed. RESULTS: A total of 104 participants were included, who switched for the following reasons: toxicity/intolerance (42.3%), convenience (27.8%), and drug interactions (17.3%). Prior regimens are protease inhibitor (56.7%), integrase strand transfer inhibitor (26.9%), and non-nucleoside reverse transcriptase inhibitor (16.3%). Efficacy at 24 weeks was 88.4% (intention to treat) and 96.8% (per protocol). Triglyceride levels were reduced, on average, by 12.7% and a mean decrease of 9.0% in the glomerular filtration rate was observed as well ( P values of .003 and .002, respectively), whereas total cholesterol, HDL cholesterol, LDL cholesterol, creatinine, and glutamic-pyruvic transaminase remained unchanged. No patient discontinued due to adverse events. CONCLUSIONS: Dolutegravir/RPV is effective and safe in long-term HIV-infected patients under any prior ART. Toxicity, convenience, and interactions were the main reasons for changing. At 24 weeks, the lipid profile improved with a decrease in triglycerides.

On the performance of natural orbital functional approximations in the Hubbard model.

Strongly correlated materials are now under intense development, and natural orbital functional (NOF) methods seem to be able to capture the physics of these systems. We present a benchmark based on the Hubbard model for a class of commonly used NOF approximations (also known as reduced density matrix functional approximations). Our findings highlight the importance of imposing ensemble N-representability conditions in order to obtain consistent results in systems with either weak or strong electronic correlation, such as the Hubbard system with a varying two-particle interaction parameter. Based on the accuracy of the results obtained using PNOF7, which retrieves a large amount of the total strong nondynamic correlation, the Hubbard model points out that N-representability gives solid foundations for NOF development.

Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance.

AIMS: To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS: We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS: PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS: Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.

A novel mutation in the E-cadherin gene in the first family with hereditary diffuse gastric cancer reported in Spain.

AIMS: Mutations of the E-cadherin gene (CDH1) result in dominantly inherited hereditary diffuse gastric cancer (HDGC). We report a study in the first family diagnosed with HDGC in Spain, examining the presence of mutations in the CDH1 gene. METHODS: The presence of mutations was studied by direct sequencing of all CDH1 exons. Immunohistochemical analysis with specific antibodies was used to detect the expression of E-cadherin in normal and tumour tissue. RESULTS: A novel 1610delC mutation in exon 11 has been found in a Spanish family diagnosed with HDGC. This mutation generates a premature stop codon at position 1667 giving rise to a truncated protein that lacks the transmembrane and beta-catenin-binding domains. The presence of a 1610delC germline mutation was confirmed in three family members diagnosed with diffuse gastric cancer, and also in six asymptomatic members. Of note, the diffuse gastric cancer coexisted with a gastric lymphoma in the proband. Furthermore, immunohistochemical analyses of tumour tissue showed the complete absence of E-cadherin in the proband, revealing a second genetic hit at the CDH1 locus. CONCLUSIONS: We have identified a HDGC family in Spain that carries a novel germline truncating mutation in the CDH1 gene.

Prognostic value of flow cytometry in surgically treated primary gastric lymphoma.

AIM: To investigate whether flow cytometry could help to define the optimal therapeutic strategy of primary gastric lymphomas. MATERIAL AND METHOD: Retrospective study of 46 patients having primary gastric lymphoma--according to Dawson criteria--in Ann Arbor stage IE and IIE, who were surgically treated. From selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by flow cytometry (FC). Other pathological tumor features were analysed by hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any possible influence on postoperative survival was investigated through statistical analysis. RESULTS: The DNA ploidy pattern was diploid in 40 cases (87%) and aneuploid (hyperdiploid) in 6 (13%). Postoperative survival probability (PSP) was 62.7% at 5 years. Statistical analysis showed significant prognostic value for Ann Arbor classification--with higher PSP for stage IE (p = 0.009)--and FC parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors having S-phase (p = 0.044) or G2-M phase values (p = 0.023) under the respective mean values had higher PSP. No influence on PSP was found for wall invasion, Helicobacter pylori infection, Isaacson's histologic type or resection margin involvement. No significant relationship was appreciated between Isaacson's histologic type and DNA ploidy patterns. CONCLUSION: FC could be useful in assessing gastric lymphoma prognosis.

[Autoimmune pancreatitis. An infrequent or underdiagnosed entity? Pathological, clinical and immunological characteristics]. / Pancreatitis autoinmune. 'Una entidad poco frecuente o infradiagnosticada? Características anatomopatológicas, clínicas e inmunológicas.

In the last few years, reports of pancreatic inflammatory diseases caused by immunological mechanisms and with good response to steroid treatment have increased. Although this entity has been known by a number of names, at present the most widely accepted is that of autoimmune chronic pancreatitis (ACP). The present report describes the clinical, immunological, morphological, functional and pathological characteristics of two patients recently studied at our unit and discusses currently used diagnostic tests. The two patients had a complete response to steroid therapy. In our opinion, ACP is probably underdiagnosed in Spain. The availability of morphological, pathological and serological diagnostic tools developed in recent years will help to precisely determine the epidemiology of this process. Thus, quantification of serum levels of anti-carbonic anhydrase II and IgG4 has greatly contributed to the diagnosis of ACP. These tests should be performed in patients with a possible diagnosis of ACP, those suffering from diabetes mellitus type I with impairment of exocrine function, and those with alcoholic pancreatitis and a poor response to alcohol elimination. Once we are able to diagnose and determine the real prevalence of ACP in our setting, the most appropriate therapy and prognosis of this disease can be established.