The goal of the study was to evaluate the effect of adding linagliptin to metformin and lifestyle on glucose levels and pancreatic β-cell function in patients with persistent impaired glucose ...tolerance (IGT) after 12 months of metformin and lifestyle. A single center parallel double-blind randomized clinical trial with 6 months of follow-up was performed in patients with persistent IGT after 12 months of treatment with metformin and lifestyle; patients were randomized to continue with metformin 850 mg twice daily (M group, n = 12) or linagliptin/metformin 2.5/850 mg twice daily (LM group, n = 19). Anthropometric measurements were obtained by standard methods and by bioelectrical impedance; glucose was measured by dry chemistry, insulin by chemiluminescence, and pancreatic β-cell function was calculated with the disposition index using glucose and insulin values during oral glucose tolerance test (OGTT) and adjusting by insulin sensitivity. The main outcomes were glucose levels during OGTT and pancreatic β-cell function. Patients in the LM group had a reduction in weight (-1.7 ± 0.6, p < 0.05) and body mass index (BMI, -0.67 ± 0.2, p < 0.05). Glucose levels significantly improved in LM group with a greater reduction in the area under the glucose curve during OGTT (AUCGluc
) as compared to the M group (-4425 ± 871 vs -1116 ± 1104 mg/dl/120 min, p < 0.001). Pancreatic β-cell function measured with the disposition index, improved only in LM group (2.3 ± 0.23 vs 1.7 ± 0.27, p 0.001); these improvements persisted after controlling for OGTT glucose levels. The differences in pancreatic β-cell function persisted also after pairing groups for basal AUCGluc
. The addition of linagliptin to patients with persistent IGT after 12 months of treatment with metformin and lifestyle, improved glucose levels during OGTT and pancreatic β-cell function after 6 months of treatment.Trial registration: Clinicaltrials.gov with the ID number NCT04088461.
Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key ...enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from
, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.
To understand the effects of frailty, geriatric syndromes, and comorbidity on quality of life and mortality in older adults with HIV (OAWH).
Cross-sectional study of the FUNCFRAIL multicenter cohort. ...The setting was outpatient HIV-Clinic. OAWH, 50 year or over were included. We recorded sociodemographic data, HIV infection-related data, comorbidity, frailty, geriatric syndromes (depression, cognitive impairment, falls and malnutrition), quality of life (QOL) and the estimated risk of all-cause 5-year mortality by VACS Index. Association of frailty with geriatric syndromes and comorbidity was evaluated using the Cochran-Mantel-Haenszel test.
Seven hundred ninety six patients were included. 24.7% were women, mean age was 58.2 (6.3). 14.7% were 65 or over. 517 (65%) patients had ≥3 comorbidities, ≥ 1 geriatric syndrome and/or frailty. There were significant differences in the estimated risk of mortality (frailty 10.8%) vs. (≥ 3 comorbidities 8.2%) vs. (≥ 1 geriatric syndrome 8.2%) vs. (nothing 6.2%); p = 0.01 and in the prevalence of fair or poor QOL (frailty 71.7%) vs. (≥ 3 comorbidities 52%) vs. (≥ 1 geriatric syndrome 58.4%) vs. (nothing 51%); p = 0.01. Cognitive impairment was significantly associated to mortality (8.7% vs. 6.2%; p = 0.02) and depression to poor QOL 76.5% vs. 50%; p = 0.01.
Frailty, geriatric syndromes, and comorbidity had negative effects on mortality and QOL, but frailty had the greatest negative effect out of the three factors. Our results should be a wake-up call to standardize the screening for frailty and geriatric syndromes in OAWH in the clinical practice.
NCT03558438.
The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques ...offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested.
Prospective cross-sectional study including PHIV and uninfected controls.
Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated.
Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (P = 0.04).
The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.
The new Eurocode 2 provides valuable information on the required concrete cover to protect reinforcement against corrosion induced by carbonation, for two design service life values of 50 and 100 ...years. However, to design structures with an even longer service life and assess existing ones, additional tools are necessary. The ‘square root of time’ relationship is a well-established method for estimating the penetration of the carbonation front, making it useful for long-term design and assessment purposes. In this article, we propose a new function that adjusts the evolution of the carbonation front to the Eurocode 2 values. This function is a powerful tool for designing extremely durable structures and assessing existing ones. To demonstrate its effectiveness, we provide two examples of its application.
The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple ...treatment with a boosted protease inhibitor (TT).
This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts.
Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT.
In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.
A tensegrity family is a group of tensegrity structures that share a common connectivity pattern. The three first members of the Octahedron family are the octahedron, the expanded octahedron and the ...double-expanded octahedron. In this work a new family is presented: the X-Octahedron family. If in the elementary rhombic cells of the Octahedron family a diagonal cable is introduced then X-rhombic cells are obtained, resulting in tensegrity forms that belongs to the new family. Three members of the family have been obtained: the X-octahedron, the X-expanded octahedron and the X-double-expanded octahedron. Several element groupings have been considered in order to find new equilibrium shapes of the members of the new family. The values of the force:length ratios which satisfy the super-stability conditions have been computed analytically.
Traditionally, reinforced concrete (RC) piles for earth retaining systems have been designed using symmetrical reinforcement. The non-symmetric or asymmetric RC pile is a recently patented structural ...element. Savings of up to 50% of longitudinal reinforcing steel can be obtained using non-symmetrically reinforced piles in comparison with traditional symmetrical ones. In this work, the calculation of the short-term deflection of cracked RC piles using the concept of effective moment of inertia is investigated. Five specimens with both symmetric and asymmetric reinforcements were tested in four-point bending tests. In addition, a numerical finite element analysis of symmetric and non-symmetric circular RC members was also carried out to enlarge the available database. The widely used expressions of effective moments of inertia proposed by Branson and Bischoff (originally conceived for rectangular sections) were adapted to fit experimental and numerical results. Both symmetrically and asymmetrically reinforced concrete elements were studied. Keywords: Bischoff equation; Branson equation; circular reinforced concrete sections; effective moment of inertia; reinforced concrete (RC); wall pile.
Abstract
Background
The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and ...safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy.
Methods
In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1–2 months (M) apart 4–18M posttransplant. Anti–glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post–dose 1, and 1M and 12M post–dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post–dose 2.
Results
Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post–dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups.
Conclusions
RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose.
Clinical Trials Registration
NCT02058589.
The adjuvanted recombinant zoster vaccine was immunogenic in renal transplant recipients receiving daily immunosuppressive treatment. Humoral and cell-mediated immune responses persisted through 1 year postvaccination. Vaccination had no impact on renal function or rejection rate. No safety concerns arose.
Octahedron family: The double-expanded octahedron tensegrity Fernández-Ruiz, Manuel Alejandro; Hernández-Montes, Enrique; Carbonell-Márquez, Juan Francisco ...
International journal of solids and structures,
06/2019, Letnik:
165
Journal Article
Recenzirano
Odprti dostop
The octahedron family of tensegrity structures is presented in this research. The octahedron and the expanded octahedron (well-known tensegrities in the literature) are the first and second ...components of the family. A new tensegrity is presented: the double-expanded octahedron. This new tensegrity form was obtained following the connectivity pattern of the octahedron family presented in this work. The values of the force densities or force:length ratios that satisfy the minimum required rank deficiency of the force density matrix were computed analytically. Two types of solutions are obtained: full and folded forms. Results show that each lower member of the octahedron family is a folded form of a superior member of this family. Several examples are shown.
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