To determine whether mitochondrial, oxidative, and apoptotic abnormalities in placenta derived from HIV and combined antiretroviral therapy (cART) containing zidovudine (AZT) could be associated with ...adverse perinatal outcome.
Cross-sectional, controlled, observational study.
We studied obstetric results and mitochondrial, oxidative, and apoptotic state in placenta of 24 treated HIV-infected and 32 -uninfected pregnant women. We measured mitochondrial DNA (mtDNA) content by quantitative reverse transcriptase-polymerase chain reaction (mtND2/n18SrRNA), oxidative stress by the spectrophotometric quantification of lipid peroxidation and apoptosis by Western blot analysis of active caspase-3 respect to β-actin content and analysis of the terminal deoxynucleotidyl transferase dUTP nick end labeling.
Global adverse perinatal outcome (defined as preterm delivery or/and small newborns for gestational age) was significantly increased in HIV pregnancies or 6.7 (1.3-33.2); P < 0.05. mtDNA content in HIV-infected women was significantly depleted (39.20% ± 2.78%) with respect to controls (0.59 ± 0.03 vs. 0.97 ± 0.07; P < 0.001). A significant 29.50% ± 9.14% increase in oxidative stress was found in placentas of HIV-infected women (23.23 ± 1.64 vs. 17.94 ± 1.03; P < 0.01). A trend toward 41.18% ± 29.41% increased apoptosis active caspase-3/β-actin was found in HIV patients (0.48 ± 0.10 vs. 0.34 ± 0.05; P = not significant), confirmed by transferase dUTP nick end labeling assay. Adverse perinatal outcome did not correlate mitochondrial, oxidative, or apoptotic findings.
Placentas of HIV-infected pregnant women under AZT cART showed evidence of mtDNA depletion, increased oxidative stress levels, and apoptosis suggestive of secondary mitochondrial failure, potential base of associated adverse perinatal outcome. Despite the fact that further demonstration of causality would need new approaches and bigger sample sizes, AZT-sparing cART should be considered in the context of pregnancy.
The elderly population frequently consults the emergency department (ED). This population could have greater use of EDs and hospital health resources. The EDEN cohort of patients aged 65 years or ...older visiting the ED allowed this association to be investigated. To analyse the association between healthcare resource use and the characteristics of patients over 65 years of age who consult hospital EDs. We performed an analysis of the EDEN cohort, a retrospective, analytical, and multipurpose registry that includes patients over 65 years of age who consulted in 52 Spanish EDs. The impact of age, sex, and characteristics of ageing on the following outcomes was studied: need for hospital admission (primary outcome) and need for observation, stay in the ED > 12 h, prolonged hospital stay > 7 days, need for intensive care unit (ICU) and return to the ED at 30 days related to the index visit (secondary outcomes). The association was analysed by calculating the adjusted odds ratios (aOR) and their 95% confidence intervals (CI), using a logistic regression model. A total of 25,557 patients with a mean age of 78.3 years were analysed, 45% were males. Of note was the presence of comorbidity, a Charlson index ≥ 3 (33%), and polypharmacy (66%). Observation in the ED was required by 26%, 25.4% were admitted to the hospital, and 0.9% were admitted to the ICU. The ED stay was > 12 h in 12.5% and hospital stay > 7 days in 13.5% of cases. There was a progressive increase in healthcare resource use based on age, with an aOR for the need for observation of 2.189 (95% CI 2.038-2.352), ED stay > 12 h 2.136 (95% CI 1.942-2.349) and hospital admission 2.579 (95% CI 2.399-2.772) in the group ≥ 85 years old. Most of the characteristics inherent to ageing (cognitive impairment, falls in the previous 6 months, polypharmacy, functional dependence, and comorbidity) were associated with significant increases in the use of healthcare resources, except for ICU admission, which was less in all the variables studied. Age and the characteristics inherent to ageing are associated with greater use of structural healthcare resources.The elderly population frequently consults the emergency department (ED). This population could have greater use of EDs and hospital health resources. The EDEN cohort of patients aged 65 years or older visiting the ED allowed this association to be investigated. To analyse the association between healthcare resource use and the characteristics of patients over 65 years of age who consult hospital EDs. We performed an analysis of the EDEN cohort, a retrospective, analytical, and multipurpose registry that includes patients over 65 years of age who consulted in 52 Spanish EDs. The impact of age, sex, and characteristics of ageing on the following outcomes was studied: need for hospital admission (primary outcome) and need for observation, stay in the ED > 12 h, prolonged hospital stay > 7 days, need for intensive care unit (ICU) and return to the ED at 30 days related to the index visit (secondary outcomes). The association was analysed by calculating the adjusted odds ratios (aOR) and their 95% confidence intervals (CI), using a logistic regression model. A total of 25,557 patients with a mean age of 78.3 years were analysed, 45% were males. Of note was the presence of comorbidity, a Charlson index ≥ 3 (33%), and polypharmacy (66%). Observation in the ED was required by 26%, 25.4% were admitted to the hospital, and 0.9% were admitted to the ICU. The ED stay was > 12 h in 12.5% and hospital stay > 7 days in 13.5% of cases. There was a progressive increase in healthcare resource use based on age, with an aOR for the need for observation of 2.189 (95% CI 2.038-2.352), ED stay > 12 h 2.136 (95% CI 1.942-2.349) and hospital admission 2.579 (95% CI 2.399-2.772) in the group ≥ 85 years old. Most of the characteristics inherent to ageing (cognitive impairment, falls in the previous 6 months, polypharmacy, functional dependence, and comorbidity) were associated with significant increases in the use of healthcare resources, except for ICU admission, which was less in all the variables studied. Age and the characteristics inherent to ageing are associated with greater use of structural healthcare resources.
Background
Acute heart failure (AHF) patients with high troponin levels have a worse prognosis. High‐sensitive troponin T (hs‐TnT) has been used as a tool to stratify prognosis in many scales but ...always as a qualitative and not as a quantitative variable.
Objectives
The main objective of this study was to determine the best hs‐TnT cut‐off for prediction of 30‐day all‐cause mortality.
Methods
The EAHFE registry, a prospective follow‐up cohort of patients with AHF, was analysed. We performed a propensity score analysis of the optimal hs‐TnT cut‐off point previously determined by receiver operating characteristic (ROC) curve analysis.
Results
Of the 13 791 patients in the EAHFE cohort, we analysed 3190 patients in whom hs‐TnT determination was available. The area under the ROC curve for 30‐day all‐cause mortality was 0.70 (CI95% 0.68 to 0.71; P < .001), establishing an optimal cut‐off of hs‐TnT of 35 ng/L. The sensitivity and specificity of this cut‐off were 76.2 and 55.5%, respectively, with a negative predictive value (NPV) of 95.3%. A propensity score was made with 34 variables showing differences based on the cut‐off of 35 ng/L for hs‐TnT. In the analysis of the population obtained with the propensity score, patients with hs‐TnT > 35 ng/L showed a greater 30‐day all‐cause mortality, with a HR of 2.95 (CI95% 1.83‐4.75; P < .001). External validation reported similar results.
Conclusions
An hs‐TnT value of 35 ng/L is an adequate cut‐off to evaluate the prediction of 30‐day all‐cause mortality with a NPV of 95.3%.
To compare the efficacy and safety of a nucleoside-sparing approach with a conventional highly active antiretroviral therapy (HAART) regimen in antiretroviral-experienced patients with prolonged ...viral suppression.
Pilot study including 31 antiretroviral-experienced patients with HIV RNA <80 copies/mL. Subjects were randomly assigned to lopinavir/ritonavir (LPV/rtv) 400/100 mg BID plus nevirapine (NVP) 200 mg BID (NVP group, n = 16) or LPV/rtv plus the 2 previous NRTIs (NRTI group, n = 15). The primary endpoint was the percentage of subjects who maintained viral suppression at week 48. Changes in lipid metabolism, mitochondrial parameters, and LPV trough levels were also assessed.
All patients maintained viral suppression after 48 weeks. No subject discontinued therapy because of adverse events. HDL cholesterol increased by 28% at week 24 (P < 0.0001) and 10% after 48 weeks of follow-up (P = 0.319) in the NVP group. In the NRTI group, LDL cholesterol increased by 14% at week 48 (P = 0.076). Mitochondrial DNA/nuclear DNA ratio and mitochondrial respiratory chain complex IV activity showed a trend toward increasing in the NVP group. Mean (SD) LPV trough levels were 6340 (2129) ng/mL in the NRTI group and 5161 (2703) ng/mL in the NVP group (P = 0.140).
In antiretroviral-experienced subjects with sustained viral suppression, dual therapy with NVP plus LPV/rtv at standard dosage was as potent and safe as standard-of-care HAART at 48 weeks of follow-up. This approach may reduce mitochondrial toxicity and improve LPV/rtv-associated lipid abnormalities. The results of this pilot study support the study of this approach in a larger, randomized trial.
The recycling and revalorization of wastes from the agri-food industry (AFI) have emerged in the scientific scenario as a multidisciplinary working field in the framework of the circular bioeconomy. ...Residues and side materials from AFI result in a great source of raw products with increasing social and economic impact. In this regard, phenolic compounds are possibly the most relevant group of phytochemicals from AFI wastes because of their multiple healthy properties, including antioxidant, anti-inflammatory, hypolipidemic, and antibacterial activities. Among other sources, olive oil, winemaking, and fruit and vegetable juice wastes have been considered to assess their revalorization. The paper reviews the recovery and characterization of AFI waste extracts to generate by-products rich in polyphenols for chemical, nutraceutical, and food science applications. Polyphenols are recovered from AFI waste by solvent extraction with conventional and advanced techniques. The resulting extracts are complex, and the major phenolic compounds should be identified and quantified. The profiling of analytes such as proanthocyanins, curcuminoids, resveratrol derivatives, caffeic acids, and oleuropein is often performed by liquid chromatography with UV/Vis or fluorescence detection. Additionally, liquid chromatography coupled to mass spectrometry is the technique of choice for the unambiguous identification of target compounds and structural elucidation of new and unknown molecules. Complementarily, the antioxidant activity of the extracts can be determined using spectrophotometric assays.
•Heart failure is a very prevalent condition in people older than 65 years and, therefore, it is important to investigate the factors that are involved in the increase of both morbidity and ...mortality.•In the era of vaccination in which we find ourselves, it is important to try continuously to show the protective effects of this medical tool, in this case, not only in patients with chronic heart failure but also in those with acute heart failure.•Spending time researching the methods can protect our patients who suffer from heart failure gives us more possibilities for improving their quality of life and their life expectancy.
To investigate the relationship of seasonal flu vaccination with the severity of decompensation and long-term outcomes of patients with heart failure (HF).
We analyzed 6147 consecutively enrolled patients with decompensated HF who presented to 33 Spanish emergency departments (EDs) during January and February of 2018 and 2019, grouped according to seasonal flu vaccination status. The severity of HF decompensation was assessed by the Multiple Estimation of Risk Based on the Emergency Department Spanish Score in Patients With Acute Heart Failure (MEESSI-AHF) + MEESSI scale, need of hospitalization and in-hospital all-cause mortality. The long-term outcomes analyzed were 90-day postdischarge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions by using 14 covariables that could act as potential confounders.
Overall median (IQR) age was 84 (IQR = 77-89) years, and 56% were women. Vaccinated patients (n = 1139; 19%) were older, had more comorbidities and had worse baseline status, as assessed by New York Heart Association class and Barthel index, than did unvaccinated patients (n = 5008; 81%). Infection triggering decompensation was more common in vaccinated patients (50% vs 41%; P < 0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%; hospitalization occurred in 72.5% and 73.7%; in-hospital mortality was 7.4% and 7.0%; 90-day postdischarge adverse events were 57.4% and 53.2%; and the 90-day mortality rate was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated patients with HF had decreased odds for hospitalization (OR = 0.823, 95%CI = 0.709–0.955).
In patients with HF, seasonal flu vaccination is associated with less severe decompensations.
Display omitted
Successful Tumor Electrochemotherapy Using Sine Waves Garcia-Sanchez, Tomas; Mercadal, Borja; Polrot, Melanie ...
IEEE transactions on bio-medical engineering/IEEE transactions on biomedical engineering,
04/2020, Letnik:
67, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Objective: The purpose of this work is to assess the ability of sine waves to perform electrochemotherapy (ECT) and to study the dependence of the frequency of the applied sine wave on the treatment ...efficacy. Methods: A subcutaneous tumor model in mice was used, and the electric field was delivered in combination with bleomycin. Sinusoidal electric fields of different frequencies, amplitudes, and durations were compared to square waves. Computer simulations were additionally performed. Results: The results confirmed the ability of a sinusoidal electric field to obtain successful ECT responses. A strong dependence on frequency was obtained. The efficacy of the treatment decreased when the frequency of the sine waves was increased. At low sinusoidal frequency, the efficacy of the treatment is very similar to that obtained with a square wave. The collateral effects such as skin burns and muscle contractions decreased for the highest frequency assayed. Conclusion: The use of sine wave burst represents a feasible option for the treatment of cancer by ECT. Significance: These results could have important implications for the treatment of cancer in the clinical world where ECT is performed with dc square pulses.
Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital ...lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b
mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b
mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.
Helper-type innate lymphoid cells (ILC) play an important role in intestinal homeostasis. Members of the NKR-P1 gene family are expressed in various innate immune cells, including natural killer (NK) ...cells, and their cognate Clr ligand family members are expressed in various specialized tissues, including the intestinal epithelium, where they may play an important role in mucosal-associated innate immune responses. In this study, we show that the inhibitory NKR-P1B receptor, but not the Ly49 receptor, is expressed in gut-resident NK cells, ILC, and a subset of γδT cells in a tissue-specific manner. ILC3 cells constitute the predominant cell subset expressing NKR-P1B in the gut lamina propria. The known NKR-P1B ligand Clr-b is broadly expressed in gut-associated cells of hematopoietic origin. The genetic deletion of NKR-P1B results in a higher frequency and number of ILC3 and γδT cells in the gut lamina propria. However, the function of gut-resident ILC3, NK, and γδT cells in NKR-P1B-deficient mice is impaired during gastrointestinal tract infection by Citrobacter rodentium or Salmonella typhimurium, resulting in increased systemic bacterial dissemination in NKR-P1B-deficient mice. Our findings highlight the role of the NKR-P1B:Clr-b recognition system in the modulation of intestinal innate immune cell functions.
PDF