Current medical guidelines consider pregnant women with COVID-19 to be a high-risk group. Since physiological gestation downregulates the immunological response to maintain “maternal-fetal ...tolerance”, SARS-CoV-2 infection may constitute a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients, a cross-sectional study was conducted. Pregnant women with COVID-19 (P-COVID-19+; n = 15) were analyzed and compared with nonpregnant women with COVID-19 (NP-COVID-19+; n = 15) or those with physiological pregnancy (P-COVID-19-; n = 13). Serological cytokine and chemokine concentrations, leucocyte immunophenotypes, and mononuclear leucocyte responses to polyclonal stimuli were analyzed in all groups. Higher concentrations of serological TNF-α, IL-6, MIP1b and IL-4 were observed within the P-COVID-19+ group, while cytokines and chemokines secreted by peripheral leucocytes in response to LPS, IL-6 or PMA-ionomicin were similar among the groups. Immunophenotype analysis showed a lower percentage of HLA-DR+ monocytes in P-COVID-19+ than in P-COVID-19- and a higher percentage of CD39+ monocytes in P-COVID-19+ than in NP-COVID-19+. After whole blood polyclonal stimulation, similar percentages of T cells and TNF+ monocytes between groups were observed. Our results suggest that P-COVID-19+ elicits a strong inflammatory response similar to NP-COVID19+ but also displays an anti-inflammatory response that controls the ATP/adenosine balance and prevents hyperinflammatory damage in COVID-19.
Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The ...antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3.
To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19.
Six different concentrations of lithium, ranging 2–12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls.
These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19′s patients.
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•Antiviral, anti-inflammatory and immune-potentiating effects of lithium salts have been described.•Lithium directly inhibits the replication of SARS-CoV-2 in Vero E6 cells in a concentration-dependent manner with an IC50 of 4 mmol/L.•Syrian hamsters treated with human therapeutic doses of lithium showed a less intense disease.
Real-life data associated with experimental outcomes are not always real-valued. In particular, opinions, perceptions, ratings, etc., are often assumed to be vague in nature, especially when they ...come from human valuations. Fuzzy numbers have extensively been considered to provide us with a convenient tool to express these vague data. In analyzing fuzzy data from a statistical perspective one finds two key obstacles, namely, the nonlinearity associated with the usual arithmetic with fuzzy data and the lack of suitable models and limit results for the distribution of fuzzy-valued statistics. These obstacles can be frequently bypassed by using an appropriate metric between fuzzy data, the notion of random fuzzy set and a bootstrapped central limit theorem for general space-valued random elements. This paper aims to review these ideas and a methodology for the statistical analysis of fuzzy number data which has been developed along the last years.
•Review on distances between fuzzy number-valued data for statistics.•Random fuzzy numbers and related summary measures.•Review on the statistical analysis of fuzzy number-valued data.
The Guadalquivir Valley is one of three major O3 hotspots in Spain. An airborne and surface measurement campaign was carried out from July 9th to 11th, 2019 to quantify the local/regional O3 ...contributions using experimental approaches. Air quality and meteorology data from surface measurements, a microlight aircraft, a helium balloon, and remote sensing data (TROPOMI-NO2-ESA) were used to obtain the 3D distribution of O3 and various tracer pollutants.
O3 accumulation over 2.5 days started with inputs from oceanic air masses transported inland by sea breezes, which drew O3 and its precursors from a local/regional origin to the northeastern end of the basin. The orographic–meteorological setting of the valley caused vertical recirculation of the air masses inside the valley that caused the accumulation by increasing regional background O3 concentration by 25–30 ppb. Furthermore, possible Mediterranean O3 contributions and additional vertical recirculation through the entrainment zone of the convective boundary layer also contributed. Using particulate matter finer than 2.5 μm (PM2.5), ultrafine particles (UFP), and black carbon (BC) as tracers of local sources, we calculated that local contributions increased regional O3 levels by 20 ppb inside specific pollution plumes transported by the breeze into the valley, and by 10 ppb during midday when flying over an area with abundant agricultural burning during the morning. Air masses that crossed the southern boundaries of the Betic system at mid-altitude (400–1850 m a.s.l.) on July 10th and 11th may have provided additional O3. Meanwhile, a decreasing trend at high altitudes (3000–5000 m a.s.l.) was observed, signifying that the impact of stratospheric O3 intrusion decreased during the campaign.
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•A complex orographic-meteorological scenario accommodated regional O3 accumulation.•The O3 accumulation increased O3 with 25–30 ppb due to the recirculating air masses.•On top of this, local contributions increased O3 levels up to 20 ppb.•Abundant agricultural burning increased O3 with 10 ppb later on the day.•Source-tracing pollutants were used to associate O3 peaks to specific sources.
This study aimed to assess whether primary health care professionals have accurate information regarding colorectal cancer (CRC) screening procedures, surveillance recommendations and referral ...strategies. This cross‐sectional descriptive study was based on a survey conducted among primary health care professionals in Barcelona, Spain. The questionnaire was used to gather information regarding CRC screening procedures as well as demographic and professional characteristics of the study subjects. A CRC and screening awareness score (ranging from 0 to 12) was created based on the survey questions. The response rate was 58.9% (206/305). The estimated mean score (standard deviation) was 8.43 (SD: 1.30). For four questions, more than 60% of the answers were incorrect: one related to risk factors, two concerning follow‐up colonoscopy, and one related to surveillance. Only 30.8% of the participants believed that they were responsible for determining the appropriate surveillance intervals and for scheduling colonoscopies. Although the professionals had sufficient knowledge of CRC screening, professional knowledge of some aspects related to the major non‐modifiable risk factors for the disease and surveillance colonoscopy procedures could be improved. Frequent communication with professionals is necessary to maintain updated screening‐related information. Possible methods for facilitating communication could include continuous briefings, regular message reminders or educational websites.
Abstract Objectives The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the ...Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. Materials and Methods The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged ≥ 65 years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. Results Mean time taken to complete the GAH scale was 11.9 ± 4.7 min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test–retest was excellent (ICC coefficients, 0.695–0.928). Conclusion Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.
Data obtained in association with many real-life random experiments from different fields cannot be perfectly/exactly quantified.\hspace{.1cm}Often the underlying imprecision can be suitably ...described in terms of fuzzy numbers/\\values. For these random experiments, the scale of fuzzy numbers/values enables to capture more variability and subjectivity than that of categorical data, and more accuracy and expressiveness than that of numerical/vectorial data. On the other hand, random fuzzy numbers/sets model the random mechanisms generating experimental fuzzy data, and they are soundly formalized within the probabilistic setting. This paper aims to review a significant part of the recent literature concerning the statistical data analysis with fuzzy data and being developed around the concept of random fuzzy numbers/sets.
Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are ...mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.
The effect of aging on indices of oxidative damage in rat mitochondria and the protective effect of the
Ginkgo biloba extract EGb 761 was investigated. Mitochondrial DNA from brain and liver of old ...rats exhibited oxidative damage that is significantly higher than that from young rats. Mitochondrial glutathione is also more oxidized in old than in young rats. Peroxide formation in mitochondria from old animals was higher than in those from young ones. According to morphological parameters (size and complexity), there are two populations of mitochondria. One is composed of large, highly complex mitochondria, and the other population is smaller and less complex. Brain and liver from old animals had a higher proportion of the large, highly complex mitochondria than seen in organs from young animals. Treatment with the
Ginkgo biloba extract EGb 761 partially prevented these morphological changes as well as the indices of oxidative damage observed in brain and liver mitochondria from old animals.
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