Sixty out-patients diagnosed as having hyperlipidaemia, with a cholesterol level of greater than 200 mg/dl and/or a triglycerides level of greater than 200 mg/dl, took part in the trial. Patients ...were divided at random into two groups to receive pharmacological treatment plus diet; one group was given 500 mg probucol twice a day and the other group 200 mg bezafibrate twice or 3-times a day for an average treatment period of 60 days. The percentage changes in serum lipids, i.e. total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol, were evaluated by comparing the values before and at the end of treatment, and tolerability of the drug in use was evaluated from the appearance of adverse reactions and the ECG and blood pressure parameters. Whereas total cholesterol and LDL-cholesterol levels were reduced to a similar extent in both groups (cholesterol - 42% bezafibrate, 38.3% probucol; LDL-cholesterol - 30.8% bezafibrate, 26.5% probucol), triglycerides were reduced to a significantly greater extent (p less than 0.05) in the benzafibrate group (55.5%) than in the probucol group (24.0%). The most significant percentage change (p less than 0.005) was found with HDL-cholesterol; in the bezafibrate group, levels increased by 19.0% compared with a 11.8% reduction in the probucol group. Four (13.3%) patients on bezafibrate and 5 (16.7%) on probucol reported mild to moderately severe side-effects, mainly gastro-intestinal, but in no case was treatment interrupted, although benzafibrate dosage was temporarily reduced. ECG changes (prolongation of QTc) were recorded in 3 patients on probucol and these reverted to normal after the end of the trial.
Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF ...inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.
•Post-COVID syndrome requires, besides symptoms, comprehensive organ damage assessment.•Post-covid syndrome is not limited to severe acute COVID19 patients.•Symptoms are mostly mild, improve with ...time, and with no identified predictors.•Radiological and spirometric changes are mild and observed in 25% of patients.•Our findings contribute to efficiently designing follow-up plans for COVID patients.
This study aims to analyze the incidence of Post-acute COVID-19 syndrome (PCS) and its components, and to evaluate the acute infection phase associated risk factors.
A prospective cohort study of adult patients who had recovered from COVID-19 (27th February to 29th April 2020) confirmed by PCR or subsequent seroconversion, with a systematic assessment 10–14 weeks after disease onset. PCS was defined as the persistence of at least one clinically relevant symptom, or abnormalities in spirometry or chest radiology. Outcome predictors were analyzed by multiple logistic regression (OR; 95%CI).
Two hundred seventy seven patients recovered from mild (34.3%) or severe (65.7%) forms of SARS-CoV-2 infection were evaluated 77 days (IQR 72–85) after disease onset. PCS was detected in 141 patients (50.9%; 95%CI 45.0–56.7%). Symptoms were mostly mild. Alterations in spirometry were noted in 25/269 (9.3%), while in radiographs in 51/277 (18.9%). No baseline clinical features behaved as independent predictors of PCS development.
A Post-acute COVID-19 syndrome was detected in a half of COVID19 survivors. Radiological and spirometric changes were mild and observed in less than 25% of patients. No baseline clinical features behaved as independent predictors of Post-acute COVID-19 syndrome development.
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Autism spectrum disorder (ASD) is a diverse group of neurodevelopmental conditions with complex origins. Individuals with ASD present various neurobiological abnormalities, including an altered ...immune response in the central nervous system and other tissues. Animal models like the C58/J inbred mouse strain are used to study biological characteristics of ASD. This strain is considered an idiopathic autism model because of its demonstrated reduced social preference and repetitive behaviours. Notably, C58/J mice exhibit alterations in dendritic arbour complexity, density and dendritic spines maturation in the hippocampus and prefrontal cortex (PFC), but inflammatory‐related changes have not been explored in these mice. In this study, we investigated proinflammatory markers in the hippocampus and PFC of adult male C58/J mice. We discovered elevated levels of interferon gamma (IFN‐γ) and monocyte chemoattractant protein 1 (MCP‐1) in the hippocampus, suggesting increased inflammation, alongside a reduction in the anti‐inflammatory enzyme arginase 1 (ARG1). Conversely, the PFC displayed reduced levels of TNF‐α and MCP‐1. Microglial analysis revealed higher levels of transmembrane protein 119 (TMEM119) and increased microglial density in a region‐specific manner of the autistic‐like mice, particularly in the PFC and hippocampus. Additionally, an augmented expression of the fractalkine receptor CX3CR1 was observed in the hippocampus and PFC of C58/J mice. Microglial morphological analysis shows no evident changes in the hippocampus of mice with autistic‐like behaviours versus wild‐type strain. These region‐specific changes can contribute to modulate processes like inflammation or synaptic pruning in the C58/J mouse model of idiopathic autism.
Our study highlights region‐specific neuroinflammatory differences in C58/J mice, an idiopathic model of autism. The hippocampus shows increased microglial density and inflammatory mediators, whereas the prefrontal cortex exhibits a trend toward increased microglial density and decreased inflammatory mediators. These findings imply distinct inflammatory and microglial activity modulation in C58/J mice with autistic‐like traits.
Abstract
A supervised intense aerobic exercise program improves the health of individuals with metabolic syndrome (MetS). However, it is unclear whether the timing of training within the 24 h day ...would influence those health benefits. The present study aimed to determine the influence of morning
vs
. afternoon exercise on body composition, cardiometabolic health and components of MetS. One hundred thirty‐nine individuals with MetS were block randomized into morning (AMEX;
n
= 42) or afternoon (PMEX;
n
= 59) exercise training groups, or a non‐training control group (Control;
n
= 38). Exercise training was comprised of 48 supervised high‐intensity interval sessions distributed over 16 weeks. Body composition, cardiorespiratory fitness (assessed by ), maximal fat oxidation (
FO
max
), blood pressure and blood metabolites were assessed before and after the intervention. Compared with the non‐training Control, both exercise groups improved similarly body composition (–0.7% fat loss;
P
= 0.002), waist circumference (–2.1 cm;
P
< 0.001), diastolic blood pressure (–3.8 mmHg;
P
= 0.004) and (3.5 mL kg
−1
min
−1
;
P
< 0.001) with no differences between training groups. AMEX, in comparison with PMEX, reduced systolic blood pressure (–4%
vs
. –1%;
P
= 0.019), plasma fasting insulin concentration (–12%
vs
. –5%;
P
= 0.001) and insulin resistance (–14%
vs
. –4%;
P
= 0.006). Furthermore, MetS
Z
score was further reduced in the AMEX compared to PMEX (–52%
vs
. –19%;
P
= 0.021) after training. In summary, high‐intensity aerobic exercise training in the morning in comparison to training in the afternoon is somewhat more efficient at reducing cardiometabolic risk factors (i.e. systolic blood pressure and insulin sensitivity).
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Key points
The effect of exercise time of day on health promotion is an area that has gained interest in recent years; however, large‐scale, randomized‐control studies are scarce.
People with metabolic syndrome (MetS) are at risk of developing cardiometabolic diseases and reductions in this risk with exercise training can be precisely gauged using a compound score sensitive to subtle evolution in each MetS component (i.e.
Z
score).
Supervised aerobic exercise for 16 weeks (morning and afternoon), without dietary restriction, improved cardiorespiratory and metabolic fitness, body composition and mean arterial pressure compared to a non‐exercise control group.
However, training in the morning, without changes in exercise dose or intensity, reduced systolic blood pressure and insulin resistance further compared to when training in the afternoon.
Thus, high‐intensity aerobic exercise training in the morning is somewhat more efficient in improving the health of individuals with metabolic syndrome.
is a plant empirically used to treat gastrointestinal and inflammatory diseases, its essential oil (EOTP) was obtained from the aerial parts, and the composition was elucidated by GC-MS. The in vivo ...and in vitro anti-inflammatory activities and the antinociceptive activity of EOTP and (1
)-(-)-verbenone (VERB) were assessed. The major compounds identified for EOTP were verbenone (33.39%), dihydrotagetone (26.88%), and tagetone (20.8%). EOTP and VERB diminished the ear oedema induced with TPA by 93.77 % and 81.13 %, respectively. EOTP and VERB decreased inflammation in a 12-O-tetradecanoylphorbol-13-acetate (TPA) chronic model with ED
= 54.95 mg/kg and 45.24 mg/kg, respectively. EOTP (15 µg/mL) inhibited the in vitro production of the pro-inflammatory mediators NO (67.02%), TNF-α (69.21%), and IL-6 (58.44%) in LPS-stimulated macrophages. In the acetic induced writhing test, EOTP and VERB showed antinociceptive effects with ED
= 84.93 mg/kg and ED
= 45.24 mg/kg, respectively. In phase 1 of the formalin test, EOTP and VERB showed no antinociceptive effects, whereas in phase 2, EOTP (ED
= 35.45 mg/kg) and VERB (ED
= 24.84 mg/kg) showed antinociceptive effects. The antinociceptive actions of ETOP and VERB were blocked with the co-administration of L-NAME. This study suggests that EOTP and VERB might be used in the treatment of pain and inflammatory problems.
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•The microbial community of lignocellulose-based composting was evaluated.•Microorganisms that persist throughout composting were identified.•Microorganisms from composting of ...biotechnological interest were selected.•The capability of selected isolates for composting bioaugmentation was studied.
The composting ecosystem is a suitable source for the discovery of novel microorganisms and secondary metabolites. This work analyzes the identity of microbial community that persists throughout lignocellulose-based composting, evaluates their metabolic activities and studies the capability of selected isolates for composting bioaugmentation. Bacterial species of the phyla Firmicutes, Actinobacteria and Proteobacteria and fungi of the phylum Ascomycota were ubiquitous throughout the composting. The species Arthrobacter russicus, Microbacterium gubbeenense, Ochrocladosporium frigidarii and Cladosporium lignicola are detected for the first time in this ecosystem. In addition, several bacterial and fungal isolates exhibited a wide range of metabolic capabilities such as polymers (lignocellulose, protein, lipids, pectin and starch) breakdown and phosphate-solubilization that may find many biotechnological applications. In particular, Streptomyces albus BM292, Gibellulopsis nigrescens FM1397 and FM1411, Bacillus licheniformis BT575, Bacillus smithii AT907 and Alternaria tenuissima FM1385 exhibited a great potential as inoculants for composting bioaugmentation.
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•CuZnO catalysts are active in hydrogenation of furfural to furfuryl alcohol.•The Cu–ZnO interaction is higher for lower copper loading.•Long term stability is improved in comparison ...with copper chromite.•Selectivity to furfuryl alcohol is higher at low H2 feed rates.
A series of Cu/ZnO catalysts (Cu:Zn molar ratio=0.2–6.0), prepared by coprecipitation and subsequent calcination and reduction, has been characterized and evaluated in the gas-phase hydrogenation of furfural (FUR). All catalysts exhibit high stability, with conversion values higher than 55mol% after 5h of time-on-stream (TOS) at 463K with a H2:FUR molar ratio of 11.5 and a WHSV of 1.5h−1. The best catalytic performance is found for the catalyst with the lowest copper loading, which maintains a conversion of 93mol% after 5h of TOS, with a selectivity of 82mol% towards furfuryl alcohol. After 24h of TOS, this catalyst still shows a furfuryl alcohol yield of 60mol%. The strong metal-support interactions in the catalysts with lower copper contents explain their higher stabilities. In all cases, the carbon percentages in the used catalysts are lower than 1.5%, thus indicating that carbonaceous deposits could be the cause of the slight deactivation of Cu/ZnO catalysts, together with metal sintering in catalysts with higher copper contents.
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