The immune response type organized against viral infection is determinant in the prognosis of some infections. This work has aimed to study Th polarization in acute COVID-19 and its possible ...association with the outcome through an observational prospective study. Fifty-eight COVID-19 patients were recruited in the Medicine Department of the hospital "12 de Octubre," 55 patients remaining after losses to follow-up. Four groups were established according to maximum degree of disease progression. T-helper cell percentages and phenotypes, analyzed by flow cytometer, and serum cytokines levels, analyzed by Luminex, were evaluated when the microbiological diagnosis (acute phase) of the disease was obtained. Our study found a significant reduction of %Th1 and %Th17 cells with higher activated %Th2 cells in the COVID-19 patients compared with reference population. A higher percent of senescent Th2 cells was found in the patients who died than in those who survived. Senescent Th2 cell percentage was an independent risk factor for death (OR: 13.88) accompanied by the numbers of total lymphocytes (OR: 0.15) with an AUC of 0.879. COVID-19 patients showed a profile of pro-inflammatory serum cytokines compared to controls, with higher levels of IL-2, IL-6, IL-15, and IP-10. IL-10 and IL-13 were also elevated in patients compared to controls. Patients who did not survive presented significantly higher levels of IL-15 than those who recovered. No significant differences were observed according to disease progression groups. The study has shown that increased levels of IL-15 and a high Th2 response are associated with a fatal outcome of the disease.
Synovitis and tenosynovitis are present in juvenile idiopathic arthritis (JIA), both as joint pain and/or inflammation, making them difficult to detect on physical examination. Although ...ultrasonography (US) allows for discrimination of the 2 entities, only definitions and scoring of synovitis in children have been established. This study was undertaken to produce consensus-based US definitions of tenosynovitis in JIA.
A systematic literature search was performed. Selection criteria included studies focused on US definition and scoring systems for tenosynovitis in children, as well as US metric properties. Through a 2-step Delphi process, a panel of international US experts developed definitions for tenosynovitis components (step 1) and validated them by testing their applicability on US images of tenosynovitis in several age groups (step 2). A 5-point Likert scale was used to rate the level of agreement.
A total of 14 studies were identified. Most used the US definitions developed for adults to define tenosynovitis in children. Construct validity was reported in 86% of articles using physical examination as a comparator. Few studies reported US reliability and responsiveness in JIA. In step 1, experts reached a strong group agreement (>86%) by applying adult definitions in children after one round. After 4 rounds of step 2, the final definitions were validated on all tendons and at all locations, except for biceps tenosynovitis in children <4 years old.
The study shows that the definition of tenosynovitis used in adults is applicable to children with minimal modifications agreed upon through a Delphi process. Further studies are required to confirm our results.
Health Staff Perceptions of Hate Violence in Spain Fernández de Castro, Patricia; Hipólito Ruiz, Natalia; Díaz Herráiz, Eduardo
International journal of environmental research and public health,
07/2021, Letnik:
18, Številka:
14
Journal Article
Recenzirano
Odprti dostop
The aim of this study of Spanish health personnel is to determine their level of knowledge about hate violence and their relevance in detecting victims of hate violence and clarifying the magnitude ...of the phenomenon. An exploratory study with a descriptive, observational, and cross-sectional design was conducted, with incidental non-probabilistic sampling and an ad hoc questionnaire to health professionals in three Autonomous Communities of Spain. Our results indicate a general lack of knowledge about hate violence by health staff who acknowledged that they do not have specific training for hate violence victims’ care, although most staff had attended to some cases of hate violence in the last year. No significant differences were found among healthcare services, professionals, training, or Autonomous Communities, which indicated a generalized lack of training and specific tools that was common in the different health services and in different Autonomous Communities in Spain. The health services that reported most cases of hate violence ex officio were those in which the professionals had more training and knowledge and in which there were specific protocols on hate violence. In conclusion, the health system constitutes “the gateway” to the care, promotion, and prevention of hate violence victims. However, political actions are necessary to avoid the lack of knowledge and lack of training and professional tools that are widespread among healthcare staff. Therefore, the training of professionals and the establishment of specific protocols for action against hate violence would improve the care and long-term monitoring of victims, and the implementation of an epidemiological registry and surveillance system of hate violence would improve the care and prevention of hate violence in Spain.
One of the proposed mechanisms for the development of diabetic nephropathy (DN) is the increase of end products of advanced glycosylation (AGEs), which bind to its receptor (RAGE), favoring nephron ...cellular damage. An isoform of this receptor is soluble RAGE (sRAGE), which can antagonize AGE-altered intracellular signaling. It has known that green tea extract (GTE) increases the expression of sRAGE, but it is unknown whether this could improve kidney function. The objective of this study was to evaluate the effect of the administration of GTE on the concentrations of sRAGE, renal function, and metabolic profile in patients with type 2 diabetes mellitus (T2DM) and DN. A randomized, double-blinded, placebo-controlled clinical trial was carried out in 39 patients who received GTE (400 mg every 12 h) or placebo for 3 months. sRAGE levels, renal function, and metabolic parameters were determined before and after the intervention. In the GTE group, there were statistically significant increase on sRAGE (320.55 ± 157.63 pg/mL vs. 357.59 ± 144.99 pg/mL;
= .04) and glomerular filtration rate (GFR; 66.44 ± 15.17 mL/min/1.73 m
vs. 71.70 ± 19.33 mL/min/1.73 m
;
= .04), and a statistically significant decrease in fasting serum glucose (7.62 ± 3.00 mmol/L vs. 5.86 ± 1.36 mmol/L;
≤ .01) and triacylglycerols (1.91 ± 0.76 mmol/L vs. 1.58 ± 0.69;
= .02). Administration of GTE increases the serum concentration of sRAGE and the GFR and decreases the concentration of fasting serum glucose and triacylglycerols. The study was registered in ClinicalTrials.gov with the identifier NCT03622762.
Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired ...pneumonia (CAP). In different regions of the world, monotherapy with a beta-lactam antimicrobial is common.
We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage.
A secondary analysis was performed using two comprehensive international databases. World regions were defined as North America (I), Europe (II), Latin America (III), and Asia and Africa (IV). Time to reach clinical stability, length of hospital stay, and mortality were compared between patients treated with and without atypical coverage.
The incidence of CAP due to atypical pathogens from 4,337 patients was 22, 28, 21, and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91, 74, 53, and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 d, p < 0.001), decreased length of stay (7.1 vs. 6.1 d, p < 0.01), decreased total mortality (11.1 vs. 7%, p < 0.01), and decreased CAP-related mortality (6.4 vs. 3.8%, p = 0.05).
The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens.
Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic ...treatment, although there are cases related to failure of the deep brain stimulation system.
Cell reprogramming in response to jasmonates requires a tight control of transcription that is achieved by the activity of JA-related transcription factors (TFs). Among them, MYC2, MYC3 and MYC4 have ...been described as activators of JA responses. Here we characterized the function of bHLH003, bHLH013 and bHLH017 that conform a phylogenetic clade closely related to MYC2, MYC3 and MYC4. We found that these bHLHs form homo- and heterodimers and also interact with JAZ repressors in vitro and in vivo. Phenotypic analysis of JA-regulated processes, including root and rosette growth, anthocyanin accumulation, chlorophyll loss and resistance to Pseudomonas syringae, on mutants and overexpression lines, suggested that these bHLHs are repressors of JA responses. bHLH003, bHLH013 and bHLH017 are mainly nuclear proteins and bind DNA with similar specificity to that of MYC2, MYC3 and MYC4, but lack a conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Moreover, expression of bHLH017 is induced by JA and depends on MYC2, suggesting a negative feed-back regulation of the activity of positive JA-related TFs. Our results suggest that the competition between positive and negative TFs determines the output of JA-dependent transcriptional activation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Objective
Our aims were to improve the understanding of the pathogenic relationship between cardiovascular diseases and periodontitis and to generate new perspectives in the prevention ...and treatment of acute myocardial infarction (AMI) and periodontitis. The present study evaluates possible differences in inflammation, oxidative stress, and autophagy markers among subject suffering AMI, periodontitis, or both, to explore possible common pathogenic mechanisms.
Material and Methods
A total of 260 subjects were enrolled in the study: 106 subjects that survived to a first AMI (AMI group) and 154 subjects had no cardiac events in their clinical record (control group). A questionnaire was used to assess age, height, weight, blood pressure, and heart rate. The clinical probing depth, clinical attachment loss, number of remaining teeth, and average number of sites with bleeding on probing were assessed. Lipid peroxidation and protein levels of phosphorylated AMP‐activated protein kinase (p‐AMPK) and microtubule‐associated proteins 1A/1B‐light chain 3‐II (LC3‐II) were determined in isolated peripheral blood mononuclear cells by thiobarbituric acid reactive substances (TBARS) assay and Western blot, respectively. Plasma levels of interleukin‐1β were determined using a commercial ELISA kit. All the obtained variables were compared between subjects suffering an AMI with or without periodontitis and control subject periodontal healthy or with periodontitis.
Results
A higher proportion of subjects suffering AMI + periodontitis than only AMI (without periodontitis) was found. Higher levels of TBARS were found in subjects with periodontitis than in subjects without periodontitis in both AMI and control subjects. Positive correlations between IL‐1β levels and TBARS and between IL‐1β levels and LC3‐II were found only in control subjects.
Conclusion
Results from the present study are consistent with the suggestion of periodontitis as a potential risk factor for AMI. Periodontitis association with circulating lipid peroxides in both AMI and control subjects were found. The absence of differences in IL‐1β levels between AMI subjects (only AMI vs AMI + periodontitis) suggests that oxidative stress could be the main pathogenic link between AMI and periodontitis.
In this work, the mutual solubility of 30 binary systems {aromatic hydrocarbon (1) + ionic liquid (2)} involving benzene, toluene, ethylbenzene, o-xylene, m-xylene, and p-xylene as aromatics and the ...ionic liquids, 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, BMpyrNTf2, 1-butyl-1-methylpyrrolidinium trifluoromethanesulfonate, BMpyrTfO, 1-butyl-1-methylpyrrolidinium dicyanamide, BMpyrDCA, butyltrimethylammonium bis(trifluoromethylsulfonyl)imide, N4111NTf2, and tributylmethylammonium bis(trifluoromethylsulfonyl)imide, N4441NTf2, were determined in the temperature range of T = (293.15 to 333.15) K at p = 0.1 MPa. The influence of the temperature and the structural characteristics of the aromatic hydrocarbons as well as the effect of the structure of the ionic liquids on the phase behavior was analyzed. A comparison between the experimental LLE of the binary systems presented in this work and those found in literature was also carried out. Finally, all the binary systems were satisfactorily modeled using the Cubic-Plus-Association (CPA) Equation of State (EoS).
The fibrotic tumor microenvironment is a pivotal therapeutic target. Nintedanib, a clinically approved multikinase antifibrotic inhibitor, is effective against lung adenocarcinoma (ADC) but not ...squamous cell carcinoma (SCC). Previous studies have implicated the secretome of tumor-associated fibroblasts (TAFs) in the selective effects of nintedanib in ADC, but the driving factor(s) remained unidentified. Here we examined the role of tissue inhibitor of metalloproteinase-1 (TIMP-1), a tumor-promoting cytokine overproduced in ADC-TAFs. To this aim, we combined genetic approaches with in vitro and in vivo preclinical models based on patient-derived TAFs. Nintedanib reduced TIMP-1 production more efficiently in ADC-TAFs than SCC-TAFs through a SMAD3-dependent mechanism. Cell culture experiments indicated that silencing TIMP1 in ADC-TAFs abolished the therapeutic effects of nintedanib on cancer cell growth and invasion, which were otherwise enhanced by the TAF secretome. Consistently, co-injecting ADC cells with TIMP1-knockdown ADC-TAFs into immunocompromised mice elicited a less effective reduction of tumor growth and invasion under nintedanib treatment compared to tumors bearing unmodified fibroblasts. Our results unveil a key mechanism underlying the selective mode of action of nintedanib in ADC based on the excessive production of TIMP-1 in ADC-TAFs. We further pinpoint reduced SMAD3 expression and consequent limited TIMP-1 production in SCC-TAFs as key for the resistance of SCC to nintedanib. These observations strongly support the emerging role of TIMP-1 as a critical regulator of therapy response in solid tumors.
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