Tissue remodelling and increased DNA damage in patients with incompetent valves in chronic venous insufficiency

Chronic venous insufficiency (CVI), in which blood return to the heart is impaired, is a prevalent condition worldwide. Valve incompetence is a complication of CVI that results in blood reflux, thereby aggravating venous hypertension. While CVI has a complex course and is known to produce alterations in the vein wall, the underlying pathological mechanisms remain unclear. This study examined the presence of DNA damage, pro-inflammatory cytokines and extracellular matrix remodelling in CVI-related valve incompetence. One hundred and ten patients with CVI were reviewed and divided into four groups according to age (<50 and ≥50 years) and a clinical diagnosis of venous reflux indicating venous system valve incompetence (R) (n = 81) or no reflux (NR) (n = 29). In vein specimens (greater saphenous vein) from each group, PARP, IL-17, COL-I, COL-III, MMP-2 and TIMP-2 expression levels were determined by RT-qPCR and immunohistochemistry. The younger patients with valve incompetence showed significantly higher PARP, IL-17, COL-I, COL-III, MMP-2 and reduced TIMP-2 expression levels and a higher COL-I/III ratio. Young CVI patients with venous reflux suffer chronic DNA damage, with consequences at both the local tissue and systemic levels, possibly associated with ageing.     

Autocuidado: nueva evidencia sobre su medida en adultos mayores

Introduction

A major challenge in today's society is getting older people, not only live longer, but to have a better life, and achieve successful aging. Self-care has been identified as relevant construct in its relation to physical, psychological, and social health. Therefore, this paper aims to provide first evidence of the psychometric properties of a scale to assess self-care in older people.

Metformin directly targets the H3K27me3 demethylase KDM6A/UTX

Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure‐ and ligand‐based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3‐specific demethylase subfamily, KDM6A/UTX. AlphaScreen and AlphaLISA assays confirmed the ability of metformin to inhibit the demethylation activity of purified KDM6A/UTX enzyme. Structural studies revealed that metformin might occupy the same set of residues involved in H3K27me3 binding and demethylation within the catalytic pocket of KDM6A/UTX. Millimolar metformin augmented global levels of H3K27me3 in cultured cells, including reversion of global loss of H3K27me3 occurring in premature aging syndromes, irrespective of mitochondrial complex I or AMPK. Pharmacological doses of metformin in drinking water or intraperitoneal injection significantly elevated the global levels of H3K27me3 in the hepatic tissue of low‐density lipoprotein receptor‐deficient mice and in the tumor tissues of highly aggressive breast cancer xenograft‐bearing mice. Moreover, nondiabetic breast cancer patients receiving oral metformin in addition to standard therapy presented an elevated level of circulating H3K27me3. Our biocomputational approach coupled to experimental validation reveals that metformin might directly regulate the biological machinery of aging by targeting core chromatin modifiers of the epigenome.     

Quality of life in patients with food allergy

Food allergy has increased in developed countries and can have a dramatic effect on quality of life, so as to provoke fatal reactions. We aimed to outline the socioeconomic impact that food allergy exerts in this kind of patients by performing a complete review of the literature and also describing the factors that may influence, to a greater extent, the quality of life of patients with food allergy and analyzing the different questionnaires available. Hitherto, strict avoidance of the culprit food(s) and use of emergency medications are the pillars to manage this condition. Promising approaches such as specific oral or epicutaneous immunotherapy and the use of monoclonal antibodies are progressively being investigated worldwide. However, even that an increasing number of centers fulfill those approaches, they are not fully implemented enough in clinical practice. The mean annual cost of health care has been estimated in international dollars (I$) 2016 for food-allergic adults and I$1089 for controls, a difference of I$927 (95 % confidence interval I$324–I$1530). A similar result was found for adults in each country, and for children, and interestingly, it was not sensitive to baseline demographic differences. Cost was significantly related to severity of illness in cases in nine countries. The constant threat of exposure, need for vigilance and expectation of outcome can have a tremendous impact on quality of life. Several studies have analyzed the impact of food allergy on health-related quality of life (HRQL) in adults and children in different countries. There have been described different factors that could modify HRQL in food allergic patients, the most important of them are perceived disease severity, age of the patient, peanut or soy allergy, country of origin and having allergy to two or more foods. Over the last few years, several different specific Quality of Life questionnaires for food allergic patients have been developed and translated to different languages and cultures. It is important to perform lingual and cultural translations of existent questionnaires in order to ensure its suitability in a specific region or country with its own socioeconomic reality and culture. Tools aimed at assessing the impact of food allergy on HRQL should be always part of the diagnostic work up, in order to provide a complete basal assessment, to highlight target of intervention as well as to evaluate the effectiveness of interventions designed to cure food allergy. HRQL may be the only meaningful outcome measure available for food allergy measuring this continuous burden.     

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

Background

Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents.

Methods

Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests.

Results

Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73).

Conclusions

Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.     

The microbiological transformation of some trachylobane diterpenoids by Gibberella fujikuroi

The microbiological transformation of ent-trachylobane, ent-7α-hydroxytrachylobane and ent-19-hydroxytrachylobane into trachylobagibberellins A₇, A₉, A₁₃, A₂₅, A₄₀ and A₄₇ by Gibberella fujikuroi is described. Whereas 7β-hydroxy- and 7β,18-dihydroxytrachylobanolides were obtained from ent-trachylobane and ent-trachyloban- 19-ol, the presence of a 7β-hydroxyl group directed metabolism exclusively into the gibberellin pathway. An 18-hydroxyl group as in ent-7α,18-dihydroxytrachylobane inhibited oxidation at C-6 affording ent-7α,18,19-trihydroxytrachylobane as the major metabolite.     

Microbiological transformation of an ent-pimaradiene hydrocarbon by Gibberella fujikuroi

The hydrocarbon 9,13-epi-ent-pimara-7,15-diene has been obtained from its 18-hydroxy derivative by treatment with Ph₃/CCl₄ and subsequent reduction with tri-n-butyltin hydride. The incubation of this diterpene with the fungus Gibberella fujikuroi afforded 1α,9α-dihydroxy-7α,8α-epoxy-13-epi-ent-pimara-15-ene. The main difference between the biotransformation of the hydrocarbon and that of the corresponding 18-alcohol is that in the former, the rearrangement of the epoxy group to give 7-oxo-derivatives was not observed. However, the sequence of reactions 7α,8α-epoxidation, hydroxylation at C-9α and subsequent C-1α hydroxylation occurred in both biotransformations.     

Crayfish burrows from Late Jurassic–Late Cretaceous continental deposits of Patagonia: Argentina. Their palaeoecological,palaeoclimatic and palaeobiogeographical significance

The trace fossil, Loloichnus baqueroensis igen. and isp. nov., from Late Jurassic–Late Cretaceous continental deposits of Patagonia, Argentina, includes thickly lined, mostly passively-filled, and Y-branched burrows. Other important features of this ichnofossil are the inner surface texture of lining showing transversal, elongated, and adjacent grooves, and less commonly, the pelletal filling of burrows. L. baqueroensis is recorded from the Bajo Grande, Bajo Tigre, Punta del Barco, and Laguna Palacios Formations, which were deposited in different volcaniclastic environments of the Deseado Massif and San Jorge Basin geological provinces, respectively. The described burrows are found in many levels of palaeosols developed in reworked piroclastic deposits, where they are the main component of the ichnofabrics, in association with meniscate and thinly lined burrows and a diffuse and complex boxwork of small diameter burrows. Root traces are also present, and in many cases, occur inside L. baqueroensis. Considering general morphology, surface texture, filling types, palaeoenvironments in which they occur, and comparisons with extant and fossil decapod burrows, the likely trace makers of L. baqueroensis were crayfishes (Decapoda: Astacidea), probably Parastacidae. The producers of L. baqueroensis inhabited soils, where their burrows probably reached the water table, and contained roots that were used for feeding. Considering climatic preferences of extant parastacids, it is proposed a temperate climate for central Patagonia during the deposition of the studied units. The widespread presence of crayfishes during Late Jurassic–Late Cretaceous times in central Patagonia, supports the monophyletic origin of this group during the Triassic, and suggests that the present restricted geographic distribution in southern South America is a relict of a broader one.     

Seasonal variability of dry matter content and its relationship with shoot growth and nonstructural carbohydrates

This study assesses how different phases of shoot growth underlie seasonal change in leaf and stem dry matter content (LDMC and SDMC, respectively) of 12 woody Mediterranean species. The relationship between LDMC and nonstructural carbohydrate (NSC) concentrations is also explored and the seasonal vs interspecies variability of LDMC compared. LDMC, SDMC and shoot elongation rate (SER) were measured on a monthly basis for a minimum of 12 months. Bud growth rate (BGR) and NSC concentrations were also assessed in several of the study species. LDMC and SDMC decreased during shoot elongation in spring and increased in summer, showing a significant negative correlation with SER, but were unrelated to BGR. Half of the species analysed showed a positive relationship between LDMC and NSC. Seasonal fluctuations of LDMC within species were higher than interspecies differences, and species ranking was significantly affected by the month of sampling, except during winter months. Seasonal changes in LDMC and SDMC are mainly related to shoot elongation phenology, and NSC sink-source relationships between old and growing organs can explain this relationship in some species. Owing to the high seasonal variability in LDMC, it is recommended that samples for comparative purposes should be collected as close to the winter as possible.     

Antigenicity of chimeric synthetic peptides based on HTLV-1 antigens and the impact of epitope orientation

The present study evaluated four chimeric synthetic peptides incorporating immunodominant sequences from HTLV-1 virus. Monomeric peptides M1, M2, and M3 represent sequences from core (p19) and envelope (gp46) of the virus. The peptide M1 is a p19 (105-124) sequence, the peptide M2 is a gp46 (190-207) sequence, and the peptide M3 is a gp 46 sequence with substitution of proline at position 192 by serine. Those peptides were arranged in such a way that permits one to obtain different combinations of chimeric peptides (M1-M2, M2-M1, M1-M3, and M3-M1). Two glycine residues were used as arm spacers for separating the two sequences. The antigenicity of these peptides was evaluated in an ultramicroenzyme-linked immunosorbent assay (UMELISA) using sera of human T cell leukemia virus type I (HTLV-I)-infected individuals (n = 24), while specificity was evaluated with anti-HTLV-II-positive samples (n = 11) and healthy blood donors (n = 25). The results were compared to plates coated with monomeric peptides M1, M2, and M3. The chimeric peptide orientation (M1-M2) and the proline at position 192 of the gp46 peptide showed higher sensitivity.