Enfermedad fúngica invasora: ¿Diagnóstico micológico convencional o molecular?

Diagnosis of invasive mycoses is a difficult challenge due to the limitations and low sensitivity of traditional microbiology methods which lead to diagnostic and therapeutic delays. The aim of this review is to summarise the state of the art of the molecular diagnosis of invasive fungal disease and to clarify its current role in the clinical practice. Conventional microbiological methods could be complemented with molecular methods in the rapid and definitive identification of fungal isolates. Biomarkers (β-glucan, galactomannan) are very useful in immunocompromised patients and have been included as probable invasive mycoses by the EORTC/MSG. Nucleic acid detection is currently used as a complementary tool for diagnosis. However, PCR can be very useful in mould invasive mycoses. Finally, the combined detection using biomarkers can improve the diagnosis. However, their applicability in the microbiology laboratory is not so easy and further studies are required for the appropriate evaluation of its clinical usefulness.     

CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development

The C-type lectin receptor CLEC-2 signals through a pathway that is critically dependent on the tyrosine kinase Syk. We show that homozygous loss of either protein results in defects in brain vascular and lymphatic development, lung inflation, and perinatal lethality. Furthermore, we find that conditional deletion of Syk in the hematopoietic lineage, or conditional deletion of CLEC-2 or Syk in the megakaryocyte/platelet lineage, also causes defects in brain vascular and lymphatic development, although the mice are viable. In contrast, conditional deletion of Syk in other hematopoietic lineages had no effect on viability or brain vasculature and lymphatic development. We show that platelets, but not platelet releasate, modulate the migration and intercellular adhesion of lymphatic endothelial cells through a pathway that depends on CLEC-2 and Syk. These studies found that megakaryocyte/platelet expression of CLEC-2 and Syk is required for normal brain vasculature and lymphatic development and that platelet CLEC-2 and Syk directly modulate lymphatic endothelial cell behavior in vitro.     

Low level laser therapy and hair regrowth: an evidence-based review

Despite the current treatment options for different types of alopecia, there is a need for more effective management options. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth. Here, we reviewed the current evidence on the LLLT effects with an evidence-based approach, focusing more on randomized controlled studies by critically evaluating them. In order to investigate whether in individuals presenting with hair loss (male pattern hair loss (MPHL), female pattern hair loss (FPHL), alopecia areata (AA), and chemotherapy-induced alopecia (CIA)) LLLT is effective for hair regrowth, several databases including PubMed, Google Scholar, Medline, Embase, and Cochrane Database were searched using the following keywords: Alopecia, Hair loss, Hair growth, Low level laser therapy, Low level light therapy, Low energy laser irradiation, and Photobiomodulation. From the searches, 21 relevant studies were summarized in this review including 2 in vitro, 7 animal, and 12 clinical studies. Among clinical studies, only five were randomized controlled trials (RCTs), which evaluated LLLT effect on male and female pattern hair loss. The RCTs were critically appraised using the created checklist according to the Critical Appraisal for Therapy Articles Worksheet created by the Center of Evidence-Based Medicine, Oxford. The results demonstrated that all the performed RCTs have moderate to high quality of evidence. However, only one out of five studies performed intention-to-treat analysis, and only another study reported the method of randomization and subsequent concealment of allocation clearly; all other studies did not include this very important information in their reports. None of these studies reported the treatment effect of factors such as number needed to treat. Based on this review on all the available evidence about effect of LLLT in alopecia, we found that the FDA-cleared LLLT devices are both safe and effective in patients with MPHL and FPHL who did not respond or were not tolerant to standard treatments. Future randomized controlled trials of LLLT are strongly encouraged to be conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement to facilitate analysis and comparison.     

Neuropathic ulcers in leprosy treated with intralesional platelet‐rich plasma

Neuropathic ulcers in leprosy represent a therapeutic challenge for clinicians. Chronic ulcers affect patient health, emotional state and quality of life, causing considerable morbidity and mortality in addition to contributing to significant health care costs. The pathogenesis is mainly related to the abnormally increased pressure in areas such as the sole of the foot, secondary to lack of sensation and deformities induced by peripheral sensory‐motor neuropathy. Conventional treatment of these wounds can be slow due to their chronic inflammatory state and the senescence of local reparative cells. Platelet‐rich plasma (PRP) may restore the healing process, leading to a reparative phase. We present two patients with four neuropathic leprosy ulcers that have responded satisfactory to PRP treatment. PRP therapy has been growing as a viable treatment alternative for chronic ulcers. However, stronger scientific evidence is required to support its potential benefit for use in chronic wounds.     

Absence of Hepatitis E virus circulation in wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis) in Mediterranean ecosystems in Spain

In recent decades, cases of autochthonous hepatitis E (HE) have sharply increased in European countries where foodborne transmission is considered the main route of HE virus (HEV) transmission. Although rabbits are considered the main reservoir of the zoonotic HEV‐3ra subtype, information on the role of wild lagomorphs in the epidemiology of HEV remains scarce. The aim of this study therefore was to assess the circulation of HEV in European wild rabbits (Oryctolagus cuniculus) and Iberian hares (Lepus granatensis), the most important lagomorph species in Spanish Mediterranean ecosystems. Liver samples from 372 wild rabbits and 78 Iberian hares were analysed using a broad‐spectrum RT‐PCR that detects HEV genotypes 1–8. None of the 450 lagomorphs tested were positive for HEV infection. To the best of our knowledge, this is the first study to assess HEV circulation in wild rabbits in Spain and the first to evaluate HEV infection in Iberian hares. Our results indicate absence of HEV circulation in wild rabbits and Iberian hares in southern Spain during the study period, which suggests that the risk of transmission of HEV from wild lagomorphs to other species, including humans, is low.     

Green alternative cosolvents to N-methyl-2-pyrrolidone in water polyurethane dispersions

N-Methyl-2-pyrrolidone is a toxic dipolar aprotic solvent widely used in the synthesis of polyurethane dispersions (PUD). Since legislation strongly restricts this substance, green alternatives are essential. Dihydrolevoglucosenone and gamma valerolactone demonstrate comparable performance to that of NMP as cosolvent in the synthesis and the film forming process of PUD.

N-Methyl-2-pyrrolidone is a toxic dipolar aprotic solvent widely used in the synthesis of polyurethane dispersions (PUD).

The use of organic solvents in commercial products like coatings or adhesives is being limited due to their toxicity and environmental hazard.^1,2 Aqueous polymeric nanodispersions are suitable alternatives to reduce the use of organic solvents. PUD are extraordinarily interesting due to their equivalent performance to the conventional solvent borne products, but with some additional advantages such as excellent adhesion, tuneable mechanical properties and functionalization, good biocompatibility and potential biodegradability.^3–5These polymeric dispersions are colloidal systems in which polyurethane (PU) particles are dispersed in aqueous media as a continuous phase. Standard polyurethanes are not dispersible in water due to the presence of isocyanates, which are hydrophobic and they also could react with water. Then, polyurethanes dispersible in water need to be modified. Generally, they are obtained by incorporating diol molecules with hydrophilic carboxylic group as internal emulsifier. After synthesising a linear thermoplastic PU prepolymer, the acids groups of the internal emulsifier are neutralized.This hydrophilic isocyanate-terminated prepolymer is subsequently extended with low molecular weight alcohols or amines to obtain the target polyurethane. The dispersion in water can take place in different stages of the process depending mainly on the chain extender used, i.e. before or after chain extension.The most common processes for synthesizing PUD are acetone and prepolymer mixing processes. In acetone process, the polymer synthesis requires acetone to obtain a homogeneous and low viscosity reaction system. However, it has the disadvantage of requiring large amounts of acetone and an extra distillation process for removing this solvent from the waterborne dispersion. This makes the industry to commonly discard this strategy.Nevertheless, in prepolymer mixing process, the medium molecular weight polymer (prepolymer) is prepared through the reaction of di-functional polyols and the internal emulsifier with a molar excess of di-isocyanates. Then, the prepolymer is extended and the dispersion in water is carried out.In this process, around 12–15 wt% of organic solvent, generally N-methyl-2-pyrrolidone (NMP), is used to reduce the viscosity of the mixture.⁶ This organic solvent remains in the dispersion in order to promote the coalescence of nanoparticles and the film formation of coatings or adhesives.⁷ Therefore, any alternative cosolvent to NMP must work as both reaction media and coalesce agent to achieve similar performance and products.NMP is a dipolar aprotic solvent with excellent coalescence capacity, but its use is restricted,⁸i.e., it shall not be placed on the market as a substance on its own or in mixtures in a concentration equal to or greater than 0.3 wt%.^9–11 Hence, there is a pressing need to achieve low toxicity alternative solvents with the suitable polarity profile. Structurally homologues substances with different length of carbon side chain like N-ethyl- or N-butyl-2-pyrrolidone (NEP/NBP)^12,13 have been promoted as alternatives to NMP. However, this was simply an attempt to use the lack of environmental and health data available at the time to keep ahead of legislation.¹⁴In addition, the studies by M. Schmidt using NBP as alternative cosolvent for PUD, an extra cosolvent is need. The coalescence process is not effective enough and extra cosolvent is incorporated in the final product formulation to complete the coalescence of polyurethane nanoparticles and the film forming.¹⁵ This drawback is also the main disadvantage of solvent free PUDs, where the formulation of coatings or adhesive includes additional solvents to achieve proper film forming in the final product.^5,16In this study, two alternative green solvents with improved Health, Environmental and Safety (HES) profile (see detailed information in Table S1 at ESI^†) have been selected. Green solvents studied are: Dihydrole-levoglucosenone (CY) and γ-valerolactone (GVL)^17,18 (Fig. 1).Open in a separate windowFig. 1Molecular structure of cosolvents studied.Dihydrolevoglucosenone (Cyrene, CY) is a biodegradable compound synthesised in a two-step process from waste cellulose.¹⁹ There are evidences that this new substance is an alternative to dipolar aprotic solvents.²⁰ Cyrene is identified as an effective solvent in different chemical applications such as the synthesis of ureas,²¹ the preparation of membranes,²² metal organic frameworks (MOF) synthesis,²³ heteroatom and alkylation reactions, in nucleophilic fluorination reactions²⁰ or in graphene dispersions.²⁴On the other hand, γ-valerolactone (GVL) is a biodegradable substance obtained from lignocellulosic biomass²⁵ that is widely used in food and perfume industries.²⁶ However, new applications as green solvent in chemical industry have been recently reported: crosscoupling reactions (Hiyama reaction),²⁷ synthesis of formamides,²⁸ synthesis of phosphatidylserine²⁹ or the production of 5-hydroxymethylfurfural³⁰ are some outstanding examples as green solvent.Physicochemical properties of these green solvents and NMP are collected in 31 and Hansen parameters have been compared, see Fig. 2 and 32,33 The Reichardt parameter, E^N_T, is extensively used for measuring empirically the polarity of different systems (organic and ionic liquids, switchable-hydrophilicity solvents, polymers, surfaces, etc.). E^N_T values measure preferably the solvent''s dipolarity/polarizability (given by π*) and hydrogen bond donor acidity (given by α).^34,35Physicochemical properties of selected cosolvents