"In-situ" formation of elastin-like recombinamer hydrogels with tunable viscoelasticity through efficient one-pot process.

Despite the remarkable progress in the generation of recombinant elastin-like (ELR) hydrogels, further improvements are still required to enhance and control their viscoelasticity, as well as limit the use of expensive chemical reagents, time-consuming processes and several purification steps. To alleviate this issue, the reactivity of carboxylic groups from glutamic (E) acid distributed along the hydrophilic block of an amphiphilic ELR (coded as E50I60) with amine groups has been studied through a one-pot amidation reaction in aqueous solutions, for the first time. By means of this approach, immediate conjugation of E50I60 with molecules containing amine groups has been performed with a high yield, as demonstrated by the 1H NMR and MALDI-TOF spectroscopies. This has resulted in the preparation of viscoelastic irreversible hydrogels through the "in-situ" cross-linking of E50I60 with another ELR (coded as VKV24) containing amine groups from lysines (K). The rheology analysis demonstrated that the gelation process takes place following a dual mechanism dependent on the ELR concentration: physical cross-linking of I60 block through the hydrophobic interactions, and covalent cross-linking of E50I60 with VKV24 through the amidation reaction. While the chemical network formed between the hydrophilic E50 block and VKV24 ELR preserves the elasticity of ELR hydrogels, the self-assembly of the I60 block through the hydrophobic interactions provides a tunable physical network. The presented investigation serves as a basis for generating ELR hydrogels with tunable viscoelastic properties promising for tissue regeneration, through an ''in-situ", rapid, scalable, economically and feasible one-pot method.

The Value of the Second QuantiFERON-TB Gold-Plus Antigen Tube at Diagnosis and at Treatment Completion in Spanish Children With Tuberculosis.

We studied 295 children (tuberculosis disease, n = 159; latent tuberculosis infection, n = 136) with positive QuantiFERON-TB Gold-Plus assay results. No significant differences between first and second antigen tube interferon-gamma responses were detected, irrespective of patient and disease characteristics at diagnosis. Of patients with a repeat assay after treatment completion (n = 65), only 16.9% converted to negative results.

Prevalence and Clinical Characteristics of Children With Nonsevere Tuberculosis in Spain.

BACKGROUND: To assess the prevalence and characteristics of nonsevere TB among children in Spain. It has been recently demonstrated that these children can be treated with a 4-month regimen instead of the classical 6-month treatment regimen, with the same effectivity and outcomes, decreasing toxicity and improving adherence. METHODS: We conducted a retrospective cohort study in a cohort of children ≤16 years of age with TB. Nonsevere TB cases included smear-negative children with respiratory TB confined to 1 lobe, with no significant airway obstruction, no complex pleural effusion, no cavities and no signs of miliary disease, or with peripheral lymph-node disease. The remaining children were considered to have severe TB. We estimated the prevalence of nonsevere TB and compared the clinical characteristics and outcomes between children with nonsevere and severe TB. RESULTS: A total of 780 patients were included [46.9% males, median age 5.5 years (IQR: 2.6-11.1)], 477 (61.1%) of whom had nonsevere TB. Nonsevere TB was less frequent in children <1 year (33% vs 67%; P < 0.001), and >14 years of age (35% vs 65%; P = 0.002), mostly diagnosed in contact tracing studies (60.4% vs 29.2%; P < 0.001) and more frequently asymptomatic (38.3% vs 17.7%; P < 0.001). TB confirmation in nonsevere disease was less frequent by culture (27.0% vs 57.1%; P < 0.001) and by molecular tests (18.2% vs 48.8%; P < 0.001). Sequelae were less frequent in children with nonsevere disease (1.7 vs 5.4%; P < 0.001). No child with nonsevere disease died. CONCLUSIONS: Two-thirds of children had nonsevere TB, mostly with benign clinical presentation and negative microbiologic results. In low-burden countries, most children with TB might benefit from short-course regimens.

Transient Viral Rebound in Children with Perinatally Acquired HIV-1 Induces a Unique Soluble Immunometabolic Signature Associated with Decreased CD4/CD8 Ratio.

BACKGROUND: To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV). METHODS: Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS, and LC-qTOF-MS. RESULTS: Comparing pre- and post-tVR time-points, HIV-1 children with tVR (n = 5) showed a trend to a decrease in ratio CD4/CD8 (p = 0.08) but no significant differences were observed in plasma metabolites, lipids, or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n = 9), paired by sex, age, and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites, and 2 lipids showed significant differences (p < 0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0), and diacylglyceride 34:1 (DG34:1) were upregulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid, and D-sucrose downregulated on post-tVR time-point compared to the reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1, and methionine (p = 0.004; ρ = 0.71, p = 0.016; ρ = -0.63; and p = 0.032; ρ = -0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p = 0.022; ρ = -0.60) and positively with D-sucrose (p = 0.001; ρ = 0.77). CONCLUSIONS: tVR followed by suppression implies changes in soluble proteins, lipids, and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.

Performance of QuantiFERON-TB Gold Plus assays in paediatric tuberculosis: a multicentre PTBNET study.

RATIONALE: In 2016, a new interferon-gamma release assay (IGRA) was introduced, QuantiFERON-TB Gold Plus (QFT-Plus), claimed to have improved sensitivity in active tuberculosis (TB). OBJECTIVES: This study aimed to determine the performance of QFT-Plus, compared with previous generation IGRAs and the tuberculin skin test (TST), in children with TB in Europe. METHODS: Multicentre, ambispective cohort study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), a dedicated paediatric TB research network comprising >300 members, capturing TB cases <18 years-of-age diagnosed between January 2009 and December 2019. MEASUREMENTS AND MAIN RESULTS: 1001 TB cases from 16 countries were included (mean age (IQR) 5.6 (2.4-12.1) years). QFT-Plus was performed in 358, QFT Gold in-Tube (QFT-GIT) in 600, T-SPOT.TB in 58 and TST in 636 cases. The overall test sensitivities were: QFT-Plus 83.8% (95% CI 80.2% to 87.8%), QFT-GIT 85.5% (95% CI 82.7% to 88.3%), T-SPOT.TB 77.6% (95% CI 66.9% to 88.3%) and TST (cut-off ≥10 mm) 83.3% (95% CI 83.3% to 86.2%). There was a trend for tests to have lower sensitivity in patients with miliary and/or central nervous system (CNS) TB (73.1%, 70.9%, 63.6% and 43.5%, respectively), and in immunocompromised patients (75.0%, 59.6%, 45.5% and 59.1%, respectively). CONCLUSIONS: The results indicate that the latest generation IGRA assay, QFT-Plus, does not perform better than previous generation IGRAs or the TST in children with TB disease. Overall, tests performed worse in CNS and miliary TB, and in immunocompromised children. None of the tests evaluated had sufficiently high sensitivity to be used as a rule-out test in children with suspected TB.

Pediatric cutaneous mucormicosis.

A 9-year-old boy diagnosed with acute myeloblastic leukemia and undergoing chemotherapy, was admitted with febrile neutropenia. During his admission, several violaceous plaques appeared on the upper extremities and anterior left hemithorax, which worsened and acquired a necrotic center. We performed a biopsy and histology showed a cutaneous infarction at the dermoepidermal and subcutaneous level. We observed abundant wide hyphae with right-angled branching and a culture isolated Rhizopus oryzae. A plastic surgery consultant performed a surgical debridement of the lesions and treatment was started with intravenous amphotericin B. The patient did well on treatment and after almost a month of hospitalization, he was discharged with oral posaconazole. Mucormycosis is an opportunistic fungal infection associated with immunosuppression, particularly involving prematurity and hematological diseases in the pediatric age group. Multiple lesions, as in our case, are infrequent. The clinical presentation is variable. Direct smear or histological observation is the quickest diagnostic technique whereas culture is the most definitive. The combination of surgical debridement and amphotericin B is the treatment with the highest survival rates.

Protease-Sensitive, VEGF-Mimetic Peptide, and IKVAV Laminin-Derived Peptide Sequences within Elastin-Like Recombinamer Scaffolds Provide Spatiotemporally Synchronized Guidance of Angiogenesis and Neurogenesis.

Spatiotemporal control of vascularization and innervation is a desired hallmark in advanced tissue regeneration. For this purpose, we design a 3D model scaffold, based on elastin-like recombinamer (ELR) hydrogels. This contains two interior and well-defined areas, small cylinders, with differentiated bioactivities with respect to the bulk. Both are constructed on a protease sensitive ELR with a fast-proteolyzed domain, but one bears a VEGF-mimetic peptide (QK) and the other a laminin-derived pentapeptide (IKVAV), to promote angiogenesis and neurogenesis, respectively. The outer bulk is based on a slow proteolytic sequence and RGD cell adhesion domains. In vitro studies show the effect of QK and IKVAV peptides on the promotion of endothelial cell and axon spreading, respectively. The subcutaneous implantation of the final 3D scaffold demonstrates the ability to spatiotemporally control angiogenesis and neurogenesis in vivo. Specifically, the inner small cylinder containing the QK peptide promotes fast endothelialization, whereas the one with IKVAV peptide promotes fast neurogenesis. Both, vascularization and innervation take place in advance of the bulk scaffold infiltration. This scaffold shows that it is possible to induce vascularization and innervation in predetermined areas of the scaffold well ahead to the bulk infiltration. That significantly increases the efficiency of the regenerative activity.

Mesenchymal Stromal Cells Combined With Elastin-Like Recombinamers Increase Angiogenesis In Vivo After Hindlimb Ischemia.

Hindlimb ischemia is an unmet medical need, especially for those patients unable to undergo vascular surgery. Cellular therapy, mainly through mesenchymal stromal cell (MSC) administration, may be a potentially attractive approach in this setting. In the current work, we aimed to assess the potential of the combination of MSCs with a proangiogenic elastin-like recombinamer (ELR)-based hydrogel in a hindlimb ischemia murine model. Human bone marrow MSCs were isolated from four healthy donors, while ELR biomaterials were genetically engineered. Hindlimb ischemia was induced through ligation of the right femoral artery, and mice were intramuscularly injected with ELR biomaterial, 0.5 × 106 MSCs or the combination, and also compared to untreated animals. Tissue perfusion was monitored using laser Doppler perfusion imaging. Histological analysis of hindlimbs was performed after hematoxylin and eosin staining. Immunofluorescence with anti-human mitochondria antibody was used for human MSC detection, and the biomaterial was detected by elastin staining. To analyze the capillary density, immunostaining with an anti-CD31 antibody was performed. Our results show that the injection of MSCs significantly improves tissue reperfusion from day 7 (p = 0.0044) to day 21 (p = 0.0216), similar to the infusion of MSC + ELR (p = 0.0038, p = 0.0014), without significant differences between both groups. After histological evaluation, ELR hydrogels induced minimal inflammation in the injection sites, showing biocompatibility. MSCs persisted with the biomaterial after 21 days, both in vitro and in vivo. Finally, we observed a higher blood vessel density when mice were treated with MSCs compared to control (p<0.0001), but this effect was maximized and significantly different to the remaining experimental conditions when mice were treated with the combination of MSCs and the ELR biomaterial (p < 0.0001). In summary, the combination of an ELR-based hydrogel with MSCs may improve the angiogenic effects of both strategies on revascularization of ischemic tissues.

Self-assembling systems comprising intrinsically disordered protein polymers like elastin-like recombinamers.

Despite lacking cooperatively folded structures under native conditions, numerous intrinsically disordered proteins (IDPs) nevertheless have great functional importance. These IDPs are hybrids containing both ordered and intrinsically disordered protein regions (IDPRs), the structure of which is highly flexible in this unfolded state. The conformational flexibility of these disordered systems favors transitions between disordered and ordered states triggered by intrinsic and extrinsic factors, folding into different dynamic molecular assemblies to enable proper protein functions. Indeed, prokaryotic enzymes present less disorder than eukaryotic enzymes, thus showing that this disorder is related to functional and structural complexity. Protein-based polymers that mimic these IDPs include the so-called elastin-like polypeptides (ELPs), which are inspired by the composition of natural elastin. Elastin-like recombinamers (ELRs) are ELPs produced using recombinant techniques and which can therefore be tailored for a specific application. One of the most widely used and studied characteristic structures in this field is the pentapeptide (VPGXG)n . The structural disorder in ELRs probably arises due to the high content of proline and glycine in the ELR backbone, because both these amino acids help to keep the polypeptide structure of elastomers disordered and hydrated. Moreover, the recombinant nature of these systems means that different sequences can be designed, including bioactive domains, to obtain specific structures for each application. Some of these structures, along with their applications as IDPs that self-assemble into functional vesicles or micelles from diblock copolymer ELRs, will be studied in the following sections. The incorporation of additional order- and disorder-promoting peptide/protein domains, such as α-helical coils or ß-strands, in the ELR sequence, and their influence on self-assembly, will also be reviewed. In addition, chemically cross-linked systems with controllable order-disorder balance, and their role in biomineralization, will be discussed. Finally, we will review different multivalent IDPs-based coatings and films for different biomedical applications, such as spatially controlled cell adhesion, osseointegration, or biomaterial-associated infection (BAI).

Performance of QuantiFERON-TB Gold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study.

INTRODUCTION: The QuantiFERON-TB Gold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay's performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting. METHODS: Cross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020. RESULTS: Of 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2-, n=2; TB1-/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations. CONCLUSIONS: Our non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay's performance substantially.

QuantiFERON-TB Gold Plus Assay Specificity in Children and Adolescents With Suspected Tuberculosis-A Multicenter Cross-sectional Study in Spain.

In this cross-sectional study of 284 children and adolescents with clinically or radiologically suspected tuberculosis in a low-endemic country, the QuantiFERON-TB Gold Plus assay specificity, sensitivity, positive predictive value and negative predictive value were 91.5%, 87.3%, 86.4%, and 91.2%, respectively. The specificity was higher than that observed in tuberculin skin tests performed simultaneously, but similar to previous-generation interferon-gamma release assays.

Combining tunable proteolytic sequences and a VEGF-mimetic peptide for the spatiotemporal control of angiogenesis within Elastin-Like Recombinamer scaffolds.

One of the main challenges in regenerative medicine is the spatiotemporal control of angiogenesis, which is key for the successful repair of many tissues, and determines the proper integration of the implant through the generation of a functional vascular network. To this end, we have designed a three-dimensional (3D) model consisting of a coaxial binary elastin-like recombinamer (ELR) tubular construct. It displays fast and slow proteolytic hydrogels on its inner and outer part, respectively, both sensitive to the urokinase plasminogen activator protease. The ELRs used to build the scaffold included crosslinkable domains to stabilize the structure and a conjugated VEGF-derived peptide (QK) to induce angiogenesis. The mechanical and morphological evaluation of the ELR hydrogels proved their suitability for soft tissue regeneration. In addition, in vitro studies evidenced the effect of the QK peptide on endothelial cell spreading and anastomosis. Moreover, immunohistochemical analyses after subcutaneous implantation of the ELR hydrogels in mice showed the induction of a low macrophage response that resolved over time. The implantation of the 3D model constructs evidenced the ability of the fast proteolytic sequence and the QK peptide to guide cell infiltration and capillary formation in the pre-designed arrangement of the constructs. These results set the basis for the application of this type of scaffolds in regenerative medicine, where spatiotemporally controlled vascularization will help in the promotion of an optimal tissue repair. STATEMENT OF SIGNIFICANCE: Herein, we show the spatiotemporal control of angiogenesis in vivo by the combination of proteolytic sequences, with fast and slow degradation kinetics, and VEGF-mimetic peptide (QK) in a coaxial binary elastin-like recombinamer (ELR) tubular scaffold. These two bioactivities have been previously described for angiogenesis purposes, but have never been combined. This work demonstrates that the bioactivities act synergistically in promoting cell infiltration and subsequent vascularization, thus leading to a controlled evolution in space and time of the vascular microstructure within the hydrogel-like tubular scaffold. This effect has not been showed before and holds great potential for future vascular applications, which might be of great interest for a substantial part of Acta Biomaterialia readership.

Interferon-Gamma Release Assays Differentiate between Mycobacterium avium Complex and Tuberculous Lymphadenitis in Children.

OBJECTIVES: To assess the performance of interferon-gamma release assays (IGRAs) in the differential diagnosis between Mycobacterium avium complex (MAC) and tuberculosis (TB) in children affected with subacute/chronic submandibular/cervical lymphadenitis. STUDY DESIGN: Multicenter observational study comparing children with microbiologically confirmed MAC lymphadenitis from the European NontuberculouS MycoBacterial Lymphadenitis in childrEn study with children with TB lymphadenitis from the Spanish Network for the Study of Pediatric TB database. RESULTS: Overall, 78 patients with MAC and 34 with TB lymphadenitis were included. Among MAC cases, 44 out of 74 (59.5%) had positive tuberculin skin test (TST) results at the 5-mm cut-off, compared with 32 out of 33 (97%) TB cases (P < .001); at the 10-mm cut-off TST results were positive in 23 out of 74 (31.1%) vs 26 out of 31 (83.9%), respectively (P < .001). IGRA results were positive in only 1 out of 32 (3.1%) patients with MAC who had undergone IGRA testing, compared with 21 out of 23 (91.3%) TB cases (P < .001). Agreement between TST and IGRA results was poor in MAC (23.3%; κ = 0.017), but good in TB cases (95.6%; κ = 0.646). IGRAs had a specificity of 96.9% (95% CI 84.3%-99.8%), positive predictive value of 95.4% (95% CI 78.2%-99.8%), and negative predictive value of 93.9% (95% CI 80.4%-98.9%) for TB lymphadenitis. CONCLUSIONS: In contrast to TST, IGRAs have high specificity, negative predictive value, and positive predictive value for TB lymphadenitis in children with subacute/chronic lymphadenopathy, and consequently can help to discriminate between TB and MAC disease. Therefore, IGRAs are useful tools in the diagnostic work-up of children with lymphadenopathy, particularly when culture and polymerase chain reaction results are negative.

Biocasting of an elastin-like recombinamer and collagen bi-layered model of the tunica adventitia and external elastic lamina of the vascular wall.

The development of techniques for fabricating vascular wall models will foster the development of preventive and therapeutic therapies for treating cardiovascular diseases. However, the physical and biological complexity of vascular tissue represents a major challenge, especially for the design and the production of off-the-shelf biomimetic vascular replicas. Herein, we report the development of a biocasting technique that can be used to replicate the tunica adventitia and the external elastic lamina of the vascular wall. Type I collagen embedded with neonatal human dermal fibroblast (HDFn) and an elastic click cross-linkable, cell-adhesive and protease-sensitive elastin-like recombinamer (ELR) hydrogel were investigated as readily accessible and tunable layers to the envisaged model. Mechanical characterization confirmed that the viscous and elastic attributes predominated in the collagen and ELR layers, respectively. In vitro maturation confirmed that the collagen and ELR provided a favorable environment for the HDFn viability, while histology revealed the wavy and homogenous morphology of the ELR and collagen layer respectively, the cell polarization towards the cell-attachment sites encoded on the ELR, and the enhanced expression of glycosaminoglycan-rich extracellular matrix and differentiation of the embedded HDFn into myofibroblasts. As a complementary assay, 30% by weight of the collagen layer was substituted with the ELR. This model proved the possibility to tune the composition and confirm the versatile character of the technology developed, while revealing no significant differences with respect to the original construct. On-demand modification of the model dimensions, number and composition of the layers, as well as the type and density of the seeded cells, can be further envisioned, thus suggesting that this bi-layered model may be a promising platform for the fabrication of biomimetic vascular wall models.

Recombinant Proteins-Based Strategies in Bone Tissue Engineering.

The increase in fracture rates and/or problems associated with missing bones due to accidents or various pathologies generates socio-health problems with a very high impact. Tissue engineering aims to offer some kind of strategy to promote the repair of damaged tissue or its restoration as close as possible to the original tissue. Among the alternatives proposed by this specialty, the development of scaffolds obtained from recombinant proteins is of special importance. Furthermore, science and technology have advanced to obtain recombinant chimera's proteins. This review aims to offer a synthetic description of the latest and most outstanding advances made with these types of scaffolds, particularly emphasizing the main recombinant proteins that can be used to construct scaffolds in their own right, i.e., not only to impregnate them, but also to make scaffolds from their complex structure, with the purpose of being considered in bone regenerative medicine in the near future.

Estudio retrospectivo de los pacientes con diagnóstico confirmado de tosferina que son atendidos en urgencias de un hospital de tercer nivel / Retrospective study of patients with a confirmed diagnosis of whooping cough treated in the emergency room of a tertiary hospital

INTRODUCCIÓN: se analizan las características clínicas, pruebas complementarias y tratamientos recibidos por los pacientes con diagnóstico de tosferina que son valorados en Urgencias de Pediatría. MATERIAL Y MÉTODOS: estudio descriptivo retrospectivo de los casos de tosferina que consultaron en Urgencias de Pediatría de un hospital de tercer nivel entre marzo de 2014 y octubre de 2017. RESULTADOS: se analizaron 89 casos (55% mujeres) con edad media de 1,67 ± 2,9 años. El 98,9% presentó tos, el 33% gallo inspiratorio y el 34,8% apneas. En el 64% de los casos había entorno epidémico de tos o tosferina. La media de visitas en urgencias durante el mismo proceso fue 1,4. Diagnósticos más frecuentes en la primera visita a urgencias: tos (36%), sospecha de tosferina (22,5%), infección respiratoria de vías altas (19,1%) y bronquiolitis (9%). Ingresaron 56 pacientes (62,9%), con una edad media de 0,38 ± 1,2 años. Se realizó cultivo para Bordetella en 88 casos (positivo para B. pertussis en 38 y B. parapertussis en tres) y reacción en cadena de la polimerasa en 73 (positivo para B. pertussis en 70 y B. parapertussis en tres). CONCLUSIONES: el diagnóstico de tosferina habitualmente es difícil, ya que la sintomatología inicialmente es inespecífica. El diagnóstico precoz es fundamental para iniciar un tratamiento inmediato y realizar una adecuada profilaxis de contactos

INTRODUCTION: the aim of the study was to analyse the clinical characteristics, diagnostic tests performed and treatment used in patients with pertussis evaluated in the paediatric emergency setting. MATERIAL AND METHODS: we conducted a retrospective descriptive study of patients with pertussis that sought care in the paediatric emergency department of a tertiary care hospital between March 2014 and October 2017. RESULTS: the sample included 89 patients with a mean age of 1.67 ± 2.9 years. Of the total, 98.9% presented with cough, 33% with inspiratory whoop and 34.8% with apnoea. Sixty-four percent of cases occurred in the context of an epidemic of cough or pertussis. The mean number of emergency visits made during a single episode of disease was 1.4. The most frequent diagnoses in the initial emergency visit were cough (36%), suspected pertussis (22.5%), upper respiratory tract infection (19.1%) and bronchiolitis (9%). Fifty-six patients were admitted to hospital (62.9%) with a mean age of 0.38 ± 1.2 years. Cultures for detection of Bordetella were performed in 88 cases (positive for B. pertussis in 38 and B. parapertussis in 3), and PCR tests in 73 (positive for B. pertussis in 70 and B. parapertussis in 3). CONCLUSIONS: the diagnosis of pertussis is usually challenging, as its initial symptoms are nonspecific. Early diagnosis is essential for early initiation of treatment and adequate contact prophylaxis

Complex Morphogenesis by a Model Intrinsically Disordered Protein.

The development of intricate and complex self-assembling structures in the micrometer range, such as biomorphs, is a major challenge in materials science. Although complex structures can be obtained from self-assembling materials as they segregate from solution, their size is usually in the nanometer range or requires accessory techniques. Previous studies with intrinsically disordered proteins (IDPs) have shown that the active interplay of different molecular interactions provides access to new and more complex nanostructures. As such, it is hypothesized that enriching the variety of intra- and intermolecular interactions in a model IDP will widen the landscape of sophisticated intermediate structures that can be accessed. In this study, a model silk-elastin-like recombinamer capable of interacting via three non-covalent interactions, namely hydrophobic, ion-pairing, and H-bonding is built. This model material is shown to self-assemble into complex stable micrometer-sized biomorphs. Variation of the block composition, pH, and temperature demonstrates the necessary interplay of all three interactions for the formation of such complex structures.

Importancia del diagnóstico y tratamiento precoz de la encefalitis herpética / Importance of early diagnosis and treatment of herpetic encephalitis

El virus del herpes simple (VHS) produce una encefalitis necrotizante aguda, afectando típicamente al lóbulo temporal. La existencia de un fármaco antiviral específico, así como el uso de medicación adyuvante como la corticoterapia, han mejorado el pronóstico de las infecciones graves. El retraso en el inicio del tratamiento con aciclovir es un factor claramente relacionado con mala evolución, así como las pautas cortas de tratamiento que se han asociado con mayor riesgo de recidivas

Herpes simplex virus (HSV) causes acute necrotizing encephalitis, typically affecting the temporal lobe. The existence of a specific antiviral drug as well as the use of adjuvant medication such as corticotherapy, have improved the prognosis of severe infections. The delay in the start of treatment with acyclovir is a factor clearly related to poor evolution, as well as short treatment guidelines that have been associated with an increased risk of recurrence