Publications by authors named "Daniel Lopez"

206 Publications

A Drastic Shift in Lipid Adducts in Colon Cancer Detected by MALDI-IMS Exposes Alterations in Specific K Channels.

Cancers (Basel) 2021 Mar 17;13(6). Epub 2021 Mar 17.

Institut d'Investigació Sanitària Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, Spain.

Even though colorectal cancer (CRC) is one of the most preventable cancers, it is one of the deadliest, and recent data show that the incidence in people <50 years has unexpectedly increased. While new techniques for CRC molecular classification are emerging, no molecular feature is as yet firmly associated with prognosis. Imaging mass spectrometry (IMS) lipidomic analyses have demonstrated the specificity of the lipid fingerprint in differentiating pathological from healthy tissues. During IMS lipidomic analysis, the formation of ionic adducts is common. Of particular interest is the [Na]/[K] adduct ratio, which already functions as a biomarker for homeostatic alterations. Herein, we show a drastic shift of the [Na]/[K] adduct ratio in adenomatous colon mucosa compared to healthy mucosa, suggesting a robust increase in K levels. Interrogating public databases, a strong association was found between poor diagnosis and voltage-gated potassium channel subunit beta-2 (KCNAB2) overexpression. We found this overexpression in three CRC molecular subtypes defined by the CRC Subtyping Consortium, making KCNAB2 an interesting pharmacological target. Consistently, its pharmacological inhibition resulted in a dramatic halt in commercial CRC cell proliferation. Identification of potential pharmacologic targets using lipid adduct information emphasizes the great potential of IMS lipidomic techniques in the clinical field.
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http://dx.doi.org/10.3390/cancers13061350DOI Listing
March 2021

Gorilla Glue Ingestion in Dogs: 22 Cases (2005-2019).

J Am Anim Hosp Assoc 2021 Mar 26. Epub 2021 Mar 26.

Gorilla Glue contains methylene diphenyl diisocyanate that expands significantly and hardens once exposed to moisture. Case reports of methylene diphenyl diisocyanate glue ingestion in dogs document gastrointestinal foreign body formation and mechanical obstruction. Medical record queries from four veterinary hospitals identified 22 dogs with Gorilla Glue ingestion. Records were evaluated retrospectively to characterize clinical presentation, diagnostic findings, treatment, and patient outcome. Vomiting was the most common clinical sign (n = 11), with a median time from ingestion to presentation of 42 hr. Abnormal abdominal palpation (e.g., pain) was the most reported examination finding (n = 13). Radiographs were performed in 18/22 dogs, with Gorilla Glue expansion described as granular or mottled soft tissue with gas in the stomach. In 73% (11/15) of dogs requiring surgery, history, clinical findings, and survey abdominal radiographs sufficed to proceed with celiotomy. Surgical removal of the Gorilla Glue foreign body was performed via gastrotomy (n = 14) or gastrotomy and duodenotomy (n = 1). Endoscopic removal was performed in one dog. One dog with suspected mechanical obstruction was euthanized owing to financial constraints. Remaining cases were managed conservatively (n = 5). Short-term prognosis following appropriate fluid therapy and surgical or endoscopic removal was very good.
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http://dx.doi.org/10.5326/JAAHA-MS-7126DOI Listing
March 2021

Transmission of SARS-CoV-2 infection among children in summer schools applying stringent control measures in Barcelona, Spain.

Clin Infect Dis 2021 Mar 12. Epub 2021 Mar 12.

BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), University of Barcelona, Barcelona, Spain.

Background: Understanding the role of children in SARS-CoV-2 transmission is critical to guide decision-making for schools in the pandemic. We aimed to describe the transmission of SARS-CoV-2 among children and adult staff in summer schools.

Methods: During July 2020 we prospectively recruited children and adult staff attending summer schools in Barcelona who had SARS-CoV-2 infection. Primary SARS-CoV-2 infections were identified through: (1) surveillance program in 22 summer schools' of 1905 participants, involving weekly saliva sampling for SARS-CoV-2 RT-PCR during 2-5 weeks; (2)cases identified through the Catalonian Health Surveillance System of children diagnosed with SARS-CoV-2 infection by nasopharyngeal RT-PCR. All centres followed prevention protocols: bubble groups, hand washing, facemasks and conducting activities mostly outdoors. Contacts of a primary case within the same bubble were evaluated by nasopharyngeal RT-PCR. Secondary attack rates and effective reproduction number in summer schools(R*) were calculated.

Results: Among the over 2000 repeatedly screened participants, 30children and 9adults were identified as primary cases. A total of 253 close contacts of these primary cases were studied (median 9 (IQR 5-10) for each primary case), among which twelve new cases (4.7%) were positive for SARS-CoV-2. The R* was 0.3, whereas the contemporary rate in the general population from the same areas in Barcelona was 1.9.

Conclusions: The transmission rate of SARS-CoV-2 infection among children attending school-like facilities under strict prevention measures was lower than that reported for the general population. This suggests that under preventive measures schools are unlikely amplifiers of SARS-CoV-2 transmission and supports current recommendations for school opening.
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http://dx.doi.org/10.1093/cid/ciab227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989514PMC
March 2021

Identification and validation of clinical phenotypes with prognostic implications in patients admitted to hospital with COVID-19: a multicentre cohort study.

Lancet Infect Dis 2021 Feb 23. Epub 2021 Feb 23.

Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain; Departamento de Medicina, Universidad de Sevilla, Seville, Spain; Instituto de Biomedicina de Sevilla, Seville, Spain. Electronic address:

Background: The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality.

Methods: In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model.

Findings: Three distinct phenotypes were derived in the derivation cohort (n=2667)-phenotype A (516 [19%] patients), phenotype B (1955 [73%]) and phenotype C (196 [7%])-and reproduced in the internal validation cohort (n=1368)-phenotype A (233 [17%] patients), phenotype B (1019 [74%]), and phenotype C (116 [8%]). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4-4·3) for patients with phenotype A, 30·5% (28·5-32·6) for patients with phenotype B, and 60·7% (53·7-67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% [95% CI 3·4-8·1] for phenotype A, 31·3% [28·5-34·2] for phenotype B, and 59·5% [48·8-69·3] for phenotype C; external validation cohort: 3·7% [2·0-6·4] for phenotype A, 23·7% [21·8-25·7] for phenotype B, and 51·4% [41·9-60·7] for phenotype C).

Interpretation: Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.

Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.
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http://dx.doi.org/10.1016/S1473-3099(21)00019-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906623PMC
February 2021

Characterization of Joints between Carbon Fiber Composite Parts Using a Microstrip Transmission Line Method.

Sensors (Basel) 2021 Feb 6;21(4). Epub 2021 Feb 6.

Radiofrequency Area, National Institute for Aerospace Technology (INTA), Torrejon de Ardoz, 28850 Madrid, Spain.

The electromagnetic performance of aerial platforms, which are composed mostly of nonmetallic materials, is a subject of great interest at present time. The behavior of this type of composite structure against electromagnetic environmental effects (E3), such as lightning, is not well-studied as in the case of metalic structures. The purpose of this article is to characterize the joints present in aerial platforms constructed mainly of nonmetallic composite materials. The study of these joints is fundamental because electrical discontinuities or preferential routes can produce changes in the electromagnetic behavior of an aircraft. The proposed measurement system for the characterization of these joints is a microstrip line. The flexibility of the test setup allows for evaluation of different joints in carbon fiber composite (CFC) samples with a different number of plies. Additionally, approximated models of the behavior of the joints as well as the detection of possible defects in the joining process are reported.
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http://dx.doi.org/10.3390/s21041142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915388PMC
February 2021

Melt-Processed Bioactive EVOH Films Incorporated with Ferulic Acid.

Polymers (Basel) 2020 Dec 26;13(1). Epub 2020 Dec 26.

Instituto de Agroquímica y Tecnología de Alimentos, IATA-CSIC, calle del Catedrático Agustín Escardino Benlloch 7, 46980 Paterna, Valencia, Spain.

In this work, antimicrobial and antioxidant films based on ethylene vinyl alcohol (EVOH) copolymer containing low amounts of ferulic acid (FA) were successfully developed by melt extrusion. Optically transparent films were obtained, and the presence of FA provided some UV blocking effect. The characterization of the thermal and barrier properties of the developed films showed that the addition of FA improved the thermal stability, decreased the glass transition temperature (T) and increased the water vapor and oxygen transmission rates when ferulic acid was loaded above 0.5 wt.%, associated with its plasticizing effect. Mechanical characterization confirmed the plasticizing effect by an increase in the elongation at break values while no significant differences were observed in Young's modulus and tensile strength. Significant antioxidant activity of all active films exposed to two food simulants, 10% ethanol and 95% ethanol, was also confirmed using the 2,2-diphenyl-1-pricylhydrazyl (DPPH) free radical scavenging method, indicating that FA conserved its well-known antioxidant properties after melt-processing. Finally, EVOH-FA samples presented antibacterial activity in vitro against and , thus showing the potential of ferulic acid as bioactive compound to be used in extrusion processing for active packaging applications.
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http://dx.doi.org/10.3390/polym13010068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795252PMC
December 2020

Kirigami Engineering-Nanoscale Structures Exhibiting a Range of Controllable 3D Configurations.

Adv Mater 2021 Feb 22;33(5):e2005275. Epub 2020 Dec 22.

Department of Electrical Engineering and Materials Research Institute, Penn State University, University Park, PA, 16802, USA.

Kirigami structures provide a promising approach to transform flat films into 3D complex structures that are difficult to achieve by conventional fabrication approaches. By designing the cutting geometry, it is shown that distinct buckling-induced out-of-plane configurations can be obtained, separated by a sharp transition characterized by a critical geometric dimension of the structures. In situ electron microscopy experiments reveal the effect of the ratio between the in-plane cut size and film thickness on out-of-plane configurations. Moreover, geometrically nonlinear finite element analyses (FEA) accurately predict the out-of-plane modes measured experimentally, their transition as a function of cut geometry, and provide the stress-strain response of the kirigami structures. The combined computational-experimental approach and results reported here represent a step forward in the characterization of thin films experiencing buckling-induced out-of-plane shape transformations and provide a path to control 3D configurations of micro- and nanoscale buckling-induced kirigami structures. The out-of-plane configurations promise great utility in the creation of micro- and nanoscale systems that can harness such structural behavior, such as optical scanning micromirrors, novel actuators, and nanorobotics. This work is of particular significance as the kirigami dimensions approach the sub-micrometer scale which is challenging to achieve with conventional micro-electromechanical system technologies.
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http://dx.doi.org/10.1002/adma.202005275DOI Listing
February 2021

A micromirror array with annular partitioning for high-speed random-access axial focusing.

Light Sci Appl 2020 Oct 29;9(1):183. Epub 2020 Oct 29.

The University of California, Berkeley and University of California, San Francisco Graduate Program in Bioengineering, Berkeley, CA, 94720, USA.

Dynamic axial focusing functionality has recently experienced widespread incorporation in microscopy, augmented/virtual reality (AR/VR), adaptive optics and material processing. However, the limitations of existing varifocal tools continue to beset the performance capabilities and operating overhead of the optical systems that mobilize such functionality. The varifocal tools that are the least burdensome to operate (e.g. liquid crystal, elastomeric or optofluidic lenses) suffer from low (≈100 Hz) refresh rates. Conversely, the fastest devices sacrifice either critical capabilities such as their dwelling capacity (e.g. acoustic gradient lenses or monolithic micromechanical mirrors) or low operating overhead (e.g. deformable mirrors). Here, we present a general-purpose random-access axial focusing device that bridges these previously conflicting features of high speed, dwelling capacity and lightweight drive by employing low-rigidity micromirrors that exploit the robustness of defocusing phase profiles. Geometrically, the device consists of an 8.2 mm diameter array of piston-motion and 48-μm-pitch micromirror pixels that provide 2π phase shifting for wavelengths shorter than 1100 nm with 10-90% settling in 64.8 μs (i.e., 15.44 kHz refresh rate). The pixels are electrically partitioned into 32 rings for a driving scheme that enables phase-wrapped operation with circular symmetry and requires <30 V per channel. Optical experiments demonstrated the array's wide focusing range with a measured ability to target 29 distinct resolvable depth planes. Overall, the features of the proposed array offer the potential for compact, straightforward methods of tackling bottlenecked applications, including high-throughput single-cell targeting in neurobiology and the delivery of dense 3D visual information in AR/VR.
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http://dx.doi.org/10.1038/s41377-020-00420-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596532PMC
October 2020

Empirical model for short-time prediction of COVID-19 spreading.

PLoS Comput Biol 2020 12 9;16(12):e1008431. Epub 2020 Dec 9.

Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Catalonia, Spain.

The appearance and fast spreading of Covid-19 took the international community by surprise. Collaboration between researchers, public health workers, and politicians has been established to deal with the epidemic. One important contribution from researchers in epidemiology is the analysis of trends so that both the current state and short-term future trends can be carefully evaluated. Gompertz model has been shown to correctly describe the dynamics of cumulative confirmed cases, since it is characterized by a decrease in growth rate showing the effect of control measures. Thus, it provides a way to systematically quantify the Covid-19 spreading velocity and it allows short-term predictions and longer-term estimations. This model has been employed to fit the cumulative cases of Covid-19 from several European countries. Results show that there are systematic differences in spreading velocity among countries. The model predictions provide a reliable picture of the short-term evolution in countries that are in the initial stages of the Covid-19 outbreak, and may permit researchers to uncover some characteristics of the long-term evolution. These predictions can also be generalized to calculate short-term hospital and intensive care units (ICU) requirements.
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http://dx.doi.org/10.1371/journal.pcbi.1008431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725384PMC
December 2020

Role of Multiparametric Prostate Magnetic Resonance Imaging before Confirmatory Biopsy in Assessing the Risk of Prostate Cancer Progression during Active Surveillance.

Korean J Radiol 2021 04 26;22(4):559-567. Epub 2020 Nov 26.

Department of Urology, Reina Sofía University Hospital, IMIBIC, Cordoba University, Córdoba, Spain.

Objective: To evaluate the impact of multiparametric magnetic resonance imaging (mpMRI) before confirmatory prostate biopsy in patients under active surveillance (AS).

Materials And Methods: This retrospective study included 170 patients with Gleason grade 6 prostate cancer initially enrolled in an AS program between 2011 and 2019. Prostate mpMRI was performed using a 1.5 tesla (T) magnetic resonance imaging system with a 16-channel phased-array body coil. The protocol included T1-weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging sequences. Uroradiology reports generated by a specialist were based on prostate imaging-reporting and data system (PI-RADS) version 2. Univariate and multivariate analyses were performed based on regression models.

Results: The reclassification rate at confirmatory biopsy was higher in patients with suspicious lesions on mpMRI (PI-RADS score ≥ 3) (n = 47) than in patients with non-suspicious mpMRIs (n = 61) and who did not undergo mpMRIs (n = 62) (66%, 26.2%, and 24.2%, respectively; < 0.001). On multivariate analysis, presence of a suspicious mpMRI finding (PI-RADS score ≥ 3) was associated (adjusted odds ratio: 4.72) with the risk of reclassification at confirmatory biopsy after adjusting for the main variables (age, prostate-specific antigen density, number of positive cores, number of previous biopsies, and clinical stage). Presence of a suspicious mpMRI finding (adjusted hazard ratio: 2.62) was also associated with the risk of progression to active treatment during the follow-up.

Conclusion: Inclusion of mpMRI before the confirmatory biopsy is useful to stratify the risk of reclassification during the biopsy as well as to evaluate the risk of progression to active treatment during follow-up.
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http://dx.doi.org/10.3348/kjr.2020.0852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005352PMC
April 2021

Cardanol /SiO Nanocomposites for Inhibition of Formation Damage by Asphaltene Precipitation/Deposition in Light Crude Oil Reservoirs. Part II: Nanocomposite Evaluation and Coreflooding Test.

ACS Omega 2020 Nov 23;5(43):27800-27810. Epub 2020 Oct 23.

Grupo de Investigación en Fenómenos de Superficie - Michael Polanyi, Facultad de Minas, Universidad Nacional de Colombia, sede Medellín 050041216, Colombia.

This study aims to evaluate the behavior of Cardanol/SiO nanocomposites in the inhibition of the asphaltene damage based on the coreflooding test at reservoir conditions. The nanocomposite design was performed in Part I (https://doi.org/10.1021/acs.energyfuels.0c01114), leading to SiO nanoparticles functionalized with different mass fractions of cardanol on the surface of 5 (5CSN), 7 (7CSN), and 9% (9CSN). In this part of the study, the nanocomposite/reservoir fluid interactions were evaluated through interfacial tension measurements and nanocomposite/rock surface interactions using water imbibition and contact angle measurements. Results showed that the designed nanocomposite leads to a reduction of interfacial tension of 82.6, 61.7, and 51.4% for 5CSN, 7CSN, and 9CSN regarding silica support (SN). Whereas, the reduction of the Si-OH functional groups from SiO nanoparticles due to the increase of the cardanol content affects the effectiveness of the wettability alteration for 7CSN and 9CSN. Nevertheless, when 5CSN is evaluated, the system is altered from an oil-wet to a mixed-wet state. Coreflooding tests at reservoir conditions were performed to evaluate the oil recovery after asphaltene damage, after damage removal and nanofluid injection, and after induction of a second asphaltene damage to check inhibition. Results show that the selected nanocomposites at a dosage of 300 mg·L enhance the oil recovery in comparison with the baseline conditions via the reduction of the interfacial/surface forces at the pore scale and wettability alteration. It is worth to remark that this improvement remains after the second asphaltene damage induction, which proves the high inhibitory capacity of the designed nanocomposite for the asphaltene precipitation/deposition. Also, the use of the nanocomposites favors the oil recovery more than 50% compared to the asphaltene damage scenario.
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http://dx.doi.org/10.1021/acsomega.0c02722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643095PMC
November 2020

Hybrid Biocomposites Based on Poly(Lactic Acid) and Silica Aerogel for Food Packaging Applications.

Materials (Basel) 2020 Oct 31;13(21). Epub 2020 Oct 31.

Instituto de Ciencia y Tecnología de Polímeros, ICTP-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.

Bionanocomposites based on poly (lactic acid) (PLA) and silica aerogel (SiA) were developed by means of melt extrusion process. PLA-SiA composite films were plasticized with 15 wt.% of acetyl (tributyl citrate) (ATBC) to facilitate the PLA processability as well as to attain flexible polymeric formulations for films for food packaging purposes. Meanwhile, SiA was added in four different proportions (0.5, 1, 3 and 5 wt.%) to evaluate the ability of SiA to improve the thermal, mechanical, and barrier performance of the bionanocomposites. The mechanical performance, thermal stability as well as the barrier properties against different gases (carbon dioxide, nitrogen, and oxygen) of the bionanocomposites were evaluated. It was observed that the addition of 3 wt.% of SiA to the plasticized PLA-ATBC matrix showed simultaneously an improvement on the thermal stability as well as the mechanical and barrier performance of films. Finally, PLA-SiA film formulations were disintegrated in compost at the lab-scale level. The combination of ATBC and SiA sped up the disintegration of PLA matrix. Thus, the bionanocomposites produced here show great potential as sustainable polymeric formulations with interest in the food packaging sector.
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http://dx.doi.org/10.3390/ma13214910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663595PMC
October 2020

Associations between wild birds and hard ticks (Acari: Ixodidae) in Colombia.

Ticks Tick Borne Dis 2020 11 3;11(6):101534. Epub 2020 Aug 3.

Grupo de Investigación GEBIOME, Departamento de Desarrollo Rural y Recursos Naturales, Facultad de Ciencias Agropecuarias, Universidad de Caldas, Calle 65 No. 26-10 A.A. 275 Manizales, Caldas, Colombia.

Ticks of the family Ixodidae are vectors of important pathogens in human and animal health. Birds are involved in long-distance transport and dispersion of hard ticks. Tick infestations on wild birds mostly involve species within the genera Amblyomma, Ixodes, and Haemaphysalis. In Colombia, tick research is scarce and there are no studies to date about the associations between wild birds and ticks. We aimed to contribute to the knowledge of the associations between wild birds and hard ticks based on the collection of 2314 wild birds belonging to 29 families in Caldas - Colombia between 2015 and 2019. In total, we collected 133 hard ticks that were found parasitizing 78 birds representing 45 species and 14 wild bird families. We report at least seven tick species on birds confirmed by morphological and molecular methods: Amblyomma longirostre, Amblyomma varium, Amblyomma dissimile, Amblyomma ovale, Amblyomma nodosum, Amblyomma calcaratum and Haemaphysalis leporispalustris. In addition, we recorded three Ixodes species, which yielded DNA sequences that did not have high identity (≤ 95 %) to any species in GenBank. Ticks were found infesting resident and migratory boreal birds. This is the first study addressing the associations between wild birds and hard ticks in Colombia. We describe new associations between birds and ticks in the Americas.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101534DOI Listing
November 2020

A Multicenter International Randomized Controlled Manikin Study on Different Protocols of Cardiopulmonary Resuscitation for Laypeople: The MANI-CPR Trial.

Simul Healthc 2020 09 23. Epub 2020 Sep 23.

From the Pavia nel Cuore (E.B., E.C., M.P., C.B.), Pavia; Robbio nel Cuore (E.B., E.C., D.B.), Robbio; Department of Molecular Medicine (E.B.), Section of Cardiology, University of Pavia; Cardiac Intensive Care Unit, Arrhythmia and Electrophysiology and Experimental Cardiology (E.B.), Fondazione IRCCS Policlinico San Matteo; AAT 118 Pavia (E.C.), AREU Lombardia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Swiss Resuscitation Council (R.B.), Bern, Switzerland; Fondazione Ticino Cuore (R.B.), Breganzona, Switzerland; Department of Public Health, Experimental and Forensic Medicine (P.B., O.E.F.), Unit of Biostatistics and Clinical Epidemiology, University of Pavia; Department of Clinical-Surgical, Pediatric and Diagnostic Sciences-Anesthesia, Intensive Care and Pain Therapy (M.P.), University of Pavia, Pavia; Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), Department of Anesthesia Intensive Care and Emergency (M.P., A.C.), Policlinico Paolo Giaccone, University of Palermo, Palermo, Italy; Federazione Cantonale Ticinese Servizi Autoambulanze (C.T.), Lugano; Accademia di Medicina d'Urgenza Ticinese (AMUT) (C.T.), Breganzona, Switzerland; Emergency Training Center (D.L.), Cugy, Switzerland; Centro Studi e Formazione Gymnasium (S.B.), Pordenone, Italy; École Supérieure d'Ambulancier et Soins d'Urgence Romande (ES-ASUR) (S.D.), Lausanne; and Formamed Sàrl (M.T.), Cortaillod, Switzerland.

Background: Compression-only cardiopulmonary resuscitation (CPR) is a suggested technique for laypeople facing out-of-hospital cardiac arrest (OHCA). However, it is difficult performing high-quality CPR until emergency medical services arrival with this technique. We aimed to verify whether incorporating intentional interruptions of different frequency and duration increases laypeople's CPR quality during an 8-minute scenario compared with compression-only CPR.

Methods: We performed a multicenter randomized manikin study selecting participants from 2154 consecutive laypeople who followed a basic life support/automatic external defibrillation course. People who achieved high-quality CPR in 1-minute test on a computerized manikin were asked to participate. Five hundred seventy-six were enrolled, and 59 were later excluded for technical reasons or incorrect test recording. Participants were randomized in an 8-minute OHCA scenario using 3 CPR protocols (30 compressions and 2-second pause, 30c2s; 50 compressions and 5-second pause, 50c5s; 100 compressions and 10-second pause, 100c10s) or compression-only technique. The main outcome was the percentage of chest compressions with adequate depth.

Results: Five hundred seventeen participants were evaluated. There was a statistically significant difference regarding the percentage of compressions with correct depth among the groups (30c2s, 96%; 50c5s, 96%; 100c10s, 92%; compression only, 79%; P = 0.006). Post hoc comparison showed a significant difference for 30c2s (P = 0.023) and for 50c5s (P = 0.003) versus compression only. Regarding secondary outcome, there were a higher chest compression fraction in the compression-only group and a higher rate of pauses longer than 10 seconds in the 100c10s.

Conclusions: In a simulated OHCA, 30c2s and 50c5s protocols were characterized by a higher rate of chest compressions with correct depth than compression only. This could have practical consequences in laypeople CPR training and recommendations.

Clinical Trial Registration: NCT02632500.
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http://dx.doi.org/10.1097/SIH.0000000000000505DOI Listing
September 2020

A reaction-diffusion model to understand granulomas formation inside secondary lobule during tuberculosis infection.

PLoS One 2020 16;15(9):e0239289. Epub 2020 Sep 16.

Department of Physics, Universitat Politècnica de Catalunya, Barcelona, Catalonia, Spain.

Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, the most extended infectious disease around the world. When Mtb enters inside the pulmonary alveolus it is rapidly phagocytosed by the alveolar macrophage. Although this controls the majority of inhaled microorganisms, in this case, Mtb survives inside the macrophage and multiplies. A posterior chemokine and cytokine cascade generated by the irruption of monocytes, neutrophils and posteriorly, by T-cells, does not necessarily stop the growth of the granuloma. Interestingly, the encapsulation process built by fibroblasts is able to surround the lesion and stop its growing. The success of this last process determines if the host enters in an asymptomatic latent state or continues into a life-threatening and infective active tuberculosis disease (TB). Understanding such dichotomic process is challenging, and computational modeling can bring new ideas. Thus, we have modeled the different stages of the infection, first in a single alveolus (a sac with a radius of 0.15 millimeters) and, second, inside a secondary lobule (a compartment of the lungs of around 3 cm3). We have employed stochastic reaction-diffusion equations to model the interactions among the cells and the diffusive transport to neighboring alveolus. The whole set of equations have successfully described the encapsulation process and determine that the size of the lesions depends on its position on the secondary lobule. We conclude that size and shape of the secondary lobule are the relevant variables to control the lesions, and, therefore, to avoid the evolution towards TB development. As lesions appear near to interlobular connective tissue they are easily controlled and their growth is drastically stopped, in this sense secondary lobules with a more flattened shape could control better the lesion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239289PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494083PMC
November 2020

Molecular α-relaxation process of exopolysaccharides extracted from Nostoc commune cyanobacteria.

Int J Biol Macromol 2020 Oct 2;161:1516-1525. Epub 2020 Aug 2.

Institute of Polymer Science and Technology, Spanish Council for Scientific Research (ICTP-CSIC), Madrid, Spain.

Broadband dielectric spectroscopy was used to investigate the molecular α-relaxation of the exopolysaccharides (EPS) extracted from Nostoc commune cyanobacteria. The EPS were modified in different ways. EPS were carboxymethylated to obtain carboxymethyl-exopolysaccharides (CEPS). EPS and CEPS were doped with ammonium iodide and 1-butyl-3-methylimidazolium chloride. An α relaxation process was observed for all specimens. The temperature dependence of the relaxation times for pure and doped, EPS and CEPS polymers exhibited non-Arrhenius behavior. This relaxation process was associated with the glass transition of the complex heteropolysaccharides produced by the cyanobacteria. The molecular mobility at the glass transition, T, was affected by both the carboxymethylation treatment and the doping. The fragility index also decreased for the doped specimens, which may be attributed to an increase in the mobility of the polymer chains due to the plasticizing effect of the doping agents.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.07.268DOI Listing
October 2020

Immune Landscape in Tumor Microenvironment: Implications for Biomarker Development and Immunotherapy.

Int J Mol Sci 2020 Aug 1;21(15). Epub 2020 Aug 1.

Lipids in Human Pathology, Health Research Institute of the Balearic Islands (IdISBa), Research Unit, University Hospital Son Espases, 07120 Palma, Spain.

Integration of the tumor microenvironment as a fundamental part of the tumorigenic process has undoubtedly revolutionized our understanding of cancer biology. Increasing evidence indicates that neoplastic cells establish a dependency relationship with normal resident cells in the affected tissue and, furthermore, develop the ability to recruit new accessory cells that aid tumor development. In addition to normal stromal and tumor cells, this tumor ecosystem includes an infiltrated immune component that establishes complex interactions that have a critical effect during the natural history of the tumor. The process by which immune cells modulate tumor progression is known as immunoediting, a dynamic process that creates a selective pressure that finally leads to the generation of immune-resistant cells and the inability of the immune system to eradicate the tumor. In this context, the cellular and functional characterization of the immune compartment within the tumor microenvironment will help to understand tumor progression and, ultimately, will serve to create novel prognostic tools and improve patient stratification for cancer treatment. Here we review the impact of the immune system on tumor development, focusing particularly on its clinical implications and the current technologies used to analyze immune cell diversity within the tumor.
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http://dx.doi.org/10.3390/ijms21155521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432816PMC
August 2020

Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers.

J Transl Autoimmun 2020 17;3:100027. Epub 2019 Dec 17.

GIRAT: Grupo de Investigación en Reumatología, Autoinmunidad y Medicina Traslacional; Fundación Valle Del Lili and Universidad Icesi, Cali, Colombia.

Background: B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and their receptors BAFF-R, BCMA, and TACI are crucial factors for the survival of B lymphocytes. Recent evidence has also demonstrated the importance of BAFF/APRIL signaling in lupus nephritis (LN). This study evaluated the relationships between LN clinical characteristics and the urinary expression levels of BAFF, APRIL, and cognate receptors to assess their potential value as disease biomarkers.

Methods: Expression levels of these genes were assessed in urine samples collected from systemic lupus erythematosus (SLE) patients before renal biopsy using reverse transcription real-time PCR.

Results: Thirty-five patients with LN were included. Most of the patients were female (82.86%) with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 15. BAFF mRNA was detectable in 28.57%, APRIL mRNA in 42.85%, BR3 mRNA in 48.57%, and TACI mRNA in 42.85% of urine samples. On the other hand, urinary (u)BCMA mRNA was not found in any sample. Urinary expression of most biomarkers was detected with greater frequency in class III and IV LN compared to class V LN. The expression level of uBR3 mRNA was correlated with SLEDAI-2K and histological activity index.

Conclusion: Urinary expression of BAFF/APRIL signaling factors, especially TACI, APRIL, and BR3 mRNAs, may be useful biomarkers for LN.
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http://dx.doi.org/10.1016/j.jtauto.2019.100027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388398PMC
December 2019

Identification and Analysis of Unstructured, Linear B-Cell Epitopes in SARS-CoV-2 Virion Proteins for Vaccine Development.

Vaccines (Basel) 2020 Jul 20;8(3). Epub 2020 Jul 20.

Intrahospital Infections Unit, National Centre for Microbiology, Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain.

The efficacy of SARS-CoV-2 nucleic acid-based vaccines may be limited by proteolysis of the translated product due to anomalous protein folding. This may be the case for vaccines employing linear SARS-CoV-2 B-cell epitopes identified in previous studies since most of them participate in secondary structure formation. In contrast, we have employed a consensus of predictors for epitopic zones plus a structural filter for identifying 20 unstructured B-cell epitope-containing loops (uBCELs) in S, M, and N proteins. Phylogenetic comparison suggests epitope switching with respect to SARS-CoV in some of the identified uBCELs. Such events may be associated with the reported lack of serum cross-protection between the 2003 and 2019 pandemic strains. Incipient variability within a sample of 1639 SARS-CoV-2 isolates was also detected for 10 uBCELs which could cause vaccine failure. Intermediate stages of the putative epitope switch events were observed in bat coronaviruses in which additive mutational processes possibly facilitating evasion of the bat immune system appear to have taken place prior to transfer to humans. While there was some overlap between uBCELs and previously validated SARS-CoV B-cell epitopes, multiple uBCELs had not been identified in prior studies. Overall, these uBCELs may facilitate the development of biomedical products for SARS-CoV-2.
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http://dx.doi.org/10.3390/vaccines8030397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564417PMC
July 2020

Retrospective evaluation on the outcome of perineal herniorrhaphy augmented with porcine small intestinal submucosa in dogs and cats.

Can Vet J 2020 06;61(6):629-637

Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, Ontario N1G 2W1.

The purpose of this study was to evaluate post-operative outcome in dogs and cats undergoing perineal herniorrhaphy using porcine small intestinal submucosa (PSIS) alone and with internal obturator muscle transposition augmented with PSIS (IOMT + PSIS). Medical records were retrospectively reviewed and information collected on signalment, pre-operative signs, operative details, and hospitalization. Data on post-operative outcome were obtained from medical records and survey. Eleven dogs and 3 cats had 18 perineal hernias repaired with IOMT + PSIS and 3 using PSIS alone. Surgical site infection developed following IOMT + PSIS in 1/21 hernias (5.6%). Short- and long-term postoperative complications occurred in 9/14 animals and 3/14 animals, respectively. Among the 21 perineal hernias, 3 recurred, 2 of which were repaired with IOMT + PSIS and 1 with PSIS alone. Use of PSIS alone or augmenting IOMT was acceptable for perineal herniorrhaphy and should be considered by surgeons if there are concerns about internal obturator muscle integrity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238463PMC
June 2020

Organic and Inorganic PCL-Based Electrospun Fibers.

Polymers (Basel) 2020 Jun 10;12(6). Epub 2020 Jun 10.

Instituto de Ciencia y Tecnología de Polímeros (ICTP-CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain.

In this work, different nanocomposite electrospun fiber mats were obtained based on poly(e-caprolactone) (PCL) and reinforced with both organic and inorganic nanoparticles. In particular, on one side, cellulose nanocrystals (CNC) were synthesized and functionalized by "" reaction, using their superficial OH- group to graft PCL chains. On the other side, commercial chitosan, graphene as organic, while silver, hydroxyapatite, and fumed silica nanoparticles were used as inorganic reinforcements. All the nanoparticles were added at 1 wt% with respect to the PCL polymeric matrix in order to compare the different behavior of the woven no-woven nanocomposite electrospun fibers with a fixed amount of both organic and inorganic nanoparticles. From the thermal point of view, no difference was found between the effect of the addition of organic or inorganic nanoparticles, with no significant variation in the Tg (glass transition temperature), Tm (melting temperature), and the degree of crystallinity, leading in all cases to high crystallinity electrospun mats. From the mechanical point of view, the highest values of Young modulus were obtained when graphene, CNC, and silver nanoparticles were added to the PCL electrospun fibers. Moreover, all the nanoparticles used, both organic and inorganic, increased the flexibility of the electrospun mats, increasing their elongation at break.
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http://dx.doi.org/10.3390/polym12061325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361952PMC
June 2020

Approaching the Strain-Free Limit in Ultrathin Nanomechanical Resonators.

Nano Lett 2020 Aug 17;20(8):5693-5698. Epub 2020 Jul 17.

Center for Nanoscale Materials, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, United States.

Ultrathin mechanical structures are ideal building platforms to pursue the ultimate limit of nanomechanical resonators for applications in sensing, signal processing, and quantum physics. Unfortunately, as the thickness of the vibrating structures is reduced, the built-in strain of the structural materials plays an increased role in determining the mechanical performance of the devices. As a consequence, it is very challenging to fabricate resonators working in the modulus-dominant regime, where their dynamic behavior is exclusively determined by the device geometry. In this Letter, we report ultrathin doubly clamped nanomechanical resonators with aspect ratios as large as / ∼5000 and working in the modulus-dominant regime. We observed room temperature thermomechanically induced motion of multiple vibration modes with resonant frequencies closely matching the predicted values of Euler-Bernoulli beam theory under an axial strain of 6.3 × 10. The low strain of the devices enables a record frequency tuning ratio of more than 50 times. These results illustrate a new strategy for the quantitative design of nanomechanical resonators with unprecedented performance.
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http://dx.doi.org/10.1021/acs.nanolett.0c01027DOI Listing
August 2020

Biodegradable and Antimicrobial PLA-OLA Blends Containing Chitosan-Mediated Silver Nanoparticles with Shape Memory Properties for Potential Medical Applications.

Nanomaterials (Basel) 2020 May 30;10(6). Epub 2020 May 30.

MacroEng Group, Instituto de Ciencia y Tecnología de Polímeros, ICTP-CSIC, C/Juan de la Cierva 3, 28006 Madrid, Spain.

To use shape memory materials based on poly (lactic acid) (PLA) for medical applications is essential to tune their transition temperature (T) near to the human body temperature. In this study, the combination of lactic acid oligomer (OLA), acting as a plasticizer, together with chitosan-mediated silver nanoparticles (AgCH-NPs) to create PLA matrices is studied to obtain functional shape memory polymers for potential medical applications. PLA/OLA nanocomposites containing different amounts of AgCH-NPs were obtained and profusely characterized relating their structure with their antimicrobial and shape memory performances. Nanocomposites exhibited shape memory responses at the temperature of interest (near physiological one), as well as excellent shape memory responses, shorter recovery times and higher recovery ratios (over 100%) when compared to neat materials. Moreover, antibacterial activity tests confirmed biocidal activity; therefore, these functional polymer nanocomposites with shape memory, degradability and biocidal activity show great potential for soft actuation applications in the medical field.
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http://dx.doi.org/10.3390/nano10061065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352577PMC
May 2020

Common and Differential Traits of the Membrane Lipidome of Colon Cancer Cell Lines and their Secreted Vesicles: Impact on Studies Using Cell Lines.

Cancers (Basel) 2020 May 20;12(5). Epub 2020 May 20.

Lipids in Human Pathology, Health Research Institute of the Balearic Islands (IdISBa), Research Unit, University Hospital Son Espases, 07120 Palma, Spain.

Colorectal cancer (CRC) is the fourth leading cause of cancer death in the world. Despite the screening programs, its incidence in the population below the 50s is increasing. Therefore, new stratification protocols based on multiparametric approaches are highly needed. In this scenario, the lipidome is emerging as a powerful tool to classify tumors, including CRC, wherein it has proven to be highly sensitive to cell malignization. Hence, the possibility to describe the lipidome at the level of lipid species has renewed the interest to investigate the role of specific lipid species in pathologic mechanisms, being commercial cell lines, a model still heavily used for this purpose. Herein, we characterize the membrane lipidome of five commercial colon cell lines and their extracellular vesicles (EVs). The results demonstrate that both cell and EVs lipidome was able to segregate cells according to their malignancy. Furthermore, all CRC lines shared a specific and strikingly homogenous impact on ether lipid species. Finally, this study also cautions about the need of being aware of the singularities of each cell line at the level of lipid species. Altogether, this study firmly lays the groundwork of using the lipidome as a solid source of tumor biomarkers.
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http://dx.doi.org/10.3390/cancers12051293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281030PMC
May 2020

Modelling the dynamics of tuberculosis lesions in a virtual lung: Role of the bronchial tree in endogenous reinfection.

PLoS Comput Biol 2020 05 20;16(5):e1007772. Epub 2020 May 20.

Departament de Física, Universitat Politècnica de Catalunya, Castelldefels, Barcelona, Catalonia, Spain.

Tuberculosis (TB) is an infectious disease that still causes more than 1.5 million deaths annually. The World Health Organization estimates that around 30% of the world's population is latently infected. However, the mechanisms responsible for 10% of this reserve (i.e., of the latently infected population) developing an active disease are not fully understood, yet. The dynamic hypothesis suggests that endogenous reinfection has an important role in maintaining latent infection. In order to examine this hypothesis for falsifiability, an agent-based model of growth, merging, and proliferation of TB lesions was implemented in a computational bronchial tree, built with an iterative algorithm for the generation of bronchial bifurcations and tubes applied inside a virtual 3D pulmonary surface. The computational model was fed and parameterized with computed tomography (CT) experimental data from 5 latently infected minipigs. First, we used CT images to reconstruct the virtual pulmonary surfaces where bronchial trees are built. Then, CT data about TB lesion' size and location to each minipig were used in the parameterization process. The model's outcome provides spatial and size distributions of TB lesions that successfully reproduced experimental data, thus reinforcing the role of the bronchial tree as the spatial structure triggering endogenous reinfection. A sensitivity analysis of the model shows that the final number of lesions is strongly related with the endogenous reinfection frequency and maximum growth rate of the lesions, while their mean diameter mainly depends on the spatial spreading of new lesions and the maximum radius. Finally, the model was used as an in silico experimental platform to explore the transition from latent infection to active disease, identifying two main triggering factors: a high inflammatory response and the combination of a moderate inflammatory response with a small breathing amplitude.
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http://dx.doi.org/10.1371/journal.pcbi.1007772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239440PMC
May 2020

Multinodular plaque on the penis.

Cutis 2020 Mar;105(3):E19-E21

Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, USA.

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March 2020

Modulation of Natural HLA-B*27:05 Ligandome by Ankylosing Spondylitis-associated Endoplasmic Reticulum Aminopeptidase 2 (ERAP2).

Mol Cell Proteomics 2020 06 7;19(6):994-1004. Epub 2020 Apr 7.

Unidad de Presentación y Regulación Inmunes, 28220 Majadahonda (Madrid), Spain. Electronic address:

The HLA-B*27:05 allele and the endoplasmic reticulum-resident aminopeptidases are strongly associated with AS, a chronic inflammatory spondyloarthropathy. This study examined the effect of ERAP2 in the generation of the natural HLA-B*27:05 ligandome in live cells. Complexes of HLA-B*27:05-bound peptide pools were isolated from human ERAP2-edited cell clones, and the peptides were identified using high-throughput mass spectrometry analyses. The relative abundance of a thousand ligands was established by quantitative tandem mass spectrometry and bioinformatics analysis. The residue frequencies at different peptide position, identified in the presence or absence of ERAP2, determined structural features of ligands and their interactions with specific pockets of the antigen-binding site of the HLA-B*27:05 molecule. Sequence alignment of ligands identified with species of bacteria associated with HLA-B*27-dependent reactive arthritis was performed. In the absence of ERAP2, peptides with N-terminal basic residues and minority canonical P2 residues are enriched in the natural ligandome. Further, alterations of residue frequencies and hydrophobicity profile at P3, P7, and PΩ positions were detected. In addition, several ERAP2-dependent cellular peptides were highly similar to protein sequences of arthritogenic bacteria, including one human HLA-B*27:05 ligand fully conserved in a protein from These findings highlight the pathogenic role of this aminopeptidase in the triggering of AS autoimmune disease.
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http://dx.doi.org/10.1074/mcp.RA120.002014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261815PMC
June 2020

The HLA-DP peptide repertoire from human respiratory syncytial virus is focused on major structural proteins with the exception of the viral polymerase.

J Proteomics 2020 06 31;221:103759. Epub 2020 Mar 31.

Unidad de Presentación y Regulación Inmunes, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda (Madrid) 28220, Spain. Electronic address:

The recognition by specific T helper cells of viral antigenic peptides complexed with HLA class II molecules exposed on the surface of antigen presenting cells is the first step of the complex cascade of immunological events that generates the protective cellular and humoral immune responses. The HLA class II-restricted helper immune response is critical in the control and the clearance of human respiratory syncytial virus (HRSV) infection, a pathogen with severe health risk in pediatric, immunocompromised and elderly populations. In this study, a mass spectrometry analysis was used to identify HRSV ligands bound to HLA-DP class II molecules present on the surface of HRSV-infected cells. Among the thousands of cellular peptides bound to HLA class II proteins in the virus-infected cells, sixty-four naturally processed viral ligands, most of them included in complex nested set of peptides, were identified bound to HLA-DP molecules. These viral ligands arose from five of six major structural HRSV proteins: attachment, fusion, matrix, nucleoprotein, and phosphoprotein. In contrast, no HLA-DP ligands were identified from polymerase protein, the largest HRSV protein that includes half of the viral proteome. These findings have important implications for analysis of the helper immune response as for antiviral vaccine design. SIGNIFICANCE: The existence of a supertype including five alleles that bind a peptide repertoire very similar make HLA-DP class II molecules an interesting target for the design of vaccines. Here, we analyze the HLA-DP-restricted peptide repertoire against the human respiratory syncytial virus, a pathogen that represents a high health risk in infected pediatric, immunocompromised and elderly populations. This repertoire is focused on major structural proteins with the exception of the viral polymerase.
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http://dx.doi.org/10.1016/j.jprot.2020.103759DOI Listing
June 2020

Assessing Front Office Staff Awareness on Mental Health Resources at Youth Friendly Clinics in Los Angeles County.

Community Ment Health J 2020 11 19;56(8):1544-1548. Epub 2020 Mar 19.

MiOra, Nonprofit, 17328 Ventura Blvd. #190, Encino, CA, 91316, USA.

Introduction: Mental illness is a global health challenge and continues to rise among minors. Community clinics are well positioned to provide mental health services to young people.

Objective: To assess community clinic front staff awareness of recent legislation mandating access by minors to mental health services and the actual services delivered by these clinics.

Methods: We conducted a face-to-face survey with front office staff at community clinics in service planning areas (SPA) 6, 7, and 8 in Los Angeles County (LAC) to understand the staff awareness of the services provided to the minor by the clinic. These SPAs have been previously identified as serving a low socioeconomic population. Fisher's exact test and the chi-square test were conducted to understand the factors influencing the front desk personnel awareness.

Results: Data were collected from 17 clinics in SPA6, 15 clinics in SPA7, and 4 clinics in SPA8. All of the clinics provided Family-PACT insurance, resources for domestic abuse, intimate partner violence, mental health (such as anxiety and depression) and alcohol/drug abuse; however responding front desk staff in twenty-five out of 36 (69.4%) clinics was aware of the availability of Family-PACT insurance to minor patients; 21 (58.3%) was aware that the clinic provided resources for domestic abuse or intimate partner violence, and 20 (55.5%) was aware that the clinic offered resources for mental health (such as anxiety or depression) or alcohol/drug abuse to minor patients.

Discussion: In this pilot study, about half of the front desk staff at the surveyed clinics in LA County did not know that the clinic is fully authorized and equipped to provide mental health services to the minors (patients under 18 years of age). These are missed opportunities. There is a need for better education of the front-desk personnel.
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http://dx.doi.org/10.1007/s10597-020-00604-9DOI Listing
November 2020

Substrate Interaction with the EssC Coupling Protein of the Type VIIb Secretion System.

J Bacteriol 2020 03 11;202(7). Epub 2020 Mar 11.

Institute for Molecular Infection Biology, Julius Maximilians University Würzburg, Würzburg, Germany

employs the type VIIb secretion system (T7SSb) to secrete effector proteins that either have antibacterial activities or promote bacterial persistence in mouse infection models. Here, we present the crystal structure of the ATPase domain D3 of the EssC coupling protein from USA300_FPR3757, an integral component of the T7SSb complex, resolved at a 1.7-Å resolution. EssC-D3 shares structural homology with FtsK/SpoIII-like ATPase domains of T7SSa and T7SSb and exhibits a conserved pocket on the surface with differential amino acid composition. In T7SSa, substrate EsxB interacts with the D3 domain through this pocket. Here, we identify amino acids in this pocket that are essential for effector protein secretion in the T7SSb. Our results reveal that the adjacent ATPase domain D2 is a substrate binding site on EssC and that substrates bound to D2 require domain D3 for further transport. Point mutations in the Walker B motif of domain D3 have diametric effects on secretion activity, either abolishing or boosting it, pointing to a critical role of domain D3 in the substrate transport. Finally, we identify ATPase domain D3 as a virulence determinant of USA300_FPR3757 using an invertebrate infection model. The emergence of antibiotic-resistant bacteria poses a rising problem in antibiotic treatment (S. Boyle-Vavra and R. S. Daum, Lab Invest 87:3-9, 2007, https://doi.org/10.1038/labinvest.3700501). We have used the multidrug-resistant USA300_FPR3757 as a model organism to study the T7SSb. Effector proteins of this system have been associated with abscess formation and bacterial persistence in mouse models (M. L. Burts, A. C. DeDent, and D. M. Missiakas, Mol Microbiol 69:736-746, 2008, https://doi.org/10.1111/j.1365-2958.2008.06324.x; M. L. Burts, W. A. Williams, K. DeBord, and D. M. Missiakas, Proc Natl Acad Sci U S A 102:1169-1174, 2005, https://doi.org/10.1073/pnas.0405620102). We determined the structure of the essential ATPase domain D3 of the T7SSb at atomic resolution and validated a surface-exposed pocket as a potential drug target to block secretion. Furthermore, our study provides new mechanistic insights into the T7SSb substrate transport.
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http://dx.doi.org/10.1128/JB.00646-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167477PMC
March 2020