The comfort perception in the critically ill patient from the Kolcaba theoretical model.

BACKGROUND: The stay in a critical care unit (CCU) has a serious impact on physical condition causing numerous discomfort factors such as pain or difficulty in communicating. All of these are associated with possible sequelae following discharge from the Intensive Care Unit (ICU) named post-ICU syndrome. The Kolcaba Comfort Theory allows, from a holistic approach, to identify care needs from the patient's perspective using instruments such as the General Comfort Questionnaire (GCQ). OBJECTIVES: To determine the comfort level of patients admitted to the CCU using the GCQ of Kolcaba and to identify the discomfort factors. METHODS: Cross-sectional descriptive observational prospective study. POPULATION: 580 patients admitted to adult CCU of two high complexity hospitals from June 2015 to March 2020 with stay ≥24 h were interviewed. Descriptive analysis, Student's t-test and ANOVA and multivariate analysis were performed using SPSS v26 and STATA v16. RESULTS: The mean age was 52,62 (16,21), 357 (61,6%) were male and 434 (74,8%) were believers. The type of admission was planned in 322 (55,5%) and the most prevalent reason for admission was surgical 486 (83,8%). The median pain score (NRS) was 3,00 [0-4] and severity score (APACHE II) was 13,26 (5,89), the median length of stay was 4,00 [2-7] days. The mean comfort level was 3,02 (0,31) showing the highest value Reanimation 3.02 (0.30) and the lowest Trauma and Emergency Unit 2.95 (0.38). Statistically significant differences were found between the units in the comfort level of patients >65 years of age (p = 0.029). The Relief comfort type obtained the lowest mean 2.81 (0.33) and the physical context 2.75 (0.41) in the three units. In the multivariate analysis, statistically significant differences were found between the comfort level and the pain level: no pain (p = 0,000) OR 4,361 CI [2,184-8,707], mild pain (p = 0,000) OR 4,007 CI [2,068-7,763], moderate pain (p = 0,007) OR 2,803 CI [1,328-5,913], and the APACHE II score equal to or greater than 10 (p = 0,000) OR 0,472 CI [0,316-0,705]. CONCLUSIONS: The comfort level showed high scores in all three units. The physical and environmental contexts and the relief comfort type negatively affected the perception of comfort. The variables that explained comfort were pain and severity of illness. The evaluation of comfort from the patient's perspective through the GCQ could be considered an indicator of quality of nursing interventions.

Field Evaluation of Fyfanon Ew Against Aedes Aegypti: A Low Odor Ultra-Low Volume Formulation of Malathion.

A low odor formulation of ultra-low volume (ULV) malathion (Fyfanon EW®) mosquito adulticide was evaluated in the field for its efficacy using caged female Aedes aegypti. Cages were placed in three rows, 30 m apart at 30, 60, and 90 m from the spray line. The product was applied at the manufacturer's suggested operational rate of 0.28 liter/min (9.5 fl oz/min) and at the maximum label rate of 0.37 liter/min (12.6 fl oz/min) with a Guardian 190ES truck mounted ULV sprayer. At 1 h post-treatment for the manufacturer's suggested operational rate, adult mortality ranged from 85% at 30 m to 46% at 90 m (overall average 65.5%). At 24 h post-treatment, mortality was significantly greater at each distance with complete control of caged mosquitoes at 30 m and >95% at 90 m. Overall, 24-h average mortality at this rate was 96.8%. At the maximum label rate, mosquito mortality at 1 h was considerably greater at all distances and ranged from about 89% to 75% with an overall average of 84.3%. At 24 h post-treatment, complete mortality was recorded at all transect distances at this higher rate. In conclusion, our results showed that at 24 h, Fyfanon EW® was considered very effective when applied by ULV truck mounted ground equipment for area-wide control of mosquitoes.

Optimal selection of suitable templates in protein interface prediction.

MOTIVATION: Molecular-level classification of protein-protein interfaces can greatly assist in functional characterization and rational drug design. The most accurate protein interface predictions rely on finding homologous proteins with known interfaces since most interfaces are conserved within the same protein family. The accuracy of these template-based prediction approaches depends on the correct choice of suitable templates. Choosing the right templates in the immunoglobulin superfamily (IgSF) is challenging because its members share low sequence identity and display a wide range of alternative binding sites despite structural homology. RESULTS: We present a new approach to predict protein interfaces. First, template-specific, informative evolutionary profiles are established using a mutual information-based approach. Next, based on the similarity of residue level conservation scores derived from the evolutionary profiles, a query protein is hierarchically clustered with all available template proteins in its superfamily with known interface definitions. Once clustered, a subset of the most closely related templates is selected, and an interface prediction is made. These initial interface predictions are subsequently refined by extensive docking. This method was benchmarked on 51 IgSF proteins and can predict nontrivial interfaces of IgSF proteins with an average and median F-score of 0.64 and 0.78, respectively. We also provide a way to assess the confidence of the results. The average and median F-scores increase to 0.8 and 0.81, respectively, if 27% of low confidence cases and 17% of medium confidence cases are removed. Lastly, we provide residue level interface predictions, protein complexes, and confidence measurements for singletons in the IgSF. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at: https://gitlab.com/fiserlab.org/interdct_with_refinement.

Chi3l1 Is a Modulator of Glioma Stem Cell States and a Therapeutic Target in Glioblastoma.

Chitinase 3-like 1 (Chi3l1) is a secreted protein that is highly expressed in glioblastoma. Here, we show that Chi3l1 alters the state of glioma stem cells (GSC) to support tumor growth. Exposure of patient-derived GSCs to Chi3l1 reduced the frequency of CD133+SOX2+ cells and increased the CD44+Chi3l1+ cells. Chi3l1 bound to CD44 and induced phosphorylation and nuclear translocation of ß-catenin, Akt, and STAT3. Single-cell RNA sequencing and RNA velocity following incubation of GSCs with Chi3l1 showed significant changes in GSC state dynamics driving GSCs towards a mesenchymal expression profile and reducing transition probabilities towards terminal cellular states. ATAC-seq revealed that Chi3l1 increases accessibility of promoters containing a Myc-associated zinc finger protein (MAZ) transcription factor footprint. Inhibition of MAZ downregulated a set of genes with high expression in cellular clusters that exhibit significant cell state transitions after treatment with Chi3l1, and MAZ deficiency rescued the Chi3L-induced increase of GSC self-renewal. Finally, targeting Chi3l1 in vivo with a blocking antibody inhibited tumor growth and increased the probability of survival. Overall, this work suggests that Chi3l1 interacts with CD44 on the surface of GSCs to induce Akt/ß-catenin signaling and MAZ transcriptional activity, which in turn upregulates CD44 expression in a pro-mesenchymal feed-forward loop. The role of Chi3l1 in regulating cellular plasticity confers a targetable vulnerability to glioblastoma. SIGNIFICANCE: Chi3l1 is a modulator of glioma stem cell states that can be targeted to promote differentiation and suppress growth of glioblastoma.

Integrated structure-based protein interface prediction.

BACKGROUND: Identifying protein interfaces can inform how proteins interact with their binding partners, uncover the regulatory mechanisms that control biological functions and guide the development of novel therapeutic agents. A variety of computational approaches have been developed for predicting a protein's interfacial residues from its known sequence and structure. Methods using the known three-dimensional structures of proteins can be template-based or template-free. Template-based methods have limited success in predicting interfaces when homologues with known complex structures are not available to use as templates. The prediction performance of template-free methods that only rely only upon proteins' intrinsic properties is limited by the amount of biologically relevant features that can be included in an interface prediction model. RESULTS: We describe the development of an integrated method for protein interface prediction (ISPIP) to explore the hypothesis that the efficacy of a computational prediction method of protein binding sites can be enhanced by using a combination of methods that rely on orthogonal structure-based properties of a query protein, combining and balancing both template-free and template-based features. ISPIP is a method that integrates these approaches through simple linear or logistic regression models and more complex decision tree models. On a diverse test set of 156 query proteins, ISPIP outperforms each of its individual classifiers in identifying protein binding interfaces. CONCLUSIONS: The integrated method captures the best performance of individual classifiers and delivers an improved interface prediction. The method is robust and performs well even when one of the individual classifiers performs poorly on a particular query protein. This work demonstrates that integrating orthogonal methods that depend on different structural properties of proteins performs better at interface prediction than any individual classifier alone.

Evaluation of Alternative Power Sources for Operating CDC Mosquito Surveillance Traps.

Several portable, rechargeable lithium-ion (Li-Ion) cell phone power banks were compared with standard 6-V gel lead-acid batteries as alternative power sources for operating mosquito surveillance equipment. In laboratory trials, ToughTested® (TT)16000 and 24000, Goal Zero Venture™ 70, and Griffin Survivor® units either met or exceeded that of sealed 6-V batteries when operating the Centers for Disease Control and Prevention (CDC) suction light traps (with incandescent light on) for an average of 24 h. No significant difference was found when continually operating traps powered by either the TT16000 or Goal Zero Venture 70 units compared with 6-V batteries (at approximately 57 h). The TT24000 unit was the only Li-Ion power bank that exceeded this threshold at an average of approximately 73 h. In field studies, there was no significant difference in species diversity or abundance of mosquitoes among the above 4 power sources when operating CDC light traps for 24 h compared with 6-V batteries. Our results indicate that portable Li-Ion cell phone power banks ≥10,050 mAh may be suitable replacements for 6-V gel lead-acid batteries when operating these light traps, especially if weight and size constraints influence the extent of mosquito surveillance during deployments.

INTERCAAT: identifying interface residues between macromolecules.

SUMMARY: The Interface Contact definition with Adaptable Atom Types (INTERCAAT) was developed to determine the atomic interactions between molecules that form a known three dimensional structure. First, INTERCAAT creates a Voronoi tessellation where each atom acts as a seed. Interactions are defined by atoms that share a hyperplane and whose distance is less than the sum of each atoms' Van der Waals radii plus the diameter of a solvent molecule. Interacting atoms are then classified and interactions are filtered based on compatibility. INTERCAAT implements an adaptive atom classification method; therefore, it can explore interfaces between a variety macromolecules. AVAILABILITY AND IMPLEMENTATION: Source code is freely available at: https://gitlab.com/fiserlab.org/intercaat. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

[Lung transplant with ex vivo lung perfusion, Chilean and Latin American first experience]. / Trasplante pulmonar ex vivo . Primera experiencia en Chile y Latinoamérica.

BACKGROUND: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. AIM: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. MATERIAL AND METHODS: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020. High risk donor lungs and rejected lungs from other transplantation centers were included. The "Toronto Protocol" was used for ex vivo lung perfusion. Donor lung characteristics and recipient outcomes were studied. RESULTS: During the study period, five ex vivo lung perfusions were performed. All lungs were reconditioned and transplanted. No complications were associated. There were no primary graft dysfunctions and only one chronic allograft dysfunction. There was no mortality during the first year. The median arterial oxygen partial pressure/fractional inspired oxygen ratio increased from 266 mm Hg in the donor lung to 419 after 3 hours of ex vivo lung perfusion (p = 0.043). CONCLUSIONS: ex vivo lung perfusion is a safe and useful tool that allows marginal donor lungs to be reconditioned and successfully transplanted.

miRNA-mediated loss of m6A increases nascent translation in glioblastoma.

Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.

Experiencia en trasplante pulmonar pediátrico en Chile / Experience with pediatric lung transplantation in Chile

El trasplante de pulmón (TP) es una opción para pacientes pediátricos con enfermedades pulmonares terminales. OBJETIVO: Evaluar resultados y sobrevida de pacientes pediátricos trasplantados de pulmón. MÉTODOS: Análisis retrospectivo de registros clínicos de pacientes TP ≤ 15 años de Clínica Las Condes. Se analizaron datos demográficos, tipo de trasplante, función pulmonar basal y post trasplante, complicaciones precoces y tardías y sobrevida. RESULTADOS: Nueve pacientes < 15 años de edad se han trasplantado. La edad promedio fue 12,7 años. La principal indicación fue fibrosis quística (7 pacientes). El IMC promedio fue de 17,6 y todos estaban con oxígeno domiciliario. El 77% utilizó soporte extracorpóreo intraoperatorio. Las principales complicaciones precoces fueron hemorragia y la disfunción primaria de injerto mientras que las tardías fueron principalmente las infecciones y la disfunción crónica de injerto. Cuatro pacientes han fallecido y la sobrevida a dos años fue de 85%. El trasplante les permitió una reinserción escolar y 3 lograron completar estudios universitarios. CONCLUSIÓN: El trasplante pulmonar es una alternativa para niños con enfermedades pulmonares avanzadas mejorando su sobrevida y calidad de vida.

Lung transplantation (TP) is a treatment option in children with terminal lung diseases. OBJECTIVE: To evaluate the results and survival of pediatrics lung transplant patients. METHODS: Retrospective analysis of clinical records of lung transplantation of patients ≤ 15 years from Clínica Las Condes, Santiago, Chile. Demographic data, type of transplant, baseline and post transplant lung function, early and late complications and survival rate were analyzed. RESULTS: Nine patients ≤ 15 years-old were transplanted. The average age at transplant was 12.7 years. The main indication was cystic fibrosis (7 patients). The average BMI was 17.6 and all the patients were with home oxygen therapy. 77% used extracorporeal intraoperative support. Average baseline FEV1 was 25.2% with progressive improvement in FEV1 of 77% in the first year. The main early complications were hemorrhage and primary graft dysfunction, while late complications were infections and chronic graft dysfunction. Four patients have died and the estimated 2 years survival was 85%. They achieved school reinsertion and three managed to complete university studies. CONCLUSION: Lung transplantation is an alternative for children with advanced lung diseases improving their survival and quality of life.

Trasplante pulmonar ex vivo: primera experiencia en Chile y Latinoamérica / Lung transplant with ex vivo lung perfusion, Chilean and Latin American first experience

Background: The number of patients waiting for a lung transplant worldwide greatly exceeds the number of available donors. Ex vivo lung perfusion is a useful tool that allows marginal donor lungs to be evaluated and reconditioned for a successful lung transplantation. Aim: To describe the first Chilean and Latin American experience in ex vivo lung perfusion for marginal donor lungs before transplantation. Material and Methods: Descriptive analysis of all ex vivo lung perfusion conducted for marginal donor lungs at a private clinic, from April 2019 to October 2020. High risk donor lungs and rejected lungs from other transplantation centers were included. The "Toronto Protocol" was used for ex vivo lung perfusion. Donor lung characteristics and recipient outcomes were studied. Results: During the study period, five ex vivo lung perfusions were performed. All lungs were reconditioned and transplanted. No complications were associated. There were no primary graft dysfunctions and only one chronic allograft dysfunction. There was no mortality during the first year. The median arterial oxygen partial pressure/fractional inspired oxygen ratio increased from 266 mm Hg in the donor lung to 419 after 3 hours of ex vivo lung perfusion (p = 0.043). Conclusions: ex vivo lung perfusion is a safe and useful tool that allows marginal donor lungs to be reconditioned and successfully transplanted.

[Prognosis of patients with COVID-19 presenting acute ischaemic stroke and receiving interventional treatment]. / Pronóstico de pacientes COVID-19 con ictus isquémico y tratamiento neurointervencionista.

Objetivo: Presentar nuestra experiencia y analizar el pronóstico de pacientes COVID-19 con ictus isquémico agudo por oclusión de grandes vasos tratados con neurointervencionismo (NIV) en la unidad de ictus. Material y métodos: Se incluyeron todos los pacientes consecutivos con ictus isquémico agudo debido a oclusión de grandes vasos tratados por NIV en nuestra institución entre marzo y abril de 2020, durante el brote de COVID-19. Se realizó una comparación entre pacientes con COVID-19 y pacientes sin infección por coronavirus. Se comunican los resultados clínicos iniciales y a corto plazo. Resultados: Del 1 de marzo al 30 de abril se realizaron 25 procedimientos de NIV por ictus isquémico agudo en nuestra institución. Ocho pacientes eran COVID-19 y 17 eran pacientes no COVID-19. La edad media de los pacientes con COVID-19 fue de 70,1 ± 12,23 años, y 7 fueron hombres (87,5%, p = 0,006). Mientras que todos los pacientes sin COVID procedían de urgencias, solo 5 pacientes con COVID-19 (62,5%) fueron atendidos desde urgencias por ictus (p = 0,01). Tres pacientes procedían de hospitalización. La tasa de mortalidad en pacientes sin COVID-19 fue del 5,8%, pero en pacientes con COVID-19 fue considerablemente alta (50%). Ningún parámetro analítico difirió entre ambos grupos. No se registraron hemorragias en esta serie.En comparación con el mismo período del año pasado, se observó una disminución de la actividad neurointervencionista del 39%. Conclusiones: La mejor terapia médica y de NIV desembocó en malos resultados y una mortalidad dramática. La pandemia de COVID-19 dificultó significativamente el funcionamiento normal de los servicios de urgencias y la atención de estos pacientes con ictus.

A Designer Quest for the Achilles' Heel of Influenza.

Monoclonal antibodies are attractive but, in certain applications, limited therapeutic modalities due to their large size and high specificity. In this issue of Structure, Sevy at al. describe a computationally designed cyclic peptide mimicking the CDRH3 loop of the C05 antibody against influenza showing the potential utility of designer biologics.

Effectiveness of Aquatain® AMF and Cocobear™ Larvicidal Oil Against Culex quinquefasciatus Larvae and Pupae in an Organically Enhanced Aquatic Habitat.

The efficacy of CocoBear™ Larvicidal Oil and Aquatain® AMF Liquid Mosquito Film against larval and pupal Culex quinquefasciatus was compared (at maximum label field application rates) when applied to concrete troughs treated with composted cow manure. At 1 h posttreatment, CocoBear provided significantly greater reduction of mosquito larvae than Aquatain, but both products were equally effective in producing >97% control at 24 h. Each product provided >98% pupal reduction at 1 h posttreatment, with complete elimination of pupae from troughs at 24 h. CocoBear and Aquatain proved to be equally effective against Cx. quinquefasciatus immatures in organically enriched aquatic habitats.

Microwave tomography with phaseless data on the calcaneus by means of artificial neural networks.

The aim of this study is to use a multilayer perceptron (MLP) artificial neural network (ANN) for phaseless imaging the human heel (modeled as a bilayer dielectric media: bone and surrounding tissue) and the calcaneus cross-section size and location using a two-dimensional (2D) microwave tomographic array. Computer simulations were performed over 2D dielectric maps inspired by computed tomography (CT) images of human heels for training and testing the MLP. A morphometric analysis was performed to account for the scatterer shape influence on the results. A robustness analysis was also conducted in order to study the MLP performance in noisy conditions. The standard deviations of the relative percentage errors on estimating the dielectric properties of the calcaneus bone were relatively high. Regarding the calcaneus surrounding tissue, the dielectric parameters estimations are better, with relative percentage error standard deviations up to ≈ 15%. The location and size of the calcaneus are always properly estimated with absolute error standard deviations up to ≈ 3 mm. Microwave tomography of the calcaneus using phaseless data. Simulations were inspired in Computed Tomography images from real heels (above). Inverse problem was solved using Multilayer Perceptron Artificial Neural Network (below).

Assessment of chemical-crosslink-assisted protein structure modeling in CASP13.

With the advance of experimental procedures obtaining chemical crosslinking information is becoming a fast and routine practice. Information on crosslinks can greatly enhance the accuracy of protein structure modeling. Here, we review the current state of the art in modeling protein structures with the assistance of experimentally determined chemical crosslinks within the framework of the 13th meeting of Critical Assessment of Structure Prediction approaches. This largest-to-date blind assessment reveals benefits of using data assistance in difficult to model protein structure prediction cases. However, in a broader context, it also suggests that with the unprecedented advance in accuracy to predict contacts in recent years, experimental crosslinks will be useful only if their specificity and accuracy further improved and they are better integrated into computational workflows.

Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum.

Plasmodium falciparum causes the most lethal form of human malaria and is a global health concern. The parasite responds to antimalarial therapies by developing drug resistance. The continuous development of new antimalarials with novel mechanisms of action is a priority for drug combination therapies. The use of transition-state analog inhibitors to block essential steps in purine salvage has been proposed as a new antimalarial approach. Mutations that reduce transition-state analog binding are also expected to reduce the essential catalytic function of the target. We have previously reported that inhibition of host and P. falciparum purine nucleoside phosphorylase (PfPNP) by DADMe-Immucillin-G (DADMe-ImmG) causes purine starvation and parasite death in vitro and in primate infection models. P. falciparum cultured under incremental DADMe-ImmG drug pressure initially exhibited increased PfPNP gene copy number and protein expression. At increased drug pressure, additional PfPNP gene copies appeared with point mutations at catalytic site residues involved in drug binding. Mutant PfPNPs from resistant clones demonstrated reduced affinity for DADMe-ImmG, but also reduced catalytic efficiency. The catalytic defects were partially overcome by gene amplification in the region expressing PfPNP. Crystal structures of native and mutated PfPNPs demonstrate altered catalytic site contacts to DADMe-ImmG. Both point mutations and gene amplification are required to overcome purine starvation induced by DADMe-ImmG. Resistance developed slowly, over 136 generations (2136 clonal selection). Transition-state analog inhibitors against PfPNP are slow to induce resistance and may have promise in malaria therapy.

A Small-Scale Investigation Into the Effect of A Larvicidal Oil On Oviposition Site Preference By Aedes aegypti.

Larvicidal oils can be used to control immature Aedes aegypti and other pestiferous mosquitoes. To test whether oil-based larvicides also act as oviposition deterrents, indoor and semi-field trials were conducted at the Navy Entomology Center of Excellence in Jacksonville, FL. In both studies, treatment cages consisted of oviposition cups lined with seed germination paper as an oviposition substrate and filled with 1-wk-old southern live oak ( Quercus virginiana) leaf litter-infused water. Treatment cages consisted of 2 cups treated with CocoBear™ Mosquito Larvicidal Oil, while 2 cups were untreated. Control cages contained oviposition cups with only oak leaf litter-infused water. Gravid Ae. aegypti were released into cages and allowed to oviposit for 24 h, after which eggs were counted. The number of eggs deposited in treatment and control cages was not significantly different (indoor P = 0.0865; outdoor P = 0.9765). However, the number of eggs deposited in untreated cups was significantly greater than that deposited in treated cups within treatment cages (indoor P < 0.0001; outdoor P = 0.0050). These results suggest that the presence of the larvicidal oil CocoBear may cause gravid female Ae. aegypti to seek alternative oviposition sites.