Neutron Scattering Analysis of Cryptococcus neoformans Polysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns.

Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length scale corresponding to 3-4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.

Combined Effects of Pressure and Ionic Strength on Protein-Protein Interactions: An Empirical Approach.

Proteins are exposed to hydrostatic pressure (HP) in a variety of ecosystems as well as in processing steps such as freeze-thaw, cell disruption, sterilization, and homogenization, yet pressure effects on protein-protein interactions (PPIs) remain underexplored. With the goal of contributing toward the expanded use of HP as a fundamental control parameter in protein research, processing, and engineering, small-angle X-ray scattering was used to examine the effects of HP and ionic strength on ovalbumin, a model protein. Based on an extensive data set, we develop an empirical method for scaling PPIs to a master curve by combining HP and osmotic effects. We define an effective pressure parameter that has been shown to successfully apply to other model protein data available in the literature, with deviations evident for proteins that do not follow the apparent Hofmeister series. The limitations of the empirical scaling are discussed in the context of the hypothesized underlying mechanisms.

Neutron Scattering Analysis of Cryptococcus neoformans Polysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns.

Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length-scale corresponding to 3 to 4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.

Intraocular Pressure Values using IcareⓇ Rebound Tonometer and Correlation with Postconceptional Age in Premature Infants.

Purpose: This study aimedto determine a normative range of intraocular pressure (IOP) values measured with Icare rebound tonometer in premature infants and evaluate IOP variation over time and its correlation with the progression of postconceptional age (PCA). By doing so, we also evaluated advantages of this IOP-measuring method in this population when compared to more traditional methods. Methods: We conducted a single-center prospective study that included premature infants (gestational age ≤32 weeks) who were admitted to the neonatal intensive care unit (NICU) in Hospital Professor Doutor Fernando Fonseca. The study took place between January and December 2021. IOP was measured using Icare tonometer on the occasion of the first retinopathy of prematurity (ROP) screening requested by the NICU and again after a two-week interval if PCA was still ≤37 weeks. IOP measurements were stopped at 37 weeks or if the infant was discharged. The evaluated outcomes were mean IOP values and their correlation with PCA. Results: Thirty-four eyes of 17 preterm infants with a mean gestational age of 29.4 ± 2.3 weeks and a mean birth weight of 1222.9 ± 361.9 gr were evaluated. The mean IOP registered was 16.1 ± 6.4 mmHg, with a median value of 15.3 mmHg. The top 90th percentile was 22.1 mmHg and the bottom 10th percentile was 9.0 mmHg. The average IOP reduction was 4.8 ± 6.7 mmHg (P = 0.0019) within the two-week interval of PCA. Conclusion: The mean IOP in premature infants was 16.1 ± 6.4 mmHg and this value significantly decreased by 4.8 ± 6.7 mmHg every two weeks of PCA.

High Pressure Light Scattering of Therapeutic Proteins To Probe Aggregation and Protein-Protein Interactions.

There is interest in the direct in situ measurement of protein aggregation and reversible protein-protein interactions at high pressure as a means to assess protein stability. This is currently limited by the availability of in-house analytical methods. High-pressure (HP) scattering instrumentation (using either neutrons, X-rays, or light sources) are relatively rare, due to extensive development hurdles and lack of standardization. This report focuses on design, operation, and application of a new HP light scattering apparatus based on commercially available equipment with a view to wider applications. HP static light scattering results were obtained for two monoclonal antibodies (MAbs) that exhibit different extents of unfolding and aggregation at these conditions. Aggregation that was observed during in situ pressure incubations varied by MAb and total ionic strength of solution. This was conducted in tandem with ex situ measurements on MAb solutions that were incubated under pressure, where monomer loss was measured with size exclusion chromatography. Pressure cycling was also used to assess the extent of pressure-induced reversible and irreversible aggregation. Finally, the ability of the HP light scattering apparatus to assess the influence of pressure on reversible protein-protein interactions in the canonical sense of second osmotic virial coefficients was assessed using lysozyme, a relatively well-characterized protein under hydrostatic pressure. The method offers a convenient and reproducible capability that complements current small angle neutron/X-ray instrumentation, providing measurements that can be used to optimize the planning and interpretation of scattering data from synchrotron or neutron research facilities. Our results address a growing demand to characterize protein aggregates and aggregation-prone partially unfolded intermediates.

Isotretinoin-Induced Distal Ileitis Mimicking Crohn's Disease.

Terminal ileitis is a common condition defined as inflammation of the terminal portion of the ileum, which is typically associated with inflammatory bowel disease (IBD), classically Crohn's disease (CD). However, it can have other etiologies, including drug-induced ones. Isotretinoin is an effective and commonly used treatment for acne vulgaris, presenting multiple adverse effects. There have been discussions over its association with enteric inflammation, particularly over IBD emergence risk. We report a case of a previously healthy 17-year-old female who presented transitory clinical, laboratory, imaging, and endoscopic evidence of distal ileitis, temporally related to extended isotretinoin treatment and mimicking CD. Repeated clinical, laboratory, imaging, and endoscopic reassessment after isotretinoin discontinuation confirmed an almost complete resolution of the condition, avoiding IBD misdiagnosis and specific medication initiation. Our case highlights the differential diagnosis of ileitis as being of critical importance to avoid further unnecessary diagnostic investigations and inadequate treatment. Serial re-evaluation may be of key importance to reach a final diagnosis. Although recent literature suggests that isotretinoin is not associated with an increased IBD risk, our case highlights the possibility of it inducing small bowel injury and inflammation, similar to what has been reported with other drugs.

A round-robin approach provides a detailed assessment of biomolecular small-angle scattering data reproducibility and yields consensus curves for benchmarking.

Through an expansive international effort that involved data collection on 12 small-angle X-ray scattering (SAXS) and four small-angle neutron scattering (SANS) instruments, 171 SAXS and 76 SANS measurements for five proteins (ribonuclease A, lysozyme, xylanase, urate oxidase and xylose isomerase) were acquired. From these data, the solvent-subtracted protein scattering profiles were shown to be reproducible, with the caveat that an additive constant adjustment was required to account for small errors in solvent subtraction. Further, the major features of the obtained consensus SAXS data over the q measurement range 0-1 Å-1 are consistent with theoretical prediction. The inherently lower statistical precision for SANS limited the reliably measured q-range to <0.5 Å-1, but within the limits of experimental uncertainties the major features of the consensus SANS data were also consistent with prediction for all five proteins measured in H2O and in D2O. Thus, a foundation set of consensus SAS profiles has been obtained for benchmarking scattering-profile prediction from atomic coordinates. Additionally, two sets of SAXS data measured at different facilities to q > 2.2 Å-1 showed good mutual agreement, affirming that this region has interpretable features for structural modelling. SAS measurements with inline size-exclusion chromatography (SEC) proved to be generally superior for eliminating sample heterogeneity, but with unavoidable sample dilution during column elution, while batch SAS data collected at higher concentrations and for longer times provided superior statistical precision. Careful merging of data measured using inline SEC and batch modes, or low- and high-concentration data from batch measurements, was successful in eliminating small amounts of aggregate or interparticle interference from the scattering while providing improved statistical precision overall for the benchmarking data set.

Temporal macular thinning and vessel density correlation in children and young adults with sickle cell disease.

Optical coherence tomography angiography (OCTA) is a recent noninvasive imaging technology that has proved to provide a comprehensive evaluation of retinal vascular abnormalities in adult patients with sickle cell disease (SCD). However, the pediatric population remains less studied. The purpose of this study is to evaluate the correlation between temporal vessel density (VD) in OCTA and temporal macular thinning in optical coherence tomography (OCT) in children and young adults with SCD. We reviewed medical records, OCT and OCTA (Spectralis®) scans from a sample of 32 eyes from 16 patients (7 female + 9 male) under 25 years old. The OCT macular thickness data and OCTA image data were processed using Python 3.9 programming language, and statistical analysis was performed. Pearson Correlation Coefficient between macular thickness and VD for inner and outer temporal areas was 0.47 (p-value = 0.006) and 0.74 (p-value < 0.001), respectively. A t-test was also performed to prove that there is a statistically significant VD difference in patients with higher and lower macular thickness (p < 0.001). These results show that children with outer temporal macular thinning on OCT have lower outer temporal VD on OCTA suggesting that microvascular insults may lead to chronic ischemic changes in the inner retinal layers.

High-Pressure, Low-Temperature Induced Unfolding and Aggregation of Monoclonal Antibodies: Role of the Fc and Fab Fragments.

The effects of high pressure and low temperature on the stability of two different monoclonal antibodies (MAbs) were examined in this work. Fluorescence and small-angle neutron scattering were used to monitor the in situ effects of pressure to infer shifts in tertiary structure and characterize aggregation prone intermediates. Partial unfolding was observed for both MAbs, to different extents, under a range of pressure/temperature conditions. Fourier transform infrared spectroscopy was also used to monitor ex situ changes in secondary structure. Preservation of native secondary structure after incubation at elevated pressures and subzero ° C temperatures was independent of the extent of tertiary unfolding and reversibility. Several combinations of pressure and temperature were also used to discern the respective contributions of the isolated Ab fragments (Fab and Fc) to unfolding and aggregation. The fragments for each antibody showed significantly different partial unfolding profiles and reversibility. There was not a simple correlation between stability of the full MAb and either the Fc or Fab fragment stabilities across all cases, demonstrating a complex relationship to full MAb unfolding and aggregation behavior. That notwithstanding, the combined use of spectroscopic and scattering techniques provides insights into MAb conformational stability and hysteresis in high-pressure, low-temperature environments.

Incidence and Risk Factors for Retinopathy of Prematurity in a Portuguese Cohort.

PURPOSE: To evaluate the incidence and risk factors for retinopathy of prematurity (ROP) in two Portuguese neonatal units with a sub-analysis of infants with a gestational age (GA) of 28 weeks or older. METHODS: This was a retrospective case series of all infants who underwent ROP screening from 2012 to 2020. Demographic, clinical, and laboratory data were collected. Univariate logistic regression was used to examine the risk factors for ROP followed by multivariate regression. RESULTS: A total of 475 infants were included with a median GA of 30 weeks (range: 23 to 36 weeks) and a median birth weight of 1,229 grams (range: 408 to 2,620 grams). ROP was diagnosed in 113 infants (23.8%) and 29 (6.1%) were treated. In the multivariate analysis, GA and hyperglycemia were significantly associated with severe ROP (P < .001). In the subgroup analysis of infants with a GA of 28 weeks or older, bronchopulmonary dysplasia, late-onset sepsis, and hyperglycemia were linked to severe ROP. CONCLUSIONS: The incidence of ROP in the cohort falls within the range of other high-income countries. Hyperglycemia overpowered all of the other risk factors. Although rare, more mature infants are also at risk for severe ROP. Infants with older GA share the same group of risk factors, but bronchopulmonary dysplasia seems to play a greater role. [J Pediatr Ophthalmol Strabismus. 2022;59(4):254-260.].

DIGIROP efficacy for detecting treatment-requiring retinopathy of prematurity in a Portuguese cohort.

BACKGROUND/OBJECTIVES: To determine the efficacy of the DIGIROP model in detecting treatment-requiring retinopathy of prematurity (TR-ROP) in a Portuguese cohort. SUBJECTS/METHODS: Multicentre, retrospective cohort study of all consecutive preterm infants who underwent ROP screening from April 2012 to May 2019 in two neonatal units. Gestational age (GA), birth weight (BW) and sex were inserted in the DIGIROP platform. The optimal cut-off point to achieve 100% sensitivity was calculated. Area under the receiver operating characteristic curve (AUC) was calculated. RESULTS: Of the 431 infants who underwent ROP screening, 257 were eligible for DIGIROP analysis and 174 infants were excluded for having a GA outside the range 24-30 weeks imposed by the DIGIROP algorithm. Median GA was 29 weeks (range 24-30) and BW was 1060 g (range 408-2080). Twenty-tree infants (8.9%) developed TR-ROP. The highest risk obtained for TR-ROP was 0.5404 (95% CI 0.4343-0.6616) with a median achieved risk of 0.0938 (range 0.0016-0.5404). The optimal cut-off point to achieve 100% sensitivity on TR-ROP was 0.0016. The number of infants receiving ROP examinations would have been reduced from 257 to 187 infants (-27.2%) if the model was applied. CONCLUSIONS: In our cohort, of 257 infants, the optimal cut-off point to achieve 100% sensitivity for TR-ROP was 0.0016 with moderate accuracy in the AUC (0.70). The number of infants requiring screening would have decreased 27.2% if the model was applied. It is essential that algorithms continue to be tested in different populations, especially in cohorts that include both younger and older GA infants.

Retrospective comparison between growth and retinopathy of prematurity model versus WINROP model.

OBJECTIVE: To compare the weight and insulin-like growth factor-1 in neonatal retinopathy (WINROP) to the growth and retinopathy of prematurity (G-ROP) model in a Portuguese cohort. DESIGN: Retrospective case series. METHODS: Clinical records of consecutive infants who underwent retinopathy of prematurity (ROP) screening from April 2012 to May 2019 were retrospectively reviewed. Both WINROP and G-ROP models were accessed for sensitivity and specificity for type 1 ROP. A separate analysis of both algorithms was performed in infants with gestational age (GA) <30 weeks. RESULTS: Of the 375 infants included in the study, 313 were eligible for G-ROP analysis and 311 for WINROP. In the G-ROP group, 22 infants developed type 1 ROP (sensitivity 90.91%, 95% confidence interval [CI] 70.84%-98.98%). In the WINROP group, 23 infants needed treatment (sensitivity of 86.96%, 95% CI 66.41%-97.22%). Both models reached 100% sensitivity for type 1 ROP if restricted to GA <30 weeks. CONCLUSIONS: Both models were easy to use and had similar sensitivities. If restricted to GA <30 weeks, both models detected all type 1 ROP.

Drug-Dependent Morphological Transitions in Spherical and Worm-Like Polymeric Micelles Define Stability and Pharmacological Performance of Micellar Drugs.

Significant advances in physicochemical properties of polymeric micelles enable optimization of therapeutic drug efficacy, supporting nanomedicine manufacturing and clinical translation. Yet, the effect of micelle morphology on pharmacological efficacy is not adequately addressed. This work addresses this gap by assessing pharmacological efficacy of polymeric micelles with spherical and worm-like morphologies. It is observed that poly(2-oxazoline)-based polymeric micelles can be elongated over time from a spherical structure to worm-like structure, with elongation influenced by several conditions, including the amount and type of drug loaded into the micelles. The role of different morphologies on pharmacological performance of drug loaded micelles against triple-negative breast cancer and pancreatic cancer tumor models is further evaluated. Spherical micelles accumulate rapidly in the tumor tissue while retaining large amounts of drug; worm-like micelles accumulate more slowly and only upon releasing significant amounts of drug. These findings suggest that the dynamic character of the drug-micelle structure and the micelle morphology play a critical role in pharmacological performance, and that spherical micelles are better suited for systemic delivery of anticancer drugs to tumors when drugs are loosely associated with the polymeric micelles.

In Situ Monitoring of Protein Unfolding/Structural States under Cold High-Pressure Stress.

Biopharmaceutical formulations may be compromised by freezing, which has been attributed to protein conformational changes at a low temperature, and adsorption to ice-liquid interfaces. However, direct measurements of unfolding/conformational changes in sub-0 °C environments are limited because at ambient pressure, freezing of water can occur, which limits the applicability of otherwise commonly used analytical techniques without specifically tailored instrumentation. In this report, small-angle neutron scattering (SANS) and intrinsic fluorescence (FL) were used to provide in situ analysis of protein tertiary structure/folding at temperatures as low as -15 °C utilizing a high-pressure (HP) environment (up to 3 kbar) that prevents water from freezing. The results show that the α-chymotrypsinogen A (aCgn) structure is reasonably maintained under acidic pH (and corresponding pD) for all conditions of pressure and temperature tested. On the other hand, reversible structural changes and formation of oligomeric species were detected near -10 °C via HP-SANS for ovalbumin under neutral pD conditions. This was found to be related to the proximity of the temperature of cold denaturation of ovalbumin (TCD ∼ -17 °C; calculated via isothermal chemical denaturation and Gibbs-Helmholtz extrapolation) rather than a pressure effect. Significant structural changes were also observed for a monoclonal antibody, anti-streptavidin IgG1 (AS-IgG1), under acidic conditions near -5 °C and a pressure of ∼2 kbar. The conformational perturbation detected for AS-IgG1 is proposed to be consistent with the formation of unfolding intermediates such as molten globule states. Overall, the in situ approaches described here offer a means to characterize the conformational stability of biopharmaceuticals and proteins more generally under cold-temperature stress by the assessment of structural alteration, self-association, and reversibility of each process. This offers an alternative to current ex situ methods that are based on higher temperatures and subsequent extrapolation of the data and interpretations to the cold-temperature regime.

Transcription Landscape of the Early Developmental Biology in Pigs.

Since pre- and postnatal development are programmed during early prenatal life, studies addressing the complete transcriptional landscape during organogenesis are needed. Therefore, we aimed to disentangle differentially expressed (DE) genes between fetuses (at 35 days old) and embryos (at 25 days old) through RNA-sequencing analysis using the pig as model. In total, 1705 genes were DE, including the top DE IBSP, COL6A6, HBE1, HBZ, HBB, and NEUROD6 genes, which are associated with developmental transition from embryos to fetuses, such as ossification, skeletal muscle development, extracellular matrix organization, cardiovascular system, erythrocyte differentiation, and neuronal system. In pathway analysis, embryonic development highlighted those mainly related to morphogenic signaling and cell interactions, which are crucial for transcriptional control during the establishment of the main organs in early prenatal development, while pathways related to myogenesis, neuronal development, and cardiac and striated muscle contraction were enriched for fetal development, according to the greater complexity of organs and body structures at this developmental stage. Our findings provide an exploratory and informative transcriptional landscape of pig organogenesis, which might contribute to further studies addressing specific developmental events in pigs and in other mammals.

Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states.

Over two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study, we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 Cl-/H+ antiporter. Integrating experimental and computational approaches, we show that monomers associate to avoid a thinned-membrane defect formed by hydrophobic mismatch at their exposed dimerization interfaces. In this defect, lipids are strongly tilted and less densely packed than in the bulk, with a larger degree of entanglement between opposing leaflets and greater water penetration into the bilayer interior. Dimerization restores the membrane to a near-native state and therefore, appears to be driven by the larger free-energy cost of lipid solvation of the dissociated protomers. Supporting this theory, we demonstrate that addition of short-chain lipids strongly shifts the dimerization equilibrium toward the monomeric state, and show that the cause of this effect is that these lipids preferentially solvate the defect. Importantly, we show that this shift requires only minimal quantities of short-chain lipids, with no measurable impact on either the macroscopic physical state of the membrane or the protein's biological function. Based on these observations, we posit that free-energy differentials for local lipid solvation define membrane-protein association equilibria. With this, we argue that preferential lipid solvation is a plausible cellular mechanism for lipid regulation of oligomerization processes, as it can occur at low concentrations and does not require global changes in membrane properties.

A cell's outer membrane is made of molecules called lipids, which band together to form a flexible thin film, just two molecules thick. This membrane is dotted with proteins that transport materials in to and out of cells. Most of these membrane proteins join with other proteins to form structures known as oligomers. Except, how membrane-bound proteins assemble into oligomers ­ the physical forces driving these molecules to take shape ­ remains unclear. This is partly because the structural, physical and chemical properties of fat-like lipid membranes are radically different to the cell's watery interior. Consequently, the conditions under which membrane oligomers form are distinct from those surrounding proteins inside cells. Membrane proteins are also more difficult to study and characterize than water-soluble proteins inside the cell, and yet many therapeutic drugs such as antibiotics specifically target membrane proteins. Overall, our understanding of how the unique properties of lipid membranes affect the formation of protein structures embedded within, is lacking and warrants further investigation. Now, Chadda, Bernhardt et al. focused on one membrane protein, known as CLC, which tends to exist in pairs ­ or dimers. To understand why these proteins form dimers (a process called dimerization) Chadda, Bernhardt et al. first used computer simulations, and then validated the findings in experimental tests. These complementary approaches demonstrated that the main reason CLC proteins 'dimerize' lies in their interaction with the lipid membrane, and not the attraction of one protein to its partner. When CLC proteins are on their own, they deform the surrounding membrane and create structural defects that put the membrane under strain. But when two CLC proteins join as a dimer, this membrane strain disappears ­ making dimerization the more stable and energetically favorable option. Chadda, Bernhardt et al. also showed that with the addition of a few certain lipids, specifically smaller lipids, cell membranes become more tolerant of protein-induced structural changes. This might explain how cells could use various lipids to fine-tune the activity of membrane proteins by controlling how oligomers form. However, the theory needs to be examined further. Altogether, this work has provided fundamental insights into the physical forces shaping membrane-bound proteins, relevant to researchers studying cell biology and pharmacology alike.

Referral to the national network of integrated care: the nurses' perception.

OBJECTIVE: to understand the referral to the National Network of Integrated Continuous Care, from the perspective of nurses who work in this care context. METHOD: an exploratory and descriptive study with a qualitative approach, with data collection between July and September 2019 through interviews with 12 nurses who work in Integrated Continuous Care Teams, in Northern Portugal. The content analysis technique was used to analyze the statements. RESULTS: the professionals revealed that there are difficulties and constraints in the process of referring users to the National Network of Integrated Continuous Care. The process is bureaucratic, complex, and time-consuming, conditioning user accessibility to timely care. CONCLUSION: the referral process is a very bureaucratic and time-consuming procedure, which not only conditions and delays users' access to the National Network of Integrated Continuous Care network, contributing to the worsening of the clinical status of some patients. The number of professionals is insufficient, inducing the demand for services through urgency. The focus on primary care should seek to improve inequalities in access, compete for more equitable and accessible care, generating more quality in health care.

Miscible Polyether/Poly(ether-acetal) Electrolyte Blends.

This study shows that it is possible to obtain homogeneous mixtures of two chemically distinct polymers with a lithium salt for electrolytic applications. This approach is motivated by the success of using mixtures of organic solvents in modern lithium-ion batteries. The properties of mixtures of a polyether, poly(ethylene oxide) (PEO), a poly(ether-acetal), poly(1,3,6-trioxocane) (P(2EO-MO)), and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt were studied by small-angle neutron scattering (SANS) and electrochemical characterization in symmetric cells. The SANS data are used to determine the miscibility window and quantify the effect of added salt on the thermodynamic interactions between the polymers. In the absence of salt, PEO/P(2EO-MO) blends are homogeneous and characterized by attractive interactions, i.e., a negative Flory-Huggins interaction parameter, χ. The addition of small amounts of salt results in a positive effective Flory-Huggins interaction parameter, χ eff, and macrophase separation. Surprisingly, miscible blends and negative χ eff parameters are obtained when the salt concentration is increased beyond a critical value. The electrochemical properties of PEO/P(2EO-MO)/LiTFSI blends at a given salt concentration were close to those obtained in PEO/LiTFSI electrolytes at the same salt concentration. This suggests that in the presence of PEO the electrochemical properties exhibited by P(2EO-MO) chains are similar to those of PEO chains. This work opens the door to a new direction for creating new and improved polymer electrolytes either by combining existing polymers and salt or by synthesizing new polymers with the specific aim of including them in miscible polymer blend electrolytes.