Relationship Between Resultant Force Vector Acting on Human Organs From Food Bolus and the Bolus Configuration During Swallowing Using Numerical Swallowing Simulation With Moving Particle Simulation Method.

This study investigates the forces exerted on organs during swallowing, specifically focusing on identifying forces other than those resulting from direct organ contact. Using a swallowing simulator based on the moving particle method, we simulated the swallowing process of healthy individuals upon the ingestion of thickened foods, which were simulated as shear-thinning flow without yield stress. We extracted the resultant force vectors acting on the organs and shape of the bolus at each time interval. The simulation results confirmed that the bolus originates from tongue movement and is transferred between the oral cavity and pharynx, with each organ's coordinated movements with the tongue occurring at their respective positions, as indicated by the balance of the resultant force vectors. Utilizing the information about the resultant force vectors obtained through simulations, we calculated the physical parameters of impulse, energy, and power. The variations in these physical parameters were aligned with the behaviors of both the biological system and the food bolus during swallowing. The force values calculated from the simulations closely approximate the theoretical values. Furthermore, the forces calculated from the simulations were relatively smaller than the force values derived from pressure information, such as that from high-resolution manometry and tongue pressure sensors. This difference can be attributed to the simulations extracting only the forces exerted on the organ by the food bolus. Force information on organs has the potential to provide a new interpretation of conventional mechanical indicators such as manometry and tongue pressure sensors.

Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression.

This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. We utilized RAFT to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane (Ad) or ß-cyclodextrin (Cd) through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels. Rheometric evaluation of the hydrogel library enabled identification of lead macromer structures comprising 15 mol% pendants (Ad or Cd) and a degree of polymerization of 1000; mixing of these Ad and Cd functionalized precursors yielded hydrogels possessing storage modulus above 1000 Pa, tan(δ) values below 1 and high yield strain, which are target characteristics of robust but injectable shear-thinning gels. This modular system proved amenable to nanoparticle integration with surface-modified nanoparticles displaying Ad. The addition of the Ad-functionalized nanoparticles simultaneously improved mechanical properties of the hydrogels and enabled extended hydrogel retention of a model small molecule in vivo. In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel. In sum, the new synthetic, shear-thinning hydrogel system presented here shows potential for further development as an injectable platform for delivery and in situ drug modulation of allograft and engineered cell therapies.

Association between hydroxychloroquine intake and damage to the outer nuclear layer in eyes without manifest retinal toxicity.

BACKGROUND: Hydroxychloroquine (HCQ) is widely used to treat various autoimmune diseases but carries a risk of retinal toxicity, particularly with prolonged use. Despite advancements, uncertainty persists regarding optimal screening methods. Recent advances in OCT have enabled early detection of retinal damage, with studies suggesting that thinning of specific retinal layers may be an early indicator of toxicity. However, there is a gap in research on outer nuclear layer (ONL) thinning in HCQ users without apparent retinal toxicity. This information is crucial for improving screening and identifying the ONL as a reliable biomarker for screening. Therefore, this study aimed to investigate the association between HCQ intake and ONL damage in eyes without manifest retinal toxicity. METHODS: A case‒control study was conducted at the ophthalmology department of Eye and Ear Hospital International from July 2022 to June 2023. The study included 20 individuals on HCQ and 20 age-matched controls. The data were obtained through chart reviews, and participants underwent comprehensive ophthalmic assessments. RESULTS: A total of 80 eyes were analyzed. Patients on HCQ exhibited significantly thinner perifoveal, parafoveal, and overall ONL compared to controls (P < .001, P < .012, and P < .004, respectively). Similarly, this association was found in the nasal, inferior, and temporal quadrants of both the inner (region 3: P < .01, region 4: P < .001, and region 5: P < .03) and outer zones (region 7: P < .04, region 8: P < .001, region 9: P < .02), most pronounced in the inferior regions. The cumulative dose was weakly associated with decreased ONL thickness only in the nasal quadrant of the inner zone (region 3: P < .047). Correlation analysis of the initial and most recent OCT scans in the same individuals revealed a weak association with ONL thinning in the central zone (region 1: P < .0048). CONCLUSION: The thickness of the ONL can significantly decrease in patients taking HCQ, even in the absence of of manifest retinal toxicity. This study is the first to evaluate this association in eyes with negative screening and diagnostic tests for HCQ retinopathy. The findings suggest that ONL thickness could serve as an early diagnostic indicator for HCQ retinal toxicity.

COVID-19 lockdown effects on adolescent brain structure suggest accelerated maturation that is more pronounced in females than in males.

Adolescence is a period of substantial social-emotional development, accompanied by dramatic changes to brain structure and function. Social isolation due to lockdowns that were imposed because of the COVID-19 pandemic had a detrimental impact on adolescent mental health, with the mental health of females more affected than males. We assessed the impact of the COVID-19 pandemic lockdowns on adolescent brain structure with a focus on sex differences. We collected MRI structural data longitudinally from adolescents prior to and after the pandemic lockdowns. The pre-COVID data were used to create a normative model of cortical thickness change with age during typical adolescent development. Cortical thickness values in the post-COVID data were compared to this normative model. The analysis revealed accelerated cortical thinning in the post-COVID brain, which was more widespread throughout the brain and greater in magnitude in females than in males. When measured in terms of equivalent years of development, the mean acceleration was found to be 4.2 y in females and 1.4 y in males. Accelerated brain maturation as a result of chronic stress or adversity during development has been well documented. These findings suggest that the lifestyle disruptions associated with the COVID-19 pandemic lockdowns caused changes in brain biology and had a more severe impact on the female than the male brain.

Influence of thinning on carbon storage mediated by soil physicochemical properties and microbial community composition in large Chinese fir timber plantation.

BACKGROUND: Thinning practices are useful measures in forest management and play an essential role in maintaining ecological stability. However, the effects of thinning on the soil properties and microbial community in large Chinese fir timber plantations remain unknown. The purpose of this study was to investigate the changes in soil physicochemical properties and microbial community composition in topsoil (0-20 cm) under six different intensities (i.e., 300 (R300), 450 (R450), 600 (R600), 750 (R750) and 900 (R900) trees per hectare and 1650 (R1650) as a control) in a large Chinese fir timber plantation. RESULTS: Compared with the CK treatment, thinning significantly altered the contents of soil organic carbon (SOC) and its fractions but not in a linear fashion; these indicators were highest in R900. In addition, thinning did not significantly affect the soil microbial community diversity indices but significantly affected the relative abundance of the core microbial community. Proteobacteria, Acidobacteria, and Actinobacteria were the dominant bacterial phyla; the relative abundances of Proteobacteria and Acidobacteria were highest in R900, and that of Actinobacteria was lowest in R900. The dominant fungal phyla were Ascomycota, Basidiomycota and Mucoromycota; the relative abundance of Ascomycota was lowest in R900, and that of Mucoromycota was highest in R900. The fungal microbial community composition was more sensitive than the bacterial community composition. The activity of the carbon-cycling genes was not linearly correlated with thinning, and the abundance of C-cycle genes was highest in R900. CONCLUSIONS: These findings are important because they show that SOC and its fractions and the abundance of the soil microorganism community in large Chinese fir timber plantations can be significantly altered by thinning, thus affecting the capacity for carbon storage. These results may advance our understanding of how the density of large timber plantations could be modified to promote soil carbon storage.

Impact of planting density and shoot thinning on alstroemeria flowering, soil attributes and cost economics.

A field experiment was conducted to assess the impact of various planting densities and levels of shoot thinning on cut flower yield, quality, soil chemical properties and cost economics in the commercially cultivated alstroemeria cultivar 'Capri'. The experiment involved three planting densities (4, 6 and 8 plants/m2) along with three shoot thinning levels (10 %, 20 % and 30 %). It was observed that higher planting density (4 plants/m2) promoted the length of cut stem, early bud formation, and flowering, optimal quality parameters, including maximum stem thickness, cut stem weight, floret quantity/stem, floret size, number of flowering stems/plant (yield) and vase life. Exclusive use of higher vegetative mass removal (30 % shoot thinning) was found to improve quality parameters such as the length of cut stem, number of flowering stems, stem thickness, weight of cut stem, floret quantity/stem, floret size, vase life, and early flowering. Soil samples were collected from each treatment and the consequent lab analysis revealed that the lower planting density and shoot thinning level resulted in maximum soil organic carbon, nitrogen, phosphorous and potassium content. In conclusion, planting density of 4 plants/m2 and 30 % shoot thinning emerged as the optimal combination for enhancing quantitative parameters in commercial alstroemeria cultivation. The study underscores the importance of strategic planting practices and vegetative mass management for maximizing yield and quality in alstroemeria production, along with ensuring higher economic returns.

Exploration of Choroidal Thinning Located Temporal to the Fovea: A Pilot Study.

Background/Objectives: Posterior staphyloma (PS) is a hallmark of pathological myopia, corresponding to a circumscribed outpouching of the eyeball with choroidal thinning and inward scleral deformation at its edges. Its pathogenesis is still unclear, thus constituting a research priority as the prevalence of myopia is increasing worldwide. Recently, it has been suggested that the optic nerve sheaths or oblique muscles are potential promoters of PS through the traction or compression effect that they apply to the eye wall. The inferior oblique muscle (IOM) inserts 1-2 mm from the macula. The projection of its insertion is accessible using Optical Coherence Tomography (OCT). Before launching prospective studies, we sought to detect any choroidal thinning (ChT) in the temporal vicinity of the macula and to measure the distance between it and the fovea (FT-distance). Methods: This retrospective cross-sectional pilot study included 120 eyes. Using Spectralis®-OCT, the area centered by the Bruch's membrane opening-fovea axis was analyzed for ChT and FT-distance. Results: Of the 112 defined eyes, 70% (78 eyes) had ChT. Pachymetry was significantly thinner (p = 0.018) in eyes with than without ChT. The mean FT-distance was 3601.9 ± 93.6 µm. Conclusions: The location of ChT coincided with the insertion distance of the IOM, suggesting a link between them. The association between the presence of ChT and a thinner pachymetry suggests a reduced scleral resistance, as a thinner pachymetry is related to a thinner sclera. Our results suggest a link between ocular deformation and the IOM, which may be relevant for the pathogenesis of PS, warranting further investigation.

Effects of thinning on structural complexity of Larix olgensis plantation.

In this paper, we collected the individual tree point cloud data in the plots of Larix olgensis plantations with different thinning intensities in Mengjiagang Forest Farm, applied the fractal analysis theory to extract box dimensions (Db) on MATLAB platform, and characterized the structural complexity of L. olgensis. We assessed the effect of different thinning intensities and tree attributes on the structural complexity of L. olgensis. The results showed significant differences in L. olgensis Db between control (CK: 1.68±0.07), low and medium intensity thinning (T1, T2, T3: 1.74±0.07), and high intensity thinning (T4: 1.81±0.06), which indicated that the thinning intensity increased tree structural complexity. For trunk attribute, the diameter at breast height and tree height was significantly positively correlated with Db, while the height-to-diameter ratio was significantly negatively correlated with Db. For canopy attribute, crown volume, surface area, projected area, and crown diameter was significantly positively correlated with Db. Hegyi competition index was significantly negatively correlated with Db in the control and low-moderate-intensity thinning treatments, but not significantly correlated with Db in the high-intensity thinning treatment. It indicated that thinning influenced L. olgensis structural complexity, with trunk attribute and canopy attribute as the main drivers of L. olgensis structural complexity.

Non-Newtonian behaviour of suspensions and emulsions: Review of different mechanisms.

The mechanisms of non-Newtonian behaviour of suspensions and emulsions in steady shear flow are reviewed. The review is divided into two parts. In the first part, the mechanisms of non-Newtonian behaviour in suspensions and emulsions composed of Newtonian matrix are reviewed. Both dilute and concentrated systems are discussed. In the second part, the mechanisms of non-Newtonian behaviour in suspensions and emulsions composed of non-Newtonian matrix are reviewed. Where appropriate, mathematical models describing the rheology are included.

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.e., brain atrophy, and retinal layer thinning). METHODS: We designed an observational prospective mono-center study in RRMS patients initiating ALZ treatment. Patients were assessed at baseline (month 0) and thereafter annually for five years with clinical measures, synthetic magnetic resonance imaging (SyMRI) and optical coherence tomography (OCT), with a re-baseline SyMRI scan and an OCT exam 24 months after initiating ALZ. Persons with neurological symptoms but without evidence of neurological disease served as symptomatic controls (SCs, n = 27). RESULTS: Forty-nine RRMS patients were included. Baseline median expanded disability status scale [2.0 (IQR 1.5)] was unchanged during follow-up, 71 % were progression-free, 33 % achieved no evidence of disease activity-3 (NEDA-3). Between baseline and month 60, SyMRI showed a reduction of brain parenchymal fraction (BPF) and grey matter (GM) volume in patients. The BPF reduction was greater in RRMS patients than in SCs (p < 0.05), and more pronounced in patients with high pre-baseline disease activity than in those without (p < 0.01). OCT showed significant thinning of macular ganglion cell and inner plexiform layers (mGCIPL) and in peripapillary retinal nerve fiber layer (pRNFL) in patients. In contrast, absolute values of white matter (WM) volume and myelin content (MyC) quantified by SyMRI, were stable or increased after re-baseline (month 24) and up to month 60, and this increase appeared limited to patients without high pre-baseline disease activity and to patients with NEDA-3 or disability worsening during follow-up. A strong positive correlation between WM volume and GM volume at baseline was lost after ALZ intervention for their delta values, i.e., change from re-baseline (month 24) to month 60. While the positive baseline correlation between WM volume and MyC increased for their delta values, the positive baseline correlation between GM volume and MyC changed to negative for their delta values. CONCLUSION: We showed that neurodegeneration continued in RRMS patients under ALZ treatment, but it appeared to be limited to BPF and GM, and more pronounced in patients with disease activity. Our data suggest that patients who respond to ALZ treatment show signs of remyelination. OCT and SyMRI have potential to quantify measures of neurodegeneration that is affected by treatment intervention in RRMS.

Retinal layer thinning for monitoring disease-modifying treatment in relapsing multiple sclerosis-Evidence for applying a rebaselining concept.

BACKGROUND: Employing a rebaselining concept may reduce noise in retinal layer thinning measured by optical coherence tomography (OCT). METHODS: From an ongoing prospective observational study, we included patients with relapsing multiple sclerosis (RMS), who had OCT scans at disease-modifying treatment (DMT) start (baseline), 6-12 months after baseline (rebaseline), and ⩾12 months after rebaseline. Mean annualized percent loss (aL) rates (%/year) were calculated both from baseline and rebaseline for peripapillary-retinal-nerve-fiber-layer (aLpRNFLbaseline/aLpRNFLrebaseline) and macular-ganglion-cell-plus-inner-plexiform-layer (aLGCIPLbaseline/aLGCIPLrebaseline) by mixed-effects linear regression models. RESULTS: We included 173 RMS patients (mean age 31.7 years (SD 8.8), 72.8% female, median disease duration 15 months (12-94) median baseline-to-last-follow-up-interval 37 months (18-71); 56.6% moderately effective DMT (M-DMT), 43.4% highly effective DMT (HE-DMT)). Both mean aLpRNFLbaseline and aLGCIPLbaseline significantly increased in association with relapse (0.51% and 0.26% per relapse, p < 0.001, respectively) and disability worsening (1.10% and 0.48%, p < 0.001, respectively) before baseline, but not with DMT class. Contrarily, neither aLpRNFLrebaseline nor aLGCIPLrebaseline was dependent on relapse or disability worsening before baseline, while HE-DMT significantly lowered aLpRNFLrebaseline (by 0.31%, p < 0.001) and aLGCIPLrebaseline (0.25%, p < 0.001) compared with M-DMT. CONCLUSIONS: Applying a rebaselining concept significantly improves differentiation of DMT effects on retinal layer thinning by avoiding carry-over confounding from previous disease activity.

Growth trends clustering: A novel method for detecting forest disturbances and extracting climate signals in tree rings.

Tree-ring widths contain valuable historical information related to both forest disturbances and climate variability and changes within forests. However, current methods are still unable to accurately distinguish between disturbances and climate signals in tree rings, especially in the case of climate anomalies. To address this issue, we developed a novel method, called Growth Trends Clustering (GTC) that uses the distribution characteristics of tree-ring widths within a stand to distinguish the effects of climate and other forest disturbances. GTC employed a Gaussian mixture model to fit the probability density distribution of annual ring-width index (RWI) in a stand. Discriminative criteria were established to cluster diverse sub-distributions from the Gaussian mixture model into categories of growth release, suppression, or normal trends. This approach allowed us to identify the occurrence, duration, and severity of forest disturbances based on percentage changes in the growth release or suppression categories of trees. And the effect of climate on tree growth was assessed according to the mean statistics of the growth normal categories. Using common forest disturbances such as defoliating insects and thinning as examples, we validated our method using tree-ring collections from six sites in British Columbia and Quebec, Canada. We found that the GTC method was superior to traditional time-series analysis methods (e.g., Radial Growth Averaging, Boundary Line, Absolute Increase, and Curve Intervention Detection) for detecting past forest disturbances and was able to significantly enhance climate signals. In summary, the GTC method presented in this study introduces a novel statistical approach for accurately distinguishing between forest disturbances and climate signals in tree rings. This is particularly important for understanding forest disturbance regimes under climate change and for developing future disturbance mitigation strategies.

Marangoni Droplets of Dextran in PEG Solution and Its Motile Change Due to Coil-Globule Transition of Coexisting DNA.

Motile droplets using Marangoni convection are attracting attention for their potential as cell-mimicking small robots. However, the motion of droplets relative to the internal and external environments that generate Marangoni convection has not been quantitatively described. In this study, we used an aqueous two-phase system [poly(ethylene glycol) (PEG) and dextran] in an elongated chamber to generate motile dextran droplets in a constant PEG concentration gradient. We demonstrated that dextran droplets move by Marangoni convection, resulting from the PEG concentration gradient and the active transport of PEG and dextran into and out of the motile dextran droplet. Furthermore, by spontaneously incorporating long DNA into the dextran droplets, we achieved cell-like motility changes controlled by coexisting environment-sensing molecules. The DNA changes its position within the droplet and motile speed in response to external conditions. In the presence of Mg2+, the coil-globule transition of DNA inside the droplet accelerates the motile speed due to the decrease in the droplet's dynamic viscosity. Globule DNA condenses at the rear part of the droplet along the convection, while coil DNA moves away from the droplet's central axis, separating the dipole convections. These results provide a blueprint for designing autonomous small robots using phase-separated droplets, which change the mobility and molecular distribution within the droplet in reaction with the environment. It will also open unexplored areas of self-assembly mechanisms through phase separation under convections, such as intracellular phase separation.

Intraspecific priority effects in response to egg hatching delay in a pond-breeding salamander.

As reproduction phenologies shift with climate change, populations can experience intraspecific priority effects, wherein early hatching cohorts experience an advantage over late-hatching cohorts, resulting in altered demography. Our study objective was to identify how variation in egg hatching phenology alters intraspecific interactions in small-mouthed salamanders, Ambystoma texanum. We addressed two research questions: (Q1) How are demographic responses altered by variation in the temporal duration of hatching between cohorts, and (Q2) How does the seasonality of hatching delays affect demographic responses? We manipulated hatching phenologies of A. texanum eggs and reared larvae in outdoor mesocosms to metamorphosis. For Q1, hatching delay exhibited non-linear relationships with survival and body size, with the greatest asynchrony in cohort additions resulting in the highest mortality and largest body sizes. For Q2, hatching delay effects were stronger (i.e., survival was lower and body sizes larger) when they occurred later in the season, potentially due to temperature differences that larvae experienced. Overall, our results demonstrate that changes in intraspecific interactions due to phenological shifts can be context-dependent, depending on the strength (i.e., temporal duration) and seasonality of such processes. Identifying context-dependencies of phenological shifts will be critical for predicting changes in organismal demographics with climatic shifts.

Determinants of carbon sequestration in thinned forests.

Given global climate change and the projected increases in the greenhouse effect, enhancing the carbon storage capacity of forest ecosystems is especially critical. To fully realize the potential carbon sequestration, it is imperative to understand the drivers affecting carbon storage in forest ecosystems, particularly with disturbances that disrupt existing balance. In this study, we explored the effects of stem-only harvest at various thinning intensities on forest structure and carbon density in middle-aged natural secondary forests, located in the northern temperate zone. Carbon density included aboveground carbon density (ACD), soil organic carbon stocks (SOCD), and total carbon density (TCD), which was the sum of ACD and SOCD. We employed the random forest analysis method to identify significant variables influencing changes in carbon density. Structural equation modelling (SEM) was then used to determine the drivers of changes in forest carbon density. The results showed that moderate thinning (20 %-35 % trees removed), is an effective management practice for increasing the TCD in forests. Although heavy thinning (35.1 %-59.9 % trees removed) accelerated individual growth, it did not fully offset the carbon removed due to thinning. It is noteworthy that light thinning (0-19.9 % trees removed) not only reduced the species richness but also caused a significant number of tree deaths. Large live trees were an important direct determining factor of ACD, but not the only one. In addition, thinning indirectly influenced ACD by reducing canopy density and deformed tree density. The increase in dead tree density had an adverse impact on SOCD, and this phenomenon increased with the passage of recovery time. Conversely, greater thinning intensity enhanced SOCD. Moreover, TCD was directly influenced by tree height, large live trees, and stand density. Furthermore, thinning altered the conifer ratio, thereby influencing tree growth and indirectly controlling the TCD. We believe that this knowledge will be highly beneficial for successful forest management and enhancing the carbon sequestration capacity of forest ecosystems.

Hybrid Nanoparticle-Hydrogel Systems for Drug Delivery Depots and Other Biomedical Applications.

Hydrogel-based depots typically tend to remain where injected and have excellent biocompatibility but are relatively poor at controlling drug release. Nanoparticles (NPs) typically have the opposite properties. The smaller the NPs are, the more likely they are to leave the site of injection. Their biocompatibility is variable depending on the material but can be poor. However, NPs can be good at controlling drug release. In these and other properties, combining NPs and hydrogels can leverage their advantages and negate their disadvantages. This review highlights the rationale for hybrid NP-hydrogel systems in drug delivery, the basic methods of producing them, and examples where combining the two systems addressed specific problems.

Soil Fungal Pathogens in Pinus pinaster Mature Reforestation: Silvicultural Treatments Effects.

Soil fungal communities play a key role in multiple functions and ecosystem services within forest ecosystems. Today, forest ecosystems are subject to multiple environmental and anthropogenic disturbances (e.g., fire or forest management) that mainly lead to changes in vegetation as well as in plant-soil interactions. Soil pathogens play an important role in controlling plant diversity, ecosystem functions, and human and animal health. In this work we analyzed the response of soil plant pathogenic fungi to forest management in a Pinus pinaster reforestation. We started from an experimental design, in which forest thinning and gap cutting treatments were applied at different intensities and sizes, respectively. The fungal communities of plant pathogens in spring were described, and the effect of the silvicultural treatments was evaluated 5 years after their application, as were the possible relationships between soil plant pathogenic fungal communities and other environmental factors. Only a strong low thinning treatment (35% basal area) was able to generate homogeneous changes in soil pathogenic diversity. In the gaps, only the central position showed significant changes in the soil plant pathogenic fungi community.

Association Between Right Bundle Branch Block and Ventricular Arrhythmia in Patients With Cardiac Sarcoidosis.

Background: Ventricular arrhythmia (VA) is a life-threatening condition associated with cardiac sarcoidosis (CS). Right bundle branch block (RBBB) is a common conduction disorder in CS; however, its association with VA remains unknown. Objectives: This study aimed to investigate the relationship between RBBB and VA in patients with CS. Methods: This was a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients with Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of CS. Eligible patients were divided into two groups based on the presence or absence of RBBB at the time of diagnosis. The primary outcome was serious ventricular arrhythmia events (SVAEs), defined as a combination of sudden cardiac death and documented ventricular fibrillation, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator therapy. Results: Overall, 312 patients were studied, with 155 (49.7%) patients presenting with RBBB (RBBB group). Patients in the RBBB group had a higher prevalence of basal interventricular septum (IVS) thinning and prominent late gadolinium enhancement in the basal IVS on cardiac magnetic resonance imaging than those in the non-RBBB group. During a median follow-up of 3.0 years (IQR: 1.6-6.0 years), 66 patients experienced SVAE. In multivariable Cox regression analysis, the RBBB group was independently associated with a higher incidence of SVAEs (HR: 1.93 [95% CI: 1.14-3.28]; P = 0.015). Conclusions: In patients with CS, RBBB was an independent predictor of SVAEs, which might reflect the specific scar distribution that is predominant in the IVS.

Antiviral activity of the host defense peptide piscidin 1: investigating a membrane-mediated mode of action.

Outbreaks of viral diseases are on the rise, fueling the search for antiviral therapeutics that act on a broad range of viruses while remaining safe to human host cells. In this research, we leverage the finding that the plasma membranes of host cells and the lipid bilayers surrounding enveloped viruses differ in lipid composition. We feature Piscidin 1 (P1), a cationic host defense peptide (HDP) that has antimicrobial effects and membrane activity associated with its N-terminal region where a cluster of aromatic residues and copper-binding motif reside. While few HDPs have demonstrated antiviral activity, P1 acts in the micromolar range against several enveloped viruses that vary in envelope lipid composition. Notably, it inhibits HIV-1, a virus that has an envelope enriched in cholesterol, a lipid associated with higher membrane order and stability. Here, we first document through plaque assays that P1 boasts strong activity against SARS-CoV-2, which has an envelope low in cholesterol. Second, we extend previous studies done with homogeneous bilayers and devise cholesterol-containing zwitterionic membranes that contain the liquid disordered (Ld; low in cholesterol) and ordered (Lo, rich in cholesterol) phases. Using dye leakage assays and cryo-electron microscopy on vesicles, we show that P1 has dramatic permeabilizing capability on the Lo/Ld, an effect matched by a strong ability to aggregate, fuse, and thin the membranes. Differential scanning calorimetry and NMR experiments demonstrate that P1 mixes the lipid content of vesicles and alters the stability of the Lo. Structural studies by NMR indicate that P1 interacts with the Lo/Ld by folding into an α-helix that lies parallel to the membrane surface. Altogether, these results show that P1 is more disruptive to phase-separated than homogenous cholesterol-containing bilayers, suggesting an ability to target domain boundaries. Overall, this multi-faceted research highlights how a peptide that interacts strongly with membranes through an aromatic-rich N-terminal motif disrupt viral envelope mimics. This represents an important step towards the development of novel peptides with broad-spectrum antiviral activity.

Rheology of Suspensions Thickened by Cellulose Nanocrystals.

The steady rheological behavior of suspensions of solid particles thickened by cellulose nanocrystals is investigated. Two different types and sizes of particles are used in the preparation of suspensions, namely, TG hollow spheres of 69 µm in Sauter mean diameter and solospheres S-32 of 14 µm in Sauter mean diameter. The nanocrystal concentration varies from 0 to 3.5 wt% and the particle concentration varies from 0 to 57.2 vol%. The influence of salt (NaCl) concentration and pH on the rheology of suspensions is also investigated. The suspensions generally exhibit shear-thinning behavior. The degree of shear-thinning is stronger in suspensions of smaller size particles. The experimental viscosity data are adequately described by a power-law model. The variations in power-law parameters (consistency index and flow behavior index) under different conditions are determined and discussed in detail.