Index Dispersion Research Articles

Advanced measures of cortical microstructural change and associations with cognitive and blood‐based biomarkers in autosomal dominant Alzheimer’s disease

AbstractBackgroundIn Alzheimer’s disease (AD), dysfunction and loss of cortical neurons occurs prior to symptom onset. Diffusion tensor imaging, measuring mean diffusivity (MD), provides a metric of microscopic change but lacks specificity for different underlying microstructural processes. We used Neurite Orientation Dispersion and Density Imaging (NODDI) to investigate specific cortical microstructural features across the disease course in autosomal dominant AD (ADAD).MethodSixty‐three ADAD family members (36 mutation carriers) (Table 1) underwent T1w and multi‐shell diffusion MRI (dMRI). Cortical thickness and cortical MD were estimated, with NODDI providing measures of tissue fraction (TF), neurite density index (NDI) and orientation dispersion index (ODI) (a proxy measure of dendritic complexity). Imaging metrics were sampled across six cortical regions of interest (ROIs) known to be particularly vulnerable to early neurodegeneration. Associations between dMRI measures and 1) disease stage as measured by estimated years to onset (EYO), 2) AD blood biomarkers, and 3) cognitive measures were assessed.ResultAcross mutation carriers, ODI (Figure 1) and TF (Figure 2) demonstrated negative associations (p<0.05) with EYO in most ROIs, while MD demonstrated positive correlations. Most associations remained after adjusting for cortical thickness. The association between ODI and EYO in the supramarginal gyrus also remained after adjustment for MD (p = 0.002). In presymptomatic carriers, EYO appeared most prominently associated with ODI (p<0.05 in 3/6 regions). ODI, TF and MD showed widespread associations with MMSE and CDR sum of boxes. TF was negatively, and MD positively, associated with serum NfL across ROIs, but for ODI this was only the case in the supramarginal gyrus. ptau181 demonstrated significant associations with ODI in the supramarginal (p = 0.0089) and inferior parietal (p = 0.033) cortices, and with MD in the entorhinal cortex (p = 0.015).ConclusionCortical dendritic complexity (modelled by ODI) and cortical tissue fraction decrease, while overall diffusivity increases as individuals approach symptom onset. ODI appears to be the metric most closely associated with presymptomatic disease stage, possibly reflecting early dendritic pruning, and is associated with ptau – a measure of early pathology – while MD and TF may be more sensitive to later larger scale changes, given their associations with serum NfL and cognitive measures.

Abstract A031: Development of poly lactic acid based biodegradable nanoparticles for co-delivery of pirarubicin and gemcitabine for synergistic anti-tumor efficacy

Abstract Nanoparticles based drug delivery systems have provided a befitted solution for the poor pharmacokinetic properties and systemic toxicity caused by the chemo drugs because of their ability to improve bioavailability of the drugs at the desired site and thereby decreasing extracellular toxicity. The present work investigates the single or dual chemo drugs loaded PLA-based biodegradable polymeric nanoparticles for improved anti-tumor efficacy as compared to free drug formulations. For the study, an amphiphilic block copolymer; mPEG PLA has been synthesized and characterized using Gel permeation chromatography (GPC) for its molecular weight and poly dispersity index as well as with Nuclear magnetic resonance (NMR) and Fourier-transform Infrared (FT-IR) spectroscopies. Thereafter, two different chemo drugs Pirarubicin (PIRA, THP analogue of Doxorubicin) and Gemcitabine (GEM) have been chemically conjugated individually to mPEG PLA block copolymer via a linker molecule, Levulinic acid to give an acid labile polymer-drug conjugate and the % drug conjugation efficiency has been calculated using High performance liquid chromatography (HPLC). The synthesized polymer-drug conjugates have been employed to prepare PIRA/GEM single or dual-loaded nanoparticles via nanoprecipitation technique and the physiochemical properties including size, zeta potential, and stability were analyzed using Dynamic Light Scattering (DLS) and High-resolution transmission electron microscopy (HR-TEM). To carry out toxicity assessment of the mPEG PLA nanoparticles, both cytocompatibility and hemocompatibility were checked using MTT assay and Hemolysis assay respectively. Moreover, the cellular internalization studies of dye-loaded mPEG PLA nanoparticles were done using Confocal microscopy on SUM-149, breast cancer cells. Besides, the drug release kinetic studies of the free PIRA/GEM from the PIRA/GEM single or dual-loaded nanoparticles were carried out in different pH environments; pH 7.4 and pH 5.0. The in-vitro cell proliferation inhibition studies of PIRA/GEM or dual-loaded nanoparticles were carried out on different human and murine breast cancer cell lines including MCF-7, MDA-MB-468, SUM 149, MDA-MB-231 and 4T1 and half-maximal inhibitory concentrations (IC50 values) were compared to that of respective free drug formulations. The overall results suggested that the prepared sub-nano sized PIRA/GEM single or dual-loaded particles are highly stable, uniformly spherical in size and biocompatible in nature. They were found to possess high cellular uptake, sustained drug release rate and synergistic efficacy and potential against both human and murine breast cancer cells in-vitro conditions. Citation Format: Priya Gupta. Development of poly lactic acid based biodegradable nanoparticles for co-delivery of pirarubicin and gemcitabine for synergistic anti-tumor efficacy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A031.

Longitudinal age effects in microstructures of the hippocampal subfields.

AbstractBackgroundThe human brain undergoes considerable morphologic change with age, which is one of the primary risk‐factors for Alzheimer’s disease (AD). Age‐related microstructural changes in the brain may be quantified by advanced diffusion MRI (dMRI) with compartment modeling. In this longitudinal study, we aimed to investigate the effects of age on the hippocampal subfields, one of the brain regions vulnerable to the early stages of AD.MethodThirty‐seven cognitively normal older adults (70.6 ± 6.7 years) were recruited from the Indiana ADRC. Participants received a baseline and a follow‐up MRI scan over 24 ± 11.7 months with a Siemens 3T Prisma scanner using a 64‐channel head coil. We applied grey‐matter‐specific multi‐compartment diffusion model (cortical‐neurite orientation dispersion and density imaging) to derive diffusion microstructural metrics, namely orientation dispersion index (ODI), volume fractions of fast isotropic diffusion (VFISO), and intracellular‐space (VFIC) in the hippocampal‐subfields (CA1‐3, CA4 and dentate gyrus (CA4‐DG), and subiculum) [1]. To study the longitudinal age effects, we investigated the rate of change in the diffusion metrics and the association between the rate of change and age. Linear regression analysis was performed using SPSS software and adjusted for sex, education, APoE e4 status, and subfield volumes (Table 1).ResultAll subjects had normal cognition (i.e., MoCA and MMSE, Table 1). The volumes of CA1‐3 and subiculum significantly decreased between the baseline and follow‐up MRI scans, (p<0.05, Table 1). During this period, while significantly increased ODI within subject was observed in CA4‐DG, significantly decreased VFISO in all the subfields and increased VFIC in the subiculum were noted (Figure 1). The decreasing rate of VFISO in CA4‐DG was significantly associated with age (Table 2), suggesting the reduction in VFISO accelerated over age.ConclusionWe demonstrated that diffusion metrics are sensitive to microstructural alterations in the hippocampal subfields of cognitively normal older adults. The cornu ammonis region 4 and dentate gyrus is the most vulnerable region affected by aging with increased tissue dispersion and age‐accelerated reduction in fast isotropic diffusion. Future studies will focus on the effects of the initial microstructural condition to its rate of change with aging.

Advanced measures of cortical microstructural change and associations with cognitive and blood‐based biomarkers in autosomal dominant Alzheimer’s disease

AbstractBackgroundIn Alzheimer’s disease (AD), dysfunction and loss of cortical neurons occurs prior to symptom onset. Diffusion tensor imaging, measuring mean diffusivity (MD), provides a metric of microscopic change but lacks specificity for different underlying microstructural processes. We used Neurite Orientation Dispersion and Density Imaging (NODDI) to investigate specific cortical microstructural features across the disease course in autosomal dominant AD (ADAD).MethodSixty‐three ADAD family members (36 mutation carriers) (Table 1) underwent T1w and multi‐shell diffusion MRI (dMRI). Cortical thickness and cortical MD were estimated, with NODDI providing measures of tissue fraction (TF), neurite density index (NDI) and orientation dispersion index (ODI) (a proxy measure of dendritic complexity). Imaging metrics were sampled across six cortical regions of interest (ROIs) known to be particularly vulnerable to early neurodegeneration. Associations between dMRI measures and 1) disease stage as measured by estimated years to onset (EYO), 2) AD blood biomarkers, and 3) cognitive measures were assessed.ResultAcross mutation carriers, ODI (Figure 1) and TF (Figure 2) demonstrated negative associations (p<0.05) with EYO in most ROIs, while MD demonstrated positive correlations. Most associations remained after adjusting for cortical thickness. The association between ODI and EYO in the supramarginal gyrus also remained after adjustment for MD (p = 0.002). In presymptomatic carriers, EYO appeared most prominently associated with ODI (p<0.05 in 3/6 regions). ODI, TF and MD showed widespread associations with MMSE and CDR sum of boxes. TF was negatively, and MD positively, associated with serum NfL across ROIs, but for ODI this was only the case in the supramarginal gyrus. ptau181 demonstrated significant associations with ODI in the supramarginal (p = 0.0089) and inferior parietal (p = 0.033) cortices, and with MD in the entorhinal cortex (p = 0.015).ConclusionCortical dendritic complexity (modelled by ODI) and cortical tissue fraction decrease, while overall diffusivity increases as individuals approach symptom onset. ODI appears to be the metric most closely associated with presymptomatic disease stage, possibly reflecting early dendritic pruning, and is associated with ptau – a measure of early pathology – while MD and TF may be more sensitive to later larger scale changes, given their associations with serum NfL and cognitive measures.

Alzheimer’s disease biomarkers of amyloid and tau influence white matter neurite alterations in dementia with Lewy bodies: a NODDI study

AbstractBackgroundCo‐morbid Alzheimer’s disease (AD) pathology in the form of amyloid‐β plaques and tau neurofibrillary tangles are frequently observed in people with probable dementia with Lewy bodies (DLB). Neurite Orientation Dispersion and Density Imaging (NODDI) is an emerging technique to characterize white matter (WM) tissue microstructure, although NODDI alterations and associations with AD biomarkers remain undefined in DLB. The objectives of this study are to compare NODDI and DTI parameters between DLB and controls and (ii) evaluate the pattern of DTI and NODDI changes associated with amyloid and tau deposition.MethodConsecutive patients within the DLB spectrum (n = 45), including probable DLB (n = 32) and probable Mild Cognitive Impairment with Lewy bodies (MCI‐LB) (n = 13) from the Mayo Clinic ADRC underwent multi‐shell diffusion MRI, [18F]‐Flortaucipir and [11C]‐PiB PET. A comparison group of 45 age‐ and gender‐matched clinically unimpaired controls (CU) was included. Voxelwise non‐parametric permutation models were used to determine pair‐wise group differences and assess the associations of AD biomarkers with fractional anisotropy (FA), mean diffusivity (MD), tissue‐weighted neurite density index (tNDI; NDI x (1 – Free water fraction)) and orientation dispersion index (ODI), controlling for age. Complementary analyses were performed using regions‐of‐interest (ROI) obtained from the JHU atlas.ResultCompared to CU, the DLB spectrum group exhibited widespread decreases in FA and tNDI and increases in MD and ODI, with the most pronounced effects in the cingulum bundles, uncinate, inferior and superior longitudinal fasciculi (Fig. 1). Greater [18F]‐Flortaucipir uptake was also associated with lower FA and tNDI, and higher MD and ODI in the DLB spectrum compared to CU, independently of age and [11C]‐PiB uptake (Fig. 2). In contrast, no associations were found between [11C]‐PiB uptake and any of the DTI or NODDI parameters. Complementary ROI analyses corroborated these findings.ConclusionWidespread loss of WM integrity was observed on DTI and NODDI in probable DLB and prodromal DLB. These findings were associated with greater cortical tau, but not with amyloid‐β deposition. Although alpha‐synuclein pathology underlies the loss of WM integrity in DLB, amyloid‐independent tau pathology may also be an important influence on white matter integrity within the DLB spectrum.

Predictable shifts in diversity and ecosystem function in phytoplankton and zooplankton communities along thermocline stratification intensity continua

Thermocline stratification is a global threat to water quality in drinking water reservoirs, though its underlying mechanisms are not clear. The impacts of thermocline stratification intensity on biodiversity-ecosystem relationships were assessed using phytoplankton and zooplankton indicators from four stages of stratification in Lake Qiandaohu. There were significant differences in biomass, species diversity, and resource use efficiency (RUEpp = phytoplankton biomass/total phosphorus) for phytoplankton between continuous stratification and mixing periods, but only in FDis and RaoQ diversity indices for zooplankton. Phytoplankton species diversity and RUE were higher in the formative and stable periods, while zooplankton species diversity and zooplankton biomass/phytoplankton biomass (RUEzp) were lower. When combining the data from the four periods, a negative linear pattern was found between phytoplankton Simpson's, functional dispersion (FDis), and Rao's Quadratic (RaoQ) diversity indices, and thermocline depth (TD). Only zooplankton FDis and RaoQ diversity indices were significantly positively related to TD. Phytoplankton RUE was significantly negatively related only to its Pielou's evenness (J) diversity, while zooplankton RUE was significantly negatively related to its J, FDis, and RaoQ diversity indices. The results of structural equation models (SEMs) showed that the R2 of RUE for phytoplankton was much higher than that for zooplankton. Thermocline stratification intensity exerted an indirect positive effect on phytoplankton RUE by affecting species diversity but had a negative effect on zooplankton RUE. These findings underscore the negative influence of thermocline stratification resulting in various biodiversity changes in freshwater ecosystems.

Pteridophytes Diversity and Distribution Along The Elevational Gradient of Mount Penanggungan's Hiking Trail, East Java, Indonesia

Pteridophytes (ferns) are a fundamental element of tropical rainforests, which provide excellent microhabitats for their development. In addition, the sensitivity of pteridophytes to shifts in microclimate and anthropogenic disturbances makes them excellent environmental bioindicators. The purpose of this study was to determine the diversity and distribution of pteridophytes along the elevational gradient of two well-known hiking trails of Mount Penanggungan, East Java, Indonesia. Using a 10x10 m2 plot and transect line, we examined the composition, species diversity using Shannon-Wiener diversity index (H'), relative abundance, and distribution pattern using Morisita index of dispersion (Id) of ferns along an elevational gradient (700–1500 m above sea level) on the hiking trails of Mount Penanggungan, i.e., Tamiajeng and Kunjorowesi. As many as 14 species from 7 families living in both terrestrial and arboreal types were identified. Species composition along the elevation gradient revealed a pattern of predominating species. The Shannon-Wiener diversity index (H') indicated a moderate level of diversity, where many pteridophytes species are found on the altitude gradient between (700-900 m dpl), and the Morisita index of dispersion (Id) indicated a clustered distribution pattern for most of the species. This pattern of diversity and distribution can be explained by changes in biotic and abiotic factors.

White matter microstructure is differently associated with executive functioning in youth born with congenital heart disease and youth born preterm.

Executive function deficits and adverse psychological outcomes are common in youth with congenital heart disease (CHD) or born preterm. Association white matter bundles play a critical role in higher order cognitive and emotional functions and alterations to their microstructural organization may result in adverse neuropsychological functioning. This study aimed to examine the relationship of myelination and axon density and orientation alterations within association bundles with executive functioning, psychosocial well-being, and resilience in youth with CHD or born preterm. Youth aged 16 to 26 years born with complex CHD or preterm at ≤33 weeks of gestational age and healthy controls completed a brain MRI and self-report assessments of executive functioning, psychosocial well-being, and resilience. Multicomponent driven equilibrium single-pulse observation of T1 and T2 and neurite orientation dispersion and density imaging were used to calculate average myelin water fraction (MWF), neurite density index (NDI), and orientation dispersion index values for eight bilateral association bundles. The relationships of bundle-average metrics with neuropsychological outcomes were explored with linear regression and mediation analyses. In the CHD group, lower MWF in several bundles was associated with poorer working memory and behavioral self-monitoring and mediated self-monitoring deficits relative to controls. In the preterm group, lower NDI in several bundles was associated with poorer emotional control and lower MWF in the left superior longitudinal fasciculus III mediated planning/organizing deficits relative to controls. No significant relationships were observed for psychosocial well-being or resilience. The findings of this study suggest that microstructural alterations to association bundles, including lower myelination and axon density, have different relationships with executive functioning in youth with CHD and youth born preterm. Future studies should aim to characterize other neurobiological, social, and environmental influences that may interact with white matter microstructure and neuropsychological functioning in these at-risk individuals.

Oxidative stress and energy metabolic response of Isochrysis galbana induced by different types of pristine and aging microplastics and their leachates

The aging process and leachate composition of different types of MPs (PS, PS-NH2, PS-COOH and PMMA) with a particle size of 1.0 μm were characterized, and marine microalgae Isochrysis galbana OA3011(I. galbana) was used as test organism to investigate the 96 h toxic effects of MPs before and after aging as well as leachate exposure. Except for polymethyl methacrylate (PMMA), all other tested microplastics showed significant aggregation in seawater, which increased with the presence of surface amino and carboxyl groups, in addition, the increase in polymer dispersibility index (PDI) values after aging reflected more severe aggregation. Fourier transform infrared spectrometer (FTIR) showed that the surface amino groups were shed during the aging of PS-NH2, which can likewise be demonstrated by the change in surface electric potential from positive to negative before and after aging. PMMA, due to the addition of plasticizers (HEHP and DIBP detected in high concentration) and its own structure, has stronger resistance to aging than the other three microplastics, and no significant aging phenomenon occurs. As for I. galbana, growth inhibition, oxidative stress and energy metabolism were tested after exposure to different microplastics and their leachate. It was found that high concentrations of A-PS had a greater negative impact on I. galbana, while the toxic effects of PS-NH2 and PS-COOH on I. galbana behaved in a diametrically opposite way before and after aging compared to PS with the inhibitory effect decreasing after aging, which was caused by the shedding of surface groups. As for PMMA, the differences in the toxic effects on microalgae before and after aging were not significant. The inhibitory effect of low concentrations of PAEs (Phthalate acid esters) in the leachate of PS-COOH on I. galbana was not significant, and the stronger inhibitory effect of 4 d L-PS-NH2 was presumed to be the shedding of positively charged groups.

ZERO-INFLATED POISSON TRANSMUTED WEIGHTED EXPONENTIAL DISTRIBUTION: PROPERTIES AND APPLICATIONS

Count observations with high frequencies of zero counts abound in diverse fields. In actuary science, for example, insurance claims are often underreported, leading to a higher frequency of zero counts. This invariably reduces the mean and leads to over-dispersion. Different techniques to model such occurrences exist. This study uses the cubic rank transmutation map to compound the weighted exponential distribution and obtain a new count distribution in the mixed Poisson paradigm. The zero-inflated form of the proposition is obtained along with some mathematical properties. Simulated skewness, kurtosis, and dispersion index for the new distributions reveal they are suitable for model dispersed observation with positive skewness. Five datasets with high frequencies of zero counts are used to assess the performance of the new distribution along with some popular count distributions by using the maximum likelihood for parameter estimation. Results show that the natural form of the new proposition performs creditably better than its zero-inflated forms, even when there is a higher proportion of zero counts. The classical negative binomial distribution is also observed to outperform its zero-inflated form in most cases. In contrast, the zero-inflated Poisson distribution better fits the datasets than the classical Poisson distribution.

Development of Linagliptin Ultra Fine Solid Supersaturated Bio-SNEDDS Using Triangular Mixture Design for Enhancement of Oral Bioavailability: Impact of P-gp Inhibition

Linagliptin (LIN) is a newly developed dipeptidyl peptidase 4 (DPP-4) inhibitor oral antidiabetic drug. LIN is considered a P-gp substrate, thus suffers from poor bioavailability (< 30%). The aim of this study was to develop and characterize LIN bioactive self-nanoemulsifying drug delivery system to circumvent its poor bioavailability and enhance its therapeutic efficacy.
 Methodology: In this study, we developed solid supersaturated bioactive self-nanoemulsifying drug delivery system (Ss-bio-SNEDDS) of LIN, using clove oil as an oil phase, cremophor CO 40 as a surfactant, labrasol as a co-surfactant and Hydroxy-propyl-B-cyclodextrin (HPBCD) as a precipitation inhibitor (PI); all components are of established P-gp inhibition activity. Optimization was performed by means of triangular mixture design based on particle size, poly dispersity index (PDI) and percent transmittance. The two optimized formulations (F4 and F8) were designated and evaluated for stability and cloud point. Also, the effect of pH on particle size and PDI was assessed. Additionally, examination of particles’ surface morphology of the two optimized formulations was performed by transmission electron microscope (TEM). The prepared liquid supersaturated-SNEDDS (s-SNEDDS) were converted into solid supersaturated-SNEDDS (Ss-SNEDDS) via adsorption on microcrystalline cellulose (MCC). Further evaluations were carried out, including in vitro drug release, in vitro precipitation and in vivo studies.
 Results: The optimized formulations F4 and F8 manifested promising characteristics concerning particle size (< 50 nm), PDI (< 0.3) and percent transmittance (> 99%). Stability study showed no phase separation or precipitation with rapid emulsification time. The two optimized formulations showed high cloud point temperature (above 70°C). TEM images of F4 and F8 showed spheroid like appearance with relatively smooth surface. Results of the in vivo study in rats revealed a significant increase in AUC of solid-F4, solid-F8 and solid supersaturated-F4 (S-F4, S-F8 and Ss-F4) by 2.32, 2.89 and 2.54 folds, respectively compared to LIN solution; with a noticeable reduction in blood glucose level at each point.
 Conclusion: In a nutshell, Ss-bio-SNEDDS are considered as auspicious nano-carriers for LIN with the virtue of augmented bioavailability and possible dose reduction.

New ex vivo method to objectively assess insulin spatial subcutaneous dispersion through time during pump basal-rate based administration

Glycemic variability remains frequent in patients with type 1 diabetes treated with insulin pumps. Heterogeneous spreads of insulin infused by pump in the subcutaneous (SC) tissue are suspected but were barely studied. We propose a new real-time ex-vivo method built by combining high-precision imaging with simultaneous pressure measurements, to obtain a real-time follow-up of insulin subcutaneous propagation. Human skin explants from post-bariatric surgery are imaged in a micro-computed tomography scanner, with optimised parameters to reach one 3D image every 5 min during 3 h of 1UI/h infusion. Pressure inside the tubing is recorded. A new index of dispersion (IoD) is introduced and computed upon the segmented 3D insulin depot per time-step. Infusions were hypodermal in 58.3% among 24 assays, others being intradermal or extradermal. Several minor bubbles and one occlusion were observed. IoD increases with time for all injections. Inter-assay variability is the smallest for hypodermal infusions. Pressure elevations were observed, synchronised with air bubbles arrivals in the tissue. Results encourage the use of this method to compare infusion parameters such as pump model, basal rate, catheter characteristics, infusion site characteristics or patient phenotype.

Vertical Changes of Organic Carbon Storage, Structural and Hydraulic Properties of a Humid Tropical Soil under Vegetation Cover in Southeast Nigeria

Changes in organic carbon storage (OCS), structural and hydraulic properties with depth of soil are important phenomena that need to be understood per soil for effective soil management in crop production. A study was conducted in a Randomized Complete Block Design (RCBD) to assess the vertical changes in OCS, structural and hydraulic properties of soil under vegetation cover. The study involved 5 levels of sampling depth replicated nine (9) times to give forty five (45) observational units. The nine points for sampling were randomly selected and the five sampling depths were 0 – 20, 20 – 40, 40 – 60, 60 – 80 and 80 – 100 cm. Auger and core soil samples were collected at the designated depths. The samples were processed and analysed in the laboratory. The results of data analyses showed that depths varied significantly (P≤0.05) in the parameters measured. The highest OCS of 38.28 ton / ha was obtained at the 0 – 20 cm depth and the lowest (10.38 ton / ha) was obtained at 80 – 100 cm depth. The highest mean weight diameter of 1.00 mm and lowest of 0.72 mm were obtained at 0 – 20 and 80 – 100 cm depths, respectively. The lowest clay dispersion index of 25.43 % and the highest clay flocculation index of 74.53 % were obtained at 80 – 100 cm depth. Clay content and bulk density (BD) increased with depth and, the highest clay content of 212.4 g / kg and highest BD of 1.65 mg / m3 were obtained at the 80 – 100 cm depth. Saturated hydraulic conductivity (Ksat), total porosity (Pt) and macroporosity (Pm) decreased with depth. The highest Ksat of 3.11 cm / hr, Pt of 47.41 % and Pm of 24.13 % were obtained at 0 – 20 cm depth. The water retention characteristics increased with depth. The highest field capacity of 24.46 %, permanent wilting point of 11.16 % and available water capacity of 13.32 % were obtained at 80 – 100 cm depth. There were consistent changes in the soil properties across the depths. The reduced drainage at the higher depths should be considered in cultivating deep rooted crops which are sensitive to poor drainage. The top soils should be managed with good agronomic practices and minimum tillage to avert damages to the microaggregates.

Functional diversity and spatial association analyses at different spatial scales reveal no changes in community assembly processes along an aridity gradient in the Atacama Desert

The structuring of plant assemblages along environmental gradients is typically explained by shifts from competition (limiting similarity) to environmental filtering as the environment becomes more stressful. However, facilitation, weaker-competitor exclusion, environmental heterogeneity, and the colonization-competition tradeoff can also structure plant assemblages along gradients. These assembly processes act on different plant traits and organs, and their prevalence varies with respect to the spatial scale. Using patterns of functional diversity, coupled with patterns of species association at two spatial scales, here we discern the assembly processes that structure shrub communities in four localities along an aridity gradient of the Atacama Desert. At each site, we calculated functional dispersion indexes for above- and below-ground traits, and patterns of species association at a patch and neighborhood scale. Our results revealed that at the patch scale in intermediate levels of aridity, the dominant assembly process was within-site environmental heterogeneity. At the neighborhood scale, communities are assembled mainly through random processes. Nonetheless, in some communities, the dominant assembly process was competition via limiting similarity or exclusion of the weaker competitor, and these did not change along the gradient. Together, these results reveal that environmental heterogeneity and competition are the main drivers of plant community assembly in a hyper-arid environment.

Study the Effect of Formulation Variables on Preparation of Nisoldipine Loaded Nano Bilosomes

Nisoldipine (NSD) is a dihydropyridine class of calcium channel blockers used for hypertension treatment, it belongs to class II BCS (low solubility with high permeability), its absolute bioavailability is only 5% due to presystemic metabolism in the gut wall. It is also a substrate for a CYP3A and P-gp.
 Bilosomes are lipid bilayer vesicles incorporating bile salts in their walls to prevent degredation by GIT bile salts.
 The aim of this study is to prepare nisoldipine bilosomes as vesicular carrier and assess the effect of different formulation variables such as type of surfactant, amount of cholesterol, surfactant and sonication time on particle size, entrapment efficiency and poly dispersity index of the prepared bilosomes.
 The prepared bilosomes were prepared by thin film hydration method and they were optimized using different types of non-ionic surfactants span20, 40 and 60 along with different amount of cholesterol and different sonication time.
 The prepared formulas have particle size between 138.3 -392.4 nm, polydispersity index 0.12- 0.4 and entrapment efficiency equal to 48-82%.
 Results showed that increasing cholesterol amount lead to increase entrapment with increase particle size further increase leads to decrease entrapment with further increase in particle size. While increase amount of surfactant (span 60) give higher entrapment of drug with decrease particle size. Span 60 give the best entrapment efficiency and increasing sonication time is associated with decrease in particle size and entrapment efficiency.

EVALUATION OF SOYBEAN FLOURS OBTAINED FROM WHOLE AND SHELLED GRAINS SUBJECTED TO HEAT TREATMENT

This study aimed to obtain and characterize soy flours from whole (WG) and shelled grains (SG) of the conventional cultivar Vmax and special cultivars used for human consumption, BRS 267 and BRS 257. For lipoxygenase enzyme inactivation, the WGs and SGs of BRS 267 and Vmax were bleached at 98 °C for 5 min, roasted at 150 °C for 30 min, milled and finally sieved through a size 40 mesh to obtain the flours. These flours were analyzed for proteins, lipids, isoflavones, Kunitz trypsin inhibitor, their nitrogen solubility index and their protein dispersibility index. The grain heat treatments caused a reduction in protein solubility, an increase in aglycone isoflavones and an 80% reduction in levels of the Kunitz trypsin inhibitor. Flours from bleached WGs were brown in color. Flours from BRS 267 had higher protein levels, while those from the cultivar Vmax had the highest lipid content. Flours from BRS 257 had greater protein solubility. Thus, varieties of special soybeans, genetically enhanced for human consumption, can be processed for better quality soy foods, promoting their acceptance.

Molecular epidemiology of sisal bole rot disease suggests a potential phytosanitary crisis in Brazilian production areas

Sisal bole rot disease is the major phytosanitary problem of Agave plantations in Brazil. The disease is caused by a cryptic species of Aspergillus: A. welwitschiae. To date, the only way to diagnose the disease was to observe external symptoms, visible only when the plant is already compromised, or through the isolation and sequencing of the pathogen, which requires cutting the entire plant for bole tissue sampling. We developed a new primer set based on a unique gene region of A. welwitschiae, which can detect the phytopathogenic strains through PCR directly from sisal leaves. Using the new marker to study the main sisal-producing areas in Brazil, we discovered a troublesome situation. The main producing areas of this crop had a pathogen incidence of 78%–88%. The dispersion index indicates a regular spatial pattern for disease distribution, suggesting that the use of contaminated suckers to establish new fields may be the main disease-spreading mechanism. Altogether, the high incidence of the pathogen, the unavailability of clean plants, the unpredictability of disease progression, and the low investment capacity of farmers reveal the vulnerability of this sector to a potential phytosanitary crisis. By correlating the disease symptomatology with soil nutritional traits, we suggest that higher potassium availability might decrease visual symptoms, while phosphorus may have the opposite effect. Also, we observe a potential cultivar effect, suggesting that common sisal may be more susceptible than hybrid cultivars (especially H400). This new molecular tool is a significant advance for understanding the disease, enabling the implementation of a monitoring program and studies that may lead to pathogen control strategies and changes in the Brazilian production model.

2 Choline as a neurodevelopmental intervention for children with fetal alcohol spectrum disorder: Long-term associations with white matter microstructure and executive function

Objective:Fetal alcohol spectrum disorder (FASD) is a life-long condition, and few interventions have been developed to improve the neurodevelopmental course in this population. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial. In this study, we examine treatment group differences in executive function (EF) outcomes and diffusion MRI of the corpus callosum using the Neurite Orientation Dispersion and Density Index (NODDI) biophysical model.Participants and Methods:The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5- to 5-year-olds with FASD. Participants in this long-term follow-up study included 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up evaluation included measures of executive functioning (WISC-V Picture Span and Digit Span; DKEFS subtests) and diffusion MRI (NODDI).Results:Children who received choline early in development outperformed those in the placebo group across a majority of EF tasks at long-term follow-up (effect sizes ranged from -0.09 to 1.27). Children in the choline group demonstrated significantly better performance on several tasks of lower-order executive function skills (i.e., DKEFS Color Naming [Cohen's d = 1.27], DKEFS Word Reading [Cohen's d = 1.13]) and showed potentially better white matter microstructure organization (as indicated by lower orientation dispersion; Cohen's d = -1.26) in the splenium of the corpus callosum compared to the placebo group. In addition, when collapsing across treatment groups, higher white matter microstructural organization was associated with better performance on several EF tasks (WISC-V Digit Span; DKEFS Number Sequencing and DKEFS Word Reading).Conclusions:These findings highlight long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that changes in white matter organization may represent an important target of choline in this population. Unique to this study is the use of contemporary biophysical modeling of diffusion MRI data in youth with FASD. Findings suggest this neuroimaging approach may be particularly useful for identifying subtle white matter differences in FASD as well as neurobiological responses to early intervention associated with important cognitive functions.

Correlation between Landscape Pattern and Net Primary Productivity of Vegetation: A Case Study in the Arid and Semi-Arid Regions of Northwest China

Human activities and environmental changes have influenced the changes in landscape patterns, which in turn profoundly impact the variation in net primary productivity (NPP) of vegetation. Understanding the relationship between landscape patterns and NPP is of significant importance for maintaining ecosystem stability and improving the ecological environment. In this study, six land use types in the arid and semi-arid regions of Northwest China were selected, and five landscape pattern indices at the landscape level and four landscape pattern indices at the class level were used. Pearson correlation and multiple linear regression models were employed to analyze the relationship between landscape indices and NPP at a 100 km × 100 km grid scale. The results indicate that there are varying degrees of correlation between landscape pattern indices and NPP from 2001 to 2020, with different levels of variation over the 20-year period. The correlation between indices and NPP is higher at the class level than at the landscape level, and the increase in landscape abundance and fragmentation promotes an increase in NPP. At the landscape level, three landscape indices, namely NP (Number of Patches), PR (Patch Richness), and SHDI (Shannon’s Diversity Index), explain 45.4% of the variation in NPP. At the class level, NP, TE (Total Edge Length), and IJI (Dispersion and Juxtaposition Index) are the main influencing factors for NPP in cropland, forestland, and grassland. Therefore, in ecological governance, it is necessary to consider landscape pattern changes appropriately to maintain ecosystem stability.

Nitazoxanide and quercetin co-loaded nanotransfersomal gel for topical treatment of cutaneous leishmaniasis with macrophage targeting and enhanced anti-leishmanial effect

PurposeAnti-leishmanial medications administered by oral and parenteral routes are less effective for treatment of cutaneous leishmaniasis (CL) and cause toxicity, hence targeted drug delivery is an efficient way to improve drug availability for CL with reduced toxicity. This study aimed to develop, characterize and evaluate nitazoxanide and quercetin co-loaded nanotransfersomal gel (NTZ-QUR-NTG) for the treatment of CL. MethodsNTZ-QUR-NT were prepared by thin film hydration method and were statistically optimized using Box-Behnken design. To ease the topical delivery and enhance the retention time, the NTZ-QUR-NT were dispersed in 2 % chitosan gel. Moreover, in-vitro drug release, ex-vivo permeation, macrophage uptake, cytotoxicity and anti-leishmanial assays were performed. ResultsThe optimized formulation indicated mean particle size 210 nm, poly dispersity index (PDI) 0.16, zeta potential (ZP) −15.1 mV and entrapment efficiency (EE) of NTZ and QUR was 88 % and 85 %, respectively. NTZ-QUR-NT and NTZ-QUR-NTG showed sustained release of the incorporated drugs as compared to the drug dispersions. Skin permeation of NTZ and QUR in NTZ-QUR-NTG was 4 times higher in comparison to the plain gels. The NTZ-QUR-NT cell internalization was almost 10-folds higher than NTZ-QUR dispersion. The cytotoxicity potential (CC50) of NTZ-QUR-NT (71.95 ± 3.32 μg/mL) was reduced as compared to NTZ-QUR dispersion (49.77 ± 2.15 μg/mL. A synergistic interaction was found between NTZ and QUR. Moreover, in-vitro anti-leishmanial assay presented a lower IC50 value of NTZ-QUR-NT as compared to NTZ-QUR dispersion. Additionally, a significantly reduced lesion size was observed in NTZ-QUR-NTG treated BALB/c mice, indicating its antileishmanial potential. ConclusionIt can be concluded that nanotransfersomal gel has the capability to retain and permeate the incorporated drugs through stratum corneum and induce synergetic anti-leishmanial effect of NTZ and QUR against cutaneous leishmaniasis.