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Georgette D Kanmogne1, Sangya Singh1, Upal Roy1, Xinming Liu1, JoEllyn McMillan1, Santhi Gorantla1, Shantanu Balkundi1, Nathan Smith1, Yazen Alnouti2, Nagsen Gautam2, You Zhou3, Larisa Poluektova1, Alexander Kabanov2, Tatiana Bronich2, Howard E Gendelman11Departments of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, 2Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE; 3Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USAAbstract: Despite the successes of antiretroviral therapy (ART), HIV-associated neurocognitive disorders remain prevalent in infected people. This is due, in part, to incomplete ART penetration across the blood–brain barrier (BBB) and lymph nodes and to the establishment of viral sanctuaries within the central nervous system. In efforts to improve ART delivery, our laboratories developed a macrophage-carriage system for nanoformulated crystalline ART (nanoART) (atazanavir, ritonavir, indinavir, and efavirenz). We demonstrate that nanoART transfer from mononuclear phagocytes (MP) to human brain microvascular endothelial cells (HBMEC) can be realized through cell-to-cell contacts, which can facilitate drug passage across the BBB. Coculturing of donor MP containing nanoART with recipient HBMEC facilitates intercellular particle transfer. NanoART uptake was observed in up to 52% of HBMEC with limited cytotoxicity. Folate coating of nanoART increased MP to HBMEC particle transfer by up to 77%. To translate the cell assays into relevant animal models of disease, ritonavir and atazanavir nanoformulations were injected into HIV-1-infected NOD/scid-γcnull mice reconstituted with human peripheral blood lymphocytes. Atazanavir and ritonavir levels in brains of mice treated with folate-coated nanoART were three- to four-fold higher than in mice treated with noncoated particles. This was associated with decreased viral load in the spleen and brain, and diminished brain CD11b-associated glial activation. We postulate that monocyte-macrophage transfer of nanoART to brain endothelial cells could facilitate drug entry into the brain.Keywords: nanoART, folate, monocyte-endothelial cell interactions, blood–brain barrier, antiretroviral therapy, nanomedicine

A theoretical model was developed for the amorphous transition in molecular beam epitaxial Si(111) grown below a certain temperature, based on the formation of stacking fault like defects as a precursor to the amorphous transition. The model was simulated based on a stochastic model technique and the results were contrasted to that of experiments for temperatures in the range of 500-900 K and growth rate in the range of 0.1-0.3 angstrom/sec. Empirical and theoretical results were in excellent agreement.

Epitaxial Cu2O films grown by reactive and ceramic radio frequency magnetron sputtering on single crystalline ZnO (0001) substrates are investigated. The films are grown on both O- and Zn-polar surface of the ZnO substrates. The Cu2O films exhibit a columnar growth manner apart from a ~5nm thick CuO interfacial layer. In comparison to the reactively sputtered Cu2O, the ceramic-sputtered films are less strained and appear to contain nanovoids. Irrespective of polarity, the Cu2O grown by reactive sputtering is observed to have (111)Cu2O∣∣(0001)ZnO epitaxial relationship, but in the case of ceramic sputtering the films are found to show additional (110)Cu2O reflections when grown on O-polar surface. The observed CuO interfacial layer can be detrimental for the performance of Cu2O/ ZnO heterojunction solar cells reported in the literature. [ABSTRACT FROM AUTHOR]

For the characterization of light materials using transmission electron microscopy, a low electron acceleration voltage of 80 kV or even 60 kV is attractive due to reduced beam damage to the specimen. The concomitant reduction in resolving power of the microscope can be restored when using spherical aberration ( Cs) correctors, which for the most part are only available in the latest and most expensive microscopes. Here, we show that upgrading of existing TEMs is an attractive and cost-effective alternative. We report on the low-voltage performance on graphitic material of a JEOL JEM-2010F built in the early 1990s and retro-fitted with a conventional imaging Cs corrector and a probe Cs corrector. The performance data show Cs retro-fitted instruments can compete very favourably against more modern state-of-the-art instruments in both conventional imaging (TEM) and scanning (STEM) modes. [ABSTRACT FROM AUTHOR]

Lack of adherence, inaccessibility to viral reservoirs, long-term drug toxicities, and treatment failures are limitations of current antiretroviral therapy (ART). These limitations lead to increased viral loads, medicine resistance, immunocompromise, and comorbid conditions. To this end, we developed long-acting nanoformulated ART (nanoART) through modifications of existing atazanavir, ritonavir, and efavirenz suspensions in order to establish cell and tissue drug depots to achieve sustained antiretroviral responses. NanoART's abilities to affect immune and antiviral responses, before or following human immunodeficiency virus type 1 infection were tested in nonobese severe combined immune-deficient mice reconstituted with human peripheral blood lymphocytes. Weekly subcutaneous injections of drug nanoformulations at doses from 80 mg/kg to 250 mg/kg, 1 day before and/or 1 and 7 days after viral exposure, elicited drug levels that paralleled the human median effective concentration, and with limited toxicities. NanoART treatment attenuated viral replication and preserved CD4(+) Tcell numbers beyond that seen with orally administered native drugs. These investigations bring us one step closer toward using long-acting antiretrovirals in humans. [ABSTRACT FROM AUTHOR]

Abstract: We report the encapsulation of the antiferromagnetic and magnetoelectric oxide Cr2O3 inside both multi - and single-walled carbon nanotubes. This is achieved by a two step post-synthesis filling process which involves the filling of nanotubes with CrO3 either from aqueous solution or from the molten phase, followed by appropriate annealing sequences. TEM imaging confirms significant filling rates for both multi- and single-walled carbon nanotubes. Analytical transmission electron microscopy implies that after secondary annealing Cr2O3 is formed inside the nanotubes. [Copyright &y& Elsevier]

Introduction: India has become the epicentre for diabetes, a stress-related disorder affecting the working skills and day-today lifestyle management of younger population. Most of the studies have reported the effect of yoga on improving Quality of Life (QoL) in diabetic patients with other comorbidities. Till date, no randomized control trial reports are available to show the effect of yoga therapy on QoL and Indian Diabetes Risk Score (IDRS) in normotensive prediabetic and diabetic young individuals. Aim: To determine the effect of 12 weeks of yoga therapy on QoL and IDRS among normotensive prediabetic and diabetic young Indian adults. Materials and Methods: A randomized control trial was conducted in Endocrinology Outpatient Department (OPD). Normotensive participants (n=310) aged 18-45 years were divided into healthy controls (n=62), prediabetics (n=124) and diabetics (n=124). Study group subjects were randomly assigned to Group II (n=62, prediabetes-standard treatment), Group III (n=62, prediabetes-standard treatment + yoga therapy), Group IV (n=62, diabetes-standard treatment) and Group V (n=62, diabetes-standard treatment + yoga therapy). Flanagan QoL scale, IDRS questionnaire, Fasting Plasma Glucose (FPG) and insulin were assessed pre and post 12 weeks of intervention. Statistical analysis was done using Student’s paired t-test and one-way ANOVA. Results: Pre-post intervention analysis showed significant improvement in QoL scale with p

Objective: Yoga is a mind-body modulation technique that has been shown to have beneficial effects on various diseases related to various systems in the body. However, the molecular basis of mechanism of action is not clear. Hence, this study was designed to study the leukocyte telomere biology and its relation with homocysteine and oxidative stress in yoga practitioners. Materials and Methods: This is a prospective case-control study involving Yoga practitioners aged 30–40 y with minimum of two years yoga practice (Yoga group) and age, gender and body mass index matched sedentary healthy general population with no medical problems (Control group). Leukocyte telomere length (LTL) was measured by using quantitative PCR (qPCR), fasting plasma homocysteine was measured by a rapid highperformance liquid chromatography assay and the oxidative stress was assessed with total antioxidant status (TAOS), malondialdehyde (MDA) measured by colorimetry. Results: The LTL was shorter in control group than in yoga group (p

Abstract: A triple yielding phenomenon resulting in high fracture strength (up to 2360±10MPa) and large ductility (up to 13.5±0.5%) during compressive deformation is first discovered and systematically investigated in metastable Cu47.5Zr47.5Al5 composites. Based on electron microscopy and X-ray diffraction studies, the major deformation mechanisms at the different stages of compression are revealed to be: (1) the constraint effect of the amorphous phase; (2) the pre-existence of a small number of microtwins and a small amount of martensitic phases; (3) the initiation and development of martensitic transformation; (4) the interplay between CuZr crystals and shear bands; and (5) the activation of partial detwinning, together with a high density of dislocations. The yield strengths of the composites are modeled as a function of the volume fraction of the constituent phases and a transition from the rule-of-mixtures to a load-bearing model is observed. The underlying ductile nature of the composites is further correlated with the unique electronic structure of the B2 CuZr intermetallics. The present results provide an understanding of the deformation mechanism of metastable CuZr-based composites and give guidance on how to improve the ductility/toughness of bulk metallic glasses. [Copyright &y& Elsevier]

Integrating light emitters based on III-V materials with silicon-based electronics is crucial for further increase in data transfer rates in communication systems since the indirect bandgap of silicon prevents its direct use as a light source. We investigate here InAs/InGaAlAs quantum dot (QD) structures grown directly on 5° off-cut Si substrate and emitting light at 1.5 μm, compatible with established telecom platform. Using different dislocation defect filtering layers, exploiting strained superlattices, and supplementary QD layers, we mitigate the effects of lattice constant and thermal expansion mismatches between III-V materials and Si during growth. Complementary optical spectroscopy techniques, i.e. photoreflectance and temperature-, time- and polarization-resolved photoluminescence, allow us to determine the optical quality and application potential of the obtained structures by comparing them to a reference sample-state-of-the-art QDs grown on InP. Experimental findings are supported by calculations of excitonic states and optical transitions by combining multiband k • p and configuration-interaction methods. We show that our design of structures prevents the generation of a considerable density of defects, as intended. The emission of Si-based structures appears to be much broader than for the reference dots, due to the creation of different QD populations which might be a disadvantage in particular laser applications, however, could be favorable for others, e.g., in broadly tunable devices, sensors, or optical amplifiers. Eventually, we identify the overall most promising combination of defect filtering layers and discuss its advantages and limitations and prospects for further improvements.

Study Objectives: An estimated 3% of the population has clinically significant restless legs syndrome. Given the limited pharmacological options in the arsenal, there is a need for a therapeutic agent with a better side effect profile., Methods: Twelve treatment naive adults (10 women and 2 men with a median age of 41.5 [32-48.5] years) with primary restless legs syndrome were recruited in our open-label pilot study; magnesium citrate 200 mg was administered daily for 8 weeks. Serum magnesium levels, International Restless Legs Syndrome Study Group Rating Scale, Kohnen quality of life scale, and multiple suggested immobilization tests (three 1-hour tests) were performed before and after supplementation. Paired t tests and Wilcoxon signed-rank tests were used for data analysis. Pearson and Spearman's analyses assessed the association between magnesium levels and restless legs syndrome variables., Results: Participants had a significant reduction in International Restless Legs Syndrome Study Group Rating Scale scores (6.67 [2.33-11] P = .006) and improved Kohnen quality of life scores (8.5 [2.09-14], P = .014) without notable differences in serum magnesium levels ( P = .3). The median periodic limb movements during wakefulness index (30.40 [5.20, 122.40] to 8.63 [0.32, 17.47] P = .043) and self-reported discomfort score (19 [14, 30.5] to 6 [0, 8] P = .0010) of all 3 multiple suggested immobilization test trials also demonstrated improvement. Serum magnesium levels negatively correlated with multiple suggested immobilization test self-reported scores and the periodic limb movements during wakefulness indices., Conclusions: Despite the limitations of open-label design, our study's positive results indicate the need for a placebo-controlled trial with a larger sample size., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: The Effect of Magnesium Citrate Supplementation in Restless Legs Syndrome (RLS); URL: https://clinicaltrials.gov/ct2/show/study/NCT04462796; Identifier: NCT04462796., Citation: Gorantla S, Ravisankar A, Trotti LM. Magnesium citrate monotherapy improves restless legs syndrome symptoms and multiple suggested immobilization test scores in an open-label pilot study. J Clin Sleep Med . 2024;20(8):1357-1361., (© 2024 American Academy of Sleep Medicine.)