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80, 95% CI (5.79, 20.17)), giving birth at home (AOR = 2.77, 95% CI (1.41, 5.46)), not knowing risks associated with pre-lacteal feeding (AOR = 3.25, 95% CI (1.72, 6.15)) and perceiving pre-lacteal feeding as beneficial (AOR = 9.56, 95% CI (4.45, 20.52)) were factors significantly associated with practice pre-lacteal feeding practices. Conclusion. Significant proportions of mothers were practicing pre-lacteal feeding in the study area. Late initiation of breastfeeding, home delivery, not knowing risks of prelacteal feeding, and perceiving pre-lacteal feeding as beneficial were contributing factors for practicing of pre-lacteal feeding. Therefore, promoting institutional delivery and timely initiation of breastfeeding would reduce prelacteal feeding in Kersa district.As smart technology use is growing in residential environments, research on how such technologies can provide opportunities for safely and actively aging in place by integrating physical activity into daily routines and reducing sedentariness is scarce. This study investigated older adults' intentions to use and attitudes toward currently available smart home technologies that could contribute to safe and active lives in and around home. The focus was on four representative technologies smart lighting, smart door locks, smart fire prevention devices, and smart home systems/home automation. This paper presents the results of a sequential mixed-methods study comprised of online and in-person surveys (n = 129), and a focus group of community-dwelling older adults, aged 50+ (n = 15). Ordinal regression analyses indicated that perceived usefulness consistently predicts older adults' attitudes and willingness to use smart home products. While smart fire prevention devices were viewed most favorably due to their potential safety benefits, perceived affordability significantly influenced older adults' intentions to use them in their homes. The focus group findings underscore technology skepticism, privacy concerns and return on investment as significant determinants of attitudes toward the smart design products. The study has implications of designers and manufacturers by providing insights on how to prioritize smart home technology integrations to homes.Family carers increasingly take on the responsibility of self-management of dementia as the condition progresses. However, research on this topic is scarce. This scoping review aimed to identify the key characteristics related to self-management of dementia by carers including its components, theoretical/conceptual frameworks that underpinned these components and measurements. A scoping review was conducted in 8 databases and 16 publications met the inclusion criteria. Twenty-two components were identified and grouped into two categories activities and carer characteristics and skills. The identified theoretical/conceptual frameworks were numerous and varied as were the measures. There was a little consistency of the key characteristics of self-management of dementia by carers. The findings assist carers and healthcare providers to understand the components involved in self-managing dementia which will guide the development and delivery of self-management support interventions for carers. Further research is required to validate these findings and to develop specialized conceptual frameworks and measures.Objective To examine the association between multidimensional sleep health and objective measures of physical functioning in older adults. Method We conducted a secondary analysis of 158 adults ≥65 years who participated in Midlife in the United States (MIDUS) 2 and MIDUS Refresher studies. Physical functioning was assessed using gait speed during a 50-foot timed walk, lower extremity strength via chair stand test, and grip strength via hand-held dynamometers. Composite multidimensional sleep health scores were derived from 1 week of sleep diaries and wrist actigraphy. Results Multiple linear regression was used to examine the associations between multidimensional sleep health and physical functioning measures. In adjusted regression analyses, multidimensional sleep health was significantly positively associated with gait speed but not lower extremity strength or grip strength. Discussion These findings suggest multidimensional sleep health may contribute to physical functioning in older adults. Longitudinal examinations are needed to determine the value of multidimensional sleep health as a therapeutic target to optimize physical functioning.We develop tunable optical filters with dual-frequency nematic liquid crystal optical retarders to enable fast switching between the passed wavelengths. The filters are composed of a series of two liquid crystal optical retarders. We select the specific thicknesses of the liquid crystal retarders and use individual biasing schemes to continuously tune the wavelength and bandwidth of the filter. This enables fine-tuned filter switching speeds of filter operation in the ms regime. We present theoretical predictions and experimental results for the electro-optical filter characterization as well as an example application for our filter in total internal reflection fluorescence microscopy. We find that our filter switching speeds can be as short as a few ms, an order of magnitude improvement over typical mechanical filter wheel switching speeds. The quality of our fluorescence images is similar to those obtained by conventional filters.Manufacturing of recombinant adeno-associated virus (rAAV) viral vectors remains challenging, with low yields and low fullempty capsid ratios in the harvest. To elucidate the dynamics of recombinant viral production, we develop a mechanistic model for the synthesis of rAAV viral vectors by triple plasmid transfection based on the underlying biological processes derived from wild-type AAV. The model covers major steps starting from exogenous DNA delivery to the reaction cascade that forms viral proteins and DNA, which subsequently result in filled capsids, and the complex functions of the Rep protein as a regulator of the packaging plasmid gene expression and a catalyst for viral DNA packaging. We estimate kinetic parameters using dynamic data from literature and in-house triple transient transfection experiments. Model predictions of productivity changes as a result of the varied input plasmid ratio are benchmarked against transfection data from the literature. Sensitivity analysis suggests that (1) the poorly coordinated timeline of capsid synthesis and viral DNA replication results in a low ratio of full virions in harvest, and (2) repressive function of the Rep protein could be impeding capsid production at a later phase. The analyses from the mathematical model provide testable hypotheses for evaluation and reveal potential process bottlenecks that can be investigated.Acute myeloid leukemia (AML) patients with minimal residual disease and receiving allogeneic hematopoietic stem cell transplantation (HCT) have poor survival. Adoptive administration of dendritic cells (DCs) presenting the Wilms tumor protein 1 (WT1) leukemia-associated antigen can potentially stimulate de novo T and B cell development to harness the graft-versus-leukemia (GvL) effect after HCT. We established a simple and fast genetic modification of monocytes for simultaneous lentiviral expression of a truncated WT1 antigen (tWT1), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon (IFN)-α, promoting their self-differentiation into potent "induced DCs" (iDCtWT1). A tricistronic integrase-defective lentiviral vector produced under good manufacturing practice (GMP)-like conditions was validated. Transduction of CD14+ monocytes isolated from peripheral blood, cord blood, and leukapheresis material effectively induced their self-differentiation. CD34+ cell-transplanted Nod.Rag.Gamma (NRG)- and Nod.Scid.Gamma (NSG) mice expressing human leukocyte antigen (HLA)-A∗0201 (NSG-A2)-immunodeficient mice were immunized with autologous iDCtWT1. Both humanized mouse models showed improved development and maturation of human T and B cells in the absence of adverse effects. Toward clinical use, manufacturing of iDCtWT1 was up scaled and streamlined using the automated CliniMACS Prodigy system. Proof-of-concept clinical-scale runs were feasible, and the 38-h process enabled standardized production and high recovery of a cryopreserved cell product with the expected identity characteristics. These results advocate for clinical trials testing iDCtWT1 to boost GvL and eradicate leukemia.Recent successes in clinical gene therapy applications have intensified the interest in using adeno-associated viruses (AAVs) as vectors for gene delivery into human liver. An inherent intriguing characteristic of AAVs is that vector variants vary substantially in their ability to transduce hepatocytes from different species. This has historically limited the value of preclinical studies using rodent models for predicting the efficiency of AAV vectors in liver-targeted gene therapy clinical studies. In this work, we aimed to investigate the key determinants of the observed differential interspecies transduction abilities among AAV variants. We took advantage of domain swapping strategies between AAV-KP1, a newly identified variant with enhanced murine liver tropism, and AAV3b, which functions poorly in mice. The systematic in vivo comparison of AAV3b/AAV-KP1 chimeric variants allowed us to identify a threonine insertion at position 265 within variable region I (VR-I) as the key residue that confers murine hepatic transduction to human-derived clade B (AAV2-like) and clade C (AAV3b-like) variants. We propose to use this insertion to generate phylogenetically related AAV surrogates in support of toxicology and dosing studies in the murine liver model.Precise clustered regularly interspaced short palindromic repeats (CRISPR)-mediated genetic and epigenetic manipulation of the immune response has become a promising immunotherapeutic approach toward combating tumorigenesis and tumor progression. CRISPR-based immunologic reprograming in cancer therapy comprises the locus-specific enhancement of host immunity, the improvement of tumor immunogenicity, and the suppression of tumor immunoevasion. To date, the ex vivo re-engineering of immune cells directed to inhibit the expression of immune checkpoints or to express synthetic immune receptors (chimeric antigen receptor therapy) has shown success in some settings, such as in the treatment of melanoma, lymphoma, liver, and lung cancer. However, advancements in nuclease-deactivated CRISPR-associated nuclease-9 (dCas9)-mediated transcriptional activation or repression and Cas13-directed gene suppression present novel avenues for the development of tumor immunotherapies. In this review, the basis for development, mechanism of action, and outcomes from recently published Cas9-based clinical trial (genetic editing) and dCas9/Cas13-based pre-clinical (epigenetic editing) data are discussed. Lastly, we review cancer immunotherapy-specific considerations and barriers surrounding use of these approaches in the clinic.Analytical band centrifugation (ABC) was first developed for the separation of macromolecules in centrifugation cells ~60 years ago. Since its development, ABC has been predominantly utilized to study macromolecular interactions or chemical reactions between two solutions in situ upon mixing. In this current study, we evaluated ABC separations on modern analytical ultracentrifugation (AUC) instruments for therapeutic adeno-associated viruses (AAVs). ABC provided sufficient separation between the genome-containing full AAV particle and the empty AAV capsid, which need to be controlled during the manufacturing process. Because ABC produces a physical separation, no complex algorithm or sophisticated software is needed to process the experimental raw data. selleck screening library ABC profiles, dubbed "centrifugrams", can be analyzed with a similar approach as typically used for electrophoretic separations to produce relative percent area. Sedimentation coefficients (s) of analytes can also be determined from ABC. The relative area percent and s value obtained in ABC experiments were shown to be consistent with those determined by conventional sedimentation velocity AUC (SV-AUC).
Read More: https://www.selleckchem.com/Proteasome.html
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