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Pharmacy (Basel, Switzerland) May 2024This study delves into the challenges of pharmaceutical forecasting within the Ethiopian public pharmaceutical supply chain, which is vital for ensuring medicine...
This study delves into the challenges of pharmaceutical forecasting within the Ethiopian public pharmaceutical supply chain, which is vital for ensuring medicine availability and optimizing healthcare delivery. t It aims to identify and analyze key hindrances to pharmaceutical forecasting in Ethiopia, employing qualitative analysis through semi-structured interviews with stakeholders. Thematic analysis using NVIVO 14 software reveals challenges including finance-related constraints, workforce shortages, and data quality issues. Financial challenges arise from funding uncertainties, causing delayed procurement and stockouts. Workforce shortages hinder accurate forecasting, while data quality issues result from incomplete and untimely reporting. Recommendations include prioritizing healthcare financing, investing in workforce development, and improving data quality through technological advancements and enhanced coordination among stakeholders.
PubMed: 38921962
DOI: 10.3390/pharmacy12030086 -
Biomimetics (Basel, Switzerland) May 2024Variable camber wing technology stands out as the most promising morphing technology currently available in green aviation. Despite the ongoing advancements in smart...
Variable camber wing technology stands out as the most promising morphing technology currently available in green aviation. Despite the ongoing advancements in smart materials and compliant structures, they still fall short in terms of driving force, power, and speed, rendering mechanical structures based on kinematics the preferred choice for large long-range civilian aircraft. In line with this principle, this paper introduces a linkage-based variable camber trailing edge design approach. Covering coordinated design, internal skeleton design, flexible skin design, and drive structure design, the method leverages a two-dimensional supercritical airfoil to craft a seamless, continuous two-dimensional wing full-size variable camber trailing edge structure, boasting a 2.7 m span and 4.3 m chord. Given the significant changes in aerodynamic load direction, ground tests under cruise load utilize a tracking-loading system based on tape and lever. Results indicate that the designed single-degree-of-freedom Watt I mechanism and Stephenson III drive mechanism adeptly accommodate the slender trailing edge of the supercritical airfoil. Under a maximum cruise vertical aerodynamic load of 17,072 N, the structure meets strength requirements when deflected to 5°. The research in this paper can provide some insights into the engineering design of variable camber wings.
PubMed: 38921192
DOI: 10.3390/biomimetics9060312 -
Patient Preference and Adherence 2024There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence... (Review)
Review
BACKGROUND
There is no consistent framework for patient-centric drug product design, despite the common understanding that drug product acceptability and preferences influence adherence and, therefore, drug product effectiveness. The aim of this review was to assess current understanding of patient acceptability and preferences for solid oral dosage form (SODF) drug product attributes, and the potential impact of these attributes on patient behaviors and outcomes.
PATIENTS AND METHODS
A scoping review was conducted. Embase, Ovid MEDLINE, and PubMed were searched for full-text articles published between January 2013 and May 2023. Following screening and assessment against predefined inclusion criteria, data were analyzed thematically.
RESULTS
Nineteen studies were included. Four overarching domains of drug product attributes were identified and summarized in a framework: appearance, swallowability, palatability, and handling. Each domain was informed by specific drug product attributes: texture, form, size, shape, color, marking, taste, mouthfeel, and smell. The most frequently studied domains were swallowability and appearance, while the most studied attributes were size, shape, and texture. Smell, marking, and mouthfeel were the least studied attributes. Texture intersected all domains, while form, shape, and size intersected appearance, swallowability, and handling. Swallowability and size appeared to be the key domain and attribute, respectively, to consider when designing drug products. Few studies explored the impact of drug product attributes on behaviors and outcomes.
CONCLUSION
While existing studies of drug product attributes have focused on appearance and swallowability, this review highlighted the importance of two less well-understood domains-palatability and handling-in understanding patients' acceptability and preferences for SODF drug products. The framework provides a tool to facilitate patient-centric design of drug products, organizing and categorizing physical drug product attributes into four overarching domains (appearance, swallowability, palatability, and handling), encouraging researchers to comprehensively assess the impact of drug product attributes on patient acceptability, preferences, and outcomes.
PubMed: 38919378
DOI: 10.2147/PPA.S443213 -
Journal of Medicinal Chemistry Jun 2024Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K),...
Structure-activity relationship studies of 2,8-disubstituted-1,5-naphthyridines, previously reported as potent inhibitors of () phosphatidylinositol-4-kinase β (PI4K), identified 1,5-naphthyridines with basic groups at 8-position, which retained PI4K inhibitory activity but switched primary mode of action to the host hemoglobin degradation pathway through inhibition of hemozoin formation. These compounds showed minimal off-target inhibitory activity against the human phosphoinositide kinases and MINK1 and MAP4K kinases, which were associated with the teratogenicity and testicular toxicity observed in rats for the PI4K inhibitor clinical candidate MMV390048. A representative compound from the series retained activity against field isolates and lab-raised drug-resistant strains of . It was efficacious in the humanized NSG mouse malaria infection model at a single oral dose of 32 mg/kg. This compound was nonteratogenic in the zebrafish embryo model of teratogenicity and has a low predicted human dose, indicating that this series has the potential to deliver a preclinical candidate for malaria.
PubMed: 38918002
DOI: 10.1021/acs.jmedchem.4c01154 -
Langmuir : the ACS Journal of Surfaces... Jun 2024The lipids located in the outermost layer of the skin, the stratum corneum (SC), play a crucial role in maintaining the skin barrier function. The primary components of...
The lipids located in the outermost layer of the skin, the stratum corneum (SC), play a crucial role in maintaining the skin barrier function. The primary components of the SC lipid matrix are ceramides (CERs), cholesterol (CHOL), and free fatty acids (FFAs). They form two crystalline lamellar phases: the long periodicity phase (LPP) and the short periodicity phase (SPP). In inflammatory skin conditions like atopic dermatitis and psoriasis, there are changes in the SC CER composition, such as an increased concentration of a sphingosine-based CER (CER NS) and a reduced concentration of a phytosphingosine-based CER (CER NP). In the present study, a lipid model was created exclusively forming the SPP, to examine whether alterations in the CER NS:CER NP molar ratio would affect the lipid organization. Experimental data were combined with molecular dynamics simulations of lipid models containing CER NS:CER NP at ratios of 1:2 (mimicking a healthy SC ratio) and 2:1 (observed in inflammatory skin diseases), mixed with CHOL and lignoceric acid as the FFA. The experimental findings show that the acyl chains of CER NS and CER NP and the FFA are in close proximity within the SPP unit cell, indicating that CER NS and CER NP adopt a linear conformation, similarly as observed for the LPP. Both the experiments and simulations indicate that the lamellar organization is the same for the two CER NS:CER NP ratios while the SPP NS:NP 1:2 model had a slightly denser hydrogen bonding network than the SPP NS:NP 2:1 model. The simulations show that this might be attributed to intermolecular hydrogen bonding with the additional hydroxide group on the headgroup of CER NP compared with CER NS.
PubMed: 38917358
DOI: 10.1021/acs.langmuir.4c00554 -
The Journal of Physical Chemistry. A Jun 2024Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated)...
Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated) have been measured. A pulsed, rotationally cold molecular beam ( = 35 kJ mol) of OH was scattered from refreshed liquid surfaces in a vacuum. Spatially and temporally resolved OH number densities were measured by pulsed, planar laser-induced fluorescence. Results are compared with those for the inert liquid perfluoropolyether. The clearly asymmetric distributions for 45° incidence add to the weight of evidence for predominantly impulsive scattering from all three liquids. However, we propose that significant differences in their shapes may be diagnostic of contrasting reaction mechanisms. Direct, near-specular trajectories survive preferentially on squalene, consistent with an addition mechanism removing those at more backward angles. This trend is reversed for squalane, as expected for direct abstraction. The results reinforce the need to consider the effects of composition-dependent contributions from different reaction mechanisms in the modeling of OH-aging of atmospheric aerosol particles.
PubMed: 38915192
DOI: 10.1021/acs.jpca.4c02917 -
Diabetes, Metabolic Syndrome and... 2024Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal... (Clinical Trial)
Clinical Trial
New Diabetic Treatment by Alleviation of Autonomic Nervous System Dysfunction Measured as Periosteal Pressure Sensitivity at Sternum Improves Empowerment, Treatment Satisfaction, and Self-Reported Health of People with Type 2 Diabetes: A Randomized Trial.
PURPOSE
Autonomic nervous system dysfunction (ANSD), for which presently no treatment exists, has a negative impact on prognosis in people with type 2 diabetes (T2D). Periosteal pressure sensitivity (PPS) on sternum may be a measure of autonomic nervous system dysfunction (ANSD). We tested if a non-pharmacological PPS-feedback-guided treatment program based on non-noxious sensory nerve stimulation, known to reduce PPS, changed empowerment, treatment satisfaction, and quality of life in people with T2D, compared to usual treatment.
PATIENTS AND METHODS
Analysis of secondary endpoints in a single center, two-armed, parallel-group, observer-blinded, randomized controlled trial of individuals with T2D. Participants were randomized to non-pharmacological intervention as an add-on to treatment as usual. Endpoints were evaluated by five validated questionnaires: Diabetes specific Empowerment (DES-SF), Diabetes Treatment Satisfaction (DTSQ), quality of life (QOL) (WHO-5), clinical stress signs (CSS), and self-reported health (SF-36). Sample size calculation was based on the primary endpoint HbA1c.
RESULTS
We included 144 participants, 71 allocated to active intervention and 73 to the control group. Active intervention compared to control revealed improved diabetes-specific empowerment (p = 0.004), DTSQ (p = 0.001), and SF-36 self-reported health (p=0.003) and tended to improve quality of life (WHO-5) (p = 0.056). The findings were clinically relevant with a Cohen's effect size of 0.5 to 0.7.
CONCLUSION
This non-pharmacological intervention, aiming to reduce PPS, and thus ANSD, improved diabetes-specific empowerment, treatment satisfaction, and self-reported health when compared to usual treatment. The proposed intervention may be a supplement to conventional treatment for T2D.
PubMed: 38910915
DOI: 10.2147/DMSO.S455216 -
Journal of Clinical and Experimental... Jun 2024Semantic verbal fluency (SVF) is a widely used measure of frontal executive function and access to semantic memory. SVF scoring metrics include the number of unique... (Review)
Review
INTRODUCTION
Semantic verbal fluency (SVF) is a widely used measure of frontal executive function and access to semantic memory. SVF scoring metrics include the number of unique words generated, perseverations, intrusions, semantic cluster size and switching between clusters, and scores vary depending on the language the test is administered in. In this paper, we review the existing normative data for Turkish, the main metrics used for scoring SVF data in Turkish, and the most frequently used categories.
METHOD
We conducted a systematic review of peer-reviewed papers using Medline, EMBASE, PsycInfo, Web of Science, and two Turkish databases, TR-Dizin and Yok-Tez. Included papers contained data on the SVF performance of healthy adult native speakers of Turkish, and reported the categories used. Versions of the SVF that required participants to alternate categories were excluded. We extracted and tabulated demographics, descriptions of groups, metrics used, categories used, and sources of normative data. Studies were assessed for level of detail in reporting findings.
RESULTS
1400 studies were retrieved. After deduplication, abstract, full text screening, and merging of theses with their published versions, 121 studies were included. 114 studies used the semantic category "animal", followed by first names ( = 14, 12%). All studies reported word count. More complex measures were rare (perseverations: = 12, 10%, clustering and switching: = 5, 4%). Four of seven normative studies reported only word count, two also measured perseverations, and one reported category violations and perseverations. Two normative studies were published in English.
CONCLUSIONS
There is a lack of normative Turkish SVF data with more complex metrics, such as clustering and switching, and a lack of normative data published in English. Given the size of the Turkish diaspora, normative SVF data should include monolingual and bilingual speakers. Limitations include a restriction to key English and Turkish databases.
PubMed: 38904178
DOI: 10.1080/13803395.2024.2331827 -
ACS Applied Polymer Materials Jun 2024Four-dimensional printing with embedded photoluminescence is emerging as an exciting area in additive manufacturing. Slim polymer films patterned with three-dimensional...
Four-dimensional printing with embedded photoluminescence is emerging as an exciting area in additive manufacturing. Slim polymer films patterned with three-dimensional lattices of multimode cylindrical waveguides (waveguide-encoded lattices, WELs) with enhanced fields of view can be fabricated by localizing light as self-trapped beams within a photopolymerizable formulation. Luminescent WELs have potential applications as solar cell coatings and smart planar optical components. However, as luminophore-photoinitiator interactions are expected to change the photopolymerization kinetics, the design of robust luminescent photopolymer sols is nontrivial. Here, we use model photopolymer systems based on methacrylate-siloxane and epoxide homopolymers and their blends to investigate the influence of the luminophore Lumogen Violet () on the photolysis kinetics of the Omnirad 784 photoinitiator through UV-vis absorbance spectroscopy. Initial rate analysis with different bulk polymers reveals differences in the pseudo-first-order rate constants in the absence and presence of , with a notable increase (∼40%) in the photolysis rate for the 1:1 blend. Fluorescence quenching studies, coupled with density functional theory calculations, establish that these differences arise due to electron transfer from the photoexcited to the ground-state photoinitiator molecules. We also demonstrate an in situ UV-vis absorbance technique that enables real-time monitoring of both waveguide formation and photoinitiator consumption during the fabrication of WELs. The in situ photolysis kinetics confirm that -photoinitiator interactions also influence the photopolymerization process during WEL formation. Our findings show that luminophores play a noninnocent role in photopolymerization and highlight the necessity for both careful consideration of the photopolymer formulation and a real-time monitoring approach to enable the fabrication of high-quality micropatterned luminescent polymeric films.
PubMed: 38903400
DOI: 10.1021/acsapm.4c00484 -
ACS Synthetic Biology Jun 2024
Topics: Synthetic Biology
PubMed: 38903005
DOI: 10.1021/acssynbio.4c00292