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A pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a "nano‐in‐micro drug delivery system". The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer. [ABSTRACT FROM AUTHOR]

Shape optimization with respect to eigenvalues of a cavity plays an important role in the design of new resonators or in the optimization of existing ones. This paper proposes a gradient‐based optimization scheme, which is enhanced with closed‐form shape derivatives of the system matrices. Based on these, accurate derivatives of eigenvalues, eigenmodes, and the cost function can be computed with respect to the geometry, which significantly reduces the computational effort of the optimizer. The work is demonstrated by applying it to the 9‐cell TESLA cavity, for which the design parameters of the computational model are considered as optimization variables to match the design criteria for devices in realistic use cases. Since eigenvalues may cross during the shape optimization of a cavity, a new algorithm based on an eigenvalue matching procedure is proposed, to ensure the optimization of the desired mode in order to also enable successful matching along large shape variations. [ABSTRACT FROM AUTHOR]

The proper functioning of neural circuits that integrate sensory signals is essential for individual adaptation to an ever-changing environment. Many molecules can modulate neuronal activity, including neurotransmitters, receptors, and even amino acids. Here, we ask whether amino acid transporters expressed by neurons can influence neuronal activity. We found that minidiscs (mnd), which encodes a light chain of a heterodimeric amino acid transporter, is expressed in different cell types of the adult Drosophila brain: in mushroom body neurons (MBs) and in glial cells. Using live calcium imaging, we found that MND expressed in α/β MB neurons is essential for sensitivity to the L-amino acids: Leu, Ile, Asp, Glu, Lys, Thr, and Arg. We found that the Target Of Rapamycin (TOR) pathway but not the Glutamate Dehydrogenase (GDH) pathway is involved in the Leucine-dependent response of α/β MB neurons. This study strongly supports the key role of MND in regulating MB activity in response to amino acids. [ABSTRACT FROM AUTHOR]

Background: There has been rapid growth of chiropractors pursuing career opportunities in both public and private hospitals and other integrated care settings. Chiropractors that prosper in integrated care settings deliver patient-centered care, focus on the institutional mission, understand and adhere to organizational rules, and are proficient in navigating complex systems. The Council on Chiropractic Education Accreditation Standards do not outline specific meta-competencies for integrated care clinical training. Objective: The purpose of this study was to develop preliminary integrated health care competencies for DC programs to guide the advancement of clinical chiropractic education. Methods: A systematic literature search was performed. Articles were screened for eligibility and extracted in duplicate. Domains and seed statements were generated from this literature, piloted at a conference workshop, and evaluated via a modified Delphi consensus process. Of 42 invited, 36 chiropractors participated as panelists. Public comment period yielded 20 comments, none resulting in substantive changes to the competencies. Results: Of 1718 citations, 23 articles met eligibility criteria. After 2 modified Delphi rounds, consensus was reached on all competency statements. A total of 78 competency statements were agreed upon, which encompassed 4 domains and 11 subdomains. The 4 domains were: 1) Collaboration, (2) Clinical Excellence, (3) Communication, and (4) Systems Administration. Conclusion: We identified 78 preliminary competencies appropriate for preparing DC students and early career chiropractors for clinical practice in integrated healthcare settings. Educational programs may consider these competencies for curricular design and reform to strengthen DC program graduates for integrated practice, advanced training, and employment. [ABSTRACT FROM AUTHOR]

During development, neurons achieve a stereotyped neuron typespecific morphology, which relies on dynamic support by microtubules (MTs). An important player is the augmin complex (hereafter augmin), which binds to existing MT filaments and recruits the γ-tubulin ring complex (γ-TuRC), to form branched MTs. In cultured neurons, augmin is important for neurite formation. However, little is known about the role of augmin during neurite formation in vivo. Here, we have revisited the role of mammalian augmin in culture and then turned towards the class four Drosophila dendritic arborization (c4da) neurons. We show that MT density is maintained through augmin in cooperation with the γ-TuRC in vivo. Mutant c4da neurons show a reduction of newly emerging higher-order dendritic branches and in turn also a reduced number of their characteristic space-filling higher-order branchlets. Taken together, our data reveal a cooperative function for augmin with the γ-TuRC in forming enough MTs needed for the appropriate differentiation of morphologically complex dendrites in vivo. [ABSTRACT FROM AUTHOR]

Objective: Multidrug-resistant organisms (MDRO), especially carbapenemresistant organisms (CRO), represent a threat for newborns. This study investigates the colonization prevalence of these pathogens in a newborn unit at a Kenyan tertiary hospital in an integrated approach combining routine microbiology, whole genome sequencing (WGS) and hospital surveillance data. Methods: The study was performed in the Kenyatta National Hospital (KNH) in 2019 over a four-month period and included 300 mother-baby pairs. A total of 1,097 swabs from newborns (weekly), mothers (once) and the hospital environment were taken. Routine clinical microbiology methods were applied for surveillance. Of the 288 detected MDRO, 160 isolates were analyzed for antimicrobial resistance genes and phylogenetic relatedness using whole genome sequencing (WGS) and bioinformatic analysis. Results: In maternal vaginal swabs, MDRO detection rate was 15% (n=45/300), including 2% CRO (n=7/300). At admission, MDRO detection rate for neonates was 16% (n=48/300), including 3% CRO (n=8/300) with a threefold increase for MDRO (44%, n=97/218) and a fivefold increase for CRO (14%, n=29/218) until discharge. Among CRO, K. pneumoniae harboring blaNDM-1 (n=20) or blaNDM-5 (n=16) were most frequent. WGS analysis revealed 20 phylogenetically related transmission clusters (including five CRO clusters). In environmental samples, the MDRO detection rate was 11% (n=18/164), including 2% CRO (n=3/164). Conclusion: Our study provides a snapshot of MDRO and CRO in a Kenyan NBU. Rather than a large outbreak scenario, data indicate several independent transmission events. The CRO rate among newborns attributed to the spread of NDM-type carbapenemases is worrisome. [ABSTRACT FROM AUTHOR]