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Fungal keratitis (FK), a severe eye infection that leads to vision impairment and blindness, poses a high risk to contact lens users, and Candida albicans remains the most common underpinning fungal pathogen in temperate climates. Patients are initially treated empirically (econazole 1% drops hourly for 24–48 h), and if there is no response, amphotericin B (AmB) 0.15% eye drops (extemporaneously manufactured to be stable for a week) are the gold-standard treatment. Here, we aim to develop a sustained-release AmB ocular film to treat FK with an enhanced corneal retention time. As there is a paucity of reliable in vitro models to evaluate ocular drug release and antifungal efficacy under flow, we developed a 3D-printed microfluidic device based on four chambers stacked in parallel, in which lenses previously inoculated with a C. albicans suspension were placed. Under the flow of a physiological fluid over 24 h, the release from the AmB-loaded film that was placed dry onto the surface of the wetted contact lenses was quantified, and their antifungal activity was assessed. AmB sodium deoxycholate micelle (dimeric form) was mixed with sodium alginate and hyaluronic acid (3:1 w/w) and cast into films (0.48 or 2.4%), which showed sustained release over 24 h and resulted in a 1.23-fold reduction and a 5.7-fold reduction in CFU/mL of C. albicans, respectively. This study demonstrates that the sustained delivery of dimeric AmB can be used for the treatment of FK and provides a facile in vitro microfluidic model for the development and testing of ophthalmic antimicrobial therapies. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI's applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI's transformative impact on the pharmaceutical industry and its broader implications for healthcare. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease with only late-stage detection; thus, diagnosis is made when it is no longer possible to treat the disease, only its symptoms. Consequently, this often leads to caregivers who are the patient's relatives, which adversely impacts the workforce along with severely diminishing the quality of life for all involved. It is, therefore, highly desirable to develop a fast, effective and reliable sensor to enable early-stage detection in an attempt to reverse disease progression. This research validates the detection of amyloid-beta 42 (Aβ42) using a Silicon Carbide (SiC) electrode, a fact that is unprecedented in the literature. Aβ42 is considered a reliable biomarker for AD detection, as reported in previous studies. To validate the detection with a SiC-based electrochemical sensor, a gold (Au) electrode-based electrochemical sensor was used as a control. The same cleaning, functionalization and Aβ1–28 antibody immobilization steps were used on both electrodes. Sensor validation was carried out by means of Cyclic Voltammetry (CV) and Electrochemical Impedance Spectroscopy (EIS) aiming to detect an 0.5 µg·mL−1 Aβ42 concentration in 0.1 M buffer solution as a proof of concept. A repeatable peak directly related to the presence of Aβ42 was observed, indicating that a fast SiC-based electrochemical sensor was constructed and may prove to be a useful approach for the early detection of AD. [ABSTRACT FROM AUTHOR]

3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice. [ABSTRACT FROM AUTHOR]

There is a trend towards the formalization of the rehabilitation process for older rehabilitants in a Challenging Rehabilitation Environment (CRE). This concept involves the comprehensive organization of care, support, and environment on rehabilitation wards. So far, literature on the principles of the CRE is scarce. This study aims to explore the perspectives regarding the CRE of healthcare professionals through a qualitative study. Therefore, between 2018 and 2020, six international and 69 Dutch professionals were interviewed in focus groups, and 180 professionals attended workshops on two Dutch congresses. Data were thematically analyzed using ATLAS.ti. Seven themes emerged regarding the rehabilitation processes: (1) rehabilitant (attention for cognitive functioning and resilience); (2) goals (setting personal goals); (3) exercise (increasing exercise intensity); (4) daily schedule (following the daily rhythm); (5) involving the client system (involving informal caregivers); (6) nutrition (influences rehabilitation capability); and (7) technology (makes rehabilitation more safe and challenging). Regarding organizational aspects, four main themes were identified: (1) environmental aspects (encourages exercises); (2) staff aspects (interdisciplinary team); (3) organizational aspects (implementing CRE requires a shared vision); and (4) factors outside the ward (a well-prepared discharge process). To offer effective rehabilitation, all elements of the CRE should be applied. To improve the CRE, specific interventions need to be developed and implemented. Consequently, the effectiveness and efficiency of the CRE need to be measured with validated tools. [ABSTRACT FROM AUTHOR]

Urban air mobility is a rapidly growing field of research. While drones or unmanned aerial vehicles have been operated mainly in the private and military sector in the past, an increasing range of opportunities is opening up for commercial applications. A new multitude of passenger-carrying drone or air taxi concepts promises to fulfill the dream of flying above congested urban areas. While early research has been focusing on vehicle development, solutions for urban air traffic management are lagging behind. This paper collects and reviews the main findings of past urban-air-mobility-related research projects at the German Aerospace Center (DLR) to serve as a basis for ongoing research from an air traffic management perspective. [ABSTRACT FROM AUTHOR]

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), along with the World Health Organization (WHO), has provided a set of guidelines (ICH Q1A-E, Q3A-B, Q5C, Q6A-B) intended to unify the standards for the European Union, Japan, and the United States to facilitate the mutual acceptance of stability data that are sufficient for registration by the regulatory authorities in these jurisdictions. Overall, ICH stability studies involve a drug substance tested under storage conditions and assess its thermal stability and sensitivity to moisture. The long-term testing should be performed over a minimum of 12 months at 25 °C ± 2 °C/60% RH ± 5% RH or at 30 °C ± 2 °C/65% RH ± 5% RH. The intermediate and accelerated testing should cover a minimum of 6 months at 30 °C ± 2 °C/65% RH ± 5% RH (which is not necessary if this condition was utilized as a long-term one) and 40 °C ± 2 °C/75% RH ± 5% RH, respectively. Hence, the ICH stability testing for industrially fabricated medicines is rigorous and tedious and involves a long period of time to obtain preclinical stability data. For this reason, Accelerated Predictive Stability (APS) studies, carried out over a 3–4-week period and combining extreme temperatures and RH conditions (40–90 °C)/10–90% RH, have emerged as novel approaches to predict the long-term stability of pharmaceutical products in a more efficient and less time-consuming manner. In this work, the conventional ICH stability studies versus the APS approach will be reviewed, highlighting the advantages and disadvantages of both strategies. Furthermore, a comparison of the stability requirements for the commercialization of industrially fabricated medicines versus extemporaneous compounding formulations will be discussed. [ABSTRACT FROM AUTHOR]

Impression materials are used to record and reproduce the exact morphology of the patient's oral cavity. The dimensional stability of a material is its ability to maintain the accuracy of recording the details of the oral cavity for a longer period of time, including the time during imprinting and immediately after. The aim of this study was to evaluate the accuracy of three different impression materials commonly used in the dental practice with the aid of an extra-oral three-dimensional (3D) scanner using an in vitro analysis. A typodont tooth model of the maxillary dental arch and mandibular dental arch, containing 16 permanent teeth, was used for evaluation. With the aid of three different impression materials, this model was imprinted fifteen times, resulting in fifteen different plaster models. A capsule extra-oral scanner device was used to digitalize the models and the same device was later used to align, compare, and measure scanned model surfaces. After performing the Kruskal–Wallis test for each measurement category (model), only two out of the fifteen measurements showed statistically significant differences between the material groups: vestibular-oral and mesial-distal width. Post hoc analysis showed that the alginate model (mean range = 29.13) had significantly higher bias scores than the addition silicone model (mean range = 16.75) (z = 2.501, p = 0.037). The difference between the average values of the model bias made from condensation-based silicone and addition-based silicone was initially significant, but after applying the Bonferroni correction for further comparisons, this relationship did not remain significant (z = 2.197, p = 0.084). Addition-based silicone models had the highest accuracy in terms of fidelity, followed by condensation-based silicones, and then by alginate models. Silicone-based impression materials improved over time, being highly used in all areas of dentistry. Alginate impressions had the lowest pattern of accuracy among those studied. [ABSTRACT FROM AUTHOR]