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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.

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.

Background: The working conditions in the South African public service, notably its challenging environment, pose significant threats to the physical health of employees. Calls exist in understanding how this can be addressed. Aim: The study investigated the predictors of physical health, accounting for the role of organisational climate and decent work. Setting: The study was conducted in Bisho in the Eastern Cape province of South Africa. Methods: An instrument was administered through a survey using a sample of 289 respondents. Descriptive and inferential statistics were used to test the hypothesised relationships. Results: No significant direct effect existed to show that the sounder an organisational climate, the better the physical health of employees will be (β = –0.014, t = –0.199, p = 0.843, 95% confidence interval [CI] [–0.153 to 0.125]). However, statistically significant evidence existed to show that the more focus on promoting decent work, the better the physical health of employees will be (β = 0.463, p = 0.001, 95% CI [0.258 to 0.668]). Finally, decent work has a full mediating effect on the relationship between organisational climate and employee physical health (β = 0.105, 95% CI [0.054 to 0.167]). Conclusion: Public service organisations need to pay attention to the role of its climate and decent working conditions in promoting employee physical health. Contribution: Interventions are needed centered on improving decent work and the organisational climate as identified predictors of employee physical health.

This study aimed to validate a food frequency questionnaire for foods high in sodium (FFQ-FHS) in a population aged ≥18 years and to test its reproducibility. This cross-sectional study included 50 individuals (≥18 years) of both sexes. In addition to the FFQ-FHS, four 24-h dietary recalls (24hRs) were conducted and a socioeconomic and lifestyle questionnaire was administered. Two 24-h urinary excretions were collected for sodium analysis, and anthropometry was performed. For validation, the triad method was applied using the validity coefficient (ρ). For reproducibility, the intraclass correlation coefficient (ICC), 95% confidence interval, kappa coefficient, and Bland-Altman plots were used to check for agreement. The Kolmogorov-Smirnov test was used to verify the data distribution. The validity coefficients for daily energy-adjusted sodium intake were high for the 24hR (ρRAI = 0.85) and weak for the FFQ-FHS (FFQAI = 0.26) and biomarker (ρBAI = 0.20). The ICC values were 0.68 for unadjusted sodium and 0.54 for energy-adjusted sodium intake. The weighed Kappa scores were 0.49 (p

There is a trend toward 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 in rehabilitation wards. So far, literature about the principles of CRE is scarce. This study aims to explore the opinions of rehabilitants and informal caregivers regarding CRE, through a qualitative study between 2019 and 2020. Three telephone interviews were conducted with informal caregivers, and also 3 focus groups with 15 rehabilitants and 3 informal caregivers, all with recent experience in rehabilitation. Nine themes emerged regarding the rehabilitation process: (1) rehabilitant (attention for resilience, motivation, cognitive and emotional aspects), (2) rehabilitant centered (goal setting, physical and cognitive functioning and coping), (3) informal caregivers (involving and attention for resilience and relation), (4) communication (aligning the rehabilitation process), (5) exercise (increasing intensity by using task-oriented exercise, patient-regulated exercise, and group training), (6) peer support (learning experiences and recognition), (7) daily schedule (influence on the planning and activities outside therapy), (8) nutrition (energy for rehabilitation), and (9) eHealth (makes rehabilitation more challenging and fun). Regarding organizational processes, 4 themes were identified: (1) environmental aspects (single bedrooms, shared room for activities and therapy options on the ward), (2) staff aspects (small team with an emphatic supportive and motivating attitude), (3) organizational aspects (organized in an efficient way), and (4) return home (the discharge process should be well prepared for instance with home visits). Organizing excellent rehabilitation care requires a thorough understanding of the concept of CRE, as it is a complex and comprehensive concept that concerns the whole rehabilitation process. Its effectiveness and efficiency should be researched in prospective studies.

Background: To address issues related to suboptimal insight in outcomes, fragmentation, and increasing costs, stakeholders are experimenting with value-based payment (VBP) models, aiming to facilitate high-value integrated care. However, insight in how, why and under what circumstances such models can be successful is limited. Drawing upon realist evaluation principles, this study identifies context factors and associated mechanisms influencing the introduction of VBP in stroke care. Methods: Existing knowledge on context-mechanism relations impacting the introduction of VBP programs (in real-world settings) was summarized from literature. These relations were then tested, refined, and expanded based on a case study comprising interviews with representatives from organizations involved in the introduction of a VBP model for integrated stroke care in Rotterdam, the Netherlands. Results: Facilitating factors were pre-existing trust-based relations, shared dissatisfaction with the status quo, regulatory compatibility and simplicity of the payment contract, gradual introduction of down-side risk for providers, and involvement of a trusted third party for data management. Yet to be addressed barriers included friction between short- and long-term goals within and among organizations, unwillingness to forgo professional and organizational autonomy, discontinuity in resources, and limited access to real-time data for improving care delivery processes. Conclusions: Successful payment and delivery system reform require long-term commitment from all stakeholders stretching beyond the mere introduction of new models. Careful consideration of creating the ‘right’ contextual circumstances remains crucially important, which includes willingness among all involved providers to bear shared financial and clinical responsibility for the entire care chain, regardless of where care is provided.

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.

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.

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.

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.

Representation of human conflict is central to theater performance. In our study, we have used self-reported measures of emotional experience and a word recall task, in order to assess the effects of theatrical representations of violence. Forty participants were randomly assigned to the role of performer or spectator, in either a realistic representation of a script or in a version that recollected the same actions of the script in a series of intertwined monologs. The script represented an aggressive interaction between two work colleagues. Our results show both statistically significant differences in the levels of depression and positive emotions reported after enacting the script, as well as differences in the performance on the word recall task containing aggressive related and non-related stimuli. The results point to stronger effects for performing theatrical representations of violent actions, as compared to recollecting or watching such actions. The fact that actors experienced higher positive emotions is in line with the two-pedal model of aggressive behavior. This model suggests that negative emotions toward aggressive behavior might change to positive emotions due to the repetition in performing violent behaviors, as a key for the transition from reactive aggression to appetitive aggression. Other implications for the study of aggression in theatrical representations are discussed.

Introduction: Integrated stroke care in the Netherlands is constantly changing to strive to better care for stroke patients. The aim of this study was to explore if and on what topics integrated stroke care has been improved in the past three years and if stroke services were further developed. Methods: A web based self-assessment instrument, based on the validated Development Model for Integrated Care, was used to collect data. In total 53 coordinators of stroke services completed the questionnaire with 98 elements and four phases of development concerning the organisation of the stroke service. Data were collected in 2012 and 2015. Descriptive-comparative statistics were used to analyse the data. Results: In 2012, stroke services on average had implemented 56 of the 89 elements of integrated care (range 15–88). In 2015 this was increased up to 70 elements on average (range 37–89). In total, stroke services showed development on all clusters of integrated care. In 2015, more stroke services were in further phases of development like in the consolidation and transformation phase and less were in the initiative and design phase. The results show large differences between individual stroke services. Priorities to further develop stroke services changed over the three years of data collection. Conclusions: Based on the assessment instrument, it was shown that stroke services in the Netherlands were further developed in terms of implemented elements of integrated care and their phase of development. This three year comparison showed unique first analyses over time of integrated stroke care in the Netherlands on a large scale. Interesting further questions are to research the outcomes of stroke care in relation to this development, and if benefits on patient level can be assessed.

Dietary non-heme iron contains ferrous [Fe(II)] and ferric [Fe(III)] iron fractions and the latter should hydrolyze, forming Fe(III) oxo-hydroxide particles, on passing from the acidic stomach to less acidic duodenum. Using conditions to mimic the in vivo hydrolytic environment we confirmed the formation of nanodisperse fine ferrihydrite-like particles. Synthetic analogues of these (~ 10 nm hydrodynamic diameter) were readily adherent to the cell membrane of differentiated Caco-2 cells and internalization was visualized using transmission electron microscopy. Moreover, Caco-2 exposure to these nanoparticles led to ferritin formation (i.e., iron utilization) by the cells, which, unlike for soluble forms of iron, was reduced (p=0.02) by inhibition of clathrin-mediated endocytosis. Simulated lysosomal digestion indicated that the nanoparticles are readily dissolved under mildly acidic conditions with the lysosomal ligand, citrate. This was confirmed in cell culture as monensin inhibited Caco-2 utilization of iron from this source in a dose dependent fashion (p

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]

Quality of care is an essential aspect of geriatric rehabilitation. Usually, there are national standards for the quality of care or indicators to measure the quality of care. However, this is not the case for geriatric rehabilitation. Therefore, the aim of this study was to develop structure, process, and outcome indicators to measure the quality of geriatric rehabilitation. To develop quality indicators for geriatric rehabilitation, a literature search was performed to identify indicators for all types of rehabilitation that can also be suitable for geriatric rehabilitation. Thereafter, in the qualitative phase, different stakeholders were inte. Indicators from the literature and indicators developed based on the interviews were merged and processed in a questionnaire. Through this questionnaire, elderly care physicians and managers of geriatric rehabilitation facilities were asked to rate the indicators on relevance and feasibility. Indicators that were considered relevant and feasible by the respondents were included in the final quality indicator set for geriatric rehabilitation. Thirty-six indicators suitable for geriatric rehabilitation were identified from the literature. Additionally, 55 quality indicators were developed based on the interviews. Merging the indicators and omitting duplicates resulted in 69 quality indicators. Analysis of the data from the questionnaires resulted in a final set of 27 quality indicators for geriatric rehabilitation that consists of 17 structure, 8 process, and 2 outcome indicators. This study contributes to the quality of geriatric rehabilitation by providing a first set of quality indicators ready to use in practice. Follow-up research is recommended and may include an assessment of the applicability, reliability, and validity of the developed indicator set. [ABSTRACT FROM AUTHOR]

Abstract Inflammatory dermatologic diseases have long been viewed as a “skin limited” disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms. Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1. The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally “skin limited” inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes.