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Background: The healthcare sector is currently undergoing a significant transformation, driven by an increased utilization of data. In this evolving landscape, surveys are of pivotal importance to the comprehension of patient needs and preferences. Moreover, the digital affinity of patients and physicians within the healthcare system is reforming the manner in which healthcare services are accessed and delivered. The utilization and donation of data are influencing the future of medical research and treatment, while artificial intelligence (AI) is empowering patients and physicians with knowledge and improving healthcare delivery. Methods: In order to evaluate the opinions of patients and physicians regarding the management of personal health data and the functionality of upcoming data management devices in the context of healthcare digitization, we conducted an exploratory study and designed a survey. The survey focused on a number of key areas, including demographics, experience with digitization, data handling, the identification of needs for upcoming digitization, and AI in healthcare. Results: A total of 40 patients and 15 physicians participated in the survey. The results indicate that data security, timesaving/administrative support, and digital communication are aspects that patients associate with patient-friendly digitization. Based on the responses provided by physicians, it might be concluded that future digital platforms should prioritize usability, time efficacy, data security, and interoperability. Conclusions: In terms of expectations for future digital platforms, there is a notable overlap between the needs expressed by patients and those identified by physicians, particularly in relation to usability, time management, data security, and digital communication. This suggests that the requirements of different stakeholders can be combined in a future system, although individual issues may still require attention. [ABSTRACT FROM AUTHOR]

Abstract Background Cathepsin K is a cysteine peptidase known for its importance in osteoclast-mediated bone resorption. Inhibitors of cathepsin K are in clinical trials for treatment of osteoporosis. However, side effects of first generation inhibitors included altered levels of related cathepsins in peripheral organs and in the central nervous system (CNS). Cathepsin K has been recently detected in brain parenchyma and it has been linked to neurobehavioral disorders such as schizophrenia. Thus, the study of the functions that cathepsin K fulfils in the brain becomes highly relevant. Results Cathepsin K messenger RNA was detectable in all brain regions of wild type (WT) mice. At the protein level, cathepsin K was detected by immunofluorescence microscopy in vesicles of neuronal and non-neuronal cells throughout the mouse brain. The hippocampus of WT mice exhibited the highest levels of cathepsin K activity in fluorogenic assays, while the cortex, striatum, and cerebellum revealed significantly lower enzymatic activities. At the molecular level, the proteolytic network of cysteine cathepsins was disrupted in the brain of cathepsin K-deficient (Ctsk-/-) animals. Specifically, cathepsin B and L protein and activity levels were altered, whereas cathepsin D remained largely unaffected. Cystatin C, an endogenous inhibitor of cysteine cathepsins, was elevated in the striatum and hippocampus, pointing to regional differences in the tissue response to Ctsk ablation. Decreased levels of astrocytic glial fibrillary acidic protein, fewer and less ramified profiles of astrocyte processes, differentially altered levels of oligodendrocytic cyclic nucleotide phosphodiesterase, as well as alterations in the patterning of neuronal cell layers were observed in the hippocampus of Ctsk-/- mice. A number of molecular and cellular changes were detected in other brain regions, including the cortex, striatum/mesencephalon, and cerebellum. Moreover, an overall induction of the dopaminergic system was found in Ctsk-/- animals which exhibited reduced anxiety levels as well as short- and long-term memory impairments in behavioral assessments. Conclusion We conclude that deletion of the Ctsk gene can lead to deregulation of related proteases, resulting in a wide range of molecular and cellular changes in the CNS with severe consequences for tissue homeostasis. We propose that cathepsin K activity has an important impact on the development and maintenance of the CNS in mice.

Cysteine cathepsins are endolysosomal cysteine proteases highly expressed in macrophages; however, their individual contributions to the elimination of bacteria and bacteria-induced cytokine production by macrophages are unknown. We assessed the contribution of cysteine cathepsins to macrophage defense pathways against Staphylococcus aureus by using chemical inhibitors and by infecting primary bone marrow-derived macrophages deficient in 1 of 7 major macrophage-expressed endolysosomal cysteine proteases. We show that cysteine cathepsins are involved in the phagocytosis and killing of S. aureus. Cathepsin L was identified as an executor of nonoxidative killing. Moreover, microarray data revealed cysteine cathepsins to be important for the maximal induction of certain proinflammatory genes, such as IL6, in response to S. aureus. Cysteine cathepsin's contribution to IL6 production was dependent on phagocytosis, and cathepsin K was identified to be a critical protease in this process. Analysis of macrophages with impaired trafficking of endolysosomal Toll-like receptors (TLRs) to the acidic compartment revealed that they were not involved in cathepsin-dependent IL6 induction. Because IL6 production was completely dependent on the TLR-adaptor protein myeloid differentiation primary response gene 88 (MyD88), it appears that other TLRs are involved. In summary, lysosomal cysteine proteases are functionally linked to the complex bactericidal and inflammatory activities of macrophages. [ABSTRACT FROM AUTHOR]

Inspired by the relatively simple morphological blueprint provided by batoid fish such as stingrays and skates, we created a biohybrid system that enables an artificial animal—a tissue-engineered ray—to swim and phototactically follow a light cue. By patterning dissociated rat cardiomyocytes on an elastomeric body enclosing a microfabricated gold skeleton, we replicated fish morphology at 1/10 scale and captured basic fin deflection patterns of batoid fish. Optogenetics allows for phototactic guidance, steering, and turning maneuvers. Optical stimulation induced sequential muscle activation via serpentinepatterned muscle circuits, leading to coordinated undulatory swimming. The speed and direction of the ray was controlled by modulating light frequency and by independently eliciting right and left fins, allowing the biohybrid machine to maneuver through an obstacle course [ABSTRACT FROM AUTHOR]

Introduction: Brodalumab, a human monoclonal antibody that selectively inhibits the interleukin (IL)-17 receptor subunit A, has been approved for the treatment of moderate-to-severe plaque psoriasis. The treatment benefit of brodalumab has been clearly demonstrated in multiple clinical studies. However, data on effectiveness for difficult-to-treat body regions, especially in everyday clinical practice, are still limited., Methods: In this exploratory observational clinical study, psoriasis patients suffering from nail and scalp involvement who received brodalumab during routine clinical care were enrolled at 7 centers in Germany. Patients were observed for over 60 weeks. The co-primary endpoints were 75% improvement in Psoriasis Scalp Severity Index (PSSI75) at week 12 and 75% improvement in Nail Psoriasis Severity Index (NAPSI75) at week 24. Secondary endpoints included assessment of general skin and disease outcomes, quality-of-life, and patient satisfaction with treatment., Results: Eighty-seven patients were included. Mean age was 46.8 years, 70.1% patients were male, and mean body mass index was 28.9 kg/m2. The co-primary endpoints were achieved by more than 90% of patients who met criteria for effectiveness analyses (n = 62): 93.6% of patients achieved PSSI75 at week 12 and 90.3% of patients achieved NAPSI75 at week 24. Median body surface area involvement improved from 14% at baseline to 1.5% and 1% at weeks 12 and 24, respectively. Median Dermatology Life Quality Index scores improved from 16 at baseline to 2 and 1 at weeks 12 and 24, respectively. Improvements were maintained in the majority of patients throughout the 60-week study. Brodalumab was well tolerated and patients were highly satisfied with the treatment., Conclusion: Outcomes assessed in this study, including assessments of scalp and nail symptoms, improved following initiation of brodalumab therapy. This study of psoriasis patients in a real-world setting supports the long-term clinical effectiveness of brodalumab on difficult-to-treat body regions., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

The human genome encodes some hundreds of proteases. Many of these are well studied and understood with respect to their biochemistry, molecular mechanisms of proteolytic cleavage, expression patterns, molecular structure, substrate preferences and regulatory mechanisms, including their endogenous inhibitors. Moreover, precise determination of protease localisation within subcellular compartments, peri- and extracellular spaces has been extremely useful in elucidating biological functions of peptidases. This can be achieved by refined methodology as will be demonstrated herein for the cysteine cathepsins. Besides localisation, it is now feasible to study in situ enzymatic activity at the various levels of subcellular compartments, cells, tissues, and even whole organisms including mouse.