Effects of cannabinoid receptor activation on Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells in vitro.

PURPOSE: Periodontitis is an inflammatory disease that results in the loss of periodontal tissue. The endocannabinoid system has anti-inflammatory properties and displays considerable potential for tissue regeneration. In this study, we aimed to explore whether the activation of this system can alleviate or reverse the inflammatory phenotype of human periodontal ligament stem cells (hPDLSCs) induced by exposure to the inflammagen lipopolysaccharide (LPS). METHODS: We investigated the effects of activating specific cannabinoid receptors (CB1 and CB2) on the inflammatory phenotype of LPS-stimulated hPDLSCs. The exogenous ligands WIN55,212-2 and JWH-133 were employed to target the cannabinoid receptors. We conducted a thorough assessment of cell proliferation, metabolic activity, and adipogenic, osteogenic, and chondrogenic differentiation potential. Additionally, we measured cytokine release using enzyme-linked immunosorbent assays. RESULTS: Exposure to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) caused an increase in cell proliferation while decreasing metabolic activity. While this exposure did not influence adipogenic or chondrogenic differentiation, it did result in reduced osteogenesis. Additionally, LPS induced the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein 1. Immunolabeling revealed the presence of CB1 and CB2 on the cellular membrane, with these receptors playing distinct roles in hPDLSCs. The CB1 agonist WIN55,212-2 was found to increase metabolic activity and promote adipogenic differentiation, whereas the CB2 agonist JWH-133 promoted cell proliferation and osteogenic differentiation. When hPDLSCs were co-exposed to Pg-LPS and CB ligands, JWH-133 slightly ameliorated the inhibition of osteogenic differentiation and suppressed the release of inflammatory cytokines. CONCLUSIONS: This study clarifies the effects of specific CB receptor activation on hPDLCs and the inflammatory phenotype. Stimulation of the endocannabinoid system through the manipulation of endogenous or the application of exogenous cannabinoids in vivo may represent a potent therapeutic option for combating periodontal inflammatory disorders.

Artificial Intelligence-Powered Hand Surgery Consultation: GPT-4 as an Assistant in a Hand Surgery Outpatient Clinic.

PURPOSE: Exploring the integration of artificial intelligence in clinical settings, this study examined the feasibility of using Generative Pretrained Transformer 4 (GPT-4), a large language model, as a consultation assistant in a hand surgery outpatient clinic. METHODS: The study involved 10 simulated patient scenarios with common hand conditions, where GPT-4, enhanced through specific prompt engineering techniques, conducted medical history interviews, and assisted in diagnostic processes. A panel of expert hand surgeons, each board-certified in hand surgery, evaluated GPT-4's responses using a Likert Scale across five criteria with scores ranging from 1 (lowest) to 5 (highest). RESULTS: Generative Pretrained Transformer 4 achieved an average score of 4.6, reflecting good performance in documenting a medical history, as evaluated by the hand surgeons. CONCLUSIONS: These findings suggest that GPT-4 can effectively document medical histories to meet the standards of hand surgeons in a simulated environment. The findings indicate potential for future application in patient care, but the actual performance of GPT-4 in real clinical settings remains to be investigated. CLINICAL RELEVANCE: This study provides a preliminary indication that GPT-4 could be a useful consultation assistant in a hand surgery outpatient clinic, but further research is required to explore its reliability and practicality in actual practice.

Integrating AI in Lipedema Management: Assessing the Efficacy of GPT-4 as a Consultation Assistant.

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI's Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4's responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4's responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

Can AI Think Like a Plastic Surgeon? Evaluating GPT-4's Clinical Judgment in Reconstructive Procedures of the Upper Extremity.

This study delves into the potential application of OpenAI's Generative Pretrained Transformer 4 (GPT-4) in plastic surgery, with a particular focus on procedures involving the hand and arm. GPT-4, a cutting-edge artificial intelligence (AI) model known for its advanced chat interface, was tested on nine surgical scenarios of varying complexity. To optimize the performance of GPT-4, prompt engineering techniques were used to guide the model's responses and improve the relevance and accuracy of its output. A panel of expert plastic surgeons evaluated the responses using a Likert scale to assess the model's performance, based on five distinct criteria. Each criterion was scored on a scale of 1 to 5, with 5 representing the highest possible score. GPT-4 demonstrated a high level of performance, achieving an average score of 4.34 across all cases, consistent across different complexities. The study highlights the ability of GPT-4 to understand and respond to complicated surgical scenarios. However, the study also identifies potential areas for improvement. These include refining the prompts used to elicit responses from the model and providing targeted training with specialized, up-to-date sources. This study demonstrates a new approach to exploring large language models and highlights potential future applications of AI. These could improve patient care, refine surgical outcomes, and even change the way we approach complex clinical scenarios in plastic surgery. However, the intrinsic limitations of AI in its current state, together with the potential ethical considerations and the inherent uncertainty of unanticipated issues, serve to reiterate the indispensable role and unparalleled value of human plastic surgeons.

Measures for Preventing Infection in Burn Surgery.

The skin is the largest human organ and an important barrier to protect against the environment. Burns damage the skin and thus destroy this anatomical barrier. This makes initially sterile wounds susceptible to colonization by pathogenic germs. In severely burned patients, immune competence decreases as part of the burn disease. Sepsis and multiple organ failure as a result of infection are the main causes of death in this cohort. Therefore, prevention and recognition of infections as well as surgical treatment and targeted anti-infective therapy are of great importance. In this article, we present up-to-date solutions for the treatment of burn wounds by means of plastic and reconstructive surgery to minimize the risk of infection. We demonstrate the principles of infection defense by the skin barrier. We outline the principles of burns and how to perform an appropriate diagnosis and therapy, from outpatient therapy to intensive care therapy, depending on the severity. We address the typical bacteria responsible for wound infections in severely burned patients and how to prevent and treat them. We also describe the hygiene measures that must be used in a severe burn unit to reduce the risk of complications such as infection and improve patient survival.

Plastic Surgery Reconstruction of Chronic/Non-Healing Wounds.

In western countries, approximately 1 % of individuals are affected by chronic wounds during their lifetime. Due to changing demographics, this incidence will likely increase in the future. Additionally, the high prevalence is accompanied by substantial treatment expenditures. Therefore, it is of global interest to find effective treatment algorithms. In this article, we present up-to-date solutions for treating chronic / difficult to heal and complex wounds by means of plastic and reconstructive surgery. We outline the principles of chronic wounds and how to perform an appropriate diagnosis. Close cooperation and interdisciplinary exchange are important for optimizing treatment. We report the principles of wound debridement and the role of negative pressure wound therapy. Moreover, we discuss the state of the art of defect reconstruction by means of skin grafting, with or without acellular dermal matrices, local tissue transfers and free tissue transfers. In very complex cases, the local macrovascular blood flow is greatly reduced and there are few, if any, recipient vessels for free flap reconstruction. We discuss the role of arteriovenous loops to overcome this problem.

N6-modified cAMP derivatives that activate protein kinase A also act as full agonists of murine HCN2 channels.

cAMP acts as a second messenger in many cellular processes. Three protein types mainly mediate cAMP-induced effects: PKA, exchange protein directly activated by cAMP (Epac), and cyclic nucleotide-modulated channels (cyclic nucleotide-gated or hyperpolarization-activated and cyclic nucleotide-modulated (HCN) channels). Discrimination among these cAMP signaling pathways requires specific targeting of only one protein. Previously, cAMP modifications at position N6 of the adenine ring (PKA) and position 2'-OH of the ribose (Epac) have been used to produce target-selective compounds. However, cyclic nucleotide-modulated ion channels were usually outside of the scope of these previous studies. These channels are widely distributed, so possible channel cross-activation by PKA- or Epac-selective agonists warrants serious consideration. Here we demonstrate the agonistic effects of three PKA-selective cAMP derivatives, N6-phenyladenosine-3',5'-cyclic monophosphate (N6-Phe-cAMP), N6-benzyladenosine-3',5'-cyclic monophosphate (N6-Bn-cAMP), and N6-benzoyl-adenosine-3',5'-cyclic monophosphate (N6-Bnz-cAMP), on murine HCN2 pacemaker channels. Electrophysiological characterization in Xenopus oocytes revealed that these derivatives differ in apparent affinities depending on the modification type but that their efficacy and effects on HCN2 activation kinetics are similar to those of cAMP. Docking experiments suggested a pivotal role of Arg-635 at the entrance of the binding pocket in HCN2, either causing stabilizing cation-π interactions with the aromatic ring in N6-Phe-cAMP or N6-Bn-cAMP or a steric clash with the aromatic ring in N6-Bnz-cAMP. A reduced apparent affinity of N6-Phe-cAMP toward the variants R635A and R635E strengthened that notion. We conclude that some PKA activators also effectively activate HCN2 channels. Hence, when studying PKA-mediated cAMP signaling with cAMP derivatives in a native environment, activation of HCN channels should be considered.