Patient Engagement Platforms: How Technology Is Impacting Perioperative Communication and Engagement in Total Hip and Knee Arthroplasty.

Orthopedic clinics are becoming strained with clinical volume outpacing resources and personnel. Patient engagement platforms can help bridge the communication and engagement gaps between patients and their healthcare teams as total hip and knee arthroplasty transitions to the outpatient setting. These platforms provide a digital infrastructure that allows patients to participate in their healthcare journey while alleviating the burdens on clinic staff. Multiple forms of patient engagement platforms exist but typically fall into one of 3 groups: patient portals, mobile health applications, and chatbots. They all play an important role in enhancing postoperative rehabilitation, patient engagement, and patient care overall. This article explores the spectrum of available patient engagement platforms and examines their advantages, limitations, and documented benefits on clinical outcomes.

Diminazene aceturate inhibits the SARS-CoV-2 spike protein-induced inflammation involving leukocyte migration and DNA extracellular traps formation.

AIMS: To investigate the SARS-CoV-2 Spike protein (Spk)-induced inflammatory response and its downmodulation by diminazene aceturate (DIZE). MATERIALS AND METHODS: Through inducing Spk inflammation in murine models, leukocyte migration to the peritoneum, levels of myeloperoxidase (MPO), malondialdehyde (MDA), rolling and adhesion of mesenteric leukocytes, and vascular permeability were investigated. Extracellular DNA traps (DETs) induced by Spk and the production of IL-6 and TNF-α were analyzed using human neutrophils, monocytes, and macrophages. In silico assays assessed the molecular interaction between DIZE and molecules related to leukocyte migration and DETs induction. KEY FINDINGS: Spk triggered acute inflammation, demonstrated by increasing leukocyte migration. Oxidative stress was evidenced by elevated levels of MPO and MDA in the peritoneal liquid. DIZE attenuated cell migration, rolling, and leukocyte adhesion, improved vascular barrier function, mitigated DETs, and reduced the production of Spk-induced pro-inflammatory cytokines. Computational studies supported our findings, showing the molecular interaction of DIZE with targets such as ß2 integrin, PI3K, and PAD2 due to its intermolecular coupling. SIGNIFICANCE: Our results outline a novel role of DIZE as a potential therapeutic agent for mitigating Spk-induced inflammation.

Congenital and Fetal Effects After Mifepristone Exposure and Continuation of Pregnancy: A Systematic Review.

Mifepristone is an anti-progestational drug that is the first component of the standard medical abortion regimen. For women who take mifepristone and then do not take misoprostol, which is the second component of the medical abortion regimen, it is possible that their pregnancy may continue to live birth. Since mifepristone is commonly used for medical abortion up to 9-10 weeks gestation, any adverse or teratogenic effects on the developing embryo/fetus must be considered, given exposure during the critical time of its development and organogenesis. Toxicology and teratology reports have cited studies demonstrating teratogenic effect of mifepristone in some animals. Current clinical guidelines for women exposed to mifepristone in the first trimester of pregnancy state that it is not known to be teratogenic based on limited published evidence from humans. The aim of this narrative systematic review was to investigate embryonic/fetal exposure to mifepristone and any association with congenital or fetal anomalies. This study was conducted by systematic searches of health databases from inception to February 2024. The references of relevant citations were manually searched to retrieve any additional citations not captured in database searching. Congenital anomalies and adverse outcomes were encountered at various doses of mifepristone exposure. A number of the congenital anomalies encountered in this review were explained by circumstances other than exposure to mifepristone. The present systematic review did not find data to support mifepristone being implicated as a teratogen.

Electrical neuromodulation for the treatment of chronic pain: derivation of the intrinsic barriers, outcomes and considerations of the sustainability of implantable spinal cord stimulation therapies.

INTRODUCTION: For over 60 years, spinal cord stimulation has endured as a therapy through innovation and novel developments. Current practice of neuromodulation requires proper patient selection, risk mitigation and use of innovation. However, there are tangible and intangible challenges in physiology, clinical science and within society. AREAS COVERED: We provide a narrative discussion regarding novel topics in the field especially over the last decade. We highlight the challenges in the patient care setting including selection, as well as economic and socioeconomic challenges. Physician training challenges in neuromodulation is explored as well as other factors related to the use of neuromodulation such as novel indications and economics. We also discuss the concepts of technology and healthcare data. EXPERT OPINION: Patient safety and durable outcomes are the mainstay goal for neuromodulation. Substantial work is needed to assimilate data for larger and more relevant studies reflecting a population. Big data and global interconnectivity efforts provide substantial opportunity to reinvent our scientific approach, data analysis and its management to maximize outcomes and minimize risk. As improvements in data analysis become the standard of innovation and physician training meets demand, we expect to see an expansion of novel indications and its use in broader cohorts.

Identifying Critical Evidence Gaps in Wound Closure and Incision Management After Total Knee Arthroplasty: Delphi Panel Insights.

INTRODUCTION: In orthopaedic surgery, particularly total knee arthroplasty (TKA), the management of surgical wounds is critical for optimal wound healing and successful patient outcomes. Despite advances in surgical techniques, challenges persist in effectively managing surgical wounds to prevent complications and infections. This study aimed to identify and address the critical evidence gaps in wound management in TKA, including preoperative optimization, intraoperative options, and for the avoidance of postoperative complications. These are important issues surrounding wound management, which is essential for improving patient recovery and the overall success of the surgery. METHODS: Utilizing the Delphi method, this study brought together 20 experienced orthopaedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 specific statements about wound management in TKA based on a comprehensive literature review. During these three stages and after further panel review, an alternative goal of the Delphi panel was to also identify critical evidence gaps in the current understanding of wound management practices for TKA. RESULTS: While the panel reached consensus on various wound management practices, they highlighted several major evidence gaps. Also, there was general consensus on issues such as wound closure methods including the use of mesh-adhesive dressings, skin glue, staples, sutures (including barbed sutures),and negative-pressure wound therapy (NPWT). However, it was deemed necessary that further evidence needs to be generated to address the cost-effectiveness of each and develop best practices for promoting patient outcomes. The identification of these gaps points to areas requiring more in-depth research and improvements to enhance wound care in TKA. DISCUSSION: The identification of these major evidence gaps underscores the need for targeted research in wound management surrounding TKA. Addressing these evidence gaps is crucial for the future development of more effective, efficient, and patient-friendly wound care strategies. Future research should prioritize these areas, focusing on comparative effectiveness studies and further developing clear guidelines for the use of emerging technologies. Bridging these gaps has the potential to improve patient outcomes, reduce complications, and elevate the overall success rate of TKA surgeries.

Structure-guided drug design targeting Abl kinase: how structure and regulation can assist in designing new drugs.

The human protein Abelson kinase (Abl), a tyrosine kinase, plays a pivotal role in developing chronic myeloid leukemia (CML). Abl's involvement in various signaling pathways underscores its significance in regulating fundamental biological processes, including DNA damage responses, actin polymerization, and chromatin structural changes. The discovery of the Bcr-Abl oncoprotein, resulting from a chromosomal translocation in CML patients, revolutionized the understanding and treatment of the disease. The introduction of targeted therapies, starting with interferon-alpha and culminating in the development of tyrosine kinase inhibitors (TKIs) like imatinib, significantly improved patient outcomes. However, challenges such as drug resistance and side effects persist, indicating the necessity of research into novel therapeutic strategies. This review describes advancements in Abl kinase inhibitor development, emphasizing rational compound design from structural and regulatory information. Strategies, including bivalent inhibitors, PROTACs, and compounds targeting regulatory domains, promise to overcome resistance and minimize side effects. Additionally, leveraging the intricate structure and interactions of Bcr-Abl may provide insights into developing inhibitors for other kinases. Overall, this review highlights the importance of continued research into Abl kinase inhibition and its broader implications for therapeutic interventions targeting kinase-driven diseases. It provides valuable insights and strategies that may guide the development of next-generation therapies.

Relative Acceleration and Maximum Velocity in Rugby Players According to Age Category and Playing Position.

ABSTRACT: Zabaloy, S, Freitas, TT, Alcaraz, PE, Gálvez-González, J, Pereira, LA, Comyns, T, Loturco, I, and Healy, R. Relative acceleration and maximum velocity in rugby players according to age category and playing position. J Strength Cond Res XX(X): 000-000, 2024-This study aimed to: (a) assess the intrasession reliability of the acceleration time constant (i.e., τ) and τ-derived measures; (b) analyze the influence of τ and maximum velocity (Vmax) on 40-m sprint performance and to compare various sprint-related outcomes among rugby players from different playing positions and age categories; and (c) explore the associations between τ and several sprint performance metrics. A total of 300 male rugby players volunteered to participate in this study and were divided into age categories (i.e., under-14 [U14]: n = 91, age: 12.6 ± 0.5 years; under-16 [U16]: n = 85, age: 14.8 ± 0.5 years; under-18 [U18]: n = 75, age: 16.6 ± 0.5 years; and Seniors: n = 49, age: 24.2 ± 4.1 years). The results demonstrated good to excellent reliability for all measured parameters (intraclass correlation coefficient >0.75 and coefficient of variation <9.0%). Younger players (i.e., U14 and U16) displayed lower τ values (effect size: moderate to large; p < 0.02) compared with their older peers (i.e., U18 and Seniors), regardless of their playing position. Moreover, τ was associated with sprint performance metrics at varying levels of correlations (Rho: small to almost perfect; p < 0.001). In conclusion, younger players exhibited lower τ values than their older counterparts, irrespective of their playing positions. The model employed in this study demonstrated its accuracy in assessing several key sprint performance metrics, offering insights that can enhance sprint training programs for rugby players, which can be based on the associations observed among these different variables.

Dopamine-mediated interactions between short- and long-term memory dynamics.

In dynamic environments, animals make behavioral decisions based on the innate valences of sensory cues and information learnt about these cues across multiple timescales1-3. However, it remains unclear how the innate valence of a sensory stimulus affects acquisition of learnt valence information and subsequent memory dynamics. Here we show that in the Drosophila brain, interconnected short- and long-term memory units of the mushroom body jointly regulate memory via dopamine signals that encode innate and learnt sensory valences. Through time-lapse, in vivo voltage-imaging studies of neural spiking in >500 flies undergoing olfactory associative conditioning, we found that protocerebral posterior lateral 1 dopamine neurons (PPL1-DANs)4 heterogeneously and bi-directionally encode innate and learnt valences of punishment, reward, and odor cues. During learning, these valence signals regulate memory storage and extinction in mushroom body output neurons (MBONs)5. In initial conditioning bouts, PPL1-γ1pedc and PPL1-γ2α'1 neurons control short-term memory formation, which weakens inhibitory feedback from MBON-γ1pedc>α/ß to PPL1-α'2α2 and PPL1-α3. During further conditioning, this diminished feedback allows these two PPL1-DANs to encode the net innate plus learnt valence of the conditioned odor cue, which gates long-term memory formation. A computational model constrained by the fly connectome6,7 and our spiking data explains how dopamine signals mediate the circuit interactions between short- and long-term memory traces, yielding predictions that our experiments confirm. Overall, the mushroom body achieves flexible learning via the integration of innate and learnt valences within parallel learning units sharing feedback interconnections. This hybrid physiologic-anatomic mechanism may be a general means by which dopamine regulates memory dynamics in other species and brain structures, including the vertebrate basal ganglia.

Variations in strength-speed-power performance across the season: do true changes occur in elite rugby players?

This study aimed to determine, through the use of a highly sensitive statistical tool, whether real changes in performance were present; and compare the rates of meaningful variations in strength, speed, and power parameters at different time-points during the competitive season in national team rugby players. Thirty-two players were assessed 5 times across the season using the following tests: squat jump and countermovement jump tests; 30-m sprint velocity; and one-repetition maximum (1RM) in the half-squat and bench-press exercises. A repeated-measures analysis of variance was conducted to test for differences between successive time-points. Individual coefficients of variation values were used to set target scores for post-measurements and examine whether changes in performance parameters were greater than the natural test variance, thus providing an indication of whether "true changes" occurred. No significant changes were detected in the vertical jump height, 1RM measures, and sprint velocity and momentum throughout the 11-month period (P > 0.05). True changes occurred much more frequently for strength-power measures than for sprint velocity and momentum. Elite rugby union players did not exhibit significant variations in neuromuscular performance across the competitive period, when a group-based analysis was conducted. However, at the individual level, "true changes" in strength-power-(but not in speed-) related qualities were consistently observed over the competitive season.

Thyroid dysgenesis associated with dwarfism, osteoporosis and spontaneous fractures in a goat.

An 11-month-old female Saanen goat, weighing 12.7 kg, was taken to the Veterinary Hospital of the Federal University of Minas Gerais because of sternal recumbency. On clinical examination, the animal was much smaller than expected and had hair similar to that of puppies and areas of hyperpigmentation on the head and dorsocervical and dorsothoracic cranial regions. Radiographic examination revealed fractures in both femurs and severe generalized osteoporosis. Given the unfavourable prognosis, the animal was euthanized. Necropsy revealed generalized pallor, muscular atrophy of the pelvic limbs and little reserve of subcutaneous adipose tissue. Both femurs had complete and closed diaphyseal fractures. The second lumbar vertebra was severely reduced in length as a result of a fracture, with dorsal displacement of the vertebral body towards the vertebral canal and compression of the spinal cord. Long bones and vertebrae had severe cortical thinning, enlargement of the medullary canal and reduced resistance. The thyroid gland was not in its normal anatomical location. A pale red nodule (1.0 × 0.4 cm) in the serosa of the middle third of the trachea, close to the thoracic entrance, was confirmed as ectopic thyroid tissue. Microscopically, the bones had evidence of growth arrest and severe osteoporosis. The ectopic thyroid nodule was hyperplastic with severe hypertrophy of follicular cells. The spinal cord was compressed by vertebral fractures and had focally extensive and severe myelomalacia. Based on the pathological features, the case was diagnosed as thyroid dysgenesis characterized by eutopic thyroid agenesis and ectopic thyroid tissue, associated with interruption of bone growth with dwarfism, osteoporosis and spontaneous secondary fractures with compression of the lumbar spinal cord.

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction.

We describe the use of bismuth(III) triflate as an efficient and environmentally friendly catalyst for the Nazarov reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones) in good to excellent yield. The reaction did not require additives and was insensitive to both air and moisture. Preliminary biological evaluation of some indanones showed a promising profile against some human cancer line cells.

Local variation in stress response of juvenile anadromous brown trout, Salmo trutta.

Habitat fragmentation may cut off anadromous salmonids from parts of their potential native habitat and separate previously connected populations. Understanding the consequences of this is vital for fish management and prioritization of restoration activities. Here, we show that there is a significant difference in the body morphology, physiological stress response, and aspects contributing to aerobic capacity between juvenile anadromous brown trout, Salmo trutta, collected at a downstream site and an upstream site, separated by 2 km and several challenging stream sections, in a small unfragmented stream system in western Sweden. Following a standardized stress test, there were significant differences between fish from the upstream and downstream sites (plasma cortisol concentration, plasma osmolality, hematocrit, hemoglobin concentration, and mean corpuscular hemoglobin concentration). Plasma glucose concentration did not significantly differ between fish from the two sites. Fish from the upstream site had larger spleen mass, although there was no evidence of differences in ventricle mass or proportion of compact ventricular myocardium. These physiological differences indicate local variation in stress response and highlight the importance of considering local trait variation in river management. If a section of the river becomes fragmented or degraded, and there are differences in the juveniles in different parts of the river, the consequence for the population might be larger than the proportional loss of habitat.

Anticonvulsant and anxiolytic-like potential of the essential oil from the Ocimum basilicum Linn leaves and its major constituent estragole on adult zebrafish (Danio rerio).

The Ocimum species present active compounds with the potential to develop drugs for treating chronic disease conditions, such as anxiety and seizures. The present study aims to investigate the anticonvulsant and anxiolytic-like effect of the essential oil from O. basilicum Linn (OEFOb) leaves and its major constituent estragole (ES) in vivo on adult zebrafish (aZF) and in silico. The aZF were treated with OEFOb or ES or vehicle and submitted to the tests of toxicity, open-field, anxiety, and convulsion and validated the interactions of the estragole on the involvement of GABAergic and serotonergic receptors by molecular docking assay. The results showed that the oral administration of OEFOb and ES did not have a toxic effect on the aZF and showed anxiolytic-like effects with the involvement of GABAA, 5-HT1, 5-HT2A/2C and 5-HT3A/3B as well on anxiety induced by alcohol withdrawal. The OEFOb and ES showed anticonvulsant potential attenuating the seizures induced by pentylenetetrazole (PTZ) by modulation of the GABAA system. Both anxiolytic and anticonvulsant effects were corroborated by the potential of the interaction of ES by in silico assay. These study samples demonstrate the pharmacological evidence and potential for using these compounds to develop new anxiolytic and anticonvulsant drugs.

Immunomethylomic profiles of long-term head and neck squamous cell carcinoma survivors on immune checkpoint inhibitors.

Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.

[Box: see text].

Unsaturation in the air spaces of leaves and its implications.

Modern plant physiological theory stipulates that the resistance to water movement from plants to the atmosphere is overwhelmingly dominated by stomata. This conception necessitates a corollary assumption-that the air spaces in leaves must be nearly saturated with water vapour; that is, with a relative humidity that does not decline materially below unity. As this idea became progressively engrained in scientific discourse and textbooks over the last century, observations inconsistent with this corollary assumption were occasionally reported. Yet, evidence of unsaturation gained little traction, with acceptance of the prevailing framework motivated by three considerations: (1) leaf water potentials measured by either thermocouple psychrometry or the Scholander pressure chamber are largely consistent with the framework; (2) being able to assume near saturation of intercellular air spaces was transformational to leaf gas exchange analysis; and (3) there has been no obvious mechanism to explain a variable, liquid-phase resistance in the leaf mesophyll. Here, we review the evidence that refutes the assumption of universal, near saturation of air spaces in leaves. Refining the prevailing paradigm with respect to this assumption provides opportunities for identifying and developing mechanisms for increased plant productivity in the face of increasing evaporative demand imposed by global climate change.

Effects of Different Conditioning Activities on the Sprint Performance of Elite Sprinters: A Systematic Review With Meta-Analysis.

PURPOSE: Postactivation performance enhancement (PAPE), which refers to the phenomena associated with the attainment of enhanced performance in sport-specific tasks after a conditioning activity, is an important objective of warming-up practices in many sports. This is even more relevant for sprinters, as potential increases in sprinting speed will directly influence their competitive results. This systematic review with meta-analysis evaluated the effects of different PAPE protocols (ie, using plyometrics, strength-power exercises, and resisted/assisted sprints) on the sprinting performance (ie, sprint time or sprint speed) of competitive sprinters. METHODS: Initially, 1205 records published until last December 18 were identified, using the following databases: PubMed/MEDLINE, Scopus, and Clarivate Web of Science. After removing duplicates and screening titles and abstracts, 14 high-quality studies met the inclusion criteria for the meta-analysis. RESULTS: Overall, there were no significant changes in sprint performance after implementing various types of conditioning activities (standardized mean difference [SMD] = 0.16 [95% CI, -0.02 to 0.33]; Z = 1.78; P = .08; I2 = 0%). In addition, when comparing prechanges and postchanges between experimental, control, and other conditions, no significant differences were found in sprint speed or time across all studies (SMD = 0.09 [95% CI, -0.10 to 0.28]; Z = 0.92; P = .36; I = 0%). CONCLUSIONS: Results revealed that different types of conditioning activities may not be capable of acutely enhancing the sprint speed of competitive sprinters. This aligns with previous observations indicating that sprinting is a highly stable physical capacity, a phenomenon that is even more consistent among elite sprinters. Coaches and sport scientists should collaborate to develop more efficient PAPE protocols for these highly specialized athletes, with special attention to study design and individualization, while considering their effects on acceleration versus top speed.