Articles

We investigated how targeted reactivation of cortical memory engrams during sleep influences systems consolidation of contextual fear memory. Using a mouse model of contextual fear conditioning (CFC), we tagged retrosplenial cortex (RSC) neurons activated during learning with channelrhodopsin-2 (ChR2) via a c-Fos-based TRAP system. Twenty-four hours post-training, animals received optogenetic stimulation of these RSC engram cells selectively during non-rapid eye movement (NREM) sleep or REM sleep. Immediately after, hippocampal activity was transiently blocked (muscimol infusion) to test hippocampal dependence. We found that NREM-specific reactivation of RSC engrams preserved contextual fear recall despite hippocampal inactivation, whereas REM stimulation or no stimulation failed to rescue memory. These results indicate that engram reactivation during NREM accelerates the transfer of memory to cortical storage. We present high-level diagrams of experimental workflow and results, and report a timeline of revisions. Abbreviations and keywords are provided. This comprehensive revision addresses all reviewer comments and renders the manuscript submission-ready.

Objective: This systematic review aimed to identify, synthesize, and critically analyze the available evidence on clinical protocols used for the prevention and treatment of prosthetic joint infection (PJI) in total hip arthroplasty (THA), based on studies published between 2000 and 2025. Methods: The review was conducted according to PRISMA guidelines. Electronic searches were performed in PubMed (MEDLINE), Scopus, Web of Science, and Embase between January and April 2025. Eligible studies included clinical trials, cohort studies, case-control studies, systematic reviews, and meta-analyses published in English that addressed either preventive or therapeutic strategies for PJI in THA. Study selection, data extraction, and quality assessment were carried out independently by two reviewers. Due to the heterogeneity of the included studies, a qualitative synthesis was performed. Results: A total of 32 studies were included. Preventive measures identified in the literature comprised combined antibiotic prophylaxis (cefazolin and gentamicin), multimodal perioperative protocols such as ACERTO, nasal decolonization for Staphylococcus aureus, silver-impregnated dressings, and structured post-discharge surveillance. Treatment strategies included DAIR (Debridement, Antibiotics, and Implant Retention), the DAPRI technique, one-stage and two-stage revision surgeries, muscle flap reconstructions, and protocols without spacers. These interventions were associated with significantly reduced infection rates and improved clinical outcomes when applied appropriately and in accordance with patient-specific factors. Conclusion: Effective prevention and treatment of PJI in total hip arthroplasty require a systematic and evidence-based approach. Integrated protocols—spanning preoperative optimization, meticulous intraoperative techniques, and rigorous postoperative monitoring—have proven effective in reducing infection incidence. In cases of established infection, surgical management must be tailored to the timing of infection, microbial profile, and host conditions. Two-stage revision remains the gold standard for complex infections, while one-stage revision and emerging techniques like DAPRI offer promising results in selected cases. This review contributes to the standardization of clinical practice and supports improved patient outcomes.

This systematic review aimed to evaluate the biomechanical properties, functional performance, and clinical outcomes of different hip prosthesis materials and designs used in total hip arthroplasty (THA). A comprehensive search strategy identified 34 peer-reviewed studies published between 2015 and 2024. The materials investigated included cobalt-chromium-molybdenum (CoCrMo), titanium alloys, PEEK, ceramics, and advanced surface coatings such as polycrystalline diamond (PCD). In addition, dual mobility systems, lattice structures, and additively manufactured and patient-specific implants were assessed. The studies utilized clinical trials, finite element analysis, and biomechanical testing to compare outcomes such as wear resistance, stress distribution, osseointegration, and range of motion. The findings demonstrated that titanium alloys and porous lattice structures reduce stress shielding, while ceramics and CoCrMo provide superior wear resistance. Dual mobility implants improved joint stability and range of motion, particularly in high-risk patients. PEEK and PCD showed promising properties but lacked robust long-term data. The integration of advanced manufacturing technologies and material innovations has led to more personalized and biomechanically efficient solutions for THA. Further longitudinal studies are needed to validate these developments. This review provides a critical synthesis of the biomechanical, functional, and clinical implications of contemporary hip prosthetic systems.

Objective: This integrative review aims to critically examine the clinical management of periprosthetic joint infections (PJI) in total hip arthroplasty (THA), emphasizing decision-making strategies, diagnostic advancements, and therapeutic innovations. The study focuses on the complexity of infection control, microbial resistance, and individualized treatment planning. Methods: A systematic review of the literature was conducted using PubMed, Scopus, Web of Science, and Google Scholar, targeting studies published between 2015 and 2025. Articles were selected based on their contribution to understanding the clinical, microbiological, and surgical aspects of PJI in THA. Fifty-five studies met the inclusion criteria and were analyzed descriptively. Results: PJI in THA is influenced by multifactorial risk profiles, including obesity, diabetes, and immunosuppression. Staphylococcus aureus, particularly MRSA, remains the most frequently isolated pathogen, followed by Gram-negative organisms and fungal species. Diagnostic innovations such as next-generation sequencing have enhanced pathogen detection, while two-stage revision remains the gold standard for chronic infections. Emerging strategies—such as antimicrobial coatings, tailored antibiotic protocols, and multidisciplinary care models—demonstrate promise in improving clinical outcomes. Conclusion: Managing PJI in THA necessitates a comprehensive and individualized approach, integrating early and accurate diagnosis, pathogen-specific treatment, and advanced preventive measures. The integration of emerging technologies and personalized care pathways is critical to optimizing outcomes and reducing the clinical and economic burden of PJI.

Background: The hippocampus plays a critical role in memory and decision-making processes, with its resting-state functional connectivity (rsFC) linked to various behavioral outcomes. This study investigates whether baseline brain-wide rsFC of the hippocampus mediates the relationship between impulsivity and subsequent substance use, specifically tobacco and marijuana use, in adolescents. Methods: Data were drawn from the baseline wave of the Adolescent Brain Cognitive Development (ABCD) study. Resting-state fMRI data were used to evaluate the functional connectivity of the hippocampus with key brain networks, including the cingulo-parietal network, visual network, sensory-motor network, and default mode network (DMN). Impulsivity was assessed using validated self-report measures, and substance use (tobacco and marijuana) was evaluated at follow-up. Mediation models were conducted to examine the extent to which hippocampal rsFC explains the association between impulsivity and substance use. Results: Baseline hippocampal rsFC with the cingulo-parietal network, visual network, sensory-motor network, and DMN showed marginal associations with future tobacco and marijuana use. Additionally, hippocampal rsFC was significantly associated with impulsivity, which, in turn, predicted higher substance use at follow-up. These findings suggest that hippocampal rsFC partially mediates the relationship between impulsivity and substance use behaviors. Conclusions: Hippocampal functional connectivity with brain networks may influence the pathway from impulsivity to future substance use in adolescence. These findings emphasize the importance of hippocampal connectivity in understanding the neural mechanisms underlying risk behaviors and may inform the development of targeted interventions to reduce substance use in this vulnerable population.

Background: Multiple epiphyseal dysplasia (MED) a rare form of skeletal dysplasia with early-onset osteoarthritis affecting the hip and knee joints. There is paucity of evidence regarding the long term outcomes of arthroplasty in this patient cohort. This is the first study to describe the outcomes of bilateral arthroplasty of the hip and knee in patients with MED. Methods: A prospective study of patients with MED who underwent bilateral staged total hip arthroplasty (THA) and bilateral simultaneous total knee arthroplasty (TKA) between July 2013 to April 2014. Preoperative and postoperative clinical and radiographic assessment including functional outcomes namely Merle d’aubigne score, Harris hip score (HHS), Knee society score (KSS) and numeric rating scale (NRS) for pain were recorded in prospective database and evaluated. Results: 3 patients (female - 1 / male - 2) with MED who underwent bilateral lower limb arthroplasty of the hip and knee were reviewed periodically with an average followup of 7.31 years. Mean preoperative Merle d'Aubigné score (6.33 ± 0.58), HHS (31.83 ± 5.31) and KSS (28.67 ± 7.97) increased following bilateral lower limb arthroplasty with mean postoperative Merle d'Aubigné score (16.33 ± 0.58), HHS (84.33 ± 5.99) and KSS (86.33 ± 7.09) (P<0.001). Mean NRS decreased from 7.33 ± 0.58 in the preoperative period to 0.67 ± 0.58 at the most recent followup (P<0.001). One patient had heterotrophic ossification following THA. There were no revisions. Conclusions: Bilateral lower limb arthroplasty of the hip and knee is a good treatment option to restore function and mobility in MED patients with advanced degenerative arthritis. Careful preoperative planning, meticulous surgical techniques, patient focussed postoperative rehabilitation with multidisciplinary team approach are vital to ensure good functional outcomes and implant survivorship.