Anatomic anterior cruciate ligament reconstruction has been successful for many years in restoring translational stability, but have we done enough to restore rotational stability? Biomechanical evidence shows that anatomic anterior cruciate ligament reconstruction alone may not restore pivot shift stability in cadaveric models. When added to anatomic anterior cruciate ligament reconstruction, lateral extra-articular tenodesis can restore pivot shift stability, even in the context of lateral meniscus root tears, increased tibial slope, tibial bone loss, and medial meniscectomy. Clinical studies (while not uniformly positive) have shown promise in reducing graft failure rates without increased risks of complications. Let's us keep pushing the indications for lateral extra-articular tenodesis while keeping track of short- and long-term outcomes-benefits continue to be shown clinically and biomechanically, while the negative impact is low.
Background/Objective: Cardiac innervation plays a critical role in regulating myocardial function and enabling the heart to adapt to physiological and pathological conditions. Although the general features of sympathetic and parasympathetic innervation of the myocardium are well described, the spatial organisation of nerve fibres within the cardiac muscle remains incompletely characterised. This study aimed to develop and validate the SKUF (Slice-Keep-Unwrap-Fuse) protocol, a multimodal framework for mapping myocardial innervation through the integration of histological data and magnetic resonance imaging (MRI). Methods: The study was performed on the heart of a 7-year-old patient who died from rupture of a cerebral vascular malformation without evidence of cardiovascular disease. Prior to histological processing, post-mortem MRI was performed to provide a precise anatomical reference. The heart was sectioned into sequential transverse rings of 4 mm thickness, yielding 71 paraffin blocks. Histological sections (3 μm) were immunostained with antibodies against UCHL-1 to visualise nerve fibres and scanned using an Aperio AT2 system (20× magnification). Automated image analysis was conducted using the SVSSlide Processor module, which included tissue segmentation, colour-based nerve fibre detection, and sliding-window density mapping. Heatmaps were assembled into ring-based myocardial reconstructions and co-registered with MRI slices using combined rigid and deformable registration, followed by three-dimensional reconstruction of innervation patterns. Results: A higher density of nerve fibres was observed in the right ventricular myocardium compared with the left ventricle, whereas larger nerve trunks were identified in the epicardium of the left ventricle. Quantitative analysis revealed a pronounced longitudinal gradient of innervation, with minimal density in the apical region and progressive increases towards the mid-ventricular segments, where maximal density and spatial organisation of neural structures were observed. The atrioventricular groove exhibited the greatest heterogeneity of innervation due to the presence of large nerve trunks and ganglionated plexuses. Integration of histological maps with MRI enabled three-dimensional visualisation of spatial clusters of nerve fibres. Conclusions: The SKUF protocol provides a robust framework for integrating histological and MRI data to generate three-dimensional maps of myocardial innervation. This approach may facilitate the development of high-resolution anatomical atlases of cardiac innervation and support future studies of neurocardiac mechanisms of arrhythmogenesis and targeted neuromodulation.
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Anesthesia is a dynamic process that has different effects on the systems in terms of hemodynamics and clinical and psychological aspects, and is not physiological. Anesthesia management and surgery follow-up are complex, and various specialties require knowledge, attitude, practice, and experience. In recent years, innovations in preoperative evaluations, new surgical methods, innovations in pharmacology, advanced technological devices in monitoring, and developments in anesthesia training have reduced morbidity and mortality. When the perioperative period is considered, adequate knowledge, attitude, behavior, awareness, and multidisciplinary and multimodal approaches of anesthesia physicians and nurses are vital. A multidisciplinary team approach (anesthesiologist, nurses, physicians from other specialties, and nurses) in the perioperative period, including medication adjustments and fasting protocols, is extremely important in comprehensive, meticulous preoperative evaluation, in adapting individualized care plans, ensuring postoperative recovery and patient safety, improving outcomes, and contributing to reducing perioperative mortality, morbidity and hospital costs. In our review, we aim to discuss the importance of improving and normalizing physiological parameters in the perioperative period in light of the literature.
Marathon running is associated with transient elevations in cardiac and skeletal muscle biomarkers, which generally normalize within 72 h. However, persistent or extreme biomarker elevations may indicate underlying pathology, such as myocarditis. Early recognition and guideline-based management are essential to prevent complications and guide safe return to exercise. A 21-year-old recreational marathon runner collapsed towards the end of a marathon race. On presentation, he exhibited markedly elevated cardiac and muscle biomarkers, including high-sensitivity cardiac troponin T, creatine kinase, creatine kinase-myocardial band, and myoglobin. The initial electrocardiogram (ECG) demonstrated a tachycardic sinus rhythm with T-wave inversion in Lead III, without evidence of significant depolarization or repolarization abnormalities. Cardiac Magnetic Resonance Imaging (MRI) confirmed acute myocarditis. The patient was managed supportively with intravenous fluids and non-steroidal anti-inflammatory drug analgesics, remained haemodynamically stable, and experienced no arrhythmias or chest pain. At 3-month follow-up, he reported good functional capacity, and both echocardiography and cardiac MRI were completely normal, demonstrating full resolution of myocardial inflammation. This case highlights the diagnostic challenge of interpreting elevated cardiac biomarkers in endurance athletes. Observational studies indicate that biomarker elevations often correlate with exercise duration rather than with demographic or training-related factors. Cardiac MRI remains essential for non-invasive diagnosis, risk stratification, and follow-up. Importantly, adherence to guideline-based management, i.e. temporary abstinence from competitive sports, monitoring of biomarkers, and serial imaging, can lead to excellent outcomes, as exemplified by the complete normalization observed in this patient. Non-steroidal anti-inflammatory drugs should be used with caution in amateur endurance athletes due to their potential to aggravate myocarditis.
We investigate whether a stable predisposition to interpret events as the result of conspiracies-conspiracism-is associated with the spontaneous generation of conspiratorial content in writing when interpreting ambiguous information. Across two studies (N = 385), participants watched the apocalyptic thriller Leave the World Behind and wrote an essay interpreting its meaning. Each essay was rated by a Large Language Model for its conspiratorial narrative content, that is, the degree to which the text contains claims that the public is being pervasively lied to about aspects of reality, enabling some groups to enact a harmful, self-serving agenda. Contrary to our preregistered hypothesis, we did not find an association between participants' conspiracism and their essays' level of conspiratorial narrative content. Exploratory linguistic analyses revealed that conspiracism was associated with greater use of conspiracy-related vocabulary (e.g., deception, government), a disproportionate use of sophisticated words, and increased syntactic complexity. These results suggest that conspiracism may emerge more readily at the lexical level rather than through fully structured narratives. We discuss potential methodological and theoretical factors contributing to these unexpected results, including the roles of context, perceived relevance, motivation, and collective social dynamics. We also consider the possibility that conspiracism may not directly translate into conspiratorial narratives. If so, we recommend comparative research on online vs offline conspiratorial writing to clarify whether conspiracy theories emerge spontaneously from genuine beliefs or are constructed strategically, detached from genuinely held beliefs.
For emergency vehicles traveling under lights and sirens to reach incidents safely and without delay, other road users must understand and comply with their legal obligation to give way and keep clear. However, reports of on-road behavior suggest many drivers may be uncertain of these requirements. This study examined drivers' understanding of the legislative requirements for sharing the road with emergency vehicles in Queensland, Australia, and whether drivers' self-rated understanding aligned with their actual knowledge of those rules. A cross-sectional in-person survey was completed by 208 licensed drivers who answered 61 multiple-choice questions (25 emergency-vehicle items embedded among general road-rule items) and rated their understanding of the road rules. Participants generally believed they had a good understanding of emergency-vehicle road rules; however, survey performance indicated gaps in their knowledge. Across the 25 emergency-vehicle items, participants answered an average of 78.77% correctly. Knowledge of basic giving-way requirements was high, but drivers showed inconsistent understanding of the rules for passing stationary emergency vehicles, and many were unsure how to keep clear when no lane was available to their left. Understanding was also poor for situations where drivers may legally proceed through a red light, when safe, to make way for an emergency vehicle. Open-license drivers scored higher than learner drivers, but self-rated understanding did not align with actual understanding: lower-knowledge participants tended to rate their understanding more highly, while higher-knowledge participants rated it more conservatively. In the present sample, these findings highlight specific situations where drivers may misunderstand what they are required to do during encounters with emergency vehicles, creating the potential for obstructions, delays, and hazardous interactions.
Estimates suggest that approximately 400 million dogs are kept as pets worldwide. Despite their popularity, around 10% to 30% are surrendered to rescue shelters each year. Shelter workers play a pivotal role in the success of dog adoptions and provide ongoing support to help owners keep these dogs in their homes. However, research that captures their perspectives and experiences regarding the dog adoption process remains limited. Royal Society for the Prevention of Cruelty to Animals Queensland shelter teams participated in six focus group discussions to share their perspectives and experiences of the dog adoption process in their shelters. Reflexive thematic analysis of the gathered data generated three themes: 1. "Doing great adoptions" starts with an inclusive, well-resourced application process and a skilled team. 2. Finding the right fit involves navigating the duality of carer and advocate through honest, informative interactions with the whole family. 3. Successful outcomes involve supporting and educating the public to care for and keep their dog. This grounded understanding of the challenges facing shelters in their work could provide valuable feedback to help shelter leaders and staff develop policies and practices that support positive adoption outcomes, tailor programmes to local needs, and reduce return rates.
The majority of electric vehicles (EVs) are charged domestically overnight, when the precise timing of power allocation is not important to the user, thus providing a source of flexibility that can be leveraged by charging control algorithms. In this paper, we show that by keeping the EV connected to a standard domestic smart plug every night, it is possible to achieve an approximate 37% annual reduction in carbon intensity compared to uncontrolled charging (based on 2022 UK National Grid data) without compromising the EV owners' charging demand. For this purpose, we use Model Predictive Control techniques to schedule power delivery with the objective of minimizing grid-average CO2 emissions over forecast windows of multiple sessions (up to seven days ahead). We find that flexibility on the part of EV owners-both their willingness to keep the EV connected at night, and to indicate a precautionary (i.e., upper bound) estimate of their required state-of-charge in the morning-allows for significant emissions reduction and accelerated decarbonization of the mobility sector.
Fractures are becoming a bigger and bigger global health problem, with an estimated 178 million new cases each year and 455 million people living with disabilities caused by fractures. Donor site morbidity, the risk of immune rejection, and limited functional integration all make current grafting techniques less effective. Biomaterials that come from nature, like collagen, gelatin, chitosan, alginate, hyaluronic acid (HA), and silk fibroin, have become promising scaffolds because they are bioactive, mimic the extracellular matrix (ECM), and can be broken down by enzymes. Crosslinking and composite reinforcement can greatly change how well they work. For example, collagen scaffolds that are highly crosslinked with glutaraldehyde keep up to 51.9% of their tensile strength after being exposed to enzymes, while non-crosslinked scaffolds only keep 12% of their strength. Chitosan-hydroxyapatite matrices, on the other hand, can reach compressive strengths of 2-12 MPa, which is close to the strength of cancellous bone. Additive manufacturing and 4D printing allow for precise control of structures and the ability to change their shape over time, which helps with vascularization and mechanical adaptation. Injectable and in situ-forming hydrogels show clinically important results, such as filling 85% of osteochondral defects in rabbits, improving left ventricular ejection fraction by up to 9% in large-animal cardiac models, and speeding up healing by 25-40% in chronic wounds. Even with these improvements, it is still hard to get batch consistency, a standardized way to test mechanical properties, and production that meets GMP (Good Manufacturing Practices) standards and can be scaled up.
The immediate and long-term effects of COVID-19 pandemic on the children go beyond just being a viral infection. A child's mental health and psychological issues like irritability, anxiety, sadness, non-attentiveness, attention deficit and hyperactive disorder needed evaluation. Based on these study queries, an investigation was carried out to correlate the psychological state and the emergency measures in children with respect to the health and wellbeing outcomes. A web-search across scientific databases like the Web of Science, Scopus and PubMed was undertaken for a situational review through available literature, and derive credible solutions. This narrative review included peer-reviewed articles published between January 2020 and February 2026 in English language, focusing on children wellbeing in wake of the COVID-19 pandemic. After analysing the authenticity and relevance of the literature, 158 articles/data were shortlisted for further analyses. The data were qualitatively validated, synthesised into discrete sections and interpreted in the context of the objective of the study. Children particularly in low-economy families were likely to experience violence and abuse if they stayed for long in high-risk settings like refugee settlements for internally displaced community. On the contrary, the children of high-economy families had weight gain issues owing to erratic consumption patterns of high-calorie food (like dairy products and sugar-rich packaged snacks) coupled with restricted or limited physical activities. Their dietary patterns and unhealthy eating habits needed monitoring and restrictions to curb obesity risk in the long run. Elevated stress, anxiety and depression levels in a child may result in cognitive impairment. The possibilities of their getting addicted, developing insomnia and acquiring non-communicable illnesses were aspects to consider. Preventive measures like social distancing, lockdowns and shutdowns and mass vaccination drives had wider and critical long-term impact on the young and adolescent. Formulating workable modalities to identify critical influencing factors of a pandemic and assess the impact on the children and beyond is essential for foolproof solutions to combat future occurrences. Identifying the associated risk factors and correlating the emergency measures and psychological health seem essential. The supply of quality food seamlessly to the affected communities and the provision of protective gears for the healthcare workers could help keep the children well-fed and relaxed while ensuring the wellbeing of healthcare workers. Maternal and infant care, child-health services, and life-saving medicines and vaccines would also help ease the pressure.
Microcins are bacterially produced peptide antimicrobials. In a recent work, Telford et al. discover an Acinetobacter baumannii amyloid-like microcin that is also a structural component of the biofilm matrix. Might cells turn biofilms into 'minefields' to keep competitors from closing in?
BackgroundLong-term evidence from resource-limited settings spanning transitions in HIV care is scarce. We describe 25-year outcomes from a pragmatic Indian cohort employing simplified regimens and strategic drug sequencing.MethodsTreatment-naïve adults initiated dual-nucleoside reverse transcriptase inhibitor therapy (2000-2025), reserving protease and integrase inhibitors for later lines ("class preservation"). Primary outcomes were survival and treatment durability.ResultsAmong 971 patients retained in care (12,438 patient-years), Kaplan-Meier survival was 95.8% at 5 years and 88.3% at 25 years. Median first-line durability was 8.3 years. Overall, 85% achieved ≥95% adherence. Opportunistic infection incidence declined from 451.5 to 69.7 per 1000 patient-years. Clinically driven monitoring saved US$7578 per patient.ConclusionsFor patients retained in continuous care, strategic sequencing, intensive adherence support, and provider continuity sustained durable outcomes over 25 years. These findings characterize outcomes achievable under sustained engagement rather than population-level results. Long-term HIV care in India: What 25 years in a resource-limited clinic teaches us about survival, affordable medicines, and helping patients take their daily pillsPlain Language SummaryHIV is now a manageable condition, but delivering lifelong care in areas with limited financial and medical resources is highly challenging. Most global health guidelines rely on expensive lab tests and newer, costly drugs. This raises an important question: how can doctors provide long-term care when patients cannot afford these standard options? This study looks at 25 years of HIV care at a single independent clinic in southern India, from 2000 to 2025. To keep care affordable and effective, the clinic used a highly practical approach. Patients were started on simple, lower-cost combinations of older HIV drugs. The newer, more expensive drugs were strictly saved as backup options, to be used only if the first medicines stopped working. Because routine blood tests to check virus levels were too expensive for most patients, the clinic focused heavily on human support instead of technology. The doctor counted the patients' pills every month to ensure they were not missing doses, proactively treated any side effects before they became severe, and provided continuous, personal encouragement. The results showed this strategy was highly successful. Among the patients who stayed with the clinic for the continuous 25-year period, nearly 90% survived and lived healthy lives. On average, their first, lowest-cost drug combination kept them healthy for over eight years before a change was needed. Furthermore, only performing lab tests when clinically necessary saved over $7,500 per patient compared to standard international guidelines. This study proves that in areas with limited technology, expensive medical tests are not the only path to success. Strong doctor-patient relationships, affordable drug planning, and careful monitoring of daily pill-taking can sustain HIV care for decades.
The rising prevalence of skin cancer worldwide emphasizes the critical need for novel therapeutic and diagnostic approaches that go beyond conventional methods. Through improved drug delivery, targeted therapy, and sophisticated diagnostic applications, nanotechnology holds revolutionary promise in the field of oncology. The safety, ethical, and regulatory aspects of nanotechnology's multifaceted role in the treatment of skin cancer are highlighted in this chapter. Systemic toxicity is reduced by nanoparticles with enhanced biocompatibility, site-specific drug delivery, and imaging precision, such as liposomes, polymeric carriers, metallic nanostructures, and quantum dots. In spite of these developments, issues with biodistribution, long-term toxicity, and possible genotoxic effects still continue to impact nanomedicine. Informed consent, fair access, environmental sustainability, and data privacy are ethical factors to be taken into account in clinical applications and nanomedical research. ssAdditionally, regulatory frameworks are still evolving as international organizations like the FDA and EMA keep establishing guidelines for post-market surveillance, safety evaluation, and characterization. The chapter emphasizes the value of interdisciplinary cooperation in ensuring the responsible development, moral application, and thorough evaluation of nanotechnology-based interventions. Transforming nanotechnological advancements into safe and efficient treatments for patients with skin cancer requires the integration of safety testing, ethical consideration, and standardized international regulation.
Developing climate-resilient wheat varieties requires combining high yield with stability across diverse environments, especially under increasingly variable precipitation and rising temperatures. This study evaluated 64 post-Green Revolution durum wheat cultivars under irrigated and rainfed conditions at two contrasting Mediterranean sites in Spain. A classification framework was developed to support genotype selection based on yield and yield stability, estimated using linear mixed models and yield slopes across environments. Genotypes were classified by interquartile thresholds, and those showing either low yield or low stability were considered undesirable for selection. High-throughput phenotyping was conducted throughout the season using ground-sensor Red-Green-Blue (RGB) and multispectral (MS) vegetation indices (VIs), along with UAV-derived RGB, MS, and thermal-infrared (TIR) data. VIs and TIR at anthesis and grain filling, and their differences (senescence proxies), were used to train Random Forests for yield and stability estimation including sequential feature selection. Environmental covariates (water input, reference evapotranspiration) were integrated in yield models, with strong outcomes (R2 > 0.74; MAPE <23.6%). Stability predictions were based on VI stability and, though moderate (R2 up to 0.56; MAPE <17.75%), outperformed previous studies. Selected features were used to evaluate seasonal reflectance phenotypes: "keep" genotypes (intermediate/high yield or/and stability) exhibited early-vigor but lower green retention by the end of grain filling, while "discard" genotypes (low yield or/and stability) showed reduced early vigor and "stay-green" behavior. This study highlights early-vigor and earlier senescence over "stay-green" for wheat selection, offering a cost-effective approach shifting the breeding focus from yield maximization to joint yield-stability evaluation, promoting sustainability.
Background and Clinical Significance: Angiotensin-converting enzyme inhibitors (ACE-Is) are commonly used for treatment of hypertension and are well known among primary care specialists. ACE-I-induced angioedema is a rare, yet possible side effect. It should not be taken lightly, as it can be life-threatening. It is characterized by erythematous or skin-coloured, self-limiting, localized, non-pitting swelling of the submucosal and/or subcutaneous layers of tissue. Usually, it develops in the first year of using the medication, although it can also start several years after using it. Herein, we describe a late-onset ACE-I-induced angioedema, which developed 7 years after using the ACE-I. This case report depicts the challenges of diagnosing ACE-I-induced angioedema, especially if it is late-onset. It highlights the importance of actively asking patients questions about possible side effects of medication even several years after using it and the patients themselves not having any complaints. Case Presentation: We present a 61-year-old Caucasian male with recurring swelling of the lips, tongue and an uncomfortable feeling in the throat, which started 7 years after using an ACE-I: perindopril. There was no airway obstruction or urticaria in any of the episodes. Hereditary angioedema was ruled out by blood analysis. Based on the clinical presentation, images and blood analysis, it was diagnosed as late-onset ACE-I-induced angioedema. After discontinuing the ACE-I, there were two more episodes of angioedema reported, which were a lot milder in symptoms and lasted a shorter time period. Since then, there have been no other episodes of angioedema. Conclusions: It is important to keep in mind angioedema as a possible side effect for patients on ACE-Is. Patients should be regularly and actively questioned about side effects, even if the medication has been started several years ago and no complaints are brought up by the patient.
As global temperatures are shifting, so too is the landscape of organismal fitness and, by extension, the role of the symbiotic microbes they house. As these host-microbe partnerships grapple with changing environments, current research struggles to keep pace with the complexity of microbial symbioses acclimating, adapting and evolving as environmental conditions change around them. Wild-caught organisms have been used to test adaptation to extreme environments, but extrapolating and interpreting data on how separate partners within a symbiosis respond to detrimental conditions is difficult. The beneficial association between bobtail squids and bioluminescent Vibrio bacteria is a model that has been used for over three decades to uncover evolutionary and ecological mechanisms of symbiogenesis. The system is highly amenable to a broad range of physiological and molecular techniques and has been used to study many dimensions of symbiotic interactions. This beneficial association has demonstrated that host selection of environmentally available Vibrio symbionts can be influenced by various abiotic conditions, such as temperature. Complex biochemical communication has been charted extensively between host and symbiont, revealing universally conserved traits that are temperature sensitive. Additionally, temperature can influence co-evolution of the partners, and this system can be used to predict symbiotic cooperation over evolutionary time scales. While one model system cannot provide exhaustive insight, the bobtail squid-Vibrio mutualism has laid extensive, pioneering groundwork that can be used to develop targeted questions about symbioses under changing climates.
The tomato leaf miner, Phthorimaea (Tuta) absoluta, Meyrick 1917 is recognized as a highly destructive pest, causing significant economic losses to crops in both greenhouse and open field environments across four continents: Asia, Africa, Europe, and South America. High genetic homogeneity among populations from various regions and countries indicates significant gene flow between P. absoluta populations, suggesting a lack of geographical barriers to dispersion. Furthermore, P. absoluta has developed resistance to insecticides due to target-site mutations or metabolic resistance, which enable the insect to withstand lethal doses of insecticides. To control this insect pest, the plant-mediated RNA interference (RNAi) is most promising host-induced gene silencing technique, utilized the plant's machinery to express double-stranded (dsRNA), which triggers the RNAi pathway in P. absoluta. Due to thermal tolerance, the P. absoluta has increased its area of invasion by 600 km per year over 9 years. Female P. absoluta releases pheromones that are recognized by males with a sophisticated olfactory circuit on their antenna. Pheromone binding proteins (PBPs) play a crucial role in mate recognition and attraction, and their expression peaks during courtship, specifically around 6:00 a.m. Given its potential to significantly alter the insect genome, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) offer a revolutionary strategy to control P. absoluta. Furthermore, this pest has developed remarkable adaptations to survive on unfavorable hosts by secreting specific proteins from its salivary glands that detoxify plant defenses. Insecticide resistance is likely the cause of field control failures of P. absoluta. Biological control, sex pheromone traps, and cultural control are the most promising approaches to address insecticide resistance resulting from these failures. Therefore, the implementation of integrated control programs and appropriate resistance management strategies is necessary to keep P. absoluta infestations under economic damage thresholds.