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BACKGROUND: The skull base is a complex region in neurosurgery, featuring numerous foramina. Accurate identification of these foramina is imperative to avoid intraoperative complications and to facilitate educational progress in neurosurgical trainees. The intricate landscape of the skull base often challenges both clinicians and learners, necessitating innovative identification solutions. We aimed to develop a computer vision model that automates the identification and labeling of the skull base foramina from various image formats, enhancing surgical planning and educational outcomes. METHODS: We employed a deep learning methodology, specifically utilizing a convolutional neural network (CNN) architecture. Our model was trained on a dataset comprising of 3,560 high-resolution, annotated images of the skull base, taken from various perspectives and lighting conditions to ensure model generalizability. Model performance was quantitatively assessed using precision and recall metrics. RESULTS: The CNN model demonstrated strong performance, achieving an average precision of 0.77. At a confidence threshold of 0.28, the model reached an optimal precision of 90.4% and a recall of 89.6%. Validation on an independent test set of images corroborated the model's capability to consistently and accurately identify and label multiple skull base foramina across diverse imaging scenarios. CONCLUSION: This study successfully introduces a highly accurate computer vision model tailored for the identification of skull base foramina, illustrating the model's potential as a transformative tool in anatomical education and intraoperative structure visualization. The findings suggest promising avenues for future research into automated anatomical recognition models, suggesting a trajectory toward increasingly sophisticated aids in neurosurgical operations and education.

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The plant species C. sativum L. is a staple in cuisine and holds significant ethnopharmacological value. Its essential oil (EO) is of particular interest, yet its toxicity profile remains a subject of inquiry. This study aimed to elucidate the chemical constituents of C. sativum L. EO and evaluate its toxicity through various parameters, including cytotoxicity assays on HaCaT keratinocytes, in vivo toxicity tests on Galleria mellonella larvae, in vivo genotoxicity assessments on mice and cytotoxicity assays on human erythrocytes. Notably, major constituents such as 2-decen-1-ol, dec-(2E)-enal, and 1,6-octadien-3-ol were found to remain predominant. The IC50 value for the essential oil on the keratinocyte cell line was determined to be 60.13 ± 2.02 µg/mL. However, in vivo toxicity tests with G. mellonella larvae demonstrated safety at doses below 4.5 g/kg. Additionally, genotoxicity assessment revealed that a single dose of 20 mg/mL (5 mg/kg) did not induce a significant increase in micronuclei formation. EO concentrations above 250 µg/mL led to significant changes in human erythrocytes cell viability (p < 0.0001), resulting in over 60% hemolysis. These findings collectively suggest that the essential oil of C. sativum L. exhibits a suitable toxicity profile for conducting preclinical studies in vertebrate animal models.

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BACKGROUND: Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient. CASE PRESENTATION: An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions. CONCLUSIONS: In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes.

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The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded ß-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant. Rabbits and mice immunized with these five PfTrx constructs produced ECL-specific Abs that promoted opsonophagocytosis of TPA by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. ECL-specific rabbit and mouse Abs also impaired viability, motility, and cellular attachment of spirochetes during in vitro cultivation. The results support the use of ECL-based vaccines and suggest that ECL-specific Abs promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.

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We previously described an in vitro single-chain fragment (scFv) library platform originally designed to generate antibodies with excellent developability properties. The platform design was based on the use of clinical antibodies as scaffolds into which replicated natural complementarity-determining regions purged of sequence liabilities were inserted, and the use of phage and yeast display to carry out antibody selection. In addition to being developable, antibodies generated using our platform were extremely diverse, with most campaigns yielding sub-nanomolar binders. Here, we describe a platform advancement that incorporates Fab phage display followed by single-chain antibody-binding fragment Fab (scFab) yeast display. The scFab single-gene format provides balanced expression of light and heavy chains, with enhanced conversion to IgG, thereby combining the advantages of scFvs and Fabs. A meticulously engineered, quality-controlled Fab phage library was created using design principles similar to those used to create the scFv library. A diverse panel of binding scFabs, with high conversion efficiency to IgG, was isolated against two targets. This study highlights the compatibility of phage and yeast display with a Fab semi-synthetic library design, offering an efficient approach to generate drug-like antibodies directly, facilitating their conversion to potential therapeutic candidates.

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The gut-liver axis plays a pivotal role in maintaining body homeostasis. Disruption of the gut-liver axis is linked to a multitude of diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Probiotic strains from the Lactobacillaceae family are commonly used to mitigate experimental MASLD. Over the years, numerous studies have demonstrated the efficacy of these probiotics, often focusing on the outcome of liver disease. This review aims to further understand MASLD as a systemic metabolic dysfunction and to highlight the effects of probiotics on multi-organ axis, including organs such as the gastrointestinal tract, pancreas, muscle, adipose tissue, and the immune system. We specifically discuss evidence on how supplementation with Lactobacillaceae strains may alleviate MASLD by not only restoring liver health but also by modulating the physiology of other organ systems.

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Commercial crocodilian farms face significant economic and livestock losses attributed to stress, which may be linked to their adopted husbandry practices. The development of appropriate and modernized husbandry guidelines, particularly those focused on stress mitigation, is impeded by the limited understanding of the crocodilian stress response. Fifteen grower Nile crocodiles were subjected to simulated acute transport stress, with blood samples collected at various intervals post-stress. Plasma levels of corticosterone (CORT), dehydroepiandrosterone (DHEA), adrenaline, and noradrenaline were determined using high-performance liquid chromatography. Glucose and lactate were measured using portable meters and the heterophil-to-lymphocyte ratio (HLR) was determined via differential leucocyte counts. Significant differences were elicited after the stressor, with acute fluctuations observed in the fast-acting catecholamines (adrenaline and noradrenaline) when compared to the baseline. Downstream effects of these catecholamines and CORT appear to be associated with a persistent increase in plasma glucose and HLR. Lactate also showed acute fluctuations over time but returned to the baseline by the final measurement. DHEA, which is used in a ratio with CORT, showed fluctuations over time with an inverted release pattern to the catecholamines. The study highlights the temporal dynamics of physiological markers under acute stress, contributing to our understanding of crocodilian stress and potentially informing improved farming practices for conservation and sustainable management.

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BACKGROUND: Symptoms such as impairment of postural balance, mobility and muscle strength can last up to 12 months post COVID-19 hospitalization, need to be better understood, as they can have repercussions in activities of daily living. RESEARCH QUESTION: What happens to postural balance, mobility, and handgrip strength of COVID-19 patients after hospitalization? METHODS: A prospective cohort study was conducted with patients of both sexes, aged ≥18, admitted to hospital diagnosed with COVID-19. Outcomes were assessed at 1, 4, 6, and 12 months post-discharge, including: postural balance - Brief-Balance Evaluation Systems Test, mobility - Timed "Up & Go" Test, and handgrip strength - dynamometry. Prevalence values of impaired postural balance and mobility and lower-than-expected handgrip strength were calculated by point estimate and 95 % confidence interval. Shapiro-Wilk test showed that our data did not have a normal distribution, so the Friedman Test and the test of proportions were used for the statistical analysis. RESULTS: Performance on postural balance was improved after four months of hospital discharge, but the improvement in mobility and handgrip strength only occurred after six months. After six months of discharge, the proportion of individuals with impairments began to decrease. A higher prevalence of impairments in postural balance and mobility occurred at one month post-discharge, which reduced over time. However, the values of impairments for postural balance and mobility were still high after 12 months of follow-up. SIGNIFICANCE: There was a high prevalence of postural balance and mobility impairment 1 month after discharge, which was still high 12 months after discharge. The prevalence of lower-than-expected handgrip strength demonstrated limited change over time. Results highlight the need for assessment of postural balance, mobility and hand grip strength in post COVID-19 related hospitalization protocols, and long-term physical therapy interventions to address these impairments when identified to improve long term outcomes.

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Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-NG-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D2-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 µM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 µM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D2-like receptors.

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The Omp85 family of outer membrane proteins are ubiquitously distributed among diderm bacteria and play essential roles in outer membrane (OM) biogenesis. The majority of Omp85 orthologs are bipartite and consist of a conserved OM-embedded 16-stranded beta-barrel and variable periplasmic functional domains. Here, we demonstrate that Leptospira interrogans encodes four distinct Omp85 proteins. The presumptive leptospiral BamA, LIC11623, contains a noncanonical POTRA4 periplasmic domain that is conserved across Leptospiraceae. The remaining three leptospiral Omp85 proteins, LIC12252, LIC12254 and LIC12258, contain conserved beta-barrels but lack periplasmic domains. Two of the three 'noNterm' Omp85-like proteins were upregulated by leptospires in urine from infected mice compared to in vitro and/or following cultivation within rat peritoneal cavities. Mice infected with a L. interrogans lic11254 transposon mutant shed tenfold fewer leptospires in their urine compared to mice infected with the wild-type parent. Analyses of pathogenic and saprophytic Leptospira spp. identified five groups of noNterm Omp85 paralogs, including one pathogen- and two saprophyte-specific groups. Expanding our analysis beyond Leptospira spp., we identified additional noNterm Omp85 orthologs in bacteria isolated from diverse environments, suggesting a potential role for these previously unrecognized noNterm Omp85 proteins in physiological adaptation to harsh conditions.

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BACKGROUND: The recent push to "decolonize nursing" has become a critical movement to address institutional racism, but the term has circulated through nursing circles enough to risk becoming a buzzword. PURPOSE: This article clarifies "decolonizing nursing" by addressing the following questions: (a) How has "decolonizing nursing" been discussed in nursing research? (b) What specific projects have been implemented to decolonize nursing? (c) How has decolonizing nursing been related to health equity? METHODS: We conducted a scoping review and searched CINAHL, PubMed, and PsycINFO databases. A total of N = 56 records were included. DISCUSSION: "Decolonization" has referred to a range of ideas related to resisting Western ideals, legitimizing Indigenous knowledge, and repatriating land and territory especially to Indigenous and dispossessed communities. Few empirical studies have examined the relationship between decolonization or colonialism and specific health outcomes. CONCLUSION: Decolonization differs from other social justice initiatives. To clarify what decolonizing nursing means, researchers can engage with historical, interdisciplinary, and community-based participatory research. In turn, nursing research will understand colonialism's historical context, provide evidence that supports policies that protect Indigenous territory, and design clinical interventions that promote health equity for dispossessed populations.

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How can short-lived molecules selectively maintain the potentiation of activated synapses to sustain long-term memory? Here, we find kidney and brain expressed adaptor protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action to maintain late-phase long-term potentiation (late-LTP) at activated synapses. Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, yet neither measurably affects basal synaptic transmission. Neither antagonist affects PKMζ-independent LTP or memory that are maintained by compensating PKCs in ζ-knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 1-month-old memory despite PKMζ turnover. Therefore, it is not PKMζ alone, nor KIBRA alone, but the continual interaction between the two that maintains late-LTP and long-term memory.

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Workplace violence (WPV) against healthcare workers (HCW) is a globally growing problem in healthcare systems. Despite decades of research and interventions violent incidents are rising in their severity and frequency. A structured review of PubMed and Scopus databases and supplementary internet searches, resulted in a synthesis of evidence covering multiple countries and healthcare worker populations. High rates of WPV are increasingly common due to unmet patient expectations, poor communication, long wait times and organizational factors such as resourcing and infrastructure. We highlight links between WPV and poor worker health outcomes, staff turnover, reduced patient safety and medical errors. Few prevention and mitigation activities have shown sustained effects, highlighting the challenges in understanding and addressing the complex interplay of factors that drive violence against HCWs. The rapidly rising incidence of WPV requires special consideration and action from multiple stakeholders including patients and visitors, healthcare providers, law enforcement, media and policy makers.

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INTRODUCTION: Pneumococcal meningitis outbreaks occur sporadically in the African meningitis belt. Outbreak control guidelines and interventions are well established for meningococcal but not pneumococcal meningitis. Mathematical modelling is a useful tool for assessing the potential impact of different pneumococcal control strategies. This work aimed to estimate the impact of reactive vaccination with pneumococcal conjugate vaccine (PCV) had it been implemented in past African meningitis belt outbreaks and assess their efficiency relative to existing routine infant immunisation with PCV. METHODS & RESULTS: Using recent pneumococcal meningitis outbreaks in Burkina Faso, Chad, and Ghana as case studies, we investigated the potential impact of reactive vaccination. We calculated the number needed to vaccinate to avert one case (NNV) in each outbreak setting and over all outbreaks and compared this to the NNV for existing routine infant vaccination. We extended previous analyses of reactive vaccination by considering longer-term protection in vaccinees over five years, incorporating a proxy for indirect effects. We found that implementing reactive vaccination in previous pneumococcal meningitis outbreaks could have averted up to 10-20 % of outbreak cases, with the biggest potential impact in Brong Ahafo, Ghana (2015-2016) and Goundi, Chad (2009). The NNV, and hence the value of reactive vaccination, varied greatly. 'Large' (80 + cumulative modelled cases per 100,000 population) and/or 'prolonged' (exceeding a response threshold of 10 suspected cases per 100,000 per week for four weeks or more) outbreaks had NNV estimates under 10,000. For routine infant vaccination with PCV, the estimated NNV ranged from 3,100-5,600 in Burkina Faso and 1,500-2,600 in Ghana. IMPLICATIONS: This analysis provides evidence to inform the design of pneumococcal meningitis outbreak response guidelines. Countries should consider reactive vaccination in each outbreak event, together with maintaining routine infant vaccination as the primary intervention to reduce pneumococcal disease burden and outbreak risk.

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The representation of distinct spaces by hippocampal place cells has been linked to changes in their place fields (the locations in the environment where the place cells discharge strongly), a phenomenon that has been termed 'remapping'. Remapping has been assumed to be accompanied by the reorganization of subsecond cofiring relationships among the place cells, potentially maximizing hippocampal information coding capacity. However, several observations challenge this standard view. For example, place cells exhibit mixed selectivity, encode non-positional variables, can have multiple place fields and exhibit unreliable discharge in fixed environments. Furthermore, recent evidence suggests that, when measured at subsecond timescales, the moment-to-moment cofiring of a pair of cells in one environment is remarkably similar in another environment, despite remapping. Here, I propose that remapping is a misnomer for the changes in place fields across environments and suggest instead that internally organized manifold representations of hippocampal activity are actively registered to different environments to enable navigation, promote memory and organize knowledge.

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Aquatic plants (macrophytes) are important for ecosystem structure and function. Macrophyte mass developments are, however, often perceived as a nuisance and are commonly managed by mechanical removal. This is costly and often ineffective due to macrophyte regrowth. There is insufficient understanding about what causes macrophyte mass development, what people who use water bodies consider to be a nuisance, or the potential negative effects of macrophyte removal on the structure and function of ecosystems. To address these gaps, we performed a standardized set of in situ experiments and questionnaires at six sites (lakes, reservoirs, and rivers) on three continents where macrophyte mass developments occur. We then derived monetary values of ecosystem services for different scenarios of macrophyte management ("do nothing", "current practice", "maximum removal"), and developed a decision support system for the management of water courses experiencing macrophyte mass developments. We found that (a) macrophyte mass developments often occur in ecosystems which (unintentionally) became perfect habitats for aquatic plants, that (b) reduced ecosystem disturbance can cause macrophyte mass developments even if nutrient concentrations are low, that (c) macrophyte mass developments are indeed perceived negatively, but visitors tend to regard them as less of a nuisance than residents do, that (d) macrophyte removal lowers the water level of streams and adjacent groundwater, but this may have positive or negative overall societal effects, and that (e) the effects of macrophyte removal on water quality, greenhouse gas emissions, and biodiversity vary, and likely depend on ecosystem characteristics and macrophyte life form. Overall, we found that aquatic plant management often does not greatly affect the overall societal value of the ecosystem, and we suggest that the "do nothing" option should not be easily discarded in the management of perceived nuisance mass developments of aquatic plants.

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Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

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ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

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