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Introduction: Preventing suicide requires identifying psychosocial characteristics and risk factors of people who do not go to the hospital. This study examined factors associated with refusal of transport to the hospital after reporting suicidal ideation or suicide attempt to emergency medical services., Methods: This retrospective observational study involved reviewing emergency medical service dispatch records collected from January 2019 to December 2020 in Gyeonggi Province, South Korea on patients seeking emergency assistance for suicidal ideation or attempt. Univariate and multivariable regression analyses were employed to identify factors associated with refusal of transport to the hospital. Additionally, predictors of refusal stratified by suicidal ideation and attempt were examined., Results: A total of 3449 cases were included in the analysis. Patients with suicidal ideation and no psychiatric or medical issues were more likely to refuse transport. In the suicide attempt group, certain patient characteristics were linked to a higher probability of refusal, including age 25 to 44 or 45 to 64, male gender, and/or not intoxicated by alcohol., Conclusions: The pre-hospital phase is a critical link between patients and mental health services. Therefore, identifying the characteristics of patients who refuse transport to the hospital and developing intervention measures for them is essential., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Earth owes much of its dynamic surface to its bimodal hypsometry, manifested by high-riding continents and low-riding ocean basins. The thickness of the crust in the lithosphere exerts the dominant control on the long-wavelength elevations of continents. However, there is a limit to how high elevations can rise by crustal thickening. With continuous crustal thickening, the mafic lower crust eventually undergoes a densifying phase transition, arresting further elevation gain-an effect clearly observed in modern orogenic belts. On early Earth, lower crust densification should also limit how high a thickening crust can rise, regardless of the thickening mechanisms. We suggest that lower crust densification combined with a thicker oceanic crust in the Archean may have limited the whole-Earth topographic relief to 3 to 5 kilometers at most-half that of the present day. Unless the oceans were far less voluminous, limited relief would inevitably lead to a water world on early Earth.

Schistosoma mansoni infection leads to chronic schistosomiasis and severe hepatic fibrosis. We designed a liver-targeted lipid nanoparticle (LNP) carrying siRNA against type I TGF-β receptor (TGFβRI) mRNA to treat schistosomiasis-induced liver fibrosis in BALB/c mice. Knockdown of TGFβRI by LNP-siTGFβRI reduced LX-2 cell activation in vitro and alleviated liver fibrosis in S. mansoni-infected mice. αSMA and Col1a1 fibrotic markers in the liver tissues of infected mice were significantly suppressed in the treatment groups. In the serum of the LNP-siTGFβRI-treated groups, cytokines IFNγ, IL-1α, IL-6, IL-12, RANTES (CCL5), and TNFα increased, while GM-CSF, IL-2, IL-4, IL-10, IL-13, and KC (CXCL1) decreased compared to the control. Cell proportions were significantly altered in S. mansoni-infected mice, with increased CD56d NK cells and decreased CD19+ B cells and CD4+ T cells compared to naïve mice. Following LNP-siTGFβRI treatment, CD56d NK cells were downregulated, while B and memory Th cell populations were upregulated. The density of fibrotic regions significantly decreased with LNP-siTGFβRI treatment in a dose-dependent manner, and no systemic toxicity was observed in the major organs. This targeted siRNA delivery strategy effectively reduced granulomatous lesions in schistosomiasis-induced liver fibrosis without detectable side effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Contralateral prophylactic mastectomy (CPM) remains a personal decision, influenced by psychosocial factors, including cosmesis and peace of mind. Although use of CPM is disproportionately low among Black patients, the degree to which these disparities are driven by patient- vs hospital-level factors remains unknown., Study Design: Patients undergoing mastectomy for nonmetastatic ductal or lobular breast cancer were tabulated using the National Cancer Database from 2004 to 2020. The primary endpoint was receipt of CPM. Multivariable logistic regression models were constructed with interaction terms between Black-serving hospital (BSH) status and patient race to evaluate associations with CPM. Cox proportional hazard models were used to evaluate long-term survival., Results: Of 597,845 women studied, 70,911 (11.9%) were Black. After multivariable adjustment, Black race (adjusted odds ratio 0.65, 95% CI 0.64 to 0.67) and treatment at BSH (adjusted odds ratio 0.84, 95% CI 0.83 to 0.85) were independently linked to lower odds of CPM. Although predicted probability of CPM was universally lower at higher BSH, Black patients faced a steeper reduction compared with White patients. Receipt of CPM was linked to improved survival (hazard ratio [HR] 0.84, 95% CI 0.83 to 0.86), whereas Black race was associated with a greater HR of 10-year mortality (HR 1.14, 95% CI 1.12 to 1.17)., Conclusions: Hospitals serving a greater proportion of Black patients are less likely to use CPM, suggestive of disparities in access to CPM at the institutional level. Further research and education are needed to characterize surgeon-specific and institutional practices in patient counseling and shared decision-making that shape disparities in access to CPM., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cardiopulmonary resuscitation training is a mandatory competency, especially for healthcare professionals. However, the spread of COVID-19 caused a sharp decline in the number of participants on advanced life support training, thereby accelerating the diversification of educational methods. Gamification is an increasingly popular method of diversifying instruction, but its effectiveness remains controversial., Aim: To evaluate the effectiveness of gamification learning in advanced life support training., Design: A cluster randomized controlled trial., Setting: A single advanced life support training center., Participants: Clinical nurses who are currently practicing in a hospital., Methods: A part of the existing advanced life support course was gamified using Kahoot! platform. Conventional learning and gamified learning were each conducted 11 times, and the level of knowledge after training was assessed. The assessment questions were categorized into advanced life support algorithms, teamwork, and cardiac arrest rhythms., Results: A total of 267 were enrolled in the study, and 148 and 139 learners were assigned to CL and GL, respectively. There was no difference in post-training knowledge related to teamwork, and cardiac arrest rhythms between the conventional learning and gamified learning groups, but knowledge related to the advanced life support algorithm was low in the gamified learning group., Conclusions: Even if the learners are the same, advanced life support gamification training can lead to negative outcomes depending on the simplicity or goal of the training content. To improve the effectiveness of the training, various methods of gamification training should be applied depending on the goal and content of the training., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

Massif-type anorthosites, enormous and enigmatic plagioclase-rich cumulate intrusions emplaced into Earth's crust, formed in large numbers only between 1 and 2 billion years ago. Conflicting hypotheses for massif-type anorthosite formation, including melting of upwelling mantle, lower crustal melting, and arc magmatism above subduction zones, have stymied consensus on what parental magmas crystallized the anorthosites and why the rocks are temporally restricted. Using B, O, Nd, and Sr isotope analyses, bulk chemistry, and petrogenetic modeling, we demonstrate that the magmas parental to the Marcy and Morin anorthosites, classic examples from North America's Grenville orogen, require large input from mafic melts derived from slab-top altered oceanic crust. The anorthosites also record B isotopic signatures corresponding to other slab lithologies such as subducted abyssal serpentinite. We propose that anorthosite massifs formed underneath convergent continental margins wherein a subducted or subducting slab melted extensively and link massif-type anorthosite formation to Earth's thermal and tectonic evolution.

Objective: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression., Design: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation., Results: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001)., Conclusions: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability., Competing Interests: Declaration of Competing Interest No author in this paper has competing interests to disclose., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Study of morphogenesis and its regulation requires analytical tools that enable simultaneous assessment of processes operating at cellular level, such as synthesis of transcription factors (TF), with their effects at the tissue scale. Most current studies conduct histological, cellular and immunochemical (IHC) analyses in separate steps, introducing inevitable biases in finding and alignment of areas of interest at vastly distinct scales of organization, as well as image distortion associated with image repositioning or file modifications. These problems are particularly severe for longitudinal analyses of growing structures that change size and shape. Here we introduce a python-based application for automated and complete whole-slide measurement of expression of multiple TFs and associated cellular morphology. The plugin collects data at customizable scale from the cell-level to the entire structure, records each data point with positional information, accounts for ontogenetic transformation of structures and variation in slide positioning with scalable grid, and includes a customizable file manager that outputs collected data in association with full details of image classification (e.g., ontogenetic stage, population, IHC assay). We demonstrate the utility and accuracy of this application by automated measurement of morphology and associated expression of eight TFs for more than six million cells recorded with full positional information in beak tissues across 12 developmental stages and 25 study populations of a wild passerine bird. Our script is freely available as an open-source Fiji plugin and can be applied to IHC slides from any imaging platforms and transcriptional factors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: The existing diagnostic methods for coronary artery disease (CAD), such as coronary angiography and fractional flow reserve (FFR), have limitations regarding their invasiveness, cost, and discomfort. We explored a novel diagnostic approach, coronary contrast intensity analysis (CCIA), and conducted a comparative analysis between it and FFR., Methods: We used an in vitro coronary-circulation-mimicking system with nine stenosis models representing various stenosis lengths (6, 18, and 30 mm) and degrees (30%, 50%, and 70%). The angiographic brightness values were analyzed for CCIA. The in vivo experiments included 15 patients with a normal sinus rhythm. Coronary angiography was performed, and arterial movement was tracked, enabling CCIA derivation. The CCIA values were compared with the FFR ( n = 15) and instantaneous wave-free ratio (iFR; n = 11) measurements., Results: In vitro FFR showed a consistent trend related to the length and severity of stenosis. The CCIA was related to stenosis but had a weaker correlation with length, except for with 70% stenosis (6 mm: 0.82 ± 0.007, 0.68 ± 0.007, 0.61 ± 0.004; 18 mm: 0.78 ± 0.052, 0.69 ± 0.025, 0.44 ± 0.016; 30 mm: 0.80 ± 0.018, 0.64 ± 0.006, 0.40 ± 0.026 at 30%, 50%, and 70%, respectively). In vitro CCIA and FFR were significantly correlated (R = 0.9442, p < 0.01). The in vivo analysis revealed significant correlations between CCIA and FFR (R = 0.5775, p < 0.05) and the iFR ( n = 11, R = 0.7578, p < 0.01)., Conclusions: CCIA is a promising alternative for diagnosing stenosis in patients with CAD. The initial in vitro validation and in vivo confirmation in patients demonstrate the feasibility of applying CCIA during coronary angiography. Further clinical studies are warranted to fully evaluate the diagnostic accuracy and potential impact of CCIA on CAD management.

Objective: To compare the efficacy and safety of ketamine alone with those of ketamine-dexmedetomidine combination for sedation during brain CT in paediatric patients with head injuries., Methods: We retrospectively analysed the data of paediatric patients who underwent sedation for brain CT at the ED. We included patients aged 6 months to 6 years with American Society of Anesthesiologists physical status I or II. The sedative protocol involved the administration of intramuscular (IM) ketamine 3 mg/kg (K), ketamine 2 mg/kg with dexmedetomidine 1.5 μg/kg (KD) or ketamine 1.5 mg/kg with dexmedetomidine 1.5 μg/kg (low-KD). The primary and secondary outcomes were sedation failure and adverse events, respectively., Results: We included 77 patients; among them, 28, 23 and 26 were in the K, KD and low-KD groups, respectively. In multivariable analysis, the combination groups (KD and low-KD groups) were significantly associated with a lower possibility of sedation failure compared to the K group (adjusted odds ratio, 0.12; 95% confidence interval, 0.02-0.56). Moreover, there were no significant differences in adverse events between the groups, and the sedation-related time variables also did not significantly differ among the three groups., Conclusions: Our findings indicated that a combination of IM ketamine-dexmedetomidine provides effective sedation for paediatric patients undergoing brain CT without significant adverse events. Further research is needed to investigate the potential benefits of using lower doses of ketamine in combination., (© 2024 Australasian College for Emergency Medicine.)

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator in development for immune-mediated inflammatory diseases (IMIDs). Here, we report the human safety, pharmacokinetics, and pharmacodynamics of etrasimod obtained from both a single ascending dose (SAD; 0.1-5 mg) study and a multiple ascending dose (MAD; 0.35-3 mg once daily) study. Overall, 99 healthy volunteers (SAD n = 40, MAD n = 59) completed the 2 studies. Evaluated single and multiple doses were well tolerated up to 3 mg without severe adverse events (AEs). Gastrointestinal disorders were the most common etrasimod-related AEs. Over the evaluated single- and multiple-dose ranges, dose-proportional and marginally greater-than-dose-proportional etrasimod plasma exposure were observed, respectively. At steady state, etrasimod oral clearance and half-life mean values ranged from 1.0 to 1.2 L/h and 29.7 to 36.4 hours, respectively. Dose-dependent total peripheral lymphocyte reductions occurred following etrasimod single and multiple dosing. Etrasimod multiple dosing resulted in reductions from baseline in total lymphocyte counts ranging from 41.1% to 68.8% after 21 days. Lymphocyte counts returned to normal range within 7 days following treatment discontinuation. Heart rate lowering from pretreatment baseline on etrasimod dosing was typically mild, with mean reductions seen after the first dose of up to 19.5 bpm (5 mg dose). The favorable safety, pharmacokinetic, and pharmacodynamic properties of etrasimod in humans supported its further development and warranted its investigation for treatment of IMIDs., (© 2024 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Introduction: There are many reasons why orthopaedic surgeons move or change careers. We asked the questions: (1) What is the geographic distribution of orthopaedic surgeons with respect to age, sex, and race and ethnicity? (2) How has our workforce changed over time with regard to these factors? (3) Are there any patterns or trends detected regarding policy or regulatory events that coincide with these differences?, Methods: The American Academy of Orthopaedic Surgeons surveys over 30,000 members, collecting data on demographics, age, race sex, and practice statistics. We calculated geographic distributions and evaluated these differences over time-potential influences from malpractice suits or tort reform were investigated., Results: Overall surgeon density increased over time. The largest negative changes were noted in District of Columbia, Wyoming, and North Dakota and positive changes in Colorado, South Dakota, and West Virginia. Age across all states increased (mean 1.7 years). Number of female surgeons increased in most states (4.6% to 5.7%). Number of  African Americans increased from 1.6% to 1.8%, Hispanic/LatinX from 1.8% to 2.2%, Asian from 5.5% to 6.7%, and multiracial from 0.8% to 1.2%. No change was noted in the percentage of Native American surgeons., Discussion: Surgeon density increased from 2012 to 2018; the cause for this change was not evident. Small increases in surgeon population, female surgeons, and in some underrepresented minorities were seen., Competing Interests: Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H905 ).

Background: The United States envisions a 90% reduction in HIV infections by 2030. However, the COVID-19 pandemic disrupted the HIV continuum and disproportionately affected access to social and health services for people at the highest vulnerability. This study shows how stakeholders in the State of Michigan handled disruptions and their key recommendations. As a case study, this study adds to the literature about preparedness for future pandemics., Methods: We interviewed 33 statewide Michigan HIV/AIDS Council members-practitioners, researchers, and community representatives, guiding service planning, improvement, and resource allocations, measuring group cohesiveness using a tested scale. We measured group cohesiveness as a proxy for how individual opinions reflected those of the Council as a group. We used qualitative questions to assess: (1) how the COVID-19 pandemic disrupted HIV prevention; (2) how disruptions were handled; and (3) recommendation to help address disruptions now and in the future. Using thematic analysis, we coded the interviews., Results: We found a high degree of cohesiveness. Participants agreed that the pandemic disrupted HIV prevention services (e.g., HIV testing, PrEP education, referrals to primary care, etcetera) offered by community organizations, hospital clinics, and health departments across the state. In response, they developed online and curbside services to maintain HIV services, abate social isolation, and address structural issues like lack of food and public transportation. We organized results in four categories: (1) HIV service disruptions (e.g., "Housing for women and children who are fleeing a legal situation"); (2) Responses to disruptions (e.g., "Some of them, we would say, hey, weather permitting, we'll come out to your car"); (3) Minoritized groups disproportionately affected (e.g., "Especially in my community, to get people if there's ever a vaccine, Black people are going to be the last people to take it"); and (4) Recommendations (below)., Conclusions: The pandemic unsettled and further exacerbated every aspect of HIV service provision. The main recommendation was to overhaul communication systems between government and organizations offering HIV services to mitigate disruptions and improve the chances of achieving a 90% reduction., (© 2024. The Author(s).)

Introduction: The heterogeneity of depressive and anxiety disorders complicates clinical management as it may account for differences in trajectory and treatment response. Self-schemas, which can be determined by Self-Referential Judgements (SRJs), are heterogeneous yet stable. SRJs have been used to characterize personality in the general population and shown to be prognostic in depressive and anxiety disorders., Methods: In this study, we used SRJs from a Self-Referential Encoding Task (SRET) to identify clusters from a clinical sample of 119 patients recruited from the Institute of Mental Health presenting with depressive or anxiety symptoms and a non-clinical sample of 115 healthy adults. The generated clusters were examined in terms of most endorsed words, cross-sample correspondence, association with depressive symptoms and the Depressive Experiences Questionnaire and diagnostic category., Results: We identify a 5-cluster solution in each sample and a 7-cluster solution in the combined sample. When perturbed, metrics such as optimum cluster number, criterion value, likelihood, DBI and CHI remained stable and cluster centers appeared stable when using BIC or ICL as criteria. Top endorsed words in clusters were meaningful across theoretical frameworks from personality, psychodynamic concepts of relatedness and self-definition, and valence in self-referential processing. The clinical clusters were labeled "Neurotic" (C1), "Extraverted" (C2), "Anxious to please" (C3), "Self-critical" (C4), "Conscientious" (C5). The non-clinical clusters were labeled "Self-confident" (N1), "Low endorsement" (N2), "Non-neurotic" (N3), "Neurotic" (N4), "High endorsement" (N5). The combined clusters were labeled "Self-confident" (NC1), "Externalising" (NC2), "Neurotic" (NC3), "Secure" (NC4), "Low endorsement" (NC5), "High endorsement" (NC6), "Self-critical" (NC7). Cluster differences were observed in endorsement of positive and negative words, latency biases, recall biases, depressive symptoms, frequency of depressive disorders and self-criticism., Discussion: Overall, clusters endorsing more negative words tended to endorse fewer positive words, showed more negative biases in reaction time and negative recall bias, reported more severe depressive symptoms and a higher frequency of depressive disorders and more self-criticism in the clinical population. SRJ-based clustering represents a novel transdiagnostic framework for subgrouping patients with depressive and anxiety symptoms that may support the future translation of the science of self-referential processing, personality and psychodynamic concepts of self-definition to clinical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tan, Wang, Tan, Ong, Ooi, Lee, Rane, Tey, Chua, Goh, Lam, Chakraborty, Yew, Ong, Kee, Lim, Hashim, Lu, Meany, Tolomeo, Lee, Tan and Keppo.)

Most of the world's biodiversity is described primarily or exclusively using morphological traits that may not always reflect the true evolutionary units. Accurate taxonomy is critical for conservation efforts and re-evaluation of traditional taxonomy may often be warranted since species and subspecies are frequently the focus of conservation and faunistic studies. Here, we test comprehensive taxonomic hypotheses of morphologically defined subspecies in the tiger beetle, Eunota togata (LaFerté-Sénectère, 1841). The four recognized subspecies were delineated based mainly on the dorsal coloration and extent of white markings termed maculations. We combine inferences from mtDNA genealogies and genome-wide multilocus data to elucidate the evolutionary relationships within the group and assess the taxonomic implications. Three of the four subspecific taxa delineated by morphology were not supported by the genomic or mtDNA data. In fact, the species-level diversity in this group was underestimated, as E. togata was found to represent three well-supported distinct species in all genetic analyses. Emerging from these analyses, we also document an intriguing example of convergent evolution in lighter colored E. togata adapting to similar white saline backgrounds. Our collective work underscores the importance of using molecular methods to reevaluate morphological based taxonomy for species and subspecies delimitation and conservation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In molecular dimers that undergo intramolecular singlet fission (iSF), efficient iSF is typically accompanied by triplet pair annihilation at rates which prohibit effective triplet harvesting. Collisional triplet pair separation and intramolecular separation by hopping to additional sites in extended oligomers are both strategies that have been reported to be effective for acene based iSF materials in the literature. Herein, a family of highly soluble diphenylhexatriene (DPH) oligomers were synthesized and investigated using transient absorption spectroscopy to determine whether these approaches can be applied to the non-acene singlet fission chromophore, DPH. While iSF proceeds rapidly for all three new materials, neither concentration nor oligomer size result in significantly enhanced triplet pair lifetime relative to the dilute dimer case. These null results indicate the fallibility of the collisional separation and oligomerisation strategies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Nervous systems of vertebrates and invertebrates show a common modular theme in the flow of information for cost-benefit decisions. Sensory inputs are incentivized by integrating stimulus qualities with motivation and memory to affect appetitive state, a system of homeostatic drives, and labelled for directionality. Appetitive state determines action responses from a repertory of possibles and transmits the decision to a premotor system that frames the selected action in motor arousal and appropriate postural and locomotion commands. These commands are then sent to the primary motor pattern generators controlling the motorneurons, with feedback at each stage. In the vertebrates, these stages are mediated by forebrain pallial derivatives for incentive and directionality (olfactory bulb, cerebral cortex, pallial amygdala, etc. ) interacting with hypothalamus (homeostasis, motivation, and reward) for action selection in the forebrain basal ganglia, the mid/hindbrain reticular formation as a premotor translator for posture, locomotion, and arousal state, and the spinal cord and cranial nuclei as primary motor pattern generators. Gastropods, like the predatory sea slug Pleurobranchaea californica , show a similar organization but with differences that suggest how complex brains evolved from an ancestral soft-bodied bilaterian along with segmentation, jointed skeletons, and complex exteroceptors. Their premotor feeding network combines functions of hypothalamus and basal ganglia for homeostasis, motivation, presumed reward, and action selection for stimulus approach or avoidance. In Pleurobranchaea , the premotor analogy to the vertebrate reticular formation is the bilateral "A-cluster" of cerebral ganglion neurons that controls posture, locomotion, and serotonergic motor arousal. The A-cluster transmits motor commands to the pedal ganglia analogs of the spinal cord, for primary patterned motor output. Apparent pallial precursors are not immediately evident in Pleurobranchaea 's central nervous system, but a notable candidate is a subepithelial nerve net in the peripheral head region that integrates chemotactile stimuli for incentive and directionality. Evolutionary centralization of its computational functions may have led to the olfaction-derived pallial forebrain in the ancestor's vertebrate descendants and their analogs in arthropods and annelids., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gribkova, Lee, Brown, Cui, Liu, Norekian and Gillette.)

Aim: This study presents the impact of COVID-19 on revisits to the emergency department comparing revisit rates and characteristics between the pre-COVID-19 and COVID-19 periods., Methods: This multi-center retrospective study included patients over 18 years of age who visited emergency departments during the pre-COVID-19 period and the COVID-19 pandemic. The revisit rates were analyzed according to five age groups; 18-34, 35-49, 50-64, 65-79, and ≥ 80 years, and three revisit time intervals; 3, 9, and 30 days. Also, we compared the diagnosis and disposition at revisit between the study periods., Results: The revisit rates increased with age in both study periods and the revisit rates among all age groups were higher in the COVID-19 period. The proportion of infectious and respiratory diseases decreased during the COVID-19 period. The ICU admission rate and mortality at the revisit among patients aged ≥ 80 years were lower in the COVID-19 period than in the pre-COVID-19 period., Conclusion: The revisit rates increased with age in both study periods and there were several changes in the diagnosis and disposition at the revisit in the COVID-19 period., (Copyright © 2023 College of Emergency Nursing Australasia. Published by Elsevier Ltd. All rights reserved.)

Introduction: In health professions education, faculty may feel frustrated or challenged by aspects of their teaching. The concept of a hidden curriculum for students describes the expectations and assumptions enacted in educational programmes that tacitly impact students' learning experiences. A hidden curriculum has been suggested as a possible influence on faculty but has not been well explored. The aim of this study was to explain how a hidden curriculum might operate for faculty in health professions education., Methods: An interpretivist perspective was used to frame this qualitative study that examined one-on-one interview data generated with 16 faculty members from six different health care professions. Participants were asked to describe teaching experiences that they perceived as demanding. Using a hidden curriculum framework, descriptions of demanding teaching experiences were analysed inductively to identify relationships between a teacher's intended practice and what they could accomplish. These relationships were interpreted as the possible ways that a hidden curriculum was operating for faculty., Results: A hidden curriculum for faculty was found to operate in three ways by undervaluing the importance of having teaching expertise, undermining teaching goals through institutional conventions and perpetuating feelings of isolation., Discussion: A hidden curriculum for faculty can be represented as multiple overlapping domains and shape how faculty experience their teaching roles. The results provide examples that reveal how a hidden curriculum may operate for faculty. Faculty developers may find the insights provided by this study useful to make the hidden curriculum visible and help their faculty make sense of and navigate demanding teaching experiences., (© 2023 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: In sports, hip flexibility is essential to reduce injuries and improve performance., Aim: This study aimed to examine the effects of auricular acupressure on hip flexibility and pain in Taekwondo participants., Method: This randomized controlled trial was performed in the Republic of Korea from January 2021 to August 2021. The Numeric Rating Scale for Pain and Hip Flexibility was used. Twenty-one participants received auricular pressure once weekly for six weeks, while 17 participants did not receive any intervention. Auricular acupressure was applied to the hip (AH13), Shinmun, and auricular acupressure points associated with the pain areas reported by the participants., Results: Auricular acupressure improved hip flexibility (t = 2.67, p = .011) and back pain (t = 2.11, p = .043). The mean difference in post-pretest hip flexibility in the experimental group was 16.24 degrees (±13.63), whereas that in the control group was 4.77 degrees (±15.07). The mean difference in the experimental group's pre-post-test scores of back pain was 1.24 (±2.64), whereas that in the control group was 0.18 (±1.41)., Conclusions: The results of this study showed that auricular acupressure could be used to treat pain and improve hip flexibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The spread of infectious diseases has accelerated the transition from face-to-face (F2F) to non-F2F (NF2F) education. To maintain the effect of successful NF2F education in cardiopulmonary resuscitation, reorganizing the curriculum to suit the NF2F educational environment is necessary. We propose an appropriate learning curriculum for NF2F basic life support (BLS) training for laypersons based on expert surveys and learners' performance outcomes. This study included three stages and used multiple methods. A draft curriculum was created through a literature review and three-round Delphi approach, and then applied as a test for actual education. After the training, the final curriculum of the NF2F BLS training for laypersons was proposed by reflecting on the performance outcomes of learners and expert opinions. NF2F theoretical education was simplified into five content items: concept of chain of survival, legal protection for first aiders, importance of bystander cardiopulmonary resuscitation, how to recognize a patient in cardiac arrest and activate the emergency medical services system, and reduced training time. In the hands-on skills session, it was recommended to practice chest compressions using a simple intuitive feedback device and to use automated external defibrillators step-by-step more than in F2F training. In conclusion, NF2F training is a suitable option for BLS training methods in situations where F2F training is difficult.

Background: Adaptive interventions are often used in individualized health care to meet the unique needs of clients. Recently, more researchers have adopted the Sequential Multiple Assignment Randomized Trial (SMART), a type of research design, to build optimal adaptive interventions. SMART requires research participants to be randomized multiple times over time, depending upon their response to earlier interventions. Despite the increasing popularity of SMART designs, conducting a successful SMART study poses unique technological and logistical challenges (e.g., effectively concealing and masking allocation sequence to investigators, involved health care providers, and subjects) in addition to other challenges common to all study designs (e.g., study invitations, eligibility screening, consenting procedures, and data confidentiality protocols). Research Electronic Data Capture (REDCap) is a secure, browser-based web application widely used by researchers for data collection. REDCap offers unique features that support researchers' ability to conduct rigorous SMARTs. This manuscript provides an effective strategy for performing automatic double randomization for SMARTs using REDCap., Methods: Between January and March 2022, we conducted a SMART using a sample of adult (age 18 and older) New Jersey residents to optimize an adaptive intervention to increase COVID-19 testing uptake. In the current report, we discuss how we used REDCap for our SMART, which required double randomization. Further, we share our REDCap project XML file for future investigators to use when designing and conducting SMARTs., Results: We report on the randomization feature that REDCap offers and describe how the study team automated an additional randomization that was required for our SMART. An application programming interface was used to automate the double randomizations in conjunction with the randomization feature provided by REDCap., Conclusions: REDCap offers powerful tools to facilitate the implementation of longitudinal data collection and SMARTs. Investigators can make use of this electronic data capturing system to reduce errors and bias in the implementation of their SMARTs by automating double randomization., Trial Registration: The SMART study was prospectively registered at Clinicaltrials.gov; registration number: NCT04757298, date of registration: 17/02/2021., (© 2023. The Author(s).)

Background and Purpose: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study., Materials and Methods: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates., Results: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c ( P  < .005) and a history of diabetic ketoacidosis at disease onset ( P  < .05). We found a statistical interaction ( P  < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM., Conclusions: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes., (© 2023 by American Journal of Neuroradiology.)

Etrasimod (APD334) is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P 1,4,5 ) in development for treatment of various immune-mediated inflammatory disorders. The disposition and mass balance of a single 2-mg [ 14 C]etrasimod dose were evaluated in 8 healthy males. An in vitro study was also conducted to identify etrasimod's oxidative metabolizing enzymes. Peak concentrations of etrasimod and total radioactivity in plasma and whole blood were typically reached 4-7 hours postdose. Etrasimod constituted 49.3% of total radioactivity plasma exposure, with multiple minor/trace metabolites making up the remainder. Etrasimod was slowly cleared mainly via biotransformation, predominantly by oxidative metabolism, with unchanged etrasimod recovered in feces accounting for only 11.2% of the dose and none in urine. The mean apparent terminal half-lives of etrasimod and total radioactivity in plasma were 37.8 and 89.0 hours, respectively. Mean cumulative recovery of radioactivity in excreta over 336 hours was 86.9% of the dose, mostly in feces. The prevalent metabolites eliminated in feces were M3 (hydroxy-etrasimod) and M36 (oxy-etrasimod sulfate), accounting for 22.1% and 18.9% of the dose, respectively. From in vitro reaction phenotyping, the predominant enzymes involved in the oxidation of etrasimod were CYP2C8, CYP2C9, and CYP3A4, with minor contributions from CYP2C19 and CYP2J2., (© 2023 Arena Pharmaceuticals, Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

This paper demonstrates an AlGaInP-based 620-nm red micro-light-emitting-diode (µ-LED) array and studies the enhancement effect of the surface treatments using (NH 4 ) 2 Sx solutions by comparing the characteristics of µ-LED arrays with and without the (NH 4 ) 2 Sx treatment. Furthermore, our µ-LED array demonstrates a measurement of the current efficiency (2.6 cd/A), which improves the light output uniformity. Also, we apply a setup for measuring the response time at the fast ns-level to analyze the effect of passivation in AlGaInP-based µ-LED arrays.

Similar design characterizes neuronal networks for goal-directed motor control across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Evidence is lacking for whether this design evolved independently in those lineages, evolved in parallel with segmentation and appendages, or could have been present in a soft-bodied common ancestor. We examined coordination of locomotion in an unsegmented, ciliolocomoting gastropod, the sea slug Pleurobranchaea californica , which may better resemble the urbilaterian ancestor. Previously, bilateral A-cluster neurons in cerebral ganglion lobes were found to compose a multifunctional premotor network controlling the escape swim and feeding suppression, and mediating action selection for approach or avoidance turns. Serotonergic As interneurons of this cluster were critical elements for swimming, turning, and behavioral arousal. Here, known functions were extended to show that the As2/3 cells of the As group drove crawling locomotion via descending signals to pedal ganglia effector networks for ciliolocomotion and were inhibited during fictive feeding and withdrawal. Crawling was suppressed in aversive turns, defensive withdrawal, and active feeding, but not during stimulus-approach turns or prebite proboscis extension. Ciliary beating was not inhibited during escape swimming. These results show how locomotion is adaptively coordinated in tracking, handling, and consuming resources, and in defense. Taken with previous results, they also show that the A-cluster network acts similarly to the vertebrate reticular formation with its serotonergic raphe nuclei in facilitating locomotion, postural movements, and motor arousal. Thus, the general scheme controlling locomotion and posture might well have preceded the evolution of segmented bodies and articulated appendages. SIGNIFICANCE STATEMENT Similar design in the neuronal networks for goal-directed motor control is seen across the complex, segmented vertebrates, insects, and polychaete annelids with jointed appendages. Whether that design evolved independently or in parallel with complexity in body and behavior has been unanswered. Here it is shown that a simple sea slug, with primitive ciliary locomotion and lacking segmentation and appendages, has similar modular design in network coordination as vertebrates for posture in directional turns and withdrawal, locomotion, and general arousal. This suggests that a general neuroanatomical framework for the control of locomotion and posture could have arisen early during the evolution of bilaterians., (Copyright © 2023 the authors.)

Erythrocyte aggregation (EA) is a highly dynamic, vital phenomenon to interpreting human hemorheology, which would be helpful for the diagnosis and prediction of circulatory anomalies. Previous studies of EA on erythrocyte migration and the Fåhraeus Effect are based on the microvasculature. They have not considered the natural pulsatility of the blood flow or large vessels and mainly focused on shear rate along radial direction under steady flow to comprehend the dynamic properties of EA. To our knowledge, the rheological characteristics of non-Newtonian fluids under Womersley flow have not reflected the spatiotemporal behaviors of EA or the distribution of erythrocyte dynamics (ED). Hence, it needs to interpret the ED affected by temporal and spatial flow variation to understand the effect of EA under Womersley flow. Here, we demonstrated the numerically simulated ED to decipher EA's rheological role in axial shear rate under Womersley flow. In the present study, the temporal and spatial variations of the local EA were found to mainly depend on the axial shear rate under Womersley flow in an elastic vessel, while mean EA decreased with radial shear rate. The localized distribution of parabolic or M-shape clustered EA was found in a range of the axial shear rate profile (-15 to 15s -1 ) at low radial shear rates during a pulsatile cycle. However, the linear formation of rouleaux was realized without local clusters in a rigid wall where the axial shear rate is zero. In vivo, the axial shear rate is usually considered insignificant, especially in straight arteries, but it has a great impact on the disturbed blood flow due to the geometrical properties, such as bifurcations, stenosis, aneurysm, and the cyclic variation of pressure. Our findings regarding axial shear rate provide new insight into the local dynamic distribution of EA, which is a critical player in blood viscosity. These will provide a basis for the computer-aided diagnosis of hemodynamic-based cardiovascular diseases by decreasing the uncertainty in the pulsatile flow calculation., Competing Interests: Declaration of competing interest The authors declare that they do not have any competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H443 ).

We are pleased to see that Marino et al. have written a Comment: "Choroidal Thickness Measurements in the Case of Diabetic Macular Edema" [...].

Objective: The purpose of the current study was to use network analysis techniques to parse relations between attention-deficit/hyperactivity disorder (ADHD) symptom domains, domains of executive function, and temperament traits., Methods: Participants were 420 children aged 6-17 years (55% boys). The majority of the participants were Caucasian (72.86%) and 50% of the sample met diagnostic criteria for ADHD. Both parents and teachers provided ratings of participants' ADHD symptom severity. Parents completed questionnaires pertaining to participants' temperament traits, and participants completed well-validated laboratory measures of executive function., Results: Results suggested effortful control as demonstrating the strongest relations with ADHD, particularly the parent-reported inattentive symptom domain. Additionally, negative effects appeared to demonstrate weaker but still notable relations primarily with the parent-reported hyperactive/impulsive symptom domain. Measures of executive function did not appear to demonstrate relations with any measures of ADHD symptoms or temperament traits. The results were generally replicated in a distinct sample ( n = 732, 7-13 years, 63% boys, 81% White), although differences emerged pertaining to the role of surgency (i.e., related to the hyperactive/impulsive symptom domain in the replication but not the primary sample)., Conclusions: Overall, findings provided support for the primary role of effortful control, as well as secondary roles for negative affect and surgency, as key risk markers for the characterization of ADHD. Additional exploration of the overlap between temperament and executive function, as pertaining to ADHD, may help clarify heterogeneity in phenotypes and suggest priorities for targeted interventions outside of traditional symptoms.

The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending nociceptive drive due to amplification of, or a failure to suppress, incoming signals from the periphery. We aimed to explore whether a putative biomarker of spinal disinhibition, impaired rate-dependent depression of the Hoffmann reflex, is associated with a mechanistically appropriate and distinct pain phenotype in patients with painful diabetic neuropathy. In this cross-sectional study, 93 patients with diabetic neuropathy underwent testing of Hoffmann reflex rate-dependent depression and detailed clinical and sensory phenotyping, including quantitative sensory testing. Compared to neuropathic patients without pain, patients with painful diabetic neuropathy had impaired Hoffmann reflex rate-dependent depression at 1, 2 and 3 Hz ( P ≤ 0.001). Patients with painful diabetic neuropathy exhibited an overall loss of function profile on quantitative sensory testing. However, within the painful diabetic neuropathy group, cluster analysis showed evidence of greater spinal disinhibition associated with greater mechanical pain sensitivity, relative heat hyperalgesia and higher ratings of spontaneous burning pain. These findings support spinal disinhibition as an important centrally mediated pain amplification mechanism in painful diabetic neuropathy. Furthermore, our analysis indicates an association between spinal disinhibition and a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction: Fruit losses in the supply chain owing to improper handling and a lack of proper control are common in the industry. As losses are caused by the inefficiency of the export method, selecting the appropriate export method is a possible solution. Several organizations employ only a single strategy, which is mainly based on a first-in-first-out approach. Such a policy is easy to manage but inefficient. Given that the batch of fruits may become overripe during transportation, frontline operators do not have the authority or immediate support to change the fruit dispatching strategy. Thus, this study aims to develop a dynamic strategy simulator to determine the sequence of delivery based on forecasting information projected from probabilistic data to reduce the amount of fruit loss., Methods: The proposed method to accomplish asynchronous federated learning (FL) is based on blockchain technology and a serially interacting smart contract. In this method, each party in the chain updates its model parameters and uses a voting system to reach a consensus. This study employs blockchain technology with smart contracts to serially enable asynchronous FL, with each party in the chain updating its parameter model. A smart contract combines a global model with a voting system to reach a common consensus. Its artificial intelligence (AI) and Internet of Things engine further strengthen the support for implementing the Long Short-Term Memory (LSTM) forecasting model. Based on AI technology, a system was constructed using FL in a decentralized governance AI policy on a blockchain network platform., Results: With mangoes being selected as the category of fruit in the study, the system improves the cost-effectiveness of the fruit (mango) supply chain. In the proposed approach, the simulation outcomes show fewer mangoes lost (0.035%) and operational costs reduced., Discussion: The proposed method shows improved cost-effectiveness in the fruit supply chain through the use of AI technology and blockchain. To evaluate the effectiveness of the proposed method, an Indonesian mango supply chain business case study has been selected. The results of the Indonesian mango supply chain case study indicate the effectiveness of the proposed approach in reducing fruit loss and operational costs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lee, Chow, Chan and Lun.)

Background: The use of coring instrumentation for osteochondral allograft (OCA) transplantation of the femoral trochlea is challenging due to the complex topography of this anatomical area., Purpose: We sought to determine the effect of flat guides versus guides contoured to the surface of the trochlea on graft step-off in trochlear OCAs performed on a foam bone model. We also determined the effect of surgeon experience level and graft size on step-off., Study Design: Controlled laboratory study., Methods: Allograft harvesters were produced in 3 different sequential sizes with either a flat or a contoured undersurface. The guides matched one another in all aspects of shape and size except for the undersurface contour. The contoured undersurface generally matched the surface of the bone model trochlea but was not customized to that surface. A total of 72 foam femora were obtained. Identical trochlear stellate lesions of 3 different sizes (small, medium, and large) were created using 3-dimensional printed surface templates. A total of 6 surgeons (3 attending and 3 resident surgeons) performed OCAs of each trochlear lesion. Each surgeon performed 1 graft for each size and each guide type (n = 6 per surgeon). A specialized digital caliper was prepared that allowed the measurement of graft step-off to within 0.01 mm at a distance of 5 mm between the 2 sensors. The measurements were performed at 8 positions around the clockface of the grafts., Results: Grafts performed with the contoured guides had a mean step-off of 0.43 ± 0.37 mm. Grafts performed with the flat guides had a mean step-off of 0.74 ± 0.78 mm ( P < .0001). Experience level did not have a significant effect on graft step-off ( P = .81). There was no identifiable pattern indicating higher step-off at any one position on the clockface., Conclusion: In this study, contoured grafts had significantly lower step-offs compared with flat guides. Experience level, clockface position, and graft size did not affect step-off., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH; grant UL1 TR001860). C.M.D. and M.H. have received education payments from Sequoia Surgical. Z.C.L. has received education payments from Sequoia Surgical and hospitality payments from Stryker. A.A.J. is the principal shareholder of Joint Preservation Solutions, which holds intellectual property rights related to the contoured guides used in this study; is a scientific advisor and has stock options in Roam Robotics; has received education payments from Evolution Surgical; and has received hospitality payments from Encore Medical, Linvatec, Stryker, and Zimmer Biomet. C.A.L. has received education payments from Sequoia Surgical; consulting fees from Hyalex, KCI, Ossur, Smith & Nephew, and Vericel; speaking fees from Smith & Nephew; honoraria from Fidia Pharma; and hospitality payments from Aesculap Biologics and RTI Surgical. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Background: Delayed neuropsychiatric sequelae are major complications of carbon monoxide poisoning; carbon monoxide triggers brain oxidation and inflammation. Corticosteroids such as dexamethasone modulate neurological damage after carbon monoxide poisoning through anti-inflammatory actions and immune response inhibition. However, it is not known whether corticosteroids prevent delayed neuropsychiatric sequelae. We thus studied whether dexamethasone reduced the incidence of delayed neuropsychiatric sequelae., Methods: This registry-based study enrolled patients with carbon monoxide poisoning treated in a Korean tertiary care hospital from March 1 st , 2020 to November 30 th , 2021. Data of patients were prospectively collected during the study period, and retrospectively analyzed. One group received intravenous dexamethasone. We performed multivariable logistic regression analysis to identify factors associated with delayed neuropsychiatric sequelae., Results: A total of 128 patients were enrolled, of which 99 patients received dexamethasone therapy and 29 patients did not. The incidences of delayed neuropsychiatric sequelae in the dexamethasone and non-dexamethasone groups were 16.2% and 37.9%, respectively. Multivariable logistic regression analysis revealed that dexamethasone use (odds ratio = 0.122, 95% confidence interval 0.031-0.489) and a higher Glasgow Coma Scale (odds ratio = 0.818, 95% confidence interval 0.682-0.981) was associated with a lower incidence of delayed neuropsychiatric sequelae., Conclusion: Early dexamethasone treatment was significantly associated with a decreased incidence of delayed neuropsychiatric sequelae. A higher Glasgow Coma Scale at presentation also was associated with a lower incidence of delayed neuropsychiatric sequelae.

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients., Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place., Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level., Competing Interests: There are no conflict of interests with the authors.

Extracorporeal cardiopulmonary resuscitation (ECPR) for refractory ventricular fibrillation/ventricular tachycardia in out-of-hospital cardiac arrest has recently been recommended for selected patients with favorable prognostic features. We aimed to identify factors affecting the willingness of emergency physicians to implement extracorporeal cardiopulmonary resuscitation (ECPR). We conducted a factorial survey with nine experimental vignettes by combining three different scene time intervals and transportation time intervals. Emergency physicians reported willingness to implement ECPR (1-100 points). Respondent characteristics that could affect the willingness were studied. Multilevel analysis of vignettes and respondent factors was conducted using a mixed-effects regression model. We obtained 486 vignette responses from 54 emergency physicians. In the case of longer scene time intervals, there was a significant difference in the willingness scores at 9 and 12 min transportation time intervals. When the pre-hospital time interval was > 40 min, emergency physicians demonstrated lower willingness to implement ECPR. Clinical experience of 15-19 years showed a significant favorable effect on willingness to implement extracorporeal membrane oxygenation (ECMO). However, the mean willingness scores of EPs for ECMO implementation were more than 75 across all vignettes. In ECPR, the prehospital time interval is an important factor, and the willingness of emergency physicians to implement ECMO could be mutually affected by scene time intervals, transportation time intervals, and total prehospital time., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)