Plasmon-Mediated Organic Photoelectrochemistry Applied to Amination Reactions.

Organic electrochemistry is currently experiencing an era of renaissance, which is closely related to the possibility of carrying out organic transformations under mild conditions, with high selectivity, high yields, and without the use of toxic solvents. Combination of organic electrochemistry with alternative approaches, such as photo-chemistry was found to have great potential due to induced synergy effects. In this work, we propose for the first time utilization of plasmon triggering of enhanced and regio-controlled organic chemical transformation performed in photoelectrochemical regime. The advantages of the proposed route is demonstrated in the model amination reaction with formation of C-N bond between pyrazole and substituted benzene derivatives. Amination was performed in photo-electrochemical mode on the surface of plasmon active Au@Pt electrode with attention focused on the impact of plasmon triggering on the reaction efficiency and regio-selectivity. The ability to enhance the reaction rate significantly and to tune products regio-selectivity is demonstrated. We also performed density functional theory calculations to inquire about the reaction mechanism and potentially explain the plasmon contribution to electrochemical reaction rate and regioselectivity.

Code generation in ORCA: progress, efficiency and tight integration.

An improved version of ORCA's automated generator environment (ORCA-AGE II) is presented. The algorithmic improvements and the move to C++ as the programming language lead to a performance gain of up to two orders of magnitude compared to the previously developed PYTHON toolchain. Additionally, the restructured modular design allows for far more complex code engines to be implemented readily. Importantly, we have realised an extremely tight integration with the ORCA host program. This allows for a workflow in which only the wavefunction Ansatz is part of the source code repository while all actual high-level code is generated automatically, inserted at the appropriate place in the host program before it is compiled and linked together with the hand written code parts. This construction ensures longevity and uniform code quality. Furthermore the new developments allow ORCA-AGE II to generate parallelised production-level code for highly complex theories, such as fully internally contracted multireference coupled-cluster theory (fic-MRCC) with an enormous number of contributing tensor contractions. We also discuss the automated implementation of nuclear gradients for arbitrary theories. All these improvements enable the implementation of theories that are too complex for the human mind and also reduce development times by orders of magnitude. We hope that this work enables researchers to concentrate on the intellectual content of the theories they develop rather than be concerned with technical details of the implementation.

Preparation and Properties of a High-Entropy Wolframite-Type Antiferromagnet, (Mn0.2Co0.2Ni0.2Cu0.2Cd0.2)WO4.

The homogeneous high-entropy wolframite-type solid solution (Mn1/5Co1/5Ni1/5Cu1/5Cd1/5)WO4 was prepared by solid-state reaction at 1000 °C. Elongated "crystals" were grown from the Na2WO4 flux, but their strongly broadened powder X-ray diffraction patterns indicated partial dissolution. Nevertheless, successive annealing of the homogeneous solid solution for 3-4 h at 800, 700, and 600 °C did not bring any sign of dissolution. Thus, the material is kinetically stable at low temperatures although thermodynamically unstable. The long-range antiferromagnetic order was established at TN ∼ 24.8 K. Based on magnetization and specific heat measurements, a magnetic phase diagram was built, demonstrating the presence of an additional field-induced phase. In contrast to the parent MnWO4, no dielectric anomaly has been found down to 2 K.

Development and verification of a full physiologically-based pharmacokinetic model for sublingual buprenorphine in healthy adult volunteers that accounts for nonlinear bioavailability.

Sublingual buprenorphine is used for opioid use disorder and neonatal opioid withdrawal syndrome (NOWS). The study aimed to develop a full physiologically-based pharmacokinetic (PBPK) model that can adequately describe dose- and formulation-dependent bioavailability of buprenorphine. Simcyp (v21.0) was used for model construction. Four linear regression models (i.e. untransformed or log-transformed for dose or proportion sublingually absorbed) were explored to describe sublingual absorption of buprenorphine across dose. Published clinical trial data not used in model development were used for verification. The PBPK model's predictive performance was deemed adequate if the geometric means of ratios between predicted and observed (P/O ratios) area under the curve (AUC), peak concentration (Cmax), and time to reach Cmax (Tmax) fell within the 1.25-fold prediction error range. Sublingual buprenorphine absorption was best described by a regression model with logarithmically transformed dose. By integrating this nonlinear absorption profile, the PBPK model adequately predicted buprenorphine pharmacokinetics (PK) following administration of sublingual tablets and solution across a dose range of 2-32 mg, with geometric mean (95% confidence interval) P/O ratios for AUC and Cmax equaling 0.99 (0.86-1.12) and 1.24 (1.09-1.40), respectively, and median (5th to 95th percentile) for Tmax equaling 1.11 (0.69-1.57). A verified PBPK model was developed that adequately predicts dose- and formulation-dependent buprenorphine PK following sublingual administration. Significance Statement The PBPK model developed in this study is the first to adequately predict dose- and formulation-dependent sublingual buprenorphine pharmacokinetics. Accurate prediction was facilitated by the incorporation of a novel nonlinear absorption model. The developed model will serve as the foundation for fetomaternal PBPK modeling to predict maternal and fetal buprenorphine exposures to optimize buprenorphine treatment for neonatal opioid withdrawal syndrome (NOWS).

Surgical quality assessment of critical view of safety in 283 laparoscopic cholecystectomy videos by surgical residents and surgeons.

INTRODUCTION: Surgical quality assessment has improved the efficacy and efficiency of surgical training and has the potential to optimize the surgical learning curve. In laparoscopic cholecystectomy (LC), the critical view of safety (CVS) can be assessed with a 6-point competency assessment tool (CAT), a task commonly performed by experienced surgeons. The aim of this study is to determine the capability of surgical residents to perform this assessment. METHODS: Both surgeons and surgical residents assessed unedited LC videos using a 6-point CVS, a CAT, using an online video assessment platform. The CAT consists of the following three criteria: 1. clearance of hepatocystic triangle, 2. cystic plate, and 3. two structures connect to the gallbladder, with a maximum of 2 points available for each criterion. A higher score indicates superior surgical performance. The intraclass correlation coefficient (ICC) was employed to assess the inter-rater reliability between surgeons and surgical residents. RESULTS: In total, 283 LC videos were assessed by 19 surgeons and 31 surgical residents. The overall ICC for all criteria was 0.628. Specifically, the ICC scores were 0.504 for criterion 1, 0.639 for criterion 2, and 0.719 for the criterion involving the two structures connected to the gallbladder. Consequently, only the criterion regarding clearance of the hepatocystic triangle exhibited fair agreement, whereas the other two criteria, as well as the overall scores, demonstrated good agreement. In 71% of cases, both surgeons and surgical residents scored a total score either ranging from 0 to 4 or from 5 to 6. CONCLUSION: Compared to the gold standard, i.e., the surgeons' assessments, surgical residents are equally skilled at assessing critical view of safety (CVS) in laparoscopic cholecystectomy (LC) videos. By incorporating video-based assessments of surgical procedures into their training, residents could potentially enhance their learning pace, which may result in better clinical outcomes.

Clinical usability study of a home-based self-administration transcranial direct current stimulation for primary dysmenorrhea: A randomized controlled trial.

This study tested the usability of a home-based self-administration transcranial direct current stimulation (tDCS) device designed specifically for women's health needs. This is a single center triple blinded clinical usability study for a new wireless, Bluetooth-controlled wearable tDCS device for women's health. The study aims to evaluate the usability and effective blinding of a home-based tDCS system. A total of forty-nine women of reproductive age were randomly allocated (1:1) to receive one session of active tDCS (n = 24) or sham tDCS (n = 25) over the motor and dorsolateral prefrontal cortex. Each participant self-administered one 20-minute session without supervision following guidance on a software application alone. The System Usability Scale (SUS) and the Patient Global Impression of Change (PGIC) were used to evaluate the usability of the system. Regardless of sham or active conditions, all users found the system easy to use without the support of researchers. Usability scores were considered to be "excellent" in both groups and no significant difference was found between sham and active groups showing effective blinding of the device (Active group: 93.7 (83.1-97.5); Sham group 90 (86.2-95) p = 0.79) and PGIC (Active group: 2 (1-2.75); Sham group 2 (1-2) p = 0.99) using an unpaired t-test or non-parametric statistical tests accordingly. The new Bluetooth-controlled wearable tDCS device is easy, safe to use and completely controlled by a smartphone app. This device is focused on women's health and will be tested as an alternative treatment for chronic pelvic pain and mood disturbance associated with menstrual cycles in further research.

Experimental and Theoretical Insights on the Structural, Electronic, and Magnetic Properties of the Quaternary Selenides EuPrCuSe3 and EuNdCuSe3.

Magnetic semiconductors EuPrCuSe3 and EuNdCuSe3 were obtained by using the halide flux method. Their crystal structures and magnetic properties were studied and discussed. Optical properties of the obtained selenides were studied by the means of diffuse reflectance spectroscopy, which revealed the values of 1.92/1.97 and 0.90/0.94 eV for the direct and indirect band gaps of Ln = Nd/Pr, respectively. The structural, electronic, and magnetic properties of the obtained compounds were additionally studied with spin-polarized density functional theory calculations, wherein both systems were found to be two new examples of semiconducting quaternary selenides with disperse conduction bands of Nd/Pr 5d character. The modeling showed that various magnetic orderings in the systems have subtle influences on the alignments/overlaps between the Se/Cu, Eu, and Pr/Nd bands, and that the spin-state energetics are very dependent upon the treatment of electron correlation, but a distinguishing feature in the case of ferromagnetic coupling is that the spin density on the Se atoms is maximized. Overall, the calculations are in good agreement with the experimental characterization of ferromagnetism in the bulk crystals, wherein the ferromagnetic transition occurs at temperatures of about 2.5 K for EuPrCuSe3 and about 3 K for EuNdCuSe3.

Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.

Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets of linked receptor-binding domains (RBDs) from a panel of SARS-like betacoronaviruses, coupled to a computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing a branched morphology, induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented in the vaccine. Equivalent antibody responses are raised to RBDs close to the nanocage or at the tips of the nanoparticle's branches. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increase the strength and breadth of an otherwise narrow immune response. A Quartet Nanocage including the Omicron XBB.1.5 'Kraken' RBD induced antibodies with binding to a broad range of sarbecoviruses, as well as neutralizing activity against this variant of concern. Quartet nanocages are a nanomedicine approach with potential to confer heterotypic protection against emergent zoonotic pathogens and facilitate proactive pandemic protection.

Polymers in 3D printing of external maxillofacial prostheses and in their retention systems.

Maxillofacial defects, arising from trauma, oncological disease or congenital abnormalities, detrimentally affect daily life. Prosthetic repair offers the aesthetic and functional reconstruction with the help of materials mimicking natural tissues. 3D polymer printing enables the design of patient-specific prostheses with high structural complexity, as well as rapid and low-cost fabrication on-demand. However, 3D printing for prosthetics is still in the early stage of development and faces various challenges for widespread use. This is because the most suitable polymers for maxillofacial restoration are soft materials that do not have the required printability, mechanical strength of the printed parts, as well as functionality. This review focuses on the challenges and opportunities of 3D printing techniques for production of polymer maxillofacial prostheses using computer-aided design and modeling software. Review discusses the widely used polymers, as well as their blends and composites, which meet the most important assessment criteria, such as the physicochemical, biological, aesthetic properties and processability in 3D printing. In addition, strategies for improving the polymer properties, such as their printability, mechanical strength, and their ability to print multimaterial and architectural structures are highlighted. The current state of the prosthetic retention system is presented with a focus on actively used polymer adhesives and the recently implemented prosthesis-supporting osseointegrated implants, with an emphasis on their creation from 3D-printed polymers. The successful prosthetics is discussed in terms of the specificity of polymer materials at the restoration site. The approaches and technological prospects are also explored through the examples of the nasal, auricle and ocular prostheses, ranging from prototypes to end-use products.

The potential of mixed carbon-helium beams for online treatment verification: a simulation and treatment planning study.

OBJECTIVE: Recently, a new and promising approach for range verification was proposed. This method requires the use of two different ion species. Due to their equal magnetic rigidity, fully ionized carbon and helium ions can be simultaneously accelerated in accelerators like synchrotrons. At sufficiently high treatment energies, helium ions can exit the patient distally, reaching approximately three times the range of carbon ions at an equal energy per nucleon. Therefore, the proposal involves adding a small helium fluence to the carbon ion beam and utilizing helium as an online range probe during radiation therapy. This work aims to develop a software framework for treatment planning and motion verification in range-guided radiation therapy using mixed carbon-helium beams. APPROACH: The developed framework is based on the open-source treatment planning toolkit matRad. Dose distributions and helium radiographs were simulated using the open-source Monte Carlo package TOPAS. Beam delivery system parameters were obtained from the Heidelberg Ion Therapy Center, and imaging detectors along with reconstruction were facilitated by ProtonVDA. Methods for reconstructing the most likely patient positioning error scenarios and the motion phase of 4DCT are presented for prostate and lung cancer sites. MAIN RESULTS: The developed framework provides the capability to calculate and optimize treatment plans for mixed carbon-helium ion therapy. It can simulate the treatment process and generate helium radiographs for simulated patient geometry, including small beam views. Furthermore, motion reconstruction based on these radiographs seems possible with preliminary validation. SIGNIFICANCE: The developed framework can be applied for further experimental work with the promising mixed carbon-helium ion implementation of range-guided radiotherapy. It offers opportunities for adaptation in particle therapy, improving dose accumulation, and enabling patient anatomy reconstruction during radiotherapy. .

The New Delivery Method for Cardioplegic Solution in Type A Aortic Dissection.

Adequate myocardial protection is crucial for a successful cardiac surgery. In type A aortic dissection, standard methods of delivery of cardioplegic solution may not be adequately effective. Ineffectiveness may happen due to both features of the anatomy of the dissection and to peculiarities of the delivery method itself. We present a new method of delivering a cardioplegic solution using a Foley catheter through the orifice of the brachiocephalic trunk or the left common carotid artery.

4'-Fluorouridine inhibits alphavirus replication and infection in vitro and in vivo.

Chikungunya virus (CHIKV) is an enveloped, positive-sense RNA virus that has re-emerged to cause millions of human infections worldwide. In humans, acute CHIKV infection causes fever and severe muscle and joint pain. Chronic and debilitating arthritis and joint pain can persist for months to years. To date, there are no approved antivirals against CHIKV. Recently, the ribonucleoside analog 4'-fluorouridine (4'-FlU) was reported as a highly potent orally available inhibitor of SARS-CoV-2, respiratory syncytial virus, and influenza virus replication. In this study, we assessed 4'-FlU's potency and breadth of inhibition against a panel of alphaviruses including CHIKV, and found that it broadly suppressed alphavirus production in cell culture. 4'-FlU acted on the viral RNA replication step, and the first 4 hours post-infection were the critical time for its antiviral effect. In vitro replication assays identified nsP4 as the target of inhibition. In vivo, treatment with 4'-FlU reduced disease signs, inflammatory responses, and viral tissue burden in mouse models of CHIKV and Mayaro virus infection. Treatment initiated at 2 hours post-infection was most effective; however, treatment initiated as late as 24-48 hours post-infection produced measurable antiviral effects in the CHIKV mouse model. 4'-FlU showed effective oral delivery in our mouse model and resulted in the accumulation of both 4'-FlU and its bioactive triphosphate form in tissues relevant to arthritogenic alphavirus pathogenesis. Together, our data indicate that 4'-FlU inhibits CHIKV infection in vitro and in vivo and is a promising oral therapeutic candidate against CHIKV infection.IMPORTANCEAlphaviruses including chikungunya virus (CHIKV) are mosquito-borne positive-strand RNA viruses that can cause various diseases in humans. Although compounds that inhibit CHIKV and other alphaviruses have been identified in vitro, there are no licensed antivirals against CHIKV. Here, we investigated a ribonucleoside analog, 4'-fluorouridine (4'-FlU), and demonstrated that it inhibited infectious virus production by several alphaviruses in vitro and reduced virus burden in mouse models of CHIKV and Mayaro virus infection. Our studies also indicated that 4'-FlU treatment reduced CHIKV-induced footpad swelling and reduced the production of pro-inflammatory cytokines. Inhibition in the mouse model correlated with effective oral delivery of 4'-FlU and accumulation of both 4'-FlU and its bioactive form in relevant tissues. In summary, 4'-FlU exhibits potential as a novel anti-alphavirus agent targeting the replication of viral RNA.

Optical coherence elastography with osmotically induced strains: Preliminary demonstration for express detection of cartilage degradation.

Optical coherence elastography (OCE) demonstrated impressive abilities for diagnosing tissue types/states using differences in their biomechanics. Usually, OCE visualizes tissue deformation induced by some additional stimulus (e.g., contact compression or auxiliary elastic-wave excitation). We propose a new variant of OCE with osmotically induced straining (OIS-OCE) and demonstrate its application to assess various stages of proteoglycan content degradation in cartilage. The information-bearing signatures in OIS-OCE are the magnitude and rate of strains caused by the application of osmotically active solutions onto the sample surface. OCE examination of the induced strains does not require special tissue preparation, the osmotic stimulation is highly reproducible, and strains are observed in noncontact mode. Several minutes suffice to obtain a conclusion. These features are promising for intraoperative method usage when express assessment of tissue state is required during surgical operations. The "waterfall" images demonstrate the development of cumulative osmotic strains in control and degraded cartilage samples.

The Association Between Task Complexity and Cortical Language Mapping Accuracy.

BACKGROUND AND OBJECTIVES: Direct cortical stimulation (DCS) mapping enables the identification of functional language regions within and around gliomas before tumor resection. Intraoperative mapping is required because glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but has decreased ability to encode information for complex tasks. It is unknown whether task complexity influenced DCS mapping results. We aim to understand correlations between audiovisual picture naming (PN) task complexity and DCS error rate. We also asked what functional and oncological factors might be associated with higher rates of erroneous responses. METHODS: We retrospectively reviewed intraoperative PN and word reading (WR) task performance during awake DCS language mapping for resection of dominant hemisphere World Health Organization grade 2 to 4 gliomas. The complexity of word tested in PN/WR tasks, patient characteristics, and tumor characteristics were compared between correct and incorrect trials. RESULTS: Between 2017 and 2021, 74 patients met inclusion criteria. At median 18.6 months of follow-up, 73.0% were alive and 52.7% remained recurrence-free. A total of 2643 PN and 978 WR trials were analyzed. A greater number of syllables in PN was associated with a higher DCS error rate (P = .001). Multivariate logistic regression found that each additional syllable in PN tasks independently increased odds of error by 2.40 (P < .001). Older age was also an independent correlate of higher error rate (P < .043). World Health Organization grade did not correlate with error rate (P = .866). More severe language impairment before surgery correlated with worse performance on more complex intraoperative tasks (P < .001). A higher error rate on PN testing did not correlate with lower extent of glioma resection (P = .949). CONCLUSION: Word complexity, quantified by the number of syllables, is associated with higher error rates for intraoperative PN tasks but does not affect extent of resection.

Correlation of Patient-Reported Social Determinants of Health With Census Tract Measures of Socioeconomic Disadvantage in Patients With GI Cancers in Eastern North Carolina.

PURPOSE: Investigating the impact of social determinants of health (SDOHs) on cancer care in large populations relies on census estimates. Routine clinic SDOH screening provides timely patient-level information which could inform best practices. This study evaluated the correlation between patient-reported SDOH needs and population-level census tract measures. METHODS: This was a retrospective cross-sectional study of a cohort of adult patients with GI malignancy screened for SDOHs such as financial insecurity, transportation, and food insecurity during initial outpatient evaluation at East Carolina University (formerly Vidant) Health Medical Center in Greenville, NC (November 2020-July 2021). Primary outcomes included number and severity of identified SDOH needs and area deprivation index (ADI) and census tract measures for each patient. Spearman rank correlations were calculated among patient-level needs and between patient-level needs and similar census tract measures. RESULTS: Of 112 patients screened, 58.9% self-identified as White (n = 66) and 41.1% as Black (n = 46). A total of 50.5% (n = 54) resided in a rural county. The collective median state ADI rank was 7 (IQR, 5-9). The median household income was $38,125 in US dollars (USD) (IQR, $31,436-$48,934 [USD]). Only 12.5% (n = 14) reported a moderate or severe financial need. Among reported needs, financial need moderately correlated with food insecurity (coefficient, 0.46; P < .001) and transportation (coefficient, 0.45; P < .001). Overall, census tract measures and reported needs poorly correlated. Lack of transportation correlated with percentage of households without a vehicle (coefficient, 0.18; P = .03) and limited access to healthy foods (coefficient, 0.18; P = .04). CONCLUSION: Given the poor correlation between reported and census needs, population-level measures may not accurately predict patient-reported needs. These findings highlight the importance of SDOH screening in the clinical setting to reduce health disparities and identify opportunities to improve care delivery.

Targeting the Plasmodium falciparum UCHL3 ubiquitin hydrolase using chemically constrained peptides.

The ubiquitin-proteasome system is essential to all eukaryotes and has been shown to be critical to parasite survival as well, including Plasmodium falciparum, the causative agent of the deadliest form of malarial disease. Despite the central role of the ubiquitin-proteasome pathway to parasite viability across its entire life-cycle, specific inhibitors targeting the individual enzymes mediating ubiquitin attachment and removal do not currently exist. The ability to disrupt P. falciparum growth at multiple developmental stages is particularly attractive as this could potentially prevent both disease pathology, caused by asexually dividing parasites, as well as transmission which is mediated by sexually differentiated parasites. The deubiquitinating enzyme PfUCHL3 is an essential protein, transcribed across both human and mosquito developmental stages. PfUCHL3 is considered hard to drug by conventional methods given the high level of homology of its active site to human UCHL3 as well as to other UCH domain enzymes. Here, we apply the RaPID mRNA display technology and identify constrained peptides capable of binding to PfUCHL3 with nanomolar affinities. The two lead peptides were found to selectively inhibit the deubiquitinase activity of PfUCHL3 versus HsUCHL3. NMR spectroscopy revealed that the peptides do not act by binding to the active site but instead block binding of the ubiquitin substrate. We demonstrate that this approach can be used to target essential protein-protein interactions within the Plasmodium ubiquitin pathway, enabling the application of chemically constrained peptides as a novel class of antimalarial therapeutics.

International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council.

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons. Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method. Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion. Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques." Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Are geriatric transfer patients with traumatic brain injury at risk for worse outcomes compared to non-geriatric? Propensity-matched study.

OBJECTIVE: To compare outcomes between geriatric and non-geriatric patients with traumatic brain injury (TBI) transferred to trauma center and effects of anticoagulants/antiplatelets (AC/AP) and reversal therapy. METHODS: A retrospective review of 1,118 patients with TBI transferred from acute care facilities to level 1 trauma center compared in groups: geriatric versus non-geriatric, geriatric with AC/AP therapy versus without, and geriatric AC/AP with AC/AP reversal therapy versus without. RESULTS: Patients with TBI constituted 54.4% of trauma transfers. Mean transfer time was 3.9 h. Propensity matched by Injury Severity Score and Abbreviated Injury Score (AIS) head geriatric compared to non-geriatric patients had more AC/AP use (53.9% vs 8.8%), repeat head computed tomography (93.7% vs 86.1%), intensive care unit (ICU) admissions (57.4% vs 45.7%) and mortality (9.8% vs 3.2%), all p < 0.004. Patients on AC/AP versus without had more ICU admissions (69.1% vs 51.8%, p < 0.001). Patients with AC/AP reversals compared to without reversals had more AIS head 5 (32.0% vs 13.1%), brain surgeries (17.8% vs 3.5%) and ICU admissions (84.8% vs 57.1%), all p < 0.001. CONCLUSION: TBI constituted half of trauma transfers and 10% required surgery. Based on higher ICU admissions, mortality, and prevalence of AC/AP therapy requiring reversal, geriatric patients with TBI on anticoagulants/antiplatelets should be considered for direct trauma center admission.

The dynamin-related protein Dyn2 is essential for both apicoplast and mitochondrial fission in Plasmodium falciparum.

Dynamins, or dynamin-related proteins (DRPs), are large mechano-sensitive GTPases mediating membrane dynamics or organellar fission/fusion events. Plasmodium falciparum encodes three dynamin-like proteins whose functions are poorly understood. Here, we demonstrate that PfDyn2 mediates both apicoplast and mitochondrial fission. Using super-resolution and ultrastructure expansion microscopy, we show that PfDyn2 is expressed in the schizont stage and localizes to both the apicoplast and mitochondria. Super-resolution long-term live cell microscopy shows that PfDyn2-deficient parasites cannot complete cytokinesis because the apicoplast and mitochondria do not undergo fission. Further, the basal complex or cytokinetic ring in Plasmodium cannot fully contract upon PfDyn2 depletion, a phenotype secondary to physical blockage of undivided organelles in the middle of the ring. Our data suggest that organellar fission defects result in aberrant schizogony, generating unsuccessful merozoites. The unique biology of PfDyn2, mediating both apicoplast and mitochondrial fission, has not been observed in other organisms possessing two endosymbiotic organelles. Highlights: PfDyn2 is essential for schizont-stage development.PfDyn2 mediates both apicoplast and mitochondrial fission.Deficiency of PfDyn2 leads to organellar fission failures and blockage of basal complex contraction.Addition of apicoplast-derived metabolite IPP does not rescue the growth defects.