Method comparison and overview of refractive measurements in children: implications for myopia management.

OBJECTIVE: This study investigated the agreement between objective wavefront-based refraction and subjective refraction in myopic children. It also assessed the impact of cyclopentolate and refraction levels on the agreement. METHODS: A total of 84 eyes of myopic children aged 6-13 years were included in the analysis. Non-cycloplegic and cycloplegic objective wavefront-based refraction were determined and cycloplegic subjective refraction was performed for each participant. The data were converted into spherical equivalent, J0 and J45, and Bland-Altman plots were used to analyse the agreement between methods. RESULTS: Linear functions were used to determine the dependency between the central myopic refractive error and the difference between the method of refraction (=bias). The influence of central myopia was not clinically relevant when analysing the agreement between wavefront results with and without cyclopentolate (comparison 1). The bias for wavefront-based minus subjective spherical equivalent refraction (comparison 2) was ≤-0.50 D (95% limits of agreement -0.010 D to -1.00 D) for myopia of -4.55 D and higher when cycloplegia was used (p<0.05). When no cyclopentolate was used for the wavefront-based refraction (comparison 3), the bias of -0.50 D (95% limits of agreement -0.020 D to -0.97 D) was already reached at a myopic error of -2.97 D. Both astigmatic components showed no clinically relevant bias. CONCLUSION: The spherical equivalent, measured without cycloplegic agents, led to more myopic measurements when wavefront-based refraction was used. The observed bias increased with the amount of myopic refractive error for comparisons 2 and 3, which needs to be considered when interpreting wavefront-refraction data. TRIAL REGISTRATION NUMBER: NCT05288335.

Chemoenzymatic total synthesis of sorbicillactone A.

The sorbicillinoid family is a large class of natural products known for their structural variety and strong, diverse biological activities. A special member of this family, sorbicillactone A, the first nitrogen-containing sorbicillinoid, exhibits potent anti-leukemic and anti-HIV activities and possesses a unique structure formed from sorbicillinol, alanine, and fumaric acid building blocks. To facilitate in-depth biological and structure-activity relationship studies of this promising natural product, we developed a chemoenzymatic approach that provides access to sorbicillactone A and several analogs with excellent yields under precise stereochemical control. The key steps of the highly convergent, stereoselective, and short route are the enantioselective oxidative dearomatization of sorbillin to sorbicillinol catalyzed by the enzyme SorbC and the subsequent Michael addition of a fumarylazlactone building block. Additionally, our synthetic findings and bioinformatic analysis suggest that sorbicillactone A is biosynthetically formed analogously.

The influence of lumbosacral transitional vertebrae on lumbar lordosis and the angle of pelvic incidence.

Pelvic incidence and lumbar lordosis have only normative values for spines comprising five lumbar and five sacral vertebrae. However, it is unclear how pelvic incidence and lumbar lordosis are affected by the common segmentation anomalies at the lumbo-sacral border leading to lumbosacral transitional vertebrae, including lumbarisations and sacralisations. In lumbosacral transitional vertebrae it is not trivial to identify the correct vertebral endplates to measure pelvic incidence and lumbar lordosis because ontogenetically the first sacral vertebra represents the first non-mobile sacral segment in lumbarisations, but the second segment in sacralisations. We therefore assessed pelvic incidence and lumbar lordosis with respect to both of these vertebral endplates. The type of segmentation anomaly was differentiated using spinal counts, spatial relationship with the iliac crest and morphological features. We found significant differences in pelvic incidence and lumbar lordosis between lumbarisations, sacralisations and the control group. The pelvic incidence in the sacralised group was mostly below the range of the lubarisation group and the control group when measured the traditional way at the first non-mobile segment (30.2°). However, the ranges of the sacralisation and lubarisation groups were completely encompassed by the control group when measured at the ontogenetically true first sacral vertebra. The mean pelvic incidence of the sacraliation group thus increased from 30.2° to 58.6°, and the mean pelvic incidence of the total sample increased from 45.6° to 51.2°, making it statistically indistinguishable from the control sample, whose pelvic incidence was 50.2°. Our results demonstrate that it is crucial to differentiate sacralisations from lumbarisation in order to assess the reference vertebra for pelvic incidence measurement. Due to their significant impact on spino-pelvic parameters, lumbosacral transitional vertebrae should be evaluated separately when examining pelvic incidence and lumbar lordosis.

Metallic Nanoalloys on Vertical GaAs Nanowires: Growth Mechanisms and Shape Control of Ni-GaAs Compounds.

GaAs nanowires are promising candidates for emerging devices in a broad field of applications (e.g., nanoelectronics, photodetection, or photoconversion). These nanostructures benefit greatly from a vertical integration, as it allows for the exhibition of the entire nanowire surface. However, one of the main challenges related to vertical integration is the conception of an efficient method to create low resistive contacts at nanoscale without degrading the device performance. In this article, we propose a complementary metal-oxide-semiconductor (CMOS)-compatible approach to form alloyed contacts at the extremities of vertical GaAs nanowires. Ni-based and Pd-based alloys on different vertical GaAs nanostructures have been characterized by structural and chemical analyses to identify the phase and to study the growth mechanisms involved at the nanoscale. It is shown that the formation of the Ni3GaAs alloy on top of nanowires following the epitaxial relation Ni3GaAs(0001)∥GaAs(111) leads to a pyramidal shape with four faces. Finally, guidelines are presented to tune the shape of this alloy by varying the initial metal thickness and nanowire diameters. It will facilitate the fabrication of a nanoalloy structure with tailored shape characteristics to precisely align with a designated application.

Biomechanical comparison of two different compression screws for the treatment of odontoid fractures in human dens axis specimen.

BACKGROUND: Lag screw osteosynthesis for odontoid fractures has a high rate of pseudoarthrosis, especially in elderly patients. Besides biomechanical properties of the different screw types, insufficient fragment compression or unnoticed screw stripping may be the main causing factors for this adverse event. The aim of the study was to compare two screws in clinical use with different design principles in terms of compression force and stability against screw stripping. METHODS: Twelve human cadaveric C2 vertebral bodies were considered. Bone density was determined. The specimens were matched according to bone density and randomly assigned to two experimental groups. An odontoid fracture was induced, which were fixed either with a 3.5 mm standard compression screw or with a 5 mm sleeve nut screw. Both screws are certified for the treatment of odontoid fractures. The bone samples were fixed in a measuring device. The screwdriver was driven mechanically. The tests were analyzed for peak interfragmentary compression and screw-in torque with a frequency of 20 Hz. FINDINGS: The maximum fragment compression was significantly higher with screw with sleeve nut at 346.13(SD ±72.35) N compared with classic compression screw at 162.68(SD ±114.13) N (p = 0.025). Screw stripping occurred significantly earlier in classic compression screw at 255.5(SD ±192.0)° rotation after reaching maximum compression than in screw with sleeve nut at 1005.2(SD ±341.1)° (p = 0.0039). INTERPRETATION: Screw with sleeve nut achieves greater fragment compression and is more robust to screw stripping compared to classic compression screw. Whether the better biomechanical properties lead to a reduction of pseudoarthrosis has to be proven in clinical studies.

Control of light emission of quantum emitters coupled to silicon nanoantenna using cylindrical vector beams.

Light emission of europium (Eu3+) ions placed in the vicinity of optically resonant nanoantennas is usually controlled by tailoring the local density of photon states (LDOS). We show that the polarization and shape of the excitation beam can also be used to manipulate light emission, as azimuthally or radially polarized cylindrical vector beam offers to spatially shape the electric and magnetic fields, in addition to the effect of silicon nanorings (Si-NRs) used as nanoantennas. The photoluminescence (PL) mappings of the Eu3+ transitions and the Si phonon mappings are strongly dependent of both the excitation beam and the Si-NR dimensions. The experimental results of Raman scattering and photoluminescence are confirmed by numerical simulations of the near-field intensity in the Si nanoantenna and in the Eu3+-doped film, respectively. The branching ratios obtained from the experimental PL maps also reveal a redistribution of the electric and magnetic emission channels. Our results show that it could be possible to spatially control both electric and magnetic dipolar emission of Eu3+ ions by switching the laser beam polarization, hence the near field at the excitation wavelength, and the electric and magnetic LDOS at the emission wavelength. This paves the way for optimized geometries taking advantage of both excitation and emission processes.

Synthesis, Stereochemical Determination, and Antimicrobial Evaluation of Myxocoumarin A.

The myxobacterial natural product myxocoumarin A from Stigmatella aurantiaca MYX-030 has remarkable antifungal activity against agriculturally relevant pathogens. To broaden the initial evaluation of its biological potential, we herein completed the first total synthesis of myxocoumarin A. This synthetic access facilitated stereochemical investigations on the natural product structure, revealing its (R)-configuration. Biological activity profiling showed a lack of activity against Candida spp. and Gram-negative bacteria but revealed strong antibiotic activities against Bacillus subtilis and Staphylococcus aureus, including MRSA.

Serum Biomarkers of a Pro-Neuroinflammatory State May Define the Pre-Operative Risk for Postoperative Delirium in Spine Surgery.

Advances in spine surgery enable technically safe interventions in older patients with disabling spine disease, yet postoperative delirium (POD) poses a serious risk for postoperative recovery. This study investigates biomarkers of pro-neuroinflammatory states that may help objectively define the pre-operative risk for POD. This study enrolled patients aged ≥60 scheduled for elective spine surgery under general anesthesia. Biomarkers for a pro-neuroinflammatory state included S100 calcium-binding protein ß (S100ß), brain-derived neurotrophic factor (BDNF), Gasdermin D, and the soluble ectodomain of the triggering receptor expressed on myeloid cells 2 (sTREM2). Postoperative changes of Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), and C-reactive protein (CRP) were assessed as markers of systemic inflammation preoperatively, intraoperatively, and early postoperatively (up to 48 h). Patients with POD (n = 19, 75.7 ± 5.8 years) had higher pre-operative levels of sTREM2 (128.2 ± 69.4 pg/mL vs. 97.2 ± 52.0 pg/mL, p = 0.049) and Gasdermin D (2.9 ± 1.6 pg/mL vs. 2.1 ± 1.4 pg/mL, p = 0.29) than those without POD (n = 25, 75.6 ± 5.1 years). STREM2 was additionally a predictor for POD (OR = 1.01/(pg/mL) [1.00-1.03], p = 0.05), moderated by IL-6 (Wald-χ2 = 4.06, p = 0.04). Patients with POD additionally showed a significant increase in IL-6, IL-1ß, and S100ß levels on the first postoperative day. This study identified higher levels of sTREM2 and Gasdermin D as potential markers of a pro-neuroinflammatory state that predisposes to the development of POD. Future studies should confirm these results in a larger cohort and determine their potential as an objective biomarker to inform delirium prevention strategies.

Significant Reduction of Radiation Exposure Using Specific Settings of the O-Arm for Percutaneous Cementoplasty in Accordance With the ALARA Principle.

BACKGROUND: Three-dimensional (3D) navigation has become routinely used in spine surgery, allowing more accurate and safe procedures. However, radiation exposure related to the use of imaging is an unresolved issue, and information about it is relatively scarce. The "as low as reasonably achievable" (ALARA) principle aims to reduce the radiation exposure for the patients as low as possible. The objective of this study was to compare the effective dose related to the use of the O-arm in standard settings with adapted features for dose reduction during percutaneous cementoplasty. METHODS: From March 2021 to October 2022, all consecutive patients who underwent navigated percutaneous cementoplasty with the use of the O-arm were prospectively included. Demographic, operative, irradiation, and radiological data were collected. The main outcome was the effective dose (E) in millisievert (mSv). Secondary outcomes were the absolute risk of cancer (AR) in percent equivalent to a whole-body exposition, operative time, and radiological results according to Garnier. In group A, patients were operated on with standard settings of the O-arm, whereas in group B, navigation on the field of view, collimation, and low-dose settings were used. RESULTS: A total of 70 patients were included in the study: 43 in group A and 27 in group B. Also, 109 vertebrae were operated: 59 in group A and 50 in group B. Mean E was significantly higher in group A than in group B (9.94 and 4.34 mSv, respectively; P < 0.01). The 3D-related E followed the same trend (7.82 and 3.97 mSv, respectively), as did 2-dimensional-related E (2.12 and 0.37 mSv, respectively; P < 0.01). Average AR was also significantly higher in group A than in group B (5.10-4% and 2.10-4% respectively; P < 0.01). Operative time was similar in both groups, but the rate of satisfactory radiological results was higher in group A than in group B (95% and 84%, respectively; P = 0.11), and we found similar rates of cement leakage (22% and 24%, respectively; P = 0.71). CONCLUSIONS: The application of settings of the O-arm in accordance with the ALARA principle helped to significantly reduce the radiation exposure and should be routinely used for O-arm-assisted cementoplasty procedures. CLINICAL RELEVANCE: This study details technical aspects and settings that may help users of the O-arm to decrease radiation exposure to patients and surgeons alike, especially in cementoplasty procedures, as well as in other procedures performed under O-arm guidance.

Duration of Surgery and Intraoperative Blood Pressure Management Are Modifiable Risk Factors for Postoperative Neurocognitive Disorders After Spine Surgery: Results of the Prospective CONFESS Study.

STUDY DESIGN: Prospective quasi-experimental observational study. OBJECTIVE: The objective of this study was to evaluate whether duration of surgery is a modifiable risk factor for postoperative delirium (POD) after spine surgery and explore further modifiable risk factors. In addition, we sought to investigate the association between POD and postoperative cognitive dysfunction and persistent neurocognitive disorders. SUMMARY OF BACKGROUND DATA: Advances in spine surgery enable technically safe interventions in elderly patients with disabling spine disease. The occurrence of POD and delayed neurocognitive complications ( e.g. postoperative cognitive dysfunction/persistent neurocognitive disorder) remain a concern since these contribute to inferior functional outcomes and long-term care dependency after spine surgery. MATERIALS AND METHODS: This prospective single-center study recruited patients aged 60 years or above and scheduled for elective spine surgery between February 2018 and March 2020. Functional (Barthel Index, BI) and cognitive outcomes [Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery; telephone Montréal Cognitive Assessment] were assessed at baseline, three (V3), and 12 months postoperatively. The primary hypothesis was that the duration of surgery predicts POD. Multivariable predictive models of POD included surgical and anesthesiological parameters. RESULTS: Twenty-two percent of patients developed POD (n=22/99). In a multivariable model, duration of surgery [OR adj =1.61/h (95% CI, 1.20-2.30)], age [OR adj =1.22/yr (95% CI, 1.10-1.36)], and baseline deviations of intraoperative systolic blood pressure [25th percentile: OR adj =0.94/mm Hg (95% CI, 0.89-0.99); 90th percentile: OR adj =1.07/mm Hg (95% CI, 1.01-1.14)] were significantly associated with POD. Postoperative cognitive scores generally improved (V3, ΔCERAD total z -score: 0.22±0.63). However, this positive group effect was counteracted by POD [beta: -0.87 (95% CI, -1.31 to 0.42)], older age [beta: -0.03/yr (95% CI, -0.05 to 0.01)], and lack of functional improvement [ΔBI; beta: -0.04/point (95% CI, -0.06 to 0.02)]. Cognitive scores at twelve months remained inferior in the POD group, adjusted for baseline cognition/age. CONCLUSIONS: This study identified distinct neurocognitive effects after spine surgery, which are influenced by perioperative risk factors. Potential cognitive benefits are counteracted by POD, rendering its prevention critical in an aging population.

Botrytis hypersensitive response inducing protein 1 triggers noncanonical PTI to induce plant cell death.

According to their lifestyle, plant pathogens are divided into biotrophic and necrotrophic organisms. Biotrophic pathogens exclusively nourish living host cells, whereas necrotrophic pathogens rapidly kill host cells and nourish cell walls and cell contents. To this end, the necrotrophic fungus Botrytis cinerea secretes large amounts of phytotoxic proteins and cell wall-degrading enzymes. However, the precise role of these proteins during infection is unknown. Here, we report on the identification and characterization of the previously unknown toxic protein hypersensitive response-inducing protein 1 (Hip1), which induces plant cell death. We found the adoption of a structurally conserved folded Alternaria alternata Alt a 1 protein structure to be a prerequisite for Hip1 to exert its necrosis-inducing activity in a host-specific manner. Localization and the induction of typical plant defense responses by Hip1 indicate recognition as a pathogen-associated molecular pattern at the plant plasma membrane. In contrast to other secreted toxic Botrytis proteins, the activity of Hip1 does not depend on the presence of the receptor-associated kinases BRI1-associated kinase 1 and suppressor of BIR1-1. Our results demonstrate that recognition of Hip1, even in the absence of obvious enzymatic or pore-forming activity, induces strong plant defense reactions eventually leading to plant cell death. Botrytis hip1 overexpression strains generated by CRISPR/Cas9 displayed enhanced infection, indicating the virulence-promoting potential of Hip1. Taken together, Hip1 induces a noncanonical defense response which might be a common feature of structurally conserved fungal proteins from the Alt a 1 family.

Pharmacokinetics of Ribavirin in the Treatment of Lassa Fever: An Observational Clinical Study at the Irrua Specialist Teaching Hospital, Edo State, Nigeria.

BACKGROUND: Lassa fever is endemic in large parts of West Africa. The recommended antiviral treatment is ribavirin. Two treatment regimens are currently endorsed in Nigeria: the "McCormick regimen" based on a study published in 1986 and the "Irrua regimen" constituting a simplified schedule developed at the Irrua Specialist Teaching Hospital, Nigeria. Evidence for the safety and efficacy of ribavirin in Lassa fever patients is poor and pharmacokinetic data for both regimens are lacking. METHODS: Polymerase chain reaction-confirmed Lassa fever patients with mild to moderate disease severity were invited to participate in this prospective, observational pharmacokinetic study. Pharmacokinetics of ribavirin, clinical, virologic, and clinical laboratory parameters were assessed. RESULTS: Using a population pharmacokinetic approach, plasma concentrations of ribavirin were best described by a 3-compartment model. Drug exposure was remarkably consistent between participants. Overall, drug clearance was 28.5% lower in female compared with male participants. Median (5th-95th percentile) time above half maximal inhibitory concentration (IC50) was 37.3% (16.9%-73.1%), 16.7% (8.2%-58.5%), and 9.6% (4.9%-38.4%) on days 1, 7, and 8, respectively. Clinical laboratory parameters indicated reduction of cell damage and development of hemolytic anemia in the course of the treatment period. CONCLUSIONS: This observational study characterizes the pharmacokinetics of ribavirin in the treatment of Lassa fever indicating consistent exposure across patients. Whereas only a short time interval of concentrations above the IC50 implies rather low antiviral efficacy in vivo, the prominent reduction of cell damage markers might point to indirect-potentially anti-inflammatory-effects of ribavirin. The role of ribavirin in the treatment of Lassa fever requires further scrutiny.

Development of a High-Fidelity Framework to Describe the Process-Dependent Viscoelasticity of a Fast-Curing Epoxy Matrix Resin including Testing, Modelling, Calibration and Validation.

Fast-curing epoxy resins enable substantial reduction of cycle times during production of thermoset polymer matrix composites. Due to the snap-cure behaviour, both characterisation and processing of these resins are associated with high complexity which motivates the development of a high-fidelity framework for the prediction of the process-dependent behaviour ranging from experiment to model validation. In order to determine influence of time, temperature, and degree of cure, a multitude of rheometer and dynamic mechanical analysis experiments are conducted and evaluated. Building on the experimental results, a material model based on a generalised Maxwell model is developed. It is calibrated on the results obtained in the tests and shown to describe the material's behaviour with high accuracy under all investigated conditions. The model's predictive capabilities are further tested by applying it to a dynamic mechanical analysis, exposing the model to previously unknown loading and temperature conditions. It is demonstrated that the model is capable of predicting such changing boundary conditions with high accuracy.

A Preclinical Study on Brugada Syndrome with a CACNB2 Variant Using Human Cardiomyocytes from Induced Pluripotent Stem Cells.

Aims: Some gene variants in the sodium channels, as well as calcium channels, have been associated with Brugada syndrome (BrS). However, the investigation of the human cellular phenotype and the use of drugs for BrS in presence of variant in the calcium channel subunit is still lacking. Objectives: The objective of this study was to establish a cellular model of BrS in the presence of a CACNB2 variant of uncertain significance (c.425C > T/p.S142F) using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and test drug effects using this model. Methods and results: This study recruited cells from a patient with Brugada syndrome (BrS) and recurrent ventricular fibrillation carrying a missense variant in CACNB2 as well as from three healthy independent persons. These cells (hiPSC-CMs) generated from skin biopsies of healthy persons and the BrS patient (BrS-hiPSC-CMs) as well as CRISPR/Cas9 corrected cells (isogenic control, site-variant corrected) were used for this study. The hiPSC-CMs from the BrS patient showed a significantly reduced L-type calcium channel current (ICa-L) compared with the healthy control hiPSC-CMs. The inactivation curve was shifted to a more positive potential and the recovery from inactivation was accelerated. The protein expression of CACNB2 of the hiPSC-CMs from the BrS-patient was significantly decreased compared with healthy hiPSC-CMs. Moreover, the correction of the CACNB2 site-variant rescued the changes seen in the hiPSC-CMs of the BrS patient to the normal state. These data indicate that the CACNB2 gene variant led to loss-of-function of L-type calcium channels in hiPSC-CMs from the BrS patient. Strikingly, arrhythmia events were more frequently detected in BrS-hiPSC-CMs. Bisoprolol (beta-blockers) at low concentration and quinidine decreased arrhythmic events. Conclusions: The CACNB2 variant (c.425C > T/p.S142F) causes a loss-of-function of L-type calcium channels and is pathogenic for this type of BrS. Bisoprolol and quinidine may be effective for treating BrS with this variant.

Major acetabular prosthetic protrusion following total hip arthroplasty: a case report of a reconstruction challenge.

Background: Acetabular protrusion is an acetabular defect caused by the shift of the femoral head through the pelvic bone. Because of bone loss, usual anatomical landmarks may be confusing or absent, leading to a particularly high demanding surgical reconstruction in case of total hip arthroplasty (THA) implantation, without adequate support of the acetabulum due to major acetabular defect. To our knowledge, no article has dealt with acetabular defects to this extent and associated femoral osteolysis, which we will attempt to do in this case report. That's why we would like to share this case in order to propose an interesting alternative for the management of these challenging pathologies. Case Description: We hereby present the case of a rare pattern of severe acetabular prosthetic protrusion through the pelvic ring on a 77-year-old patient without any trauma. He was surgically treated with acetabular metal augment and a wide femoral modular reconstruction prosthesis. An instability was revealed after 6 weeks, so he underwent an early surgical revision with a constraint cup, overwhelming the absence of abductor apparatus. After this, his recovery was complete and uneventful, with effective function of the reconstructed hip joint and adequate stability of the prosthesis. Conclusions: Although acetabular protrusion is a rare complication in total hip replacement patients, we would like to draw attention to the challenging nature of this complication, both in terms of initial assessment and surgical management. The described strategy showed effective function of the reconstructed hip joint and final adequate stability of the prosthesis despite the absence of a competent abductor apparatus.

Virus persistence after recovery from acute Lassa fever in Nigeria: a 2-year interim analysis of a prospective longitudinal cohort study.

BACKGROUND: There is anecdotal evidence for Lassa virus persistence in body fluids. We aimed to investigate various body fluids after recovery from acute Lassa fever, describe the dynamics of Lassa virus RNA load in seminal fluid, and assess the infectivity of seminal fluid. METHODS: In this prospective, longitudinal, cohort study we collected plasma, urine, saliva, lacrimal fluid, vaginal fluid, and seminal fluid from Lassa fever survivors from Irrua Specialist Teaching Hospital in Edo State, Nigeria. Inclusion criteria for participants were RT-PCR-confirmed Lassa fever diagnosis and age 18 years or older. Samples were taken at discharge from hospital (month 0) and at months 0·5, 1, 3, 6, 9, 12, 18, and 24 after discharge. The primary objective of this study was to quantitatively describe virus persistence and clearance and assess the infectivity of seminal fluid. Lassa virus RNA was detected using real-time RT-PCR. Infectivity was tested in cell culture and immunosuppressed mice. We used a linear mixed-effect model to analyse the dynamics of virus persistence in seminal fluid over time. FINDINGS: Between Jan 31, 2018, and Dec 11, 2019, 165 participants were enrolled in the study, of whom 159 were eligible for analysis (49 women and 110 men). Low amounts of Lassa virus RNA were detected at month 0 in plasma (49 [45%] of 110 participants), urine (37 [34%]), saliva (five [5%]), lacrimal fluid (ten [9%]), and vaginal fluid (seven [21%] of 33 female participants). Virus RNA was cleared from these body fluids by month 3. However, 35 (80%) of 44 male participants had viral RNA in seminal fluid at month 0 with a median cycle threshold of 26·5. Lassa virus RNA remained detectable up to month 12 in seminal fluid. Biostatistical modelling estimated a clearance rate of 1·19 log10 viral RNA copies per month and predicted that 50% of male survivors remain Lassa virus RNA-positive in seminal fluid for 83 days after hospital discharge and 10% remain positive in seminal fluid for 193 days after discharge. Viral RNA persistence in seminal fluid for 3 months or more was associated with higher viraemia (p=0·006), more severe disease (p=0·0075), and longer hospitalisation during the acute phase of Lassa fever (p=0·0014). Infectious virus was isolated from 48 (52%) of 93 virus RNA-positive seminal fluid samples collected between month 0 and 12. INTERPRETATION: Lassa virus RNA is shed in various body fluids after recovery from acute disease. The persistence of infectious virus in seminal fluid implies a risk of sexual transmission of Lassa fever. FUNDING: German Federal Ministry of Health, German Research Foundation, Leibniz Association.

Cytotoxicity of 3D-printed, milled, and conventional oral splint resins to L929 cells and human gingival fibroblasts.

OBJECTIVES: Evidence on the biocompatibility of three-dimensional (3D)-printed and milled resins for oral splints is limited. This in vitro study assessed the influence of the manufacturing method on the cytotoxicity of oral splint resins on L929 cells and human gingival fibroblasts (GF1). MATERIALS AND METHODS: Standardized specimens of four 3D-printed, two-milled, one-thermoformed, and one-pressed splint resin were incubated with L929 and GF1 cells for 24 h. Immunofluorescence and WST-8 assay were performed to evaluate cytotoxic effects. One-way analysis of variance and Tukey's multiple comparison test were applied with the variables "splint resin" and "manufacturing method" (p < .05). RESULTS: Immunofluorescence showed attachment of L929 and GF1 cells to the splint resins. Irrespective of the manufacturing method, the WST-8 assay revealed significant differences between splint resins for the viability of L929 and GF1 cells. L929 cells generally showed lower viability rates than GF1 cells. The evaluation of cell viability by the manufacturing method showed no significant differences between 3D printing, milling, and conventional methods. CONCLUSIONS: The cytotoxic effects of 3D-printed, milled, and conventional oral splint resins were similar, indicating minor influence of the manufacturing method on biocompatibility. Cytotoxicity of the resins was below a critical threshold in GF1 cells. The chemical composition might be more crucial than the manufacturing method for the biocompatibility of splint resins.

Conservative management of a specific subtype of Maisonneuve fractures: a report of two cases.

Background: Maisonneuve fractures are most commonly characterised by a specific pattern with a medial malleolar fracture or deltoid ligament rupture, a disruption of the ankle syndesmosis ligaments and a fracture of the proximal fibula. Case Description: We hereby describe for the first time two cases of conservative therapy of Maisonneuve fracture with intact medial structures and with associated posterior malleolus fracture. Patients were assessed with ankle radiographs and magnetic resonance imaging (MRI). The distal fibula was anatomically positioned in its notch and the deltoid ligament and interosseous membrane (IOM) were intact. In addition, the posterior malleolus fracture was not associated with talar subluxation or articular impaction, and the mortise remained anatomically positioned on the initial radiographs. Based on clinical and imaging evaluations, the decision was made to follow conservative treatment. Follow-up showed stability criteria on standing radiographs, and their evolution was clinically uneventful with a good AOFAS score after 1 year. Conclusions: The discussion emphasized the scarce description of conservative therapy of Maisonneuve fractures for which surgical treatment is considered to be the gold standard. The good results of these two cases are in favour with conservative therapy, avoiding adverse events and complications related to surgery, and showed that conservative therapy should be also considered as an effective therapeutic option in selected cases. We also emphasize that the results of our two cases are, moreover, in favor of an early weight-bearing protocol.

Climate shapes the seed germination niche of temperate flowering plants: a meta-analysis of European seed conservation data.

BACKGROUND AND AIMS: Interactions between ecological factors and seed physiological responses during the establishment phase shape the distribution of plants. Yet, our understanding of the functions and evolution of early-life traits has been limited by the scarcity of large-scale datasets. Here, we tested the hypothesis that the germination niche of temperate plants is shaped by their climatic requirements and phylogenetic relatedness, using germination data sourced from a comprehensive seed conservation database of the European flora (ENSCOBASE). METHODS: We performed a phylogenetically informed Bayesian meta-analysis of primary data, considering 18 762 germination tests of 2418 species from laboratory experiments conducted across all European geographical regions. We tested for the interaction between species' climatic requirements and germination responses to experimental conditions including temperature, alternating temperature, light and dormancy-breaking treatments, while accounting for between-study variation related to seed sources and seed lot physiological status. KEY RESULTS: Climate was a strong predictor of germination responses. In warm and seasonally dry climates the seed germination niche includes a cold-cued germination response and an inhibition determined by alternating temperature regimes and cold stratification, while in climates with high temperature seasonality opposite responses can be observed. Germination responses to scarification and light were related to seed mass but not to climate. We also found a significant phylogenetic signal in the response of seeds to experimental conditions, providing evidence that the germination niche is phylogenetically constrained. Nevertheless, phylogenetically distant lineages exhibited common germination responses under similar climates. CONCLUSION: This is the first quantitative meta-analysis of the germination niche at a continental scale. Our findings showed that the germination niches of European plants exhibit evolutionary convergence mediated by strong pressures at the macroclimatic level. In addition, our methodological approach highlighted how large datasets generated by conservation seed banking can be valuable sources to address questions in plant macroecology and evolution.

Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo.

The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.