DFT-Assisted Investigation of the Electric Field and Charge Density Distribution of Pristine and Defective 2D WSe2 by Differential Phase Contrast Imaging.

Most properties of solid materials are defined by their internal electric field and charge density distributions which so far are difficult to measure with high spatial resolution. Especially for 2D materials, the atomic electric fields influence the optoelectronic properties. In this study, the atomic-scale electric field and charge density distribution of WSe2 bi- and trilayers are revealed using an emerging microscopy technique, differential phase contrast (DPC) imaging in scanning transmission electron microscopy (STEM). For pristine material, a higher positive charge density located at the selenium atomic columns compared to the tungsten atomic columns is obtained and tentatively explained by a coherent scattering effect. Furthermore, the change in the electric field distribution induced by a missing selenium atomic column is investigated. A characteristic electric field distribution in the vicinity of the defect with locally reduced magnitudes compared to the pristine lattice is observed. This effect is accompanied by a considerable inward relaxation of the surrounding lattice, which according to first principles DFT calculation is fully compatible with a missing column of Se atoms. This shows that DPC imaging, as an electric field sensitive technique, provides additional and remarkable information to the otherwise only structural analysis obtained with conventional STEM imaging.

Arabidopsis mRNA export factor MOS11: molecular interactions and role in abiotic stress responses.

Transcription and export (TREX) is a multi-subunit complex that links synthesis, processing and export of mRNAs. It interacts with the RNA helicase UAP56 and export factors such as MOS11 and ALYs to facilitate nucleocytosolic transport of mRNAs. Plant MOS11 is a conserved, but sparsely researched RNA-binding export factor, related to yeast Tho1 and mammalian CIP29/SARNP. Using biochemical approaches, the domains of Arabidopsis thaliana MOS11 required for interaction with UAP56 and RNA-binding were identified. Further analyses revealed marked genetic interactions between MOS11 and ALY genes. Cell fractionation in combination with transcript profiling demonstrated that MOS11 is required for export of a subset of mRNAs that are shorter and more GC-rich than MOS11-independent transcripts. The central α-helical domain of MOS11 proved essential for physical interaction with UAP56 and for RNA-binding. MOS11 is involved in the nucleocytosolic transport of mRNAs that are upregulated under stress conditions and accordingly mos11 mutant plants turned out to be sensitive to elevated NaCl concentrations and heat stress. Collectively, our analyses identify functional interaction domains of MOS11. In addition, the results establish that mRNA export is critically involved in the plant response to stress conditions and that MOS11 plays a prominent role at this.

Use of hydroxocobalamin to treat intraoperative vasoplegic syndrome refractory to vasopressors and methylene blue during liver transplantation.

INTRODUCTION: For patients with catecholamine-resistant vasoplegic syndrome (VS) during liver transplantation (LT), treatment with methylene blue (MB) and/or hydroxocobalamin (B12) has been an acceptable therapy. However, data on the effectiveness of B12 is limited to case reports and case series. METHODS: We retrospectively reviewed records of patients undergoing LT from January 2016 through March 2022. We identified patients with VS treated with vasopressors and MB, and abstracted hemodynamic parameters, vasopressor requirements, and B12 administration from the records. The primary aim was to describe the treatment efficacy of B12 for VS refractory to vasopressors and MB, measured as no vasopressor requirement at the conclusion of the surgery. RESULTS: One hundred one patients received intraoperative VS treatment. For the 35 (34.7%) patients with successful VS treatment, 14 received MB only and 21 received both MB and B12. Of the 21 patients with VS resolution after receiving both MB and B12, 17 (89.5%) showed immediate, but transient, hemodynamic improvements at the time of MB administration and later showed sustained response to B12. CONCLUSION: Immediate but transient hemodynamic response to MB in VS patients during LT supports the diagnosis of VS and should prompt B12 administration for sustained treatment response.

The Effect of Stereocomplexation and Crystallinity on the Degradation of Polylactide Nanoparticles.

Polymeric nanoparticles (PNPs) are frequently researched and used in drug delivery. The degradation of PNPs is highly dependent on various properties, such as polymer chemical structure, size, crystallinity, and melting temperature. Hence, a precise understanding of PNP degradation behavior is essential for optimizing the system. This study focused on enzymatic hydrolysis as a degradation mechanism by investigation of the degradation of PNP with various crystallinities. The aliphatic polyester polylactide ([C3H4O2]n, PLA) was used as two chiral forms, poly l-lactide (PlLA) and poly d-lactide (PdLA), and formed a unique crystalline stereocomplex (SC). PNPs were prepared via a nanoprecipitation method. In order to further control the crystallinity and melting temperatures of the SC, the polymer poly(3-ethylglycolide) [C6H8O4]n (PEtGly) was synthesized. Our investigation shows that the PNP degradation can be controlled by various chemical structures, crystallinity and stereocomplexation. The influence of proteinase K on PNP degradation was also discussed in this research. AFM did not reveal any changes within the first 24 h but indicated accelerated degradation after 7 days when higher EtGly content was present, implying that lower crystallinity renders the particles more susceptible to hydrolysis. QCM-D exhibited reduced enzyme adsorption and a slower degradation rate in SC-PNPs with lower EtGly contents and higher crystallinities. A more in-depth analysis of the degradation process unveiled that QCM-D detected rapid degradation from the outset, whereas AFM exhibited delayed changes of degradation. The knowledge gained in this work is useful for the design and creation of advanced PNPs with enhanced structures and properties.

Soil macrofauna communities in Brazilian land-use systems.

Background: Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery. New information: Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences.

Engagement of basal amygdala-nucleus accumbens glutamate neurons in the processing of rewarding or aversive social stimuli.

Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to estrous female (social reward, SR) and/or aggressive-dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c-Fos expression in a high and similar number/density of BA-NAc neurons in the anteroposterior intermediate BA (int-BA), whereas activation was predominantly by SA in posterior (post-)BA. In Fos-TRAP2 mice, compared with SR-SR or SA-SA controls, exposure to successive presentation of SR-SA or SA-SR, followed by assessment of tdTomato reporter and/or c-Fos expression, demonstrated that many int-BA-NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int-BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int-BA-NAc neurons during social and sexual interactions. Therefore, populations of BA-NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence-specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio-emotional processing.

Elastometry - The biomechanical analysis of the lateral nasal wall.

'Elastometry' is a novel technique that allows for the quantitative assessment of elastic properties of the nasal tissues, providing valuable insights into the dynamic behavior of the external, soft lateral nasal wall. This study aimed to explore the application of 'elastometry' in understanding the biomechanics of the lateral nasal wall and its implications for nasal function in 'elastometry' measurements. After validation of safety and reliability of this method, we investigated mechanical properties of the lateral nasal wall by 'elastometry' using specifically developed measurement forceps with end pieces including sensors applied on 30 healthy volunteers, aged 18 to 82 without a history of severe trauma or surgery. By measuring normal stress and path length between the end pieces the modulus of elasticity was calculated. Among 360 measurements, the mean value determined for healthy female volunteers was E = 0.135 [N/mm2] and for healthy males E = 0.169 [N/mm2], fitting the range reported in the literature. A tendency of an age-related degree of elastic behavior of the lateral nasal wall was observed, whereby a decrease in elasticity with age in female and a slight increase in elasticity with age in male was detected. Our research showed that 'elastometry' is a cost and time-efficient method to calculate the modulus of elasticity, and could be used in conjunction with 4-phase rhinomanometry (4 PR) to extend diagnostic yield.

Insights into ageing rates comparison across tissues from recalibrating cerebellum DNA methylation clock.

DNA methylation (DNAm)-based age clocks have been studied extensively as a biomarker of human ageing and a risk factor for age-related diseases. Despite different tissues having vastly different rates of proliferation, it is still largely unknown whether they age at different rates. It was previously reported that the cerebellum ages slowly; however, this claim was drawn from a single clock using a relatively small sample size and so warrants further investigation. We collected the largest cerebellum DNAm dataset (N = 752) to date. We found the respective epigenetic ages are all severely underestimated by six representative DNAm age clocks, with the underestimation effects more pronounced in the four clocks whose training datasets do not include brain-related tissues. We identified 613 age-associated CpGs in the cerebellum, which accounts for only 14.5% of the number found in the middle temporal gyrus from the same population (N = 404). From the 613 cerebellum age-associated CpGs, we built a highly accurate age prediction model for the cerebellum named CerebellumClockspecific (Pearson correlation=0.941, MAD=3.18 years). Ageing rate comparisons based on the two tissue-specific clocks constructed on the 201 overlapping age-associated CpGs support the cerebellum has younger DNAm age. Nevertheless, we built BrainCortexClock to prove a single DNAm clock is able to unbiasedly estimate DNAm ages of both cerebellum and cerebral cortex, when they are adequately and equally represented in the training dataset. Comparing ageing rates across tissues using DNA methylation multi-tissue clocks is flawed. The large underestimation of age prediction for cerebellums by previous clocks mainly reflects the improper usage of these age clocks. There exist strong and consistent ageing effects on the cerebellar methylome, and we suggest the smaller number of age-associated CpG sites in cerebellum is largely attributed to its extremely low average cell replication rates.

Live stream of prehospital point-of-care ultrasound during cardiopulmonary resuscitation - A feasibility trial.

BACKGROUND: Current resuscitation guidelines recommend that skilled persons could use ultrasound to detect reversible causes during cardiopulmonary resuscitation (CPR) where the examination can be safely integrated into the Advanced Life Support (ALS) algorithm. However, in a prehospital setting performing and rapidly interpreting ultrasound can be challenging for physicians. Implementing remote, expert-guided, and real-time transmissions of ultrasound examinations offers the opportunity for tele-support, even during an out-of-hospital cardiac arrest (OHCA). The aim of this feasibility study was to evaluate the impact of tele-supported ultrasound in ALS on hands-off time during an OHCA. METHODS: In an urban setting, physicians performed point-of-care ultrasound (POCUS) on patients during OHCA using a portable device, either with tele-support (n = 30) or without tele-support (n = 12). Where tele-support was used, the ultrasound image was transmitted via a remote real-time connection to an on-call specialist in anaesthesia and intensive care medicine with an advanced level of critical care ultrasound expertise. The primary safety endpoint of this study was to evaluate whether POCUS can be safely integrated into the algorithm, and to provide an analysis of hands-off time before, during, and after POCUS during OHCA. RESULTS: In all 42 cases it was possible to perform POCUS during regular rhythm analyses, and no additional hands-off time was required. In 40 of these 42 cases, the physicians were able to perform POCUS during a single regular rhythm analysis, with two periods required only in two cases. The median hands-off time during these rhythm analyses for POCUS with tele-support was 10 (8-13) seconds, and 11 (9-14) seconds for POCUS without tele-support. Furthermore, as a result of POCUS, in a quarter of all cases the physician on scene altered their diagnosis of the primary suspected cause of cardiac arrest, leading to a change in treatment strategy. CONCLUSIONS: This feasibility study demonstrated that POCUS with tele-support can be safely performed during OHCA in an urban environment. Trial Registration (before patient enrolment): ClinicalTrials.gov, NCT04817475.

Safety and Feasibility of a Fast-Track Pathway for Neurosurgical Craniotomy Patients: Bypassing the Intensive Care Unit.

Objective: To describe the safety and feasibility of a fast-track pathway for neurosurgical craniotomy patients receiving care in a neurosciences progressive care unit (NPCU). Patients and Methods: Traditionally, most craniotomy patients are admitted to the neurosciences intensive care unit (NSICU) for postoperative follow-up. Decreased availability of NSICU beds during the coronavirus disease-2019 delta surge led our team to establish a de-novo NPCU to preserve capacity for patients requiring high level of care and would bypass routine NSICU admissions. Patients were selected a priori by treating neurosurgeons on the basis of the potential need for high-level ICU services. After operation, selected patients were transferred to the postoperative care unit, where suitability for NPCU transfer was reassessed with checklist-criteria. This process was continued after the delta surge. Results: From July 1, 2021 to September 30, 2022, 57 patients followed the NPCU protocol. Thirty-four (59.6%) were women, and the mean age was 56 years. Fifty-seven craniotomies for 34 intra-axial and 23 extra-axial lesions were performed. After assessment and application of the checklist-criteria, 55 (96.5%) were transferred to NPCU, and only 2 (3.5%) were transferred to ICU. All 55 patients followed in NPCU had good safety outcomes without requiring NSICU transfer. This saved $143,000 and led to 55 additional ICU beds for emergent admissions. Conclusion: This fast-track craniotomy protocol provides early experience that a surgeon-selected group of patients may be suitably monitored outside the traditional NSICU. This system has the potential to reduce overall health care expenses, increase capacity for NSICU bed availability, and change the paradigm of NSICU admission.

The Controversial Effect of Antibiotics on Methicillin-Sensitive S. aureus: A Comparative In Vitro Study.

Methicillin-sensitive Staphylococcus (S.) aureus (MSSA) bacteremia remains a global challenge, despite the availability of antibiotics. Primary treatments include ß-lactam agents such as cefazolin and flucloxacillin. Ongoing discussions have focused on the potential synergistic effects of combining these agents with rifampicin or fosfomycin to combat infections associated with biofilm formation. Managing staphylococcal infections is challenging due to antibacterial resistance, biofilms, and S. aureus's ability to invade and replicate within host cells. Intracellular invasion shields the bacteria from antibacterial agents and the immune system, often leading to incomplete bacterial clearance and chronic infections. Additionally, S. aureus can assume a dormant phenotype, known as the small colony variant (SCV), further complicating eradication and promoting persistence. This study investigated the impact of antibiotic combinations on the persistence of S. aureus 6850 and its stable small colony variant (SCV strain JB1) focusing on intracellular survival and biofilm formation. The results from the wild-type strain 6850 demonstrate that ß-lactams combined with RIF effectively eliminated biofilms and intracellular bacteria but tend to select for SCVs in planktonic culture and host cells. Higher antibiotic concentrations were associated with an increase in the zeta potential of S. aureus, suggesting reduced membrane permeability to antimicrobials. When using the stable SCV mutant strain JB1, antibiotic combinations with rifampicin successfully cleared planktonic bacteria and biofilms but failed to eradicate intracellular bacteria. Given these findings, it is reasonable to report that ß-lactams combined with rifampicin represent the optimal treatment for MSSA bacteremia. However, caution is warranted when employing this treatment over an extended period, as it may elevate the risk of selecting for small colony variants (SCVs) and, consequently, promoting bacterial persistence.

Efficacy of automated insulin delivery (AID) systems in type 1 diabetes: protocol of a systematic review and network meta-analysis of outpatient randomised controlled trials.

INTRODUCTION: Automated insulin delivery (AID), also known as artificial pancreas system or 'closed-loop system', represents a novel option for current treatments for type 1 diabetes (T1D). The objective of this systematic review and meta-analysis is to assess the efficacy of AID systems in comparison with current intensified insulin therapy for glycaemic control and patient-reported outcomes in individuals with T1D. METHODS AND ANALYSIS: Studies will be eligible if they are randomised controlled trials (RCTs) in people with T1D of all ages, and if they compare an AID system for self-administration during the day and night period with any other type of insulin therapy for at least 3 weeks. The primary outcome will be time in the glucose target range of 70-180 mg/dL. A systematic review will be conducted in the MEDLINE, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov registries from their inception dates. Two authors will independently screen all references based on titles and abstracts against the eligibility criteria. For data extraction, standard forms will be developed and tested before extraction. All information will be assessed independently by at least two reviewers. The risk of bias of the included studies will be assessed using the Cochrane Risk of Bias 2 tool. The data synthesis will include a random-effects pairwise and network meta-analysis (NMA) in a frequentist framework. Where applicable and if sufficient RCTs are available, sensitivity analyses will be performed, and heterogeneity and publication bias will be assessed. The certainty of evidence from the NMA will be evaluated following the Grading of Recommendations Assessment, Development, and Evaluation working group guidance. ETHICS AND DISSEMINATION: No ethical approval is needed. The results will be reported to the funder, presented in a peer-reviewed scientific journal and at conferences, and disseminated via press release, social media and public events. PROSPERO REGISTRATION NUMBER: CRD42023395492.

Different elongation factors distinctly modulate RNA polymerase II transcription in Arabidopsis.

Various transcript elongation factors (TEFs) including modulators of RNA polymerase II (RNAPII) activity and histone chaperones tune the efficiency of transcription in the chromatin context. TEFs are involved in establishing gene expression patterns during growth and development in Arabidopsis, while little is known about the genomic distribution of the TEFs and the way they facilitate transcription. We have mapped the genome-wide occupancy of the elongation factors SPT4-SPT5, PAF1C and FACT, relative to that of elongating RNAPII phosphorylated at residues S2/S5 within the carboxyterminal domain. The distribution of SPT4-SPT5 along transcribed regions closely resembles that of RNAPII-S2P, while the occupancy of FACT and PAF1C is rather related to that of RNAPII-S5P. Under transcriptionally challenging heat stress conditions, mutant plants lacking the corresponding TEFs are differentially impaired in transcript synthesis. Strikingly, in plants deficient in PAF1C, defects in transcription across intron/exon borders are observed that are cumulative along transcribed regions. Upstream of transcriptional start sites, the presence of FACT correlates with nucleosomal occupancy. Under stress conditions FACT is particularly required for transcriptional upregulation and to promote RNAPII transcription through +1 nucleosomes. Thus, Arabidopsis TEFs are differently distributed along transcribed regions, and are distinctly required during transcript elongation especially upon transcriptional reprogramming.

Cytosolic RGG RNA-binding proteins are temperature sensitive flowering time regulators in Arabidopsis.

mRNA translation is tightly regulated by various classes of RNA-binding proteins (RBPs) during development and in response to changing environmental conditions. In this study, we characterize the arginine-glycine-glycine (RGG) motif containing RBP family of Arabidopsis thaliana representing homologues of the multifunctional translation regulators and ribosomal preservation factors Stm1 from yeast (ScStm1) and human SERBP1 (HsSERBP1). The Arabidopsis genome encodes three RGG proteins named AtRGGA, AtRGGB and AtRGGC. While AtRGGA is ubiquitously expressed, AtRGGB and AtRGGC are enriched in dividing cells. All AtRGGs localize almost exclusively to the cytoplasm and bind with high affinity to ssRNA, while being capable to interact with most nucleic acids, except dsRNA. A protein-interactome study shows that AtRGGs interact with ribosomal proteins and proteins involved in RNA processing and transport. In contrast to ScStm1, AtRGGs are enriched in ribosome-free fractions in polysome profiles, suggesting additional plant-specific functions. Mutant studies show that AtRGG proteins differentially regulate flowering time, with a distinct and complex temperature dependency for each AtRGG protein. In conclusion, we suggest that AtRGGs function in fine-tuning translation efficiency to control flowering time and potentially other developmental processes in response to environmental changes.

A Novel Model to Generate Heterogeneous and Realistic Time-Series Data for Post-Stroke Rehabilitation Assessment.

The application of machine learning-based tele-rehabilitation faces the challenge of limited availability of data. To overcome this challenge, data augmentation techniques are commonly employed to generate synthetic data that reflect the configurations of real data. One such promising data augmentation technique is the Generative Adversarial Network (GAN). However, GANs have been found to suffer from mode collapse, a common issue where the generated data fails to capture all the relevant information from the original dataset. In this paper, we aim to address the problem of mode collapse in GAN-based data augmentation techniques for post-stroke assessment. We applied the GAN to generate synthetic data for two post-stroke rehabilitation datasets and observed that the original GAN suffered from mode collapse, as expected. To address this issue, we propose a Time Series Siamese GAN (TS-SGAN) that incorporates a Siamese network and an additional discriminator. Our analysis, using the longest common sub-sequence (LCSS), demonstrates that TS-SGAN generates data uniformly for all elements of two testing datasets, in contrast to the original GAN. To further evaluate the effectiveness of TS-SGAN, we encode the generated dataset into images using Gramian Angular Field and classify them using ResNet-18. Our results show that TS-SGAN achieves a significant accuracy increase of classification accuracy (35.2%-42.07%) for both selected datasets. This represents a substantial improvement over the original GAN.

Monocular 3D Human Pose Markerless Systems for Gait Assessment.

Gait analysis plays an important role in the fields of healthcare and sports sciences. Conventional gait analysis relies on costly equipment such as optical motion capture cameras and wearable sensors, some of which require trained assessors for data collection and processing. With the recent developments in computer vision and deep neural networks, using monocular RGB cameras for 3D human pose estimation has shown tremendous promise as a cost-effective and efficient solution for clinical gait analysis. In this paper, a markerless human pose technique is developed using motion captured by a consumer monocular camera (800 × 600 pixels and 30 FPS) for clinical gait analysis. The experimental results have shown that the proposed post-processing algorithm significantly improved the original human pose detection model (BlazePose)'s prediction performance compared to the gold-standard gait signals by 10.7% using the MoVi dataset. In addition, the predicted T2 score has an excellent correlation with ground truth (r = 0.99 and y = 0.94x + 0.01 regression line), which supports that our approach can be a potential alternative to the conventional marker-based solution to assist the clinical gait assessment.

BMP-2 (and partially GDF-5) coating significantly accelerates and augments bone formation close to hydroxyapatite/tricalcium-phosphate/brushite implant cylinders for tibial bone defects in senile, osteopenic sheep.

Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (ß-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing.

Comparison of onset of neuromuscular blockade with electromyographic and acceleromyographic monitoring: a prospective clinical trial.

BACKGROUND: Reliable devices that quantitatively monitor the level of neuromuscular blockade after neuromuscular blocking agents' administration are crucial. Electromyography and acceleromyography are two monitoring modalities commonly used in clinical practice. The primary outcome of this study is to compare the onset of neuromuscular blockade, defined as a Train-Of-Four Count (TOFC) equal to 0, as measured by an electromyography-based device (TetraGraph) and an acceleromyography-based device (TOFscan). The secondary outcome was to compare intubating conditions when one of these two devices reached a TOFC equal to 0. METHODS: One hundred adult patients scheduled for elective surgery requiring neuromuscular blockade were enrolled. Prior to induction of anesthesia, TetraGraph electrodes were placed over the forearm of patients' dominant/non-dominant hand based on randomization and TOFscan electrodes placed on the contralateral forearm. Intraoperative neuromuscular blocking agent dose was standardized to 0.5 mg.kg-1 of rocuronium. After baseline values were obtained, objective measurements were recorded every 20 seconds and intubation was performed using video laryngoscopy once either device displayed a TOFC = 0. The anesthesia provider was then surveyed about intubating conditions. RESULTS: Baseline TetraGraph train-of-four ratios were higher than those obtained with TOFscan (Median: 1.02 [0.88, 1.20] vs. 1.00 [0.64, 1.01], respectively, p < 0.001). The time to reach a TOFC = 0 was significantly longer when measured with TetraGraph compared to TOFscan (Median: 160 [40, 900] vs. 120 [60, 300] seconds, respectively, p < 0.001). There was no significant difference in intubating conditions when either device was used to determine the timing of endotracheal intubation. CONCLUSIONS: The onset of neuromuscular blockade was longer when measured with TetraGraph than TOFscan, and a train-of-four count of zero in either device was a useful indicator for adequate intubating conditions. CLINICAL TRIAL NUMBER AND REGISTRY: URL NCT05120999, https://clinicaltrials.gov/ct2/show/NCT05120999.

Stress deficits in reward behaviour are associated with and replicated by dysregulated amygdala-nucleus accumbens pathway function in mice.

Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress.