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Brain dissection is typically an important part of teaching neuroscience in health professional programs. This results in the need to effectively remove brains, which is often performed in a gross anatomy laboratory in the same curriculum. The aim of this study was to determine the most effective method of brain removal based on the time required for removal, difficulty of removal, and preservation of key brain structures for educational purposes. Six different dissectors performed each of the three calvaria removal approaches and three different spinal cord transection methods rating them for difficulty and tracking the time required. The combination of calvaria and brainstem approaches and the order of completion was randomized to control for fatigue and previous individual experience. After all brains were removed, each was evaluated by neuroscience faculty for utility in education contexts. The study found little difference between the individual approaches for both calvaria removal and spinal cord transection in regards to quality of outcome. The use of a circumferential cut only proved to be the most time-effective method for calvaria removal while a posterior cut between C1 and C2 was the most time-effective and least difficult method for brainstem release. There was no one technique that proved to be most beneficial across all three measures. However, different approaches resulted in a different combination of benefits across the time, difficulty, and outcome ratings that should be considered in light of the individual needs of any program or researcher.

This visualization provides a snapshot of social isolation in America over a 20-year period. The author leverages data from the American Time Use Survey to estimate the percentage of Americans who report a complete lack of social contact during a single day. Contrary to prior claims, there was no clear evidence of increasing isolation during the 2000s and 2010s. There was, however, a marked increase in the percentage of Americans who were socially isolated during the coronavirus pandemic. Adopting a micro view of social isolation contributes to contemporary debates by highlighting social interactions rather than broad assessments of social integration such as social relationships or group participation. Although these latter concepts are important in their own ways, focusing on social interactions speaks to issues that are often considered synonymous with social integration such as the exchange of support, resources, and feelings of belongingness.

Polyunsaturated fatty acids (PUFAs) and their analogs play a significant role in modulating the activity of diverse ion channels, and recent studies show that these lipids potentiate acid-sensing ion channels (ASICs), leading to increased activity. The potentiation of the channel stems from multiple gating changes, but the exact mechanism of these effects remains uncertain. We posit a mechanistic explanation for one of these changes in channel function, the increase in the maximal current, by applying a combination of electrophysiology and all-atom molecular dynamics simulations on open-state hASIC3. Microsecond-scale simulations were performed on open-state hASIC3 in the absence and presence of a PUFA, docosahexaenoic acid (DHA), and a PUFA analogue, N -arachidonyl glycine (AG). Intriguingly, our simulations in the absence of PUFA or PUFA analogs reveal that a tail from the membrane phospholipid POPC inserts itself into the pore of the channel through lateral fenestrations on the sides of the transmembrane segments, obstructing ion permeation through the channel. The binding of either DHA or AG prevented POPC from accessing the pore in our simulations, which relied on the block of ionic conduction by phospholipids. Finally, we use single-channel recording to show that DHA increases the amplitude of the single-channel currents in ASIC3, which is consistent with our hypothesis that PUFAs relieve the pore block of the channel induced by POPCs. Together, these findings offer a potential mechanistic explanation of how PUFAs modulate the ASIC maximal current, revealing a novel mechanism of action for PUFA-induced modulation of ion channels.

Thoracic and abdominal aortic aneurysms (TAAs and AAAs, respectively) share morphological features but have distinct clinical and hereditary characteristics. Studies using bulk RNA comparisons revealed distinct patterns of gene expression in human TAA and AAA tissues. However, given the summative nature of bulk RNA studies, these findings represent the totality of gene expression without regards to the differences in cellular composition. Single-cell RNA sequencing provides an opportunity to interrogate cell-type-specific transcriptomes. Single cell RNA sequencing datasets from mouse TAA (GSE153534) and AAA (GSE164678 and GSE152583) with respective controls were obtained from the Gene Expression Omnibus. Bioinformatic analysis was performed with the Seurat 4, clusterProfiler, and Connectome software packages (V1.0.1). Immunostaining was performed with standard protocols. Within normal and aneurysmal aortae, three unique populations of cells that express smooth muscle cell (SMC) markers were identified (SMC1, SMC2, and SMCmod). A greater proportion of TAA SMCs clustered as a unique population, SMCmod, relative to the AAA SMCs (38% vs. 10-12%). These cells exhibited transcriptional features distinct from other SMCs, which were characterized by Igfbp2 and Tnfrsf11b expression. Genes upregulated in TAA SMCs were enriched for the Reactome terms "extracellular matrix organization" and "insulin-like growth factor (IGF) transport and uptake by IGF binding proteins (IGFBPs)", indicating a role for Igfbp2 in TAA pathogenesis. Regulon analysis revealed transcription factors enriched in TAAs and AAAs. Validating these mouse bioinformatic findings, immunostaining demonstrated that both IGFBP2 and TNFRSF11B proteins increased in human TAAs compared to AAAs. These results highlight the unique cellular composition and transcriptional signature of SMCs in TAAs and AAAs. Future studies are needed to reveal the pathogenetic pathways of IGFBP2 and TNFRSF11B .

Purpose: Adolescent soccer players experience distinct physiological changes due to chronological and biological maturation, impacting their soccer performance. Here, we explored age-related variations and associations between quadriceps geometry and strength in male national-level adolescent soccer players., Patients and Methods: We used ultrasonography to examine the regional architecture and morphology of the rectus femoris (RF) and vastus lateralis (VL) muscles, and we assessed knee extension strength by isometric and isokinetic dynamometry. Players were categorized into four age groups: under (U) 15 (n=18, age=13.7±0.5 years), U16 (n=15, age=14.7±0.5), U17 (n=19, age=15.7±0.5), U18 (n=18, age=16.7±0.5) and U21 (n=25, age=18.5±0.5)., Results: The absolute and relative strengths were higher in the U16 compared to U15 by 12-15% and 6-8%, 11-12% and 6-7% in the U17 compared to U16, 5-7% and -1-2% in the U18 compared to U17 and 0-15% and -1-11% in the U21 compared to U18 age groups, respectively. VL architecture did not change relevantly between the age groups. The muscle anatomical cross-sectional area (ACSA) of the VL and RF differed non-uniformly and muscle region-specific by 10-36%, with highest values in the U21 age group. Moderate correlations between the VL architecture and knee extension strength in both legs were observed only in the U16 age group. The quadriceps ACSA showed age-specific correlations with knee extension strength., Conclusion: Our findings highlight non-uniform differences in quadriceps muscle morphology and absolute and relative strength among male national-level adolescent soccer players in different age groups. The correlations observed between muscle morphology or architecture and strength were muscle, muscle region, leg and age dependent., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Ritsche et al.)

Difficulties in empathy are frequent among children with autism spectrum disorder (ASD), and often considered a core feature of autism. Reduced empathy during the second year of life has been shown to predict subsequent ASD diagnosis. However, links between empathy in the first year and ASD have not yet been investigated. Moreover, prior work focused on empathy for others' distress but not for others' joy. To address these gaps, this prospective longitudinal study followed 60 infants (33% girls), 39 at high genetic risk of ASD (siblings of children with ASD) and a matching control group. Infants' empathic responses to others' distress and happiness were assessed at ages 6, 9, and 12 months, using simulations by the mother/experimenter and videos of crying and laughing infants. Diagnosis was determined between 18 and 36 months. Infants later diagnosed with ASD showed a reduced empathic response toward a person simulating distress, but not toward a video of a crying peer, and not in response to others' joy (either in simulation or video). Overall, reduced empathic concern during the first year of life appears to be an early prodromal marker of subsequent ASD. Implications for theory, research, and practice are discussed.

Purpose: To examine the feasibility and effects of a functional high-intensity exercise intervention performed in a group-setting on functionality, cardiovascular health and physical performance in adolescents with cerebral palsy (CP)., Methods: Ten adolescents with a diagnosis of CP (2 females; 16.6 ± 3.4 years; GMFCS: I-II) participated in a 12-week training intervention, containing progressive resistance training using free weights and high-intensity workouts twice a week. The six-minute walking test, arterial stiffness and physical performance (strength and power tests) were measured before and after the intervention., Results: No adverse events were reported. We measured small increases in the six-minute walking test (Δ = 28.8 m, 95% CI [-1.78;52.7]; g  = 0.34 [-0.04;0.72]) and a small reduction in arterial stiffness (Δ = -4.65% [-10.90;1.25]; g  = -0.46 [-1.36;0.21]). All measures of physical performance increased (0.24 ≤  g  ≤ 0.88)., Conclusion: Functional training with free weights in high-functioning adolescents with CP is safe and effective in increasing parameters of physical performance and cardiovascular health. Positively influenced indicators of everyday independence (i.e. strength parameters) showed a transfer into movements of daily life. Concerns about adverse events through high-intensity training in adolescents with CP appear unjustified when training is performed progressively, following basic training principles.

We investigate the phase ordering (pattern formation) of systems of two-dimensional core-shell particles using Monte Carlo (MC) computer simulations and classical density functional theory (DFT). The particles interact via a pair potential having a hard core and a repulsive square shoulder. Our simulations show that on cooling, the liquid state structure becomes increasingly characterized by long wavelength density modulations and on further cooling forms a variety of other phases, including clustered, striped, and other patterned phases. In DFT, the hard core part of the potential is treated using either fundamental measure theory or a simple local density approximation, whereas the soft shoulder is treated using the random phase approximation. The different DFTs are benchmarked using large-scale grand-canonical-MC and Gibbs-ensemble-MC simulations, demonstrating their predictive capabilities and shortcomings. We find that having the liquid state static structure factor S(k) for wavenumber k is sufficient to identify the Fourier modes governing both the liquid and solid phases. This allows us to identify from easier-to-obtain liquid state data the wavenumbers relevant to the periodic phases and to predict roughly where in the phase diagram these patterned phases arise., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Voltage-gated sodium (Na v ) channels are pivotal for cellular signaling and mutations in Na v channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function (GoF), loss-of-function (LoF) effects, or both. However, the mechanism behind this functional divergence of mutations at equivalent positions remains elusive. Through hotspot analysis, we identified three gating charges (R1, R2, and R3) as major mutational hotspots in VSDs. The same amino-acid substitutions at equivalent gating-charge positions in VSD I and VSD II of the cardiac sodium channel Na v 1.5 show differential gating-property impacts in electrophysiology measurements. We conducted 120 μs molecular dynamics (MD) simulations on wild-type and six mutants to elucidate the structural basis of their differential impacts. Our μs-scale MD simulations with applied external electric fields captured VSD state transitions and revealed the differential structural dynamics between equivalent R-to-Q mutants. Notably, we observed transient leaky conformations in some mutants during structural transitions, offering a detailed structural explanation for gating-pore currents. Our salt-bridge network analysis uncovered VSD-specific and state-dependent interactions among gating charges, countercharges, and lipids. This detailed analysis elucidated how mutations disrupt critical electrostatic interactions, thereby altering VSD permeability and modulating gating properties. By demonstrating the crucial importance of considering the specific structural context of each mutation, our study represents a significant leap forward in understanding structure-function relationships in Na v channels. Our work establishes a robust framework for future investigations into the molecular basis of ion channel-related disorders., Competing Interests: Declaration of Interests The authors declare no competing interests.

Background: The University of Jyvaskyla Active Aging Scale (UJACAS) assesses active aging through willingness, ability, opportunity, and frequency of involvement in activities. Recognizing the lack of a German version, the Finnish original was translated (UJACAS-G). This study aimed: (1) to evaluate the test-retest reliability of UJACAS-G; and (2) to explore correlations with health-related parameters (concurrent validity)., Methods: The study (test-retest design) targeted healthy older adults aged 65+. Reliability of UJACAS-G (total and subscores) was assessed using Bland-Altman analyses and Intraclass Correlation Coefficients (ICCs). Furthermore, correlations (Spearman's rho) between UJACAS-G scores and physical function (walking speed, handgrip strength, balance, 6-minute walk distance), physical activity (International Physical Activity Questionnaire), life-space mobility (Life-Space Assessment), and health-related quality of life (Short Form-36 Health Survey) were calculated., Results: Bland-Altman analyses (N = 60; mean age 72.3, SD 5.9 years; 50% women) revealed mean differences close to zero and narrow limits of agreement for all scores (total score: mean difference -1.9; limits -31.7 to 27.9). The ability subscore showed clustering at its upper limit. ICC was 0.829 (95% CI 0.730 to 0.894) for the total score and ranged between 0.530 and 0.876 for subscores (all p-values < 0.001). The total score correlated with walking speed (rho = 0.345; p = 0.008), physical activity (rho = 0.279; p = 0.033) and mental health (rho = 0.329; p = 0.010)., Conclusions: UJACAS-G is reliable for assessing active aging among German-speaking healthy older adults. A potential 'ceiling effect' regarding the ability subscore should be considered when applying UJACAS-G to well-functioning populations. Analyses of concurrent validity indicated only weak correlations with health-related parameters., (© 2024. The Author(s).)

Optical imaging plays a central role in biology and medicine but is hindered by light scattering in live tissue. We report the counterintuitive observation that strongly absorbing molecules can achieve optical transparency in live animals. We explored the physics behind this observation and found that when strongly absorbing molecules dissolve in water, they can modify the refractive index of the aqueous medium through the Kramers-Kronig relations to match that of high-index tissue components such as lipids. We have demonstrated that our straightforward approach can reversibly render a live mouse body transparent to allow visualization of a wide range of deep-seated structures and activities. This work suggests that the search for high-performance optical clearing agents should focus on strongly absorbing molecules.

Competing Interests: Die Autorinnen und Autoren dieser Publikation haben alle relevanten Informationen über mögliche Interessenskonflikte offengelegt. Sollten Sie weitere Informationen zu diesem Thema wünschen, wenden Sie sich bitte an die Geschäftsstelle unter: info@swissmemoryclinics.ch, (© 2024 Aerzteverlag medinfo AG.)

Earth's stratosphere is characterized by hypobaric conditions, low temperatures, and high intensities of ultraviolet (UV) and cosmic radiation as well as low water and nutrient availability. While it is not considered a permanent habitat for microorganisms, they can be transported to the stratosphere by storms, volcanic action, or human activity. The impact of those extreme conditions on microorganisms and their survival were tested by sending a sample gondola to the stratosphere. The sample gondola was built to allow exposure of Bacillus subtilis endospores at different angles to the sun. It moreover had holders for three environmental samples to test the effect of stratospheric conditions on complex microbial communities. The gondola attached to a stratospheric balloon was launched near Kiruna, Sweden, ascended to ~25 km, and drifted eastward for ~200 km. Samples were exposed to pressures as low as 2 kPa and temperatures as low as -50°C as well as high UV radiation. Survival rates of B. subtilis were determined by comparing the numbers of colony-forming units (CFUs) for the different exposure angles. Survival was negatively correlated with exposure angle, indicating the significant impact of UV radiation. The effect of stratospheric conditions on environmental samples was assessed by comparing most probable numbers, microbial community composition, and substrate-use profiles to controls that had stayed on the ground. Cultivation was possible from all samples with survival rates of at least 1%, and differences in community composition were observed. Survival of environmental microorganisms might have been supported by the sample matrix, which provided protection from radiation and desiccation., Importance: Earth's stratosphere is a hostile environment that has challenged microbial survival. We set out to test the effect of stratosphere exposure on survival of single species ( Bacillus subtilis ) and complex microbial communities from soils and sediment. B. subtilis survival was strongly impacted by sun exposure, i.e., ultraviolet (UV) radiation, with only 1% survival at full sun exposure. Complex microbial communities had high survival rates, and the soil or sediment matrix may have provided protection against radiation and desiccation, supporting the survival of environmental microorganisms., Competing Interests: The authors declare no conflict of interest.

One of the overarching goals in nuclear science is to understand how the nuclear chart emerges from the underlying fundamental interactions. The description of the structure of nuclei from first principles, using ab initio methods for the solution of the many-nucleon problem with inputs from chiral effective field theory, has advanced dramatically over the past two decades. We present an overview over the available ab initio tools with a specific emphasis on electromagnetic observables, such as multipole moments and transition strengths. These observables still pose a challenge for ab initio theory and are one of the most exciting domains to exploit synergies with modern experiments. Precise experimental data are vital for the validation of the theory predictions and the refinement of ab initio methods. We discuss some of the past and future experimental efforts highlighting these synergies. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.

The Facility for Antiproton and Ion Research (FAIR) is in its final construction stage next to the campus of the Gesellschaft für Schwerionenforschung Helmholtzzentrum for heavy-ion research in Darmstadt, Germany. Once it starts its operation, it will be the main nuclear physics research facility in many basic sciences and their applications in Europe for the coming decades. Owing to the ability of the new fragment separator, Super-FRagment Separator, to produce high-intensity radioactive ion beams in the energy range up to about 2 GeV/nucleon, these can be used in various nuclear reactions. This opens a unique opportunity for various nuclear structure studies across a range of fields and scales: from low-energy physics via the investigation of multi-neutron systems and halos to high-density nuclear matter and the equation of state, following heavy-ion collisions, fission and study of short-range correlations in nuclei and hypernuclei. The newly developed reactions with relativistic radioactive beams (R 3 B) set up at FAIR would be the most suitable and versatile for such studies. An overview of highlighted physics cases foreseen at R 3 B is given, along with possible future opportunities, at FAIR. This article is part of the theme issue 'The liminal position of Nuclear Physics: from hadrons to neutron stars'.

Patchy particles are an intriguing subject of study and indeed a model system in the field of soft matter physics. In recent years, patchy particle models have been applied to describe a wide variety of systems, including colloidal crystals, macromolecular interactions, liquid crystals, and nanoparticle assemblies. Given the importance of the topic, rationalizing and capturing the basic features of these models is crucial to their correct application in specific systems. In this study, we extend the ion-activated attractive patchy particles model previously employed to elucidate the phase behavior of protein solutions in the presence of trivalent salts. Our extension incorporates the effect of repulsion between unoccupied and occupied binding sites, depicted as patches. Furthermore, we examine the influence of model parameters on the liquid-vapor coexistence region within the phase diagram, employing numerical methods. A deeper understanding of this model will facilitate a better comprehension of the effects observed in experiments., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

We developed impedance-matched metal-powder low-pass filters based on coplanar waveguide design and characterized them at room temperature and 77.4 K. The coplanar waveguide metal-powder (CPW-MP) filters have a return loss better than 9.8 dB at frequencies up to 10 GHz at 77.4 K. We find that the filter attenuation per length scales linearly with frequency from 29 to 220 dB/m within the 1-5 GHz frequency range at 77.4 K, achieving the total attenuation above 100 dB for the 1 m-long CPW-MP filter at frequencies above 2 GHz. The CPW-MP filter integrated with the multipole LC filter demonstrates the low cut-off frequency, the attenuation above 100 dB in the stop band, and the high roll-off of 590 dB per decade. The proposed CPW-MP filter is easy to fabricate, has very good thermal-shock resistance, is flexible for integration with other types of low-pass filters, delivers the same performance as classical cryogenic filters, is more compact compared to 50 Ω coax cables with the same type of lossy dielectric, and provides ample opportunities for further miniaturization., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/).)

Introduction: The 2 aims of this observational study are (a) to describe the implementation and feasibility of a bed mobility skills simulation-based mastery learning (SBML) curricular module for physical therapist students and (b) to measure learning outcomes and student perceptions of this module., Review of Literature: Simulation-based mastery learning is an outcome-based educational approach that has been successful in other health professions but has not been explored in physical therapy education., Subjects: Eighty-seven students in a single cohort of a Doctor of Physical Therapy program., Methods: The SBML module in this pretest-posttest study included a pretest, instruction, initial posttest, and additional rounds of instruction and assessment as needed for all learners to achieve the minimum passing standard (MPS) set using the Mastery Angoff and Patient Safety methods. Outcome measures were bed mobility assessment pass rates and scores, additional student and faculty time compared with a traditional approach, and student perceptions of their self-confidence and the module., Results: All students achieved the MPS after 3 rounds of training and assessment beyond the initial posttest. Mean Total Scores improved from 67.6% (12.9%) at pretest to 91.4% (4.8%) at mastery posttest (P < .001, Cohen's d = 1.8, 95% CI [1.4-2.1]); mean Safety Scores improved from 75.2% (16.0%) at pretest to 100.0% (0.0%) at mastery posttest (P < .001, Cohen's d = 1.5, 95% CI [1.2-1.9]). Students who did not achieve the MPS at the initial posttest (n = 30) required a mean of 1.2 hours for additional instruction and assessment. Survey results revealed an increase in student confidence (P < .001) and positive student perceptions of the module., Discussion and Conclusion: Implementation of this SBML module was feasible and resulted in uniformly high levels of bed mobility skill acquisition. Based on rigorous learning outcomes, feasible requirements for implementation, and increased student confidence, SBML offers a promising approach for wider implementation in physical therapy education., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Academy of Physical Therapy Education, APTA.)

Background: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries., Methods: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF))., Results: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01)., Conclusions: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

While converging research suggests that increased white matter hyperintensity load is associated with poorer cognition, and the presence of hypertension is associated with increased white matter hyperintensity load, the relationship among hypertension, cognition and white matter hyperintensities is not well understood. We sought to determine the effect of white matter hyperintensity burden on the relationship between hypertension and cognition in individuals with post-stroke aphasia, with the hypothesis that white matter hyperintensity load moderates the relationship between history of hypertension and cognitive function. Health history, Fazekas scores for white matter hyperintensities and Wechsler Adult Intelligence Scale Matrix Reasoning subtest scores for 79 people with aphasia collected as part of the Predicting Outcomes of Language Rehabilitation study at the Center for the Study of Aphasia Recovery at the University of South Carolina and the Medical University of South Carolina were analysed retrospectively. We found that participants with a history of hypertension had increased deep white matter hyperintensity severity ( P < 0.001), but not periventricular white matter hyperintensity severity ( P = 0.116). Moderation analysis revealed that deep white matter hyperintensity load moderates the relationship between high blood pressure and Wechsler Adult Intelligence Scale scores when controlling for age, education, aphasia severity and lesion volume. The interaction is significant, showing that a history of high blood pressure and severe deep white matter hyperintensities together are associated with poorer Matrix Reasoning scores. The overall model explains 41.85% of the overall variation in Matrix Reasoning score in this group of participants. These findings underscore the importance of considering cardiovascular risk factors in aphasia treatment, specifically hypertension and its relationship to brain health in post-stroke cognitive function., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Premature brain aging is associated with poorer cognitive reserve and lower resilience to injury. When there are focal brain lesions, brain regions may age at different rates within the same individual. Therefore, we hypothesize that reduced gray matter volume within specific brain systems commonly associated with language recovery may be important for long-term aphasia severity. Here we show that individuals with stroke aphasia have a premature brain aging in intact regions of the lesioned hemisphere. In left domain-general regions, premature brain aging, gray matter volume, lesion volume and age were all significant predictors of aphasia severity. Increased brain age following a stroke is driven by the lesioned hemisphere. The relationship between brain age in left domain-general regions and aphasia severity suggests that degradation is possible to specific brain regions and isolated aging matters for behavior., (© 2024. The Author(s).)

Objective: To (1) establish extensive physiological profiles of highly trained CrossFit® athletes using gold-standard tests and (2) investigate which physiological markers best correlate with CrossFit Open performance., Methods: This study encompassed 60 participants (30 men and 30 women), all within the top 5% of the CrossFit Open, including 7 CrossFit semifinalists and 3 CrossFit Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement-jump height and maximum isometric midthigh-pull strength were assessed on a force plate. Peak oxygen uptake (VO2peak) was measured by a cardiopulmonary exercise test, and critical power and W' were evaluated during a 3-minute all-out test, both on a cycle ergometer., Results: Male and female athletes' median (interquartile range) VO2peak was 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) L·min-1, critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) W, and midthigh pull 3158 (2690, 3462) and 2035 (1728, 2347) N. Linear-regression analysis showed strong evidence for associations between different anthropometric variables and CrossFit Open performance in men and women, whereas for markers of cardiorespiratory fitness such as VO2peak, this was only true for women but not men. Conventional laboratory evaluations of strength, however, manifested minimal evidence for associations with CrossFit Open performance across both sexes., Conclusions: This study provides the first detailed insights into the physiology of high-performing CrossFit athletes and informs training optimization. Furthermore, the results emphasize the advantage of athletes with shorter limbs and suggest potential modifications to CrossFit Open workout designs to level the playing field for athletes across different anthropometric characteristics.

Thymus serpyllum L. (Lamiaceae), known in English as 'wild thyme', is primarily found in the Palearctic realm (Eurasia, North Africa) and has been utilized traditionally for culinary, nutritional, medicinal, and aromatic purposes. The essential oil extracted from wild thyme is particularly noteworthy, being used extensively in the food industry as a flavoring agent and preservative. The plant's aerial parts are commonly employed as an element of the diet (e.g., tea)/for culinary uses and in local/traditional medicine (primarily for managing respiratory and gastrointestinal conditions), similar to the use of common thyme. There is practically no information available on the species' nutritional benefits. Pharmacological studies, including in vitro and in vivo research, alongside a limited number of clinical trials, have investigated extracts of Thymus serpyllum , although these extracts are often phytochemically poorly characterized in different experimental protocols and models. These studies have demonstrated a range of therapeutic effects, such as antimicrobial (notably the essential oil) and anti-inflammatory, as well as its preventative health benefits and nutritional value of wild thyme. Preclinical studies have corroborated the plant's anti-inflammatory potential, particularly in conditions like inflammatory bowel diseases (IBD) and irritable bowel syndromes (IBS). Additionally, evidence of hepatoprotective activities and benefits in managing metabolic syndrome and cardiovascular health issues, such as lipid metabolism regulation, cholesterol reduction, antidiabetic, antihypertensive, and immunomodulatory effects, have been observed predominantly in rodent models. Phytochemical analysis of wild thyme reveals an essential oil fraction below 1%, along with non-volatile compounds predominantly comprising phenolic acids (such as rosmarinic, salvianolic, and caffeic acids) and flavonoids (mainly glucosides of luteolin, apigenin, and their derivatives). These components are believed to contribute significantly to the plant's medicinal, nutritional, and preventive health properties. Despite promising findings, there is a need for more rigorously designed controlled clinical trials using phytochemically characterized wild thyme. The plant has an excellent safety and tolerability record. This review at the interface of nutritional/preventive health properties and as pharmacological activities highlights the current role of wild thyme in nutrition and general healthcare as well as its future potential, and also points to important gaps in the literature., Competing Interests: IP and BJ received some financial support from Finzelberg GmbH & Co. KG, Andernach, Germany, for the analysis of the data and the development of the manuscript. RS, CS, AB, BF, and RR-E are employed by Finzelberg GmbH & Co. KG. Finzelberg is a company producing and distributing botanical extracts and their input into this project relates to specific aspects/questions like the assessment of the IP status, production techniques and product analysis. The team is working in research and development of new products. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jalil, Pischel, Feistel, Suarez, Blainski, Spreemann, Roth-Ehrang and Heinrich.)

Background: During sprinting, the biceps femoris long head predominantly gets injured, while hamstring strengthening exercises predominantly activate the semitendinosus more effectively. Understanding how joint dominance influences hamstring activity may offer clarity on appropriate exercise selection in strengthening programs., Purpose: This study compared three hip-dominant hamstring exercises: the rocker, perpetuum mobile fast and slow (PMfast and PMslow) and the Nordic Hamstring exercise (NHE) on their potential to simulate sprint-like activity and kinematics., Methods: Muscle activity of the posterior kinetic chain (biceps femoris, semitendinosus, gluteus maximus, and medial gastrocnemius) was measured with surface electromyography (sEMG) during the exercises and treadmill running at 75% of the individual maximal sprint velocity in male athletes. sEMG data were normalized to maximal sprinting. 3D-motion capture was employed to assess hip and knee angles., Results: Eight male athletes were included (age: 24.0 years ± SD 2.9; body mass: 76.8 kg ± 7.7; height: 1.79 m ± 0.08). Greater activity of the hamstrings occurred during the explosive exercises ranging from 63.9% [95%CI: 56.3-71.5%] (rocker) to 49.0% [95%CI: 40.4-57.6%] (PMfast) vs. 34.0% [95%CI: 29.1-38.9%] (NHE) to 32.1% [95%CI: 26.9-37.3%] (PMslow). The rocker showed greatest hamstring and gluteus maximus activity. Biceps femoris consistently showed greater activity than the semitendinosus across all exercises in peak (mean difference: 0.16, [95%CI: 0.07-0.26]) and average (mean difference: 0.06, [95%CI: 0.01-0.11]) activity. PMfast, PMslow and NHE demonstrated less hip flexion angle at peak hamstring activity than the rocker and high-speed running and every exercise showed less hamstring elongation stress than during high-speed running., Discussion: Hamstring activity is comparable to high-intensity treadmill running for NHE and PMslow, and greater for the rocker and PMfast. Gluteus maximus activity varied, with the rocker and PMfast showing greater activity than in sprinting. All examined exercises demonstrated their peak activity at short hamstring muscle length., Level of Evidence: 3b., (© The Author(s).)

Arbuscular mycorrhizal (AM) symbiosis is a mutualistic interaction between fungi and most land plants that is underpinned by a bidirectional exchange of nutrients. AM development is a tightly regulated process that encompasses molecular communication for reciprocal recognition, fungal accommodation in root tissues and activation of symbiotic function. As such, a complex network of transcriptional regulation and molecular signaling underlies the cellular and metabolic reprogramming of host cells upon AM fungal colonization. In addition to transcription factors, small RNAs (sRNAs) are emerging as important regulators embedded in the gene network that orchestrates AM development. In addition to controlling cell-autonomous processes, plant sRNAs also function as mobile signals capable of moving to different organs and even to different plants or organisms that interact with plants. AM fungi also produce sRNAs; however, their function in the AM symbiosis remains largely unknown. Here, we discuss the contribution of host sRNAs in the development of AM symbiosis by considering their role in the transcriptional reprogramming of AM fungal colonized cells. We also describe the characteristics of AM fungal-derived sRNAs and emerging evidence for the bidirectional transfer of functional sRNAs between the two partners to mutually modulate gene expression and control the symbiosis., (© 2023 The Authors. New Phytologist © 2023 New Phytologist Foundation.)

A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon α/β receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 μg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine. In a follow up trial, mice were vaccinated with an adjuvanted nine-serotype multivalent VP2 vaccine in a prime boost strategy and resulted in the desired neutralising antibody titres of 1:320, previously demonstrated to confer protective immunity in IFNAR-/- mice. In addition, the plant-produced VP2 vaccine performed favourably when compared to the commercial vaccine. Here we provide compelling data for a nonavalent VP2-based vaccine candidate, with the VP2 from each serotype being antigenically distinguishable based on LC-MS/MS and ELISA data. This is the first preclinical trial demonstrating the ability of an adjuvanted nonavalent cocktail of soluble, plant-expressed AHS VP2 proteins administered in a prime-boost strategy eliciting high antibody titres against all 9 AHSV serotypes. Furthermore, elevated T helper cells 2 (Th2) and Th1, indicative of humoral and cell-mediated memory T cell immune responses, respectively, were detected in mouse serum collected 14 days after the multivalent prime-boost vaccination. Both Th2 and Th1 may play a role to confer protective immunity. These preclinical immunogenicity studies paved the way to test the safety and protective efficacy of the plant-produced nonavalent VP2 vaccine candidate in the target animals, horses., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Plant-produced chimaeric Orbivirus VLPs is patent protected (PCT/IB2017/052236, WO 2017/182958 A1, US 11,053,509 B2, ARIPO AP 6697 registered, invented by authors DR and MMO). The AHSV VP2 fusions proteins are protected by a patent application (PCT/IB2023/058808, invented by MMO and YL). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no additional patents, products in development or marketed products associated with this research to declare, (Copyright: © 2024 O’Kennedy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type)., Methods: This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment., Results: Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F (1)=4.23, p =0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit ( R =0.35, p =0.03)., Conclusions: These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

In the quest for heightened protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, we engineered a prototype vaccine utilizing the plant expression system of Nicotiana benthamiana, to produce a recombinant SARS-CoV-2 virus-like particle (VLP) vaccine presenting the S-protein from the Beta (B.1.351) variant of concern (VOC). This innovative vaccine, formulated with either a squalene oil-in-water emulsion or a synthetic CpG oligodeoxynucleotide adjuvant, demonstrated efficacy in a golden Syrian Hamster challenge model. The Beta VLP vaccine induced a robust humoral immune response, with serum exhibiting neutralization not only against SARS-CoV-2 Beta but also cross-neutralizing Delta and Omicron pseudoviruses. Protective efficacy was demonstrated, evidenced by reduced viral RNA copies and mitigated weight loss and lung damage compared to controls. This compelling data instills confidence in the creation of a versatile platform for the local manufacturing of potential pan-sarbecovirus vaccines, against evolving viral threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Abstract: Keller, M, Lichtenstein, E, Roth, R, and Faude, O. Balance training under fatigue: a randomized controlled trial on the effect of fatigue on adaptations to balance training. J Strength Cond Res 38(2): 297-305, 2024-Balance training is an effective means for injury prevention in sports. However, one can question the existing practice of putting the balance programs at the start of a training session (i.e., train in an unfatigued state) because the occurrence of injuries has been associated with fatigue. Therefore, the aim of this study was to assess the influence of balance training in a fatigued or an unfatigued state on motor performance tested in fatigued and unfatigued conditions. Fifty-two, healthy, active volunteers (28.0 years; 19 women) were randomly allocated to 1 of 3 different training groups. The BALANCE group completed 6 weeks of balance training. The other 2 groups completed the identical balance tasks either before (BALANCE-high-intensity interval training [HIIT]) or after (HIIT-BALANCE) a HIIT session. Thus, these groups trained the balance tasks either in a fatigued or in an unfatigued state. In PRE and POST tests, balance (solid ground, soft mat, wobble board) and jump performance was obtained in fatigued and unfatigued states. Balance training resulted in reduced sway paths in all groups. However, the linear models revealed larger adaptations in BALANCE-HIIT and BALANCE when compared with HIIT-BALANCE ( d = 0.22-0.71). These small to moderate effects were-despite some uncertainties-consistent for the "unfatigued" and "fatigued" test conditions. The results of this study revealed for the first time that balance training under fatigue results in diminished adaptations, even when tested in a fatigued state. Therefore, the data indicate that balance training should be implemented at the start of a training session or in an unfatigued state., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the National Strength and Conditioning Association.)

Background: Dispatcher assistance can help to save lives during layperson cardiopulmonary resuscitation during cardiac arrest. The aim of this study was to investigate the influence of different camera positions on the evaluation of cardiopulmonary resuscitation performance during video-assisted cardiopulmonary resuscitation., Methods: For this randomized, controlled simulation trial, seven video sequences of cardiopulmonary resuscitation performance were recorded from three different camera positions: side, foot and head position. Video sequences showed either correct cardiopulmonary resuscitation performance or one of the six typical errors: low and high compression rate, superficial and increased compression depth, wrong hand position or incomplete release. Video sequences with different cardiopulmonary resuscitation performances and camera positions were randomly combined such that each evaluator was presented seven individual combinations of cardiopulmonary resuscitation and camera position and evaluated each cardiopulmonary resuscitation performance once. A total of 46 paramedics and 47 emergency physicians evaluated seven video sequences of cardiopulmonary resuscitation performance from different camera positions. The primary hypothesis was that there are differences in accuracy of correct assessment/error recognition depending on camera perspective. Generalized linear multi-level analyses assuming a binomial distribution and a logit link were employed to account for the dependency between each evaluator's seven ratings., Results: Of 651 video sequences, cardiopulmonary resuscitation performance was evaluable in 96.8% and correctly evaluated in 74.5% over all camera positions. Cardiopulmonary resuscitation performance was classified correctly from a side perspective in 81.3%, from a foot perspective in 68.8% and from a head perspective in 73.6%, revealing a significant difference in error recognition depending on the camera perspective ( p  = .01). Correct cardiopulmonary resuscitation was mistakenly evaluated to be false in 46.2% over all perspectives., Conclusions: Participants were able to recognize significantly more mistakes when the camera was located on the opposite side of the cardiopulmonary resuscitation provider. Foot position should be avoided in order to enable the dispatcher the best possible view to evaluating cardiopulmonary resuscitation quality., Competing Interests: Declaration of conflicting interestsBernd W. Böttiger is European Resuscitation Council (ERC) Board Director Science and Research; Chairman of the German Resuscitation Council (GRC); Member of the Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR); Member of the executive committee of the German Interdisciplinary Association for Intensive and Emergency Medicine (DIVI); Associated Editor of the European Journal of Anaesthesiology (EJA), Co-Editor of “Resuscitation”; Editor of the Journal “Notfall + Rettungsmedizin.” He received professional fees for lectures from the following companies: “Forum für medizinische Fortbildung (FomF),” ZOLL Medical Deutschland GmbH, C. R. Bard GmbH, GS Elektromedizinische Geräte G. Stemple GmbH. The other authors do not have a conflict of interest.