Improving MPI and hyperthermia performance of superparamagnetic iron oxide nanoparticles through fractional factorial design of experiments.

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biomedical applications, including magnetic particle imaging (MPI) and magnetic hyperthermia. The co-precipitation method is one of the most common synthetic routes to obtain SPIONs, since it is simple and does not require extreme conditions, such as high temperatures. Despite its prevalence, however, the co-precipitation synthesis presents some challenges, most notably the high batch-to-batch variability, as multiple factors can influence nanoparticle growth. In this study, we utilized a fractional factorial design of experiments to identify key factors influencing SPION growth, properties, and performance in MPI and magnetic hyperthermia, namely Fe3+ content, pH, temperature, stirring, and atmosphere. Notably, our study unveiled secondary interactions, particularly between temperature and Fe3+ content, as well as pH and Fe3+ content, for which simultaneous changes of both parameters promoted greater effects than the sum of each factor effect alone, emphasizing the impact of synergistic effects on SPION growth and performance. These findings provide a deeper understanding of the growth mechanism of SPIONs, reconcile discrepancies in the existing literature, and underscore the importance of characterizing secondary interactions to improve the performance of SPIONs for biomedical applications.

Assessing inorganic nanoparticle toxicity through omics approaches.

In the last two decades, the development of nanotechnology has resulted in inorganic nanoparticles playing crucial roles in key industries, ranging from healthcare to energy technologies. For instance, gold and silver nanoparticles are widely used in rapid COVID-19 and flu tests, titania and zinc oxide nanoparticles are commonly found in cosmetic products, and superparamagnetic iron oxide nanoparticles have been clinically exploited as contrast agents and anti-anemia medicines. As a result, human exposure to nanomaterials is continuously increasing, raising concerns about their potential adverse health effects. Historically, the study of nanoparticle toxicity has largely relied on macroscopic observations obtained in different in vitro and in vivo models, resulting in readouts such as median lethal dose, biodistribution profile, and/or histopathological assessment. In recent years, omics methodologies, including transcriptomics, epigenomics, proteomics, metabolomics, and lipidomics, are increasingly used to characterize the biological interactions of nanomaterials, providing a better and broader understanding of their impact and mechanisms of toxicity. These approaches have been able to identify important genes and gene products that mediate toxicological effects, as well as endogenous functions and pathways dysregulated by nanoparticles. Omics methods improve our understanding of nanoparticle biology, and unravel mechanistic insights into nanomedicine-based therapies. This review aims to provide a deeper understanding and new perspectives of omics approaches to characterize the toxicity and biological interactions of inorganic nanoparticles, and improve the safety of nanoparticle applications.

Distinct Neural Drives along the Semitendinosus Muscle.

INTRODUCTION: Conflicting results have been reported on the functional role of the proximal and distal compartments of the semitendinosus (ST) muscle. This study compared the discharge characteristics of motor units (MUs) in the two compartments at three knee-joint angles (0°: long length, 45°: intermediate length, and 90°: short length). METHODS: Twenty men (21.4 ± 2.3 years) performed steady isometric contractions with the knee flexors at four target forces: 10%, 20%, 40%, and 60% of maximum voluntary contraction (MVC). High-density electromyography (EMG) signals were recorded to examine the MU discharge characteristics in the two compartments. Measurements included recruitment threshold (RT), mean discharge rate (MDR), coefficient of variation for interspike interval (CoV for ISI), and the standard deviation of filtered cumulative spike train (SD of fCST). Additionally, the within- and between-compartment association of the neural drive was calculated. RESULTS: Analysis of variance indicated that maximal force, absolute EMG amplitude during the MVCs, and force steadiness (CoV for force) were greater at the longest muscle length than the other two lengths (P < 0.05). Linear mixed models showed that both RT and CoV for ISI were similar between compartments (P > 0.05) at each of the three knee-joint angles. However, MDR and the variability in neural drive were greater for the proximal than the distal compartment (P < 0.05). The between-compartment association in neural drive (fCST) was relatively low. CONCLUSIONS: There were distinct differences in motor unit discharge characteristics between the proximal and distal compartments of ST across its operating range of muscle lengths and each compartment received a relatively distinct neural drive. These findings emphasize the importance of recognizing differences in neural control of the ST compartments to guide related interventions and inform rehabilitation strategies.

Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.

PURPOSE: There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils. METHODS: SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aß)42, K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies. RESULTS: We optimized the protocol for the immobilization of Aß42, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aß in arcAß mice, and AT-8/AT-100-positivity in pR5 mice. CONCLUSION: SPR measurements of small molecules binding to Aß42, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies.

EMG coherence of foot and ankle muscles increases with a postural challenge in men.

BACKGROUND: The functional role of intrinsic foot muscles in the control of standing balance is often overlooked in rehabilitation, partly because the interactions with ankle muscles are poorly understood. RESEARCH QUESTION: How does coactivation of Flexor Digitorum Brevis (FDB) and soleus (SOL) vary across standing tasks of increasing difficulty. METHODS: Postural sway (Centre of Pressure, CoP) and the electromyographic (EMG) activity of FDB, SOL, Medial Gastrocnemius (MG) and Tibialis Anterior (TA) were measured during bipedal standing, tandem stance, one-legged balance, and standing on toes. Coherence of the rectified EMG signals for SOL and FDB in two bandwidths (0-5 and 10-20 Hz) was calculated as a coactivation index. RESULTS AND SIGNIFICANCE: The CoP sway and the EMG activity of all muscles was greater (P<0.05) for the three difficult tasks. Significant coherence between the SOL and FDB EMG activity was found in both frequency regions: 0-5 and 10-20 Hz. The coherence integral increased with the difficulty of the postural task, especially in the 10-20 Hz band. The findings underscore the important role of FDB in the control of standing balance across tasks and its coactivation with SOL. Clinical recommendations to improve balance control need to consider the interaction between the plantar flexor and intrinsic-foot muscles.

Low-profile versus standard-profile stent grafts in the treatment of abdominal aortic aneurysm: a case-matched study.

Introduction: Endovascular aortic repair (EVAR) is nowadays a widespread method of managing abdominal aortic aneurysm (AAA). Low-profile stent grafts (LPSGs) enable treatment of patients with complex and anatomically challenging aneurysms, and facilitate a percutaneous and thus less invasive procedure. Aim: To assess the outcomes of EVAR with low-profile versus standard-profile stent grafts (SPSGs). Material and methods: Thirty-one patients with abdominal aortic aneurysms (AAA) were treated by endovascular aortic repair (EVAR) using LPSGs. The control group of patients treated with SPSGs was matched with MedCalc software. The clinical records and the preoperative and follow-up computed tomography angiography of patients who underwent endovascular treatment of AAA were included in this study. Results: Patients in the LPSG group had significantly more often low access vessel diameter (< 6 mm) compared to the SPSG group (38.7% vs. 6.7%, p = 0.003). In 1-year follow-up, there was no rupture, no infection, no conversion to open repair and no aneurysm-related death. Five secondary interventions were necessary in the SPSG group and only 1 in the LPSG group (p = 0.09). Type of stent graft was not a risk factor of perioperative complications, presence of endoleak or reintervention (p > 0.05). Risk factors for perioperative complications were COPD and conical neck (OR = 6.3, 95% CI: 1.5-25, p = 0.01 and OR = 6.2, 95% CI: 1-39.76, p = 0.04). The risk factor for endoleak was lower maximal aneurysm diameter. The risk factor for reintervention was proximal neck diameter (OR = 0.77, 95% CI: 0.-0.97, p = 0.03). Conclusions: Our study showed that use of LPSGs is a safe and viable method for patients with narrow access vessels who are not eligible for standard-profile systems.

Geometric morphometric analysis of an ontogenetic cranial series of the Permian dicynodont Diictodon feliceps.

The Karoo Basin of South Africa is renowned for its abundance and diversity of therapsid fossils. Among the most ubiquitous and persistent of the Permian fauna is the small herbivorous dicynodont Diictodon feliceps. Intraspecific variation in Diictodon is historically confounding, and while ontogeny is frequently cited as a potential source of variation, observable developmental changes have never been calibrated. The present study revisits this issue, comparing three-dimensional landmark configurations of 82 Diictodon crania to investigate the association between shape, size and dimorphism. Beyond the statistically significant relationship between shape and allometry, our results determine the shape differences between juvenile and adult skulls of Diictodon, aligned with common craniofacial features documented in other tetrapod taxa. Functionally, these changes are attributed to development of the jaw musculature for feeding on larger, tougher plant matter during later ontogeny. Cranial morphological variation owing to sexual dimorphism is negligible, but distinct differences are noted in the allometric trajectories of each morphotype. A component of non-allometric variation cannot be accounted for, and we propose that this represents natural variation, rather than an artefact of taphonomic deformation.

Can ß-blockers prevent intracranial aneurysm rupture? - insights from Computational Fluid Dynamics analysis.

AIM: Hypertension is a risk factor for intracranial aneurysm rupture. We analyzed whether the intake of drugs from specific classes of anti-hypertensive medications affects hemodynamic parameters of intracranial aneurysm dome. METHODS AND RESULTS: We recorded medical history including medications and the in-hospital blood pressure values. We then obtained 3D reconstruction of each patients' aneurysm dome and the feeding artery. Using OpenFOAM software we performed Computational Fluid Dynamics analysis of blood flow through the modeled structures. Blood was modeled as Newtonian fluid, using the incompressible transient solver. As the inlet boundary condition we used the patient-specific Internal Carotid Artery blood velocity waves obtained with Doppler ultrasound. We calculated haemodynamic parameters of the aneurysm dome. All presented analyses are cross-sectional.We included 72 patients with a total of 91 unruptured intracranial aneurysms. The history of ß-blocker intake significantly influenced hemodynamic parameters of aneurysm dome. The patients on ß-blockers had significantly smaller aneurysm domes (5.09 ± 2.11 mm vs. 7.41 ± 5.89 mm; p = 0.03) and did not have aneurysms larger than 10 mm (0% vs 17.0%; p = 0.01). In the Computational Fluid Dynamics analysis, walls of aneurysms in patients who took ß-blockers were characterized by lower Wall Shear Stress Gradient (1.67 ± 1.85 Pa vs. 4.3 ± 6.06 Pa; p = 0.03), Oscillatory Shear Index (0.03 ± 0.02 vs. 0.07 ± 0.10; p = 0.04) and Surface Vortex Fraction (16.2% ± 5.2% vs. 20.0% ± 6.8%; p<0.01). After controlling for covariates, we demonstrated difference of Surface Vortex Fraction (F[1, 48] = 4.36; p = 0.04) and Oscillatory Shear Index (F[1, 48] = 6.51; p = 0.01) between patients taking and not taking ß-blockers, respectively. CONCLUSION: Intake of ß-blockers might contribute to more favorable hemodynamics inside aneurysmal sac. Other antihypertensive medication classes were not associated with differences in intracranial aneurysm parameters.

Consensus for experimental design in electromyography (CEDE) project: Application of EMG to estimate muscle force.

Skeletal muscles power movement. Deriving the forces produced by individual muscles has applications across various fields including biomechanics, robotics, and rehabilitation. Since direct in vivo measurement of muscle force in humans is invasive and challenging, its estimation through non-invasive methods such as electromyography (EMG) holds considerable appeal. This matrix, developed by the Consensus for Experimental Design in Electromyography (CEDE) project, summarizes recommendations on the use of EMG to estimate muscle force. The matrix encompasses the use of bipolar surface EMG, high density surface EMG, and intra-muscular EMG (1) to identify the onset of muscle force during isometric contractions, (2) to identify the offset of muscle force during isometric contractions, (3) to identify force fluctuations during isometric contractions, (4) to estimate force during dynamic contractions, and (5) in combination with musculoskeletal models to estimate force during dynamic contractions. For each application, recommendations on the appropriateness of using EMG to estimate force and justification for each recommendation are provided. The achieved consensus makes clear that there are limited scenarios in which EMG can be used to accurately estimate muscle forces. In most cases, it remains important to consider the activation as well as the muscle state and other biomechanical and physiological factors- such as in the context of a formal mechanical model. This matrix is intended to encourage interdisciplinary discussions regarding the integration of EMG with other experimental techniques and to promote advances in the application of EMG towards developing muscle models and musculoskeletal simulations that can accurately predict muscle forces in healthy and clinical populations.

Predicting Outcomes in Frail Older Community-Dwellers in Western Australia: Results from the Community Assessment of Risk Screening and Treatment Strategies (CARTS) Programme.

Understanding risk factors for frailty, functional decline and incidence of adverse healthcare outcomes amongst community-dwelling older adults is important to plan population-level health and social care services. We examined variables associated with one-year risk of institutionalisation, hospitalisation and death among patients assessed in their own home by a community-based Aged Care Assessment Team (ACAT) in Western Australia. Frailty and risk were measured using the Clinical Frailty Scale (CFS) and Risk Instrument for Screening in the Community (RISC), respectively. Predictive accuracy was measured from the area under the curve (AUC). Data from 417 patients, median 82 ± 10 years, were included. At 12-month follow-up, 22.5% (n = 94) were institutionalised, 44.6% (n = 186) were hospitalised at least once and 9.8% (n = 41) had died. Frailty was common, median CFS score 6/9 ± 1, and significantly associated with institutionalisation (p = 0.001), hospitalisation (p = 0.007) and death (p < 0.001). Impaired activities of daily living (ADL) measured on the RISC had moderate correlation with admission to long-term care (r = 0.51) and significantly predicted institutionalisation (p < 0.001) and death (p = 0.01). The RISC had the highest accuracy for institutionalisation (AUC 0.76). The CFS and RISC had fair to good accuracy for mortality (AUC of 0.69 and 0.74, respectively), but neither accurately predicted hospitalisation. Home assessment of community-dwelling older patients by an ACAT in Western Australia revealed high levels of frailty, ADL impairment and incident adverse outcomes, suggesting that anticipatory care planning is imperative for these patients.

Foot-dominance does not influence force variability during ankle dorsiflexion and foot adduction.

The aim of our study was to compare the force steadiness and the discharge characteristics of motor units in the tibialis anterior (TA) during ankle dorsiflexion and foot adduction produced by submaximal isometric contractions with the dominant and non-dominant foot. Fifteen young men performed maximal and submaximal contractions at five target forces with both legs, and motor unit activity in TA was recorded using high-density electromyography. Maximal force and the fluctuations in force during submaximal contractions were similar between the two legs (p > 0.05). Motor unit activity was characterized by measures of mean discharge rate (MDR), coefficient of variation for interspike interval (CoV for ISI), and standard deviation of the filtered cumulative spike train (SD of fCST). There were no statistically significant differences in motor unit activity between legs during ankle dorsiflexion. In contrast, the MDR and the CoV for ISI but not the SD of fCST, were greater for the non-dominant foot compared with the dominant foot during foot adduction. Nonetheless, these differences in motor unit activity were not sufficient to influence the force fluctuations during the submaximal contractions. These results indicate that control of the force produced by TA during the two actions was not influenced by limb dominance.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Abnormal alpha-synuclein (αSyn) and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim to visualize αSyn inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. The fluorescent pyrimidoindole derivative THK-565 probe was characterized by means of recombinant fibrils and brains from 10- to 11-month-old M83 mice. Concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging were subsequently performed in vivo. Structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 T as well as scanning transmission x-ray microscopy (STXM) were performed to characterize the iron deposits in the perfused brains. Immunofluorescence and Prussian blue staining were further performed on brain slices to validate the detection of αSyn inclusions and iron deposition. THK-565 showed increased fluorescence upon binding to recombinant αSyn fibrils and αSyn inclusions in post-mortem brain slices from patients with PD and M83 mice. Administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 min post-intravenous injection by wide-field fluorescence compared to nontransgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. In conclusion, we demonstrated in vivo mapping of αSyn by means of noninvasive epifluorescence and vMSOT imaging and validated the results by targeting the THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

Giant stem tetrapod was apex predator in Gondwanan late Palaeozoic ice age.

Current hypotheses of early tetrapod evolution posit close ecological and biogeographic ties to the extensive coal-producing wetlands of the Carboniferous palaeoequator with rapid replacement of archaic tetrapod groups by relatives of modern amniotes and lissamphibians in the late Carboniferous (about 307 million years ago). These hypotheses draw on a tetrapod fossil record that is almost entirely restricted to palaeoequatorial Pangea (Laurussia)1,2. Here we describe a new giant stem tetrapod, Gaiasia jennyae, from high-palaeolatitude (about 55° S) early Permian-aged (about 280 million years ago) deposits in Namibia that challenges this scenario. Gaiasia is represented by several large, semi-articulated skeletons characterized by a weakly ossified skull with a loosely articulated palate dominated by a broad diamond-shaped parasphenoid, a posteriorly projecting occiput, and enlarged, interlocking dentary and coronoid fangs. Phylogenetic analysis resolves Gaiasia within the tetrapod stem group as the sister taxon of the Carboniferous Colosteidae from Euramerica. Gaiasia is larger than all previously described digited stem tetrapods and provides evidence that continental tetrapods were well established in the cold-temperate latitudes of Gondwana during the final phases of the Carboniferous-Permian deglaciation. This points to a more global distribution of continental tetrapods during the Carboniferous-Permian transition and indicates that previous hypotheses of global tetrapod faunal turnover and dispersal at this time2,3 must be reconsidered.

Differentiation of different dibenzothiophene (DBT) desulfurizing bacteria via surface-enhanced Raman spectroscopy (SERS).

Fossil fuels are considered vital natural energy resources on the Earth, and sulfur is a natural component present in them. The combustion of fossil fuels releases a large amount of sulfur in the form of SO x in the atmosphere. SO x is the major cause of environmental problems, mainly air pollution. The demand for fuels with ultra-low sulfur is growing rapidly. In this aspect, microorganisms are proven extremely effective in removing sulfur through a process known as biodesulfurization. A major part of sulfur in fossil fuels (coal and oil) is present in thiophenic structures such as dibenzothiophene (DBT) and substituted DBTs. In this study, the identification and characterization of DBT desulfurizing bacteria (Chryseobacterium sp. IS, Gordonia sp. 4N, Mycolicibacterium sp. J2, and Rhodococcus sp. J16) based on their specific biochemical constituents were conducted using surface-enhanced Raman spectroscopy (SERS). By differentiating DBT desulfurizing bacteria, researchers can gain insights into their unique characteristics, thus leading to improved biodesulfurization strategies. SERS was used to differentiate all these species based on their biochemical differences and different SERS vibrational bands, thus emerging as a potential technique. Moreover, multivariate data analysis techniques such as principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to differentiate these DBT desulfurizing bacteria on the basis of their characteristic SERS spectral signals. For all these isolates, the accuracy, sensitivity, and specificity are above 90%, and an AUC (area under the curve) value of close to 1 was achieved for all PLS-DA models.

VHEE FLASH sparing effect measured at CLEAR, CERN with DNA damage of pBR322 plasmid as a biological endpoint.

Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.08 Gy/s), intermediate (96 Gy/s) and ultra-high dose rates (UHDR, (2 × 109 Gy/s) at the CERN Linear Electron Accelerator (CLEAR) user facility. UHDRs were used to determine if the biological FLASH effect could be measured in the plasmid model, within a hydroxyl scavenging environment. Two different concentrations of the hydroxyl radical scavenger Tris were used in the plasmid environment to alter the proportions of indirect damage, and to replicate a cellular scavenging capacity. Indirect damage refers to the interaction of ionising radiation with molecules and species to generate reactive species which can then attack DNA. UHDR irradiated plasmid was shown to have significantly reduced amounts of damage in comparison to conventionally irradiated, where single strand breaks (SSBs) was used as the biological endpoint. This was the case for both hydroxyl scavenging capacities. A reduced electron energy within the VHEE range was also determined to increase the DNA damage to pBR322 plasmid. Results indicate that the pBR322 plasmid model can be successfully used to explore and test the effect of UHDR regimes on DNA damage. This is the first study to report FLASH sparing with VHEE, with induced damage to pBR322 plasmid DNA as the biological endpoint. UHDR irradiated plasmid had reduced amounts of DNA single-strand breaks (SSBs) in comparison with conventional dose rates. The magnitude of the FLASH sparing was a 27% reduction in SSB frequency in a 10 mM Tris environment and a 16% reduction in a 100 mM Tris environment.

SERS characterization of biochemical changes associated with biodesulfurization of dibenzothiophene using Gordonia sp. HS126-4N.

In this study, Gordonia sp. HS126-4N was employed for dibenzothiophene (DBT) biodesulfurization, tracked over 9 days using SERS. During the initial lag phase, no significant spectral changes were observed, but after 48 h, elevated metabolic activity was evident. At 72 h, maximal bacterial population correlated with peak spectrum variance, followed by stable spectral patterns. Despite 2-hydroxybiphenyl (2-HBP) induced enzyme suppression, DBT biodesulfurization persisted. PCA and PLS-DA analysis of the SERS spectra revealed distinctive features linked to both bacteria and DBT, showcasing successful desulfurization and bacterial growth stimulation. PLS-DA achieved a specificity of 95.5 %, sensitivity of 94.3 %, and AUC of 74 %, indicating excellent classification of bacteria exposed to DBT. SERS effectively tracked DBT biodesulfurization and bacterial metabolic changes, offering insights into biodesulfurization mechanisms and bacterial development phases. This study highlights SERS' utility in biodesulfurization research, including its use in promising advancements in the field.

Tuneable redox-responsive albumin-hitchhiking drug delivery to tumours for cancer treatment.

This paper outlines a novel drug delivery system for highly cytotoxic mertansine (DM1) by conjugating to an albumin-binding Evans blue (EB) moiety through a tuneable responsive disulfide linker, providing valuable insights for the development of effective drug delivery systems toward cancer therapy.

Is it the people or the place? The remarkable 30-year period of integrative physiology research in the Carlson Gymnasium at the University of Colorado Boulder.

Historically, programs of physical education and sport were housed in gymnasium buildings on academic campuses. As physical education evolved to the more scientifically focused successor departments of exercise science and kinesiology, faculty specialization developed in the physiology of exercise. With time, some faculty broadened their research to study the integrative physiology of other biological states and stressors. Through this series of events, a small group of integrative physiologists was formed in the Carlson Gymnasium at the University of Colorado Boulder during the 1990s with the goal of conducting novel biomedical research. The challenges were daunting: no contemporary core laboratory facilities, lack of temperature control, piercing external noise, pests, regular flooding, electrical power outages, and lack of funds for renovation. Despite these obstacles, the group established an innovative program of translational physiological research ranging from high-throughput molecular analyses to cell models to rodent studies to clinical trials in humans. These investigators supported their work with grant awards from the National Institutes of Health (NIH), Department of Defense, National Aeronautics and Space Administration (NASA), American Heart Association, and private research foundations totaling ∼$80 M in direct costs from the late 1980s to 2020. Collectively, the faculty and their laboratory personnel published ∼950 articles in peer-reviewed scientific journals. Over that period, 379 undergraduate students, 340 graduate students, 84 postdoctoral fellows, and dozens of junior research faculty received scientific training in Carlson, supported by >$21 M in extramural funding. What was accomplished by this handful of integrative physiologists speaks to the importance of the qualities of the investigators rather than their research facilities in determining scientific success.

Effects of plyometric training techniques on vertical jump performance of basketball players.

The aim of our study was to compare the effects of two different plyometric training programs (targeting knee extensors or plantar flexors) on jump height and strength of leg muscles. Twenty-nine male basketball players were assigned to the knee-flexed (KF), knee-extended (KE), or control groups. In addition to regular training, the KF group performed plyometric jumps (10 sets of 10 jumps, 3 sessions/week, 4 weeks) from 50 cm boxes with the knee flexed (90°-120°), whereas the KE group performed the jumps from 30 cm boxes with the knee much more extended (130°-170°). Jumping ability was evaluated with squat jumps (SJs), countermovement jumps (CMJs), and drop jumps from 20 cm (DJ20) and 40 cm (DJ40). Knee and ankle muscles were assessed during maximal isokinetic and isometric tests, and EMG activity was recorded from vastus lateralis and medial gastrocnemius. The KF group increased SJ (+10%, d = 0.86) and CMJ (+11%, d = 0.70) but decreased DJ40 height (-7%, d = -0.40). Conversely, the KE group increased DJ20 (+10%, d = 0.74) and DJ40 (+12%, d = 0.77) but decreased SJ height (-4%, d = -0.23). The reactivity index during DJs increased (+10% for DJ20, d = 0.47; +20% for DJ40, d = 0.91) for the KE group but decreased (-10%, d = -0.48) for the KF group during DJ40. Plantar flexor strength increased for the KE group (d = 0.72-1.00) but not for the KF group. Negative transfer across jumps is consistent with the principle of training specificity. Basketball players interested to perform fast rebounds in their training should avoid plyometric jumps with large knee flexions and long contact times.

Explaining the influence of practice on the grooved pegboard times of older adults: role of force steadiness.

The purpose was to identify the variables that can explain the variance in the grooved pegboard times of older adults categorized as either fast or slow performers. Participants (n = 28; 60-83 years) completed two experimental sessions, before and after 6 practice sessions of the grooved pegboard test. The 2 groups were identified based on average pegboard times during the practice sessions. Average pegboard time during practice was 73 ± 11 s for the fast group and 85 ± 13 s for the slow group. Explanatory variables for the pegboard times before and after practice were the durations of 4 peg-manipulation phases and 12 measures of force steadiness (coefficient of variation [CV] for force) during isometric contractions with the index finger abductor and wrist extensor muscles. Time to complete the grooved pegboard test after practice decreased by 25 ± 11% for the fast group and by 28 ± 10% for the slow group. Multiple regression models explained more of the variance in the pegboard times for the fast group before practice (Adjusted R2 = 0.85) than after practice (R2 = 0.51), whereas the variance explained for the slow group was similar before (Adjusted R2 = 0.67) and after (Adjusted R2 = 0.64) practice. The explanatory variables differed between before and after practice for the fast group but only slightly for the slow group. These findings indicate that performance-based stratification of older adults can identify unique adjustments in motor function that are independent of chronological age.