Changes In Kinetics Research Articles

Exercise training-induced speeding of kinetics is not intensity domain-specific or correlated with indices of exercise performance.

This study examined the effect of 3 and 6weeks of intensity domain-based exercise training on kinetics changes and their relationship with indices of performance. Eighty-four young healthy participants (42M, 42 F) were randomly assigned to six groups (14 participants each, age and sex-matched) consisting of: continuous cycling in the (1) moderate (MOD)-, (2) lower heavy (HVY1)-, and (3) upper heavy-intensity (HVY2)- domain; interval cycling in the (4) severe-intensity domain (i.e., high-intensity interval training (HIIT), or (5) extreme-intensity domain (i.e., sprint-interval training (SIT)); or (6) control (CON). Training participants completed two three-week phases of three supervised sessions per week, with physiological evaluations performed at PRE, MID and POST intervention. All training protocols, except SIT, were work-matched. There was a significant time effect for the time constant ( ) between PRE (31.6 ± 10.4s) and MID (22.6 ± 6.9s) (p < 0.05) and PRE and POST (21.8 ± 6.3s) (p < 0.05), but no difference between MID and POST (p > 0.05) and no group or interaction effects (p > 0.05). There were no PRE to POST differences for CON (p < 0.05) in any variables. Despite significant increases in maximal ( ), estimated lactate threshold (θLT), maximal metabolic steady state (MMSS), and peak power output (PPO) for the intervention groups (p < 0.05), there were no significant correlations from PRE to MID or MID to POST between and (r = - 0.221, r = 0.119), ΔPPO (r = - 0.112, r = - 0.017), ΔθLT (r = 0.083, r = 0.142) and ΔMMSS (r = - 0.213, r = 0.049)(p > 0.05). This study demonstrated that (i) the rapid speeding of kinetics was not intensity-dependent; and (ii) changes in indices of performance were not significantly correlated with .

Investigating Interaction Dynamics of an Enantioselective Peptide‐Catalyzed Acylation Reaction

Modern nuclear magnetic resonance (NMR) methods like carbon relaxation dispersion in the rotating frame (13C‐R1ρ) and proton chemical exchange saturation transfer (1H‐CEST) are key methods to investigate molecular recognition in biomacromolecules and to detect molecular motions on the µs to s timescale, revealing transient conformational states. Changes in kinetics can be linked to binding, folding, or catalytic events. Here, we investigated whether these methods allow detection of changes in the dynamics of a small, highly selective peptide catalyst during recognition of its enantiomeric substrates. The flexible tetrapeptide Boc‐l‐(π‐Me)‐His‐AGly‐l‐Cha‐l‐Phe‐OMe, used for the monoacetylation of cycloalkane‐diols, is probed at natural abundance using 13C‐R1ρ and 1H‐CEST. Indeed, we detected differences in dynamics of the peptide upon interaction with the diol. Importantly, these differ depending on the enantiomer of the substrate used. These enantiospecific influences of the substrates on the dynamics of the peptide are rationalized using computational techniques. We find that even though one enantiomer reacts faster, as confirmed by reaction monitoring, the other is more tightly bound in DCM (as confirmed by 1H‐saturation transfer difference (STD) measurements). These findings provide insights into the recognition of the substrates and explain the selectivity differences observed between the solvents toluene and DCM.

Investigating Interaction Dynamics of an Enantioselective Peptide‐Catalyzed Acylation Reaction

Modern nuclear magnetic resonance (NMR) methods like carbon relaxation dispersion in the rotating frame (13C‐R1ρ) and proton chemical exchange saturation transfer (1H‐CEST) are key methods to investigate molecular recognition in biomacromolecules and to detect molecular motions on the µs to s timescale, revealing transient conformational states. Changes in kinetics can be linked to binding, folding, or catalytic events. Here, we investigated whether these methods allow detection of changes in the dynamics of a small, highly selective peptide catalyst during recognition of its enantiomeric substrates. The flexible tetrapeptide Boc‐l‐(π‐Me)‐His‐AGly‐l‐Cha‐l‐Phe‐OMe, used for the monoacetylation of cycloalkane‐diols, is probed at natural abundance using 13C‐R1ρ and 1H‐CEST. Indeed, we detected differences in dynamics of the peptide upon interaction with the diol. Importantly, these differ depending on the enantiomer of the substrate used. These enantiospecific influences of the substrates on the dynamics of the peptide are rationalized using computational techniques. We find that even though one enantiomer reacts faster, as confirmed by reaction monitoring, the other is more tightly bound in DCM (as confirmed by 1H‐saturation transfer difference (STD) measurements). These findings provide insights into the recognition of the substrates and explain the selectivity differences observed between the solvents toluene and DCM.

Clarithromycin For Improved Clinical Outcomes in Community-Acquired Pneumonia: A Subgroup Analysis of the ACCESS Study.

In the ACCESS trial the addition of clarithromycin to standard-of-care (SoC) antibiotics enhanced early clinical response and attenuated the inflammatory burden in adults with community-acquired pneumonia (CAP) requiring hospitalization. A post-hoc analysis was performed to investigate the benefit in specific subgroups. The primary endpoint comprised two conditions to be met during the first 72 hours: ≥50% decrease of respiratory symptom severity score; and any of ≥30% decrease of SOFA score and favourable change of kinetics of procalcitonin (defined as ≥80% PCT decrease or PCT <0.25 ng/ml). In this exploratory post-hoc analysis achievement of the study composite primary endpoint was compared between the two treatment groups within subsets differentiated by demographic characteristics, comorbidities, CAP severity, baseline laboratory findings and corticosteroid co-administration. The impact of clarithromycin treatment on the need for mechanical ventilation (MV) in all subgroups was also analysed. The addition of clarithromycin significantly increased the proportion of patients achieving the primary endpoint across all subgroups and decreased the need for MV in many subgroups. For instance, the primary endpoint was attained by 32.7% of placebo-treated patients and in 67% of clarithromycin-treated patients with CURB-65 score ≥2 (p<0.0001) whereas MV was required in 18.8% and 7.4% respectively (p=0.022). The addition of corticosteroids alone was not as clinically advantageous as the use of clarithromycin alone. Adding clarithromycin to SoC in the ACCESS study achieved early clinical anti-inflammatory responses and decreased the need for MV in subgroups of hospitalized patients with CAP. EudraCT 2020-004452-15; ClinicalTrials.gov NCT04724044.

A comparison of kinematic and kinetic characteristics of intrinsic flexor muscles of the foot exercises: Effect on the medial longitudinal arch of the foot

Background Standing toe curl (STC) has an immediate effect on muscle activity, but the kinematics of the exercise and its effect on the medial longitudinal arch of the foot are unknown. Objective The purpose of this study was to examine the differences in kinematic and kinetic changes during toe flexion while performing towel curl (TC) in a standing position and STC. Methods Ten healthy adults with normal feet (18 limbs) participated in this study. Using a three-dimensional motion analysis system, we calculated the toe flexion angle, medial longitudinal arch (MLA) angle, MLA height, MLA length, ankle joint angle, center of foot pressure, and center position of the hip joint during toe flexion using TC and STC exercises. Results The TC exercise resulted in a decrease in the MLA due to the backward shift in the center of pressure and ankle dorsiflexion. On the other hand, STC did not demonstrate any significant difference in the position of the center of pressure or ankle joint angle, allowing the toes to flex while maintaining a standing posture and resulting in an increase in the MLA. Conclusions STC was suggested to be effective in maintaining MLA for weight support.

Combined dual-channel fluorescence depth sensing of indocyanine green and protoporphyrin IX kinetics in subcutaneous murine tumors.

Fluorescence sensing within tissue is an effective tool for tissue characterization; however, the modality and geometry of the image acquisition can alter the observed signal. We introduce a novel optical fiber-based system capable of measuring two fluorescent contrast agents through 2cm of tissue with simple passive electronic switching between the excitation light, simultaneously acquiring fluorescence and excitation data. The goal was to quantify indocyanine green (ICG) and protoporphyrin IX (PpIX) within tissue, and the sampling method was compared with wide-field surface imaging to contrast the value of deep sensing versus surface imaging. This was achieved by choosing filters for specific wavelengths that were mutually exclusive between ICG and PpIX and coupling these filters to two separate detectors, which allows for direct swapping of the excitation and emission channels by switching the on-time of each excitation laser between 780- and 633-nm wavelengths. This system was compared with two non-contact surface imaging systems for both ICG and PpIX, which revealed that the fluorescence depth sensing system was superior in its ability to resolve kinetics differences in deeper tissues that would normally be dominated by strong signals from skin and other surface tissues. Specifically, the system was tested using pancreatic adenocarcinoma tumors injected into murine models, which were imaged at several time points throughout tumor growth to its diameter. This demonstrated the system's capability to track longitudinal changes in ICG and PpIX kinetics that result from tumor growth and development, with larger tumors showing sluggish uptake and clearance of ICG, which was not observable with surface imaging. Similarly, PpIX was quantified, which showed slower kinetics over different time points, and was further compared with the wide-filed imager. These results were further validated through depth measurements in tissue phantoms and model-based interpretation. This fluorescence depth sensing system can be used to sample the interior blood flow characteristics by ICG sensing of tissue as deep as 20mm into the tissue with sensitivity to kinetics that are superior to surface imaging and may be combined with other imaging modalities such as ultrasound to provide guided deep fluorescence measurements.

The Relationship Between Length and Active Force for Submaximal Skeletal Muscle Contractions: a Review.

The force-length relationship is usually obtained for isometric contractions with maximal activation, but less is known about how sarcomere length affects force during submaximal activation. During submaximal activation, length-dependent alterations in calcium sensitivity, owing to changes in cross-bridge kinetics (rate of attachment and/or detachment), result in an activation-dependent shift in optimal length to longer sarcomere lengths. It is known that sarcomere length, as well as temperature and phosphorylation of the regulatory light chains of myosin, can modify Ca2⁺ sensitivity by altering the probability of cross-bridge interaction. This altered calcium sensitivity is particularly important for submaximal force levels, as it can change the shape of the length dependence of force, with peak force occurring at sarcomere lengths longer than those associated with maximal filament overlap. In athletic contexts, contractions typically do not reach maximal intensity. Therefore, understanding that the ability to produce force under both maximal and submaximal conditions can differ, and that peak force can be generated at different lengths, could influence the development of targeted training regimens optimal for each sport.

Establishment of CD1b-restricted immunity to lipid antigens in the pulmonary response to Mycobacterium tuberculosis infection.

CD1 is an antigen-presenting glycoprotein homologous to MHC I; however, CD1 proteins present lipid rather than peptide antigens. CD1 proteins are well established to present lipid antigens of Mycobacterium tuberculosis (Mtb) to T cells, but understanding the role of CD1-restricted immunity in vivo in response to Mtb infection has been limited by the availability of animal models naturally expressing the CD1 proteins implicated in human response: CD1a, CD1b, and CD1c. Guinea pigs, in contrast to other rodent models, express four CD1b orthologs, and here we utilize the guinea pig to establish the kinetics of gene and protein expression of CD1b orthologs, as well as the Mtb lipid-antigen and CD1b-restricted immune response at the tissue level over the course of Mtb infection. Our results indicate transient upregulation of CD1b expression during the effector phase of adaptive immunity that wanes with disease chronicity. Gene expression indicates that the upregulation of CD1b is the result of transcriptional induction across all CD1b orthologs. We show high CD1b3 expression on B cells, and identify CD1b3 as the predominant CD1b ortholog in pulmonary granuloma lesions. We identify ex vivo cytotoxic activity directed against CD1b that parallels the kinetic changes in CD1b expression in Mtb-infected lungs and spleen. This study confirms that CD1b expression is modulated by Mtb infection in lung and spleen, leading to pulmonary and extrapulmonary CD1b-restricted immunity as a component of the antigen-specific response to Mtb infection.

Aqueous dissolution rate of nuclear waste glasses as a function of aqueous Si concentration and pH

The aqueous dissolution rate was measured precisely for two kinds of reference nuclear waste glasses, ISG and P0798, as a function of aqueous Si concentration and pH of a solution by using the micro-channel flow-through test method with Si isotopes. The glass dissolution rate determined from the Si dissolution rate decreased with increasing aqueous Si concentration at pH 9. In contrast, the dissolution rate at pH 4 was not affected by the Si concentration or increased slightly with an increase in the Si concentration. Therefore, the glass dissolution mechanism with the altered surface properties depended sensitively on pH, causing large changes in the glass dissolution kinetics.

Kinetic changes of gait initiation in individuals with chronic ankle instability: A systematic review.

Gait initiation (GI) in individuals with chronic ankle instability (CAI) has shown differences in the center of pressure (COP) and muscular measures compared to healthy controls. Some studies reported that these alterations appeared when GI was with the affected leg, while others indicated that they occurred when GI was with the non-affected leg. This systematic review aimed to understand kinetic and muscular differences between individuals with CAI, healthy controls, and the affected and non-affected legs of individuals with CAI. PubMed, Science Direct, Web of Science, Google Scholar, and Scopus databases (1990-2023) were searched using the Population, Exposure, Comparator, and Outcome measure. The PRISMA guidelines were followed. The outcome measures were the peak and rate of COP displacement in the medial-lateral and anterior-posterior directions, and resultant plane during phases 1, 2, and 3 of COP trace during GI and the duration of each phase. The other measures included the onset time of the tibialis anterior and soleus muscle activity between individuals with CAI, healthy controls, and the affected and non-affected legs of the individuals with CAI. The studies' quality assessment was conducted based on the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Five studies were included in the final evaluation. The results of included studies showed, individuals with CAI spent less time during phases 1 and 2, as well as a shorter peak of COP displacement in the lateral direction during phase 1 compared to healthy controls, regardless of whether the GI was with the affected or non-affected leg. Individuals with CAI have probably adopted a strategy involving adjusting the peak of COP displacement to manage internal sway while in a single-leg stance. Overall, there was no comprehensive conclusion about differences between the two legs in individuals with CAI.

Heterotropic Allosteric Modulation of CYP3A4 In Vitro by Progesterone: Evidence for Improvement in Prediction of Time Dependent Inhibition for Macrolides.

Predictions of drug-drug interactions resulting from time-dependent inhibition (TDI) of CYP3A4 have consistently overestimated or mis-predicted (i.e. false positives) the interaction that is observed in vivo. Recent findings demonstrated that the presence of the allosteric modulator progesterone (PGS) in the in vitro assay could alter the in vitro kinetics of CYP3A4 TDI with inhibitors that interact with the heme moiety, such as metabolic-intermediate complex (MIC) forming inhibitors. The impact of the presence of 100 µM PGS on the TDI of molecules in the class of macrolides typically associated with MIC formation was investigated. Presence of PGS resulted in varied responses across the inhibitors tested. The TDI signal was eliminated for five inhibitors, and unaltered in the case of one, fidaxomicin. The remaining molecules erythromycin, clarithromycin, and troleandomycin, were observed to have a decrease in both potency and maximum inactivation rate ranging from 1.7-fold to 6.7-fold. These changes in TDI kinetics led to a >90% decrease in inactivation efficiency. In order to determine in vitro conditions that could reproduce in vivo inhibition, varied concentrations of PGS were incubated with clarithromycin and erythromycin. Resulting in vitro TDI kinetics were incorporated into dynamic physiologically-based pharmacokinetic (PBPK) models to predict clinically observed interactions. The results suggested that a concentration of ~45 µM PGS would result in TDI kinetic values that could reproduce in vivo observations and could potentially improve predictions for CYP3A4 TDI. Significance Statement The impact of the allosteric heterotropic modulator progesterone on the CYP3A4 time-dependent inhibition kinetics was quantified for a set of metabolic-intermediate complex forming mechanism-based inhibitors. We identify the in vitro conditions that optimally predict time-dependent inhibition for in vivo drug-drug interactions through dynamic physiologically-based pharmacokinetic modeling. The optimized assay conditions improve in vitro to in vivo translation and prediction of time-dependent inhibition.

Investigating the Potential of Cr3+-Doped Pyroxene for Highly Sensitive Optical Pressure Sensing.

Luminescent manometry has gained significant popularity in recent years due to its capability to provide in situ pressure measurements in a remote manner. Therefore, there is a growing need to identify phosphors with pressure-dependent spectroscopic properties that can be utilized to develop highly sensitive pressure sensors operating over a wide pressure range. Hence, we present a novel temperature-invariant luminescent manometer based on Cr3+ ion emission in pyroxene Ca0.8Sr0.2MgSi2O6:Cr3+. We utilized two readout modes, including an innovative luminescent pressure sensing ratiometric approach based on the broad emission band associated with the 4T2g → 4A2g electronic transition of Cr3+ ions. This approach provided an exceptionally high sensitivity of SR = 50.7 ± 0.5% GPa-1 and ensured temperature-independent pressure measurements, thus offering highly reliable readouts. Furthermore, the proposed readout mode, which leverages changes in luminescence kinetics, demonstrated high sensitivity at high pressure at around 5 GPa (SR ∼ 8 ± 0.2% GPa-1) surpassing the performance of luminescence kinetics-based manometers reported to date. Consequently, Ca0.8Sr0.2MgSi2O6:Cr3+ emerges as a highly promising phosphor with significant application potential for pressure sensing across a broad pressure range.

Acute kidney injury in relation to high-sensitivity cardiac troponin T levels in the emergency department

Abstract Background The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in all-comers with AKI in the emergency department (ED) is largely unknown. Purpose To investigate the prevalence of myocardial injury, associations between serum-creatinine concentrations (SCC) and hs-cTnT kinetics, and the accuracy of established hs-cTnT-based myocardial infarction (MI) risk stratification algorithm criteria in patients with AKI. Methods This observational cohort study was based on patient visits to 7 EDs in Sweden from December 9, 2010 to August 31, 2017. All visits by patients ≥18 years fulfilling criteria for AKI with ≥1 hs-cTnT measurement and the exposure was dynamic change in SCC (ΔSCC) during the visits. Linear mixed models were used to estimate linear predictors of kinetic change in hs-cTnT (Δhs-cTnT). Logistic regression models were applied to calculate odds ratios (ORs) for Δhs-cTnT indicative of acute myocardial injury (Δhs-cTnT &amp;gt;20% and elevated hs-cTnT) in relation to ΔSCC among patients without MI, and to assess the diagnostic performance of hs-cTnT for MI in a subgroup of patients presenting with chest pain. Results A total of 15,211 visits by patients with AKI were included, of whom 1174 (8%) had an MI. Four of five (81%) patients without MI had myocardial injury (hs-cTnT &amp;gt;14 ng/l), and almost one of three (31%) had acute myocardial injury. These entities were common in both cardiac and non-cardiac conditions. The Δhs-cTnT in non-MI patients was 1.8-fold (β: 1.78, 95% CI: 1.62-1.96) in the highest quartile of ΔSCC and was paralleled by a 2-fold risk of acute myocardial injury (OR: 2.32, 95% CI: 2.08-2.59), compared with the lowest ΔSCC quartile. Using a 0 h hs-cTnT cut-off ≥52 ng/l assigned 627 (26%) patients to a high-risk group in whom the specificity and positive predictive value (PPV) for MI was low (78.5% (95% CI: 76.7-80.2) and 27.6% (95% CI: 24.1-31.3), respectively). Conclusions Hs-cTnT concentrations indicative of acute myocardial injury are frequently observed among all-comers with AKI in the ED and are associated with dynamic changes in SCC. These observations are accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification in patients with chest pain.

Elucidating temperature-dependent local structure change and optical properties in GeTe phase-change material

Phase-change memory emerges as a top contender for non-volatile data storage applications. We report here a systematic change in local structure and crystallization kinetics of binary GeTe thin films using temperature-dependent resistivity measurements, which offers single-stage crystallization at around 187 °C, corroborated with x-ray diffraction. Furthermore, the change in chemical bonding upon crystallization is determined through x-ray photoelectron spectroscopy core level spectra, which reveals the existence of Ge and Te components that align with the GeTe crystal structure. Also, an investigation was carried out employing a UV–Vis–NIR spectrophotometer to explore the evolution of optical bandgaps (Eg), Tauc parameter (B) representing the local disorder, and Urbach energy (Eu) of the GeTe material, as it undergoes the transition from a disordered amorphous state to a crystalline state. As crystallization progresses, a consistent shift of Eg from 0.92 to 0.70 eV corresponds to as-deposited amorphous at room temperature and crystalline at 250 °C, respectively. In addition, the reduction in Eu (from 199.87 to 141.27 meV) and a sudden increase of B around crystallization temperature is observed upon increasing temperature, indicating direct observation of enhanced medium-range order and distortion in short-range order, respectively, in GeTe thin films, revealing improved structural and optical properties. These enhancements make the GeTe material ideal for data storage applications of phase-change memory for next-generation computing technology.

Should individuals with unilateral transtibial amputation carry a load on their intact or prosthetic side?

Carrying side loads often occurs during activities of daily living. As walking is most unstable mediolaterally, side load carriage may further compromise gait biomechanics, especially for transtibial amputees (TTAs). This study investigated the effects of side load carriage on gait kinetics during steady-state walking to determine which side, intact or prosthetic, TTAs should carry a load. Twelve unilateral TTAs wore a passive-elastic foot and carried a side load of 13.6 kg while walking at their self-selected speed. Kinetic metrics, including ground reaction force peaks and impulses, loading and unloading rates, and joint moments and powers, were analyzed. TTAs had smaller propulsive forces on their intact limb during the prosthetic side load condition. During the intact side load condition, they had smaller hip flexor moment in late stance and smaller knee flexor moment at the end of swing on their intact limb. They had higher hip and knee abductor moments on their intact limb and prosthetic limb in early and late stance during the contralateral side load condition. TTAs generated higher hip extensor power at weight acceptance during the ipsilateral side load. Significant interactions were observed in hip extensor power and abductor moment, suggesting strong associations between hip extensor power generation and the ipsilateral side load and between hip abductor moment and the contralateral side load. These mixed results demonstrate some kinetic changes due to side load carriage and suggest that the side TTAs should carry a load depends on the desired effects, primarily on their intact limb.

Improved hydrogen production in immobilized Chlamydomonas reinhardtii cells with inhibited inter-photosystem electron transfer

The production of molecular hydrogen (H2) by microalgae holds great promise, and immobilization techniques offer potential for further advancement in this field. The current study focuses on investigating the positive impact of immobilization on maintaining the stability and activity of photosystem II (PSII) over incubation time, with the aim of enhancing H2 production potential in green microalgae Chlamydomonas reinhardtii. For this purpose, immobilized cells within alginate beads were treated with small concentrations of 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB) inhibitor to induce the partial inhibition of inter-photosystem electron transport, recently reported as a novel approach for sustaining microalgal H2 production. A comparative analysis of fluorescence decay kinetic changes and EPR spectroscopy of the cell beads revealed the superior capacity of immobilization for sustaining PSII stability and activity in batch culture over time. Treatment of the cell beads with 3.5 μM DBMIB led to sustained H2 production yielding over 200 μmol H2/mg Chl within 3 weeks, with an average H2 production rate of approximately 10 μmol/mg Chl per day, both of which were roughly twice as high as those observed in free cells treated with DBMIB. Our findings underscore the significance of integrating immobilization with a proven and effective method for H2 production, thereby enhancing its sustainability and productivity.

Suppressed Arm Swing While Running: No Change In Sagittal Plane Joint Kinetics

Suppressed Arm Swing While Running: No Change In Sagittal Plane Joint Kinetics

A Holistic Focus of Attention Enhances Vertical Jump Performance Among Inexperienced Individuals.

A holistic focus (HF) has been found to significantly improve performance over an internal focus (IF), in a similar way to an external focus (EF). There is a need to understand the effectiveness of a HF by investigating kinematic and kinetic outcome measures. 19 college-aged adults performed 12 vertical jumps under four conditions in a counterbalanced design. The conditions were, IF, EF, HF, and control, or no focus condition. All participants performed the vertical jumps on a force plate with 16 reflective markers placed on the lower extremities. Separate repeated measures ANOVAs with Sidak post-hoc were used to analyze jump height, flight height, peak force, takeoff velocity, and knee and hip flexion. A significant main effect for jump height was observed (p < 0.001). HF and EF jumped significantly higher than IF (p < 0.001; p < 0.001). EF also jumped significantly higher than control (p<.05). No significant main effects were observed for any kinematic or kinetic dependent variables. The results of this experiment support previous research by observing performance benefits of HF and EF over an IF. However, the benefits of HF and EF cannot be attributed to the kinetic or kinematic changes.

Effects of a Simulated Game and Doubleheader Inning on Peak Kinetics in Softball Pitching Across Pitch Types

Background: Softball pitchers frequently pitch at high volumes. Previous research has demonstrated changes in mechanics, range of motion, and perceived levels of fatigue and pain at high workloads. To date, little research has assessed changes in kinetics at high workloads across pitch types to understand the injury risk. Purpose: To examine changes in peak kinetics of the shoulder, elbow, and wrist of the pitching arm throughout a simulated game and doubleheader inning. Study Design: Descriptive laboratory study. Methods: A total of 19 high school softball pitchers (mean age, 15.1 ± 1.5 years; mean height, 1.6 ± 0.2 m; mean weight, 76.3 ± 16.9 kg) participated. Pitchers threw 4 innings of 25 randomly assigned pitches to mimic a game's high pitch count. Participants then rested for 30 minutes before subsequently proceeding to pitch the first inning of a doubleheader. Each pitcher threw a fastball, drop ball, curveball, and changeup. Peak shoulder, elbow, and wrist kinetics were compared across the first, last, and doubleheader innings and pitch types. Results: Compared with the first inning, significant decreases in kinetics were observed at the shoulder, elbow, and wrist in the last (P < .016) and doubleheader (P < .016) innings, particularly for shoulder and elbow compression force during the drop ball and curveball pitch types and wrist net force for all pitch types but the changeup. Significant decreases in elbow and wrist kinetics were observed during the changeup between the last and doubleheader innings (P < .016). Furthermore, differences in kinetics were observed between pitch types (P < .008); notably, the changeup had reduced kinetics compared with the fastball and breaking ball pitch types (drop ball, curveball) across innings. Conclusion: Across innings, attenuations in select joint kinetics of the pitching arm occurred that were specific to the pitch type. Across pitch types, peak kinetics was often greater during the fastball, while the changeup displayed the lowest peak kinetics. Clinical Relevance: The joints examined in this study are common sites of overuse injuries in pitchers. This work adds to previous findings on decrements in neuromuscular function as well as self-reported fatigue and pain with tournament-style pitching that may increase the injury risk. Collectively, these findings support developing a protocol combining functional testing and player-reported outcomes to aid sports specialists’ decisions for pitchers to continue to pitch or return to play, which may help prevent musculoskeletal injuries and time loss from sports participation.

Changes of Procalcitonin Kinetics According to Renal Clearance in Critically Ill Patients with Primary Gram-Negative Bloodstream Infections.

This study aimed to investigate the relationship between procalcitonin (PCT) kinetic and estimated glomerular filtration rates (eGFR) in critically ill patients who had Gram-negative primary bloodstream infection (GN-BSI) and responded to the antimicrobial therapy. This single-centered study was retrospective and observational. Critically ill GN-BSI patients over 18 years old who had clinical and microbiological responses to antibiotic treatment were included in the study. Patients were divided into two groups according to eGFR (eGFR <30 mL/min/1.73m2 and ≥30 mL/min/1.73m2) and compared for PCT kinetic at seven different measurement points as initial, first, third, fifth, seventh, tenth, and fourteenth days. The study included 138 patients. Initial PCT levels were higher in patients with eGFR <30 mL/min/1.73m2 (4.58 [1.36-39.4] ng/mL) than in eGFR ≥30 mL/min/1.73m2 (0.91 [0.32-10.2]) (p<0.001). This elevation was present at all measurement points (p<0.05). The decrease in PCT values by ≥30% (26.0% vs 47.9%; p=0.024) on the third day and ≥50% (69.2% vs 76.6%; p=0.411) on the fifth day was less in the low eGFR (<30 mL/min/1.73m2) group. The effect of low GFR on serum PCT kinetic was present in both fermenter and non-fermenter GN-BSIs but was more prominent in the fermenter group. Serum PCT levels during therapy were higher in patients with low eGFR. Early PCT (<5 days) response was not obtained in non-fermenter GN-BSI patients with low eGFR. Antibiotic revision decisions should be made more carefully in patients with low eGFR due to high initial PCT levels and slow PCT kinetic.