Subsequent Peak Research Articles

Wastewater Surveillance of SARS-CoV-2 in Slovenia: Key Public Health Tool in Endemic Time of COVID-19

With the reclassification of COVID-19 as an endemic disease and the relaxation of measures, Slovenia needed a complementary system for monitoring SARS-CoV-2 infections. This article provides an overview of the epidemiological situation of SARS-CoV-2 in Slovenia using a wastewater surveillance system, demonstrating its usefulness as a complementary tool in epidemiological surveillance. This study found that estimated SARS-CoV-2 infections in Slovenia peaked in September 2022 and showed a declining trend with subsequent lower peaks in March–April and December 2023, mirroring the trends observed from clinical data. Based on both surveillance systems, the most prevalent variant in 2022 was BA.5. By 2023, BQ.1 and other Omicron variants increased in prevalence. By the end of 2023, XBB sublineages and the BA.2.86 variant had become predominant, demonstrating consistent dynamic shifts in variant distribution across both monitoring methods. This study found that wastewater surveillance at wastewater treatment plants in Slovenia effectively tracked SARS-CoV-2 infection trends, showing a moderate to strong correlation with clinical data and providing early indications of changes in infection trends and variant emergence. Despite limitations during periods of low virus concentration, the system proved significant in providing early warnings of infection trends and variant emergence, thus enhancing public health response capabilities.

Resonant tunneling properties of laser dressed hyperbolic Pöschl-Teller double barrier potential

We examine the resonant tunneling properties of the laser-dressed hyperbolic Pöschl-Teller double quantum barrier structure. We use the non-equilibrium Green's function method to investigate structure parameters and electric field bias on the transmission properties of the system. The transmission probabilities and resonance energy levels are significantly influenced by the well widths and barrier heights. The barrier height increases, resonance energy levels shift toward higher values, and the resonance peak width narrows, leading to sharper and more selective tunneling behavior. Our results show that increasing the electric field bias leads to a decrease in the transmission probability at the first resonance peak, but this effect is not as strong for the subsequent peaks. Moreover, we find that changes in the laser field's parameter and structure parameters allow for fine control over the electronic spectra, allowing for modifications like red or blue shifts based on particular needs. The significance of comprehending the interaction among structural factors, external fields, and transmission qualities in quantum barrier structures is highlighted by our research, providing valuable information for the development and enhancement of electronic and optoelectronic systems with customized functionality. Our findings show the laser field has a considerable impact on resonant tunneling properties, opening the door to new device applications.

Association Between Climatic Factors and Varicella Incidence in Wuxi, East China, 2010-2019: Surveillance Study.

Varicella is a common infectious disease and a growing public health concern in China, with increasing outbreaks in Wuxi. Analyzing the correlation between climate factors and varicella incidence in Wuxi is crucial for guiding public health prevention efforts. This study examines the impact of meteorological variables on varicella incidence in Wuxi, eastern China, from 2010 to 2019, offering insights for public health interventions. We collected daily meteorological data and varicella case records from January 1, 2010, to December 31, 2019, in Wuxi, China. Generalized cross-validation identified optimal lag days by selecting those with the lowest score. The relationship between meteorological factors and varicella incidence was analyzed using Poisson generalized additive models and segmented linear regression. Subgroup analyses were conducted by gender and age. The study encompassed 64,086 varicella cases. Varicella incidence in Wuxi city displayed a bimodal annual pattern, with peak occurrences from November to January of the following year and lower peaks from May to June. Several meteorological factors influencing varicella risk were identified. A decrease of 1°C when temperatures were ≤20°C corresponded to a 1.99% increase in varicella risk (95% CI 1.57-2.42, P<.001). Additionally, a decrease of 1°C below 22.38°C in ground temperature was associated with a 1.36% increase in varicella risk (95% CI 0.96-1.75, P<.001). Each 1 mm increase in precipitation above 4.88 mm was associated with a 1.62% increase in varicella incidence (95% CI 0.93-2.30, P<.001). A 1% rise in relative humidity above 57.18% increased varicella risk by 2.05% (95% CI 1.26-2.84, P<.001). An increase in air pressure of 1 hPa below 1011.277 hPa was associated with a 1.75% rise in varicella risk (95% CI 0.75-2.77, P<.001). As wind speed and evaporation increased, varicella risk decreased linearly with a 16-day lag. Varicella risk was higher with sunshine durations exceeding 1.825 hours, with a 14-day lag, increasing by 1.30% for each additional hour of sunshine (95% CI 0.62-2.00, P=.006). Subgroup analyses revealed that teenagers and children under 17 years of age faced higher varicella risks associated with temperature, average ground temperature, precipitation, relative humidity, and air pressure. Adults aged 18-64 years experienced increased risk with longer sunshine durations. Additionally, males showed higher varicella risks related to ground temperature and air pressure compared with females. However, no significant gender differences were observed regarding varicella risks associated with temperature (male: P<.001; female P<.001), precipitation (male: P=.001; female: P=.06), and sunshine duration (male: P=.53; female: P=.04). Our preliminary findings highlight the interplay between varicella outbreaks in Wuxi city and meteorological factors. These insights provide valuable support for developing policies aimed at reducing varicella risks through informed public health measures.

Relationship between fat embolism and endothelial glycocalyx

Fat embolism (FE) is acknowledged as one of the significant causes of sudden death following traumatic injury. To clarify the relevance of vascular endothelial glycocalyx (EGC) damage and FE, temporal changes in the mRNA levels of inflammatory cytokines associated with EGC components were investigated in an experimental fat embolization rat model. Nine-week-old rats were used as FE models through triolein injection (TO) and femoral fracture (FX), and physiological saline was administered to the control group. RT-qPCR and fat staining were performed. The target genes were Il6, Il10, Tnf, Elane, Sdc1, Sdcbp, Vcan, Hyal1, Fn1, and CD14. Notably, FE was detected in 100% and 5.6% of the TO and FX groups, respectively, using fat staining. Bimodal peaks in the mRNA expression levels of Sdc1, Tnf, Elane, IL6, and IL10 were observed 4 and 20 h after treatment in both groups. In the TO group, mRNA expression peaked at 4 h and then declined to the lowest level at 16 h. The incidence of fat emboli due to trauma was consistent with that reported in previous studies. Bimodal mRNA peaks may correspond to FE progression, in which physical obstructions are followed by biochemical reactions. The fluctuation in Sdc1 expression suggests that the initial peak resulted from physical EGC damage. The subsequent peak could be because of EGC damage caused by the secretion of inflammatory cytokines induced by oleic acid from lipid droplet decomposition. These results suggest that EGC disorders caused by lipid droplets may induce lung damage during FE.

Model based fitting of pattern reversal visually evoked potentials provides a reliable characterization of waveform components

ObjectiveTo introduce a novel approach to analyzing pattern reversal visual evoked potentials (prVEPs) using a difference-of-gammas model-based fitting method. MethodsprVEP was recorded from uninjured youth ages 11–19 years during pre- or post-season sports evaluation. A difference-of-gammas model fit was used to extract the amplitude, peak time, and peak width of each of four gamma components. The within session reliability and stability of fits across a 6-month period were determined. To demonstrate an application of this analysis, changes in parameters across age were determined. ResultsA difference-of-gammas model consisting of four gamma functions was fit to the prVEP of 151 youth. Peak times and amplitudes of functions corresponded to standard measures of the N75, P100, and N135 components respectively, and a late gamma peak (mean peak time 219 ms). We extracted the peak width, which increased with each subsequent temporal peak. Parameter fits were reliable within sessions (correlation coefficient > 0.92 for all measured parameters; good agreement on Bland-Altman calculation) and were stable between sessions separated by less than 6 months (correlation coefficient > 0.90). Standard peak analysis metrics extracted from the difference-of-gamma model fits were largely consistent with gold-standard peak analysis measurements. ConclusionsThe difference-of-gammas model provides a stable and reliable within-participant representation of the global temporal variability of prVEP waveforms across a large sample of youth. SignificanceUsing difference-of-gammas model to characterize the global temporal variability of the prVEP waveform offers a promising direction to enhance analysis for identifying and following subtle changes in neurologic conditions.

Changes in entire acute bronchiolitis seasons before, during, and after the COVID-19 pandemic in Spain

Paediatric acute bronchiolitis normally occurs from October to April in the temperate northern hemisphere, peaking in January. Nonpharmacological measures to control the spread of COVID-19 resulted in a decrease in the number of cases of bronchiolitis during the 2020-21 season. The discontinuation of these measures created an uncertain scenario. To describe the epidemiological evolution of acute bronchiolitis seasons and the changes in the demographics of the affected population before, during, and after the implementation of nonpharmacological interventions for COVID-19 in Spain. This was a multicentre and descriptive study. A total of 6,334 infants aged up to 12 months who were diagnosed with acute bronchiolitis were recruited from sixteen Spanish hospitals. We collected data from participants from September 1st, 2021, through August 31st, 2023, as part of the ECEALHBA research project. The study periods were before (P1), during (P2), and after (P3) the COVID-19 pandemic. In P2 and after the discontinuation of nonpharmacological interventions, an unexpected increase in the number of acute bronchiolitis cases was observed from June-August 2021, resulting in an out-of-season peak. A subsequent peak was observed in November 2021, earlier than expected for the 2021-22 season. In the 2022-23 season, admissions followed a historical trend, with a greater number of cases than in the two previous seasons. Statistically significant differences in the length of stay (p<0.001), number of RSV infections (p=0.021), and number of paediatric intensive care unit admissions (p<0.001) were observed among the periods. Two out-of-season peaks in the number of acute bronchiolitis cases were observed in 2020-2021 and 2021-2022. However, following the relaxation of nonpharmacological intervention measures, the peak observed in 2022-2023, although occurring 2-6 weeks earlier, was more similar to the peaks observed in the prepandemic seasons. Additionally, increased case severity was observed during these periods.

Analysis of clinical management and radiological affection of coronavirus disease 2019 patients under isolation: an experience from a University Hospital

Background During the coronavirus disease 2019 (COVID-19) pandemic, Egypt was among the minor epidemic areas. COVID-19 has wide variations in the clinical presentation manifesting as a heterogeneous disease severity varying from mild, moderate, and severe to critical illness. Objective This study aimed to identify the potential clinical, radiological, and laboratory characteristics and prognosis of the COVID-19 patients obtained during the first peak of this pandemic at a University Hospital in Egypt, and to provide a reference for the pandemic management in the subsequent peaks. Patients and methods A single-center prospective study was done on patients with COVID-19 admitted to Fayoum University Hospital during the period from May to July 2020. All patients had full medical history taking, clinical examination, laboratory assessment, oxygen-saturation monitoring, chest computed tomography (CT), and reverse transcriptase-PCR testing. All the patients were treated with the treatment protocol accredited by the Egyptian Ministry of Health and accordingly disease outcome was determined. Results The study included 162 COVID-19 patients, 80 (49.4%) had mild cases, 40 (24.7%) had moderate cases, and 26 (16.0%) and 16 (9.9%) had severe and critical cases, respectively. The median CT-severity score was 10 (3.75–11.25). Significantly high serum levels of C-reactive protein, D-dimer, lactate dehydrogenase, and ferritin levels were observed in severe cases (P&lt;0.01 for all) in comparison with mild/moderate cases. By comparing died cases with other severe cases, the proportion of cases with CURB 65 score (comorbidity, confusion, urea, respiratory rate, blood pressure, and 65 years of age or older score) more than or equal to 4, PaO2/FiO2 less than 300, hypoxemia less than 85%, higher levels of ferritin, D-dimer, alanine aminotransferase, aspartate aminotransferase, CT severity, and consolidation score were significantly higher in died cases than other severe cases. By regression analysis, among severe cases, predictors of death were the presence of comorbidity and increased consolidation size. Conclusion All healthcare workers should understand the presentation of the disease, workup, and supportive care experienced from the first outbreak and offer an evidence-based management for succeeding outbreaks in our community.

Timing patterns of initial respiratory syncytial virus infection and factors influencing disease severity in hospitalized infants with different health status.

This study aimed to determine the timing patterns of the initial respiratory syncytial virus (RSV) infection and to identify the factors influencing disease severity in infants of varying health status. A retrospective study was conducted at the Affiliated Children's Hospital of Chongqing Medical University from 2012 to 2022. The timing of the first RSV infection was estimated in infants with differing health status using correlation analysis, considering their birth time. Logistic regression was utilized to identify factors influencing severe RSV infection in these infants.RSV detection primarily occurred in the winter and spring. Epidemic season and peak timing of RSV were not significantly affected by health status or the COVID-19 pandemic. A strong positive correlation was observed between the age at RSV infection and the interval from birth to the RSV peak season. Infants born during the RSV epidemic season exhibited a higher likelihood of infection within the first 2 months postbirth. In contrast, those born outside the RSV epidemic season were more susceptible to infection during the subsequent peak. Notably, infants with pre-existing health conditions contracted RSV at an earlier age compared to their healthy counterparts. Among healthy infants, severe RSV infection was associated with sex, age, and timing of infection. For infants with underlying conditions, severe RSV infection was primarily related to age and timing of infection. The initial timing of RSV infection in infants varied depending on their health status. Young age and infection timing during the RSV epidemic season were significant risk factors for severe RSV infection. These findings provide a theoretical basis for optimizing immunization strategies for infants with diverse health conditions.

Research on the hazards of gas leakage and explosion in a full-scale residential building

The gas explosion in residential building has always been a highly concerned problem. Explosions in homogeneous mixtures have been extensively studied. However, mixtures are often inhomogeneous in the practical scenarios due to the differences in the densities of methane and air. In order to investigate the effects of gas explosions in inhomogeneous mixtures, experimental studies involving gas leakage and explosion are conducted in a full-scale residential building to reproduce the process of gas explosion. By fitting the dimensionless buoyancy as a function of dimensionless height and dimensionless time, a distribution model of gas in large-scale spaces is established, and the mechanism of inhomogeneous distribution of methane is also be revealed. Furthermore, the stratified reconstruction method (SRM) is introduced for efficiently setting up inhomogeneous concentration fields in FLACS. The simulation results highlight that for the internal overpressure, the distribution of methane has no effect on the first overpressure peak (ΔP1), while it significantly influences the subsequent overpressure peak (ΔP2), and the maximum difference between the overpressure of homogeneous and inhomogeneous distribution is 174.3%. Moreover, the initial concentration distribution also has a certain impact on the external overpressure.

Application of modified kaolinite in improving thermal stability of polydimethylsiloxane

AbstractThis research investigated the chemical structure and morphology of the hydrogenated tallow amine (HTA)‐intercalated kaolinite by XRD, FT‐IR, and TEM measurements. The experimental outcomes show that intercalation of kaolinite by HTA, with an intercalation rate of 63.2%, expands the interlayer distance with a subsequent dominant basal XRD peak at 2θ ≈ 7.9°. Furthermore, a composite was created from the HTA‐intercalated kaolinite and polydimethylsiloxane (PDMS) through a favorable interaction between the end silanol groups of PDMS and the modified kaolinite surface. Thermogravimetry‐differential scanning calorimetry results indicate that introducing the HTA‐intercalated kaolinite into the PDMS matrix increases the thermal stability of the composite from 178 to 343 °C. However, the thermal stability of the composite is lower than that of other published materials. The synthesis of kaolinite/PDMS composite with enhanced structural and thermal stability outcomes has been provided via a simple and effective solution method that should have further applications.

ASSESSMENT OF ANGIOTENSIN II-INDUCED CALCIUM SIGNALS IN PRIMARY HUMAN ADRENOCORTICAL CELLS

Objective: Primary aldosteronism (PA), a common form of secondary hypertension, is characterized by an increase of cytosolic intracellular Ca2+ concentrations [Ca2+]i. Our aim is to investigate transients and oscillations of [Ca2+]i in a human model of isolated CD56+ aldosterone-producing adenoma (APA) cells and normal surrounding adrenocortical (NAC) cells. Design and method: We monitored [Ca2+]i, in CD56+ NAC and APA cells in basal condition and after Angiotensin II (Ang II) stimulation using Fura-2 dye and live confocal microscopy, and we developed a custom-made pipeline to analyze calcium signals in terms of frequency and peak parameters like amplitude, full width at half maximum (FWHM) and area under the curve (AUC). To investigate the potential role of the two-pore domain K+ TASK- 2 channel in regulating Ca2+ signals, TASK-2 channels of NAC cells were pharmacologically inhibited using Quinidine (20 microM) 20’ prior to [Ca2+]i imaging acquisition. Results: Resting [Ca2+]i basal levels in NAC (n=11) were higher (0.76 a.u.+- 0.04) than in APA (n=12) (0.56 a.u.+- 0.05, p= 0.0087). NAC TASK-2 inhibition decreased resting [Ca2+]i to 0.58 a.u. +- 0.07 (p &gt; 0.05). Spontaneous Ca2+ activity was higher in NAC with significant higher amplitude and AUC parameters compared to APA cells. Quinidine further increased spontaneous activity in NAC while decreased Amplitude and AUC. For both cell types stimulation with 2 doses of Ang II concentrations [10 -8 and 10 -9 mM], higher Ang II doses promoted higher Ca2+ peak parameters, amplitude and AUC, and a significant decrease in events frequency. Comparison between APA and NAC revealed that, regardless of Ang II dose, first Ca2+ transient parameters are intensified in NAC. However, APA showed consistent elevated subsequent Ca2+ oscillations parameters (Amplitude and AUC), frequency, and degree of oscillation compared to NAC cells stimulated with similar Ang II doses. NAC TASK-2 inhibited cells, when stimulated with [10 -9 mM] Ang II, displayed only increased subsequent peak parameters. Conclusions: The bias-free approach designed to quantitatively assess [Ca2+]i signals, revealed significant differences in [Ca2+]i dynamics of human NAC and APA cells.

Impact of river capture on erosion rates and offshore sedimentation revealed by geological and in situ 10Be cosmogenic data (Corsica, western Mediterranean)

Quantitative analysis of fluvial topography and sediment yield changes are often independently used to detect major river capture events and episodes of drainage reorganization. Here we use a unique set of geological and in situ 10Be cosmogenic data from Corsica, Western Mediterranean, to provide evidence of major river capture events affecting the former Paleo-Ostriconi river catchment during the Pliocene, and to illustrate how the landscape of Corsica is still reacting to the disequilibrium caused by the late Miocene uplift of Alpine Corsica. We found that ∼1280 km2 of basin area originally draining towards the Ligurian Sea were abruptly connected to the Tyrrhenian Sea by the capturing Tavignano and Golo rivers, which led to the formation of a large Pliocene-Quaternary submarine fan offshore the Tyrrhenian coast. The increased sediment yield towards the Tyrrhenian margin after river capture in the Pliocene was three times greater than the average sediment yield in the same source-to-sink system during the Holocene (410±100 t·km−2·a−1 vs ∼131±8 t·km−2·a−1) and greater magnitude than any subsequent peaks in sediment yield during late Pleistocene glaciations. 10Be-derived denudation rates reveal that focused erosion still affects retreating knickpoints near the sites of former river capture in central Corsica, suggesting persistence of landscape disequilibrium for several millions of years. Our results demonstrate the potentially large impact of river capture on the stratigraphic record and highlight the importance of full consideration of landscape response times to onshore disturbances for any reliable interpretation of the offshore sedimentary archive.

Experiments and simulations for dynamic yarn pull-out response of Kevlar® fabrics

This work presents a novel experimental method for performing dynamic yarn pull-out using a modified tensile split Hopkinson pressure bar. The pull yarn is fixed to a piezoelectric load cell, while the woven fabric specimen is displaced at pull-out velocities ranging from 22 to 32 m/s. Pull-out force, displacement, and energy absorption over time are quantified for commercially available Kevlar® KM2+ woven fabric with pull lengths L = 5 mm and 27 mm in both quasi-static (QS) and dynamic loading. Dynamic peak pull-out force increases over QS by as much as 290–460% and 170–220% for L = 5 mm and L = 27 mm, respectively, and overall energy absorption increases by 140–420% and 40–140% for L = 5 mm and L = 27 mm, respectively. In QS loading, stick–slip interactions result in forces dropping by approximately 70–80% between oscillating peaks for L = 5 mm and 30–40% between peaks for L = 27 mm, and displacements between peaks are typically 1.5 mm, corresponding to two yarn crossings or two spans. However, at dynamic rates, stick–slip stage force drops by 100% after the first and all subsequent peaks due to the dynamic release of the pull yarn from the fabric, resulting in the pull yarn passing through multiple yarn crossings. To better understand the underlying mechanisms for these observations, finite element simulations of the experiments are performed. Strain rate dependent longitudinal shear stiffness of the yarn is found to significantly affect the dynamic yarn pull-out response and explain the enhanced dynamic yarn pull-out peak force and energy absorption. While the shorter yarn of L = 5 mm experiences a more uniform loading along the entire length, non-uniform loading via progressive uncrimping is observed in the longer yarn of L = 27 mm along the length.

The relationship between extreme inter-individual variation in macrophage gene expression and genetic susceptibility to inflammatory bowel disease

The differentiation of resident intestinal macrophages from blood monocytes depends upon signals from the macrophage colony-stimulating factor receptor (CSF1R). Analysis of genome-wide association studies (GWAS) indicates that dysregulation of macrophage differentiation and response to microorganisms contributes to susceptibility to chronic inflammatory bowel disease (IBD). Here, we analyzed transcriptomic variation in monocyte-derived macrophages (MDM) from affected and unaffected sib pairs/trios from 22 IBD families and 6 healthy controls. Transcriptional network analysis of the data revealed no overall or inter-sib distinction between affected and unaffected individuals in basal gene expression or the temporal response to lipopolysaccharide (LPS). However, the basal or LPS-inducible expression of individual genes varied independently by as much as 100-fold between subjects. Extreme independent variation in the expression of pairs of HLA-associated transcripts (HLA-B/C, HLA-A/F and HLA-DRB1/DRB5) in macrophages was associated with HLA genotype. Correlation analysis indicated the downstream impacts of variation in the immediate early response to LPS. For example, variation in early expression of IL1B was significantly associated with local SNV genotype and with subsequent peak expression of target genes including IL23A, CXCL1, CXCL3, CXCL8 and NLRP3. Similarly, variation in early IFNB1 expression was correlated with subsequent expression of IFN target genes. Our results support the view that gene-specific dysregulation in macrophage adaptation to the intestinal milieu is associated with genetic susceptibility to IBD.

A temporal record of microplastic accumulation in sediment cores of the Great Lakes, North America, reflects macroeconomic and regional influences

Documented plastic pollution throughout the Laurentian Great Lakes system prompted investigation of microplastics (MPs) in sediment cores. We examined offshore sediment cores from Lake Huron (LH43) and Lake Ontario (403A) to understand temporal trends and changes in microplastic (MP) pollution in the size range 53 µm to 2 mm. MP abundances varied from 18.1 to 280.1 particles per g of dry weight sediment ( N g−1 dw) in LH43, and 8.2–488.4 g−1 dw in core 403A. The 15 cm cores are equivalent to 56 years of accumulation in Lake Huron and 72 years of accumulation in Lake Ontario. Analysis of the two cores shows an increasing trend in MP accumulation from 1964 to 1989, which mirrors the global plastic production rate. Subsequent peaks and troughs in the MP abundance profiles reflect macroeconomic changes and regional controls. These results show how changing abundances of MPs in lake sediment cores can act as proxies for global perturbations in oil supply as well as national economic shifts.

Enhanced Muscle Activation Using Robotic Assistance Within the Electromechanical Delay: Implications for Rehabilitation?

Robotic rehabilitation has been shown to match the effects of conventional physical therapy on motor function for patients with neurological diseases. Rehabilitation robots have the potential to reduce therapists' workload in time-intensive training programs as well as perform actions that are not replicable by human therapists. We investigated the effects of one such modality that cannot be achieved by a human therapist: assistance and resistance within the electromechanical delay between muscle activation and muscle contraction during arm extension. We found increased muscle activation when providing robotic assistance within this electromechanical delay. Assistance provided within this delay moves the participant's arm quicker than their own muscle and increases the subsequent peak voluntary muscle activation compared to normal arm extension by 68.97 ± 80.05 % (SE = 0.021; p = 0.007 ). This is surprising since all previous literature shows that muscle activation either decreases or does not change when participants receive robotic assistance. As a consequence, traditional robotic rehabilitation incrementally reduces assistance as the patient improves to maintain levels of muscle activation which is suggested to be important for neuronal repair. The present result may enable therapists to no longer have to choose between providing assistance or increasing muscle activation. Instead, therapists may be able to provide assistance while also increasing muscle activation.

Incline and decline running alters joint moment contributions but not peak support moments in individuals with an anterior cruciate ligament reconstruction and controls.

Individuals with an anterior cruciate ligament reconstruction (ACLR) commonly exhibit altered gait patterns, potentially contributing to an increased risk of osteoarthritis (OA). Joint moment contributions (JMCs) and support moments during incline and decline running are unknown in healthy young adults and individuals with an ACLR. Understanding these conditional joint-level changes could explain the increased incidence of OA that develops in the long term. Therefore, this knowledge may provide insight into the rehabilitation and prevention of OA development. We aimed to identify the interlimb and between-group differences in peak support moments and subsequent peak ankle, knee, and hip JMCs between individuals with an ACLR and matched controls during different sloped running conditions. A total of 17 individuals with unilateral ACLR and 17 healthy individuals who were matched based on sex, height, and mass participated in this study. The participants ran on an instrumented treadmill at an incline of 4°, decline of 4°, incline of 10°, and decline of 10°. The last 10 strides of each condition were used to compare the whole-stance phase support moments and JMCs between limbs, ACLR, and control groups and across conditions. No differences in JMCs were identified between limbs or between the ACLR and healthy control groups across all conditions. Support moments did not change among the different sloped conditions, but JMCs significantly changed. Specifically, ankle and knee JMCs decreased and increased by 30% and 33% from an incline of 10° to a decline of 10° running. Here, the lower extremities can redistribute mechanics across the ankle, knee, and hip while maintaining consistent support moments during incline and decline running. Our data provide evidence that those with an ACLR do not exhibit significant alterations in joint contributions while running on sloped conditions compared to the matched controls. Our findings inform future research interested in understanding the relationship between sloped running mechanics and the incidence of deleterious acute or chronic problems in people with an ACLR.

Temporal dynamics of muscle mitochondrial uncoupling-induced integrated stress response and ferroptosis defense.

Mitochondria play multifaceted roles in cellular function, and impairments across domains of mitochondrial biology are known to promote cellular integrated stress response (ISR) pathways as well as systemic metabolic adaptations. However, the temporal dynamics of specific mitochondrial ISR related to physiological variations in tissue-specific energy demands remains unknown. Here, we conducted a comprehensive 24-hour muscle and plasma profiling of male and female mice with ectopic mitochondrial respiratory uncoupling in skeletal muscle (mUcp1-transgenic, TG). TG mice are characterized by increased muscle ISR, elevated oxidative stress defense, and increased secretion of FGF21 and GDF15 as ISR-induced myokines. We observed a temporal signature of both cell-autonomous and systemic ISR in the context of endocrine myokine signaling and cellular redox balance, but not of ferroptotic signature which was also increased in TG muscle. We show a progressive increase of muscle ISR on transcriptional level during the active phase (night time), with a subsequent peak in circulating FGF21 and GDF15 in the early resting phase. Moreover, we found highest levels of muscle oxidative defense (GPX and NQO1 activity) between the late active to early resting phase, which could aim to counteract excessive iron-dependent lipid peroxidation and ferroptosis in muscle of TG mice. These findings highlight the temporal dynamics of cell-autonomous and endocrine ISR signaling under skeletal muscle mitochondrial uncoupling, emphasizing the importance of considering such dissociation in translational strategies and sample collection for diagnostic biomarker analysis.

Application of distributed lag models and spatial analysis for comparing the performance of the COVID-19 control decisions in European countries

Over the past three years, the COVID-19 outbreak has become a major worldwide problem, affecting the health systems and economies of countries. The mean delays, the expected time to observe the average effect of the number of new cases on the number of deaths, are gold times for decision-making regarding disease control and treatment facilities to reduce the fatality rate. The interest of the present study is estimating the mean delays and adjusted fatality rates of COVID-19 with the new application of Distributed Lag Models (DLM) and their spatial distributions. The daily cases and deaths data of COVID-19 for 39 European countries was obtained from two sources; the "European Centre for Disease Prevention and Control" and the "Our World in Data" database. The mean delay and the Adjusted Fatality Rate (AFR) for each country at three-time intervals; the first and subsequent peaks before and after vaccination were estimated by the Distributed Lag Models. The spatial analysis was applied to find the spatial correlation of the mean delays and adjusted fatality rates among European countries. In the three-time intervals, the first and the subsequent peaks before vaccination, and after vaccination, the median and interquartile range of the mean delays; and AFRs were: 1.1 (0.4, 3.2); 0.024 (0.016, 0.044), 9.2 (6.2, 12.40); 0.013 (0.005, 0.020) and 7.3 (4.4, 11.0); 0.001 (0.001, 0.005), respectively. In the subsequent peaks before vaccination, the mean delays considerably increased, and the AFRs decreased for most European countries. After vaccination, the AFRs decreased considerably. Except for the first peak, the spatial correlations of AFRs were not significant among neighboring countries. Consecutive outcomes will occur with delays in outbreaks of infectious disease. Also, the fatality rates for these outcomes should be adjusted on delays. Estimating the mean delays and adjusted fatality rates by Distributed lag Models and the spatial distributions of theme in outbreaks showed that prevention and medical policies after the first peak as well as vaccination were effective to reduce the fatality rate of COVID-19, but these effects were different between countries. These results recommended policymakers and governments assign prevention and medical resources more effectively.

Premovement activity in the mesocortical system links peak force but not initiation of force generation under incentive motivation.

Motivation facilitates motor performance; however, the neural substrates of the psychological effects on motor performance remain unclear. We conducted a functional magnetic resonance imaging experiment while human subjects performed a ready-set-go task with monetary incentives. Although subjects were only motivated to respond quickly, increasing the incentives improved not only reaction time but also peak grip force. However, the trial-by-trial correlation between reaction time and peak grip force was weak. Extensive areas in the mesocortical system, including the ventral midbrain (VM) and cortical motor-related areas, exhibited motivation-dependent activity in the premovement "Ready" period when the anticipated monetary reward was displayed. This premovement activity in the mesocortical system correlated only with subsequent peak grip force, whereas the activity in motor-related areas alone was associated with subsequent reaction time and peak grip force. These findings suggest that the mesocortical system linking the VM and motor-related regions plays a role in controlling the peak of force generation indirectly associated with incentives but not the initiation of force generation.