Peak Time Research Articles

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor.

Preclinical evaluation of drugs in animals helps researchers to select potentially informative clinical laboratory markers for human trials. To assess the utility of animal thrombin generation (TG) assay, we studied the sensitivity of animal plasmas to triggers of TG, human Tissue Factor (TF), and Activated Factor XI (FXIa). Pooled human, mouse, rat, guinea pig, rabbit, bovine, sheep, and goat plasmas were used in this study. TF- or FXIa-triggered TG and clotting were measured via fluorescence and optical density, respectively. Thrombin peak height (TPH) and time (TPT), clot time (CT), and fibrin clot density (FCD) were all analyzed. The trigger low and high sensitivity borders (LSB and HSB) for each assay parameter were defined as TF and FXIa concentrations, providing 20 and 80% of the maximal parameter value, unless the baseline (no trigger) value exceeded 20% of the maximal, in which case, LSB was derived from 120% of baseline value. Normal human samples demonstrated lower TPH HSB than most of the animal samples for both TF and FXIa. Animal samples, except mice, demonstrated lower TPT LSB for FXIa versus humans. Most rodent and rabbit samples produced baseline TG in the absence of TG triggers that were consistent with the pre-activation of blood coagulation. FCD was not sensitive to both TF and FXIa in either of the plasmas. Animal plasmas have widely variable sensitivities to human TF and FXIa, which suggests that optimization of trigger concentration is required prior to test use, and this complicates the extrapolation of animal model results to humans.

Temporal evolution characteristics of the excited species in a pulsed needle-water discharge: effect of voltage and frequency

Transient spark discharge has broad application prospects due to its excellent performance in generating reactive oxygen species, but there is currently limited research on transient excited species, which are important precursors for the formation of these species. In this paper, we obtained a transient spark discharge with a needle-water electrode configuration, and then developed an optical detection system based on a photomultiplier to measure the temporal evolution of four excited species. It is observed that N2 (C) is produced mainly in the streamer phase, while H (n = 3), O (3p), and OH (A) are produced mainly in the spark phase, which results from the difference in threshold energy and pathway for generating different species. To investigate the variation mechanism of peak time and peak intensity during the evolution process, the gas temperature T g, electron density n e, and electron excitation temperature T exc were calculated by using the optical emission spectroscopy under different pulse voltage and pulse repetition frequency conditions. The results indicate that the discharge conditions influence the physical parameters of T g, n e, and T exc as well as the output voltage waveform, and then they jointly determine the evolution characteristics of excited species. These insights contribute to understanding the characteristics of excited species which affect the formation of reactive species by influencing the chemical chain reaction in the transient spark discharge.

Spatial and Temporal Variability of Extreme Precipitation Events in the Southeastern United States

Much of the Southeastern United States (SeUS) has experienced an increasing number of extreme precipitation events in recent decades. Characterizing these extreme precipitation events is critical for assessing risk from future hydroclimatic extremes and potential flash flooding. A threshold of one inch per hour (1IPH) was used to indicate an extreme precipitation event. Non-parametric tests were run to identify trends in 1IPH event frequency and locate time series change points. In the last 20 years, 1IPH events increased by 53 percent in the SeUS, and 21/61 stations recorded significant increasing trends. A change point is identified in 15/61 stations. June, July, and August are generally the peak time for 1IPH events, but Florida, Louisiana, and Mississippi recorded longer peak seasons. For the time between events, 17/61 stations recorded significant decreasing trends, implying that 1IPH events are increasing in frequency. Four teleconnection indices were positively correlated with 1IPH events. The SeUS experiences considerable tropical cyclone-induced extreme precipitation, yet only seven percent of 1IPH events overlapped with tropical cyclones. Therefore, the increasing frequency of 1IPH events is likely the result of a combination of baroclinic frontal zones or regional and mesoscale convective features. Causes for the increasing frequency of 1IPH events require further research.

Analysis of naphthenic acids in produced water samples by capillary electrophoresis-mass spectrometry.

A capillary electrophoresis-mass spectrometry method was used to analyze naphthenic acids in produced water samples. It was possible to detect cyclopentanecarboxylic, benzoic, cyclohexanebutyric, 1-naphthoic, decanoic, 3,5-dimethyladamantane-1-carboxylic, 9-anthracenecarboxylic, and pentadecanoic acids within ca. 13min using a buffer composed of 40mmol/L ammonium hydroxide, 32mmol/L acetic acid and 20% v/v isopropyl alcohol, pH 8.6. The proposed method showed good repeatability, with relative standard deviation (RSD) values of 6.6% for the sum of the peak areas and less than 2% for the analysis time. In the interday analysis, the RSD values for the sum of the peak areas and migration time were 10.3% and 10%, respectively. The developed method demonstrated linear behavior in the concentration range between 5 and 50mg/L for benzoic, decanoic, 3,5-dimethyladamantane-1-carboxylic and 9-anthracenecarboxylic acids, and between 10 and 50mg/L for cyclopentanecarboxylic, cyclohexanebutyric, 1- naphthoic, and pentadecanoic acids. The detection limits values ranged from 0.31 to 1.64mg/L. Six produced water samples were analyzed and it was possible to identify and quantify cyclopentanecarboxylic, benzoic, cyclohexanebutyric, and decanoic acids. The concentrations varied between 4.8 and 98.9mg/L, proving effective in the application of complex samples.

The range of hydropower projects and their effects on the environment

A Peak load capacity of hydropower facilities has become more necessary as electricity grids have expanded. The ratio of power demands during peak times to those during off-peak times has increased in several power plant systems. One way to meet the rising need for affordable peak power is by using reversible pump turbines. Depending on the sorts of facilities used to generate hydropower, there are several types of hydropower plants. We'll talk about the most efficient and reliable hydropower sources, as well as various hydropower plant types based on the varied hydropower generation facilities, which will be the subject of this review investigation.

Physicochemical and sensory attributes of some selected varieties of white yam (<i>Dioscorea rotundata</i>)

The physicochemical and sensory properties of five varieties of Dioscorea rotundata were investigated for their potential end uses. The water absorption capacity, water binding capacity, swelling power, solubility index, pH, and pasting properties of flour processed from the yam tubers were determined. Also, the sensory attributes of pounded yam produced from the tubers were evaluated. In terms of colour, Gbongi had the highest whiteness value (82.27). Lasinrin had the highest moisture content (39.47 %) and swelling capacity (6.11g/g), Efuru had the highest water absorption capacity (132.50%) and pH (6.75). Gbongi had the highest solubility index (13.82%). Awana had the highest peak viscosity (293.70RVU) holding strength viscosity (279.20RVU) and peak time (7.00min). Lasinrin had the highest breakdown viscosity (140.25RVU) setback viscosity (295.00RVU) and pasting temperature (82.55oC) while Efuru had the highest final viscosity (437.83RVU). All the varieties had good ratings for the pounded yam sensory attributes (stretchability, stickiness, mouldability, smoothness, colour, hardness). All the varieties were acceptable regarding the general acceptability of the pounded yam. The qualities of yam cultivars suggested their appropriateness as an alternative for other flour-based pastestypically consumed by Nigerians.

Artificial Intelligence in Prehospital Emergency Health Care

What Is the Issue? Health care systems in Canada, including prehospital emergency health care services, are facing staffing shortages and increased patient volumes, and are looking for creative solutions to ensure the provision of high-quality care. What Is the Technology? Artificial intelligence (AI) combines computer science and data to mimic human thought processes, problem solving, and responses. AI relies on statistical models, algorithms, data analysis, and machine learning to make predictions based on past behaviours or results (predictive AI) or to learn from past data to generate new content (generative AI). Chatbots, such as ChatGPT, are examples of generative AI. What Is the Potential Impact? In health care settings, AI can be used to automate some clinical and administrative processes to create efficiencies and reduce burden on health care providers and health administrators. In a prehospital setting, this can include AI used at the dispatch stage (e.g., analyzing the conversation and prompting a dispatcher with additional questions, or translating speech to help a dispatcher understand a caller in real time) or in an ambulance (e.g., providing traffic analysis or information to support optimal patient management). What Else Do We Keed to Know? The use of AI in prehospital emergency health care is still in the early stages of development and implementation. Early implementation of AI programs such as those to detect out of hospital cardiac events and to triage emergency calls during peak times are underway in some countries. More real-world clinical trials and research are required before widespread implementation will take place.

Cold water storage tank enhancement using response surface methodology leading cooling peak shaving along with load shifting

In hot areas, electricity consumption in the cooling sector holds 66% of the electricity usage by residential buildings. The need for electricity during peak times causes various problems in the electricity supply network. Adding a cold water storage tank can achieve two goals: 1- peak load shifting and 2- peak load shaving. In this study, first, the volume of the storage tank was calculated by energy analysis for the day with the maximum cooling needs. Owing to installing the tank, the electricity consumption not only reaches zero during the peak time (7 a.m.–11 p.m.) but also the total electricity demand decreases by 5.1%. According to the ASHRAE, throughout the 8760 h in one year, the deviation of the interior temperature from the setpoint should not exceed the 300-h threshold (i.e., unmet hours <300 h). Considering the allowable amount of unmet hours as a constraint, optimal points were acquired using Response Surface Methodology (RSM). This method reduces the cold storage tank by 40% and decreases the electricity need by 16.5% compared to the reference case (without a storage tank). Furthermore, the optimal storage tank eliminates the cooling-associated electricity demand to zero during peak periods.

Thiamphenicol and florfenicol combination in Nile tilapia: Simultaneous detection and quantification in plasma and muscle plus skin samples, and pharmacokinetics following single oral administration

Thiamphenicol (TAP) and florfenicol (FFC) combination has in vitro and in vivo synergistic activity against fish bacterial pathogens. However, a lack of information on its pharmacokinetics (PK) and pharmacodynamics (PD) in fish limits its further application. Therefore, this study aimed to develop and validate analytical methods for simultaneous detection and quantification of TAP and FFC in tilapia plasma and muscle plus skin samples and to determine the PK in freshwater tilapia at 30 ± 0.32 °C after a single oral dose of 5 mg kg−1 TAP +3.75 mg kg−1 FFC. Antimicrobial concentrations were analyzed by HPLC-MS. The PK characteristics were estimated by a non-compartmental model (linear up/log down). Precise, and sensitive methods were developed using ethyl acetate (plasma) and a modified QuEChERS (muscle plus skin) for extraction. Both methods were successfully applied to analyze the plasma and muscle plus skin samples in the PK study. The highest concentrations of TAP and FFC were detected at 0.5 h (6.34 and 3.34 μg mL−1) and 16 h (8.20 and 11.37 μg mL−1) post-administration in plasma and muscle, respectively. There was no significant difference between the peak concentration and apparent volume of distribution during the terminal phase of each antimicrobial in different tissues. However, the peak time, the area under the concentration-time curve, and mean residence time were higher in the muscle, for both antimicrobials (P < 0.05). The calculated PK parameters and the curve obtained for both antimicrobials emphasize their fast absorption and distribution even when used in combination. The results from this study could help establish antimicrobial susceptibility testing interpretative categories and design rational dosing regimens for TAP and FFC combination.

Pathway and Policy for China's Provincial Carbon Emission Peak

An effective way for China to achieve a carbon emission peak by 2030 is to encourage developed regions to take the lead in attaining carbon peaking at the regional level. Considering Jiangsu Province as an example, this study established a provincial low emissions analysis platform (LEAP-Jiangsu) model. It combined the improved multilevel logarithmic mean Divisia index (M-LMDI) model, Tapio decoupling model, and the synergistic effect of pollution and carbon reduction model to explore the key influencing factors of carbon emissions and carbon reduction paths. The improved M-LMDI model was used to analyze the factors influencing historical and future carbon emissions in Jiangsu Province. Based on the analysis results and planning objectives, a LEAP-Jiangsu model involving various development scenarios was established to predict the time and value of carbon emission peaks. The Tapio decoupling and synergistic effect models were used to clarify the relationship between carbon emissions and economic development, the synergistic effect of carbon, and air pollutant emission reduction. The prediction results demonstrated that the total primary energy demand of Jiangsu Province in 2035 was predicted to be approximately 401.2-474.6 Mt, and the final energy demand would be approximately 319.2-382.3 Mt. Jiangsu Province was most likely to achieve the goal of carbon peaking in 2025-2030, and the peak carbon emission was approximately 815.3-845.7 Mt. The contribution rates of energy conservation and emission reduction measures such as energy intensity reduction, industrial structure optimization, terminal electrification improvement, and energy structure adjustment were 33.1%, 26.8%, 21%, and 15.2%, respectively.

Changes in Ozone Pollution Trend Characteristics and Sensitivity in Jinan from 2015 to 2020

The surface ozone (O3) spatiotemporal distribution, variations, and its causes in Ji'nan from 2015 to 2020 were revealed based on the air quality monitoring network data and satellite retrievals from the Ozone Monitoring Instrument (OMI). The results showed that the ozone concentration in Ji'nan gradually increased from 2015 to 2020. The annual 90th percentile of the daily maximum 8-h average (MDA8) O3(namely the annual evaluation value) and the MDA8 O3(April-September) increased by 4.8 μg·(m3·a)-1 and 3.8 μg·(m3·a)-1, respectively. The trend of the ozone levels in the high-concentration range increased faster than that in the low-concentration range. The MDA8 in June increased by 7.4 μg·(m3·a)-1, and the rate range of increases was 2.6-3.9 μg·(m3·a)-1 in the cool seasons (December-February); thus, the O3 control in winter cannot be ignored. It is apparent from the diurnal variations in ozone from 2015 to 2020 in April-September that the average ozone levels have risen in recent years. The growth rate in the daytime was higher than that at night. The capacity of photochemical production has been increasing, especially in recent years. Additionally, it is noteworthy that the peak time for ozone levels occurred approximately 1-2 h earlier. The disparity of ozone concentrations among different stations gradually decreased in recent years. Compared with that in 2015, the range of areas with high O3 concentrations in 2019-2020 was further expanded. The significant positive trends in MDA8-90th and MDA8 (April-September) were observed in 16.1% and 22.6% of the monitoring sites in Ji'nan (P<0.05), most of which were located in urban areas and the suburbs close to urban areas. The temporal and spatial changes in ozone in Jinan had been affected by the changes in VOCs and NOx emissions since 2015. Satellite remote sensing data from 2015 to 2020 revealed that the NO2 tropospheric columns (April-September) showed reductions of 20.6%, with a decreasing rate of 0.3×1015 mole·(cm2·a)-1, especially in the urban areas and suburbs. The detected variation trends of tropospheric HCHO were weak and insignificant, which suggested that the decrease in NOx emissions was much greater than the decrease in VOCs emissions, and the gap had become more obvious in the urban areas. With responses to precursor emissions, the chemical sensitivity of O3 formation had been changing. The VOCs-limited regimes continuously decreased, and the mixed NOx/VOCs-sensitive regimes and NOx-limited regimes increased. In general, such an extremely inappropriate control ratio of ozone precursor NOx/VOCs led to an overall trend of slow increasing fluctuations of O3 in Ji'nan. The findings clearly indicate that the reduction of VOCs in Ji'nan was far from sufficient, and strengthening the current control of VOCs emissions is an effective measure to control the growth trend of O3 pollution in Ji'nan in the near future, especially in urban and surrounding suburban areas.

Epidemic dynamics with time-varying transmission risk reveal the role of disease stage-dependent infectiousness

A key characteristic of acute communicable diseases is the infectiousness that varies over time as the infection dynamics evolve within a host, which influences the risk of transmission in different stages of the disease. Despite the evidence of time-varying transmission risk, most dynamic models of epidemics assume a constant transmission rate during the infectious period. Recent work has shown the difference in epidemic dynamics when this assumption is relaxed and different transmission rates are used by discretizing the infectious period into multiple sub-periods. Here, we develop an age-structured model to integrate a continuous time-varying transmission risk, based on an established correlation between the viral dynamics and infectiousness profile. Taking into account the natural history and parameter estimates of COVID-19 caused by the original strain of SARS-CoV-2, we demonstrate the difference in temporal epidemic dynamics when a continuous time-varying transmission probability is used as compared to multiple constant transmission probabilities. Our results show a significant difference between the incidence curves in terms of the magnitude and peak time, even when the reproduction number and total number of infections are the same for continuous and discrete transmission probabilities. Finally, we demonstrate the spurious outcome of preventing an epidemic through the isolation of infectious individuals when constant transmission probabilities are used, highlighting the importance of integrating a continuous time-dependent transmission parameter in dynamic models. These findings suggest a more cautious interpretation of model outcomes, especially those that are intended to evaluate the effectiveness of interventions and inform policy decisions for disease mitigation strategies.

Epidemiological characteristics of pulmonary tuberculosis in Motuo County, Tibet Autonomous Region from 2012 to 2021

To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Motuo County from 2012 to 2021 and provide evidence for the prevention and control of PTB. A total of 223 cases of PTB were reported from 2012 to 2021 in Motuo County, with an average annual reported incidence rate of 171.39/100 000. Joinpoint regression model analysis showed that the average decline rate was 9.2% (P<0.001) from 2012 to 2021. Among the various types of PTB patients reported from 2012 to 2021, there were 69 cases of etiologic-positive cases which increased from 28.57% to 52.63%. Results from the circular distribution methods showed that there was no obvious peak time of PTB in Motuo County. There was no statistical difference in the average annual incidence of PTB between different genders (χ2=0.108, P=0.743). Among all age groups, the 20-29 years group had the highest proportion (26.91%, 60/223). The Monpa ethnic group (153 cases, 68.61%) had the largest number of cases, followed by the Lhoba people (44 cases, 19.73%) and the Tibetan (22 cases, 9.87%). Farmers (168 cases, 75.34%) had the highest occupational composition ratio, followed by students (40 cases, 17.94%). The main detection methods of PTB were clinical consultation and transferring consultation. Overall, the incidence rate of PTB decreased from 2012 to 2021. The majority of PTB patients were young adults with high transmission risk. It is necessary to pay more attention to the key populations and strengthen the comprehensive prevention and control for reducing the risk of PTB.

INVASION AND SUPERINFECTION IN DETERMINISTIC AND STOCHASTIC TWO-STRAIN DENGUE MODELS WITH DEMOGRAPHIC AND SEASONAL VARIATION

The effects of seasonality on disease invasion and superinfection are investigated in dengue epidemic models with two viral strains. A two-strain host–vector nonautonomous ODE is formulated with seasonal periodicity in either vector recruitment or transmission. The basic reproduction number is derived and the dynamics of the single-strain periodic subsystem are summarized. Conditions for uniform persistence and existence of a single-strain periodic solution are verified and the invasion reproduction number is derived. A time-nonhomogeneous, continuous-time Markov chain (CTMC) is formulated from the ODE framework. The basic and invasion reproduction numbers apply to the ODE and CTMC. In the case of invasion, after one strain is established and the invasion reproduction number exceeds one, the ODE predicts a successful invasion, but in the CTMC, there is a periodic probability of invasion that depends on time and size of the invasion. A multitype branching process approximation of the CTMC provides an analytical method to predict the periodic probability of invasion. The numerical results show that the peak time of invasion is related to the current endemic strain and the dominant seasonal driver but it often precedes the peak time of the seasonal driver.

New-generation geostationary satellite reveals widespread midday depression in dryland photosynthesis during 2020 western U.S. heatwave.

Emerging new-generation geostationary satellites have broadened the scope for studying the diurnal cycle of ecosystem functions. We exploit observations from the Geostationary Operational Environmental Satellite-R series to examine the effect of a severe U.S. heatwave in 2020 on the diurnal variations of ecosystem photosynthesis. We find divergent responses of photosynthesis to the heatwave across vegetation types and aridity gradients, with drylands exhibiting widespread midday and afternoon depression in photosynthesis. The diurnal centroid and peak time of dryland gross primary production (GPP) substantially shift toward earlier morning times, reflecting notable water and heat stress. Our geostationary satellite-based method outperforms traditional radiation-based upscaling methods from polar-orbiting satellite snapshots in estimating daily GPP and GPP loss during heatwaves. These findings underscore the potential of geostationary satellites for diurnal photosynthesis monitoring and highlight the necessity to consider the increased diurnal asymmetry in GPP under stress when evaluating carbon-climate interactions.

Transcriptional signatures measured in whole blood correlate with protection against tuberculosis in inbred and outbred mice.

Although BCG has been used for almost 100 years to immunize against Mycobacterium tuberculosis, TB remains a global public health threat. Numerous clinical trials are underway studying novel vaccine candidates and strategies to improve or replace BCG, but vaccine development still lacks a well-defined set of immune correlates to predict vaccine-induced protection against tuberculosis. This study aimed to address this gap by examining transcriptional responses to BCG vaccination in C57BL/6 inbred mice, coupled with protection studies using Diversity Outbred mice. We evaluated relative gene expression in blood obtained from vaccinated mice, because blood is easily accessible, and data can be translated to human studies. We first determined that the average peak time after vaccination is 14 days for gene expression of a small subset of immune-related genes in inbred mice. We then performed global transcriptomic analyses using whole blood samples obtained two weeks after mice were vaccinated with BCG. Using comparative bioinformatic analyses and qRT-PCR validation, we developed a working correlate panel of 18 genes that were highly correlated with administration of BCG but not heat-killed BCG. We then tested this gene panel using BCG-vaccinated Diversity Outbred mice and revealed associations between the expression of a subset of genes and disease outcomes after aerosol challenge with M. tuberculosis. These data therefore demonstrate that blood-based transcriptional immune correlates measured within a few weeks after vaccination can be derived to predict protection against M. tuberculosis, even in outbred populations.

Hypothesis on the pathophysiology of syringomyelia based on analysis of phase-contrast magnetic resonance imaging of Chiari-I malformation patients.

Background: Despite several hypotheses, our understanding of syringomyelia's pathophysiology remains limited. The hypothesis proposed by Oldfield et al. suggests that piston-like movement of the cerebellar tonsils propels the cerebrospinal fluid (CSF) into the syrinx via the spinal perivascular space. However, a significant question remains unanswered: how does the CSF enter and stay in the syrinx, which has a higher pressure than the subarachnoid space. In the current study, we attempted to verify Oldfield's hypothesis using phase-contrast magnetic resonance imaging (MRI) data from patients with syringomyelia. Methods: We analyzed phase-contrast MRI scans of 18 patients with Chiari-I malformation associated with syringomyelia, all of whom underwent foramen magnum decompression, and 21 healthy volunteers. We obtained velocity waveforms for CSF and brain tissue from regions of interest (ROI) set at the various locations. These waveforms were synchronized at the peak timing of downward CSF flow. We compared the preoperative patient data with the control data and also compared the preoperative patient data with the postoperative patient data. Results: The syrinx shrank in 17 (94%) of the patients, and they experienced significant clinical improvement. When comparing pre- and postoperative MRI results, the only significant difference noted was the preoperative elevated velocity of the cerebellar tonsil, which disappeared post-surgery. The CSF velocities in the subarachnoid space were higher in the preoperative patients than in the controls, but they did not significantly differ in the postoperative MRI. The tonsillar velocity in the preoperative MRI was significantly lower than that of the CSF, suggesting that the elevated tonsillar velocity was more of an effect, rather than the cause, of the elevated CSF velocity. Conclusions: Given these findings, a completely new paradigm seems necessary. We, therefore, propose a novel hypothesis: the generative force of syringomyelia may be the direction-selective resistance to CSF flow in the subarachnoid space.

Full-field electroretinogram recorded with skin electrodes in 6- to 12-year-old children

PurposeTo determine the full-field electroretinogram (ffERG) parameters, including the light-adapted (LA) 3 ERG and the photopic negative response (PhNR), in 6- to 12-year-old children.MethodsffERG data were obtained from 214 eyes of 214 healthy subjects. The amplitudes and peak time of the ffERG responses were obtained from children divided into 6- to 8-year-old and 9- to 12-year-old groups. Using a skin electrode, electrical signals were measured in response to white stimulating light and white background light (LA 3 ERG). A blue background light and red flashes were then used to elicit the PhNR.ResultsThe a-wave amplitude ranged from 0.40 to 9.20 μV, the b-wave ranged from 4.70 to 30.80 μV, and the PhNR ranged from 1.30 to 39.90 μV. The b-wave peak time (33.20 ms) of 6- to 8-year-old groups was slightly shorter than that of the 9- to 12-year-old groups (33.60 ms, P = 0.01), but no differences in amplitudes or in peak time of other components. There were significant correlations between the amplitudes (a-wave and b-wave: r = 0.43, p < 0.001; a-wave and PhNR: r = 0.25, p < 0.001; b-wave and PhNR: r = 0.45, p < 0.001). There was a moderate correlation between the a-wave and b-wave peak time (r = 0.31, P < 0.001).ConclusionsWe determined the largest dataset of the LA 3 ERG and PhNR parameters in a population of healthy children, aged 6–12 years, which may provide a useful reference value when evaluating children with potential retinal defects.

Unique patterns of medial meniscus extrusion during walking and its association with limb kinematics in patients with knee osteoarthritis

Medial meniscus extrusion (MME) is exacerbated by repeated mechanical stress. Various factors would affect MME; however, there is limited information about the behaviour of the medial meniscus during walking in patients with knee osteoarthritis (KOA). This study aimed to investigate the pattern of MME during walking and its association with limb biomechanics in patients with KOA. Fifty-five patients with KOA and ten older adult volunteers as a control group were involved in this study. The MME and limb biomechanics during walking were evaluated simultaneously by ultrasound and a motion analysis system, respectively. The waveform was constructed from the values of MME, and the point showing the highest value of MME was identified during the gait cycle. According to the peak timing of MME in the waveform, the pattern of the waveform was evaluated and compared to the control group. Lateral thrust, knee adduction moment (KAM), and flexion moment were obtained from motion analysis, and their association with the MME was evaluated. The patients with KOA demonstrated unique peak timing during walking. Compared to the control group, there were three groups of MME waveforms, early (< 59%), normal (60–83%), and late (> 84%) from the peak timing in the gait cycle. The pattern of MME waveform in early, normal, and late groups was correlated with the first KAM and lateral thrust, second KAM, and knee flexion moment, respectively. A unique MME pattern during walking was demonstrated, and these patterns were associated with limb biomechanics in patients with KOA.

Development and In Vitro-In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro-in vivo correlation (IVIVC) to predict bioavailability. The tablets' mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger-Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.