Lag Time Research Articles

Multi-Temporal and Time-Lag Responses of Terrestrial Net Ecosystem Productivity to Extreme Climate from 1981 to 2019 in China

The escalating frequency and severity of extreme climate greatly impact the carbon dynamics of terrestrial ecosystems worldwide. To understand the multi-temporal response of net ecosystem productivity (NEP) to extreme climate, we investigated 11 temperature and precipitation extreme indices across different vegetation types in China. From 1981 to 2019, the results showed that NEP in China increased at a rate of 0.64 g·m−2·a−2. Extreme climate demonstrated a significant warming trend and a non-significant moistening trend; specifically, maximum daily minimum temperature (TNx) exhibited a significant increase at a rate of 0.34 °C/10 a, while maximum 5-day precipitation (Rx5day) showed an insignificant increase at a rate of 1.78 mm/10 a. NEP was significantly impacted by extreme temperature at the annual, seasonal, and monthly scales, but moderately impacted by extreme precipitation. Specifically, extreme temperature had the most significant effect on grassland, with minimal influence on cropland. In contrast, extreme precipitation had the most significant effect on forest, with minimal impact on cropland. Moreover, the lagged time for extreme precipitation was longer than that for extreme temperature. Extreme precipitation exhibited a corresponding lagged time of at least 2 months (p < 0.01), while extreme temperature exhibited a lagged time of at least 1 month (p < 0.01). The maximum lag time observed was 4 months (p < 0.01). Our findings provide valuable insights into the multi-temporal response of NEP to extreme climate in China and inform sustainable development practices in the region.

Preparation, In-vitro, and Ex-vivo Evaluation of Ondansetron Loaded Invasomes for Transdermal Delivery

Invasomes are newly developed types of nanovesicles. A vesicular drug delivery system is considered one of the approaches for transdermal delivery to enhance permeation and improve drug bioavailability. Ondansetron is a serotonin receptor antagonist used for treating vomiting associated with different clinical cases. The study aimed to prepare invasomal dispersions for improving permeation of ondansetron across the skin with a controlled release pattern. Twenty-seven formulas of ondansetron-loaded invasomes were prepared by a modified mechanical dispersion method. These formulas were optimized by studying the effect of variables on entrapment efficiency. Vesicle size, polydispersity, zeta potential, in-vitro release and ex-vivo permeation studies were done for the optimized formulas. The selected formula was )F25( had )88.24%±0.04 (entrapment, (317.7 nm) vesicle size, (0.29) polydispersity, and (-31.5mV) zeta potential. In-vitro release study showed That (F25) had 75% release after (12) hrs., and dissolution followed the Korsmeyer-Peppas model with anomalous diffusion. Ex-vivo permeation study showed steady-state flux was 340.2 µg/cm2.hr with no lag time using rat skin tissue. A transmission electron microscope was done to visualize the selected formula. Invasomes are considered promising drug delivery systems for transdermal delivery of ondansetron, ensuring efficient permeation with a sustained release pattern.

Diagnosis of Imported Dengue and Zika Virus Infections in Italy from November 2015 to November 2022: Laboratory Surveillance Data from a National Reference Laboratory.

Dengue (DENV) and Zika (ZIKV) viruses are mosquito-borne human pathogens. In Italy, the presence of the competent vector Aedes albopictus increases the risk of autochthonous transmission, and a national plan for arboviruses prevention, surveillance, and response (PNA 2020-2025) is in place. The results of laboratory diagnosis of both viruses by the National Reference Laboratory for arboviruses (NRLA) from November 2015 to November 2022 are presented. Samples from 655 suspected cases were tested by both molecular and serological assays. Virus and antibody kinetics, cross-reactivity, and diagnostic performance of IgM ELISA systems were analysed. Of 524 cases tested for DENV, 146 were classified as confirmed, 7 as probable, while 371 were excluded. Of 619 cases tested for ZIKV, 44 were classified as confirmed, while 492 were excluded. All cases were imported. Overall, 75.3% (110/146) of DENV and 50% (22/44) of ZIKV cases were confirmed through direct virus detection methods. High percentages of cross reactivity were observed between the two viruses. The median lag time from symptoms onset to sample collection was 7 days for both DENV molecular (range 0-20) and NS1 ELISA (range 0-48) tests, with high percentages of positivity also after 7 days (39% and 67%, respectively). For ZIKV, the median lag time was 5 days (range 0-22), with 16% positivity after 7 days. Diagnostic performance was assessed with negative predictive values ranging from 92% to 95% for the anti-DENV systems, and of 97% for the ZIKV one. Lower positive predictive values were seen in the tested population (DENV: 55% to 91%, ZIKV: 50%). DENV and ZIKV diagnosis by molecular test is the gold standard, but sample collection time is a limitation. Serological tests, including Plaque Reduction Neutralization Test, are thus necessary. Co-circulation and cross-reactivity between the two viruses increase diagnostic difficulty. Continuous evaluation of diagnostic strategies is essential to improve laboratory testing.

Prediction of Influenza-Like Illness Incidence in Cheras, Malaysia based on Environmental Data using the Generalised Additive Model

Influenza-like illness (ILI) accounts for 500,000 fatalities worldwide yearly. Environmental factors contribute to spread of respiratory infections. This study describes the epidemiological trends of ILI in Cheras, Kuala Lumpur, Malaysia and seeks scientific evidence on ILI activity and environmental factors. Cheras Health District collected ILI surveillance data and the nearest weather station which provided environmental data on mean temperature, humidity, wind speed, cumulative rainfall, particulate matter (PM)10 and PM2.5 levels. A total of 51,245 ILI cases were reported from 1st December 2021 to 30th April 2023. The non-linear relationship between ILI incidence and environmental variables was modelled using the Generalised Additive Model (GAM). The lag time for mean temperature, mean humidity, cumulative rainfall, mean wind speed, PM 10 level, and PM 2.5 level was 2, 3, 3, 3, 0, and 3 days, respectively. The model with the optimal lag better describes ILI case variance (R2=0.5, explained deviance=58%) than the model without lag selection (R2=0.5, explained deviance=57.2%). The Lag Model indicates a significant p-value for PM10 but no significant concurvity between predictor variables. Thus, the final model (R2=0.5, explained deviance=59.2%) has k=15. Higher rainfall, relative humidity, colder temperature, and decreased wind speed increased ILI incidence. PM2.5 and PM10 also contributes to ILI.

Study on the Cause Analysis and Trend Prediction of Typical Landslide Disasters in Pukou District

This paper takes the typical soil-rock binary structure landslide on the east side of the middle section of Yanshan Avenue in Pukou District as the research object. Through field investigation, geological surveying and mapping, Lidar scanning, drilling, rainfall and deformation monitoring data analysis and other means, the basic characteristics of the landslide and the factors affecting the stability of the landslide are analyzed. It is found that the expansibility of kaolin and the floating support force of temporary confined water are one of the factors affecting the stability of the slope. Through real-time monitoring to explore the relationship between rainfall and surface horizontal displacement and vertical displacement, it is found that the surface deformation is greatly affected by the season. When the rainfall is large, the impact of temporary confined water has a large time lag. The faster the speed to reach the saturated state, the shorter the lag time, and vice versa. On this basis, the relationship model between landslide and rainfall is established, and the development trend of landslide is predicted.

Evaluation of the Lag Time Between Onset of Symptoms and Diagnosis in Childhood Cancers

Evaluation of the Lag Time Between Onset of Symptoms and Diagnosis in Childhood Cancers

The thrombin generation capability of the Chacma baboon (Papio ursinus): implications for haemostatic disease models

Baboon models are often used to investigate haemostatic diseases, such as acquired thrombotic thrombocytopenic purpura or bacterial sepsis-induced disseminated intravascular coagulation, and their potential treatment with novel drugs. Thrombin generation is vital for these models, and an important potential therapeutic target. We investigated the thrombin generation profile of the Chacma baboon (Papio ursinus – a common pre-clinical model) including the effects of sex and ABO blood group. Thrombin generation curves, lag times, peak heights, times-to-peak, velocity indexes and Endogenous Thrombin Potentials (ETPs) of 40 adult Chacma baboons were assessed and compared with normal human plasma, using a low concentration of tissue factor (1 pM) and phospholipids. Reference intervals were calculated, and results compared between O and non-O ABO blood groups, and between males and females. Lag times of all baboons fell within the human reference interval. Most animals (n = 32; 80%) had times-to-peak above, and velocity indexes and peak heights markedly below (n = 27; 68%) the human range. However, 97.5% of baboons had an ETP above the human reference interval, indicating greater overall thrombin generation. ABO blood group had no effect, but males (n = 14; 35%) had less potent thrombin generation than females (n = 26; 65%), with significantly longer lag times (p = 0.0475), lower peak thrombin concentrations (p = 0.0203), and lower ETPs (p = 0.0238). Chacma baboons have greater overall endogenous thrombin generation potentials than humans, which is even more prominent in females. This should be considered when designing future baboon model experiments involving the haemostatic system, or when evaluating novel therapies in these animals.

Analytical Expressions of the Markov Chain of K-Ras4B Protein within the Catalytic Environment and a New Markov-State Model

The finite Markov chain to which there correspond the qualities of the conformational dynamics of the K-Ras4B proteins in the catalytic reaction is written. The corresponding Markov-Sates models are studied. The properties of the K-Ras4B processes Markov chain allow one to define a new two-state MSM for the analytical description of the final-state transition. The time evolution of the eigenvalue corresponding to the final-state transition in the Galerkin description is written. The tools for the analytical calculations of the relative error are therefore prepared. New analytical formulations of the time evolution of the eigenvalue corresponding to the final-state transition are newly written from the experimental data and form the properties of the lag time in shaping the discretization error. The features of the discretization error are newly studied. A comparison with the experimental data is proposed.

Effects of hydrogen pressure on stabilization with improved denitrification in a hydrogen-based membrane biofilm reactor

Although start-up is a critical procedure in biofilm-based processes, systematic research aimed at improving start-up efficiency in hydrogen-based membrane biofilm reactors (H2-MBfRs) is lacking. In this study, we investigated the effects of H2 pressure on the stabilized denitrification performance of H2-MBfRs during start-up. Following inoculation with anoxic sludge, the biomass was acclimated to various H2 pressures. The increase in denitrifying microbial activity under high H2 pressures (i.e., H2 flux) shortened the denitrification lag time and reduced NO3–N removal flux, indicating an improved acclimation efficiency. The acclimated biomass was attached to membranes under different H2 pressures. High H2 pressures impeded biomass attachment, possibly because of bubble-less evaporation. Reducing the H2 pressure appeared to be necessary for improving the biomass attachment. However, this measure decreased previously acclimated denitrification activity. Therefore, the loss of both acclimation and biomass adhesion must be considered during the attachment phase. The highest removal flux (0.63 e- eq/m2-d) was obtained after just 3.5 d of acclimated biomass attachment (i.e., activated sludge floc) at 1.6 bar. During Phase 3, the initial performance was further improved to 0.89 e- eq/m2-d by gradually increasing the H2 pressure. These results provide a start-up strategy for improving the initial performance of H2-MBfRs.

In-vitro Evaluation and Optimization of Sacubitril and Valsartan Floating Tablet using Natural Polymer

Oral systems have become gradually extensive for human consumption because of their numerous advantages, such as formulation efficiency, cost-effectiveness, and patient safety compliance. These systems offer a versatile platform for controlled drug release, allowing precise targeting of absorption site in the gastrointestinal tract. Accomplishing ideal therapeutic results for certain medications often requires precise control of drug release at specific locations within the gastrointestinal tract. In this study, our goal was to create a floating drug delivery system for two vital cardiovascular medications, sacubitril and valsartan. Our specific objectives were to extend floating time, prolong stomach residency, and reduce floating lag time. The strategy involved harnessing the synergistic potential of natural polymers in optimal proportions to enhance drug activity. Following the principles of quality by design (QbD), we systematically explored various formulation factors to optimize the drug delivery system. Analysis of tablet characteristics revealed significant variations in key parameters, such as swelling index, floating lag time (FLT), total floating time (TFT), and drug content for both sacubitril and valsartan. The enhanced formulation (F12) stood out with a remarkable swelling index of 93.4%, a floating lag time of 6.7 seconds, and an impressive total floating time of 12 hours. Furthermore, high drug content percentages were achieved, with sacubitril at 98.70% and valsartan at 94.65%. The successful development and optimization of the floating tablet formulation carry substantial clinical implications. The extended gastric retention, controlled drug release, and high drug content of the optimized formulation suggest enhanced bioavailability and therapeutic efficacy for both sacubitril and valsartan. The prolonged total floating time offers convenience to patients, potentially improving medication adherence in managing cardiovascular diseases. In conclusion, this study highlights the formulation and optimization of floating tablets as a noteworthy advancement in drug delivery technology, promising improved therapeutic outcomes and enhanced patient convenience.

Time-Lagged Response of Streamflow in the Lower Yellow River to the Water Regulation by Xiaolangdi Reservoir: Implication for Efficient Water Supply

The Lower Yellow River (LYR) is a vital water resource for agriculture, industry, and domestic use in the surrounding areas. Understanding the delayed response of local streamflow response to remote reservoir operations is crucial for effective water management and flood control. In this work, we utilize historical hydrological data and statistical analysis techniques to investigate the time-lagged response of streamflow in the LYR to water regulation by the Xiaolangdi Reservoir. The results demonstrate that there is a time lag of 1.98 days, 2.86 days, and 3.93 days between the record of water regulation at Xiaolangdi Reservoir and the arrival time at Gaocun, Aishan, and Lijin stations, respectively. Time lag correction is proven to be crucial when establishing the relationship between the daily streamflows in the LYR and those at Xiaolangdi station. Further analysis reveals that the travel distance of streamflow is the dominant factor determining the lag time, with a time lag coefficient of 0.57 days per hundred kilometers. It is expected that the findings in this study could offer a fundamental basis for decision-makers in water resource management.

Markov State Models for Electrostatic Channeling in Bioelectrocatalysis

Multistep biocatalytic cascades benefit from channeling mechanisms that guide intermediate transport between active sites. Channeling approaches such as electrostatic interactions and steric confinement are best exemplified in natural biocatalytic complexes such as tryptophan synthase and malate dehydrogenase–citrate synthase, but are also amenable to application in de novo cascades designed to accomplish chemical conversion and energy production.We have recently conducted an extensive computational study of the Malate Dehydrogenase–Citrate Synthase (MDH-CS) complex, which displays a positively charged patch on its surface, capably of electrostatically channeling a negatively-charged oxaloacetate intermediate. Our collaborators have demonstrated experimentally that mutation of residues in the positively-charged patch can strongly effect intermediate transport, as measured by lag time, the time required for the second of a two-reaction cascade to approach steady state [1].Using classical molecular dynamics approaches to study the transport of oxaloacetate in the presence of the charged surface, we created a Markov State model that effectively maps the prevalence of the intermediate across the enzyme surface as well as in bulk solution. Building the model involved seeding the possible states of the intermediate using metadynamics to force the intermediate out of low-energy states and to explore the overall energy landscape. Once assembled, this model enables us to study the dominant pathways of intermediate transport, for example contrasting transport along the charged enzyme surface with diffusion into the bulk solution. A “hub score” approach enabled identification of key residues that control intermediate traversal over the charged surface, and we are able to calculate pathway efficiency that is directly relatable to lag time [2].We will discuss a new, fast finite-difference approach to predict lag times for these multidimensional complexes. The steady-state transition matrix of the Markov state model is easily converted to a material balance for each node in the network. Using the model, the lag time of MDH-CS was determined computationally to be comparable to experiment for both the original and mutant complex. Using the model, the the dynamics of each of the four possible reaction pathways between the the two source (MDH) active sites and the two sink (CS) sites could be studied independently. This analysis provides a dynamic model for intermediate transport in an electrostatically channeled system, and can be used as a predictive tool to provide mechanistic insight into path dominance. B. Bulutoglu, K. E. Garcia, F. Wu, S. D. Minteer and S. Banta, ACS Chem. Bio., 11, 2847–2853 (2016). doi:10/f9c5cpY. Xie, S. D. Minteer, S. Banta and S. C. Barton, ACS Nanosci. Au, 2, 414 (2022). doi:10/gqkvtq

Time-kill kinetics of Piper betle L. ethanolic leaf extract on methicillin-sensitive Staphylococcus aureus

Staphylococcus aureus is one of the main pathogens in community and hospital infections that could cause mild skin infections to severe life-threatening bacteremia. Piper betle has shown antibacterial activities against S. aureus but its pharmacodynamics remains unclear despite its widespread availability in many over-the-counter preparations. This study aimed to describe the time-kill kinetics of P. betle extract against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA). Time-kill kinetics were conducted to describe the killing rate of P. betle extract by its effects on MSSA lag time duration, growth rate, and maximum optical density. The surviving colonies at different time-points after exposure to P. betle extract at minimum bactericidal concentration were also determined. Subinhibitory concentrations elucidated its concentration-dependent antibacterial activity by maintaining a trend of increasing lag time, decreasing growth rate, and decreasing maximum optical density as the concentration increases. In particular, concentration at 1250 μg/mL or 0.5 x minimum inhibitory concentration (MIC) showed consistent significant findings across these parameters. Concentrations at MIC and above did not show growth, indicating MSSA growth inhibition or death. P. betle extract’s bactericidal effect started immediately within two (2) hours and was sustained until no growth was observed from the eighth hour and beyond. P. betle extract maintained antibacterial activities against MSSA at subinhibitory concentrations and has also exhibited immediate and sustained bactericidal effect at minimum bactericidal concentration (MBC).

Global cascade of kinetic energy in the ocean and the atmospheric imprint.

Here, we present an estimate for the ocean's global scale transfer of kinetic energy (KE), across scales from 10 to 40,000 km. Oceanic KE transfer between gyre scales and mesoscales is induced by the atmosphere's Hadley, Ferrel, and polar cells, and the intertropical convergence zone induces an intense downscale KE transfer. Upscale transfer peaks at 300 gigawatts across mesoscales of 120 km in size, roughly one-third the energy input by winds into the oceanic general circulation. Nearly three quarters of this "cascade" occurs south of 15°S and penetrates almost the entire water column. The mesoscale cascade has a self-similar seasonal cycle with characteristic lag time of ≈27 days per octave of length scales; transfer across 50 km peaks in spring, while transfer across 500 km peaks in summer. KE of those mesoscales follows the same cycle but peaks ≈40 days after the peak cascade, suggesting that energy transferred across a scale is primarily deposited at a scale four times larger.

Low molecular weight heparin decreases pro-coagulant activity in clinical MSC products

Background aimsMesenchymal stromal cells (MSCs) are multipotent adult cells that can be isolated from tissues including bone marrow [MSC(BM)], adipose [MSC(AT)] and umbilical cord [MSC(CT)]. Previous studies have linked expression of tissue factor (TF) on MSC surfaces to a procoagulant effect. Venous thromboembolism (VTE), immediate blood-mediated inflammatory reaction (IBMIR) and microvascular thrombosis remain a risk with intravascular MSC therapy. We examined the effect of low molecular weight heparin (LMWH) on clinical-grade MSCs using calibrated automated thrombography (CAT). MethodsClinical grade MSC(BM)s, MSC(AT)s and MSC(CT)s harvested at passage 4 were added to normal pooled plasma (NPP) to a final concentration of either 400 000 or 50 000 cells/mL. LMWH was added to plasma in increments of 0.1 U/mL. Thrombin generation (TG) was measured using CAT. Flow cytometry was conducted on the cells to measure MSC phenotype and TF load. ResultsPresence of MSCs decreased lag time and increased peak TG. All cell lines demonstrated a dose response to LMWH, with MSC(AT) demonstrating the least thrombogenicity and most sensitivity to LMWH. TG was significantly reduced in all cell lines at doses of 0.2 U/mL LMWH and higher. DiscussionAll MSC types and concentrations had a decrease in peak thrombin and TG with increasing amounts of LMWH. While this in vitro study cannot determine optimal dosing, it suggests that LMWH can be effectively used to lower the risk of VTE associated with intravascular administration of MSCs. Future in vivo work can be done to determine optimal dosing and effect on IBMIR and VTE.

Experiment and Simulation of Groundwater Salt Transport Based on Different Contact Relations in Heterogeneous Soil Layers

With the expansion of reserve cultivated land resources in coastal saline–alkali areas, the problem of soil salinization is becoming more and more prominent. In order to reveal the influence of different soil media and contact modes on soil water movement, a two-domain Hydrus-3D model was established to verify its performance in heterogeneous soil layers, and the characteristics of water, salt, and wet peak transport of surface soil and sandy soil under horizontal contact and inclined contact conditions were analyzed through experiments and simulations. The measured data show that in horizontal contact mode, probe 3 and probe 2 are close to the interface of the two layers of soil, and their maximum values are measured in about 60 min. The time difference between probe 1 and probe 2 is about 15 min. In the inclined contact mode, probe 4 in the topsoil reached 45% in 10 min and remained stable; the peak lag time of probes 3 and 2 was 10 min, and the peak lag time of probes 2 and 1 was 15 min; the water in the surface soil gradually increases and then stabilizes; and the water in the sand soil is similar to the normal curve. The salt characteristics in the surface soil are similar to the normal curve, while the salt characteristics in the sandy soil gradually increase and then stabilize. The simulation results show that the water content in the topsoil is more than 40%, and the maximum water content in the center of the sand is only 36.9%, which is roughly the same as the experimental results. The results showed that the Hydrus-3D model had a good simulation effect on the groundwater salt transport of heterogeneous soil under two contact methods. The RMSE value and E value are close to 0 and 1, respectively, indicating that the simulation has good feasibility and can be applied to the simulation of water and salt transport processes under different contact modes of soil media.

Impact of financial incentives for infection prevention and management on antibiotic use: A Korea National Health Insurance cohort study

BackgroundThe Korean government implemented financial incentives to enhance infection prevention and management within general hospital settings. This study aimed to evaluate the impact of infection control compensation on antibiotic usage using a controlled interrupted time series analysis. MethodsThe main unit of analysis was 270,901 inpatient episodes extracted from the Korean National Health Insurance Service Cohort Database from 2013 to 2019. The 96-month period was examined before and after the intervention, which was set to September 1, 2017, by applying a 1-year lag time after the incentive was introduced. Segmented regression was used to estimate the effects of interventions in a controlled interrupted time series. Hospitals that received nationwide financial incentives for infection prevention and management were included in the analysis. The study’s primary outcome was the use of antibiotics based on the WHO Access, Watch, and Reserve (AWaRe) classification of antibiotics, and the secondary outcome was the number of days of antibiotic use as days of therapy (DOTs) per patient day (PD). ResultsThe probability of overall antibiotic use decreased between incentivized and unincentivized hospitals (odds ratio [OR], 0.922; 95% confidence interval [CI], 0.859–1.000). The difference in level change in the use of third-generation cephalosporins (OR,0.894; 95% CI, 0.817–0.977) and carbapenem (OR,0.790; 95% CI, 0.630–0.992) was significantly reduced between incentivized and unincentivized hospitals. The difference in slope change on DOTs/PD of glycopeptides was − 0.005 DOT/PDs, and that of carbapenem was − 0.003 between incentivized and unincentivized hospitals. ConclusionWe observed that incentives for infection prevention and management have had a positive impact on some aspects of antibiotic usage. A partial decrease was observed in antibiotic use, accompanied by a modest reduction in DOTs/PD, particularly for antibiotics aimed at addressing multidrug-resistant pathogens. Further investigation is necessary to establish evidence for extending these incentives.

The Development of Alternative Dosage Form for Creatine Monohydrate: A Floating Tablet

Creatine monohydrate has been developed as a neuroprotective agent and can penetrate in vitro model of the blood-brain barrier. However, its delivery is hampered by its limited capacity of creatine transporter. The floating system is known to increase the residence time of drugs in the stomach; thus, the active substances can be absorbed more optimally. Therefore, this study is aimed to develop creatine monohydrate floating tablets by optimizing the proportion of HPMC K100M and NaHCO2 and evaluating the quality of floating tablets. The formula was designed Simplex Lattice Design method. Tablets were prepared by the wet granulation method and evaluated for granule and tablet parameters. The results showed that HPMC K100M significantly increased flow time, absorption rate, hardness, floating time, swelling index; decreased index tap, fragility, and floating lag time. Meanwhile, an increase in NaHCO2 significantly affects an increase in floating lag time. The optimum formula obtained was 18.87% HPMC K100M and 21.12% NaHCO2. Verification of the optimum formula showed that tablet parameters were not significantly different from the predicted formula. The studies suggest that this prototype can be developed to increase creatine residence time in the stomach.

No Detectable Coagulation Activation After Vitamin K (MK-7) Supplementation in Patients on Dialysis With Functional Vitamin K Deficiency: A One-Year Randomized, Placebo-Controlled Study

Patients on dialysis treatment have poor functional vitamin K status, and this may increase the risk of vascular calcification. Vitamin K supplementation may therefore be relevant in patients on dialysis, but the procoagulant effects have not been studied. We evaluated effects of menaquinone-7 (MK-7) supplementation on biomarkers of coagulation in patients on dialysis. Double-blinded, placebo-controlled study in 123 patients on dialysis randomized to 52weeks of vitamin K (MK-7, 360μg/daily, n=61) or placebo (n=62). Measurements at baseline and after 52weeks of intervention included thrombin generation (endogenous thrombin potential, peak thrombin concentration, time to peak, and lag time); clot activities of vitamin K-dependent coagulation factors (F) II, VII, IX, and X; prothrombin fragment 1+2 (F1+2); and proteins induced by vitamin K absence II (PIVKA-II). Between-group differences (vitamin K vs. placebo) at 52weeks were determined with an analysis of covariance. Within-group changes in vitamin K and placebo groups were analyzed with a paired t-test. Vascular adverse events and serious adverse events were registered based on hospital records, laboratory data, and participant interviews and compared between groups using Fisher's exact test or Pearson's Chi-Squared test. A between-group difference at 52weeks was observed for PIVKA-II (P<.001). PIVKA-II decreased significantly from baseline to 52weeks in the vitamin K group, but not in the placebo group. We observed no between-group differences or within-group changes for biomarkers of coagulation, except for FVII clot activity which was reduced in the placebo group (P=.04), and no between-group differences in adverse events and serious adverse events. One year of vitamin K supplementation in patients on dialysis has no detectable effects on biomarkers of coagulation activation, clot activities of vitamin K-dependent coagulation factors, and vascular events or death, indicating no procoagulant effects of this treatment.

Increased ambient outdoor temperatures are associated with increased disease flaring in hidradenitis suppurativa.

Despite evidence to suggest a relationship between time of year and hidradenitis suppurativa (HS) flaring, no studies have been conducted to date to establish a relationship directly between temperature and flaring. In this study, we aim to validate a classification approach based on administrative data for identifying medical encounters that likely represent HS flares in patient with a known diagnosis of HS within the Mass General Brigham Health System (MGB) and examine the relationship between average daily temperatures and HS disease flaring among patients in Boston. This is a retrospective cohort study. Participants were individuals with HS presenting to emergency departments or dermatology outpatient clinics with disease flares between January 2017 and January 2022. The average number of encounters for HS flares was compared with the temperature for that day and the 3- and 7-day periods prior. There were 2567 patient encounters for HS flares included in the study. Of the total identified HS flares, 75.6% occurred in females and 39.1% occurred in patients who identified as Black. Uniformly small but statistically significant relationships were noted between increased temperature and presentations for hidradenitis suppurativa flare with the highest correlation coefficient (0.0768) noted with a 3-day lag time between the heat experienced and day of presentation for flare. Increased temperature is associated with a small, but statistically significant increase in HS disease flaring. As such, HS disease flaring may rise as global temperatures do, suggesting an increase in the global burden of HS as climate change persists.