Potential Threshold Research Articles

Saltatory conduction and intrinsic electrophysiological properties at the nodes of ranvier of Aα/β-afferent fibers and Aα-efferent fibers in rat sciatic nerves.

Large-diameter myelinated fibers in sciatic nerves are composed of both Aα/β-afferent fibers and Aα-efferent fibers to convey sensory and motor impulses, respectively, via saltatory conduction for rapid leg responses. Saltatory conduction and electrophysiological properties at the nodes of Ranvier (NRs) of these sciatic nerve fibers have not been directly studied. We used ex vivo sciatic nerve preparations from rats and applied patch-clamp recordings at the NRs of both Aα/β-afferent fibers and Aα-efferent fibers in the sciatic nerves to characterize their saltatory conduction and intrinsic electrophysiological properties. The velocity and frequency of saltatory conduction in both types of fibers were similar. Resting membrane potentials (RMPs), input resistance, action potential (AP) threshold, and AP rheobase were also not significantly different at the NRs of the two types of fibers in the sciatic nerves. In comparison with Aα/β-afferent fibers, Aα-efferent fibers in the sciatic nerves show higher amplitude and broader width of APs at their NRs. At the NRs of both types of fibers, depolarizing voltages evoked transient inward currents followed by non-inactivating outward currents, and the inward currents and non-inactivating outward currents at the NRs were not significantly different between the two types of fibers. Using AP-clamp, inward currents during AP upstroke were found to be insignificant difference, but amplitudes of non-inactivating outward currents during AP repolarization were significantly lower at the NRs of Aα-efferent fibers than at the NRs of Aα/β-afferent fibers in the sciatic nerves. Collectively, saltatory conduction, ionic currents, and intrinsic electrophysiological properties at the NRs of Aα/β-afferent fibers and Aα-efferent fibers in the sciatic nerves are generally similar, but some differences were also observed.

Drip fertigation triggered by soil matric potential reduces residual soil nitrate content and improves maize nitrogen uptake and yield stability in an arid area

Effective water and fertilizer management is crucial for enhancing nitrogen (N) use efficiency and ensuring regional food security, especially in arid regions. Drip fertigation can synchronize water and fertilizer supply with crop demand, but its maximum benefits can only be achieved with appropriately designed and well-managed irrigation systems. In this study, we built on our previous work on optimizing the design of drip irrigation systems and evaluated the effect of drip fertigation regimes on soil nitrate nitrogen (NO3-N) supply, crop N uptake, yield, and yield stability. We conducted a five-year field experiment using drip fertigation to grow maize (Zea mays L.) in the Hetao Irrigation District, Northwest China, from 2016 to 2020. We implemented three water levels by controlling soil matric potential (SMP) threshold values [− 10 kPa (S1), − 30 kPa (S3), and − 50 kPa (S5)] under the same N fertilization rate (150 kg N ha−1 broadcast as basal fertilizer, 150 kg N ha−1 applied with drip fertigation). Our results indicated that soil NO3-N in 0–60 cm profile was typically distributed in the non-mulched zone at maturity. Compared with S5, S1 and S3 on average significantly decreased NO3-N accumulation in the 0–60 cm profile by 66% and 47%, and S1 and S3 significantly decreased NO3-N accumulation in the 60–120 cm profile by 31% and 30%. In addition, the S3 significantly decreased NO3-N accumulation in the 120–200 cm profile by 52% and 35% compared with S1 and S5. S3 significantly improved crop grain yield by 45%, sustainable yield index by 26%, N uptake by 28%, and N utilization efficiency by 11% compared with S5. In contrast, S3 decreased the irrigation amount by 40% compared with S1, with no significant differences in grain yield, yield stability, and N uptake in most years. We recommend using an SMP threshold value of − 30 kPa combined with a drip fertigation rate of 150 kg N ha−1 to reduce residual NO3-N and improve yield and yield stability in arid regions. Furthermore, we also recommend using drip fertigation with 208–253 mm irrigation water in wet years and > 253 mm in dry years (irrigation every four days from V6 to R3 stage), with 13.6 kg ha−1 N applied per irrigation (from VT to R3 stage) to facilitate farmer operations. Our research provides valuable technical guidance to promote a stable and sustainable agricultural production in arid regions.

Loss or Dilution-A New Diagnostic Method to Assess the Impact of Dilution on Standard Laboratory Parameters.

Intraoperative fluid therapy is regularly used in patients undergoing cardiac surgery procedures with cardiopulmonary bypass (CPB). Although fluid administration has several advantages, it unavoidably leads to hemodilution. The hemodilution may further influence the interpretation of concentration-based laboratory parameters like hemoglobin (Hgb), platelet count (PLT) or prothrombin time (PT). These all parameters are commonly used to guide blood product substitution. To assess the impact of dilution on these values, we performed a prospective observational study in 174 patients undergoing elective cardiac surgery. We calculated the total blood volume according to Nadler's formula, and fluid therapy was correlated with a newly developed dilution coefficient formula at the end of CPB. Intravenously applied fluids were measured from the beginning of the anesthesia (baseline, T0) and 15 min after the end of protamine infusion (end of CPB, T1). The amount of the administered volume (crystalloids or colloids) was calculated according to the percentage of the intravascular fluid effect, and intraoperative diuresis was further subtracted. The median blood volume increased by 148% in all patients at T1 compared to the calculated total blood volume at T0. This led to a dilution-dependent decrease of 38% in all three parameters (Hgb 24%, corrCoeff = 0.53; PLT 41%, corrCoeff = 0.68; PT 44%, corrCoeff = 0.54). The dilution-correlated decrease was significant for all parameters (p < 0.001), and the effect was independent from the duration of CPB. We conclude that the presented calculation-based approach could provide important information regarding actual laboratory parameters and may help in the guidance of the blood product substitution and potential transfusion thresholds. Further research on the impact of dilution and related decision-making for blood product substitution, including its impact on morbidity and mortality, is warranted.

Understory fuel loads and the impact factors of Quercus mongolica natural secondary forest in Hebei Pro-vince, China.

We investigated understory fuel loads of Quercus mongolica natural secondary forests in Hebei Province, China. We analyzed the effects of stand factors, topographic factors, and ground cover factors on the quantity and composition of fuel, established the dynamic models of understory fuel loads, and proposed management measures. The results showed that the understory total fuel load in Q. mongolica natural secondary forests was 11.68 t·hm-2, which exceeded the forest fire potential threshold (10 t·hm-2). The understory dead fuel load was mainly humus, and the understory living fuel load was mainly shrubs. The 1 h time-lag fuel load increased significantly with increasing canopy density, stand density, stand age, and litter thickness. The 10 h time-lag fuel load increased signi-ficantly with increasing stand density, average tree height, and litter thickness. Humus load decreased significantly with increasing altitude and increased significantly with increasing humus thickness. Herb load increased significantly with increasing sunny slope orientation and herbal coverage. Shrub load increased significantly with increasing slope degree, shrub coverage, and humus thickness. Understory total fuel load decreased significantly with increasing altitude, and increased significantly with increasing stand density, humus thickness, and litter thickness. The results of stepwise regression analysis indicated that stand density, humus thickness, and altitude could better predict the understory total fuel load (Radj2=0.775). Therefore, more attention should be paid on the control of stand density of Q. mongolica natural secondary forest in Hebei Province. Cleaning of litters and humus on the ground would help prevent forest fires scientifically and effectively.

Relative diagnostic accuracy of point-of-care tests to rule-in Dirofilaria immitis infection in clinically suspect dogs: A systematic review and meta-analysis.

Canine heartworm, Dirofilaria immitis, can cause severe disease and sometimes death of the host. Associated clinical signs, lack of preventative usage and regional endemicity are unlikely sufficient by themselves to reach a definitive diagnosis. Several point-of-care (POC) diagnostic tests are commercially available to aid in-clinic diagnosis, however, there is variable diagnostic accuracy reported and no synthesis of published evidence. This systematic review aims at meta-analysing the likelihood ratio of a positive result (LR+) to inform the selection and interpretation of POC tests in practice to rule-in heartworm infection when there is clinical suspicion. Three literature index interfaces (Web of Science, PubMed, Scopus) were searched on November 11th, 2022, for diagnostic test evaluation (DTE) articles assessing at least one currently commercialised POC test. Risk of bias was assessed adapting the QUADAS-2 protocol and articles with no evidence of high risk of bias were meta-analysed if deemed applicable to our review objective. Substantial between DTE heterogeneity was investigated including potential threshold or covariate effects. A total of 324 primary articles were sourced and 18 were retained for full text review of which only three had low risk of bias in all four QUADAS-2 domains. Of the nine heartworm POC tests evaluated, only three, IDEXX SNAP (n DTEs = 6), Zoetis WITNESS (n DTEs = 3) and Zoetis VETSCAN (n DTEs = 5) could be analysed. Both WITNESS and VETSCAN DTEs showed substantial heterogeneity due to a putative threshold effect and no summary point estimates could be reported. SNAP DTEs showed acceptable heterogeneity, and a summary LR+ was estimated at 559.0 (95%CI: 24.3-12,847.4). The quality and heterogeneity of heartworm POC test DTEs was highly variable which restricted our summary of the diagnostic accuracy to only the SNAP test. A positive result from the SNAP test provides strong evidence of the presence of an infection with adult heartworm(s) in a dog patient and this test is warranted to rule-in clinical suspicion(s) in clinics. However, our review did not appraise the literature to assess the fitness of SNAP test, or any other POC tests, to rule-out heartworm infection in dogs without clinical suspicion or following heartworm therapy.

Detecting social-ecological resilience thresholds of cultural landscapes along an urban–rural gradient: a methodological approach based on Bayesian Networks

ContextThe difficulty of analysing resilience and threshold responses to changing environmental drivers becomes evident in the social-ecological systems framework due to their inherent complexity. Research is needed to develop new tools able to deal with such challenges and determine potential thresholds for SES variables that primarily influence tipping point behaviour.ObjectivesIn this paper, a methodology based on the application of Bayesian Networks (BNs) has been developed to quantify the social-ecological resilience along an urban–rural gradient in Madrid Region, detecting the tipping point values of the main socioeconomic indicators implying critical transitions at landscape stability thresholds.MethodTo do this, the spatial–temporal trends of the landscape in an urban–rural gradient from Region de Madrid (Spain) were identified, to then quantify the intensity of the changes and explain them using BNs based on regression models. Finally, through inference propagation the thresholds of landscape change were detected.ResultsThe results obtained for the study area indicate that the most resilient landscapes analysed are those where the traditional silvo-pastoral activity was maintained by elderly people and where there is cohesion between neighbouring rural municipalities.ConclusionThe method developed has allowed us to detect the tipping points from which small changes in socioeconomic indicators generate large changes at the landscape level. We demonstrate that the use of BNs is a useful tool to achieve an integrated social-ecological spatial planning.

Features of processor fitting in patients with different types of cochlear implant electrode array

Introduction. The results of cochlear implantation in patients with bilateral sensorineural hearing loss are influenced by many factors, including the type of electrode array. The location of the electrodes in relation to neurons of spiral ganglion affects on levels of perception of the patient's hearing sensations.Aim. To evaluate the dependence of electrically evoked compound action potential (ECAP) thresholds values and comfortable levels depends on electrode array type.Materials and methods. 26 patients with bilateral sensorineural hearing loss with cochlear implantation systems were examined. The patients were divided into 2 groups: 1) patients with a straight electrode array (n = 14); 2) patients with a perimodiolar electrode array (n = 12). We tested speech intelligibility and ECAP thresholds. The difference in the values of both parameters was estimated.Results. For both groups of patients, the relationship between the threshold's profiles of ECAP thresholds and maximum comfortable stimulation levels was detected. For patients from the first group (straight electrode array), the differences in values between the studied parameters were 30.6 ± 6.1%. In patients from the second group, the differences in the values of the thresholds for ECAP thresholds and the levels of comfortable stimulation ranged 2.4 ± 2.1%.Conclusion. The perimodiolar electrode array is located closer to the neurons of the spiral ganglion, which may explain the greater relationship between the values of the ECAP thresholds and the levels of comfortable stimulation. This pattern must be considered when programming the processor of the cochlear implantation system.

Development of an open-source soil water potential management system for horticultural applications, “Open_Irr”

Development of data driven, sensor-based irrigation has become possible with recent advancements in technology, yet due to a cost-barrier to entry, equitable adoption remains out of reach. Therefore, a simple microcontroller based LoRa platform, Open_Irr, was developed in the Arduino IDE to record resistive measures of soil matric potential and automate irrigation events. A single Open_Irr Node may connect with ≤ 16 Watermark® soil sensors and manage 4 irrigation groups, with Node sampling frequency, irrigation settings, and radio transmission settings being end-user adjustable without programming knowledge. Multiple Nodes may connect with a single Gateway to provide a scale-neutral solution for irrigation automation. A preliminary trial was conducted in spring 2022 to validate the performance of the Open_Irr platform in water deficit scenarios. Open_Irr recorded soil matric potentials in line with a commercial Watermark® sensor reader (n = 655); regression analysis yielded a coefficient of determination of 0.91 with Bland-Altman estimated fixed bias of ∼ 2 kPa. The Open_Irr platform was demonstrated to automate dripline irrigation events at several matric potential thresholds through connection to external solenoid valves. This demonstration directly conveys suitability for commercial and academic horticultural applications where automation of irrigation events or imposition of edaphic water stress is desired.

Deficient AMPK activity contributes to hyperexcitability in peripheral nociceptive sensory neurons and thermal hyperalgesia in lupus mice.

Patients with systemic lupus erythematosus (SLE) often suffer from chronic pain. Little is known about the peripheral mechanisms underlying the genesis of chronic pain induced by SLE. The aim of this study was to investigate whether and how membrane properties in nociceptive neurons in the dorsal root ganglions (DRGs) are altered by SLE. We found elevation of resting membrane potentials, smaller capacitances, lower action potential thresholds and rheobases in nociceptive neurons in the DRGs from MRL/lpr mice (an SLE mouse model) with thermal hyperalgesia. DRGs from MRL/lpr mice had increased protein expressions in TNFα, IL-1β, and phosphorylated ERK but suppressed AMPK activity, and no changes in sodium channel 1.7 protein expression. We showed that intraplantar injection of Compound C (an AMPK inhibitor) induced thermal hyperalgesia in normal mice while intraplantar injection of AICAR (an AMPK activator) reduced thermal hyperalgesia in MRL/Lpr mice. Upon inhibition of AMPK membrane properties in nociceptive neurons from normal control mice could be rapidly switched to those found in SLE mice with thermal hyperalgesia. Our study indicates that increased excitability in peripheral nociceptive sensory neurons contributes to the genesis of thermal hyperalgesia in mice with SLE, and AMPK regulates membrane properties in nociceptive sensory neurons as well as thermal hyperalgesia in mice with SLE. Our study provides a basis for targeting signaling pathways regulating membrane properties of peripheral nociceptive neurons as a means for conquering chronic pain caused by SLE.

Investigating microglia-neuron crosstalk by characterizing microglial contamination in human and mouse patch-seq datasets

Microglia are cells with diverse roles, including the regulation of neuronal excitability. We leveraged Patch-seq to assess the presence and effects of microglia in the local microenvironment of recorded neurons. We first quantified the amounts of microglial transcripts in three Patch-seq datasets of human and mouse neocortical neurons, observing extensive contamination. Variation in microglial contamination was explained foremost by donor identity, particularly in human samples, and additionally by neuronal cell type identity in mice. Gene set enrichment analysis suggests that microglial contamination is reflective of activated microglia, and that these transcriptional signatures are distinct from those captured via single-nucleus RNA-seq. Finally, neurons with greater microglial contamination differed markedly in their electrophysiological characteristics, including lowered input resistances and more depolarized action potential thresholds. Our results generalize beyond Patch-seq to suggest that activated microglia may be widely present across brain slice preparations and contribute to neuron- and donor-related electrophysiological variability invitro.

Exposure to ambient air pollutants is associated with an increased incidence of hyperuricemia: A longitudinal cohort study among Chinese government employees

BackgroundIt is widely recognized that ambient air pollution can induce various detrimental health outcomes. However, evidence linking ambient air pollutants and hyperuricemia incidence is scarce. ObjectivesTo assess the association between long-term air pollution exposure and the risk of hyperuricemia. MethodsIn this study, a total of 5854 government employees without hyperuricemia were recruited and followed up from January 2018 to June 2021 in Hunan Province, China. Hyperuricemia was defined as serum uric acid (SUA) level of >420 μmol/L for men and >360 μmol/L for women or use of SUA-lowering medication or diagnosed as hyperuricemia during follow-up. Data from local air quality monitoring stations were used to calculate individual exposure levels of PM10, PM2.5, SO2 and NO2 by inverse distance weightingn (IDW) method. Cox proportional hazard model was applied to evaluate the causal relationships between air pollutant exposures and the risk of hyperuricemia occurrence after adjustment for potential confounders and meanwhile, restricted cubic spline was used to explore the dose-response relationships. ResultsThe results indicated that exposures to PM10 (hazard ratio, HR = 1.042, 95% conficence interal, 95% CI: 1.028, 1.057), PM2.5 (HR = 1.204, 95% CI: 1.141, 1.271) and NO2 (HR = 1.178, 95% CI: 1.125,1.233) were associated with an increased HR of hyperuricemia. In addition, a nonlinear dose-response relationship was found between PM10 exposure level and the HR of hyperuricemia (p for nonlinearity = 0.158) with a potential threshold of 50.11 μg/m3. Subgroup analysis demonstrated that participants usually waking up at night and using natural ventilation were more vulnerable to the exposures of PM10, PM2.5, NO2, and SO2. ConclusionLong-term exposures to ambient PM10, PM2.5 and NO2 are associated with an increased incidence of hyperuricemia among Chinese government employees.

Dynamic alteration of intrinsic properties of the cerebellar Purkinje cell during the motor memory consolidation

Intrinsic plasticity of the cerebellar Purkinje cell (PC) plays a critical role in motor memory consolidation. However, detailed changes in their intrinsic properties during memory consolidation are not well understood. Here, we report alterations in various properties involved in intrinsic excitability, such as the action potential (AP) threshold, AP width, afterhyperpolarization (AHP), and sag voltage, which are associated with the long-term depression of intrinsic excitability following the motor memory consolidation process. We analyzed data recorded from PCs before and 1, 4, and 24 h after cerebellum-dependent motor learning and found that these properties underwent dynamic changes during the consolidation process. We further analyzed data from PC-specific STIM1 knockout (STIM1PKO) mice, which show memory consolidation deficits, and derived intrinsic properties showing distinct change patterns compared with those of wild-type littermates. The levels of memory retention in the STIM1PKO mice were significantly different compared to wild-type mice between 1 and 4 h after training, and AP width, fast- and medium-AHP, and sag voltage showed different change patterns during this period. Our results provide information regarding alterations in intrinsic properties during a particular period that are critical for memory consolidation.

Insulin potentiates inhibitory synaptic currents between fast-spiking and pyramidal neurons in the rat insular cortex

Insulin plays roles in brain functions such as neural development and plasticity and is reported to be involved in dementia and depression. However, little information is available on the insulin-mediated modulation of electrophysiological activities, especially in the cerebral cortex. This study examined how insulin modulates the neural activities of inhibitory neurons and inhibitory postsynaptic currents (IPSCs) in rat insular cortex (IC; either sex) by multiple whole-cell patch-clamp recordings. We demonstrated that insulin increased the repetitive spike firing rate with a decrease in the threshold potential without changing the resting membrane potentials and input resistance of fast-spiking GABAergic neurons (FSNs). Next, we found a dose-dependent enhancement of unitary IPSCs (uIPSCs) by insulin in the connections from FSNs to pyramidal neurons (PNs). The insulin-induced enhancement of uIPSCs accompanied decreases in the paired-pulse ratio, suggesting that insulin increases GABA release from presynaptic terminals. The finding of miniature IPSC recordings of the increased frequency without changing the amplitude supports this hypothesis. Insulin had little effect on uIPSCs under the coapplication of S961, an insulin receptor antagonist, or lavendustin A, an inhibitor of tyrosine kinase. The PI3–K inhibitor wortmannin or the PKB/Akt inhibitors, deguelin and Akt inhibitor VIII, blocked the insulin-induced enhancement of uIPSCs. Intracellular application of Akt inhibitor VIII to presynaptic FSNs also blocked insulin-induced enhancement of uIPSCs. In contrast, uIPSCs were enhanced by insulin in combination with the MAPK inhibitor PD98059. These results suggest that insulin facilitates the inhibition of PNs by increases in FSN firing frequency and IPSCs from FSNs to PNs. (250 words).

Whole body vibration accelerates the functional recovery of motor nerve components in sciatic nerve-crush injury model rats.

This study aimed to investigate the effect of whole body vibration (WBV) on the sensory and motor nerve components with sciatic nerve injury model rats. Surgery was performed on 21 female Wister rats (6-8 weeks) under intraperitoneal anesthesia. The nerve-crush injuries for the left sciatic nerve were inflicted using a Sugita aneurysm clip. The sciatic nerve model rats were randomly divided into two groups (n=9; control group, n=12; WBV group). The rats in the WBV group walked in the cage with a vibratory stimulus (frequency 50 Hz, 20 min/day, 5 times/wk), while those in the control group walked in the cage without any vibratory stimulus. We used heat stimulation-induced sensory threshold and lumbar magnetic stimulation-induced motor-evoked potentials (MEPs) to measure the sensory and motor nerve components, respectively. Further, morphological measurements, bilateral hind-limb dimension, bilateral gastrocnemius dimension, and weight were evaluated. Consequently, there were no significant differences in the sensory threshold at the injury side between the control and WBV groups. However, at 4 and 6 weeks postoperatively, MEPs latencies in the WBV group were significantly shorter than those in the control group. Furthermore, both sides of the hind-limb dimension at 6 weeks postoperatively, the left side of the gastrocnemius dimension, and both sides of the gastrocnemius weight significantly increased. In conclusion, WBV especially accelerates the functional recovery of motor nerve components in sciatic nerve-crush injury model rats.

Exploring thresholds and interaction effects among antibiotic usage, covariates, and their effect on antibiotic resistance using an extended-spectrum β-Lactamase–producing Klebsiella pneumoniae case

ABSTRACT Background This study was aimed to explore thresholds with interaction effects among antibiotic usage, covariates (alcohol-based hand rub (ABHR)), and their effect on extended-spectrum β-lactamase–producing Klebsiella pneumoniae (ESBL-producing K. pneumoniae) in hospitalized patients. Methods Multivariate Adaptive Regression Spline models were used. These considered second-order interactions among antibiotic use and ABHR in addition to potential thresholds that further improve explained variance in the ESBL-producing K. pneumoniae response. The study involved collecting monthly hospital-level data for January 2017–December 2021. Results Analysis of the main effects showed that third-generation cephalosporins above 2.00 DDD/100 occupied bed days (OBD) generally increased ESBL-producing K. pneumoniae incidence (cases/100 OBD). Levels of ABHR above 6.61 L/100 OBD were shown to generally decrease ESBL-producing K. pneumoniae incidence. Second-order interactions revealed that when third-generation cephalosporin use was greater than 3.71 DDD/100 OBD, and ABHR was greater than 6.6 L/100 OBD (same as main effect threshold), ABHR partially lost effectiveness in its ability to reduce ESBL-producing K. pneumoniae incidence. This demonstrates the importance of not exceeding the identified thresholds of 3.71 DDD/100 OBD for third-generation cephalosporin use. Conclusion The main-effect thresholds in third-generation cephalosporins and ABHR, and the identified interaction between third-generation cephalosporins and ABHR can inform effective hospital antimicrobial stewardship.

P-134 An artificial intelligence method based on time-lapse images and deep learning may predict if a day2/3 embryo will form a utilizable blastocyst

Abstract Study question Can iDAScore v2.0 predict likelihood of development into a utilizable blastocyst from time-lapse images captured during the first two or three days of embryo development? Summary answer iDAScore v2.0 predicts utilizable blastocyst formation from time-lapse images of early embryo development. Specific score thresholds can be established to ensure high specificity of prediction. What is known already Treatment efficacy would benefit from a reliable method to predict the potential of early embryos to develop into utilizable blastocysts and select fresh IVF treatment cycles suitable for blastocyst culture. Reports indicate that time-lapse images captured during the first few days of development and analyzed by deep learning methods may be an accurate approach. A fully automated AI model, iDAScore, is reported to be more accurate than routine morphology and morphokinetics for prediction of implantation. However, the applicability of iDAScore calculated on day 2 and 3 as a tool to predict blastocyst development has yet to be tested. Study design, size, duration This is a retrospective multicenter cohort study including time-lapse videos of 9111 embryos cultured to blastocyst stage, from 1283 fresh IVF treatments between 2016-2021 at two ART clinics together performing &amp;gt; 2000 OPU per year. Images captured during the first days of culture were used to calculate iDAScores (at 48 and 66 hours post insemination) and determine the ability to discriminate embryos likely to develop into utilizable blastocysts according to Gardner score of 3BB or more. Participants/materials, setting, methods Patients were required to be undergoing IVF treatment using their own (autologous) oocytes whereby all zygotes were cultured up to the blastocyst stage in GTL® culture medium using the Embryoscope+® time-lapse system (Vitrolife, Gothenburg, Sweden). At least two experienced embryologists graded blastocysts on day 5/6, selecting utilizable blastocysts for transfer/vitrification. To evaluate the performance of iDAScore to predict development into utilizable blastocysts, sensitivity, specificity, and area under ROC curve (AUC) values were calculated. Main results and the role of chance The blastocyst utilization rate was 43.8% (3990 utilizable blastocysts of 9111 day 2/3 embryos developing from 2PN zygotes). Prediction of utilizable blastocysts obtained AUCs of 0.768 (0.759 - 0.778) and 0.782 (0.773 - 0.791) for day 2 and day 3, respectively. These results suggest IDAScore prediction performed slightly better when calculated on day 3 than on day 2. The ability to discriminate between utilizable and non-utilizable blastocysts at different thresholds of iDAScore on day 2 and on day 3, suggests that embryos should have a minimum iDAscore of 5 on day 2 to obtain a high specificity of 89%, and a threshold of 6 on day 3 to obtain a high specificity of 88%. Lower sensitivities were observed for these potential thresholds, 35% on day 2 and 41% on day 3. Limitations, reasons for caution This is a retrospective analysis where most cycles have at least five zygotes that supported subsequent blastocyst development, limiting relevance for patients with fewer zygotes. IDAScore is developed to predict implantation potential, not utilizable blastocyst, thus could be an underestimation of the potential performance of a model for utilization prediction. Wider implications of the findings The iDAScore v2.0 may provide valuable information for embryologists and be useful as a prognostic tool to select patients with high chance to obtain blastocysts based on day2/3 time-lapse images and thereby may achieve similar live birth rate per transfer with no need for extended culture. Trial registration number Not applicable

A study of the soil water potential threshold values to trigger irrigation of ‘Shimizu Hakuto’ peach at pivotal fruit developmental stages

Water management is an important practice that affects fruit size and quality. Effective implementation of irrigation scheduling requires knowledge of the appropriate indicators and thresholds, which are established manly based on the effects of water deficits on final fruit quality. Few studies have focused on the real-time effects of water status on fruit and shoot growth. To establish soil water potential (ψsoil) thresholds to trigger irrigation of peach at pivotal fruit developmental stages, photogrammetry, 13C labelling, and other techniques were used in this study to investigate real-time changes in stem diameter, fruit projected area, net leaf photosynthetic rate (Pn), and allocation of photoassimilates to fruit under soil water potential conditions ranging from saturation to stress in 6-year-old ‘Shimizu hakuto’ peach. Stem growth, fruit growth, and Pn exhibited gradually decreasing sensitivity to water deficits during fruit developmental stages I, II, and III. Stem diameter growth was significantly inhibited when ψsoil dropped to −8.5, −7.6, and −5.4 kPa, respectively. Fruit growth rate was low, reaching zero when the ψsoil was −9.0 to −23.1, −14.9 to −21.4, and −16.5 to −23.3 kPa, respectively, and Pn decreased significantly when the ψsoil reached −24.2, −22.7, and −20.4 kPa, respectively. In addition, more photoassimilates were allocated to fruit under moderate ψsoil conditions (−10.1 to −17.0 kPa) than under other ψsoil values. Our results revealed three ψsoil thresholds, −10.0, −15.0, and −15.0 kPa, suitable for triggering irrigation during stages I, II, and III, respectively. These thresholds can be helpful for controlling excessive tree vigor, maintaining rapid fruit growth and leaf photosynthesis, and promoting the allocation of more photoassimilates to fruit.

Threshold effect of urinary chromium on kidney function biomarkers: Evidence from a repeated-measures study

Chronic kidney disease (CKD) is a public health concern worldwide, and chromium exposure may be a risk factor due to its potential nephrotoxicity. However, research on the association between chromium exposure and kidney function especially the potential threshold effect of chromium exposure is limited. A repeated-measures study involving 183 adults (641 observations) was conducted from 2017 to 2021 in Jinzhou, China. Urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured as kidney function biomarkers. Generalized mixed models and two-piecewise linear spline mixed models were used to assess the dose-response relationship and potential threshold effect of chromium on kidney function, respectively. Temporal analysis was conducted by the latent process mixed model to depict the longitudinal change of kidney function over age. Urinary chromium was associated with CKD (odds ratio [OR] = 1.29; 95 % confidence interval [CI], 6.41, 14.06) and UACR (Percent change = 10.16 %; 95 % CI, 6.41 %, 14.06 %), and we did not find significant association between urinary chromium and eGFR (Percent change = 0.06 %; 95 % CI, −0.80 %, 0.95 %). The threshold analyses suggested the existence of threshold effects of urinary chromium, with inflection points at 2.74 μg/L for UACR and 3.95 μg/L for eGFR. Furthermore, we found that chromium exposure exhibited stronger kidney damage over age. Our study provided evidence for the threshold effects of chromium exposure on kidney function biomarkers and the heightened nephrotoxicity of chromium in older adults. More attention should be paid to the supervision of chromium exposure concentrations for preventing kidney damage, especially in older adults.

Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of down syndrome carrying human chromosome 21

Children with Down syndrome (DS, trisomy of chromosome 21) have an increased risk of infantile spasms (IS). As an epileptic encephalopathy, IS may further impair cognitive function and exacerbate neurodevelopmental delays already present in children with DS. To investigate the pathophysiology of IS in DS, we induced IS-like epileptic spasms in a genetic mouse model of DS that carries human chromosome 21q, TcMAC21, the animal model most closely representing gene dosage imbalance in DS. Repetitive extensor/flexor spasms were induced by the GABAB receptor agonist γ-butyrolactone (GBL) and occurred predominantly in young TcMAC21 mice (85%) but also in some euploid mice (25%). During GBL application, background electroencephalographic (EEG) amplitude was reduced, and rhythmic, sharp-and-slow wave activity or high-amplitude burst (epileptiform) events emerged in both TcMAC21 and euploid mice. Spasms occurred only during EEG bursts, but not every burst was accompanied by a spasm. Electrophysiological experiments revealed that basic membrane properties (resting membrane potential, input resistance, action-potential threshold and amplitude, rheobase, input-output relationship) of layer V pyramidal neurons were not different between TcMAC21 mice and euploid controls. However, excitatory postsynaptic currents (EPSCs) evoked at various intensities were significantly larger in TcMAC21 mice than euploid controls, while inhibitory postsynaptic currents (IPSCs) were similar between the two groups, resulting in an increased excitation-inhibition (E-I) ratio. These data show that behavioral spasms with epileptic EEG activity can be induced in young TcMAC21 DS mice, providing proof-of-concept evidence for increased IS susceptibility in these DS mice. Our findings also show that basic membrane properties are similar in TcMAC21 and euploid mice, while the neocortical E-I balance is altered to favor increased excitation in TcMAC21 mice, which may predispose to IS generation.

Cardiac Substructure Radiation Dose and Risk of Late Cardiac Disease in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

Radiation-associated cardiac disease is a major cause of morbidity/mortality among childhood cancer survivors. Radiation dose-response relationships for cardiac substructures and cardiac diseases remain unestablished. Using the 25,481 5-year survivors of childhood cancer treated from 1970 to 1999 in the Childhood Cancer Survivor Study, we evaluated coronary artery disease (CAD), heart failure (HF), valvular disease (VD), and arrhythmia. We reconstructed radiation doses for each survivor to the coronary arteries, chambers, valves, and whole heart. Excess relative rate (ERR) models and piecewise exponential models evaluated dose-response relationships. The cumulative incidence 35 years from diagnosis was 3.9% (95% CI, 3.4 to 4.3) for CAD, 3.8% (95% CI, 3.4 to 4.2) for HF, 1.2% (95% CI, 1.0 to 1.5) for VD, and 1.4% (95% CI, 1.1 to 1.6) for arrhythmia. A total of 12,288 survivors (48.2%) were exposed to radiotherapy. Quadratic ERR models improved fit compared with linear ERR models for the dose-response relationship between mean whole heart and CAD, HF, and arrhythmia, suggesting a potential threshold dose; however, such departure from linearity was not observed for most cardiac substructure end point dose-response relationships. Mean doses of 5-9.9 Gy to the whole heart did not increase the risk of any cardiac diseases. Mean doses of 5-9.9 Gy to the right coronary artery (rate ratio [RR], 2.6 [95% CI, 1.6 to 4.1]) and left ventricle (RR, 2.2 [95% CI, 1.3 to 3.7]) increased risk of CAD, and to the tricuspid valve (RR, 5.5 [95% CI, 2.0 to 15.1]) and right ventricle (RR, 8.4 [95% CI, 3.7 to 19.0]) increased risk of VD. Among children with cancer, there may be no threshold dose below which radiation to the cardiac substructures does not increase the risk of cardiac diseases. This emphasizes their importance in modern treatment planning.