Temporary Increase Research Articles

The potential link between gas diffusion and embolism spread in angiosperm xylem: Evidence from flow-centrifuge experiments and modelling.

Understanding xylem embolism formation is challenging due to dynamic changes and multiphase interactions in conduits. Here, we hypothesise that embolism spread involves gas diffusion in xylem, and is affected by time. We measured hydraulic conductivity (Kh) in flow-centrifuge experiments over 1 h at a given pressure and temperature for stem samples of three angiosperm species. Temporal changes in Kh at 5, 22, and 35°C, and at various pressures were compared to modelled gas concentration changes in a recently embolised vessel in the centre of a centrifuge sample. Temporal changes in Kh were logarithmic and species-specific. Maximum relative increases of Kh between 6% and 40% happened at 22°C for low centrifugal speed (<3250 RPM), while maximum decreases between 41% and 61% occurred at higher speeds. These reductions in Kh were experimentally shown to be associated with a temporal increase of embolism at the centre of centrifuge samples, which was likely associated with gas concentration increases in recently embolized vessels. Although embolism is mostly pressure-driven, our experimental and modelled data indicate that time, conduit characteristics, and temperature are involved due to their potential role in gas diffusion. Gas diffusion, however, does not seem to cover the entire process of embolism spread.

Buprenorphine Prescribing Characteristics Following Relaxation of X-Waiver Training Requirements

Local-level data are needed to understand whether the relaxation of X-waiver training requirements for prescribing buprenorphine in April 2021 translated to increased buprenorphine treatment. To assess whether relaxation of X-waiver training requirements was associated with changes in the number of clinicians waivered to and who prescribe buprenorphine for opioid use disorder and the number of patients receiving treatment. This serial cross-sectional study uses an interrupted time series analysis of 2020-2022 data from the HEALing Communities Study (HCS), a cluster-randomized, wait-list-controlled trial. Urban and rural communities in 4 states (Kentucky, Massachusetts, New York, and Ohio) with a high burden of opioid overdoses that had not yet received the HCS intervention were included. Relaxation of X-waiver training requirements (ie, allowing training-exempt X-waivers) on April 28, 2021. The monthly number of X-waivered clinicians, X-waivered buprenorphine prescribers, and patients receiving buprenorphine were each summed across communities within a state. Segmented linear regression models to estimate pre- and post-policy change by state were used. The number of individuals in 33 participating HCS communities included 347 863 in Massachusetts, 815 794 in Kentucky, 971 490 in New York, and 1 623 958 in Ohio. The distribution of age (18-35 years: range, 29.4%-32.4%; 35-54 years: range, 29.9%-32.5%; ≥55 years: range, 35.7%-39.3%) and sex (female: range, 51.1%-52.6%) was similar across communities. There was a temporal increase in the number of X-waivered clinicians in the pre-policy change period in all states, which further increased in the post-policy change period in each state except Ohio, ranging from 5.2% (95% CI, 3.1%-7.3%) in Massachusetts communities to 8.4% (95% CI, 6.5%-10.3%) in Kentucky communities. Only communities in Kentucky showed an increase in the number of X-waivered clinicians prescribing buprenorphine associated with the policy change (relative increase, 3.2%; 95% CI, 1.5%-4.9%), while communities in other states showed no change or a decrease. Similarly, only communities in Massachusetts experienced an increase in patients receiving buprenorphine associated with the policy change (relative increase, 1.7%; 95% CI, 0.8%-2.6%), while communities in other states showed no change. In this serial cross-sectional study, relaxation of X-waiver training requirements was associated with an increase in the number of X-waivered clinicians but was not consistently associated with an increase in the number of buprenorphine prescribers or patients receiving buprenorphine. These findings suggest that training requirements may not be the primary barrier to expanding buprenorphine treatment.

Deacetylase SIRT2 Inhibition Promotes Microglial M2 Polarization Through Axl/PI3K/AKT to Alleviate White Matter Injury After Subarachnoid Hemorrhage.

White matter injury (WMI) subsequent to subarachnoid hemorrhage (SAH) frequently leads to an unfavorable patient prognosis. Previous studies have indicated that microglial M1 polarization following SAH results in the accumulation of amyloid precursor protein (APP) and degradation of myelin basic protein (MBP), thereby catalyzing the exacerbation of WMI. Consequently, transitioning microglial polarization towards the M2 phenotype (neuroprotective state) represents a potential therapeutic approach for reversing WMI. The SIRT2 gene is pivotal in neurological disorders such as neurodegeneration and ischemic stroke. However, its function and underlying mechanisms in SAH, particularly how it influences microglial function to ameliorate WMI, remain unclear. Our investigations revealed that in post-SAH, there was a temporal increase in SIRT2 expression, predominantly in the cerebral corpus callosum area, with notable colocalization with microglia. However, following the administration of the SIRT2 inhibitor AK-7, a shift in microglial polarization towards the M2 phenotype and an improvement in both short-term and long-term neuronal functions in rats were observed. Mechanistically, CO-IP experiments confirmed that SIRT2 can interact with the receptor tyrosine kinase Axl within the TAM receptor family and act as a deacetylase to regulate the deacetylation of Axl. Concurrently, the inhibition of SIRT2 by AK-7 can lead to increased expression of Axl and activation of the anti-inflammatory pathway PI3K/Akt signaling pathway, which regulates microglial M2 polarization and consequently reduces WMI. However, when Axl expression was inhibited by the injection of the shAxl virus into the lateral ventricles, the downstream signaling pathways were significantly suppressed. Rescue experiments also confirmed that the neuroprotective effects of AK-7 can be reversed by PI3K inhibitors. These data suggest that SIRT2 influences WMI by affecting microglial polarization through the Axl/PI3K/AKT pathway, and that AK-7 could serve as an effective therapeutic drug for improving neurological functions in SAH patients.

Safety pharmacology of human endogenous retrovirus-enveloped baculoviral DNA vaccines against SARS-CoV-2 in Sprague-Dawley rats and beagle dogs

The coronavirus disease 2019 (COVID-19) emerged as a major global health crisis, posing significant health, economic, and social challenges. Vaccine development has been a crucial response to the severe-acute-respiratory-syndrome-related coronavirus-2 pandemic owing to the critical role of immunization in controlling infectious diseases, leading to the expedited development of several effective vaccines. Although mRNA platform-based COVID-19 vaccines authorized under emergency-use authorization have been administered globally, concerns regarding the vaccines have increased owing to the occurrence of various side effects. The present study aimed to evaluate the safety of a non-replicating recombinant baculovirus expressing the human endogenous retrovirus envelope gene (AcHERV) vaccine encoding SARS-CoV-2 antigens. Owing to the limited number of existing safety pharmacology studies on AcHERV as a viral vector vaccine, we conducted neurobehavior (Modified Irwin’s Test), body temperature, and respiratory function studies in rats and cardiovascular system studies in male beagle dogs, which were administered the AcHERV-COVID-19 vaccine using telemetry. The safety assessment revealed no significant toxicological alterations. However, in rats, both sexes administered with the AcHERV-COVID-19 vaccine exhibited a temporary increase in body temperature, which normalized or showed signs of recovery. In conclusion, AcHERV-COVID-19 demonstrates a sufficient safety profile that supports its potential evaluation in future clinical trials.

Global food value chains and obesity in low- and middle-income countries

Low- and middle-income countries (LMICs) are experiencing disproportional increases in overweight or obesity rates. Parallel to this trend, many LMICs are witnessing significant growth in their participation in global food value chains (GFVCs). This paper aims to shed light on the public health implications of increasing participation in GFVCs. Leveraging macro- and micro-level data spanning 25 years, we study the relationship between countries’ participation in GFVCs and women’s overweight or obesity rates. We explore heterogeneous implications by disaggregating countries’ participation into backward and forward linkages in GFVCs, as well as across rural and urban areas. We find that temporal increases in countries’ participation in GFVCs are significantly associated with increasing overweight or obesity rates, primarily when countries participate in backward linkages and for urban populations. Participation in GFVCs involving forward linkages appears to have negligible implications, and the relationship between participation in GFVCs and obesity disappears for rural women. Furthermore, we find that an increase in countries’ participation in GFVCs is associated with an increase in consumption of energy-dense foods such as sugar, commonly linked with obesity. Our findings have important implications for informing public policies aimed at addressing the increasing obesity rates and associated economic and health burdens in LMICs.

THE POST-ACTIVATION EFFECT OF COMBINED RESISTED AND ASSISTED SPRINTS

Resisted and assisted training methods aim to increase neural activation, or post-activation potentiation (PAP), to enhance sprint performance. A preloaded stimulus causes a temporary performance increase that is more significant than what warm-up alone can provide. Resistance activities have traditionally been used to induce post-activation potentiation. Little is known when assisted and resisted sprints are combined and their effect on PAP. Therefore, this study aimed to examine the acute potentiating effect of combined resisted and assisted sprints on subsequent 20 m sprint performance. Sixteen physically active young males performed a baseline 20 m sprint followed by four assisted 20 m and four 20 m resisted sprints using a bungee cord. After the assisted-resisted stimulus, the participants performed one 20 m sprint at 4, 6, and 8 minutes. There was no significant improvement in 5, 10, or 20-m sprint times following the assisted-resisted stimulus. Therefore, the additive effect of assisted-resisted sprints failed to induce post-activation potential. The additive effect of assisted-resisted sprints could not induce post-activation potential to enhance subsequence sprint performance.

Blue petrel electrocardiograms measured through a dummy egg reveal a slow heart rate during egg incubation

BackgroundSeabirds like penguins and petrels, living in Antarctic and sub-Antarctic regions, often feed hundreds or even thousands of kilometers away from the islands where they breed. They therefore adapted to endure prolonged fasting during egg incubation, enabling their partner to undertake foraging trips that can last up to two weeks. Aside from accumulating and consuming fat reserves, it is unclear whether seabirds have developed further adaptations to extended fasting periods. This lack of knowledge is in part due to their remote nesting location and their extreme sensitivity to manipulation. To overcome this lack of knowledge, we developed a non-invasive device to record the heart rate (HR) of burrow-nesting blue petrels (Halobaena caerulea) during egg incubation. For that, we encapsulated a small-size logger in a dummy egg to record electrocardiograms (ECGs) through the featherless incubation patch of the birds.ResultsThe blue petrels’ HR (208 ± 15 beats per min [bpm]; n = 6) that we recorded during egg incubation was slower than the HR predicted by two different allometric functions regressing HR against body mass (242 and 250 bpm). Blue petrels’ HR also presented cyclical variation correlated to respiration, resembling the physiological Respiratory Sinus Arrhythmia (RSA) described in humans and other species, and that is mainly modulated by the vagal nerve. Moreover, the basal HR of incubating blue petrels increased about every minute during egg movements that presumably reflect egg turning, important for embryo survival and development. During these events, blue petrels’ HR increased up to a maximum of 296 ± 27 bpm for 18 ± 2 s (n = 6). We estimated that those egg movements increased energy expenditure (EE) by 8.4 ± 1.3%, which is approximately 10 times less than the energy increase induced by the disturbance linked with the removal of the dummy egg at the end of the experiment. Interestingly, we noticed that the beginning of HR increase preceded egg movements by 4.3 ± 0.9 s (n = 6), as if birds needed to gradually increase their metabolism to achieve the following action. As well, blue petrels needed 9.1 ± 1.3 s (n = 6) to recover basal levels of HR after the end of egg movements.ConclusionWe recorded for the first time ECGs, HR and RSA in blue petrels in a completely non-invasive way. This allowed us to observe (1) slow basal HR during egg incubation, which could save energy for prolonged fasting and (2) temporal HR increase, possibly necessary to reposition the egg for proper embryonic development.

Recent temporal trends, characteristics and outcomes of patients with non-COVID-19 community-acquired pneumonia at two tertiary hospitals in Australia: an observational study.

Community-acquired pneumonia (CAP) leads to considerable morbidity and mortality globally. However, data on CAP burden in Australia, especially during the coronavirus disease 2019 (COVID-19) pandemic, are limited. We characterised and assessed clinical outcomes of non-COVID-19 CAP hospitalisations over a 6-year period at two major hospitals in South Australia. All non-COVID-19 CAP hospitalisations were identified using the International Statistical Classification of Diseases and Related Health Problems, Tenth revision, Australian modification (ICD-10-AM) codes, between 1 January 2018 and 31 December 2023, at two tertiary hospitals in Adelaide. Clinical outcomes included in-hospital and 30-day mortality, length of stay (LOS) in, intensive care unit (ICU) admission and 30-day readmissions. Multilevel regression models were utilised to identify predictors of clinical outcomes. Over the 6-year period, there were 7853 non-COVID-19 CAP hospitalisations, with a temporal increase from 100 per 100 000 population in 2018 to 208 per 100 000 population in 2023 (P < 0.001). The mean (SD) age was 75.1 (17.6) years, and 54.6% were males. The mean age declined over time (P < 0.05), while other characteristics remained stable. Streptococcus pneumoniae was the most commonly identified bacterium (21.8% of cases). In-hospital mortality occurred in 7.8% of patients, with 30-day mortality and readmission rates of 14.3% and 16.9% respectively. LOS declined significantly during the pandemic years; however, mortality remained stable over time. Frailty status, malnutrition and number of comorbidities significantly predicted 30-day mortality and LOS, in addition to pneumonia severity and ICU admission. There has been an increasing trend of hospitalisations for non-COVID-19 CAP during the COVID-19 pandemic, with a concomitant trend towards shorter LOS and no significant shift in other clinical outcomes.

Higher‐order dissimilarity in biodiversity: Identifying dissimilarities of spatial or temporal dissimilarity structures

Abstract Elucidating biodiversity patterns and their background processes is critical in biodiversity science. Dissimilarity, which is calculated based on multivariate biological quantities, is a major component of biodiversity. As spatial and temporal biodiversity information availability increases, the scope of dissimilarity studies has been expanded to cover various levels and types of spatiotemporal biodiversity facets (e.g. gene, community and ecosystem function), and diverse pairwise dissimilarity indices have been developed. However, further development of the dissimilarity concept is required in comparative studies on spatiotemporal structures of biodiversity compositional patterns, such as those exploring commonalities of biogeographical boundaries among taxa, compared to the conventional ones to consider higher dimensions of dissimilarity: dissimilarity of dissimilarity structures. This study proposes a novel and general concept, higher‐order dissimilarity (HOD), for quantitatively evaluating the dissimilarities of spatial or temporal dissimilarity structures among different datasets, proposes specific implementations of HOD as operational indices, and illustrates the potential resolution of scientific and practical questions through HOD. We further demonstrate the advantages of the HOD concept by applying it to actual patterns, such as long‐term and/or large‐spatial hypothetical monitoring datasets. Our conceptual framework on HOD extends the existing framework of biodiversity science and is versatile, with many potential applications in acquiring more valuable information from ever‐increasing biodiversity data.

Incompleteness of natural disaster data and its implications on the interpretation of trends

ABSTRACT We use data from a leading global database, primarily the reported numbers of fatal ‘hydrological’, ‘meteorological’ and ‘geophysical’ disasters and associated fatalities, to elucidate long-term trends in natural disaster impact. There are very strong upward trends in the number of reported disasters. However, we show that these trends are strongly biased by progressively improving reporting. We apply well-established methods based on analysing evolving differences in the patterns of large (many fatalities) to small (fewer fatalities) events to assess and quantify this bias. For all disaster types investigated, the long-term (multi-decade) true number of disasters appears to be unexpectedly stable over time. There was, however, a clear temporary increase between 1980 and 1990 for hydrological and meteorological disasters. Importantly, there has been a large long-term decline in total fatalities reported for weather-related disasters, attributable to very effective mitigation for larger disasters. Probably due to improved mitigation rather than reduced hazard, data for the most recent decades shows a systematic decrease in the number of larger (more fatality) weather-related disasters compared to smaller ones. In contrast, for the geophysical disasters, predominantly earthquakes, the relative numbers of larger versus smaller disasters, are fairly constant, as are total fatalities.

Dupilumab-associated (hyper)eosinophilia in patients with atopic dermatitis: a single-center cohort study of the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry.

This study investigated the incidence and progression of (hyper)eosinophilia in patients with atopic dermatitis (AD) treated with dupilumab, using data from the TREAT NL registry cohort. In total, 38.5% of patients had (hyper)eosinophilia at baseline and/or during dupilumab treatment. (Hyper)eosinophilia was present at baseline in 43 (55.8%) patients and developed in 34 (44.2%) patients during treatment. Eosinophilia was transient, peaking at 6 months and normalizing by 18–24 months. One patient discontinued dupilumab due to persistent hypereosinophilia, but generally, eosinophilia did not affect treatment outcomes. In conclusion, dupilumab is found viable for patients with AD regardless of baseline eosinophilia, with temporary increases in eosinophil counts that are often not clinically significant.

Additive effects of N addition and changing precipitation on soil respiration in a climate transitional forest

Global carbon (C) cycling can be greatly affected by the increasing nitrogen (N) deposition and changing precipitation regimes in terrestrial ecosystems. Nevertheless, whether N enrichment and precipitation variability interactively or additively influence soil C release during a long-term period remain largely elusive. Here, a seven-year (2016–2022) field experiment was conducted to explore the responses of soil respiration to N addition, decreased and increased precipitation in a subtropical-warm temperate forest in Central China. The results showed soil respiration was elevated by 11.0%, 12.2%, and 12.3% under N addition, decreased precipitation, and increased precipitation, respectively, primarily originating from the enhancements in plant root respiration. Increased precipitation led to a temporal increase in soil respiration over the experimental period, mostly due to the elevating understory richness and reducing soil C/N ratio. There were additive effects between N addition and changing precipitation on soil respiration observed in our study, suggesting that the impacts of concurrent global change drivers can be predicted from their respective influences. These findings indicated that global change may intensify soil C release from climate transition forests, thus helping to accurately assess the climate change–C feedback in natural ecosystems.

NEW APPROACH TOWARDS THE PROBLEM OF SOMATIC CRITERIA OF SECULAR TRENDS. SEXUAL SOMATIC DIMORPHISM

Introduction. The goal of study is description of secular dynamics of sex dimorphism (SD) of height, weight, chest girth of children aged 9 years and teenagers 13 years old from Russia and neighboring countries through 1920–2010. Materials and methods. The main source of data — materials of books on physical development of children and adolescents from cities and rural regions of Russia and USSR, collected and processed according to the universal methodical standards of Research Institute of Hygiene of children and adolescents. The quantitative estimation of SD value was held using Kullback divergence. One-year age groups, contrastive in biological essence, are under discussion. The estimation of the vector and level of associations of SD of anthropometric traits and secular factor was held using correlation analysis. The analysis of local patterns of secular SD dynamics of separate traits was carried out. Results. Secular variability of height and weight SD of 9-year-old children is not significant. While secular dynamics of three body dimensions of 13-year-old teenagers is significant, the highest determination coefficient is fixed for weight. For Moscow samples the decrease of height and weight SD is fixed through the historic interval 1960s – 70s with the following recovery up to the level of 1920s in 2000s. Temporal dynamics of SD of 9-year-old children of St. Petersburg through the interval 1960s – 2000s consists of macrosomization of girls; the tendency for 13-year-old teenagers is opposite. Temporal dynamics of somatic SD of 9-year-old Russian children of Kazan reveals stability through the interval 1960th-1990th; for 13-year-old teenagers’ parameters of transversal body development demonstrate secular stability, as to height – boys compensate their lag compared to girls. For Kirovsk city (Murmansk region) through the interval 1950s – 1970s temporal fluctuations of height and weight SD of 9-year-old children are less than 0,2 standard deviations; height and weight SD of 13-year-old teenagers reveal temporal increase (0,4–0,6 standard deviations). Conclusion. The results confirm the importance of somatic SD as the criterion of secular dynamics for 13-year-old teenagers and witness, as a whole, to the temporal stability of SD during second childhood (9 years). Local differences do not contribute significantly to the intensity of secular dynamics of SD. The process of secular macrosomization of one sex as compared to the other is not the exclusive prerogative of boys and male teenagers.

Longitudinal trajectories and associated risk factors of paternal mental illness in the nine years surrounding the transition to fatherhood

BackgroundThe arrival of one's first child is a known risk factor for mental illness, yet investigations on fathers' mental health are limited. We conducted a longitudinal investigation on paternal depression and anxiety in the nine years surrounding the transition to fatherhood. MethodsUsing a national cohort of French men (CONSTANCES, n = 6299), we investigated the prevalence and associated risk factors of mental illness amongst first-time fathers. Responses to the Center for Epidemiological Studies Depression (CES-D) and 12-item General Health Questionnaire (GHQ-12) scales were used to identify clinically significant symptom scores. Self-declared mental illness was also reported by participants. Group-based modelling was used to identify latent trajectory groups for both measures. ResultsLevels of self-declared anxiety (averaging 4.9 % pre-fatherhood, 7.8 % post) exceeded that of depression (1.9 % pre- fatherhood, 3.3 % post) or other disorders. However, rates of clinically significant symptom scores (17–27 %) were consistently higher. Participants' mental health appeared to worsen from two-years prior to their child's arrival and improve from two-years after. We identified three trajectory groups for fathers' self-declared mental illness: Low stable (90.3 %); Low risk with high temporary increase (5.6 %); and Consistent high risk (4.1 %). Risk factors associated with worsening mental health trajectories were unemployment, not living with one's partner, having had adverse childhood experiences and foregoing healthcare due to financial reasons. LimitationsAll measures of mental illness relied on participant self-reports and are thus subject to bias. ConclusionsThis study reveals an important period of heightened psychological vulnerability amongst first-time fathers, emphasising the need for increased and better adapted paternal mental health screening.

Insights on long-term ecosystem changes from stable isotopes in historical squid beaks

BackgroundAssessing the historical dynamics of key food web components is crucial to understand how climate change impacts the structure of Arctic marine ecosystems. Most retrospective stable isotopic studies to date assessed potential ecosystem shifts in the Arctic using vertebrate top predators and filter-feeding invertebrates as proxies. However, due to long life histories and specific ecologies, ecosystem shifts are not always detectable when using these taxa. Moreover, there are currently no retrospective stable isotopic studies on various other ecological and taxonomic groups of Arctic biota. To test whether climate-driven shifts in marine ecosystems are reflected in the ecology of short-living mesopredators, ontogenetic changes in stable isotope signatures in chitinous hard body structures were analysed in two abundant squids (Gonatus fabricii and Todarodes sagittatus) from the low latitude Arctic and adjacent waters, collected between 1844 and 2023.ResultsWe detected a temporal increase in diet and habitat-use generalism (= opportunistic choice rather than specialization), trophic position and niche width in G. fabricii from the low latitude Arctic waters. These shifts in trophic ecology matched with the Atlantification of the Arctic ecosystems, which includes increased generalization of food webs and higher primary production, and the influx of boreal species from the North Atlantic as a result of climate change. The Atlantification is especially marked since the late 1990s/early 2000s. The temporal patterns we found in G. fabricii’s trophic ecology were largely unreported in previous Arctic retrospective isotopic ecology studies. Accordingly, T. sagittatus that occur nowadays in the high latitude North Atlantic have a more generalist diet than in the XIXth century.ConclusionsOur results suggest that abundant opportunistic mesopredators with short life cycles (such as squids) are good candidates for retrospective ecology studies in the marine ecosystems, and to identify ecosystem shifts driven by climate change. Enhanced generalization of Arctic food webs is reflected in increased diet generalism and niche width in squids, while increased abundance of boreal piscivorous fishes is reflected in squids’ increased trophic position. These findings support opportunism and adaptability in squids, which renders them as potential winners of short-term shifts in Arctic ecosystems.

Temporal Trends in End-Tidal Capnography and Outcomes in Out-of-Hospital Cardiac Arrest

While widely measured, the time-varying association between exhaled end-tidal carbon dioxide (EtCO2) and out-of-hospital cardiac arrest (OHCA) outcomes is unclear. To evaluate temporal associations between EtCO2 and return of spontaneous circulation (ROSC) in the Pragmatic Airway Resuscitation Trial (PART). This study was a secondary analysis of a cluster randomized trial performed at multicenter emergency medical services agencies from the Resuscitation Outcomes Consortium. PART enrolled 3004 adults (aged ≥18 years) with nontraumatic OHCA from December 1, 2015, to November 4, 2017. EtCO2 was available in 1172 cases for this analysis performed in June 2023. PART evaluated the effect of laryngeal tube vs endotracheal intubation on 72-hour survival. Emergency medical services agencies collected continuous EtCO2 recordings using standard monitors, and this secondary analysis identified maximal EtCO2 values per ventilation and determined mean EtCO2 in 1-minute epochs using previously validated automated signal processing. All advanced airway cases with greater than 50% interpretable EtCO2 signal were included, and the slope of EtCO2 change over resuscitation was calculated. The primary outcome was ROSC determined by prehospital or emergency department palpable pulses. EtCO2 values were compared at discrete time points using Mann-Whitney test, and temporal trends in EtCO2 were compared using Cochran-Armitage test of trend. Multivariable logistic regression was performed, adjusting for Utstein criteria and EtCO2 slope. Among 1113 patients included in the study, 694 (62.4%) were male; 285 (25.6%) were Black or African American, 592 (53.2%) were White, and 236 (21.2%) were another race; and the median (IQR) age was 64 (52-75) years. Cardiac arrest was most commonly unwitnessed (n = 579 [52.0%]), nonshockable (n = 941 [84.6%]), and nonpublic (n = 999 [89.8%]). There were 198 patients (17.8%) with ROSC and 915 (82.2%) without ROSC. Median EtCO2 values between ROSC and non-ROSC cases were significantly different at 10 minutes (39.8 [IQR, 27.1-56.4] mm Hg vs 26.1 [IQR, 14.9-39.0] mm Hg; P < .001) and 5 minutes (43.0 [IQR, 28.1-55.8] mm Hg vs 25.0 [IQR, 13.3-37.4] mm Hg; P < .001) prior to end of resuscitation. In ROSC cases, median EtCO2 increased from 30.5 (IQR, 22.4-54.2) mm HG to 43.0 (IQR, 28.1-55.8) mm Hg (P for trend < .001). In non-ROSC cases, EtCO2 declined from 30.8 (IQR, 18.2-43.8) mm Hg to 22.5 (IQR, 12.8-35.4) mm Hg (P for trend < .001). Using adjusted multivariable logistic regression with slope of EtCO2, the temporal change in EtCO2 was associated with ROSC (odds ratio, 1.45 [95% CI, 1.31-1.61]). In this secondary analysis of the PART trial, temporal increases in EtCO2 were associated with increased odds of ROSC. These results suggest value in leveraging continuous waveform capnography during OHCA resuscitation. ClinicalTrials.gov Identifier: NCT02419573.

Contagion and interdependencies between BRICS-plus Countries on the Markets of Commodities and Derivative Financial Instruments

Purpose: This study was started on the main macroeconomic data (2010-2019), coming from the countries of the BRICS-plus group. While a significant contribution of these emerging economies to global economic output has generally been observed, this has also been accompanied by persistent domestic imbalance. Design/Methodology/Approach: Regarding the model, we state and contextualize the (long-term) risk co-incidence of the set of macroeconomic variables for this coalition of countries. Particular attention was paid to a valuation, description and forecasting model based on the calculation of the Dynamic Conditional Correlation (DCC) in a Generalized AutoRegressive Conditional Heteroscedasticity (GARCH) process on the time series of credit default swaps (CDS). Findings: The empirical analysis and calculations carried out have verified the significance of the parameters and confirmed the conditional dynamic correlation between the economies of the Brics “expanded”, especially in the presence of shocks, which also involve mutual contagion (temporary increase in DCC) and even interdependence (increasing DCC leads to new, less unstable levels). Implications/Originality/Value: The research offers a look at the most current trends in terms of international economic balances and the entire global system, focusing on commodity markets, financial derivatives and the impacts of trade at the dawn of the new BRICS-plus coalition.

Altered levels of phospholipases C, diacylglycerols, endocannabinoids, and N-acylethanolamines in patients with hereditary angioedema due to FXII mutation.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII-HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and eCB-related N-acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII-HAE. Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals. Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls. BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets.

Effects of High-Mobility Group Box-1 on Mucosal Immunity and Epithelial Differentiation in Colitic Carcinoma.

Abnormalities in mucosal immunity are involved in the onset and progression of ulcerative colitis (UC), resulting in a high incidence of colorectal cancer (CRC). While high-mobility group box-1 (HMGB1) is overexpressed during colorectal carcinogenesis, its role in UC-related carcinogenesis remains unclear. In the present study, we investigated the role of HMGB1 in UC-related carcinogenesis and sporadic CRC. Both the azoxymethane colon carcinogenesis and dextran sulfate sodium colitis carcinogenesis models demonstrated temporal increases in mucosal HMGB1 levels. Activated CD8+ cells initially increased and then decreased, whereas exhausted CD8+ cells increased. Additionally, we observed increased regulatory CD8+ cells, decreased naïve CD8+ cells, and decreased mucosal epithelial differentiation. In the in vitro study, HMGB1 induced energy reprogramming from oxidative phosphorylation to glycolysis in CD8+ cells and intestinal epithelial cells. Furthermore, in UC dysplasia, UC-related CRC, and hyperplastic mucosa surrounding human sporadic CRC, we found increased mucosal HMGB1, decreased activated CD8+ cells, and suppressed mucosal epithelial differentiation. However, we observed increased activated CD8+ cells in active UC mucosa. These findings indicate that HMGB1 plays an important role in modulating mucosal immunity and epithelial dedifferentiation in both UC-related carcinogenesis and sporadic CRC.

Downward migration of 137Cs promotes self-cleaning of forest ecosystem by reducing root uptake of Japanese cedar in Fukushima

Approximately 70 % of the area highly 137Cs-contaminated by the Fukushima Daiichi Nuclear Power Plant accident is forested. Decontamination works in most of these forests have not progressed, and the forestry industry remains stagnant. Although the long-term dynamics of 137Cs in the forest ecosystem will be controlled by the amount of 137Cs absorbed by roots in the future, temporal changes in 137Cs of tree roots have rarely been reported. In the present study, we monitored the depth distribution of 137Cs in the soil and absorptive very fine (VF) roots of 0.5 mm or less in a Japanese cedar forest from 2011 to 2023. As a result, the 137Cs inventory in the mineral soil increased over time due to the migration from the forest canopy and litter layers, whereas that in the VF roots tended to decrease since 2020, although there was a large variation. Temporal decrease in the exchangeable 137Cs fraction with fixation and temporal increase in VF root biomass with their growth were not clearly observed, the 137Cs concentration in the VF roots at 0–2 cm decreased with the decrease in 137Cs concentration in the litter layers. Although the 137Cs concentration in the VF roots below 2 cm tended to increase with increasing 137Cs concentration in the soil at the same depth, the downward migration of 137Cs within the soil can reduce the amount of 137Cs absorbed by roots because the VF root biomass decreases exponentially with depth. In other words, 137Cs can be removed from the long-term active cycles of forest ecosystems as they migrate deeper into the soil. This natural migration process can be regarded as a “self-cleaning” of the forest ecosystem, the green and sustainable remediation using such self-cleaning should be actively adopted for the future forest management.