Important Changes Research Articles

Genome scale metabolic network modelling for metabolic profile predictions.

Metabolic profiling (metabolomics) aims at measuring small molecules (metabolites) in complex samples like blood or urine for human health studies. While biomarker-based assessment often relies on a single molecule, metabolic profiling combines several metabolites to create a more complex and more specific fingerprint of the disease. However, in contrast to genomics, there is no unique metabolomics setup able to measure the entire metabolome. This challenge leads to tedious and resource consuming preliminary studies to be able to design the right metabolomics experiment. In that context, computer assisted metabolic profiling can be of strong added value to design metabolomics studies more quickly and efficiently. We propose a constraint-based modelling approach which predicts in silico profiles of metabolites that are more likely to be differentially abundant under a given metabolic perturbation (e.g. due to a genetic disease), using flux simulation. In genome-scale metabolic networks, the fluxes of exchange reactions, also known as the flow of metabolites through their external transport reactions, can be simulated and compared between control and disease conditions in order to calculate changes in metabolite import and export. These import/export flux differences would be expected to induce changes in circulating biofluid levels of those metabolites, which can then be interpreted as potential biomarkers or metabolites of interest. In this study, we present SAMBA (SAMpling Biomarker Analysis), an approach which simulates fluxes in exchange reactions following a metabolic perturbation using random sampling, compares the simulated flux distributions between the baseline and modulated conditions, and ranks predicted differentially exchanged metabolites as potential biomarkers for the perturbation. We show that there is a good fit between simulated metabolic exchange profiles and experimental differential metabolites detected in plasma, such as patient data from the disease database OMIM, and metabolic trait-SNP associations found in mGWAS studies. These biomarker recommendations can provide insight into the underlying mechanism or metabolic pathway perturbation lying behind observed metabolite differential abundances, and suggest new metabolites as potential avenues for further experimental analyses.

Thepparatia vines (Hibisceae subtribe Trionum) phylogenomics and evolution

Abstract Hibisceae subtribe Trionum is the largest clade within Hibiscus s.l. and contains genera with a wide range of growth forms: herbaceous (Abelmoschus), shrubs (Malvaviscus), trees (Wercklea), and exceptionally lianas. The rare and localized Thepparatia species are unique in that they combine a lianescent habit and trioecy. Several problems have delayed the study of Hibisceae classification including low genetic variability, lack of synapomorphic morphological characters, transoceanic dispersal events, and allopolyploidy. Here, we present a comprehensive phylogenomic hypothesis of Thepparatia based on analyses of the maternally inherited chloroplast and biparentally inherited nuclear ribosomal cistron sequences, and compare these results with its speciation, karyology, and breeding system. Chloroplast genomes in subtribe Trionum were highly conserved except in Abelmoschus where four additional genes were duplicated. Recent diploid interspecific hybridization is suggested in Thepparatia sipsongpannaensis between T. fragrans and T. scandens during the Pleistocene, around 640 000 years ago. Our observations also indicate Thepparatia have a trioecious breeding system that combined with a unique habit, and a highly localized distribution pattern, have created cross-pollination barriers and ecological specialization. This suggests hybridization events are rare but evolutionary significant in subtribe Trionum. Finally, our study supports important nomenclature changes: the synonymization of Hibiscus austroyunnanensis with Thepparatia fragrans and the publication of a new species, Thepparatia sipsongpannaensis.

A DFT investigation for the Dopamine adsorption on the pristine and defected blue arsenic-phosphorus monolayers

In this study, the adsorption mechanism of the Dopamine (DA) molecule on the pristine and vacancy-defected b-AsP monolayers was investigated using DFT methods in order to reveal the drug carrying and sensing potential of b-AsP. For this purpose, the structural and electronic properties of many possible adsorption models on the pristine and defected b-AsP surfaces were calculated. According to the results, vacancy defects in the monolayer significantly increase the adsorption energy of the DA molecule. Additionally, the presence of defects triggers some important changes in the electronic and magnetic structure, revealing a prediction that b-AsP can be used as a sensor for DA-type molecules. The spin dependence of electronic properties also points out that these defected structures may be good candidates for some spintronic applications. The flattening of the DA molecule parallel to the surface in some models indicates the possibility that AsP could be a substrate candidate for molecule polymerization.

The analysis of continuous data from n-of-1 trials using paired cycles: a simple tutorial

N-of-1 trials are defined and the popular paired cycle design is introduced, together with an explanation as to how suitable sequences may be constructed.Various approaches to analysing such trials are explained and illustrated using a simulated data set. It is explained how choosing an appropriate analysis depends on the question one wishes to answer. It is also shown that for a given question, various equivalent approaches to analysis can be found, a fact which may be exploited to expand the possible software routines that may be used.Sets of N-of-1 trials are analogous to sets of parallel group trials. This means that software for carrying out meta-analysis can be used to combine results from N-of-1 trials. In doing so, it is necessary to make one important change, however. Because degrees of freedom for estimating variances for individual subjects will be scarce, it is advisable to estimate local standard errors using pooled variances. How this may be done is explained and fixed and random effect approaches to combining results are illustrated.

Perioperative Analysis of Patients Undergoing Liver Transplantation at the Hospital de Clínicas da Unicamp in the Context of SARS-Cov-2 Pandemic

Introduction: SARS-CoV-2 began in 2020 and caused important changes in the number of transplants performed in hospitals and in the protocols for admitting candidates to perform the procedure. The Brazilian Association of Organ Transplantation (ABTO) recommends not performing transplants from donors with active COVID-19 infection, positive test results or with Severe Acute Respiratory Syndrome. The hepatic repercussions related to COVID-19 are presented in some reports in the medical literature. Liver changes resulting from other corona viruses such as SARS-CoV and MERS-CoV are well documented. The Hospital de Clínicas of the State University of Campinas is a tertiary center that performs solid organ transplants. Objectives: To carry out a perioperative, retrospective, descriptive analysis of liver transplants in the context of the SARS-CoV-2 pandemic carried out at the Hospital das Clínicas of the State University of Campinas from March 2020 to July 2021. Materials and Methods: Retrospective, descriptive, longitudinal cohort study based on the review of medical records of patients undergoing liver transplantation in the context of the SARS-CoV-2 pandemic from March 2020 to July 2021 at the clinical hospital of the State University of Campinas. Results:Retrospective analysis was performed on 57 patients in the period. Only 1 patient needed to be excluded because he was under 18 years old. Of the 56 patients, 52 underwent RT-PCR laboratory testing and chest tomography (CT). Of these 52 patients, only 2 tested positive, one pre-transplant (TX) and one post-operatively (post-op). Regarding chest CT scans, none of them showed typical changes for COVID pre-TX, in the post-op 4 patients presented typical chest CT scans. The average age was 55.86 years. The mortality rate was 38% and no deaths were attributed to COVID 19. The average MELD-Na scale was 20.94. Conclusion: The present study carried out at the Hospital de Clínicas da Unicamp analyzed the clinical, laboratory and radiological association to better elucidate the variables determined by COVID-19 in its diagnosis and in-hospital management. It is concluded that the SARS-CoV-2 pandemic had an impact on the routine of liver transplantation worldwide and on the service in which the study was carried out.

Measurement Properties of the Oxford Shoulder Score and Minimal Clinically Important Changes After Primary Total Shoulder Replacement Surgery.

We evaluated the measurement properties of the Oxford Shoulder Score (OSS) and estimated the minimal clinically important change (MCIC) in patients undergoing primary total shoulder replacement in Australia. Deidentified data from the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. Pre- and 6-month postoperative OSS scores were used, with the 5-level EuroQoL quality of life instrument and shoulder pain scores used as comparators. Floor and ceiling effects, internal consistency reliability, construct validity, and responsiveness to change were evaluated using standard psychometric methods. Mean change and predictive modeling approaches (with and without adjustment for the proportion of improved patients) were used to calculate MCIC thresholds, with patient-perceived improvement after surgery as the anchor. Preoperative OSS data were available for 1,117 patients (59% female; 90% aged ≥60 years) undergoing primary total shoulder replacement. No floor or ceiling effects were observed pre- or postoperatively. The OSS showed high internal consistency reliability (Cronbach alpha >0.89), good construct validity, and high responsiveness to change (effect size 1.88). The MCIC derived from the mean change method was 6.50 points (95% confidence interval [95% CI] 4.41-8.61). The predictive modeling approach produced an MCIC estimate of 8.42 points (95% CI 5.68-12.23) after adjustment. The OSS has good measurement properties to capture pain and function outcomes after shoulder replacement procedures and is highly responsive to change. Based on robust methods, an increase in OSS scores of at least eight points can be considered as meaningful improvement after surgery from the patient's perspective.

A shift in redox conditions near the Ediacaran/Cambrian transition and its possible influence on early animal evolution, Corumbá Group, Brazil

The Ediacaran–Cambrian transition witnessed some of the most important biological, tectonic, climatic and geochemical changes in Earth’s history. Of utmost importance for early animal evolution is the likely shift in redox conditions of bottom waters, which might have taken place in distinct pulses during the late Ediacaran and early Paleozoic. To track redox changes during this transition, we present new trace element, total organic carbon and both inorganic and organic carbon isotopes, and the first iron speciation data on the Tamengo and Guaicurus formations of the Corumbá Group in western Brazil, which record important paleobiological changes between 555 Ma to < 541 Ma. The stratigraphically older Tamengo Formation is composed mainly of limestone with interbedded marls and mudrocks, and bears fragments of upper Ediacaran biomineralized fossils such as Cloudina lucianoi and Corumbella werneri. The younger Guaicurus Formation represents a regional transgression of the shallow carbonate platform and is composed of a homogeneous fine-grained siliciclastic succession, bearing meiofaunal bilateral burrows. The new iron speciation data reveal predominantly anoxic and ferruginous (non-sulfidic) bottom water conditions during deposition of the Tamengo Formation, with FeHR/FeT around 0.8 and FePy/FeHR below 0.7. The transition from the Tamengo to the Guaicurus Formation is marked by a stratigraphically rapid drop in FeHR/FeT to below 0.2, recording a shift to likely oxic bottom waters, which persist upsection. Redox-sensitive element (RSE) concentrations are muted in both formations, but consistent with non-sulfidic bottom water conditions throughout. We interpret the collected data to reflect a transition between two distinct paleoenvironmental settings. The Tamengo Formation represents an environment with anoxic bottom waters, with fragments of biomineralized organisms that lived on shallower, probably mildly oxygenated surficial waters, and that were then transported down-slope. Similar to coeval successions (e.g., the Nama Group in Namibia), our data support the hypothesis that late Ediacaran biomineralized organisms lived in a thin oxygenated surface layer above a relatively shallow chemocline. The Guaicurus Formation, on the other hand, records the expansion of oxic conditions to deeper waters during a sea level rise. Although the relationship between global biogeochemical changes and the activities of early bioturbators remains complex, these results demonstrate an unequivocal synchronous relationship between oxygenation of the Corumbá basin and the local appearance of meiofaunal bioturbators.

Directionality of FIV3 ground-motion intensities during the 6 February 2023 Kahramanmaraş, Türkiye earthquake doublet

At present time, ground-motion prediction models neglect the directionality observed in horizontal components of earthquake ground motions, that is, the important changes in ground-motion intensity that occur with changes in azimuth. This study presents an investigation of the directionality of a recently proposed measure of ground-motion intensity during the 6 February 2023, Mw 7.8 Pazarcık and Mw 7.5 Elbistan earthquake doublet in the Kahramanmaraş region of Türkiye, which resulted in the collapse of more than 35,000 buildings and caused almost 60,000 fatalities. The studied intensity measure is referred to as FIV3, which has been shown to be better correlated with structural collapse than the spectral acceleration at the fundamental period of the structure. The improved intensity measure is period-dependent and is computed as the sum of the three largest incremental velocities with the same polarity obtained from the area under segments of a low-pass filtered ground acceleration time series. The following aspects are studied in this article: variation of FIV3 intensity with changes in the orientation; variation of FIV3 intensity with changes in the period of vibration; attenuation of FIV3 intensities with increasing distance; and spatial distribution of the orientation of maximum FIV3 intensity. This study is based on 231 pairs of records from the Mw 7.8 main event and 222 pairs of records from the Mw 7.5 event. Similarly to the directionality of spectral ordinates, it is found that the directionality of FIV3 intensity also increases with increasing period. Strong directionality occurred not only in the near field but up to distances as large as 400 km from the epicenter. The orientation of maximum FIV3 intensity is found to occur close to the transverse orientation, consistent with observations for the orientation of maximum spectral ordinates during strike-slip earthquakes.

A New Topsis Method Based Mutual Information for Mobile Phone Selection

Information knowledge and telecommunication manufacture are going through most important changes newly with the access of mobile phones. The present learn propose a multi-criteria decision making (MCDM) setting to judge various mobile phone alternative based on customer desire Gülçin Büyüközkan. This study wishes for build up an approach based on entropy technique for order performance by similarity to ideal solution (TOPSIS) for ranking suitable mobile phone choice. The uniqueness of the document appears from its talent to offer an effectual evaluation of mobile phone selection with for the first time. Used for indicating the capability of this method, an example is given to select the most suitable phone for clients.

Future changes in North Atlantic winter cyclones in CESM-LE – Part 2: A Lagrangian analysis

Abstract. Future changes in extratropical cyclone structure and dynamics may lead to important impacts but are not yet fully understood. In the first part of this study, we have applied a composite approach together with potential vorticity (PV) inversion to study such changes in the dynamics of North Atlantic cyclones. Here, this is complemented with the help of a Lagrangian perspective, making use of air parcel trajectories to investigate the causes of altered PV anomalies as well as the role that cyclone airstreams play in shaping these changes. Intense cyclones in the extended winter seasons of two periods, 1990–2000 and 2091–2100, are studied in Community Earth System Model Large Ensemble (CESM-LE) simulations, and backward trajectories are calculated from the cyclone area as a basis to construct cyclone-centered composites of Lagrangian tendencies and their projected future changes. Our results show that diabatic processes on a timescale of 24 h shape the cyclones' low-level PV distribution and corroborate that the increasing moisture content along with enhanced ascent in warm conveyor belts leads to amplified latent heat release and larger low- and mid-level PV anomalies near the cyclone center in a warmer climate. In contrast, projected upper-level PV changes are due to a combination of several processes. These processes include cloud diabatic PV changes, anomalous PV advection, and likely also radiative PV generation in the lower stratosphere above the cyclone center. For instance, enhanced poleward advection is the primary reason for a projected decrease in upper-level PV anomalies south of the cyclone center. Warm conveyor belt outflow regions are projected to shift upward, but there is not robust change in the associated upper-level PV anomalies due to compensation between enhanced low-level PV generation and upper-level PV destruction. In summary, our two-part study points to future changes in the relative importance of different processes for the dynamics of intense North Atlantic cyclones in a warming climate, with important consequences for the near-surface wind pattern. In particular, a larger role of cloud diabatic processes is projected, affecting the cyclones through PV production in the lower troposphere. The role of other mechanisms, in particular radiative changes near the tropopause, should be investigated in more detail in future studies.

Non-native English-speaking applicants and the likelihood of physician assistant program matriculation

ABSTRACT Purpose Effective communication is critical in patient care. Multilingual medical providers, including Physician Assistants (PAs) can contribute to improved health care among patients with limited English proficiency; however, this is contingent upon matriculating multilingual providers. In this study, the association between prospective applicants’ self-reported English as second language (ESL) status and their likelihood of matriculation into a PA program was investigated. Methods Participants included applicants to five admission cycles of the Centralized Application Service for Physician Assistant from 2012 to 2020. Logistic regression was utilized to investigate association between applicant ESL status and odds of program matriculation in both bivariate and multivariable regression models. Models were adjusted for citizenship status, undergraduate grade point average, gender, age, race/ethnicity, number of programs applied to, and patient care hours. Results In unadjusted and adjusted models, ESL status was associated with a significantly lower odds of matriculation to a PA program across all study years. In adjusted multivariable models, associations were strongest for 2014–2015 where ESL status was associated with a 35% lower odds of matriculation (odds ratio 0.65, 95% confidence interval 0.56, 0.76) when controlling for demographics, citizenship status, patient care experience, and academic achievement. In sensitivity analyses restricting to (a) those with TOEFL scores ≥ 100, and (b) restricting to those ESL applicants without TOEFL scores, we did not observe important changes in our results. Conclusions Results indicated that non-native English-speaking applicants have lower odds of PA program matriculation. Decrements in matriculation odds were large magnitude, minimally impacted by adjustment for confounders and persistent across the years. These findings suggest that PA program admission processes may disadvantage non-native English-speaking applicants. While there are potential explanations for the observed findings, they are cause for concern. Matriculating and training PAs who have language concordance with underserved populations are important means of improving patient outcomes.

Measurement properties of the childhood bladder and bowel dysfunction questionnaire.

The childhood bladder and bowel dysfunction questionnaire (CBBDQ) was previously found feasible, structurally valid, with good internal consistency. The purpose of this study was to evaluate the remaining measurement properties according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A prospective cohort study among parents of children aged 5-12 years was conducted. Calculated were the area under the curve (AUC) (criterion validity, responsiveness, interpretability) and intra-class correlation coefficients (ICCagreement ) (construct validity and test-retest reliability). One hundred and seventy-two parents were included from March 2019 to April 2021. Correlating the bladder subscales of the CBBDQ with the Vancouver symptom score for dysfunctional elimination (VSSDES) and proxy-reported pediatric incontinence quality of life (p-PinQ) showed convergent validity (ICCsagreement : 0.76 and 0.74). Divergent validity was found when correlating the bowel subscales of the CBBDQ with the VSSDES (ICCagreement : 0.52). Excellent criterion validity (AUC: 0.98); excellent test-retest reliability (ICCagreement : 0.94) and, at 6 months, fair responsiveness (AUC: 0.74) were found. The minimal important change was 4.5, with cut-off value of 11. The CBBDQ has been developed according to COSMIN standards. The items were defined using the consensus-based ICCS standards and Rome-III criteria. The measurement properties were identified using enough participants. Although interpretability is not considered a measurement property, interpretability aspects are reported here as they refer to what instrument scores mean. The 18-item-CBBDQ met the measurement properties of validity, reliability, and responsiveness, as defined by COSMIN. The CBBDQ is suitable for self-administration by parents, and completion takes little time.

A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase-Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

Multidecadal Changes in the Flow Velocity and Mass Balance of the Hailuogou Glacier in Mount Gongga, Southeastern Tibetan Plateau

Maritime glaciers in the southeastern Tibetan Plateau (TP) have experienced important changes in mass and dynamics over the past decades, challenging the regional water supply and glacier-related hazards. However, knowledge about long-term variations in the surface velocity and mass balance of maritime glaciers remains incomplete due to the lack of representative observations in the southeastern TP. In this study, offset tracking is employed to measure spatiotemporal variation in the surface velocity of the Hailuogou Glacier (HLG) in Mount Gongga of the southeastern TP using Sentinel-1A imagery, while the time series of the HLG mass balance is reconstructed since 1950 by a physically based energy–mass balance model. Our satellite-based results find that HLG surface velocity shows significant spatial heterogeneity with a double-peak pattern along the flow line, and sustained slowdown below the icefall zone has been observed during the past nearly 40 years, although the icefall zone and the area above it have become relatively active. Our modeling indicates a persistent increase in mass loss over the last seven decades with an average rate of −0.58 m water equivalent (w.e.) year−1, which has accelerated in the past two decades. Sustained slowdown on the glacier is concomitant with pronounced negative mass balance, thereby enhancing glacier wastage in recent decades. The long-term trend in HLG mass loss is mainly driven by an increase in positive air temperature that decreases surface albedo and solid precipitation ratio and increases longwave incoming radiation, besides the influence of supraglacial debris cover. Large-scale atmospheric circulation patterns in the Eurasian region provide important implications for regional-to-local climate variability, unsustainably intensifying the trend of the negative mass balance of the HLG in the southeastern TP in the past two decades.

Assessing Reassortment between Bluetongue Virus Serotypes 10 and 17 at Different Coinfection Ratios in Culicoides sonorenesis.

Bluetongue virus (BTV) is a segmented, double-stranded RNA orbivirus listed by the World Organization for Animal Health and transmitted by Culicoides biting midges. Segmented viruses can reassort, which facilitates rapid and important genotypic changes. Our study evaluated reassortment in Culicoides sonorensis midges coinfected with different ratios of BTV-10 and BTV-17. Midges were fed blood containing BTV-10, BTV-17, or a combination of both serotypes at 90:10, 75:25, 50:50, 25:75, or 10:90 ratios. Midges were collected every other day and tested for infection using pan BTV and cox1 (housekeeping gene) qRT-PCR. A curve was fit to the ∆Ct values (pan BTV Ct-cox1 Ct) for each experimental group. On day 10, the midges were processed for BTV plaque isolation. Genotypes of the plaques were determined by next-generation sequencing. Pairwise comparison of ∆Ct curves demonstrated no differences in viral RNA levels between coinfected treatment groups. Plaque genotyping indicated that most plaques fully aligned with one of the parental strains; however, reassortants were detected, and in the 75:25 pool, most plaques were reassortant. Reassortant prevalence may be maximized upon the occurrence of reassortant genotypes that can outcompete the parental genotypes. BTV reassortment and resulting biological consequences are important elements to understanding orbivirus emergence and evolution.

High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System.

Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1µM, 5µM, and 10µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5µM and 10µM) and affected the viability of NPCs than at lower concentrations (1µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.

Remaking the Qualities of Turkish Olive Oil

The geography that is now Turkey has produced olives and their oil for millennia, but major changes in the industry have been underway in the last decade, with many producers now focusing on quality over quantity. Based on fieldwork with olive oil producers, harvesters, laboratory technicians, equipment engineers, and others in the industry, this article describes this “quality turn,” what is driving it, who is involved in it, how it unfolds, and what its effects are. Some of the players involved in producing olive oil in Turkey for decades or longer have witnessed important generational changes, including more women entering the sector and technological innovation. Prominent roles are now played by laboratories and tasting competitions, involving the recalibration of human sense perceptions on the part of producers (and, more slowly, consumers) to be commensurate with international standards for defining target aroma profiles in olive oil.

Plant diversity and functional identity drive grassland rhizobacterial community responses after 15 years of CO2 and nitrogen enrichment

Abstract Improved understanding of bacterial community responses to multiple environmental filters over long time periods is a fundamental step to develop mechanistic explanations of plant–bacterial interactions as environmental change progresses. This is the first study to examine responses of grassland root‐associated bacterial communities to 15 years of experimental manipulations of plant species richness, functional group and factorial enrichment of atmospheric CO2 (eCO2) and soil nitrogen (+N). Across the experiment, plant species richness was the strongest predictor of rhizobacterial community composition, followed by +N, with no observed effect of eCO2. Monocultures of C3 and C4 grasses and legumes all exhibited dissimilar rhizobacterial communities within and among those groups. Functional responses were also dependent on plant functional group, where N2‐fixation genes, NO3−‐reducing genes and P‐solubilizing predicted gene abundances increased under resource‐enriched conditions for grasses, but generally declined for legumes. In diverse plots with 16 plant species, the interaction of eCO2+N altered rhizobacterial composition, while +N increased the predicted abundance of nitrogenase‐encoding genes, and eCO2+N increased the predicted abundance of bacterial P‐solubilizing genes. Synthesis: Our findings suggest that rhizobacterial community structure and function will be affected by important global environmental change factors such as eCO2, but these responses are primarily contingent on plant species richness and the selective influence of different plant functional groups.

Changes in splenic tissue and immune response profile of Schistosoma mansoni infected mice submitted to chronic ethanol intake.

In Schistosoma mansoni infection, the spleen is one of the organs affected, causing its enlargement (splenomegaly). Intake of ethanol through alcoholic beverages can cause spleen atrophy and interfere with immune activity. To gain knowledge of this association on the spleen and on the immune response profile, male mice were used as an experimental model. These animals were divided into four groups: C. control; EC. uninfected/ethanol gavage; I. infected; and IE. infected/ethanol gavage. Groups I and IE were infected with about 100 cercariae (BH strain) of S. mansoni and in the fifth week of infection, gavage 200 μL/day/animal of 18 % ethanol was started for 28 consecutive days. At the end of the gavage (9th week of infection) all animals were euthanized. The spleen was removed and longitudinally divided in two parts. After histological processing, the sections were stained with H&E and Gomori's Reticulin for histopathological and stereological analyses, white pulp morphometry and quantification of megakaryocytes. The other fragment was macerated (in laminar flow) and the cell suspension, after adjusting the concentration (2 × 106), was plated to obtain cytokines produced by spleen cells that were measured by flow cytometry (Citometric Bead Array). Histopathological and quantitative analyzes in the spleen of the IE group showed an increase in the number of trabeculae and megakaryocytes, a decrease in reticular fibers, as well as important organizational changes in the white pulp and red pulp. Due to the decrease in the levels of cytokines measured and the result of the calculation of the ratio between the IFN-y and IL-10 cytokines (p = 0.0079) of the infected groups, we suggest that ethanol decreased the inflammatory and anti-inflammatory response generated by the infection (group IE, the production of cytokines was significantly decreased (p < 0.01). These changes demonstrate that ethanol ingestion interferes with some parameters of experimental S. mansoni infection, such as changes in splenic tissue and in the pattern of cytokine production.

Establishing the Minimally Important Difference for the KOOS-Joint Replacement and PROMIS Global-10 in Patients After Total Knee Arthroplasty.

Despite the overall prevalence and success of total knee arthroplasty (TKA), a significant portion of patients are dissatisfied with their outcomes. To assess the responsiveness and determine the minimally important difference (MID) of 2 patient-reported outcome measures (PROMs)-the Knee injury and Osteoarthritis Outcome Score-Joint Replacement (KOOS-JR) and the Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS 10)-in patients after TKA. Cohort study (diagnosis); Level of evidence, 3. Included were patients who underwent TKA from August 2015 through August 2019 and completed baseline and postoperative KOOS-JR and PROMIS 10 surveys. The PROMIS 10 consists of 2 domains: physical health and mental health. Estimates for the reliable change index (RCI) and MID, using anchor-based and distribution-based methods, were calculated for each PROM. Regression modeling was used to determine whether patient and clinical factors predicted MID thresholds or MID achievement. A total of 1315 patients were included. Distribution-based MIDs, calculated using various methods from baseline scores, ranged from 19.3 to 31 for the KOOS-JR, and the RCI was 4.38. Of these patients, 293 (22.3%) demonstrated small or moderate improvement, and this cohort was included in the calculation of anchor-based MIDs. The anchor-based MIDs were 16.9 and 24.3 at 3-month and 1-year follow-up, respectively, and 66% of patients achieved the MID at 12 months. Higher preoperative PROM score, male sex, non-White race, and current smoker status were predictive of failing to achieve the anchor-based MID for KOOS-JR at 1 year postoperatively (P < .05). Higher preoperative PROM score and any 90-day adverse event predicted lower thresholds of important change in anchor-based MIDs. Higher baseline PROM scores, younger age, male sex, non-White ethnicity, higher American Society of Anesthesiologists classification, preoperative narcotics use, not smoking, and longer hospital stay were all associated with lower odds of achieving the MID on the KOOS-JR or either of the PROMIS 10 subscales. The study results demonstrated relevant values for interpretation of the KOOS-JR and PROMIS 10. While patient demographics did not accurately predict which patients would achieve the MID, some potential factors predicting successful patient-reported outcomes after TKA were identified.