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Abstract Background Effects of the renin‐angiotensin‐aldosterone system (RAAS) inhibitors enalapril and telmisartan on circulating RAAS in dogs with proteinuric chronic kidney disease (pCKD) are undescribed. Objectives To characterize the RAAS in untreated dogs with pCKD compared to healthy, life‐stage‐ and sex‐matched controls, and in dogs with pCKD after 30 days of treatment with enalapril or telmisartan. Animals Dogs with pCKD (n = 36) and healthy controls (n = 20). Methods Retrospective study of banked samples and previously collected data. Day 0 serum equilibrium concentrations of angiotensin I, II, III, IV, 1‐5, and 1‐7, and aldosterone, and urinary aldosterone‐to‐creatinine ratio (UACR) from pCKD dogs were compared to values on day 30 of treatment with enalapril (0.5 mg/kg PO q12) or telmisartan (1 mg/kg PO q24h) and to those of healthy dogs. Data were analyzed using linear mixed models. Results Compared with healthy dogs, pCKD dogs had significantly higher Ang I, III, 1‐5, and 1‐7 concentrations, and UACR. Relative to pretreatment values, day 30 Ang II concentrations were significantly increased and decreased in telmisartan‐ and enalapril‐treated pCKD dogs, respectively (both P

Abstract Traditional bacteriocin screening methods often face limitations due to diffusion‐related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion‐related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell‐free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S‐07‐4, and SK‐106‐1). The inhibition of the CFS by proteinase K suggested that the antimicrobial activity was proteinaceous in nature, potentially bacteriocins. The activity of E. coli PUTS 58 and SK‐106‐1 was enhanced in an artificial urine medium, with both inhibiting all eight UPECs. A putative microcin H47 operon was identified in E. coli SK‐106‐1, along with a previously identified microcin V and colicin E7 in E. coli PUTS 37 and PUTS 58, respectively. These findings indicate that ABU bacteriocin‐producers could serve as viable prophylactics and therapeutics in the face of increasing antibiotic resistance among uropathogens.

Molecular diagnostics has the potential to revolutionise the field of clinical microbiology. Microbial identification and nomenclature have, for too long, been restricted to phenotypic characterisation. However, this species-level view fails to wholly account for genetic heterogeneity, a result of lateral gene transfer, mediated primarily by mobile genetic elements. This genetic promiscuity has helped to drive virulence development, stress adaptation, and antimicrobial resistance in several important bacterial pathogens, complicating their detection and frustrating our ability to control them. We argue that, as clinical microbiologists at the front line, we must embrace the molecular technologies that allow us to focus specifically on the genetic elements that cause disease rather than the bacterial species that express them. This review focuses on the evolution of microbial taxonomy since the introduction of molecular sequencing, the role of mobile genetic elements in antimicrobial resistance, the current and emerging assays in clinical laboratories, and the comparison of phenotypic versus genotypic analyses. In essence, it is time now to refocus from species to genes as part of a new diagnostic paradigm.

Objective: To investigate the prognostic value of illness perception (IP) on knee pain, quality of life (QoL) and functional level in elderly individuals reporting knee pain. Design: A prospective cohort study of 1552 elderly with knee pain comparing two previously established clusters based on the Brief Illness Perception questionnaire. Cluster 1 (“Concerned optimists” [hypothesized unfavorable profile]; n ​= ​642) perceived their knee pain as a greater threat to them than Cluster 2 (“Unconcerned confident” [hypothesized favorable profile]; n ​= ​910). Primary outcome was the change from baseline to year 2 in the KOOS Pain subscale. Secondary outcomes were changes from baseline in quality of life (EuroQol-5 Domain and EQ VAS) and in the KOOS subscales Symptom, Activities of Daily Living, Knee-related QoL and Sports and recreation. Analyses were done on the original Intention-To-Survey (ITS) population, using repeated measures mixed linear models. Results: Among the ITS population, 841 (54%) responded to the 2-year survey. There was a statistically significant but clinically irrelevant cluster difference in the 2-year change from baseline in KOOS pain (mean difference: 6.0 KOOS points [95% CI: 7.3 to −4.7]) explained by a minor improvement in Cluster 1: (6.2 points) and no changes in Cluster 2: (0.2 points). Comparable results were found across the secondary outcomes. Clinically irrelevant cluster changes in IP were seen. Conclusion: In a cohort of people with knee pain, IP phenotype (i.e., Clusters) were of no prognostic value for the 2-year changes in pain, function, and QoL. Targeting IP may not be relevant in this patient population. Trial registration number and date of registration: The Frederiksberg Cohort study was pre-registered at clinicaltrials.gov (NCT03472300) on March 21, 2018.

Due to its adsorption with aluminum and iron hydroxides, phosphorus viability is low in acidic soils; thus, the aim of this study was to isolate and identify bacteria from the rhizosphere of four legumes growing in acidic soils of the Cumbaza Sub-basin, San Martín, Peru, as well as to characterize their ability to solubilize aluminum phosphate and iron phosphate. The isolation process was conducted on TSA medium and the isolates were classified based on their origin and morphocolonial characteristics, with the bacillary shape being the most frequent, followed by cocci. To assess the solubilization of aluminum and iron phosphates, the liquid medium GELP was employed. Sixteen strains were selected, among which three stood out for their effectiveness in solubilizing AlPO4 (Sfcv-098-02, 22.65 mg L−1; Sfc-093-04, 26.50 mg L−1; and Sfcv-041-01-2, 55.98 mg L−1) and one for its ability to solubilize FePO4 (Sfcr-043-02, 32.61 mg L−1). These four strains were molecularly characterized, being identified as Enterobacter sp., Pseudomonas sp., and Staphylococcus sp. Additionally, a decrease in pH was observed in the reactions, with values ranging from 5.23 to 3.29, which enhanced the phosphate of solubilization. This suggests that the selected bacteria could be used to improve phosphorus availability in agricultural soils.

Objective To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA).Methods We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393.Results We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids’ NMA effect sizes were −0.18 (95% credible interval −0.36 to 0.02) and −0.54 (−0.83 to −0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs’ NMA effect sizes were 0.22 (−0.08 to 0.51), 0.25 (0.00 to 0.51), −0.01 (−0.19 to 0.18), and −0.14 (−0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA.Conclusion Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

Abstract Background The role of the renin‐angiotensin‐aldosterone system in cats with chronic kidney disease (CKD) is incompletely understood. Objective To characterize components of the intrarenal renin‐angiotensin system (RAS) in cats with CKD. Animals Eleven cats with naturally occurring CKD (CKD group) and 8 healthy control cats. Methods Renal tissue samples were evaluated by reverse‐transcription polymerase chain reaction for renin, angiotensinogen, angiotensin‐converting enzyme (ACE), and angiotensin II type 1 receptor transcript levels, and by liquid chromatography‐mass spectrometry for quantification of angiotensin I, II, III, and IV concentrations. Linear mixed models were used to compare gene transcript levels and concentrations of angiotensin peptides between groups. Results Cats of the CKD group were significantly older (P

Undiagnosed concussions increase the risk of additional concussion and persistent symptoms from concussion. Because there are no reliable objective markers of concussion, self-reporting of subjective and non-visible symptoms are critical to ensuring proper concussion management. For this reason, educational interventions target concussion reporting, but the majority of studies have examined the efficacy of single educational interventions or compared interventions to one another. This randomized crossover study sought to identify whether there was benefit to administering multiple concussion education programs in tandem, back to back. The study randomized 313 male high school football players to first receive CrashCourse concussion education (CC) or Centers for Disease Control and Prevention video concussion education (CDC) followed by crossover with the other education. Athlete concussion-reporting intention, attitudes, subjective norms, perceived behavioral control, and enjoyment of education were assessed at baseline and after each intervention. There were statistically significant improvements across all measures, both after single intervention and crossover (all p?0.001). Secondary analyses examining differences between education found that athletes reported higher enjoyment of concussion education immediately after participating in CC, as compared to CDC (p?

ABSTRACT: Floor pen trials are an efficient way to evaluate the effectiveness of potential Salmonella control interventions in broiler chickens. When treatments are allocated at the pen level, and outcomes are measured at the individual bird level, floor pen studies are considered to be cluster randomized trials. Estimating the sample size required to achieve a desired level of statistical power for a cluster randomized trial requires an estimate of the intra-cluster correlation (ICC) as an input. In this study, ICCs were estimated for the untreated challenged control group from 40 broiler chicken Salmonella pen trials performed using a seeder bird challenge model. The ICCs for ceca Salmonella prevalences ranged from 0.00 to 0.64, with a median of 0.17. The ICCs for ceca Salmonella log10(MPN/g + 1) ranged from 0.00 to 0.52, with a median of 0.14. These findings indicate that the effect of pen-level clustering is substantial in Salmonella floor pen trials, and it must be considered during both the study design and analysis. In a multivariable regression analysis, ICCs for ceca Salmonella prevalences were associated with the challenge status of sampled birds, age of birds at the time of challenge, and Salmonella serovar. ICCs were lower for studies in which a combination of direct (seeder) and indirect (horizontal) challenged birds were sampled, and for studies in which birds were challenged on the day of hatch or at one day of age. ICCs were higher for studies in which Salmonella Heidelberg was used as the challenge strain. These findings may be useful for investigators that are planning pen trials to evaluate Salmonella control interventions in broiler chickens. Choosing study design elements associated with a lower ICC may improve efficiency by leading to a larger effective sample size for the same number of experimental units.

Genomic imprinting is an epigenetic phenomenon defined as the silencing of an allele, at least partially, at a given locus based on the sex of the transmitting parent. The objective of the present study was to detect the presence of SNP-phenotype imprinting associations for carcass weight (CW), carcass conformation (CC) and carcass fat (CF) in cattle. The data used comprised carcass data, along with imputed, high-density genotype data on 618,837 single nucleotide polymorphisms (SNPs) from 23,687 cattle; all animal genotypes were phased with respect to parent of origin. Based on the phased genotypes and a series of single-locus linear models, 24, 339, and 316 SNPs demonstrated imprinting associations with CW, CC, and CF, respectively. Regardless of the trait in question, no known imprinted gene was located within 0.5 Mb of the SNPs demonstrating imprinting associations in the present study. Since all imprinting associations detected herein were at novel loci, further investigation of these regions may be warranted. Nonetheless, knowledge of these associations might be useful for improving the accuracy of genomic evaluations for these traits, as well as mate allocations systems to exploit the effects of genomic imprinting.

The addition of cricket flour into foods has been extensively examined giving its great economic, nutritional, and environmental advantages. Even though entomophagy presents great economic, nutritional, and environmental benefits, there is yet a notable reluctance to insects as foods. Consequently, the use of edible-cricket flour (ECF) in foods is quite challenging. For this reason, the aim of this study was to evaluate the physicochemical and sensory properties of barbecue sauce (BS) as affected by cricket flour. Barbecue sauce formulations without (Control) and with 5% (T1), 10% (T2) & 15% (T3) w/w were evaluated by 100 panelists (color, aroma, texture, flavor, overall liking, and purchase intent) under the following informed condition: without ECF (ECF-) and with ECF + benefits (ECF+). In addition, the pH, brix, viscosity, color (L*, a*, b*, browning index), and texture (firmness & adhesiveness) were analyzed. The crickets were farmed and the ECF was made by, baking, grounding, and drying processes. The addition of ECF into BS did not drive to a significant (P < 0.05) difference in the pH while ECF affected color, brix, texture, and viscosity. When compared to control, the color, aroma, texture, flavor, and overall liking did not differ significantly (P < 0.05) only among samples containing 5% of ECF (T1). Furthermore, purchase intent and overall liking were significantly (P < 0.05) increased with the beneficiary statement only among T1 samples. To sum up, 5% of ECF can be added when improving the nutritional profile of barbecue sauce. Keywords: Gryllus assimilis, barbecue sauce, cricket flour, physico-chemical, sensory characteristics.

Natal philopatry—the return of an animal to its place of birth to reproduce—can shape population genetics and link essential habitats across generations, yet examples from long-term mark-recapture studies are rare. In this study, we observed 136 nests of Northern Map Turtles at Mount Union, Pennsylvania, between 2000 and 2008 and then individually marked and released 691 hatchling turtles into the Juniata River. During a recent six-year period (from 2017 to 2022), 46 of the hatchling-marked turtles (6.7%) returned to Mount Union as adult females to nest. The ages of these turtles ranged from 11–22 years at first recapture, and their mean age was 17 years. Forty-one hatchling-marked females came from observed nests with known mothers, and remarkably, just four (of 52) mothers produced over half of the returning females. The minimum ages of the oldest female turtles were estimated at 39 years, with reproductive lifetimes of at least 23 years. Our results indicate that a few long-lived Super Moms have made extraordinary contributions to hatchling recruitment and population viability of Northern Map Turtles of the Juniata River. The timing of release also had a significant influence on the probability of a turtle returning, with hatchlings released in May returning at a higher rate than those released earlier in the spring. In addition, morphological characteristics of hatchling-marked females suggest that factors causing shell shape abnormalities in adult turtles have not abated over the past two decades as previously theorized and likely involve exposure of juveniles to contaminants in the Juniata River rather than any maternal influence.

Debosree Roy,1 Margaret Meador,2 Nana Sasu,2 Kate Whelihan,1 Joy H Lewis1 1School of Osteopathic Medicine in Arizona, A.T. Still University, Mesa, Arizona, USA; 2National Association of Community Health Centers, Bethesda, MD, USACorrespondence: Debosree RoySchool of Osteopathic Medicine in Arizona, A.T. Still University Email debosreeroy@atsu.eduIntroduction: Self-measured blood pressure monitoring (SMBP) helps diagnose and manage hypertension from outside the clinic, which has implications for patient empowerment and outcomes, continuity of care, and resilience in care communities catering to vulnerable populations.Methods: We instituted a protocol for SMBP among hypertensive patients at 9 community health centers in 3 states and administered questionnaires to patients before and after the protocol was instituted to assess knowledge and engagement with disease management, beliefs and attitudes towards, and experience doing SMBP. Questionnaires included 16 items designed to evaluate patient perceptions and beliefs about SMBP. These included a series of questions using a 5-point Likert scale, binary questions related to their perceived ability to comply with specific SMBP guidelines and open-ended questions to obtain descriptions of experiences with SMBP.Results: The pre-questionnaire was completed by 478 patients and the post-questionnaire was completed by 372. Seventy-seven percent of respondents knew their ideal blood pressure and their engagement with blood pressure management increased significantly (p=0.0024) after completing the protocol. Additionally, 85% of respondents said that they had a positive experience doing SMBP. Open-ended responses revealed insight regarding why patients chose to do SMBP and factors patients appreciated about SMBP.Discussion: When trained properly and supported, community health center patients are capable of and motivated to perform accurate SMBP. Our study provides evidence that health center patients can follow detailed SMBP protocols and monitor their own blood pressure from the safety of their homes, which is critical to their care continuum, particularly in days of a pandemic.Keywords: SMBP, self-measured blood pressure monitoring, home blood pressure monitoring, patient engagement, community health centers

Abstract Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutics and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery controlling their transcription. Recent findings suggest that the σ54 system, which includes σ54-loaded RNA polymerase and transcriptional activators called enhancer binding proteins (EBPs), might be a common regulator of natural product genes. Here, we explored this idea by analyzing a selected group of putative σ54 promoters identified in Myxococcus xanthus natural product gene clusters. We show that mutations in putative σ54-RNA polymerase binding regions and in putative Nla28 EBP binding sites dramatically reduce in vivo promoter activities in growing and developing cells. We also show in vivo promoter activities are reduced in a nla28 mutant, that Nla28 binds to wild-type fragments of these promoters in vitro, and that in vitro binding is lost when the Nla28 binding sites are mutated. Together, our results indicate that M. xanthus uses σ54 promoters for transcription of at least some of its natural product genes. Interestingly, the vast majority of experimentally confirmed and putative σ54 promoters in M. xanthus natural product loci are located within genes and not in intergenic sequences.

Abstract Background Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the ‘active’ ingredients are unknown. Designing and executing an adequate and ‘blindable placebo’ version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used ‘state-of-art’ exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. Methods In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients’ global assessment of disease impact, physical performance tests, and presence of knee joint swelling. Discussion This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. Trial registration www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

Abstract Molecular interactions are studied as independent networks in systems biology. However, molecular networks do not exist independently of each other. In a network of networks approach (called multiplex), we study the joint organization of transcriptional regulatory network (TRN) and protein–protein interaction (PPI) network. We find that TRN and PPI are non-randomly coupled across five different eukaryotic species. Gene degrees in TRN (number of downstream genes) are positively correlated with protein degrees in PPI (number of interacting protein partners). Gene–gene and protein–protein interactions in TRN and PPI, respectively, also non-randomly overlap. These design principles are conserved across the five eukaryotic species. Robustness of the TRN–PPI multiplex is dependent on this coupling. Functionally important genes and proteins, such as essential, disease-related and those interacting with pathogen proteins, are preferentially situated in important parts of the human multiplex with highly overlapping interactions. We unveil the multiplex architecture of TRN and PPI. Multiplex architecture may thus define a general framework for studying molecular networks. This approach may uncover the building blocks of the hierarchical organization of molecular interactions.

Abstract Aim Conduct a time trend analysis that describes 2 groups of patients admitted to a large tertiary children's hospital that presented with appendicitis and determine if there was an increase in complicated appendicitis when compared between 2 time periods before and during the early coronavirus disease 2019 (COVID‐19) pandemic of 2020. Methods We conducted a retrospective analysis of all children presenting to a single‐center site with appendicitis between March 23 and August 31, 2020, in the Central Texas region. We compared 507 patients presenting with appendicitis from the non‐COVID‐19 era in 2019 with n = 249 to patients presenting during the COVID time period with n = 258. All patients with appendicitis within those time periods were reviewed with analysis of various characteristics in regard to presentation, diagnosis of uncomplicated versus complicated appendicitis, and management outcomes. Results There were no significant demographic differences or change in the number of appendicitis cases noted between the 2 time periods of comparison. There was no significant difference in rates of complicated appendicitis or presentation time following symptom onset between the 2 eras. There was no significant difference in intraoperative or postoperative complications. There was a statistically significant increase in the use of computed tomography (CT) scans (P‐value = 0.004) with patients 1.81 times more likely to have a CT scan in the pandemic era after adjusting for patient‐level factors. The effect of severe acute respiratory syndrome coronavirus 2 status on outcomes was not part of the data analysis. Conclusion Our study is the largest to date examining appendicitis complications in the era of COVID. In the time of the COVID‐19 pandemic, we found no delay in presentation in children presenting to the emergency department and no increase in complicated appendicitis. We did identify an increase in the use of CT scans for definitive diagnosis of appendicitis noted in the pandemic era. Although COVID‐19 status was not studied, the finding of increased CT use for a definitive diagnosis of appendicitis was a distinctive finding of this study showing a change in practice in pediatric emergency medicine.

Remarkable progress in bioengineering over the past two decades has enabled the formulation of fundamental design principles for a variety of medical and non-medical applications. These advancements have laid the foundation for building multicellular engineered living systems (M-CELS) from biological parts, forming functional modules integrated into living machines. These cognizant design principles for living systems encompass novel genetic circuit manipulation, self-assembly, cell–cell/matrix communication, and artificial tissues/organs enabled through systems biology, bioinformatics, computational biology, genetic engineering, and microfluidics. Here, we introduce design principles and a blueprint for forward production of robust and standardized M-CELS, which may undergo variable reiterations through the classic design-build-test-debug cycle. This Review provides practical and theoretical frameworks to forward-design, control, and optimize novel M-CELS. Potential applications include biopharmaceuticals, bioreactor factories, biofuels, environmental bioremediation, cellular computing, biohybrid digital technology, and experimental investigations into mechanisms of multicellular organisms normally hidden inside the “black box” of living cells.

Strawberries (Fragaria ×ananassa) are one of the major high-value crops in North America. There is increasing interest in commercial strawberry production for local markets in Virginia and surrounding states, but information on the performance of newer cultivars is extremely limited. We tested 10 commercially available June-bearing cultivars [Benicia, Camarosa, Camino Real, Chandler, Strawberry Festival, Flavorfest, FL Radiance, Treasure, Sweet Charlie, and Winterstar™ (FL 05-107)] and two day-neutral cultivars (Albion and San Andreas) for their spring and summer fruiting capacity in Virginia production systems in a randomized, replicated study, at three on-farm locations. Data were collected on vegetative growth, yield performance, fruit quality, sweetness, and fruit diameter. Cultivars with the highest total yields averaged across all three locations were Benicia, Camino Real, Chandler, and Camarosa. ‘Camino Real’ had the highest marketable yield at all three locations, not significantly different from ‘Chandler’, and ‘Benicia’ and ‘Camarosa’ had the highest marketable yield at two of the three locations. ‘Flavorfest’ and ‘Sweet Charlie’ had the highest total soluble solids concentration for the harvest season. Overall, for all locations, ‘Benicia’ and ‘Camino Real’ had the largest fruit diameter, and ‘Strawberry Festival’ had the smallest fruit diameter.

Abstract Background Increased gene transcription of hypoxia‐induced mediators of fibrosis in renal tissue has been identified in experimentally induced, ischemic chronic kidney disease (CKD). Objective To characterize hypoxia‐induced profibrotic pathways in naturally occurring CKD in cats. Animals Twelve client‐owned cats with CKD and 8 healthy control cats. Methods In this prospective, cross‐sectional study, bilateral renal tissue samples were assessed histologically for inflammation, tubular atrophy, and fibrosis, and by reverse transcription‐quantitative PCR for characterization of transcript levels of hypoxia‐inducible factor‐1α (HIF1A), matrix metalloproteinases‐2 (MMP2), ‐7 (MMP7), and ‐9 (MMP9), tissue inhibitor of metalloproteinase‐1 (TIMP1), transforming growth factor‐β1 (TGFB1), and vascular endothelial growth factor‐A (VEGFA). Linear mixed models were used to compare gene transcription between diseased and healthy kidneys, and to examine the association between transcript levels and serum creatinine concentration for all cats, and between transcript levels and histologic scores of diseased kidneys. Results Kidneys from cats with CKD had significantly higher transcript levels of HIF1A, MMP2, MMP7, MMP9, TIMP1, and TGFB1 (all P < .001), and lower levels of VEGFA (P = .006) than those from control cats. Transcript levels of MMP7 (P = .05) and TIMP1 (P = .005) were positively associated with serum creatinine in cats with CKD, but not in control cats. In diseased kidneys, transcript levels of MMP2 (P = .002), MMP7 (P = .02), and TIMP1 (P = .02) were positively, whereas those of VEGFA (P = .003) were negatively, associated with histologic score severity. Conclusion and Clinical Significance Evaluation of the expression of the corresponding proteins in larger populations could identify therapeutic targets and/or biomarkers of tubulointerstitial fibrosis in cats.

Abstract Background Joint replacements continue to occur during a rheumatoid arthritis (RA) patient’s lifetime despite significant advances in available treatment options. The purpose of this study was to examine and quantify synovitis in surgically operated joints by ultrasound (US) in RA patients starting a new therapeutic agent. Methods RA subjects were enrolled in either tocilizumab or tofacitinib open-label, investigator-initiated trials and were assessed by ultrasound. In a subset of RA patients with joint replacements and/or operations of joint areas (OJA; e.g. joint arthroscopies, fusions, and synovectomies), joint-level scores of synovitis were compared between replaced joints, OJAs, and native joints. Joint-level synovitis was measured by grayscale (GSUS (0–3)) and power Doppler (PDUS (0–3)) at baseline and follow-up (3–6 months). McNemar’s test or Wilcoxon signed rank test utilized the mixed effects ordinal logistic regression models. Results Twenty RA patients had a total of 25 replaced joints and 24 OJA. All replaced joints had GSUS> 1 and 92% had PDUS> 1 at baseline, while OJA and native joints had lower evidence of GSUS> 1 (37.5, 38% respectively) and PDUS> 1 (45.8, 62% respectively). GSUS and PDUS semiquantitative scores improved significantly with treatment in replaced joints (p = 0.01, p = 0.007), and native joints (p

Background and Aim: Salmonella Enteritidis (SE) is a significant foodborne pathogen that can often be traced to poultry and poultry products. This study aims to evaluate the ability of three commonly used non-antimicrobial feed additives in reducing the amount of SE in the ceca of laying type pullets. Materials and Methods: On day 0, 60 Hy-Line Brown pullets aged 9 weeks were allocated to individual cages in 15 replicate blocks of four pens. Pullets were administered a mash feed provided ad libitum without supplementation (control) or with dietary supplementation of 454 g/ton yeast cell wall (YCW), or 454 g/ton Bacillus spp. probiotic, or 1133 g/ton yeast culture (YC). On day 3 of the trial, all birds were orally administered 3×107 CFU of a nalidixic acid-resistant SE. On day 10, 7 days after inoculation, all birds were humanely euthanized, and the ceca were aseptically removed for analysis. Results: There was no significant difference in the prevalence of SE among treatments. The mean quantity of SE detected in the ceca expressed in log10 most probable number/g was 2.52 in the control, 2.49 in the YCW treatment, 1.73 in the probiotic treatment, and 1.66 in the YC treatment. The reduction between control and probiotic and control and YC was significant (p=0.021). Conclusion: This study demonstrates the ability of the novel probiotic and the YC to reduce the load of SE in layer ceca.

The objective of the present study was to quantify the association between both pedigree and genome-based measures of global heterozygosity and carcass traits, and to identify single nucleotide polymorphisms (SNPs) exhibiting non-additive associations with these traits. The carcass traits of interest were carcass weight (CW), carcass conformation (CC) and carcass fat (CF). To define the genome-based measures of heterozygosity, and to quantify the non-additive associations between SNPs and the carcass traits, imputed, high-density genotype data, comprising of 619,158 SNPs, from 27,213 cattle were used. The correlations between the pedigree-based heterosis coefficient and the three defined genomic measures of heterozygosity ranged from 0.18 to 0.76. The associations between the different measures of heterozygosity and the carcass traits were biologically small, with positive associations for CW and CC, and negative associations for CF. Furthermore, even after accounting for the pedigree-based heterosis coefficient of an animal, part of the remaining variability in some of the carcass traits could be captured by a genomic heterozygosity measure. This signifies that the inclusion of both a heterosis coefficient based on pedigree information and a genome-based measure of heterozygosity could be beneficial to limiting bias in predicting additive genetic merit. Finally, one SNP located on Bos taurus (BTA) chromosome number 5 demonstrated a non-additive association with CW. Furthermore, 182 SNPs (180 SNPs on BTA 2 and two SNPs on BTA 21) demonstrated a non-additive association with CC, while 231 SNPs located on BTA 2, 5, 11, 13, 14, 18, 19 and 21 demonstrated a non-additive association with CF. Results demonstrate that heterozygosity both at a global level and at the level of individual loci contribute little to the variability in carcass merit.

Genetic evaluations separate phenotypes into their contributing additive genetic effects and non-(additive) genetic effects, with the former termed best linear unbiased predictions, and the latter termed best linear unbiased estimates (BLUEs). For the purpose of the present study, genetic evaluations, along with phenotypic data from 4 137 376 animals, were used to generate herd, year of slaughter and sex contemporary group BLUEs for various slaughter-related traits. These slaughter traits included carcass weight (CW), carcass conformation (CC) and carcass fat (CF). For the 4 665 herds that were consistently slaughtering ≥10 animals/year between the years 2014 and 2018, inclusive, all relevant contemporary group BLUEs were collapsed into a single herd-year value; results herein relate to these herds. The within-year herd-year BLUE correlations between CW and CC, between CW and CF, and between CC and CF were 0.51, 0.10 and −0.04, respectively. The repeatability across years of the herd-year BLUEs for CW, CC and CF was 0.66, 0.59 and 0.50, respectively. Furthermore, when the herds were stratified, within year, on the percentile rank of their herd-year BLUEs, herds had the greatest probability of remaining in the same BLUE stratum from one year to the next. In addition, results from the present study determined that various herd characteristics are associated with differences in the herd BLUEs. Results from the present study could be used to advise beef producers on the most promising strategy to improve the carcass merit of their animals.

The protozoan parasite Cryptosporidium has emerged as a leading cause of diarrhoeal illness worldwide, posing a significant threat to young children and immunocompromised patients. While endemic in the vast majority of developing countries, Cryptosporidium also has the potential to cause waterborne epidemics and large scale outbreaks in both developing and developed nations. Anthroponontic and zoonotic transmission routes are well defined, with the ingestion of faecally contaminated food and water supplies a common source of infection. Microscopy, the current diagnostic mainstay, is considered by many to be suboptimal. This has prompted a shift towards alternative diagnostic techniques in the advent of the molecular era. Molecular methods, particularly PCR, are gaining traction in a diagnostic capacity over microscopy in the diagnosis of cryptosporidiosis, given the laborious and often tedious nature of the latter. Until now, developments in the field of Cryptosporidium detection and research have been somewhat hampered by the intractable nature of this parasite. However, recent advances in the field have taken the tentative first steps towards bringing Cryptosporidium research into the 21st century. Herein, we provide a review of these advances.

The Electron-Ion Collider (EIC), a state-of-the-art facility for studying the strong force, is expected to begin commissioning its first experiments in 2028. This is an opportune time for artificial intelligence (AI) to be included from the start at this facility and in all phases that lead up to the experiments. The second annual workshop organized by the AI4EIC working group, which recently took place, centered on exploring all current and prospective application areas of AI for the EIC. This workshop is not only beneficial for the EIC, but also provides valuable insights for the newly established ePIC collaboration at EIC. This paper summarizes the different activities and R&D projects covered across the sessions of the workshop and provides an overview of the goals, approaches and strategies regarding AI/ML in the EIC community, as well as cutting-edge techniques currently studied in other experiments.

Summary: Human immunodeficiency virus (HIV) can infect cells and take a quiescent and nonexpressive state called latency. In this study, we report insights provided by label-free, gradient light interference microscopy (GLIM) about the changes in dry mass, diameter, and dry mass density associated with infected cells that occur upon reactivation. We discovered that the mean cell dry mass and mean diameter of latently infected cells treated with reactivating drug, TNF-α, are higher for latent cells that reactivate than those of the cells that did not reactivate. Cells with mean dry mass and diameter less than approximately 10 pg and 8 μm, respectively, remain exclusively in the latent state. Also, cells with mean dry mass greater than approximately 28-30 pg and mean diameter greater than 11–12 μm have a higher probability of reactivating. This study is significant as it presents a new label-free approach to quantify latent reactivation of a virus in single cells.

Background and study aims Incidence of Post-ERCP pancreatitis (PEP) ranges from 1 % to 10 % in unselected patients and as high as 25 % to 30 % in high-risk patients. Rectal indomethacin administered before or immediately after an ERCP and prophylactic pancreatic duct stent placement (PPS) are associated with a reduction in the incidence of PEP. We sought to investigate the utilization rate for prophylactic rectal indomethacin and PPS in average and high-risk patients undergoing ERCP between 2014 and 2019. Patients and methods We performed a retrospective analysis in the IBM Explorys database, a pooled, national de-identified clinical database of over 72 million unique patients from 26 health care networks and 300 hospitals across the United States from 2014 to 2019. Average and high-risk patients undergoing ERCP were identified using Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) diagnosis codes. PEP was defined by the presence of SNOMED CT diagnosis of acute pancreatitis and an inpatient admission within 5 days of an ERCP procedure. Results Out of 31,050 adults who had undergone ERCP from 2014 to 2019, only 10,500 individuals (33.8 %) had a PEP prophylaxis. Rectal indomethacin and PPS accounted for 82.4 % and 12.9 % respectively. Individuals with three risk factors had the highest PEP rates followed by individuals with two risk factors. Conclusions Only one-third of all patients undergoing ERCP received prophylaxis in the form of rectal indothemacin and/or PPS in this large population-based data. Increased implementation of prophylactic use is needed in patients undergoing ERCP as supported by current guidelines.

We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI’s efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.

Joy H Lewis,1 Kate Whelihan,1 Debosree Roy21Department of Public Health, A.T. Still University School of Osteopathic Medicine in Arizona, Mesa, AZ, USA; 2A.T. Still Research Institute, A.T. Still University Arizona School of Health Sciences, Mesa, AZ, USACorrespondence: Joy H LewisDepartment of Public Health, A.T. Still University School of Osteopathic Medicine in Arizona, 5850 E. Still Circle, Mesa, AZ 85206, USATel +1 307 200 7009Fax +1 480 219 6159Email jhlewis@atsu.eduPurpose: Social determinants of health (SDH) are responsible for significant health disparities, morbidity and mortality. It is important to acculturate trainees to identify and document SDH. This can elevate their perceptions related to the importance and relevance of SDH. Documentation can encourage trainees to see SDH as factors which medical providers should address.Patients and methods: Researchers devised a novel approach to demonstrate the value of SDH to undergraduate medical students. Proprietary diagnostic codes for SDH and procedure codes for action taken to address them, were developed. Students were encouraged to log these into electronic records for clinical encounters. Students’ voluntary use of these codes was evaluated. Additionally, students were surveyed on their familiarity with the concept of SDH, their perceptions of the importance of SDH, as well as documenting SDH, twice in the study period, and results were compared. In their second year of use, proprietary codes were compared to newly available SDH related ICD-10 codes.Results: Students utilized proprietary codes more often than SDH related ICD-10 codes. Over 20,000 codes were logged. Comparison of survey items showed modest increases in students’ positive perception about the role of SDH in patient health.Conclusion: Students’ voluntary logging of SDH codes demonstrates they perceived these factors to be important and relevant to patient encounters. Future analyses will examine students’ knowledge, attitudes, beliefs and practice patterns related to SDH.Keywords: social determinants of health, medical education, constructivist learning, electronic health record

Abstract Widespread recent volcanic rocks occur across the Cordillera landward of the current/recent volcanic arc Mexico to Alaska and most other subduction backarcs. We conclude that most are produced by partial melt in the upper asthenosphere where two conditions are met: (1) thin lithosphere, shallow hot asthenosphere. Most of the Cordillera is uniformly hot with thin lithosphere such that the hot asthenosphere extends up to a sufficiently shallow depth to intersects the wet solidus; (2) wet upper asthenosphere. There is substantial water in the upper asthenosphere that reduces the solidus sufficiently for partial melting. We integrate geochemical analyses that constrain the partial melt source temperature and depth, seismic velocities that define the upper mantle temperature and partial melt zones, and seismic receiver functions that define the lithosphere‐asthenosphere boundary (LAB). Geochemical data for the Canadian Cordillera are integrated with data from the western United States. Upper mantle xenoliths indicate a dry strong lithosphere, 250 ppm, is indicated by the volcanics, facilitating small‐scale convection. Geochemical equilibration averages ∼1,350°C, at ∼65 km. Receiver functions also define the LAB at ∼65 km for the western Cordillera, deeper in the eastern US Cordillera, and asthenosphere tomography velocities indicate ∼1,350°C. Low velocities above ∼150 km suggest a few percent partial melt that percolates upward and ponds at the base of the lithosphere until enough accumulates to locally penetrate upward. The 65‐km depth may be controlled by the spinel‐garnet phase transition. Mechanisms are discussed for the spatial distribution of recent volcanics.

Undiagnosed concussions increase risk of additional injuries and can prolong recovery. Because of the difficulties recognizing concussive symptoms, concussion education must specifically target improving athlete concussion reporting. Many concussion education programs are designed without significant input from athletes, resulting in a less enjoyable athlete experience, with potential implications on program efficacy. Athlete enjoyment of previous concussion education programs moderates the improvement in concussion-reporting intention after experiencing the research version of CrashCourse (CC) concussion education. Prospective cohort study. Level of evidence: Level IV. Quantitative assessment utilizing ANOVA with moderation analysis of 173 male high school football players, aged 13 to 17, who completed baseline assessments of concussion knowledge, concussion reporting, and attitudes about prior educational interventions. Athletes were subsequently shown CC, before a follow-up assessment was administered assessing the same domains. At baseline, only 58.5% of athletes reported that they enjoyed their previous concussion education. After CC, athletes were significantly more likely to endorse that they would report a suspected concussion (from 69.3% of athletes to 85.6%; P

Summary: Reactivation of human immunodeficiency virus 1 (HIV-1) from latently infected T cells is a critical barrier to cure patients. It remains unknown whether reactivation of individual latent cells occurs stochastically in response to latency reversal agents (LRAs) or is a deterministic outcome of an underlying cell state. To characterize these single-cell responses, we leverage the classical Luria-Delbrück fluctuation test where single cells are isolated from a clonal population and exposed to LRAs after colony expansion. Data show considerable colony-to-colony fluctuations with the fraction of reactivating cells following a skewed distribution. Modeling systematic measurements of fluctuations over time uncovers a transient heritable memory that regulates HIV-1 reactivation, where single cells are in an LRA-responsive state for a few weeks before switching back to an irresponsive state. These results have enormous implications for designing therapies to purge the latent reservoir and further utilize fluctuation-based assays to uncover hidden transient cellular states underlying phenotypic heterogeneity.

Pitch is an important perceptual feature; however, it is poorly understood how its cortical correlates are shaped by absolute vs relative fundamental frequency (f0), and by neural adaptation. In this study, we assessed transient and sustained auditory evoked fields (AEFs) at the onset, progression, and offset of short pitch height sequences, taking into account the listener's musicality. We show that neuromagnetic activity reflects absolute f0 at pitch onset and offset, and relative f0 at transitions within pitch sequences; further, sequences with fixed f0 lead to larger response suppression than sequences with variable f0 contour, and to enhanced offset activity. Musical listeners exhibit stronger f0-related AEFs and larger differences between their responses to fixed vs variable sequences, both within sequences and at pitch offset. The results resemble prominent psychoacoustic phenomena in the perception of pitch contours; moreover, they suggest a strong influence of adaptive mechanisms on cortical pitch processing which, in turn, might be modulated by a listener's musical expertise.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

Background. Kidney transplantation with hepatitis C viremic (dHCV+) donors appears safe for recipients without HCV when accompanied by direct acting antiviral (DAA) treatment. However, US programs have been reluctant to embrace this approach due to concern about insurance coverage. While the cost of DAA treatment is currently offset by the reduction in waiting time, increased competition for dHCV+ organs may reduce this advantage. This analysis sought to demonstrate the financial benefit of dHCV+ transplant for third-party health insurers to expand coverage availability. Methods. An economic analysis was developed using a Markov model for 2 decisions: first, to accept a dHCV+ organ versus wait for a dHCV uninfected organ; or second, accept a high kidney donor profile index (KDPI) (>85) organ versus wait for a better quality dHCV+ organ. The analysis used Medicare payments, historical survival data, cost report data, and an estimated cost of DAA of $29 874. Results. In the first analysis, using dHCV+ kidneys reduced the cost of end-stage kidney disease care if the wait for a dHCV uninfected organ exceeded 11.5 months. The financial breakeven point differed according to the cost of DAA treatment. In the second analysis, declining a high-KDPI organ in favor of a waiting dHCV+ organ was marginally clinically beneficial if waiting times were

Cryptosporidium species subtypes are generally identified via DNA sequencing of the gp60 gene tandem repeat motif region. Due to the immunogenic nature of its glycoprotein products, gp60 is subject to host selective pressures, genetic recombination and evolutionary processes that drive extensive polymorphism at this locus. The elucidation of the polymorphic nature of this gene has led to the current mainstay in Cryptosporidium subtyping nomenclature.This study aimed to develop a real-time polymerase chain reaction based method utilising a post-PCR application, high resolution melting (HRM) analysis, in conjunction with the abovementioned gp60 nomenclature system, in order to differentiate between Cryptosporidium parvum gp60 subtypes. Subtype differentiation is based on the difference between the melting temperatures of individual subtypes conferred by variations in the polymorphic region of gp60.• Nested gp60 primers were designed to amplify a target region of

Abstract Background The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM coupled with PCR amplification of a suitable target. Results Mycobacterium smegmatis was used as a model organism to provide a proof of principle for a method to recover bacteria from a stained sample on a glass slide using a laser capture system. Ziehl-Neelsen (ZN) stained cells were excised and catapulted into tubes. Recovered cells were subjected to DNA extraction and pre-amplified with multiple displacement amplification (MDA). This system allowed a minimum of 30 catapulted cells to be detected following a nested real-time PCR assay, using rpoB specific primers. The combination of MDA and nested real-time PCR resulted in a 30-fold increase in sensitivity for the detection of low numbers of cells isolated using LCM. Conclusions This study highlights the potential of LCM coupled with MDA as a tool to improve the recovery of amplifiable nucleic acids from archived glass slides. The inclusion of the MDA step was essential to enable downstream amplification. This platform should be broadly applicable to a variety of diagnostic applications and we have used it as a proof of principle with a Mycobacterium sp. model system.

Seaweeds are potentially sustainable crops and are receiving significant interest because of their rich bioactive compound content; including fatty acids, polyphenols, carotenoids, and complex polysaccharides. However, there is little information on the in vivo effects on gut health of the polysaccharides and their low-molecular-weight derivatives. Herein, we describe the first investigation into the prebiotic potential of low-molecular-weight polysaccharides (LMWPs) derived from alginate and agar in order to validate their in vivo efficacy. We conducted a randomized; placebo-controlled trial testing the impact of alginate and agar LWMPs on faecal weight and other markers of gut health and on composition of gut microbiota. We show that these LMWPs led to significantly increased faecal bulk (20–30%). Analysis of gut microbiome composition by sequencing indicated no significant changes attributable to treatment at the phylum and family level, although FISH analysis showed an increase in Faecalibacterium prausnitzii in subjects consuming agar LMWP. Sequence analysis of gut bacteria corroborated with the FISH data, indicating that alginate and agar LWMPs do not alter human gut microbiome health markers. Crucially, our findings suggest an urgent need for robust and rigorous human in vivo testing—in particular, using refined seaweed extracts.