Operant demand and public health

Collaboration rules: A narrative comparison of engineering students and practicing engineers' collaboration experiences and beliefs using structuration theory

Abstract Background Collaboration—including coordination, communication, and teamwork—is crucial to engineering practice. However, engineering students are often perceived as lacking key collaboration skills at the time of graduation. Purpose We used structuration theory to explore how differences between students and practitioners' collaboration beliefs related to differences between academic and professional collaboration contexts. We sought to demonstrate that the perceived collaboration “skill gap” in engineering students can be explained by differences between academic and professional social systems. Methods We conducted interviews with 30 undergraduate engineering students and 28 practicing engineers, and from these interviews produced 98 discrete narratives of participants' collaboration experiences. We thematically analyzed these 98 collaboration narratives to identify student and practitioner collaboration beliefs. We further coded four narratives for organizational enablements and constraints to show how differences in student and practitioner collaboration beliefs related to differences in organizational collaboration “rules.” Findings Students described boosting productivity through teamwork and limiting social bonding with teammates. These beliefs represented reasonable approaches to collaboration given observed organizational constraints including short project durations, single‐discipline teams, and an inability to choose teammates. Practitioner beliefs about the importance of cross‐functional collaboration and building collaborator rapport across projects reflected organizational enablements that facilitated collaborations with these qualities. Conclusions Students' beliefs about appropriate academic collaboration practices did not translate to professional contexts. Instructors can prepare students for work by strategically easing collaboration constraints to allow for more diverse collaboration experiences. Work mentors should explain the collaboration expectations of their workplaces to facilitate new hire socialization.

Stream pathogenic bacteria levels rebound post‐population control of wild pigs

Abstract The range and density of one of North America's most destructive and invasive mammalian species, wild pigs ( Sus scrofa ), has expanded rapidly over the past several decades. Alongside this growth, their fecal contamination of surface waters has impaired water quality through significantly increased levels of pathogenic bacteria, raising concerns over the potential for zoonotic disease transmission. Significant remediation of these water quality impacts has been shown as a result of reductions in wild pig populations due to control efforts; however, the duration of these remediation effects as populations rebound remains unclear. Our study sought to determine the longevity of water quality remediation resulting from wild pig population control efforts. We found that median concentrations of Escherichia coli and fecal coliform (CFU/100 mL) increased by 746% and 159% in the year following the conclusion of removal efforts, resulting in median concentrations of 79% and 159% greater than those observed prior. We also found increased public health risk, with samples exceeding E. coli and fecal coliform guidelines 10% and 12% more often than pre‐removal, respectively. While further research into wild pig population dynamics and fecal contamination is necessary, we conclude that ongoing population control efforts may be necessary to remediate water quality impacts and public health risks associated with invasive wild pigs.

Inhibitors of Tax1‐PDZ Interactions Block HTLV‐1 Viral Transmission by Changing EV Composition

ABSTRACT Extracellular vesicles (EVs) are known to facilitate infection by enveloped RNA viruses including the Human T‐cell leukemia virus type‐1 (HTLV‐1). HTLV‐1‐encoded proteins, like the transactivator and oncoprotein Tax‐1, are loaded into EVs but their precise impact on EV cargos is not yet known. Here, we report a comprehensive interaction map between Tax‐1 and the human PDZ (PSD95/DLG/ZO‐1) proteins that regulate EVs formation and composition. We show that Tax‐1 interacts with more than one‐third of hPDZome components, including proteins involved in cell cycle, cell–cell junctions, cytoskeleton organization and membrane complex assembly. We extensively characterized Tax‐1 interaction with syntenin‐1, an evolutionary conserved PDZ hub that controls EV biogenesis. Using nuclear magnetic resonance (NMR) spectroscopy, we have determined the structural basis of the interaction between the C ‐terminal PDZ binding motif of Tax‐1, and two PDZ domains of syntenin‐1. Importantly, we show that a small molecule able to inhibit HTLV‐1 cell‐to‐cell transmission breaks the Tax‐1/syntenin‐1 interaction, impacts the levels of syntenin‐1 and viral proteins in EVs, and shifts the EV composition toward cellular antiviral proteins and microRNAs, including the miR‐320 family. Consequently, we demonstrate that mimics of miR‐320c, encapsulated into EVs, have antiviral activities with a potential to be used against HTLV‐1 induced diseases.

Mechanistic insight into human milk extracellular vesicle‐intestinal barrier interactions

Abstract Human milk extracellular vesicles (EVs) are crucial mother‐to‐baby messengers that transfer biological signals. These EVs are reported to survive digestion and transport across the intestine. The mechanisms of interaction between human milk EVs and the intestinal mucosa, including epithelial uptake remain unclear. Here, we studied the interaction of human milk EVs with the gut barrier components, including intestinal biofluids, enzymes, mucus and epithelium. Additionally, we probed the endocytic mechanisms mediating the EV intestinal uptake. Finally, using proteomic analysis, we determined the existence and identification of proteins enriched in the EV fraction transported across the intestinal epithelium. We show that human milk EVs are largely stable in the biochemical gut barriers and demonstrate high mucus diffusivity. EVs show a high level of epithelial cell uptake (∼70%) and efficient transport across Caco‐2 monolayers. Whilst cell uptake of EVs was mediated by multiple routes, none of the pathway‐specific inhibitors inhibited their epithelial translocation. Proteomic analysis of EVs transported across Caco‐2 monolayers identified 14 enriched EV proteins that may facilitate intestinal transport. These findings significantly expand our understanding of the interactions between human milk EVs and the gut barriers, including their intestinal uptake.

Outer Membrane Vesicles From Bacteroides fragilis Contain Coding and Non‐Coding Small RNA Species That Modulate Inflammatory Signalling in Intestinal Epithelial Cells

ABSTRACT Alterations to the community structure and function of the microbiome are associated with changes to host physiology, including immune responses. However, the contribution of microbe‐derived RNAs carried by outer membrane vesicles (OMVs) to host immune responses remains unclear. This study investigated the role of OMVs and OMV‐associated small RNA (sRNA) species from pathogenic and commensal Bacteroides fragilis (ETBF and NTBF, respectively) in eliciting different immune responses from intestinal epithelial cells. To distinguish the differences in the sRNA profiles of the two strains and their OMVs, RNA‐seq, qRT‐PCR, and northern blotting were conducted to identify enrichment of discrete sRNA species in OMVs, which were also differentially expressed between the two strains. Specifically, coding and non‐coding RNAs were enriched in OMVs from NTBF and ETBF, with BF9343_RS22680 and BF9343_RS17870 being significantly enriched in ETBF OMVs compared to NTBF. To understand the effects of OMVs on pattern recognition receptors, reporter cells of Toll‐like receptor (TLR) activation were treated with OMVs, demonstrating activation of TLRs 2, 3, and 7. Treatment of Caco‐2 and HT29‐MTX cells with OMVs demonstrated increased expression of IL‐8. Surprisingly, we discovered that degradation of RNase‐accessible RNAs within ETBF OMVs, but not NTBF OMVs, resulted in vesicles with enhanced capacity to stimulate IL‐8 expression, indicating that these extravesicular RNAs exert an immunosuppressive effect. This suggests a dual role for OMV‐associated RNAs in modulating host immune responses, with implications for both bacterial pathogenesis and therapeutic applications.

Development of a Japanese version of the patient perceptions of deprescribing – Short form

Abstract Background Deprescribing is a critical component of clinical practice, especially in geriatric medicine. Nevertheless, the attributes of patients who are prepared for, interested in, and could potentially benefit from deprescribing have not been well examined. The Patient Perceptions of Deprescribing (PPoD) evaluates patients' overall readiness for deprescribing and is complemented by an 11‐item validated short form (SF‐PPoD). The objective of this study was to develop a Japanese version of the SF‐PPoD and assess its reliability and validity within Japanese older adults with polypharmacy. Methods The SF‐PPoD was translated, back‐translated, and assessed in a cognitive interview. We conducted a cross‐sectional survey with 196 patients aged 65 years or older with five or more medications using the Japanese version to test for reliability and validity. We examined internal consistency and construct validity to determine if the Japanese sample responses reproduce the two subscales in the original SF‐PPoD. Finally, we examined intra‐person replicability using the intraclass correlation coefficient, in which 100 participants were invited and 93 participated. Results 118 males and 78 females, with a mean age of 79.2 [SD 6.5] years, completed the survey. Confirmatory factor analysis of the Japanese version of SF‐PPoD revealed satisfactory structural validity with two‐dimensional structure, “Motivation for Deprescribing” and “Primary Care Physician Relationship.” Cronbach's alpha showed good internal consistency, and test–retest demonstrated acceptable intra‐rater reliability. Conclusions We developed and validated a Japanese version of SF‐PPoD with an 11‐item, two‐dimensional structure consistent with the original SF‐PPoD. This scale may facilitate shared decision‐making for medication optimization among older adults living with multimorbidity.

Independent Sets of Random Trees and Sparse Random Graphs

ABSTRACT An independent set of sizekin a finite undirected graphGis a set ofkvertices of the graph, no two of which are connected by an edge. Letx k ( G )be the number of independent sets of sizekin the graphGand letα ( G ) = max { k ≥ 0 : x k ( G ) ≠ 0 }. In 1987, Alavi, Malde, Schwenk, and Erdős asked if the independent set sequencex 0 ( G ) , x 1 ( G ) , … , x α ( G )( G )of a tree is unimodal (the sequence goes up and then down). This problem is still open. In 2006, Levit and Mandrescu showed that the last third of the independent set sequence of a tree is decreasing. We show that the first 46.8% of the independent set sequence of a random tree is increasing with (exponentially) high probability as the number of vertices goes to infinity. So, the question of Alavi, Malde, Schwenk, and Erdős is “four‐fifths true,” with high probability. We also show unimodality of the independent set sequence of Erdős–Rényi random graphs, when the expected degree of a single vertex is large (with [exponentially] high probability as the number of vertices in the graph goes to infinity, except for a small region near the mode). A weaker result is shown for random regular graphs. The structure of independent sets of sizekaskvaries is of interest in probability, statistical physics, combinatorics, and computer science.

Chronic Severe Neutropenia Associated With Intravenous Immunoglobulin for Multifocal Motor Neuropathy

ABSTRACT Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy derived from pooled donor immunoglobulins and used for treatment of various autoimmune conditions. Here we report the diagnosis and management of IVIG‐induced chronic severe neutropenia with absolute neutrophil count <0.5×10 3 /µL in a patient with multifocal motor neuropathy. Serial blood count showed a cyclical pattern of neutropenia: worsening 24–48 h post‐IVIG, then gradually improving before the next infusion. IVIG‐induced neutropenia is rare, with previous reports of predominantly mild transient neutropenia. Our case describes chronic severe neutropenia that developed years after starting IVIG. We summarize available evidence and management strategies for IVIG‐associated neutropenia.

Safety, Efficacy, and Patient‐Reported Outcomes From a Phase 2 Randomized Trial of Pozelimab and Cemdisiran Combination in Patients With Paroxysmal Nocturnal Hemoglobinuria

ABSTRACT Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra‐rare, life‐threatening disease associated with chronic intravascular hemolysis due to uncontrolled complement activation. PNH results in anemia with an increased risk of thrombosis, and often causes severe fatigue, and decreased physical function and health‐related quality of life (QoL). We investigated the efficacy, safety, and patient‐reported outcomes data of the combination of pozelimab (a fully human monoclonal antibody) and cemdisiran (an N ‐acetylgalactosamine‐conjugated small interfering ribonucleic acid) from a Phase 2 trial (NCT04811716) in patients with PNH who transitioned from pozelimab monotherapy. Methods In this randomized, open‐label, Phase 2 study, patients were randomized (1:1) to one of two treatment arms; both arms received subcutaneous cemdisiran 200 mg every 4 weeks (Q4W) plus subcutaneous pozelimab 400 mg either Q4W (Arm 1) or every 2 weeks (Arm 2). Results Twenty‐four patients were treated with combination dosing. During the 28‐week open‐label treatment period (OLTP), 20 patients (83.3%) maintained control of lactate dehydrogenase (≤ 1.5 × upper limit of normal) at all timepoints. The majority of patients (92%) did not require a blood transfusion. While most patients (66.7%) experienced treatment‐emergent adverse events, the majority of these events were mild to moderate in severity. No meningococcal infections, thrombotic events, or deaths were reported. The combination therapy maintained improvements in patient‐reported fatigue, physical functioning, and QoL throughout the OLTP. Conclusion Combination treatment maintained adequate hemolysis control and was generally well tolerated. Administration of pozelimab Q2W did not improve disease control as compared to pozelimab Q4W. Trial Registration ClinicalTrials.gov/NCT04811716