Translating clinical and patient-reported data to tailored shared decision reports with predictive analytics for knee and hip arthritis

INTRODUCTION: New informatics tools can transform evidence-based information to individualized predictive reports to serve shared decisions in clinic. We developed a web-based system to collect patient-reported outcomes (PROs) and medical risk factors and to compare responses to national registry data. The system generates predicted outcomes for individual patients and a report for use in clinic to support decisions. We present the report development, presentation, and early experience implementing this PRO-based, shared decision report for knee and hip arthritis patients seeking orthopedic evaluation. METHODS: Iterative patient and clinician interviews defined report content and visual display. The web-system supports: (a) collection of PROs and risk data at home or in office, (b) automated statistical processing of responses compared to national data, (c) individualized estimates of likely pain relief and functional gain if surgery is elected, and (d) graphical reports to support shared decisions. The system was implemented at 12 sites with 26 surgeons in an ongoing cluster randomized trial. RESULTS: Clinicians and patients recommended that pain and function as well as clinical risk factors (e.g., BMI, smoking) be presented to frame the discussion. Color and graphics support patient understanding. To date, 7891 patients completed the assessment before the visit and 56% consented to study participation. Reports were generated for 98% of patients and 68% of patients recalled reviewing the report with their surgeon. CONCLUSIONS: Informatics solutions can generate timely, tailored office reports including PROs and predictive analytics. Patients successfully complete the pre-visit PRO assessments and clinicians and patients value the report to support shared surgical decisions

Universal Relationship between Conductivity and Solvation-Site Connectivity in Ether-Based Polymer Electrolytes

We perform a joint experimental and computational study of ion transport properties in a systematic set of linear polyethers synthesized via acyclic diene metathesis (ADMET) polymerization. We measure ionic conductivity, σ, and glass transition temperature, T_g, in mixtures of polymer and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt. While T_g is known to be an important factor in the ionic conductivity of polymer electrolytes, recent work indicates that the number and proximity of lithium ion solvation sites in the polymer also play an important role, but this effect has yet to be systematically investigated. Here, adding aliphatic linkers to a poly(ethylene oxide) (PEO) backbone lowers T_g and dilutes the polar groups; both factors influence ionic conductivity. To isolate these effects, we introduce a two-step normalization scheme. In the first step, Vogel–Tammann–Fulcher (VTF) fits are used to calculate a temperature-dependent reduced conductivity, σ_r(T), which is defined as the conductivity of the electrolyte at a fixed value of T – T_g. In the second step, we compute a nondimensional parameter f_(exp), defined as the ratio of the reduced molar conductivity of the electrolyte of interest to that of a reference polymer (PEO) at a fixed salt concentration. We find that f_(exp) depends only on oxygen mole fraction, x_0, and is to a good approximation independent of temperature and salt concentration. Molecular dynamics simulations are performed on neat polymers to quantify the occurrences of motifs that are similar to those obtained in the vicinity of isolated lithium ions. We show that f_(exp) is a linear function of the simulation-derived metric of connectivity between solvation sites. From the relationship between σ_r and f_(exp) we derive a universal equation that can be used to predict the conductivity of ether-based polymer electrolytes at any salt concentration and temperature

Aborted microspores acts as a master regulator of pollen wall formation in Arabidopsis

Mature pollen is covered by durable cell walls, principally composed of sporopollenin, an evolutionary conserved, highly resilient, but not fully characterized, biopolymer of aliphatic and aromatic components. Here, we report that ABORTED MICROSPORES (AMS) acts as a master regulator coordinating pollen wall development and sporopollenin biosynthesis in Arabidopsis thaliana. Genome-wide coexpression analysis revealed 98 candidate genes with specific expression in the anther and 70 that showed reduced expression in ams. Among these 70 members, we showed that AMS can directly regulate 23 genes implicated in callose dissociation, fatty acids elongation, formation of phenolic compounds, and lipidic transport putatively involved in sporopollenin precursor synthesis. Consistently, ams mutants showed defective microspore release, a lack of sporopollenin deposition, and a dramatic reduction in total phenolic compounds and cutin monomers. The functional importance of the AMS pathway was further demonstrated by the observation of impaired pollen wall architecture in plant lines with reduced expression of several AMS targets: the abundant pollen coat protein extracellular lipases (EXL5 and EXL6), and CYP98A8 and CYP98A9, which are enzymes required for the production of phenolic precursors. These findings demonstrate the central role of AMS in coordinating sporopollenin biosynthesis and the secretion of materials for pollen wall patterning

Genetic risk, adherence to healthy lifestyle and acute cardiovascular and thromboembolic complications following SARS-COV-2 infection

Current understanding of determinants for COVID-19-related cardiovascular and thromboembolic (CVE) complications primarily covers clinical aspects with limited knowledge on genetics and lifestyles. Here, we analysed a prospective cohort of 106,005 participants from UK Biobank with confirmed SARS-CoV-2 infection. We show that higher polygenic risk scores, indicating individual's hereditary risk, were linearly associated with increased risks of post-COVID-19 atrial fibrillation (adjusted HR 1.52 [95% CI 1.44 to 1.60] per standard deviation increase), coronary artery disease (1.57 [1.46 to 1.69]), venous thromboembolism (1.33 [1.18 to 1.50]), and ischaemic stroke (1.27 [1.05 to 1.55]). These genetic associations are robust across genders, key clinical subgroups, and during Omicron waves. However, a prior composite healthier lifestyle was consistently associated with a reduction in all outcomes. Our findings highlight that host genetics and lifestyle independently affect the occurrence of CVE complications in the acute infection phrase, which can guide tailored management of COVID-19 patients and inform population lifestyle interventions to offset the elevated cardiovascular burden post-pandemic.</p

Variation in Suicide Risk among Subgroups of Sexual and Gender Minority College Students

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163395/2/sltb12637_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163395/1/sltb12637.pd

9G4 Autoreactivity Is Increased in HIV-Infected Patients and Correlates with HIV Broadly Neutralizing Serum Activity

The induction of a broadly neutralizing antibody (BNAb) response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs) have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE) patients, both of which positively correlated with HIV viral load. Compared to the global 9G4−IgD− memory B cell population, the 9G4+IgD− memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward “IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019) with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL) did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in tolerance, but rather a more intricate expansion of selective autoreactive B cells and antibodies

Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin‐1

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101864/1/expphysiol.2013.074930.pd

Signalling pathways regulating galactosaminoglycan synthesis and structure in vascular smooth muscle: implications for lipoprotein binding and atherosclerosis

Atherosclerosis commences with the trapping of low density lipoproteins (LDLs) in blood vessels by modified proteoglycans (PGs) with hyperelongated glycosaminoglycan (GAG) chains. GAG chain synthesis and growth factor mediated hyperelongation regulates the composition and size of PGs in a manner that would cause low density lipoprotein (LDLs) retention in vessel wall. Galactosaminoglycans are a class of GAGs, commonly observed on PGs. Multiple enzymes are involved in galactosaminoglycan biosynthesis. Galactosaminoglycan synthesis is regulated by various signalling pathways which are amenable to pharmacological manipulation to treat atherosclerosis. Receptor mediated signalling pathways including protein tyrosine kinase receptors (PTKRs), serine/threonine kinase receptors (S/TKRs) and G-protein coupled receptors (GPCRs) pathways regulate galactosaminoglycan synthesizing enzyme expression. Increased expression of these enzymes modify galactosaminoglycan chain structure by making them hyperelongated. This review focuses on the signalling pathways regulating the expression of genes involved in galactosaminoglycan synthesis and modification. Furthemore, there are multiple other processes for inhibiting the interactions between LDL and galactosaminoglycans such as peptide mimetics of ApoB100 and anti-galactosaminoglycan antibodies and the therapeutic potential of these strategies is also addressed

Universal Relationship between Conductivity and Solvation-Site Connectivity in Ether-Based Polymer Electrolytes

We perform a joint experimental and computational study of ion transport properties in a systematic set of linear polyethers synthesized via acyclic diene metathesis (ADMET) polymerization. We measure ionic conductivity, σ, and glass transition temperature, T_g, in mixtures of polymer and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) salt. While T_g is known to be an important factor in the ionic conductivity of polymer electrolytes, recent work indicates that the number and proximity of lithium ion solvation sites in the polymer also play an important role, but this effect has yet to be systematically investigated. Here, adding aliphatic linkers to a poly(ethylene oxide) (PEO) backbone lowers T_g and dilutes the polar groups; both factors influence ionic conductivity. To isolate these effects, we introduce a two-step normalization scheme. In the first step, Vogel–Tammann–Fulcher (VTF) fits are used to calculate a temperature-dependent reduced conductivity, σ_r(T), which is defined as the conductivity of the electrolyte at a fixed value of T – T_g. In the second step, we compute a nondimensional parameter f_(exp), defined as the ratio of the reduced molar conductivity of the electrolyte of interest to that of a reference polymer (PEO) at a fixed salt concentration. We find that f_(exp) depends only on oxygen mole fraction, x_0, and is to a good approximation independent of temperature and salt concentration. Molecular dynamics simulations are performed on neat polymers to quantify the occurrences of motifs that are similar to those obtained in the vicinity of isolated lithium ions. We show that f_(exp) is a linear function of the simulation-derived metric of connectivity between solvation sites. From the relationship between σ_r and f_(exp) we derive a universal equation that can be used to predict the conductivity of ether-based polymer electrolytes at any salt concentration and temperature