Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study.

OBJECTIVES: Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another. METHODS: 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients. RESULTS: Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001]. CONCLUSION: Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout.

Brush-first synthesis of core-photodegradable miktoarm star polymers via ROMP: towards photoresponsive self-assemblies.

This report describes the synthesis of miktoarm brush-arm star polymers (BASPs) from branched and linear norbornene-terminated macromonomers (MMs) via the brush-first ring-opening metathesis polymerization (ROMP) method. First, a polystyrene (PS)-branch-poly(lactic acid) (PLA) MM is synthesized via a combination of atom transfer radical polymerization (ATRP), tin(II)-mediated ring opening polymerization, and copper-catalyzed azide-alkyne cycloaddition reactions. Graft-through ROMP of this MM followed by in situ cross-linking with a photo-cleavable bis-norbornene derivative provided nanoscopic BASPs with photodegradable cores and a precise 1:1 PS:PLA arm composition. Three-miktoarm BASPs are prepared in an analogous manner via copolymerization of the same PS-branch-PLA MM with a poly(ethylene glycol) (PEG) MM prior to cross-linking. Intramolecular phase segregation of these miktoarm BASPs is characterized by transmission electron microscopy (TEM); a UV-induced structural rearrangement from three-faced Janus particles to micelles is observed.

Microbial Metabolite Trimethylamine N-Oxide Promotes Campylobacter jejuni Infection by Escalating Intestinal Inflammation, Epithelial Damage, and Barrier Disruption.

The interactions between Campylobacter jejuni , a critical foodborne cause of gastroenteritis, and the intestinal microbiota during infection are not completely understood. The crosstalk between C. jejuni and its host is impacted by the gut microbiota through mechanisms of competitive exclusion, microbial metabolites, or immune response. To investigate the role of gut microbiota on C. jejuni pathogenesis, we examined campylobacteriosis in the IL10KO mouse model, which was characterized by an increase in the relative abundance of intestinal proteobacteria, E. coli , and inflammatory cytokines during C. jejuni infection. We also found a significantly increased abundance of microbial metabolite Trimethylamine N-Oxide (TMAO) in the colonic lumens of IL10KO mice. We further investigated the effects of TMAO on C. jejuni pathogenesis. We determined that C. jejuni senses TMAO as a chemoattractant and the administration of TMAO promotes C. jejuni invasion into Caco-2 monolayers. TMAO also increased the transmigration of C. jejuni across polarized monolayers of Caco-2 cells, decreased TEER, and increased C. jejuni -mediated intestinal barrier damage. Interestingly, TMAO treatment and presence during C. jejuni infection of Caco-2 cells synergistically caused an increased inflammatory cytokine expression, specifically IL-1ß and IL-8. These results establish that C. jejuni utilizes microbial metabolite TMAO for increased virulence during infection.

Protein-protein interactions with G3BPs drive stress granule condensation and gene expression changes under cellular stress.

Stress granules (SGs) are macromolecular assemblies that form under cellular stress. Formation of these condensates is driven by the condensation of RNA and RNA-binding proteins such as G3BPs. G3BPs condense into SGs following stress-induced translational arrest. Three G3BP paralogs (G3BP1, G3BP2A, and G3BP2B) have been identified in vertebrates. However, the contribution of different G3BP paralogs to stress granule formation and stress-induced gene expression changes is incompletely understood. Here, we identified key residues for G3BP condensation such as V11. This conserved amino acid is required for formation of the G3BP-Caprin-1 complex, hence promoting SG assembly. Total RNA sequencing and ribosome profiling revealed that disruption of G3BP condensation corresponds to changes in mRNA levels and ribosome engagement during the integrated stress response (ISR). Moreover, we found that G3BP2B preferentially condenses and promotes changes in mRNA expression under endoplasmic reticulum (ER) stress. Together, this work suggests that stress granule assembly promotes changes in gene expression under cellular stress, which is differentially regulated by G3BP paralogs.

Iron modified biochar enables recovery and recycling of phosphorus from wastewater through column filters and flow reactors.

Controlling water pollution by phosphorus (P) and satisfying high demand of P fertilizer in agriculture are two global challenges for sustainable development. This paper presents a novel application of iron modified biochar as an adsorbent to recover P from wastewater and reuse it as P fertilizer. Granular iron biochar (GIB) and ball milled powder iron biochar (PIB) were prepared from pinewood pretreated with iron salt. The biochars were characterized to determine their surface properties. Their effectiveness in P removal from wastewater was evaluated with packed column filters for GIB and continuous flow reactors for PIB. The spent biochar was tested to determine if it is safe for agricultural application as alternative P fertilizer. The results showed that GIB and PIB were highly porous, had high specific surface area (385 and 331 m2 g-1, respectively), and contained high levels of iron (mainly γ-Fe2O3). Both GIB and PIB showed excellent performance for P removal from wastewater. The P adsorption capacity of GIB in the column filter was 16 times larger than that of sand. A fast P adsorption kinetic rate (0.144 min-1) was observed for PIB in the flow reactor. The spent biochars showed no negative effects on bean germination or even some positive effects on seedling growth, indicating they can be safely used as P fertilizer. This study provides the technical basis of a sustainable wastewater treatment strategy that can capture the full values of water, P, and biochar.

Primary care providers' perceptions on the integration of community-led advance care planning activities with primary care: a cross-sectional survey.

BACKGROUND: Advance care planning (ACP) is a process intended to help ensure people receive medical care that is consistent with their values, goals, and preferences during serious and chronic illness. Barriers to implementing ACP in primary care settings exist. Community-led ACP initiatives exist in British Columbia to engage the public directly. These initiatives may help prepare people for conversations with their primary care providers. The objectives of this study were to elicit primary care providers' perceptions of the utility and desired content of community-led ACP activities and suggestions for integrating community-led ACP activities with primary care. METHODS: We conducted an online cross-sectional survey of primary care providers practicing in British Columbia, Canada in 2021. Both quantitative and qualitative survey questions addressed ACP engagement in practice, the perceived role and desired outcomes of community-led ACP activities, and ways to integrate community-led ACP activities with primary care. RESULTS: Eighty-one providers responded. Over 80% perceived a moderate or greater potential impact of community-led ACP activities. The most common reasons for not referring a patient to a community-led ACP activity were lack of awareness of the option locally (62.1%) and in general (44.8%). Respondents wanted their patients to reflect on their values, wishes and preferences for care, to have at least thought about their goals of care and to have chosen a substitute decision maker in the community. They indicated a desire for a summary of their patient's participation and a follow-up discussion with them about their ACP. They suggested ways to integrate referral to programs into existing health care system structures. CONCLUSIONS: Community-led ACP activities were perceived to be useful to engage and prepare patients to continue ACP discussions with clinicians. Efforts should be made to establish and integrate community-based ACP initiatives within existing primary care systems to ensure awareness and uptake.

Assessment of tophus size: a comparison between physical measurement methods and dual-energy computed tomography scanning.

BACKGROUND: Dual-energy computed tomography (DECT) has recently been described as a sensitive method to detect urate deposits in patients with gout. OBJECTIVES: The aim of this study was to compare the reproducibility of DECT with various physical measurement methods of tophus size assessment. METHODS: Sixty-four tophi from 25 patients were analyzed. Each tophus was assessed by 2 independent observers using Vernier calipers and tape measure. All patients proceeded to DECT scanning of both feet. Urate volume within index tophi was assessed by 2 independent observers using automated DECT volume assessment software (n = 55 tophi). Five patients returned within 1 week for repeat physical assessment of tophus size. Dual-energy computed tomography scans from the returning patients were scored twice by both observers. Intraobserver and interobserver reproducibility was assessed by intraclass correlation coefficient (ICC) and limits-of-agreement analysis. RESULTS: Overall, DECT was more reproducible than the physical methods with interobserver ICCs for DECT of 0.95, for calipers 0.78, and for tape measurement 0.88, and intraobserver ICCs for DECT of 1.00, for calipers 0.75, and for tape measurement 0.91. Vernier caliper and tape measurements correlated highly with each other (rs = 0.84, P < 0.0001) but less well with DECT (for index tophi, r(s) = 0.46, P = 0.004 for both). Large variation was observed in the amount of urate deposits documented by DECT in tophi of similar physical size. CONCLUSIONS: Dual-energy computed tomography scanning is a highly reproducible method for measuring urate deposits within tophi. This imaging modality reveals the composition of tophi that contain variable urate deposits embedded within soft tissue.

Life cycle assessment of environmental impact of disposable drinking straws: A trade-off analysis with marine litter in the United States.

Sound environmental management to control marine plastic pollution requires a careful assessment of environmental costs and benefits of replacing single-use plastics with their biodegradable counterparts. This research employs the standard life cycle assessment (LCA) approach to assess and compare the environmental impact of plastic straws made from polypropylene (PP), and its biodegradable alternatives made from polylactic acid (PLA) and paper (PA) in the United States. Eight environmental impact categories, not including marine litter, were analyzed and a composite relative environmental impact index (REI) was derived for quantitative comparison. The results show that US daily consumption of disposable drinking straws (500 million straws daily) may carry significant environmental burdens regardless of straw types, with the feedstock manufacture stage of the life cycle creating most of the contribution. The REI index values were 2.4 for PP straws, 6.4 for PLA straws, and 5.1 for PA straws with landfill and 3.2 for PP straws, 6.8 for PLA straws, and 4.9 for PA straws with incineration. A sensitivity analysis did not show much change in REI with increasing marine litter rate, demonstrating that replacing PP straws with PLA or PA straws for controlling marine plastic pollution would come with environmental costs in other categories. The trade-off can be quantitatively represented by the difference in REI between PP straws and PA or PLA straws. Our analysis also indicates close-loop recycling can greatly reduce the environmental impact of PP straws, serving as a technological development to control plastic pollution. While disposable straws were used as a case study in this work, the findings are extensive to other single-use products.

The health impacts of the COVID-19 pandemic on adults who experience imprisonment globally: A mixed methods systematic review.

BACKGROUND: The prison setting and health status of people who experience imprisonment increase the risks of COVID-19 infection and sequelae, and other health impacts of the COVID-19 pandemic. OBJECTIVES: To conduct a mixed methods systematic review on the impacts of the COVID-19 pandemic on the health of people who experience imprisonment. DATA SOURCES: We searched Medline, PsycINFO, Embase, the Cochrane Library, Social Sciences Abstracts, CINAHL, Applied Social Sciences Index and Abstracts, Sociological Abstracts, Sociology Database, Coronavirus Research Database, ERIC, Proquest Dissertations and Theses, Web of Science, and Scopus in October 2021. We reviewed reference lists for included studies. STUDY ELIGIBILITY CRITERIA: Original research conducted in or after December 2019 on health impacts of the COVID-19 pandemic on adults in prisons or within three months of release. STUDY APPRAISAL AND SYNTHESIS METHODS: We used the Joanna Briggs Institute's Critical Appraisal Checklist for Qualitative Research for qualitative studies and the Joanna Briggs Institute's Critical Appraisal Checklist for Studies Reporting Prevalence Data for quantitative studies. We qualitized quantitative data and extracted qualitative data, coded data, and collated similar data into categories. RESULTS: We identified 62 studies. People in prisons had disproportionately high rates of COVID-19 infection and COVID-19 mortality. During the pandemic, all-cause mortality worsened, access to health care and other services worsened, and there were major impacts on mental wellbeing and on relationships with family and staff. There was limited evidence regarding key primary and secondary prevention strategies. LIMITATIONS: Our search was limited to databases. As the COVID-19 pandemic is ongoing, more evidence will emerge. CONCLUSIONS: Prisons and people who experience imprisonment should be prioritized for COVID-19 response and recovery efforts, and an explicit focus on prisons is needed for ongoing public health work including emergency preparedness. PROSPERO REGISTRATION NUMBER: 239324.

Subjective social isolation or loneliness in older adults residing in social housing in Ontario: a cross-sectional study.

BACKGROUND: Older adults face greater risk of social isolation, but the extent of social isolation among low-income older adults living in social housing is unknown. This study aims to explore the rate of, and risk factors contributing to, subjective social isolation or loneliness among older adults in social housing. METHODS: We conducted a cross-sectional study of data collected from a community program held in the common rooms of 55 social housing buildings in 14 communities across Ontario, Canada, from May 2018 to April 2019. Participants were program attendees aged 55 years and older who resided in the buildings. Program implementers assessed social isolation using the 3-Item Loneliness Scale from the University of California, Los Angeles and risk factors using common primary care screening tools. We extracted data for this study from the program database. We compared the rate of social isolation to Canadian Community Health Survey data using a 1-sample χ2 test, and evaluated associations between risk factors and social isolation using univariate and multivariate logistic regressions. RESULTS: We included 806 residents in 30 buildings for older adults and 25 mixed-tenant buildings. Based on the 3-Item UCLA Loneliness Scale, 161 (20.0%) of the 806 participants were socially isolated. For those aged 65 and older, the rate of social isolation was nearly twice that observed in the same age group of the general population (36.1% v. 19.6%; p < 0.001). Risk factors were age (65-84 yr v. 55-64 yr adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01-3.93), alcohol consumption (adjusted OR 2.45, 95% CI 1.09-5.54), anxiety or depression (adjusted OR 6.05, 95% CI 3.65-10.03) and income insecurity (adjusted OR 2.10, 95% CI 1.24-3.53). Protective factors were having at least 1 chronic cardiometabolic disease (adjusted OR 0.44, 95% CI 0.24-0.80), being physically active (adjusted OR 0.47, 95% CI 0.30-0.73) and having good to excellent general health (adjusted OR 0.60, 95% CI 0.39-0.90). INTERPRETATION: The high rate of social isolation in low-income older adults living in social housing compared with the general population is concerning. Structural barriers could prevent engagement in social activities or maintenance of social support, especially for older adults with income insecurity and anxiety or depression; interventions are needed to reduce subjective social isolation in this population.

Correlation of the multifocal visual evoked potential and standard automated perimetry in compressive optic neuropathies.

PURPOSE: To evaluate the relationship between abnormalities detected by the multifocal visual-evoked potential (mfVEP) compared with those detected by static achromatic automated perimetry in patients with compressive optic neuropathy. METHODS: Fifteen patients of mean age 50.8 years, with known compressive optic neuropathy from chiasmal lesions, underwent monocular mfVEP and 24-2 SITA-standard Humphrey visual field (HVF; Carl Zeiss Meditec, Dublin CA) testing in each eye. Visual field spatial agreement and extent of involvement were analyzed by assigning a severity score to each quadrant, based on pattern deviation and amplitude deviation probability plots. RESULTS: HVF mean deviation (MD) was -6.54 +/- 7.43 dB (mean), and the mfVEP mean AccuMap Severity Index (ASI; ObjectiVision Pty. Ltd., Sydney, Australia) score was 81 +/- 74. MD and ASI correlated significantly (r = -0.55, P = 0.024). Although both mfVEP and HVF reported approximately the same proportion of visual fields as abnormal (70%, 21/30, and 87%, 26/30, respectively), 19% (5/26) with abnormal HVF were labeled normal or borderline by mfVEP. The agreement for field quadrants between instruments was 69% (kappa = 0.33). mfVEP severity scores for quadrants and hemifields were higher than scores for HVF in the same eyes. The superotemporal quadrant showed the strongest correlation between techniques (r = 0.73, P = 0.002). CONCLUSIONS: In the first study to compare mfVEP to HVF in patients with compressive optic neuropathy, there was good qualitative and quantitative agreement between tests, though findings were in only modest agreement in some areas. The injury caused by compressive optic neuropathy may be usefully identified by mfVEP. Improved methods of analysis may increase the diagnostic utility of the method.

Iterative exponential growth of stereo- and sequence-controlled polymers.

Chemists have long sought sequence-controlled synthetic polymers that mimic nature's biopolymers, but a practical synthetic route that enables absolute control over polymer sequence and structure remains a key challenge. Here, we report an iterative exponential growth plus side-chain functionalization (IEG+) strategy that begins with enantiopure epoxides and facilitates the efficient synthesis of a family of uniform >3 kDa macromolecules of varying sequence and stereoconfiguration that are coupled to produce unimolecular polymers (>6 kDa) with sequences and structures that cannot be obtained using traditional polymerization techniques. Selective side-chain deprotection of three hexadecamers is also demonstrated, which imbues each compound with the ability to dissolve in water. We anticipate that these new macromolecules and the general IEG+ strategy will find broad application as a versatile platform for the scalable synthesis of sequence-controlled polymers.

Synthesis of Acid-Labile PEG and PEG-Doxorubicin-Conjugate Nanoparticles via Brush-First ROMP.

A panel of acid-labile bis-norbornene cross-linkers was synthesized and evaluated for the formation of acid-degradable brush-arm star polymers (BASPs) via the brush-first ring-opening metathesis polymerization (ROMP) method. An acetal-based cross-linker was identified that, when employed in conjunction with a poly(ethylene glycol) (PEG) macromonomer, provided highly controlled BASP formation reactions. A combination of this new cross-linker with a novel doxorubicin (DOX)-branch-PEG macromonomer provided BASPs that simultaneously degrade and release cytotoxic DOX in vitro.

Particles without a box: brush-first synthesis of photodegradable PEG star polymers under ambient conditions.

Convenient methods for the rapid, parallel synthesis of diversely functionalized nanoparticles will enable discovery of novel formulations for drug delivery, biological imaging, and supported catalysis. In this report, we demonstrate parallel synthesis of brush-arm star polymer (BASP) nanoparticles by the "brush-first" method. In this method, a norbornene-terminated poly(ethylene glycol) (PEG) macromonomer (PEG-MM) is first polymerized via ring-opening metathesis polymerization (ROMP) to generate a living brush macroinitiator. Aliquots of this initiator stock solution are added to vials that contain varied amounts of a photodegradable bis-norbornene crosslinker. Exposure to crosslinker initiates a series of kinetically-controlled brush+brush and star+star coupling reactions that ultimately yields BASPs with cores comprised of the crosslinker and coronas comprised of PEG. The final BASP size depends on the amount of crosslinker added. We carry out the synthesis of three BASPs on the benchtop with no special precautions to remove air and moisture. The samples are characterized by gel permeation chromatography (GPC); results agreed closely with our previous report that utilized inert (glovebox) conditions. Key practical features, advantages, and potential disadvantages of the brush-first method are discussed.