Receipt of rheumatology care and lupus-specific labs among young adults with systemic lupus erythematosus: A US Medicare retention in care cohort study.

OBJECTIVE: In systemic lupus erythematosus, poor disease outcomes occur in young adults, patients identifying as Black or Hispanic, and socioeconomically disadvantaged patients. These identities and social factors differentially shape care access and quality that contribute to lupus health disparities in the US. Thus, our objective was to measure markers of care access and quality, including rheumatology visits (longitudinal care retention) and lupus-specific serology testing, by race and ethnicity, neighborhood disadvantage, and geographic context. METHODS: This cohort study used a geo-linked 20% national sample of young adult Medicare beneficiaries (ages 18-35) with lupus-coded encounters and a 1-year assessment period. Retention in lupus care required a rheumatology visit in each 6-month period, and serology testing required ≥1 complement or dsDNA antibody test within the year. Multivariable logistic regression models were fit for visit-based retention and serology testing to determine associations with race and ethnicity, neighborhood disadvantage, and geography. RESULTS: Among 1,036 young adults with lupus, 39% saw a rheumatologist every 6 months and 28% had serology testing. White beneficiaries from the least disadvantaged quintile of neighborhoods had higher visit-based retention than other beneficiaries (64% vs 30%-60%). Serology testing decreased with increasing neighborhood disadvantage quintile (aOR 0.80; 95% CI 0.71, 0.90) and in the Midwest (aOR 0.46; 0.30, 0.71). CONCLUSION: Disparities in care, measured by rheumatology visits and serology testing, exist by neighborhood disadvantage, race and ethnicity, and region among young adults with lupus, despite uniform Medicare coverage. Findings support evaluating lupus care quality measures and their impact on US lupus outcomes.

Development of the American College of Rheumatology Patient-Reported Outcome Quality Measures for Systemic Lupus Erythematosus.

OBJECTIVE: As part of a Centers for Disease Control and Prevention-funded American College of Rheumatology (ACR) initiative, we sought to develop quality measures related to Patient Reported Outcome Measure (PROM) use for systemic lupus erythematosus (SLE) clinical care. METHODS: An expert workgroup composed of physician, patient, and researcher representatives convened to identify patient-reported outcome (PRO) domains of greatest importance to people with SLE. A patient advisory panel separately ranked domains. PROMs assessing priority domains were identified through structured literature review, and detailed psychometric reviews were conducted for each PROM. In a Delphi process, the expert workgroup rated PROMs on content validity, psychometric quality, feasibility of implementation, and importance for guiding patient self-management. The patient advisory panel reviewed PROMs in parallel and contributed to the final recommendations. RESULTS: Among relevant PRO domains, the workgroup and patient partners ranked depression, physical function, pain, cognition, and fatigue as high-priority domains. The workgroup recommended at least once yearly measurement for (1) assessment of depression using the Patient Health Questionnaire or Patient Reported Outcomes Measurement Information System (PROMIS) depression scales; (2) assessment of physical function using PROMIS physical function scales or the Multi-Dimensional Health Assessment Questionnaire; and (3) optional assessments of fatigue and cognition. Pain scales evaluated were not found to be sufficiently superior to what is already assessed in most SLE clinic visits. CONCLUSION: Expert workgroup members and patient partners recommend that clinicians assess depression and physical function at least once yearly in all people with SLE. Additional PROMs addressing cognition and fatigue can also be assessed. Next steps are to incorporate PROM-based quality measures into the ACR The Rheumatology Informatics System for Effectiveness registry.

Reference Range of Hydroxychloroquine Blood Levels That Can Reduce Odds of Active Lupus and Prevent Flares.

OBJECTIVE: Recent data show that lower hydroxychloroquine (HCQ) doses are associated with a two- to six-fold higher risk of lupus flares. Thus, establishing an effective reference range of HCQ blood levels with upper and lower bounds for efficacy may support individualizing HCQ dosing to prevent flares. METHODS: HCQ levels in whole blood and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were measured during the baseline visit and again during a standard of care routine follow-up visit. Active cross-sectional lupus at baseline was defined as SLEDAI ≥6; a within subject flare was defined as a subsequent three-point increase in SLEDAI with clinical symptoms requiring therapy change. We examined associations between active lupus and HCQ blood levels at baseline and flares and HCQ levels during 6 to 12-month routine lupus follow-up visits using mixed regression analysis. RESULTS: Among 158 baseline patient visits, 19% had active lupus. Odds of active lupus were 71% lower in patients with levels within a 750 to 1,200 ng/mL range (adjusted odds ratio 0.29, 95% confidence interval 0.08-0.96). Using convenience sampling strategy during a pandemic, we longitudinally followed 42 patients. Among those patients, 17% flared during their follow-up visit. Maintaining HCQ levels within 750 to 1,200 ng/mL reduced the odds of a flare by 26% over a nine-month median follow-up. CONCLUSION: An effective reference range of HCQ blood levels, 750 to 1,200 ng/mL, was associated with 71% lower odds of active lupus, and maintaining levels within this range reduced odds of flares by 26%. These findings could guide clinicians to individualize HCQ doses to maintain HCQ levels within this range to maximize efficacy.

Exploring potential soybean bradyrhizobia from high trehalose-accumulating soybean genotypes for improved symbiotic effectiveness in soybean / Exploración de bradirizobios potenciales de la soja a partir de genotipos de soja con alto contenido de trehalosa para mejorar la eficacia simbiótica en la soja

Drought is the most important factor limiting the activity of rhizobia during N-fixation and plant growth. In the present study, we isolated Bradyrhizobium spp. from root nodules of higher trehalose-accumulating soybean genotypes and examined for moisture stress tolerance on a gradient of polyethylene glycol (PEG 6000) amended in yeast extract mannitol (YEM) broth. In addition, the bradyrhizobial strains were also evaluated for symbiotic effectiveness on soybean. Based on 16S rDNA gene sequences, four bradyrhizobial species were recovered from high trehalose-accumulating genotypes, i.e., two Bradyrhizobium liaoningense strains (accession number KX230053, KX230054) from EC 538828 and PK-472, respectively, one Bradyrhizobium daqingense (accession number KX230052) from PK-472, and one Bradyrhizobium kavangense (accession number MN197775) from Valder genotype having low trehalose. These strains, along with two native strains, viz., Bradyrhizobium japonicum (JF792425), Bradyrhizobium liaoningense (JF792426), and one commercial rhizobium, were studied for nodulation, leghaemoglobin, and N-fixation abilities on soybean under sterilized sand microcosm conditions in a completely randomized design. Among all the strains, D-4A (B. daqingense) followed by D-4B (B. liaoningense) was found to have significantly higher nodulation traits and acetylene reduction assay (ARA) activity when compared to other strains and commercial rhizobia. The bradyrhizobia isolates showed plant growth promotion traits such as indole acetic acid (IAA), exopolysaccharide (EPS), and siderophore production, phosphate-solubilizing potential, and proline accumulation. The novel species B. daqingense was reported for the first time from Indian soil and observed to be a potential candidate strain and should be evaluated for conferring drought tolerance in soybean under simulated stress conditions.(AU)

Clarifying misbeliefs about hydroxychloroquine (HCQ): developing the HCQ benefits versus harm decision aid (HCQ-SAFE) per low health literacy standards.

BACKGROUND: Up to 83% of patients with SLE stop taking hydroxychloroquine (HCQ) within the first year due to knowledge gaps regarding the survival benefits of HCQ versus inflated fears of rare toxicity. Thus, there is a need for a shared decision-making tool that highlights HCQ's significant benefits versus rare harms to improve patients' understanding and align treatments with their values. The objective of this study was to describe development and piloting of a decision aid (HCQ-SAFE) to facilitate HCQ adherence, and safe, effective use by engaging patients in therapeutic decision-making. METHODS: HCQ-SAFE was developed via a collaborative process involving patients, clinicians, implementation scientists and health literacy experts. The initial prototype was informed by Agency for Healthcare Research and Quality (AHRQ) low literacy principles and key themes about HCQ use from six prior patient and clinician focus groups, with iterative expert and stakeholder feedback to deliver a final prototype. We implemented HCQ-SAFE in four clinics to examine usability and feasibility on Likert scales (0-7) and net promoter score (0%-100%). RESULTS: The final HCQ-SAFE shared decision-making laminated tool organises data using pictograms showing how HCQ use reduces risk of organ damage, early death and blood clots versus low risk of eye toxicity.HCQ-SAFE was reviewed in all eligible patient visits (n=40) across four clinics on an average of ~8 min, including 25% non-English-speaking patients. All patients scored 100% on the knowledge post-test; no decisional conflicts were noted after using HCQ-SAFE. HCQ-SAFE garnered high clinician and patient satisfaction with 100% likelihood to recommend to peers. CONCLUSIONS: HCQ-SAFE is a stakeholder-informed feasible shared decision-making tool that enhances communication and can potentially improve knowledge, clarify misbeliefs and engage patients in treatment decisions, including those with limited English proficiency.

Development of American College of Rheumatology Quality Measures for Systemic Lupus Erythematosus: A Modified Delphi Process With Rheumatology Informatics System for Effectiveness (RISE) Registry Data Review.

OBJECTIVE: We aimed to develop readily measurable digital quality measure statements for clinical care in systemic lupus erythematosus (SLE) using a multistep process guided by consensus methods. METHODS: Using a modified Delphi process, an American College of Rheumatology (ACR) workgroup of SLE experts reviewed all North American and European guidelines from 2000 to 2020 on treatment, monitoring, and phenotyping of patients with lupus. Workgroup members extracted quality constructs from guidelines, rated these by importance and feasibility, and generated evidence-based quality measure statements. The ACR Rheumatology Informatics System for Effectiveness (RISE) Registry was queried for measurement data availability. In 3 consecutive Delphi sessions, a multidisciplinary Delphi panel voted on the importance and feasibility of each statement. Proposed measures with consensus on feasibility and importance were ranked to identify the top 3 measures. RESULTS: Review of guidelines and distillation of 57 quality constructs resulted in 15 quality measure statements. Among these, 5 met high consensus for importance and feasibility, including 2 on treatment and 3 on laboratory monitoring measures. The 3 highest-ranked statements were recommended for further measure specification as SLE digital quality measures: 1) hydroxychloroquine use, 2) limiting glucocorticoid use >7.5 mg/day to <6 months, and 3) end-organ monitoring of kidney function and urine protein excretion at least every 6 months. CONCLUSION: The Delphi process selected 3 quality measures for SLE care on hydroxychloroquine, glucocorticoid reduction, and kidney monitoring. Next, measures will undergo specification and validity testing in RISE and US rheumatology practices as the foundation for national implementation and use in quality improvement programs.

Exploring potential soybean bradyrhizobia from high trehalose-accumulating soybean genotypes for improved symbiotic effectiveness in soybean.

Drought is the most important factor limiting the activity of rhizobia during N-fixation and plant growth. In the present study, we isolated Bradyrhizobium spp. from root nodules of higher trehalose-accumulating soybean genotypes and examined for moisture stress tolerance on a gradient of polyethylene glycol (PEG 6000) amended in yeast extract mannitol (YEM) broth. In addition, the bradyrhizobial strains were also evaluated for symbiotic effectiveness on soybean. Based on 16S rDNA gene sequences, four bradyrhizobial species were recovered from high trehalose-accumulating genotypes, i.e., two Bradyrhizobium liaoningense strains (accession number KX230053, KX230054) from EC 538828 and PK-472, respectively, one Bradyrhizobium daqingense (accession number KX230052) from PK-472, and one Bradyrhizobium kavangense (accession number MN197775) from Valder genotype having low trehalose. These strains, along with two native strains, viz., Bradyrhizobium japonicum (JF792425), Bradyrhizobium liaoningense (JF792426), and one commercial rhizobium, were studied for nodulation, leghaemoglobin, and N-fixation abilities on soybean under sterilized sand microcosm conditions in a completely randomized design. Among all the strains, D-4A (B. daqingense) followed by D-4B (B. liaoningense) was found to have significantly higher nodulation traits and acetylene reduction assay (ARA) activity when compared to other strains and commercial rhizobia. The bradyrhizobia isolates showed plant growth promotion traits such as indole acetic acid (IAA), exopolysaccharide (EPS), and siderophore production, phosphate-solubilizing potential, and proline accumulation. The novel species B. daqingense was reported for the first time from Indian soil and observed to be a potential candidate strain and should be evaluated for conferring drought tolerance in soybean under simulated stress conditions.

Corticosteroids, Plasmapheresis, Argatroban, Rituximab, and Sirolimus Provided Clinical Benefit for Catastrophic Antiphospholipid Syndrome in a Patient with a History of Heparin-Induced Thrombocytopenia.

We report a patient with catastrophic antiphospholipid syndrome who had significant improvement after corticosteroids, plasmapheresis, argatroban, rituximab, and sirolimus. Argatroban was used instead of heparin due to a history of heparin-induced thrombocytopenia.

Timing and Predictors of Incident Cardiovascular Disease in Systemic Lupus Erythematosus: Risk Occurs Early and Highlights Racial Disparities.

OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black people 2 to 3 times more frequently than non-Black people and is associated with higher morbidity and mortality. In total, 4 studies with predominantly non-Black SLE cohorts highlighted that cardiovascular disease (CVD) is no longer primarily a late complication of SLE. This study assessed the timing and predictors of incident CVD in a predominantly Black population-based SLE cohort. METHODS: Incident SLE cases from the population-based Georgia Lupus Registry were validated as having a CVD event through review of medical records and matching with the Georgia Hospital Discharge Database and the National Death Index. The surveillance period for an incident CVD event spanned a 15-year period, starting from 2 years prior to SLE diagnosis. RESULTS: Among 336 people with SLE, 253 (75%) were Black and 56 (17%) had an incident CVD event. The frequency of CVD events peaked in years 2 and 11 after SLE diagnosis. There was a 7-fold higher risk of incident CVD over the entire 15-year period; this risk was 19-fold higher in the first 12 years in Black people as compared to non-Black people with SLE. Black people with SLE (P < 0.001) and those with discoid rash (hazard ratio 3.2, 95% CI 1.4-7.1) had a higher risk of incident CVD events. CONCLUSION: The frequency of incident CVD events peaked in years 2 and 11 after SLE diagnosis. Being Black or having a discoid rash were strong predictors of an incident CVD event. Surveillance for CVD and preventive interventions, directed particularly toward Black people with recent SLE diagnoses, are needed to reduce racial disparities.

Improvement in Cutaneous Lupus Erythematosus After Twenty Weeks of Belimumab Use: A Systematic Review and Meta-Analysis.

OBJECTIVE: Cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE), can be debilitating and cause psychological distress. Belimumab, a monoclonal antibody that inhibits B cell activation, is a Federal Drug Administration-approved SLE medication, but less is known on its use in CLE. Moreover, the time to response after starting belimumab in CLE is unknown, which may lead to premature discontinuation in the absence of early perceivable benefits. Thus, the objectives of this meta-analysis were to examine the efficacy of belimumab, as well as the time to response after starting belimumab in patients with CLE with or without SLE. METHODS: A comprehensive literature search was performed to include studies that examined clinical response in patients with CLE with or without SLE receiving belimumab. A clinical response at 52 weeks in belimumab users versus nonusers was summarized in a random-effects model. Additionally, we calculated the pooled odds ratio (OR) for each consecutive 4-week observation interval to identify time to a clinical response in CLE with or without SLE after starting belimumab. RESULTS: Among 747 screened studies, 14 were included. The pooled odds of clinical response at 52 weeks in belimumab users were 44% higher compared to nonusers (OR 1.44 [95% confidence interval (95% CI) 1.20-1.74], I2  = 0%). A clinical response was first noted after 20 weeks of starting belimumab (OR 1.35 [95% CI 1.01-1.81], I2  = 0%), with a sustained clinical response through 1 year. CONCLUSION: The findings support belimumab as an effective therapy for CLE with SLE. Likewise, the findings inform patient counseling regarding estimates of 20 weeks to achieve a response.

Patient and healthcare team recommended medication adherence strategies for hydroxychloroquine: results of a qualitative study informing intervention development.

OBJECTIVE: Patients identified as black and from disadvantaged backgrounds have a twofold higher hydroxychloroquine (HCQ) non-adherence, which contributes to worse lupus outcomes and disparities. Yet, most adherence interventions lack tailored strategies for racially and socioeconomically diverse patients who face unique challenges with HCQ. We aimed to examine a broadly representative group of patients with SLE and physician perspectives on HCQ adherence and adherence strategies to redesign an adherence intervention. METHODS: We conducted four virtual focus groups (90 min each) with 11 racially and socioeconomically diverse patients with SLE recruited from two health systems. Additionally, we hosted two focus group meetings with nine healthcare advisors. In focus groups, patients: (1) shared their perspectives on using HCQ; (2) shared concerns leading to non-adherence; (3) discussed strategies to overcome concerns; (4) prioritised strategies from the most to least valuable to inform an adherence intervention. In two separate focus groups, healthcare advisors gave feedback to optimise an adherence intervention. Using content analysis, we analysed transcripts to redesign our adherence intervention. RESULTS: Worry about side effects was the most common barrier phrase mentioned by patients. Key themes among patients' concerns about HCQ included: information gaps, logistical barriers, misbeliefs and medication burden. Finally, patients suggested adherence strategies and ranked those most valuable including co-pay assistance, personal reminders, etc. Patient and healthcare advisors informed designing a laminate version of an adherence intervention to link each barrier category with four to six patient-recommended adherence strategies. CONCLUSION: We developed a patient stakeholder-informed and healthcare stakeholder-informed tailored intervention that will target non-adherence at the individual patient level.

Cell-free prototyping enables implementation of optimized reverse ß-oxidation pathways in heterotrophic and autotrophic bacteria.

Carbon-negative synthesis of biochemical products has the potential to mitigate global CO2 emissions. An attractive route to do this is the reverse ß-oxidation (r-BOX) pathway coupled to the Wood-Ljungdahl pathway. Here, we optimize and implement r-BOX for the synthesis of C4-C6 acids and alcohols. With a high-throughput in vitro prototyping workflow, we screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selectivity. Implementation of these pathways into Escherichia coli generates designer strains for the selective production of butanoic acid (4.9 ± 0.1 gL-1), as well as hexanoic acid (3.06 ± 0.03 gL-1) and 1-hexanol (1.0 ± 0.1 gL-1) at the best performance reported to date in this bacterium. We also generate Clostridium autoethanogenum strains able to produce 1-hexanol from syngas, achieving a titer of 0.26 gL-1 in a 1.5 L continuous fermentation. Our strategy enables optimization of r-BOX derived products for biomanufacturing and industrial biotechnology.

X-linked genes exhibit miR6891-5p-regulated skewing in Sjögren's syndrome.

Many autoimmune diseases exhibit a strikingly increased prevalence in females, with primary Sjögren's syndrome (pSS) being the most female-predominant example. However, the molecular basis underlying the female-bias in pSS remains elusive. To address this knowledge gap, we performed genome-wide, allele-specific profiling of minor salivary gland-derived mesenchymal stromal cells (MSCs) from pSS patients and control subjects, and detected major differences in the regulation of X-linked genes. In control female MSCs, X-linked genes were expressed from both paternal and maternal X chromosomes with a median paternal ratio of ~ 0.5. However, in pSS female MSCs, X-linked genes exhibited preferential expression from one of the two X chromosomes. Concomitantly, pSS MSCs showed decrease in XIST levels and reorganization of H3K27me3+ foci in the nucleus. Moreover, the HLA-locus-expressed miRNA miR6891-5p was decreased in pSS MSCs. miR6891-5p inhibition in control MSCs caused XIST dysregulation, ectopic silencing, and allelic skewing. Allelic skewing was accompanied by the mislocation of protein products encoded by the skewed genes, which was recapitulated by XIST and miR6891-5p disruption in control MSCs. Our data reveal X skewing as a molecular hallmark of pSS and highlight the importance of restoring X-chromosomal allelic balance for pSS treatment. KEY MESSAGES: X-linked genes exhibit skewing in primary Sjögren's syndrome (pSS). X skewing in pSS associates with alterations in H3K27me3 deposition. pSS MSCs show decreased levels of miR6891-5p, a HLA-expressed miRNA. miR6891-5p inhibition causes H3K27me3 dysregulation and allelic skewing.

A randomized controlled trial to compare antibiotic prophylaxis in elective gynecological surgeries: Single dose of cefazolin versus single dose of cefazolin and tinidazole.

Objectives: To evaluate if addition of an anti-anaerobic agent to standard drug-cefazolin for antimicrobial prophylaxis would further decrease postoperative infectious morbidity or not. This is relevant as most of the infections in gynecological surgeries are anaerobic but cefazolin does not protect against anaerobes. Materials and Methods: The study design was a parallel randomized controlled trial. Two hundred patients undergoing benign gynecological surgeries were divided into two groups of 100 each. Group A received 2 g cefazolin 30-60 min before incision and Group B received 2 g cefazolin 30-60 min and 1.6 g tinidazole 60-120 min before incision. The patients were followed for any infectious morbidity for 1 month postoperatively. The analysis was done separately for abdominal, laparoscopic, and vaginal surgeries. The analysis was also done for surgeries according to the wound category, i.e. clean and clean-contaminated. Results: The two groups were comparable for age and body mass index (BMI). The two groups were comparable for the factors affecting infectious morbidity such as duration of surgery, blood loss, blood transfusions, duration of hospital stay, and need for additional antibiotics. The postoperative infectious morbidity was analyzed in terms of fever, surgical site infection (SSI), and urinary tract infection (UTI). No patient in vaginal and laparoscopic groups suffered from infectious morbidity. In abdominal surgeries group, postoperative fever occurred in 6/74 (8.1%) and 11/74 patients (14.8%) in Groups A and B, respectively (P = 0.38). SSI occurred in 1/74 (1.3%) and 2/74 (2.7%) patients in Groups A and B, respectively (P = 1.0). UTI occurred in 5/74 patients (6.7%) and 2/74 patients (2.7%) in Groups A and B, respectively (P = 0.44). The data were also analyzed for infectious morbidity for clean and clean-contaminated wound categories, and the results were nonsignificant between both groups for each type of wound category (P > 0.05). Conclusion: Cefazolin alone is a sufficient antibiotic prophylaxis for benign gynecological procedures.

Multidisciplinary Lupus Nephritis Clinic Reduces Time to Renal Biopsy and Improves Care Quality.

OBJECTIVE: Patients with lupus nephritis (LN) have a 26-fold higher mortality rate compared with their peers. Kidney biopsy, the gold standard diagnostic method for LN, may have an average wait time of more than 50 days. Other gaps in quality process measures during LN visits have also been reported. A subspecialty multidisciplinary clinic (MDC) can provide better care and quality in LN; therefore, we aimed to examine how an LN MDC impacted time to biopsy, time to treatment, and other quality measures. METHODS: We included all validated patients with LN who underwent diagnostic kidney biopsies between the 2011 to 2017 pre-MDC period and the 2018 to 2020 post-MDC period. We compared time to biopsy and treatment and quality measures between the two periods and examined factors associated with timely LN diagnosis, defined as a biopsy within 21 days. RESULTS: During the pre- and post-MDC periods, 53 and 21 patients with LN underwent a diagnostic biopsy, respectively. We found a decrease in the median time to biopsy from 26 days to 16 days after starting the LN clinic (P = 0.014). Beyond clinical factors, the presence of social factors, such as being of a non-White race and having food insecurity, were associated with 54% lower odds of timely diagnosis (adjusted Hazards Ratio [aHR] = 0.46; 95% confidence interval: 0.22-0.93; P = 0.031). We found higher odds of quality measure performance during the post- versus pre-MDC period. CONCLUSION: Wait times to diagnose LN decreased by 40% and higher quality measure performance was noted after establishing an LN MDC. Systemic and social barriers predicted delays in diagnosis that may be addressed by MDCs.

Stereoselective synthesis of tri-substituted tetrahydrothiophenes and their in silico binding against mycobacterial protein tyrosine phosphatase B.

A facile approach to tri-substituted tetrahydrothiophenes via thia-Michael/aldol has been developed. The cascade reaction was carried out in the presence of 5 mol% of DABCO in ethyl acetate to afford diversely functionalized tetrahydrothiophenes (THTs) with excellent diastereoselectivity. The present methodology has broad substrate tolerance. Gram-scale reaction proceeds with equal efficiency. Functional group transformations further highlight the synthetic potential of the THTs. An asymmetric version of the cascade reaction has also been investigated and a maximum of 72% ee was observed with cinchonidine derived squaramide. Moreover, in silico based molecular docking followed by deep learning based affinity prediction and molecular dynamics simulation analysis indicate the synthesized THT derivatives can act as potent competitive inhibitors of MptpB at low micromolar to nanomolar concentrations. In silico ADME analysis further suggests the plausibility of these compounds to act as future anti-mycobacterial therapeutic leads.

Advances in systems metabolic engineering of autotrophic carbon oxide-fixing biocatalysts towards a circular economy.

High levels of anthropogenic CO2 emissions are driving the warming of global climate. If this pattern of increasing emissions does not change, it will cause further climate change with severe consequences for the human population. On top of this, the increasing accumulation of solid waste within the linear economy model is threatening global biosustainability. The magnitude of these challenges requires several approaches to capture and utilize waste carbon and establish a circular economy. Microbial gas fermentation presents an exciting opportunity to capture carbon oxides from gaseous and solid waste streams with high feedstock flexibility and selectivity. Here we discuss available microbial systems and review in detail the metabolism of both anaerobic acetogens and aerobic hydrogenotrophs and their ability to utilize C1 waste feedstocks. More specifically, we provide an overview of the systems-level understanding of metabolism, key metabolic pathways, scale-up opportunities and commercial successes, and the most recent technological advances in strain and process engineering. Finally, we also discuss in detail the gaps and opportunities to advance the understanding of these autotrophic biocatalysts for the efficient and economically viable production of bioproducts from recycled carbon.

Association of Renal Arteriosclerosis With Atherosclerotic Cardiovascular Disease Risk in Lupus Nephritis.

OBJECTIVE: Lupus nephritis (LN) predicts a 9-fold higher atherosclerosis cardiovascular disease (ASCVD) risk, highlighting the urgent need to target ASCVD prevention. Studies in IgA nephropathy reported that severe renal arteriosclerosis (r-ASCL) in diagnostic biopsies strongly predicted ASCVD risk. We recently found that 50% of LN pathology reports overlooked r-ASCL reporting, which could explain prior negative LN ASCVD risk studies. The present study was undertaken to examine associations between a composite of reported and overread r-ASCL and ASCVD events in LN. METHODS: Data were abstracted from all LN patients who underwent diagnostic biopsy between 1994 and 2017, including demographic information, ASCVD risk factors, and pathology reports at the time of LN diagnosis. We manually validated all incident ASCVD events. We overread 25% of the biopsies to grade r-ASCL using the Banff criteria. We supplemented the overread r-ASCL grade, when available, to determine the composite of reported and overread r-ASCL grade. RESULTS: Among 189 incident LN patients, 78% were female, 73% White, and the median age was 25 years. Overall, 31% had any reported r-ASCL, and 7% had moderate-to-severe r-ASCL. After incorporating systematically re-examined r-ASCL grade, the prevalence of any and moderate-to-severe r-ASCL increased to 39% and 12%, respectively. We found 22 incident ASCVD events over 11 years of follow-up. Using a composite of reported and overread r-ASCL grade, we found that severe r-ASCL in diagnostic LN biopsies was associated with 9-fold higher odds of ASCVD. CONCLUSION: Severe r-ASCL can predict ASCVD in LN; therefore, larger studies are required to systematically report r-ASCL and examine ASCVD associations.