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Purpose of the Review: Apolipoprotein (APO) A1, the main apolipoprotein of plasma high-density lipoproteins (HDLs), has several well documented cardioprotective functions. A number of additional potentially beneficial functions of APOA1 have recently been identified. This review is concerned with the therapeutic potential of all of these functions in multiple disease states., Recent Findings: Knowledge of the beneficial functions of APOA1 in atherosclerosis, thrombosis, diabetes, cancer, and neurological disorders is increasing exponentially. These insights have led to the development of clinically relevant peptides and APOA1-containing, synthetic reconstituted HDL (rHDL) preparations that mimic the functions of full-length APOA1. APOA1 is a multifunctional apolipoprotein that has therapeutic potential in several diseases. Translation of this knowledge into the clinic is likely to be dependent on the efficacy and bioavailability of small peptides and synthetic rHDL preparations that are currently under investigation, or in development.

Background and Aims: There is some evidence of a cross-sectional, and possibly causal, relationship of lipid levels with leukocyte counts in mice and humans. This study investigates the cross-sectional and longitudinal relationship of blood lipid and lipoprotein levels with leukocyte counts in the UK Biobank cohort., Methods: The primary cross-sectional analysis included 417,132 participants with valid data on lipid measures and leukocyte counts. A subgroup analysis was performed in 333,668 participants with valid data on lipoprotein(a). The longitudinal analysis included 9058 participants with valid baseline and follow-up data on lipid and lipoprotein levels and leukocyte counts. The association of lipid and lipoprotein levels with leukocyte counts was analysed by multivariable linear regression., Results: Several relationships were significant in both cross-sectional and longitudinal analysis. After adjustment for demographic, socioeconomic and other confounding factors, a higher eosinophil count was associated with lower HDL cholesterol and apolipoprotein A-I concentration (p < 0.001). Higher triglycerides levels were associated with higher total leukocyte, basophil, eosinophil, monocyte and neutrophil counts (all p < 0.01). A higher lymphocyte count was associated with a higher apolipoprotein B level (p < 0.001). In the longitudinal analysis, lipoprotein(a) was inversely associated with basophil count in men but not women (p < 0.001)., Conclusions: Triglyceride levels demonstrate a robust positive association with total and differential leukocyte counts suggesting they may be directly involved in leukogenesis. However, unlike in murine models, the remainder of these relationships is modest, which suggests that cholesterol and lipoproteins are minimally involved in leukogenesis in humans., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tolosa-Hunt syndrome (THS) is a rare syndrome of painful ophthalmoplegia secondary to an idiopathic granulomatous inflammation affecting the cavernous sinus, superior orbital fissure or orbit. Pregnancy and pregnancy-related hormones have been identified as potential triggers. A 39-year-old gravida-2 para-1 woman with prior chronic intake of combined oral contraceptives (COC) suffered two episodes of painful ophthalmoplegia-the first event with spontaneous remission and the relapse occurring during pregnancy and with complete resolution following steroid treatment. MRI revealed a postinflammatory mass at the junction of the left orbital apex and anterior cavernous sinus, supporting the diagnosis of THS. To our knowledge, this is the first report of a THS relapse occurring during pregnancy following a chronic history of COC intake. This case adds to the growing evidence supporting the relationship between immune and hormonal factors that may be present during pregnancy and the disease pathogenesis of THS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As a platform chemical with various applications, succinic acid (SA) is currently produced by petrochemical processing from oil-derived substrates such as maleic acid. In order to replace the environmental unsustainable hydrocarbon economy with a renewable environmentally sound carbohydrate economy, bio-based SA production process has been developed during the past two decades. In this review, recent advances in the valorization of solid organic wastes including mixed food waste, agricultural waste and textile waste for efficient, green and sustainable SA production have been reviewed. Firstly, the application, market and key global players of bio-SA are summarized. Then achievements in SA production by several promising yeasts including Saccharomyces cerevisiae and Yarrowia lipolytica are detailed, followed by calculation and comparison of SA production costs between oil-based substrates and raw materials. Lastly, challenges in engineered microorganisms and fermentation processes are presented together with perspectives on the development of robust yeast SA producers via genome-scale metabolic optimization and application of low-cost raw materials as fermentation substrates. This review provides valuable insights for identifying useful directions for future bio-SA production improvement., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Previous studies suggested a potential relationship between plasma lipoprotein (a) [Lp(a)] and elevated depressive symptoms. We aimed to investigate any such relationship in the Multi-Ethnic Study of Atherosclerosis participants who were free of cardiovascular events. Analysis included 4938 participants without elevated depressive symptoms and with Lp(a) levels measured at baseline. Participants were examined at four clinic visits over a 10-year period. Elevated depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D) and were defined as a CES-D score ≥16 or use of anti-depressants. Lp(a) level was measured with a latex-enhanced turbidimetric immunoassay. After adjusting for demographics, socioeconomic factors and other confounding factors in Cox regression analyses, a higher ln-transformed Lp(a) level was associated with new elevated depressive symptoms since baseline (hazard ratio [95% CI] = 1.09 [1.02-1.16] per SD increment in ln-transformed level, P = 0.01). However, no association was found when elevated Lp(a) levels were assessed using clinical cut-off point (≥30 or 50 mg/dL), nor in sensitivity analyses using alternative definitions of elevated depressive symptoms. No significant interaction with race/ethnicity was found for all the above analyses. Also, no significant association was found between baseline Lp(a) levels and absolute or relative changes in CES-D score between baseline and last follow-up visits. Our study suggests a potential association between Lp(a) level and new elevated depressive symptoms, but such association was not robust in the sensitivity analyses. Future studies are warranted to investigate the role of Lp(a) in depressive symptoms in other cohorts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222, and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222, and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222, and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an increase in cholesterol efflux capacity (r = 0.326, P = 0.027 and r = 0.349, P = 0.017, respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy participants versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction and may lead to the development of novel treatment strategies for obesity and related metabolic disorders., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate determinants of circulating levels of adipocyte-fatty acid binding protein (A-FABP) and lipocalin-2 (LCN2), their relationships with cardiovascular disease (CVD) and microvascular events, and effects of fenofibrate in type 2 diabetes (T2D)., Methods: A-FABP and LCN2 were quantified in baseline plasma from 2000 T2D adults in a Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial sub-study and correlates thereof determined. In a subset (n = 200) adipokines were also measured on-trial., Results: Female sex, older age, higher body mass index (BMI), HbA1c, insulin resistance index, triglycerides, plasma creatinine and homocysteine, shorter diabetes duration, and use of oral hypoglycaemic agents alone were independent determinants of higher A-FABP. Higher BMI, fibrinogen and homocysteine, Caucasian race, and lower fasting glucose, HDL-cholesterol, apolipoprotein A-II and estimated glomerular filtration rate were independent predictors of higher LCN2 levels. Baseline A-FABP and LCN2 levels were associated with multiple new CVD and microvascular events over 5-years, though significance was lost after risk factor adjustment. Fenofibrate increased A-FABP but did not change LCN2 levels., Conclusions: Baseline plasma A-FABP and LCN2 levels were associated with concurrent CVD risk factors, and on-trial chronic complications, likely mediated via traditional risk factors. Fenofibrate increased A-FABP modestly but did not affect LCN2 levels., Clinical Trial Registration: ISRCTN 64783481., Competing Interests: Declaration of Competing Interest Fournier Pharma (now part of Abbott Pharmaceuticals) sponsored the FIELD trial but had no role in data collection, analyses or interpretation. A.J.J. has served as a diabetes advisory panel member for Abbott, Medtronic and Sanofi, has received remuneration for lectures from Novo, and has received peer-reviewed research support from Abbott and Medtronic. A.C.K. has served as an Advisory Board member for Amgen, Bayer and Sanofi, and has received speaker and/or advisor honoraria from Abbott, AstraZeneca and Pfizer, research support from Mylan, Novartis and Sanofi, and honoraria from Abbott and Amgen. R.C.M. has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi and Tricida, and honoraria for consultancy or lectures from AstraZeneca and Boehringer Ingelheim. All other authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: We studied changes in opioid prescriptions and corticosteroid injection use for knee osteoarthritis patients before and after intra-articular hyaluronic acid (HA) use and opioid prescriptions before and after knee arthroplasty (KA). Materials & methods:  A total of 1,017,578 knee osteoarthritis members were ascertained from a commercial claims database (Health Intelligence Company LLC, IL, USA) using ICD9/ICD10 diagnosis codes. Results:  Eighty two percent of HA patients did not fill opioid prescriptions postinjection, with 54% of opioid users discontinuing fills. Two-thirds of KA patients filled opioid prescriptions within 6 months postsurgery, with 78% of opioid users continuing fills and 62% of nonusers initiating use. Conclusion: Alternative therapies, such as HA, that reduce opioid use may alleviate opioid addiction risks for KA patients who use opioids in the pre- and postoperative periods.

Background: We compared the revision risk between metal-on-polyethylene (MOP) and ceramic-on-polyethylene (COP) total hip arthroplasty patients and evaluated temporal changes in short-term revision risks for MOP patients., Methods: Primary MOP (n = 9480) and COP (n = 3620) total hip arthroplasties were evaluated from the Medicare data set (October 2005 to December 2015) for revision risk, with up to 10 years of follow-up using multivariate analysis. Temporal change in the short-term revision risk for MOP was evaluated (log-rank and Wilcoxon tests)., Results: Revision incidence was 3.8% for COP and 4.3% for MOP. MOP short-term revision risk did not change over time (P ≥ .844 at 1 year and .627 at 2 years). Dislocation was the most common reason for revision (MOP: 23.5%; COP: 24.8%). Overall adjusted revision risks were not different between MOP and COP up to 10 years of follow-up (P ≥ .181)., Conclusions: Concerns with corrosion for metal heads do not appear to result in significantly elevated revision risk for MOP at up to 10 years. Corrosion does not appear as a primary reason for revision compared to other mechanisms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To compare reoperation risk after total elbow arthroplasty (TEA) and open reduction internal fixation (ORIF) for intra-articular distal humerus fractures in elderly patients., Design: Retrospective comparative., Setting: Five percent Medicare Part B claims database., Patients: Patients older than 65 years of age with closed distal humerus fractures undergoing TEA or ORIF from 1996 to 2016., Intervention: TEA and ORIF., Main Outcome Measure: Reoperation risk based on multivariate Cox proportional hazards modeling., Results: A total of 142 TEA and 522 ORIF cases were identified. TEA patients had a greater age and Charlson Comorbidity Index , as well as a higher prevalence of rheumatoid arthritis and osteoporosis than ORIF patients (P < 0.05). Although reoperation risk was lower for TEA than that for ORIF within the entire cohort (11.3% vs. 25.1%; hazard ratio = 0.49; P = 0.014), no significant difference was found for TEA and ORIF performed between 2006 and 2016 (12.6% vs. 18.4%; hazard ratio = 0.73; P = 0.380). The death rate was 65.5% in the TEA group at 3.6 years and 55.7% in the ORIF group at 4.9 years., Conclusions: TEA was associated with a decreased reoperation risk compared with ORIF, although this difference did not exist for more recent procedures after popularization of the locking plate technology and half of the reoperations after ORIF were for instrumentation removal. The high death rate within several years of the index procedure may contribute to the low TEA revision rate beyond the short-term when following patients into the medium and long term. Further study comparing TEA and locked plating using prospective, randomized data with long-term follow-up and functional outcomes is warranted., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background: Several nonoperative options have been recommended for the treatment of knee osteoarthritis (OA), with varying degrees of evidence. Adhering to the American Academy of Orthopaedic Surgeons clinical practice guidelines has been suggested to decrease direct treatment costs by 45% in the year before knee arthroplasty, but this does not consider the cost of the entire episode of care, including the cost of surgery and postsurgery care., Objectives: To analyze the total treatment costs after a diagnosis of knee OA, as well as the proportion of arthroplasty interventions as part of the total knee OA-related costs, and whether the total costs differed for patients who received intra-articular hyaluronic acid and/or had knee arthroplasty., Methods: We identified patients newly diagnosed with knee OA using the 5% Medicare data sample from January 2010 to December 2015. Patients were excluded if they were aged <65 years, had incomplete claim history, did not reside in any of the 50 states, had claim history <12 months before knee OA diagnosis, or did not enroll in Medicare Part A and Part B. The study analyzed knee OA-related costs from a payer perspective in terms of reimbursements provided by Medicare, as well as the time from the diagnosis of knee OA to knee arthroplasty for patients who had knee arthroplasty, and the time from the first hyaluronic acid injection to knee arthroplasty for those who received the injection. We compared patients who received hyaluronic acid and those who did not receive hyaluronic acid injections. Patients who received hyaluronic acid injection who subsequently had knee arthroplasty were also compared with those who did not have subsequent knee arthroplasty., Results: Of the 275,256 patients with knee OA, 45,801 (16.6%) received a hyaluronic acid injection and 35,465 (12.9%) had knee arthroplasty during the study period. The median time to knee arthroplasty was 16.4 months for patients who received hyaluronic acid versus 5.7 months for those who did not receive hyaluronic acid. Non-arthroplasty-related therapies and knee arthroplasty accounted for similar proportions of knee OA-related costs, with hyaluronic acid injection comprising 5.6% of the total knee OA-related costs. For patients who received hyaluronic acid injections and subsequently had knee arthroplasty, hyaluronic acid injection contributed 1.8% of the knee OA-related costs versus 76.6% of the cost from knee arthroplasty. Patients who received hyaluronic acid injections and did not have knee arthroplasty incurred less than 10% of the knee OA-related costs that patients who had surgery incurred., Conclusion: Although limiting hyaluronic acid use may reduce the knee OA-related costs, in this study hyaluronic acid injection only comprised a small fraction of the overall costs related to knee OA. Among patients who had knee arthroplasty, those who received treatment with hyaluronic acid had surgery delayed by a median of 10.7 months and associated costs for a significant period. The ability to delay or avoid knee arthroplasty altogether can have a substantial impact on healthcare costs., (Copyright © 2020 by Engage Healthcare Communications, LLC.)

Phytophthora -induced foot rot, also known as gummosis, is an important disease affecting citrus production worldwide. In Texas, the third-largest citrus-producing state in the United States, limited information is available on the etiology and epidemiology of foot rot in commercial orchards. This study comprises a survey of foot rot incidence and severity in Texas and the characterization of Phytophthora isolates associated with the disease. Surveys in 2015 and 2017 of 30 orchards in the Lower Rio Grande Valley (LRGV) region where commercial citrus production is concentrated in the state revealed that foot rot occurred in 97% of the orchards assessed. Overall, foot rot symptoms were observed on 33.7% of the trees evaluated and the disease severity index in the region was rated at 14.2 and 16.5% in 2015 and 2017, respectively. Lesions were mostly present on the scion, while the rootstock (sour orange) was not affected. Phytophthora nicotianae was the only Phytophthora sp. isolated from the surveyed orchards and from five additional residential sites on the Texas Coastal Bend (TCB). Sporangia and chlamydospores from 34 representative LRGV isolates of P. nicotianae were larger than those of TCB isolates. In both LRGV and TCB, A1 and A2 mating types were present in the same location, albeit the A2 mating type was more prevalent. All isolates were sensitive to mefenoxam (50% inhibition in the presence of mefenoxam [EC 50 ] < 0.5 µg/ml), except for one TCB isolate (EC 50 = 143.6 µg/ml). Our research indicates that treatment for Phytophthora foot rot in the region is necessary and, although mefenoxam is still useful, alternating chemistries for resistance management are required.

Background: Limiting treatment to those recommended by the American Academy of Orthopaedic Surgeon Clinical Practice Guidelines has been suggested to decrease costs by 45% in the year prior to total knee arthroplasty, but this only focuses on expenditures leading up to, but not including, the surgery and not the entire episode of care. We evaluated the treatment costs following knee osteoarthritis (OA) diagnosis and determined whether these are different for patients who use intra-articular hyaluronic acid (HA) and/or knee arthroplasty., Methods: Claims data from a large commercial database containing de-identified data of more than 100 million patients with continuous coverage from 2012 to 2016 was used to evaluate the cumulative cost of care for over 2 million de-identified members with knee OA over a 4.5-year period between 2011 and 2015. Median cumulative costs were then stratified for patients with or without HA and/or knee arthroplasty., Results: Knee OA treatment costs for 1,567,024 patients over the 4.5-year period was $6.60 billion (mean $4210/patient) as calculated by the authors. HA and knee arthroplasty accounted for 3.0 and 61.5% of the overall costs, respectively. For patients who underwent knee arthroplasty, a spike in median costs occurred sooner for patients without HA use (around the 5- to 6-month time point) compared to patients treated with HA (around the 16- to 17-month time point)., Conclusions: Non-arthroplasty therapies, as calculated by the authors, accounted for about one third of the costs in treating knee OA in our cohort. Although some have theorized that limiting the use of HA may reduce the costs of OA treatment, HA only comprised a small fraction (3%) of the overall costs. Among patients who underwent knee arthroplasty, those treated with HA experienced elevated costs from the surgery later than those without HA, which reflects their longer time to undergoing knee arthroplasty. The ability to delay or avoid knee arthroplasty altogether can have a substantial impact on the cost to the healthcare system.

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk., Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as "at increased risk of severe COVID-19" in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection-hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection-hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies., Findings: We estimated that 1·7 billion (UI 1·0-2·4) people, comprising 22% (UI 15-28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186-787) people (4% [3-9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3-12) of males to be at high risk compared with 3% (2-7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease., Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds., Funding: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to determine the risk factors associated with reinfection in patients treated with irrigation and debridement (I&D) with liner exchange for an acute (less than 3 months) prosthetic joint infection following the index primary total knee arthroplasty (TKA). Medicare claims database was queried to identify patients with periprosthetic joint infection within 3 months of their index TKA who underwent I&D with tibial polyethylene liner exchange. Exclusion criteria included age < 65 years and < 1 year of claims prior to TKA. A total of 341 patients met our criteria and were analyzed by age, sex, diabetes, obesity, Charlson comorbidity score, and time between TKA and I&D with liner exchange. Average time to I&D with liner exchange following primary TKA was 38.5 ± 21.3 days and multivariate analysis showed a significantly higher risk of reinfection within 1 year in patients > 85 years old ( p  < 0.001) and diabetes ( p  < 0.02). The risk of reinfection was lowest for patients treated with I&D with liner exchange within 14 days after TKA ( p  = 0.028). The incidence of reinfection was 223% greater if I&D with liner exchange was performed 2 to 4 weeks after primary TKA ( p  < 0.03), and 277% higher if performed > 6 weeks after index procedure compared with those performed within 2 weeks. Patients older than 85 years, diabetics, or treated with I&D with liner exchange > 14 days following the primary TKA had a significantly higher risk of reinfection within 1 year. Patients should be cautioned on the risk of reinfection prior to proceeding with I&D with liner exchange > 2 weeks following the index procedure., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Both aging and diet play an important role in influencing the gut ecosystem. Using premature senescent rats induced by D-galactose and fed with high-fat diet, this study aims to investigate the effects of different potential probiotic strains on the dynamic changes of fecal microbiome and metabolites. In this study, male Sprague-Dawley rats were fed with high-fat diet and injected with D-galactose for 12 weeks to induce aging. The effect of Lactobacillus plantarum DR7, L. fermentum DR9, and L. reuteri 8513d administration on the fecal microbiota profile, short-chain fatty acids, and water-soluble compounds were analyzed. It was found that the administration of the selected strains altered the gut microbiota diversity and composition, even at the phylum level. The fecal short-chain fatty acid content was also higher in groups that were administered with the potential probiotic strains. Analysis of the fecal water-soluble metabolites revealed that administration of L. plantarum DR7 and L. reuteri 8513d led to higher fecal content of compounds related to amino acid metabolism such as tryptophan, leucine, tyrosine, cysteine, methionine, valine, and lysine; while administration of L. fermentum DR9 led to higher prevalence of compounds related to carbohydrate metabolism such as erythritol, xylitol, and arabitol. In conclusion, it was observed that different strains of lactobacilli can cause difference alteration in the gut microbiota and the metabolites, suggesting the urgency to explore the specific metabolic impact of specific strains on the host.

Background: Prader-Willi syndrome (PWS) is a complex genetic condition, affecting between 1:10,000 and 1:30,000. The prevalence of hip dysplasia in children with PWS is reportedly between 8% and 30%, but the long-term consequences of residual hip dysplasia remain largely unknown in this population. The purpose of this study was to comparatively estimate the number of total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures performed on adults with and without PWS, using a national hospital discharge database, in an effort to elucidate long-term outcomes and guide clinicians treating orthopaedic concerns in younger individuals with PWS., Methods: The National Inpatient Sample of the Healthcare Cost and Utilization Project is the largest all-payer inpatient care database, containing annual data from >7 million hospital stays; sampling weights and stratification variables are provided for producing estimates of >35 million hospitalizations nationwide. THA and TKA procedures were identified, then stratified by whether or not the patient had a diagnosis of PWS. The ages of the 2 groups and sex mix were compared, as was the length of stay for the procedure, and discharge status., Results: From 2004 to 2014, 9.4 million patients nationwide, by weighted estimate, underwent THA (3.1 million) or TKA (6.3 million). Sixty-five patients were identified as having the diagnosis of PWS (39 with THA, 26 with TKA); 7 patients per million having hip or knee arthroplasties had PWS. Sixty-eight percent of those with PWS were younger than 50 years, compared with only 7% of those without PWS (P<0.001). The female:male prevalence was 47:53 for patients with PWS and 60:40 for the total group. The mean length of stay was similar, but patients with PWS were more likely to be transferred to another facility after surgery (77% vs. 36%; P=0.008)., Conclusions: Hip dysplasia prevalence is higher in persons with PWS, but the rate of late treatment with THA is much lower than in the general population. We recommend only active observation for stable and improving hips in young children with PWS, as the consequences of overtreatment can be serious, including further delaying their neuromuscular development, and exposure to possibly unnecessary perioperative risks., Level of Evidence: Nation-wide database analysis, Level IV.

Klebsiella pneumoniae is a pathogen responsible for significant proportions of nosocomial and health care-associated infections and is known to acquire multiple antibiotic resistance genes. Here, we announce the full genome sequences of 12 K. pneumoniae bacteriophages from samples collected in wastewater treatment facilities across the western United States., (Copyright © 2020 Thurgood et al.)

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with inflammation and atherogenic lipoprotein abnormalities. Previous studies suggest an association of fibroblast growth factor 21 (FGF21) with NAFLD. Therefore, we assessed the association of circulating FGF21 levels with inflammatory markers, lipoprotein profile and NAFLD in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: Among 6814 participants free of apparent cardiovascular disease at baseline (2000-2002), 3634 participants had valid data on variables of interest. After excluding participants with excessive alcohol consumption, 3446 participants were included in the analysis. NAFLD was defined using non-contrast cardiac computed tomography with a liver-to-spleen ratio (LSR) < 1 or liver attenuation <40 Hounsfield units (HU)., Results: The mean age of the participants was 63.5 years with 54% females, 36% Caucasian, 10% Chinese American, 31% African American and 23% Hispanic. 17% of the participants had NAFLD. After adjustment for demographic, socioeconomic and other confounders, a 1-SD increment in ln-transformed FGF21 level was associated with a 5.1% higher IL-6 level, a 0.31 nm larger very-low-density lipoprotein particle diameter, a 0.014 nm smaller high-density lipoprotein particle diameter, and a 5.25 nmol/L lower intermediate-density lipoprotein particle concentration (all p < 0.05). A 1-SD increment in ln-transformed FGF21 level was associated with LSR<1 and liver attenuation <40 HU (OR = 1.38 and 1.48; both p < 0.01), even after adjusting for the aforementioned inflammation and lipoprotein parameters., Conclusions: This study suggests an association between FGF21 and NAFLD, independent of inflammation and atherogenic lipoprotein abnormalities. Further studies are needed to assess FGF21 as a biomarker for future NAFLD risk., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The number of patients who have end-stage renal disease undergoing primary total hip arthroplasty (THA) has increased over the past decade. The purpose of this study is to evaluate mortality, complications, and 90-day readmission incidences in patients who have end-stage renal disease undergoing THA., Methods: Patients who had a primary THA between January 1, 2007, and December 31, 2016, were identified from the 5% Medicare database. A total of 55,297 THA patients were stratified into 3 groups: renal dialysis (without transplant), renal transplant, and those without such renal problems. Risk of readmissions, dislocations, periprosthetic joint infections (PJIs), venous thromboembolic diseases, and mortalities up to 5 years following primary THA was compared. Multivariate Cox regression analyses were used to evaluate the effect of patient and hospital characteristics on the adjusted complication risks., Results: Mortalities at 5 years was 62.6% in the renal dialysis group, 37.3% in the renal transplant group, compared to 15.0% in the nonrenal group. Dislocations (7.6%) and PJIs (7%) were significantly higher in the dialysis group (P < .001). No significant differences in venous thromboembolic diseases (all timepoints) and revisions (all timepoints except at 90 days) between the renal groups were observed. The 90-day readmission risks were significantly greater in both the dialysis (55%) and transplant (43%) groups compared to the nonrenal cohort (30%) (P < .001)., Conclusion: Renal dialysis patients undergoing THA are at increased risk of PJIs (7%), dislocations (7.6%), revisions, and mortalities at 90 days compared to transplant and nonrenal patients. Both dialysis and transplant patients are high-risk groups with significantly increased 90-day readmission incidences of 55% and 43%, respectively, which makes their inclusion into a bundled payment model challenging., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Identification of biomarkers can help monitor and prevent cardiovascular disease (CVD) risk. We performed an exploratory analysis to identify potential biomarkers for coronary heart disease (CHD) in participants from the Life Conditions, Stress, and Health study. A total of 1,007 participants (50% women), randomly selected from the general population, were followed for incident CHD at 8 and 13 years of follow-up. Plasma levels of 184 CVD-related biomarkers were measured in samples collected at baseline in 86 cases with CHD and 184 age- and sex-matched controls by proximity extension assay. Biomarker levels were presented as normalized protein expression values (log 2 scale). After adjusting for confounding factors, 6 biomarkers showed significant association with incident CHD at 13 years. In a sensitivity analysis, this association remained significant at 8 years for 3 biomarkers; collagen α-1(I) chain (COL1A1), bone morphogenetic protein-6 (BMP-6), and interleukin-6 receptor α chain (IL-6Rα). When entering these biomarkers in the full adjustment model simultaneously, their association with incident CHD at 13 years remained significant, hazards ratio being 0.671, 0.335, and 2.854, respectively per unit increase in normalized protein expression values. Subjects with low COL1A1, low BMP-6, and high IL-6Rα levels had a hazards ratio of 5.097 for incident CHD risk (p = 0.019), compared with those without. In conclusion, we identified COL1A1, BMP-6 and IL-6Rα as biomarkers for incident CHD over a long-term follow-up in this exploratory analysis. For COL1A1 and BMP-6 this has not been previously reported. Further studies are needed to confirm our findings and establish their clinical relevance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Prolene polypropylene ("Prolene") meshes demonstrate no in vivo degradation, yet some claim degradation continues until no more Prolene polypropylene can be oxidized. We studied whether implantation time affects the morphology/extent of previously reported as cracking/degradation of completely cleaned Prolene explants., Methods: Urogynecological explants (248 patients) were collected. After excluding non-Prolene/unknown meshes and those without known implantation times, completely cleaned explants (n = 205; 0.2-14.4 years implantation) were analyzed with light microscopy, scanning electron microscopy, and Fourier transform infrared spectroscopy. Based on implant times and storage (fixative or dry), representative specimens were randomly selected for comparison. Controls were unused ("exemplar") TVT specimens with and without intentional oxidation via ultraviolet light exposure., Results: Prolene explants included 31 dry (18 TVT; 7 Prolift; 4 Gynemesh; 2 others) and 174 wet (87 TVT; 47 Prolift; 10 Gynemesh; 30 others) specimens. Specimens had similar morphologies before cleaning. Progressive cleaning removed tissue and cracked tissue-related material exposing smooth, unoxidized, and nondegraded fibers, with no visible gradient-type/ductile damage. Fourier transform infrared spectroscopy of the explants confirmed progressive loss of proteins. Cleaning intentionally oxidized exemplars did not remove oxidized carbonyl frequencies and showed deep cracks and gross fiber rupture/embrittlement, unlike the explants and nonoxidized exemplars., Conclusions: If in vivo Prolene degradation exists, there should be wide-ranging crack morphology and nonuniform crack penetration, as well as more cracking, degradation, and physical breakage for implants of longer implantation times, but this was not the case. There is no morphologic or spectral/chemical evidence of Prolene mesh degradation after up to 14.4 years in vivo.

Development of cost effective and highly efficient process for bio-based succinic acid (SA) production is a main concern for industry. The metabolically engineered Y. lipolytica strain PGC01003 was successfully used for SA production with high titre. However, this strain possesses as main drawback with a low growth rate when glycerol is used as a feedstock. Herein, gene GUT1, encoding glycerol kinase, was overexpressed in strain PGC01003 with the aim to improve glycerol uptake capacity. In the resulting strain RIY420, glycerol uptake was 13.5% higher than for the parental strain. GUT1 gene overexpression also positively influences SA production. In batch bioreactor, SA titre, yield and productivity were 32%, 39% and 143% higher, respectively, than for the parental strain PGC01003. Using a glycerol feeding strategy, SA titre, yield and productivity were further improved by 11%, 5% and 10%, respectively. Moreover, the process duration to yield the highest concentration of SA in the culture supernatant was reduced by 9%. This demonstrated the contribution of metabolically engineered strain RIY420 to lower SA process cost and increase the efficiency of bio-based SA production., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The number needed to treat is a commonly used statistical term in modern neurointerventional practice. It represents the number of patients that need to be treated for one patient to benefit from an intervention. Given its growing popularity in reflecting study results, understanding the basics behind this statistic is of practical value to the neurointerventionalist., Methods: Here, we review the basic theory and calculation of the number needed to treat, its application to stroke interventions, and its limitations. In addition, we demonstrate several simple methods of calculating the number needed to treat utilizing recent thrombectomy trial results. By presenting the number needed to treat as a universal metric, we provide a comprehensive comparative of the number needed to treat for key stroke therapies, including mechanical thrombectomy, tissue plasminogen activator, carotid endarterectomy, and prevention with antiplatelet and statin drugs., Conclusions: In comparison with available stroke therapies, mechanical thrombectomy stands out as the most effective acute intervention in patients with emergent large-vessel occlusions. Understanding how the number needed to treat is derived and its implications helps provide perspective to clinical trial data, identify health-care resource priorities, and improve communication with patients, health-care providers, and additional key stakeholders.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathologies ranging from uncomplicated hepatic fat accumulation to a state of lobular inflammation and hepatocyte ballooning, known as non-alcoholic steatohepatitis (NASH). Currently, there are no reliable biomarkers or effective therapeutic options established for NAFLD. Nevertheless, there are several molecular targets in the pipeline, of which fibroblast growth factor 21 (FGF21) is one. FGF21 is secreted primarily from liver and has a plethora of metabolic functions. Pre-clinical and epidemiological studies indicate a relationship between circulating FGF21 levels and hepatic fat content in both mice and humans. Moreover, animal studies have clearly shown that aberrant FGF21 signalling is a key pathological step in the development and progression of NAFLD. A recent Phase II clinical trial demonstrated that administration of an FGF21 analogue significantly reduced hepatic fat in subjects with NASH. As such, FGF21 provides a novel target for future biomarker and therapeutic studies. This review appraises preclinical data to outline the current understanding of FGF21 function in both normal hepatic function and NAFLD. Epidemiological evidence is explored to delineate the relationship between circulating FGF21 levels and NAFLD in humans. Finally, we review the therapeutic effects of FGF21 in the treatment of NAFLD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Metabolic disorders are associated with an increased risk of cardiovascular disease (CVD), and are commonly characterized by a low plasma level of high-density lipoprotein cholesterol (HDL-C). Although cholesterol lowering medications reduce CVD risk in these patients, they often remain at increased risk of CVD. Therapeutic strategies that raise HDL-C levels and improve HDL function are a potential treatment option for reducing residual CVD risk in these individuals. Over the past decade, understanding of the metabolism and cardioprotective functions of HDLs has improved, with preclinical and clinical studies both indicating that the ability of HDLs to mediate reverse cholesterol transport, inhibit inflammation and reduce oxidation is impaired in metabolic disorders. These cardioprotective effects of HDLs are supported by the outcomes of epidemiological, cell and animal studies, but have not been confirmed in several recent clinical outcome trials of HDL-raising agents. Recent studies suggest that HDL function may be clinically more important than plasma levels of HDL-C. However, at least some of the cardioprotective functions of HDLs are lost in acute coronary syndrome and stable coronary artery disease patients. HDL dysfunction is also associated with metabolic abnormalities. This review is concerned with the impact of metabolic abnormalities, including dyslipidemia, obesity and Type 2 diabetes, on the metabolism and cardioprotective functions of HDLs., (© 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Previous small studies have reported an association between circulating fibroblast growth factor 21 (FGF21) levels and pericardial fat volume in post-menopausal women and high cardiovascular disease (CVD) risk patients. In this study, we investigated the relationship of FGF21 levels with pericardial fat volume in participants free of clinical CVD at baseline. We analysed data from 5765 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) with both pericardial fat volume and plasma FGF21 levels measured at baseline. 4746 participants had pericardial fat volume measured in at least one follow-up exam. After adjusting for confounding factors, ln-transformed FGF21 levels were positively associated with pericardial fat volume at baseline (β = 0.055, p < 0.001). When assessing change in pericardial fat volume over a mean duration of 3.0 years using a linear mixed-effects model, higher baseline FGF21 levels were associated with higher pericardial fat volume at baseline (2.381 cm 3 larger in pericardial fat volume per one SD increase in ln-transformed FGF21 levels), but less pericardial fat accumulation over time (0.191 cm 3 /year lower per one SD increase in ln-transformed FGF21 levels). Cross-sectionally, higher plasma FGF21 levels were significantly associated with higher pericardial fat volume, independent of traditional CVD risk factors and inflammatory markers. However, higher FGF21 levels tended to be associated with less pericardial fat accumulation over time. Nevertheless, such change in pericardial fat volume is very modest and could be due to measurement error. Further studies are needed to elucidate the longitudinal relationship of baseline FGF21 levels with pericardial fat accumulation.

Coronary artery bypass grafting is among the most commonly performed of all cardiovascular surgical procedures. However, graft failure due to stenosis reduces the long-term benefit of the intervention. This study asks if elevating plasma high density lipoprotein cholesterol (HDL-C) levels by inhibition of cholesteryl ester transfer protein (CETP) activity with des-fluoro-anacetrapib, an analog of the CETP inhibitor anacetrapib, prevents vein bypass-induced neointimal hyperplasia. NZW rabbits were placed on a normal chow diet or chow containing 0.14% (wt/wt) des-fluoro-anacetrapib for 6 weeks. Bypass grafting of the jugular vein to the common carotid artery was performed 2 weeks after starting dietary des-fluoro-anacetrapib supplementation. The animals were euthanised 4 weeks post-bypass grafting. Relative to control, dietary supplementation with des-fluoro-anacetrapib reduced plasma CETP activity by 89 ± 6.9%, increased plasma apolipoprotein A-I levels by 24 ± 5.5%, increased plasma HDL-C levels by 93 ± 26% and reduced intimal hyperplasia in the grafted vein by 38 ± 6.2%. Des-fluoro-anacetrapib treatment was also associated with decreased bypass grafting-induced endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), endothelial dysfunction, and smooth muscle cell (SMC) proliferation in the grafted vein. In conclusion, increasing HDL-C levels by inhibiting CETP activity is associated with inhibition of intimal hyperplasia in grafted veins, reduced inflammatory responses, improved endothelial function, and decreased SMC proliferation.

Objective: There is debate about the effectiveness of intra-articular (IA) hyaluronic acid (HA) injections. We asked the following questions: (1) What is the epidemiology of IA HA use in knee arthroplasty (KA) patients? (2) Is Synvisc associated with a delay to KA? (3) Is there a difference in the delay to KA with the number of HA courses?, Design: The Optum Clinformatics data set (2006-June 2016) was used to identify patients with knee osteoarthritis (OA). Patients who did not receive IA HA were identified, along with those who received Synvisc or non-Synvisc HA. The median duration from knee OA to KA was compared using quantile regression modeling with propensity score weighting. The trend in time to KA with each HA course was evaluated., Results: Of 4,027,848 knee OA patients, 141,305 patients underwent KA. Overall median time from knee OA diagnosis to KA was 1.2 years (average: 1.9 ± 1.9 years; interquartile range of 0.4-2.8 years). HA patients had significantly longer adjusted median time to KA by at least 7 months ( P < 0.001). After adjusting for the time to HA and number of injections, Synvisc patients had 1.7 months longer time to KA than non-Synvisc HA patients ( P < 0.001). There was a trend toward longer time to KA with more HA courses., Conclusions: Most KA patients did not use HA (73.7%) and when received, it was associated with a longer median time to KA by at least 7 months, though the cause and effect could not be examined. The delay to KA increased with more HA courses.

Background: Previous studies have demonstrated that elevated cholesterol results in increased white blood cell counts in mouse models. However, there is insufficient evidence to support this in humans., Objective: The objective of the study was to investigate the relationship of plasma lipids with white blood cell counts (basophils, eosinophils, monocytes, neutrophils and lymphocytes) in the Multi-Ethnic Study of Atherosclerosis., Methods: The analysis included 2873 Multi-Ethnic Study of Atherosclerosis participants with a complete white blood count and differential analysis. The cross-sectional association of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels with different white blood cell counts was analyzed by multivariable linear regression., Results: After adjusting for sociodemographic and confounding factors including red blood cell counts, platelet counts, use of lipid-lowering medication, cardiovascular disease risk factors and other lipid measures, and multiple testing correction, a one-standard deviation increment in total cholesterol and low-density lipoprotein cholesterol was associated with 2.8% and 2.3% lower total white blood cell counts, 3.7% and 3.0% lower monocyte counts, and 3.4% and 2.7% lower neutrophil counts (all P < .01). The same increment in logarithm-transformed triglyceride levels was associated with 2.3% higher total white blood cell counts and 4.5% higher lymphocyte counts (both P < .001). Similar results were obtained after excluding participants taking lipid-lowering medication. A one-standard deviation increase in high-density lipoprotein cholesterol was associated with a 1.5% lower white blood cell count (P = .018) but was not significantly associated with changes in any individual cell type., Conclusion: While significant associations were observed between plasma lipid levels and white blood cell populations, the heterogeneous and modest nature of these relationships makes it hard to support the hypothesis that lipids are in the causal pathway for leukogenesis in humans., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Fibroblast growth factor 21 (FGF21) has been suggested as a novel biomarker for cardiovascular disease (CVD), especially in people with high CVD risk. However, it is not known whether FGF21 is a CVD biomarker in an initially healthy cohort. We therefore investigated the relationship of plasma FGF21 levels with measures of subclinical atherosclerosis and cardiovascular events in Multi-Ethnic Study of Atherosclerosis participants without known CVD at baseline., Methods: A total of 5788 participants had plasma FGF21 levels measured at the baseline exam (2000-2002). Carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcification (CAC) were measured at baseline. Participants were followed up for incident CVD events over a median period of 14 years., Results: In cross-sectional analyses adjusting for socio-demographic variables, participants with higher FGF21 levels had higher carotid IMT, lower ABI, and higher prevalence of CAC (p < 0.001). However, these associations were not significant after simultaneously adjusting for demographic, socioeconomic and lifestyle factors, traditional CVD risk factors, and biomarkers of inflammation and hemostasis. Among 5768 patients with follow-up data, 820 developed incident CVD endpoints. Higher baseline FGF21 levels were not associated with the risk for incident CVD endpoints after adjusting for multiple confounding factors (odds ratio 1.03; 95% confidence interval, 0.94-1.12, per SD increase in ln-transformed FGF21 levels)., Conclusions: Although FGF21 has been suggested as a CVD biomarker for people with high CVD risk, our findings do not support a role of FGF21 as a CVD biomarker in those without a history of CVD., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Unicondylar knee arthroplasty (UKA) has superior functional outcomes compared to total knee arthroplasty (TKA) with good mid-term and long-term survival data from high-volume institutions. We sought to quantify the risk of complications, re-operation/revision, hospital re-admission for any reason, and mortality of knee arthroplasty patients in the US patient population using 2 large databases., Methods: UKA and TKA patients who were identified in the 2002-2011, 5% sample of Medicare data and 2004-2012 (June) MarketScan Commercial and Medicare Supplemental Databases were followed to evaluate the risk of complications, hospital re-admission for any reason, and mortality within 90 days of surgery. Survival probability defined by re-operation was calculated using the Kaplan-Meier method at 0.5, 2, 5, 7, and up to 10 years post-operatively., Results: Compared to UKA, complication rates for TKA patients were significantly higher, including wound complication, pulmonary embolism, stiffness, peri-prosthetic joint infection, myocardial infarction, re-admission, and death. Age was found to be a significant risk factor (P < .05) for all complications in the Medicare cohort, except stiffness (P = .839), and all complications in the MarketScan cohort, except re-admission (P = .418), whereas gender had a variable effect on complications based on age. Survivorship of UKA was lower than TKA at all time points. Additionally, younger age adversely affected implant survival. By 7 years post-surgery, UKA survivorship in the Medicare and MarketScan cohorts was 80.9% and 74.4%, respectively. In contrast, TKA survivorship for the same cohorts was 95.7% and 91.9% by the same time point., Conclusion: Patients undergoing UKA have fewer post-operative complications and re-admissions than those undergoing TKA. However, patients undergoing UKA have a higher rate of re-operation and revision at up to 10 years of follow-up. It appears that age, as well as surgeon and hospital volume significantly impacts implant survivorship while gender does not have a relation., Level of Evidence: Level III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Apolipoprotein A-I (apoA-I), the main protein constituent of HDLs, increases insulin synthesis and insulin secretion in pancreatic β cells. ApoA-I also accepts cholesterol that effluxes from cells expressing ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G 1 (ABCG1). Mice with conditional deletion of ABCA1 and ABCG1 in β cells [β-double knockout (DKO) mice] have increased islet cholesterol levels and reduced glucose-stimulated insulin secretion (GSIS). The project asks whether metabolic pathways are dysregulated in β-DKO mouse islets and whether this can be corrected, and GSIS improved, by treatment with apoA-I. β-DKO mice were treated with apoA-I or PBS, and islets were isolated for determination of GSIS. Total RNA was extracted from β-DKO and control mouse islets for microarray analysis. Metabolic pathways were interrogated by functional enrichment analysis. ApoA-I treatment improved GSIS in β-DKO but not control mouse islets. Plasma lipid and lipoprotein levels and islet cholesterol levels were also unaffected by treatment with apoA-I. Cholesterol metabolism, glucose metabolism, and inflammation pathways were dysregulated in β-DKO mouse islets. This was not corrected by treatment with apoA-I. In summary, apoA-I treatment improves GSIS by a cholesterol-independent mechanism, but it does not correct metabolic dysregulation in β-DKO mouse islets.-Hou, L., Tang, S., Wu, B. J., Ong, K.-L., Westerterp, M., Barter, P. J., Cochran, B. J., Tabet, F., Rye, K.-A. Apolipoprotein A-I improves pancreatic β-cell function independent of the ATP-binding cassette transporters ABCA1 and ABCG1.

Purpose: Mobile health (mHealth) interventions have great potential to promote health. To increase consumer engagement in mHealth interventions it is necessary to address factors that influence the target demographic. The Growing healthy (GH) program is the first obesity prevention program delivered via a smartphone app and website offering evidence-based information on infant feeding from birth until 9 months of age. This sub-study aimed to explore how the design features, quality of the app and participant characteristics influenced parents' engagement with the GH app. Methods: A sequential mixed methods design was used. The GH app participants (225/301) were considered for this sub-study. Participant app engagement was measured through a purpose-built Engagement Index (EI) using app metrics. Participants were categorized as low, moderately or highly engaged based on their EI score upon completing the 9 months program and were then invited to participate in semi-structured telephone interviews. Participants who used the app program, given an EI score and expressed interest to participate in these interviews were eligible. The interviews explored factors that influenced app engagement including delivery features and quality. Thematic analysis networks was used for analysis. Results: 108/225 expressed interest and 18 interviews were conducted from low ( n = 3), moderately ( n = 7), or highly ( n = 8) engaged participants based on purposeful sampling. Participants defined as highly engaged were likely to be a first-time parent, felt the app content to be trustworthy and the app design facilitated easy navigation and regularly opened the push notifications. Participants defined as having low or moderate engagement were likely to have experience from previous children, felt they had sufficient knowledge on infant feeding and the app did not provide further information, or experienced technological issues including app dysfunction due to system upgrades. Conclusions/Implications: This study demonstrated a novel approach to comprehensively analyse engagement in an mHealth intervention through quantitative (Engagement Index) and qualitative (interviews) methods. It provides an insight on maximizing data collected from these programs for measuring effectiveness and to understand users of various engagement levels interaction with program features. Measuring this can determine efficacy and refine programs to meet user requirements.

Background: Plant chloroplasts and mitochondria utilize nuclear encoded proteins to replicate their DNA. These proteins are purposely built for replication in the organelle environment and are distinct from those involved in replication of the nuclear genome. These organelle-localized proteins have ancestral roots in bacterial and bacteriophage genes, supporting the endosymbiotic theory of their origin. We examined the interactions between three of these proteins from Arabidopsis thaliana: a DNA helicase-primase similar to bacteriophage T7 gp4 protein and animal mitochondrial Twinkle, and two DNA polymerases, Pol1A and Pol1B. We used a three-pronged approach to analyze the interactions, including Yeast-two-hybrid analysis, Direct Coupling Analysis (DCA), and thermophoresis., Results: Yeast-two-hybrid analysis reveals residues 120-295 of Twinkle as the minimal region that can still interact with Pol1A or Pol1B. This region is a part of the primase domain of the protein and slightly overlaps the zinc-finger and RNA polymerase subdomains located within. Additionally, we observed that Arabidopsis Twinkle interacts much more strongly with Pol1A versus Pol1B. Thermophoresis also confirms that the primase domain of Twinkle has higher binding affinity than any other region of the protein. Direct-Coupling-Analysis identified specific residues in Twinkle and the DNA polymerases critical to positive interaction between the two proteins., Conclusions: The interaction of Twinkle with Pol1A or Pol1B mimics the minimal DNA replisomes of T7 phage and those present in mammalian mitochondria. However, while T7 and mammals absolutely require their homolog of Twinkle DNA helicase-primase, Arabidopsis Twinkle mutants are seemingly unaffected by this loss. This implies that while Arabidopsis mitochondria mimic minimal replisomes from T7 and mammalian mitochondria, there is an extra level of redundancy specific to loss of Twinkle function.

The aims of this study were to investigate the effects of Lactobacillus plantarum DR7 isolated from bovine milk against upper respiratory tract infections (URTI) and elucidate the possible mechanisms underlying immunomodulatory properties. The DR7 strain (9 log cfu/d) was administered for 12 wk in a randomized, double-blind, and placebo-controlled human study involving 109 adults (DR7, n = 56; placebo, n = 53). Subjects were assessed for health conditions monthly via questionnaires, and blood samples were evaluated for cytokine concentrations, peroxidation and oxidative stress, and gene expression in T cells and natural killer (NK) cells. The administration of DR7 reduced the duration of nasal symptoms (mean difference 5.09 d; 95% CI: 0.42-9.75) and the frequency of URTI (mean difference 0.32; 95% CI: 0.01-0.63) after 12 and 4 wk, respectively, compared with the placebo. The DR7 treatment suppressed plasma proinflammatory cytokines (IFN-γ, TNF-α) in middle-aged adults (30 to 60 yr old), while enhancing anti-inflammatory cytokines (IL-4, IL-10) in young adults (<30 yr old), accompanied by reduced plasma peroxidation and oxidative stress levels compared with the placebo. Young adults who received DR7 showed higher expression of plasma CD44 and CD117 by 4.50- and 2.22-fold, respectively, compared with the placebo. Meanwhile, middle-aged adults showed lower expression of plasma CD4 and CD8 by 11.26- and 1.80-fold, respectively, compared with the placebo, indicating less T-cell activation. In contrast, both young and middle-aged adults who received DR7 showed enhanced presence of nonresting and mature NK cells compared with those who received the placebo. We postulate that DR7 alleviated the symptoms of URTI by improving inflammatory parameters and enhancing immunomodulatory properties., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background: Fibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: The analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year)., Results: At baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05)., Conclusions: Our study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Objective- Insulin resistance and inflammation in pregnancy are risk factors for gestational diabetes mellitus. Increased plasma HDL (high-density lipoprotein) and apo (apolipoprotein) A-I levels have been reported to improve glucose metabolism and inhibit inflammation in animals and humans. This study asks whether increasing plasma apoA-I levels improves insulin sensitivity and reduces inflammation in insulin-resistant pregnant rats. Approach and Results- Insulin-resistant pregnant rats received intravenous infusions of lipid-free apoA-I (8 mg/kg) or saline on days 6, 9, 12, 15, and 18 of pregnancy. The rats were then subjected to a euglycemic-hyperinsulinemic clamp. Glucose uptake was increased in white and brown adipose tissue by 57±13% and 32±10%, respectively ( P<0.05 for both), and in quadriceps and gastrocnemius muscle by 35±9.7% and 47±14%, respectively ( P<0.05 for both), in the apoA-I-treated pregnant rats relative to saline-infused pregnant rats. The pregnant rats that were treated with apoA-I also had reduced plasma TNF-α (tumor necrosis factor-α) levels by 57±8.4%, plasma IL (interleukin)-6 levels by 67±9.5%, and adipose tissue macrophage content by 54±8.2% ( P<0.05 for all) relative to the saline-treated pregnant rats. Conclusions- These studies establish that apoA-I protects against pregnancy-induced insulin resistance in rats by increasing insulin sensitivity in adipose tissue and skeletal muscle and inhibiting inflammation. This identifies apoA-I as a potential target for preventing pregnancy-induced insulin resistance and reducing the incidence of gestational diabetes mellitus.

Aims: Cephalomedullary nails (CMNs) are commonly used for the treatment of intertrochanteric hip fractures. Total hip arthroplasty (THA) may be used as a salvage procedure when fixation fails in these patients. The aim of this study was to analyze the complications of THA following failed intertrochanteric hip fracture fixation using a CMN., Patients and Methods: Patients who underwent THA were identified from the 5% subset of Medicare Parts A/B between 2002 and 2015. A subgroup involving those with an intertrochanteric fracture that was treated using a CMN during the previous five years was identified and compared with the remaining patients who underwent THA. The length of stay (LOS) was compared using both univariate and multivariate analysis. The incidence of infection, dislocation, revision, and re-admission was compared between the two groups, using multivariate analysis adjusted for demographic, hospital, and clinical factors., Results: The Medicare data yielded 56 522 patients who underwent primary THA, of whom 369 had previously been treated with a CMN. The percentage of THAs that were undertaken between 2002 and 2005 in patients who had previously been treated with a CMN (0.346%) more than doubled between 2012 and 2015 (0.781%). The CMN group tended to be older and female, and to have a higher Charlson Comorbidity Index and lower socioeconomic status. The mean LOS was 1.5 days longer (5.3 vs 3.8) in the CMN group (p < 0.0001). The incidence of complications was significantly higher in the CMN group compared with the non-CMN group: infection (6.2% vs 2.6%), dislocation (8.1% vs 4.5%), revision (8.4% vs 4.3%), revision for infection (1.1% vs 0.37%), and revision for dislocation (2.2% vs 0.6%)., Conclusion: The incidence of conversion to THA following failed intertrochanteric hip fracture fixation using a CMN continues to increase. This occurs in elderly patients with increased comorbidities. There is a significantly increased risk of infection, dislocation, and LOS in these patients. Patients with failed intertrochanteric hip fracture fixation using a CMN who require THA should be made aware of the increased risk of complications, and steps need to be taken to reduce this risk. Cite this article: Bone Joint J 2019;101-B(6 Supple B):91-96.

Aim: Neural plastic changes are experience and learning dependent, yet exploiting this knowledge to enhance clinical outcomes after stroke is in its infancy. Our aim was to search the available evidence for the core concepts of neuroplasticity, stroke recovery, and learning; identify links between these concepts; and identify and review the themes that best characterise the intersection of these three concepts., Methods: We developed a novel approach to identify the common research topics among the three areas: neuroplasticity, stroke recovery, and learning. A concept map was created a priori , and separate searches were conducted for each concept. The methodology involved three main phases: data collection and filtering, development of a clinical vocabulary, and the development of an automatic clinical text processing engine to aid the process and identify the unique and common topics. The common themes from the intersection of the three concepts were identified. These were then reviewed, with particular reference to the top 30 articles identified as intersecting these concepts., Results: The search of the three concepts separately yielded 405,636 publications. Publications were filtered to include only human studies, generating 263,751 publications related to the concepts of neuroplasticity ( n = 6,498), stroke recovery ( n = 79,060), and learning ( n = 178,193). A cluster concept map (network graph) was generated from the results; indicating the concept nodes, strength of link between nodes, and the intersection between all three concepts. We identified 23 common themes (topics) and the top 30 articles that best represent the intersecting themes. A time-linked pattern emerged., Discussion and Conclusions: Our novel approach developed for this review allowed the identification of the common themes/topics that intersect the concepts of neuroplasticity, stroke recovery, and learning. These may be synthesised to advance a neuroscience-informed approach to stroke rehabilitation. We also identified gaps in available literature using this approach. These may help guide future targeted research.

Background: Patients undergoing primary total hip arthroplasty (THA) following lumbar spine fusion have an increased incidence of dislocation compared to those without prior lumbar fusion. The purpose of this study is to determine if timing of THA prior to or after lumbar fusion would have an effect on dislocation and revision incidence in patients with both hip and lumbar spine pathology., Methods: One hundred percent Medicare inpatient claims data from 2005 to 2015 were used to compare dislocation and revision risks in patients with primary THA with pre-existing lumbar spine fusion vs THA with subsequent lumbar spine fusion within 1, 2, and 5 years after the index THA. A total of 42,300 patients met inclusion criteria, 28,668 patients of which underwent THA with pre-existing lumbar spinal fusion (LSF) and 13,632 patients who had prior THA and subsequent LSF. Patients who had THA first followed by LSF were further stratified based on the interval between index THA and subsequent LSF (1, 2, and 5 years), making 4 total groups for comparison. Multivariate cox regression analysis was performed adjusting for age, socioeconomic status, race, census region, gender, Charlson score, pre-existing conditions, discharge status, length of stay, and hospital characteristics., Results: Patients with prior LSF undergoing THA had a 106% increased risk of dislocation compared to those with LSF done 5 years after THA (P < .001). Risk of revision THA was greater in the pre-existing LSF group by 43%, 41%, and 49% at 1, 2, and 5 years post THA compared to the groups with THA done first with subsequent LSF. Dislocation was the most common etiology for revision THA in all groups, but significantly higher in the prior LSF group (26.6%)., Conclusion: Results of this study demonstrate that sequence of surgical intervention for concomitant lumbar and hip pathology requiring LSF and THA respectively significantly impacts the fate of the THA performed. Patients with prior LSF undergoing THA are at significantly higher risk of dislocation and subsequent revision compared to those with THA first followed by delayed LSF., Level of Evidence: 3., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomised, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×10 9 cfu/day) for 12 weeks reduced symptoms of stress ( P =0.024), anxiety ( P =0.001), and total psychological scores ( P =0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 ( P <0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning ( P <0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo ( P <0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.

Background: Higher plasma fibroblast growth factor 21 (FGF21) levels predict incident cardiovascular events in type 2 diabetes patients. However, whether FGF21 levels predict cardiovascular events in statin-treated patients in the general population is unknown. We investigated whether FGF21 levels predict major cardiovascular event (MCVE) in the Treating to New Targets (TNT) trial participants., Methods: After 8-week run-in on atorvastatin 10 mg/day, 10,001 patients with stable coronary disease in the TNT trial were randomized to 10 mg or 80 mg/day of atorvastatin for a median of 4.9 years. We analyzed data from 1996 patients with plasma FGF21 levels measured at randomization. Among them, 1835 patients had FGF21 measured one-year post-randomization., Results: Higher ln-transformed FGF21 levels at randomization were associated with higher risk of incident MCVE (adjusted hazards ratio per SD increase = 1.18, P = 0.019). At 1-year post-randomization, FGF21 levels were lower in patients randomized to receive 80 mg versus 10 mg atorvastatin (186.9 versus 207.5 pg/mL respectively, P = 0.006). Higher ln-transformed FGF21 levels at 1-year post-randomization were also associated with higher subsequent risk of MCVEs (adjusted hazards ratio per SD increase = 1.24, P = 0.009). However, changes in FGF21 levels over 1-year were not related to subsequent MCVE risk. FGF21 levels had significant incremental value in net reclassification improvement in MCVE risk prediction., Conclusions: Higher plasma FGF21 levels are associated with higher CVD risk in statin-treated high-risk patients. Higher dose atorvastatin is associated with a reduction in FGF21 levels. FGF21 provides incremental value in CVD risk prediction in statin-treated patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate a multimodal pain management program incorporating periarticular injections of liposomal bupivacaine after hemiarthroplasty treatment of femoral neck fractures. This retrospective study selected patients treated with periarticular injections of liposomal bupivacaine within the multimodal pain management program (LBUP) ( n = 100) and a control group of patients treated without local infiltration ( n = 78). Similar pain control was achieved between both groups from day 1 to day 4 postsurgery (min p = .392). Length of stay was significantly lower for LBUP patients (4.8 days vs. 5.7 days, p = .013), and LBUP patients were significantly more likely to be ambulatory at discharge (82% vs. 69%, p = .013). LBUP patients were also less likely to need the intensive care unit (4% vs. 14%, p = .027). The percentage of patients with at least one opioid-related adverse event was lower in the LBUP group (3% vs. 8%, p = .156) as was the 90-day mortality rate (2% vs. 8%, p = .069), but the differences were not statistically significant. (Journal of Surgical Orthopaedic Advances 28(1):58-62, 2019).

Background and Aims: Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. We have investigated the relationship of plasma FGF21 levels with both prevalent and incident metabolic syndrome (MetS) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA)., Methods: 5783 participants from four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American) were included in the cross-sectional analysis. Longitudinal analysis involved 3479 participants without MetS at baseline, of whom 1100 participants developed incident MetS over 9.2 years., Results: Elevated FGF21 levels were found in participants with prevalent MetS (median [interquartile range] = 189.4 [114.4-302.1] vs. 123.7 [65.9-210.3] pg/mL, p < 0.001) or incident MetS (145.6 [84.9-240.8] vs 112.0 [57.0-194.5] pg/mL, p < 0.001), compared to those without. After adjusting for baseline demographic, socioeconomic and lifestyle factors, as well as cardiovascular risk factors and biomarkers, and compared to the lowest quartile, the highest FGF21 quartile was associated with prevalent MetS (odds ratio 2.80; 95% confidence interval, 2.30-3.40, p < 0.001). Among participants without MetS at baseline, the highest FGF21 quartile was associated with higher risk of incident MetS (hazards ratio 1.76; 95% confidence interval, 1.46-2.12, p < 0.001). Similar results were obtained when assessing ln-transformed FGF21 levels. Overall, no significant interaction was found with age, sex, and race/ethnicity for both prevalent and incident MetS., Conclusions: Higher FGF21 levels significantly predict the development of MetS in an ethnically diverse population followed long term. Further studies are needed to confirm the potential role of FGF21 as a biomarker for MetS., (Copyright © 2018. Published by Elsevier B.V.)

SummaryMouse and lamb oocytes were vitrified with, or exposed to, different cryoprotectants and evaluated for their effects on their survival and developmental competence after in vitro fertilization (IVF) and activation treatments. Control oocytes remained untreated, whilst the remainder were exposed to three different combinations of vitrification solutions [dimethyl sulfoxide (DMSO) + ethylene glycol (EG), EG only, or propanediol (PROH) + EG] and either vitrified or left unfrozen (exposed groups). Oocytes in the control and vitrified groups underwent IVF and developmental competence was assessed to the blastocyst stage. In lambs, survival rate in vitrified oocytes was significantly lower than for oocytes in the exposed groups (P &lt;0.05). Blastocyst development was low in vitrified oocytes compared with controls (&lt;6% vs 38.9%, P &lt;0.01). Parthenogenetic activation was more prevalent in vitrified lamb oocytes compared with controls (P &lt;0.05). No evidence of zona pellucida hardening or cortical granule exocytosis could account for reduced fertilization rates in vitrified lamb oocytes. Mouse oocytes demonstrated a completely different response to lamb oocytes, with survival and parthenogenetic activation rates unaffected by the vitrification process. Treatment of mouse oocytes with DMSO + EG yielded significantly higher survival and cleavage rates than treatment with PROH + EG (87.8% and 51.7% vs 32.7% and 16.7% respectively, P &lt;0.01), however cleavage rate for vitrified oocytes remained lower than for the controls (51.7% vs 91.7%, P &lt;0.01) as did mean blastocyst cell number (33 ± 3.1 vs 42 ± 1.5, P &lt;0.05). From this study, it is clear that lamb and mouse show different tolerances to cryoprotectants commonly used in vitrification procedures, and careful selection and testing of species-compatible cryoprotectants is required when vitrifying oocytes to optimize survival and embryo development.

The association between fibroblast growth factor 21 (FGF21) and kidney function has been extensively studied in recent years in both animal and human studies. However, the exact functional role of FGF21 in the kidney remains unclear. Previous animal studies have shown that administration of FGF21 ameliorates kidney function, morphological glomerular abnormalities, dyslipidemia, hyperglycemia, insulin resistance, oxidative stress and obesity. In human studies, FGF21 levels negatively correlated with estimated glomerular filtration rate. FGF21 levels were elevated in patients with end-stage renal disease. The elevation of FGF21 levels in presence of kidney disease has also raised questions as to whether FGF21 is a potential biomarker for detecting a decline in renal function. In recent clinical trials, an FGF21 analogue reduced insulin levels and body weight, and ameliorated dyslipidemia in patients with type 2 diabetes mellitus and obesity, all of which are well-known risk factors for kidney disease. Thus, FGF21 may be a potential therapeutic target for the treatment of kidney disease, although adverse side effects should also be considered when administering FGF21 since FGF21 may affect bone development and reproduction. This review will assess current knowledge on the relationship between FGF21 and kidney function., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated. The phosphorylation of AMPK by these three LAB strains was more evident in U2OS and C2C12 cells, compared to the other cell lines and control (P < .05). Using premature senescent Sprague-Dawley rats induced by D-galactose (D-gal), the administration of LAB (10 log CFU/rat/day) for 12 weeks prevented the shortening of telomere length in D-gal-treated rats compared to the untreated control (P < .05). LF-DR9 lowered gene expression of p53, a known senescent biomarker, in gastrocnemius muscle and tibia compared to the control. The selected LAB strains also enhanced lipid, renal, and liver profile of rats, suggesting added potential of the strains in preventing aging-induced metabolic diseases. Strain LP-0291 and LH-1515 showed ability to adhere to mucin, no antibiotic resistance, tolerated and proliferated under gastric and intestinal simulated conditions, and inhibited the growth of pathogens Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis, comparable to commercial probiotic LF-DR9 and Lactobacillus sakei Probio 65. This study provided an insight into the potential of LAB for exhibiting antisenescence effects, with potentials as new medicinal foods for targeted antiaging therapies.