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Simple Summary Gallic acid (GA) has been demonstrated to have antioxidant, antimicrobial, anti-inflammatory, and health-promoting properties. In pigs, GA supplementation has been shown to decrease di-arrhea incidence of weaned piglets and improve their intestinal integrity. The present experiment was conducted to test the hypothesis that growth performance and diarrhea after weaning could be improved by supplementing the diet with 400 mg/kg GA to weaned piglets, especially for low weaning weight piglets. Abstract This study evaluated the effects of dietary gallic acid (GA) on growth performance, diarrhea incidence and plasma antioxidant status of weaned piglets regardless of whether weaning weight was high or low. A total of 120 weaned piglets were randomly allocated to four treatments in a 42-day experiment with a 2 × 2 factorial treatment arrangement comparing different weaning weights (high weight (HW) or low weight (LW), 8.49 ± 0.18 kg vs. 5.45 ± 0.13 kg) and dietary treatment (without supplementation (CT) or with supplementation of 400 mg/kg of GA). The results showed that HW piglets exhibited better growth performance and plasma antioxidant capacity. Piglets supplemented with GA had higher body weight (BW) on day 42 and average daily gain (ADG) from day 0 to 42 compared to the control piglets, which is mainly attributed to the specific improvement on BW and ADG of LW piglets by the supplementation of GA. The decreased values of diarrhea incidence were seen in piglets fed GA, more particularly in LW piglets. In addition, dietary GA numerically reduced malondialdehyde (MDA) content in plasma of LW piglets. In conclusion, our study suggests that dietary GA may especially improve the growth and health in LW weaned piglets.

OBJECTIVES This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury. DESIGN Retrospective observational single-center cohort study. SETTING Tertiary care PICU. PATIENTS Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI. INTERVENTIONS Extracorporeal membrane oxygenation support. MEASUREMENTS AND MAIN RESULTS Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence. CONCLUSIONS Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

Our previous study found that soybean isoflavones in soybean meal play an important role in improving growth performance and antioxidant capacity in pigs. However, it is still unknown whether long-term supplementation with daidzein, an active molecule deglycosylated from daidzin, in a corn-soybean meal diet can enhance growth performance in pigs. Thus, in the present study, an animal trial was carried out to investigate the effects of dietary supplementation with daidzein on the growth performance and antioxidant capacity of pigs. A total of 80 weaned piglets (40 barrows and 40 females) were assigned to 4 treatments with 5 pens per treatment and 4 piglets per pen and fed a diet supplemented with 0, 25, 50 and 100 mg/kg daidzein for a 72-day trial. In addition, porcine intestinal epithelial cells (IPEC-J2) were used as an in vitro model to explore the underlying antioxidant mechanisms of daidzein. IPEC-J2 cells were treated with 0.6 mM hydrogen peroxide (H

Hypophosphatemia is a common and dangerous complication of acute liver failure (ALF) of various etiologies. While various mechanisms for ALF-associated hypophosphatemia have been proposed including high phosphate uptake into regenerating hepatocytes, acetaminophen (APAP)-associated hypophosphatemia was linked to renal phosphate wasting, and APAP-induced renal tubular injury was proposed as underlying mechanism. We studied 30 normophosphatemic and 46 hypophosphatemic (serum phosphate < 2.5 mg/dL) patients from the Acute Liver Failure Study Group registry with APAP- or non-APAP-induced ALF. Since kidney injury affects phosphate excretion, patients with elevated serum creatinine (>1.2 mg/dL) were excluded. Maximal amount of renal tubular phosphate reabsorption per filtered volume (TmP/GFR) was calculated from simultaneous serum and urine phosphate and creatinine levels to assess renal phosphate handling. Instead of enhanced renal phosphate reabsorption as would be expected during hypophosphatemia of non-renal causes, serum phosphate was positively correlated with TmP/GFR in both APAP- and non-APAP-induced ALF patients (R(2) = 0.66 and 0.46, respectively; both p < 0.0001), indicating renal phosphate wasting. Surprisingly, there was no evidence of kidney damage based on urinary markers including neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C even in the APAP group. Additionally, there was no evidence that the known serum phosphatonins parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), and α-Klotho contribute to the observed hypophosphatemia. We conclude that the observed hypophosphatemia with renal phosphate wasting in both APAP- and non-APAP-mediated ALF is likely the result of renal tubular phosphate leak from yet-to-be identified factor(s) with no evidence for proximal tubular damage or contribution of known phosphatonins.

Dietary supplementation with 0.4 or 0.8% L-arginine (Arg) to gilts between days 14 and 25 of gestation enhances embryonic survival and vascular development in placentae; however, the underlying mechanisms are largely unknown. This study tested the hypothesis that Arg supplementation stimulated placental expression of mRNAs and proteins that enhance angiogenesis, including endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), placental growth factor (PGF), GTP cyclohydrolase-I (GTP-CH1), ornithine decarboxylase (ODC1), and vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2). Beginning on the day of breeding, gilts were fed daily 2 kg of a corn-soybean meal-based diet supplemented with 0.0 (control), 0.4, or 0.8% Arg. On day 25 of gestation, gilts were hysterectomized to obtain uteri and conceptuses for histochemical and biochemical analyses. eNOS and VEGFR1 proteins were localized to endothelial cells of maternal uterine blood vessels and to the uterine luminal epithelium, respectively. Compared with the control, dietary supplementation with 0.4 or 0.8% Arg increased (P 0.05) the amounts of nitrite plus nitrate (NOx; oxidation products of NO) and polyamines in allantoic and amniotic fluids, concentrations of NOx, tetrahydrobiopterin (BH4, an essential cofactor for all NOS isoforms) and polyamines in placentae, as well as placental protein abundances of GTP-CH1 (the key enzyme for BH4 production) and ODC1 (the key enzyme for polyamine synthesis). Placental mRNA levels for GTP-CH1, eNOS, PGF, VEGF, and VEGFR2 increased in response to both 0.4% and 0.8% Arg supplementation. Collectively, these results indicate that dietary Arg supplementation to gilts between days 14 and 25 of pregnancy promotes placental angiogenesis by increasing the expression of mRNAs and proteins for angiogenic factors as well as NO and polyamine syntheses.

Aim To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. Materials and methods The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes. Results We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of -1.1% (95% CI -2.0% to -0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of -3.7 kg (95% CI -5.8 to -1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)]. Conclusions In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

Background Incarceration and human immunodeficiency virus (HIV) are associated with sexually transmitted infections (STIs); however, little is known about STI prevalence among people living with HIV (PLWH) during and after incarceration. Methods Electronic medical records from the Dallas County Jail and community HIV clinics were reviewed to determine the frequency and results of testing for gonorrhea, chlamydia, syphilis, and hepatitis B virus (HBV) among PLWH incarcerated in Dallas County Jail between 2010 and 2013. HIV viral loads (VL) and evidence of STI symptoms and treatment were also collected. Results During 2473 incarcerations, 6 (3%) of 190 tests were positive for gonorrhea, 7 (4%) of 190 for chlamydia, 231 (21%) of 1082 for syphilis, of which 53 (23%) were new diagnoses, and 48 (5%) of 1005 for HBV surface antigen. Among 1631 releases to the community, 808 followed up in community clinics, where 21 (4%) 553 tests were positive for gonorrhea, 23 (4%) of 555 for chlamydia, 150 (19%) of 808 for syphilis, of which 31 (21%) were new diagnoses, and 24 (6%) of 421 for HBV surface antigen. The majority of new STI cases, 51 (80%) of 64 in jail and 43 (77%)of 56 in the community, had a concurrent detectable (>200 copies/mL) HIV VL. Conclusions Testing for gonorrhea and chlamydia was low, particularly in jail, which was attributed to testing protocols. High proportions of PLWH tested positive for syphilis and HBV infection in both settings. The majority of patients with active STIs had a detectable HIV VL. Routine, opt-out screening for STIs for PLWH during and after incarceration has the potential to identify a high proportion of STIs and improve secondary HIV prevention.

Context Patients with very severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL; 22.6 mmol/L) require aggressive treatment. However, little research exists on the underlying etiologies and management of very severe hypertriglyceridemia. Objective We hypothesized (i) very severe hypertriglyceridemia in adults is mostly associated with secondary causes and (ii) most patients with very severe hypertriglyceridemia lack appropriate follow-up and treatment. Design We queried electronic medical records at Parkland Health and Hospital Systems for lipid measurements in the year 2016 and identified patients with serum triglyceride levels ≥2000 mg/dL (22.6 mmol/L). We extracted data on demographics, underlying causes, lipid-lowering therapy, and follow-up. Results One hundred sixty-four serum triglyceride measurements were ≥2000 mg/dL (22.6 mmol/L) in 103 unique patients. Of these, 60 patients were admitted to the hospital (39 for acute pancreatitis). Most were Hispanic (79%). The major conditions associated with very severe hypertriglyceridemia included uncontrolled diabetes mellitus (74%), heavy alcohol use (10%), medication use (7%), and hypothyroidism (2%). Two patients were known to have monogenic causes of hypertriglyceridemia. After the index measurement of triglycerides ≥2000 mg/dL (22.6 mmol/L), the use of triglyceride-lowering drugs increased, most prominently the use of fish oil supplements, which increased by 80%. However, in follow-up visits, hypertriglyceridemia was addressed in only 50% of encounters, and serum triglycerides were remeasured in only 18%. Conclusion In summary, very severe hypertriglyceridemia was quite prevalent (∼0.1% of all lipid measurements) in our large county health care system, especially in Hispanic men. Most cases were related to uncontrolled diabetes mellitus, and follow-up monitoring was inadequate.

Two-dimensional MXene Ti3C2T x nanosheets with peroxide decoration (p-Ti3C2T x ) are synthesized by a sonication-assisted MILD etching method. The obtained MXenes can generate hydroxyl radical species and act as an initiator for free-radical polymerization of a series of acrylic monomers without the use of light illumination or co-initiators. The monomers analyzed include acrylamide, N-isopropylacrylamide (NIPAM), N,N-dimethylacrylamide, methyl methacrylate, and hydroxyethyl methacrylate. By simply mixing N-isopropylacrylamide monomers and p-Ti3C2T x nanosheets under deoxygenated conditions, PNIPAM-based nanocomposite hydrogels are synthesized using a high concentration of the monomer. The nanocomposite hydrogels have a photothermal conversion efficiency of 34.7% and photothermal stability superior to that of pristine Ti3C2T x . Taking advantage of the thermal responsive behavior of PNIPAM, the nanocomposite hydrogels are successfully exploited as remotely near-infrared light controlled "smart" windows, fluidic valves and photodetectors.

PURPOSE: To evaluate the effect of renin-angiotensin system (RAS) inhibiting medications prior to admission on the severity of kidney injury in patients presenting with sepsis-associated acute kidney injury (SA-AKI). MATERIALS AND METHODS: A single center, retrospective cohort study of critically ill adult patients admitted with diagnoses of both sepsis and AKI. RAS inhibition was defined as angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The primary outcome was Kidney Disease: Improving Global Outcomes stage AKI upon hospital admission. RESULTS: Of 707 individuals studied, patients receiving RAS inhibition prior to admission (vs. those not) had more stage 3 AKI (40.1% vs. 28.7%; p=0.008) and more frequently reached stage 3 AKI during the first week (49.8% vs. 41.1%; p=0.047). In an adjusted multinomial regression model, patients receiving RAS inhibition (vs. those not) had an increased relative risk of presenting with stage 3 AKI on admission (vs. stage 1 AKI reference): RRR 2.32 (95% CI 1.50–3.59). Similar findings were observed in a propensity score matched analysis. CONCLUSION: Patients receiving RAS inhibition (vs. those not) prior to an admission with SA-AKI presented with more severe AKI on admission and during the first week. Hospital mortality and kidney function at discharge were similar between groups.

Gallic acid is a phenolic compound that exhibits antibacterial, antioxidative and anti-inflammatory functions. In a previous study, we found that dietary supplementation with gallic acid decreased incidence of diarrhoea and protected intestinal integrity in weaning piglets. However, the underlying mechanism remains unclear. Here, a pig intestinal epithelial cell line (IPEC-J2) was used as an in vitro model to explore the antioxidant and anti-inflammatory capacity of gallic acid. IPEC-J2 cells were stimulated with hydrogen peroxide (H2 O2 ) and lipopolysaccharide (LPS) to establish oxidative and inflammatory models, respectively. Results showed that H2 O2 significantly decreased catalase (CAT) secretion and CAT mRNA abundance in the cells (p < 0.05), while pretreatment with gallic acid did not prevent the decrease in CAT expression induced by H2 O2 . However, gallic acid pretreatment mitigated the increased expression of the tumour necrosis factor-α and interleukin-8 genes caused by LPS in IPEC-J2 cells (p < 0.05). In addition, pretreatment with gallic acid significantly suppressed phosphorylation of NF-κB and IκBα in LPS-stimulated IPEC-J2 cells. Moreover, LPS stimulation decreased the protein abundance of zona occludens 1 (ZO-1) and occludin, while pretreatment with gallic acid preserved expression level of tight junction proteins ZO-1 and occludin in LPS-stimulated IPEC-J2 cells (p < 0.05). In conclusion, gallic acid may mitigate LPS-induced inflammatory responses by inhibiting the NF-κB signalling pathway, exerting positive effects on the barrier function of IPEC-J2 cells.

Background Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. Methods Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5–7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. Results Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. Conclusions In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.

Background New therapies to achieve hepatitis B surface antigen (HBsAg) clearance are under development. However, gaps in knowledge exist in understanding the incidence and predictors of HBsAg clearance in a racially diverse HIV population. Methods We examined the incidence and risk of HBsAg clearance in a retrospective cohort of people with HIV/hepatitis B virus (HBV). Included patients had sufficient data to establish chronic infection based on Centers for Disease Control and Prevention guidelines. We examined the incident rate for HBsAg loss and hazard rate ratios to evaluate predictors for HBsAg clearance in a multivariable model. Results Among 571 HIV/HBV patients, 87% were male, 61% were Black, 45% had AIDS, 48% were HBeAg positive, and the median follow-up was 88 months. Incident HBsAg clearance was 1.5 per 100 person-years. In the multivariate model, those with AIDS at baseline (adjusted hazard ratio [aHR], 2.43; 95% CI, 1.37–4.32), Hispanics (aHR, 3.57; 95% CI, 1.33–9.58), and those with injection drug use as an HIV risk factor (aHR, 3.35; 95% CI, 1.26–8.89) were more likely to lose HBsAg, whereas those who were HBeAg positive (aHR, 0.34; 95% CI, 0.19–0.63) were less likely to lose HBsAg. The median change in CD4 cell count during the observation period was 231 cells/mm3 in those with HBsAg loss vs 112 cells/mm3 in those with HBsAg persistence (P = .004). Conclusions HBsAg loss occurs in about 10% of those with chronic HBV infection. Being Hispanic, having AIDS at baseline, having an injection drug use history, and having HBeAg-negative status at baseline predicted the likelihood of HBsAg loss. Immune restoration may be a mechanism through which HBsAg loss occurs in HIV patients.

Context Radiofrequency ablation (RFA) has only recently gained popularity in the United States for treatment of thyroid nodules (TNs), with a limited number of patients having undergone the procedure in this country. Objective To evaluate the safety and efficacy of RFA of TNs performed in an outpatient setting in the United States. Methods This is a retrospective, single-center study of 53 patients who underwent RFA of 58 TNs between November 2018 and January 2021. The reduction in volume of nodule, cosmetic and symptomatic improvement, effect on thyroid function, and complications following RFA were assessed. Results Eleven out of 53 patients were excluded from the analysis. A total of 47 benign TNs (23 nonfunctioning thyroid nodules [NFTNs] and 24 autonomously functioning thyroid nodules [AFTNs]), were assessed after RFA. The median reduction in volume was 70.8% after a median follow-up period of 109 days, with symptomatic and cosmetic improvement (P Conclusion RFA is a safe and efficacious treatment for symptomatic NFTNs and AFTNs in our population and is especially effective for smaller nodules. RFA should be considered an alternative for TNs in patients who cannot or do not want to undergo surgery.

Nephrolithiasis is associated with an increased risk of chronic kidney disease, and its incidence varies with age. However, little is known on the combined impact of aging and declining renal function on urinary risk factors for calcium oxalate stone formation. A retrospective analysis was performed on 24-hour urine collections from 993 calcium oxalate stone-forming patients. We first tested for interactions between age and creatinine clearance on various urinary determinants of calcium oxalate nephrolithiasis, and then examined their separate and combined effects in univariable and multivariable analyses adjusting for demographic and biochemical covariates. We identified significant interactions between age and creatinine clearance in predicting 24-hour urine pH, calcium, and citrate. In view of the small number of stone formers with low creatinine clearance, we limited further regression analyses to patients with creatinine clearance ≥60 mL/min. In multivariable analyses, urine citrate, oxalate, and total volume were positively correlated with age, whereas urine pH, citrate, calcium, oxalate, total volume, and RSR of calcium oxalate all significantly decreased with lower creatinine clearance. A decrease in creatinine clearance from 120 to 60 ml/min was associated with clinically significant decreases in the daily excretion rate of citrate (by 188 mg/day), calcium (by 33 mg/day), and oxalate (by 4 mg/day), and in RSR calcium oxalate (by 1.84). Age and creatinine clearance are significant and independent predictors of several urinary determinants of calcium oxalate nephrolithiasis. The impacts of aging and declining renal function should be considered during the management of calcium oxalate stone-forming patients.

Background: In previous study, we found that soybean isoflavones in soybean meal play important roles in improving growth performance and antioxidant properties in pigs. However, it is still not known whether long-term supplementation with daidzein, an active molecule deglycosylated from daidzin, in a corn-soybean meal diet can enhance growth performance in pigs. Thus, in the present study, an animal trial was carried out to investigate the effects of dietary supplementation with daidzein on the growth performance and antioxidant capacity of pigs. Porcine intestinal epithelial cells (IPEC-J2) were also used as an in vitro model to explore the underlying antioxidant mechanisms of daidzein. Weanling pigs were fed a diet supplemented with 0, 25, 50, and 100 mg/kg daidzein, and IPEC-J2 cells were treated with 0.6 mM hydrogen peroxide (H2O2) in the presence or absence of 40 μM daidzein. Results: Adding 50 mg/kg daidzein to the diet significantly improved body weight on day 72, average daily gain during days 0-72 and plasma superoxide dismutase activity on day 42 (P < 0.05). Treatment with 0.6 mM H2O2 for 1 h significantly decreased cell viability and catalase (CAT) activities and increased intracellular reactive oxygen species (ROS) levels and malondialdehyde (MDA) content (P < 0.05), while pretreatment with 40 μM daidzein prevented the decrease in cell viability and CAT activities and the increase in intracellular ROS levels and MDA content caused by H2O2 (P < 0.05). In addition, H2O2 stimulation significantly suppressed the expression of nuclear factor erythoid-2-related factor 2 (Nrf2), CAT, occludin and zonula occludens-1 (ZO-1), while pretreatment with daidzein preserved the expression of Nrf2, CAT, occludin and ZO-1 in H2O2-stimulated IPEC-J2 cells (P < 0.05).Conclusions: Long-term dietary supplementation with 50 mg/kg daidzein improved growth performance and antioxidative properties in pigs. Daidzein exerted protective effects against H2O2-induced oxidative stress in IPEC-J2 cells, and the underlying mechanism may be related to the activation of the Kelch-like ECH-associated protein 1-Nrf2/antioxidant response element signaling pathway.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity, this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.

Doping heteroatom, an effective way to enhance the electrochemical performances of graphene, has received wide attention, especially related to nitrogen. Alternating voltage electrochemical exfoliation, as a low cost and green electrochemical approach, has been developed to construct in-situ N-doped graphene (N-Gh) material. The N-Gh presents a much higher capacity than that of pure graphene prepared via the same method, which might be attributed to the introduction of nitrogen, which has much more effects and a disordered structure. As-prepared N-Gh exhibits a low O/C ratio that is helpful in maintaining high electrical conductivity. And the effects and disorder structure are also conductive to reduce the overlaps of graphene layers. A symmetric supercapacitor assembled with N-Gh electrodes displays a satisfactory rate behavior and long cycling stability (92.3% retention after 5,000 cycles).

24-hour urine collections are used to assess excretion of various analytes. Although concomitant measurement of creatinine excretion adjusted for body weight (BW) is utilized to determine adequacy of collection, no gold standard exists for determining completeness of a collection. Use of current reference ranges for daily creatinine excretion/BW of 15–20 mg creatinine/kg BW/day in women and 20–25 mg creatinine/kg/d in men established prior to the rising prevalence of obesity has resulted in a large proportion of contemporary individuals appearing to have “incomplete” urine collections. Our objective was to evaluate the range of creatinine excretion in accurately collected urine specimen from adults with a wide spread of age and BW, and to generate an equation that accurately predicts 24-hour urine creatinine excretion rate from readily available clinical parameters to aid in assessing adequacy of a 24-hour urine collection. We analyzed data from participants who completed two consecutive 24-hour urine collections while consuming a fixed metabolic diet during inpatient research admissions. Results from participants with 24-hour urine creatinine excretion rate differing by >10% between the two consecutive collections were excluded. In the initial 115 pairs of inpatient 24-hour urine collections (50 female, 65 male) participants, creatinine excretion/BW fell outside the currently accepted reference ranges in >50% of collections. The proportion below the reference range increased with higher BMI. In this derivation dataset, linear regression models were then constructed to predict 24-hr urine creatinine excretion from race, sex, age, weight and height. Reliable prediction of observed 24-hr urine creatinine excretion was confirmed in a validation dataset that included 50 pairs of 24-hour urine samples similarly collected in an inpatient research setting. This new prediction model performed significantly better than the currently used reference ranges in a large outpatient dataset including 1,399 pairs of 24-hour urine collections. In women, actual creatinine excretion fell within the 95% prediction intervals for our derived equation in 90% of cases using the new interval vs 46% using the current reference range. The corresponding values were 90% and 33% in men. In both genders, the superiority of the new prediction over the current reference range was more pronounced at higher BMI. We therefore propose revision of currently used criteria to define adequacy of 24-hour urine collection to account for the impact of obesity. The proposed equation incorporates readily available demographic parameters to predict urine creatinine excretion. These findings have wide implications on patient care and research studies, and future studies should test this equation in different settings, diets, and populations.

Familial partial lipodystrophy (FPLD), a rare autosomal dominant disorder, is characterized by marked loss of subcutaneous (sc) fat from the extremities, and predisposition to insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis. FPLD2 and FPLD3 due to causal variants in LMNA and PPARG, respectively, are the two most common subtypes. Due to extremely rare prevalence of FPLD3 and limited reports in the literature, whether there are phenotypic differences between the two subtypes remain unclear. Therefore, we compared the anthropometric measurements and prevalence of metabolic abnormalities among 32 FPLD3 subjects (4 M, 28 F; mean ± SD age, 41 ± 17.2 y; body mass index (BMI), 26 ± 4.0 kg/m2) with 271 FPLD2 subjects (66 M, 205 F; age, 37.4 ± 17.0 y; BMI, 26 ± 5.0 kg/m2) from two referral centers in the United States. As compared to those with FPLD2, FPLD3 subjects had borderline higher prevalence of hypertriglyceridemia (66% vs 84%; P = 0.063), but significantly higher prevalence of diabetes (44% vs 72%; P = 0.004), past history of acute pancreatitis (13% vs 52%; P

Using a retrospective cohort analysis of inmates released from Dallas County Jail between January 2011 and November 2013, this study characterizes people living with HIV/AIDS (PLWHA) who are lost to care after release from jail. We used Kaplan-Meier analysis to estimate the risk of becoming lost to post-release HIV care and a Cox proportional hazards regression model to identify associated factors. The majority of individuals (78.2%) were men and 65.5% were black. Of the incarcerations that ended with release to the community, approximately 43% failed to link to community HIV care. Non-Hispanic Whites were more likely than Hispanics or Blacks to drop out of care after release. Individuals with histories of substance use or severe mental illness were more likely to become lost, while those under HIV care prior to incarceration and/or who had adhered to antiretroviral therapy (ART) were more likely to resume care upon release. Targeted efforts such as rapid linkage to care and re-entry residence programs could encourage formerly incarcerated individuals to re-engage in care.

Acute kidney injury (AKI) is a common and morbid complication in patients with severe burn. The reported incidence of AKI and mortality in this population varies widely due to inconsistent and changing definitions. They aimed to examine the incidence, severity, and hospital mortality of patients with AKI after burn using consensus criteria. This is a retrospective cohort study of adults with thermal injury admitted to the Parkland burn intensive care unit (ICU) from 2008 to 2015. One thousand forty adult patients with burn were admitted to the burn ICU. AKI was defined by KDIGO serum creatinine criteria. Primary outcome includes hospital death and secondary outcome includes length of mechanical ventilation, ICU, and hospital stay. All available serum creatinine measurements were used to determine the occurrence of AKI during the hospitalization. All relevant clinical data were collected. The median total body surface area (TBSA) of burn was 16% (IQR: 6%–29%). AKI occurred in 601 patients (58%; AKI stage 1, 60%; stage 2, 19.8%; stage 3, 10.5%; and stage 3 requiring renal replacement therapy [3-RRT], 9.7%). Patients with AKI had larger TBSA burn (median 20.5% vs 11.0%; P < .001) and more mechanical ventilation and hospitalization days than patients without AKI. The hospital death rate was higher in those with AKI vs those without AKI (19.7% vs 3.9%; P < .001) and increased by each AKI severity stage (P trend < .001). AKI severity was independently associated with hospital mortality in the small burn group (for TBSA ≤ 10%: stage 1 adjusted OR 9.3; 95% CI, 2.6–33.0; stage 2–3 OR, 35.0; 95% CI, 9.0–136.8; stage 3-RRT OR, 30.7; 95% CI, 4.2–226.4) and medium burn group (TBSA 10%–40%: stage 2–3 OR, 6.5; 95% CI, 1.9–22.1; stage 3-RRT OR, 35.1; 95% CI, 8.2–150.3). AKI was not independently associated with hospital death in the large burn group (TBSA > 40%). Urine output data were unavailable. AKI occurs frequently in patients after burn. Presence of and increasing severity of AKI are associated with increased hospital mortality. AKI appears to be independently and strongly associated with mortality in patients with TBSA ≤ 40%. Further investigation to develop risk-stratification tools tailoring this susceptible population is direly needed.

Aims To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux-en-Y gastric bypass (RYGB) and specifically the contribution of the concurrent peri-operative dietary restrictions, which may also alter glucose metabolism. Materials and methods In order to assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled 10 patients with type 2 diabetes scheduled to undergo RYGB. All patients underwent a 10-day inpatient supervised dietary intervention equivalent to the peri-operative diet (diet-only period), followed by, after a re-equilibration (washout) period, an identical period of pair-matched diet in conjunction with RYGB (diet and RYGB period). We conducted extensive metabolic assessments during a 6-hour mixed-meal challenge test, with stable isotope glucose tracer infusion performed before and after each intervention. Results Similar improvements in glucose levels, β-cell function, insulin sensitivity and post-meal hepatic insulin resistance were observed with both interventions. Both interventions led to significant reductions in fasting and postprandial acyl ghrelin. The diet-only intervention induced greater improvements in basal hepatic glucose output and post-meal gastric inhibitory polypeptide (GIP) secretion. The diet and RYGB intervention induced significantly greater increases in post-meal glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and glucagon levels. Conclusions Strict peri-operative dietary restriction is a main contributor to the rapid improvement in glucose metabolism after RYGB. The RYGB-induced changes in the incretin hormones GLP-1 and PYY probably play a major role in long-term compliance with such major dietary restrictions through central and peripheral mechanisms.

ObjectiveTo compare infant and toddler anthropometric measurements, feeding practices and mean nutrient intakes by race/ethnicity and income.DesignCross-sectional analysis using general linear modelling. Ten years of survey data (2003–2012) were combined to compare anthropometric measurements, feeding practices and mean nutrient intakes from a nationally representative US sample.SettingThe 2003–2012 National Health and Nutrition Examination Survey (NHANES).SubjectsInfants and toddlers (n3669) aged 0–24 months.ResultsRates of overweight were higher among Mexican-American infants and toddlers (P=0·002). There were also several differences in feeding practices among groups based on race/ethnicity. Cessation of breast-feeding occurred earlier for non-Hispanic black and Mexican-Americanv. non-Hispanic white infants (3·6 and 4·2v. 5·3 months;PP=0·001). Age at first feeding of solids was earlier for white than Mexican-American infants (5·3v. 5·7 months;P=0·02). There were differences in almost all feeding practices based on income, including the lowest-income infants stopped breast-feeding earlier than the highest-income infants (3·2v. 5·8 months,PConclusionsOur study indicates that disparities in overweight, feeding practices and mean nutrient intakes exist among infants and toddlers according to race/ethnicity, which cannot be disentangled from income.

Background Low serum magnesium (SMg) has been linked to increased mortality and cardiovascular disease (CVD) in the general population. We examined whether this association is similar in participants with versus without prevalent chronic kidney disease (CKD) in the multiethnic Dallas Heart Study (DHS) cohort. Methods SMg was analyzed as a continuous variable and divided into tertiles. Study outcomes were all-cause death, cardiovascular (CV) death or event, and CVD surrogate markers, evaluated using multivariable Cox regression models adjusted for demographics, comorbidity, anthropometric and biochemical parameters including albumin, phosphorus and parathyroid hormone, and diuretic use. Median follow-up was 12.3 years (11.9-12.8, 25th percentile-75th percentile). Results Among 3551 participants, 306 (8.6%) had prevalent CKD. Mean SMg was 2.08 ± 0.19 mg/dL (0.85 ± 0.08 mM, mean ± SD) in the CKD and 2.07 ± 0.18 mg/dL (0.85 ± 0.07 mM) in the non-CKD subgroups. During the follow-up period, 329 all-cause deaths and 306 CV deaths or events occurred. In a fully adjusted model, every 0.2 mg/dL decrease in SMg was associated with ∼20-40% increased hazard for all-cause death in both CKD and non-CKD subgroups. In CKD participants, the lowest SMg tertile was also independently associated with all-cause death (adjusted hazard ratio 2.31; 95% confidence interval 1.23-4.36 versus 1.15; 0.55-2.41; for low versus high tertile, respectively). Conclusions Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD in the DHS cohort. Randomized clinical trials are important to determine whether Mg supplementation affects survival in CKD patients.

PURPOSE Fewer than 1 in 5 patients with cirrhosis receive hepatocellular carcinoma (HCC) surveillance; however, most studies were performed in select patient populations, which may not be informative of practice patterns in population-based community practices. Further, few reported guideline-concordant consistent surveillance rates. GOALS Characterize guideline-concordant HCC surveillance rates and patient-level factors associated with surveillance among a population-based cohort of patients with cirrhosis. STUDY We retrospectively characterized HCC surveillance among cirrhosis patients followed between January 2010 and December 2012 at an integrated health care delivery system in Washington state. Consistent surveillance was defined as an ultrasound every 6 months, and inconsistent surveillance was defined as ≥1 ultrasound during the 2-year follow-up period. Univariate and multivariate analyses were conducted to identify correlates of HCC surveillance receipt. RESULTS Of 1137 patients with cirrhosis, 22 (2%) underwent consistent surveillance, 371 (33%) had inconsistent surveillance, and 744 (65%) received no surveillance during follow-up. Correlates of HCC surveillance receipt in multivariate analysis included Gastroenterology/Hepatology subspecialty care [odds ratio (OR), 1.88; 95% confidence interval (CI), 1.44-2.46], Child Pugh B/C cirrhosis (OR, 1.61; 95% CI, 1.07-2.43), elevated aspartate aminotransferase (OR, 1.63; 95% CI, 1.13-2.35), and etiology of liver disease. Compared with hepatitis C-infected patients, patients with hepatitis B infection were more likely to undergo surveillance (OR, 2.72; 95% CI, 1.28-5.81), whereas patients with alcohol-related cirrhosis (OR, 0.63; 95% CI, 0.42-0.93) and nonalcoholic steatohepatitis (OR, 0.39; 95% CI, 0.28-0.56) were less likely to undergo surveillance. CONCLUSIONS Although one third of patients undergo inconsistent HCC surveillance

Pioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants. Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters. In this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45 mg/day) or matching placebo for 1 year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity. Results were available for 37 subjects who completed the baseline and 1-year evaluations. At 12 months, BM fat increased with pioglitazone (absolute change, +4.1%, p = 0.03), whereas BM fat content in the placebo group decreased non-significantly (−3.1%, p = 0.08) (p = 0.007 for the pioglitazone–placebo response difference). Total hip BMD declined in the pioglitazone group (−1.4%) and increased by 0.8% in the placebo group (p = 0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = −0.56, p = 0.01) in the pioglitazone group, but not within the placebo group (rho = −0.29, p = 0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects. Pioglitazone use for 12 months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.

In patients requiring high-dose insulin treatment, a randomized, double-blind, placebo-controlled study showed that liraglutide improved glycaemic control and treatment satisfaction while promoting weight loss. We performed a post hoc analysis to evaluate if patients' baseline characteristics impact the efficacy of liraglutide, and which outcomes correlate with treatment satisfaction. We used regression analysis to model the change in HbA1c and weight, with treatment assignment and baseline characteristics [HbA1c, age, body mass index (BMI), total daily dose (TDD) of insulin, duration of insulin treatment, and type of insulin regimen] as independent variables. Improvement in HbA1c was best predicted by treatment with liraglutide, followed by higher baseline HbA1c, BMI and age. Changes in weight were only associated with liraglutide treatment, independent of all baseline characteristics. Improvement in HbA1c was the only significant predictor of improvement in treatment satisfaction, while weight loss, change in TDD of insulin and rate of hypoglycaemia did not influence treatment satisfaction. In patients treated with high-dose insulin, liraglutide significantly improved glycaemic control and led to weight loss regardless of patients' baseline characteristics. Improvement in HbA1c was the most important predictor of patients' treatment satisfaction.

The myometrium undergoes structural and functional remodeling during pregnancy. We hypothesize that myometrial genomic elements alter correspondingly in preparation for parturition. Human myometrial tissues from nonpregnant (NP) and term pregnant (TP) human subjects were examined by RNAseq, ATACseq and PGR ChIPseq assays to profile transcriptome, assessible genome and PGR occupancy. NP and TP specimens exhibit 2890 differentially expressed genes, reflecting an increase of metabolic, inflammatory and PDGF signaling, among others, in adaptation to pregnancy. At the epigenome level, patterns of accessible genome change between NP and TP myometrium, leading to altered enrichment of binding motifs for hormone and muscle regulators such as the progesterone receptor (PGR), Krüppel-like factors and MEF2A transcription factors. PGR genome occupancy exhibits a significant difference between the two stages of the myometrium, concomitant with distinct transcriptomic profiles including genes such as ENO1, LHDA, and PLCL1 in the glycolytic and calcium signaling pathways. Over-representation of SRF, MYOD and STAT binding motifs in PGR occupying sites further suggests interactions between PGR and major muscle regulators for myometrial gene expression. In conclusion, changes in accessible genome and PGR occupancy are part of the myometrial remodeling process and may serve as mechanisms to formulate the state-specific transcriptome profiles.

Background Polyamines are essential for cell growth and beneficial for intestinal maturation. To evaluate the effects of putrescine on alleviating intestinal atrophy and underlying molecular mechanisms, both in vivo feeding trial and in vitro cell culture were conducted. Weanling pigs were fed a diet supplemented with 0, 0.1%, 0.2% or 0.3% putrescine dihydrochloride, whereas porcine intestinal epithelial cells (IPEC-J2) were challenged with lipopolysaccharide (LPS) in the presence of 200 μmol/L putrescine. Results Dietary supplementation with 0.2% putrescine dihydrochloride decreased the incidence of diarrhea with an improvement in intestinal integrity. Inhibition of ornithine decarboxylase activity decreased the proliferation and migration of IPEC-J2 cells, and this effect was alleviated by the supplementation with putrescine. The phosphorylation of extracellular signal regulated kinase and focal adhesion kinase was enhanced by putrescine. LPS increased the expression of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-8], and inhibited cell proliferation and migration in IPEC-J2 cells. Adding exogenous putrescine suppressed the expression of TNF-α, IL-6 and IL-8, and recovered cell migration and proliferation in LPS-treated IPEC-J2 cells. Dietary putrescine supplementation also reduced the mRNA levels of TNF-α, IL-6 and IL-8 and their upstream regulator nuclear receptor kappa B p65 subunit in the jejunal mucosa of piglets. Conclusions Dietary supplementation with putrescine mitigated mucosal atrophy in weanling piglets through improving anti-inflammatory function and suppressing inflammatory response. Our results have important implications for nutritional management of intestinal integrity and health in weanling piglets and other neonates.

Peroxide-decorated Ti3C2Tx plays a role as an initiator for free-radical polymerization and leads to new opportunities for intelligent optoelectronic devices., Two-dimensional MXene Ti3C2Tx nanosheets with peroxide decoration (p-Ti3C2Tx) are synthesized by a sonication-assisted MILD etching method. The obtained MXenes can generate hydroxyl radical species and act as an initiator for free-radical polymerization of a series of acrylic monomers without the use of light illumination or co-initiators. The monomers analyzed include acrylamide, N-isopropylacrylamide (NIPAM), N,N-dimethylacrylamide, methyl methacrylate, and hydroxyethyl methacrylate. By simply mixing N-isopropylacrylamide monomers and p-Ti3C2Tx nanosheets under deoxygenated conditions, PNIPAM-based nanocomposite hydrogels are synthesized using a high concentration of the monomer. The nanocomposite hydrogels have a photothermal conversion efficiency of 34.7% and photothermal stability superior to that of pristine Ti3C2Tx. Taking advantage of the thermal responsive behavior of PNIPAM, the nanocomposite hydrogels are successfully exploited as remotely near-infrared light controlled “smart” windows, fluidic valves and photodetectors.

ObjectiveMedication adherence is impacted by regimen complexity. The SIMPLE (Simple basal Insulin titration, Metformin Plus Liraglutide for type 2 diabetes with very Elevated HbA1c) study compared GLP1RA plus basal insulin (GLP1RA+BI) to basal-bolus insulin (BBI) regimen in participants with very uncontrolled type 2 diabetes mellitus (T2DM). This analysis aimed to evaluate medication adherence to GLP1RA+BI compared with BBI, the effect of adherence on clinical and patient-reported outcomes, and baseline predictors of adherence.Research design and methodsThis was an analysis of the SIMPLE study based on prespecified outcome. The study took place in pragmatic, real-world setting. A total of 120 adults with T2DM and HgbA1c≥10% were randomized to detemir plus liraglutide, or detemir plus aspart before each meal; 6-month follow-up. The main outcomes evaluated were: adherence, HgbA1c, weight, quality of life, and hypoglycemia. Adherence rate was calculated for each study medication at each follow-up visit; participants were classified as ≥80% or ResultA higher percentage of participants in the GLP1RA+BI compared with the BBI group had ≥80% adherence to detemir (59.3% vs 35.7%, p=0.02) as well as liraglutide versus aspart (57.4% vs 30.4%, p=0.007). Higher age was predictive of ≥80% adherence (OR per 5-year increment=1.48, 95% CI 1.09 to 2.0, p=0.01). Higher adherence led to greater improvement in HbA1c and weight in both groups. Treatment with GLP1RA+BI compared with BBI led to greater improvement in HbA1c, weight, and quality of life and lower risk of hypoglycemia even after adjusting for the difference in adherence between groups.ConclusionsAdherence was higher with the simplified regimen of GLP1RA+BI compared with BBI. Greater adherence to the simpler regimen amplified the treatment effect on HbA1c, weight, quality of life, and risk of hypoglycemia, yet statistically significant greater benefits were noted even when adjusted for adherence.Trial registration numberNCT01966978

FPLD2 is a rare autosomal dominant disorder characterized by loss of subcutaneous (sc) fat from the extremities but increased fat deposition in the face, neck and abdomen. Most FPLD2 patients (~75%) have “typical” heterozygous missense LMNA mutations affecting the arginine 482 residue and have severe loss of sc fat from the extremities and develop moderate to severe metabolic complications. Other patients have “atypical” mutations with variable loss of sc fat from the extremities and mild to severe metabolic complications. Since genetic testing is expensive, the diagnosis of FPLD2 is usually missed or delayed. Thus, there exists a need for an objective screening tool which can aid in the diagnosis of FPLD2. Therefore, we determined the predictive value of skinfold thickness measurements and various DEXA-based regional body fat parameters for diagnosis of FPLD2. We compared body fat data of 49 adult females (F) and 5 males (M) with FPLD2 to the sex- and age-matched controls (2,459 F, 3,459 M) from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Thirty nine patients had “typical” heterozygous p.R482W or p.R482Q LMNA mutation. The other heterozygous LMNA mutations included p.R582S (n = 1), p.R582H (n = 1), p.S583L (n = 3), p.R349W (n = 1), p.R25L (n = 1), p.G523R (n = 2), p.D192V (n = 1), p.L241P (n = 1), p.R62G (n = 2) and p.K515E (n = 2). The mean ± SD age and body mass index of affected F was 42 ± 13.5 y and 25.6 ± 4.5 kg/m2, respectively; and of affected M was 45.4 ± 11.6 y and 29.2 ± 7.0 kg/m2, respectively. Hypertriglyceridemia and diabetes mellitus were present in 74% and 52% of the FPLD2 patients, respectively. Our data revealed that the lower limb fat %, as well as the ratio of lower limb fat %/ truncal fat %, in all affected females were ≤ 1st percentile (%ile) of the controls, except in two patients, one of whom had a p.G523R mutation, and the other had a p.R482Q mutation but had an unusual excess fat accumulation in the medial part of the thighs and knees. All FPLD2 females had triceps skinfold thickness values ≤ 1st %ile of NHANES except in three patients. The subscapular skinfold thickness values in females on the other hand, were between the 5th to 99th %ile of NHANES. Unfortunately, data for thigh skinfold thickness were not available from NHANES. The lower limb fat % in affected males was below 25th %ile of controls. We conclude that DEXA-derived lower limb fat % and the ratio of lower limb fat %/ truncal fat % are the best predictors of FPLD2 diagnosis in females but not in males. Women with values of lower limb fat % (~ 20% or less) and the ratio of lower limb fat %/ truncal fat % (~ 0.85 or less), both of which are below the 1st %ile of NHANES data, should be further evaluated for diagnosis of FPLD2, especially if presenting with metabolic complications.

Survivors of acute kidney injury (AKI) are at risk of adverse outcomes. Post-discharge nephrology care may improve patients' AKI knowledge and prevent post-AKI complications.The purpose of this study was to examine patients' awareness about their AKI diagnosis and self-rated knowledge and severity of AKI before and after their first post-discharge AKI Clinic encounter.We conducted a pre- and post-survey study among AKI survivors who attended a post-discharge AKI Clinic.AKI Clinic at the University of Kentucky Medical Center (October 2016 to December 2017). Education about AKI was based on transformative learning theory and provided through printed materials and interdisciplinary interactions between patients/caregivers and nurses, pharmacists, and nephrologists.A total of 104 patients completed the survey and were included in the analysis.Three survey questions were administered before and after the first AKI Clinic encounter: Question 1 (yes-no) for awareness, and questions 2 and 3 (Likert scale, 1 = lowest to 5 = highest) for self-rated knowledge and severity of AKI.Two mixed-model analysis of variance (ANOVA) was used for between-group (AKI severity) and within-group (pre- and post-encounter) comparisons. Logistic regression was used to examine parameters associated with the within-group change in self-perceived knowledge.Twenty-two out of 104 (21%) patients were not aware of their AKI diagnosis before the clinic encounter. Patients' self-ratings of their AKI knowledge significantly increased after the first AKI Clinic encounter (mean ± SEM: pre-visit = 1.94 ± 0.12 to post-visit = 3.88 ± 0.09,Our study population may not be representative of the general AKI survivor population. Administered surveys are subject to response-shift bias.Patients' self-perceived knowledge about AKI significantly increased following the first post-discharge AKI Clinic encounter that included interdisciplinary education. This is the first survey study examining self-perceived AKI knowledge in AKI survivors. Further examination of AKI literacy in survivors of AKI and its effect on post-AKI outcomes is needed.Not applicable.Les survivants d’un épisode d’insuffisance rénale aiguë (IRA) risquent de souffrir de pathologies associées. Un suivi en néphrologie après la sortie de l’hôpital pourrait accroître les connaissances des patients sur la maladie et prévenir les complications.L’étude était bipartite : i) savoir si les patients connaissaient leur diagnostic; ii) mesurer, par auto-évaluation, les connaissances des patients sur l’IRA et sur sa gravité, avant et après une consultation dans une clinique d’IRA.Un sondage mené auprès de survivants d’un épisode d’IRA, avant et après une consultation en clinique d’IRA suivant leur congé de l’hôpital.La clinique d’IRA du centre médical de l’université du Kentucky (d’octobre 2016 à décembre 2017). L’information fournie suivait la théorie de l’apprentissage transformationnel et était transmise sous forme de documents imprimés et d’interactions interdisciplinaires entre les patients/fournisseurs de soins et les infirmières, les pharmaciens et les néphrologues.L’étude porte sur 104 patients ayant complété le sondage.Trois questions ont été posées aux patients avant et après une première consultation à la clinique. Une question portait sur leur connaissance du diagnostic (oui -non) et deux autres auto-évaluaient leurs connaissances sur l’IRA et sa gravité (échelle de Likert, de 1 [plus faible] à 5 [plus élevé]).Deux modèles mixtes d’analyse de variance ont été employés pour établir des comparaisons inter-groupes (gravité de l’IRA) et intra-groupes (pré et post-consultation). Une régression logistique a été utilisée pour analyser les paramètres associés aux changements du niveau auto-évalué des connaissances dans un même groupe.Des 104 patients inclus à l’étude, 22 (21 %) ignoraient leur diagnostic d’IRA avant la consultation. L’auto-évaluation des connaissances a augmenté après la première consultation (moyenne ± SEM : 1,94 ± 0,12 [pré-visite]; 3,88 ± 0,09 [post-visite],La population étudiée pourrait ne pas être représentative de la population générale des survivants d’un épisode d’IRA. Les sondages sont sujets aux biais liés aux changements de réponses.L’auto-évaluation des connaissances a augmenté significativement après une première consultation à la clinique d’IRA lorsque celle-ci incluait de l’information interdisciplinaire. Il s’agit de la première étude portant sur l’auto-évaluation des connaissances de survivants d’un épisode d’IRA. Il est nécessaire d’examiner davantage la littératie de l’IRA chez les survivants de la maladie et ses effets sur les pathologies qui en découlent.

Hypomagnesemia associates with inflammation and risk of diabetes and hypertension, which may contribute to kidney function decline. We hypothesized that low serum magnesium (SMg) levels independently associate with a significant decline in estimated glomerular filtration rate (eGFR). We analyzed SMg levels in 2056 participants from the Dallas Heart Study, a longitudinal, population‐based, multiethnic, cohort study involving residents of Dallas County, Texas, USA. The primary study outcome was the change in eGFR using multivariable linear regression models adjusted for demographics, anthropometric and biochemical parameters, medications, C reactive protein levels, prevalent hypertension and diabetes. During a median follow-up of 7.0 years (25th, 75th percentile: 6.5, 7.6), the median decrease in eGFR was −0.71 (25th, 75th percentile: −2.43, +0.68) mL/min/1.73 m2 per year in the entire cohort. In a fully adjusted model, the lowest SMg quintile (≤1.9 mg/dL or ≤0.8 mM) was associated with a −0.50 mL/min/1.73 m2 per year drop in eGFR (95% CI −0.95 to –0.05; p=0.028) compared with the highest SMg quintile (≥2.3 mg/dL or ≥1.0 mM). Every 0.2 mg/dL (0.08 mM) decrease in SMg was associated with an eGFR decline of −0.23 mL/min/1.73 m2 per year (95% CI −0.38 to –0.08; p=0.003), a decline that was more pronounced in participants with prevalent diabetes compared with patients without diabetes (−0.51 vs −0.18 mL/min/1.73 m2 per year, respectively). In conclusion, low SMg was independently associated with eGFR decline. Further studies are needed to determine whether Mg repletion can ameliorate inflammation, lower blood pressure and serum glucose and ultimately prevent or retard kidney function decline.

Figure S4. ERK inhibitor inhibited IPEC-J2 cells growth and ERK1/2 phosphorylation. A. The IPEC-J2 cells were seeded in 2% FBS containing DMEM/F12 supplemented with or without 200 μmol/L putrescine in the presence or absence of ulixertinib, a specific inhibitor for ERK. Cell numbers were determined at 0 h, 24 h, 48 h, 72 h, 96 h and 120 h with the CCK-8 kit. Ulixertinib inhibited the growth of IPEC-J2 cells from 48 h to 120 h with or without putrescine. B. Western blotting of Phospho-ERK1/2 for different treatment. C. Western blotting of total-ERK1/2. Values are means ± SE, n = 4. Means with different letters are different (P

Figure S2. Effect of adding different level putrescine in the medium on the growth of IPEC-J2. The IPEC-J2 cells were seeded in 2% FBS containing DMEM/F12 supplemented with 0, 12.5, 25, 50, 100, or 200 μmol/L putrescine, cell numbers were determined at 0 h, 24 h, 48 h, 72 h, 96 h and 120 h with the CCK-8 kit. Cell growth was presented with plotting diagram (A), and was presented with histogram (B) to show the detail of difference among groups. Growth differences were presented with bar chart. Values are means ± SE, n = 4. Means with different letters are different (P

Figure S5. FAK inhibitor inhibited IPEC-J2 cells migration and FAK phosphorylation. A. The IPEC-J2 cells were seeded in 6 well plates, and pretreated for 48 h with or without 200 μmol/L putrescine, followed by the addition of 2 μg/mL Mitomycin C for 24 h. The cells were then treated with or without 100 μg/mL defactinib for 4 h before scratching. Images were taken immediately after scratching (0 h) and at 8 h post scratching to calculate the area covered by cell migration, the scratched borders were enhanced with black lines. B. Western blotting of phospho-FAK. C. Western blotting of total-FAK. Values are means ± SE, n = 4. Means with different letters are different (P

Figure S1. Effects of putrescine supplementation on tight junction gene expression in the jejunal mucosa of piglets. A. The mRNA level of ZO-1. B. The mRNA level of claudin-1. C. The mRNA level of occludin. Values are means ± SE, n = 6. Means with different letters are different (P