Respective Time Points Research Articles

Validation of Single-Item, Self-Rated Diet Quality Measure Among Adults in Puerto Rico

Abstract Objectives To evaluate the validity of a single-item diet quality measured as a rapid and cost-effective means of dietary assessment among adults living in Puerto Rico (PR), a population with access to and a cultural preference for specific foods. Methods This cross-sectional study used data from the PR Assessment of Diet, Lifestyle, and Diseases (2015). Self-perception of diet quality was reported (n = 247, age = 35–75 y) for the current day, young adulthood, and childhood (five-point scale: excellent to poor). We used a culturally adapted food frequency questionnaire to measure dietary intake, and computed diet quality (range: 0–110) with the Alternate Healthy Eating Index-2010 (AHEI). We conducted multivariable generalized linear models to assess relationships between current AHEI and perception of diet quality at three-time points. Results We categorized current self-rated diet quality into ‘excellent or very good’ (37%), ‘good’ (35%), or ‘fair or poor’ (28%); the overall mean AHEI was 60.1 +/– 11.0. Sensitivity of single-item measure was 60% and specificity was 34%. Current self-rated diet quality was not significantly associated with AHEI score, although adjusted mean scores for fruit and or long-chain fatty acids were significantly lower among participants reporting fair or poor diet, vs. excellent or very good (β = −0.49, 95% CI = −0.97, −0.014; β = −0.52, 95% CI = −0.98, −0.049). In contrast, mean adjusted AHEI score was significantly higher among those rating their diet quality as fair or poor in young adulthood (36%; β = 6.4, 95% CI = 2.4,10.5), and marginally higher among those reporting fair or poor diet quality in childhood (27%; β = 3.99; 95% CI = −0.01,8.04), vs. those rating their diet as excellent or very good, at respective time points. Conclusions A single-item perceived diet measure is not a valid assessment of current diet quality for adults in PR. Interestingly, perception of low diet quality in earlier life stages is associated with higher quality of the actual current diet. Nutrition researchers may use self-rated diet quality in earlier life stages to estimate current diet quality; the mechanisms driving this relationship warrant further investigation. Funding Sources CG is supported by an NIH/NCI training grant. PRADLAD was funded with anonymous donations and an NIH/NHLBI award.

Analysis of treatment efficacy in the GEM-CESAR trial for high-risk smoldering multiple myeloma patients: Comparison between the standard and IMWG MRD criteria and QIP-MS including FLC (QIP-FLC-MS).

8512 Background: The GEM-CESAR trial is a potentially curative strategy for high-risk smoldering multiple myeloma (HRsMM) patients (pts) in which the primary endpoint is the achievement of sustained minimal residual disease (MRD) negativity in the bone marrow (BM) by next generation flow (NGF). The value of BM MRD assessment in MM is proven, but alternative, non-invasive methods, accurately reflecting disease burden are needed. Methods: Pts received six 4-week cycles of KRd as induction (K:36mg/m2 twice weekly, R: lenalidomide 25mg po od days 1-21 and d:dexamethasone 40mg po weekly) followed by melphalan 200mg/m2, two further cycles of KRd as consolidation and up to 2 years of Rd (R:10mg/d, d:20mg/week). Efficacy was analyzed in parallel in BM samples by NGF and in serum by SPEP/IFE and QIP-MS/QIP-FLC-MS in 52 out of the 90 pts enrolled in the trial. Standard and MRD responses were carried out as per the IMWG guidelines. For QIP-MS serum immunoglobulins were purified using polyclonal antibodies (anti-IgG, -IgA, -IgM, -total κ and -total λ light chain, -free κ and -free λ light chain). Mass spectra were generated on a MALDI-TOF-MS system. Results: Overall response rate (ORR) was 98% post-induction, 98% post-ASCT, and 100% post-consolidation; 38.4%, 61.5% and 68.6% of pts reached ≥ complete response at each time-point and, among them, 23%, 44% and 55% achieved flow MRD-negativity. Using the combination of QIP-MS/QIP-FLC-MS, the percentage of pts without detectable disease at each timepoint lowered to 12%, 27% and 38% reflecting the higher sensitivity of the method. Against NGF, QIP-MS/QIP-FLC-MS provided negative predictive values of 67%, 92% and 89% (p = 0,0206; p < 0,001; p = 0,003) and identified disease in 95%, 97% and 92% of pts that were positive by NGF-MRD at each respective timepoint. Three pts from this cohort have progressed so far: two were NGF+/MS+ at the three timepoints whilst 1 remained NGF- but QIP-MS/FLC-MS+ throughout. Conclusions: The GEM-CESAR treatment strategy induces a high ORR in HRsMM pts, and the % of cases achieving flow-MRD negativity post-ASCT meets the primary endpoint of the trial. The combined use of QIP-MS and FLC-MS offers higher sensitivity relative to standard methods and may provide relevant information about the right timing for performing a BM aspirate/biopsy. Clinical trial information: NCT02415413 .

Mechanoadaptive strain and functional osseointegration of dental implants in rats.

Spatiotemporal implant-bone biomechanics and mechanoadaptive strains in peri-implant tissue are poorly understood. Physical and chemical characteristics of an implant-bone complex (IBC) were correlated in three-dimensional space (along the length and around a dental implant) to gather insights into time related integration of the implant with the cortical portion of a jaw bone in a rat. Rats (N=9) were divided into three experimental groups with three rats per time point; 3-, 11-, and 24-day. All rats were fed crumbled hard pellets mixed with water (soft-food diet) for the first 3days followed by a hard-food diet with intact hard-food pellets (groups of 11- and 24-day only). Biomechanics of the IBCs harvested from rats at each time point was evaluated by performing mechanical testing in situ in tandem with X-ray imaging. The effect of physical association (contact area) of a loaded implant with adapting peri-implant tissue, and resulting strain within was mapped by using digital volume correlation (DVC) technique. The IBC stiffness at respective time points was correlated with mechanical strain in peri-implant tissue. Results illustrated that IBC stiffness at 11-day was lower than that observed at 3-day. However, at 24-day, IBC stiffness recovered to that which was observed at 3-day. Correlative microscopy and spectroscopy illustrated that the lower IBC stiffness was constituted by softer and less mineralized peri-implant tissue that contained varying expressions of osteoconductive elements. Lower IBC stiffness observed at 11-day was constituted by less mineralized peri-implant tissue with osteoconductive elements that included phosphorus (P) which was co-localized with higher expression of zinc (Zn), and lower expression of calcium (Ca). Higher IBC stiffness at 24-day was constituted by mineralized peri-implant tissue with higher expressions of osteoconductive elements including Ca and P, and lower expressions of Zn. These spatiotemporal correlative maps of peri-implant tissue architecture, heterogeneous distribution of mineral density, and elemental colocalization underscore mechanoadaptive physicochemical properties of peri-implant tissue that facilitate functional osseointegration of an implant. These results provided insights into 1) plausible "prescription" of mechanical loads as an osteoinductive "therapeutic dose" to encourage osteoconductive elements in the peri-implant tissue that would facilitate functional osseointegration of the implant; 2) a "critical temporal window" between 3 and 11days, and perhaps it is this acute phase during which key candidate regenerative molecules can be harnessed to accelerate osseointegration of an implant under load.

Oral consumption of Garcinia kola(Bitter kola) lowers intraocular pressure.

Garcinia kola (bitter kola) is locally ingested across the West African subregion. It has ocular hypotensive effects similar to some commonly used glaucoma medications when administered topically. The study assessed the effect of oral ingestion of G.kola on intraocular pressure (IOP). A randomized, single-blind, placebo-controlled, cross-over design was used in this study. Forty-six healthy subjects, aged between 19 and 27years were recruited and randomized into two groups (A and B). Subjects in group A ingested 100mg/kg body weight bitter kola in a 200ml solution on their first visit and group B ingested 200ml of water. On the second visit, the order of treatment was reversed, IOP was measured at baseline and every 45min interval for 135min. The mean difference between the baseline and post-treatment IOP measurements were tested for statistical significance using repeated-measures analysis of variance (95% confidence intervals [CIs]). Mean IOP measurements decreased by 7.9, 18.2 and 20.6% at 45, 90 and 135min, respectively, after G.kola treatment. The reduction, though variable across subjects, was statistically significant (F [2.13, 95.62]=90.35, p<0.0001) across the respective time points. Repetition of an identical protocol without G. kola caused clinically negligible changes in IOP. There was no statistically significant influence of gender or age in G.kola effect on IOP reading. Oral ingestion of G.kola lowered the intraocular pressure of healthy young adults by 21%. Such an effect may be of therapeutic benefit to patients with POAG or ocular hypertension in low-income settings.

Spinal Cord Injury Acutely Alters Diurnal Testosterone Secretion in Male Rats

BackgroundHealthy young adult men and male Sprague‐Dawley rats both exhibit diurnal variations in testosterone (T) secretion. Spinal cord injury (SCI) has been shown to decrease serum T concentrations in men compared to age‐matched healthy persons, with lower T concentrations correlated to more recent and more severe injury.PurposeTo determine if recent SCI alters the diurnal variation in T secretion in a rodent severe contusion SCI model.Methods17‐wk‐old male Sprague‐Dawley (SD) rats were matched on body mass and stratified to receive T9 laminectomy (SHAM surgery, N=4) or severe (250 kilodyne) T9 contusion SCI (N=6) via computer‐controlled impactor. Tail blood was acquired every 2‐h during daytime hours (7am–5pm) at baseline (1‐wk pre‐surgery), 3‐d post‐surgery, and 7‐d post‐surgery, with serum T evaluated via ELISA. SAS JMP was used to assess changes in T over time via repeated measures ANOVA and differences between individual time points via one‐way ANOVA with non‐parametric Wilcoxon post‐hoc testing (significance at p&lt;0.05). T concentrations are reported as means ± standard deviation in ng/ml.ResultsBaseline T concentrations averaged 3.36 ± 2.22, with minimal non‐significant changes occurring across daytime hours. T secretion did not change after SHAM surgery, except for a decrease at 5pm on 3‐d post‐surgery vs the respective baseline time point (0.61 ± 0.17 vs. 2.96 ± 1.67 respectively; 80% decline). Serum T reverted to baseline at 7‐d post‐surgery in SHAMs, with no differences in daytime T area under the curve (AUC) values present at any time point. SCI produced 60–90% lower serum T at all 3‐d post‐SCI time points vs baseline and T remained 70–85% lower than baseline between 7–11am at 7‐d post‐SCI, while afternoon T was similar to baseline concentrations. Daytime T AUC values for SCI animals were 37.8 ± 15.2 (baseline), 7.4 ± 4.6 (3‐d post‐SCI), and 12.9 ± 4.0 (7‐d post‐SCI), with 3‐d and 7‐d AUC values approaching significance vs baseline (p=0.06 for both).ConclusionSham surgery did not influence serum T concentrations and did not appear to alter diurnal T secretion. In comparison, serum T was dramatically suppressed during daytime hours at 3‐d post‐SCI and remained suppressed at 7‐d post‐SCI only during the morning hours, indicating disruption of normal diurnal T secretion. The mediators of suppressed T after SCI remain to be elucidated, but may involve reduced gonadotropin releasing hormone (GnRH) and/or leuteinizing hormone (LH) secretion, impaired splanchnic innervation that may interfere with LH receptor regulation, reduced gonadal blood flow that may alter LH delivery to the testes, and/or disruption of neural pathways between the central nervous system and the testes that regulate Leydig cell function independently of the anterior pituitary.Support or Funding InformationThis work was supported by the Presidential Early Career Award to Scientists and Engineers (PECASE) #B9290‐O to JFY from the White House Office of Science and Technology Policy and VA Rehabilitation R&amp;D Service.Serum testosterone at "B" baseline (1 week pre‐SCI), "3D" (3 days post‐SCI), and "7D" (7 days post‐SCI). 17 week old (n=6) male Sprague‐Dawley rats had significantly lower (p&lt;0.05) serum testosterone at 3D and 7D post‐SCI. * indicates sig. less than baseline. Cross bars indicate median and inter‐quartile range.Figure 1

Influence of Casein kinase II inhibitor CX-4945 on BCL6-mediated apoptotic signaling in B-ALL in vitro and in vivo

BackgroundCasein kinase II (CK2) is involved in multiple tumor-relevant signaling pathways affecting proliferation and apoptosis. CK2 is frequently upregulated in acute B-lymphoblastic leukemia (B-ALL) and can be targeted by the ATP-competitive CK2 inhibitor CX-4945. While reduced proliferation of tumor entities including B-ALL after CX-4945 incubation has been shown in vitro and in vivo, the detailed way of action is unknown. Here, we investigated the influence on the PI3K/AKT and apoptosis cascades in vivo and in vitro for further clarification.MethodsA B-ALL xenograft model in NSG mice was used to perform in vivo longitudinal bioluminescence imaging during six day CX-4945 treatment. CX-4945 serum levels were determined at various time points. Flow cytometry of bone marrow and spleen cells was performed to analyze CX-4945-induced effects on tumor cell proliferation and distribution in B-ALL engrafted mice. ALL cells were enriched and characterized by targeted RNA sequencing. In vitro, B-ALL cell lines SEM, RS4;11 and NALM-6 were incubated with CX-4945 and gene expression of apoptosis regulators BCL6 and BACH2 was determined.ResultsIn B-ALL-engrafted mice, overall tumor cell proliferation and distribution was not significantly influenced by CK2 inhibition. CX-4945 was detectable in serum during therapy and serum levels declined rapidly after cessation of CX-4945. While overall proliferation was not affected, early bone marrow and spleen blast frequencies seemed reduced after CK2 inhibition. Gene expression analyses revealed reduced expression of anti-apoptotic oncogene BCL6 in bone marrow blasts of CX-4945-treated animals. Further, BCL6 protein expression decreased in B-ALL cell lines exposed to CX-4945 in vitro. Surprisingly, levels of BCL6 opponent and tumor suppressor BACH2 also declined after prolonged incubation. Simultaneously, increased phosphorylation of direct CK2 target and tumor initiator AKT was detected at respective time points, even in initially pAKT-negative cell line NALM-6.ConclusionsThe CK2 inhibitor CX-4945 has limited clinical effects in an in vivo B-ALL xenograft model when applied as a single drug over a six day period. However, gene expression in B-ALL cells was altered and suggested effects on apoptosis via downregulation of BCL6. Unexpectedly, the BCL6 opponent BACH2 was also reduced. Interactions and regulation loops have to be further evaluated.

Hemodynamic effects of intravenous paracetamol in critically ill children with septic shock on inotropic support

BackgroundTreatment with intravenous paracetamol may impair hemodynamics in critically ill adults. Few data are available in children. The aim of this study was to investigate the frequency, extent, and risk factors of hypotension following intravenous paracetamol administration in children with septic shock on inotropic support.MethodsWe retrospectively reviewed the electronic medical charts of all children aged 1 month to 18 years with septic shock who were treated with intravenous paracetamol while on inotropic support at the critical care unit of a tertiary pediatric medical center in 2013–2018. Data were collected on patient demographics, underlying disease, Pediatric Logistic Organ Dysfunction (PELOD) score, hemodynamic parameters before and up to 120 min after paracetamol administration, and need for inotropic support or intravenous fluid bolus. The main outcome measures were a change in blood pressure, hypotension, and hypotension requiring intervention.ResultsThe cohort included 45 children of mean age 8.9 ± 5.1 years. The mean inotropic support score was 12.1 ± 9.5. A total of 105 doses of paracetamol were administered. The lowest mean systolic pressure (108 ± 15 mmHg) was recorded at 60 min (p = 0.002). Systolic blood pressure decreased at 30, 60, 90, and 120 min after delivery of 50, 67, 61, and 59 drug doses, respectively. There were 5 events of systolic hypotension (decrease of 1 to 16 mmHg below systolic blood pressure hypotensive value). Mean arterial pressure decreased by ≥ 15% in 8 drug doses at 30 min (7.6%, mean − 19 ± 4 mmHg), 18 doses at 60 min (17.1%, mean − 20 ± 7 mmHg), 16 doses at 90 min (15.2%, mean − 20 ± 5 mmHg), and 17 doses at 120 min (16.2%, mean − 19 ± 5 mmHg). Mean arterial hypotension occurred at the respective time points in 2, 13, 10, and 9 drug doses. After 12 drug doses (11.4%), patients required an inotropic dose increment or fluid bolus.ConclusionsHypotensive events are not uncommon in critically ill children on inotropic support treated with intravenous paracetamol, and physicians should be alert to their occurrence and the need for intervention.

Value and Safety of High Flow Oxygenation in the Treatment of Inpatient Asthma: A Randomized, Double-blind, Pilot Study.

This study was aimed to compare the value and safety of high-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) in patients with asthma exacerbation. In this randomized double-blind study, forthy patients with moderate-to-severe asthma exacerbations, aged 18 years or older were enrolled. Patients were randomly assigned to receive either HFNC or COT for 24 hours. Dyspnea scale, O2 saturation, spirometer indexes, respiratory and heart rate, and arterial blood gas (ABG) were compared within 2 and 24 hours of intervention. Dyspnea scale decreased significantly from 7.58±1.04 to 6.45±0.51 (p=0.000), and from 7.84±1.7 to 6.89±0.9 (p=0.049) within 2 hours in HFNC and COT groups, respectively. In the HFNC group, forced expiratory volume in one second (FEV1) was 1.48 ±0.94 L at the time of admission and increased to 1.61±0.66 L (p=0.19) and 1.82±0.92 L (p=0.003) after 2 and 24 hours of experience, respectively. In addition, in the COT group, FEV1 increased from 1.43±0.65 L to 1.46±0.53 L and 1.64±0.6 L in the respective time-points, (p=0.071, 0.079). PaO2 and O2 saturation increased significantly in both groups during the first 2 hours. Two patients in the HFNC group had the complaint of nasal irritation and the device-produced heat; while one patient in the COT group needed more respiratory care. HFNC could be a therapeutic option for asthma exacerbation among adult patients after considering the patient's selection.

Dietary protease improves growth performance, nutrient digestibility, and intestinal morphology of weaned pigs.

This study was conducted to evaluate effects of dietary protease (PR) on growth performance, nutrient digestibility, and intestinal morphology of weaned pigs. A total of 75 weaned pigs [7.06 ± 0.18 kg of average body weight (BW); 28 day old] were randomly allotted to 3 dietary treatments in a randomized complete block design (blocks = BW and sex): a diet based on corn and soybean meal to meet the requirement of crude protein (CP) as a positive control (PC; CP = 24.49%), a low protein diet as a negative control (NC; CP = 22.51%), and NC + 0.02% PR. The PR used in this study was a commercial product containing 75,000 protease units/g derived from Nocardiopsis prasina produced in Bacillus licheniformis. Pigs were fed the dietary treatments for 6 weeks and the diets containing 0.2% chromic oxide for the last week of this study. Blood, feces, ileal digesta, and ileum samples were collected from randomly selected two pigs in each pen on respective time points. Measurements were growth performance, apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of dry matter (DM), CP, and energy, frequency of diarrhea, packed cell volume (PCV), and ileal morphology of weaned pigs. Pigs fed PC and PR had higher (p < 0.05) final BW, average daily gain (ADG), and gain to feed ratio (G:F) during overall experimental period than those fed NC. Pigs fed PC and PR had higher (p < 0.05) AID or ATTD of DM, CP, or energy than those fed NC. Moreover, pigs fed PR had higher ratio between villus height and crypt depth (p < 0.05) and number of goblet cells (p < 0.05) than those fed NC. Addition of PR decreased (p < 0.05) frequency of diarrhea for the first two weeks after weaning compared with PC and NC. In addition, pigs fed PR had lower (p < 0.05) PCV on d 14 after weaning than those fed PC and NC. In conclusion, addition of PR in nursery diets with a low protein level significantly improved growth performance, nutrient digestibility, and intestinal morphology of weaned pigs.

Qip-Mass Spectrometry in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment

Qip-Mass Spectrometry in High Risk Smoldering Multiple Myeloma Patients Included in the GEM-CESAR Trial: Comparison with Conventional and Minimal Residual Disease IMWG Response Assessment

Sagittal Reconstruction and Clinical Outcome Using Traditional ACDF, Versus Stand-alone ACDF Versus TDR: A Systematic Review and Quantitative Analysis.

Systematic review. To determine the difference in postoperative sagittal alignment when single level cervical radiculopathy or myelopathy is treated with an anterior cervical discectomy and fusion (ACDF) using a structural graft and plate, a stand-alone ACDF, or a total disc arthroplasty (TDR). We also wanted to determine if postoperative sagittal alignment impacted clinical outcomes in this patient population. Although there are several accepted techniques for interbody reconstruction during single level anterior cervical surgery, little is known on the impact of any of them on segmental and regional sagittal alignment. A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines of the PubMed, Embase, and Cochrane databases. Only studies which contained pre and postoperative C2-7 Cobb angles as well as Neck Disability Index (NDI) scores following single level traditional ACDF with plate and cage, stand-alone ACDF, or TDR with at least 1 year follow up were included. There were 12 publications that fulfilled the inclusion criteria with a total of 658 patients. Cluster regression analysis showed no difference between treatment arms at each respective time-point or in the overall change in NDI from preoperative to postoperative (P = 0.88). Cluster regression analysis showed no difference between treatment arms at each respective time point or in the overall change in lordosis from pre-op to post-op (P = 0.93). This review provides evidence that while NDI scores improved across all devices, there was no significant difference in NDI improvement or C2-7 Cobb angle change between single level traditional ACDF, stand-alone ACDF, or TDR. Although TDR has not been considered a lordosis producing operation, our investigation shows it does not differ significantly in sagittal profile from other cervical fusion techniques. Moreover, we show that the NDI score improved, regardless of device implanted. 1.

P3512Sex differences in rats with heart failure with preserved ejection fraction and the effect of autonomic modulation

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) accounts for 50% of HF and sudden death is the leading cause of mortality. There are considerable sex differences in cardiac structure and function, which may be related to outcomes in HFpEF. Transcutaneous vagus nerve stimulation (tVNS) is antiarrhythmic. Purpose To describe sex differences in mortality, autonomic tone and ECG parameters in rats with HFpEF and examine the effect of tVNS on these outcomes. Methods Dahl salt sensitive (DS) rats of either sex were randomized into high salt (HS, 8% NaCl) or low salt (LS) diet (0.3% NaCl) at 7 weeks of age. After 6 weeks of LS or HS diets, HS rats were randomized to receive active or sham tVNS, 30min daily (20Hz, 3mA) for 4 weeks. The rats were monitored daily for 4 weeks for the development of HFpEF. ECG and echocardiogram were performed at 13 weeks (baseline) and 17 weeks (endpoint). Heart rate variability (HRV) was calculated at the respective time points. ECG and HRV parameters were analyzed in a blinded fashion. Logistic regression analysis was performed to identify independent predictors of mortality. Results A total of 58 rats were included (5 male LS, 6 female LS, 22 male HS and 25 female HS). HS rats developed significant hypertension and signs of HFpEF, while 24% of females and 53% of males died (P=0.004). There were 4 sudden cardiac deaths in males (with ventricular tachycardia documented in 1 rat), whereas all the females died of HF or stroke. Corrected QT (QTc) at baseline significantly prolonged in HS compared to LS rats (250.5±14.4ms vs. 226.8±13.9ms, respectively, p=0.0007), while all other ECG parameters did not differ significantly between groups. In HS rats, QTc prolongation was significantly more pronounced in males compared to females (259.4±20.6ms vs. 243.8±14.5ms, respectively, P=0.002). In univariate analysis, prolonged baseline QTc (OR=1.04; 95% CI 1.01–1.06, p=0.003) and male sex (OR=3.21, 95% CI 1.19–8.66, p=0.016) predicted mortality. However, in multivariate analysis, QTc was the only significant predictor of mortality (OR=1.04; 95% CI 1.01–1.06, p=0.003). After 4 weeks of treatment, active tVNS significantly decreased QTc compared to sham (244.6±13.8ms vs. 255.8±14.0ms, respectively, p=0.017) in both male and female rats in a similar manner. The low frequency to high frequency ratio (LF/HF) of HRV, which reflects sympathovagal balance, was significantly decreased in active tVNS rats compared to sham (0.21±0.13 vs. 0.54±0.14, respectively; p=0.001) in both male and female rats in a similar manner. Conclusions Male rats with HFpEF exhibit worse survival compared to females and are at higher risk for sudden death. QTc prolongation accounts for the increased risk of sudden death in males compared to females. Autonomic modulation with tVNS attenuates the unfavorable changes in QTc and HRV induced by HS diet and may be used to prevent ventricular arrhythmias in patients with HFpEF.

P724Antibody treatment against pathological pancreatic islet amyloid polypeptide (IAPP) aggregates restores endothelial dysfunction in human-IAPP transgenic rats

Abstract Background Islet amyloid polypeptide (IAPP; or amylin) is produced in pancreatic B-cells and co-secreted with insulin in response to nutrients. In insulin resistance and type 2 diabetes (T2D), higher secretion and impaired processing of IAPP results in its aggregation, contributing to amyloid-induced apoptosis of pancreatic B-cells. Insight into IAPP's role in diabetic endothelial dysfunction is scarce. Purpose Rats transgenic for human IAPP (hIAPP), which in contrast to rodent IAPP produces amyloid deposits and contributes to diabetes due to B-cell failure, were studied to understand the mechanisms of endothelial dysfunction in T2D and test the vasoprotective actions of an anti-hIAPP antibody. Methods Male hemizygous transgenic Sprague-Dawley rats with islet B-cell expression of hIAPP (TG) and wild-type (WT) controls were sacrificed at 2, 3, 6- and 9-months age to assess endothelial function. In a second experiment, TG rats received weekly injections of antibody against aggregated hIAPP (3 mg/kg; TG-Ab) from 3–12 months of age; TG and WT controls received PBS. Oral glucose tolerance was assessed before harvesting. At the respective time points (12 mts in exp. 2), thoracic aortic rings were isolated and subjected to ex vivo isometric tension recording. After contraction with norepinephrine (NE 1x10–7 mol/L), cumulative relaxation responses were performed to glucagon-like peptide-1 (GLP-1; 10–12 to 10–6 mol/L) and insulin (10–11 to 10–6 mol/L). Pancreas and aortic arch samples were used for immunostaining of hIAPP antibody engagement. Results GLP-1 and insulin-mediated vasodilation was impaired in 3 month-old TG rats compared to WT. Glucose intolerance appeared in TG rats at 6 months in comparison to WT (p&lt;0.0001), indicating that endothelial dysfunction in TG rats precedes the onset of glucose intolerance. Anti-hIAPP antibody showed selectivity against aggregated IAPP in pancreatic islets, but there was no target engagement in the aortic arch, questioning a pathogenic role of IAPP deposition in the aortic wall. At 12 months, glucose control in TG-Ab rats was improved in comparison to TG control rats (p&lt;0.013). Vasodilatation in TG-Ab rats was restored in response to GLP-1 (35.5% ± 4.6 vs. 16.0% ± 3.1 in TG controls), similar to that of WT rats (35.5% ± 6.5). Vasodilatation in response to insulin (48.9% ± 4.2) was improved in comparison to both TG (29.4% ± 3.0) and WT controls (32.5% ± 5.7) (p&lt;0.0001; 2-way ANOVA, n=6–11 for all groups. Conclusion Early endothelial dysfunction develops in hIAPP rats compared to WT. Endothelial dysfunction is restored by the anti-hIAPP antibody treatment via improved oral glucose tolerance, but it remains unclear whether this effect is due to a local action in the aorta or a secondary effect, e.g. due to a reduction in pancreatic IAPP deposition.

Identification of Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) responsive miRNAs in banana root

The fungus, Fusarium oxysporum f. sp. cubense (Foc), is the causal agent of Fusarium wilt disease, which is the most serious disease affecting the whole banana industry. Although extensive studies have characterized many Foc-responsive genes in banana, the molecular mechanisms on microRNA level underlying both banana defense and Foc pathogenesis are not yet fully understood. In this study, we aimed to reveal the role of miRNA during banana-Foc TR4 interactions. Illumina sequencing was used to reveal the changes in small RNAome profiles in roots of Foc TR4-inoculated ‘Tianbaojiao’ banana (Musa acuminata cv. Tianbaojiao) in the early stages (i.e. 5 h, 10 h and 25 h post Foc TR4 inoculation, respectively). The expression of some differentially expressed (DE) miRNAs and their predicted target genes was studied by using quantitative real time PCR (qRT-PCR). Totally, 254 known miRNAs from 31 miRNA families and 28 novel miRNAs were identified. Differential expression analysis identified 84, 77 and 74 DE miRNAs at the three respective Foc TR4 infection time points compared with control healthy banana (CK). GO and KEGG analysis revealed that most of the predicted target genes of DE miRNAs (DET) were implicated in peroxisome, fatty acid metabolism, auxin-activated signaling pathway, sulfur metabolism, lignin metabolism and so on, and many known stress responsive genes were identified to be DETs. Moreover, expected inverse correlations were confirmed between some miRNA and their corresponding target genes by using qRT-PCR analysis. Our study revealed that miRNA play important regulatory roles during the banana-Foc TR4 interaction by regulating peroxidase, fatty acid metabolism, auxin signaling, sulfur metabolism, lignin metabolism related genes and many known stress responsive genes.

Predictors of short and long term urinary incontinence after radical prostatectomy in prostate MRI: Significance and reliability of standardized measurements

PurposeTo evaluate standardized measurements of the membranous urethra length (MUL), the membranous urethra angle (MUA) and the prostate’s apex type (AT) among further clinical parameters as potential preoperative risk factors of urinary incontinence (UI) after radical prostatectomy (RP). MethodOur institutional review board approved this retrospective single center study. 316 patients (mean age 65 years) underwent MRI at 3 T prior to prostatectomy. MUL, MUA and AT were measured according to a standardized approach on T2w- sagittal sequences. In a second reading the inter-rater agreement for the MUL was determined. Image findings and clinical data were correlated by logistic regression to UI as evaluated by a standardized questionnaire determining the number of necessary hygiene pads (HP) at three different time points with corresponding patient subsets (one week, six months and 12 months after RP). ResultsThere was a significant impact of the MUL on postoperative UI with odds ratios (OR) of 0.8 [p < 0.001; confidence interval (CI) 0.73-0.91], 0.8 (p = 0.01; CI 0.68-0.94) and 0.7 (p < 0.01; CI 0.56-0.89) at the respective time points. No significant impact was demonstrated regarding the MUA and AT. Of all clinical parameters there was significant impact of the patients’ age and the degree of nerve-sparing surgery. Inter-rater agreement with respect to the MUL was good with an intraclass correlation coefficient of 0.82. The mean deviation of raters measuring the MUL was 1.2 mm. ConclusionsA shorter MUL in mpMRI should be considered as a risk factor of UI after RP. Standardized measurements enabling good inter-rater agreement should be considered for routine assessments to facilitate prospective classifications.

Can We Help Patients Forget Their Joint? Determining a Threshold for Successful Outcome for the Forgotten Joint Score

BackgroundClinically important thresholds improve interpretability of patient-reported outcomes. A threshold for a successful outcome does not exist for the Forgotten Joint Score (FJS). The purpose of this study is to determine a threshold score for the FJS, 1 and 2 years after total hip arthroplasty (THA). MethodsA retrospective analysis of 247 primary THA recipients between December 2012 and April 2017 was performed. A binary “successful treatment” was defined as achieving a composite criterion of pain, function, and satisfaction. Receiver operator characteristic analysis determined thresholds for successful outcome at 1 and 2 years postoperatively, subanalyzed by demographics. Results were validated by a 75th centile comparison. The ceiling effect of FJS was also assessed. ResultsThe average FJS was 70.06 ± 29.39 and 75.05 ± 28.73 at 1 and 2 years, respectively (P < .001). The proportion of patients meeting the composite criteria for success was 66.8% at 1 year and 76.5% at 2 years (P = .017). The receiver operator characteristic analysis for FJS at 1 and 2 years yielded excellent accuracy as defined by area under the curve (0.91 and 0.92, respectively). The threshold values were 73.96 and 69.79 at the respective time points. A mild ceiling effect was found with 16% and 23% of cases achieving a score of 100 at 1 and 2 years, respectively. ConclusionThe FJS has excellent accuracy in demonstrating successful outcome following THA. The FJS threshold for success at 1 and 2 years postoperatively is 73.96 and 69.79, respectively. The higher rates of success at 2 years, along with a rise in the mean FJS, may indicate continued clinical improvement up to 2 years after THA.

Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program

ObjectiveWe have previously shown that cannabidiol (CBD; Epidiolex®) significantly affects levels of clobazam/N-desmethylclobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In the present study, we tested whether the presence of concomitant clobazam affected seizure frequency and severity (treatment response) 12 weeks after initiation of therapy with CBD in patients with treatment-resistant epilepsy (TRE). The secondary questions were whether the presence of any of the other antiepileptic drugs (AEDs) had an effect on seizure frequency or severity at 12, 24, or 48 weeks after therapy initiation. MethodsOne hundred and thirty-two adults and children with TRE receiving CBD were studied prospectively. Participants were separated into two groups — either taking (CBD + clobazam) or not taking concomitant clobazam (CBD − clobazam). In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED). Seizure counts and Chalfont Seizure Severity Scale (CSSS) were obtained at baseline, 12, 24, and 48 weeks. Groups were compared at each respective time point in the study using generalized estimating equations (GEE) analyses. ResultsAll groups demonstrated statistically significant reductions in seizure frequency and severity from baseline (all P < 0.05). When participants on CBD + clobazam were compared with CBD − clobazam, there were no significant differences in seizure frequency and severity reduction between the groups at 12 weeks (both P > 0.05). When comparing groups with iAEDs vs. group without iAEDs, independent of coadministration of clobazam, no differences in treatment response were observed (all P > 0.05). Longitudinal analyses up to 48 weeks after therapy initiation did not reveal any differences in treatment response between groups. ConclusionThese analyses suggest that concomitant to CBD, AEDs may not have an effect on reducing seizure frequency and severity in patients with TRE.

Susceptibility of Tilapia Lake Virus to buffered Povidone-iodine complex and chlorine

Tilapia Lake Virus (TiLV) is an emergent orthomyxo-like virus affecting the global tilapia (Oreochromis sp.) aquaculture industry. Mortality in affected farms can reach 80–90% in severe outbreaks. Effective vaccines and chemotherapeutic treatments are currently unavailable. The aim of this study was to identify the virucidal efficacy of two commonly used disinfectants, namely household bleach (free-chlorine) and a Buffered Povidone-iodine (PVP Iodine) complex, against TiLV. An archived TiLV isolate was cultured on an endothelial Oreochromis mossambicus bulbus arteriosus cell line (TmB). Bleach and PVP ranging from 10 to 100 mg/L (ppm) were diluted the day of the assay in autoclaved well water collected from an aquaculture facility in California, USA and added to TiLV cultures for 0.5, 1, or 24 h. At each respective timepoint, sodium thiosulphate or fetal bovine serum were added to inactivate the available iodine and free chlorine, respectively. All aliquots were then titrated on TmB cells to determine the TCID50/ml. Virucidal reductions in titer >4 log10 TCID50/ml were obtained with ≥20 ppm free chlorine and ≥ 50 ppm available iodine after just 30 min contact time. When contact time was increased to 24 h, ≥10 ppm free chlorine and ≥ 25 ppm available iodine were required to achieve virucidal reductions in titer >4 log10 TCID50/ml. This information should be taken into consideration when developing biosecurity protocols in tilapia aquaculture to prevent the spread of TiLV.

Server-Side Traffic Analysis Reveals Mobile Location Information over the Internet

Users can attempt to thwart third-party services from discovering their location by disabling location services on their mobile device. In this paper, we show that web services can use throughput information to reveal the path taken by the phone and its owner among a set of possibilities. For example, a TCP-based music streaming service can compile a sequence of throughputs over several minutes. We collected hundreds of traces of music that we streamed to phones in two different scenarios: a user traveling to four different towns from campus (or the reverse direction); and a user traveling within our campus. We evaluate three classifiers: $k$k-Nearest Neighbors ($k$k-NN), which compares a test sequence with respective time points of training sequences; a Hidden Markov Model (HMM), which computes the transition and emission probabilities of different geographic areas and chooses the most likely sequence of a test trace; and a Naive Bayes Classifier with KDE-based throughput estimates (NB-KDE), which looks at the density of throughputs at each time point along a path. In our study, the $k$k-NN, HMM, and NB-KDE approaches can distinguish between a small number of geographic routes taken by mobile users using only throughput measurements. The NB-KDE method performed best, using throughput alone to identify the path and direction among two roads within a University campus (four classes) with 77 percent accuracy, and the path and direction among four roads (eight classes) out of town with 83 percent accuracy. Furthermore, it was able to classify among eight paths with greater than 59 percent accuracy after one minute. We examine the limitations of these techniques.

Protective effect of carbon monoxide releasing molecules 2 on post-resuscitation myocardial dysfunction in rats

Objective: To investigate the protective effect of carbon monoxide releasing molecule 2 (CORM-2) on post-resuscitation myocardial dysfunction in rats. Methods: Forty male SD rats which were healthy were randomly divided into 5 groups: sham operated group(sham group), cardiopulmonary resuscitation(PCR) group, DMSO group, inactivated CORM-2(iCORM-2) group and CORM-2 group (n=8 each). Established the model of post-cardiac arrest myocardial dysfunction by intravenous potassium chloride (4 ℃) injection combined with asphyxiation for 4 minutes and then followed by artificial chest compression for 3 minutes. Sham group: rats were instrumented with catheter without inducing cardiac arrest and resuscitation, and intraperitoneal injection of 0.9% normal saline (4 ml/kg) was performed 12 hours before catheterization. CPR group: rats were instrumented with catheters and underwent CPR, and intraperitoneal injection of 0.9% normal saline (4 ml/kg) was performed 12 hours before surgery.CORM-2 group: rats were instrumented with catheters and underwent CPR, intraperitoneally injected the prepared CORM-2 solution (4 mg/kg) at 12 hours before surgery. DMSO group: rats were instrumented with catheters and underwent CPR, intraperitoneally injected the prepared DMSO solution (4 ml/kg) at 12 hours before surgery. iCORM-2 group: rats were instrumented with catheters and underwent CPR, iCORM-2 solution (4 mg/kg) was intraperitoneally injected at 12 hours before surgery. Hemodynamic data (MAP, +dp/dtmax, -dp/dt) were continuously monitored and recorded for 4 hours after resuscitation (or catheterization) in each group. Myocardial tissue specimen and blood samples were taken after resuscitation (or catheterization). The myocardial ultrastructure was observed by transmission electron microscope. Lactate dehydrogenase (LDH) activity was measured by lactate-pyruvate method. Serum creatine kinase isoenzyme (CK-MB) concentration was measured by ELISA. Western blot was used to detect the levels of Caspase-3, Caspase-9 and Cyt-C protein in myocardial tissue. Results: MAP, +dp/dtmax and -dp/dt at 0.5, 1, 2, 3 and 4 hours post resuscitation were significantly lower than those immediately after catheterization in CRP, DMSO, iCORM-2 groups (all P<0.05). MAP at 0.5, 1, 2, 3, and 4 hours post resuscitation were significantly lower in CRP, DMSO and iCORM-2 groups than those at respective time points in sham group (all P<0.05), while MAP was similar between CORM-2 group and Sham group at these time points (all P>0.05). +dp/dtmax and -dp/dt values at 0.5, 1, 2, 3, and 4 hours post resuscitation were lower than those at respective time points in sham group and significance was found at 0.5, 1 and 2 hours post resuscitation (both P<0.05), while +dp/dtmax and -dp/dt values were similar between CORM-2 group and sham group at various time points (all P>0.05). Myocardial ultrastructure, especially mitochondrial structural integrity was better preserved in the CORM-2 group than those in the other resuscitation groups at 4 hours after resuscitation. Serum LDH activity and CK-MB concentration were significantly elevated at 4 hours after resuscitation in the CPR group, DMSO group and iCORM-2 group than those in sham group (all P<0.01); CK-MB concentration was also higher in CORM-2 group than that in sham group,and LDH level was similar between CORM-2 group and sham group (P>0.05). Serum LDH activity and CK-MB concentrations were significantly lower in the CORM-2 group than those in the other resuscitation groups (all P<0.01). The myocardial expressions of Caspase-3, Caspase-9 and Cyt-C at 4 hours after resuscitation were significantly higher in the CPR group, DMSO group and iCORM-2 group than those in sham group; the myocardial expressions of Caspase-3 and Caspase-9 were significantly higher in CORM-2 group than those in sham group (both P<0.05), while Cyt-C expression was similar between CORM-2 group and sham group. The expressions of the above 3 proteins were significantly lower in the CORM-2 group than those in the other resuscitation groups (all P<0.05). Conclusions: CORM-2 can effectively alleviate post-resuscitation myocardial injury in rats with cardiopulmonary resuscitation and improve cardiac function. Protecting myocardial mitochondria and inhibiting mitochondrial apoptosis pathway may serve as the protective mechanisms in this model.