Recent and lifetime maternal substance use: Rurality and economic distress.

Research on opioid use disorder (OUD) in pregnancy has mainly considered women in urban areas receiving treatment, with less known about women in rural areas. We sought to describe demographics and substance use characteristics of pregnant women with OUD and to compare the women based on urbanicity, in a state (Kentucky) with unfavorable economic conditions in many rural counties; we hypothesized that pregnant women in rural areas would have greater adversity, broadly defined, related to substance use. Using data collected from a larger project between 2017 and 2020, we analyzed characteristics of 93 pregnant women (59 rural and 34 urban) with OUD; we examined data in medical, employment, substance use, legal, family history, relationship, and psychiatric health domains, both overall and within rural (population <50,000) and urban (population ≥50,000) strata. Pregnant women with OUD from rural and urban areas were similar on almost all attributes. Among the few significant differences, 30% from urban areas perceived inadequate prenatal care versus 11% from rural areas (p = 0.024); 21% of urban women used amphetamines/methamphetamines in the month before delivery versus 0% of rural women (p < 0.001); and rural women had longer most recent abstinence from substance use than their urban counterparts (medians 7.0 and 2.8 months, p = 0.049). The few significant differences that were discovered favored rural women. These findings, contrary to our hypothesis, suggest that tailoring interventions may require more than focusing on geography. The participants in this study were pregnant women being treated for OUD, and as such there is patient contribution of data.

Associations of potential ADRD plasma biomarkers in cognitively normal volunteers.

INTRODUCTION: This study examined the relationships between 13 novel blood-plasma biomarkers and dementia-related demographic and health factors in a cohort of 237 cognitively normal research volunteers whose average age was ≈82 years and who were 63% female. METHODS: We regressed each biomarker on selected covariates to explore the associations between the biomarkers and selected factors to assess whether they may contribute to biomarker values. Post hoc sensitivity analyses were done with updated data and consistent variable sets for robustness and batch effects. RESULTS: Biomarker concentrations were largely not associated with demographics or health conditions, but some expected associations (e.g., apolipoprotein E [APOE] status with amyloid beta [Aß]42/Aß40) were observed. Post hoc results remained similar to those of the main analysis. DISCUSSION: The absence of strong associations between the biomarkers with age, gender, or medical conditions suggests that changes in these biomarkers, when observed, may be attributable to neuropathological changes. HIGHLIGHTS: Among N = 237 cognitively normal adults, we studied candidate Alzheimer's disease and related dementia (ADRD) plasma biomarkers. Biomarkers were largely not associated with demographic or health factors. Apolipoprotein E (APOE) status was associated with amyloid beta (Aß)42/Aß40 ratio. These results support hypotheses that plasma biomarkers are informative for ADRD.

A Comparison of Methods for Predicting Future Cognitive Status: Mixture Modeling, Latent Class Analysis, and Competitors.

PURPOSE: The present work compares various methods for using baseline cognitive performance data to predict eventual cognitive status of longitudinal study participants at the University of Kentucky's Alzheimer's Disease Center. METHODS: Cox proportional hazards models examined time to cognitive transition as predicted by risk strata derived from normal mixture modeling, latent class analysis, and a 1-SD thresholding approach. An additional comparator involved prediction directly from a numeric value for baseline cognitive performance. RESULTS: A normal mixture model suggested 3 risk strata based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) T scores: high, intermediate, and low risk. Cox modeling of time to cognitive decline based on posterior probabilities for risk stratum membership yielded an estimated hazard ratio of 4.00 with 95% confidence interval 1.53-10.44 in comparing high risk membership to low risk; for intermediate risk membership versus low risk, the modeling yielded hazard ratio=2.29 and 95% confidence interval=0.98-5.33. Latent class analysis produced 3 groups, which did not have a clear ordering in terms of risk; however, one group exhibited appreciably greater hazard of cognitive decline. All methods for generating predictors of cognitive transition yielded statistically significant likelihood ratio statistics but modest concordance statistics. CONCLUSION: Posterior probabilities from mixture modeling allow for risk stratification that is data-driven and, in the case of CERAD T scores, modestly predictive of later cognitive decline. Incorporating other covariates may enhance predictions.

Implantation of Left Ventricular Assist Device Results in Immediate Improvement of Glucose Metabolism in Patients With and Without Diabetes Mellitus.

BACKGROUND: Several studies demonstrated improvement in diabetes mellitus (DM) following left ventricular assist device (LVAD) implantation, but the timing of these changes has not been identified. We sought to determine if favourable metabolic changes occur immediately, within the initial hospitalisation following LVAD implantation. We also wanted to see whether favourable changes in glucose metabolism occur in patients without diabetes. METHODS: This is a retrospective analysis of patients receiving LVADs at our institution. We collected the data on fasting blood glucose (FBG) and total daily insulin requirements before the LVAD implantation and before the discharge. Patients served as their own controls. RESULTS: We studied 70 consecutive patients, half of them diabetic. In both diabetics and non-diabetics there was a significant reduction in FBG after LVAD implantation. In diabetic patients, there was an overall reduction in insulin requirements from the average 29.2 units of insulin per day before the LVAD to 16.2 units per day (p=0.038) before discharge. Specifically, insulin requirement decreased in 16 patients by a median of 25.2 units per day (the interquartile range [IQR)]: -47.8 to -9.2), increased in 10 patients (by 7.3 units/day, IQR 0.7 to 15.3), and remained unchanged in six patients. CONCLUSIONS: Favourable metabolic changes on LVAD support occurred almost immediately, within initial hospitalisation, in diabetics and non-diabetics alike. Decline in insulin requirements should be considered when managing diabetics following LVAD implantation.

Left ventricular assist device-related infections: does the time of onset matter?

A frequent complication of left ventricular assist devices (LVAD) is the LVAD-associated infections (LVADIs). Contamination may occur during initial surgery/admission or at a later time. We studied the clinical manifestations and outcomes of LVADIs depending on the time of the onset. Patients implanted with LVADs at our institution between August 2009 and December 2014 were included. Patients were stratified into 2 groups based on whether the infection occurred early (< 180 days) or late (≥ 180 days) after LVAD implantation. Out of 37 overall LVADI episodes, 16 (43%) and 21 (57%) occurred early or late after device implantation, respectively. Median time to first LVADI was 88 ± 35 vs. 456 ± 187 days between groups. While superficial driveline-related infection was the most common LVADI type for both groups (56 vs. 71%, p = 0.489), driveline drainage was more prevalent in the late group (24 vs. 69%; p = 0.009). Early LVADIs involved more gram-positive flora, mostly Staphylococcus aureus (69 vs. 33%, p = 0.049), whereas late LVADIs involved more gram-negative pathogens, mostly Pseudomonas aueroginosa (25 vs. 57%; p = 0.045). High rates of treatment failure were consistent between groups (88 vs. 71%, p = 0.384). Compared with superficial LVADI, deeper infections were associated with an increase in mortality (13 vs 46%, p = 0.046). We concluded that early onset with likely in-hospital contamination involved more gram-positive flora, whereas late infection involved more gram-negative flora. Regardless of timing, success of antibacterial treatment was dismal, and infection depth correlated with poorer outcomes.

Female Mice With an XY Sex Chromosome Complement Develop Severe Angiotensin II-Induced Abdominal Aortic Aneurysms.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a deadly pathology with strong sexual dimorphism. Similar to humans, female mice exhibit far lower incidences of angiotensin II-induced AAAs than males. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, we defined the effect of female (XX) versus male (XY) sex chromosome complement on angiotensin II-induced AAA formation and rupture in phenotypically female mice. METHODS: Female low-density lipoprotein receptor (Ldlr) deficient mice with an XX or XY sex chromosome complement were infused with angiotensin II for 28 days to induce AAAs. Abdominal aortic lumen diameters were quantified by ultrasound, whereas AAA diameters were quantified at study end point. DNA microarrays were performed on abdominal aortas. To mimic males, female mice were administered a single dose of testosterone as neonates or as adults before angiotensin II infusions. RESULTS: Female Ldlr-/- deficient mice with an XX and XY sex chromosome complement had similar sex organ weights and low serum testosterone concentrations. Abdominal aortas from female XY mice selectively expressed Y chromosome genes, whereas genes known to escape X inactivation were higher in XX females. The majority of aortic gene differences in XY versus XX females fell within inflammatory pathways. AAA incidences doubled and aneurysms ruptured in XY females. AAAs from XY females exhibited inflammation, and plasma interleukin-1ß concentrations were increased in XY females. Moreover, aortas from XY females had augmented matrix metalloproteinase activity and increased oxidative stress. Last, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY in comparison with XX adult females. CONCLUSIONS: An XY sex chromosome complement in phenotypic females profoundly influenced aortic gene expression profiles and promoted AAA severity. When XY females were exposed to testosterone, aneurysm rupture rates were striking. Mechanisms for augmented AAA severity in XY females include increased inflammation, augmented matrix metalloproteineases, and oxidative stress. Our results demonstrate that genes on the sex chromosomes regulate aortic vascular biology and contribute to sexual dimorphism of AAAs. Sex chromosome genes may serve as novel targets for sex-specific AAA therapeutics.

Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study.

BACKGROUND: Whether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data. METHODS: MSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time-varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data. RESULTS: Among 4,060 patients in AFFIRM, 660 (16.3%) died during follow-up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11-1.60, P  =  0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07-1.72, P  =  0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96-1.72, P  =  0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%. CONCLUSIONS: Digoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.

Relationship between serum trimethylamine N-oxide and exposure to dioxin-like pollutants.

Trimethylamine N-oxide (TMAO) is a diet and gut microbiota-derived metabolite that has been linked to cardiovascular disease risk in human studies and animal models. TMAO levels show wide inter and intra individual variability in humans that can likely be accounted for by multiple factors including diet, the gut microbiota, levels of the TMAO generating liver enzyme Flavin-containing monooxygenase 3 (FMO3) and kidney function. We recently found that dioxin-like (DL) environmental pollutants increased FMO3 expression to elevate circulating diet-derived TMAO in mice, suggesting that exposure to this class of pollutants might also contribute to inter-individual variability in circulating TMAO levels in humans. To begin to explore this possibility we examined the relationship between body burden of DL pollutants (reported by serum lipid concentrations) and serum TMAO levels (n = 340) in the Anniston, AL cohort, which was highly exposed to polychlorinated biphenyls (PCBs). TMAO concentrations in archived serum samples from the Anniston Community Health Survey (ACHS-II) were measured, and associations of TMAO with 28 indices of pollutant body burden, including total dioxins toxic equivalent (TEQ), were quantified. Twenty-three (22 after adjustment for multiple comparisons) of the 28 indices were significantly positively associated with TMAO. Although the design of ACHS-II does not enable quantitative assessment of the contributions of previously known determinants of TMAO variability to this relationship, limited multivariate modeling revealed that total dioxins TEQ was significantly associated with TMAO among females (except at high BMIs) but not among males. Our results from this cross-sectional study indicate that exposure to DL pollutants may contribute to elevated serum TMAO levels. Prospective longitudinal studies will be required to assess the joint relationship between DL pollutant exposures, other determinants of TMAO, and health outcomes.

Bidirectional Relations of Impulsive Personality and Alcohol Use Across Three Waves of Data Collection.

OBJECTIVE: To explore the bidirectional relations between alcohol use and three impulsive personality traits, to advance understanding of risk processes. PARTICIPANTS: 525 college students (mean age = 18.95 years) recruited in August 2008 and 2009 and followed up annually for three years. METHODS: Personality and past/current substance use were assessed. RESULTS: T2 sensation seeking mediated the predictive relationship between T1 and T3 alcohol use, and T2 alcohol use mediated the predictive relationship between T1 and T3 sensation seeking. In addition, T2 alcohol problems mediated the predictive relationship between T1 alcohol use and T3 negative urgency. CONCLUSIONS: Findings support a bidirectional relationship between sensation seeking and alcohol use, and drinking anticipates drinking problems, which predict increases in negative urgency. For some individuals, there appears to be an ongoing process of increased risk in the form of increases in both drinking and high-risk personality traits.

Prevention of renal apoB retention is protective against diabetic nephropathy: role of TGF-ß inhibition.

Animal studies demonstrate that hyperlipidemia and renal lipid accumulation contribute to the pathogenesis of diabetic nephropathy (DN). We previously demonstrated that renal lipoproteins colocalize with biglycan, a renal proteoglycan. The purpose of this study was to determine whether prevention of renal lipid (apoB) accumulation attenuates DN. Biglycan-deficient and biglycan wild-type Ldlr-/- mice were made diabetic via streptozotocin and fed a high cholesterol diet. As biglycan deficiency is associated with elevated transforming growth factor-ß (TGF-ß), in some experiments mice were injected with either the TGF-ß-neutralizing antibody, 1D11, or with 13C4, an irrelevant control antibody. Biglycan deficiency had no significant effect on renal apoB accumulation, but led to modest attenuation of DN with ∼30% reduction in albuminuria; however, biglycan deficiency caused a striking elevation in TGF-ß. Use of 1D11 led to sustained suppression of TGF-ß for approximately 8 weeks at a time. The 1D11 treatment caused decreased renal apoB accumulation, decreased albuminuria, decreased renal hypertrophy, and improved survival, compared with the 13C4 treatment. Thus, prevention of renal apoB accumulation is protective against development of DN. Furthermore, this study demonstrates that prevention of renal apoB accumulation is a mechanism by which TGF-ß inhibition is nephroprotective.

Obesity paradox in heart failure: statistical artifact, or impetus to rethink clinical practice?

The "obesity paradox" in heart failure (HF) is a phenomenon of more favorable prognosis, especially better survival, in obese versus normal-weight HF patients. Various explanations for the paradox have been offered; while different in their details, they typically share the premise that obesity per se is not actually the cause of reduced mortality in HF. Even so, there is a lingering question of whether clinicians should refrain from, or at least soft-pedal on, encouraging weight loss among their obese HF patients. Against the backdrop of recent epidemiological analysis by Banack and Kaufman, which speculates that collider stratification bias may generate the obesity paradox, we seek to address the aforementioned question. Following a literature review, which confirms that obese HF patients are demographically and clinically different from their normal-weight counterparts, we present four hypothetical data sets to illustrate a spectrum of possibilities regarding the obesity-mortality association. Importantly, these hypothetical data sets become indistinguishable from each other when a crucial variable is unmeasured or unreported. While thorough, the discussion of these data sets is intended to be accessible to a wide audience, especially including clinicians, without a prerequisite of familiarity with advanced epidemiology. We also furnish intuitive visual diagrams which depict a version of the obesity paradox. These illustrations, along with reflection on the distinction between weight and weight loss (and, furthermore, between voluntary and involuntary weight loss), lead to our recommendation for clinicians regarding the encouragement of weight loss. Finally, our conclusion explicitly addresses the questions posed in the title of this article.

Using a respiratory navigator significantly reduces variability when quantifying left ventricular torsion with cardiovascular magnetic resonance.

BACKGROUND: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion. METHODS: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure and then enforce variability in end-expiratory position between all LV basal and apical acquisitions. From these data, we quantified the inter-test variability of torsion in the absence and presence of enforced end-expiratory position variability, which established an upper bound for the expected torsion variability. For the second experiment (in 20 new, healthy volunteers), 10 pairs of cine DENSE basal and apical images were each acquired from consecutive breath-holds and consecutive navigator-gated scans (with a single acceptance position). Inter-test variability of torsion was compared between the breath-hold and navigator-gated scans to quantify the variability due to natural breath-hold variation. To demonstrate the importance of these variability reductions, we quantified the reduction in sample size required to detect a clinically meaningful change in LV torsion with the use of a respiratory navigator. RESULTS: The mean torsion was 3.4 ± 0.2°/cm. From the first experiment, enforced variability in end-expiratory position translated to considerable variability in measured torsion (0.56 ± 0.34°/cm), whereas inter-test variability with consistent end-expiratory position was 57% lower (0.24 ± 0.16°/cm, p < 0.001). From the second experiment, natural respiratory variability from consecutive breath-holds translated to a variability in torsion of 0.24 ± 0.10°/cm, which was significantly higher than the variability from navigator-gated scans (0.18 ± 0.06°/cm, p = 0.02). By using a respiratory navigator with DENSE, theoretical sample sizes were reduced from 66 to 16 and 26 to 15 as calculated from the two experiments. CONCLUSIONS: A substantial portion (22-57%) of the inter-test variability of LV torsion can be reduced by using a respiratory navigator to ensure a consistent breath-hold position between image acquisitions.

Association between left ventricular mechanics and diffuse myocardial fibrosis in patients with repaired Tetralogy of Fallot: a cross-sectional study.

BACKGROUND: Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse biventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this dysfunction, such as diffuse myocardial fibrosis, may provide insights into poor long-term outcomes. We hypothesized that left ventricular (LV) diffuse fibrosis is related to impaired LV mechanics. METHODS: Patients with TOF were evaluated with cardiac magnetic resonance in which modified Look-Locker (MOLLI) T1-mapping and spiral cine Displacement encoding (DENSE) sequences were acquired at three LV short-axis positions. Linear mixed modeling was used to define the association between regional LV mechanics from DENSE based on regional T1-derived diffuse fibrosis measures, such as extracellular volume fraction (ECV). RESULTS: Forty patients (26 ± 11 years) were included. LV ECV was generally within normal range (0.24 ± 0.05). For LV mechanics, peak circumferential strains (-15 ± 3%) and dyssynchrony indices (16 ± 8 ms) were moderately impaired, while peak radial strains (29 ± 8%) were generally normal. After adjusting for patient age, sex, and regional LV differences, ECV was associated with log-adjusted LV dyssynchrony index (ß = 0.67) and peak LV radial strain (ß = -0.36), but not LV circumferential strain. Moreover, post-contrast T1 was associated with log-adjusted LV diastolic circumferential strain rate (ß = 0.37). CONCLUSIONS: We observed several moderate associations between measures of fibrosis and impaired mechanics, particularly the LV dyssynchrony index and peak radial strain. Diffuse fibrosis may therefore be a causal factor in some ventricular dysfunction in TOF.

Acute Effects of Implantable Cardioverter-Defibrillator Shocks on Biomarkers of Myocardial Injury, Apoptosis, Heart Failure, and Systemic Inflammation.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT. METHODS: We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT-). RESULTS: Sixty-three patients were enrolled, 40 in the DFT+ group and 23 in the DFT- group. Average levels of troponin I, hsCRP, Calprotectin, N-terminal pro B-type natriuretic peptide (NTproBNP), and sFas increased by >50% after cardiac device implantation compared to baseline. Increase in troponin never exceeded the 50-fold upper limit of normal (2 ng/mL). Troponin trended higher in the DFT+ group at 8 hours (median 0.18 ng/mL, interquartile range [IQR] 0.11-0.48) versus the DFT- group (0.10 ng/mL, IQR 0.06-0.28, P = 0.0501); NTproBNP had a similar trend (P = 0.0581). sFas significantly increased in the DFT+ group from baseline (median 4663 pg/mL, IQR 2908-5679) to 24 hours (5039 pg/mL, IQR 3274-6261; P = 0.0338) but not in the DFT- group (P = 0.4705). CONCLUSION: DFT testing is associated with acutely increased plasma levels of troponin and sFas, a biomarker of apoptosis, along with a trend toward higher NTproBNP.

Atrioventricular dyssynchrony from empiric device settings is common in cardiac resynchronization therapy and adversely impacts left ventricular morphology and function.

BACKGROUND: Echocardiographic atrioventricular (AV) optimization after cardiac resynchronization therapy (CRT) is uncommon due to time constraints and the use of vendor-specific device algorithms. It remains unclear whether optimization of mitral inflow velocities can still be useful. We aimed to investigate post implantation left ventricular (LV) inflow patterns to determine the incidence of AV dyssynchrony from empirically set devices. METHODS: This was a retrospective study of patients undergoing CRT using empiric device settings. Forty-eight patients with clinical, echocardiographic, and pacemaker follow-up were grouped by their post implantation LV filling pattern. Baseline characteristics and echocardiographic measurements were compared with post implantation findings at median 6.3 months (interquartile range [IQR], 3.9-17.0). RESULTS: Twenty-four patients demonstrated AV dyssynchrony (Group 1) after CRT, and 24 patients did not (Group 2). Group 1 patients had less LV reverse remodeling compared to Group 2 patients (ΔLV end-diastolic volume: -3.6 mL vs -49.5 mL, P<.05; ΔLV end-systolic volume: -16.9 mL vs -53.5 mL, P<.05) and did not experience significant improvements in LV outflow tract velocity time integral, stroke volume, or LV ejection fraction. There were no differences in new-onset atrial fibrillation, heart failure readmissions, or mortality between groups. CONCLUSION: Our study suggests that up to 50% of patients with empiric device settings have AV dyssynchrony at 6 months despite atrioventricular delay optimization (AVO) algorithms. As AV dyssynchrony is common and has proven to be modifiable, a strategic approach to Doppler echocardiography-guided AVO after CRT is warranted, particularly in nonresponders where the LV filling pattern is fused or truncated.

Outpatient versus observation/inpatient parotidectomy: patient factors and perioperative complications.

The objective of this manuscript is to review a single institution's experience with superficial or total parotidectomy in outpatient and observation/inpatient groups. All patients who underwent superficial or total parotidectomy between 2009 and 2015 were identified. Patients were excluded if they had undergone concurrent surgery such as neck dissection, had prior radiation treatment or surgery at the operative site. Main outcomes were perioperative complications in both groups. 215 consecutive patients were included in the study, 116 (54%) patients in the inpatient group and 99 (46%) in the outpatient group. Aside from a higher observed rate of cardiac disease in the outpatient group (24.2 vs. 11.2%, p = 0.014) and larger mean body mass index (BMI) in the inpatient group (32.448 vs. 30.034, p = 0.017), there were no significant differences for age, sex or smoking status. Average operative time differed between groups with 2 h 42 min for inpatients and 2 h 18 min for outpatients (p < 0.001). There were 26 complications in the inpatient group (22.4%, including two hematomas) and 8 in the outpatient group (8.1%). The rate of seroma/sialocele formation was significantly higher in the inpatient group at 15.5% (n = 18) compared with the outpatient group at 3% (n = 3, p = 0.001). Our study shows that parotidectomy, superficial or total, was performed safely as an outpatient procedure without significant increase in complications when compared to patients observed for at least one night after surgery.

Impact of individual acute phase serum amyloid A isoforms on HDL metabolism in mice.

The acute phase (AP) reactant serum amyloid A (SAA), an HDL apolipoprotein, exhibits pro-inflammatory activities, but its physiological function(s) are poorly understood. Functional differences between SAA1.1 and SAA2.1, the two major SAA isoforms, are unclear. Mice deficient in either isoform were used to investigate plasma isoform effects on HDL structure, composition, and apolipoprotein catabolism. Lack of either isoform did not affect the size of HDL, normally enlarged in the AP, and did not significantly change HDL composition. Plasma clearance rates of HDL apolipoproteins were determined using native HDL particles. The fractional clearance rates (FCRs) of apoA-I, apoA-II, and SAA were distinct, indicating that HDL is not cleared as intact particles. The FCRs of SAA1.1 and SAA2.1 in AP mice were similar, suggesting that the selective deposition of SAA1.1 in amyloid plaques is not associated with a difference in the rates of plasma clearance of the isoforms. Although the clearance rate of SAA was reduced in the absence of the HDL receptor, scavenger receptor class B type I (SR-BI), it remained significantly faster compared with that of apoA-I and apoA-II, indicating a relatively minor role of SR-BI in SAA's rapid clearance. These studies enhance our understanding of SAA metabolism and SAA's effects on AP-HDL composition and catabolism.

Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.

Lipid accumulation in liver and skeletal muscle contributes to co-morbidities associated with diabetes and obesity. We made a transgenic mouse in which the adiponectin (Adipoq) promoter drives expression of lipoprotein lipase (LPL) in adipocytes to potentially increase adipose tissue lipid storage. These mice (Adipoq-LPL) have improved glucose and insulin tolerance as well as increased energy expenditure when challenged with a high fat diet (HFD). To identify the mechanism(s) involved, we determined whether the Adipoq-LPL mice diverted dietary lipid to adipose tissue to reduce peripheral lipotoxicity, but we found no evidence for this. Instead, characterization of the adipose tissue of the male mice after HFD challenge revealed that the mRNA levels of peroxisome proliferator-activated receptor-γ (PPARγ) and a number of PPARγ-regulated genes were higher in the epididymal fat pads of Adipoq-LPL mice than control mice. This included adiponectin, whose mRNA levels were increased, leading to increased adiponectin serum levels in the Adipoq-LPL mice. In many respects, the adipose phenotype of these animals resembles thiazolidinedione treatment except for one important difference, the Adipoq-LPL mice did not gain more fat mass on HFD than control mice and did not have increased expression of genes in adipose such as glycerol kinase, which are induced by high affinity PPAR agonists. Rather, there was selective induction of PPARγ-regulated genes such as adiponectin in the adipose of the Adipoq-LPL mice, suggesting that increasing adipose tissue LPL improves glucose metabolism in diet-induced obesity by improving the adipose tissue phenotype. Adipoq-LPL mice also have increased energy expenditure.

Effect of peripheral circadian dysfunction on metabolic disease in response to a diabetogenic diet.

BMAL1 is a core component of the transcription/translation machinery that regulates central and peripheral circadian rhythms that coordinate behavior and metabolism, respectively. Our objective was to determine the impact of BMAL1 in adipose alone or in combination with liver on metabolic phenotypes. Control, adipose-Bmal1 knockout (ABKO), and liver- and adipose-Bmal1 knockout (LABKO) female mice were placed in TSE System metabolic chambers for metabolic phenotyping. A second cohort of male mice was fed a control or diabetogenic diet, and body weight and composition, glucose tolerance, insulin sensitivity, and serum and hepatic lipids were measured. Both female ABKO and LABKO mice exhibited increased food consumption compared with control mice. ABKO mice also exhibited increased overall activity predominantly during the light phase compared with both control and LABKO mice and were protected from increased weight gain. When the male cohort was challenged with a diabetogenic diet, LABKO mice had increased body weight due to increased fat mass compared with control and ABKO mice. However, these mice did not present further impairments in glycemic control, adipose inflammation, or liver injury. LABKO mice had increased hepatic cholesterol and elevated expression of cholesterol synthesis and uptake genes. Our data indicate that deletion of this allele in adipose or in combination with liver alters feeding behavior and locomotor activity. However, obesity is exacerbated only with the combination of liver and adipose deletion.

A multivariate generalized Cp and surface estimation.

We propose a new multivariate generalized Cp (MGCp) criterion for tuning parameter selection in nonparametric regression, applicable when there are multiple covariates whose values may be irregularly spaced. Apart from an asymptotically negligible remainder, the MGCp criterion has expected value equal to the sum of squared errors of a fitted derivative (rather than of a fitted mean response). Thus, unlike traditional criteria for tuning parameter selection, MGCp is not prone to undersmoothed derivative estimation. We illustrate a scientific application in a case study that explores the relationship among three measures of liver function. Since recent technological developments hold promise for assessing two of these measures outside of medical and laboratory facilities, better understanding of the aforementioned relationship may allow enhanced monitoring of liver function, especially in developing countries and among persons for whom access to medical and laboratory facilities is limited.