Interaction of sodium acetate supplementation and dietary fiber level on feeding behavior, digestibility, milk synthesis, and plasma metabolites.

Acetate supplementation has been shown to increase milk fat yield in diets with low risk of biohydrogenation-induced milk fat depression. The interaction of acetate supplementation with specific dietary factors that modify rumen fermentation and short-chain fatty acid (FA) synthesis has not been investigated. The objective of this experiment was to determine the effect of acetate supplemented as sodium acetate at 2 dietary fiber levels. Our hypothesis was that acetate would increase milk fat production more in animals fed the low-fiber diet. Twelve lactating multiparous Holstein cows were arranged in a 4 × 4 Latin square design balanced for carryover effects with a 2 × 2 factorial arrangement of dietary fiber level and acetate supplementation with 21-d experimental periods. The high-fiber diet had 32% neutral detergent fiber and 21.8% starch, and the low-fiber diet had 29.5% neutral detergent fiber and 28.7% starch created by substitution of forages predominantly for ground corn grain. Acetate was supplemented in the diet at an average 2.8% of dry matter (DM) to provide approximately 10 mol/d of acetate as anhydrous sodium acetate. Acetate supplementation increased DM intake by 6%, with no effect on meal frequency or size. Furthermore, acetate supplementation slightly increased total-tract apparent DM digestibility and tended to increase organic matter digestibility. Acetate supplementation increased milk fat concentration and yield by 8.6 and 10.5%, respectively, but there was no interaction with dietary fiber. The increase in milk fat synthesis was associated with 46 and 85 g/d increases in the yield of de novo (<16C) and mixed source (16C) FA, respectively, with no changes in yield of preformed FA (>16C). There was a 9% increase in the concentration of milk mixed-source FA and a 7% decrease in milk preformed FA with acetate supplementation, regardless of dietary fiber level. Acetate supplementation also increased the concentrations of plasma acetate and ß-hydroxybutyrate, major metabolic substrates for mammary lipogenesis. Overall, acetate supplementation increased milk fat yield regardless of dietary fiber level through an increase mostly caused by an increase in longer-chain de novo FA, suggesting stimulation of mammary lipogenesis. The heightened mammary de novo lipogenesis was supported by an increase in the concentration of metabolic substrates in plasma.

Effect of 2-hydroxy-4-(methylthio)butanoate (HMTBa) on milk fat, rumen environment and biohydrogenation, and rumen protozoa in lactating cows fed diets with increased risk for milk fat depression.

Biohydrogenation-induced milk fat depression (MFD) is a reduction in milk fat synthesis caused by bioactive fatty acids (FA) produced during altered ruminal microbial metabolism of unsaturated FA. The methionine analog 2-hydroxy-4-(methylthio)butanoate (HMTBa) has been shown to reduce the shift to the alternate biohydrogenation pathway and maintain higher milk fat yield in high-producing cows fed diets lower in fiber and higher in unsaturated FA. The objective of this experiment was to verify the effect of HMTBa on biohydrogenation-induced MFD and investigate associated changes in rumen environment and fermentation. Twenty-two rumen cannulated high-producing Holstein cows [168 ± 66 d in milk; 42 ± 7 kg of milk/d (mean ± standard deviation)] were used in a randomized design performed in 2 blocks (1 = 14 cows, 2 = 8 cows). Treatments were control (corn carrier) and HMTBa (0.1% of diet dry matter). The experiment included a 7-d covariate period followed by 3 phases that fed diets with increasing risk of MFD. The diet during the covariate and low-risk phase (7 d) was 32% neutral detergent fiber with no additional oil. The diet during the moderate-risk phase (17 d) was 29% neutral detergent fiber with 0.75% soybean oil. Soybean oil was increased to 1.5% for the last 4 d. The statistical model included the random effect of block and time course data were analyzed with repeated measures including the random effect of cow and tested the interaction of treatment and time. There was no effect of block or interaction of block and treatment or time. There was no overall effect of treatment or treatment by time interaction for dry matter intake, milk yield, and milk protein concentration and yield. Overall, HMTBa increased milk fat percent (3.2 vs. 3.6%) and yield (1,342 vs. 1,543 g/d) and there was no interaction of treatment and dietary phase. Additionally, HMTBa decreased the concentration of trans-10 18:1 in milk fat and rumen digesta. Average total ruminal concentration of volatile FA across the day and total-tract dry matter and fiber digestibility were not affected by HMTBa, but HMTBa increased average rumen butyrate and decreased propionate concentration and increased total protozoa abundance. Additionally, HMTBa increased the fractional rate of α-linoleic acid clearance from the rumen following a bolus predominantly driven by a difference in the first 30 min. Plasma insulin was decreased by HMTBa. In conclusion, HMTBa prevented the increase in trans FA in milk fat associated with MFD through a mechanism that is independent of total volatile FA concentration, but involves modification of rumen biohydrogenation. Decreased propionate and increased butyrate and ruminal protozoa may also have functional roles in the mechanism.

Comparison of the effects of short-term feeding of sodium acetate and sodium bicarbonate on milk fat production.

Supplementation with sodium acetate (NaAcet) increases milk fat production through an apparent stimulation of de novo lipogenesis in the mammary gland. Sodium acetate increases acetate supply to the mammary gland, but it also increases dietary cation-anion difference, which can also increase milk fat yield. The objective of this study was to determine if the effect of NaAcet on milk fat production was due to an increase in acetate supply or an increase in dietary cation-anion difference. The study included 12 multiparous cows in a replicated 3 × 3 Latin square design balanced for carryover effects, with 14-d experimental periods. Treatments were a basal total mixed ration (31.8% neutral detergent fiber, 14.8% crude protein, 25.5% starch, and 4.4% fatty acids on a dry matter basis) as a no-supplement control, acetate supplemented at 3.25% of dry matter as NaAcet, and sodium bicarbonate (NaHCO3) providing an equal amount of sodium to the NaAcet treatment. The NaAcet and NaHCO3 were mixed into the basal diet before feeding. Milk samples were taken at each milking during the last 3 d of each period. Plasma samples were taken every 9 h during the last 3 d (a total of 8 times) to determine concentrations of plasma metabolites and hormones. Eating behavior was monitored during the last week of each period using an automated system. The NaAcet and NaHCO3 treatments increased milk fat concentration and yield compared to the no-supplement control. The NaAcet treatment increased milk fat production predominantly by increasing the yield of de novo and mixed-source fatty acids. The NaHCO3 treatment increased the yield of preformed and de novo fatty acids, suggesting different mechanisms for the 2 treatments. The NaAcet treatment increased plasma acetate concentration in a period of the day concurrent with the highest dry matter intake. The NaAcet treatment increased milk fat production by stimulating the production of de novo fatty acids, a mechanism consistent with previous reports, possibly by increasing acetate supply to the mammary gland. The NaHCO3 treatment increased milk fat production by increasing the production of all biological categories of fatty acids, except for odd and branched-chain fatty acids, possibly by increasing overall diet digestibility.

Higher diet quality in university students is associated with higher academic achievement: a cross-sectional study.

BACKGROUND: Unhealthy diets are typical of university students and the effects may be wider reaching than health. The present study aimed to describe the association between dietary intake and academic achievement in a sample of Australian university students. METHODS: A cross-sectional analysis of data from an online survey of 278 students from the University of Newcastle (UON), Australia [mean (SD) age 26.9 (10.5) years; 70.9% female] was conducted. Dietary intake, in terms of diet quality score [Australian Recommended Food Score (ARFS)], including individual sub-scales, and percentage energy per day from energy-dense nutrient poor (EDNP) foods, including individual sub-groups, was assessed using the validated Australian Eating Survey Food Frequency Questionnaire, and academic achievement was assessed as self-reported grade point average (GPA). The association between GPA and dietary intake was explored using linear regression, with adjustment for socio-demographic and student characteristics. RESULTS: Higher GPA was associated with higher diet quality (ARFS) (ß = 0.02, P = 0.011), higher sub-scale scores for vegetables (ß = 0.03, P = 0.026) and fruit (ß = 0.05, P = 0.029) and with lower percentage energy per day from EDNP foods overall (ß = -0.01, P = 0.047) and also from sweetened drinks (ß = -0.06, P < 0.001). CONCLUSIONS: The results of the present study demonstrate small associations between a healthier dietary intake and higher academic achievement, as well as vice versa. Given that the associations were small, they may not be particularly meaningful. However, this evidence could be used as a motivator for efforts aiming to improve dietary intake among university students.

Effect of hyoscine butylbromide on prostate multiparametric MRI anatomical and functional image quality.

AIM: To evaluate the effect of the spasmolytic agent hyoscine butylbromide (HBB) on the quality of anatomical and functional imaging of the prostate. MATERIALS AND METHODS: One hundred and seventy-three patients were included in this retrospective study. Eighty-seven patients received intravenous HBB prior to scanning (HBB group) and 86 patients did not (non-HBB group). Multiparametric (mp) 3 T magnetic resonance imaging (MRI) was performed using a 32-channel body coil. Two radiologists independently evaluated the image quality of T2-weighted imaging (WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps, using a five-point Likert scale. DWI was further assessed for distortion and artefact (four-point Likert scale), and T2WI for the presence of motion artefact or blurring. Dynamic contrast-enhanced (DCE) image quality was assessed by recording the number of corrupt contrast curve data points. RESULTS: T2W image quality in the HBB group was significantly higher than in the non-HBB group (3.63±1.11 versus 2.84±0.899); p<0.001. The HBB group also showed significantly less T2W motion and T2W blur than the non-HBB group (23% and 51.7% versus 53.5% and 83.7%, respectively; p<0.001); however, there was no significant improvement in DWI or ADC image quality, or DWI degree of distortion or artefact. There was a trend towards a lower number of corrupted data points from the contrast curve (2.47±2.44 versus 3.68±2.64), but this did not reach significance (p=0.052). CONCLUSION: Administration of HBB significantly improves the image quality of T2WI images. These results provide evidence for the use of HBB in routine patient preparation prior to prostate mpMRI.

Diet quality and 10-year healthcare costs by BMI categories in the mid-age cohort of the Australian Longitudinal Study on Women's Health.

BACKGROUND: Better diets, as evaluated by diet quality indices, are associated with lower rates of morbidity and mortality. Although governments and researchers alike recognise the burden that obesity incurs for increased healthcare spending, there is insufficient evidence for the role of diet quality on healthcare costs. METHODS: Diet quality was assessed by the Australian Recommended Food Score (ARFS) for 6328 women aged 50-55 years from the Australian Longitudinal Study on Women's Health. The ARFS was ranked by quintile, and 10-year cumulative data on healthcare costs from Medicare (Australia's Universal healthcare cover) were reported by body mass index category, using generalised linear modelling. RESULTS: Healthy weight women with the highest diet quality were found to make significantly fewer Medicare claims (P = 0.012) compared to those with the lowest diet quality. In healthy weight and overweight women, the number of healthcare claims and charges was inversely associated with consuming a greater variety of vegetables. For every 1 point increase in the ARFS vegetable component score, healthy weight women made 1.9 fewer healthcare claims and were charged $139 less, whereas overweight women made 2.3 fewer claims and were charged $176 less for healthcare over 10 years. CONCLUSIONS: The results of the present study support the need to prioritise an improved diet quality with the aim of reducing healthcare claims and overall costs in a population-based sample of Australian females. As the burden of overweight and obesity on the healthcare system increases, strategies to improve diet quality may be of particular importance; however, more research is required to further establish this relationship.

The association of lipophilic phospholipids with native bovine casein micelles in skim milk: Effect of lactation stage and casein micelle size.

A known biological role of casein micelles is to transport calcium from mother to young and provide amino acids for growth and development. Previous reports demonstrated that modified casein micelles can be used to transport and deliver hydrophobic probes. In this study, the distribution of lipid-soluble phospholipids, including sphingomyelins (SM) and phosphatidylcholines (PC), was quantified in whole raw milk, skim raw milk, and casein micelles of various sizes during early, mid, and late lactation stages. Low-pressure size exclusion chromatography was used to separate casein micelles by size, followed by hydrophobic extraction and liquid chromatography-mass spectrometry for the quantification of PC and SM. Results showed that the SM d18:1/23:0, d18:1/22:0, d18:1/16:0, d16:1/22:0, d16:1/23:0, and d18:1/24:0 and the PC 16:0/18:1, 18:0/18:2, and 16:0/16:0 were dominating candidates appearing in maximum concentration in whole raw milk obtained from late lactation, with 21 to 50% of total SM and 16 to 35% of total PC appearing in skim milk. Of the total SM and PC found in skim milk, 35 to 46% of SM and 22 to 29% of PC were associated with the casein micelle fraction. The highest concentrations of SM d18:1/22:0 (341 ± 17 µg/g of casein protein) and PC 16:0/18:1 (180 ± 20 µg/g of casein protein) were found to be associated with the largest casein micelles (diameter = 149 nm) isolated in milk from late lactation, followed by a decrease in concentration as the casein micelle size decreased.

Tolerogenic dendritic cells generated with dexamethasone and vitamin D3 regulate rheumatoid arthritis CD4+ T cells partly via transforming growth factor-ß1.

Tolerogenic dendritic cells (tolDC) are a new immunotherapeutic tool for the treatment of rheumatoid arthritis (RA) and other autoimmune disorders. We have established a method to generate stable tolDC by pharmacological modulation of human monocyte-derived DC. These tolDC exert potent pro-tolerogenic actions on CD4+ T cells. Lack of interleukin (IL)-12p70 production is a key immunoregulatory attribute of tolDC but does not explain their action fully. Here we show that tolDC express transforming growth factor (TGF)-ß1 at both mRNA and protein levels, and that expression of this immunoregulatory cytokine is significantly higher in tolDC than in mature monocyte-derived DC. By inhibiting TGF-ß1 signalling we demonstrate that tolDC regulate CD4+ T cell responses in a manner that is at least partly dependent upon this cytokine. Crucially, we also show that while there is no significant difference in expression of TGF-ßRII on CD4+ T cells from RA patients and healthy controls, RA patient CD4+ T cells are measurably less responsive to TGF-ß1 than healthy control CD4+ T cells [reduced TGF-ß-induced mothers against decapentaplegic homologue (Smad)2/3 phosphorylation, forkhead box protein 3 (FoxP3) expression and suppression of (IFN)-γ secretion]. However, CD4+ T cells from RA patients can, nonetheless, be regulated efficiently by tolDC in a TGF-ß1-dependent manner. This work is important for the design and development of future studies investigating the potential use of tolDC as a novel immunotherapy for the treatment of RA.

Simultaneous Bistability of a Qubit and Resonator in Circuit Quantum Electrodynamics.

We explore the joint activated dynamics exhibited by two quantum degrees of freedom: a cavity mode oscillator which is strongly coupled to a superconducting qubit in the strongly coherently driven dispersive regime. Dynamical simulations and complementary measurements show a range of parameters where both the cavity and the qubit exhibit sudden simultaneous switching between two metastable states. This manifests in ensemble averaged amplitudes of both the cavity and qubit exhibiting a partial coherent cancellation. Transmission measurements of driven microwave cavities coupled to transmon qubits show detailed features which agree with the theory in the regime of simultaneous switching.

Smoking affects the oral glucose tolerance test profile and the relationship between glucose and HbA1c in gestational diabetes mellitus.

AIMS: Current smokers in the general population have a lower 2 h plasma glucose after an oral glucose tolerance test (OGTT) and a higher HbA1c than non-smokers, but the relationships between OGTT/HbA1c and smoking status have not been addressed in pregnancy. We analysed glycaemic measurements in women with gestational diabetes mellitus in relation to smoking status. METHODS: We performed a review of the prospectively collected database of the diabetes and pregnancy clinic. We included women with gestational diabetes mellitus and a singleton pregnancy who delivered between 1986 and 2006. Bivariate and multivariate analyses were used to evaluate patient characteristics in relation to smoking status. RESULTS: A total of 2361 women met the inclusion criteria: 556 (23.5%) were active smokers, 266 (11.3%) quit during pregnancy and 1539 (65.2%) were non-smokers. Most baseline characteristics were similar across groups. Diagnostic OGTT was performed at a gestational age of [median (25th, 75(th) centiles)] 29 weeks (26, 33). Women who smoked at the beginning of pregnancy had a higher 1-h plasma glucose than non-smokers [11.8 (11, 12.7), 11.6 (11, 12.6) and 11.5 (10.8, 12.5) mmol/l, for active smokers, those who quit during pregnancy and non-smokers, respectively, P < 0.001] and a lower 3-h plasma glucose [7.3 (5.9, 8.4), 7.6 (6.4, 8.7) and 8.0 (6.8, 9.0) mmol/l, respectively, P < 0.001]. HbA1c was higher in women who smoked at the beginning of pregnancy. Multiple regression analysis confirmed the independent association of smoking status with HbA1c and OGTT plasma glucose. CONCLUSIONS: In women with gestational diabetes mellitus who smoke at the beginning of pregnancy, the shape of the OGTT is consistent with accelerated glucose absorption, and HbA1c is higher than expected for glycaemic values.

Amniotic fluid volume: Rapid MR-based assessment at 28-32 weeks gestation.

OBJECTIVES: This work evaluates rapid magnetic resonance projection hydrography (PH) based amniotic fluid volume (AFV) estimates against established routine ultrasound single deepest vertical pocket (SDVP) and amniotic fluid index (AFI) measurements, in utero at 28-32 weeks gestation. Manual multi-section planimetry (MSP) based measurement of AFV is used as a proxy reference standard. METHODS: Thirty-five women with a healthy singleton pregnancy (20-41 years) attending routine antenatal ultrasound were recruited. SDVP and AFI were measured using ultrasound, with same day MRI assessing AFV with PH and MSP. The relationships between the respective techniques were assessed using linear regression analysis and Bland-Altman method comparison statistics. RESULTS: When comparing estimated AFV, a highly significant relationship was observed between PH and the reference standard MSP (R(2) = 0.802, p < 0.001). For the US measurements, SDVP measurement related most closely to amniotic fluid volume, (R(2) = 0.470, p < 0.001), with AFI demonstrating a weaker relationship (R(2) = 0.208, p = 0.007). CONCLUSION: This study shows that rapid MRI based PH measurement is a better predictor of AFV, relating more closely to our proxy standard than established US techniques. Although larger validation studies across a range of gestational ages are required this approach could form part of MR fetal assessment, particularly where poly- or oligohydramnios is suspected. KEY POINTS: • MR projection hydrography can be used to estimate amniotic fluid volume. • MR projection hydrography relies on the T2w signal from amniotic fluid. • Amniotic fluid volume (AFV) is more accurately assessed than with ultrasound.

Medical humanities: a closer look at learning.

The inclusion of medical humanities with medical curricula is a question that has been the focus of attention for many within the evolving field. This study addressed the question from a medical education perspective and aimed to investigate what students at Trinity College Dublin learned from participating in a short medical humanities student-selected module in their first year of an undergraduate medical programme. A total of 156 students provided a written reflection on a memorable event that occurred during their student-selected module. The reflections were analysed using the Reflection Evaluation for Learners' Enhanced Competencies Tool (REFLECT) and through qualitative thematic analysis of the written reflections. Evidence of learning from the REFLECT quantitative analysis showed that 50% of students displayed higher levels of reflection when describing their experience. The reflection content analysis supported the heterogeneous nature of learning outcome for students, with evidence to support the idea that the module provided opportunities for students to explore their beliefs, ideas and feelings regarding a range of areas outside their current experience or world view, to consider the views of others that they may have not previously been aware of, to reflect on their current views, and to consider their future professional practice.

Electronic medication reconciliation and medication errors.

OBJECTIVE: To measure the impact of electronic medication reconciliation implementation on reports of admission medication reconciliation errors (MREs). DESIGN: Quality improvement project with time-series design. SETTING: A large, urban, tertiary care children's hospital. PARTICIPANTS: All admitted patients from 2011 and 2012. INTERVENTIONS: Implementation of an electronic medication reconciliation tool for hospital admissions and regular compliance reporting to inpatient units. The tool encourages active reconciliation by displaying the pre-admission medication list and admission medication orders side-by-side. MAIN OUTCOME MEASURE: Rate of non-intercepted admission MREs identified via a voluntary reporting system. RESULTS: During the study period, there were 33 070 hospital admissions. The pre-admission medication list was consistently recorded electronically throughout the study period. In the post-intervention period, the use of the electronic medication reconciliation tool increased to 84%. Reports identified 146 admission MREs during the study period, including 95 non-intercepted errors. Pre- to post-intervention, the rate of non-intercepted errors decreased by 53% (P = 0.02). Reported errors were categorized as intercepted potential adverse drug events (ADEs) (35%), non-intercepted potential ADEs (42%), minor ADEs (22%) or moderate ADEs (1%). There were no reported MREs that resulted in major or catastrophic ADEs. CONCLUSIONS: We successfully implemented an electronic process for admission medication reconciliation, which was associated with a reduction in reports of non-intercepted admission MREs.

Are small olfactory bulbs a risk for olfactory loss following an upper respiratory tract infection?

Considering the correlation between olfactory function and size of the human olfactory bulb (OB), it may be that OB volume is representative of the average number of functional olfactory receptor neurons in the nose. We observed a woman (64-year-old) with a 3-week history of hyposmia following an upper respiratory tract infection. Interestingly, both OB volumes were below the tenth percentile of the general population which seems to be difficult to explain by rapid, adaptive changes in the OB volume. It is hypothesized that small OBs may be a risk factor for acquiring olfactory loss.

BRG1 establishes the neuroectodermal chromatin landscape to restrict dorsal cell fates.

Cell fate decisions are achieved with gene expression changes driven by lineage-specific transcription factors (TFs). These TFs depend on chromatin remodelers including the Brahma-related gene 1 (BRG1)-associated factor (BAF) complex to activate target genes. BAF complex subunits are essential for development and frequently mutated in cancer. Thus, interrogating how BAF complexes contribute to cell fate decisions is critical for human health. We examined the requirement for the catalytic BAF subunit BRG1 in neural progenitor cell (NPC) specification from human embryonic stem cells. During the earliest stages of differentiation, BRG1 was required to establish chromatin accessibility at neuroectoderm-specific enhancers. Depletion of BRG1 dorsalized NPCs and promoted precocious neural crest specification and enhanced neuronal differentiation. These findings demonstrate that BRG1 mediates NPC specification by ensuring proper expression of lineage-specific TFs and appropriate activation of their transcriptional programs.

Ex vivo discovery of synergistic drug combinations for hematologic malignancies.

Combination therapies have improved outcomes for patients with acute myeloid leukemia (AML). However, these patients still have poor overall survival. Although many combination therapies are identified with high-throughput screening (HTS), these approaches are constrained to disease models that can be grown in large volumes (e.g., immortalized cell lines), which have limited translational utility. To identify more effective and personalized treatments, we need better strategies for screening and exploring potential combination therapies. Our objective was to develop an HTS platform for identifying effective combination therapies with highly translatable ex vivo disease models that use size-limited, primary samples from patients with leukemia (AML and myelodysplastic syndrome). We developed a system, ComboFlow, that comprises three main components: MiniFlow, ComboPooler, and AutoGater. MiniFlow conducts ex vivo drug screening with a miniaturized flow-cytometry assay that uses minimal amounts of patient sample to maximize throughput. ComboPooler incorporates computational methods to design efficient screens of pooled drug combinations. AutoGater is an automated gating classifier for flow cytometry that uses machine learning to rapidly analyze the large datasets generated by the assay. We used ComboFlow to efficiently screen more than 3000 drug combinations across 20 patient samples using only 6 million cells per patient sample. In this screen, ComboFlow identified the known synergistic combination of bortezomib and panobinostat. ComboFlow also identified a novel drug combination, dactinomycin and fludarabine, that synergistically killed leukemic cells in 35 % of AML samples. This combination also had limited effects in normal, hematopoietic progenitors. In conclusion, ComboFlow enables exploration of massive landscapes of drug combinations that were previously inaccessible in ex vivo models. We envision that ComboFlow can be used to discover more effective and personalized combination therapies for cancers amenable to ex vivo models.

An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.

PURPOSE: Recent developments in genomics have led to expanded carrier screening panels capable of assessing hundreds of causal mutations for genetic disease. This new technology enables simultaneous measurement of carrier frequencies for many diseases. As the resultant rank-ordering of carrier frequencies impacts the design and prioritization of screening programs, the accuracy of this ranking is a public health concern. METHODS: A total of 23,453 individuals from many obstetric, genetics, and infertility clinics were referred for routine recessive disease carrier screening. Multiplex carrier screening was performed and results were aggregated for this study. RESULTS: Twenty-four percent of individuals were identified as carriers for at least one of 108 disorders, and 5.2% were carriers for multiple disorders. We report tabulations of carrier frequency by self-identified ethnicity and disease. CONCLUSION: To our knowledge, this study of a large, ethnically diverse clinical sample provides the most accurate measurements to date of carrier frequencies for hundreds of recessive alleles. The study also yields information on the clinical considerations associated with routine use of expanded panels and provides support for a pan-ethnic screening paradigm that minimizes the use of "racial" categories by the physician, as recommended by recent guidelines.

Not all cholecystitis is created equal: Disparities contributing to ED presentation and failure of the outpatient algorithm.

BACKGROUND: The majority of final surgical pathology (FSP) from both emergency department (ED) and outpatient clinic (OC) patients is chronic cholecystitis. We aimed to differentiate these presentations and identify disparities associated with ED utilization and OC failure. METHODS: Retrospective chart review of single institution ED and OC cholecystectomies for cholelithiasis. Clinical presentation, FSP, demographics, and zip code poverty (ZCP) levels were evaluated. Data analysis by summary statistics, bivariate comparisons, and logistic regression. RESULTS: Of 299 OC and 308 ED patients, OC was more likely to be Caucasian (78% vs 46%, p < 0.0001) and insured (89% vs. 32%, p < 0.0001). 71.8% of OC with ZCP <10% had insurance versus only 32.5% in ZCP >20%. Uninsured ED OR was 13.1 (95% CI 8.7-22.9). CONCLUSION: Uninsured ED patients are vulnerable to fail the outpatient algorithm, especially when misdiagnosed by US. Clinical diagnosis of cholecystitis in this population should warrant offering of urgent cholecystectomy.

Completeness of West Nile virus testing in patients with meningitis and encephalitis during an outbreak in Arizona, USA.

Accurate data on West Nile virus (WNV) cases help guide public health education and control activities, and impact regional WNV blood product screening procedures. During an outbreak of WNV disease in Arizona, records from patients with meningitis or encephalitis were reviewed to determine the proportion tested for WNV. Of 60 patients identified with meningitis or encephalitis, 24 (40%) were tested for WNV. Only 12 (28%) of 43 patients aged <50 years were tested for WNV compared to 12 (71%) of 17 patients aged ≥50 years (P<0·01). Patients with clinical signs of weakness or paralysis, elevated CSF protein, admitted to an inpatient facility, or discharged to a rehabilitation facility were also more likely to have WNV testing performed. The lack of testing in younger age groups and in those with less severe disease probably resulted in substantial underestimates of WNV neuroinvasive disease burden.