Characteristics Associated with Treatment Response and Satisfaction in Women Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency Urinary Incontinence.

PURPOSE: We sought to identify clinical and demographic characteristics associated with treatment response and satisfaction in women undergoing onabotulinumtoxinA and sacral neuromodulation therapies. MATERIALS AND METHODS: We analyzed data from the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation versus BoTulinum Toxin Assessment) trial. Baseline participant characteristics and clinical variables were associated with 2 definitions of treatment response, including 1) a reduction in mean daily urgency incontinence episodes during 6 months and 2) a 50% or greater decrease in urgency incontinence episodes across 6 months. The OAB-S (Overactive Bladder-Satisfaction) questionnaire was used to assess satisfaction. RESULTS: A greater reduction in mean daily urgency incontinence episodes was associated with higher HUI-3 (Health Utility Index-3) scores in the onabotulinumtoxinA group and higher baseline incontinence episodes (each p <0.001) in the 2 groups. Increased age was associated with a lesser decrease in incontinence episodes in the 2 groups (p <0.001). Increasing body mass index (adjusted OR 0.82/5 points, 95% CI 0.70-0.96) was associated with reduced achievement of a 50% or greater decrease in incontinence episodes after each treatment. Greater age (adjusted OR 0.44/10 years, 95% CI 0.30-0.65) and a higher functional comorbidity index (adjusted OR 0.84/1 point, 95% CI 0.71-0.99) were associated with reduced achievement of a 50% or greater decrease in urgency incontinence episodes in the onabotulinumtoxinA group only (p <0.001 and 0.041, respectively). In the onabotulinumtoxinA group increased satisfaction was noted with higher HUI-3 score (p = 0.002) but there was less satisfaction with higher age (p = 0.001). CONCLUSIONS: Older women with multiple comorbidities, and decreased functional and health related quality of life had decreased treatment response and satisfaction with onabotulinumtoxinA compared to sacral neuromodulation for refractory urgency incontinence.

Chained Bell Inequality Experiment with High-Efficiency Measurements.

We report correlation measurements on two ^{9}Be^{+} ions that violate a chained Bell inequality obeyed by any local-realistic theory. The correlations can be modeled as derived from a mixture of a local-realistic probabilistic distribution and a distribution that violates the inequality. A statistical framework is formulated to quantify the local-realistic fraction allowable in the observed distribution without the fair-sampling or independent-and-identical-distributions assumptions. We exclude models of our experiment whose local-realistic fraction is above 0.327 at the 95% confidence level. This bound is significantly lower than 0.586, the minimum fraction derived from a perfect Clauser-Horne-Shimony-Holt inequality experiment. Furthermore, our data provide a device-independent certification of the deterministically created Bell states.

Non-native Co-, Mn-, and Ti-oxyhydroxide nanocrystals in ferritin for high efficiency solar energy conversion.

Quantum dot solar cells seek to surpass the solar energy conversion efficiencies achieved by bulk semiconductors. This new field requires a broad selection of materials to achieve its full potential. The 12 nm spherical protein ferritin can be used as a template for uniform and controlled nanocrystal growth, and to then house the nanocrystals for use in solar energy conversion. In this study, precise band gaps of titanium, cobalt, and manganese oxyhydroxide nanocrystals within ferritin were measured, and a change in band gap due to quantum confinement effects was observed. The range of band gaps obtainable from these three types of nanocrystals is 2.19-2.29 eV, 1.93-2.15 eV, and 1.60-1.65 eV respectively. From these measured band gaps, theoretical efficiency limits for a multi-junction solar cell using these ferritin-enclosed nanocrystals are calculated and found to be 38.0% for unconcentrated sunlight and 44.9% for maximally concentrated sunlight. If a ferritin-based nanocrystal with a band gap similar to silicon can be found (i.e. 1.12 eV), the theoretical efficiency limits are raised to 51.3% and 63.1%, respectively. For a current matched cell, these latter efficiencies become 41.6% (with an operating voltage of 5.49 V), and 50.0% (with an operating voltage of 6.59 V), for unconcentrated and maximally concentrated sunlight respectively.

Contribution of Clostridium difficile infection to the development of lower gastrointestinal adverse events during autologous stem cell transplantation.

BACKGROUND: Lower gastrointestinal (GI) adverse events (LGAE) are common afflictions of patients undergoing stem cell transplantation (SCT). Unfortunately, the pathophysiology remains poorly characterized. Emerging data suggest a prominent role of intestinal microbiota; however, contributions of pathogenic gut microbiota such as Clostridium difficile are not well defined. We performed a genome-wide association study (GWAS) to investigate clinical and genetic factors associated with development of LGAE. METHODS: A total of 972 patients undergoing autologous SCT were graded for LGAE based on Common Terminology Criteria for Adverse Events (v 4.0). Germline DNA material was obtained from leukapharesis products and genotyped using Illumina(®) Whole Genome Genotyping Infinium chemistry and HumanOmni1-Quad Bead chips containing over 1.1 million single nucleotide polymorphisms (SNPs) (Illumina, San Diego, California, USA). Statistical models incorporating clinical factors, genetic factors, and a combination of clinical plus genetic factors were utilized to compare patients who developed severe LGAE (grade 2 or above) and others. RESULTS: Among 972 patients, 459 (47.2%) developed severe LGAE. Baseline hemoglobin and hematocrit, estimated glomerular filtration rate, ß2-microglobulin, protocol type, and C. difficile infection (CDI) were associated with severe LGAE on univariate analysis, Genomic comparisons between groups did not reveal any SNPs associated with severe LGAE and neither did incorporation of genetic factors into the clinical model. In addition, 11 candidate SNPs associated with upper GI mucositis were evaluated, alongside clinical factors in a multivariate model. Only CDI was found to be associated with severe LGAE in all models. CONCLUSION: CDI is a prominent factor in the development of LGAE in patients undergoing autologous SCT.

Hypomagnesaemia linked to depression: a systematic review and meta-analysis.

BACKGROUND: The reported risk of depression in patients with hypomagnesaemia is controversial. AIM: The objective of this meta-analysis was to assess the association between depression and hypomagnesaemia. METHODS: A literature search was performed using MEDLINE, EMBASE, Cochrane Database and clinicaltrials.gov from inception through October 2014. Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of depression in patients with hypomagnesaemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Six observational studies (three cohort studies, two cross-sectional studies and a case-control study) with a total of 19,137 patients were identified and included in the data analysis. The pooled RR of depression in patients with hypomagnesaemia was 1.34 (95% CI, 1.01-1.79, I(2) = 33%). The association between depression and hypomagnesaemia was marginally insignificant after the sensitivity analysis including only cohort and case-control studies, with a pooled RR of 1.38 (95% CI, 0.92-2.07, I(2) = 24%). CONCLUSION: Our study demonstrates a potential association between hypomagnesaemia and depression. Further studies assessing the benefits of treatment of hypomagnesaemia in patients with depression are needed.

Admission serum magnesium levels and the risk of acute respiratory failure.

BACKGROUND: The association between admission serum magnesium (Mg) levels and risk of acute respiratory failure (ARF) in hospitalised patients is limited. The aim of this study was to assess the risk of developing ARF in all hospitalised patients with various admission Mg levels. METHODS: This is a single-center retrospective study conducted at a tertiary referral hospital. All hospitalised adult patients who had admission Mg available from January to December 2013 were analysed in this study. Admission Mg was categorised based on its distribution into six groups (less than 1.5, 1.5-1.7, 1.7-1.9, 1.9-2.1, 2.1-2.3 and greater than 2.3 mg/dl). The primary outcome was in-hospital ARF occurring after hospital admission. Logistic regression analysis was performed to obtain the odds ratio of ARF of various admission Mg levels using Mg of 1.7-1.9 mg/dl as the reference group. RESULTS: Of 9780 patients enrolled, ARF occurred in 619 patients (6.3%). The lowest incidence of ARF was when serum Mg within 1.7-1.9 mg/dl. A U-shaped curve emerged demonstrating higher incidences of ARF associated with both hypomagnesemia (< 1.7) and hypermagnesemia (> 1.9). After adjusting for potential confounders, both hypomagnesemia (< 1.5 mg/dl) and hypermagnesemia (> 2.3 mg/dl) were associated with an increased risk of developing ARF with odds ratios of 1.69 (95% CI: 1.19-2.36) and 1.40 (95% CI: 1.02-1.91) respectively. CONCLUSION: Both admission hypomagnesemia and hypermagnesemia were associated with an increased risk for in-hospital ARF.

Chronic kidney disease and end-stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to assess the clinical outcomes of Clostridium difficile infection (CDI) in patients with chronic kidney diseases (CKD) and end-stage renal disease (ESRD). METHODS: A literature search was performed from inception through February 2015. Studies that reported relative risks, odds ratios or hazard ratios comparing the clinical outcomes of CDI in patients with CKD or ESRD and those without CKD or ESRD were included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method. RESULTS: Nineteen studies (a case-control and 18 cohort studies) with 116,875 patients assessing clinical outcomes of CDI were included in the meta-analysis. Pooled RR of severe or complicated CDI in CKD patients was 1.51 (95% CI: 1.00-2.28). The risk of recurrent CDI is significant higher in patients with a pooled RR of 2.73 (95% CI: 1.36-5.47). The pooled RR of mortality risk of CDI in patients with CKD, ESRD and CKD or ESRD were 1.76 (95% CI: 1.26-2.47), 1.58 (1.37-1.83) and 1.76 (1.32-2.34) respectively. CONCLUSION: This meta-analysis demonstrates poor outcomes of CDI including severe and recurrent CDI in CKD patients. History of CKD and ESRD are both associated with increased mortality risk in patients with CDI.

Sensitive detection of surface- and size-dependent direct and indirect band gap transitions in ferritin.

Ferritin is a protein nano-cage that encapsulates minerals inside an 8 nm cavity. Previous band gap measurements on the native mineral, ferrihydrite, have reported gaps as low as 1.0 eV and as high as 2.5-3.5 eV. To resolve this discrepancy we have used optical absorption spectroscopy, a well-established technique for measuring both direct and indirect band gaps. Our studies included controls on the protein nano-cage, ferritin with the native ferrihydrite mineral, and ferritin with reconstituted ferrihydrite cores of different sizes. We report measurements of an indirect band gap for native ferritin of 2.140 ± 0.015 eV (579.7 nm), with a direct transition appearing at 3.053 ± 0.005 eV (406.1 nm). We also see evidence of a defect-related state having a binding energy of 0.220 ± 0.010 eV . Reconstituted ferrihydrite minerals of different sizes were also studied and showed band gap energies which increased with decreasing size due to quantum confinement effects. Molecules that interact with the surface of the mineral core also demonstrated a small influence following trends in ligand field theory, altering the native mineral's band gap up to 0.035 eV.

Time-Delay Cosmography: Measuring the Hubble Constant and Other Cosmological Parameters with Strong Gravitational Lensing.

Multiply lensed images of a same source experience a relative time delay in the arrival of photons due to the path length difference and the different gravitational potentials the photons travel through. This effect can be used to measure absolute distances and the Hubble constant ( H 0 ) and is known as time-delay cosmography. The method is independent of the local distance ladder and early-universe physics and provides a precise and competitive measurement of H 0 . With upcoming observatories, time-delay cosmography can provide a 1% precision measurement of H 0 and can decisively shed light on the current reported 'Hubble tension'. This manuscript details the general methodology developed over the past decades in time-delay cosmography, discusses recent advances and results, and, foremost, provides a foundation and outlook for the next decade in providing accurate and ever more precise measurements with increased sample size and improved observational techniques.

Distinct phenotypes of hospitalized patients with hyperkalemia by machine learning consensus clustering and associated mortality risks.

BACKGROUND: Hospitalized patients with hyperkalemia are heterogeneous, and cluster approaches may identify specific homogenous groups. This study aimed to cluster patients with hyperkalemia on admission using unsupervised machine learning (ML) consensus clustering approach, and to compare characteristics and outcomes among these distinct clusters. METHODS: Consensus cluster analysis was performed in 5133 hospitalized adult patients with admission hyperkalemia, based on available clinical and laboratory data. The standardized mean difference was used to identify each cluster's key clinical features. The association of hyperkalemia clusters with hospital and 1-year mortality was assessed using logistic and Cox proportional hazard regression. RESULTS: Three distinct clusters of hyperkalemia patients were identified using consensus cluster analysis: 1661 (32%) in cluster 1, 2455 (48%) in cluster 2 and 1017 (20%) in cluster 3. Cluster 1 was mainly characterized by older age, higher serum chloride and acute kidney injury (AKI), but lower estimated glomerular filtration rate (eGFR), serum bicarbonate and hemoglobin. Cluster 2 was mainly characterized by higher eGFR, serum bicarbonate and hemoglobin, but lower comorbidity burden, serum potassium and AKI. Cluster 3 was mainly characterized by higher comorbidity burden, particularly diabetes and end-stage kidney disease, AKI, serum potassium, anion gap, but lower eGFR, serum sodium, chloride and bicarbonate. Hospital and 1-year mortality risk was significantly different among the three identified clusters, with highest mortality in cluster 3, followed by cluster 1 and then cluster 2. CONCLUSION: In a heterogeneous cohort of hyperkalemia patients, three distinct clusters were identified using unsupervised ML. These three clusters had different clinical characteristics and outcomes.

Impaired c-Jun amino terminal kinase activity and T cell differentiation in death receptor 6-deficient mice.

During an immune response naive T helper (Th) cells differentiate into two functionally distinct subsets, Th1 and Th2, based on their cytokine secretion profile and immunomodulatory function. c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. We have recently identified a TNFR superfamily death domain-containing molecule, death receptor (DR)6, which potently activates JNK. T cells from DR6-deficient mice are substantially impaired in JNK activation. When DR6(-/-) mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. In addition, DR6(-/)- T cells showed preference toward Th2 differentiation in vitro. The phenotype seen in the DR6(-/)- mice is not due to the apoptotic pathway. Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response. This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general.

Quantum Logic Spectroscopy with Ions in Thermal Motion.

A mixed-species geometric phase gate has been proposed for implementing quantum logic spectroscopy on trapped ions, which combines probe and information transfer from the spectroscopy to the logic ion in a single pulse. We experimentally realize this method, show how it can be applied as a technique for identifying transitions in currently intractable atoms or molecules, demonstrate its reduced temperature sensitivity, and observe quantum-enhanced frequency sensitivity when it is applied to multi-ion chains. Potential applications include improved readout of trapped-ion clocks and simplified error syndrome measurements for quantum error correction.

A small viral RNA is required for in vitro packaging of bacteriophage phi 29 DNA.

A small RNA of Bacillus subtilis bacteriophage phi 29 is shown to have a novel and essential role in viral DNA packaging in vitro. This requirement for RNA in the encapsidation of viral DNA provides a new dimension of complexity to the attendant protein-DNA interactions. The RNA is a constituent of the viral precursor shell of the DNA-packaging machine but is not a component of the mature virion. Studies of the sequential interactions involving this RNA molecule are likely to provide new insight into the structural and possible catalytic roles of small RNA molecules. The phi 29 assembly in extracts and phi 29 DNA packaging in the defined in vitro system were strongly inhibited by treatment with the ribonucleases A or T1. However, phage assembly occurred normally in the presence of ribonuclease A that had been treated with a ribonuclease inhibitor. An RNA of approximately 120 nucleotides co-purified with the phi 29 precursor protein shell (prohead), and this particle was the target of ribonuclease action. Removal of RNA from the prohead by ribonuclease rendered it inactive for DNA packaging. By RNA-DNA hybridization analysis, the RNA was shown to originate from a viral DNA segment very near the left end of the genome, the end packaged first during in vitro assembly.

Feasibility of a school reintegration programme for children with acute lymphoblastic leukaemia.

Despite children with acute lymphoblastic leukaemia missing a significant amount of school, little empirical literature guides the optimal content, setting and timing of a school reintegration programme. We examined the feasibility of a 4-month school reintegration intervention by: (1) developing collaboration with a community-based advocacy organisation; (2) developing intervention modules and observable end points; and (3) determining how the study achieved recruitment expectations. Eight families with children aged 6-12 years diagnosed with acute lymphoblastic leukaemia and parents were enrolled in the study. An experienced advocate implemented a series of eight modules over a 4-month period (twice per month) with the families. Participants completed pre-post measures. Successful collaboration with the advocacy organisation and the development of an intervention module series were achieved. Recruitment aims proved more difficult: enrolment was extended when recruitment for the original 1- to 6-month post-diagnosis window proved difficult. The advocate was able to complete between three and seven of the modules (mean = 5.2, standard deviation = 1.5). Families preferred clinic-based intervention. Challenges faced and lessons learned include: (1) advocacy organisations may be useful resources for school reintegration interventions; (2) school reintegration interventions must be flexibly applied; and (3) measurement end points constructed to gauge programme effectiveness.

Lipoprotein metabolism by rat hepatomas. Studies on the etiology of defective dietary feedback inhibition of cholesterol synthesis.

In contrast to normal liver, it is known that in vivo hepatomas fail to decrease their rate of cholesterol biosynthesis in response to increased dietary cholesterol. From a consideration of the available data it has been hypothesized that the defect might lie in the delivery of cholesterol to the hepatoma cell. To study this further, lipoprotein interactions with rat hepatoma cells in tissue culture (HTC 7288C) and with the same cell line in vivo were investigated. HTC cells grown in a medium containing 10% calf serum exhibited saturable, specific, calcium-dependent binding of rat 125I-chylomicron remnants at 4 degrees C with half maximal saturation at 4.8 micrograms protein/ml and maximum binding of 96 ng protein/10(6) cells. At 4 degrees C, HTC cells also bound human 125I-low density lipoprotein (LDL) specifically, but bound it with a much lower affinity. These cells also exhibited specific binding for rat LDL and rat hypercholesterolemic very low density lipoprotein (VLDL). All these lipoproteins were degraded by HTC cells. Thus, it was concluded that hepatoma cells possess lipoprotein receptors that recognize and process LDL, VLDL, and chylomicron remnants. Overnight incubation of HTC cells in lipid-depleted medium containing 0.5 microM compactin increased binding of rat chylomicron remnants and of hypercholesterolemic VLDL approximately 1.7-fold without a significant change in binding affinity. LDL binding also increased, by approximately 3.5-fold. These changes were also observed when binding and internalization were measured at 37 degrees C. After HTC cells were incubated in lipid-depleted medium, the rate at which [14C]acetate was incorporated into [14C]cholesterol increased 2.5-fold. Inclusion of rat chylomicron remnants at 5-10 micrograms protein/ml prevented this increase in acetate incorporation or, if added after culture in lipid-depleted medium, reduced the increased levels back to control values. However, the rate of acetate incorporation into cholesterol by cells grown in complete medium was not decreased to levels below base line by rat chylomicron remnants. Inclusion of human LDL only partially prevented the rise or only partially reduced the increased levels back to control and did not reduce control levels below base line. Hypercholesterolemic VLDL, which contain more cholesterol per particle than chylomicron remnants, did reduce [14C]acetate incorporation to below control levels. Therefore, the intracellular mechanism for down regulation of cholesterol synthesis by lipoproteins is intact in these cells. Based on these results we hypothesized that a relative lack of lipoprotein receptors expressed by hepatomas in vivo in comparison with those expressed by normal liver would explain the apparent absence of feedback inhibition of cholesterol synthesis. Consistent with this hypothesis, the binding of chylomicron remnants to liver cell membranes was 3-5 times greater than to membranes from tumors grown in vivo subcutaneously or intramuscularly. Membranes from tumor cells grown in vitro bound remnants least well. It is proposed that the relative lack of receptors places the hepatoma at a disadvantage in competing with the liver for lipoproteins of dietary origin and may account for the lack of feedback regulation of cholesterol synthesis in hepatomas.

Regulation of rat biliary cholesterol secretion by agents that alter intrahepatic cholesterol metabolism. Evidence for a distinct biliary precursor pool.

Propensity for cholesterol gallstone formation is determined in part by biliary cholesterol content relative to bile salts and phospholipid. We examined the hypothesis that the rate of biliary cholesterol secretion can be controlled by availability of an hepatic metabolically active free cholesterol pool whose size is determined in part by rates of sterol synthesis, as reflected by activity of the primary rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase and of sterol esterification, as reflected by the activity of the enzyme acyl coenzyme A/cholesterol acyltransferase (ACAT). Rats were prepared with biliary, venous, and duodenal catheters. The enterohepatic circulation of biliary lipids was maintained constant by infusion of a bile salt, lecithin, cholesterol replacement solution. Administration of 25-hydroxycholesterol decreased HMG CoA reductase activity, increased ACAT activity, and decreased biliary cholesterol output 26% by 1 h. By 2 h, ACAT activity and biliary cholesterol secretion were at control levels. Administration of mevinolin, a competitive inhibitor of HMG CoA reductase, had no effect on ACAT activity and decreased biliary cholesterol secretion 16%. Administration of progesterone, an inhibitor of ACAT, had no effect on HMG CoA reductase and increased biliary cholesterol output 32% at 1 h. By 2 h, all parameters were near control levels. None of these agents had any significant effect on biliary bile salt or phospholipid secretion. Thus, acutely altering rates of esterification and/or synthesis can have profound effects on biliary cholesterol secretion independent of the other biliary lipids. These experiments suggest the existence of a metabolically active pool of free cholesterol that serves as a precursor pool for biliary cholesterol secretion. Furthermore, the size of this precursor pool is determined in part both by rates of cholesterol synthesis and esterification and is a key determinant of biliary cholesterol secretion.

Apolipoprotein A-I is required for cholesteryl ester accumulation in steroidogenic cells and for normal adrenal steroid production.

In addition to its ability to remove cholesterol from cells, HDL also delivers cholesterol to cells through a poorly defined process in which cholesteryl esters are selectively transferred from HDL particles into the cell without the uptake and degradation of the lipoprotein particle. The HDL-cholesteryl ester selective uptake pathway is known to occur in human, rabbit, and rodent hepatocytes where it may contribute to the clearance of plasma cholesteryl ester. The selective uptake pathway has been studied most extensively in steroidogenic cells of rodents in which it accounts for 90% or more of the cholesterol destined for steroid production or cholesteryl ester accumulation. In this study we have used apo A-I-, apo A-II-, and apo E-deficient mice created by gene targeting in embryonic stem cells to test the importance of the three major HDL proteins in determining cholesteryl ester accumulation in steroidogenic cells of the adrenal gland, ovary, and testis. apo E and apo A-II deficiencies were found to have only modest effects on cholesteryl ester accumulation. In contrast, apo A-I deficiency caused an almost complete failure to accumulate cholesteryl ester in steroidogenic cells. These results suggest that apo A-I is essential for the selective uptake of HDL-cholesteryl esters. The lack of apo A-I has a major impact on adrenal gland physiology causing diminished basal corticosteroid production, a blunted steroidogenic response to stress, and increased expression of compensatory pathways to provide cholesterol substrate for steroid production.

Impact of admission serum potassium on mortality in patients with chronic kidney disease and cardiovascular disease.

BACKGROUND: Little is known about the effect of admission potassium (K) on risk of in-hospital mortality in chronic kidney disease (CKD) and cardiovascular disease (CVD) patients. AIM: The aim of this study was to assess the relationship between admission serum K and in-hospital mortality in all hospitalized patients stratified by CKD and/or CVD status. DESIGN AND METHODS: All adult hospitalized patients who had admission serum K between years 2011 and 2013 were enrolled. Admission serum K was categorized into seven groups (<3.0, 3.0-3.5, 3.5-4.0, 4.0-4.5, 4.5-5.0, 5.0-5.5 and ≥5.5 mEq/L). The odds ratio (OR) of in-hospital mortality by admission serum K, using K 4.0-4.5 mEq/L as the reference group, was obtained by logistic regression analysis. RESULTS: 73,983 patients were studied. The lowest incidence of in-hospital mortality was associated with serum K within 4.0-4.5 mEq/L. A U-shaped curve emerged demonstrating higher in-hospital mortality associated with both serum K < 4.0 and >4.5 mEq/L. After adjusting for potential confounders, both serum K < 4.0 mEq/L and >5.0 mEq/L were associated with increased in-hospital mortality with ORs of 3.26 (95% CI 2.03-4.98), 2.40 (95% CI 1.89-3.04), 1.38 (95%CI 1.15-1.66), 1.89 (95% CI 1.49-2.38) and 3.62 (95%CI 2.73-4.76) when serum K were within <3.0, 3.0-3.5, 3.5-4.0, 5.0-5.5, and ≥5.5 mEq/L, respectively. In CVD patients, the highest in-hospital mortality was associated with serum K < 3.0 mEq/L (OR 1.70, 95%CI 1.31-2.18). In CKD patients, the highest in-hospital mortality was associated with serum K ≥ 5.5 mEq/L (OR 3.26, 95%CI 2.14-4.90). CONCLUSION: Admission serum K < 4.0 mEq/L and >5.0 mEq/L were associated with increased in-hospital mortality. The mortality risk among patients with various admission potassium levels was affected by CKD and/or CVD status.

Dopamine innervation of the monkey mediodorsal thalamus: Location of projection neurons and ultrastructural characteristics of axon terminals.

Dopamine (DA) axons and receptors have recently been identified in the primate thalamus, including the mediodorsal thalamic nucleus (MD). In order to determine whether the DA innervation of the primate MD shares the anatomical features of the mesocortical or nigrostriatal DA projections, we performed tract-tracing and immunocytochemistry studies in macaque monkeys (Macaca fascicularis) to identify the location of the DA neurons that project to MD and immuno-electron microscopy to determine the distribution of the dopamine transporter (DAT) in axons within the MD. Similar to the mesocortical projection, retrogradely-labeled, tyrosine hydroxylase-containing neurons were present in dorsal tier ventral mesencephalic nuclei, such as the ventral tegmental area and the dorsal portion of the substantia nigra pars compacta. In contrast, no dual-labeled neurons were present in the ventral tier nuclei, the primary origin of the nigrostriatal DA pathway. In addition, like the DA projection to the prefrontal cortex, DAT immunoreactivity was predominantly localized to the pre-terminal portion of axons in the MD, and was infrequently found in association with synaptic vesicles, in contrast to nigrostriatal DA axons. These findings indicate that the DA projection to the MD shares anatomical features with the mesocortical DA system, suggesting that the functional properties of DA neurotransmission in the MD might be more similar to those in the cortex than in the striatum.