Cognitive performance and mortality among patients receiving autologous hematopoietic stem cell transplant.

OBJECTIVES: Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality. METHODS: Participants (N = 51; 11 patients deceased) completed tasks of processing speed, working memory, executive-mediated learning, and visual recall using the computerized CogState battery prior to HCT, 30 days post-autologous HCT, and 100 days post-autologous HCT. RESULTS: Slower processing speed (HR = 3.00) and more errors on an executive-mediated visual learning task (HR = 2.78) prior to HCT were associated with an increased risk of death following HCT. Our sample size limited longitudinal analyses of whether cognitive change predicted survival, however descriptive cognitive data of the deceased versus living patient's performances over time suggested different patterns of performance across groups. CONCLUSIONS: Pre-HCT cognition may have utility as an indicator of mortality risk following autologous HCT. More research is needed to examine whether cognitive changes after HCT could also predict mortality.

Murder and psychosis: Neuropsychological profiles of homicide offenders with schizophrenia.

BACKGROUND: Neurocognitive dysfunction, a core feature of schizophrenia, is thought to contribute to the impulsive violent aggression manifested by some individuals with schizophrenia, but not enough is known about how homicidal individuals with schizophrenia perform on neuropsychological measures. AIMS: The primary aim of our study was to describe the neuropsychological profiles of homicide offenders with schizophrenia. Supplementary analyses compared the criminal, psychiatric and neuropsychological features of schizophrenic homicide offenders with and without God/Satan/demon-themed psychotic symptoms. METHODS: Twenty-five men and women diagnosed with schizophrenia who had killed another person - 21 convicted of first-degree murder and 4 found not guilty by reason of insanity - completed neuropsychological testing during forensic evaluations. RESULTS: The sample was characterised by extensive neurocognitive impairments, involving executive dysfunction (60%), memory dysfunction (68%) and attentional dysfunction (50%), although those with God/Satan/demon-themed psychotic symptoms performed better than those with nonreligious psychotic content. CONCLUSIONS: Our findings indicate that impaired cognition may play an important role in the commission of homicide by individuals with schizophrenia. A subgroup with God/Satan/demon delusions seem sufficiently less impaired that they might be able to engage in metacognitive treatment approaches, aimed at changing their relationship to their psychotic symptoms, thus reducing the perception of power and omnipotence of hallucinated voices and increasing their safety. Copyright © 2016 John Wiley & Sons, Ltd.

Neurocognitive change over the course of a multiday external lumbar drain trial in patients with suspected normal pressure hydrocephalus.

Objective: To characterize neurocognitive response to cerebrospinal fluid (CSF) diversion during a multiday external lumbar drainage (ELD) trial in patients with suspected normal pressure hydrocephalus (NPH). Methods: Inpatients (N = 70) undergoing an ELD trial as part of NPH evaluation participated. Cognition and balance were assessed using standardized measures before and after a three-day ELD trial. Cognitive change pre- to post-ELD trial was assessed in relation to change in balance, baseline neuroimaging findings, NPH symptoms, demographics, and other disease-relevant clinical parameters. Results: Multiday ELD resulted in significant cognitive improvement (particularly on measures of memory and language). This improvement was independent of demographics, test-retest interval, number of medical and psychiatric comorbidities, NPH symptom duration, estimated premorbid intelligence, baseline level of cognitive impairment, cerebrovascular disease burden, degree of ventriculomegaly, or other NPH-related morphological brain alterations. Balance scores evidenced a greater magnitude of improvement than cognitive scores and were weakly, but positively correlated with cognitive change scores. Conclusions: Findings suggest that cognitive improvement associated with a multiday ELD trial can be sufficiently captured with bedside neurocognitive testing. These findings support the utility of neuropsychological consultation, along with balance assessment, in informing clinical decision-making regarding responsiveness to temporary CSF diversion for patients undergoing elective NPH evaluation. Implications for the understanding of neuroanatomical and cognitive underpinnings of NPH are discussed.

Is age a risk factor for cognitive changes following hematopoietic cell transplantation?

Cognitive deficits following hematopoietic cell transplantation (HCT) are common and affect post-HCT treatment regimen adherence and quality-of-life. Little is known about effects of age on cognition following HCT. The current study aimed to identify the effects of age on cognition one-year post-HCT, compared to pre-HCT baseline functioning. Participants were 78 autologous and allogeneic transplant recipients who underwent neuropsychological assessments at baseline and one-year post-HCT. Mixed model analyses indicated that no statistically significant main effect of age was observed for any cognitive variable. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Index Score and Trail Making Test (parts A and B) showed significant interaction effects between age and transplant type. These findings indicate that older autologous and allogeneic transplant recipients were predicted to perform similarly; however, young allogeneic HCT recipients were predicted to perform substantially below young autologous transplant recipients. Hierarchical regressions indicated that age failed to predict changes in neuropsychological test performance between baseline and one-year post-HCT. These findings indicate that advanced age may not be a risk factor for worse cognitive outcome post-HCT, though younger allogeneic transplant recipients may be at risk for worse cognitive outcomes, relative to younger autologous recipient counterparts. Clinical implications are discussed.

The utility of cognitive changes in identifying those with acute graft vs. host disease following allogeneic hematopoietic cell transplant.

Objectives: Acute graft versus host disease (aGVHD) is a common complication of allogeneic hematopoietic cell transplant (HCT) and is associated with morbidity and mortality. Identifying those at risk for developing aGVHD is crucial for early intervention. The current study assessed whether scores on a brief cognitive screening measure could identify those that develop aGVHD by 100 days post-HCT.Methods: Participants were 37 patients undergoing allogeneic HCT, assessed prior to transplant, and at 30- and 100-days post-HCT. Of those completing all evaluations, patients were divided into those who did (n = 14) and did not (n = 16) develop aGVHD by day 100 post-HCT. At 100 days post-transplant, groups did not differ on relevant demographic factors, disease, conditioning regimen, relatedness of donor, stem cell source, steroid use, total body irradiation use, human leukocyte antigens (HLA) match, or frequency of infection.Results: At 100 days post-HCT, those with aGVHD performed significantly worse on a working memory measure than those without aGvHD. The presence of aGVHD at day 100 increased significantly with every one standard deviation decrease in working memory from baseline to 30 days post-HCT (odds ratio = 3.08; 95% CI: 1.00-9.36). These findings were observed despite a small sample size and statistically controlling for multiple analyses.Conclusions: While this study is exploratory in nature, and has a small sample size, findings suggest that early detection of working memory declines could coincide with, or signal the development of, aGVHD. Potential etiologies are discussed. Implementing early cognitive screening within the first 30 days post-HCT may be useful in identifying patients at risk for aGVHD.

Further case of Rubinstein-Taybi syndrome due to a deletion in EP300.

Rubinstein-Taybi syndrome (RSTS) is a heterogeneous disorder with approximately 45-55% of patients showing mutations in the CREB binding protein and a further 3% of patients having mutations in EP300. We report a male child with a deletion of exons 3-8 of the EP300 gene who has RSTS. He has a milder skeletal phenotype, a finding that has been described in other cases with EP300 mutations. The mother suffered from pre-eclampsia and HELLP syndrome in the pregnancy. She subsequently developed a mullerian tumor of her cervix 6 years after the birth of her son.

Evidence for pre- to postsynaptic mismatch of the cardiac sympathetic nervous system in ischemic congestive heart failure.

UNLABELLED: Pre- and postsynaptic cardiac sympathetic function is altered in ischemic congestive heart failure (CHF). Whether there is a presynaptic-to-postsynaptic mismatch or whether mismatch is related to adverse cardiac events is unknown. METHODS: In 13 patients with ischemic CHF and 25 aged-matched healthy volunteers, presynaptic function was measured by PET of (11)C-meta-hydroxyephedrine ((11)C-mHED), a norepinephrine (NE) analog. Postsynaptic function, beta-adrenergic receptor (BAR) density (B'(max)), was measured by imaging (11)C-CGP12177. Myocardial blood flow (MBF) was measured by imaging (15)O-water. Each heart was analyzed both globally and regionally, excluding infarcted regions, and a mismatch score, defined as the ratio of B'(max) to NE uptake (PS(nt))(,) was used to indicate mismatch of post- and presynaptic function. RESULTS: Global and regional MBF was not different between CHF and healthy subjects. The global measure of PS(nt) was lower in CHF (0.32 +/- 0.34) than that in healthy subjects (0.81 +/- 0.33, P < 0.0001) and in all 12 regions. Global B'(max) tended to be lower in CHF than that in healthy subjects (10.0 +/- 6.4 pmol/mL vs. 13.4 +/- 4.2, P = 0.056) and in all 12 regions. The global mismatch score (B'(max):PS(nt)) in CHF patients was significantly greater than that in healthy subjects (50.3 +/- 50.7 vs. 19.3 +/- 9.7, P = 0.005) and also greater in 11 of 12 regions. After 1.5 y of follow-up, 4 individuals had an adverse outcome (CHF death, new or recurrent sudden death, or progressive CHF leading to transplantation). Three of the 4 had mismatch scores > 3 times that of the healthy subjects or the CHF patients without an adverse outcome. CONCLUSION: Mismatch between pre- and postsynaptic left ventricular sympathetic function is present in patients with severe CHF and may be more marked in those with adverse outcomes.

Differences in Neuropsychological Functioning Between Homicidal and Nonviolent Schizophrenia Samples.

Few studies have compared performance on neurocognitive measures between violent and nonviolent schizophrenia samples. A better understanding of neurocognitive dysfunction in violent individuals with schizophrenia could increase the efficacy of violence reduction strategies and aid in risk assessment and adjudication processes. This study aimed to compare neuropsychological performance between 25 homicide offenders with schizophrenia and 25 nonviolent schizophrenia controls. The groups were matched for age, race, sex, and handedness. Independent t-tests and Mann-Whitney U-tests were used to compare the schizophrenia groups' performance on measures of cognition, including composite scores assessing domain level functioning and individual neuropsychological tests. Results indicated the violent schizophrenia group performed worse on measures of memory and executive functioning, and the Intellectual Functioning composite score, when compared to the nonviolent schizophrenia sample. These findings replicate previous research documenting neuropsychological deficits specific to violent individuals with schizophrenia and support research implicating fronto-limbic dysfunction among violent offenders with schizophrenia.

Institutionalizing One Health: From Assessment to Action.

A One Health approach is critical to strengthening health security at country, regional, and global levels. However, operationally its uptake remains limited. Recent momentum in assessing capacity to effectively prevent, detect, and respond to disease threats has resulted in identification of gaps that require dedicated action. This article highlights relevant tools, standards, and guidance to assist countries and institutions in meeting the collective vision articulated at the 2018 Prince Mahidol Award Conference on "Making the World Safe from the Threats of Emerging Infectious Diseases." Taking stock of assessment findings, resources, priorities, and implementation initiatives across human and animal health, environment and disaster risk reduction sectors can help expand participation in global health security, target risk drivers, and form synergies for collective action and shared gains for both emerging and endemic disease challenges. In addition to health security gains, a multisectoral, One Health approach can drive benefits for wider health sector and global development goals.

Assessment of the Effects of Age, Gender, and Exercise Training on the Cardiac Sympathetic Nervous System Using Positron Emission Tomography Imaging.

BACKGROUND: Using positron emission tomography (PET) imaging, we sought to determine whether normal age or exercise training cause changes in the cardiac sympathetic nervous system function in male or female healthy volunteers. METHODS: Healthy sedentary participants underwent PET studies before and after 6 months of supervised exercise training. Presynaptic uptake by the norepinephrine transporter-1 function was measured using PET imaging of [(11)C]-meta-hydroxyephedrine, a norepinephrine analog, and expressed as a permeability-surface area product (PSnt in mL/min/mL). Postsynaptic function was measured as ß-adrenergic receptor density (ß'max in pmol/mL tissue) by imaging the ß-receptor antagonist [(11)C]-CGP12177. Myocardial blood flow (MBF in mL/min/mL tissue) was measured by imaging [(15)O]-water. RESULTS: At baseline, there was no age difference in ß'max or MBF but PSnt declined with age (1.12±0.11 young vs 0.87±0.06 old, p = .036). Before training, women had significantly greater MBF (0.87±0.03 vs 0.69±0.03, p < .0001) and PSnt (1.14±0.08 vs 0.75±0.07, p < .001) than men. Training increased VO2 max by 13% (p < .0001), but there were no training effects on ß'max, PSnt, or MBF. Greater MBF in females and a trend to increased PSnt post-training persisted. CONCLUSION: With age, presynaptic uptake as measured by PSnt declines, but there were no differences in ß'max. Endurance training significantly increased VO2 max but did not cause any changes in the measures of cardiac sympathetic nervous system function. These findings suggest that significant changes do not occur or that current PET imaging methods may be inadequate to measure small serial differences in a highly reproducible manner.

Exercise training bradycardia is largely explained by reduced intrinsic heart rate.

INTRODUCTION: Resting heart rate (RHR) declines with exercise training. Possible mechanisms include: 1) increased parasympathetic tone, 2) decreased responsiveness to beta-adrenergic stimulation, 3) decreased intrinsic heart rate or 4) combination of these factors. OBJECTIVE: To determine whether an increase in resting parasympathetic tone or decrease in response to beta-adrenergic stimulation contributes to the decrease in RHR with training. METHODS: 51 screened healthy subjects aged 18-32 (n=20, mean age 26, 11 female) or 65-80 (n=31, mean age 69, 16 female) were tested before and after 6months of supervised exercise training. Heart rate response to parasympathetic withdrawal was assessed using atropine and beta-adrenergic responsiveness during parasympathetic withdrawal using isoproterenol. RESULTS: Training increased VO2 max by 17% (28.7±7.7 to 33.6±9.20ml/kg/min, P<0.001). RHR decreased from 62.8±6.6 to 57.6±7.2 beats per minute (P<0.0001). The increase in heart rate in response to parasympathetic withdrawal was unchanged after training (+37.3±12.8 pre vs. +36.4±12.2 beats per min post, P=0.41). There was no change in the heart rate response to isoproterenol after parasympathetic blockade with training (+31.9±10.9 pre vs. +31.0±12.0 post beats per min, P=0.56). The findings were similar in all four subgroups. CONCLUSIONS: We did not find evidence that an increase in parasympathetic tone or a decrease in responsiveness to beta-adrenergic activity accounts for the reduction in resting heart rate with exercise training. We suggest that a decline in heart rate with training is most likely due to decrease in the intrinsic heart rate.

Effects of aging on cardiovascular responses to parasympathetic withdrawal.

OBJECTIVES: The study was done to determine whether the effects of parasympathetic withdrawal on heart rate, blood pressure (BP), and systolic and diastolic function are altered with normal aging. BACKGROUND: Cardiac responses to beta-adrenergic sympathetic stimulation decline with aging as does the heart rate response to parasympathetic withdrawal, but the extent to which other responses to parasympathetic withdrawal decrease is less clear. METHODS: Heart rate, BP, systolic function, and diastolic filling responses to parasympathetic withdrawal induced by atropine (0.02 mg/kg) were compared in 50 healthy subjects, 28 older (ages 65 to 80 years, mean 70 years; 18 females all on estrogen) and 22 young (age 18 to 32 years, mean 26 years; 12 females) subjects, using radionuclide angiography. RESULTS: Parasympathetic withdrawal in the older group caused less of an increase in heart rate (+33 vs. +48 beats/min), cardiac index (+0.6 vs. +1.5 l/m(2)), systolic blood pressure (-1 vs. +7 mm Hg), and early diastolic filling rate (+1.7 vs. +2.4 end-diastolic volumes/s) (all p < or = 0.01). At similar declines in the diastolic filling period, end-diastolic volume index (EDVI) fell substantially more in the older group (-11.6 vs. -2.4 ml/m(2), p < 0.001). The only gender difference was in diastolic filling rate, which was similar in the young males and females, but significantly less in older males than in older females. CONCLUSIONS: The responses to parasympathetic withdrawal as well as sympathetic stimulation decline with aging, and both contribute to the reduced cardiovascular responses to stress with advancing age.

Comparison of tissue Doppler and propagation velocity to invasive measures for measuring left ventricular filling pressures.

The utility of tissue Doppler and propagation velocity in identifying patients with abnormal left ventricular filling pressures was assessed in 50 patients who underwent catheterization and echocardiography on the same day. The ratios of the peak velocity of early mitral inflow to early mitral annular velocity (E/Ea) and the velocity of propagation (E/Vp) were compared with invasive measurements of pre-A-wave left ventricular pressures. Echocardiography measures were 77% to 92% accurate in identifying patients with a pre-A-wave pressure >15 mm Hg. Tissue Doppler imaging is more accurate than propagation velocity.

Photocatalytic coatings for environmental applications.

A series of nano- and micronparticle-grade anatase and rutile titanium dioxide pigments have been prepared with various densities of surface treatments, particle size and surface area. Their photocatalytic activites have been determined in a series of paint films by FTIR, chalking, color, gloss change and weight loss after artifical weathering. The pigments have also been examined by rapid assessment methodologies using photodielectric microwave spectroscopy, 2-propanol oxidation and hydroxyl analysis. The microwave response under light and dark cycles provides an extended timescale probe of charge-carrier dynamics in the pigments. Pigment particle size, surface area and properties clearly play an important role in dispersion and any polymer-pigment interactions. Photooxidation studies on several types of paint films show a clear demarcation between nanoparticle- and pigmentary-grade titanium dioxide, with the former being more active because of their greater degree of catalytic surface activity. The photosensitivity of titanium dioxide is considered to arise from localized sites on the crystal surface (i.e. acidic OH), and occupation of these sites by surface treatments inhibits photoreduction of the pigment by ultraviolet radiation; hence, the destructive oxidation of the binder is inhibited. Coatings containing 2-5% by weight alumina or alumina and silica are satisfactory for general-purpose paints. If greater resistance to weathering is desired, the pigments are coated more heavily to about 7-10% weight. The coating can consist of a combination of several materials, e.g. alumina, silica, zirconia, aluminum phosphates of other metals. For example, the presence of hydrous alumina particles lowers van der Waals forces between pigments particles by several orders of magnitude, decreasing particle-particle attractions. Hydrous aluminum oxide phases appear to improve dispersibility more effectively than most of the other hydroxides and oxides. Coated nanoparticles are shown to exhibit effective light stabilization in various water- and oil-based paint media in comparison with conventional organic stabilizers. Hindered piperidine stabilizers are shown to provide no additional benefits in this regard, often exhibiting strong antagonism. The use of photocatalytic titania nanoparticles in the development of self-cleaning paints and microbiological surfaces is also demonstrated in this study. In the former case, surface erosion is shown to be controlled by varying the ratio of admixture of durable pigmentary-grade rutile (heavily coated) and a catalytic-grade anatase nanoparticle. For environmental applications in the development of coatings for destroying atmospheric pollutants such as nitrogen oxide gases (NO(X)), stable substrates are developed with photocatalytic nanoparticle-grade anatase. In this study, porosity of the coatings through calcium carbonate doping is shown to be crucial in the control of the effective destruction of atmospheric NO(X) gases. For the development of microbiological substrates for the destruction of harmful bacteria, effective nanoparticle anatase titania is shown to be important, with hydrated high surface area particles giving the greatest activity.

Biomechanical efficiency is decreased in heart failure during low-level steady state and maximal ramp exercise.

BACKGROUND: Previous studies of biomechanical efficiency (external work/energy input--Watt/O(2) consumed) in heart failure (HF) using cardiopulmonary exercise testing (CPET) and magnetic resonance spectroscopy (MRS) have had discordant results with increased efficiency by CPET and decreased efficiency by MRS. AIMS: Compare biomechanical efficiency of HF subjects and normal controls during steady state (SS=35 W for 6 min) and ramp cycle ergometer exercise. The hypothesis was that HF subjects would have impaired biomechanical efficiency that correlated with HF symptoms. METHODS: Biomechanical efficiency used the actual Vo(2) during exercise and recovery. Gross (Vo(2) above zero), Net (Vo(2) above the resting Vo(2)) and Work (Vo(2) above the unloaded pedaling Vo(2)) efficiencies were calculated. RESULTS: HF subjects had an 18% higher Vo(2) during SS exercise (P=0.029). Biomechanical efficiency was reduced during SS exercise (gross -15%, P=0.019, net -15%, P=0.062, and work -35%, P=0.002). Gross Efficiency during SS exercise had the strongest correlation with HF symptoms (r=0.55). During ramp exercise gross (-26%), net (-10%) and work (-8%) biomechanical efficiency were all reduced (all P<0.05). The slope of the Vo(2)/Watt relationship during ramp exercise had the best correlation with HF symptoms (r=0.46). CONCLUSIONS: HF subjects have an increased O(2) cost/Watt during SS and ramp exercise that correlates with HF symptoms of fatigue and breathlessness. Methods to improve biomechanical efficiency in HF subjects by exercise training or medications may improve the symptoms and the impaired exercise capacity associated with HF.

PET measures of pre- and post-synaptic cardiac beta adrenergic function.

Positron Emission Tomography was used to measure global and regional cardiac beta-adrenergic function in 19 normal subjects and 9 congestive heart failure patients. [(11)C]-meta-hydroxyephedrine was used to image norepinephrine transporter function as an indicator of pre-synaptic function and [(11)C]-CGP12177 was used to measure cell surface beta-receptor density as an indicator of post-synaptic function. Pre-synaptic, but not post-synaptic, function was significantly different between normals and CHF patients. Pre-synaptic function was well matched to post-synaptic function in the normal hearts but significantly different and poorly matched in the CHF patients studied. This imaging technique can help us understand regional sympathetic function in cardiac disease.

Insight, neurocognition, and schizophrenia: predictive value of the wisconsin card sorting test.

Lack of insight in schizophrenia is a key feature of the illness and is associated with both positive and negative clinical outcomes. Previous research supports that neurocognitive dysfunction is related to lack of insight, but studies have not examined how neurocognition relates to change in insight over time. Therefore, the current study sought to understand how performance on the Wisconsin Card Sorting Test (WCST) differed between participants with varying degrees of change in insight over a 6-month period. Fifty-two patients with schizophrenia or schizoaffective disorder were administered the WCST and Positive and Negative Syndrome Scale (PANSS) at baseline, and the PANSS was again administered at a 6-month follow-up assessment. Results indicated that while neurocognition was related to insight at baseline, it was not related to subsequent change in insight. The implications of findings for conceptualization and assessment of insight are discussed.