Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that ...display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder.
Ultralight Metallic Microlattices Schaedler, T. A.; Jacobsen, A. J.; Torrents, A. ...
Science (American Association for the Advancement of Science),
11/2011, Letnik:
334, Številka:
6058
Journal Article
Recenzirano
Ultralight (< 10 milligrams per cubic centimeter) cellular materials are desirable for thermal insulation; battery electrodes; catalyst supports; and acoustic, vibration, or shock energy damping. We ...present ultralight materials based on periodic hollow-tube microlattices. These materials are fabricated by starting with a template formed by self-propagating photopolymer waveguide prototyping, coating the template by electroless nickel plating, and subsequently etching away the template. The resulting metallic microlattices exhibit densities ρ > 0.9 milligram per cubic centimeter, complete recovery after compression exceeding 50% strain, and energy absorption similar to elastomers. Young's modulus Å scales with density as E ~ p², in contrast to the £ ~ p³ scaling observed for ultralight aerogels and carbon nanotube foams with stochastic architecture. We attribute these properties to structural hierarchy at the nanometer, micrometer, and millimeter scales.
Additive manufacturing of polymer-derived ceramics Eckel, Zak C.; Zhou, Chaoyin; Martin, John H. ...
Science (American Association for the Advancement of Science),
01/2016, Letnik:
351, Številka:
6268
Journal Article
Recenzirano
The extremely high melting point of many ceramics adds challenges to additive manufacturing as compared with metals and polymers. Because ceramics cannot be cast or machined easily, three-dimensional ...(3D) printing enables a big leap in geometrical flexibility. We report preceramic monomers that are cured with ultraviolet light in a stereolithography 3D printer or through a patterned mask, forming 3D polymer structures that can have complex shape and cellular architecture. These polymer structures can be pyrolyzed to a ceramic with uniform shrinkage and virtually no porosity. Silicon oxycarbide microlattice and honeycomb cellular materials fabricated with this approach exhibit higher strength than ceramic foams of similar density. Additive manufacturing of such materials is of interest for propulsion components, thermal protection systems, porous burners, microelectromechanical systems, and electronic device packaging.
In order to survive and reproduce, flowering plants must balance the conflicting selective pressures of herbivore avoidance and pollinator attraction. Links between herbivory and reproduction are ...often attributed to indirect effects of leaf damage on pollination via reductions in floral allocation, or increases in chemical defenses on herbivore-damaged plants. However, the impacts of herbivory on pollinators have the potential to extend beyond initial floral visits when plant defenses impact pollinator health, foraging behavior, and reproductive success. Here, we examine important but underexplored ways in which herbivory may alter floral phenotype and thus impact pollinators. First, we outline genetic and biochemical mechanisms predicted to underlie floral changes following herbivory, as they impact the floral resources (nectar and pollen) sought by pollinators. Next, we discuss how the consumption of secondary compounds might impact pollinator fitness, including carryover effects on subsequent foraging, mating success, and transgenerational effects on offspring. We consider how pollinator health, life history, and coevolutionary history might result in context-dependent impacts of plant defensive chemistry on pollinator fitness. Finally, we call for studies that measure the impact of herbivore-induced plant defenses on the full spectrum of flower visitors, and contrast case studies on conventional pollinators (for example, generalized bees) versus insects whose larvae are herbivores on the same plants that adults pollinate (such as several butterflies and moths). By linking these consequences of herbivory to fitness effects on both herbivores and pollinators, we will better understand how coevolution between plants, herbivores, and pollinators shapes both defensive and reproductive plant traits.
In order to survive and reproduce, flowering plants must balance the conflicting selective pressures of herbivore avoidance and pollinator attraction. Here, Jacobsen and Raguso examine the ways in which herbivory may alter floral phenotype and how the coevolution between plants, herbivores, and pollinators shapes both defensive and reproductive plant traits.
Objectives
To determine the prevalence, recognition, co‐occurrence, and recent onset of geriatric syndromes in individuals transferred from the hospital to a skilled nursing facility (SNF).
Design
...Quality improvement project.
Setting
Acute care academic medical center and 23 regional partner SNFs.
Participants
Medicare beneficiaries hospitalized between January 2013 and April 2014 and referred to SNFs (N = 686).
Measurements
Project staff measured nine geriatric syndromes: weight loss, lack of appetite, incontinence, and pain (standardized interview); depression (Geriatric Depression Scale); delirium (Brief Confusion Assessment Method); cognitive impairment (Brief Interview for Mental Status); and falls and pressure ulcers (hospital medical record using hospital‐implemented screening tools). Estimated prevalence, new‐onset prevalence, and common coexisting clusters were determined. The extent to which treating physicians commonly recognized syndromes and communicated them to SNFs in hospital discharge documentation was evaluated.
Results
Geriatric syndromes were prevalent in more than 90% of hospitalized adults referred to SNFs; 55% met criteria for three or more coexisting syndromes. The most‐prevalent syndromes were falls (39%), incontinence (39%), loss of appetite (37%), and weight loss (33%). In individuals who met criteria for three or more syndromes, the most common triad clusters were nutritional syndromes (weight loss, loss of appetite), incontinence, and depression. Treating hospital physicians commonly did not recognize and document geriatric syndromes in discharge summaries, missing 33% to 95% of syndromes present according to research personnel.
Conclusion
Geriatric syndromes in hospitalized older adults transferred to SNFs are prevalent and commonly coexist, with the most frequent clusters including nutritional syndromes, depression, and incontinence. Despite the high prevalence, this clinical information is rarely communicated to SNFs on discharge.
Background Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children. ...Objective We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis. Methods Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines. Results We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases). Conclusion Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat.
Probably the foremost hypothesis of depression is the 5-hydroxytryptamine (5-HT, serotonin) deficiency hypothesis. Accordingly, anomalies in putative 5-HT biomarkers have repeatedly been reported in ...depression patients. However, whether such anomalies in fact reflect deficient central 5-HT neurotransmission remains unresolved. We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question. We report that Tph2 knockin mice have reduced basal and stimulated levels of extracellular 5-HT (5-HT(Ext)). Interestingly, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and fenfluramine-induced plasma prolactin levels are markedly diminished in the Tph2 knockin mice. These data seemingly confirm that low CSF 5-HIAA and fenfluramine-induced plasma prolactin reflects chronic, endogenous central nervous system (CNS) 5-HT deficiency. Moreover, 5-HT(1A) receptor agonist-induced hypothermia is blunted and frontal cortex 5-HT(2A) receptors are increased in the Tph2 knockin mice. These data likewise parallel core findings in depression, but are usually attributed to anomalies in the respective receptors rather than resulting from CNS 5-HT deficiency. Further, 5-HT(2A) receptor function is enhanced in the Tph2 knockin mice. In contrast, 5-HT(1A) receptor levels and G-protein coupling is normal in Tph2 knockin mice, indicating that the blunted hypothermic response relates directly to the low 5-HT(Ext). Thus, we show that not only low CSF 5-HIAA and a blunted fenfluramine-induced prolactin response, but also blunted 5-HT(1A) agonist-induced hypothermia and increased 5-HT(2A) receptor levels are bona fide biomarkers of chronic, endogenous 5-HT deficiency. Potentially, some of these biomarkers could identify patients likely to have 5-HT deficiency. This could have clinical research utility or even guide pharmacotherapy.
Abstract Background Medical data or clinical guidelines have not adequately addressed the ideal blood pressure (BP) treatment targets for survival and renal outcome. Objectives This study sought to ...evaluate ranges of treated BP in a large hypertension population and compare risk of mortality and end-stage renal disease (ESRD). Methods A retrospective cohort study within the Kaiser Permanente Southern California health system was performed from January 1, 2006, to December 31, 2010. Treated hypertensive subjects ≥18 years of age were studied. Cox proportional hazards regression models were used to evaluate the risks (hazard ratios) for mortality and/or ESRD among different BP categories with and without stratification for diabetes mellitus and older age. Results Among 398,419 treated hypertensive subjects (30% with diabetes mellitus), mortality occurred in 25,182 (6.3%) and ESRD in 4,957 (1.2%). Adjusted hazard ratios (95% confidence intervals CI) for composite mortality/ESRD in systolic BP <110, 110 to 119, 120 to 129, 140 to 149, 150 to 159, 160 to 169, and ≥170 compared with 130 to 139 mm Hg were 4.1 (95% CI: 3.8 to 1.3), 1.8 (95% CI: 1.7 to 1.9), 1.1 (95% CI: 1.1 to 1.1), 1.4 (95% CI: 1.4 to 1.5), 2.3 (95% CI: 2.2 to 2.5), 3.3 (95% CI: 3.0 to 3.6), and 4.9 (95% CI: 4.4 to 5.5) respectively. Diastolic BP 60 to 79 mm Hg were associated with the lowest risk. The nadir systolic and diastolic BP for the lowest risk was 137 and 71 mm Hg, respectively. Stratified analyses revealed that the diabetes mellitus population had a similar hazard ratio curve but a lower nadir at 131 and 69 mm Hg but age ≥70 had a higher nadir (140 and 70 mm Hg). Conclusions Both higher and lower treated BP compared with 130 to 139 mm Hg systolic and 60 to 79 mm Hg diastolic ranges had worsened outcomes. Our study adds to the growing uncertainty about BP treatment targets.
Artifact Subspace Reconstruction (ASR) is an adaptive method for the online or offline correction of artifacts comprising multichannel electroencephalography (EEG) recordings. It repeatedly computes ...a principal component analysis (PCA) on covariance matrices to detect artifacts based on their statistical properties in the component subspace. We adapted the existing ASR implementation by using Riemannian geometry for covariance matrix processing. EEG data that were recorded on smartphone in both outdoors and indoors conditions were used for evaluation (
= 27). A direct comparison between the original ASR and Riemannian ASR (rASR) was conducted for three performance measures: reduction of eye-blinks (sensitivity), improvement of visual-evoked potentials (VEPs) (specificity), and computation time (efficiency). Compared to ASR, our rASR algorithm performed favorably on all three measures. We conclude that rASR is suitable for the offline and online correction of multichannel EEG data acquired in laboratory and in field conditions.
CONTEXT Heart failure incidence increases with advancing age, and approximately half of patients with heart failure have preserved left ventricular ejection fraction. Although diastolic dysfunction ...plays a role in heart failure with preserved ejection fraction, little is known about age-dependent longitudinal changes in diastolic function in community populations. OBJECTIVE To measure changes in diastolic function over time and to determine the relationship between diastolic dysfunction and the risk of subsequent heart failure. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort of participants enrolled in the Olmsted County Heart Function Study. Randomly selected participants 45 years or older (N = 2042) underwent clinical evaluation, medical record abstraction, and echocardiography (examination 1 1997-2000). Diastolic left ventricular function was graded as normal, mild, moderate, or severe by validated Doppler techniques. After 4 years, participants were invited to return for examination 2 (2001-2004). The cohort of participants returning for examination 2 (n = 1402 of 1960 surviving 72%) then underwent follow-up for ascertainment of new-onset heart failure (2004-2010). MAIN OUTCOME MEASURES Change in diastolic function grade and incident heart failure. RESULTS During the 4 (SD, 0.3) years between examinations 1 and 2, diastolic dysfunction prevalence increased from 23.8% (95% confidence interval CI, 21.2%-26.4%) to 39.2% (95% CI, 36.3%-42.2%) (P < .001). Diastolic function grade worsened in 23.4% (95% CI, 20.9%-26.0%) of participants, was unchanged in 67.8% (95% CI, 64.8%-70.6%), and improved in 8.8% (95% CI, 7.1%-10.5%). Worsened diastolic dysfunction was associated with age 65 years or older (odds ratio, 2.85 95% CI, 1.77-4.72). During 6.3 (SD, 2.3) years of additional follow-up, heart failure occurred in 2.6% (95% CI, 1.4%-3.8%), 7.8% (95% CI, 5.8%-13.0%), and 12.2% (95% CI, 8.5%-18.4%) of persons whose diastolic function normalized or remained normal, remained or progressed to mild dysfunction, or remained or progressed to moderate or severe dysfunction, respectively (P < .001). Diastolic dysfunction was associated with incident heart failure after adjustment for age, hypertension, diabetes, and coronary artery disease (hazard ratio, 1.81 95% CI, 1.01-3.48). CONCLUSIONS In a population-based cohort undergoing 4 years of follow-up, prevalence of diastolic dysfunction increased. Diastolic dysfunction was associated with development of heart failure during 6 years of subsequent follow-up.
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