Postoperative delirium after major orthopedic surgery.

BACKGROUND: Postoperative delirium (POD) is one of the most common complications in older adult patients undergoing elective surgery. Few studies have compared, within the same institution, the type of surgery, risk factors and type of anesthesia and analgesia associated with the development of POD. AIM: To investigate the following three questions: (1) What is the incidence of POD after non-ambulatory orthopedic surgery at a high-volume orthopedic specialty hospital? (2) Does surgical procedure influence incidence of POD after non-ambulatory orthopedic surgery? And (3) For POD after non-ambulatory orthopedic surgery, what are modifiable risk factors? METHODS: A retrospective cohort study was conducted of all non-ambulatory orthopedic surgeries at a single orthopedic specialty hospital between 2009 and 2014. Patients under 18 years were excluded from the cohort. Patient characteristics and medical history were obtained from electronic medical records. Patients with POD were identified using International Classification of Diseases, 9th Revision (ICD-9) codes that were not present on admission. For incidence analyses, the cohort was grouped into total hip arthroplasty (THA), bilateral THA, total knee arthroplasty (TKA), bilateral TKA, spine fusion, other spine procedures, femur/pelvic fracture, and other procedures using ICD-9 codes. For descriptive and regression analyses, the cohort was grouped, using ICD-9 codes, into THA, TKA, spinal fusions, and all procedures. RESULTS: Of 78492 surgical inpatient surgeries, the incidence from 2009 to 2014 was 1.2% with 959 diagnosed with POD. The incidence of POD was higher in patients undergoing spinal fusions (3.3%) than for patients undergoing THA (0.8%); THA patients had the lowest incidence. Also, urgent and/or emergent procedures, defined by femoral and pelvic fractures, had the highest incidence of POD (7.2%) than all other procedures. General anesthesia was not seen as a significant risk factor for POD for any procedure type; however, IV patient-controlled analgesia was a significant risk factor for patients undergoing THA [Odds ratio (OR) = 1.98, 95% confidence interval (CI): 1.19 to 3.28, P = 0.008]. Significant risk factors for POD included advanced age (for THA, OR = 4.9, 95%CI: 3.0-7.9, P \u3c 0.001; for TKA, OR = 2.16, 95%CI: 1.58-2.94, P \u3c 0.001), American Society of Anesthesiologists score of 3 or higher (for THA, OR = 2.01, 95%CI: 1.33-3.05, P \u3c 0.001), multiple medical comorbidities, hyponatremia (for THA, OR = 2.36, 95%CI: 1.54 to 3.64, P \u3c 0.001), parenteral diazepam (for THA, OR = 5.05, 95%CI: 1.5-16.97, P = 0.009; for TKA, OR = 4.40, 95%CI: 1.52-12.75, P = 0.007; for spine fusion, OR = 2.17, 95%CI: 1.19-3.97, P = 0.01), chronic opioid dependence (for THA, OR = 7.11, 95%CI: 3.26-15.51, P \u3c 0.001; for TKA, OR = 2.98, 95%CI: 1.38-6.41, P = 0.005) and alcohol dependence (for THA, OR = 5.05, 95%CI: 2.72-9.37, P \u3c 0.001; for TKA, OR = 6.40, 95%CI: 4.00-10.26, P \u3c 0.001; for spine fusion, OR = 6.64, 95%CI: 3.72-11.85, P \u3c 0.001). CONCLUSION: POD is lower (1.2%) than previously reported; likely due to the use of multi-modal regional anesthesia and early ambulation. Both fixed and modifiable factors are identified

Supersize the label: The effect of prominent calorie labeling on sales

Objectives Calorie labeling has been suggested as an antiobesity measure; however, evidence on its effects is scarce and formatting guidance not well defined. The aim of this study was to test the effects of prominent calorie labeling on sales of the labeled items. Methods Prominent calorie labels were posted in front of two popular items for a period of 1 mo. Sales were recorded for 2 mo consecutively, before and during labeling. Results Muffins sales (the higher-calorie item) fell by 30%, whereas sales of scones rose by 4%, a significant difference (χ2 = 10.258; P = 0.0014). Conclusions Calorie labeling is effective when noticed. Wider adoption of calorie labeling for all food businesses and strengthening legislation with formatting guidelines should be the next step in public health policy

Optical and Ionospheric Phenomena at EISCAT under continuous X-mode HF pumping

We present experimental results from multiinstrument observations in the high-latitude ionospheric F2 layer at the EISCAT (European Incoherent Scatter Scientific Association) heating facility. The results come from a set of experiments, when an X-polarized HF pump wave at high heater frequencies (fH > 6.0 MHz) was injected into the F region of the ionosphere toward the magnetic zenith. Experiments were carried out under quiet magnetic conditions with an effective radiated power of 458–548 MW. HF pumping was produced at different heater frequencies, away from electron gyroharmonic frequencies, and different durations of heater pulses. We show the first experimental evidence of the excitation of artificial optical emissions at red (630 nm) and green (557.7 nm) lines in the high-latitude ionospheric F2 layer induced by an X-polarized HF pump wave. Intensities at red and green lines varied in the range 110–950 R and 50–350 R, respectively, with a ratio of green to red line of 0.35–0.5. The results of optical observations are compared with behaviors of the HF-enhanced ion and plasma lines from EISCAT UHF incoherent scatter radar data and small-scale field-aligned artificial irregularities from Cooperative UK Twin Located Auroral Sounding System observations. It was found that the X-mode radio-induced optical emissions coexisted with HF-enhanced ion and plasma lines and strong artificial field-aligned irregularities throughout the whole heater pulse. It is indicative that parametric decay or oscillating two-stream instabilities were not quenched by fully established small-scale field-aligned artificial irregularities excited by an X-mode HF pump wave

Surface effects in color superconducting strange-quark matter

Surface effects in strange-quark matter play an important role for certain observables which have been proposed in order to identify strange stars, and color superconductivity can strongly modify these effects. We study the surface of color superconducting strange-quark matter by solving the Hartree-Fock-Bogoliubov equations for finite systems ("strangelets") within the MIT bag model, supplemented with a pairing interaction. Due to the bag-model boundary condition, the strange-quark density is suppressed at the surface. This leads to a positive surface charge, concentrated in a layer of ~1 fm below the surface, even in the color-flavor locked (CFL) phase. However, since in the CFL phase all quarks are paired, this positive charge is compensated by a negative charge, which turns out to be situated in a layer of a few tens of fm below the surface, and the total charge of CFL strangelets is zero. We also study the surface and curvature contributions to the total energy. Due to the strong pairing, the energy as a function of the mass number is very well reproduced by a liquid-drop type formula with curvature term.Comment: 13 pages, v2: more detailed explanations, discussion adde

BTDAzo: A Photoswitchable TRPC5 Channel Activator

Photoswitchable reagents can be powerful tools for high-precision biological control. TRPC5 is a Ca2+-permeable cation channel with distinct tissue-specific roles, from synaptic function to hormone regulation. Reagents giving spatiotemporally-resolved control over TRPC5 activity may be key to understanding and harnessing its biology. Here we develop the first photoswitchable TRPC5-modulator, BTDAzo, to address this goal. BTDAzo can photocontrol TRPC5 currents in cell culture, as well as controlling endogenous TRPC5-based neuronal Ca2+ responses in mouse brain slices. BTDAzos are also the first reported azo-benzothiadiazines, an accessible and conveniently derivatised azoheteroarene with strong two-colour photoswitching. BTDAzo ' s ability to control TRPC5 across relevant channel biology settings makes it suitable for a range of dynamically reversible photoswitching studies in TRP channel biology, with the aim to decipher the various biological roles of this centrally important ion channel

Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication-dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat cis elements within the bidirectional histone3–histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X chromosome. Therefore, CLAMP binding to GA repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome

Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons

Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes–hours) and long period of time (days–weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons

Serum and glucocorticoid-inducible kinase1 increases plasma membrane wt-CFTR in human airway epithelial cells by inhibiting its endocytic retrieval

Background: Chloride (Cl) secretion by the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) located in the apical membrane of respiratory epithelial cells plays a critical role in maintenance of the airway surface liquid and mucociliary clearance of pathogens. Previously, we and others have shown that the serum and glucocorticoid-inducible kinase-1 (SGK1) increases wild type CFTR (wt-CFTR) mediated Cl transport in Xenopus oocytes by increasing the amount of wt-CFTR protein in the plasma membrane. However, the effect of SGK1 on the membrane abundance of wt-CFTR in airway epithelial cells has not been examined, and the mechanism whereby SGK1 increases membrane wt-CFTR has also not been examined. Thus, the goal of this study was to elucidate the mechanism whereby SGK1 regulates the membrane abundance of wt-CFTR in human airway epithelial cells. Methods and Results: We report that elevated levels of SGK1, induced by dexamethasone, increase plasma membrane abundance of wt-CFTR. Reduction of SGK1 expression by siRNA (siSGK1) and inhibition of SGK1 activity by the SGK inhibitor GSK 650394 abrogated the ability of dexamethasone to increase plasma membrane wt-CFTR. Overexpression of a constitutively active SGK1 (SGK1-S422D) increased plasma membrane abundance of wt-CFTR. To understand the mechanism whereby SGK1 increased plasma membrane wt-CFTR, we examined the effects of siSGK1 and SGK1-S442D on the endocytic retrieval of wt-CFTR. While siSGK1 increased wt-CFTR endocytosis, SGK1-S442D inhibited CFTR endocytosis. Neither siSGK1 nor SGK1-S442D altered the recycling of endocytosed wt-CFTR back to the plasma membrane. By contrast, SGK1 increased the endocytosis of the epidermal growth factor receptor (EGFR). Conclusion: This study demonstrates for the first time that SGK1 selectively increases wt-CFTR in the plasma membrane of human airway epithelia cells by inhibiting its endocytic retrieval from the membrane. © 2014 Bomberger et al

All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysis.

BACKGROUND Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25° × 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 μg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 μg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING Australian Research Council and the Australian National Health and Medical Research Council