Panlobular emphysema is associated with COPD disease severity: A study of emphysema subtype by computed tomography.

BACKGROUND: Computed tomography has the potential to inform COPD prognosis. We sought to determine associations of emphysema phenotype with clinical parameters including lung function, inflammatory markers, and quality of life. METHODS: Participants of this single-center observational cohort (n = 83) were 40-80 years old, had ≥10 pack-year smoking, and a diagnosis of COPD confirmed by spirometry. All participants had available historic chest CT scans which were systematically reviewed by a single expert radiologist and scored for emphysema subtype, extent, and distribution. Associations between radiographic findings and clinical parameters were determined. RESULTS: Median age of participants was 72 years, median smoking 40 pack-years, and median FEV1 59% predicted. 84% of the participants had radiographic emphysema. Of those, 26% had panlobular emphysema (PLE), 68% centrilobular emphysema (CLE), and 6% paraseptal emphysema (PSE). As compared to the participants with no radiographic emphysema, the presence of PLE-dominant emphysema was associated with a lower BMI (P = 0.012) and greater extent of emphysema (P = 0.014). After adjusting for age, sex, and pack-years smoking history, PLE was associated with greater airflow obstruction by FEV1% (48% vs 71%, P = 0.005), greater symptom burden by CAT score (18 vs 9, P = 0.015), worse quality of life by SGRQ score (43 vs 22, P = 0.025), and more systemic inflammation by erythrocyte sedimentation rate (P = 0.001). CLE- or PSE-dominant emphysema were not similarly associated with clinical features or symptom burden. CONCLUSIONS: The presence of PLE-dominant emphysema was associated with greater extent of emphysema, greater airflow obstruction, increased respiratory symptoms, worse quality of life, and systemic inflammation. Further investigation is indicated to explore the pathogenesis of the PLE phenotype and the prognostic and treatment implications of PLE.

Sequential Dispersive Measurement of a Superconducting Qubit.

We present a superconducting device that realizes the sequential measurement of a transmon qubit. The device disables common limitations of dispersive readout such as Purcell effect or transients in the cavity mode by turning on and off the coupling to the measurement channel on demand. The qubit measurement begins by loading a readout resonator that is coupled to the qubit. After an optimal interaction time with negligible loss, a microwave pump releases the content of the readout mode by upconversion into a measurement line in a characteristic time as low as 10 ns, which is 400 times shorter than the lifetime of the readout resonator. A direct measurement of the released field quadratures demonstrates a readout fidelity of 97.5% in a total measurement time of 220 ns. The Wigner tomography of the readout mode allows us to characterize the non-Gaussian nature of the readout mode and its dynamics.

Demonstration of an Effective Ultrastrong Coupling between Two Oscillators.

When the coupling rate between two quantum systems becomes as large as their characteristic frequencies, it induces dramatic effects on their dynamics and even on the nature of their ground state. The case of a qubit coupled to a harmonic oscillator in this ultrastrong coupling regime has been investigated theoretically and experimentally. Here, we explore the case of two harmonic oscillators in the ultrastrong coupling regime. Probing the properties of their ground state remains out of reach in natural implementations. Therefore, we have realized an analog quantum simulation of this coupled system by dual frequency pumping a nonlinear superconducting circuit. The pump amplitudes directly tune the effective coupling rate. We observe spectroscopic signature of a mode hybridization that is characteristic of the ultrastrong coupling. We experimentally demonstrate a key property of the ground state of this simulated ultrastrong coupling between modes by observing simultaneous single- and two-mode squeezing of the radiated field below vacuum fluctuations.

Oral Health Literacy, Preventive Behavior Measures, and Chronic Medical Conditions.

The purpose of this study was to examine the association between oral health literacy, preventive orientation and behaviors, and chronic medical conditions-specifically, hypertension and diabetes. A cross-sectional study was conducted with dental school patients attending the dental clinics in Los Angeles, California, and Baltimore, Maryland. Their health literacy levels were measured using the short Test of Functional Health Literacy in Adults (Short-TOFHLA) and the Rapid Estimate of Adult Literacy in Medicine and Dentistry (REALM-D). The medical history and existing medical conditions-specifically, hypertension and diabetes status-were extracted from patient health history and electronic records. Ten items were asked about preventive behaviors (e.g., brushing teeth in evening, smoking, exercise, drinking soda) and 3 preventive health services (dental checkup, flu shot, medical checkup). Six locus of control items were asked (e.g., good health is a matter of good fortune, what happens to my health is God's will). Out of 793 subjects, 221 had a documented history of hypertension, 88 with diabetes. There was an association between Short-TOFHLA scores and both diabetes and hypertension, but after controlling for sociodemographic and preventive variables, the association was no longer significant. In multivariate analysis, women, people with at least some college, Asians or non-Hispanic Whites, younger people, those who spoke English as a child, those who sought health information from the Internet or health care professionals, and those who smoked reported lower utilization of preventive health services, and those who had less locus of control reported higher Short-TOFHLA scores. There were no significant differences in mean REALM-D scores between patients who had hypertension or diabetes versus not having the condition. Multivariate models showed that people with higher REALM-D scores had at least some college, were other race/ethnicity or non-Hispanic White, spoke English as a child, and sought health information via the Internet. Knowledge Transfer Statement: The results of this study show that dental school patients exhibit a range of health literacy abilities and preventive behaviors, and health literacy measures positively correlated with some preventive behaviors but not others. Dental schools receive a significant number of patients with chronic diseases, and students should be educated to use effective patient communication skills to reinforce positive health behaviors among these patients.

Kidney injury secondary to endovascular treatment of renal artery stenosis. / Povrezhdenie pochki posle éndovaskuliarnogo vmeshatel'stva pri stenoze pochechnoi arterii.

In this paper, we present a case of kidney injury as a complication of renal artery angioplasty in a 54-year-old female patient that suffered from resistant renovascular hypertension. This case emphasises the unpredictable nature of endovascular procedures, the need for careful post-procedure evaluation and the role of 'old fashioned' surgical techniques in resolving complications of endovascular procedures.

Morphologic predictors of in hospital mortality in acute type III aortic dissection. / Morfologicheskie prediktory gospital'noi smertnosti u bol'nykh s ostrym rassloeniem aorty III tipa.

INTRODUCTION: In-hospital mortality of acute aortic type III dissection ranged about 12%. Complicated dissections represent about 18% of all cases, and require open surgery or TEVAR. More morphological predictors of in hospital mortality are needed to differentiate patients who should be selected for immediate, surgical or endovascular intervention. METHODS: From January 2009 to December 2014, 74 patients with acute aortic type III dissection were enrolled at Clinic of Vascular and Endovascular Surgery in Belgrade Serbia and retrospectively analyzed. Every MSCT was observed in regard to morphologic characteristics of dissection. RESULTS: By analyzing morphologic parameters in patients between survival and non-survival group only localization of intimal tear showed statistical significance (p=0,020). The size of the intimal tear didn't reach statistical significance with the tendency of doing so in a larger sample of patients (p=0,063) with the cut-off value of 9.55mm. The shape of the true lumen was on the border of statistical significance (p=0,053). CONCLUSION: Inner curvature intimal tear localization, huge intimal tear as well as elliptic shape of the true lumen together should raise awareness to a subgroup at risk for in hospital mortality. More liberal endovascular treatment in this subgroup of patients is advocated.

Independent risk factors of 30-day outcomes in 1264 patients with peptic ulcer bleeding in the USA: large ulcers do worse.

BACKGROUND: Predictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique. AIMS: To determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs). METHODS: A large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006-2011) were also analysed. RESULTS: A total of 1264 patients were included. For ulcers ≥10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30-day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size≥10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods. CONCLUSIONS: Ulcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management.

Bilirubin degradation in methanol induced by continuous UV-B irradiation: a UHPLC--ESI-MS study.

Degradation of bilirubin in aerobic methanol solution by continuous UV-B irradiation has been investigated in this work. The purpose of this study was to shed more light on bilirubin interaction with the UV-B component of natural sunlight, since bilirubin is a very efficient UV-B absorber located in the skin epidermis. The degradation products have been detected and studied by a combined method of Ultra High Performance Liquid Chromatography-Electrospray Ionization Mass Spectrometry (UHPLC-ESI-MS). Bilirubin, a toxic pigment which itself is a product of (hemoglobin) degradation in organisms, undergoes its own degradation under aerobic conditions of UV-B continuous irradiation (e.g. photooxidation) that can be partly self-sensitized. Two dipyrrolic structures have been identified as a result of the bilirubin degradation, not including the bilirubin derivative biliverdin whose increase in the irradiated system is synchronous with a time dynamics of bilirubin degradation. It appears that one of dipyrrolic products originates directly from bilirubin and biliverdin molecules, while the other one is probably connected to bilirubin self-sensitized degradation. The precursor role of biliverdin in the degradation process--related to the detected dipyrroles--has not been confirmed.

Glucocorticoid receptor mediates the expansion of splenic late erythroid progenitors during chronic psychological stress.

Stress evokes an integrated neuroendocrine response perturbing the homeostasis of different physiological systems. In contrast to well established physiologica linteractions between neuroendocrine and immune systems during chronic stress, there has been relatively little information on the effects of psychological stress on erythroid cells. Since stress-induced erythropoiesis occurs predominantly in the spleen, in the current study, we investigated the influence of chronic psychological stress on splenic erythroid progenitors and examined a role of glucocorticoid receptor (GR) in observed effect using a mouse model of restraint. The adult male mice were subjected to 2 hours daily restraint stress for 7 or 14 consecutive days and the role of GR in erythropoietic response to stress was assessed by pretreatment of mice with GR antagonist mifepristone 60 min prior to restraint. The results showed that chronic restraint stress induced an increase in spleen weight as well as in the cellularity of red pulp, as compared to controls. Furthermore, 7 and 14 days of restraint stress resulted in markedly increased number of both splenic early (BFU-E) and late (CFU-E) erythroid progenitors. Blockade of GR with mifepristone did not affect the number of BFU-E in stressed mice, but it completely abolished the effect of repeated psychological stress on CFU-E cells. Additionally, plasma corticosterone concentration was enhanced whereas the GR expression was significantly decreased within splenic red pulp after one and two weeks of stress exposure. Obtained findings suggest for the first time an indispensable role for GR in the expansion of CFU-E progenitors in the spleen under conditions of chronic psychological stress.

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

OBJECTIVES: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. METHODS: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1(-/-)) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. RESULTS: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1(-/-) mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1(-/-) mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1(-/-) mice. CONCLUSIONS: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity.

Substantial bone loss in the mandibular central incisors area as a complication of tongue piercing: a case report.

BACKGROUND: Along with the increasing popularity of oral piercings, the number of reported complications and side effects increases, too. CASE REPORT: The aim of this report is to present a case of substantial bone loss in the area of the mandibular central incisors caused by lingual piercing and persistent bad habits. Dentist should be aware of potential complications associated with oral piercings and warn patients about them.

Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs.

Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN) assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA) levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5-nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN) assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA) levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

The effect of gender and gender match on mortality in pediatric heart transplantation.

The effect of organ-recipient gender match on pediatric heart transplant mortality is unknown. We analyzed the effects of gender and donor-recipient gender matching. Based on Organ Procurement and Transplant Network data, we performed a historical cohort study in a population of 3630 heart transplant recipients less than 18 years old. We compared unadjusted and adjusted mortality by recipient gender, donor gender and between gender-matched and gender-mismatched recipients. Female recipients had decreased survival compared to male recipients (unadjusted hazard ratio [HR] 1.16, confidence interval [CI] 1.02-1.31; p = 0.020). Organ-recipient gender mismatch did not affect mortality for either male or female recipients, though gender-mismatched females had the worst survival compared to gender-matched males, who had the best survival (unadjusted HR 1.26, CI 1.07-1.49; p = 0.005). After adjustment for other risk factors affecting transplant mortality, female recipients had decreased survival compared to male recipients (HR 1.27, CI 1.12-1.44; p = 0.020) and gender matching had no effect. In conclusion, gender mismatch alone did not increase long-term mortality for pediatric heart transplant recipients. However, there may be additive effects of gender and gender matching affecting survival. There are insufficient data at this time to support that recipient and donor gender should affect heart allocation in children.

Liver transplantation outcome in patients with angiographically proven coronary artery disease: a multi-institutional study.

Over the last decade the age of liver transplant (LT) recipients and the likelihood of coronary artery disease (CAD) in this population have increased. There are no multicenter studies that have examined the impact of CAD on LT outcomes. In this historical cohort study, we identified adult LT recipients who underwent angiography prior to transplantation at seven institutions over a 12-year period. For each patient we recorded demographic data, recipient and donor risk factors, duration of follow-up, the presence of angiographically proven obstructive CAD (≥50% stenosis) and post-LT survival. Obstructive CAD was present in 151 of 630 patients, the CAD(+) group. Nonobstructive CAD was found in 479 patients, the CAD(-) group. Patient survival was similar for the CAD(+) group (adjusted HR 1.13, CI = [0.79, 1.62], p = 0.493) compared to the CAD(-) group. The CAD(+) patients were further stratified into severe (CADsev, >70% stenosis, n = 96), and moderate CAD (CADmod, 50-70% stenosis, n = 55) groups. Survival for the CADsev (adjusted HR = 1.26, CI = [0.83, 1.91], p = 0.277) and CADmod (adjusted HR = 0.93, CI = [0.52, 1.66], p = 0.797) groups were similar to the CAD(-) group. We conclude that when current CAD treatment strategies are employed prior to transplant, post-LT survival is not significantly different between patients with and without obstructive CAD.

Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression.

Glioma cells release soluble factors, which induce the expression of membrane type 1 matrix metalloprotease (MT1-MMP) in tumor associated microglia and then exploit MT1-MMP mediated matrix degradation for invasion. Here, we show that minocycline blocked the increase in MT1-MMP expression and activity in cultivated microglia stimulated with glioma conditioned medium. Glioma growth within an organotypic brain slice preparation was reduced by minocycline and this reduction depended on the presence of microglia. Glioma growth in an experimental mouse model was strongly reduced by the addition of minocycline to drinking water, compared to untreated controls. Coherently, we observed in our orthotopic glioma implantation model, that MT1-MMP was abundantly expressed in glioma associated microglia in controls, but was strongly attenuated in tumors of minocycline treated animals. Overall, our study indicates that the clinically approved antibiotic minocycline is a promising new candidate for adjuvant therapy against malignant gliomas.

Cage enrichment with paper tissue, but not plastic tunnels, increases variability in mouse model of asthma.

Environmental enrichment, besides having a great impact on animal welfare, can also be a potential variable in experimental research. Thus, we investigated whether enrichment of cages with paper tissues or plastic tunnels affects scientific outcome in the well-described mouse model of allergic asthma. BALB/cJ mice were introduced to paper tissues as nesting material, transparent plastic tunnels serving as shelters or kept in non-enriched cages. Afterwards, mice were sensitized to chicken egg ovalbumin (OVA) precipitated in aluminium sulphate and then intranasally challenged with OVA to induce allergic lung inflammation. Mice housed in cages enriched with paper tissues, but not with plastic tunnels, had increased total cell number, eosinophil number and IL-13 concentration in bronchoalveolar lavage fluid in comparison with the non-enriched control group. These results indicate that the effect of environmental enrichment on mice asthma models depends on the type of enrichment used. Therefore, it is important to consider the potential effects of any environmental enrichment on animal welfare and more importantly, on research results in order to standardize and obtain more accurate data from rodent studies.

Self-organized chaos through polyhomeostatic optimization.

The goal of polyhomeostatic control is to achieve a certain target distribution of behaviors, in contrast to homeostatic regulation, which aims at stabilizing a steady-state dynamical state. We consider polyhomeostasis for individual and networks of firing-rate neurons, adapting to achieve target distributions of firing rates maximizing information entropy. We show that any finite polyhomeostatic adaption rate destroys all attractors in Hopfield-like network setups, leading to intermittently bursting behavior and self-organized chaos. The importance of polyhomeostasis to adapting behavior in general is discussed.

Case series: clinical findings and oral rehabilitation of patients with amelogenesis imperfecta.

BACKGROUND: Children with amelogenesis imperfecta (AI) experience many oral difficulties including sensitivity and aesthetics. The methods of treating AI children are limited and therefore a program of care was evaluated in order to assess the clinical efficacy of providing preventive and restorative treatments. CASE REPORTS: A non-randomised convenience sample of 12 patients with AI was evaluated. A comprehensive patient history was recorded, followed by a clinical and radiographic assessment of oral health. In 8/12 patients a hypoplastic form of AI was diagnosed, in 2/12 cases hypomaturation and in 2/12 cases hypocalcified form were noted. Chief complaints were mainly related to unsatisfactory aesthetics and dental sensitivity. In 8 patients there was active dental caries. Most of the patients had gingivitis and showed fair oral hygiene. The presence of non-enamel dental anomalies was recorded in 9 patients. TREATMENT: All patients received meticulous preventive care. Initial treatment depended on AI type and oral health of the patient. During the transition period, both conventional and resin modified glassionomer cements, as well as composite resin materials, were used to restore posterior teeth. Direct composite resin restorations were used to improve the appearance of anterior teeth. In 4 patients a long-lasting interdisciplinary approach including orthodontics, metal-ceramic crowns and fixed partial dentures, and direct composite restorations was required. FOLLOW-UP: Follow-up periods varied between 2-11 years. All children have been regularly recalled at 3 monthly intervals. Caries prevalence has remained low during the follow-up postoperative period and patients have reported satisfaction with the treatment they have received. CONCLUSION: AI is associated with multiple non-enamel anomalies and requires a complex treatment. Treatment planning is related to the age of the patient, the type and severity of the disorder, and the oral health of the patient. Early diagnosis, preventive care and timely treatment are of foremost importance to improve oral health in children with AI.