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Competing Interests: Conflict of interest: None declared.

Background: Myocardial ischaemia with non-obstructive coronary arteries (INOCA) represents a challenging and frequent, but largely underdiagnosed, condition., Aims: We aimed to investigate the feasibility and diagnostic value of angiography-derived coronary microcirculatory resistance in patients with INOCA syndrome., Methods: This is an investigator-driven, prospective and blinded study. The diagnostic yield of angiography-derived index of coronary microcirculatory resistance (angio-IMR) was investigated against thermodilution-derived IMR (thermo-IMR) in patients with clinically indicated coronary angiography due to suspected myocardial ischaemia and angiographically normal or non-obstructive coronary arteries. The angio-IMR was derived from resting angiograms (contrast-flow angio-IMR [cAngio-IMR]) by an expert analyst blinded to the thermo-IMR. An independent, blinded, physiology core laboratory analysed the raw intracoronary physiology data and provided the final thermo-IMR values., Results: A total of 104 patients (108 coronary vessels) were analysed after fulfilling predefined inclusion criteria. Most patients were female (67%). Obstructive epicardial disease was angiographically (percent diameter stenosis <50%) and physiologically (fractional flow reserve>0.80) ruled out in all cases. Median thermo-IMR and cAngio-IMR were 16.6 (12.7, 23.0) and 16.8 (12.8, 23.1) units, respectively (median difference -0.31, 95% confidence interval: -1.53 to 1.00; p=0.654). cAngio-IMR showed good correlation (Pearson coefficient 0.76; p<0.001), agreement (mean bias 0.4), discriminatory power (area under the curve from the receiver operator characteristics 0.865; p<0.001) and accuracy (85%), compared to thermo-IMR (≥25 U)., Conclusions: Evaluating coronary microcirculatory resistance in patients with INOCA syndrome using cAngio-IMR is feasible and accurate. By circumventing the need of coronary instrumentation and hyperaemic drugs, this method may facilitate the assessment of coronary microcirculatory resistance in patients with suspected INOCA., Clinicaltrials: gov: NCT04827498.

Background: A high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake, and exposed playa or lakebed, may contribute components with a specific role in promoting asthma symptoms., Objectives: Our hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions may be concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. To test this hypothesis, we used a mouse model of aerosol exposures to assess the effects of playa dust., Methods: From dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-h and chronic 7-day exposures were compared, with lungs analyzed for inflammatory cell recruitment and gene expression., Results: Dust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-h but reduced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria., Conclusion: Lung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the possibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed., Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze., Design, Setting, and Participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021., Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment., Main Outcomes and Measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze., Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P < .001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003)., Conclusions and Relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health., Trial Registration: ClinicalTrials.gov Identifier: NCT03203603.

Marine chromophoric dissolved organic matter (m-CDOM) mediates many vital photochemical processes at the ocean's surface. Isolating m-CDOM within the chemical complexity of marine dissolved organic matter has remained an analytical challenge. The SeaSCAPE campaign, a large-scale mesocosm experiment, provided a unique opportunity to probe the in situ production of m-CDOM across phytoplankton and microbial blooms. Results from mass spectrometry coupled with UV-VIS spectroscopy reveal production of a chemodiverse set of compounds well-correlated with increases in absorbance after a bacterial bloom, indicative of autochthonous m-CDOM production. Notably, many of the absorbing compounds were found to be enriched in nitrogen, which may be essential to chromophore function. From these results, quinoids, porphyrins, flavones, and amide-like compounds were identified via structural analysis and may serve as important photosensitizers in the marine boundary layer. Overall, this study demonstrates a step forward in identifying and characterizing m-CDOM using temporal mesocosm data and integrated UV-VIS spectroscopy and mass spectrometry analyses.

Misophonia can be characterized both as a condition and as a negative affective experience. Misophonia is described as feeling irritation or disgust in response to hearing certain sounds, such as eating, drinking, gulping, and breathing. Although the earliest misophonic experiences are often described as occurring during childhood, relatively little is known about the developmental pathways that lead to individual variation in these experiences. This literature review discusses evidence of misophonic reactions during childhood and explores the possibility that early heightened sensitivities to both positive and negative sounds, such as to music, might indicate a vulnerability for misophonia and misophonic reactions. We will review when misophonia may develop, how it is distinguished from other auditory conditions (e.g., hyperacusis, phonophobia, or tinnitus), and how it relates to developmental disorders (e.g., autism spectrum disorder or Williams syndrome). Finally, we explore the possibility that children with heightened musicality could be more likely to experience misophonic reactions and develop misophonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mednicoff, Barashy, Gonzales, Benning, Snyder and Hannon.)

Critical antibody titers have been described as factors associated with hemolysis in ABO plasma-incompatible platelet (PLT) transfusions. This study was carried out to describe the frequency of high-titers anti-A and antiB IgM and IgG antibodies in group O apheresis platelet donors, and to explore differences according to the donor characteristics. A cross-sectional study was carried out at the Blood Bank of a National Hospital in Peru from January to March 2019. IgM and IgG antibodies against A1 and B antigens were quantified in 339 platelet donors using the direct hemagglutination technique and the solid-phase adherence technique, respectively. For analysis purposes, two cut-off points; ≥128 and ≥64, were used to define a critical titer for IgM due to a lack of consensus. An IgG titer of ≥256 was also defined as critical. Of the donors, 22.1 % had critical IgM titers when the cut-off point was defined as ≥128. However, when the IgM cut-off was ≥64, the frequency of platelet donors with critical titers increased to 54.0 %. The frequency of donors with critical IgG titers was 23.5 %. Higher IgG titers were associated with female donors while higher IgM titers were negative associated with age. One in two or three platelet donors, depending on the cutoff point used to define a critical IgM titer, had at least one critical titer of anti-A or anti-B antibodies. Early identification of platelet donors with critical antibody titers could prevent passive transfusion of ABO antibodies to non-isogroup recipients., (Copyright © 2021. Published by Elsevier Ltd.)

Down syndrome (DS) or Trisomy 21 is the most common genetic cause of mental retardation with severe learning and memory deficits. DS is due to the complete or partial triplication of human chromosome 21 (HSA21) triggering gene overexpression and protein synthesis alterations responsible for a plethora of mental and physical phenotypes. Among the diverse brain target systems that affect hippocampal-dependent learning and memory deficit impairments in DS, the upregulation of the endocannabinoid system (ECS), and notably the overexpression of the cannabinoid type-1 receptor (CB1), seems to play a major role. Combining various protein and gene expression targeted approaches using western blot, qRT-PCR and FISH techniques, we investigated the expression pattern of ECS components in the hippocampus (HPC) of male Ts65Dn mice. Among all the molecules that constitute the ECS, we found that the expression of the CB1 is altered in the HPC of Ts65Dn mice. CB1 distribution is differentially segregated between the dorsal and ventral part of the HPC and within the different cell populations that compose the HPC. CB1 expression is upregulated in GABAergic neurons of Ts65Dn mice whereas it is downregulated in glutamatergic neurons. These results highlight a complex regulation of the CB1 encoding gene (Cnr1) in Ts65Dn mice that could open new therapeutic solutions for this syndrome., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the prevalence, characteristics, and outcomes of neonates needing emergent resuscitation within the level 4 neonatal intensive care units (NICU). Clinical factors prior to and following resuscitation event or characteristics of those who require chest compressions versus those without compressions has not been previously delineated. The aim of this study is to describe characteristics and outcomes of neonates who have compressive vs. non-compressive resuscitative events., Methods: Retrospective observational study of neonates with a resuscitative event in the Children's Mercy Hospital level 4 NICU between January 2012 and April 2017. Data were derived from the NICU Code Blue database and the electronic medical record. Primary outcome was survival to hospital discharge., Result: Of the 641 resuscitative events, most were in the non-compressive group (n = 481). Those requiring chest compressions longer than 1 minute had significantly different clinical characteristics and decreased survival. There was no difference between groups in gestational age or birth weight., Conclusion: Non-compressive events are more common in the NICU setting than are compressive events. Neonates requiring chest compressions longer than 1 minute are more likely to have a higher respiratory severity score, need for vasopressors, worse renal function post-event, and decreased survival to discharge.

Despite the central role of Rho GTPases in neuronal development, their functions in adult hippocampal neurogenesis remain poorly explored. Here, by using a retrovirus-based loss-of-function approach in vivo, we show that the atypical Rho GTPase Rnd2 is crucial for survival, positioning, somatodendritic morphogenesis, and functional maturation of adult-born dentate granule neurons. Interestingly, most of these functions are specific to granule neurons generated during adulthood since the deletion of Rnd2 in neonatally-born granule neurons only affects dendritogenesis. In addition, suppression of Rnd2 in adult-born dentate granule neurons increases anxiety-like behavior whereas its deletion in pups has no such effect, a finding supporting the adult neurogenesis hypothesis of anxiety disorders. Thus, our results are in line with the view that adult neurogenesis is not a simple continuation of earlier processes from development, and establish a causal relationship between Rnd2 expression and anxiety., (© 2021. The Author(s).)

Hypothalamic pro-opiomelanocortin (POMC) neurons are known to trigger satiety. However, these neuronal cells encompass heterogeneous subpopulations that release γ-aminobutyric acid (GABA), glutamate, or both neurotransmitters, whose functions are poorly defined. Using conditional mutagenesis and chemogenetics, we show that blockade of the energy sensor mechanistic target of rapamycin complex 1 (mTORC1) in POMC neurons causes hyperphagia by mimicking a cellular negative energy state. This is associated with decreased POMC-derived anorexigenic α-melanocyte-stimulating hormone and recruitment of POMC/GABAergic neurotransmission, which is restrained by cannabinoid type 1 receptor signaling. Electrophysiology and optogenetic studies further reveal that pharmacological blockade of mTORC1 simultaneously activates POMC/GABAergic neurons and inhibits POMC/glutamatergic ones, implying that the functional specificity of these subpopulations relies on mTORC1 activity. Finally, POMC neurons with different neurotransmitter profiles possess specific molecular signatures and spatial distribution. Altogether, these findings suggest that mTORC1 orchestrates the activity of distinct POMC neurons subpopulations to regulate feeding behavior., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Bile acids (BAs) improve metabolism and exert anti-obesity effects through the activation of the Takeda G protein-coupled receptor 5 (TGR5) in peripheral tissues. TGR5 is also found in the brain hypothalamus, but whether hypothalamic BA signaling is implicated in body weight control and obesity pathophysiology remains unknown. Here we show that hypothalamic BA content is reduced in diet-induced obese mice. Central administration of BAs or a specific TGR5 agonist in these animals decreases body weight and fat mass by activating the sympathetic nervous system, thereby promoting negative energy balance. Conversely, genetic downregulation of hypothalamic TGR5 expression in the mediobasal hypothalamus favors the development of obesity and worsens established obesity by blunting sympathetic activity. Lastly, hypothalamic TGR5 signaling is required for the anti-obesity action of dietary BA supplementation. Together, these findings identify hypothalamic TGR5 signaling as a key mediator of a top-down neural mechanism that counteracts diet-induced obesity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Youth of color are one of the fastest growing segments of the U.S., Population: Collaborative equitable approaches to research and action present potential avenues to engage youth of color meaningfully in health research and action initiatives., Objectives: This article explores community-based participa-tory research (CBPR) as an approach that presents valuable opportunities to engage youth and young adults of color in leadership in public health initiatives to create healthy communities., Methods: Integrating a CBPR approach, we partnered with grassroots leaders and community organizations across five cities to engage youth and young adults of color (n = 35) in identifying health assets and threats to young people's well-being using mixed-methods including surveys, photovoice, field observations, and interviews., Results: This article focuses on presenting three major themes that emerged from the youth-led health assessment across five cities: 1) relations with police, 2) stress, and 3) safety. Findings indicate youth are well aware of the role that interlocking structures play in individual and collective health and well-being., Conclusions: CBPR presents promising approaches to engage youth meaningfully in health promotion initiatives providing the opportunities for youth researchers to document accurately nuanced understandings of social determinants of health impacting the health and well-being of youth of color.

Background: Low-density lipoprotein cholesterol (LDL-C) contributes decisively to the development of cardiovascular disease (CVD). In the LYNX registry we determined the rate of achievement of the target value of LDL-C, the use of lipid-lowering therapy (LLT) and the predictive factors of not reaching the target in patients with stable coronary heart disease (CHD)., Methods: LYNX included consecutive patients with stable CHD treated at the University Hospital of Caceres, Extremadura (Spain) from September 2016 to September 2018, and those who must have an LDL-C target below 70 mg/dL according to the European Society of Cardiology (ESC) 2016 guidelines. The variables independently associated with the breach of the LDL-C objective were evaluated by multivariable logistic regression., Results: A total of 674 patients with stable CHD were included. The average LDL-C levels were 68.3 ± 24.5 mg/dL, with 56.7% showing a level below 70 mg/dL. LLT was used by 96.7% of patients, 71.7% were treated with high-powered statins and 30.1% with ezetimibe. The risk of not reaching the target value of LDL-C was higher in women, in active smokers, and in those who had multivessel CHD or had atrial fibrillation. Patients with diabetes mellitus, those who took potent statins or co-administration treatment with ezetimibe were more likely to reach the target level of LDL-C., Conclusions: The treatment of dyslipidemia in patients with chronic CHD remains suboptimal; however, an increasing number of very high-risk patients achieve the LDL-C objective, although there is still enormous potential to improve cardiovascular outcome through the use of more intensive LLT., Competing Interests: There are no conflicts of interest., (Copyright 2020, Gomez-Barrado et al.)

Of all hypotheses advanced for why zebras have stripes, avoidance of biting fly attack receives by far the most support, yet the mechanisms by which stripes thwart landings are not yet understood. A logical and popular hypothesis is that stripes interfere with optic flow patterns needed by flying insects to execute controlled landings. This could occur through disrupting the radial symmetry of optic flow via the aperture effect (i.e. generation of false motion cues by straight edges), or through spatio-temporal aliasing (i.e. misregistration of repeated features) of evenly spaced stripes. By recording and reconstructing tabanid fly behaviour around horses wearing differently patterned rugs, we could tease out these hypotheses using realistic target stimuli. We found that flies avoided landing on, flew faster near, and did not approach as close to striped and checked rugs compared to grey. Our observations that flies avoided checked patterns in a similar way to stripes refutes the hypothesis that stripes disrupt optic flow via the aperture effect, which critically demands parallel striped patterns. Our data narrow the menu of fly-equid visual interactions that form the basis for the extraordinary colouration of zebras.

Background: Vitamin C (500 mg·day -1 ) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported., Objective: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age., Methods: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day -1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance., Results: FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec -1 for FEF 75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec -1 for FEF 50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec -1 for FEF 25-75 (95% CI, 9.7 to 100.5; p=0.013)., Conclusions: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway., (Copyright ©ERS 2020.)

Background: Postdischarge follow-up is a critical step for increasing effectiveness of hospital smoking cessation treatment. A quality improvement project was undertaken at an academic medical center tobacco cessation consult service to evaluate whether a tailored message (TM) linking immediate risks of continued smoking-particularly carbon monoxide exposure-to hospital recovery would stimulate more patient interest in the hospital's cessation treatment, including agreement to postdischarge follow-up, compared to patients receiving the usual treatment protocol with a standard message (SM) regarding more general health benefits of abstinence., Methods: Data from 697 smokers ordered/referred for smoking cessation treatment in 2013 who received either the SM (January-April; n = 323) or the TM (April-November; n =374) were analyzed., Results: Multivariate regression analysis showed that the TM was associated with significantly greater agreement for follow-up (odds ratio [OR] = 10.83, 95% confidence interval [CI] = 3.66-32.04, p < 0.0001) than the SM. Those patients who received the TM were more willing to try to remain abstinent postdischarge (willingness score = 10, p = 0.0052) and engaged in longer consults (consult time > 10 minutes, p = 0.0075) than SM patients. TM patients also self-reported a higher continuous abstinence rate (OR = 2.07, 95% CI = 1.17-3.66, p = 0.0130] at follow-up than SM., Conclusion: Linking risks of continued smoking, particularly carbon monoxide exposure, to hospital patients' immediate recovery following discharge in a treatment protocol resulted in longer consult times and increased agreement to follow-up compared to the usual protocol message. The TM was integrated into the hospital tobacco cessation intervention as standard of care., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico-pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Textile manufacturing industries generate large amounts of viscose yarn waste (VW) that causes serious environmental pollution. In this study, VW was used as raw material to successfully extract nanocellulose (NC) in a facile one-step extraction process, without any pretreatment. Different hydrolysis reaction times (5-60 min) were employed, and the extracted material was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning and transmission electron microscopies, atomic force microscopy, and thermogravimetric analysis. Interestingly, it was possible to obtain NC in only 5 min of reaction without any pretreatment and with an increase of 50% in the crystallinity, which was attributed to the pretreatments VW undergone in textile industry that swell cellulose chains and make them more accessible to further reactions. The higher crystallinity index was observed after 30 min of reaction (87%), and through microscopy, it was verified that the morphology of the VW was completely changed to irregular nanoparticles with average size of 42 nm. The obtained NC showed interesting properties to be used in several potential applications, including stabilization of oil/water Pickering emulsions. These results indicate that VW is an attractive source to obtain NC, making the extraction of NC from VW a value-added alternative to recycle this textile waste., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF 75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF 50 and FEF 25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C ( n  = 113) had the following FEFs at 3 months of age compared with those randomized to placebo ( n  =  109) as measured by FEF 75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P  = 0.10), FEF 50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P  = 0.02), and FEF 25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P  = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF 75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF 50 and FEF 25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF 50 and FEF 25-75 ) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

Four-arm star poly(ε-caprolactone) with a central poly(ethylene glycol) PEG unit bridged with 2,2- bis (methyl) propionic acid, (PCL)₂- b -PEG- b -(PCL)₂, and six-arm star PCL homopolymer with a central dipentaerythritol units were hydrolysed using a lipase from Pseudomonas cepacia and the Thermobifida cellulosilytica cutinase Thc&#95;Cut1. For comparative analysis, Y-shaped copolymers containing methylated PEG bridged with bisMPA, MePEG-(PCL)₂, and linear triblock copolymers PCL- b -PEG- b -PCL were also subjected to enzymatic hydrolysis. The hydrophilic nature of the polymers was determined using contact angle analysis, showing that a higher PEG content exhibited a lower contact angle and higher surface wettability. Enzymatic hydrolysis was monitored by % mass loss, scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). A higher rate of mass loss was found for lipase catalysed hydrolysis of those polymers with the highest PEG content, leading to significant surface erosion and increase in crystallinity within the first two days. Liquid chromatography (LC) and size exclusion chromatography (SEC) of samples incubated with the cutinase showed a significant decrease in molecular weight, increase in dispersity, and release of ε -CL monomer units after 6 h of incubation.

Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) is an mRNA-binding protein that reduces inflammation by binding to cytokine transcripts and promoting their degradation. We hypothesized that myeloid-specific deficiency of Zfp36 would lead to increased adipose tissue inflammation and reduced insulin sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became obese and diabetic on a high-fat diet, and obese mice with myeloid-specific loss of Zfp36 [knockout (KO)] demonstrated increased adipose tissue and liver cytokine mRNA expression compared with Control mice. Unexpectedly, in glucose tolerance testing and hyperinsulinemic-euglycemic clamp studies, myeloid Zfp36 KO mice demonstrated improved insulin sensitivity compared with Control mice. Obese KO and Control mice had similar macrophage infiltration of the adipose depots and similar peripheral cytokine levels, but lean and obese KO mice demonstrated increased Kupffer cell (KC; the hepatic macrophage)-expressed Mac2 compared with lean Control mice. Insulin resistance in obese Control mice was associated with enhanced Zfp36 expression in KCs. Compared with Control mice, KO mice demonstrated increased hepatic mRNA expression of a multitude of classical (M1) inflammatory cytokines/chemokines, and this M1-inflammatory hepatic milieu was associated with enhanced nuclear localization of IKKβ and the p65 subunit of NF-κB. Our data confirm the important role of innate immune cells in regulating hepatic insulin sensitivity and lipid metabolism, challenge-prevailing models in which M1 inflammatory responses predict insulin resistance, and indicate that myeloid-expressed Zfp36 modulates the response to insulin in mice.

Ciliary neurotrophic factor (CNTF) potently decreases food intake and body weight in diet-induced obese mice by acting through neuronal circuits and pathways located in the arcuate nucleus (ARC) of the hypothalamus. CNTF also exerts pro-inflammatory actions within the brain. Here we tested whether CNTF modifies energy balance by inducing inflammatory responses in the ARC and whether these effects depend upon the mechanistic target of rapamycin complex 1 (mTORC1) pathway, which regulates both energy metabolism and inflammation. To this purpose, chow- and high fat diet (HFD)- fed mice lacking the S6 kinase 1 (S6K1 -/- ), a downstream target of mTORC1, and their wild-type (WT) littermates received 12 days continuous intracerebroventricular (icv) infusion of the CNTF analogue axokine (CNTF Ax15 ). Behavioral, metabolic and molecular effects were evaluated. Central chronic administration of CNTF Ax15 decreased body weight and feed efficiency in WT mice only, when fed HFD, but not chow. These metabolic effects correlated with increased number of iba-1 positive microglia specifically in the ARC and were accompanied by significant increases of IL-1β and TNF-α mRNA expression in the hypothalamus. Hypothalamic iNOS and SOCS3 mRNA, molecular markers of pro-inflammatory response, were also increased by CNTF Ax15 . All these changes were absent in S6K1 -/- mice. This study reveals that CNTF Ax15 requires a functional S6K1 to modulate energy balance and hypothalamic inflammation in a diet-dependent fashion. Further investigations should determine whether S6K1 is a suitable target for the treatment of pathologies characterized by a high neuroinflammatory state., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study was to compare the mechanical resistance of three different plates used to treat fractures of the mandibular angle: a regular 4-hole plate, a longer 4-hole plate (both positioned using the Champy technique), and a 3-dimensional plate positioned over the oblique line. Three equal groups of replicas of human dentate mandibles made out of polyurethane resin were used (n=21 in each group). The force was applied perpendicular to the occlusal plane at a rate of 2mm/minute at three different points: the first molar on the sectioned side; the first molar on the contralateral side; and between the central incisors. This was followed by a resistance-to-load test. The two varying factors (type of plate and site-of-load application) were tested by analysis of variance, and probabilities of less than 0.05 were accepted as significant. There were no significant differences between the subgroups, or between the mean values of the different types of plates (p=0.925). The three types of plates showed similar mechanical behaviour, which showed that the 3-dimensional plates positioned over the oblique line can produce mechanical scores similar to those of conventional plates., (Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The objective was to detect Gram-negative bacilli and Gram-positive cocci isolated from the environmental microbiota of the Intensive Care Unit (ICU) departments of Neonatology, Pediatrics, and Transplants (kidney, liver, and general) in a Lima hospital and determine their antimicrobial sensitivity. Eighty samples were obtained from inanimate surfaces using a wet swab. A total of 61 bacterial strains were identified, including Staphylococcus epidermis (46.0%), Alcaligenes sp. (21.3%), Pseudomonas aeruginosa (16.4%), Acinetobacter sp. (13.1%), Staphylococcus aureus (1.6%), and Staphylococcus haemolyticus (1.6%). Acinetobacter sp. and P. aeruginosa showed a heightened sensitivity to the antibiotics assessed, while Alcaligenes sp. and S. epidermidis presented the highest antimicrobial resistance. It is recommended that sustained asepsis and monitoring methods be used in ICUs.

In this paper, we describe the design and implementation of a low-cost, open-source prosthetic hand that enables both motor control and sensory feedback for people with transradial amputations. We integrate electromyographic pattern recognition for motor control along with contact reflexes and sensory substitution to provide feedback to the user. Compliant joints allow for robustness to impacts. The entire hand can be built for around $550. This low cost makes research and development of sensorimotor prosthetic hands more accessible to researchers worldwide, while also being affordable for people with amputations in developing nations. We evaluate the sensorimotor capabilites of our hand with a subject with a transradial amputation. We show that using contact reflexes and sensory substitution, when compared to standard myoelectric prostheses that lack these features, improves grasping of delicate objects like an eggshell and a cup of water both with and without visual feedback. Our hand is easily integrated into standard sockets, facilitating long-term testing of sensorimotor capabilities.

Introduction: Following complicated appendicitis, there are limited data available to guide the surgeon regarding antibiotic selection, specifically in regards to route of administration. We hypothesized that among children with appendicitis who are discharged home with antibiotic therapy, the post-discharge readmission and complication rates do not differ between those children who receive IV antibiotics and those who receive PO antibiotics., Methods: We performed a retrospective review of all children discharged home on antibiotics following appendectomy at a single institution between 11/10-10/14. We compared outcomes including ED and hospital readmission rates, and development of postoperative complications, between those children who were discharged on IV antibiotics and those discharged on PO antibiotics., Results: 325 children were discharged with antibiotics following appendectomy (n=291 PO antibiotics group; n=34 IV group). On both univariate and multivariate analysis, rate of each complication did not differ between the two groups including inpatient readmission (5% PO vs. 6% IV; p=0.8), ED readmission (10% vs. 11%; p=0.8), postdischarge complications related to the operation (10% vs. 15%; p=0.4), or abscess development post-discharge (4% vs. 3%; p=1)., Conclusions: Among children with complicated appendicitis who are discharged home with ongoing antibiotic therapy, our data demonstrate no differences in outcomes between those children who receive IV and PO antibiotics. Further data, collected in a prospective fashion, are needed to clarify the role of IV and PO antibiotics among children with perforated appendicitis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes (T2D) in lean individuals is not well studied and up to 26% of diabetes occurs in these individuals. Although the cause is not well understood, it has been primarily attributed to nutritional issues during early development., Objective: Our objective was to develop a lean T2D model using gestational low-protein (LP) programming., Study Design: Pregnant rats were fed control (20% protein) or isocaloric LP (6%) diet from gestational day 4 until delivery. Standard diet was given to dams after delivery and to pups after weaning. Glucose tolerance test was done at 2, 4, and 6 months of age. Magnetic resonance imaging of body fat for females was done at 4 months. Rats were sacrificed at 4 and 8 months of age and their perigonadal, perirenal, inguinal, and brown fat were weighed and expressed relative to their body weight. Euglycemic-hyperinsulinemic clamp was done around 6 months of age., Results: Male and female offspring exposed to a LP diet during gestation developed glucose intolerance and insulin resistance (IR). Further, glucose intolerance progressed with increasing age and occurred earlier and was more severe in females when compared to males. Euglycemic-hyperinsulinemic clamp showed whole body IR in both sexes, with females demonstrating increased IR compared to males. LP females showed a 4.5-fold increase in IR while males showed a 2.5-fold increase when compared to their respective controls. Data from magnetic resonance imaging on female offspring showed no difference in the subcutaneous, inguinal, and visceral fat content. We were able to validate this observation by sacrificing the rats at 4 and 8 months and measuring total body fat content. This showed no differences in body fat content between control and LP offspring in either males or females. Additionally, diabetic rats had a similar body mass index to that of the controls., Conclusion: LP gestational programming produces a progressively worsening T2D model in rats with a lean phenotype without obesity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Hospital-acquired pressure ulcer occurrences have declined over the past decade as reimbursement policies have changed, evidence-based practice guidelines have been implemented, and quality improvement initiatives have been launched. However, the 2006-2008 Institute for Healthcare Improvement goal of zero pressure ulcers remains difficult to achieve and even more challenging to sustain. Magnet hospitals tend to have lower hospital-acquired pressure ulcer rates than non-Magnet hospitals, yet many non-Magnet hospitals also have robust pressure ulcer prevention programs. Successful programs share commonalities in structure, processes, and outcomes. A national summit of 55 pressure ulcer experts was convened at the Virginia Commonwealth University Medical Center in March 2014. The group was divided into 3 focus groups; each was assigned a task to develop a framework describing components of a proposed Magnet-designated Center of Pressure Ulcer Prevention Excellence. Systematic literature reviews, analysis of exemplars, and nominal group process techniques were used to create the framework. This article presents a framework describing the proposed Magnet-designated Centers of Pressure Ulcer Prevention Excellence. Critical attributes of Centers of Excellence are identified and organized according to the 4 domains of the ANCC model for the Magnet Recognition Program: transformational leadership; structural empowerment; exemplary professional practice; and new knowledge innovation and improvements. The structures, processes, and outcome measures necessary to become a proposed Center of Pressure Ulcer Prevention Excellence are discussed.

Purpose: Recent data demonstrate that surgical lung biopsy in immunocompromised children, including oncology patients, alters therapy in only 50% of cases. We hypothesized that there are factors identifiable preoperatively which can predict the patients who will or will not benefit from surgical biopsy., Methods: We reviewed the medical records of all children with malignancy who underwent surgical lung biopsy between 2004 and 2013 at a single institution, excluding those children who had previously undergone a solid organ or bone marrow transplant., Results: Eighty lung wedge biopsies were performed (median age 13 years, IQR 5.25-16; 63% male, n=50) 53 (66%) of which led to a change in patient management. The majority of biopsies were performed to diagnose a new mass or differentiate infection from metastases (mass group) (n=68, 85%), and 12 biopsies (15%) were performed to diagnose a known infection for antibiotic guidance (infection group). Children in the infection group were more likely to be febrile preoperatively, were more likely to be an inpatient preoperatively, and had a lower absolute neutrophil count at the time of biopsy. Patients in the infection group had higher postoperative mortality rates and higher rates of major complications., Conclusion: In pediatric oncology patients, surgical lung biopsy has a lower diagnostic yield and higher complication rate when performed for antibiotic guidance. Prior to proceeding with biopsy in this high-risk patient population, surgeons and oncologists should carefully weigh the potential risks and benefits., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The paraventricular nucleus of the hypothalamus (PVN) regulates energy balance by modulating not only food intake, but also energy expenditure (EE) and brown adipose tissue thermogenesis. To test the hypothesis that cannabinoid type 1 (CB1) receptor in PVN neurons might control these processes, we used the Cre/loxP system to delete CB1 from single-minded 1 (Sim1) neurons, which account for the majority of PVN neurons. On standard chow, mice lacking CB1 receptor in Sim1 neurons (Sim1-CB1-knockout [KO]) had food intake, body weight, adiposity, glucose metabolism, and EE comparable with wild-type (WT) (Sim1-CB1-WT) littermates. However, maintenance on a high-fat diet revealed a gene-by-diet interaction whereby Sim1-CB1-KO mice had decreased adiposity, improved insulin sensitivity, and increased EE, whereas feeding behavior was similar to Sim1-CB1-WT mice. Additionally, high-fat diet-fed Sim1-CB1-KO mice had increased mRNA expression of the β3-adrenergic receptor, as well as of uncoupling protein-1, cytochrome-c oxidase subunit IV and mitochondrial transcription factor A in the brown adipose tissue, all molecular changes suggestive of increased thermogenesis. Pharmacological studies using β-blockers suggested that modulation of β-adrenergic transmission play an important role in determining EE changes observed in Sim1-CB1-KO. Finally, chemical sympathectomy abolished the obesity-resistant phenotype of Sim1-CB1-KO mice. Altogether, these findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.

Paracoccidioidomycosis is a fungal disease which can compromise the central nervous system (CNS).We present a case of an immunocompetent 45 year old man from Satipo, Peru who developed paracoccidioidomycosis in the CNS without any apparent point of entry or infection. The patient was diagnosed by imaging with a cerebellar granuloma, followed by a craniotomy where tissue and secretion of the granuloma abscess was obtained. Histological and microbiological diagnoses were performed on the tissue and secretion, respectively. Yeasts were observed in the histological section and growth of the fungus in the culture. The patient initially received antifungals, then acquired an intrahospital infection, received colistin and subsequently died. The case report emphasizes the importance of early and correct diagnosis for good outcomes of paracoccidioidomycosis cases.

The efficacy and safety of retreatment with varenicline in smokers attempting to quit were evaluated in this randomized, double-blind, placebo-controlled, multicenter trial (Australia, Belgium, Canada, the Czech Republic, France, Germany, the United Kingdom, and the United States). Participants were generally healthy adult smokers (≥ 10 cigarettes/day) with ≥ 1 prior quit attempt (≥ 2 weeks) using varenicline and no quit attempts in ≤ 3 months; they were randomly assigned (1:1) to 12 weeks' varenicline (n = 251) or placebo (n = 247) treatment, with individual counseling, plus 40 weeks' nontreatment follow-up. The primary efficacy end point was the carbon monoxide-confirmed (≤ 10 ppm) continuous abstinence rate for weeks 9-12, which was 45.0% (varenicline; n = 249) vs. 11.8% (placebo; n = 245; odds ratio: 7.08; 95% confidence interval: 4.34, 11.55; P < 0.0001). Common varenicline group adverse events were nausea, abnormal dreams, and headache, with no reported suicidal behavior. Varenicline is efficacious and well tolerated in smokers who have previously taken it. Abstinence rates are comparable with rates reported for varenicline-naive smokers.

Metabolic flexibility allows rapid adaptation to dietary change, however, little is known about the CNS mechanisms regulating this process. Neurons in the hypothalamic ventromedial nucleus (VMN) participate in energy balance and are the target of the metabolically relevant hormone leptin. Cannabinoid type-1 (CB1) receptors are expressed in VMN neurons, but the specific contribution of endocannabinoid signaling in this neuronal population to energy balance regulation is unknown. Here we demonstrate that VMN CB1 receptors regulate metabolic flexibility and actions of leptin. In chow-fed mice, conditional deletion of CB1 in VMN neurons (expressing the steroidogenic factor 1, SF1) decreases adiposity by increasing sympathetic activity and lipolysis, and facilitates metabolic effects of leptin. Conversely, under high-fat diet, lack of CB1 in VMN neurons produces leptin resistance, blunts peripheral use of lipid substrates and increases adiposity. Thus, CB1 receptors in VMN neurons provide a molecular switch adapting the organism to dietary change.

Importance: Maternal smoking during pregnancy adversely affects offspring lung development, with lifelong decreases in pulmonary function and increased asthma risk. In a primate model, vitamin C blocked some of the in-utero effects of nicotine on lung development and offspring pulmonary function., Objective: To determine if newborns of pregnant smokers randomized to receive daily vitamin C would have improved results of pulmonary function tests (PFTs) and decreased wheezing compared with those randomized to placebo., Design, Setting, and Participants: Randomized, double-blind trial conducted in 3 sites in the Pacific Northwest between March 2007 and January 2011. One hundred fifty-nine newborns of randomized pregnant smokers (76 vitamin C treated and 83 placebo treated) and 76 newborns of pregnant nonsmokers were studied with newborn PFTs. Follow-up assessment including wheezing was assessed through age 1 year, and PFTs were performed at age 1 year., Interventions: Pregnant women were randomized to receive vitamin C (500 mg/d) (n = 89) or placebo (n = 90)., Main Outcomes and Measures: The primary outcome was measurement of newborn pulmonary function (ratio of the time to peak tidal expiratory flow to expiratory time [TPTEF:TE] and passive respiratory compliance per kilogram [Crs/kg]) within 72 hours of age. Secondary outcomes included incidence of wheezing through age 1 year and PFT results at age 1 year. A subgroup of pregnant smokers and nonsmokers had genotyping performed., Results: Newborns of women randomized to vitamin C (n = 76), compared with those randomized to placebo (n = 83), had improved pulmonary function as measured by TPTEF:TE (0.383 vs 0.345 [adjusted 95% CI for difference, 0.011-0.062]; P = .006) and Crs/kg (1.32 vs 1.20 mL/cm H2O/kg [95% CI, 0.02-0.20]; P = .01). Offspring of women randomized to vitamin C had significantly decreased wheezing through age 1 year (15/70 [21%] vs 31/77 [40%]; relative risk, 0.56 [95% CI, 0.33-0.95]; P = .03). There were no significant differences in the 1-year PFT results between the vitamin C and placebo groups. The effect of maternal smoking on newborn lung function was associated with maternal genotype for the α5 nicotinic receptor (rs16969968) (P < .001 for interaction)., Conclusions and Relevance: Supplemental vitamin C taken by pregnant smokers improved newborn PFT results and decreased wheezing through 1 year in the offspring. Vitamin C in pregnant smokers may be an inexpensive and simple approach to decrease the effects of smoking in pregnancy on newborn pulmonary function and respiratory morbidities., Trial Registration: clinicaltrials.gov Identifier: NCT00632476.

The authors used a multipronged approach to gain resident involvement in institutional quality improvement over a 3-year period; the initiative included a survey, a retreat, workgroups, a resurvey, and another retreat. Survey results (from 2007 compared with those of 2010) demonstrated significant improvement in almost all the top issues concerning patient safety for residents-emergency department boarding and crowding, adequacy of patient flow through the institution, adequacy of nursing and technical support staffing, and laboratory specimen handling (initial overall mean concern level was 2.87, and final concern level was 2.19; P < .01). This perceived improvement in patient safety concerns for residents was associated with observable improvements in areas of high concern for hospital leaders. By surveying residents and students, prioritizing concerns, convening a hospital-wide retreat with key leaders, and implementing accountable plans, the authors have demonstrated that resident perceptions of quality and safety can help drive quality improvement and engage residents in improvement efforts at an institutional level.

Background: Adult hippocampal neurogenesis, which is involved in the physiopathology of hippocampal functions, is genetically determined and influenced by early life events. However, studies on the interaction of these determining forces are lacking. This prompted us to investigate whether adult hippocampal neurogenesis can be modulated by maternal care and whether this influence depends upon the genetic background of the individual., Methods: We used a model of fostering that allows singling out the influence of the genetic make-up of the pups on the outcome of maternal behavior. Mice from two different inbred strains (C57BL/6J and DBA/2J) known to differ in their baseline neurogenesis as well as in their sensitivity to the influence of environmental experiences were raised by nonrelated mothers from the AKR/Ola (AKR) and C3H/He (C3H) strains exhibiting low- and high-pup-oriented behavior, respectively. Neurogenesis was then assessed in the dentate gyrus of the adult adopted C57BL/6J and DBA/2J mice., Results: We show that both the number and the morphological features of newborn granule cells in the dentate gyrus are determined by the maternal environment to which mice were exposed as pups and that this sensitivity to maternal environment is observed only in genetically vulnerable subjects., Conclusions: Altogether, our data indicate interplay between early environment and the genetic envelop of an individual in determining adult hippocampal neurogenesis. Our experimental approach could thus contribute to the identification of factors determining the neurogenic potential of the adult hippocampus., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

The results of experiments performed, measuring the Lα x-rays emitted by Au due to excitation by photons of various energies from an (241)Am sample at forward-scattered angles in the range 0° to 65°, are compared to the predictions of the Monte Carlo code, PENELOPE. The experimental data are in good agreement with the predictions of the program. A comparison of the angular distributions of the probability densities (as predicted by the program) related to the Au Lα and Lβ x-rays suggests that PENELOPE does not simulate the phenomena described by Flügge et al. (1972)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: Excision repair cross-complementation group 1 (ERCC1) is a protein involved in repair of DNA platinum adducts and stalled DNA replication forks. We and others have previously shown the influence of ERCC1 expression upon survival rates and benefit of cisplatin-based chemotherapy in patients with resected non-small-cell lung cancer (NSCLC). However, little is known about the molecular characteristics of ERCC1-positive and ERCC1-negative tumors., Experimental Design: We took advantage of a cohort of 91 patients with resected NSCLC, for which we had matched frozen and paraffin-embedded samples to explore the comparative molecular portraits of ERCC1-positive and ERCC1-negative tumors of NSCLC. We carried out a global molecular analysis including assessment of ERCC1 expression levels by using both immunohistochemistry (IHC) and quantitative reverse transcriptase PCR (qRT-PCR), genomic instability, global gene and miRNA expression, and sequencing of selected key genes involved in lung carcinogenesis., Results: ERCC1 protein and mRNA expression were significantly correlated. However, we observed several cases with clear discrepancies. We noted that ERCC1-negative tumors had a higher rate of genomic abnormalities versus ERCC1-positive tumors. ERCC1-positive tumors seemed to share a common DNA damage response (DDR) phenotype with the overexpression of seven genes linked to DDR. The miRNA expression analysis identified miR-375 as significantly underexpressed in ERCC1-positive tumors., Conclusions: Our data show inconsistencies in ERCC1 expression between IHC and qRT-PCR readouts. Furthermore, ERCC1 status is not linked to specific mutational patterns or frequencies. Finally, ERCC1-negative tumors have a high rate of genomic aberrations that could consequently influence prognosis in patients with resected NSCLC., (©2011 AACR.)

Background: Physicians may avoid code status discussions for fear of decreasing patient or surrogate satisfaction., Methods: Charts of patients admitted to medical services at 6 university hospitals were reviewed for documentation of a code status discussion in the first 24 hours of admission. Satisfaction with care provided during the hospitalization was assessed by telephone 1 month after discharge., Results: Of the 11 717 patients with 1-month follow-up, 1090 (9.3%) had a code status discussion documented. Patient or surrogate satisfaction did not differ by whether a discussion was documented. The lack of association persisted after adjusting for patient's severity of illness and using propensity adjustment for likelihood of having a discussion., Conclusions: Discussing code status on admission to the inpatient setting did not affect patient or surrogate satisfaction.

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Aims: We assessed to what degree smokers who fail to quit on the target quit date (TQD) or lapse following TQD eventually achieve success with continued treatment., Design: A secondary analysis of pooled data of successful quitters treated with varenicline (306 of 696), bupropion (199 of 671) and placebo (121 of 685) from two identically-designed clinical trials of varenicline versus bupropion sustained-release and placebo., Setting: Multiple research centers in the US., Participants: Adult smokers (n==2052) randomized to 12 weeks drug treatment plus 40 weeks follow-up., Measurement: The primary end-point for the trials was continuous abstinence for weeks 9-12. TQD was day 8. Two patterns of successful quitting were identified. Immediate quitters (IQs) were continuously abstinent for weeks 2-12. Delayed quitters (DQs) smoked during 1 or more weeks for weeks 2-8., Findings: Cumulative continuous abstinence (IQs + DQs) increased for all treatments during weeks 3-8. Overall IQs and DQs for varenicline were (24%; 20%) versus bupropion (18.0%, P=0.007; 11.6%, P<0.001) or placebo (10.2%, P<0.001; 7.5%, P<0.001). However, DQs as a proportion of successful quitters was similar for all treatments (varenicline 45%; bupropion 39%; placebo 42%) and accounted for approximately one-third of those remaining continuously abstinent for weeks 9-52. No gender differences were observed by quit pattern. Post-treatment relapse was similar across groups., Conclusions: Our data support continuing cessation treatments without interruption for smokers motivated to remain in the quitting process despite lack of success early in the treatment., (© 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.)