The effects of electronic cigarette smoking in adolescents

Electronic nicotine delivery systems (ENDS), or electronic cigarettes (e-cigarettes), are battery-powered handheld devices designed to aerosolize a solution of nicotine and other chemicals for inhalation. The specific mechanical and chemical features of different ENDS affect the systemic exposure and bioavailability of the different chemicals in e-juices. E-cigarettes can come with different cartridge sizes, power outputs, e-liquid constituents, and nicotine delivery. User puff topography also contributes to varying toxicant exposure. ENDS have demonstrated potential as a cessation tool or alternative cigarette product due to its safety profile relative to the combustible cigarette. E-cigarettes have significantly lower concentrations of biomarkers of tobacco-related toxicant exposure and produce less and less harmful second-hand smoke compared to CC. However, ENDS users have significantly greater concentrations of those same biomarkers, highlighting that e-cigarettes do pose a harm to users’ health, even if that may be lower than CC. The same is observed in e-cigarette second-hand smoke as nicotine and aerosol particles were detected in statistically significant amounts. Its toxicity is only amplified by the misconception that they are safer than CC and thus pose no absolute risk, misleading users to use without caution. Therefore, although ENDS do have the potential in reducing smoking in adults who are already addicted to nicotine, it comes with the risk of dual use of conventional and electronic cigarettes and of attracting non-smokers, especially as seen in the youth. The rise in adolescent e-cigarette use can be attributed to its appeal, of both its flavored e-liquids and its image amongst youth that is perpetuated through the intentional marketing of e-cigarette manufacturers. The latent consequences of e-cigarettes are compounded in adolescents, who are in critical stages of brain development, habit formation, and social development. Youth report having experienced short-term clinical symptoms such as cough, lightheadedness, headache, and shortness of breath. Physiologically, vaping has been found to affect the pulmonary and cardiovascular systems. Vaping alters the equilibrium of the mucociliary clearance system in the pulmonary system and increases the risk of chronic bronchitis, cough, and phlegm. There is increased in pro-inflammatory cytokine secretions, increased alveolar macrophage apoptosis, impairment of phagocytosis, decreased ciliary beating, inhibition of the CFTR channel, and increased mucin expression. In the cardiovascular system, e-cigarette aerosol extract alters angiogenesis, oxidative stress, endothelial dysfunction, sympathetic nerve system activation, platelet activation and anticoagulation inhibition, and cardiac remodeling. E-cigarettes and e-cigarette smoke have also been associated with carcinogenesis in lung epithelium and possibly urothelium. Although e-cigarettes have, on average, less nicotine compared to CC, the significant risk for adolescents to graduate to combustible cigarettes renders this moot. The factors influencing this graduation is modeled through the catalyst model, which details the transition from ‘no use’ to ‘e-cigarette use’ and the transition from ‘e-cigarette use’ to ‘tobacco use.’ Schneider and Diehl hypothesized that the first transition is facilitated through a variety of factors, including flavor, health, price, role models, concealment, and acceptance. The subsequent transition can be attributed to the addiction hypothesis, accessibility hypothesis, and the experience hypothesis. It is clear from the numerous studies conducted, which show students who used e-cigarettes were 4-7 times more likely to report CC use, that e-cigarettes play a catalytic role in enabling the transition to conventional cigarettes. And with increased nicotine exposure, adolescents are subject to impairments in working and verbal memory during abstinence, changes in drug sensitivity and reward-related manifestations in adulthood, more severe dependence during adolescence, and deficits in attentional performance, impaired serial pattern learning, impaired context conditioning and increased anxiety and depressive-like behaviors in adults. They also have reduced control of motivation, reward, and pleasure. This culminates to the gateway hypothesis which states that nicotine can serve as a gateway drug that lowers the youths’ threshold for addiction to opioids, alcohol, and other agents. Recently, there has been a dramatic increase in cases of EVALI or e-cigarette or vaping associated lung injury, particularly in the adolescent population that is more likely to use illicit e-cigarettes than their adult counterparts. EVALI presents with a wide range of respiratory, gastrointestinal, and constitutional symptoms and is characterized as a sterile exogenous pneumonitis-like reaction with variable degrees of diffuse alveolar damage. Vitamin E acetate, common in illicit products, is strongly linked to this outbreak due to its presence in a vast majority of bronchoalveolar lavage fluid samples of confirmed EVALI cases. As ENDS use has increased amongst adolescents, so have its latent consequences. A coordinated effort from policy makers, public health agencies, healthcare providers, researchers, and especially parents and educators is essential for successful protection of this vulnerable population

Smartphone-based pathogen diagnosis in urinary sepsis patients.

BackgroundThere is an urgent need for rapid, sensitive, and affordable diagnostics for microbial infections at the point-of-care. Although a number of innovative systems have been reported that transform mobile phones into potential diagnostic tools, the translational challenge to clinical diagnostics remains a significant hurdle to overcome.MethodsA smartphone-based real-time loop-mediated isothermal amplification (smaRT-LAMP) system was developed for pathogen ID in urinary sepsis patients. The free, custom-built mobile phone app allows the phone to serve as a stand-alone device for quantitative diagnostics, allowing the determination of genome copy-number of bacterial pathogens in real time.FindingsA head-to-head comparative bacterial analysis of urine from sepsis patients revealed that the performance of smaRT-LAMP matched that of clinical diagnostics at the admitting hospital in a fraction of the time (~1 h vs. 18-28 h). Among patients with bacteremic complications of their urinary sepsis, pathogen ID from the urine matched that from the blood - potentially allowing pathogen diagnosis shortly after hospital admission. Additionally, smaRT-LAMP did not exhibit false positives in sepsis patients with clinically negative urine cultures.InterpretationThe smaRT-LAMP system is effective against diverse Gram-negative and -positive pathogens and biological specimens, costs less than $100 US to fabricate (in addition to the smartphone), and is configurable for the simultaneous detection of multiple pathogens. SmaRT-LAMP thus offers the potential to deliver rapid diagnosis and treatment of urinary tract infections and urinary sepsis with a simple test that can be performed at low cost at the point-of-care. FUND: National Institutes of Health, Chan-Zuckerberg Biohub, Bill and Melinda Gates Foundation

Place preference induced by nucleus accumbens amphetamine is impaired by local blockade of Group II metabotropic glutamate receptors in rats

BACKGROUND: The nucleus accumbens (NAc) plays a critical role in amphetamine-produced conditioned place preference (CPP). In previous studies, NAc basal and amphetamine-produced DA transmission was altered by Group II mGluR agents. We tested whether NAc amphetamine CPP depends on Group II mGluR transmission. RESULTS: NAc injections (0.5 μl/side) of the Group II mGluR antagonist (2 S)- a-ethylglutamic acid (EGLU: 0.01–0.8 μg but not 0.001 μg) impaired CPP. The drug did not block the acute locomotor effect of amphetamine. CONCLUSION: Results suggest that Group II mGluRs may be necessary for the establishment of NAc amphetamine-produced CPP. These receptors may also mediate other forms of reward-related learning dependent on this structure

Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia

The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLAmatched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P <_ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P <_ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (<_18 months; HR, 1.93; P < .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P < .001) and grade 3 to 4 aGVHD (HR, 1.97; P < .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission

Characterizing Acupuncture Stimuli Using Brain Imaging with fMRI - A Systematic Review and Meta-Analysis of the Literature

Background The mechanisms of action underlying acupuncture, including acupuncture point specificity, are not well understood. In the previous decade, an increasing number of studies have applied fMRI to investigate brain response to acupuncture stimulation. Our aim was to provide a systematic overview of acupuncture fMRI research considering the following aspects: 1) differences between verum and sham acupuncture, 2) differences due to various methods of acupuncture manipulation, 3) differences between patients and healthy volunteers, 4) differences between different acupuncture points. Methodology/Principal Findings We systematically searched English, Chinese, Korean and Japanese databases for literature published from the earliest available up until September 2009, without any language restrictions. We included all studies using fMRI to investigate the effect of acupuncture on the human brain (at least one group that received needle-based acupuncture). 779 papers were identified, 149 met the inclusion criteria for the descriptive analysis, and 34 were eligible for the meta-analyses. From a descriptive perspective, multiple studies reported that acupuncture modulates activity within specific brain areas, including somatosensory cortices, limbic system, basal ganglia, brain stem, and cerebellum. Meta-analyses for verum acupuncture stimuli confirmed brain activity within many of the regions mentioned above. Differences between verum and sham acupuncture were noted in brain response in middle cingulate, while some heterogeneity was noted for other regions depending on how such meta-analyses were performed, such as sensorimotor cortices, limbic regions, and cerebellum. Conclusions Brain response to acupuncture stimuli encompasses a broad network of regions consistent with not just somatosensory, but also affective and cognitive processing. While the results were heterogeneous, from a descriptive perspective most studies suggest that acupuncture can modulate the activity within specific brain areas, and the evidence based on meta-analyses confirmed some of these results. More high quality studies with more transparent methodology are needed to improve the consistency amongst different studies

Activation of NF-κB by R5 and X4 Human Immunodeficiency Virus Type 1 Induces Macrophage Inflammatory Protein 1α and Tumor Necrosis Factor Alpha in Macrophages

NF-κB is a transcriptional activator that often regulates inflammatory responses. We demonstrate that human immunodeficiency virus type 1 activates nuclear localization of NF-κB in macrophages in a manner dependent upon virus strain but independent of virus replication. Through the use of an inhibitor, NF-κB activation was found to be responsible for the cytokine and chemokine induction that we recently reported

A circuit from the locus coeruleus to the anterior cingulate cortex modulates offspring interactions in mice

Summary: Social sensitivity to other individuals in distress is crucial for survival. The anterior cingulate cortex (ACC) is a structure involved in making behavioral choices and is influenced by observed pain or distress. Nevertheless, our understanding of the neural circuitry underlying this sensitivity is incomplete. Here, we reveal unexpected sex-dependent activation of ACC when parental mice respond to distressed pups by returning them to the nest (“pup retrieval”). We observe sex differences in the interactions between excitatory and inhibitory ACC neurons during parental care, and inactivation of ACC excitatory neurons increased pup neglect. Locus coeruleus (LC) releases noradrenaline in ACC during pup retrieval, and inactivation of the LC-ACC pathway disrupts parental care. We conclude that ACC maintains sex-dependent sensitivity to pup distress under LC modulation. We propose that ACC’s involvement in parenting presents an opportunity to identify neural circuits that support sensitivity to the emotional distress of others

Heavy Metals in California Women Living in a Gold Mining-Impacted Community

Gold mining activities occurred throughout the foothills of the Sierra Nevada Mountains in California, leaving behind persistent toxic contaminants in the soil, dust, and water that include arsenic and cadmium. Despite a high level of concern among local residents about potential exposure and high breast cancer rates, no biomonitoring data has been collected to evaluate the levels of heavy metals. We conducted a study to characterize the urinary levels of heavy metals among women in this region by working with the community in Nevada County. Sixty women provided urine samples and completed a questionnaire. We examined levels of arsenic, cadmium, and other metals in relation to the length of residency in the area, age, dietary factors, recreational activities, and smoking. We compared urinary metal levels in participants to levels in the United States National Health and Nutrition Examination Survey (NHANES). Overall, study participants had higher urinary levels of arsenic than women in the national sample. Cadmium levels were similar to the national average, although they were elevated in women &ge;35 years who had lived in the region for 10 years or more. Arsenic levels were higher among women who smoked, ate fish, ate home-grown produce, and who reported frequent hiking or trail running, although these differences were not statistically significant. This study established a successful community&ndash;research partnership, which facilitated community dialogue about possible human health consequences of living in a mining-impacted area

Airway inflammatory cell responses to intra-amniotic lipopolysaccharide in a sheep model of chorioamnionitis

Chorioamnionitis, a risk factor for bronchopulmonary dysplasia in preterm infants, causes an influx of inflammatory cells into the fetal lung. Using a fetal sheep model, we evaluated the time course of activation, functional maturity, and apoptosis of the leukocytes recruited to the fetal air spaces by lipopolysaccharide (LPS). Time-mated sheep were given intra-amniotic injections with 10 mg of Escherichia coli LPS or saline 2 or 7 days before preterm delivery at 124 days of gestation (term is 150 days). Both neutrophils and monocytes in bronchoalveolar lavage fluid (BALF) had activated NF-κB after 2- and 7-day LPS exposures. These neutrophils and monocytes expressed the activation factor CD11b and the maturation factor PU.1 at 2 days, and increased PU.1 expression was detected in macrophages at 7 days. Leukocyte oxidative burst activity was greatest at 7 days. BALF lipid peroxidation increased fivefold at 2 days, while protein carbonyls increased eightfold at 7 days. Nitrative stress was not detected in the BALF, but leukocytes in the lung expressed nitric oxide synthase (NOS)II (inducible NOS). BALF leukocytes expressed the antioxidant peroxiredoxin V. Lung glutathione peroxidase was also increased with LPS exposure. There was minimal apoptosis of airway and lung leukocytes assessed by caspase-3 activation. Intra-amniotic LPS recruits leukocytes to the fetal air space that have a persistent activation. These results have implications for the pathogenesis of lung inflammatory disorders in the preterm