Electronic cigarettes: How confident and effective are allergists, pulmonologists, and primary care physicians in their practice behavior?

Background: There has been a striking increase in electronic cigarette (EC) use in the United States. The beliefs and practices toward ECs among physicians are unknown. Objective: The purpose of this study was to investigate EC practice patterns among allergists, pulmonologists, and primary care physicians. Methods: An anonymous survey was sent to physicians. The survey contained 32 questions and addressed issues related to demographics, cessation counseling behaviors, personal use, and knowledge and beliefs about ECs. Statistical analysis was performed by using analysis of variance, the Pearson χ² test, Fisher exact test, and logistic regression. Results: A total of 291 physicians completed the survey (222 primary care physicians, 33 pulmonologists, and 36 allergists) for a response rate of 46%. The allergists asked about tobacco cigarette use as frequently as did the pulmonologists and more than the primary care physicians (p < 0.001), but they rarely asked about EC use. The pulmonologists scored highest on self-reported knowledge on ECs, although all the groups answered <40% of the questions correctly. The allergists did not feel as comfortable about providing EC cessation counseling as did the pulmonologists and primary care physicians (p < 0.001). All three groups were equally unlikely to recommend ECs as a cessation tool for tobacco cigarette users. Conclusion: Allergists lacked knowledge and confidence in providing education and cessation counseling for EC users. As the number of patients who use these products continues to increase, there is an urgent need for all physicians to be comfortable and knowledgeable with counseling about ECs.

The Role of KIT Mutations in Anaphylaxis.

PURPOSE OF REVIEW: Gain of function KIT mutations are detected in clonal mast cell diseases, namely mastocytosis and monoclonal mast cell activation syndrome. Timely diagnosis and treatment of these disorders are crucial because of their association with severe and life-threatening anaphylaxis. KIT mutations also have implications for targeted therapies of mast cell disorders. This review article strives to serve as an overview of the role of clonal mast cell disorders in anaphylaxis while elucidating current and future therapies. RECENT FINDINGS: Clonal mast cell disease has been increasingly diagnosed in patients with severe hymenoptera allergy and those with recurrent unexplained anaphylaxis. The current state of knowledge of the epidemiology, pathophysiology, diagnosis, and treatment of mastocytosis with a particular focus on anaphylaxis and its triggers which are described in this context. Novel and forthcoming treatments are discussed including the relevance of KIT mutation status. This review provides an overview of the role of KIT mutations in mastocytosis and anaphylaxis, and highlights emerging therapies for mastocytosis, targeting these mutations.

Secondhand hookah smoke: an occupational hazard for hookah bar employees.

BACKGROUND: Despite the increasing popularity of hookah bars, there is a lack of research assessing the health effects of hookah smoke among employees. This study investigated indoor air quality in hookah bars and the health effects of secondhand hookah smoke on hookah bar workers. METHODS: Air samples were collected during the work shift of 10 workers in hookah bars in New York City (NYC). Air measurements of fine particulate matter (PM2.5), fine black carbon (BC2.5), carbon monoxide (CO), and nicotine were collected during each work shift. Blood pressure and heart rate, markers of active smoking and secondhand smoke exposure (exhaled CO and saliva cotinine levels), and selected inflammatory cytokines in blood (ineterleukin (IL)-1b, IL-6, IL-8, interferon γ (IFN-γ), tumour necrosis factor (TNF-α)) were assessed in workers immediately prior to and immediately after their work shift. RESULTS: The PM2.5 (gravimetric) and BC2.5 concentrations in indoor air varied greatly among the work shifts with mean levels of 363.8 µg/m3 and 2.2 µg/m3, respectively. The mean CO level was 12.9 ppm with a peak value of 22.5 ppm CO observed in one hookah bar. While heart rate was elevated by 6 bpm after occupational exposure, this change was not statistically significant. Levels of inflammatory cytokines in blood were all increased at postshift compared to preshift testing with IFN-Υ increasing from 0.85 (0.13) to 1.6 (0.25) (mean (standard error of the mean; SEM)) pg/mL (p<0.01). Exhaled CO levels were significantly elevated after the work shift with 2 of 10 workers having values >90 ppm exhaled CO. CONCLUSIONS: These results demonstrate that hookah bars have elevated concentrations of indoor air pollutants that appear to cause adverse health effects in employees. These data indicate the need for further research and a marked need for better air quality monitoring and policies in such establishments to improve the indoor air quality for workers and patrons.

Nursing Education to Reduce Use of Tobacco and Alternative Tobacco Products: Change Is Imperative.

BACKGROUND: Tobacco use continues to be the leading cause of preventable death worldwide. OBJECTIVE: To assess perceived tobacco educational preparation of undergraduate and graduate nurses in a large urban university. DESIGN: A cross-sectional web-based survey of all nursing students in an urban college of nursing was conducted to assess perceived tobacco educational content, skills, and self-efficacy for cessation counseling with patients who smoke cigarettes and use alternative tobacco products (e.g., hookah and e-cigarettes). RESULTS: Participants reported the most education about health effects of tobacco use (67%), and less than 6% reported education about alternative tobacco products. While the majority of nurses agreed that advising patients to quit is a priority, less than 40% reported receiving sufficient training in cessation counseling. CONCLUSIONS: There continues to be a compelling need articulated by leaders in tobacco policy and research over the past decade for a more vigorous response by nurses to the tobacco epidemic.

Knowledge, Beliefs, Behaviors, and Social Norms Related to Use of Alternative Tobacco Products Among Undergraduate and Graduate Nursing Students in an Urban U.S. University Setting.

PURPOSE: The purpose of the study was to assess nursing students' knowledge, beliefs, behaviors, and social norms regarding use of alternative tobacco products (ATPs). DESIGN AND METHODS: This anonymous online survey was conducted with all students enrolled in a college of nursing. The survey utilized measures from several national tobacco studies to assess knowledge and beliefs about ATPs (hookahs, cigars or cigarillos, bidis, kreteks, smokeless tobacco, electronic cigarettes) compared to cigarettes, health effects of ATPs, personal use of ATPs, and social norms. Data were analyzed in SPSS 22.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics and frequencies were performed for basic sociodemographic data. Paired samples t tests were performed to determine differences for scaled measures. FINDINGS: Nursing students demonstrated very low levels of knowledge about ATPs and their health consequences, despite high rates of ATP personal use. About 76% of participants reported use of one or more ATPs once or more in their lifetimes. A greater proportion of students had used hookahs or waterpipes (39.6%) compared to cigarettes (32.7%). CONCLUSIONS: Nurses' lack of knowledge about the emerging use and health threats associated with ATPs may undermine their ability to provide appropriate tobacco cessation counseling. Research is needed to identify gaps in nurses' education regarding tobacco cessation counseling and to develop new counseling approaches specific to use of ATPs. CLINICAL RELEVANCE: Nurses play critical roles in counseling their patients for tobacco cessation. Further research and education about the risks presented by ATPs are critical to reducing excess tobacco-related mortality.

Perception of e-cigarette harm and its correlation with use among U.S. adolescents.

INTRODUCTION: U.S. adolescents increasingly use e-cigarettes. The perceived harm of e-cigarettes has not been described, nor has the correlation between harm perception and e-cigarette use been assessed. This study examines correlates of e-cigarette harm perception and use of e-cigarettes in a national survey. METHODS: We used cross-sectional nationally representative data from the 2012 National Youth Tobacco Survey (n = 24,658). Cross-tabulations and multivariate ordered probit and logistic regression models were employed to assess relative harm perception and e-cigarette use. RESULTS: Half of U.S. adolescents had heard of e-cigarettes. Of these, 13.2% (95% confidence interval [CI] = 11.7-14.9) and 4.0% (95% CI = 3.4-4.7) reported ever or currently using e-cigarettes, respectively. Of those aware of e-cigarettes, 34.2% (95% CI = 32.8-35.6) believed e-cigarettes were less harmful than cigarettes. Among those trying e-cigarettes, 71.8% (95% CI = 69.0-74.5) believed e-cigarettes were comparatively less harmful. Females and those ≥ 17 years old were more likely to perceive e-cigarettes as more harmful relative to cigarettes, while on average Whites, users of other tobacco products, and those with family members who used tobacco were more likely to perceive e-cigarettes as comparatively safer. Among cigarette-naive e-cigarette users, use of other tobacco products and perceived harm reduction by e-cigarettes were, respectively, on average associated with 1.6 and 4.1 percentage-point increases in e-cigarette use. CONCLUSIONS: Perception of e-cigarettes as less harmful than conventional cigarettes was associated with increased e-cigarette use, including among cigarette-naive e-cigarette users. These findings should prompt further scientific investigation and merit attention from regulators.

Air quality in New York City hookah bars.

BACKGROUND: Hookahs are increasingly being used in the USA and elsewhere. Despite the popularity of hookah bars, there is a paucity of research assessing the health effects of hookah smoke, and although New York City (NYC) bans indoor tobacco smoking, hookah lounges claim that they only use herbal products without tobacco. This study investigated levels of multiple indices of indoor air pollution in hookah bars in NYC. METHODS: Air samples were collected in 8 hookah bars in NYC. Along with venue characteristics, real-time measurements of fine particulate matter (PM2.5), black carbon (BC), and carbon monoxide (CO), and total gravimetric PM, elemental carbon (EC), organic carbon (OC), and nicotine were collected in 1-2 hour sessions. RESULTS: Overall, levels of indoor air pollution increased with increasing numbers of active hookahs smoked. The mean (SD) real time PM2.5 level was 1179.9 (939.4) µg/m(3), whereas the filter-based total PM mean was 691.3 (592.6) µg/m(3). The mean real time BC level was 4.1 (2.3) µg/m(3), OC was 237.9 (112.3) µg/m(3), and CO was 32 (16) ppm. Airborne nicotine was present in all studied hookah bars (4.2 (1.5) µg/m(3)). CONCLUSIONS: These results demonstrate that despite the ban on smoking tobacco products, at the very least, some NYC hookah bars are serving tobacco-based hookahs, and have elevated concentrations of indoor air pollutants that may present a health threat to visitors and employees. Therefore, there is an urgent need for better air quality monitoring in such establishments and policies to combat this emerging public health threat.

Single neonatal estrogen implant sterilizes female animals by decreasing hypothalamic KISS1 expression.

Reproductive sterilization by surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive behaviors and diseases. This study explored the use of a single-injection method to induce sterility in female animals as an alternative to surgical ovariohysterectomy. The idea was based on our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin (KISS1), the neuropeptide that triggers and regulates pulsatile secretion of GnRH. Neonatal female rats were dosed with estradiol benzoate (EB) either by daily injections for 11 days or by subcutaneous implantation of an EB-containing silicone capsule designed to release EB over 2-3 weeks. Rats treated by either method did not exhibit estrous cyclicity, were anovulatory, and became infertile. The EB-treated rats had fewer hypothalamic Kisspeptin neurons, but the GnRH-LH axis remained responsive to Kisspeptin stimulation. Because it would be desirable to use a biodegradable carrier that is also easier to handle, an injectable EB carrier was developed from PLGA microspheres to provide pharmacokinetics comparable to the EB-containing silicone capsule. A single neonatal injection of EB-microspheres at an equivalent dosage resulted in sterility in the female rat. In neonatal female Beagle dogs, implantation of an EB-containing silicone capsule also reduced ovarian follicle development and significantly inhibited KISS1 expression in the hypothalamus. None of the treatments produced any concerning health effects, other than infertility. Therefore, further development of this technology for sterilization in domestic female animals, such as dogs and cats is worthy of investigation.

The Performance of the Semigeneralized Partial Credit Model for Handling Item-Level Missingness.

The semi-generalized partial credit model (Semi-GPCM) has been proposed as a unidimensional modeling method for handling not applicable scale responses and neutral scale responses, and it has been suggested that the model may be of use in handling missing data in scale items. The purpose of this study is to evaluate the ability of the unidimensional Semi-GPCM to aid in the recovery of person parameters from item response data in the presence of item-level missingness, and to compare the performance of the model with two other proposed methods for handling such missingness: a multidimensional modeling approach for missingness and full information maximum likelihood estimation. The results indicate that the Semi-GPCM performs acceptably in an absolute sense when less than 30% of the item data is missing but does not outperform the other two methods under any particular conditions. We conclude with a discussion about when practitioners may or may not want to use the Semi-GPCM to recover person parameters from item response data with missingness.

Progesterone Receptor Serves the Ovary as a Trigger of Ovulation and a Terminator of Inflammation.

Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2), in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here, we show that the PGR plays an additional essential role: it attenuates ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the nuclear factor κB (NF-κB), a transcription factor required for Ptgs2 expression. When the expression of PGR is ablated in granulosa cells, the ovary undergoes a hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. The PGR-driven termination of PTGS2 expression may protect the ovary from ovulatory inflammation.

Germline-dependent transmission of male reproductive traits induced by an endocrine disruptor, di-2-ethylhexyl phthalate, in future generations.

In males, defective reproductive traits induced by an exposure to an endocrine disruptor are transmitted to future generations via epigenetic modification of the germ cells. Interestingly, the impacted future generations display a wide range of heterogeneity in their reproductive traits. In this study, the role that the Y chromosome plays in creating such heterogeneity is explored by testing the hypothesis that the Y chromosome serves as a carrier of the exposure impact to future generations. This hypothesis implies that a male who has a Y chromosome that is from a male that was exposed to an endocrine disruptor will display a more severe reproductive phenotype than a male whose Y chromosome is from an unexposed male. To test this hypothesis, we used a mouse model in which F1 generation animals were exposed prenatally to an endocrine disruptor, di-2-ethylhexyl phthalate (DEHP), and the severity of impacted reproductive traits was compared between the F3 generation males that were descendants of F1 males (paternal lineage) and those from F1 females (maternal lineage). Pregnant dams (F0 generation) were exposed to the vehicle or 20 or 200 µg/kg/day of DEHP from gestation day 11 until birth. Paternal lineage F3 DEHP males exhibited decreased fertility, testicular steroidogenic capacity, and spermatogenesis that were more severely impaired than those of maternal lineage males. Indeed, testicular transcriptome analysis found that a number of Y chromosomal genes had altered expression patterns in the paternal lineage males. This transgenerational difference in the DEHP impact can be attributed specifically to the Y chromosome.

Curcumin prevents the oxidation and lipid modification of LDL and its inhibition of prostacyclin generation by endothelial cells in culture.

Low-density lipoprotein (LDL) was isolated from human plasma and oxidized by 5microM copper sulfate for 4h at 37 degrees C in the absence and presence of 1, 3, 5, 10, or 20microM of curcumin. LDL oxidized in the absence of curcumin (oxLDL) showed an increased levels of conjugated dienes, lipid peroxides (TBARS) and lysolecithin (lysoPC) and a significant loss of polyunsaturated fatty acids (PUFA). LDL oxidized with 5microM copper sulfate in the presence of curcumin caused a significant decrease of conjugated diene, lipid peroxides, lysoPC and significant increase of PUFA compared to oxLDL. These changes were dose dependent and reached a maximum at 5microM curcumin. Incubation of human endothelial cells (EC) with 200microg protein/ml of oxLDL caused a significant decrease of prostacyclin (PGI(2)) generation. LDL oxidized in presence of 5microM curcumin did not show any inhibition of PGI(2) generation compared to the control cells. These results indicate that curcumin is an effective chain-breaking antioxidant which prevents oxidation and lipid modification of LDL. The inhibition of oxLDL on PGI(2) is considered a contributing factor in the pathogenesis of thrombosis and atherosclerosis. Curcumin supplementation could be an effective strategy in preventing LDL oxidation and its impact on atherosclerosis and lesion formation.

Vitamin B6 compounds are capable of reducing the superoxide radical and lipid peroxide levels induced by H2O2 in vascular endothelial cells in culture.

Pyridoxamine, pyridoxine, and pyridoxal phosphate were tested to examine if they have antioxidant properties. Endothelial cells exposed to 0.5 mM H(2)O(2) for 2 hours increased the superoxide anion and lipid peroxide levels as biomarkers of oxidative stress. The increase of superoxide was mainly due to the activation of NADPH-oxidase by H(2)O(2). Preincubation of the endothelial cells with 0.1 or 1.0 mM of pyridoxamine or pyridoxal phosphate for one-half hour before H(2)O(2) exposure significantly reduced the superoxide and lipid peroxide compared to the cells exposed to H(2)O(2) only. Preincubation of the cells with 0.1 or 1.0 mM of pyridoxine also significantly reduced the lipid peroxide but did not significantly affect the superoxide level unless the preincubation time was extended to 24 hours. The prostacyclin release by endothelial cells was also significantly inhibited by H(2)O(2). However, the preincubation of endothelial cells with 1.0 mM of pyridoxamine, pyridoxine, or pyridoxal phosphate did not prevent that inhibition. These results indicate that pyridoxamine, pyridoxine, and pyridoxal phosphate acted as antioxidants and reduced the superoxide and lipid peroxides induced by H(2)O(2), but did not protect the cells from the effects directly related to H(2)O(2) itself.

Sanitary pads and diapers contain higher phthalate contents than those in common commercial plastic products.

Sanitary pads and diapers are made of synthetic plastic materials that can potentially be released while being used. This study measured the amounts of volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) and phthalates (DBP, DEHP, DEP, and BBP) contained in sanitary pads and diapers. In sanitary pads, 5,900- and 130-fold differences of VOC and phthalate concentrations were seen among the brands. In the diapers, 3- and 63-fold differences of VOC and phthalate concentrations were detected among the brands. VOC concentrations from the sanitary pads and diapers were similar to that of the residential air. However, phthalate concentrations of sanitary pads and diapers were significantly higher than those found in common commercial plastic products. As sanitary pads and diapers are in direct contact with external genitalia for an extended period, there is a probability that a considerable amount of VOCs or phthalates could be absorbed into the reproductive system.

Structural basis for the docking of mTORC1 on the lysosomal surface.

The mTORC1 (mechanistic target of rapamycin complex 1) protein kinase regulates growth in response to nutrients and growth factors. Nutrients promote its translocation to the lysosomal surface, where its Raptor subunit interacts with the Rag guanosine triphosphatase (GTPase)-Ragulator complex. Nutrients switch the heterodimeric Rag GTPases among four different nucleotide-binding states, only one of which (RagA/B•GTP-RagC/D•GDP) permits mTORC1 association. We used cryo-electron microscopy to determine the structure of the supercomplex of Raptor with Rag-Ragulator at a resolution of 3.2 angstroms. Our findings indicate that the Raptor α-solenoid directly detects the nucleotide state of RagA while the Raptor "claw" threads between the GTPase domains to detect that of RagC. Mutations that disrupted Rag-Raptor binding inhibited mTORC1 lysosomal localization and signaling. By comparison with a structure of mTORC1 bound to its activator Rheb, we developed a model of active mTORC1 docked on the lysosome.

A case of paraneoplastic cerebellar ataxia secondary to renal cell carcinoma.

A 64-year-old female patient presented with acute cerebellar ataxia. After ruling out vascular, infectious, metastatic, demyelinating, and medication etiologies, a paraneoplastic origin for her illness was determined. A renal mass was discovered and found to be renal cell carcinoma. Her symptoms resolved after a radical nephrectomy. Physicians should consider the diagnosis of paraneoplastic neurologic syndromes whenever a thorough evaluation fails to explain neurologic abnormalities.

An Integrated Double-Filtration Microfluidic Device for Detection of Extracellular Vesicles from Urine for Bladder Cancer Diagnosis.

Extracellular vesicles (EVs) are present in a variety of bodily fluids and they play an important role in cellular communications and signal transduction mechanisms. Studies have shown that the number of EVs and EV-associated biomarkers (i.e., proteins, nucleic acids and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for EV isolation, it is not practical for clinical settings. Here, we developed an integrated double-filtration device that isolated and enriched EVs from urine, and subsequently detected/quantified EVs from urine via microchip ELISA. Results showed that the concentration of EVs was significantly elevated compared to healthy controls. Receiver operating characteristic analysis demonstrated that this integrated EV quantification device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and eight healthy controls). Thus, this integrated device shows great potential to supplement urine cytology for diagnosis of bladder cancer in point-of-care (POC) settings.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer.

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30-200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings.

A Study of the Use, Knowledge, and Beliefs About Cigarettes and Alternative Tobacco Products Among Students at One U.S. Medical School.

PURPOSE: In the United States, the prevalence of the use of alternative tobacco products (ATPs) (e.g., hookahs, e-cigarettes, cigars/cigarillos) has increased sharply. As future health care providers, medical students will play a critical role in health promotion and disease prevention. This study investigated medical students' use, knowledge, and beliefs about cigarettes and ATPs. METHOD: In 2014, the authors surveyed all students enrolled at one medical school in New York City. The survey included questions about personal use of tobacco products, perceptions about the harms of ATPs and their role in disease causation, education about ATPs, and cessation training and practices related to ATPs and cigarettes. The authors compared results across medical school classes. RESULTS: Of 720 students, 431 (59.9%) completed the survey. Of those, 64 (14.7%) were current users of tobacco or smoking products, including cigarettes (17; 3.9%), ATPs (21; 4.8%), or marijuana (39; 8.9%). Many believed that ATPs contributed less than cigarettes to various diseases. Respondents received less cessation training regarding ATPs than cigarettes (P < .0001). They felt less confident providing ATP cessation counseling than cigarette cessation counseling (P < .0001) and were less likely to report counseling patients on ATP cessation than cigarette cessation (46 [10.7%] versus 280 [64.8%], P < .0001). CONCLUSIONS: A concerning percentage of surveyed medical students use tobacco products, including ATPs, and lack the knowledge, education, and cessation counseling skills to provide accurate information about them to patients. ATP education should be added to medical school curricula to address this gap.