Influence of measurement setting and home smoking policy on smoking topography

While cigarette puffing style, measured by smoking topography, is highly variable between individuals, smoking behavior or style tends to vary relatively little within individuals. Recent research has demonstrated that certain situational factors may produce variation in smoking topography, including location of smoking. Smoking topography directly observed by researchers in a laboratory may differ from that indirectly observed via portable measurement devices at participants' homes. The introduction of clean indoor air laws may also influence smokers' puffing styles, as smokers modify their smoking topography to ensure a quicker, more efficient smoking style. The goal of this analysis was to examine whether directly observed laboratory measures are representative of indirectly observed smoking behavior and to examine the influence of smokers' preference for indoor or outdoor home smoking on puffing style. Overall, participants smoked more intensively in the directly observed setting than when in the indirectly observed setting in terms of total volume intake, inter-puff interval, and total time spent smoking. This difference was most pronounced among individuals who reported smoking indoors when at home. The data suggest that adherence to an indoor home smoking policy may further influence an individual's smoking behavior.     

卡维地洛对中度心衰患者日常活动能力的影响

目的探讨卡维地洛对中度心衰患者日常活动能力的影响.方法选择6分钟步行试验距离在300～450m之间的心衰患者52例,分两组,均用常规心衰治疗,其中一组加用卡维地洛,稳态治疗6个月后再做6分钟步行试验.结果 6个月治疗后卡维地洛组的6分钟步行试验距离的增加大于对照组,具有统计学意义.结论卡维地洛能增加中度心衰患者日常活动能力.     

Bimanual anterior vitrectomy using a 25-gauge high-speed cutter to manage vitreous loss during phacoemulsification

We examined the usefulness of bimanual anterior vitrectomy with a 25-gauge high-speed cutter and infusion cannula for managing vitreous loss during phacoemulsification. Three eyes underwent phacoemulsification under topical anesthesia, during which, posterior capsule rupture occurred, resulting in vitreous loss and residual nuclear fragments. A 25-gauge high-speed cutter (2,500 cuts/min) and a 25-gauge infusion cannula were inserted into the 3 and 9 o’clock ports. Anterior vitrectomy was performed by employing a bimanual technique. A viscoelastic substance and infusion cannula prevented nuclear fragments from falling into the vitreous. The cutter allowed the easy excision of nuclear fragments and sharp excision of the vitreous. The vitreous incarcerated in the iris at 12 o’clock was removed by manipulating the cutter like a spatula. Bimanual anterior vitrectomy, using a 25-gauge high-speed cutter and infusion cannula, allows effective excision of the lost vitreous, while preserving a closed anterior chamber under topical anesthesia. Financial support: This study was financed by regular departmental research funds. No financial or material support was received from other sources. Proprietary interests: None of the authors have proprietary interests.     

Oral administration of TRAIL-inducing small molecule ONC201/TIC10 prevents intestinal polyposis in the Apcmin/+ mouse model

Colorectal cancer (CRC) incidence is rising globally. Hence, preventing this disease is a high priority. With this aim, we determined the CRC prevention potential of the TRAIL-inducing small molecule ONC201/TIC10 using a preclinical model representing high-risk familial adenomatous polyposis (FAP) patients, Apc ^min/+ mice. Prior to the efficacy study, optimal and non-toxic doses of ONC201 were determined by testing five different doses of ONC201 (0-100 mg/kg body weight (BW); twice weekly by oral gavage) in C57BL/6J mice (n=6/group) for 6 weeks. BW gain, organ weights and histopathology, blood profiling, and the plasma liver enzyme profile suggested no toxicities of ONC201 at doses up to 100 mg/kg BW. For efficacy determination, beginning at six weeks of age, groups of Apc ^min/+ male and female mice (n≥20) treated with colon carcinogen azoxymethane (AOM) (AOM-Apc ^min/+) were administered ONC201 (0, 25, and 50 mg/kg BW) as above up to 20 weeks of age. At termination, efficacy was determined by comparing the incidence and multiplicity of intestinal tumors between vehicle- and drug-treated groups. ONC201 showed a strong suppressive effect against the development of both large and small intestinal tumors in male and female mice. Apc ^min/+ mice treated with ONC201 (50 mg/kg BW) showed >50% less colonic tumor incidence (P<0.0002) than controls. Colonic tumor multiplicity was also significantly reduced by 68% in male mice (0.44 ± 0.11 in treated vs. 1.4 ± 0.14 in controls; P<0.0001) and by 75% in female mice (0.30 ± 0.10 in treated vs. 1.19 ± 0.19 in controls; P<0.0003) with ONC201 treatment (50 mg/kg BW). Small intestinal polyps were reduced by 68% in male mice (11.40 ± 1.19 in treated vs. 36.08 ± 2.62 in controls; P<0.0001) and female mice (9.65 ± 1.15 in treated vs. 29.24 ± 2.51 in controls; P<0.0001). Molecular analysis of the tumors suggested an increase in TRAIL, DR5, cleaved caspases 3/7/8, Fas-associated death domain protein (FADD), and p21 (WAF1) in response to drug treatment. Serum analysis indicated a decrease in pro-inflammatory serum biomarkers, such as IL1β, IL6, TNFα, G-CSF, and GM-CSF, in the ONC201-treated mice compared with controls. Our data demonstrated excellent chemopreventive potential of orally administered ONC201 against intestinal tumorigenesis in the AOM-Apc ^min/+ mouse model.