Preoperative smoking cessation program in patients undergoing intermediate to high-risk surgery: a randomized, single-blinded, controlled, superiority trial

BACKGROUND At present, effectively implementing smoking cessation programs in the health care system constitutes a major challenge. A unique opportunity to initiate smoking cessation focuses on smokers scheduled for surgery. These patients are not only highly motivated to quit smoking but also likely to benefit from a reduction in postoperative complications which may translate into a decrease of costs. Nevertheless, surgical patients are not routinely informed about the benefits of preoperative smoking cessation. Potential reasons for this missed opportunity may be the lack of time and training of surgeons and anaesthesiologists. We therefore aim to analyse the impact of a preoperative high-intensity smoking cessation intervention on surgical complications up to a 90-day postoperative period in patients of various surgical disciplines. The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing intermediate to high-risk surgery. METHODS The present study is a single-centre, randomized trial with two parallel groups of smokers scheduled for surgery comparing surgery alone and surgery with preoperative smoking cessation. We plan to randomize 251 patients. The primary objective is to compare complications between patients with an institutional multifaceted smoking cessation intervention starting 4 weeks before surgery compared to patients in the advice-only group (control group) within a 90-day postoperative period. The primary endpoint is the Comprehensive Complication Index (CCI®) within 90 days of surgery. Secondary outcomes include the length of hospital stay, cost of care, quality of life, smoking abstinence, and reduction in nicotine consumption. DISCUSSION The hypothesis is that a preoperative smoking cessation program improves outcomes in smokers undergoing surgery. TRIAL REGISTRATION BASEC #2021-02004; ClinicalTrials.gov: NCT05192837 . Registered on January 14, 2022

Transcriptional activity of the 5′-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines

Thyroid transcription factor-1 (TTF-1, NKX2-1) is a homeodomain-containing transcriptional factor that binds to and activates the promoters of thyroid and lung-specific genes, such as thyroglobulin, thyroid peroxidase, and thyroid stimulating hormone receptor. TTF-1 is known to play a key role in the development of the thyroid. However, the precise mechanism of TTF-1 gene transcription in human thyroid cells has not been studied. The expression of transcriptional activity in various lengths of the 5′-flanking region of the human TTF -1 gene was studied in TTF-1 positive and negative human thyroid cell lines. Increased transcriptional activity was observed in thyroid cell lines containing plasmids that coded for a sequence proximal to the transcription start site of exon 1 of the TTF-1 gene. However, we did not observe any difference in promoter activity in the region up to −2.6 kb from the proximal transcription start site of the TTF-1 gene between TTF-1 positive and negative cells. These results suggest that the proximal 5′-flanking region of the human TTF -1 gene does not contain sufficient cis-active regulatory information to direct gene expression in thyroid cells, and that other cis- or trans-acting factors participate in the thyroid specific gene expression of TTF-1

Nitrogen Oxides and Ozone in the Tropopause Region of the Northern Hemisphere: Measurements from Commercial Aircraft in 1995/96 and 1997

Measurements of nitrogen oxides (NO and NO2) and ozone (O3) were performed from a Swissair B-747 passenger aircraft in two extended time periods (May 1995 to May 1996, August to November 1997) in the framework of the Swiss NOXAR and the European POLINAT 2 project. The measurements were obtained on a total of 623 flights between Europe and destinations in the United States and the Far East. NO2 measurements were obtained only after December 1995 and were less precise than the NO measurements. Therefore daytime NO2 values were derived from measured NO and O3 concentrations assuming photostationary equilibrium. The completed NOx data set (measured NO, measured NO2 during night, and calculated NO2 during day) includes a complete annual cycle and is the most extensive and representative data set currently available for the upper troposphere (UT) and the lower stratosphere (LS) covering a significant proportion of the northern hemisphere between 15°N and 65°N. NOx concentrations in midlatitudes (30°−60°N) showed a marked seasonal variation both in the UT and the LS with a maximum in summer (median/mean values of 159/264 pptv in UT, 199/237 pptv in LS) and a minimum in winter (51/99 pptv in UT, 67/91 pptv in LS). Mean NOx concentrations were generally much higher than the respective median values, in particular in the UT, which reflects the important contribution from comparatively few very high concentrations observed in large-scale convection/lightning and small-scale aircraft plumes. Seasonal mean NOx concentrations in the UT were up to 3–4 times higher over continental regions than over the North Atlantic during summer. Lightning production of NO and convective vertical transport from the polluted boundary layer thus appear to have dominated the upper tropospheric NOx budget over these continental regions, particularly during summer. Ozone concentrations at aircraft cruising levels typically varied by an order of magnitude due to the strong vertical gradient in the LS. Seasonal mean values were dominated by large-scale dynamical processes controlling the altitude of the tropopause and the O3 abundance in the LS. O3 in the UT in midlatitudes showed a broad maximum between June and August, typical of observations in the free troposphere

The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.

Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically, we show that after immunization of mice with protein, the miRNA cluster miR-17∼92 was critical for robust differentiation and function of TFH cells in a cell-intrinsic manner that occurred regardless of changes in proliferation. In a viral infection model, miR-17∼92 restrained the expression of genes 'inappropriate' to the TFH cell subset, including the direct miR-17∼92 target Rora. Removal of one Rora allele partially 'rescued' the inappropriate gene signature in miR-17∼92-deficient TFH cells. Our results identify the miR-17∼92 cluster as a critical regulator of T cell-dependent antibody responses, TFH cell differentiation and the fidelity of the TFH cell gene-expression program