Does offering small financial incentives to smokers at the time of being wait-listed for surgery increase smoking cessation by the day of surgery? A randomised feasibility trial.

OBJECTIVE: This study aims to assess whether offering small financial incentives to smokers on elective surgery wait-lists is feasible and increases quitting before surgery. DESIGN: Randomised controlled trial, prospective, double-blinded. SETTING: Single-centre, Australian metropolitan public hospital. PARTICIPANTS: 620 adult smokers (≥10 cigarettes per day) were randomised on being wait-listed for elective surgery and 404 underwent operations (28 January 2021-31 July 2022) at the hospital (65.2%) by trial's end. INTERVENTION: Intervention participants were offered at wait-listing an $A70 supermarket voucher for verified abstinence on the day of surgery, provided they registered an intention to quit before surgery. Registrants intending to quit were also referred to Quitline. Neither intervention was offered to control participants (usual care). Smokers wait-listed from 17 May 2021 were offered an increased incentive of $A140. MAIN OUTCOME MEASURES: Primary outcome, quitting at least 24 hours before surgery, verified by exhaled carbon monoxide testing. Feasibility outcomes were the proportion taking up offers, ease of patient contact and disputes about quit status. RESULTS: Of 620 randomised participants (control 312, intervention 308), 404 had surgery at the hospital during the trial (control 214, intervention 190), which was lower than expected (for COVID-19 reasons). Offering $A70 resulted in 21.9% registering to quit, increasing to 32.6% with $A140. Telephone calls were the most effective means to gain registrations. The proportion of intervention group patients verified quit at least 24 hours before surgery was similar to controls (9.5% vs 8.9%, OR 1.1, 95% CI 0.5 to 2.2). Quitline contact was higher in the intervention group (13.2% vs 2.3%, OR 6.3, 95% CI 2.3 to 21.6). Disputes over test results did not occur, but 17.4% of intervention participants claiming quit failed verification. CONCLUSION: A single offer of financial rewards for perioperative cessation was feasible, without achieving clinically important quit differences. TRIAL REGISTRATION NUMBER: ACTRN12620000130965.

Carnosic acid inhibits secretion of allergic inflammatory mediators in IgE-activated mast cells via direct regulation of Syk activation.

Mast cells are essential regulators of inflammation most recognized for their central role in allergic inflammatory disorders. Signaling via the high-affinity immunoglobulin E (IgE) receptor, FcεRI, leads to rapid degranulation of preformed granules and the sustained release of newly synthesized proinflammatory mediators. Our group recently established rosemary extract as a potent regulator of mast cell functions, attenuating MAPK and NF-κB signaling. Carnosic acid (CA)-a major polyphenolic constituent of rosemary extract-has been shown to exhibit anti-inflammatory effects in other immune cell models, but its role as a potential modulator of mast cell activation is undefined. Therefore, we sought here to determine the modulatory effects of CA in a mast cell model of allergic inflammation. We sensitized bone marrow-derived mast cells with anti-trinitrophenyl IgE and activated with allergen (TNP-BSA) under stem cell factor potentiation, in addition to treatment with CA. Our results indicate that CA significantly inhibits allergen-induced early phase responses including Ca2+ mobilization, ROS production, and subsequent degranulation. We also show CA treatment reduced late phase responses, including the release of all cytokines and chemokines examined following IgE stimulation and corresponding gene expression excepting that of CCL2. Importantly, we determined that CA mediates its inhibitory effects through modulation of tyrosine kinase Syk and downstream effectors TAK1 (Ser412) and Akt (Ser473) as well as NFκB signaling, while phosphorylation of FcεRI (γ chain) and MAPK proteins remained unaltered. These novel findings establish CA as a potent modulator of mast cell activation, warranting further investigation as a putative anti-allergy therapeutic.

Robotic LINX Placement: Is it Worth It?

Background: Laparoscopic Nissen fundoplication is considered the current gold standard of surgical treatment of gastroesophageal reflux disease. Magnetic sphincter augmentation with the LINX® device was developed as a less technically challenging alternative that has proven to be a safe and effective surgical antireflux procedure. Despite rapid adoption of the robotic platform in many areas of general surgery, no studies have compared laparoscopic and robotic approaches to placement of the LINX device. This retrospective study is the first to compare the robotic platform with the laparoscopic approach for minimally invasive LINX placement. Methods: We conducted a retrospective review of a total cohort of 20 patients who underwent LINX placement with hiatal hernia repair at our institution. Half of the patients underwent surgery using laparoscopy and the other half with robotic technology. Patient characteristics, surgical outcomes, and charge differences were analyzed. Results: We found that there were no significant differences in hospital length of stay, surgical outcomes, use of proton pump inhibitors (PPIs) postoperatively, or postoperative dysphagia. Patients undergoing robotic surgery had longer operative time (139 ± 25 minutes versus 81 ± 14 minutes, P < .01), higher intraoperative charges ($8980 ± 275 versus $7239 ± 355, P < .01), and higher charges associated with their hospital stay ($45,037 ± 4112.41 versus $39,565 ± 3731.64, P < .01). Conclusions: In comparison with laparoscopic LINX procedures, robotic LINX does not offer superior surgical outcomes in terms of postoperative PPI use, dysphagia, or hospital length of stay. Robotic LINX procedures are associated with increased operative time and overall charges.

Colorimetric Polymerase Chain Reaction Enabled by a Fast Light-Activated Substrate Chromogenic Detection Platform.

Miniaturization of nucleic acid tests (NATs) into portable, inexpensive detection platforms may aid disease diagnosis in point-of-care (POC) settings. Colorimetric signals are ideal readouts for portable NATs, and it remains of high demand to develop color readouts that are simple, quantitative, and versatile. Thus motivated, we report a fast light-activated substrate chromogenic polymerase chain reaction (FLASH PCR) that uses DNA intercalating dyes (DIDs) to enable colorimetric nucleic acid detection and quantification. The FLASH system is established on our finding that DID-DNA intercalation can promote the rapid photooxidation of chromogenic substrates through light-induced production of singlet oxygen. Using this principle, we have successfully converted DID-based fluorescent PCR assays into colorimetric FLASH PCR. To demonstrate the practical applicability of FLASH PCR to POC diagnosis, we also fabricated two readout platforms, including a portable electronic FLASH reader and a paper-based FLASH strip. Using the FLASH reader, we were able to detect as low as 60 copies of DNA standards, a limit of detection (LOD) comparable with commercial quantitative PCR. The FLASH strip further enables the reader-free detection of PCR amplicons by converting the colorimetric signal into the visual measurement of distance as a readout. Finally, the practical applicability of the FLASH PCR was demonstrated by the detection and/or quantification of nucleic acid markers in diverse clinical and biological samples.

Attenuation of allergen-mediated mast cell activation by rosemary extract (Rosmarinus officinalis L.).

Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro-inflammatory mediators in the late-phase. The MAPK and NF-κB pathways are established as critical intracellular mechanisms directing mast cell-induced inflammation. Rosemary extract (RE) has been shown to modulate the MAPK and NF-κB pathways in other cellular contexts in vitro and in vivo. However, the effect of RE on mast cell activation has not been explored, and thus we aim to evaluate the potential of RE in modulating mast cell activation and FcεRI/c-kit signaling, potentially via these key pathways. Primary murine mast cells were sensitized with anti-TNP IgE and stimulated with cognate allergen (TNP-BSA) under stem cell factor (SCF) potentiation while treated with 0-25 µg/ml RE. RE treatment inhibited phosphorylation of p38 and JNK MAPKs while also impairing NF-кB transcription factor activity. Gene expression and mediator secretion analysis showed that RE treatment decreased IL-6, TNF, IL-13, CCL1, and CCL3, but major component polyphenols do not contribute to these effects. Importantly, RE treatment significantly inhibited early phase mast cell degranulation (down to 15% of control), with carnosic acid and carnosol contributing. These findings indicate that RE is capable of modulating mast cell functional outcomes and that further investigation of the underlying mechanisms and its potential therapeutic properties in allergic inflammatory conditions is warranted.

TAK1 signaling activity links the mast cell cytokine response and degranulation in allergic inflammation.

Mast cells drive the inappropriate immune response characteristic of allergic inflammatory disorders via release of pro-inflammatory mediators in response to environmental cues detected by the IgE-FcεRI complex. The role of TGF-ß-activated kinase 1 (TAK1), a participant in related signaling in other contexts, remains unknown in allergy. We detect novel activation of TAK1 at Ser412 in response to IgE-mediated activation under SCF-c-kit potentiation in a mast cell-driven response characteristic of allergic inflammation, which is potently blocked by TAK1 inhibitor 5Z-7-oxozeaenol (OZ). We, therefore, interrogated the role of TAK1 in a series of mast cell-mediated responses using IgE-sensitized murine bone marrow-derived mast cells, stimulated with allergen under several TAK1 inhibition strategies. TAK1 inhibition by OZ resulted in significant impairment in the phosphorylation of MAPKs p38, ERK, and JNK; and mediation of the NF-κB pathway via IκBα. Impaired gene expression and near abrogation in release of pro-inflammatory cytokines TNF, IL-6, IL-13, and chemokines CCL1, and CCL2 was detected. Finally, a significant inhibition of mast cell degranulation, accompanied by an impairment in calcium mobilization, was observed in TAK1-inhibited cells. These results suggest that TAK1 acts as a signaling node, not only linking the MAPK and NF-κB pathways in driving the late-phase response, but also initiation of the degranulation mechanism of the mast cell early-phase response following allergen recognition and may warrant consideration in future therapeutic development.

Cutaneous basal cell carcinoma mimicking small cell carcinoma.

Neuroendocrine differentiation seen in basal cell carcinomas (BCC) is not generally appreciated by oncologists and can introduce a component of confusion when diagnosing a tumor and developing a management plan. Understanding that BCC commonly have this feature can assist the treating oncologist.

Effects of Resveratrol against Lung Cancer: In Vitro and In Vivo Studies.

Uncontrolled cell growth and resistance to apoptosis characterize cancer cells. These two main features are initiated in cancer cells through mutations in key signaling molecules, which regulate pathways that are directly involved in controlling cell proliferation and apoptosis. Resveratrol (RSV), a naturally occurring plant polyphenol, has been shown to have biological effects counteracting different diseases. It has been found to provide cardio-protective, neuro-protective, immuno-modulatory, and anti-cancer health benefits. RSV has been found to inhibit cancer cell proliferation, induce cell cycle arrest and apoptosis, and these anticancer effects may be due to its ability to modulate signaling molecules involved in these processes. The present review summarizes the existing in vitro and in vivo studies on resveratrol and its anti-lung cancer properties.

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies.

Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival and these mutations allow them to develop resistance to many chemotherapeutic agents, highlighting the need for development of new potent anti-cancer agents. Metformin has long been used as a treatment for type 2 diabetes and has recently attracted attention as a potential agent to be used in the treatment of cancer. The present review summarizes the existing in vitro and in vivo animal studies focusing on the anti-lung cancer effects of metformin and its effects on key proliferative and anti-apoptotic signaling pathways.

Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols.

Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival. Compounds of plant origin, including food components, have attracted scientific attention for use as agents for cancer prevention and treatment. The exploration into natural products offers great opportunity to evaluate new anticancer agents as well as understand novel and potentially relevant mechanisms of action. Rosemary extract has been reported to have antioxidant, anti-inflammatory, antidiabetic and anticancer properties. Rosemary extract contains many polyphenols with carnosic acid and rosmarinic acid found in highest concentrations. The present review summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of rosemary extract and the rosemary extract polyphenols carnosic acid and rosmarinic acid, and their effects on key signaling molecules.