Factors associated with a change in smoking habit during the first COVID-19 lockdown: an Italian cross-sectional study among ever-smokers

Background: The COVID-19 pandemic and the lockdown period lasted from March to May 2020, resulted in a highly stressful situation yielding different negative health consequences, including the worsening of smoking habit. Methods: A web-based cross-sectional study on a convenient sample of 1013 Italian ever smokers aged 18 years or more was conducted. Data were derived from surveys compiled by three different groups of people: subjects belonging to Smoking Cessation Services, Healthcare Providers and Nursing Sciences' students. All institutions were from Northern Italy. The primary outcome self-reported worsening (relapse or increase) or improvement (quit or reduce) of smoking habit during lockdown period. Multiple unconditional (for worsening) and multinomial (for improving) logistic regressions were carried out. Results: Among 962 participants, 56.0% were ex-smokers. Overall, 13.2% of ex-smokers before lockdown reported relapsing and 32.7% of current smokers increasing cigarette intake. Among current smokers before lockdown, 10.1% quit smoking and 13.5% decreased cigarette intake. Out of 7 selected stressors related to COVID-19, four were significantly related to relapse (OR for the highest vs. the lowest tertile ranging between 2.24 and 3.62): fear of being infected and getting sick; fear of dying due to the virus; anxiety in listening to news of the epidemic; sense of powerlessness in protecting oneself from contagion. In addition to these stressors, even the other 3 stressors were related with increasing cigarette intensity (OR ranging between 1.90 and 4.18): sense of powerlessness in protecting loved ones from contagion; fear of losing loved ones due to virus; fear of infecting other. Conclusion: The lockdown during the COVID-19 pandemic was associated with both self-reported relapse or increase smoking habit and also quitting or reduction of it

A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM).Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing.Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia and macroscopical lesions (>1 mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis.Conclusions: MD-MIX was able to counteract CRC development in mice under different dietary backgrounds through the regulation of apoptosis and gut microbiota

Tissue-specific dysregulation of 11\u3b2-hydroxysteroid dehydrogenase type 1 in overweight/obese women with polycystic ovary syndrome compared with weight-matched controls

CONTEXT:Abnormal cortisol metabolism in polycystic ovary syndrome (PCOS) has been invoked as a cause of secondary activation of the hypothalamic-pituitary-adrenal axis and hence androgen excess. However, this is based on urinary excretion of cortisol metabolites, which cannot detect tissue-specific changes in metabolism and may be confounded by obesity. OBJECTIVE:To assess cortisol clearance and whole-body and tissue-specific activities of 11\u3b2-hydroxysteroid dehydrogenase type 1 (11\u3b2-HSD1 (HSD11B1)) in PCOS. DESIGN:Case-control study. SETTING:Medical center. PATIENTS:A total of 20 overweight-obese unmedicated Caucasian women with PCOS, aged 18-45 years, and 20 Caucasian controls matched for age, BMI, body fat distribution, and HSD11B1 genotypes (rs846910 and rs12086634). MAIN OUTCOME MEASURES:Cortisol metabolites were measured in 24\u200ah urine. During steady-state 9,11,12,12-[(2)H]4-cortisol infusion, cortisol clearance was calculated and whole-body HSD11B1 activity was assessed as the rate of appearance of 9,12,12-(2)H3-cortisol (d3-cortisol). Hepatic HSD11B1 activity was quantified as the generation of plasma cortisol following an oral dose of cortisone. Subcutaneous adipose HSD11B1 activity and HSD11B1 mRNA were measured, ex vivo, in biopsies. RESULTS:Urinary cortisol metabolite excretion, deuterated cortisol clearance, and the rate of appearance of d3-cortisol did not differ between patients with PCOS and controls. However, hepatic HSD11B1 conversion of oral cortisone to cortisol was impaired (P<0.05), whereas subcutaneous abdominal adipose tissue HSD11B1 mRNA levels and activity were increased (P<0.05) in women with PCOS when compared with controls. CONCLUSIONS:Tissue-specific dysregulation of HSD11B1 is a feature of PCOS, over and above obesity, whereas increased clearance of cortisol may result from obesity rather than PCOS

Effect of Different Tube Feeding Methods on the Delivery of Docosahexaenoic and Arachidonic Acid: An In Vitro Pilot Study

Background: Arachidonic acid (AA) and docosahexaenoic acid (DHA) are crucial for neural and visual development after premature birth. Preterm infants usually require tube feeding (TF) until the achievement of adequate oral feeding skills; the impact of TF on DHA and AA delivery has not been investigated yet. This study aimed to evaluate the effect of different TF techniques on the delivery of AA and DHA contained in human milk (HM). Methods: HM samples (65 mL each) were collected and divided into three 20-mL aliquots. The remaining 5 mL served as baseline. Three TF techniques were simulated (1 for each aliquot): gravity bolus feeding (BF), 3-hour continuous feeding using a horizontal feeding pump, and 3-hour continuous feeding with the feeding pump angled at 45°. For horizontal continuous feeding (HCF) and 45° angled continuous feeding (ACF), aliquots delivered between 0 and 90 minutes (T1) and 91 and 180 minutes (T2) were collected separately. AA and DHA concentration was analyzed by gas chromatography/mass spectrometry and compared among the TF methods. DHA and AA delivery at T1 and T2 was also evaluated. Results: Fifty-one simulated feeds were performed. DHA and AA amounts after BF and ACF did not differ significantly compared with baseline, whereas HCF resulted in significantly lower DHA and AA concentration. During T2, ACF delivered almost twice the DHA and AA amounts compared with T1. Conclusion: The delivery of HM AA and DHA is significantly affected by TF, with potential clinical implications. When BF is not tolerated, ACF might represent a feasible alternative to reduce TF-related DHA and AA loss

Maternal Supplementation With Krill Oil During Breastfeeding and Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) Composition of Human Milk: A Feasibility Study

Background: Docosahexaenoic acid (DHA) is amajor constituent of neuronal and retinal membranes and plays a crucial role in brain and visual development within the first months of life. Dietary intakes are fundamental to provide neonates with adequate DHA supply; hence, maternal supplementation might represent a useful strategy to implement DHA contents in breast milk (BM), with possible benefits on neonatal neurodevelopment. Antarctic krill is a small crustacean rich in highly available phospholipid-bound DHA. This pilot study aimed to evaluate whether maternal supplementation with krill oil during breastfeeding increases long-chain polyunsaturated fatty acids (LCPUFAs) BM contents.Methods: Mothers of infants admitted to the Neonatal Intensive Care Unit were enrolled in this open, randomized-controlled study between 4 and 6 weeks after delivery and randomly allocated in 2 groups. Group 1 received an oral krill oil-based supplement providing 250mg/day of DHA and 70mg/day of eicosapentaenoic acid (EPA) for 30 days; group 2 served as control. BM samples from both groups were collected at baseline (T0) and day 30 (T1) and underwent a qualitative analysis of LCPUFAs composition by gas chromatography/mass spectrometry.Results: Sixteen breastfeeding women were included. Of these, 8 received krill-oil supplementation and 8 were randomized to the control group. Baseline percentage values of DHA (% DHA), arachidonic acid (% AA), and EPA (% EPA) did not differ between groups. A significant increase in % DHA (T0: median 0.23% [IQR 0.19; 0.38], T1: 0.42%[0.32; 0.49], p 0.012) and% EPA (T0: median 0.10%[IQR 0.04; 0.11], T1: 0.11% [0.04; 0.15], p 0.036) and a significant reduction in % AA (T0: median 0.48% [IQR 0.42; 0.75], T1: 0.43% [0.38; 0.61], p 0.017) between T0 and T1 occurred in Group 1, whereas no difference was seen in Group 2. Consistently, a significant between-group difference was observed in percentage changes from baseline of DHA (Delta% DHA, group 1: median 64.2% [IQR 27.5; 134.6], group 2: -7.8% [-12.1;-3.13], p 0.025) and EPA (Delta% EPA, group 1: median 39% [IQR 15.7; 73.4]; group 2: -25.62% [-32.7;-3.4], p 0.035).Conclusions: Oral krill oil supplementation effectively increases DHA and EPA contents in BM. Potential benefits of this strategy on brain and visual development in breastfed preterm neonates deserve further evaluation in targeted studies

Inflammation increases NOTCH1 activity via MMP9 and is counteracted by Eicosapentaenoic Acid-free fatty acid in colon cancer cells

Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fatty acid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free Fatty Acid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA

A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota

Objectives: Unhealthy dietary patterns have been associated with colorectal cancer (CRC) onset while Mediterranean Diet (MD) has been proposed for CRC prevention. This study evaluated the effect of a Mediterranean Diet Mix (MD-MIX) on colonic tumors development in A/J mice fed a low-fat (LFD) or a high-fat western diet (HFWD), and injected with the procarcinogen azoxymethane (AOM). Materials and Methods: Forty A/J male mice were randomly assigned into four feeding arms (10 mice/arm; LFD, LFD-MD-MIX, HFWD, HFWD-MD-MIX) to be treated with AOM. Ten mice were exposed to the diets alone (Healthy LFD and Healthy HFWD) to be used as control. Tumor incidence and multiplicity were evaluated at sacrifice. Mucosal fatty acid content and urinary phenolic compounds were assayed by mass spectrometry. Apoptosis was evaluated by TUNEL assay and gene expression markers. Cell proliferation was evaluated by Ki67 immunohistochemistry. Microbiota composition was assessed at different time points by 16S RNA sequencing. Results: A tumor incidence of 100% was obtained in AOM-treated mice. The MD-MIX supplementation was able to reduce the number of colonic lesions in both LFD and HFWD-fed mice and to induce apoptosis, in particular in the LFD-MD-MIX arm. Moreover, a preventive effect on low-grade dysplasia andmacroscopical lesions (>1mm) development was found in HFWD-fed mice together with a regulation of the AOM-driven intestinal dysbiosis. Conclusions: MD-MIX was able to counteract CRC development inmice under different dietary backgrounds through the regulation of apoptosis and gut microbiota

Short-term treatment with eicosapentaenoic acid improves inflammation and affects colonic differentiation markers and microbiota in patients with ulcerative colitis

Patients with long-standing ulcerative colitis (UC) have an increased colorectal cancer (CRC) risk. In this pilot study we evaluated the effect of Eicosapentaenoic acid as free fatty acid (EPA-FFA) supplementation on mucosal disease activity, colonic differentiation markers and microbiota composition in UC patients. Twenty long-standing UC patients in stable clinical remission and with fecal calprotectin (FC)\u2009>\u2009150\u2009\ub5g/g were enrolled (T0) and supplemented with EPA-FFA 2\u2009g/daily for 90 days (T3). Endoscopic and histologic disease activities were measured by Mayo and Geboes scores, respectively. HES1, KLF4, STAT3, IL-10 and SOCS3 levels were determined using western blotting and qRT-PCR, while phospho-STAT3 levels were assessed by western blotting. Goblet cells were stained by Alcian blue. Microbiota analyses were performed on both fecal and colonic samples. Nineteen patients completed the study; seventeen (89.5%) were compliant. EPA-FFA treatment reduced FC levels at T3. Patients with FC\u2009>\u2009150\u2009\ub5g/g at T3 (n\u2009=\u20092) were assumed as non-responders. EPA-FFA improved endoscopic and histological inflammation and induced IL-10, SOCS3, HES1 and KLF4 in compliant and responder patients. Importantly, long-term UC-driven microbiota composition was partially redressed by EPA-FFA. In conclusion, EPA-FFA supplementation reduced mucosal inflammation, promoted goblet cells differentiation and modulated intestinal microbiota composition in long-standing UC patients