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Lung cancer screening by helical low-dose computed tomography detects nonsolid nodules that may be lung adenocarcinoma precursors. Aspirin's anti-inflammatory properties make it an attractive target for prevention of multiple cancers, including lung cancer. Therefore, we conducted a phase IIb trial (NCT02169271) to study the efficacy of low-dose aspirin to reduce the size of subsolid lung nodules (SSNs). A total of 98 current or former smokers (67.3% current) undergoing annual low-dose computed tomography screening with persistent SSNs were randomly assigned to receive aspirin 100 mg/day or placebo for 1 year. There was no difference in change in the sum of the longest diameters of target nodules in the placebo and aspirin arm after 12 months of treatment (-0.12 mm [SD = 1.55 mm] and +0.30 mm [SD= 2.54 mm], respectively; 2-sided P = .33 primary endpoint). There were no changes observed in subgroup analyses by individual characteristics or nodule type. One year of low-dose aspirin did not show any effect on lung SSNs. SSNs regression may not be the proper target for aspirin, and/or longer duration may be needed to see SSNs modifications.

Background: Melissa officinalis standardised extracts, characterised by the presence of hydroxycinnamic acids, have been experimentally demonstrated to be endowed with anti-anxiety and anti-insomnia pharmacological actions. These effects, probably attributable, at least in part, to the role played by rosmarinic acid on GABA-T, have not always been observed in a reproducible manner in humans, perhaps due to the poor bioavailability of these compounds. Methods: as nutraceuticals and botanicals could be an alternative option to prescription medications for alleviating symptoms of mild anxiety and insomnia, we have verified in a prospective, double-blind, placebo-controlled, and cross-over study the supporting role on sleep quality played by a Melissa officinalis highly standardised extract, formulated as Phytosome™ (MOP) to improve the oral bioavailability of its active polyphenolic components. Results: results showed a significant reduction in the ISI score in the treated group, with an average of 6.8 ± 4.1 compared to 9.7 ± 3.7 in the placebo group, indicating a significant reduction of 2.9 points (p = 0.003). The SWS phase duration increased by an average of 15%, while the REM phase decreased by 10%. Additionally, 87% of participants in the treated group reported improved sleep quality, compared to 30% in the placebo group, with significant differences measured by chi-square test (χ2(4) = 21.01, p = 0.0003), highlighting the effects due to Melissa officinalis L. No significant changes in physical activity or anxiety levels were observed. Conclusions: these findings suggest that MOP may represent a natural and safe alternative to traditional pharmacological treatments for insomnia. [ABSTRACT FROM AUTHOR]

This case report examines the correlation between hydration, weight variation, and perceived effort in a 43-year-old amateur athlete during a self-supported 81.5 km crossing of Death Valley, completed over 3 days with significant elevation changes. Studies have shown that a body mass loss greater than 2–3% can lead to an increased perception of effort and a decline in performance. Specifically, during passive and active heat exposures, the average body mass loss was found to be 1.4 ± 0.3% and 4.1 ± 0.7%, respectively. Salivary osmolarity has demonstrated a sensitivity of 86% and specificity of 91% in diagnosing dehydration of ≥ 2%, suggesting its potential as a non-invasive indicator of hydration status. The subject monitored their own body weight, hydration (via salivary osmolarity), and perceived effort using a rate of perceived exertion (RPE) scale. Nutritional intake included isocaloric meals and nutritional bars, and hydration was managed using water and a hydroelectrolytic solution. Key bioimpedance parameters were measured to assess body composition and hydration status. A progressive decrease in body weight correlated with an increase in perceived effort (RPE score) and salivary osmolarity. Resistance (Rx) remained stable, while reactance (Xc) showed a biphasic trend and was inversely correlated with the sodium/potassium ratio (NAK). There were significant linear correlations between perceived effort and both weight loss and salivary osmolarity, indicating that salivary osmolarity is a potential early predictor of these changes. The findings highlight a linear correlation between weight loss, perceived effort, and salivary osmolarity, suggesting that monitoring salivary osmolarity would be useful for the field assessment of hydration and exertion. Further research with larger populations is necessary to validate these observations. [ABSTRACT FROM AUTHOR]

Intrapartum antibiotic prophylaxis, considered able to prevent streptococcal transmission from mother to newborn and its severe negative consequences, leads to microbiota dysbiosis, described as having a negative impact on well-being in both elements of the dyad. Enterococcus faecium L3 is a probiotic strain capable of exerting strong antagonistic activity against most streptococci, including S. agalactiae, due to the production of bacteriocins (known as enterocins A and B). A proprietary probiotic mixture containing the strain L3 demonstrated, in 2016, a significant reduction in episodes of PROM in pregnant women, with a less-than-expected effect on the vaginal–rectal presence of the pathogen S. agalactiae. With the aim of confirming the role exerted by the probiotic mixture in PROM episodes and to better understand the value of its impact on the clinical detection of S. agalactiae, we have retrospectively analyzed the results obtained in 125 L3-treated (over 12 weeks) women versus 125 untreated controls. Despite some limitations, our analysis has confirmed the role exerted by the probiotic in significantly reducing the following: (1) episodes of PROM, (2) vaginal–rectal positivity for S. agalactiae, and (3) the need to administer intrapartum antibiotics for prophylaxis. It likely also suggests operating using a cultural method very specific to S. agalactiae when testing women who were administered an Enterococcus-based probiotic. [ABSTRACT FROM AUTHOR]

Recent investigations have highlighted, both experimentally and clinically, that probiotic strains equipped with arabinofuranosidase, in particular abfA and abfB, favor regular intestinal motility, thus counteracting constipation. By analyzing the gene expression and the proliferative response in the presence of arabinan of the probiotic B. longum W11, a strain previously validated as an anti-constipation probiotic, we have speculated that its response mechanism to arabinan can effectively explain its clinical action. Our approach could be used in the future to select probiotics endowed with arabinofuranosidase-related anti-constipation effects. [ABSTRACT FROM AUTHOR]

The discovery of immune checkpoints (CTLA-4, PD-1, and PD-L1) and their impact on the prognosis of oncological diseases have paved the way for the development of revolutionary oncological treatments. These treatments do not combat tumors with drugs "against" cancer cells but rather support and enhance the ability of the immune system to respond directly to tumor growth by attacking the cancer cells with lymphocytes. It has now been widely demonstrated that the presence of an adequate immune response, essentially represented by the number of TILs (tumor-infiltrating lymphocytes) present in the tumor mass decisively influences the response to treatments and the prognosis of the disease. Therefore, immunotherapy is based on and cannot be carried out without the ability to increase the presence of lymphocytic cells at the tumor site, thereby limiting and nullifying certain tumor evasion mechanisms, particularly those expressed by the activity (under positive physiological conditions) of checkpoints that restrain the response against transformed cells. Immunotherapy has been in the experimental phase for decades, and its excellent results have made it a cornerstone of treatments for many oncological pathologies, especially when combined with chemotherapy and radiotherapy. Despite these successes, a significant number of patients (approximately 50%) do not respond to treatment or develop resistance early on. The microbiota, its composition, and our ability to modulate it can have a positive impact on oncological treatments, reducing side effects and increasing sensitivity and effectiveness. Numerous studies published in high-ranking journals confirm that a certain microbial balance, particularly the presence of bacteria capable of producing short-chain fatty acids (SCFAs), especially butyrate, is essential not only for reducing the side effects of chemoradiotherapy treatments but also for a better response to immune treatments and, therefore, a better prognosis. This opens up the possibility that favorable modulation of the microbiota could become an essential complementary treatment to standard oncological therapies. This brief review aims to highlight the key aspects of using precision probiotics, such as Clostridium butyricum, that produce butyrate to improve the response to immune checkpoint treatments and, thus, the prognosis of oncological diseases. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted a possible correlation between microbiota composition and the pathogenesis of various oncological diseases. Also, many bacterial groups are now directly or indirectly associated with the capability of stimulating or inhibiting carcinogenic pathways. However, little is known about the importance and impact of microbiota patterns related to the efficacy and toxicity of cancer treatments. We have recently begun to understand how oncological therapies and the microbiota are closely interconnected and could influence each other. Chemotherapy effectiveness, for example, appears to be strongly influenced by the presence of some microorganisms capable of modulating the pharmacokinetics and pharmacodynamics of the compounds used, thus varying the real response and therefore the efficacy of the oncological treatment. Similarly, chemotherapeutic agents can modulate the microbiota with variations that could facilitate or avoid the onset of important side effects. This finding has or could have considerable relevance as it is possible that our ability to modulate and modify the microbial structure before, during, and after treatment could influence all the clinical parameters related to pharmacological treatments and, eventually, the prognosis of the disease. [ABSTRACT FROM AUTHOR]

Abstract Background Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. Methods-Design From 2005 to 2011, 150 women with a history of estrogen receptor negative ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. Discussion This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible procedure, the treatment is well tolerated and the safety blood tests do not show any significant liver toxicity. There is an urgent need to confirm in the clinical setting the potential efficacy of other compounds in contrasting hormone non-responsive breast cancer. This paper is focused on the methodology and operational aspects of the clinical trial. Trial Registration (ClinicalTrials.gov Identifier: NCT01500577)