Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial

Constipation is a major issue for 10–20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18–59 years) received either 11 g or 5.5 g of BiotisTM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.

Effects of high-dilutions in behavioural models: a commentary on critical issues, from reproducibility to plausibility

As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-field), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this field, disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.

1473Early life immune modulatory exposures and allergy risk in Japanese children

Background Incidence of allergies among children is increasing and is an important public health issue. We examined whether early life immune modulating exposures and surrogate measures are associated with a reduced risk of allergic diseases among Japanese children. Methods We analyzed data from the Health Diary Study comprising a nationally representative cross-sectional sample of children/adolescents aged 1 to 17 years in Japan. Data were collected on early life factors and diagnosed allergic diseases using a self-administered questionnaire. Multivariable logistic regression was conducted evaluating the effects of delivery method, breastfeeding, infections in infancy, older siblings, and daycare on the risk of any allergy and specific types. Results Among 744 children included (mean age=9.5 years; 52% males), 41% experienced an allergic condition. Infection in infancy was associated with an increased risk of asthma (OR = 1.77, 95% CI: 1.09-2.85) especially related to bronchitis and ear infection, and showed a dose-response effect with increasing number of infections (p=0.04). Having older sibling(s) modified the effect of infections on asthma risk (p-interaction=0.11). Reduction in risk of allergic rhinitis was suggestive related to exclusive breastfeeding and having two or more siblings. Conclusions Evidence is unclear regarding a protective role of early life immune modulatory exposures in allergy risk in Japanese children. In contrast, infectious episodes in infancy may increase the risk of asthma. Key messages While multiple mechanisms may be at play, infections in infancy may increase the risk of asthma which supports protection against infectious transmissions.

Response to Therapeutic Abortion in Lactating Dairy Cows Carrying Dead Twins during the Late Embryo/Early Fetal Period

This study examined the dose–response effect of prostaglandin F2α (PGF2α) when used to induce abortion in cows with two dead twins at pregnancy diagnosis 28–34 days post-AI (late embryonic period: LE) or at pregnancy confirmation 49–55 days post-AI (early fetal period: EF). The study population consisted of 415 cows receiving a single PGF2α dose (PG1 group: 254 LE and 161 EF cows) and 200 receiving a 1.5 × PGF2α dose (PG1.5 group: 121 LE and 79 EF cows). The induced abortion rate was significantly lower (chi-square test; p < 0.0001) in the EF (34.6%) than LE cows (88%), and was also reduced (p = 0.001) in the EF PG1 group (28%) compared with the EF PG1.5 group (48.1%). High milk production (≥45 kg) was the only factor influencing the induced abortion rate in LE cows (odds ratio 0.2; p < 0.0001), whereas the odds ratio for induced abortion of PG1.5 cows was 2.3 (p = 0.005) in EF cows. In conclusion, an increased PGF2α dose had no effect on abortion induction during the late embryonic period and its rate was inversely associated with milk production. This higher PGF2α dose did, however, offer benefits during the early fetal period.

Relationship Between Serum Albumin and Risk of Atrial Fibrillation: A Dose-Response Meta-Analysis

Background: The dose–response association between serum albumin and atrial fibrillation is not well known. This study aims to assess the relationship between albumin and atrial fibrillation and the potential dose–response effect.Methods: Studies reported that the serum albumin and AF were identified by searching the EMBASE, PubMed, and Cochrane Library databases. The potential dose–response effect was performed by using a stage robust error meta-regression.Results: Nine studies were included with a total of 32,130 individuals. Patients with high albumin level were associated with a decreased risk of atrial fibrillation compared with patients with low serum albumin (OR[odds ratio]: 0.62, 95% CI [0.44, 0.89]; I2 = 76%; P = 0.009). In the dose–response analysis, for each 10 g/L increase in serum albumin level, the risk of atrial fibrillation decreased by 36% (95% CI: 0.51–0.81, I2 = 87%, P &lt; 0.001). Furthermore, a significant negative linear relationship between serum albumin and the risk of atrial fibrillation (Pnonlinearity = 0.33) was found.Conclusion: Our dose–response meta-analysis suggests that low serum albumin level is associated with an increased risk of atrial fibrillation. Further studies are needed to explore the effect of induction of elevated serum albumin levels on the prevention of atrial fibrillation.

Interference of Polydatin/Resveratrol in the ACE2:Spike Recognition during COVID-19 Infection. A Focus on Their Potential Mechanism of Action through Computational and Biochemical Assays

In the search for new therapeutic strategies to contrast SARS-CoV-2, we here studied the interaction of polydatin (PD) and resveratrol (RESV)—two natural stilbene polyphenols with manifold, well known biological activities—with Spike, the viral protein essential for virus entry into host cells, and ACE2, the angiotensin-converting enzyme present on the surface of multiple cell types (including respiratory epithelial cells) which is the main host receptor for Spike binding. Molecular Docking simulations evidenced that both compounds can bind Spike, ACE2 and the ACE2:Spike complex with good affinity, although the interaction of PD appears stronger than that of RESV on all the investigated targets. Preliminary biochemical assays revealed a significant inhibitory activity of the ACE2:Spike recognition with a dose-response effect only in the case of PD.

p53 Mutation at Serine 249 and Its Gain of Function Are Highly Related to Hepatocellular Carcinoma after Smoking Exposure

<b><i>Background:</i></b> It has been convincingly suggested that a close correlation exists between the incidence of hepatocellular carcinoma (HCC) and cigarette smoking. However, the underlying effect of smoking on HCC is not clear. <b><i>Methods:</i></b> A binary unconditional logistic regression was used for the data on a total of 300 cases and 612 controls. The approach of functional analysis of separated alleles in yeast and direct sequencing of TP53 mutations were applied to analyze the p53 status in the HCC group. The relationship between p53 mutation at serine 249 (p53-RS) and smoking was assessed. Quantitative reverse transcription PCR was employed for the evaluation to transcriptional activity of p53 and p53-RS. <b><i>Results:</i></b> Smoking was linked to the risk of HCC with an increased dose-response effect. Moreover, among subjects who did not drink, the risks of HCC were significantly increased for smokers between HCC and controls. Besides, there was an increase in the number of HCC in smokers compared to nonsmokers after exclusion of HBV and/or HCV infection. Also, a significant difference was observed in the incidence of p53-RS between smokers and nonsmokers the HCC group. Furthermore, the p53-RS transcriptional activity was significantly increased in tumor tissues. <b><i>Conclusions:</i></b> It strongly demonstrated that tobacco smoking is positively and independently associated with HCC, which may be attributed to p53-RS and its gain of function.

Role of physical activity and metabolic syndrome in determining the risk of postmenopausal breast cancer: a systematic review

Physical activity (PA) and metabolic syndrome (MetS) have emerged as crucial factors in facilitating the incidence of postmenopausal (PM) breast cancer (BC). The association of PA, MetS and its components with PM BC was explored in this study. PRISMA guideline was followed and online databases were searched comprehensively to find relevant cohort and case-control studies until 18 February 2021 using keywords such as “physical activity”, “metabolic syndrome” and “breast cancer”. Eligible studies evaluating BC in postmenopausal women with a clear definition and measure of PA, MetS and its individual components were selected. A total of twenty-three articles related to PA and fifteen articles for MetS met the eligibility criteria and were assessed thoroughly. PA and MetS were significantly associated with PM BC. There was evidence of dose-response effect of PA and Mets on PM BC. Obesity, diabetes and dyslipidaemia were independently associated with PM BC and posed an increased risk on PM BC whereas the association of HPTN with PM BC was not prominent. Consistent and sustained long term PA throughout one’s lifetime was observed to decrease PM BC risk whereas increasing number of MetS components increased the risk of PM BC. Routine screening for PM women with ≥2 MetS components and obese or overweight women with any of the MetS components may be beneficial in early BC detection. Lifestyle modifications with emphasis on long term PA would be beneficial to public health in preventing and improving MetS outcomes as well as a primary prevention of sporadic PM BC.

Hand Hygiene Practices and the Risk of Human Coronavirus Infections in a UK Community Cohort

Background: Hand hygiene may mitigate the spread of COVID-19 in community settings; however, empirical evidence is limited. Given reports of similar transmission mechanisms for COVID-19 and seasonal coronaviruses, we investigated whether hand hygiene impacted the risk of acquiring seasonal coronavirus infections. Methods: Data were drawn from three successive winter cohorts (2006-2009) of the England-wide Flu Watch study. Participants (n=1633) provided baseline estimates of hand hygiene behaviour. Coronavirus infections were identified from nasal swabs using RT-PCR. Poisson mixed models estimated the effect of hand hygiene on personal risk of coronavirus illness, both unadjusted and adjusted for confounding by age and healthcare worker status. Results: Moderate-frequency handwashing (6-10 times per day) predicted a lower personal risk of coronavirus infection (adjusted incidence rate ratio (aIRR) =0.64, p=0.04). There was no evidence for a dose-response effect of handwashing, with results for higher levels of hand hygiene (>10 times per day) not significant (aIRR =0.83, p=0.42). Conclusions: This is the first empirical evidence that regular handwashing can reduce personal risk of acquiring seasonal coronavirus infection. These findings support clear public health messaging around the protective effects of hand washing in the context of the current COVID-19 pandemic.